Antimicrobial resistance (AMR) is a global public health concern that requires transdisciplinary and bio-social approaches. Despite the continuous calls for a transdisciplinary understanding of this problem, there is still a lack of such studies. While microbiology generates knowledge about the biomedical nature of bacteria, social science explores various social practices related to the acquisition and spread of these bacteria. However, the two fields remain disconnected in both methodological and conceptual levels. Focusing on the acquisition of multidrug resistance genes, encoding extended-spectrum betalactamases (CTX-M) and carbapenemases (NDM-1) among a travelling population of health students, this article proposes a methodology of ‘stool and stories’ that combines methods of microbiology and sociology, thus proposing a way forward to a collaborative understanding of AMR.A longitudinal study with 64 health students travelling to India was conducted in 2017. The study included multiple-choice questionnaires (n = 64); a collection of faecal swabs before travel , in the first week in India , the second week in India ; and semi-structured interviews (n = 11). Stool samples were analysed by a targeted metagenomic approach. Data from semi-structured interviews were analysed using the method of thematic analysis.The incidence of ESBL- and carbapenemase resistance genes significantly increased during travel indicating it as a potential risk; for CTX-M from 11% before travel to 78% during travel and for NDM-1 from 2% before travel to 11% during travel. The data from semi-structured interviews showed that participants considered AMR mainly in relation to individual antibiotic use or its presence in a clinical environment but not to travelling.The microbiological analysis confirmed previous research showing that international human mobility is a risk factor for AMR acquisition. However, sociological methods demonstrated that travellers understand AMR primarily as a clinical problem and do not connect it to travelling. These findings indicate an important gap in understanding AMR as a bio-social problem raising a question about the potential effectiveness of biologically driven AMR stewardship programs among travellers. Further development of the ‘stool and stories’ approach is important for a transdisciplinary basis of AMR stewardship.The online version contains supplementary material available at 10.1186/s12879-021-06713-4. Antimicrobial resistance (AMR) is a growing global public health concern, which has been defined by its bio-social nature . AlthougTo present the methodology of stool and stories, in this article we focus on the acquisition of multidrug resistance genes encoding the extended-spectrum beta-lactamase (ESBL) enzymes of the CTX-M group and the NDM-1 carbapenemases among a population of health students who travelled to India from different parts of the world. The mobility of healthy human populations has been shown to contribute to the dissemination of AMR globally , 11. MicApplying the methodology of stool and stories to understand AMR and travelling we studied both incidence of AMR in a particular travellers’ group, and how these travellers give meaning to AMR. By making use of these different methods to understand AMR and travelling we aim to learn about potential linkages between the laboratory and social worlds of AMR. Learning about such linkages is crucial for a transdisciplinary understanding of AMR and the development of AMR stewardship programs that attune to diverse everyday practices.The study involved 64 people from a total cohort of 207 master students studying global health from a university in the Netherlands and a university in Canada of different nationalities. In 2017 these students were travelling from the Netherlands, Canada, Colombia, and Thailand to the south of India to participate in a two-week education symposium. The decision to focus on students was dictated by two important features of this travelling group: first, health students might be familiar with AMR and potential routes of its acquisition, which could be beneficial for our explorative research; and, second, due to the characteristics of their education program, students experienced multiple recent travels prior to this study.The stool and stories approach included three methods of data collection: laboratory analysis of faecal swabs samples, multiple-choice questionnaire  travel history; history of antibiotic use during the previous year; health-related preparation for the trip to India; and demographic characteristics of the study group. The data were analysed using the software IBM SPSS Statistics Desktop Version 25.0. . All 64 participants filled in the questionnaire. Most of the students filled in the questionnaire when they were in India (70%).Of the 64 total participants, 45 participated in specimen collection. We provided participants with collection kits for faecal swabs, and this enabled them to collect samples themselves. The faecal samples were collected and stored in DNA/RNA shield  to ensure the stability of the metagenome during unrefrigerated transport and travel. Sampling time-points were: before travel (T0), during the first week in India (T1), and at the second week in India (T2). There was a small difference in participation for the faecal swabs at the moments in time. Before travel (T0), a total of 45 stool specimens were collected, from which 28 were collected in the Netherlands and 17 were collected directly at arrival to India for students coming from Colombia, Thailand, and Canada. During the first week in India (T1), 44 specimens were collected. In the second week in India (T2), 41 specimens were collected.Faecal swabs were processed at the medical microbiology laboratory in the Netherlands after travel as follows: For the extraction of metagenomic DNA, 200 μL of the suspended faecal swabs were added to a 2 mL vial containing 0.5 g of 0.1 mm zirconia/silica beads  and 1 mL of lysis buffer from QIAmp DNA stool kit (Qiagen). Samples were disrupted in a Magna Lyser device  in 3 cycles of 1 min. at 5,500 rpm. Subsequently, metagenomics DNA was isolated from the samples by using the QIAamp DNA stool kit according to the manufacturer’s instructions. DNA was eluted in 200 μL elution buffer and stored at − 20 °C until further analysis.blaCTX-M-1,blaCTX-M-2 and blaCTX-M-9 and blaNDM  was used as a significant cut-off. Statistical tests were performed by using IBM SPSS Statistics Desktop Version 25.0.The semi-structured interviews were conducted with 11 of the 64 participants to get a deeper understanding of how some of the participants viewed relationships between travelling, antibiotics, and AMR. In addition, we explored stories of participants about their health preparation for the trip to India, and precautionary health measures they thought were necessary before and during international travel. All interviews were conducted in April 2017, 2 interviews were conducted one week before the trip and 9 interviews were conducted within the first 2 weeks after arrival to India. The number of interviews was determined by data saturation. All interviews were conducted in person with the use of voice-recorder and transcribed verbatim. The analysis of the transcribed data was conducted in the NVivo 9 qualitative data analysis software with the use of thematic analysis .All students who participated in the study were registered and recruited through the university in the Netherlands. The study protocol was submitted to and approved by the local Medical Review Ethics Committee in the Netherlands. All participants signed informed consent forms. Although the students originated from partner universities in other geographic locations, ethical approvals from the partner universities were not required as all recruited participants were registered as students at the university in the Netherlands.blaCTX-M genes, of which 4 swabs contained genes from blaCTX-M-1 group and 1 swab blaCTX-M-9 group. During the stay in India, 35 students tested positive for blaCTX-M genes leading to a total positivity rate for these genes of 78%, which is a significant increase (p < 0.001). Thirty-two of 45 students (68%) acquired a new or additional type of blaCTX-M gene. Of the 45 students, 40 were tested at both time-points during the trip (T1 and T2). Of this subset 27 acquired a new blaCTX-M type during the trip and the majority: 13/27 (58%) were positive at both time-points, 6 only acquired a new blaCTX-M type in T2 and 8 students acquired blaCTX-M or an additional type of blaCTX-M at T1, but lost them again at T2. For blaNDM, only 1 of 45 had a faecal swab positive for this gene prior to travel. An additional 4 students acquired blaNDM during the stay and also this was a significant increase (p < 0.05)  students showed a faecal swab positive for 1% studenThe analysis of the questionnaires showed that the median age of the participants was 27, and the majority of students were female (73%). The cohort of respondents represented a very mobile group, which was shown by their travelling practices. The majority (83%) of respondents visited more than 2 countries within the last three months before their arrival to India. The primary travel destinations were within Europe and included Belgium (37%), Germany (35%), and the Netherlands (30%), but also Canada (13%) and Thailand (10%). All of the participants visited India. These travelling trajectories can be explained by the international nature of the education program that students were involved in. Canada, Thailand and India were the three countries students could opt to go to for an elective. In addition, the proximity of the Netherlands to Belgium and Germany could also have contributed to the high students’ mobility between these countries.Most of the participants did not take any antibiotics within the last year prior to the study , only a quarter of people took one course of antibiotics , and several people took 2 or 3 courses . Among those who did take antibiotics within the last year prior to the study, more than half was prescribed by a physician . However, 41% (n = 11) of those who used antibiotics within the last year informed us that they used non-prescribed antibiotics, which they got either from a family member or from a pharmacist without prescription in countries where it was possible.Concerning their travel preparation to India, 14 out of 64 respondents reported that they brought antibiotics with them to the trip. The most prevalent antibiotics were azithromycin , amoxicillin , and ciprofloxacin . Two students indicated that it was important to take some antibiotics with them when travelling to India as a precautionary health measure.While microbiological methods analysed how international travelling may contribute to the acquisition of resistant bacteria, the method of semi-structured interviews was aimed at gaining a deeper contextual understanding of the daily practices that students exercised during their travel. Exploring the meanings of AMR, the interviewees often described this phenomenon in biomedical terms—as an ‘evolution of bacteria to resist antibiotics’. Such descriptions were not surprising as our participants had a background education in health. In addition, the interviewees were also participating in the collection of stool samples and the survey, and therefore they were previously exposed to information about AMR.Building on a biomedical understanding of AMR our participants described several ways of how AMR can be developed and acquired. We distinguished two of such interrelated ways: first, AMR as an individual responsibility, and AMR as a medical phenomenon that can be acquired in clinical settings. This means that students associated mechanisms of AMR development with antibiotic use, and they connected AMR acquisition with clinical facilities.Specific bacterial strains are becoming resistant to antibiotics because of the really often use of antibiotics (S21)Antibiotic resistance is due to the fact that some people in many countries just taking many multi-resistant [antibiotics]. … The other reason is that many people don’t take the whole prescription that they’re supposed to take (S36)In the interviews, students explained that the development of AMR is determined by individual use of antibiotics, including self-treatment, interruption of prescribed antibiotic treatment and its overuse. For instance, our participants explained,Individual behaviour with respect to antibiotic use was defined by students as a major cause of AMR. In particular, the excessive amount of antibiotic use was associated with risks of resistance development.I know that especially some parts of the world, there is a lot of antibiotic use and because of this, this creates like bacteria that are already resistant to antibiotics and stay alive, and if this happened too much you create a resistance strain of antibiotics and I think this is becoming a more urgent issue. (S47)So I am aware of different countries have different levels of antibiotic resistance. Probably if I get treated in a country where there is like a hospital where there is a lot of bacteria around that are resistant and I am exposed to this, then I might not be able to have them treated. (S20)Apart from the individual use of antibiotics, several students highlighted that environmental and infrastructural factors may play a role in AMR acquisition. Some students distinguished between a ‘risky country’ where antibiotics are used inappropriately, and a ‘risky environment’ like hospitals where AMR can be easily acquired by visitors and patients. However, these two definitions of ‘risky’ places are interrelated, as a respondent below explained that the risk of acquiring AMR is higher if a person gets admitted to a hospital in a particular country:I always think about it [AMR] if I ever prescribed antibiotics and when I take it, not when I think of it when I am travelling or some kind, no, no, no. (S42)AMR, therefore, has been understood by our participants as rooted in individual practices of antibiotic use and in clinical practices of certain countries that create risks for AMR acquisition. These understandings were mirrored in students’ reflections on their health practices and travel preparations. Participants were surprised by our questions about the connection between AMR and travelling and they elaborated that they did not see such as a connection:While being aware of AMR, its biomedical nature and mechanisms, our participants argued that AMR as a problem was located in clinical settings rather than in public spaces. They did not associate and connect their international travelling practices with the potential risks of acquiring resistant bacteria unless they were admitted to a foreign hospital. This may indicate that while microbiological data highlight the importance of travellers’ social practices for understanding AMR, travellers themselves do not see AMR as a part of their social worlds but rather locate it in the clinical world.In 2018, more than 6 billion people moved across the world, which included more than 4.3 billion air travellers , approxiblaNDM during the trip was higher as compared to other studies [The different methods result in a different understanding of the relation between AMR and travelling. The microbiological findings from our study confirmed previous research , 16 poin studies , 16. We  studies . The datOur research had limitations. The sample size for all three methods was relatively small and the population was rather specific: health students who have prior knowledge of AMR. We understand that different results can be obtained from another group of travellers without an educational background in health. Moreover, the sample size for microbiological analysis was not equal at each moment as not all of the students who participated before travel (T0) were able to further participate in the study. However, this research demonstrates the potential fruitfulness of a transdisciplinary methodology of stool and stories.From the results, it becomes clear that the relations between AMR and travelling are understood differently by microbiological and sociological methods. While the analysis of stool showed how participants acquired resistant genes regardless of their antibiotic consumption; the analysis of the stories showed that participants constructed their understanding of AMR as a result of antibiotics use. Participants did not see travelling from one territory to another as a risk in itself see Fig. .Fig. 2AlThis discrepancy in understanding of AMR sheds an interesting light on the current practices and policies related to antibiotic stewardship. The analysis of stool raises questions about the potential practices of travellers that could have contributed to their acquisition of resistant genes, like consumption of antibiotics, travellers’ diarrhoea and different food choices –15. HoweReflecting on the results of sociological analysis, it is striking that the participants understanding regarding AMR is very much in line with international documents such as the Global Action Plan, a European One Health Action plan or the influential review on AMR developed by the British economist O’Neil, that highlight that it is the ‘systematic misuse and overuse’ of antibiotics that ‘put every nation at risk’ , 23, 24.Positioning stool and stories into a transdisciplinary dialogue challenges the current policy assumptions about AMR being primarily a problem of antibiotic consumption or a lack of antibiotic awareness. Rather, it may suggest a need for re-conceptualisation of AMR as a problem of environmental concern, broadening its current narrow focus on antibiotics and looking at various interactions between microorganisms, travellers, as well as local environments. This way AMR can become part of the world of travellers where some bacteria exist beyond the clinical settings and the world of travellers can become part of the laboratory where not all travelling practices are considered to be risky.Without the integration of diverse perspectives on AMR, the health risks and preventive strategies highlighted by the laboratory can fail to be attuned to the social realities of travellers that may not see bacteria to be part of their daily life. We suggest that to improve the alignments of laboratory and societal practices, and to get more insight into the added value of transdisciplinary research, it is important to further develop the stool and stories approach. By bringing it into the dialogue and challenging the methodological and conceptual understandings of AMR in microbiology and sociology, stool and stories may help to create new and more systematic approaches to AMR.Additional file 1. Survey Questionnaire. Interview guide


Mikania micrantha Kunth is among the most invasive weeds in the world, causing extensive damage to both natural ecosystems and agroforestry systems. Mechanical removal is one of the most effective and straightforward approaches to controlling this weed, but this results in extensive lignocellulosic waste, and effective approaches to exploiting this abundant biomass are limited. Coptotermes formosanus Shiraki is not only an important subterranean termite pest species but also a considerable decomposer with the ability to digest lignocellulose. In this study, we evaluated the effects of a diet composed of M. micrantha leaves on C. formosanus workers. The workers increased their dietary intake when fed M. micrantha leaves, with a concomitant gradual increase in mortality rate. From the metabolic profiles, changes in metabolites and their related metabolic pathways suggested that termites can utilize M. micrantha-derived lignocellulose, but their antioxidant activity and signal transduction may be suppressed. Overall, this study identified key metabolites and pathways associated with the response of these termites to dietary changes and the effect of M. micrantha on termites.Mikania micrantha Kunth are limited. Termites have been a focus of significant attention as mediators of biomass-processing owing to their ability to digest lignocellulose. Here, the GC/TOF-MS approach was employed to assess the effects of a diet composed of M. micrantha leaves on Coptotermes formosanus workers, with the growth performance of these workers also being assessed. The workers increased their dietary intake when fed M. micrantha leaves, with a concomitant gradual increase in mortality rate. A total of 62 differentially abundant metabolites and nine significantly affected pathways were found when comparing termites fed M. micrantha leaves to pinewood. Key metabolites, including carbohydrates, polyols, 4-hydroxyphenylacetic acid, and their related metabolic pathways, suggested that termites can digest and utilize M. micrantha-derived lignocellulose. However, changes in the tryptophan metabolism, tyrosine metabolism, and sphingolipid metabolism suggest an adverse effect of M. micrantha leaves on antioxidant activity and signal transduction in termites. Overall, this study identified the key metabolites and pathways associated with the response of these termites to dietary changes and the effect of M. micrantha on termites.Effective approaches to exploiting the biomass of the abundant invasive weed  Owing to their ability to decompose lignocellulose, termites are among the most ecologically important invertebrate detritivore species in the world . TermiteMetabolomics studies evaluate changes in small-molecule <1500 Da) metabolites in a given biological system , with th00 Da metMikania micrantha Kunth (Asteraceae) is an invasive weed that is widely distributed throughout Southern China, Southeast Asia, and the Pacific Islands, where it has caused serious damage to forests and agricultural lands [M. micrantha infestations, but this results in extensive lignocellulosic waste [M. micrantha plants, not including the roots, are 19.1 ± 0.7 and 61.5 ± 1.4 wt% raw biomass, respectively [M. micrantha leaves contain amino acids, proteins, saponins, flavonoids, and phenolic compounds [M. micrantha holds great promise as a sustainable food source for lignocellulolytic organisms and may also exert biological effects on these organisms, although the current understanding of these effects remains limited.al lands . Mechaniic waste . The ligectively . The cruectively . Moreoveompounds ,27. Someompounds . As suchCoptotermes formosanus Shiraki species can feed on a range of lignocellulosic substrates and can be readily maintained under laboratory conditions [C. formosanus workers in response to diets composed of M. micrantha leaves or pinewood. This work was undertaken to understand the ability of wood-feeding termites to consume weed-based waste biomass and the beneficial and/or harmful effects of M. micrantha on termites, and offer additional insight into the development and utilization of M. micrantha-derived lignocellulose.As one of the most evolved transitional taxa between the lower and higher termites , Coptotenditions ,4,21,30.C. formosanus colonies collected from Guangzhou International Biotech Island and South China University of Technology campus  were used for this study. No specific permissions were required to utilize colonies from these locations. Soldier or alate morphology was used to facilitate species identification. Worker termites used for this study were identified based upon the absence of wing buds and abdominal distension. Individual colonies were placed into separate plastic containers containing a diet of pinewood , and were maintained for at least one month in a climate-controlled chamber  .Two M. micrantha leaf (ML) diet, leaves of M. micrantha were collected from Sun Yat-sen University campus in Guangzhou, Guangdong Province, China. These leaves were separated, allowed to air dry in an open area for one week, and ground to a fine powder. This powder was then compressed to yield 3.5 cm diameter ML “cookies”. Cookies were dried for 48 h at 50 °C and weighed prior to feeding. A pinewood (PW) diet was prepared using these same methods as an experimental control.To prepare an experimental t-tests was used to compare differences in termite survival or dietary intake between groups, and the generalized linear model  was used to analyze the effects of diet and time on cumulative termite mortality, using the SPSS Statistics 22 software  .Three replicates of each diet were tested for each of the two studied termite colonies to yield six replicates. The selected worker termites were sound and similar in size. Each diet was placed in the center of a 50 mL glass beaker and saturated with deionized water. A total of 150 termite workers and 15 soldiers were added to each beaker after having been starved for 24 h. Beakers were incubated in a climate-controlled chamber (28 ± 1 °C and 80 ± 5% relative humidity), with deionized water being added to the diet on days 2, 4, 6, and 8 to prevent desiccation. The number of live workers was measured once per day for 10 days. At the end of this 10-day period, any remaining food was collected, dried in an oven, and weighed to quantify diet consumption. The effects of termite colony on bioassay results were assessed, revealing no significant differences between similar colonies . StudentC. formosanus workers and 13 soldiers were fed ML and PW diets as above, with six replicates per treatment. At the end of the 10-day treatment period, 100 workers were selected at random from each beaker, snap-frozen with liquid nitrogen, and stored at −80 °C. A 30 mg aliquot of each sample was then ground into a fine powder in liquid nitrogen, after which chloroform and methanol were used for extraction. l-2-Chlorophenylalanine was added to each sample as an internal standard. Samples were homogenized at 45 Hz for 4 min in a ball mill, ultrasonicated for 5 min in an ice water bath, and subjected to centrifugation for 15 min at 13,000× g at 4 °C. Supernatants were then transferred into fresh GC/MS glass vials and dried in an unheated vacuum concentrator. Each dried extract was then combined with 30 μL of methoxyamination hydrochloride (20 mg/mL in pyridine), followed by incubation at 80 °C for 30 min. Samples were then derivatized for 90 min using bistrimethyl-silyl-triflouroacetamide (BSTFA) containing 1% trimethylchlorosilane (TMCS) (40 μL) at 70 °C.For GC/TOF-MS (gas chromatography/time-of-flight mass spectrometry) analyses, 130 −1 to 310 °C and then maintained at this temperature for 8 min. The temperatures of the injection, transfer line, and ion source were 280 °C, 270 °C, and 220 °C, respectively. The energy was −70 eV in electron impact mode. MS data were acquired in full-scan mode at 20 spectra per second following a 455 s solvent delay with a mass-to-charge ratio (m/z) range of 50–500.An Agilent 7890B gas chromatograph instrument  equipped with a Pegasus HT time-of-flight mass spectrometer  was used to conduct GC/TOF-MS analyses with a DB-5MS capillary column coated with 5% diphenyl cross-linked with 95% dimethylpolysiloxane . A 1 μL sample volume was injected in splitless mode, with helium as a carrier gas at a flow rate of 1 mL/min. The column was maintained at 50 °C for 1 min, after which it was heated at 10 °C minRaw GC/TOF-MS data were analyzed as in prior reports . Raw peap-values < 0.05 (Student’s t-test). KEGG pathways associated with these metabolites were identified using MetaboAnalyst 5.0  [p-values from pathway enrichment analyses or impact values for pathway topological analyses [p) values > 2.0 served as significance threshold for this analysis.The resultant 3D data, including peak number, sample name, and normalized peak area, were introduced into the SIMCA 14.1 software package  to facilitate principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projections to latent structures-discriminate analysis (OPLS-DA). Candidate metabolites of interest were selected based upon Variable Importance for the Projection (VIP) values extracted from the first principal component in the OPLS-DA analysis. Significantly differentially abundant metabolites, which were those that were most reliably able to differentiate termite treatment groups, were identified based on VIP value > 1.0 and a st 2021) . Signifianalyses ,35. ImpaC. formosanus workers fed a M. micrantha leaves (ML) or pinewood (PW) diet. Survival rates for termites fed an ML diet for 10 days (79.11 ± 0.09%) were significantly lower than those for termites fed a PW diet (95.13 ± 0.02%) . Termite cumulative mortality was significantly impacted by dietary composition  and the number of days , but was not affected by their interaction     A. Moreov, n = 6) B.C. formosanus physiology associated with the differential feeding performance observed above would be reflected by metabolite levels in these animals. GC/TOF-MS analyses yielded 766 valid peaks, of which 731 were retained following quality control filtering. Using the LECO-Fiehn Rtx5 Metabolomics Library, 299 metabolites were quantified in these samples, including 66 with an SV > 700 and 227 metabolites with an SV of 200–700.We hypothesized that changes in 2X value of the PCA model representing the explained variance was 0.794. All samples in the resultant score plots fell within the 95% Hotelling’s T-squared ellipse, consistent with an absence of any outliers among these evaluated samples.To decrease the overall complexity of the resultant metabolite dataset, multivariate PCA and OPLS-DA analyses were conducted, enabling the visualization of similarities and differences between treatment groups. PCA analyses of these GC/TOF-MS metabolic profiles revealed clear separation between termites fed ML and PW diets, with PC1 and PC2, respectively accounting for 38.6% and 24.4% of the overall variation A. Relati2X = 0.399, R2Y = 0.995, and Q2 = 0.833, all of which were stable and effective for fitness and prediction. Respective R2 and Q2 intercept values determined following 200 permutations were 0.92 and −0.54 , a total of 62 metabolites were found to be differentially abundant between these two termite groups , amino acids and derivatives thereof , and fatty acids   values. Based upon VIP threshold cut-offs  . Neverthe in ML3 . An addie in ML3 . Likewise in ML3 .C. formosanus workers (p) and pathway impact values, were the glycine, serine and threonine metabolism, tryptophan metabolism, starch and sucrose metabolism, and galactose metabolism pathways, all of which had impact values of greater than 0.25  and lignin  content [Previous grass-diet  studies in lower termites, val rate ,21. The  content , potenti content , resultiM. micrantha (around 25:1) is much lower than of p. massoniana (around 673:1), which suggests that M. micrantha may contain much more protein than pinewood [M. micrantha leaves by photosynthesis with various enzymes (proteins). In light of these facts, the enrichment of the glycine, serine and threonine metabolism, tryptophan metabolism, and starch and sucrose metabolism pathways may also be attributable to the digestion of the proteins and starch present within M. micrantha leaves. Accordingly, the changes in these metabolites and pathways suggest that termites together with their symbionts increase their digestion and utilization of M. micrantha-derived lignocellulose and other substrates.Metabolic profiling and functional analyses of associated metabolic pathways provided insight regarding differences in metabolic status associated with the two experimental diets in the present study . Changespinewood ,42. Priol-tryptophan (5-HTP), were significantly reduced in termites fed an ML diet. Kynurenine can control responses to environmental stress, dietary changes, or infection [Changes in the levels of certain metabolites may be indicative of shifts in the physiology or behavioral status of the analyzed termites. For example, levels of two key metabolites associated with tryptophan metabolism, kynurenine and 5-hydroxy-nfection ,44,45,46nfection ,48,49. Rnfection . Increasnfection ,52, furtnfection ,54. DecrChanges in the levels of certain metabolites may be characteristic of changes in antioxidant, immunological, signal transduction, and other metabolic processes in termites fed an ML diet. Tyrosine can serve as a neurotransmitter, antioxidant, and plays a key role in the context of protein modification ,56,57. DM. micrantha leaves may influence the structure and function of gut symbionts. For instance, the downregulation of 5-aminovaleric acid may be one of the indicators, which is an important intermediate during bacteria catabolize lysine via the 5-aminopentanoate  pathway to obtain carbon, nitrogen, and energy [Furthermore, termite symbionts not only participate in the digestion of lignocellulose, but may also be affected by the diet. Because lignin has positive effects on the maintenance of termite symbionts , the lowd energy .C. formosanus workers to feed on M. micrantha leaves and to metabolize lignocellulose and other substrates derived from these leaves. According to their metabolic profiles, M. micrantha leaf-based diets may promote increased feeding behavior and food consumption in termites, but may also adversely suppress termite responses to harmful substances and have chronic toxicity. Hence, C. formosanus cannot be fed on M. micrantha for a long time, and it would be inappropriate for M. micrantha to be a single feed source of C. formosanus. It may be possible to utilize M. micrantha as an additive in termite baits. Further research, however, is necessary to more fully establish the roles of these metabolites in other dietary contexts and to determine how they relate to changes in gene expression.Our results demonstrate the ability of


Alternative systemic treatments are needed for patients who develop chemotherapy-refractory KS. Anti-angiogenic therapies constitute interesting therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis, and could represent attractive alternatives. Immune checkpoints blockade could also be an interesting therapeutic approach in order to restore anti-HHV-8 immunity and tumor control.In patients with Kaposi’s sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects. Since 1996, combined antiretroviral therapy (cART) has dramatically decreased the risk of acquired immunodeficiency syndrome (AIDS), improved immune function and survival, and reduced the incidence of AIDS-defining cancers in people living with HIV (PLWH) ,3. Cause− and CD57+) in patients with KS compared to those without it  and GCV , but not ACV  [Several studies have evaluated the risk of developing KS in PLWH ,60,63,64 = 0.40) .p = 0.001) [Systemic symptoms frequently occur during KS, similarly to other HHV-8-related diseases such as Castleman’s disease, KSHV inflammatory cytokine syndrome (KICS), or IRIS–KS ,67. Only= 0.001) . Moreove= 0.001) .Tumor-induced angiogenesis is crucial in the development of many cancers to ensure sufficient nutrient and oxygen supply and allow metastatic spread. Multiple proteins have been identified as angiogenic factors and are currently targeted by therapeutic agents. Illustrating the quest for efficient anti-angiogenic drugs, a basking shark cartilage extract was commercialized in the early 2000s (Neovastat or AE-941) based on the assumption that sharks are not affected by cancers . DespiteAside from this particular setback, anti-angiogenic drugs are increasingly used in cancer clinical management. The effect of these drugs remains modest in both preclinical and clinical trials, with frequent intrinsic or acquired tumor resistance . HoweverThe link between angiogenesis and immune dysregulation is epitomized by the natural history of KS. Abundant vasculature with increased permeability constitutes an early and prominent histological characteristic of KS, forming purplish and reddish macules, papules, and nodules on the skin and other organs. Aberrant angiogenesis in KS results from the production of pro-angiogenic factors by HHV-8-infected spindle cells, including VEGF-A, platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) ,81,82. TIn recent years, the most interesting results of anti-angiogenic drugs have been achieved with thalidomide and its derivatives . After tTargeting directly VEGF, bevacizumab is a humanized anti-VEGF-A monoclonal antibody that is licensed for various cancers, including colorectal, lung, and breast cancers. In 2012, a phase II study evaluated the effect of this drug in 17 PLWH with KS persistence or progression despite cART introduction and reported a 31% complete or partial response at 8 months . HoweverGiven the importance during KS development of PDGF and c-KIT receptors, which are two receptor tyrosine kinases selectively inhibited by imatinib, the clinical utility of imatinib has also been tested in KS. In a pilot phase II study, 30 patients with HIV-related KS (with or without ART exposure) were treated with imatinib for a median duration of 22.5 weeks . Ten patInhibitors of the mTOR pathway as sirolimus (rapamycin) and temsirolimus have also been reported to have activity on KS. In vitro, those agents were shown to exhibit anti-angiogenic properties by inhibiting VEGF secretion by KS tumor cells . In soliInfluencing several cellular pathways, HIV PIs have also been suggested to exert a direct inhibitory effect on AIDS-KS, independently of virological suppression and CD4 reconstitution . AlthougImmunotherapy has dramatically improved the prognosis of many cancers, such as non-small-cell lung cancer, gastric carcinoma, head and neck squamous cell carcinoma, and renal cell carcinoma. These therapies consist in reversing the anergy of immune cells, induced by the tumor and its microenvironment, in order to efficiently kill tumor cells. Such a restoration of immune function is based on the blockade of immune checkpoints by monoclonal antibodies. Ipilimumab, blocking CTLA-4, was the first agent to be commercialized. It was followed by nivolumab and pembrolizumab, blocking PD-1, and finally by atezolizumab, targeting PD-L1.Immunotherapy could constitute an interesting therapeutic approach in patients with KS ,103,104.To date, there is no marketing approval for anti-immune checkpoint antibodies in KS. However, a few clinical cases and series, although including a limited number of patients, have been published  113,114,120,121.The adverse event profile of immune checkpoint inhibitors has been evaluated in patients with cancer ,124. In Apart from immune checkpoint inhibitors, interferon-α is also a biologic response modifier that has been shown to exert a direct antiviral effect against HHV-8 in KS-infected cells ,131. In New therapeutic targets are needed to efficiently treat patients with chemotherapy-refractory KS. Anti-angiogenic therapies constitute potential therapeutical targets due to the central role of angiogenesis in KS pathogenesis and could represent alternatives to chemotherapy. Pomalidomide seems to currently constitute the most promising agent and has been recently approved by the FDA, while other pathways could be targeted, and innovative molecules are being tested. Combinations with other anticancer drugs, in particular, immunotherapies could enhance their efficacy and thus need further investigations. Although suggested by in vitro studies, the role of anti-herpetic agents in KS treatment remains unclear. It needs to be noted that only few studies were performed in sub-Saharan Africa, despite the disproportionate health burden caused by KS in this region. This knowledge gap may be explained by the unavailability of such expensive and novel therapies in low-income countries and highlights the critical need for research at a global level.All in all, those drugs could, however, constitute elements of combination therapies for refractory KS, for instance combined with chemotherapy regimens, at least in high-income countries where those drugs are available. Immune checkpoints blockade also needs to be further evaluated in this context. The frequency of refractory KS as well as recently reported cases of relapsing AIDS-related KS despite suppressed HIV viremia and apparently restored immunity on cART highlight the need of such alternative treatments. However, larger well-conducted clinical trials will be necessary to shed light on the efficacy of immunotherapy, anti-angiogenic agents, and antiviral drugs in KS.


Escherichia coli and Bacillus subtilis might, at first glance, come across as “been there, done that.” And yet, looking closely at a topic well studied is often a route to new knowledge and can allow us to test heretofore unrecognized assumptions in new ways. Such is the importance of condensing our ever-expanding knowledge into one thorough and digestible text.To a molecular biologist, a textbook so heavily focused on the classical genetics of model systems such as The history of Snyder and Champness Molecular Genetics of Bacteria goes back more than 24 years . As a trReading through each chapter, the reader can follow along with a sort of classical genetics take on molecular biology. That is, the book has a logical flow through 13 chapters, beginning with DNA structure, replication, and gene expression and ending at DNA repair, regulation, and genomic analysis. The introduction and first chapter, The Bacterial Chromosome, are designed to provide a basic background in genetics. They include historical perspectives and information on the molecular tree of life and the basic building blocks of DNA. The ensuing chapters build upon that introductory material and include more specific examples primarily centered around the most well-studied and understood bacteria.Escherichia coli, lacZ mutations producing blue pigment, and the stages of Bacillus subtilis sporulation. The authors subtly introduce the reader to primary sources, in addition to bridging the gap between research and the classroom.Results from peer-reviewed scientific articles are woven in throughout the book. Examples include the carbon storage regulator global regulatory network in The new final chapter, Genomes and Genomic Analysis, is a welcome addition that provides background on laboratory techniques. The sections on sequencing methods could use more detail on new strategies . In addition, and of lesser importance, the Sanger sequencing “cart” is, if you will, presented before the PCR “horse.” Perhaps the next edition can delve deeper into these ever-evolving technologies.Overall, the book contains material perfect for teaching a university-level course on bacterial molecular genetics. It also includes information for students and professionals  seeking to update their knowledge to the current state of the art of bacterial genetics.


Majority of the patients affected by Kaposi sarcoma (KS) have human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) lessened the incidence of AIDS (acquired immunodeficiency syndrome)- related KS. Cutaneous signs are the most common, but involving the gastrointestinal (GI) tract is very important and dangerous because of serious complications including perforation and bleeding.This report is a rare case of gastric-KS presenting as melena in a non-AIDS 67-year-old woman. We describe the diagnosis and management of this rare complication.GI-KS is often asymptomatic with different endoscopic appearances, and maybe present without cutaneous lesions. Thus, a high diagnostic suspicion is needed and we should attend these GI complications. Moritz Kohn Kaposi described Kaposi sarcoma (KS) in 1872 as a low grade tumor of the vascular endothelium . The DNA of human herpesvirus 8 (HHV-8) has been detected in more than 95% of KS lesions as the causative agent . KS has The majority are clinically silent and most visceral KS remain unidentified. Therefore, some experts have suggested screening endoscopy for the early detection and initiation of treatment to improve survival outcome . We presA 67-year-old woman presented our hospital with complaints of pallor and weakness for a few days. She had a mild abdominal pain and black tarry stool. Her past medical history was not significant. The patient was well nourished with multiple, plaque-like, violaceous skin lesions increasing in both lower extremities since last year . PhysicaUpper GI endoscopy revealed multiple friable polypoid and nodular lesions of varying sizes in the stomach . EndoscoThe diagnosis of KS in the gut should be considered in elderly men from Eastern Europe and Mediterranean regions and specially in immunosuppressed and AIDS patients. Greater-than-50% is the incidence of GI-KS is in AIDS patients with cutaneous KS . AlthougThe diagnosis of KS with a negative HIV test should lead to the consideration of other causes such as iatrogenic or lymphoproliferative disorders-related immunosuppression . IatrogeGI appearances in endoscopy are variable as flat ulcerated, polypoid/nodular, and volcano-shaped lesions. Biopsy is the gold diagnostic test of both the cutaneous and GI lesions. In Histology, they have typical features and morphology in hematoxylin and eosin staining . If it iTherapy depends on the clinical subtype and organ involvement and it is usually palliative and aimed at improving symptoms and preventing progression. For visceral involvement and AIDS-associated KS, chemotherapy combined with highly active antiretroviral therapy (HAART) may be indicated . In patiIn conclusion, GI-KS is often asymptomatic with different endoscopic appearances, and maybe present without cutaneous lesions. Thus, a high diagnostic suspicion is needed and we should attend these GI complications.


Their corresponding photodeformable behaviors such as twisting, bending, hopping, bursting, and curling, as well as the potential applications, are also discussed. Furthermore, the challenges and prospective development directions of photodeformable crystals are highlighted.Photodeformable materials are a class of molecules that can convert photon energy into mechanical energy, which have attracted tremendous attention in the last few decades. Owing to their unique photoinduced deformable properties, including fast light-response and diverse mechanical behaviors, photodeformable materials have exhibited great potential in many practical applications such as actuators, photoswitches, artificial muscles, and bioimaging. In this review, we sort out the current state of photodeformable crystals and classify them into six categories by molecular structures: diarylethenes, azobenzenes, anthracenes, olefins, triarylethylenes, and other systems. Three distinct light-responsive mechanisms, photocyclization,  Stimuli-responsive materials have attracted enormous attention over the past few decades, due to their promising applications in sensing, bioimaging, data storage, deformation detectors, switches, security systems, etc. –4. Thesecis-trans isomerization upon light irradiation, which shows great potential in the fields of drug storage and drug transportation  and [4 + 4] cycloaddition reactions. A significant change in the size and arrangement of original molecular crystals will occur during the photodimerization process, which may lead to the micro- or macromechanical changes. Overall, photodeformable process is closely related to molecular structures and crystal arrangements.Upon light exposure, a large diversity of mechanical motions can be observed, mostly deriving from the change of molecular structures or packing modes. Therefore, different photosensitive chromophores may have different mechanisms for various photoresponsive behaviors . AccordiAll the excellent properties endow photodeformable materials with tremendous attentions in both academia and industry, representing their future trend in many applications –43 inclutrans-cis isomerization. For anthracenes and olefins, another common photodeformable mechanism of photodimerization play an important role. By summarizing these systems, we aim to present the structure-property relationship of these photomechanical materials in details and try to figure out the following questions: (i) is it possible to control the light intensity and exposure time to manipulate the mechanical direction and magnitude? (ii) how to manipulate the molecular level motions to achieve the large-scale mechanical change? (iii) what new applications can be derived from the materials? Finally, the challenges and possible development directions in the future are also discussed.In this review, different types of photoinduced deformation systems are categorized according to their molecular structures. A variety of molecular examples on the latest progress as well as photodeformable behaviors and their potential applications are presented showing a comprehensive review. The commonly used building blocks for photodeformable materials include diarylethenes, azobenzenes, anthracenes, olefins, triarylethylenes, and some other systems, as shown in Diarylethene-based photochromic and photodeformable materials are a class of compounds containing five-membered heterocyclic rings, which have great thermal stability and high sensitivity. They have been widely reported as potential and indispensable candidates in the fields of optical memory  and moleIn 2007, two photodeformable single crystals based on diarylethenes were reported by Kobatake and coworkers . As showIn 2010, the same group designed a two-component photodeformable cocrystal, consisting of a photochromic diarylethene derivative (4) and perfluoronaphthalene (FN) . The phoIn order to improve the fatigue resistance, the idea of preparing the mixture was proposed by Terao et al. in 2011 . The phoSome researchers have been devoted to investigating the factors that lead to different photoinduced deformation behaviors of the same crystal. Back to 2008, Uchida and his colleagues found that reversible photoinduced bending of crystals can be achieved in both convex and concave forms . They reθ of 0°). By gradually increasing irradiation angles, crystal 10o could progressively change into a cylindrical helix shape. When it was increased close to 90°, 10o was bent instead of twisting. The experimental results indicated that the irradiation direction can manipulate the stress tensor of crystal surface. Although the mechanism of this phenomenon still needs to be studied, the incident angle could be used to control the photoinduced deformation, which lays a solid foundation for further study of photodeformable devices.In 2013, a diarylethene crystal (9o) showing photoinduced twisting behaviors was reported by Kitagawa and coworkers  54]. Th. Th54]. Various photodeformable behaviors, such as bending, twisting, curling, shrinkage, and expansion, have been reported in a series of diarylethylene crystals. In 2016, a photoinduced rapid explosive process was reported in the photochromic process of diarylethylene crystals 11o and 12o  57]. Fi. Fi57]. In 2017, Kitagawa et al. found that both photochromic reaction and reversible thermodynamic phase transition can trigger photoinduced bending behaviors with good repeatability in a diarylethene derivative crystal 13o . The phoExcept for the aforementioned photodeformable materials based on pure molecular crystals, the combination of organic crystals and inorganic components is also a promising way to design photodeformable materials. In 2019, Kajiya and coworkers explored the properties of diarylethene siloxane hybrid, inspired by previously reported azobenzene siloxane hybrid . To combLater on, Dong and his colleagues tried a few methods to characterize composites composed of inorganic and organic components to explore the influence of nanostructures on the photomechanical properties . They detrans-cis isomerization processes driven by light irradiation. This isomerization might lead to the deformation of the crystals in shapes and sizes . Bo. Bocis-aIn the beginning, the qualitative bilayer model was used to clarify the mechanisms of the photodeformable behaviors in azobenzenes. However, this model was unable to analyze both internal and external factors on the photodeformable properties. In 2014, Nath and coworkers proposed a new dynamic model, by using a simple mathematical description to depict the quasistatic and time-varying photobending of the macroscopic single crystals . In thiscis-trans photoisomerization of 28 and the alignment change of the mesogens. Another example was reported by Liu and coworkers in 2013, by combining an upconverting nanoparticles with integrated azobenzene (29)-modified mesoporous silica  photocycloaddition reactions, provided they could meet the conditions of parallel molecular packing and proper distance between two anthracene planes satisfying the Schmidt rules. The chemical structures of anthracene derivatives discussed in this section are shown in 2. In addition, the millimeter and micron-scale crystals showed anisotropic expansion which then decomposed to smaller irregular crystals. The results indicated that the crystalline shape changes were mainly attributed to the crystal-to-crystal photodimerization. The single-crystal analyses indicated that the volume per anthracene moiety showed an increase of 9.7%, changing from 371 A3 in the monomer crystal to 407 A3 in the dimer crystal. In addition, they tried to test the reversibility of dimer with short wave UV light. However, the crystal dimensions did not shrink back to their initial state. Based on the previous work, they used a new model, by combining ensemble oriented-crystal solid-state NMR, X-ray diffraction, and first principle computational modeling, to figure out the atomic resolution and molecular mechanism of nanorods 31 with photoinduced expansion  photodimerization reaction in crystal 9-methylanthracene (37), trying to figure out how the crystal morphology and photodimerization dynamics affect its deformation in 2014 . By chanBased on previous work, Tong et al. employed a new surfactant-assisted seeded-growth method to grow single-crystal platelets consisting of 37 in 2018 . It showBesides crystals 32 and 37, some other anthracene derivatives with (E)- and (Z)-isomers were also reported. Anthracene derivative 38 is very stable at darkroom temperature and can be easily crystallized in different organic solvents . There iApart from [4 + 4] reactions, [2 + 2] photocycloaddition reactions of olefins can also lead to the photoinduced motions. The photoreaction mechanism of olefins resembles that of anthracenes. The molecular structures of olefins discussed in this section are shown in In 2015, Nath's group reported a photoluminescence effect (photoinduced transition) of three coordinated complex crystals induced by [2 + 2] photocycloaddition reactions for the first time, like popcorn popping on a hot surface . Unlike Trans-1,2-bis(4-pyridyl)ethylene is a kind of photoactive molecule that can undergo the photoinduced [2 + 2] cycloaddition reaction under certain conditions. The photodeformable motion based on the 4,4′-bpe derivative, 1-(4-carboxybenzyl)-4-[2-(4-pyridyl)-vinyl]-pyridinium chloride (41) prepared by substituting the carboxybenzyl group onto one end of the 4,4′-bpe molecule, was reported by Sun and coworkers -2--benzo[d]oxazole (42), which exhibited obviously interesting photomechanical behaviors . Under Utrans-2-(4-fluorostyryl)benzo[d]oxazole (45) and trans-2-benzo[d]oxazole (46) [T direction and shrank in the FL direction, leading to a bending towards the light. In contrast, crystals 47, vertically in a “head-to-head” manner on the photoreaction surface, showed a totally different deformation. The photoreaction surface expanded in the FL direction and shrank in the FT direction forming an upward contraction, which resulted in its bend away behavior. This was mainly due to the crucial impact of C-H···F interaction in their different molecular packing, leading to the positive/negative phototropism of the actuators. This research opens a new door for crystal engineering.Recently, the same group explored the unique bending behaviors of ole (46) . Both moole (46) . Moreoveole (46) . It showDiarylethylene-based photochromic materials have made certain progress in the fields of biological detection, photoswitchable molecular devices, optical information storage, and light-controlled self-assembly. However, there are still some challenges remaining, such as complex structures and complicated synthesis steps, which greatly hinder the development of photochromic materials. To simplify molecular structures while maintaining their excellent photochromic properties, the idea of designing and synthesizing triarylethylene photochromic materials was proposed, which can effectively improve poor photochromic performance caused by light isomerization. For triarylethylene, there is no need to embed the double bond in five-membered or six-membered rings when designing molecules, which makes triarylethylene easy to synthesize and modify. Particularly, unlike the systems previously discussed that exhibit evident macroscale photoinduced deformation, some triarylethylene derivatives show photoinduced microinterface properties, whose surface morphology would change under the microscope upon UV irradiation. The chemical structures of triarylethylenes discussed in this section are shown in The first triarylethylene-based photochromic material, triphenylethylene derivative (49), was reported by Ou et al. in 2016 . It exhiSubsequently, a carbazole containing triphenylethylene derivative (50) was designed and synthesized in 2017, which exhibited multiple properties including AIE, piezochromism, and photochromism . The pie2 substrate switched from cone-shape to hump-shape under UV irradiation, accompanied by the change of the contact angle of the water droplets on the surface from 43° to 95°. After 5 minutes of white light irradiation, this hump-shaped nanoaggregates 53 gradually became conical, and the contact angle decreased to its initial value  , by conta axis on the (00-1) face. When this (00-1) face was irradiated by UV light, the front crystal surface shrank diagonally, while the back crystal surface did not shrink due to a lack of photoisomerization. This led to a platelike crystal twisting toward the incident light in a right-handed helix, as shown in Besides, the influence of chirality on the photodeformation was explored by Koshima and Asahi in 2016, by designing platelike crystals of S- and R-enantiomers of photochromic N-3,5-di-tert-butylsalicylidene-1-phenylethylamine (57). Upon the UV irradiation, chiral crystal 57 twisted due to the longitudinal and transverse contraction of the irradiated surface in enol form . AccordiLater on, four diphenylcyclopropenone crystals  were reported by Gong et al. in 2017, which involved various molecular interactions encoded in individual molecular structures . By analπ-conjugation. However, aggregation-induced emission was observed in the photodimer of 63 with enhanced fluorescence peaking at 415 nm. It was mainly attributed to the efficient intramolecular through-space conjugation and restriction of intramolecular vibrations. The unique property endowed this kind of photodeformable molecules with promising applications in smart optoelectronic devices and bionic science.Unlike the generally discussed crystals, some interesting phenomena were also reported. In 2018, Samanta and coworkers successfully designed a novel diindene derivative compound (62), which can undergo photopolymerization under visible light and depolymerization after heating . As showThe photodeformable behaviors of molecular crystals can be manipulated by many factors, including the light wavelength, time, density, and irradiation sites. In 2020, De and coworkers designed a new crystal 1,3-bis(diphenylamino)squaraine (64) , which eFurthermore, some spiropyran derivatives were reported showing both photochromic and photodeformable properties when combined with gels or liquid crystals, which endowed them with huge application prospects in biomedicine. In 2016, Xiao and coworkers prepared a supramolecular hydrogel consisting of spiropyran (65)-conjugated galactose for photocontrolled delivery of microRNAs. The hydrogel showed great advantage in delivering the released microRNAs to specific cells . MoreovePhotodeformable materials have captured enormous attention in both academia and industry owing to their excellent photoinduced properties. The controllable and reversible photodeformation, such as bending, curling, and twisting, can mimic the movement of creatures by utilizing the energy generated from the photoinduced motions, which have been widely used for bionic devices . Besides, some photodeformable systems combining photochromic derivatives with liquid crystals or gels also show great potential in biomedical fields for targeted drug delivery.In 2010, Morimoto and Irie reported a molecular crystal cantilever made of a cocrystal 4o·FN, which showed a reversible bending motion under alternative UV and visible light . As showBy incorporating photodeformable molecular crystals  to connective polymer , a simple and generic strategy to prepare artificial muscles named as “mixed-matrix membrane” was proposed by Yu et al. in 2018 . The desApart from artificial muscles, soft robot is another typical application of composite materials based on photodeformable crystals. The structural diversity and controllability of photodeformable crystals make them promising for flexible robotic applications. In 2018, Lu and coworkers designed a light-controlled polymer “crane,” composed of a photodeformable nanocomposite, which was synthesized by doping gold nanorods into azobenzene liquid-crystalline dynamic networks . It exhiExcept for the UV light, the visible- and NIR-driven photodeformable crystals for the manipulation of micro- or nano-sized objects show great utility in biomedical field. Liu and coworkers reported a NIR light-absorbing molecular crystal by combining an upconverting nanoparticle with integrated azobenzene (29)-modified mesoporous silica . The phoIn summary, the current progress of typical photodeformable organic crystals, including diarylethenes, azobenzenes, anthracenes, olefins, triarylethylenes, and their derivatives, as well as their photoreaction mechanisms and promising applications is reviewed. Molecular crystals with different structures tend to have different photodeformable behaviors, such as bending, twisting, hopping, curling, and bursting. Their corresponding photomechanical behaviors, excitation conditions, and color changes are summarized in With the joint efforts of numerous researchers, the study of photoderformable crystals has achieved impressive progresses, particularly in the development of materials based on the photocyclizations , photoisomers , and photodimerizations . Some of them also exhibit multiple stimulus responses, such as heat, pH, and forces. The excellent mechanical response of molecules to light irradiation provides a great potential in the applications of photoactuators, molecular rotors, molecular robots, artificial muscles, biomedicine, photoswitches, micro- and nanomechanical devices, etc. However, pure molecular crystals are still faced with problems of poor stability, controllability, and inflexibility, which can hardly meet the needs of practical applications. Therefore, there is still plenty of space for valuable research directions to improve the applicability. First of all, it is crucial to design and synthesize photodeformable crystals towards excellent mechanical properties, such as high efficiency, fast response, high fatigue resistance, and flexibility, which are essential for the applications of photoactuators and artificial intelligent muscles. Secondly, how to improve the controllability of mechanical response of photodeformable crystals is also of great challenge. Only by effectively controlling the responsive type, direction, and degree of mechanical motions could photodeformable crystals be widely taken advantage of. Thirdly, as the intrinsic photodeformation occurs by converting photon energy into molecular macro- or micromechanical energy, how to improve the energy conversion rate is extremely significant for the applications. Fourthly, nanoscale photodeformable microcrystals should be taken into account seriously by researchers due to their performances in micro- and nanomechanical devices. Moreover, achieving excitable photodeformation upon visible light or NIR light irradiation is also a potential research direction of photodeformable crystals, as there are few relevant studies at present, which will greatly diversify their applications. Last but not the least, pure molecular crystals are found hard to be directly used in many complex practical applications due to their inherent physical properties, such as low water solubility, poor biocompatibility, and biodegradability. To develop more high-performance and diverse applications, the exploration of photodeformable materials can be expanded from small molecular crystals to polymeric materials, such as polymers and COFs. Combing all the advantages of photodeformable materials, designing hybrid and composite materials by introducing photodeformable groups into gels, liquid crystals, polymers, or COFs is also of great prospect to develop promising candidates for the applications in bionic and biomedical fields, such as photoactuators, soft robots, and anticancer carriers. To address all these issues, additional efforts need to be made to comprehensively understand the fundamental scientific mechanisms and promote the material system explorations. We hope this review could provide a basic guidance for further development of photomechanical materials.


CAR T cell therapy has shown dramatic clinical success in relapsed or refractory B-ALL and other hematological malignancies. However, the loss of specific antigens, cell fratricide, T cell aplasia, and normal T cell separation are challenges in treating T cell leukemia/lymphoma with CAR T therapy. CD99 is a promising antigen to target T-ALL and AML as it is strongly expressed on the majority of T-ALL and AML. Here, we isolated a low-affinity CD99 (12E7) antibody, which specifically recognizes leukemia cells over normal blood cells. Moreover, T cells transduced with an anti-CD99-specific CAR that contained the 12E7 scFv expanded with minor fratricide and without normal blood cells toxicity. We observed that our anti-CD99 CAR T cells showed robust cytotoxicity specifically against CD99+ T-ALL cell lines and primary tumor cells in vitro and significantly prolonged cell line-derived xenografts (CDXs) or patient-derived xenografts (PDXs) models survival in vivo. Together, our results demonstrate that anti-CD99 CAR T cells could specifically recognize and efficiently eliminate CD99+ leukemia cells.The online version contains supplementary material available at 10.1186/s13045-021-01178-z. To the editor:T-ALL is an aggressive hematological malignancy accounting for 15% of pediatric and 25% of adult ALL cases , 4. Nove–8 M, which is lower than the 1021527 (5.76 × 10–9 M) and 3B2/TA8 (1.93 × 10–9 M)  Relative CD99 expression was calculated as CD99 fragments per kilobase of exon model per million mapped fragments (FPKM) on T-ALL samples (n=264) and normal PBMC samples (n=23). Data from Dvinge H et al. PNAS, 2014 and Liu Y et al. Nature genetic. 2017. (b) The relative CD99 protein level was calculated as the CD99 mean fluorescence intensity (MFI) on T-ALL samples (n=22) and normal T cell samples (n=5) by flow cytometry. (c) Relative CD99 expression was calculated as FPKM on ETP ALL (n=19), nearETP ALL (n=24) and nonETP ALL (n=146) samples. Data from Liu Y et al. Nature genetic. 2017.(d) Relative CD99 expression was calculated as CD99 FPKM on T-ALL subgroup, including LMO2_LYL(n=18), LMO1/2(n=10), HOXA(n=33), TLX3(n=46), TLX1(n=26), NKX2_1(n=14), TAL1(n=87), TAL2(n=8) and unknown(n=22) samples. Data from Data from Liu Y et al. Nature genetic. 2017. (e) Representative immunohistochemistry (IHC) images of human normal paraffin tissue sections with the CD99 (12E7) mAb. IgG as the negative control.Additional file 2: Fig. S1. (f) Binding kinetics of anti-CD99 antibodies (1021527 and 3B2/TAB) with CD99 protein. Analysis of the interaction between the antibodies and CD99 protein using BLItz biolayer interferometry. (g) The CD99 expression level in NIH 3T3 human CD99-overexpression cell line, and anti-CD99 CAR T cells specifically lysis efficiency at different effector-to-target ratios (1:1/5:1/25:1). (h) The CD99 expression level in MOLT-4 human CD99 knockdown cell line, and anti-CD99 CAR T cells specifically lysis efficiency at effector-to-target ratios (25:1). (i) The gating strategy of blast cells from T-ALL patients and the CD99 expression level in four patients’ blasts  Upper: Flow cytometry showing CD99 expression in different AML cell lines. Lower: Cytotoxic activity of anti-CD99 CAR T cells against AML cell lines as determined by calcein release assay at different E:T ratios (1:1/5:1/25:1) after 2-3h of co-culture. (k) Upper: Flow cytometry showing CD99 expression in different solid tumour cell lines. Lower: Cytotoxic activity of anti-CD99 CAR T cells against various solid tumour cell lines as determined by calcein release assay at different E:T ratios (1:1/5:1/25:1) after 2-3h of co-culture. ***p ≤ 0.001,**p ≤ 0.01,NS = no significant, Scale bar, 50 μm or 200 μm.Additional file 4: Fig. S2. (a) Spleens from T cell and anti-CD99 CAR T cell treatment groups were weighed and photographed from the PDX-1. (b) The proportion of human CD7 positive cells in the spleen of PDX-1 models. (c) Spleens from T cell and anti-CD99 CAR T cell treatment groups were weighed and photographed from the PDX-2. (d) The proportion of human CD7 positive cells in the spleen of PDX-2 models. (e) Histological features of the spleen in the T cell and anti-CD99 CAR T cell treatment groups . Scale bar, 50μm or 200μm.Additional file 5. The patient-related information.Additional file 6. Methods and Materials.


Aedes aegypti). We found that exposing the first developmental stages of mosquito larvae to a modified form of carbon black EMPEROR® 1800 (E1800), caused concentration-dependent mortality within 48 h of exposure; however, the development of larvae exposed to sub-lethal concentrations of E1800 was not disrupted. Analyses of E1800 suspensions suggest this carbon black forms CNPs that coalesce into larger aggregations. Microscopic observations of dead larvae showed the presence of CNP aggregations in the digestive tract and on external structures associated with swimming, breathing, and food uptake. Our results suggest carbon black is a source of CNPs that may have potential use for treating sources of standing water that mosquitoes use as breeding sites.Nanoparticles have previously shown potential to control mosquito vectors. The present study examined whether carbon black, an industrial source of carbon-based nanoparticles (CNPs), was toxic to larvae of the yellow fever mosquito  derived from natural sources have previously been shown to have toxic effects on mosquito larvae and offer a potential alternative to chemical insecticides such as pyrethroids, for which mosquitoes have evolved resistance. However, CNPs derived from industrial sources, such as carbon black, have not previously been evaluated as larvicides. Here, we evaluate the effects of a commercially-available carbon black, EMPEROR® 1800 (E1800), on mortality and development of pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of Ae. aegypti. We found that E1800 exhibited concentration-dependent mortality against 1st instar larvae of both strains within the first 120 h after exposure, but after this period, surviving larvae did not show delays in their development to adults. Physical characterization of E1800 suspensions suggests that they form primary particles of ~30 nm in diameter that fuse into fundamental aggregates of ~170 nm in diameter. Notably, larvae treated with E1800 showed internal accumulation of E1800 in the gut and external accumulation on the respiratory siphon, anal papillae, and setae, suggesting a physical mode of toxic action. Taken together, our results suggest that E1800 has potential use as a larvicide with a novel mode of action for controlling PS and PR mosquitoes.The yellow fever mosquito  Aedes aegypti  is a vector of many arboviruses that debilitate human health worldwide, including chikungunya, dengue, yellow fever, and Zika. Each year, hundreds of millions of people are infected with these viruses, leading to millions of hospitalizations and tens of thousands of deaths [Ae. aegypti and other mosquito vectors [The yellow fever mosquito f deaths ,4,5,6. I vectors . Thus, tRecently, nanoparticles have shown potential to control mosquito vectors. Nanoparticles range in size between 1–100 nm and can consist of novel shapes, surface compositions, and solubility. The physical and chemical properties of nanoparticles can be tailored to interact with various cellular structures or deliver ‘cargo’ to elusive biological targets, making them potentially exciting materials for developing novel and safe tools for mosquito control ,10,11. PCarbon-based nanoparticles (CNPs) have recently been evaluated as potential larvicidal agents for mosquito control . CNPs arCarbon black is a nanostructured carbon material composed of elemental carbon and is frequently used as a pigment, rubber reinforcer, ultraviolet protectant, and conductive agent in a variety of elastomers, plastics, and coatings ,32,33. AAe. aegypti. We evaluated the commercially available carbon black, EMPEROR® 1800 , which is widely used in formulations for water-based automobile coatings. We hypothesized that the ability of E1800 to fully disperse in water would disrupt larval mosquito survival and/or development.The goal of this study was to test the larvicidal efficacy of a modified-form of carbon black against pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of the yellow fever mosquito Ae. aegypti mosquito larvae were reared following established protocols [Ae. aegypti were obtained through the MR4 as part of the BEI Resources Repository, NIAID, NIH . Larvae of the Puerto Rico strain are over 100-fold resistant to the pyrethroid cypermethrin compared to the Liverpool strain [rotocols ,39. Eggs® 1800  was added to 10 mL of distilled water (dH2O) in a 20 mL scintillation vial  and vortexed vigorously for 20 s. The E1800 suspensions used for the experiments to evaluate larval mortality and development were prepared by diluting the 10 mg/mL stock with dH2O.Unless indicated otherwise, fresh 10 mg/mL stock suspensions of E1800 were prepared on the day of an experiment. In brief, 0.1 g of Modified Carbon Black EMPERORAe. aegypti larvae of both PS and PR strains were placed in wells of a 24-well Falcon® Multiwell plate  containing 995 μL of a E1800 suspension and 5 μL of food solution . The final concentrations of E1800 used to generate a concentration-response curve (CRC) were 0.01, 0.1, 0.5, 1.0, 2.5, 5.0, or 10.0 mg/mL. Control wells received 995 μL of dH2O and 5 μL of food solution. All plates were held under standard rearing conditions for 48 h before larval mortality was evaluated. Larvae were considered dead if they did not move after gently touching their abdomen with a fine needle or pipette tip. All mortality values were corrected for control mortality using Abbott’s formula [To determine the acute (within 48 h) toxicity of E1800 against 1st instar larvae, we used an established assay . Briefly formula . On aver® Multiwell plate containing 990 μL of E1800 solution  and 10 μL of food solution. Control wells received 995 μL of dH2O and 5 μL of food solution. Acute mortality of these life stages was assessed 48 h after E1800 exposure by considering them dead if they did not move after gently touching their abdomen with a fine needle or pipette tip. All mortality values were corrected for control mortality using Abbott´s formula [Groups of three 3rd instar larvae or pupae were placed in each well of a 24-well Falcon formula . In thesAe. aegypti larvae to different concentrations of the same E1800 stock that had been prepared 0 (fresh), 2, 4, 8, or 12 weeks prior to an experiment. Acute toxicity was determined at 48 h as described in ‘Acute toxicity assay: 1st instar larvae’ above. The final E1800 concentrations used for these experiments were 0.1, 1.0, or 5.0 mg/mL. Control wells received 995 μL of dH2O and 5 μL of food solution. All mortality values were corrected for control mortality using Abbott´s formula [To evaluate whether the acute toxicity of E1800 suspensions in water changed over time, we exposed 1st instar  formula . In thesAe. aegypti larvae of the PS or PR strain were placed in 150 mm × 25 mm Falcon® petri dishes containing 100 mL of E1800 at 0.1 or 0.25 mg/mL. Control dishes received 100 mL of dH2O. Each dish was provided with 13 mg of pulverized fish food daily for the first seven days. After seven days, each dish received 20 mg of pulverized fish food daily to accommodate the increase of larval body size. Plates were held under standard rearing conditions. Larvae were examined daily for 14 days through an Olympus SZ6145TR Stereo Microscope  equipped with a GO3 Digital Color Camera . Larvae were considered dead if they did not move after gently touching their abdomen with a fine needle or pipette tip. Once pupae appeared in the dishes, the standard lids of the dishes were replaced with ones containing a funnel and a small receptacle with 10% sucrose-soaked cotton balls to collect any adults that emerged. Images of larvae were captured with the GO3 Digital Color Camera and edited using Olympus CellSens Entry 2.2 software . All mortality values were corrected for control mortality using Abbott´s formula [To assess the toxic effects of E1800 on larvae beyond 48 h and determine potential effects on development into adults, we monitored survival of mosquito larvae and their emergence into adults for 10 days. Briefly, thirty 1st instar  formula . On averTo measure the size of the nanoparticles derived from E1800, we used scanning electron microscopy (SEM) and the solvent casting method. In brief, E1800 was suspended in 200 proof ethanol at 0.5 mg/mL, spin coated onto an aluminum 12 mm slotted head specimen mount  and dried under nitrogen for 30 min. Adhesive carbon paper tabs measuring 12mm  were placed onto separate specimen mounts and a 50 nm layer of gold was deposited using a Quorum EMS 150R ES sputter coater . Following sputter coating, the solvent-casted E1800 was adhered to the gold-sputtered adhesive specimen mounts by pressing the gold-sputtered specimen mounts to the solvent-casted specimen mounts and uniformly lifting the particles off the aluminum surface. All specimen mounts were cleaned with 100% isopropyl alcohol before use. The porosity of the carbon paper tabs led to some cracking of the gold layer especially where samples were exposed to the electron beam for longer durations. Specimens were visualized on a FEI Helios Nanolab 600 Dual Beam Focused Ion Beam/Scanning Electron Microscope  in The Ohio State University Center for Electron Microscopy and Analysis .In addition to SEM, we used a dynamic light scattering (DLS) approach to measure E1800 particle size ,42. In b50) or median lethal time (LT50), percent mortalities were first plotted against log transformations of concentrations or times, respectively. Then, the data were fitted with non-linear regressions using the ‘log(agonist) vs. normalized response’ function to calculate LC50 or LT50. Statistical comparisons of the LC50 or LT50 values were performed through F-tests. In experiments testing the stability of E1800 toxicity against larvae over time, percent mortalities were compared using a one-way analysis of variances (ANOVA) and Tukey´s multiple comparison test.Data analysis and plotting were performed using GraphPad Prism (version 6.07) software  and MATLAB . To determine the median lethal concentration  was significantly greater  than that of the PS strain , suggesting a minor degree of resistance (~1.7 fold) of the PR strain to E1800 in this assay. We also assessed the acute toxicity of a few concentrations of E1800  against 3rd instar larvae and pupae, but none of these treatments resulted in mortality  at several time points after preparation over a 12-week period. Similar to the results of Higher concentrations of E1800 showed less remarkable changes in toxicity over time. Similar to the results of Ae. aegypti. However, as the E1800 suspension ages, its toxicity against the PR strain appears to increase or remain the same, whereas its toxicity against the PS strain appears to decrease or remain the same  in the presence of E1800 (0.1 or 0.25 mg/mL) and monitoring their survival and development to adults. As shown in 50 of the PR strain  was significantly lower  than that of the PS strain , indicating that, in this assay, larvae of the PR strain are slightly more susceptible to E1800 than those of the PS strain. The larvae that survived this treatment continued development to adults in a similar fashion as controls  suggested that E1800 forms individual nanoparticles of ~30 nm diameter that fuse into fundamental aggregates of ~170 nm . A DLS aAe. aegypti in a concentration-dependent manner. However, the toxicity of E1800 was only effective when applied against 1st instar larvae and E1800 did not have detectable developmental effects on larvae. Our results are consistent with those of previous studies that suggest a variety of nanoparticles have potential use as larvicides [−1 produced ~30–35% mortality) against larval Anopheles, Culex, and Aedes, but also impaired the growth and development of larvae that survived wsCNP treatment at a concentration of 3.0 mg L−1. Moreover, Barik et al. [Ae. aegypti compared to silver-based nanoparticles (AgNPs), but the siNPs elicited pupicidal activity and inhibited development [The present study is the first to demonstrate that carbon black is toxic to mosquito larvae. Our results suggest that suspensions of a modified form of carbon black E1800) in water form nanoparticles and primary aggregates that kill 1st instar larvae of PS and PR strains of 00 in watrvicides ,46,47,48rvicides  found thk et al.  found thelopment . Thus, tAlthough the specific mode of toxic action of E1800 on mosquito larvae is unknown, our results suggest that a physical component is likely involved. Notably, as observed in Our experiments demonstrated that 1st instar larvae are most susceptible to E1800; the majority died within 48–72 h of treatment . After tOne of the more intriguing and enigmatic findings of the present study was the apparent selective increase of toxic potency of E1800 suspensions over time to 1st instar larvae of the PR strain. As shown in It is unclear why such potential changes would selectively increase toxicity to the PR over the PS strain, but it is widely appreciated that mutations contributing to resistance of insects to chemical insecticides  are often associated with fitness costs in the absence of a selective pressure from the chemical . In our Despite our inability to explain the above increased toxicity of E1800 to the PR strain over time, the phenomenon carries potential applied relevance if an E1800-like product were to be used as a larvicide in the field. That is, our findings suggest that mosquito breeding sites could potentially be treated with E1800 several weeks in advance of oviposition and the water would remain toxic to 1st instar larvae. Moreover, the E1800-treated water would be most toxic to pyrethroid-resistant individuals, perhaps facilitating the management of pyrethroid resistance in mosquito populations. If the toxic properties of an E1800-like insecticide are specific to mosquitoes, which remains to be determined, then we could envision this application being especially useful for treating predictable mosquito breeding sites, such as bird baths near residences and storm water catch basins.Even though nanoparticles appear to have low impact on non-target organisms, there are still many concerns regarding their use in terrestrial and aquatic environments due to the limited information available . Carbon


Fs) caused by the factors affecting the property. By developing or selecting molecular descriptors that are directly proportional to ΔGFs, we built a general linear free energy relationship (LFER) for predicting the property with the molecular descriptors as predictive variables. The LFER can be used to construct models for predicting various specific properties from partition coefficients. Validations show that the models constructed according to the LFER have high predictive power and their performance is independent of the compounds used, including the models for the properties having little correlation with partition coefficients. The findings in this study are highly useful for applications in drug development and environmental safety.Developing models for predicting molecular properties of organic compounds is imperative for drug development and environmental safety; however, development of such models that have high predictive power and are independent of the compounds used is challenging. To overcome the challenges, we used a thermodynamics-based theoretical derivation to construct models for accurately predicting molecular properties. The free energy change that determines a property equals the sum of the free energy changes (ΔG Therefore, the development of techniques for predicting these properties via computational tools is imperative . Quantitndex (ω) . For exaccuracy, , Robust edictors . The robedictors . For a gedictors . Howeveredictors . It is tow) for a solute is directly proportional to the standard free energy change for transferring the solute from water to the organic solvent (ΔGtr). The ΔGtr in turn depends on the standard enthalpy change (ΔHtr) and entropy change (ΔStr) of the phase-transferring process. Thus, at a given temperature, the model logPow = b1ΔHtr + b2ΔStr + c  is absolutely correct and has high predictive power for predicting logPow. This example indicates that the models developed via thermodynamics-based theoretical derivations may overcome the shortages of the models developed by using mathematical and statistical tools. A large number of physicochemical properties, ADME/Tox qualities, and many other properties of organic compounds depend on the changes in free energy caused by the intermolecular noncovalent interactions of the compounds with their environments. The enormous catalytic power of many enzymes depends on the noncovalent interactions between substrates and enzymes , logPchl (the logarithm of the partition coefficient between chloroform and water), logPaln (the logarithm of the partition coefficient between aniline and water), logKbrain (the logarithm of the partition coefficient from air to human brain) and logKp are collected from literatures , Nc4 is the number of sp3 carbons connecting four heavy atoms (fluoride is not included).In M_HBD values of solutes were calculated based on the approach reported in a previous study . The flexibility of the C—C bond in RCH2—CH2R  bond, thCH2—CH2R  and thustr_depol) were calculated based on the method reported in previous study (oct (or logPchl) and ΔGtr_depol values of nonpolar compounds, the model for the regression of logPoct (or logPchl) against ΔGtr_depol was developed. This model was then used to calculate the logPoct (or logPchl) values for depolarized solutes. For a solute containing HBAs but no HBDs, the difference between the calculated logPoct (or logPchl) for the depolarized solute and the experimental logPoct (or logPchl) of the solute is the effect of HBAs on the logPoct (or logPchl) of the solute.The free energy changes for transferring depolarized solutes from water to hexadecane , and hydrogen-bond donors (HBDs) of the solutes, which was demonstrated in a previous study . Many prF values are constant for a given property. Theoretically, if the molecular descriptors apply to various properties, The km”. The Sm values of organic compounds represent the relative molecular sizes of the compounds and can be easily calculated from their molecular formulas . For example, the Sm for catechol (formula: C6H6O2) is 9.8  against the Sm values for the compounds from tr_depol against Sm further supports that Sm is an ideal molecular descriptor for quantifying the effect of molecular size on the properties depending on noncovalent interactions. Thus, Sm is an ideal molecular descriptor for molecular size and applies to various properties.The molecular descriptor we developed for quantifying the effects of molecular size on properties is denoted by “Sompounds . The log logPoct . We thus solutes . The R2 M_HBA.” The definition indicates that HM_HBA is an ideal molecular descriptor for quantifying the effects of HBAs on logP16. We next explored whether HM_HBA is an ideal molecular descriptor for logPoct and logPchl. The strong linear associations between the effect of HBAs on logPoct and HM_HBA   . In a pr(HM_HBD) . We also(HM_HBD) . Thus, w1, k2, k3, k4 and c are constants for a give property. Organic compounds usually contain multiple HBAs and the HBAs affect each other. The accurate calculation of HM_HBA for many organic compounds is not easy. M_HBA is replaced by logPow because logPow is a well-known molecular descriptor for predicting properties . Thus, for many properties that are affected by molecular size, HBAs, HBDs and flexibility, they can be quantified with the following equationoperties  and can oct, logP16, and logPchl values (16 against logPoct and logPchl against logPoct for various types of compounds are shown in 2 (squared correlation coefficient) values of the regressions range from 0.501 to 0.972 . The R2 values of the models range from 0.947 to 0.992  is weak (R2 < 0.1) (brain and logP16 (or logPoct) in a previous study  . Supplemus study . Based o16 as predictive variable is better than the model with logPoct as predictive variable. The predicted logKbrain obtained from the LOO cross-validation (logP16 is used) and the observed logKbrain show a robust linear association  with logP16 and Sm as predictive variables , the model for predicting the property should consider H-bond interactions individually, rather than the overall H-bond interactions. In our further study, we will explore how to develop models for the properties related to rigid environments, which can be used to develop scoring functions for predicting protein-ligand binding affinities and develop QSAR models for screening databases of ligands. Furthermore, in this study, we demonstrated to effectiveness of the LFER for predicting the properties of neutral organic compounds. If a dataset contains ionizable compounds, it will be necessary to include molecular descriptors for the ionized forms. Although several approaches currently exist for considering the effects of ionization on various molecular properties , our futIn this study, we used a thermodynamics-based theoretical derivation to develop a general LFER for accurately predicting various properties from partition coefficients. The theoretical derivation ensures that many specific properties can be accurately quantified with the molecular descriptors in the LFER. It overcomes the shortages of constructing QSPR models by using mathematical and statistical tools. It is expected that the thermodynamics-based theoretical derivation can be used to solve many difficult problems, including the accurate prediction of protein-ligand binding affinities.