The possibility of integrating thismaterial into two different transducing schemes for gas sensing isproposed since the nanomaterial changes both its electrical resistivityand optical properties when exposed to gases and at room temperature.Particularly, when implemented in a chemoresistive device, the Mo6@Graphene hybrid showed an outstanding sensing performancetoward NO2, revealing a limit of quantification of about10 ppb and excellent response repeatability (0.9% of relative error).While the Mo6@Graphene chemoresistor was almost insensitiveto NH3, the use of an optical transduction scheme (changesin photoluminescence) provided an outstanding detection of NH3 even for a low loading of Mo6. Nevertheless, thephotoluminescence was not affected by the presence of NO2. In addition, the hybrid material revealed high stability of itsgas sensing properties over time and under ambient moisture. Computationalchemistry calculations were performed to better understand these results,and plausible sensing mechanisms were presented accordingly. Theseresults pave the way to develop a new generation of multi-parametersensors in which electronic and optical interrogation techniques canbe implemented simultaneously, advancing toward the realization ofhighly selective and orthogonal gas sensing.This paper reportsfor the first time a gas-sensitivenanohybridbased on octahedral molybdenum iodide clusters supported on grapheneflakes (Mo This is why automated air quality control stations arefew and sparsely distributed in specific areas. However, effectivepollution monitoring can only be achieved through a network of denseranalysis locations (higher granularity) distributed over wider areas.2 In other words, the ubiquitous, unattended, andreal-time detection of harmful gases would protect human health byallowing the taking of pertinent actions in space and time. In thisperspective, the development of gas sensors with the ability to monitorlow concentrations of flammable, combustible, or toxic gases in realtime is crucial. These devices should gather essential propertiessuch as reliability, sensitivity, selectivity, repeatability, accuracy,and long-term stability together with inexpensiveness and low powerconsumption.Air pollution is probably the largestenvironmental health threatworldwide, accounting for 7 million premature deaths every year.3 For decades, metal oxide (MOX) semiconductors have dominated thefield of gas detection because of their high sensitivity, non-toxicity,and availability.4 However, their poorselectivity and power-hungriness (operation temperatures are highabove room temperature) are still preventing their effective implementationin commercial applications for air quality monitoring stations orunattended gas sensing networks. Therefore, the development of newand energy-efficient gas-sensitive nanomaterials is still much needed.Among the different technologies for developinggas sensors, chemoresistivedevices have attracted great research efforts owing to their simpledriving and readout instrumentation, durability, high potential forminiaturization, and industrial scalability.5 Room-temperature-operated gas sensors are energy efficient and helpreduce fabrication costs (as no heating elements are needed), whichmakes them very attractive for being integrated into air quality monitoringnetworks. Despite the noteworthy properties of graphene, such as highsurface area to volume ratios, low noise levels, high carrier densityand mobility, and affordable production costs,6 there are still some issues to be overcome. Graphene, especiallyin its pristine form, shows limited sensitivity and selectivity. Inthis sense, large research efforts have been focused on modifyingor functionalizing carbon-based films for improving their sensingproperties. The most direct functionalization strategies are probablythe modification of graphene via plasma treatments for creating defectsand replacing carbon atoms with others of different nature,7 or the use of wet chemistry processes for thecovalent or non-covalent functionalization of the graphene surface.8 With these approaches, the sensitivity of thegraphene layers is generally improved, but usually the selectivityissue remains only partially addressed, owing to the poor specificityof the atoms and functional groups present on the graphene surface.Another well-known strategy is the functionalization of graphene withorganic compounds such as macrocycles, aptamers, or cavitands.10 This approach significantly improves the selectivity because ofthe high specificity of the organic compounds  toward specific gases. However, the organic nature of thisfunctionalization, which is prone to degradation under operationalconditions, may compromise long-term device stability. Additionally,high specificity may result in limited reversibility of the gas–solidinteractions, which compromises response repeatability. Finally, thelast mainly used strategy is the decoration of graphene with metalor MOX nanoparticles.12 With that, it is possible tosignificantly increase the sensitivity and tune the selectivity tosome extent. However, these MOX nanoparticles usually need moderateor high operating temperatures for activating their sensing properties.Therefore, the achievement of low-power and inexpensive devices canbe jeopardized.In recent years, carbon nanomaterial-based sensors, especiallythose employing graphene, have become a common approach for developingdevices that operate at room temperature.15 These nanostructured semiconductors vary in composition and morphology,which impacts their sensing performance.17 Besides, the fabrication of molybdenum sensors is attractive dueto their abundance and low toxicity, the development of thin filmsand nanoparticles being the most common strategy.18 However, there is significant scope remaining to explorenew molybdenum materials with advanced properties for large-scalefabrication. Particularly, materials composed of architectured nanometer-sizedoctahedral molybdenum clusters (<2 nm) are very attractive forgas sensing purposes.19 These [Mo6Li8La6] cluster unitsare robust entities composed of inner halide ligands (Li) and organic or inorganic apical  ligands (La). Mo6 clusters act as powerful photosensitizers and arealso efficient luminophores that, under photoactivation, either exhibitphosphorescence in the 550–900 nm window or react with oxygento provide singlet molecular oxygen (1O2) directedto cell damage by oxidative stress and to theranostic applications.Until now, the existing literature on analyte sensing using Mo6 cluster-based nanomaterials encompasses optical oxygen sensors,24 optical sensing of antibiotics and nitroaromatic compounds in solution,26 and cluster dependence on environmental parameters, such as humidityor light.28 However, Mo6 clusters have notbeen applied to the detection of air pollutants until now, and theresearch of the materials composed of Mo6 clusters andgraphene and graphene oxide was limited to the photocatalytic field.32As an alternative, molybdenum chalcogenidesand their derivativeshave been extensively explored for gas detection in the last few years.6@Graphene nanohybridcomposed of a crystalline octahedral molybdenum iodide cluster materialsupported on graphene, and the integration of this hybrid onto a transducingplatform, enabling chemoresistive and optical gas sensing. The detectionof two gaseous species such as nitrogen dioxide (NO2) andammonia (NH3) is studied. NO2 is an electron-withdrawingcompound mainly released by automotive emissions and combustion ofconventional fossil fuels, which has become a major environmentalconcern because it contributes to the formation of photochemical smog,acid rain, and particulate matter through chemical reactions in theatmosphere. Ammonia emissions are associated with industrial livestock,fertilizer production processes, and crop agriculture. As a highlytoxic and corrosive agent, they threatenhuman health and the environment.33 Besides reporting the sensing properties ofthe Mo6@Graphene hybrid nanomaterial, its thorough morphologicaland compositional characterization is reported as well. Finally, thegas sensing mechanisms involved in the chemoresistive and opticaldetection are presented and discussed.To the best of our knowledge, the use of hexanuclear molybdenumcluster nanomaterials for the detection of pollutant species in thegas phase remains unexplored. Therefore, this paper encompasses, forthe first time, the preparation of a Mo6Ii8(OH)a4(H2O)a2]·2H2O (Mo6) material and its derived nanohybrid (Mo6@Graphene)were prepared and analyzed using several techniquessuch as Raman spectroscopy, powder X-ray diffraction, field-emissionscanning electron microscopy (FESEM), and high-resolution transmissionelectron microscopy (HR-TEM). The synthesis of Mo6 wasachieved by the hydrolysis of (Bu4N)2[Mo6Ii8(O2CCH3)a6].29 The immobilization of Mo6 on graphene was doneby mixing the respective precursors dispersed in dichloromethane andconfirmed through Raman spectroscopy , resulting in Mo6@Graphene. In this regard, the Ramanshifts below 360 cm–1 are associated with the presenceof molybdenum clusters present in the Mo6 material , while at higher frequencies, thecharacteristic D, G, 2D, and D′ bands of graphene appear at1347, 1588, 2712, and 2938 cm–1, respectively. TheD band is associated with the presence of structural defects, disorderedcarbon atoms in the sp2 configuration, and carbonaceousimpurities, while the G band is related to in-plane vibrations ofsp2 carbon bonds. Thereby, the D/G ratio revealed low crystallinegraphene, and the presence of defects and oxygenated functional groupsgrafted to the graphene is probably supporting the immobilizationof molybdenum clusters. The immobilized inorganic clusters at thegraphene surface are essential in gas sensing performance, enablinghigher interactions with gas compounds. Furthermore, the integrityand crystallinity of the cluster-based materials after the thermaltreatment (60 °C) needed for the preparation of the resultingMo6@Graphene were studied. Figure S1b shows intense bands with Raman shifts at 129, 153, 292, and 357cm–1 associated with the Mo–Mo, Mo–I,and Mo–O vibrations of the cluster.34 These Raman shifts are similar to those reported for similar hexamolybdenumclusters with iodide materials, revealing that the thermal treatmentapplied during the experimental protocol does not damage the clustercrystallinity owing to the lack of differences between both spectra.The suitable cluster synthesis and integrity after the thermal treatmentwere also confirmed through powder X-ray diffraction. Figure S2a depicts the diffractogram of the Mo6 material, which shows a family of planes associated witha preferential orientation of the crystalline material upon depositiononto the glass surface.29 The Mo6 crystallinity was preserved after the thermal process applied duringthe deposition step . Figure S2c shows the diffractogram of the Mo6@Graphene after the deposition process. Considering the lowgraphene crystallinity, it is noteworthy that some intense peaks associatedwith the crystallinity of Mo6 can be noticed in the nanohybrid,evidencing the presence of supported cluster crystals. Thereby, theX-ray diffraction also confirms that the synthesis and depositionprocesses developed avoided the degradation of molybdenum cluster-basedmaterial. The robustness of the prepared cluster materials is an advantagefor preparing gas sensors and conducting the resistive and opticalmeasurements described below. Regarding the binding interaction betweenthe crystalline cluster phase and the graphene sheets, we think thatit could mainly be associated with supramolecular interactions, suchas Van der Waals and charge electrostatic and polar interactions,due to the polarity induced by the cluster units and the presenceof water molecules embedded into the hydrogen-bonded network of thecrystalline cluster phase and the preference of such water moleculesto adsorb on residual defects and sites with oxygen-containing functionalgroups.36 However, thecluster immobilization of {Mo6Ii8}4+ cluster cores through coordinative bonds to such oxygenfunctionalities, as occurs with GO, cannot be discarded.29 Additional research on the study of the bindinginteractions involved is under current investigation.The crystalline cluster sites are preferentially exposed to gas adsorption, thesensing is probably promoted by hydrogen bonding between the apicalcluster ligand (hydroxo or water) and the gaseous analytes. To revealthe interactions between the [Mo6Ii8(OH)a4(H2O)a2] clusters and target molecules, DFT calculations were performedusing the BPE0 functional because of its robustness and excellentperformance for treating hydrogen bonds.56 Two stereoisomers, namely trans and cis-[Mo6Ii8(OH)a4(H2O)a2], were built as representativemodels for adsorption sites, and the reliability of this functionalwas confirmed by the analysis of the computed geometries of the isomers,which shows a good fit to the X-ray diffraction structure . The energetic interactions betweenthe cluster compound and the gas molecules were studied by computingthe binding energies (BEs) associated with the formation of a cluster-gasmolecule (NH3 or NO2) adduct in a 1:1 ratio.In all the adducts, the gas interacts directly with water and hydroxoligands (S13) by hydrogen bonding in most cases, withBEs in good agreement to H-bonding energies (Table S1). ca. −18 and −7kcal/mol, associated with the isomers with H2N···HOHand NO2···HOH interactions, respectively.The gas-cluster adducts become energetically more unstable when thehydroxo ligand is involved (Table S1).In all cases, BEs are negative, indicating that the formation of cluster-gasmolecule adducts is exothermic. Thus, NH3 and NO2 molecules are likely to be adsorbed onto the surface of the cluster-basedcrystalline material.The factor responsiblefor this orthogonal behavior is related to the interaction betweenthe target gas analytes and the molybdenum cluster-based material.The integrity of the Moligands 7 and S13tructure S12. The 6Ii8(OH)a4(H2O)a2] toward NH3 andNO2 under resistive and optical conditions is representedin 2 would favor the increase of positive charges in graphenelayers, resulting in a major chemoresistive response. In the presenceof NH3, its electron donor ability practically does notinfluence the electronic characteristics of the clusters, and, asa consequence, they would remain intact to exchange charges with graphene.This could be associated with the difficulty in the reduction of the{Mo6Ii8}4+ cluster corecompounds, considering their intrinsic redox properties.57 One question remains open regarding the smallchemoresistive response of Mo6@graphene in the presenceof ammonia in comparison with one of the bare graphenes 30 would promotethe transfer of some holes from the graphene layer to the metalliccluster and concomitant compensation of charges, giving rise to adiminution of the resistive response.A tentative description of the sensing mechanismof . This was prepared by properlyadapting the synthetic procedures reported in the literature fromthe (Bu4N)2[Mo6Ii8Ia6] and silver acetate materials.61 In a typical procedure for preparationof Mo6, the cluster precursor (30 mg) was dispersed ina mixture (15 mL) of water, acetone, and triethylamine in 50/45/5%v/v, respectively, in a round-bottom flask with continuous magneticstirring (500 rpm) at room temperature. Afterward, a bubbler was connectedto the flask, and the resulting yellow-orange suspension was heatedto 35 °C for 1 h. Over time, the mixture evolved to a solution,which was added into a 10 mL vial sealed with a holey parafilm forits slow evaporation for 5–7 days. Finally, red microcrystalswere collected from the remaining solution. The crystalline materialwas washed twice with acetone and once with Milli-Q water (10 mL).Notably, the optimum crystal size is achieved when the solution becomestransparent.The synthesis of Mo2/g,Strem Chemicals Inc., USA). Then, the resulting suspension was placedin an ultrasonic tip for achieving a proper graphene exfoliation.Particularly, a pulsed sonication (1s on/2s off) at 280 W for 90 minwas applied. A 1 mL suspension of Mo6 (0.25 mg/mL) in dichloromethanewas prepared by sonication for 30 min in an ultrasonic bath. Afterward,the Mo6 mixture was added to the graphene suspension, resultingin graphene loaded with a 5% wt of the Mo6 cluster. Themixture was homogenized for 10 min under stirring. Subsequently, thesolution was sonicated in an ultrasonic bath for 1 h, resulting ina suitable distribution of molybdenum clusters supported on graphene(Mo6@Graphene). For the characterization of the nanomaterial,the resulting suspension was deposited onto appropriate wafers directedto each characterization technique and placed onto a hotplate at amoderate temperature (60 °C). For sensing studies, the suspensionwas deposited via spray coating on alumina substrates comprising platinumscreen-printed electrodes .First, the substrates were placed onto a hotplate at a moderate temperature(60 °C), and then, the deposition process was started after fewminutes for ensuring the correct heating up of the substrate. Thespray coating deposition was performed using nitrogen as the carriergas for about 45 s. As a result, homogeneous sensitive films wereobtained with an average thickness of 1 μm  and optical profilometermeasurement ).For supporting the molybdenum clusterson graphene, two solutionswere prepared in parallel. First, a 10 mL graphene suspension (0.5mg/mL) in dichloromethane was performed employing graphene nanoplateletaggregates . FESEM imageswere recorded with a Zeiss Ultra 55 field FESEM apparatus  equipped with a BSE detector. Samples for HR-TEM were depositedonto carbon-coated copper grids. HR-TEM images were recorded by usinga JEOL JEM2100F microscope operating at 200 kV. The molybdenum andiodine contents of the Mo6@Graphene sample were determinedby dark-field scanning transmission electron microscopy (STEM) EDSanalysis conducted by using an EDAX system (Oxford Instruments) attachedto a JEOL JEM2100F electronic microscope. The thickness of the filmwas measured with a MicroXAM-100 3D surface profilometer. The cross-sectionwas examined by FESEM (Zeiss Ultra 55 instrument).UV–vis spectra wereacquired at 20 °C, employing a Varian Cary 50 Conc spectrophotometerequipped with 10 × 10 mm quartz cells. Steady-state PL measurementswere recorded in an Edinburgh Instruments FLS1100 spectrofluorometerusing a 450 W xenon lamp light equipped with a double monochromatorfor excitation and emission coupled to a cooled photomultiplier (PMT-980).The Raman spectra were obtained from solid samples previously depositedonto quartz substrates using a “Reflex” Renishaw spectrometerequipped with an Olympus microscope. The exciting wavelength was 514nm of an ArFigure S14), thegas sensors were placed in an airtight testing chamber (dead volumeof 35 cm3). The chamber was subsequently connected to agas mixing and delivery system comprising different calibrated gascylinders. A pure dry air atmosphere (air premier purity: 99.999%)was employed during the sensing test and used as a carrier gas forthe target gases. It is worth highlighting that a residual amountof relative humidity (3–4%) is present in dry conditions. Theoverall flow was adjusted at a low rate (100 mL/min) using a set ofmass-flow controllers and electro-valves. Since it is well known that higher flow rateslead to greater resistance changes, it is worth noting that the lowflow rate applied sacrifices response intensity but has the advantageof enabling lower power consumption and working under more realisticexperimental conditions. The effect of the ambient moisture on thesensor’s performance was also assessed by using a controllerevaporator mixer  forhumidifying the atmosphere.Once homogeneouslayers were achieved (R/R0) expressedin percentage. Where R0 is defined as the resistance levelof the sensor in the air, while ΔR correspondsto the resistance changes obtained over 5 min of gas exposure.The sensor resistances were monitoredusing a multimeter , registering the resistancechanges induced by different concentrations of gases. Specifically,the sensors were exposed to given concentrations of target gases for5 min and subsequently stabilized for 15 min under dry airflow. Severalconcentrations of gas species were applied by performing successivedilutions with pure dry air, and the sensing responses were definedas (Δ6 or Mo6@Graphene) in 1mL of acetonitrile and sonicated for 10 min. Subsequently, the suspensionswere deposited by drop-casting on an acid-treated quartz substrate(Mo6 sample) and an alumina substrate (Mo6@Graphenesample) placed on a hotplate at 50 °C. Then, the samples wereplaced inside a screw cap cuvette and fixed with a small piece ofcommercial Blu-Tack . The sampleswere purged for 20 min with Ar, air, and NO2  before each in situ measurement. The measurementswith NH3 were done by gas diffusion of 10 μL of ammoniumhydroxide solution  placed atthe bottom of the cuvette. The amount of gaseous NH3 wascalculated from Henry’s law (Hcp = 0.58 M/Pa at298.15 K) considering the equilibrium concentration of ammonia insolution (kb = 1.8 × 10–5).Samples for carryingout UV–vis and PL experiments were prepared by dispersing 5mg of the sample  before and after exposureto NO63 Relativisticelectron core potentials from the Stuttgart group and its associatedbasis sets64 were used to represent themolybdenum65 and iodine atoms66 and augmented in the case of Mo by an f polarizationfunction (Mo/α = 1.043)67 and inthe case of I, with a d polarization function (I/α = 0.289).68 The 6-31G basis set was used to representthe remaining atoms  of the molecular systems. The geometryoptimizations were performed in the gas phase without any symmetryconstraint, followed by analytical frequency calculations to confirmthat a minimum has been reached. Zero-point energies were includedin BE calculations, and the BEs were calculated using BE = Ecluster-molecule – [Ecluster + Emolecule].The calculationswere conductedwith the Gaussian 09 program suite. Density functional theory wasapplied with the PBE0 functional.trans- and cis-[Mo6Ii8(OH)a4(H2O)a2] isomers were built as representativemodels for adsorption sites due to the fact that water and hydroxopositioning around the octahedral metal framework cannot be inferredfrom the X-ray diffraction structure. The guess geometries of thegas–cluster adducts were raised considering a random positioningof the gas analyte with respect to all the cluster ligands  of the two cluster isomers.The


Trichilia dregeana Sond are traditionally used to treat wounds. Even though there have been in vitro studies and claims supporting wound healing, there are no scientific data on in vivo wound healing and anti-inflammatory activities of the leaves of T. dregeana.  The leaves of T. dregeana in mice.  This study aimed to evaluate wound healing and anti-inflammatory activity of 80% methanol crude extract and solvent fractions of T. dregeana were dried, ground, and macerated with 80% methanol three times successively. The crude extract was fractioned by water, ethyl acetate, and hexane separately. The acute dermal and oral toxicity tests were done by applying 2000 mg/kg of 10% (w/w) crude extract ointment (CEO) topically and 2000 mg/kg of crude extract orally, respectively. The wound healing activity of the crude extract was evaluated on excision, incision, and burn wound models while the fractions were evaluated only on excision wound model. The anti-inflammatory activity of the crude extract was evaluated on xylene-induced ear edema and cotton pellet granuloma tests.  The leaves of p < 0.001) wound contraction and period of epithelialization from day 4 onwards as compared to simple ointment (SO) on both excision and burn wounds. The tensile strength was increased significantly (p < 0.001) for the CEO-treated mice as compared to both untreated and SO groups. The crude extract also showed anti-inflammatory activity at 100, 200, and 400 mg/kg by inhibiting ear edema, exudate, and granuloma formation as compared to the SO group.  Both acute dermal and oral toxicity tests were found to be safe after topical application of 2000 mg/kg of 10% (w/w) CEO and oral administration of 2000 mg/kg of crude extract suspension, respectively. Both 5% and 10% (w/w) CEO produced significant (T. dregeana for wound healing. The increase in wound contraction, reduction in period of epithelialization, and increase in tensile strength support the traditional claims of  Wound is defined as damage to the integrity of biological tissues, including skin, mucous membranes, and organ tissues, due to various types of trauma . The losTrichilia dregeana Sond which is commonly known as Cape Mahogany and Forest Natal Mahogany in South Africa is a large, up to 35 m in height and 1.8 m in diameter, evergreen tree which inhabits forests in high rainfall areas. It has beautiful dark foliage and a large rounded crown from the Meliaceae family [e family  , hard paraffin , white soft paraffin (Queens Hygenic Industries plc), cetostearyl alcohol , methanol absolute , n-hexane , ethyl acetate , distilled water , nitrofurazone skin ointment 0.2% , ketamine hydrochloride injection USP , diazepam injection , 70% alcohol , normal saline 0.9% , bees wax , formalin 10% , hematoxylin , eosin , Glacial acetic acid , potassium iodide , ammonia solution , mercuric chloride , iron chloride , lead acetate , trihydrate, and Tween 80  were procured from legal suppliers as per the required standard and analytic grade.Sensitive digital weighing balance , lyophilizer, rotary evaporator , dry oven , light, vacuum pump, desiccator, deep freezer, water bath, mortar and pestle, ointment slab, sharp sterilized scissors, surgical threads with curved needles, forceps, surgical scalpel blade, Erlenmeyer conical flask, Whatman filter paper (No 1) , beaker, Buchner funnel, syringe with needle, glove, cotton swab adhesive plaster zinc oxide, face mask, head cover, gauze, gloves, cotton swab, permanent marker, and transparent polythene graph paper were used.Trichilia dregeana Sond leaves were collected in early March 2021 from Yebbu town, Jimma Zone, Ethiopia. It was identified and authenticated by Mr. Wondie Mebrat, Department of Biology, College of Natural and Computational Science, Debre Tabor University, and a voucher specimen was deposited with collection number DG001.The fresh Healthy, either sex, adults, 20–30 grams of weight, and 6–8 weeks of age Swiss albino mice were obtained from animal house facilities of the Department of Pharmacology, University of Gondar. The mice were caged individually at room temperature and under 12 hours of light and dark cycles with a standard pellet diet and free water access  and alloThe debris from the collected plant materials was rinsed with tap water and subjected to shade drying. The dried plant materials were ground to a coarse powder using mortar and pestle and stored in an air-tight container until extraction was started.A total of 2.5 kg powder was macerated in 15 L of 80% methanol (1 : 6 w/v) in round bottom flask with intermittent shaking for three days. On the third day, the extract was filtered using surgical gauze and Whatman filter paper number 1 consecutively. The marc was re-macerated twice in the same manner, and the filtrates were collected and evaporated using a rotary evaporator set at 40°C, and concentrated aqueous solution remained. The remaining concentrated aqueous solution was further evaporated using a dry oven at 40°C. By using a deep freezer, the concentrated filtrate was frozen overnight at −40°C, and then the frozen filtrate was lyophilized at vacuum pressure 0.200 mBar and −40°C to remove water. The dried powder was weighted, packed in an air-tight container, and stored at 4°C temperature. The yield obtained after extraction of dried powder material was 182.25 g (7.29%).For fractionation, a total of 115 g of the crude extract was suspended in 690 ml of distilled water (1 : 6 w/v) using a separatory funnel. Then, the same amount of n-hexane was added, mixed well, and allowed to settle and form distinct layers. Once the distinct layers were formed, n-hexane fraction was separated by eluting the bottom aqueous layer from the separatory funnel. This step was repeated two more times, and the n-hexane fractions were collected in the same container. To get ethyl acetate fractions, an equal amount of ethyl acetate to that of distilled water was added to the aqueous fraction. The ethyl acetate fraction was separated after a distinct layer was formed between ethyl acetate and aqueous fraction by collecting the bottom aqueous layer. This process was also repeated two more times, and ethyl acetate fractions were collected in the same container. The fractions of all n-hexane and ethyl acetate were evaporated using a rotary evaporator while aqueous fraction was concentrated using an oven at 40°C before undergoing lyophilization at vacuum pressure 0.200 mBar and −40°C. The percent yields of the dried fractions were 33.75%, 6.63%, and 56.21% for n-hexane, ethyl acetate, and aqueous fractions, respectively. The fractions were stored at 4°C in the refrigerator .Using the formula described in British Pharmacopeia , the simAll ingredients were weighted properly. Based on their descending order of melting points which are hard paraffin, cetostearyl alcohol, wool fat, and white soft paraffin, all ingredients were placed and added to the evaporating dish and melted over a water bath. The mixture was stirred continuously to ensure homogeneity . This siT. dregeana leaves was screened based on standard procedures [The presence of alkaloids, saponins, flavonoids, phenols, steroids, glycosides, tannins, anthraquinones, and terpenoids in the crude extract as well as n-hexane, ethyl acetate, and aqueous fractions of ocedures .Acute oral toxicity test was carried out based on OECD 425: “Limit test at 2000 mg/kg” [An acute dermal toxicity test of 80% methanol crude extract of the plant was carried out and evaluated according to OECD 402 and 404 guidelines , 22. FivTrichilia dregeana Sond leaves, a total of 186 mice were used. To evaluate the wound healing activity of the extract, 24 mice were grouped into four groups for each excision and burn wound model while 30 mice were grouped into five for the incision wound model. Each group contains six mice. In all three models, group I was treated with simple ointment (serve as negative control), groups II and III were treated by 5% and 10% (w/w) extract ointment, respectively. Group VI was treated with nitrofurazone 0.2% w/v ointment (served as positive control). Group V of incision wound model was left untreated (served as an untreated control group).For evaluation of wound healing and anti-inflammatory activities of Solvent fractions were evaluated on an excision wound model using eight groups (each has six mice). Group I was treated with simple ointment. Groups II and III were treated with 5% (w/w) and 10% (w/w) aqueous fraction (AQF) ointment formulations, respectively. Groups IV and V were treated with 5% (w/w) and 10% (w/w) ethyl acetate fraction (EAF) ointment formulations, respectively. Groups VI and VII were treated with 5% (w/w) and 10% (w/w) n-hexane fraction (NHF) ointment formulations, respectively. Group VIII was treated with 0.2% (w/v) nitrofurazone ointment.To evaluate the anti-inflammatory activity of the extract, five groups (each containing six mice) were used for each of xylene-induced ear edema model and cotton pellet-induced granuloma model. Group I was treated with 2% Tween 80 at a dose of 10 ml/kg (served as negative control). Groups II, III, and IV were treated with 100 mg/kg, 200 mg/kg, and 400 mg/kg extract, respectively. Group V was treated with indomethacin 10 mg/kg (served as positive control). At the end of the experiment, each mouse was euthanized by using high doses of ketamine  and diazepam. Finally, the remnants were buried in a proper area to avoid environmental contamination.2 circular area and 2 mm depth was created using forceps and scissors  and left undressed. From day 1, the ointments were applied once daily for 9 days. On post-wounding day 8, the suture was removed and the extent of healing was assessed by measuring the tensile strength using continuous water flow method on post-wounding day 10. Two forceps were inflexibly applied at 3 mm away from the edge of the wound facing each other on the opposite sides of the incision wound to the anesthetized mice on the operating table. One of the forceps was secure on stands while the other was connected to a freely suspended lightweight plastic of volume 500 ml into which the water flowed continuously and gently. The water flow was stopped at the moment the wound was opened up and the volume of the collected water in the reservoir was recorded as tensile strength . The bre(1) Burn Wound Model. Twenty-four mice were anesthetized, fur from the back was shaved, and they were decontaminated similarly to that of excision and incision models. A circular cylinder of 300 mm2 opening into which the molten wax at 80°C was poured in was placed on the shaven part of the mice for 10–12 minutes until the poured hot molten wax gets solidified, and then the wax was removed. This created a partial-thickness circular burn on the area. Then, the mice were placed back in their cage individually. Treatments were applied over the wounded area daily until the wound is epithelialized. The healing progress was assessed every 2 days, and the percentage of wound contraction was calculated, period of epithelialization was recorded, and histopathological analysis was performed [erformed .(1) Xylene-Induced Ear Edema Model. The methods previously used by Manouze et al. [e et al.  were fole et al. .(3)Ear s(2) Cotton Pellet-Induced Granuloma. A chronic anti-inflammatory effect of 80% methanol extract of the plant was carried out according to previously used methods by Gou et al. [u et al.  with somu et al. . The disPercentage protection from granuloma development was calculated using the following formula:p < 0.05 was considered statistically significant.The results of the experiment were expressed as mean ± standard error of the mean, and SPSS version 26 was used to analyze the results. One-way analysis of variance (ANOVA) was used for the test of statistical significance followed by Tukey's post hoc test. Phytochemical screening of 80% methanol crude extract and solvent fractions showed the presence of different secondary metabolites .No sign of toxicity was observed after oral administration of 2000 mg/kg of the extract as well as dermal application of 2000 mg/kg of the 10% (w/w) extract ointment within the first 24 and 48 hours, and no death was registered after 14 days of follow-up. The result suggests that oral LD50 of the plant extract is greater than 2000 mg/kg in mice.(1) Healing Activity of the Crude Extract. Treatment with 10% (w/w) extract ointment showed significant wound contraction (p < 0.01) on day 2 and on other post-wounding days (p < 0.001) as compared to simple ointment. Similarly, treatment with 5% (w/w) extract ointment showed significant wound contraction on all post-wounding days, on day 2 (p < 0.05), and on the rest of the post-wounding days (p < 0.001) as compared to simple ointment.p < 0.001) and day 6 (p < 0.01) as compared to 5% (w/w) extract ointment. Treatment with 10% (w/w) extract ointment also showed better wound contraction on most post-wounding days as compared to 0.2% nitrofurazone ointment though the differences were insignificant (Treatment with both 10% (w/w) extract and 0.2% nitrofurazone ointments showed significant wound contraction on day 4 (nificant .Complete percentage of wound contraction for groups treated with 10% (w/w) extract ointment, 5% (w/w) extract ointment, 0.2% (w/v) nitrofurazone ointment, and simple ointment was observed on day 16, 18, 18, and beyond, respectively Figures  and 5.p < 0.001) short period of epithelialization as compared to simple ointment. Mean period of epithelialization in mice treated with 5% (w/w) extract ointment, 10% (w/w) extract ointment, and 0.2% (w/v) nitrofurazone ointment has been reduced by 24.99%, 26.54%, and 25.79%, respectively, as compared to simple ointment (Treatment with both 5% (w/w) and 10% (w/w) extract ointment as well as 0.2% (w/v) nitrofurazone ointment showed significantly (ointment .p < 0.001) wound contraction on all post-wounding days as compared to all simple, 5% (w/w) ethyl acetate fraction, 10% (w/w) ethyl acetate fraction, 5% (w/w) hexane fraction, and 10% (w/w) hexane fraction ointments. Similarly, 5% (w/w) aqueous fraction ointment showed significant wound contraction (p < 0.001) as compared to simple ointment (p < 0.01) as compared to all 5% (w/w) ethyl acetate fraction, 10% ethyl acetate fraction, 5% (w/w) hexane fraction, and 10% (w/w) hexane fraction ointments on post-wounding day 2. From post-wounding day 4 onwards, 5% (w/w) aqueous fraction ointments showed highly significant (p < 0.001) wound contraction when compared to all simple, 5% (w/w) ethyl acetate fraction, 10% (w/w) ethyl acetate fraction, 5% (w/w) hexane fraction, and 10% (w/w) hexane fraction ointments.Treatment with 10% (w/w) aqueous fraction ointment showed significant (p < 0.05) and from day 14 onwards (p < 0.01) as compared to simple ointment, while 10% (w/w) ethyl acetate fraction ointment showed significant wound contraction from day 6 to 8 (p < 0.05), from day 10 to 12 (p < 0.01), and from day 14 onwards (p < 0.001) as compared to simple ointment.Treatment with 5% (w/w) ethyl acetate fraction ointment showed significant contraction from day 10 to 12 (p < 0.05) and from day 12 onwards (p < 0.01) as compared to simple ointment, while 10% (w/w) hexane fraction ointment showed significant wound contraction from day 4 to 8 (p < 0.05), from day 10 to 12 (p < 0.01), and from day 14 onwards (p < 0.001) as compared to simple ointment. Nitrofurazone also showed significant wound contraction (p < 0.001) on all post-wounding days as compared to simple ointment (Treatment with 5% (w/w) hexane fraction ointment showed significant contraction on day 10 (ointment .Mice treated with 10% (w/w) aqueous fractions ointment showed complete wound closure by day 16 while it took beyond day 16 for complete wound closure by other fraction ointments Figures .p < 0.001) as compared to all simple, 5% (w/w) ethyl acetate fraction, and 5% (w/w) hexane fraction ointments. It also showed significantly short period of epithelialization (p < 0.01) as compared to both 10% (w/w) ethyl acetate fraction and 10% (w/w) hexane fraction ointments. Treatment with 10% (w/w) aqueous fraction ointment reduced period of epithelialization significantly (p < 0.001) when compared to all simple, 5% (w/w) ethyl acetate fraction, 10% (w/w) ethyl acetate fraction, 5% (w/w) hexane fraction, and 10% (w/w) hexane fraction ointments.Treatment with 5% (w/w) aqueous fraction ointment showed significantly short period of epithelialization  as compared to simple ointment. Similarly, treatments with both 5% and 10% (w/w) hexane fraction ointments also reduced the period of epithelialization significantly  as compared to simple ointment.Groups treated with both 5% and 10% (w/w) ethyl acetate fraction ointments reduced the period of epithelialization significantly (Treatment with 10% (w/w) aqueous fraction ointment showed the highest percentage of reduction in the period of epithelialization, 20.85%; on the contrary, treatment with 5% (w/w) ethyl acetate fraction ointment showed the lowest percentage, 6.65%, as compared to simple ointment .p < 0.001) increases in breaking resistance as compared to both simple ointments and left untreated groups. Treatment with 10% (w/w) extract ointment showed the highest percentage of tensile strength, 74.00%, while the simple ointment group showed the least percentage of tensile strength, 12.56%, as compared to left untreated group (Groups treated with 5% and 10% (w/w) extract ointment showed significant (ed group .(1) Wound Contraction. Mice treated with 10% (w/w) extract ointment showed significant wound contraction on day 2 (p < 0.05), on day 4 (p < 0.01), and on the rest of the post-wounding days (p < 0.001) as compared to simple ointment. Similarly, mice treated with 5% (w/w) extract ointment showed significant wound contraction on day 4 (p < 0.05) and on other post-wounding days (p < 0.001) as compared to simple ointment.p < 0.05) and day 8 (p < 0.01) as compared to 5% (w/w) extract ointment. Similarly, treatment with 0.2% (w/v) nitrofurazone ointment showed significant contraction on day 8 (p < 0.05) as compared to 5% (w/w) extract ointment (Treatment with 10% (w/w) extract ointment showed significant wound contraction on day 6 (ointment .Complete wound closure after treatment with 5% (w/w) extract ointment, 10% (w/w) extract ointment, 0.2% (w/v) nitrofurazone ointment, and simple ointment was observed on day 22, 20, 22, and beyond, respectively Figures  and 9.p < 0.001) short period of epithelialization as compared to simple ointment. Mice treated with 10% (w/w) extract ointment also showed significantly (p < 0.05) short period of epithelialization when compared to 5% (w/w) extract ointment.Treatment with 5% and 10% (w/w) extract ointments showed significantly (Treatment with 5% (w/w) extract ointment, 10% (w/w) extract ointment, and 0.2% (w/v) nitrofurazone ointment reduced period of epithelialization by 11.36%, 17.74%, and 14.17%, respectively, when compared to simple ointment .Wound treated with 10% (w/w) extract ointments showed high fibroblast proliferation, collagen deposition, and neovascularization as well as few numbers of inflammatory cells while 5% (w/w) extract ointment-treated wound showed high fibroblast proliferation, moderate collagen deposition, and neovascularization. Nitrofurazone-treated wound showed moderate fibroblast proliferation, collagen deposition, and neovascularization . The hisMice treated with 5% (w/w) aqueous fraction ointment showed high fibroblast proliferation, moderate collagen deposition, and high neovascularization while treatment with 10% (w/w) aqueous fraction showed high fibroblast proliferation, collagen deposition, and neovascularization. Groups treated with 5% (w/w) ethyl acetate fraction, 10% (w/w) ethyl acetate fraction, 5% (w/w) hexane fraction, and 10% (w/w) hexane fraction ointments showed moderate to high number of inflammatory cells, low fibroblast proliferation, invisible to low collagen deposition, and low neovascularization .Treatment with 10% (w/w) extract ointments showed high fibroblast proliferation and collagen deposition while 5% (w/w) extract ointment showed moderate fibroblast proliferation and collagen deposition. Treatment with 10% (w/w) and 5% (w/w) extract ointments also showed moderate and low neovascularization, respectively . As showp < 0.001) at 100, 200, and 400 mg/kg as compared to 2% Tween 80. Treatment with 400 mg/kg also showed significant (p < 0.001) ear edema inhibition as compared to both 100 and 200 mg/kg. Similarly, indomethacin-treated mice showed significant (p < 0.001) inhibition in ear edema as compared to all groups treated with 100 mg/kg, 200 mg/kg, and 400 mg/kg as well 2% Tween 80.The extract inhibited ear edema significantly  inhibits both wet weight (exudate) and dry weight (granuloma) of the cotton pellet as compared to 2% Tween 80. Similarly, treatment with extract at 200 mg/kg and 400 mg/kg significantly (p < 0.001) inhibits the wet weight of the cotton pellet when compared to 100 mg/kg.At 100 mg/kg, 200 mg/kg, and 400 mg/kg, the extract significantly  as compared to 100 mg/kg. Treatment with 400 mg/kg also significantly reduces (p < 0.001) both wet and dry weight of the cotton pellet formation when compared to 200 mg/kg.The extract at 200 mg/kg and 400 mg/kg showed a significant reduction in dry cotton pellet weight (p < 0.001) inhibition in exudative deposits when compared to 100 mg/kg, 200 mg/kg, and 400 mg/kg as well as 2% Tween 80. Similarly, indomethacin at 10 mg/kg showed significant inhibition (p < 0.001) in proliferative deposits when compared to all 200 mg/kg, 100 mg/kg, and 2% Tween 80 as well as 400 mg/kg (p < 0.01).Indomethacin at 10 mg/kg showed significant  wound contraction in excision wound model. The percent of wound contraction produced by 10% (w/w) extract ointment on day 14 (98.25%) is comparable to that of Becium grandiflorum Lam which showed 100% contraction by day 14 [Treatment with 5% and 10% (w/w) extract ointment showed significant  of albicans , 40. Bacalbicans . Antimic healing .In the excision wound model of solvent fractions, the aqueous fractions showed a better effect. This difference could be related to either the accumulation of the majority of secondary metabolites in an aqueous fraction . High fiTrichilia dregeana Sond leaf crude extracts could be due to the plant extract's role in promoting collagen synthesis, maturation, and stabilization.The crude extract was also evaluated for wound healing activity in incision wounds by measuring the tensile strength, the resistance of the tissue to break under external force. The significant resistance to breaking might be related to the quality of the repaired tissue which is mainly determined by the regeneration of collagen. Collagen gives strength and integrity to the healed wound that helps the cells to adhere together and resist breaking tension . This siTrichilia dregeana Sond leaves possess antioxidant, antimicrobial, and anti-inflammatory activity [Wound healing activity of the plant extract was also evaluated in the partial-thickness burn wound model in which it showed significant contraction. The creation of partial-thickness burn wound forms three zones which are zone of necrosis at the area of applications, zone of hypoperfusion in the area surrounding the zone of necrosis, and zone of inflammation just next to a zone of hypoperfusion. Microbial colonization, persistent hypoperfusion, excessive free radical generation, and severe inflammation advance the partial-thickness wound to full-thickness wound which delays the healing and makes it more complicated . In prevactivity , 39, 40.Trichilia dregeana Sond leaf extracts contain alkaloids, phenols, tannins, flavonoids, anthraquinones, terpenoids, steroids, and saponins as evidenced by phytochemical tests. This finding is consistent with the phytochemical content of Trichilia emetica Vahl, a plant from the same genus [me genus . Differeme genus .Trichilia dregeana Sond leaf extracts significantly inhibited ear edema formation in the xylene-induced ear edema model. This suggests the plant extract has activity against acute inflammation. This anti-inflammatory activity of the plant is in line with in vitro tests done previously which showed that different solvent extracts of Trichilia dregeana Sond leaves possess anti-inflammatory activity by inhibiting COX 1 and 2 [ 1 and 2 , 40, 47. 1 and 2 .Achyranthes aspera L. [In the cotton-induced granuloma formation test model, the extract significantly inhibited exudate and granuloma formation which is comparable to the effect shown by spera L. . These aspera L. . ExudateThe extract also inhibits the formation of granuloma significantly. More monocytes were drawn to the area, where they joined to create granulomas around the foreign body that were multinucleated giant cells . ProstagT. dregeana showed wound healing activity by increasing wound contraction, decreasing period of epithelialization, and increasing resistance to breakage in different wound models. Besides, the plant extract also showed anti-inflammatory activity by inhibiting ear edema formation, exudate formation, and granuloma formation in different inflammation models. The aqueous fraction showed wound-healing activity by accelerating wound contraction and shortening the period of epithelialization in the excision wound model, which supports the conventional uses in which traditional healers first soak the plant in water before applying it to the wound.Eighty percent methanol extract of


The LSPR was affected by the plasma treatment, but it was completely recovered using subsequent annealing. It was found that the presence of defects increased the response for toluene and water while decreasing it for acetone.Graphene-covered silver nanoparticles were prepared directly on highly oriented pyrolytic graphite substrates and characterized by atomic force microscopy. UV–Vis reflectance spectroscopy was used to measure the shift in the local surface plasmon resonance (LSPR) upon exposure to acetone, ethanol, 2-propanol, toluene, and water vapor. The optical responses were found to be substance-specific, as also demonstrated by principal component analysis. Point defects were introduced in the structure of the graphene overlayer by O Noble metal nanoparticles (NPs) are widely used for chemical and biological sensing because of their local surface plasmon resonance (LSPR) ,2 and suThe synthesis of Ag NPs can be accomplished using a variety of strategies  dependin−7 mbar and an evaporation rate of 0.1 nm s−1. The deposited Ag films were covered with CVD graphene grown on copper foil (Graphenea), immediately after the opening of the evaporation chamber. We applied polymer tape as mechanical support to transfer large-area graphene samples. The copper foil was removed using an etchant composed of copper (II) chloride aqueous solution (20%) and hydrochloric acid (37%) in a 4:1 volume ratio. After rinsing and drying, the polymer tape with the graphene was pressed onto the evaporated Ag films. The tape was removed by lifting it with tweezers. To form nanoparticles, both bare and graphene-covered Ag thin films were annealed at 400 °C under an inert gas (Ar) atmosphere for 1.5 h. The obtained samples (samples #1 and #2) were characterized by tapping-mode AFM on a MultiMode 8 system , as well as SEM using a Thermo Scientific Scios2  instrument. Point defects were introduced in the atomic structure of the graphene overlayer (sample #2) by 5 s of O2 plasma treatment  at 50 W, followed by annealing (400 °C) in Ar gas for 60 min.Silver films of 7 nm nominal thickness were evaporated onto HOPG substrates at a background pressure of 5 × 102, 20% O2) and saturated volatile vapors through gas bubblers in the required ratio. During the measurements, a constant gas flow of 1000 mL/min was sustained through the cell. Vapor detection experiments were performed by varying the concentration and type of test vapor while tracking spectral variations over time. To purge the cell, a 20 s vapor flow at a given concentration was followed by a 60 s flow of synthetic air. In addition, before introducing the next vapor type, a 120 s purge was used to recover the initial reflectance of the sample.Optical reflectance and vapor sensing measurements were carried out by mounting the samples in an airtight aluminum box covered with a fused silica window to provide UV transmission. The samples were illuminated using an Avantes AvaLight DH-S-BAL light source. The initial reflectance of the samples in synthetic air was measured with an Avantes HS 1024 × 122TEC spectrometer  by capturing the specularly reflected signal (measured under 15°). For vapor sensing experiments, five types of volatile vapors were passed through the cell’s gas inlet and vented through the outlet: acetone, ethanol, 2-propanol, toluene, and water . Vapor concentration was adjusted by switching digital mass flow controllers  to pass synthetic air  separated by several nanometers, as shown in The adsorption of organic molecules to graphene is influenced by the presence of defects, as shown by recent calculations . This, i2O phases [This abrupt change in the optical characteristics is ascribed to the silver reacting with oxygen, and the formation of AgO or AgO phases . These oO phases .R = (R / R0) × 100%, where R0 is the initial reflectance of the sample in synthetic air. The calculated reflectance change spectra clearly showed an increasing signal as a function of the vapor concentration. A higher number of adsorbed molecules increased the effective refractive index of the medium more significantly. A positive peak followed by a negative peak represent a redshift of the LSPR. In this way, the original small changes in the LSPR could be effectively compared for all investigated samples and substances.In the following, we used both graphene-covered Ag NP samples in VOC-sensing experiments: sample #1 with pristine graphene, and sample #2 with a defected graphene overlayer. Saturated vapors of acetone, ethanol, 2-propanol, toluene, and water were diluted with synthetic air in ten different concentrations and the resulting wavelength shift of the LSPR peak was measured. As a control experiment, a bare HOPG surface was used in the same vapor sensing measurement, which resulted in only a slight decrease in the intensity as the vapor concentration was increased see . The effThe optical responses of graphene-covered Ag NPs obtained for saturated vapors are plotted in To investigate in more detail the VOC sensing data, principal component analysis (PCA) of the measured data sets was carried out and the resulting score plots were compared. As both samples showed a much higher response to acetone compared to the other four substances, and because the UV absorbance of this vapor was in the range of the LSPR, the data on acetone were omitted from the analysis. The PCA score plots of ethanol, 2-propanol, toluene, and water are shown in Here, each vapor had a unique trajectory. To facilitate the comparison, the data points were projected on the PC1–PC2 planes of the graphs. All trajectories originated from a common point, which was the data point of the initial synthetic air spectrum. Away from this, as the concentration of the vapors increased, the calculated points branched apart, resulting in a clear separation of the trajectories. This showed that the VOC detection by the graphene-covered Ag NPs was substance-specific. One can see on the PC1–PC2 projected plane that the third dimension is needed to properly separate the signal of ethanol and 2-propanol, as the trajectories are overlapping in the 2D projection. Furthermore, to observe the effect of defects in the graphene overlayer, we compared the maximal intensities of the peak (near the LSPR) in the reflectance change spectra to the maximal intensities obtained with the pristine graphene overlayer. These maximal peak intensities are plotted as a function of concentration in One can observe that there were differences in the maximal responses of the two samples, especially for acetone, water, and toluene. The defected graphene overlayer increased the sensitivity to water and toluene. This agrees with recent calculations showing that toluene  and wateWe investigated the morphology, optical, and vapor sensing properties of graphene-covered Ag NPs elaborated directly on HOPG substrates. We showed that the prepared hybrid nanostructures displayed pronounced optical responses upon exposure to organic vapors . The observed concentration-dependent shifts in the LSPR were substance-specific, as demonstrated by reflectance change spectra and PCA. We further showed that, by introducing structural defects in the graphene overlayer, the optical response of the graphene/Ag NPs increased for toluene and water, while it decreased for acetone detection. These findings can stimulate further research towards increasing the selectivity in VOC sensing.


Irregularities in breathing patterns can be detected using breath monitor sensors, and this help clinicians to predict health disorders ranging from sleep disorders to heart failures. Variations in humidity during the inhalation and exhalation of breath have been utilized as a marker to detect breath patterns, and graphene-based devices are the favored sensing media for relative humidity (RH). In general, most graphene-based RH sensors have been used to explore resistance change as a measurement parameter to calibrate against the RH value, and they are prone to noise interference. Here, we fabricated RH sensors using graphene ink as a sensing medium and printed them in the shape of interdigital electrodes on glossy paper using an office inkjet printer. Further, we investigated the capacitance change in the sensor for the RH changes in the range of 10–70%. It exhibited excellent sensitivity with 0.03 pF/% RH, good stability, and high intraday and interday repeatability, with relative standard deviations of 1.2% and 2.2%, respectively. Finally, the sensor was embedded into a face mask and interfaced with a microcontroller, and capacitance change was measured under three different breathing situations: normal breathing, deep breathing, and coughing. The result show that the dominant frequency for normal breath is 0.22 Hz, for deep breath, it is 0.11 Hz, and there was no significant dominant cough frequency due to persistent coughing and inconsistent patterns. Moreover, the sensor exhibited a short response and recovery time (<5 s) during inhalation and exhalation. Thus, the proposed paper-based RH sensor is promising wearable and disposable healthcare technology for clinical and home care health applications. Abnormalities in the human respiration rate is a vital sign of health disorders. For a healthy adult at rest, the normal breathing rate ranges from 12 to 20 breaths per minute. By detecting irregularities in the breathing rate and respiration pattern, clinicians can predict acute events such as chronic obstructive pulmonary disease (COPD) , chronicIn general, there are two methods for measuring the respiratory rate, i.e., contact-based and contactless ones . ContactIn recent years, paper has been considered as a promising sensor substrate owing to its low cost, flexibility, lightweight, biodegradability, and disposability ,14. GreaThe ideal humidity level that comforts the human body is between 40% and 70% at the appropriate temperature . The humAnother consideration is the sensor readout, which can be either resistive or capacitive. Many humidity sensors are resistive-type ones, which respond to a change in the resistance with relative humidity ,38. HoweAccordingly, we present an inexpensive, disposable, and sensitive capacitive-and paper based humidity sensor for respiration sensing. The sensor was fabricated through one-step fabrication technique, which only required an inkjet printer, glossy paper, and graphene printing ink. In addition, the paper-based humidity sensor was designed with an interdigitated electrode (IDE) pattern to increase the effective sensing area and the capacitance of the sensor. The RH-sensing characteristics of the fabricated sensor were investigated in the range of 10–70% RH. To demonstrate that the sensor enables continuous, real-time breathing monitoring, the sensor was studied under three different breathing situations  and the respiratory frequency rates and patterns were analyzed.Graphene printing ink with a viscosity in the range of 10–20 cP was purchased from GO Advanced Sdn. Bhd. . A4 glossy inkjet photo paper (180 gsm) and dual-sided conductive copper tape (5 mm × 20 m) were obtained from INRO Electronic . The Arduino Mega2560 and BME680 environmental sensors were purchased from Cytron Sdn. Bhd. .−1 range using Raman Spectroscopy (Renishaw InVia Raman Microscope). The surface contact angles for a 20 μL droplet on the surfaces of glossy paper with printed graphene and without printed graphene were measured using a goniometer .All the paper sensors were prepared using Brother Model MFC-J200 inkjet printer. The surface morphology of graphene-printed glossy paper was characterized using a field emission scanning electron microscope (FESEM) . The chemical composition of the graphene-printed surface was characterized by X-ray photoelectron spectroscopy (XPS) . Raman spectra characterization with a 532 nm excitation was performed in the 3200–100 cmThe device fabrication protocol for the paper-based Inkjet-printed-graphene sensor is schematically shown in 3 with two peripheral holes that acted as the inlet and outlet. The inlet and outlet were always open for the continuous flow of gas mixture through the chamber to achieve a constant gas pressure. Purified nitrogen, N2, gas was supplied by a gas tank  at a pressure of 1.5 bar was regulated by both of the MFCs . During humidification, the N2 gas was flowed through a bubbler filled with deionized water into the sensing chamber at a fixed flow rate of 200 sccm, which was regulated by MFC2. The chamber was dehumidified by flowing dry N2 gas through the chamber at flow rate 711 sccm, which was regulated by MFC1. The fabricated paper sensor was placed in a homemade sensing chamber that was interfaced with the microcontroller for the humidity detection tests. Further, a data logging system was utilized to record the RH conditions using a PC. The operating ranges of the chamber for RH were controlled and monitored to stay within the range from 10% to 70%. The sensitivity of the sensor is expressed as Equation (1), where ΔC is the capacitance change due to the humidity, and ΔRH is the relative humidity variation [The RH sensing setup is illustrated in ariation .(1)S=[lThe description of the experimental setup used to investigate the response of the printed paper sensor to variable breath conditions is as follows: The paper sensor was embedded into a commercial KN94 mask for human respiration monitoring, as shown in FESEM was applied to examine the morphology of the printed sensing material at varied magnifications. The SEM images of the bare glossy paper (i–iii) and the graphene-printed glossy paper (iv–vi) at magnifications of 10 K, 20 K, and 50 K are shown in Hydrophilicity was investigated by measuring the water drop contact angle of the bare paper substrate and graphene ink film samples. 3 carbon and aromatic sp2 carbon are within the range of 284.5–285 eV [−) could be due to the water vapor on the graphene-printed paper surface and its origin in the surrounding environment [−1) and broad G-band (1584 cm−1), indicating the graphene layer that was inkjet printed onto the paper substrate [2 bonded carbon atoms in the graphitic structure [2 crystal structure due to oxidation [In addition, the elemental composition analysis on the energy dispersive XPS chart of the graphene-printed paper surface further confirms this result, illustrating the expected elemental peaks of carbon (C1s) and oxygen (O1s). From the XPS survey spectra in 5–285 eV ,45. The ironment . In Figuubstrate . The pretructure . The prexidation ,50.p value is 0.247 , which indicates that a not statistically significant difference occurred from day 1 to day 10. As a result, paper sensors can maintain good short-term stability during humidity testing. The repeatability of test on the paper sensor was evaluated by performing three cycles within the intraday (within same day) and interday (between days) range from 10% to 70% RH. The results of the paper sensor are considered to be highly repeatable, with relative standard deviations (RSD) of 1.2%  in terms of the capacitance (pF) value and the breathing pattern, with fast response and recovery times of 2.46 s ± 0.34 and 3.86 s ± 0.56 for the exhalation rise time, and 2.63 s ± 0.49 and 4.27 s ± 1.02 for the inhalation fall time under normal breathing and deep breathing conditions, respectively. The prototype sensor has a low cost, and it is disposable when it is used for frequent breathing pattern recognition. The sensor requires the simple inkjet printing of graphene ink on glossy paper using a typical office inkjet printer. The method is also suitable for mass production at a low cost. However, there are limitations in terms of aligning the layer features while one is printing multiple layers on same piece of paper. Furthermore, functionalized graphene ink for the selectively sensing of volatile organic compound molecules in breathe can be investigated in future studies.


Among the different graphene derivatives, graphene oxide is the most intensively studied material as it exhibits reliable and repeatable resistive switching. The operative mechanisms that are responsible for resistive switching are being intensively investigated, and three models explaining the change in the resistive states have been developed. These models are grounded in the metallic-like filamentary conduction, contact resistance modification and the oxidation of/reduction in the graphene oxide bulk. In this work, using Al/GO/n-Si structures, we demonstrate that all three of these operative mechanisms can simultaneously participate in the resistive switching of graphene oxide. Multiple point-like conduction channels in the graphene oxide films were detected by the electron beam-induced current (EBIC) technique. At the same time, large areas with increased conductivity were also revealed by EBIC. An analysis of these areas by Raman spectroscopy indicates the change in the graphene oxide bulk’s resistive properties. The EBIC data along with the measurements of the capacitance–voltage characteristics provided strong evidence of the involvement of an aluminum/graphene oxide interface in the switching processes. In addition, by using Al/GO/n-Si structures, we were able to identify unique local properties of the formed conductive channels, namely the change of the charge state of a conductive channel due to the creation of negatively charged traps and/or an increase in the GO work function. The research and development of materials, devices and processes that are related to non-volatile resistive memory is of great interest due to the prospects of the important practical applications including large-volume memory arrays , systemsIn our previous work , the HRSIn this work, we used Al/GO/n-Si metal–insulator–semiconductor (MIS) structures to investigate the resistive switching mechanisms and determine the locations of the conductive channels in the graphene oxide films by the electron beam-induced current (EBIC) technique ,21. To tThe graphene oxide that was used in this work was synthesized by the oxidation of graphite using the modified Hummers’ method ,23, and −11 A to minimize the irradiation dose. To monitor the e-beam irradiation effect during the EBIC mapping, the switching characteristics were measured on more than 20 MOS structures before and after their irradiation with an electron beam. After the experiments on resistive switching and the EBIC characterization, the aluminum electrodes were chemically removed, and the underlying GO film was characterized using the SENTERRA Bruker Raman microscope at the laser wavelength of 532 nm. A schematic presentation of the MIS structure and the experimental setup for the current–voltage and EBIC measurements is given in AC and DC measurements, respectively. Note that the capacitance playing a major role during the C–V measurements at a frequency of 100 kHz had an infinite value during the DC voltage sweep. The presence and role of aluminum oxide are explained in The investigations of the resistive switching characteristics and operative switching mechanisms in the GO films were carried out on the MIS structures that were made on phosphorous-doped Si wafer pieces with the GO film thickness of 40 nm. The top electrodes of circular shape and 1 mm in diameter were made by the sputtering of Al or Pt; the ohmic contact to the bottom Si electrode was formed by scratching the InGa paste. The use of the MIS structures with the bottom electrode of the n-type silicon allows us to determine the charges in the graphene oxide, evaluate its dielectric permittivity and provide the injection of holes under the negative bias that was applied to the top electrode. The use of aluminum as a top metal electrode allows the experimental verification of one of the switching mechanisms that is listed above, whereas Al fusibility can be employed to visualize the conductive channels under a high current flow. The use of the MIS structures also makes it possible to apply the method of electron beam-induced current to detect the conductive channels that are formed during the resistive switching processes. The GO film switching characteristics were studied by the DC current–voltage measurements using the Keithley 2450 Source Meter. To evaluate the presence of the charge traps in the GO film, the capacitance–voltage (C–V) characteristics were measured using the Keithley 4200A-SCS parametric analyzer at 100 kHz. The EBIC study was carried out using the scanning electron microscope (SEM) Jeol JSM-840 and using the Keithly 428 current amplifier at room temperature with a beam energy that was in the range from 8 keV to 30 keV and a beam current that was lower than 10−10 A, can be caused by a non-uniformity of the Al film thickness or they may reflect the difference in the conductivity of the GO flakes. An increase in a negative voltage during the subsequent I–V measurements up to 10 V resulted in a sharp increase in the current at about −5 V  are formed at higher voltages, and they can be directly detected by the EBIC due to the formation of local rectifying barriers at the GO/Si interface. These local barriers over-compensate a barrier in the pristine GO film, as shown by the change in the diode polarity in To illustrate the formation and disappearance of the conductive channels in the Al/GO/n-Si MIS structure, The presence of the GO bulk traps for the holes was established by measuring the GO-based MIS capacitors . A notabWe have investigated the operative mechanisms that are responsible for the resistive switching in the graphene oxide-based MIS structures. To the best of our knowledge, the EBIC method was used for the first time to reveal the conductive channels that are formed in graphene oxide due to resistive switching. The employment of the EBIC method enabled us to detect multiple point-like conductive channels under applied voltages of both polarities. Some of these channels can be disrupted under the bias of a reversed polarity and that is typical for bipolar resistive switching, while some new conductive channels can be formed. In addition, by using the Al/GO/n-Si MIS structures, we were able to identify unique local properties of the conductive channels. These properties are associated with a change in the charge state of a conductive channel near/at the GO/Si interface. This change is caused by either the creation of negatively charged traps or an increase in the GO work function. By increasing the maximum current that is flowing through the MIS structure, the conductive channels can be visualized by local changes to the aluminum electrode morphology. At the same time, large areas with an increased conductivity are revealed by the EBIC, and they may indicate the change of the GO bulk resistive properties. The important role of aluminum oxide in resistive switching is revealed by the C–V characteristics. An unusual dependence of the accumulation capacitance of the Al/GO/n-Si MIS structure on the bias that is in depletion is explained by the presence of a thin aluminum oxide which is connected in a series with the graphene oxide. The drift of the oxygen vacancies that are accumulated in the top GO layer is believed to be responsible for the formation of conductive filaments in a thin aluminum oxide layer. The formation of the conductive channels results in an increase in the conductivity and electrical shortening of the aluminum oxide. The presence of traps for the holes in the GO bulk may affect the resistive switching processes by accumulating and releasing the positive charge.In conclusion, at least two out of three major resistive switching mechanisms, namely metallic-like filamentary conduction and contact resistance modification due to the drift of the oxygen vacancies can operate simultaneously in the graphene oxide-based MIS structures. The third mechanism which is related to the oxidation of/reduction in the graphene oxide bulk due to the sp2–sp3 transitions cannot be excluded from consideration, but it needs additional experimental verification. The conductive channels in the GO can be revealed by the EBIC only when the local rectifying barriers are formed near/at the GO/Si interface. The creation of negatively charged traps or the change in the value of the GO work function can be responsible for the formation of such rectifying barriers.


Chinese Materia Medica and Jiangsu New Medical College record that Radix Veratri root is Liliaceae Veratrum taliense Loses. f. and the root of Veratrum stenophyllum Diels. According to traditional Chinese medicine (TCM) example, Radix Veratri is a Liliaceae plant Veratrum taliense. Another literature pointed out that the aliases of Veratrum taliense and Veratrum angustifolia are both Radix Veratri, and their effects are basically the same. The main active ingredient of Veratrum is veratramine, of which veratramine and Jervine are higher in content, reaching 24.60% and 21.28% of the total alkaloids, respectively. Veratrum alkaloids are both toxic and effective ingredients. In addition to its good clinical efficacy, attention should also be paid to its pharmacokinetic characteristics in vivo. It is particularly important to study the pharmacokinetic characteristics of veratramine and Jervine in vivo.  The goal of this study was to develop a simple and effective method for measuring veratramine and Jervine in rat plasma at the same time. This method was used to study the pharmacokinetic characteristics of veratramine and Jervine in the alcohol extract of Radix Veratri in rats, to provide a reasonable basis for the clinical use of Radix Veratri. m/z, Jervine quantitative ion pair was 426.2⟶114.1m/z, and Bullatine B (IS) quantitative ion pair was 438.2⟶420.1m/z. In the positive ion mode, the multireaction monitoring (MRM) mode was used to determine the blood concentration of veratramine and Jervine. DAS 3.3.0 was used to calculate the relevant pharmacokinetic parameters.  Eighteen SD rats were randomly assigned into three groups, half male and half female, and were given 0.04 g/kg, 0.08g/kg, and 0.16 g/kg Radix Veratri alcohol extract, respectively. Blood samples were collected at different time points and were analyzed by LC-MS/MS after protein precipitation. Bullatine was set as the internal standard; the plasma samples were extracted with ethyl acetate. After the sample was processed, acetonitrile-10 mM ammonium acetate, whose pH was adjusted to 8.8 with ammonia water, was taken as the mobile phase. Veratramine quantitative ion pair was 410.1⟶295.1r of three consecutive batches of the standard curve was greater than 0.995. Veratramine's lower quantification limit was 0.745 ng/mL, Jervine's was 1.11 ng/mL, and precision and accuracy were both less than 15%. The accuracy of veratramine was between 88.96% and 101.85%, and the accuracy of Jervine was between 92.96% and 104.50%. This method was adopted for the pharmacokinetic study of alcohol extracts of Radix Veratri. The results showed that only Cmax of veratramine female rats did not show linear kinetic characteristics in the dose range of Radix Veratri alcohol extract from 0.04 g/kg to 0.16 g/kg. For AUCt0‐ and Cmax of veratramine and Jervine, it could not determine whether the Radix Veratri alcohol extract showed linear kinetic characteristics within the dosage range of 0.04 g/kg~0.16 g/kg. Veratramine and Jervine showed obvious gender differences in the absorption and elimination stages. The absorption rate of veratramine and Jervine by male mice was about 10 times higher than that of female mice, and the elimination rate of male mice is about 20 times lower than that of female mice. It was suggested that the clinical application of the steroidal alkaloids veratramine and Jervine in Radix Veratri required rational use of drugs based on gender.  Veratramine had a good linear relationship in the concentration range of 0.0745~18.2 ng/mL, and that of Jervine was 1.11~108 ng/mL. The correlation coefficient  An LC-MS/MS analysis method suitable for the pharmacokinetic study of veratramine and Jervine in Radix Veratri in SD rats was established to provide a basis for in vivo pharmacokinetic studies. The pharmacokinetic characteristics of veratramine and Jervine in the alcohol extract of Radix Veratri were significantly different in female and male rats. During the clinical use of Radix Veratri, it should pay close attention to the obvious gender differences that may occur after the medication. Radix Veratri is also known as small Veratri, Veratrum, small brown bag, human hair, etc. The taste is bitter, cool in nature, and highly toxic. It has the effects of dispelling blood stasis and swelling, analgesic and hemostasis, lowering blood pressure –3, expecThe paper's organization paragraph is as follows: The materials and methods are presented first. Second are experimental results of the proposed work. Thirdly, it consists of the results and discussion sections. Finally, the research work is concluded.Veratramine and Jervine reference substances' purity was no less than 98%, which were purchased from Nanjing SenBeiJia Biological Technology Co., Ltd. . Bullatine B  was purchased from the Beijing Shengshikangpu Chemical Technology Research Institute (batch number: N-019-150906). Heparin sodium  was purchased from Aladdin (batch number: C162031). Ammonium acetate  was purchased from Aladdin (batch number: k1616041). Methanol  was purchased from MERCK (batch number: I0887507 717). Sinopharm Chemical Reagent Co., Ltd. provided analytical pure ethyl acetate (batch number: 20170824). Sichuan Xilong Chemical Co., Ltd. provided the ammonia  (batch number: 150324). The water was ultrapure water made by the Drug Safety Evaluation Center of Yunnan Institute of Materia Medica.μL. The mass spectrum parameters were as follows: veratramine m/z: 410.1⟶295.1, Jervine m/z: 426.2⟶114.1, and Bullatine B m/z: 438.2⟶420.1. Ion source parameters were as follows: CUR: 20.00 psi, IS: 5,500.00 V, TEM: 500.0°C, GS1: 50.0 psi, GS2: 50.0 psi, CAD: medium, and interface heater(ihe): on.The researchers used an API-3200 triple quadrupole tandem mass spectrometer and an electrospray ionisation ion source (ESI). Multiple reaction monitoring (MRM) was used to quantify the sample, which was separated on an Agilent ZORBAX Extend C18 column. The mobile phase was A (10 mmol/L ammonium acetate) and B (acetonitrile), 0-0.2 min, 10% B; 0.2-2 min, 10%-90% B; 2-5 min, 90% B; 5-5.1 min, 90%-10%B; and 5.1-7.5 min, 10%B. The flow rate was 0.4 mL/min, the column temperature was set to 20°C, and the measurement solution was 10 μg/mL, 553 μg/mL, 496 μg/mL, and 513 μg/mL. Diluted with methanol, the concentrations of veratramine were 0.745, 2.24, 6.70, 20.2, 60.5, and 182 ng/mL; those of Jervine standard working fluid were 11.1, 27.8, 69.5, 174, 434, and 1,080 ng/mL; those of veratramine were 0.745, 2.70, 25.6, and 143 ng/mL; and those of Jervine quality control working solution were 1.11, 31.6, 194, and 724 ng/mL. Quality control samples were used for precision, accuracy, matrix effect, recovery, and stability investigations. The same method was used to prepare Bullatine B (IS) internal standard working solution with a concentration of 128 ng/mL, and all working solutions were stored in a refrigerator at 2-8°C.5.45 mg and 5.53 mg of veratramine reference substance and 4.96 mg and 5.13 mg Jervine reference substance were taken, two copies each. Methanol was diluted to stock solutions with concentrations of 545 μL internal standard working solution was added into a 2 mL EP tube, blown and dried with nitrogen at room temperature, and added with 100 μL of plasma sample mixed in vortex for 2 min. Then, 40 μL 25% ammonia water was added and mixed in vortex for 1 min, and 1 mL ethyl acetate was added and mixed in vortex for 3 min and centrifuged at 6,000 r/min at room temperature for 10 min. 600 μL of the supernatant was taken and blown and dried with nitrogen at room temperature. It was reconstituted with 150 μL methanol and mixed in vortex for 2 minutes and centrifuged at 15,000 r/min at room temperature for 10 minutes, and the supernatant was taken for analysis.10 It was fully verified according to the US Food and Drug Administration's bioanalytical method verification guidelines, as illustrated in Figures y = 0.291x + 17.1 × 10−4 (r = 0.9965). The Jervine standard curve was y = 0.0462x − 5.51 × 10−3 (r = 0.9981). The lower limits of quantification of veratramine and Jervine were 0.0745 and 1.11 ng/mL, respectively, and those of RSD% were 5.49% and 0.12%, respectively.The standard curve was obtained by measuring no less than six points for each compound. The veratramine concentrations were 0.0745, 0.224, 0.670, 2.02, 6.05, and 18.2 ng/mL, respectively. The Jervine concentrations were 1.11, 2.78, 6.95, 17.4, 43.4, and 108 ng/mL, respectively. The lowest detectable concentration was used to define the lower limit of quantification. It was also repeated six times to ensure precision and accuracy. The veratramine standard curve was n = 6) and intraday (n = 6) were determined after four concentrations of quality control samples were measured, those of veratramine were 0.745, 2.70, 25.6, and 143 ng/mL, respectively, and those of Jervine were 1.11, 31.6, 194, and 724 ng/mL, respectively (The accuracy and precision of intraday (ectively . The absn = 6) was veratramine of 2.70, 25.6, and 143 ng/mL, respectively, and Jervine of 31.6, 194, and 724 ng/mL, respectively. The extraction recoveries of the two compounds were veratramine of 81.22%~94.42% and Jervine of 81.65%~87.98%  2015-030, and the laboratory animal quality certificate number was No. 51203500004128. There are 9 females and 9 males each, 7-8 weeks, the weight range of female rats was 200-230 g, and the weight range of male rats was 200-230 g. The weight difference of the grouped animals was not more than 20% of the average weight of all animals, and they were rolled into low, medium, and high dose groups, with half males and half females. Samples were collected at 0.15, 0.5, 1, 3, 6, 9, 18, 30, 48, 72, and 96 h before intragastric administration (0 h) and after administration. 0.3 mL of blood was collected from the rat's retroorbital venous plexus, placed in a centrifuge tube soaked in 2 mL of heparin sodium, and centrifuged  for 15 min, and the plasma was frozen and stored at -20°C for testing.t0‐, AUC0−∞, and T1/2. Cmax and Tmax adopted actual measured values, and other pharmacokinetic parameters adopted statistical moment parameters.The pharmacokinetic parameters were calculated using the DAS 3.3.0 pharmacokinetic program to calculate the main pharmacokinetic parameters AUCα · Dβ  was used for multidose linear relationship analysis. α, β, and the 90% confidence interval (90% CI) of the β value in the power function model were calculated using the DAS 3.3.0 pharmacokinetic program. The linear judgment interval after the criterion was changed using the DAS 3.3.0 pharmacokinetic program was 0.839-1.161, based on the bioequivalence criterion of 0.8 to 1.25. When the 90% CI of the β value fell within the linear judgment interval, the linear relationship was considered to be established; otherwise, the linear relationship did not hold.Power function model PK = The absorption rate of male mice was higher than that of female mice, and the elimination rate of male mice was lower than that of female mice, showing obvious gender differences in veratramine  and JervPower Model in the hypothesis test method was used according to the standard of 0.8~1.25, and the linear interval calculated by 1 ± ln(θL)/ln(DH/DL) < β < 1 ± ln(θH)/ln(DH/DL) should be between 0.839 and 1.161. The results of determinations of whether veratramine and Jervine in the alcohol extract of Radix Veratri showed linear kinetic characteristics within the dose range of 0.04 g/kg to 0.16 g/kg are presented in DAS 3.3.0 was employed, the In the initial selection of internal standards, the first selected compounds were aconitine, hypaconitine, Bullatine A, Wilforgine, and Bullatine B. The response of aconitine and hypaconitine could not reach the linear medium concentration, and the response was extremely unstable. Although Bullatine A and Wilforgine could achieve the required response, their chromatographic peaks were far from the target peak, and the analysis time was long, which increased the experimental cost. The peak shape of Bullatine B was good, it can be completely separated from the target peak, and it can be better dissolved in the sample. After testing, there was no Bullatine B in Radix Veratri, so Bullatine B was selected as the internal standard.Cmax of veratramine female rats did not show linear kinetic characteristics within the dosage range of 0.04 g/kg~0.16 g/kg of Radix Veratri alcohol extract. For others, it cannot be judged whether AUCt0‐ and Cmax were linear kinetic characteristics within the dosage range of 0.04 g/kg~0.16 g/kg of Radix Veratri alcohol extract.t0‐ and average Cmax of males were much higher than those of females. Female rats have considerably greater CLz/F clearance rates of veratramine and Jervine than male rats. However, there was no discernible variation in the half-life of veratramine in male and female rats, while the half-life of Jervine was considerably different in female and male rats. This was due to the fact that female rats had a considerably higher volume of veratramine dispersion than male rats, and Jervine was removed faster in female rats than in male rats. The above situation showed that after administration of the alcohol extract of Radix Veratri, veratramine and Jervine were more widely distributed in female rats than in male rats, but the clearance rate was much lower than that in female rats. In addition, at the dosage designed in this experiment, the average AUCt0‐ and average Cmax of males were much higher than that of females. The drug exposure in male rats was much higher than that of female rats, but the clearance rate was much lower than that of female rats. Male rats were more prone to accumulate toxicity in the course of long-term administration, and the symptoms of toxicity were greater than that of females.In the low-dose group, middle-dose group, and high-dose group, the average AUCThe blood drug concentration and main pharmacokinetic parameters of the Radix Veratri alcohol extract group were analyzed. The absorption rate of veratramine and Jervine by males was higher than that of female rats. Although Bullatine A and Wilforgine were able to provide the desired response, their chromatographic peaks were distant from the intended peak, and the analysis time was considerable, increasing the expense of the experiment. Male mice had a lower elimination rate than female mice, indicating clear gender differences. Finally, the clinical usage of the steroidal alkaloids veratramine and Jervine in Radix Veratri necessitates gender-based medication selection.


Furthermore, the c-GAFs were fabricated into strain sensors and showed better stability and sensitivity compared with GAF-based sensors. This work revealed the mechanism of the tunable conductivity and presented a facile and universal method for improving the electrical conductivity of macro-graphene materials in a controllable manner and proved the potential applications of such materials in flexible electronics like antennas, sensors, and wearable devices.Graphene and graphene-based materials gifted with high electrical conductivity are potential alternatives in various related fields. However, the electrical conductivity of the macro-graphene materials is much lower than their metal counterparts. Herein, we improved the electrical conductivity of reduced graphene oxide (rGO) based graphene assembled films (GAFs) by applying a series of compressive stress and systematically investigated the relationship between the compressive stress and the electrical conductivity. The result indicates that with increasing applied compressive stress, the sheet resistance increased as well, while the thickness decreased. Under the combined effect of these two competing factors, the number of charge carriers per unit volume increased dramatically, and the conductivity of compressed GAFs (c-GAFs) showed an initial increasing trend as we applied higher pressure and reached a maximum of 5.37 × 10 Graphene, as the thinnest two-dimensional material with a honeycomb lattice nanostructure that contains numerous double bonds, has been attracting prevalent attention ,2 in the3 S/m [7 S/m.Electrical conductivity is an extremely important fundamental property that represents the ability of the material to conduct current. It is also one of the determining properties of graphene and graphene-based materials for electrical applications such as sensors, electromagnetic shielding, antennas, and flexible electronics. Since the discovery of graphene, various efforts have been made to improve its electrical conductivity. For example, the relation between the distances among neighbor holes and the conductivity of graphene was predicted by simulation by Pavel et al. . To impr3 S/m . However5 S/m under the optimal compressive stress of 450 MPa and then decreased. Further, the obtained compressed graphene films were applied as strain sensors which showed good stability and sensitivity. This work provides general guidance on controlling the electrical conductivity for macro graphene materials to achieve different applications [Given the widest applicability of film materials within common macro graphene materials, this work investigated subsequent compression for improving the electrical conductivity based on graphene-assembled films (GAF) by thermal annealing. The result showed that the electrical conductivity of GAF could be regulated by applied pressure and peaked at 5.37 × 10ications ,35,36,37The GO powder purchased from Wuxi Chengyi Education & Technology Co., Ltd.  was dispersed in deionized water with solid contents of 2–4%. The obtained suspension was then stirred at 450 rpm for 4–6 h until it transformed into a gel. After carefully pouring the polyethylene terephthalate (PET) substrate into a glass mold at the proper height, the GO gel was dried up at room temperature until the GO film was formed. This newly formed GO film was peeled off from the PET substrate and then thermally annealed with the heating rate of 10 °C/min under argon shielding at 1300 °C for 2 h and 3000 °C for 1 h. The GAF was obtained after cooling to room temperature.The obtained GAF was cut into square or rectangular pieces and was then set between two PET films forming a sandwich-like structure (PET-GAF-PET) to avoid damage from the tiny machine marks on the metal plate on the test machine. The laminated structure was then compressed by a testing machine (MTS with force capacities from 1 to 3000 kN) at a speed of 0.2 mm/min until reaching the set pressure. The pressure was kept constant for 12 h. After the compression process, the PET films were peeled off from the GAF, and the c-GAF was obtained.The high-resolution transmission electron microscope  was used to observe the morphology of GO and rGO nanosheets. The cross-sectional images of GO and GAF were captured by the field-emission scanning electron microscope . The 3D reconstruction for surface morphology and cross-section of the c-GAF specimens were processed by the digital microscope . The sheet resistance of c-GAF was measured by the four-point probe system (RTS-9). The defects of molecular structures in GO and GAF were examined by the confocal Raman microscope .The c-GAFs were cut into rectangles (5 mm × 70 mm) and fabricated into strain sensors. The c-GAF strain sensors were fixed on the glass fiber-reinforced plastic (GFRP) by polydimethylsiloxane (PDMS). Foil gages (BE120-5AA) were fixed on the opposite sides of each GFRP specimen to indicate the deformations. All GFRP specimens with strain sensors were stretched by the universal testing machine  at a speed of 0.5 mm/min. The resistance of the c-GAF sensors was measured by a digital multimeter . The outputs of the foil gages were recorded by the strain gauge .2. When those gas compounds were expelled from the interior of the reduced GO film, micro-gasbags sprouted in assembled graphene nanosheets and contributed to the porous microstructures of GAF. The HRTEM image of GO nanosheets in −1 could be observed, which informs the defective carbon structure in GO film. After annealing at 3000 °C, the D peak can hardly be observed for GAF, and instead, the intensity of the G peak at 1600 cm−1 increases significantly, which indicates its higher crystallinity than GO film. In addition, the new-emerged 2D peak at 2700 cm−1 confirms the existence of graphene layers. The ratio of ID/IG was estimated to be 0.052, indicating the excellent crystal structure. The X-ray photoelectron spectroscopy (XPS) results further corroborate the much higher graphitization degree in GAF than in GO with diminished C-O peak and higher intensity of C-C peak at 284.5 eV  measurement was also conducted to characterize the functional groups as depicted in To characterize the molecular structures of the films before and after reduction systematically, Raman spectroscopy was applied. As presented in 284.5 eV b. The X-= 10.95° c indicatσ = Gl/A where G is the conductance which is the reciprocal of the resistance R, l, and A are the length and cross-sectional area of the specimen, respectively. However, the result of traditional methods to measure the resistance between any two gauging points can hardly expose the conductance of specimens in practice. To understand the rules about the electrical conductivity of the obtained GAFs, the sheet resistance which is only related to the thickness of the given material has been used. A four-point probe is a commonly used equipment to measure the sheet resistance for conductive materials, especially films with relatively large lateral dimensions. Once sheet resistance sR is obtained, the conductivity can be determined using σ = 1/sdR, where d is the thickness of the specimen. This formula indicates that the most effective way to improve the electrical conductivity is by reducing the sheet resistance and thickness of the specimen. Given that the dense structure provides a superior electric conductive network, compressing the specimen with flat plates might be a feasible method. Thus, we treated the graphene films under different flat compression loads by the universal test machine and measured the conductivity for each c-GAF to systematically investigate the relation between applied stress and electrical conductivity of c-GAF.Electrical conductivity is one of the most important indicators to evaluate the ability to conduct electricity. To a specific specimen, the electrical conductivity σ can be calculated by 5 S/m and then showed a decrease to 4.36 × 105 S/m with the stress of 550 MPa. Assume the symbol p as the compressive stress to describe the relationship between the conductivity and the applied pressure; the fit result is shown in σ = −7 × 10−10p4 + 8 × 10−7p3 − 0.0003p2 + 0.0436p + 1.4289. Together with the monotonically increasing sheet resistance , the damaged area could be observed, and the resistance increased dramatically. The sensor was broken completely when the strain approached about 0.60%; the resistance cannot be measured.In consideration of the mechanical properties of the c-GAF and GFRP, including elastic range and ultimate strain, the tensile tests for c-GAF strain sensors on GFRP were conducted by the test machine at a speed of 0.5 mm/min and maximum strain of 1%. During the stretching process, the resistance of different c-GAF strain sensors was collected at a frequency of 10 Hz by a data acquisition system, and the results are displayed in To verify the reliability of the c-GAF for application in strain sensor, the fatigue test with strain ranging from 0–0.6% (elastic range) was conducted with a c-GAF-450 sensor on the GFRP specimen. As depicted in 5 S/m to a maximum value of 5.37 × 105 S/m. It also proved that there is optimal stress at 450 MPa for c-GAF to gain the most excellent electrical conductivity, and further increasing the pressure resulted in decreasing conductivity. Furthermore, as part of the exploration of the application, comparative uniaxial tensile tests and fatigue tests for the performance of c-GAF sensors were conducted, which demonstrated the outstanding sensitivity and reliability of the c-GAF-450-based strain sensor. Based on the experimental results, our further work will focus on the conductive mechanism of the c-GAF and try to expose the rule of electrical conductivity theoretically.In summary, we proposed a universal strategy to tailor the electrical conductivity for the synthesized GAF by thermal annealing. The GAFs were compressed with stress ranging from 0 to 550 MPa to experimentally study the relation between the applied compress stress and the electrical conductivity. Encouragingly, by affecting both the thickness and the sheet resistance at the same time, the number of the charge carriers per unit volume was changed, and the electrical conductivity of the c-GAF was tunable ranged from 0.88 × 10