Furthermore, the energy loss characteristics revealed that the hysteresis loss attributable to the free chain ends of LqBR was dominant.Liquid butadiene rubber (LqBR) which used as a processing aid play a vital role in the manufacturing of high-performance tire tread compounds. However, the studies on the effect of molecular weight, microstructure, and functionalization of LqBR on the properties of compounds are still insufficient. In this study, non-functionalized and center-functionalized liquid butadiene rubbers  were synthesized with low vinyl content and different molecular weights using anionic polymerization. In addition, LqBR was added to the silica-filled SSBR compounds as an alternative to treated distillate aromatic extract (TDAE) oil, and the effect of molecular weight and functionalization on the properties of the silica-filled SSBR compound was examined. C-LqBR showed a low Payne effect and Mooney viscosity because of improved silica dispersion due to the ethoxysilyl functional group. Furthermore, C-LqBR showed an increased crosslink density, improved mechanical properties, and reduced organic matter extraction compared to the N-LqBR compound. LqBR reduced the glass transition temperature (T Liquid butadiene rubber (LqBR) is widely used as a vulcanizable plasticizer in the fields of plastics, tire, printing inks, paints, coatings, and sealants, etc. . Low molg) and no migration. Accordingly, the demand and interest in LqBR began to increase gradually.Since 1995, European processing oil producers and tire manufacturers have begun to develop processing aids to replace highly aromatic oils  that contain polycyclic aromatic hydrocarbons (PAHs), which are carcinogenic substances. In fact, the use of DAE oils is prohibited in tire manufacturing, and oils with a low PAH content, such as treated distillate aromatic extract (TDAE) oil, are being used as alternative processing aids in accordance with European Registration, Evaluation, Authorization and Restriction of Chemicals (EU REACH) regulations in 2010 ,7. Howevg by minimizing the vinyl content of the non-functionalized LqBR, which was found to have reduced the migration of LqBR through co-vulcanization with a solid polymer tetrasulfide  was used as a silane coupling agent. Moreover, TDAE oil  was used as a processing aid for mixing. ZnO and stearic acid  were used as activators, and N--N-phenyl-p-phenylenediamine  was used as an antioxidant in the compound. Additionally, sulfur  was used as a crosslinking agent. N-cyclohexyl benzothiazole-2-sulfenamide  and 1,3-diphenylguanidine  were used as cure accelerators.SSBR  was used as the base polymer. Silica  surface area: 160–175 mMolecular weight and molecular weight distribution were measured using gel permeation chromatography (GPC) system . The GPC system consisted of a solvent delivery unit, reflective index detector, and three types of Styragel columns: HT 6E , HMW 7 column , and HMW 6E column (15–20 µm 7.8 mm × 300 mm). Further, the measured molecular weight was corrected using a polystyrene standard sample .1H NMR; Varian, Unity Plus 300 spectrometer, Garden State Scientific, Morristown, NJ, USA). LqBRs were dissolved in a 5 mm NMR tube at a concentration of 15 mg/mL using deuterochloroform  as a solvent.The vinyl content in LqBR was evaluated using proton nuclear magnetic resonance spectroscopy (g) was carried out on a differential scanning calorimeter . The curves for samples (3–6 mg) were obtained by heating sample from −120 to −20 °C at a heating rate of 10 °C/min under nitrogen atmosphere.The determination of glass-transition temperature  was used to evaluate the silica dispersion and filler–filler interaction of the compound according to ASTM D8059. The storage modulus (G′) of the uncured compound was measured at a temperature of 60 °C in the range of 0.28%–40.04% strain. The G′ value is large in the low-strain region because the silica agglomerates are not destroyed, whereas the G′ value decreased in the high-strain region as the agglomerates are destroyed. Therefore, the change in G′, i.e., △G′ (G′ at 0.28% − G′ at 40.04%) is called the Payne effect, which indicates the degree of filler–filler interaction.A Mooney viscometer , which evaluates the processability of rubber by measuring the torque when the rotor rotates in a space filled with uncured rubber compound according to ASTM D1646, was used. The rotation speed of the rotor was set to 2 rpm, and the temperature was set to 100 °C. The torque value was measured by rotating the rotor for 4 min after preheating for 1 min.min), maximum torque (Tmax), scorch time (t10), and optimal cure time (t90) were measured.For measuring the cure characteristics of the compound, a moving die rheometer  was operated for 30 min, maintaining a vibration angle of ±1° and temperature of 160 °C while the minimum torque , cM is the average molecular weight between crosslink points (g/mol), rν is the volume fraction of rubber in the swollen gel at equilibrium in Equation (2), sV is the molar volume of solvent (cm3/mol), ρ is the density of rubber sample (g/cm3), and χ is the polymer–solvent interaction parameter in Equation (3).dryw is the weight of dry sample, fillerw is the weight of filler in the dry sample, swollenw is the weight of the swollen sample, rubberρ is the density of the rubber, and solventρ is the density of the solvent.ν0 is the molar volume of solvent, pẟ is the solubility parameter of polymer, sẟ is the solubility parameter of solvent.The crosslink density is defined as the number of crosslink points in the vulcanizates. The higher crosslinking density means that the molecular weight between the crosslink points decreases, and the number of crosslink points increases. In the swelling tests, the higher the crosslinking density, the less the number of solvent molecules can permeate between the crosslinked rubber chains, and thus relatively less swelling. The vulcanizates with dimensions of 10 mm × 10 mm × 2 mm were weighed and immersed in tetrahydrofuran  and n-hexane  at 25 °C for 2 days to remove organic additives inside the sample. Subsequently, the weight was measured after the sample was dried at 25 °C for 1 day to determine the mass fraction of the extracted organic additive. The weight of the sample immersed and swollen in a toluene solvent for 1 day at room temperature was measured after measuring the weight of the dry sample in order to calculate the total crosslink density. Moreover, the total crosslink density and average molecular weight between the crosslink points, equation ,19,20,21A 100 mm (length) × 25 mm (width) dumbbell-shaped specimen that was prepared according to ATSM D 412 was measured at a speed of 500 mm/min using a universal testing machine  to measure the mechanical properties  of vulcanizates.The abrasion resistance was measured according to DIN 53516 using a Deutsche Industrie Normen (DIN) abrasion tester. The specimen was prepared in a cylindrical shape with a diameter of 16 mm and thickness of 8 mm. The mass reduction after moving the specimen 40 m across the surface of an abrasive sheet mounted on a cylindrical drum revolving at 40 ± 1 rpm was measured by applying a load of 5 N.For the dynamic viscoelastic properties of the compound, the storage modulus (G′), loss modulus (G″), and tan ẟ were measured from −60 to 70 °C under a 10 Hz frequency at 0.5% strain using a strain-controlled rheometer .1H NMR.The formulation for N-LqBRs and C-LqBRs polymerization is shown in 90).The compound was prepared using an internal mixer  based on the formulation shown in 1H NMR analysis results of N-LqBRs and C-LqBRs are shown in 1H chemical shift of the 1H in the alkoxy group (SiO-CH2-) varies based on the number of alkoxy groups bonded to the silicon atom [1H in the alkoxy group peak also decreased as the molecular weight of C-LqBR increased.The GPC and con atom ,31. The n) before and after the coupling reaction [The coupling number (CN), which represents the number of coupled polybutadiene chains of C-LqBR, was calculated as the ratio of the number average molecular weight (Mreaction .(4)CoupThe CN of C-LqBR ranged from 1.9 to 2.3, indicating that the coupling reaction of two polybutadiene chains b was domThe Payne effect, as shown in Sufficient viscosity and shearing force are required during the mixing process for the outstanding silica dispersion of the compound. LqBR, which has a higher molecular weight than TDAE oil (molecular weight < 500 g/mol), has a high viscosity, thereby showing a high torque peak value during the mixing process, as shown in min value of the LqBR-applied compound was lower than that of the TDAE compound. This is a result of the improvement in the silica dispersion when LqBR was applied as in the Payne effect result. In addition, C-LqBR showed a lower Tmin value compared to N-LqBR of similar molecular weight because the functional group can hydrophobize the silica surface through a silanization reaction.The results of Mooney viscosity related to the processability of the compound are shown in max − Tmin) value in the MDR curve is known to be affected by the filler morphology and crosslink density [In the case of silica compounds, the ΔT  value increased because the crosslink density increased along with an increase in the molecular weight of LqBR, and C-LqBR, which is capable of the coupling reaction, had a higher M300 value than N-LqBR.The modulus value in the stress–strain curves had a high correlation with the crosslink density result, as shown in 300 value than that of the TDAE compound in all compounds except N-1 and C-1, as the crosslink density was similar to that of the TDAE compound by controlling the sulfur and accelerator.LqBR generally acts as a lubricant between the base polymer chains to facilitate slippage and decreases the modulus owing to a decrease in the crosslink density value by consuming sulfur. However, it showed a higher Mg, filler–rubber interaction, and toughness of the polymer [g than TDAE oil, showed outstanding abrasion resistance by significantly lowering the Tg of the compound. The crosslink density increased with an increase in the molecular weight of LqBR, while the toughness calculated using the area of the stress–strain curves decreased. Thus, since the two factors affect abrasion resistance, the best abrasion resistance was confirmed in the N-2 and C-2 compounds.The mechanical properties and DIN abrasion loss measurement results are shown in  polymer ,40,41,42g decreased the compound Tg and increased the flexibility of the compound at low temperatures. In the case of G″ at 0 °C, as shown in g of vulcanizates. C-LqBR compounds are determined to have shown lower G″ at 0 °C than N-LqBR because the effective filler volume fraction was decreased as the silica dispersion was improved, similar to the Payne effect results earlier.When the tire, to which the vehicle load is applied, rotates, energy loss occurs as all parts of the tire repeat deformation and recovery. This phenomenon is called hysteresis loss, which is the main cause of energy loss related to tire rolling resistance (RR). Moreover, during the braking, energy is lost as the tire is rapidly deformed on the road surface, which is related to the frictional force between the tire and the road surface. This hysteresis loss is attributable to the viscoelastic properties of the rubber compound and is measurable in the laboratory to predict tire performance. Among the viscoelastic properties, the storage modulus (G′) value in the low-temperature region below −10 °C is an indicator of snow traction and is known to improve snow traction at lower values ,44. Thisc in vulcanizate, most of the LqBR chains are in a state where they cannot be bonded to the base polymer. However, the ratio of LqBR chains that can be bonded to the base polymer gradually increases as the molecular weight of LqBR increases, and this dangling chain causes hysteresis by behaving as free chain ends. In contrast, when most LqBRs reach the molecular weight range that can be bonded to the base polymer, such as N-3 and C-3, it is determined that the effect of decreasing the number of chains and chain end is more dominant than the dangling end effect. Therefore, tan δ at 60 °C tended to decrease due to a decrease in the number of LqBR chains from the molecular weight range beyond N-3 and C-3. In the case of C-LqBR, the value of tan δ at 60 °C was lower than that of the N-LqBR compound, which was attributed to the improvement of silica dispersion and the decrease in chain mobility due to the coupling reaction.The tan δ value at 60 °C increased and then decreased as the molecular weight of N-LqBR and C-LqBR increased, as shown in g of the compound, thereby improving the snow traction. In the case of tan δ at 60 °C, the maximum value was observed because of both effects of the dangling ends from co-vulcanization and the decrease in the number of chains with the increase in molecular weight.This study examined the effect of the molecular weight and modification of LqBR applied as a processing aid to silica-filled SSBR compounds on physical properties. Moreover, the properties were compared after controlling the sulfur and accelerator contents to have a crosslink density similar to that of the TDAE oil-applied compound. LqBR improved the Payne effect and processability without deteriorating the mechanical properties. In particular, C-LqBR with a functional group showed a lower Payne effect and Mooney viscosity compared to N-LqBR. N-LqBR compounds showed lower ΔT values than the TDAE compound by consuming sulfur during vulcanization, whereas C-LqBR showed a higher ΔT value as the functional group not only was fixed to the silica surface but also formed a chemical bond with the base polymer through a crosslink reaction. As the molecular weight of LqBR increased, the amount of organic matter extracted was reduced because it was more advantageous to the crosslink reaction with the base polymer. In terms of the mechanical properties, the modulus increased and the toughness decreased as the molecular weight of LqBR increased. The abrasion resistance showed optimum points in the N-2 and C-2 compounds. In particular, it was determined that not only the increase in the filler-rubber interaction but also the increase in toughness affected abrasion resistance. In terms of the dynamic properties, LqBR significantly lowered the TThese characteristics of LqBR are suitable for winter tires that require high traction and long-term flexibility on the ice, and the results presented in this study are expected to provide the basis for optimal LqBR design and selection required for manufacturing LqBR-applied tires.


Beef cattle are the third most numerous terrestrial farmed animals worldwide. Factors such as geographical region, animal category, breed, and rearing system pose specific animal welfare challenges that can have an impact on animal and public health. This article uses text mining (TM) and topic analysis (TA) to explore the scientific literature on beef cattle welfare published in English from 1990 to 2019. Our aim was to reveal the main research topics and their evolution over time. Our analysis showed that the three most relevant themes in research since 1990 have to do with calf behaviour and management, efficiency, and environmental sustainability, and the effects of transport and slaughter on meat quality. Topics showing the most marked increase in the number of papers published deal with stakeholders' perceptions and market opportunities for added-value beef products and risk factors for morbidity and mortality, especially in relation to calf health, antimicrobial use, and antimicrobial resistance. The results indicate a particular focus on the welfare of calves, especially in the veal industry. Pain relief during the castration of calves and bulls also featured prominently. Research is also increasingly assessing aspects of beef cattle welfare that are interlinked to meat quality, the social and environmental sustainability of the sector in relation to market opportunities, and public health. The identified topics represent a basic source of information that can be used for further and more detailed analyses  focussed on specific research themes or geographical areas. Beef cattle  are the third most numerous farmed animals worldwide (after poultry and pigs), with 71.61 million tonnes produced globally in 2018. In the same year, the EU produced 10.64 million tonnes of beef meat . Each reThe science of animal welfare has considerably evolved from the 1990s to the present day, and with it the recognition that animals are sentient beings, deserving of “a good life,” which includes opportunities to experience positive affective states . It is t©. The keywords used were “bovine meat welfare,” “meat cattle welfare,” “veal welfare,” “beef welfare,” “beef cattle welfare,” and “heifer welfare.” The search was performed in January 2020. The initial timespan considered was between 1960 and 2019. As less than one relevant paper per year was published in the period 1960–1989, only papers published from 1990 onwards were retained for the full statistical analysis. An electronic Excel workbook was used to collect the data extracted from the identified papers. The spreadsheet was built in a 2-way table format considering every paper (record) as a row and its descriptive information in columns. A list of the descriptors used and additional information on data format are provided as A literature search protocol was set up to identify peer-reviewed papers with at least an English abstract that covered the topic of beef cattle welfare using Scopus®, the abstracts and citation database of Elsevierhttps://www.wordclouds.com/) in which a bigger character size indicates a higher TF-IDF value. The statistical analysis was conducted with R package (2017) using the libraries tm, stringr, and SnowballC.A TM analysis was performed on the abstracts of the selected papers to find important patterns in text data as described by Wang et al.  and Conttopicmodels package in R . The second most important area of provenance of authors was North America (25%), followed by South America (11%), Oceania (9%), Asia (6%) and, lastly, Africa (3%).A breakdown of articles per country of the European block is shown in The distribution of published papers by journal title (with at least 10 papers published on the topic in the period considered) is shown in Research articles represented the most common type of retained paper (76%) followed by reviews (13%), conference papers (6%), and others (5%). The papers were published in 310 scientific journals. As a whole, the 983 articles had collected—as of January 2020—a total of 15,208 citations. The most cited article was published in 2004, collecting 392 citations, followed by an article published in 2010 that collected 235 citations.Text mining analysis was performed to identify the most important words of the data corpus. The pre-processing of the data produced 106,108 words and after reduction of sparseness (exclusion of the “rare words”) 1,490 terms were retained from the selected 983 documents. The most relevant words according to the TFIDF ponderation system (TFIDF≥5) are represented in We created a visualisation (histograms) of the ten most probable words of the topics in LDA taking into account five, ten, 15 and 20 topics, respectively. The cumulative probability of the ten most frequent words for LDA with five topics was smaller than that for LDA with ten, 15 and 20 topics. The average cumulative probability of the ten most frequent words was 0.19, 0.26, 0.31, and 0.35 for 5, 10, 15, and 20 topics, respectively. This is because if a small number of topics is assumed, a few words may not convey a topic meaning sufficiently and different issues will be lumped together . The tokenised words belonging to this topic were “calv-, group-, behaviour-, observ-, differ-, calf-, wean-, indic-, studi-, frequenc-.” The articles retained in the database reveal a scientific focus on aspects of animal welfare at calving and the optimisation of calf welfare  to reduce stress and improve growth. Some aspects were common to the literature on beef and dairy cattle, whereas others were specific to each sector. A common aspect is the correct management of difficult calving (dystocia) from the perspective of the health and welfare of both the cow and calf , 26. SevThe second most important topic identified by the statistical analysis was “efficiency and environmental sustainability” (topic 8). The word stems making up this theme are “product-, system-, increase-, organ-, environment-, improv-, effici-, chang-, sustain-, nutrit-.” The recurring theme in this group of papers is a recognition that the beef industry is under public scrutiny for several respects  and that several adaptations will be necessary to address all of these concerns , 39. AccThe third most important topic dealt with “transport, slaughter and carcass quality” (topic 12). The word stems included in this topic are “slaughter, transport, carcass-, stun-, qualiti-, bruis-, load-, handl-, time, loss-.” The identified literature reflects a tension between the economically driven pressure to increase slaughter speed on the one hand, and the need to minimise financial losses due to bruising, guarantee meat quality, and protect animal welfare and public health on the other . MinimisAlthough not included in the first three most statistically relevant topics, “castrat-“ was among the first ten most important word stems according to the TFIDF analysis and is included in Topic 3 (“pain management”). The castration of male calves or mature bulls is a common practice in many parts of the world and is carried out to facilitate management and prevent unwanted breeding . CastratAnother interesting aspect that emerged from this study is the evolution of different topics over time. Topic n. 2 (“stakeholders' perceptions”) showed the most pronounced upward trend throughout the years. This topic deals with the attitudes, beliefs, expectations and preferences of different stakeholders  toward animal welfare and other attributes of beef meat. Such aspects have important implications for the treatment of animals on the one hand, and for the market on the other, since they influence purchase decisions. Consumers' perceptions of the beef cattle industry—and the livestock industry at large—are constantly changing and can influence willingness to pay for meat produced and marketed in certain ways –84. At tThe second topic showing the most significant upward trend in terms of papers published was n. 7 . Papers in this thematic group deal with risk factors for health and mortality in all categories of beef cattle. They are all quite recent, dating from 2002 onwards. The topics that feature most prominently in this thematic group are (a) antimicrobial use and resistance and (b) calf health, with particular reference to factors affecting morbidity and early mortality. The two topics are interdependent: veal calves are typically transported to specialised fattening facilities when still unweaned, sometimes passing via auction markets, and often with insufficient passive immunity . TranspoText mining with LDA is a methodology that enables researchers to have a good overview of the current state of a given domain or topic and provide indications for further research if relevant, especially when the number of documents to consider is large . HoweverBased on the analysis of the top ten word stems, the most important topics statistically, and the emerging trends, two considerations can be made. The first one is that animal welfare is now perceived as an important component of beef cattle management, and one that can have a positive impact on animal and human health. This is perfectly in line with the OneHealth framework, especially concerning the global fight against antimicrobial resistance . The secOur LDA topic analysis of scholarly articles on beef cattle welfare published in English between 1990 and 2019 shows an increasing scrutiny into the health and welfare of calves, including behavioural aspects. There is also a growing interest in sustainability issues and organic farming practices. Animal welfare during pre-slaughter and stunning, especially during transport, has an impact on meat quality and is therefore also an important research topic. In this specific case, there is a clear convergence of interest between financial gains and improved cattle welfare in the pre-slaughter and slaughter phases. The results indicate a particular focus on the welfare of calves, especially in the veal industry. Research is also increasingly assessing aspects of beef cattle welfare that are interlinked to meat quality, the social and environmental sustainability of the sector in relation to market opportunities, and public health. The issue of pain relief during castration featured prominently and is likely to become increasingly important as societal scrutiny into the ethical treatment of farmed animals converges with the scientific evidence on the acute and chronic painfulness of routine husbandry practices. The topic showing the most significant increase in popularity in the scientific literature on beef cattle welfare had to do with attitudes of consumers, farmers, and other stakeholders in the beef supply chain and their role in driving higher welfare practices and market opportunities. Another cluster of topics that has shown a marked increase in the literature since 2002 has to do with risk factors for morbidity and mortality, in particular in relation to the high use of antimicrobials in veal calf fattening facilities, which should be reduced by better addressing certain calf health and welfare issues. Although in some cases the focus is still on animal health and production parameters such as meat quality, our analysis shows that research on beef cattle welfare is increasingly incorporating and analysing environmental and societal topics that are relevant for the development of future local and global policies on livestock productions. The identified topics represent a basic source of information that can be used for further and more detailed analyses  focussed on specific research themes or geographical areas.The original contributions presented in the study are included in the article/EN, FG, and GC contributed to the conceptualisation and methodology of the original draft. BC performed the formal analysis. EN, BC, FG, and GC contributed to writing, reviewing, and editing the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Morphology, structure, chemical composition, and optical properties of the prepared sample were characterized using XRD, FESEM, FTIR, XPS, and DRS. The anchoring of SO42−-Ag3PO4 nanoparticles on the surface of PAN-electrospun nanofibers was evidenced by the change in color of the PAN nanofibers mat from white to yellow after ion-exchange reaction. FESEM analysis revealed the existence of numerous SO42−-Ag3PO4 nanoparticles on the surface of PAN nanofibers. Photocatalytic activity and stability of the prepared sample was tested for the degradation of Methylene blue (MB) and Rhodamine B (RhB) dyes under visible light irradiation for three continuous cycles. Experimental results showed enhanced photodegradation activity of SO42−-Ag3PO4/PAN-electrospun nanofibers compared to that of sulfate undoped sample (Ag3PO4/PAN-electrospun nanofibers). Doping of SO42− into Ag3PO4 crystal lattice could increase the photogenerated electron–hole separation capability, and PAN nanofibers served as support for nanoparticles to prevent from agglomeration.Present work reports the enhancement in photocatalytic performance of Ag Thus, generated ROS are responsible for its photocatalytic activities [3PO4 as a visible light-driven photocatalyst is limited due to poor chemical stability, when applied in absence of sacrificial agent [3PO4-based photocatalysts to overcome this limitation and improve their performance. In this regard, various studies have been reported, such as fabricating composites [The breakthrough work carried out by Yi et al.  opened amicrobes ,3,4,5. Ad gap 2.3 eV semictivities . Applicaal agent ,8. Theremposites ,11,12,13mposites ,15 and dmposites ,17,18. Omposites .3PO4 via cations doping into its crystal lattice have been reported [3PO4 doped with suitable anions have not been reported frequently. Meanwhile, a recent report has demonstrated the enhanced photocatalytic activity of sulfur-doped Ag3PO4 on the basis of hybrid density-functional calculation [3PO4 crystal lattice seems more difficult. Therefore, instead of sulfur, SO42− might be a suitable anion as a dopant to replace PO43− from Ag3PO4 crystal lattice due to smaller radius of SO42− (0.218 nm) compared to that of PO43− (0.230 nm) [On that note, various results regarding the enhanced photocatalytic performance of Agreported ,21. On tculation ; however PO43− 0.0 nm [23,.230 nm) . On the .230 nm) . In addi.230 nm) ,27,28. D.230 nm) ,30.3PO4 nanoparticles and PAN-electrospun nanofibers as support, our work is focused on the fabrication of SO42−-Ag3PO4/PAN-electrospun nanofibers by combining electrospinning and ion-exchange reaction. Visible light photocatalytic activity of as fabricated sample was evaluated by observing photodegradation of MB and RhB dye solutions. Finally, we hope this visible-light-driven photocatalyst would be a promising candidate for the degradation of organic dyes from waste water to avoid negative effects to the dependent living ecology. To the best of our knowledge this type of work has not been reported so far.Hence to realize the synergistic effect of sulfate-doped Ag2HPO4.2H2O, Sigma-Aldrich, St. Louis, MO, USA), Silver nitrate , Sodium sulfate , Methylene blue , Rhodamine B  and N, N-dimethylformamide . All the chemicals were of AR grade and used without further purification. Distilled water was used to prepared aqueous solutions.The chemicals used in this work are Polyacrylonitrile , Disodium hydrogen phosphate dihydrate (Na2HPO4 (0.46 g) was dispersed in DMF (14 mL) and ultrasonicated for 1h. Then 1.5 g powder of PAN polymer was added to the above dispersion and magnetically stirred for 12h to prepare electrospinning solution. Electrospinning of the prepared solution was carried out by loading into a plastic syringe fitted with plastic micro-tip. The applied voltage and distance between needle tip to collector were set as 18 kV and 12 cm, respectively. The developing nanofibers were collected on rotating drum collector connected to DC motor. Thus obtained Na2HPO4/PAN-electrospun nanofibers were vacuum dried for 12 h at 70 °C.First, fine powder of Na42−-Ag3PO4/PAN-electrospun nanofibers were prepared following ion-exchange reaction. Briefly, Na2HPO4/PAN nanofiber mat (0.1 g) was immersed in 500 mL of AgNO3 solution containing SO42− ions for 30 min. Concentration of AgNO3 and Na2SO4 was maintained at 0.02 M and 0.01 M, respectively. Change in color of nanofibers mat from white to yellow during ion-exchange reaction indicated the anchoring of SO42−-Ag3PO4 nanoparticles on the surface of PAN nanofibers. For comparison, Ag3PO4/PAN-electrospun nanofibers were also fabricated without adding SO42− ions into the AgNO3 solution under similar conditions. The resulting nanofibers mats were washed with deionized water and dried at 60 °C for 6 h before characterization. The schematic for the fabrication of SO42−-Ag3PO4/PAN-electrospun nanofibers is illustrated in 3PO4/PAN-electrospun nanofibers, and SO42−-Ag3PO4/PAN-electrospun nanofibers, respectively.SO42−-doped/undoped samples was studied using X-ray photoelectron spectroscopy , and the light absorption properties of the prepared samples was evaluated from UV-vis diffusive reflectance spectra (DRS) obtained from UV-vis spectrophotometer .Crystalline nature of the samples was investigated using X-ray diffractometer  with Cu Kα (λ = 1.540 Å) radiation over Bragg angles ranging from 10° to 80°. Field emission scanning electron microscope  equipped with energy dispersive X-ray spectroscopy (EDS) was used to study the morphology and elemental composition of the samples. Bonding configuration of the samples was characterized applying Fourier-transform infrared  through attenuated total reflectance mode (ATR). Furthermore, the surface element composition analysis of SOTo investigate the photocatalytic performance, as fabricated samples  were utilized as visible-light-driven photocatalysts for the degradation of MB and RhB solutions at 10 ppm using a solar simulator having an internal xenon lamp  equipped with a UV cutoff filter. The experiments were carried out in a glass vial containing dye solution (50 mL) and photocatalyst (100 mg). Prior to irradiation, the suspension was magnetically stirred under dark conditions for 30 min to establish adsorption/desorption equilibrium. Afterward, visible light obtained from the 200-W xenon lamp was irradiated under continuous magnetic stirring. Aliquots were taken at regular time intervals (10 min) and the concentration of the dye solution was measured spectrophotometrically by recording the absorbance using a UV-vis spectrophotometer . The total organic carbon (TOC) content in residual solution was determined with a TOC analyzer .3PO4 crystal lattice. 3PO4, respectively (JCPDS card No: 06-0505). Effect of sulfate doping into Ag3PO4 crystal lattice was examined by observing the magnified XRD patterns of AP/PAN and SAP/PAN   b and (SA(AP/PAN) c was no n insets a−c. In on insets d, the usn insets d. The ED SAP/PAN . As show−1 in all samples is assigned to the nitrile group (C≡N) of PAN. Similarly, all samples possessing characteristics bands attributed to aliphatic CH group vibrations of different modes in the methylene group of PAN were located in the regions 1220–1270 cm−1, 1350–1380 cm−1, 1450–1460 cm−1, and 2870–2931 cm−1 [−1 and 3400–3500 cm−1 were assigned to stretching vibration of H-O-H and bending O-H to denote the presence of physically absorbed water molecules [−1 and 981 cm−1 in AP/PAN and SAP/PAN were due to the molecular vibration of PO43− [−1 [42− in SAP/PAN was not apparent, which could be due to overlapping with the absorption band of PO43− or small amount of SO42−. Hence, all these FTIR results suggested SO42−-doped/undoped Ag3PO4 nanoparticles were immobilized on PAN nanofibers.931 cm−1 . Moreoveolecules . Furtherof PO43− ,34. HoweO43− [−1  correspo42− in Ag3PO4 and PAN in SAP/PAN was confirmed by performing XPS analysis. As shown in survey spectrum  of pristine PAN, AP/PAN, and SAP/PAN were measured to determine their light absorption behavior and the results are plotted in t/Co) with irradiation time, where Co is the initial concentration and Ct is remaining concentration of dyes solution at time t. As presented in figure, pristine PAN could show negligible capability of photodegradation of MB and RhB dye solutions. In contrary, more than 95% of MB was degraded by SAP/PAN within 40 min, while only 88% of MB was degraded within this time period utilizing AP/PAN. Likewise, SAP/PAN could exhibit superior performance over AP/PAN towards the photodegradation of RhB. In this case, SAP/PAN could degrade 95% of RhB within 50 min, but within this time period, AP/PAN could degrade about 87% of RhB. On the basis of these results, SAP/PAN was found to be a more advantageous visible-light-driven photocatalyst over AP/PAN. Photodegradation performances of different samples under visible light irradiation were investigated using MB and RhB dye solutions and results are presented in The changes of TOC during photodegradation of MB and RhB utilizing SAP/PAN under visible light irradiation are displayed in Photodegradation stability of SAP/PAN was examined by performing cycling experiments for MB and RhB degradation under visible light irradiation a,b. For o = 10 mg/L), equation (1) can be considered a pseudo first-order kinetics equation [o and Ct represent the initial concentration and concentration at time (t), respectively. kapp is the apparent rate constant (min−1), which can be obtained by plotting ln (Co/Ct) vs. reaction time. Hence, degradation kinetics of MB and RhB solutions were calculated by applying equation (2) and the results are shown in o/Ct) vs. reaction time suggested the pseudo first-order kinetics of photodegradation. From the results, apparent rate constants of MB degradation utilizing AP/PAN and SAP/PAN were determined to be 0.057 min−1 and 0.075 min−1, respectively. Similarly, the apparent rate constants 0.043 min−1 and 0.064 min−1 were determined for RhB degradation utilizing AP/PAN and SAP/PAN, respectively. All these results indicated that sulfate doping could provide significant capability to Ag3PO4 to enhance its photodegradation performance.Since the initial concentration of MB and RhB was very low (Cequation  as(2)ln3PO4, being a semiconductor material, generates electron–hole pairs under visible light irradiation. The photo-excited electrons travel to conduction band (CB) from valence band (VB) and react with dissolved oxygen molecules to produce ROS, i.e., oxygen peroxide radicals (O2• −), which are strong oxidizing agents and degrade dye molecules effectively. On the other hand, holes at VB directly react with dye molecules [On the basis of above results, an overall mechanism is proposed for photodegradation of organic dyes. Agolecules . In this42− as dopant, which could play an important role to trap and transfer photoinduced electrons to CB, thereby providing improved separation capability of electron–hole pairs to SO42−-Ag3PO4 (42−-Ag3PO4 could receive additional electrons due to higher electronegativity of S than that of P. As a result, the Fermi level of SO42−-Ag3PO4 gets shifted towards CB and possesses n-type conductivity. In this way, doping of SO42− into the Ag3PO4 crystal lattice can improve its separation capability and lower recombination rate of photoinduced electron–hole pairs, which ultimately increases the production of ROS and enhances the photocatalytic performance of SO42−-Ag3PO4 [It is well known that semiconductor photocatalysts having improved separation capability and low recombination rate of photoinduced electron–hole pairs can exhibit enhanced performances. Hence, in this work the enhanced photocatalytic performances of SAP/PAN compared to that of AP/PAN can be explained with the role of SO−-Ag3PO4 . Moreove−-Ag3PO4 ,46,47.42−-Ag3PO4/PAN-electrospun nanofibers were fabricated successfully by combining electrospinning and ion-exchange reaction. Different characterization techniques were used to study the morphology, structure, chemical composition, and optical properties of the samples. Photocatalytic activity of the fabricated samples was investigated by photodegradation of MB and RhB dye solutions under visible light irradiation. In both investigations, SO42−-Ag3PO4/PAN-electrospun nanofibers could show enhanced performance compared to Ag3PO4/PAN-electrospun nanofibers. We believe that the enhanced performances of SO42−-Ag3PO4/PAN-electrospun nanofibers were attributed to the sufficient electron–hole separation capability of SO42−-Ag3PO4 nanoparticles to produce ROS due to doping effect of SO42− ions into the Ag3PO4 crystal lattice. Therefore, thus fabricated SO42−-Ag3PO4/PAN-electrospun nanofibers can find potential application as visible-light-driven photocatalyst with good flexibility and reusability for wastewater treatment.In summary, SO


Addressing AMR has been most problematic in low- and middle-income countries, which lack infrastructure, diagnostic capacity, and robust data management systems, among other factors. The implementation of locally-led efforts in a low-income country to develop sustainability and build capacity for AMR control within the existing infrastructure has not been well documented.We detail current AMR control initiatives at Queen Elizabeth Central Hospital, a tertiary referral government hospital in Malawi with limited resources, and present the activities accomplished to date, lessons learned, and challenges ahead.The key areas of AMR control initiatives that the group focused on included laboratory diagnostics and surveillance, antimicrobial stewardship, infection prevention and control, pharmacy, leadership, education, and funding.The hospital AMR Control Working Group increased awareness, built capacity, and implemented activities around AMR control throughout the hospital, in spite of the resource limitations in this setting. Our results are based on the substantial leadership provided by the working group and committed stakeholders who have taken ownership of this process.Limited resources pose a challenge to the implementation of AMR control activities in low- and middle-income countries. Leadership is central to implementation. Future efforts will need to transition the initiative from an almost fully personal commitment to one with wider engagement to ensure sustainability. Antimicrobial resistance (AMR) has reached alarming levels globally, and is estimated to cause 4.95 million deaths globally, with the highest rates being in sub-Saharan Africa . AddressEnterobacteriaceae have been detected at QECH  setting, Queen Elizabeth Central Hospital (QECH) has played a central role in documenting the emergence of AMR in Malawi. QECH, established in 1964 and the largest tertiary care hospital in Malawi, serves a population of over 7 million people, handles over 400,000 outpatients in its various specialized clinics and admits over 75,000 patients annually. Health services are offered free of charge to all patients, and the government with support from various donors funds all services through the Ministry of Health and the Ministry of Local Government. The QECH hospital laboratory was set up in 1954, providing microscopy services initially with eventual scale-up to full culture and susceptibility testing. In the 1990s, the Malawi-Liverpool Wellcome Programme (MLW), a research institution based at QECH, started offering partial microbiology services support in form of high-quality and robust blood and cerebrospinal fluid (CSF) surveillance to the medical and paediatric wards at QECH. Through this surveillance programme, MLW documented a concerning increase in AMR at QECH from 1998-2016 , with an at QECH , possiblAt about the same time, doctors practicing in other departments which are not covered by MLW microbiology services noticed an increasing incidence of infections that were resistant to commonly available antibiotics in the hospital. In response to this, in January 2019, a one-day workshop was held at QECH where a commitment was made to combat AMR at QECH. The workshop also resolved to create an AMR Control Working Group, among other interventions, with the aim of minimizing the emergence of AMR, developing a hospital laboratory microbiological surveillance platform beyond the blood and CSF culture surveillance provided by MLW, and increasing awareness and visibility of AMR initiatives and management.AMR control, antimicrobial stewardship (AMS), and infection prevention and control (IPC) initiatives have been described extensively in high-income country settings . HoweverAs a tertiary referral centre for the southern region of the country, QECH requires laboratory diagnostics to serve its patient population, and good quality, robust, and representative microbiology data are needed to develop locally relevant AMS and IPC interventions. The collapse of funding for health care delivery in Malawi in the 1990s  resultedMLW surveillance does not include other sections of the hospital  nor body fluids other than blood and CSF. To address this gap, the QECH microbiology laboratory has been developing the capacity to process wound swabs, pus, urine, and other body fluid cultures from all patients that come to QECH. However, comprehensive isolate and susceptibility testing has usually remained a challenge due to a lack of equipment, susceptibility tests, and reagents.In 2018, Malawi received a grant from the Fleming Fund which was aimed at supporting microbiology services in low- and middle-income countries (LMICs). QECH, together with all public tertiary hospitals in Malawi, was included as one of the beneficiaries of this support. This support has included the rehabilitation of the hospital microbiology laboratory section, establishing provision of equipment performing blood culture tests, training in accurate isolate identification, susceptibility testing according to currently available antibiotics, and also surveillance for AMR trends. The Fleming Fund also provided start-up reagents for 3 months, and after that, the hospital took over those costs. The support did not include the hiring of new staff or extra money for the existing microbiology laboratory staff.As QECH re-establishes a robust and quality-assured microbiology service, there are a number of challenges that need to be addressed, including staff shortages, patient specimens disappearing between patient collection to delivery to the laboratory, regular stockouts of reagents, and quality control of microbiological testing. To address the latter issue, the laboratory has been participating in different external quality assessment schemes, such as the National Health Laboratory Service (NHLS), CDC, and External Quality Assessment for Africa (EQuAFRICA), and has been earmarked for Southern Africa Development Community Accreditation Services (SADCAS) and is expected to have its initial assessment towards the end of 2023.Targeted AMR efforts have become even more urgent in the post-COVID-19 era, which has been associated with increased antibiotic use . AMS proOveruse of broad-spectrum antibiotics has been documented in other LMIC hospitals , and theIn addition, AMS rounds on patient wards provide an opportunity for clinicians to interact with the AMS team, ask questions on optimal antimicrobial usage and address patient management issues. AMS rounds in paediatric hospital care were found to encourage participants to critically evaluate antimicrobial choices and to engage in discussion with the AMS team, and also for participants to gain confidence in prescribing antimicrobials . At QECHParticularly for vulnerable populations such as neonates, hospital-acquired infections with AMR pathogens contribute to an extended hospital stay, increasing hospital costs, and are a leading cause of morbidity and mortality . HoweverEngagement of the hospital pharmacy including an understanding of antibiotic availability and consumption is essential in developing robust antimicrobial prescribing practices in the context of high AMR rates in hospital settings. Some  hospitals have demonstrated that, in settings where there are no infectious diseases physicians or microbiologists, pharmacist-led AMS programmes can be effective in reducing the consumption of antimicrobials and therefore retard the development of AMR .At QECH, the hospital pharmacy is supported by the Ministry of Health and deals with roughly 10,000 prescriptions per month. More than half of these prescriptions contain an antibiotic. Medicines are provided free of charge to patients and costs are borne by the Ministry of Health.Medicines are managed by qualified pharmacists and pharmacy technicians, who provide patient education and counselling on proper use of antimicrobials. In addition to coordinating the QECH Drug and Therapeutic Committee, a hospital committee involved in the selection, quantification and procurement of medicines and antimicrobials, the pharmacy has been promoting and encouraging the use of prescription pads for all antimicrobial prescriptions, and the exchange of empty vials and use of patient files when collecting antimicrobials from the pharmacy.Challenges include inadequate staff, the limited spectrum of antimicrobials on the central hospital essential medicines list provided by the Malawi Ministry of Health, and frequent stockouts of medicines on the essential medicines list. This makes it challenging to implement the World Health Organisation AWaRe principles which encourage the widening of the spectrum of antibiotics available for use, in order to reduce the overuse of popular antibiotics and impact on AMR .Currently, medical trainees receive about 60 hours of education in pharmacy as medical students, but only a handful of lectures on AMS. Clinical officers, who are part of a 3-year education programme, receive even less. Therefore, clinician antimicrobial prescribing practices tend to be based on hospital guidelines and observed practice, whether correct or not. Focused AMS training may need to be considered for specific units such as pharmacy, and wards such as Accident & Emergency, where the majority of initial antibiotic regimens are prescribed. It is important to note that in the training for the older graduates, whom are now supervisors and mentors of the new medical graduates, AMS was not covered in their curriculum. This means that senior staff need to be educated and trained first on these principles before they can influence the prescribing practices of the younger generation.Leadership and good governance are needed for sustainability, as this ensures retention of skilled staff, maintenance of equipment, and adoption of a quality mindset . AMR iniIn resource-limited settings such as in Malawi, investment in human resources, training, surveillance, monitoring, quality control, and leadership are acutely needed, in order to build capacity, and incentivize and empower local personnel. While much of the AMR control activities have been a local initiative, external funding from the Fleming Fund and Pfizer has supported some AMR activities, including the time of AMR champions and hosting of hospital-wide AMR control awareness activities. However, internal funding is scarce and hospital management and leadership will need to prioritise funds to the QECH AMR Control Working Group to ensure sustainability.In summary, the key areas of AMR control initiatives that the group focused on included laboratory diagnostics and surveillance, AMS, IPC, pharmacy, leadership, education, and funding. Since its inception, the QECH AMR Control Working Group has made considerable headway in increasing awareness, building capacity, and implementing hospital activities around AMR control, in spite of the resource limitations in this setting. Our status is similar to AMS programmes in public sector hospitals in KwaZulu Natal, South Africa, where only 75% of hospitals have an AMS committee, 47% have a formal written statement of support from the leadership, and 7% receive budgeted financial support . What ha


The integration of molecular robots and synthetic biology allows for the creation ofsophisticated behaviors at the molecular level. Similar to the synergy betweenbioelectronics and soft robotics, synthetic biology provides control circuitry formolecular robots. By encoding perception-action modules within synthetic circuits,molecular machines can advance beyond repeating tasks to the incorporation of complexbehaviors. In particular, cell-free synthetic biology provides biomolecular circuitryindependent of living cells. This research update reviews the current progress in usingsynthetic biology as perception-action control modules in robots from molecular robots tomacroscale robots. Additionally, it highlights recent developments in molecular roboticsand cell-free synthetic biology and suggests their combined use as a necessity for futuremolecular robot development. Bioelectronics translates biological signals into electrical outputs, creatingbio-electronic interfaces and enabling the successful development of biomedical devices suchas pacemakers, deep-brain stimulators, and electronic skins.With advances in nanotechnology, a variety of nanomaterials, such as nanotubesAlternatively, pairing nanoelectronics with soft materials can improve the stretchabilityand comfort of bioelectronic sensors.Furthermore, incorporating soft materials grants self-healing abilities to bioelectronicsensors.While soft robots are used for monitoring electrical signals in human bodies, molecularrobots can monitor biochemical, molecular signals inside human bodies. Robotics at nanoscaleand microscale is a promising technology for applications such as active therapeuticdelivery and minimally invasive surgery.The ultimate goal of building autonomous robots is to combine sensing, computation, andaction.This research update will explore how synthetic biology can be integrated into nanomachinesto build molecular robots. We will first briefly review the current progress of molecularmachines and robots. Next, we will highlight the cell-free synthetic biology toolset andshowcase how cell-free synthetic biology, in particular, can play an important role infuture molecular robot developments. Furthermore, we will focus on the current progress inusing synthetic biology tools as perception-action modules in robots at the macroscale andmicroscale.Molecular machinery can be categorized into two major categories based on theircomposition: non-biological and biological molecular robots. Catenanes and rotaxanes, twoprimary molecular machines, have dominated the field of non-biological machinery since the1990s.Imitating macroscopic mechanical machines at the molecular level can spark the developmentof molecular motors.Seeking to emulate how ATP, a single chemical fuel, can power molecular machines inside ofcells, Wilson and co-workers introduced a catenane-based molecular motor that continuouslymoves as long as a chemical fuel, 9-fluorenylmethoxycarbonyl chloride, is present.While catenanes allow rotatory motions, the ring on rotaxanes can shuttle along the axlemolecule. This property is used to create molecular switches to regulate catalysis events,switching on and off a catalyst by varying added chemical fuels.Molecular robots are not limited to catenane- and rotaxane-based structures. Kassem andco-workers created a molecular assembler that moves substrates between various activatingsites to synthesize different productsBiological molecular robots exploit the characteristics of biological molecules asactuators and perception-action loops. For example, Valero and co-workers employedtranscription machines to build a DNA nanoengine.Because of its unique sequence-dictated structural and functional features, DNA has beenwidely adopted to construct molecular robots. Their selective and sensitive responses tosmall molecules, proteins, and nucleic acids allow DNA structures to be responsive tovarious input molecules.Furthermore, DNA is highly stable and programmable, allowing precise and predictablenanostructure designs via base-pairing rules. By designing a sequence of DNA buildingblocks, these DNA fragments can self-assemble into almost any arbitrary structure on thenanoscale level. This process is called DNA origami. Through dynamic interactions betweenbuilding blocks, these DNA structures can change shapes in response to input stimuli viasequence-specific binding.In addition to forming arbitrary structures, the base-pairing rule can be used to implementperception-action behaviors in autonomous molecular robots. Qian and co-workers developed anautonomous DNA robot capable of performing cargo-sorting tasks.2 DNA origami plate. The arm was connected to the plate via a flexiblesingle-stranded DNA, allowing the arm to rotate freely relative to the platform. Since DNAis a charged molecule, DNA moved in response to applied electric fields. The researchersutilized this property to control the DNA robot arm with an externally applied electricfield. Protruding single-stranded DNA monomers were placed on the platform to latch down themolecular robot arm temporarily, achieving precise control of the DNA arm. As a result, acomputer-controlled electric field switched the molecular robot arm between predefinedpositions within milliseconds. Next, the team used the developed molecular robot arm totransport molecules and nanoparticles over tens of nanometers, which can be useful forcontrolling photonic and plasmonic processes. The team proposed that adopting nanostructureelectrodes may enable control over individual robot arms, which have the potential to becomemolecular mechanical memory.Even though sequence-specific actuation can be precisely designed, DNA hybridization is aslow process. To increase translational speed, recently, Bazrafshan and co-workers developeda DNA motor that can run at up to 100 nm/min, which is ten times faster than previousmotors.Most of the above-mentioned DNA molecular robots utilize base-pairing properties to createactuation and perception-action behaviors, while encoded genetic information remainsunderexplored. Repurposing and reprogramming molecular modules, synthetic biology hasutilized the encoded genetic information to construct perception-action behaviors on livingorganisms, generating designed outputs in response to specific inputs. Perception-actionbehaviors are programmed in synthetic genetic circuits. Transcription and translationprocesses drive synthetic circuits and generate output, such as proteins, according toencoded algorithms.Inspired by electrical engineering, synthetic biology has developed a variety of geneticcircuits reminiscent of electronic circuits in biological systems, such as the toggleswitch.in vitro protein synthesis.Cell-free systems contain essential enzymes for transcription and translation, allowing thesynthetic genetic circuit to be transcribed and translated without cells. Furthermore, theflexibility of cell-free platforms enables the customization and optimization of reactions,such as adding proteins or small molecules to improve the synthetic genetic circuitperformance.The use of whole-cells as the chassis requires laborious genetic engineering and suffersfrom unpredictable interplays between designed and natural systems due to the complexenvironment within living organisms.Logic-operating synthetic genetic circuits are also available in cell-free platforms. Eventhough some synthetic genetic circuits may be limited to specific cell types, recentdevelopments of synthetic genetic circuits improve transferability. Chen and co-workersdeveloped a set of logic gates including gates with multiple inputs that function incell-free systems, yeast, and human cells.Cell-free platforms provide a new paradigm for building autonomous molecular robots withactuator and perception-action behaviors. For example, Franco and co-workers utilized acell-free oscillator to operate a DNA-based nanomechanical device termed the DNAtweezerTo minimize the downstream load effect on the oscillator circuit, the researchers added aninsulator to the genetic circuit reminiscent of an amplifier stage in electric circuits. Theinsulator genelets, Ins, operated in parallel with an oscillator switch SW12, which allowedfor Ins activation by A2 and inhibition by rI2. The insulator produced a new RNA species,InsOut, which opened the tweezers previously closed by the DNA strand, TwCls. Next, theTwCls·InsOut complex was degraded, creating free TwCIs. The insulator stage enabled theoscillator to drive the opening and closing of more tweezers while isolating tweezeroperation from oscillators. Recently, Green and co-workers used a similar cell-freeoscillator module to control the DNA molecular machine self-assemblyInstead of using cell-free circuits to drive perception-action behaviors, Hamada andco-workers developed an onboard metabolism system on DNA robots with a cell-freeplatform.Despite all the exciting developments, synthetic biology is confined to lab settings due tothe need to maintain reactions at specific conditions. Cell-free systems offer a way out.Cell-free platforms can be freeze-dried and stored at room temperature. At the time of need,simply adding water to the freeze-dried cell-free solution can activate it. This featureoffers solutions to deploying synthetic genetic tools in the field for applications,including diagnostics and biomanufacturing.in vitro diagnosticsIn order to develop molecular robots that can be more broadly deployed outside of thelaboratory, an ability to manufacture these robots at the point-of-use would be ideal.Fortunately, portability is one of the key benefits of using a cell-free synthetic biologyapproach. For example, Pardee and co-workers successfully moved synthetic biology outside ofthe lab by embedding the freeze-dried cell-free solution and genetic constructs ontopaper.lacI transcription and used as anoptical reporter molecule. Isopropyl-β-D-thiogalactoside (IPTG) repressed protein LacR(transcripted and translated from lacI), which induces the production ofprotein λcI. Protein λcI repressed GFP and LacR production. When UV light was introduced tothe toggle switch, it caused DNA damage and led to enhanced λcI protein degradation, andtherefore, rescued GFP production. The researchers incorporated engineered bacteria carryingthis genetic toggle switch with microrobots and deployed them to detect UV light in aworkspace [Synthetic biology has been adopted to provide perception-action behaviors in robots atmacroscale and microscale. Apart from the cardiomyocytes in the robotic ray discussedearlier,orkspace . When miin silico model of a microbiome consisting of engineered cells carryingsynthetic genetic circuits, together with a robotic host housing an onboard microfluidicchemostat and microscope. The onboard microfluidic chemostat was used to mimic a microbiomeenvironment within an organism. Heyde and Ruder used this system to simulate how variousgenetically engineered bacteria could affect the robot behavior. With the increasedcomplexity of genetic circuits, a variety of behaviors emerged, such as stalk-pause-strikepredation. Their model provides a tool to investigate host–microbiome interactions andoffers a novel paradigm to create perception-action loops in autonomous robots. Theseexamples of robots at the macroscale and microscale with synthetic biology-basedperception-action modules reveal how synthetic biological circuits could be deployed withrobotic counterparts at the molecular level.Apart from using genetic toggle switches in microrobots, macroscale robots can adoptsynthetic biology tools as their perception-action loop modules. Heyde and Ruder proposedusing engineered bacteria equipped with genetic toggle switches to maneuver a biomimetic,macroscale robotFrom macroscale to molecular robotics, robots at various scales have taken advantage ofsynthetic biology tools to achieve complex perception-action behaviors. Syntheticbiology-based perception-action modules are of particular interest to molecular robots sincethey can be readily integrated at the molecular scale. Embarking from catenanes androtaxanes, molecular machines have gradually evolved into molecular robots capable of morecomplex tasks.Compared to their macroscale counterparts, there is a considerable gap between molecularmachines and molecular robots. Similar to the synergy between bioelectronics and softrobotics, synthetic biology offers perception-action modules, which we believe can fill thegap between molecular machines and molecular robots. We have highlighted a myriad ofsynthetic genetic circuits reminiscent of electronic digital circuits available to engineermolecular robots. The complexity of molecular robot behaviors can improve with advances inbiocomputing synthetic genetic circuits. At present, synthetic biologists have gene-basedversions of CPU. In the future, synthetic circuits can confer intelligence and become thecontrol system for autonomous molecular robots.Cell-free systems power synthetic genetic circuits without reliance on living cells,extending synthetic biology into the real world. If molecular robots adopt syntheticbiology-based tools as their perception-action modules, their movements and functions willno longer be confined to specific reaction criteria. Cell-free systems have freed syntheticbiology from lab settings. Likewise, cell-free platforms can help molecular robots stepoutside the laboratory in the future.Biological components have changed the actuation system of robots at small scales.Furthermore, DNA based actuators and sensors can be integrated with molecular robotsconsisting of carbon nanotubes and magnetic nanoparticles. Systems integrating biomoleculesand carbon nanotubes have been used as biosensors to build complex nanostructures fornanobioelectronics.Ultimately, we envision that the next generation of molecular robots with advanced autonomywill be biohybrid robots containing synthetic biology-based perception-action modulesencoded within DNA molecules. For example, a magnetic particle based molecular robot couldbe anchored to DNA molecules encoding synthetic biology-based perception-action modules. The magData sharing is not applicable to this article as no new data were created or analyzed inthis study.


Self-healing on the engineering applications is smart, decisive research for prolonging the life span of the materials and the innovations have been mounting still smarter. Connecting to advancements in self-healing carriers, in altering the chemical structure by optimizing the brittleness for self-healing performance and introducing the bio-degradability, for the first time TPS was blended to PVDF for the synthesis of nanofibers, as carriers of a vinyl ester (VE) resin (medication), by the coaxial electrospinning technique. TPS was mechanically mixed with PVDF base polymer and optimized the TPS content (10 wt%) based on mechanical performance. The novel nanofibers were characterized via field emission scanning electron microscopy (FESEM), Fourier-transform infrared spectroscopy, X-ray diffraction, thermal, moisture analysis, and a mechanical line with FESEM and energy-dispersive X-ray analysis studied the self-healing. The TPS/PVDF fibers having hydrogen bonding and increased the crystallinity (40.57 → 44.12%) and the diameter (115 → 184 nm) along with the surface roughness of the fibers with increasing the TPS content. Microanalysis presented the flow-out of the VE resin at the scratched parts in the pierced fibers; interestingly, after some time, the etched part was cured automatically by the curing of the spread resin. Mechanical stretching of the nanofibers in the tensile tests up in the plastic region showed a decrement in the elasticity (TPS/PVDF fibers) and an increment in the brittle nature (cured VE resin) with the increase in Young’s modulus at each stretching, clearly elucidating the healing performance. The usage of self-healing nanofibers can extend the usability and life span of materials/composites. Nanofibers have excellent properties, such as a large surface area to volume ratio, a high degree of flexibility, and good mechanical properties2. Electrospinning has become a well-known technique to investigators for the preparation of nanofibers owing to its easy operation under optimized conditions compared to all the methods3. In this technique, an electrostatic force is applied to eject a polymer solution jet from the tip of a droplet to form nanofibers. In the early years of the twenty-first century, technological developments led researchers to modify the electrospinning method to prepare tube-like structure (core–shell) nanofibers with distinctive features by installing a particular type of nozzle, called a coaxial nozzle6. In the self-healing field, this innovation tremendously promoted the use of self-healing carriers as regenerative medicine in tissue engineering7, releasing healing resin in mechanical engineering8, etc.In the present decade, researchers have been mostly interested in using nanofibers as smart carriers for self-healing applications, e.g., curing microcracks, corrosion protection coatings for metals, and wound healing11. In fact, microsphere reinforcement in composites by the vacuum-assisted resin transfer molding (VARTM) process is highly complex. Moreover, the hardener microspheres should be distributed on the resin microspheres, particularly at the cracked parts, which is highly impossible in composites for achieving an effective self-healing process12. Recently Maryam et al., studied self-healing behavior by developing silane coupled cellulose-functionalized halloysite nanotube/epoxy nanocomposites13.The utilization of nanofibers in self-healing applications is particularly attractive compared to the existing self-healing carriers, e.g., microspheres and vascular networks, owing to the limitations of uniform distribution and uneven surfaces of the latter in real products. Importantly, in the above two cases, more carriers are required for both the healing resins along with a curing agent, which increases the density of the corresponding composites and makes the healing mechanism complex15. PVDF is a well-known polymer mostly used to produce nanofibers owing to its excellent mechanical, thermal, and electrical properties16. It has a semi-crystalline structure and is non-biodegradable and hydrophobic in nature. Numerous researchers have studied the development of the electrical behavior of PVDF nanofibers of chemical modifications and reinforcement of various additives18; in addition, a few of them have focused on their mechanical properties and hybridization. For example,  self-healing internal electric field is proposed and successfully endowed to a designed helical structural composite microfiber polyvinylidene fluoride/g-C3N4) based on the bio inspired simple harmonic vibration19. Aatif et al. confirmed an improvement in the mechanical properties of the β-phase fraction of PVDF nanofibers when bentonite nano clay particles were introduced into the PVDF dope solution for electrospinning20. Pu et al. observed an increment in Young’s moduli, tensile strength, and thermal stabilities of PVDF nanofibers when combined with ZnO nanowires21. Seyyed et al. proved that the mechanical properties of PVDF nanofibers varied with the increase in nano silica content and stated that with higher SiO2 content, PVDF nanofibers with better tensile strength, more toughness, and smaller elongation to break were obtained22.Several thermoplastic polymers have been used to synthesize nanofibers by the electro-spinning method such as polyacrylamide (PAM), polyvinyl alcohol (PVA), polyvinyledene fluoride (PVDF), etc.23. Wook et al. used PVDF as shell material in self-healing nanofibers; the authors encapsulated two components (a resin monomer and a hardener) separately in the cores of PVDF nano and microfibers formed by solution blowing using compressed air. The self-healing properties of such nano and microfiber mats were explored using blister tests along with periodic bending fatigue tests24. PVA/PVDF core–shell nanofibers were synthesized by Yuhua et al., and showed that MBT-loaded coaxial nanofibers decreased the corrosion activity of coatings25. Choolaei et al. confirmed the improvement in the crystallinity of PVDF-HPF nanocomposites by adding GO nanoparticles through a heterogeneous nucleation mechanism26.In fact, PVDF nanofiber-reinforced composites are suitable to be used as self-healing carriers. Mahanty et al. fabricated PVDF/MWCNT composite electrospun nanofibers followed by piezoelectric pressure sensor directly as self-powered electronic skin (e-skin)27. Optimizing brittleness for achieving adequate healing performance, especially in connection to micro-cracks in fiber-reinforced self-healing composites is a critical task until no researchers focused. Hence, the current research attempts to practically realize the above-mentioned hypothesis advancements and problems in PVDF, for the first time by chemical blending low-cost starch in the form of a thermoplastic polymer for optimizing the brittle nature towards effective self-healing performance as well as introducing biodegradability. A coaxial electrospinning instrument  was used to produce core–shell nanofibers with uni-diameters. The mechanical properties were studied for various weight percentages of thermoplastic cornstarch (TPS) . As expected, the crystallinity and the modulus of the fibers increased with the increase in the TPS weight percentage in PVDF, which, in turn, increased their diameter, as confirmed by X-ray diffraction (XRD), tensile tests, and field emission scanning electron microscopy (FESEM). 10 wt% of TPS blended PVDF polymer was chosen to use for further study, even though the higher percentage of TPS (15 and 20 wt%) showing higher properties such as mechanical strength, surface roughness, degree of crystallinity, water absorption etc., due to mainly on the structure formation of the uniform diameter of nanofiber without any obstructions. The self-healing roles of the fabricated nanofibers were investigated by periodic stretching by tensile loading up in their elastic zone. The variation in the modulus and morphology significantly affected the healing performance of the TPS/PVDF core–shell nanofibers.Indeed the flexible nature of PVDF Nanofibers is not well support the significant self-healing performance due to damage issues under loadingsPVDF and glycerol (ACS reagent ≥ 99.5%) were purchased from Sigma-Aldrich, USA, and dimethylformamide (DMF) (99.0%) was purchased from Samchun Chemicals, South Korea. Corn starch (72% amylopectin and 28% amylose) was received from Samyang Corporation Ltd., South Korea. Vinyl ester (VE) (viscosity = 150 cps and specific gravity = 1.03), methyl ethyl ketone peroxide (MEKP) , and cobalt naphthalate (accelerator) were procured from CCP Composites, Korea.The fabrication process of TPS/PVDF core–shell nanofibers as shown in Fig. Step 1: Synthesis of TPS28.TPS was prepared by a simple process in which glycerol and deionized (DI) water were taken in a 3:1 ratio and stirred at a temperature of 80 °C for more than 10 min to form a homogeneous solution. Subsequently, the obtained solution and starch were mixed together in a ratio of 1:2 for producing the required TPSStep 2: Preparation of TPS/PVDF blend solutionA 1:3 (w/w) acetone/DMF mixture was used as the solvent, to which 18 wt% PVDF was added. The mixture was stirred at 80 °C for 8 h, and the prepared TPS (10 wt%) was then added to the PVDF solution. The stirring was continued for 6 h at 80 °C until a homogeneous TPS/PVDF solution was obtained.Step 3: Preparation of core solutions (VE–CN and MEKP)The effective curing process of vinyl ester (VE) requires both accelerators (CN) and catalyst (MEKP). Hence, three types of core have to prepare such as VE, CN, and MEKP. However, to minimize the density of the nanofibers only two types of core materials (VE–CN and MEKP) used based on chemical nature. VE–CN solution was prepared by adding the required amount of CN to the VE (100:1) and mixing thoroughly on an overhead stirrer for 10 min at room temperature. MEKP was used directly without further modification.Step 4: Synthesizing green PVDF nanofibersPVDF and TPS/PVDF nanofibers were synthesized using an electrospinning machine with an electrospinning needle. To synthesize the core–shell nanofibers by coaxial electrospinning, a coaxial nozzle with an inner diameter of 0.8 mm and an outer diameter of 1.6 mm was used, as shown in Fig. −1. XRD patterns were obtained using an X-ray diffractometer . The samples were mounted on the sample holder, and the patterns were recorded by running the instrument at a speed of 2°/min and a 2θ range of 10°–40°. The crystallite sizes of the nanofibers were calculated by Scherrer’s equation  at a cross-head speed of 1 mm/min. Attenuated total reflection (ATR)–Fourier-transform infrared (FTIR) spectra of the fibers were measured by an FTIR spectrometer . The FTIR spectra were collected in a range of 4000–400 cm0) and after (m1) the soaking were noted, and the water absorption (Q) was calculated using the formula, 29. Five samples were tested for each type of nanofiber, and all the samples were pressed with tissue paper and dried before weighing.The thermal stability was characterized via thermogravimetric analysis (TGA)  within a temperature range of 30–700 °C and at a rate of 20 °C/min under a nitrogen atmosphere. To study the surface morphology, the specimens were examined via FESEM  at an accelerated voltage of 5–30 kV with an energy-dispersive X-ray (EDX) analyzer. All the samples were sputter-coated with gold using an automated fine coater (JEOL JFC-1600). A water absorption test was conducted on the nanofibers by soaking them in water for 24 h. The weights of the specimen before , beta (β), gamma (γ), and the monoclinic delta (δ) phase in terms of its crystallization conditions. However, in PVDF nanofibers, the FTIR spectral doesn’t show any vibrational bands at 976, 796, 764 and 614 cm−1 and also at 1232, 833, 812 and 776 cm−1 which indicates the absence of α phase and γ phase in which PVDF neat possessed34. Thus, the peaks 1401, 1274 and 840 cm−1 exclusively represent the characteristics of the β phase.The interfacial interaction and confirmation of hydrogen bonding were characterized using FTIR. Figure −1 (CH and OH stretching bands), 1640 cm−1 (absorbed water), 1152, 1018 and 1103 cm−1 (CC and CO stretching) 916 and 988 cm−1 (CC vibration)  and 1008 cm−1 (CO–H bending vibration)35 were the combinations of starch and glycerol.Observing the FTIR peaks of TPS, the characteristic bands around at 3425, 3270 and 2923 cm−1 and the disappearance of weak peak at 2901 cm−1 in Pn and forming a weak broadband of 2882 cm−1 for 5TPn, 2872 cm−1 for 10TPn, 2876 cm−1 for 15TPn, and 2879 cm−1 for 20TPn. Since both polymers exhibiting thermoplastic behavior, the reactive sites of TPS in oxygen molecules readily react with the reactive sites of PVDF with hydrogen forming hydrogen bonding. Consequently, as the % of TPS increases by 5% in every sample, the hydrogen bonding increases indirect proportional since starch is a stereo-regular polymer with chirality and a high density of hydrogen bonding36.After the preparation of PVDF nanofibers, the gradual addition of TPS in 5% interval figures the appearance of new peaks as shown in two insets, Fig. …F–C due to the stronger polarity of the hydroxyl groups as observed in O–H stretching vibration in the range of 3500–3150 cm−137. In addition, as investigated by Mi et al., the dipoles of β crystals relating to the peaks 1401, 1274 and 840 cm−1 are in the orthogonal direction and corresponding relative intensity can be used to determine the lattice orientation38. Meanwhile the interaction between C–H…F–C is a dipolar dispersion force, wherein PVDF, a non-conjugated linear fluorinated hydrocarbons and TPS also contain carbon and hydrogen resulting in transient dipole moment lead a separate transient dipole moment in neighboring molecule, initiating a fleeting attraction between the C–H molecules39. The remaining characteristic bands were mostly contributed by PVDF which as follows: (1) 3400–3427 cm−1: stretching vibration mode of the hydrogen-bonded O H groups of starch, (2) 1625–1629 cm−1: double bond interaction of C to C; (3) 1185–1190 cm−1 the retain stretching vibration of C–F; and the (4) 883–884 cm−1: confirmed the C=C bonding in bending movement.Figure 40.XRD is an analytical technique used to identify the crystallinity of a material; it was conducted on the TPS/PVDF nanofibers to study the effect of TPS in the PVDF fibers. Figure Tensile tests were performed on the TPS/PVDF nanofibers to determine the change in the properties after the addition of TPS in PVDF. Table The tensile moduli of Pn, 5TPn, 10TPn, 15TPn, and 20TPn are 0.036, 0.054, 0.070, 0.078, and 0.02 GPa, respectively, as tabulated in Table The tensile strength of the TPS/PVDF nanofibers presents the same trend as the modulus. The strength of the TPS/PVDF nanofibers increases as the percentage of TPS increases by up to 15%, and subsequently, it reduces at 20% TPS. Compared to Pn, the tensile strength of 5, 10, and 15TPn is increased by 16, 29, and 29% respectively. All the fiber mats were tested after being conditioned in a laboratory environment (23 °C and 35% relative humidity) for 24 h under identical conditions. However, as the TPS content is further increased, both the tensile stress and modulus are decreased. The tensile strength and modulus of 20TPn are much lower compared to those of Pn. As the weight percentage of TPS in the nanofibers is further increased (20%), it agglomerates, which subsequently decreases the strength and modulus of the nanofibers. Moreover, the agglomeration of TPS increases the beads in the nanofibers, and thus, decreases the strength of the fibers. However, these agglomeration problems are negligible at low weight percentages.Samples 10TPn and VM–10TPn underwent tensile tests, and the stress–strain curves are as shown in Fig. TGA is a technique that measures the thermal stability of a given specimen and is conducted on TPS/PVDF nanofibers. Figure 41. The clearest demonstration of the quantity of the core materials (VE–CN and MEKP) in V–10TPn and M–10TPn has depicted via a 3D column graph in Fig. TGA explains the thermal degradation of the nanofibers, based on which the amount of the core material in the core–shell nanofibers can also be assessed. V–10TPn and M–10TPn were tested along with three control samples, 10TPn, and VE resin combined with CN and MEKP. Figure Water absorption tests were conducted on the TPS/PVDF nanofibers to evaluate the effect of TPS on water absorption, and the results are tabulated in Table 42.A scratch test was performed on a VM–10TPn mat to understand the healing phenomena of the above self-healing nanofibers. Figure 43.Figure Tensile tests (stretching) are performed on 10TPn and VM–10TPn periodically in time intervals of 24 h  and with a 25% strain range; the corresponding results are shown in Fig. Figure 0) with the number of stretching for 10TPn and VM–10TPn, as shown in Fig. 0) is calculated by considering the modulus of the first stretching as numerator (E) and the modulus of each case as the denominator (E0). The modulus variations of 10TPn and VM–10TPn are reduced by 85% and 29%, respectively. Both the plots apparently significantly vary owing to the nature of the fabricated nanofiber polymer and the spill out of the healing polymer. As explained in the Introduction section, PVDF is a thermoplastic polymer that is elastic in nature  and crystallinity (40.5 → 44.1%) of the PVDF nanofibers with TPS. Spectral analysis proved the formation of the green PVDF compound by chemical interaction. The TGA results of V–10TPn and M–10TPn confirmed the presence and also the quantity of VE–CN (22%) and MEKP (26%) in the core–shell nanofibers. Periodic tensile loadings within the elastic zone on the nanofibers and core–shell nanofibers showed marginal differences in the modulus. They evidentially confirmed the self-healing behavior by observing the recovery of the modulus in each stretching of the core–shell nanofibers. Moreover, microanalysis further confirmed clearly the flow of the healing resin (VE resin) at the scratched portion in the pierced fibers, and curing process was conducted automatically by interacting with the curing agents after some time. Overall, this self-healing finding may have the capability to apply the real-time structural implementation in aerospace, automobile, electronic, bio-medicinal, etc., especially for recovery of micro damages in natural/synthetic fiber-reinforced composites, the authors’ continuous future study. Moreover, these findings strongly support the research on self-healing for its further advancement and create a unique path in the direction of biodegradability, which is a major global issue in the present engineering sectors.


Crystal structure prediction has been one of the fundamental and challenging problems in materials science. It is computationally exhaustive to identify molecular conformations and arrangements in organic molecular crystals due to complexity in intra- and inter-molecular interactions. From a geometrical viewpoint, specific types of organic crystal structures can be characterized by ellipsoid packing. In particular, we focus on aromatic systems which are important for organic semiconductor materials. In this study, we aim to estimate the ellipsoidal molecular shapes of such crystals and predict them from single molecular descriptors. First, we identify the molecular crystals with molecular centroid arrangements that correspond to affine transformations of four basic cubic lattices, through topological analysis of the dataset of crystalline polycyclic aromatic molecules. The novelty of our method is that the topological data analysis is applied to arrangements of molecular centroids intead of those of atoms. For each of the identified crystals, we estimate the intracrystalline molecular shape based on the ellipsoid packing assumption. Then, we show that the ellipsoidal shape can be predicted from single molecular descriptors using a machine learning method. The results suggest that topological characterization of molecular arrangements is useful for structure prediction of organic semiconductor materials. Although ab initio calculations are powerful, versatile, and efficient, they are still computationally expensive for several important classes of problems [Finding novel materials with desired properties often requires exhaustive search. In computational materials science, problems . An alteproblems , 3. In pproblems –12.One of the challenging problems in materials science is crystal structure prediction (CSP). The goal of CSP is to accurately predict plausible crystal structures from atomistic and/or molecular information. The properties of molecular crystalline materials, such as energies and electronic characteristics, are highly sensitive to the arrangement of molecules due to complex intra- and inter-molecular interactions . TherefoFrom a geometrical viewpoint, some organic crystal structures are characterized by molecular packing , 19. TheMany organic semiconductor materials are involved in aromatic systems. Motivated by this fact, we focus on the dataset of polycyclic aromatic molecules which are used to assess the effectiveness of our method. We first employ topological data analysis to identify the organic molecular crystals where the arrangement of molecular centroids coincides with affine transformations of basic cubic lattices. Then, we estimate the shapes of ellipsoids packed in the identified organic crystals under the ellipsoid packing assumption. Moreover, we show that the ellipsoidal shapes can be predicted from single molecular descriptors using a machine learning method for the dataset of polycyclic aromatic molecules. The ellipsoid radii can correspond to the approximate intracrystalline molecular shape, and therefore, our method is useful for predicting partial information of crystal structures.An overview of our method for estimating ellipsoidal molecular shapes is shown in Crystal structures have been interpreted in terms of packing of atoms and molecules in crystallography. Some inorganic crystal structures have been explained as close packing of spheres which approximate atomic bodies with high symmetry. The two models that achieve dense packing of identical spheres are known to be cubic closest packing (ccp) and hexagonal closest packing (hcp) , 22. Thehematics . As for hematics . It was hematics .In this study, we deal with organic crystal structures from the viewpoint of ellipsoid packing following the above report, although an unusual case of densest crystal ellipsoid packing was later found in the glassy phases  and alsoTopological data analysis is an emerging mathematical technology to analyze topological properties of structural data using applied algebraic topology and computational geometry –31. It er > 0, centered at the four data points. As r is increased from 0, the initially separated disks start to overlap with each other at a certain value of r. The change in the r value means a change in the resolution. If the union of disks makes a hole at r = b and the hole vanishes at r = d as in b, d) in the persistence diagram as shown in I discrete points in a 3D space is defined as follows:J is the number of holes and q is the dimensionality of holes, e.g. q = 0 for connected components, q = 1 for rings, and q = 2 for cavities. We use the multi-set {Dq(P) | q = 0, 1, 2} to characterize a topological feature of the point cloud P.The persistence diagram for a point cloud α. Denoting the point clouds for type-P, type-C, type-I, and type-F lattices by PP, PC, PI, and PF, respectively, we obtain the following results:We analytically derived the persistence diagrams for the four cubic lattices shown in For type-P,For type-C,For type-I,For type-F,The corresponding persistence diagrams are shown in X and Y, can be measured with the following bottleneck distance [η is a bijection between X and Y, and the L∞-distance between points u =  and v =  is defined as follows:The similarity between two persistence diagrams, distance :dBα = 0.1 nm by an affine transformation. This normalization transformation is necessary because a persistence diagram is robust against a rotation of the targeted point cloud and noise but largely affected by a difference in the scales. Then, we compute persistence diagrams Dq(PM)  for a point cloud PM in the cube, corresponding to a set of molecular centroids. If the multi-set Dq(PM) is sufficiently close to one of those in Eqs , if the following inequality is satisfied:ϵ represents the acceptable error. In later numerical experiments, we set ϵ at 0.001 nm. For numerically generating persistence diagrams for molecular centroids, we used Dionysus 2 which is a library for computing persistent homology [Using this similarity measure, we identify the crystals where the molecular arrangements correspond to affine transformations of the cubic lattices in e in Eqs , then thhomology .x = ⊤ is a 3D coordinate. The diagonal matrix R is represented as follows:ri denotes the radius in the direction of xi for i = 1, 2, 3.Once we identify a crystal that has a structure corresponding to an affine transformation of a cubic lattice, we can estimate the shape of identical ellipsoids around the molecular centroids packed in the identified cubic lattice. In general, an ellipsoid is expressed as follows:RZ for Z = P, C, I, or F are calculated as follows:α is the length of each side of the unit cell.For ellipsoids (or spheres) packed in the four cubic lattices, the diagonal matrices v is a 3D coordinate and Q is an unknown diagonal matrix determining the shape of the ellipsoid. We denote by W the affine transformation used to normalize the unit cell of a crystal when generating the persistence diagram. Then the coordinate transformation is represented as x = Wv. The ellipsoid in W into the ellipsoid x⊤RZx = 1 with a known diagonal matrix RZ . By substituting x = Wv into x⊤RZx = 1, we obtainW⊤RZW is a symmetric matrix. The radii ri  of the ellipsoid approximating the intracrystalline molecular shape are computed as i  represent the eigenvalues of W⊤RZW.Now we assume that an ellipsoid approximating a molecular shape in a crystal is represented as follows:The above-mentioned method gives approximate ellipsoidal molecular shapes represented as ellipsoid radii. We test whether these ellipsoidal shapes can be predicted from single molecular descriptors using a machine learning method. Molecular descriptors represent a set of features of single molecules, which have many possible representations. Molecular fingerprint is one of the widely used descriptors to determine the similarity of chemical structures , 36. A mWe employ Extended Connectivity Fingerprint (ECFP)  which isN. The nth teacher data is given by a pair of input and output, where the input is an ECFP for the molecule and the output is the estimated ellipsoid radii The ellipsoidal shape prediction is performed with a feedforward neural network with one hidden layer in a supervised learning framework. The hidden layer has 64 units. Each node has the hyperbolic tangent (tanh) activation function. The number of training data is denoted by Molecular crystals are versatile materials which can be found in pharmaceuticals, organic semiconductors, solid-state reactions, and plastic materials . For insPolycyclic aromatic hydrocarbons (PAHs): 75 crystals of polycyclic aromatic hydrocarbons that contain only hydrogens and carbons.Polycyclic aromatics with hetero atoms (PAHAs): 404 crystals of polycyclic aromatic hydrocarbons that can contain hetero elements  in their skeletons but have no substituents other than halogens.Polycyclic aromatics (PAs): 8787 crystals of polycyclic aromatic hydrocarbons that can contain hetero elements in their skeletons and arbitrary substituents.PAHs are included in PAHAs which are included in PAs, as shown in The topological data analysis was applied to molecular centroids of each crystal structure in the datasets. It was determined whether each crystal structure corresponds to an affine transformation of one of the four cubic lattices shown in r1, r2, and r3, satisfying r1 ≥ r2 ≥ r3. The different marks correspond to different types of cubic lattices in V = (4/3)πr1r2r3 calculated from the estimated radii and the molecular volume calculated based on the electron density through Monte-Carlo integration in Gaussian 16 [We assume that identical ellipsoids around the molecular centroids are packed in the crystals that were identified in ssian 16 . The resr1 tends to be elongated. Benzophenanthrene  from molecular fingerprints given by ECFPs. We trained a neural network model by using the Adam (Adaptive moment estimation) optimizer with learning rate 0.001 and mini-batch size 32 [r1 prediction are close to the diagonal line as shown in r2 and r3 tend to be smaller than the actual values when their values are large as shown in We performed a machine learning prediction of the ellipsoidal radii for PAs from single molecular information. This is regarded as a simplified task of CSP, because the information of arrangements of molecular centroids and molecular shapes are useful for identifying crystal structures. The task is to predict the radii of ellipsoids  can be classified into basic lattices via affine transformations. This is analogous to the fact that spatial arrangements of atoms in crystals are characterized by Bravais lattices. A further study on topological classification of molecular arrangements would be effective for understanding molecular structures in crystals.The focus of our study has been limited to the crystals with specific structures obtained by affine transformations of the basic cubic lattices, which cover triclinic, monoclinic, orthorhombic, tetragonal, and cubic crystal families. The remaining family is the hexagonal crystal family. We have excluded this family in this study due to the difficulty in analytical derivation of the corresponding persistence diagram and the ellipsoid radii under the dense packing condition. A future work is to extend our method such that the crystals having structures corresponding to affine transformations of hexagonal lattices are also handled. Another issue is that the affine transformation restricts the molecular orientations. To distinguish diverse orientations such as a herringbone motif, it would be necessary to apply other transformations between molecular centroids and basic lattices.ab initio calculations with force fields and DFT would be appropriate [ϵ in ϵ in The proposed method has several limitations. First, it does not give information about the arrangements of atoms in each crystalline molecule. For a full CSP, a conformational search of the arrangements of atoms after applying the proposed method would be necessary. Second, the assumptions in our method are applicable only to a part of crystal structures. For instance, the approximation of molecules with ellipsoids would be valid for rigid molecules but not for highly flexible molecules. A possible approach for examining how much molecular flexibility is permitted is to investigate the effect of the number of dihedral angles, representing the flexibility level, on the prediction accuracy. The dense packing assumption would also not be applicable to structures with substituents such as -CHO hydrogen bond, because they can be low-density structures. For such structures, ropriate . Third, S1 Figr1, r2, and r3 for PAHs. (d)-(f) the prediction results on r1, r2, and r3 for PAHAs.The horizontal axis represents the teacher data and the vertical axis represents the predicted value. (a)-(c) the prediction results on (EPS)Click here for additional data file.