The manipulation of single molecules has attracted extensive attention because of their promising applications in chemical, biological, medical, and materials sciences. Optical trapping of single molecules at room temperature, a critical approach to manipulating the single molecule, still faces great challenges due to the Brownian motions of molecules, weak optical gradient forces of laser, and limited characterization approaches. Here, we put forward localized surface plasmon (LSP)-assisted trapping of single molecules by utilizing scanning tunneling microscope break junction (STM-BJ) techniques, which could provide adjustable plasmonic nanogap and characterize the formation of molecular junction due to plasmonic trapping. We find that the plasmon-assisted trapping of single molecules in the nanogap, revealed by the conductance measurement, strongly depends on the molecular length and the experimental environments, i.e., plasmon could obviously promote the trapping of longer alkane-based molecules but is almost incapable of acting on shorter molecules in solutions. In contrast, the plasmon-assisted trapping of molecules can be ignored when the molecules are self-assembled (SAM) on a substrate independent of the molecular length. Accurately controlling nanometer-scale objects has attracted huge interest due to the broad prospects in medical, biological, life, and chemical applications ,2. SinceIn recent years, the wide applications of mechanically controllable break junctions (MCBJs) and scanning tunneling microscopy break junctions (STM-BJs) have rapidly promoted the investigation of electron transport across single-molecule junctions ,15,16. MHerein, we carried out a systematic study to address the LSP-assisted trapping of single molecules by employing STM-BJ approaches and make the following clear observations: (1) The conductance histogram shows negligible changes upon plasmon excitation for the molecules self-assembled on the electrode surface. In contrast, the conductance histogram presents considerable changes upon plasmon excitation when the measurement is performed in solution with suspending molecules; (2) Only for those molecules with a longer length does the conductance histogram show obvious change upon plasmon excitation; (3) The length of the plateaus presented in the 2-dimension conductance traces almost remains unchanged upon plasmon excitation, which reflects the almost unchanged junction lifetimes. Based on these solid observations, we claim that localized plasmons truly can be used to trap the molecules inside the nanogap and thus promote the formation of molecular junctions in solutions, which contrasts the previous expectation that (sub) nanoscale molecules cannot be trapped because the applied optical force decreases exponentially as the acting object volume decreases.4(SH)2), 1,6-Hexanedithiol (C6(SH)2), 1,8-Octanedithiol (C8(SH)2), and 1,10-Decanedithiol (C10(SH)2) were employed as probe molecules. The molecular lengths for C4(SH)2, C6(SH)2, C8(SH)2, and C10(SH)2 are, respectively, 0.88 nm, 1.13 nm, 1.38 nm, and 1.63 nm, entering the sub-2 nm region. All these alkyl-based molecules have an anchoring group at two ends, which offers probabilities to form electrode–molecule–electrode junctions between two nanogapped electrodes. For the conductance measurement of SAMs-based junctions, the above four molecules were first diluted in acetonitrile solvents (1 mM). Subsequently, gold substrates were placed into the target solution for 24 h self-assembly, respectively. Finally, the substrates were blown dry with nitrogen for STM-BJ measurements. In contrast, we diluted these four molecules into 1,2,4-Trichlorobenzene (TCB) solvent (0.1 mM) for the STM measurements in solution because TCB is a stable nonpolar solvent that offers a wide access window for conductance measurement and evaporates at a slow speed [As shown in ow speed .6 W/m2) was introduced into the STM-BJ setup, illuminating the nanogap with the electric vector parallel to the gold nanoelectrode axis to excite the localized plasmon [ plasmon ,24,27. T−6 to 101G0.When more molecules are trapped into the nanogap through optical field gradient force, the probability of molecular junction formation will be obviously enhanced. Thus, the relative heights of the normalized histogram peaks could directly reflect yield contrasts of molecule junctions and thus indicate how much the plasmon trapping effects would lead to the changes of molecular junction yields [The STM-BJ experiments were performed at an applied bias of 100 mV. The current through the STM tips was measured at room temperature using a lab-built current-voltage converter with a sensitivity of 1 pA and a sampling rate of 30 kHz. Thousands of conductance traces were recorded and compiled into a 1-dimension (1D) histogram for each kind of molecule by repeatedly forming and then breaking point contacts between a gold STM tip and substrate covered with the SAMs or immersed in solutions. When two electrodes were bridged by a molecule via anchoring groups at two ends, a discernible molecular conductance plateau can thus be observed in a single recorded conductance–distance trace, which can be utilized to distinguish the formation of molecule junctions ,29. Whenn yields .4(SH)2, C6(SH)2, C8(SH)2, and C10(SH)2 are approximately 24.3%, 22.1%, 38.6%, and 39.9%, respectively. Upon laser illumination, the yield of molecule junction changes to 22.4%, 21.8%, 37.0%, and 40.3%. Here, a molecular junction formation judged by the conductance trace is recognized as the appearance of 15 subsequent data points detected in the corresponding molecular conductance range. The change of junction yield at the level of 2% can be regarded as free fluctuations due to a minor deviation of STM tips, which means that the laser illumination and the resulting plasmonic force have minor effects on the yields of molecule junction for all four types of SAM junctions. This observation is reasonable because the SAM molecules bond to the bottom gold substrate, hindering the free movement of molecules, i.e., the optical gradient force smaller than the anchoring bond force is insufficient to trap/manipulate molecules [olecules .8(SH)2 and C10(SH)2) as the experiment is performed in solutions. Upon light illumination, the molecular junction yield for C4(SH)2, C6(SH)2, C8(SH)2, and C10(SH)2 increases from 23.3%, 22.0%, 25.5%, and 32.6% to 24.7%, 24.5%, 33.7%, and 47.1%, respectively, which means the increments for longer C8(SH)2 and C10(SH)2 are 8.2% and 14.5% respectively. We attributed the molecular length dependent observation to LSP-assisted molecule trapping because of the plasmonic gradient force applying on the object scales with the third power of the object size so that the laser trapping effect might become much weaker as the molecule size decreases [In contrast to the SAM environment, the peak height increases upon light illumination, especially for the longer molecules  of conductance versus displacement distance of STM tip in different environments; see The horizontal shape of the plateau indicates the junction conductance does not vary significantly during the junction elongation process, and the sloped shape of the plateau indicates the junction conductance varies across a range until a final break. The distinguished features presented in It is known that the lifetime of molecular junctions can also strongly affect the peak height presented in the 1D conductance histogram, e.g., a longer lifetime of molecule junction even with fixed junction yield can still generate a more pronounced peak ,39. To e8(SH)2 and C10(SH)2 molecules in solutions, the considerable increments of junction yield demonstrate the plasmonic trapping effects occurring in flexible solution environments. Most importantly, we prove that the change of peak heights in the 1D conductance histogram does not originate from the change of the junction’s lifetime (judged by the length of conductance plateau), thus confirming that the increase of conductance peak truly originates from the plasmon-assisted trapping. Thus, we present an effective plasmon-assisted enhancement of molecular junction formation probabilities by a non-invasive combination of optical trapping and STM-BJ platform. Our work advances the understanding of single-molecule optical trapping and provides wide applicability to diverse sets of target molecules and electrode materials, thus paving the way for improved single-molecule sensing, manipulation, and recognition in chemical, biological, medical, and materials sciences.In our work, STM-BJ renders a feasible approach to simultaneously achieve plasmonic molecular capturing and in situ single-molecule conductance sensing with size down to sub-2 nm in solution. This novel indicator of junction formation probabilities to characterize trapping capability is beyond the traditional limitations of highly-focused laser and the narrow selection of target materials. We demonstrate the nearfield trapping ability of both SAMs and molecular solutions for four probe molecules by quantifying the relative height of normalized counts of molecular junctions. For SAM, non-obvious changes in normalized counts have been observed, possibly because of the insusceptible immobilizing properties. Meanwhile, for longer CSample preparation. The bottom gold substrate was magnetron-sputtered by 2 nm Cr and 200 nm gold on silicon. The STM tip was prepared by burning one end of a gold wire  with a methane flame. For measurement with SAM, the substrates were thoroughly rinsed with ethanol and blown dry with nitrogen after the self-assembling process.Optical setup. We utilized a fiber laser  to illuminate the junctions. The laser intensity was 30 mW by choosing 100 mA electrical current on laser control panel. A linear polarizer with vertical polarization was placed in the middle of laser source and STM break junctions.G0 and additional steps appear at a lower conductance, marking that molecules bridge two electrodes to form molecular junctions. The conductance traces recorded during the electrode separation process were used to construct the 1D and 2D conductance histograms.Conductance measurement. The single-molecule conductance measurements of target molecules were performed using the STM-BJ technique. A positive 100 mV bias voltage was applied to the STM tip and the bottom electrode was connected to the ground. A feedback system was utilized to control the piezo for the STM tip, repeatedly forming and then breaking point contacts between a gold STM tip and substrate. The conductance trace was recorded as a function of tip–substrate displacement (denoted as “length” in the main text). These conductance–length traces exhibit steps at integer multiples of the conductance quantum Generation of conductance histogram. Notably, the tip may be gradually distorted after long-time measurements, which may result in systematical error. To avoid this problem, we alternatively switched on or off the laser every five minutes and classified corresponding data into two packages according to dark or illuminating conditions.4(SH)2 solutions under illumination and dark, the ratio of conductance trace counts is 3728/3676 = 1.014. For all the probe molecules of C4(SH)2, C6(SH)2, C8(SH)2, and C10(SH)2, the normalization method is identical unless otherwise noted. As for the calculation of molecular junction yields, we recognized a conductance trace as successful formation of molecular junction by the appearance of at least 15 subsequent data points detected in the corresponding molecular conductance range. Finally, the numbers of these molecular junction traces are counted and then divided by total counts of junction traces to obtain molecular junction yields. Total counts of junctions include both tunneling junctions without the trap of molecules and molecular junctions.Data processing. The total counts (y axis) before normalization in


Carbon nanotubes (CNT)  are by far the most popular nanomaterials thanks to their high electrical and thermal conductivities and mechanical strength, specific optical and sorption properties, low cost, and easy preparation, among other interesting characteristics ,2,3,4. CNanomaterials, Applied Sciences, and Materials. The presented knowledge embraces numerical simulations [In total, twenty-three articles are published on this Topic in the participating journals ulations ,9,10,11 ulations ,21,22,23The research community has been particularly active in modelling and simulating different scenarios to better understand the behaviour of natural convection, energy absorption, and thermal and mass transport, as well as the mechanical, electronic, and optical properties.Khan et al. ,9 conducMolecular dynamic simulations have provided deep theoretical insights into the heat transfer mechanisms of branched CNT  and imprThe other articles on this Topic delve into different experimental approaches for the synthesis of new (nano)materials or the development of new analytical tools. A large set of new (nano)materials is under scrutiny, namely, silica-microsphere-supported N-doped CNT for electromagnetic wave absorption , low cryIt is worth mentioning that analytical strategies were also addressed in this Topic by designing a novel biosensor based on SWNT/DNAzyme for calcium determination in milk  and charThe remarkable applications of CNT are already uncountable, but their potential is undoubtedly yet to be fully developed. Advances in their synthesis, characterization, and application, as concluded by reading the reported studies on this Topic, involve merging multi- and transdisciplinary knowledge ranging from fundamental science to technological innovations.


During the first year of the coronavirus disease 2019 (COVID-19) pandemic, the number of incarcerated people in the USA decreased by at least 17%—the largest, fastest reduction in prison population in American history4. Here we ask how this reduction influenced the racial composition of US prisons and consider possible mechanisms for these dynamics. Using an original dataset curated from public sources on prison demographics across all 50 states and the District of Columbia, we show that incarcerated white people benefited disproportionately from the decrease in the US prison population and that the fraction of incarcerated Black and Latino people sharply increased. This pattern of increased racial disparity exists across prison systems in nearly every state and reverses a decade-long trend before 2020 and the onset of COVID-19, when the proportion of incarcerated white people was increasing amid declining numbers of incarcerated Black people5. Although a variety of factors underlie these trends, we find that racial inequities in average sentence length are a major contributor. Ultimately, this study reveals how disruptions caused by COVID-19 exacerbated racial inequalities in the criminal legal system, and highlights key forces that sustain mass incarceration. To advance opportunities for data-driven social science, we publicly released the data associated with this study at Zenodo6.The criminal legal system in the USA drives an incarceration rate that is the highest on the planet, with disparities by class and race among its signature features A study shows that, although the number of incarcerated people in the USA decreased during the first year of the COVID-19 pandemic, the fraction of incarcerated Black and Latino individuals increased. Owing to a combination of structural inequities and discriminatory enforcement, Black and Latino people are more likely to be stopped by police11, held in jail pre-trial12, charged with more serious crimes13 and sentenced more harshly than white people15. These practices have made Black men in the USA six times as likely and Latino men 2.5 times as likely to be incarcerated as white men17.Mass incarceration in the USA is distinguished by striking racial disparities and a rate of imprisonment that surpasses that of all other nations, with 2.12 million people in prisons and jails in 2019 , but a meaningful increase in the proportion of incarcerated Black, Latino and other non-white people. We conclude that sentencing patterns are a central mechanism driving the racial disparity.In this study, we demonstrate how the COVID-19 pandemic—which produced the largest, most rapid single-year decrease in prison population in US history—amplified existing inequities in the nation’s criminal legal systemThe trend we identify represents a substantial deviation from patterns preceding the pandemic. Before COVID-19, incarcerated Black people accounted for a declining share of the total prison population: roughly 41.6% of people incarcerated in state prisons were Black in March 2013, and by March 2020 this number had fallen to 38.9%—a decline of 2.7 percentage points over seven years. During the height of COVID-19 closures, from March 2020 to November 2020, this percentage increased by 0.9 points, erasing much of the progress over the last decade  and did so steadily throughout the pandemic. Other states’ prison populations dropped sharply in the early months of the pandemic but saw their prison populations begin to increase again by January 2021  or by July 2021 . In Supplementary Fig. 19—began to approach pre-pandemic rates in early 2021.Despite an overall decline in the total incarcerated population during the pandemic, there was an increase in the proportion of incarcerated Black people Fig. . This inAlthough the national trend we identify in Fig. Ultimately, these observations lead us to outline three explanations that could bring about the trends from Fig. Consider a time series of a state’s prison population that does not notably change over several years. For this to occur, there needs to be approximately the same number of admissions and releases. For the demographic makeup of the prison population to remain stable, the relative number of admissions and releases by race also needs to be roughly equivalent over time. If there are sustained periods with more admissions (or releases) of a certain demographic, that will skew the overall distribution of the prison population.Understanding the dynamics of admissions, releases and sentencing offers us a path towards identifying and isolating potential mechanisms that could bring about a steadily declining rate of incarceration of Black individuals (seen for nearly a decade before the pandemic), and the subsequent spike in the proportion of incarcerated Black people during the COVID-19 pandemic. Namely, the observed spike in Fig. 23). The Virginia Department of Corrections acknowledges the causal effect of court closures on the state’s incarcerated population in their 2020 Annual Report24, “The reduction in [average daily population] is directly attributed to the suspension of intake due to COVID-19”. Similarly, a spokesperson for the Michigan Department of Corrections estimated that half of the reductions in incarcerated population were due to a decline in new admissions from courts and county jails25 .In every state except Nebraska, courts closed at the beginning of the pandemic. These closures substantially reduced or altogether halted admissions into prisons for several months, starting around April 2020  and have an approved address to stay at after their release.In an effort to reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, several states enacted policies designed to de-densify prisons. Depending on the state, these directives came from executive orders from the governor, state legislatures or governing boards. In Utah, for example, policies around releases are designed, approved and implemented by the Board of Pardons and Parole—an entirely separate entity from the courts and the Department of Corrections. According to the Board of Pardons and Parole, incarcerated people who are eligible for early release needed to be already characterized as a non-violent offender, be within 90 days of release (this was later extended to 180 days27)) made 1,243 incarcerated people eligible for early release as of 30 April 2020. Those deemed eligible needed to have a parole plan in place, be medically screened  and undergo final approval by the Arkansas Department of Corrections director to be released. In Supplementary Section In Arkansas, an authorization from Governor Hutchinson . Thus, when court proceedings or transfers from county jails are disrupted , the racial disproportionality in the total prison population accelerates, as observed in Figs. 14, led to the abrupt nationwide increase in the percentage of incarcerated Black people, starting in March 2020. Differences in the length of sentence by race seem to be a key factor in producing the trends from Fig. Before the COVID-19 pandemic, racial disparities in admissions were smaller than disparities in the prison population, as recent trends show a migration towards a class-driven disparity, with lower-educated white people steadily increasing in their rate of admission30 42. We were able to quantify disparities in some states’ efforts to de-densify prisons . For every state in our dataset, we sought the most temporally resolved data as possible. We collected population data at either weekly, monthly, quarterly or, for some states, yearly levels. The most common form of data we were able to collect is the number of people incarcerated at a given time in a given state, on a monthly timescale. In Supplementary Table 44—and find high overlap between all three of the datasets. In Supplementary Section We compared the data collected here to data from other organizations that report statistics about the US prison population—the Bureau of Justice Statistics and the Vera Institute for JusticeFor every state in this dataset, the total prison population includes both male and female incarcerated people . In Alaska, New Mexico, Vermont and California, “Transgender”, “Other” or “Non-Binary” are also listed as gender categories, although this practice is not widely adopted in reporting statistics about the incarcerated population. In 27 states, incarcerated race statistics are separated by “male”, “female” and “total”, and further characterizing the interaction between race and sex in biases in admissions and releases during the COVID-19 pandemic remains future work.Qualitative data on the closure and reopening of all 50 state court systems were collected primarily through the administrative orders and/or press releases of each state system’s Supreme or Superior Court or chief judicial officer as well as through local news coverage. Most states suspended all in-person proceedings with the exception of limited emergency matters between 12 March and 20 March 2020. Several states that adopted policies early in this period issued increasingly strict guidance as the pandemic worsened. New Jersey, for example, suspended new trials on 12 March and issued a 2-week suspension on municipal court proceedings on 14 March before finally suspending all proceedings (with emergency exceptions) on 15 March. In addition to closing judicial buildings and suspending proceedings, most court closures also extended statute of limitations and filing deadlines owing to pandemic disruption. A handful of states, Pennsylvania and Texas among them, permitted or encouraged courts to begin conducting remote proceedings in their initial closure orders, although the adoption of remote proceedings was not widespread in this initial lockdown stage.Court reopening policies were more heterogeneous than the initial closures, although trials remained suspended in most states through at least early summer 2020 . The earliest such policies appeared at the beginning of April 2020, with most aimed at giving regional and local judges discretion to begin hearing proceedings remotely . A substantially larger group of states adopted reopening guidelines between late April and mid May, many of which allowed essential judicial staff to return to offices following new public health guidance while also maintaining remote proceedings and expanding the number of non-trial proceedings that courts could conduct remotely. Further reopenings and the resumption of limited in-person proceedings took place in many states throughout June, July and August 2020, although trial proceedings remained suspended. Notably, several states, especially those that adopted phased reopening plans, restricted in-person proceedings and further delayed trial resumption with the autumn–winter 2020–2021 COVID-19 surge. In many states, most administrative orders restricting court operations have at the time of publishing been rescinded, although others, California notably among them, still retain certain accommodations including the option for remote proceedings.Data on COVID-19 release policies, when they existed, were collected from states’ individual corrections and prison bureau systems, governors’ executive orders and local news coverage. Fifteen states did not adopt any official release policy, although our data nevertheless show that there were still reductions in the overall prison population during the pandemic in all of these states. The remaining 35 states adopted policies with varying degrees of specificity and effectiveness, although many overlapped in their broadest contours, allowing consideration for early release to be granted to incarcerated people at increased public health risk  and for those nearing parole and/or the end of their prison sentences.45, from 24 April 2020.Almost all states with such policies did, however, adopt a restriction preventing the release of those incarcerated for violent crimes or sex offences. North Dakota was an outlier in this regard. Of the 120 people the state initially released from prison in March 2020, 14 were serving time for violent crime convictions and 11 were convicted of sex offences. New York’s release policy was notably more restrictive (on paper at least) than that of many other states—only those incarcerated for “non-criminal technical parole violations” were eligible for COVID release. As an example of one state’s release policy, we include below an excerpt from the Virginia Department of Corrections’ policy on releases“The Director of the Department of Corrections is authorized to consider early release for individuals with less than one year left to serve while the COVID-19 emergency declaration is in effect. Offenders convicted of a Class 1 felony or a sexually violent offense are not eligible for consideration. The exact number of individuals eligible for early release consideration will change depending on the length of the emergency declaration order. The [Department of Corrections] will identify those that are eligible for consideration using the procedures it has developed to ensure public safety and will notify offenders who are to be released under the early release plan. A diagnosis of COVID-19 is not a release factor.Release Date: The inmate’s Good Time Release Date must be calculated and verified in order for the incarcerated to be considered.Inmate Medical Condition: The inmate’s medical condition will be considered.Offense History: By legislative mandate, early release does not apply to inmates convicted of a Class 1 felony or a sexually violent offense. Consideration for early release will be based on the seriousness of the current offense, in descending order as follows: Non-violent Offense, Felony Weapons Offenses, Involuntary Manslaughter, Voluntary Manslaughter, Robbery, Felony Assault, Abduction, Murder, Sex Offense.Viable Home Plan: The incarcerated person must have a documented approved home plan to be considered.Good Time Earning Level: The inmate’s current good time earning level must be I or II to be considered.No Active Detainers: Inmates must have no active detainer to be considered.No Sexually Violent Predator Predicate Offenses: Inmates convicted of one or more sexually violent offenses established in §37.2-903 of the Code of Virginia are not eligible pursuant to legislation.Recidivism Risk: Inmates must have a risk of recidivism of medium (5-7) or low (1-4), as identified by the validated COMPAS instrument, to be considered.”The following Early Release Criteria will be utilized in considering an incarcerated person for early release pursuant to legislation:51. COMPAS, in particular, has been the subject of a number of studies that take a critical look at the effectiveness—and ethics—of these risk assessment tools in the justice system52; in one study, COMPAS was found to predict recidivism 61% of the time, but at the same time, Black people were almost twice as likely to be labelled as high risk for reoffending but not actually reoffend52.Note especially the inclusion of the COMPAS risk assessment tool, which is used in court systems across the USA as a way of quantifying an offender’s likelihood of reoffending (recidivism). Over the past several years, we have seen a growing body of scholarly work devoted to identifying problematic and harmful racial and economic biases that arise when algorithmic risk assessment tools are used in practice53.Further research is needed to quantify demographic patterns in the incarcerated individuals who were released across different states, and because there was such high heterogeneity in different states’ policies, it remains an open question whether we will see the same broad, systematic racial differences among the people who were released. However, as has been the case throughout the COVID-19 pandemic, the heterogeneity of policy responses across localities has typically had detrimental effects on our collective response to the pandemicThe data that we collected for the study used definitions of racial and ethnic groups that were determined by the agencies that collected the data. When the authors are discussing race and ethnicity in their interpretations, they are referring to the historical categories that have social, cultural and political consequences. We use the term Latino to describe people who are otherwise described as Hispanic in many settings. We have used the term non-white in select locations, as not all states had data disaggregated into the same set of categories. Thus, for some analyses, the term non-white directly describes the available data. For a list of the race categories reported by every state in our dataset, see Supplementary Table 54. This is of critical importance to health equity and racial justice, and although in this work we rely on race statistics reported by states’ Departments of Correction, future work will critically examine the differences in approaches for reporting race and ethnicity statistics of incarcerated populations. Notably, it is important to know whether a state’s statistical reports use race categories that have been self-reported by the incarcerated person or whether it is interviewer-observed, which is often the case in administrative databases. These approaches are quite different and often result in inaccuracies in measurement of racial disparities55. Last, in Supplementary Section Recent advances in medical conventions have prompted discipline-wide introspection about the ways that race and ethnicity are discussed and used in researchFurther information on research design is available in the Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41586-023-05980-2.Supplementary InformationThis file contains Supplementary Sections 1–5 and includes Supplementary Figs. 1–23 and Supplementary Tables 1–7.Reporting SummaryPeer Review File


Diabetes mellitus is a prevalent endocrine condition. We aimed to investigate the anti-diabetic effects of 3-hydroxybakuchiol (HYD) by exploring its potential targets and molecular mechanisms through bioinformatics analysis and cell experiments.We performed an extensive search and screening of HYD and its potential targets for diabetes mellitus across various databases. Enrichment analyses were conducted using the ClusterProfiler package. PPI networks of the identified genes were constructed using STRING, and topological analysis was performed to identify core targets. The results were further confirmed through molecular docking. To validate the findings of our bioinformatics analysis, we conducted cell experiments using insulin resistance-induced HepG2 cells and C2C12 cells.We discovered 260 common targets of HYD and diabetes mellitus, which were primarily related to the MAPK signaling pathway, PI3K-Akt signaling pathway, and endocrine resistance. A topological analysis of the PPI network identified four core targets . Molecular docking studies further confirmed the strong binding ability between HYD and these core targets. In cell experiments, we observed that HYD enhanced glucose uptake and suppressed gluconeogenesis in HepG2 cells and C2C12 cells. This resulted in an improvement in glucose metabolism, potentially through the regulation of the PI3K-Akt pathway.This study provides valuable insights into the pharmacological effects of HYD on diabetes mellitus, suggesting its potential as a promising treatment option for the disease.The online version contains supplementary material available at 10.1186/s12906-023-04248-6. Type 2 diabetes mellitus (T2DM) is a complex metabolic disease linked to beta-cell dysfunction, insulin resistance, and impaired insulin secretion . This reBakuchiol, a prenylated monoterpene extracted from Psoralea corylifolia seeds, has various pharmacological effects, including hypoglycemic, anti-depression, anti-cancer, anti-inflammatory, and antibacterial effects –15. It iThe use of network pharmacology has gained popularity in drug research due to advancements in bioinformatics and related databases. This approach allows researchers to uncover relationships between drugs, pathways, and targets , 20. MolIn this study, we employed a network pharmacology approach, along with molecular docking technology and cell experiments, to investigate the biological pathways linked to the therapeutic effects of HYD in managing diabetes. This study is the first to thoroughly explore the mechanisms and effects of HYD, leading to a solid theoretical basis for its clinical use. Figure https://prediction.charite.de/index.php), PharmMapper (http://www.lilab-ecust.cn/pharmmapper/), and SwissTargetPrediction (http://www.swisstargetprediction.ch/). Related genes were obtained after the duplicated genes were removed.All the targets of HYD have been obtained by using the following three databases: Super-PRED (https://www.genecards.org/), Therapeutic Target Database (https://db.idrblab.net/ttd/), and Comparative Toxicogenomics Database (https://ctdbase.org/). Duplicate targets were removed and a list of targets associated with diabetes disease was obtained.To identify targets related to diabetes, we performed a comprehensive search using the keyword “type 2 diabetes” on three databases: GeneCards (Construction of protein-protein interaction (PPI) network and identification of core targets.https://version-12-0.string-db.org/) to construct a PPI network for these shared targets. The PPI network was then imported into Cytoscape (version 3.7.2) software for visual analysis, and the cytoHubba plug-in was employed to screen for critical targets within the network [To identify target genes related to both HYD and diabetes, we utilized the Venn tool for analysis. This allowed us to determine the target genes of HYD that are also associated with diabetes. Subsequently, we utilized the STRING database  was used to eliminate the water molecules and original ligands of the target protein. We utilized ChemDraw 19.0 software to draw the molecular structures of small molecule compounds individually for ligand molecule processing. The resulting format files were then imported into Chem3D 19.0 software to optimize the energy using the program, and saved in PDB format. Next, we imported the PDB format file into AutoDockTools 1.5.6 software to adjust the ligand charge and saved it as a PDBQT file. Subsequently, AutoDock software (1.5.6) was employed for molecular docking analysis. Here is a detailed procedure for molecular docking: the AutoDockTools 1.5.6 software was used to open the PDBQT file of the receptor macromolecule and ligand. To identify the active binding site for molecular docking, we utilized the coordinates of the co-crystallized ligand. After identifying the active pocket of the target protein, we proceeded to define the coordinates and size of the grid box. The parameters for the grid box were as follows: a spacing of 0.5 Å, 80 points in the x-dimension, 80 points in the y-dimension, and 80 points in the z-dimension. The docking process utilized the Vina force field and the Lamarckian GA (4.2) algorithm. Throughout this study, 100 GA runs were performed while maintaining the default settings for other docking criteria. The results were then visualized using PyMOL. Furthermore, information regarding the absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics of HYD was acquired from the pkCSM database, accessible at HepG2 cells and C2C12 myoblasts  were cultured in Dulbecco’s modified Eagle’s medium supplemented with 10% FBS and 100 IU/mL penicillin-streptomycin. The cells were incubated at 37 °C in a 5% CO2 environment. To induce the insulin resistance model, we followed the protocol outlined in the previous study . HepG2 o−3 mol/L. All cells were then incubated at 37 °C in a 5% CO2 atmosphere for 24 h.The study involved dividing cells into five groups: control, model, HYD low dose , HYD high dose , and metformin (MET). Cells in the control group were maintained in Dulbecco’s modified Eagle’s medium. To induce insulin resistance, cells in the model, HYD, and MET groups were subjected to the method mentioned above. After induction, the HYD groups were treated with either a low or high dose of HYD, while the MET group was treated with a dose of 10The viability of cells treated differently (HYD) for 24 h was assessed using the CCK-8 test kit  based on the instructions of the manufacturer.Glucose consumption was evaluated using a modified version of the methodology described in a previous study . HepG2 c–ΔΔCt method. The primer sequences used for qRT-PCR can be found in Table STo perform qRT-PCR, total RNA was extracted from cells using TRIzol Reagent  following the manufacturer’s protocol. The extracted RNA was then converted into cDNA using cDNA synthesis kits . We conducted the qRT-PCR analysis on a StepOnePlus Real-time PCR system  and determined the mRNA expression levels using a 2P < 0.05.Data analysis was performed using GraphPad Prism 8.0 software. Experimental results are presented as mean ± standard deviation (SD). Group differences were compared by one-way analysis of variance. Statistical significance was defined as As presented in Fig. p-values < 0.05, mainly included MAPK signaling pathway, PI3K-AKT signaling pathway, Rap1 signaling pathway, progesterone-mediated oocyte maturation, central carbon metabolism in cancer, endocrine resistance, acute myeloid leukemia, EGFR tyrosine kinase inhibitor resistance, regulation of lipolysis in adipocytes, and VEGF signaling pathway. Combined with previous studies, we speculated that the PI3K-AKT signaling pathway may play a vital role in the treatment of diabetes by HYD  category, these target genes showed significant enrichment in the response to chemical, regulation of biological quality, response to organic substance, cellular response to chemical stimulus, etc. Fig. A; in theFigure Molecular docking studies were conducted to investigate the interactions between HYD and four potential target genes  at a molecular level. The AutoDock Tools software was employed for these studies, resulting in a total of four docking results. Among these results, one docking score below − 5.0 kcal/mol was obtained. The docking score, which is presented in Table SIn this study, we utilized pkCSM to evaluate the ADMET properties of HYD. The results presented in Table SThe CCK8 assays were used to assess the cytotoxic effects of HYD. As shown in Fig. P < 0.001). Both HYD and metformin were found to significantly elevate glucose consumption in insulin resistant HepG2 cells and C2C12 cells, with statistical significance observed at P < 0.05 or P < 0.001.As illustrated in Fig. P < 0.01 or P < 0.001).In this study, we utilized qRT-PCR to examine the impact of HYD on the mRNA expression of AKT, PI3K, GS, PEPCK, and G6Pase Fig. . CompareType 2 diabetes mellitus is a chronic endocrine and metabolic disorder associated with severe complications. The development of type 2 diabetes mellitus is multifactorial, involving both environmental and genetic factors, along with insulin resistance, which poses significant clinical challenges. Recently, there has been increasing interest in exploring new therapeutic strategies for type 2 diabetes mellitus, including the use of traditional medicine as a complementary treatment –29. PrevIn this study, a comprehensive approach was employed to predict the interactions between HYD and its potential protein targets. Targets from publicly available databases on diabetes were integrated, and the various signaling pathways and networks in which HYD targets are involved were explored. Docking studies were also conducted to predict specific interactions between HYD and its predicted protein targets. The results of molecular docking demonstrated that hydrogen bonding was the primary mode of interaction for HYD. In addition, the cytoHubba plug-in has identified four key targets  that have a significant connection to the pathogenesis and treatment of type 2 diabetes mellitus. HSP90AA1 was previously identified as a node in a protein-protein interaction network in diabetes through bioinformatics analysis , 31. TheBased on the results of KEGG pathway, HYD may treat diabetes through multiple pathways, such as MAPK signaling pathway, PI3K-AKT signaling pathway, endocrine resistance, EGFR tyrosine kinase inhibitor resistance, regulation of lipolysis in adipocytes, VEGF signaling pathway, etc. The PI3K/AKT signaling pathway is crucial in cellular physiology as it helps transmit growth factor signals during organismal growth and essential cellular processes. These processes encompass cell proliferation, cell survival, and protein synthesis, as well as glucose homeostasis and lipid metabolism . ImpaireIn conclusion, this study utilized cell experiments, network pharmacology, and molecular docking to investigate the potential mechanism of HYD in treating diabetes. The findings offered a preliminary understanding of how HYD may work and provided a new avenue for further research on its mechanism in diabetes treatment. Additionally, these results serve as a theoretical foundation for the clinical application of HYD in the treatment of diabetes.Additional file 1: Table S1. Sequences of primers used quantitative real-time PCR. Table S2. Binding energy between HYD and four core targets. Table S3. ADMET parameters of HYD predicted using pkCSM. Figure S1. (A) Cell viability at different concentrations of HYD on C2C12 cells. (B) Effect of HYD on glucose consumption in insulin resistance model (C2C12 cells). ###P < 0.001, vs. the control group; **P< 0.01, ***P < 0.001, vs. the model group. Figure S2. Effect of HYD on the PI3K/Akt signaling pathway in insulin resistance model (C2C12 cells). The relative mRNA level of AKT (A), PI3K (B), GS (C), PEPCK (D), G6Pase (E) was measured by qRT-PCR analysis. ###P< 0.001, vs. the control group; *P < 0.05, **P < 0.01, ***P < 0.001, vs. the model group.


Nanofibers have gained much attention because of the large surface area they can provide. Thus, many fabrication methods that produce nanofiber materials have been proposed. Electrospinning is a spinning technique that can use an electric field to continuously and uniformly generate polymer and composite nanofibers. The structure of the electrospinning system can be modified, thus making changes to the structure, and also the alignment of nanofibers. Moreover, the nanofibers can also be treated, modifying the nanofiber structure. This paper thoroughly reviews the efforts to change the configuration of the electrospinning system and the effects of these configurations on the nanofibers. Excellent works in different fields of application that use electrospun nanofibers are also introduced. The studied materials functioned effectively in their application, thereby proving the potential for the future development of electrospinning nanofiber materials. Nanofiber materials have attracted much attention because of their extraordinary advantages that can bring many benefits to applications . Since tMany fabrication methods for nanofibers have been proposed in the literature, including the uses of hard, soft, and free templates. While hard and soft templates release a large amount of chemicals into the environment, the free template seems to be more environment-friendly, in which case, electrospinning is a free template technique that uses an electrical field to fabricate the polymer and polymer composite nanofibers ,11,12,13Though the mechanism of electrospinning is simple, many improvements can be carried out on the components of the system ,16,17. THerein, the manuscript proposes a critical review of the electrospinning system. First, the modifications made to components  of the electrospinning system are introduced, together with the effects on the shape of nanofibers. Later, the recent applications of nanofibers that are fabricated by electrospinning are suggested. Many modifications of nanofibers, including freeze-drying, deposition, and thermal treatment, can be applied to achieve suitable properties for many advanced applications.The basic electrospinning system consists of a syringe pump, material solution, nozzle, collector, and power source . The matA solution with one or many polymers that are well dissolved in a low boiling point solvent can be used as material for the electrospinning process. The viscosity of the solution material can be considered the most important factor when operating an electrospinning system ,32. It cThe multiphase structures of the electrospun nanofibers are formed through the phase separations of the polymers in an emulsion solution. Even though the polymers are well mixed in the solvents, the surface tension between materials separates them from each other. Here, one of the polymers acts as the continuous phase (surrounding), while the other acts as the discontinuous phase (droplet). As the solvent is removed, the polymer hardens and forms many complicated structures ,50. At tLee et al. electrospun the solution containing a mixer of poly(acrylonitrile) (PAN) and poly(vinylpyrrolidone) (PVP) a 52]. I. I52]. IThe ratio between the component polymers has been proven to be a decisive factor that affects their contribution in volume within the nanofibers. Narumi et al. electrospun the mixed solution of poly(styrene) (PS) and PVP in the N,N-dimethylformamide (DMF) solvent c 54]. T. T54]. TAnother option for the material for single nozzle electrospinning is the use of block copolymers. Although there is no major phase separation, the self-assembly process can also occur at the nanoscale . The volRecently, Zhou et al. proposed carbon fibers that are the result of the carbonization of the PMMA−PAN block copolymer a 67]. T. T67]. TRuotsalainen et al. made a clear investigation of the block copolymer polystyrene-block-poly(4–vinyl pyridine) (PSS–b–P4DP) fraction’s ratios and their effect on the morphology of the fibers b 68]. T. T68]. TThe different individual blocks in the block copolymer can exhibit their various properties independently. However, their interaction can contribute, and make the material suitable to be applied as a smart interface material. Li et al. introduced the electrospun block polymer poly(dimethylsiloxane)–block-poly(4–vinylpyridine) (PDMS–b–P4VP) as a switchable oil/water separate membrane c 69]. U. U69]. UAnother modification that has been carried out on the electrospun nanofiber, besides the selection of polymer materials, is the addition of fillers into the polymer matrix . Though 4 and PVP−ZnAc2) to fabricate PAN composite nanofibers as the precursor for carbonization  nanofiber composite used to store medicine and release it after a predicted period b 82]. I. I82]. Inization c 83]. A. A4 and In the electrospinning technique, a low boiling point solvent and a high boiling point solvent can be combined as co-solvents for the electrospinning solution. Because the vaporization rate of the solvent has a great impact on the formation of the polymer nanofibers, modification of the solvent can generate some special morphological structure for the material. On the other hand, the dependence of solvent vaporization rates on the environment can also vary, thereby opening the opportunity for the structure to be modified even further ,96. ThouZaarour et al. used the combination of acetone and DMF to prepare the solution for the production of electrospun polyvinylidene fluoride (PVDF) nanofibers a 98]. W. W98]. W2 that can be generated simply using a thermal treatment on composite nanofibers  and the fiber solidifying, the high vaporization rate results in the hollow structure of the core. Meanwhile, Yoon et al. dissolved PVP in DMF and water together with RuCl3/Mn(OAc)2 (1:2) (3 and Mn(OAc)2 are the precursors of the RuO2/Mn2O3 complex. During the calcination process, the DMF quickly vaporizes, forming a hollow metal oxide outer shell, since it is the first solvent to vaporize. Water is vaporized at higher temperatures, and finally forms the core of the metal oxide fibers. In this study, the heating rate of the calcination process also plays an important role in the formation of the morphology of the fibers.When there are fillers in the solution, special structures can also be formed. Lee et al. introduced a tube-in-tube structure of SnOnofibers b 100]. . 2 that )2 (1:2) c 101]. . 2 that As mentioned, the nozzle is one of the main components of the electrospinning system. That is the medium to transport the potential charge from the power source to the solution. The nozzle is usually made from stainless steel to prevent any unwanted reaction while having high electrical conductivity. The used nozzle can have different sizes depending on the viscosity of the material solution; the high-viscosity solution with high surface tension can make it hard for the solution to flow through a small sized nozzle. However, the nozzle with a higher gauge  can produce smaller nanofibers. With one single nozzle acting as the only output for the material solution, there are fewer parameters to control. However, the spinning process can be conducted stably, and uniform nanofibers can be collected. Therefore, to date, it remains a favorable technique in the electrospinning process. Note that many simple nozzles can be used at the same time, and each of them can be provided with different polymer solutions ,107. TheThe coaxial nozzle  is a special nozzle, where a larger nozzle covers a smaller nozzle a. The noIn the application of oil–water separation, the membrane material must have good physical properties. The coaxial nozzle was used by Ma et al. to fabricate the fibers with the polyimide (PI) as the core, and CA as the shell of the fibers b 112]. . 112]. AHowever, the size of the outer nozzle has to be large enough to cover the inner nozzle, leading to the large diameter of fibers. The large diameter of fibers may be a disadvantage of this nozzle set, reducing the surface area of the nanofibers. Lee et al. sought to reduce the size of the fibers by using a mixture of PAN and PVP as material for the outer nozzle, and PMMA as material for the inner nozzle c 113]. . 113]. T4 dissolved in ethanol was loaded into the outer nozzle. After the carbonization, TiO2 fibers with the desired inner channel were obtained as the oil, and the PVP decomposed. It is clearly shown that each inner nozzle loaded in the outer nozzle is responsible for the formation of a single channel. Using this method, the number of channels in the nanofibers can be controlled. However, the number of channels that can be loaded seems to be limited, due to the relationship in size between the inner and outer nozzles.The number of inner nozzles seems to be able to be increased to the desired number. For example, Zhao et al. surveyed how the number of inner nozzles affects the morphology of the nanofibers d 116]. . 116]. IThe purpose of the side-by-side double nozzle is to fabricate a Janus interface material (Janus system), where the two materials with different wettability are attached to each other a. The elKnapczyk–Korczak et al. introduced Janus nanofibers constructed from PS and CA using side-by-side nozzle electrospinning b 130]. . 130]. IIn industrial production, multiple nozzles and nozzles with less electrospinning can be used to increase the production rate, but excellent control is required for the uniformity of the nanofibers ,134. MulIn addition to enhancing the fiber production rate, the multiple-nozzle system makes it possible to fabricate fibers from different materials simultaneously . HoweverTo address some drawbacks of nozzle-based electrospinning systems, nozzle-less electrospinning has been developed. Theoretically, the polymer jets of this system are generated by an external force (high voltage) added to create perturbances and obtain conical spike surface waves like Taylor cones . A nanofBy loading extremely high voltages on the free liquid surface, numerous jets can be obtained simultaneously, which means a high production capacity can be achieved in the nozzle-less electrospinning technique. Moreover, obstacles caused by nozzles are absent in this system, like electrospinning of colloidal suspensions or needle clogging . HoweverPlanar is the simplest structure of a collector, where a metal plate is used as a collector. Though the structure is simple, most of the fibers can be collected without the loss of material. The collected fibers are arranged in random directions. However, there are situations where the fibers are swollen. In this case, a large amount of solvent is hard to vaporize during the spinning process, which can be caused by the environmental condition, or the component of the electrospun solution. The remaining solvent pulls the surrounding polymer materials together and slowly dissolves them. To overcome this limitation, another type of collector has been developed.The rotational collector (drum-type collector), whose working mechanism is similar to that of a winder machine, can be used to collect the electrospun nanofibers a. The drThe nanofibers that were collected by the traditional planar collector can have a very random orientation. However, some of the advanced applications can have specific requirements for the structure of the membrane material. Many efforts have been made to align the electrospun nanofibers following a designed pattern.Because of the limitation in aligning fibers using a drum-type collector, Tan et al. proposed a method to align the electrospun nanofibers using a 3D collector a 146]. . 146]. TIt was declared that topography is still one of the most critical conditions for cell culture, especially stem and bone tissues . To dateThough most of the nanofibers should be collected in a dry environment, there are some exceptions. In some cases, the electrospun nanofibers can be collected in a bath collector containing liquid base material.Many methods have been proposed to generate porous structures for the polymer fibers. However, these methods usually require sacrificial materials, but the removal of the sacrificial materials can also affect the main materials. McCann et al. electrospun a PAN solution directly into a bath of cryogenic liquid (nitrogen liquid) to create highly porous PAN nanofibers a 150]. . 150]. BA variation of electrospinning is sol–gel electrospinning, where the nanofibers still hold solvents inside the fibers. One example of sol–gel electrospinning was when the poly amid 6/66 (dissolved in formic acid and acetic acid) was used as the material. To overcome the limitation, Franco et al. spun the nanofiber directly into a bath containing distilled water b 151]. . 151]. TTo intensify the electric field and enhance jet stabilization in the electrospinning system, auxiliary electrodes are employed, which control the deposition and diameter of electrospun nanofibers . Ring, cOther than the electric field derived from auxiliary electrodes, a magnetic field derived from permanent magnets can also be used to assist the electrospinning to produce highly aligned fibers. The most common setup is a pair of permanent magnets installed between the collector of the conventional electrospinning with no direct contact between them a. When tNearfield electrospinning was designed to completely overcome the shortcomings in random nanofibers generated by traditional electrospinning systems. Here, the distance between the nozzle and the collector is dramatically reduced a. It was−1. Such high feeding rates open up the potential for electrospinning techniques on an industrial scale.Traditionally, the electrospinning technique has utilized direct current (DC). However, during the development of the electrospinning technique, alternating current (AC) was applied to limit the accumulation of electrical charge on the collected nanofibers. Here, the frequencies and waveforms of AC used for the electrospinning process were proposed in Electrospinning can produce outstanding candidate materials for a wide range of applications. However, there are many applications where the enhanced performance can be carried out by the modification in nanofibers morphology are few in number. Some of the representative applications can be named including air purification, sound absorption, heat retention, etc. ,169,170.The after-treatment of the electrospun nanofibers also opens up the potential for more advanced applications. The most popular treatment is the carbonization process at high temperatures. There, electrospun nanofibers are converted into materials with different compositions depending on the carbonization conditions. The conditions that contribute to the properties and structure of the outcome material are the electrospun solution component, carbonized temperature, environment, and heating rate. While the polymer can act as the precursor that is converted into carbon material, it can also serve as the template for the structure formation of metal or metal oxide. Though the high surface area of the product nanofibers can improve the performance in the application by prioritizing the interaction between the active material and the working environment, their low physical properties limit their use in the mentioned applications. Instead, excellent electrical conductivities make them ideal materials for the development of applications involving electrochemical activities .2) blend solution  (PVDF) fibers. Consequently, the PVDF−SiO2 nanofibers exhibited a separation flux of 2963 L·m−2h−1 and a separation efficiency value of 99.4%, which indicates its suitability for use for oil/water separation. Du et al. represented a functional separation membrane through a one-step electrospinning method. They produced a PVDF/PVP−TiO2 hydrophilic nanofiber membrane by using a blend solution  blensolution b 176]. . 2) blenIn another example, Wang et al. produced a switchable oil–water separation membrane based on natural loofah and PVDF through side-by-side nozzles c 177]. . 177]. TTissue engineering, known as regenerative medicine, has in recent years been developed rapidly as an effective treatment method for tissue injuries by providing the appropriate physiological microenvironment. One of the most important components of tissue engineering is the scaffold that supports the growth of cells and provides a vector that delivers the biochemical factors . BecauseIn bone tissue engineering, the prioritized properties of the scaffold are the high porosity and mechanical properties of the membrane. Since electrospun nanofibers can construct a membrane with extraordinarily high porosity, fillers can be added to the nanofibers to improve their mechanical properties. In addition to the polyhydroxybutyrate (PHB) matrix in the nanofibers, Toloue et al. added chitosan and alumina nanowires as the filler for the nanofibers a 179]. . 179]. T−1 at a current density of 1 A·g−1. Moreover, to improve the capacitance performance, introducing heterogeneous elements to the CNF’s surface by oxygen plasma treatment was conducted. As a result, the capacity value is enhanced more than 1.5 times the non-plasma-treated CNFs (358.2 F·g−1 at 1 A·g−1). In another approach, Serrano et al. developed a strategy to generate flexible porous CNFs derived from electrospun PMMA-block-PAN copolymers nanofibers , which empowers the synthesis of nanomaterials with precisely controlled porosities and morphologies (2O3/nanoporous carbon (NPC) and Fe3C, respectively. Through electrospinning using a mixed solution of MIL-88A, PMMA, and PAN, following hydrothermal treatment and carbonization to obtain Fe2O3/NPC decorated on Fe3C implanted porous carbon nanofibers. The resulting MOF-derived electrode materials exhibit a high specific capacitance of 531 F·g−1 at 1 A·g−1. It is worth noting that porosity plays an important role in enhancing supercapacitor performance, and highly porous supercapacitor electrode materials can simply be obtained using an electrospinning system.Supercapacitors could improve performance by varying the morphology of electrospun nanofibers. In particular, porous carbon nanofibers are actively studied to maximize the supercapacitor performance due to their high surface-to-volume ratio with the electrolyte, thereby efficiently transporting electrons in the longitudinal direction. For instance, Nam et al. electrospun the solutions using mixed PAN and PS to obtain polymer nanofibers a 184]. . 184]. Dnofibers b 185]. . −1 at ahologies c 186]. . −1 at a3O4) and nickel oxide (NiO) nanofibers were obtained as alternative anode materials through a similar process . . 3O4) anstrategy b 194]. . 3O4) an4Ti5O12, CuFe2O4, ZnCo2O4, and TiNb24O62) which are well-known for their low-toxicity, reduction total cost, and tunability of working voltage and energy density by varying the metal ratio . . −1 cm−22 nanotubes  and the capability of detecting low-level acetone (10 ppb). To induce a change in the surface of nanofibers, as well as the addition of a hetero-component to the as-spun solution, exposing the nanofiber to oxygen plasma also promotes an increase in the sensor’s response. For example, oxygen-plasma-treated ZnO nanofibers show excellent acetone-sensing properties, due to their specific surface area and porosity increase (In recent years, attention to electrospinning metal oxide nanofibers in gas sensing applications has increased due to their unique structures and good electrical properties . Needlesanotubes a 203]. . 2 nanotincrease b 204]. . 2 nanotElectrospinning is a method of manufacturing nanofibers. Though the materials for the electrospinning processes are usually polymer solutions, the treatments on the nanofibers and extensive choices of materials allow many kinds of materials to be produced. To date, the materials that can be provided by electrospinning include polymer, polymer composite, metal, and metal oxide nanofibers. On the other hand, modifications to the electrospinning system configuration can lead to various changes in the collected nanofiber membrane. Firstly, not only does the use of special nozzles and collectors alter the morphology of the electrospun nanofibers, but the combination of different solvents and materials in one single electrospun solution can also lead to the same results. Furthermore, the after-treatment carried out on the nanofibers can convert them into different materials. Especially carbon nanofibers, which have a significantly high surface area created from the removal of sacrificing materials, can be harvested from the carbonization of electrospun nanofibers. Secondly, the addition of extra parts, which are used to control the pathway of the electrical field, can align the nanofibers following a designed pattern. In short, there is no limitation in the morphology and alignment of nanofibers that can be produced by electrospinning, opening up the potential to be further developed in the future. However, the disadvantages of the electrospinning process are that it is highly dependent on the environment humidity and stability of the power source, restricting the use of the technique in specific conditions. The applications of these nanofibers were also introduced in the review. It is clear that the electrospun nanofibers have been used in many applications, from simple applications, such as sound absorption and air purification, to highly advanced applications, like sensors, catalysts, and energy storage. The electrospinning method has great potential to provide materials with excellent properties, while it also offers many opportunities for further improvement.


Antimicrobial resistance (AMR) is an urgent threat to global public health and development. Mitigating this threat requires substantial short-term action on key AMR priorities. While international legal agreements are the strongest mechanism for ensuring collaboration among countries, negotiating new international agreements can be a slow process. In the second article in this special issue, we consider whether harnessing existing international legal agreements offers an opportunity to increase collective action on AMR goals in the short-term. We highlight ten AMR priorities and several strategies for achieving these goals using existing “legal hooks” that draw on elements of international environmental, trade and health laws governing related matters that could be used as they exist or revised to include AMR. We also consider the institutional mandates of international authorities to highlight areas where additional steps could be taken on AMR without constitutional changes. Overall, we identify 37 possible mechanisms to strengthen AMR governance using the International Health Regulations, the Agreement on the Application of Sanitary and Phytosanitary Measures, the Agreement on Trade-Related Aspects of Intellectual Property Rights, the Agreement on Technical Barriers to Trade, the International Convention on the Harmonized Commodity Description and Coding System, and the Basel, Rotterdam, and Stockholm conventions. Although we identify many shorter-term opportunities for addressing AMR using existing legal hooks, none of these options are capable of comprehensively addressing all global governance challenges related to AMR, such that they should be pursued simultaneously with longer-term approaches including a dedicated international legal agreement on AMR. Antimicrobial resistance (AMR) poses an urgent threat to global public health and development. Actors at all levels—consumers, prescribers, countries, and international agencies—need to move quickly if we are to mitigate the threat posed by AMR. Reconciling this urgent need for global action on AMR with the slow pace of international law-making is one of the main challenges to crafting a global governance system that can effectively, fairly and feasibly manage the antimicrobial commons.Legally binding international agreements represent the strongest formal mechanisms through which countries can make commitments to each other . A grandNegotiating a complex international legal agreement on this vast scale, however, requires significant political mobilization and substantial financial commitments. The level of investment needed for global health treaties has rarely been forthcoming. Substantial international leadership is required to convene countries for negotiations, and substantial costs are associated with negotiating and maintaining treaty governance structures . DevelopInternational law, however, may still offer valuable opportunities in the short-term, even without a grand bargain or broader longer-term legal agreement that comprehensively addresses all drivers and dimensions of AMR. International law is a valuable tool which can provide a regulatory framework that makes country commitments transparent, provides accountability for fulfilling those commitments, and disincentivizes deviation. The far-reaching nature of AMR and its root social causes mean that action is needed in domains that are already governed by existing international laws and institutions. In this article, we identify opportunities for strengthening the global governance of AMR through existing channels using “legal hooks” in various international agreements or using the structures within mandates of existing international organizations. We do this analysis by developing a list of ten key global actions needed to address AMR and then surveying the existing legal landscape for existing mechanisms through which these actions could be pursued. Overall, we identified 37 opportunities for acting on AMR using existing international legal mechanisms.One consequence of the complex and far-reaching nature of AMR is that facets of the problem fall into domains already governed by international law. These domains could provide legal hooks for AMR regulations, wherein existing legal provisions or principles governing closely related matters can be used either as they exist or revised to address part of what is needed for AMR. These legal hooks include existing legally binding commitments between state parties in international law that authorize necessary AMR actions or that have mandates within which new AMR-specific provisions could easily be added. For example: the International Health Regulations (IHR) already require state parties to take rapid action to detect and respond to public health risks; the World Trade Organization (WTO) Agreement on the Application of Sanitary and Phytosanitary Measures (SPS) already establishes regulations on food safety and animal and plant health standards for WTO members; and the Basel, Rotterdam, and Stockholm conventions already govern the use, trade, and disposal of hazardous chemicals, products, and wastes. After excluding regional bodies, including some very impressive developments in European Union legal frameworks on veterinary medicinal products , market Additionally, as part of their respective constitutions, many international organizations—including the World Health Organization (WHO), United Nations Food and Agriculture Organization (FAO), and United Nations Environment Program (UNEP)—have powers to create international legal agreements. Specifically, both WHO and FAO’s constitutions (Articles 19 and 14 respectively) allow their plenary decision-making bodies  to adopt agreements that become legally binding on their membership after a two-thirds majority vote and subsequent ratification at the domestic level , 23. TheOne important limitation is that each international organization is restricted to making legal agreements that are consistent with their own constitutional mandates. A broad agreement that addresses all drivers and dimensions of AMR would likely need to transcend these sectoral divisions and require immense collaboration between these bodies; however, given their powers to convene countries and recommend international policy, these agencies are in a position—individually or collaboratively—to support the creation of legally binding obligations within their specific mandate areas. Each of these technical agencies, along with the World Organization for Animal Health (OIE), have substantial powers to collect and interpret scientific data, recommend national and international actions, and provide funding and technical assistance to achieve global aims within their particular domains. Leading non-governmental organizations can also take important steps towards addressing AMR by mobilizing awareness, interest, and action. Additionally, the Global Fund to Fight AIDS, Tuberculosis & Malaria, Gavi, and UNITAID could incorporate AMR into their portfolios.access to antimicrobials, action is required to: (1) develop equitable pricing and licensing models to support access to antimicrobials in resource limited settings; (2) end the manufacturing, sale and export of substandard, falsified and banned antimicrobial products; and (3) strengthen health systems to improve infection prevention and control and reduce the need for antimicrobials. On the conservation front, more concerted international action is needed to: (4) strengthen surveillance of antimicrobial use and antimicrobial resistance in humans, animals and the environment; (5) promote the responsible use of antimicrobials in humans; (6) promote the responsible use of antimicrobials in animals and agriculture; (7) safeguard the effectiveness of newly developed antimicrobials; and (8) limit antimicrobial contamination in the environment. For innovation, global action is needed to: (9) incentivize the development of new antimicrobials and related technologies; and (10) facilitate the development of new antimicrobials and related technologies (Table To explore opportunities for addressing AMR through existing legal mechanisms, we developed a list of ten key global actions to address AMR across access, conservation and innovation. To improve ettings;  end the Banning the manufacture, sale and export of substandard and falsified drugs is a prime opportunity for addressing AMR access concerns through international law. These substandard and falsified drugs are a growing global problem that can cause morbidity and mortality. Substandard drugs have not passed the usual standard and quality testing protocols and include falsified medicines that have been deliberately mislabeled with respect to their origin or contents . A speciAnother way to improve access to safe and effective medicine is through patent licensing . Under tInternational law could be a powerful tool to address the continuing rise of non-human antimicrobial use. A ban on non-therapeutic antimicrobial use through the FAO, or by employing regulations on trade through the SPS, could substantially enhance global antimicrobial stewardship. Either mechanism could include a minimum requirement of a universal ban of antimicrobial growth promotion and could also require parties to phase out prophylactic and metaphylactic non-human use of all antimicrobials by a certain year, such as 2030. Although the impact on human health remains imprecise, the non-human use of antimicrobials vastly exceeds global human use and has historically repeatedly selected for resistance factors that have impacted human health , 11, 22.Revisions to the TBT, SPS, and IHR could also be made to promote appropriate antimicrobial use such as by banning the commercial advertisement, marketing, and sales promotion of antimicrobials. These international efforts could reduce misinformation about antimicrobial effectiveness, dampen the transnational spread of this misinformation through social media, and strengthen efforts to curb the substantial international grey and black markets supplying substandard and falsified antimicrobials.Beyond legal hooks, the mandates of various international organizations with the power to create international laws could be used to promote conservation goals. A WHO treaty could start by protecting human health and end with a call to transition away from using critically important antimicrobials in agriculture, and an FAO treaty could start with a call to transition away from critically important antimicrobials and end with a focus on developing, promoting, and supporting sustainable agricultural practices. Such treaties might emanate from Article 19 or 21 of the WHO’s constitution and Article 14 of the FAO’s constitution respectively, engage with WHO’s AWaRe framework, create provisions to limit the agricultural use of critically important antimicrobials for human health, and set standards to protect any new antimicrobials for future human health needs. In addition to being feasible within the existing legal mandates of the WHO and FAO, at least one large pharmaceutical company has committed not to license new antimicrobials for animal use , demonstA third possible avenue could be to strengthen surveillance and data sharing by adopting new legally binding regulations with existing institutional powers. New international standards are also required to standardize antimicrobial usage data collection, which should include statutory national reporting requirements of domestic and international sales data by commercial antimicrobial producers and distributors. A global surveillance infrastructure has to be politically neutral, transparent, and overseen by appropriate technical organizations. Ultimately these data must be gathered in a way that elicits trust. To avoid underreporting and geographic biases, the international community will probably have to establish and finance an integrated network of independent AMR reference laboratories around the world. At present there are a limited number of countries participating in WHO’s GLASS program as a result of data sharing concerns, different standards for data collection and reporting, different definitions of AMR, and limited data collection capacity in some countries , 24. GivInternational law presents several opportunities to address the existing governance and market failures that have led to insufficient levels of antimicrobial innovation and to incentivize and facilitate the development of new antimicrobials and related technologies. The IHR, for example, could be revised to require national investments in research and development for new antimicrobials, alternative therapeutics, diagnostics, social interventions and infection prevention approaches that are proportional to national economic capacity and antimicrobial use. Existing legal mechanisms can also explore new and innovative funding models. In fact, some new and promising government and joint public–private partnerships have already arisen in response to the global challenge of restoring the pipeline for new antimicrobials . But druLegal mechanisms can also be used to facilitate the development of new antimicrobials and their alternatives. At the very least, a dynamic list of all AMR-related research and development needs can be compiled and published by WHO, FAO, OIE and UNEP which could help to reduce inefficient duplications . Such a Overall, we have identified 37 possible mechanisms to strengthen AMR governance in the short-term using existing legal hooks and structures. All of these mechanisms have the theoretical potential to expedite AMR action by focusing on narrowly defined issues and amending or employing elements of existing agreements. In many cases, these mechanisms also offer an opportunity to engage with actors that do not usually participate in AMR policymaking. However, adapting existing international law to meet AMR challenges also presents several practical challenges, among which are a lack of appetite for revising existing international agreements, the proliferation of uncoordinated global AMR actions, and the difficulty of consolidating enough expertise on every treaty’s unique procedures and norms while also ensuring enough future expertise on AMR in those governing bodies. For these reasons, we suspect that efforts to use amend existing law to create short-term action on AMR will be more fragmented, less focused, and ultimately less successful than long-term efforts to create an enduring legal agreement for AMR.Future attempts to curb AMR should be comprehensive in scope and coordinated at the international level. But significant challenges exist when creating responses beyond the national level. The most pressing of these challenges are prioritization, inequality, implementation, and metrics . AMR goaAlthough AMR is a One Health problem—and the WHO-FAO-OIE tripartite has taken admirable steps to ensure that it is seen as such—many countries continue to see AMR exclusively as a human health issue. This leads to AMR being addressed separately from animal, agricultural, environmental and trade issues. Successfully using the various international legal mechanisms we have identified above will require breaking down these silos and ensuring that officials in other sectors recognize AMR as being sufficiently important for their attention, action and leadership. The absence of a clear linear correlation between antimicrobial usage and AMR burdens means that regulatory interventions will have to go beyond simply addressing antimicrobial consumption, yet communicating these challenges outside health and veterinary fields remains difficult.Every use of an antimicrobial can theoretically select for resistant organisms and resistance genes, with repercussions for global AMR. Reducing antimicrobial use across the human health, animal and agricultural sectors will thus reduce but not eliminate the likelihood of AMR proliferation. As a “silver bullet” solution to AMR is unlikely to ever exist, it is important to protect antimicrobial effectiveness using the strongest available tools for international commitment and cooperation. While an all-encompassing treaty would likely be best for ensuring equity, minimizing duplication of efforts, and avoiding loopholes that threaten the common pool of antimicrobial effectiveness, negotiating such a grand bargain could take several years. Substantial action is required in the short-term to safeguard human health and development. The idea of negotiating a series of revisions to existing international legal agreements is not incompatible with the idea of a single comprehensive grand bargain and, in the short-term, may permit quicker progress on specific dimensions of AMR that in turn help to build momentum for greater progress thereafter. Making revisions to several existing treaties may not be as efficient or elegant as a single treaty fully encompassing of a grand bargain, however, pursuing some, or several, of these strategies in parallel could promote continued and increasing international cooperation on AMR, and offer opportunities to increase meaningful One Health cooperation with actors situated outside the traditional AMR sphere.


Women in science–Precision medicine 2021, to celebrate the invaluable contributions of female scientists as they advance the frontiers of science.Recently, while attending the Precision Medicine and Functional Genomics 2022 Symposium, I heard Her Excellency Dr. Maryam Matar present on Precision Health in the United Arab Emerits. Her remarkable work served as a powerful reminder of the vital role women play in the field of science. As a matter of fact, 35% of the presenters at the meeting were female. While the halls of science were once dominated by men, these days the unmistakable sound of high heel pumps can be heard echoing through them. This Research Topic, In the eight manuscripts presented here, we have leading female authors hailing from over four countries and three continents, representing a diverse range of institutions, and tackling topics spanning from bench to bedside. Among the papers, three focus on topics related to careful observations of new case reports of unusual tumors, obesity in relation to dosing for cancer treatment, and the influence of CYP2D6 and CYP3A5 polymorphisms specifically in bisoprolol treatment of Chinese hypertensive patients. Identifying pharmacokinetics and pharmacodynamics with biomarkers in ethnicity, particularly outside the Caucasian population, is of utmost importance. These brilliant female investigators possess an incredible ability to recognize even the smallest changes and uncover crucial medical findings from these subtle differences that may be overlooked by others.Additionally, seven of the articles in this Research Topic are in the field of oncology, addressing various aspects of precision medicine in this rapidly developing area. These women explore topics ranging from the fundamentals of how to properly dose patients to the intricate mechanisms of developing agents in the age of molecular targets. Their research covers a wide spectrum of cancers, from the most common, such as breast cancer, to the rare craniopharyangioma. These scientists are also delving into preclinical studies to understand the origins of cancer, pathways, and clinical studies to examine patient response to treatment.We are thrilled to present this topic and highlight the success of the vast array of women scientists making their mark in every corner of science. I eagerly anticipate the next round of female scientists who will share their findings under the new Research Topic: Women in Science–Precision Medicine 2023.AC worked on the Research Topic, edited some of the manuscripts, and wrote the editorial. AT worked on the Research Topic, edited some of the manuscript, and reviewed and revised the editorial. All authors contributed to the article and approved the submitted version.


The emergence of positive psychology in the broader field of psychology has resulted in an epistemological and theoretical revolution and paradigm shift that have, in turn, had numerous implications on research orientations  scale with an intercultural perspective that measures the internal and external conflicts with religion and spirituality experienced among Zimbabwean adolescents living with HIV.The very particular topic that is spirituality leads to stances that sometimes question the process of quantification. However, refusing to measure is to disqualify spirituality from a part of science. The following articles propose several scales for evaluating different aspects of spirituality. In their article, following up on James Fowler's work on the development of faith, Ford et al. discuss the links between spirituality and the study of character in positive psychology using different methods to better understand latent profiles such as the spiritual character.Finally, To conclude this introduction, we would like to emphasize two points that put this special Research Topic into perspective. First, is the popular culture which views spirituality as being positive and the source of wellbeing. This caricatured view is evident, for example, in the opposition that views religion as negative and spirituality as positive, a Manichean view that has been noted many times (Zinnbauer et al., The second point relates to the focus on a strictly positive vision of existence, which prevents us from grasping the complexity of human life. From a dialectical perspective, negative emotions can serve the adaptive functions of survival and self-fulfillment. As it happens, these existential questions are easily anchored to spirituality whose essential function is a search for meaning. The existential perspective of positive psychology Wong, , aims atNR acted as the co-ordinator of the Research Topic and wrote the first draft of the editorial. CRB, CB, NB, ON, CT-F, LVZ, and ER made significant intellectual contributions to the Research Topic and provided input on the editorial. All authors contributed to the article and approved the submitted version.


This commentary defines what shared yet differentiated ethical responsibilities to tackle antimicrobial resistance (AMR) mean, by introducing a threefold principled account of AMR global governance. It argues that the principles of solidarity, subsidiarity, and stewardship can be especially helpful for further justifying some of the universal, differentiated, and individual responsibilities that Van Katwyk et al propose. The upshot of my threefold principled account of AMR global governance is a less ambitious AMR treaty, one that can only justify (i) universal duties of global coordination (as per the principle of solidarity); (ii) differentiated duties to local communities, which bear the primary AMR responsibilities (as per the principle of subsidiarity); and (iii) individualized duties for ensuring truthful, evidence-based, consistent, and timely shared accountable communication (as per the principle of stewardship). Global health experts have widely debated the need for an effective global governance structure to regulate the global collective problem of antimicrobial resistance (AMR) –3. An efgood global governance structure for AMR regulation. By ‘good’ I mean a global governance structure that is ethical and effective in upholding the common good. By ‘common good’ I do not mean the maximized welfare for the greatest number. Rather, I mean the set of values and reasons that justify collaboration with others in a way that enables mutual flourishing. My proposed threefold principled account of AMR global governance provides the practical reasons that justify why some of the treaty provisions that Van Katwyk et al. [Building on Van Katwyk et al.’s model , my commk et al.  suggest The proposed AMR treaty establishes universal duties of global coordination, including for example, setting a global target and benchmark of progress, organizing an annual multi-stakeholder forum coupled with an independent scientific stock-take to inform policy decisions on AMR , 3. I woThe universally-shared responsibilities that the AMR treaty contains are predicated on the principle of solidarity because they are grounded on our shared vulnerability to the problem of the reduction of antimicrobial effectiveness . This isIt is not clear, however, whether these two criteria are equally relevant in determining obligations or whether one criterion takes precedence. Stipulating contribution is typically relevant for establishing the legal causal link between the problem and those who, having caused it, have a legal duty to remedy it. Contribution is therefore key if the purpose of the AMR treaty is to assign legal responsibilities for addressing the AMR problem. However, if the AMR problem goes beyond what is legally required and calls also for more general, ethical responsibilities – as I think it does -- then the broader criterion of capacity should be the chief one for allocating differentiated responsibilities. My second principle of AMR global governance explains why and how.prima facie best positioned to effectively solve problems requiring the coordination of persons, institutions across sectors, and nations. The principle of subsidiary justifies delegating to higher levels of governance only as necessary, when the local capacity to solve a problem has proven insufficient [As a structural principle, subsidiarity justifies a bottom-up approach to decisional authority allocation among multi-level stakeholders , 6, 8. Afficient , 6, 8. IThe principle of subsidiarity and its emphasis on local communities’ primary responsibility may challenge Van Katwyk et al.’s model, according to which high income countries (HIC) ‘have a greater moral obligation to shoulder greater burdens when it comes to tackling the resulting global fallout of AMR’ . One wayFirst, the fact that a certain group of powerful nations has contributed more to the global burden of AMR does not automatically give such a group license to interfere—for example, through an international AMR fund—in developing countries’ domestic affairs and in how they should manage their AMR issues. This is not to say that all AMR treaty provisions should be banished because they all interfere with domestic affairs. There is a relevant moral difference between (i) an international AMR fund that dictates how locals should micro-manage their AMR problems, and (ii) an AMR treaty where parties establish together a global target and benchmark of global progress, and multilaterally agree to an annual forum and an independent scientific stock-take to help inform AMR policies , 3. As aAlthough Van Katwyk et al.’s model does not explicitly adopt a top-down global governance approach, it leaves room for this kind of top-down measure  that would need further justification to be reasonably accepted. For example, if certain top-down interferences in local affairs were more efficient and cost-effective than leaving local governments to first try to manage their AMR problems by themselves, then it seems that Van Katwyk et al.’s model, predicated on a utilitarian cost-benefit analysis, would favor such interferences. However, if one were to follow the ethical reasons that the principle of subsidiarity provides, one would object to them, for the purpose of taking inclusion and participation of local communities seriously. Subsidiarity would tolerate certain inefficiencies for the sake of respecting local communities’ right to address their own AMR issues prior to asking for other countries’ assistance.prima facie and ceteris paribus greater stewardship capacity, given their better knowledge of the epidemiological reality and the medical culture in their community. This leads me to the third principle of AMR global governance.Secondly, the fact that a certain group of powerful nations has more greatly contributed to the global burden of AMR does not automatically entail that such group also possesses greater capacity effectively and ethically to address the AMR global problem. Likewise, the fact that a certain group of powerful nations has more financial capacity to address AMR problems does not automatically entail that such group also possesses greater AMR stewardship capacity. On the contrary, local communities have As a governing principle, stewardship justifies when intervening and assisting are reasonable and legitimate acts of care and when not, further complementing and specifying the principles of solidarity and subsidiarity . The priVan Katwyk et al. claim that “one of the greatest hurdles for global antimicrobial stewardship has been the lack of internationally standardized and transparent data collection on antimicrobial usage and AMR” . I wouldIn discharging the AMR mandate to conserve antibiotic effectiveness, the principle of stewardship calls for the virtues of clarity and prudence in striving to share truthful and accountable communication with other stakeholders. The AMR treaty entrusts this mandate to all parties to the treaty. In doing so, parties become stewards of the AMR mandate. The virtue of clarity would require stewards to focus on honing their AMR communication skills with one another. The virtue of prudence would require stewards to move with caution, by limiting their mandates to fulfilling their mission of sharing truthful and accountable communications necessary to conserve antibiotic effectiveness. The principle of stewardship therefore would justify a less ambitious AMR treaty -- one that channels global health’s and AMR’s limited resources towards sharing truthful and accountable communications. This should be AMR mandate’s priority in conserving antibiotic effectiveness. Under my proposed account of AMR global governance, any treaty provisions that go beyond this priority would need to be further justified.I have defined what shared yet differentiated ethical responsibilities to tackle AMR mean, by introducing a threefold principled account of AMR global governance. I argued that the principles of solidarity, subsidiarity, and stewardship can be especially helpful for further justifying some of the universal, differentiated, and individual responsibilities that Van Katwyk et al. propose . The ups