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IntroductionObesity, a pervasive global epidemic, has heightened susceptibility to chronic ailments and diminished the overall life expectancy on a global scale. Probiotics and inulin (IN) have been documented to mitigate obesity by exerting an influence on the composition of the gut microbiota. Whether heat-killed Bifidobacterium longum BBMN68 (MN68) and IN have an anti-obesity effect remains to be investigated.MethodsIn this study, Wistar rats were fed a high-fat diet (HFD), and orally administered heat-killed MN68 (2 × 1011 CFU/kg) and/or inulin (0.25 kg/kg) for 12 weeks. Histological analysis, serology analysis and 16S rRNA gene sequencing were performed.ResultsHeat-killed MN68 + IN treatment showed an enhanced effect on preventing weight gain, diminishing fat accumulation, and regulating lipid metabolism, compared to either heat-killed MN68 treatment or inulin treatment. Gut microbiota results showed that heat-killed MN68 + IN treatment significantly increased the relative abundance of Bacteroidota, Oscillospira, Intestinimonas, Christensenella, and Candidatus_Stoquefichus, and reduced the relative abundance of Enterococcus. Furthermore, heat-killed MN68 + IN significantly increased the SCFA levels, which were correlated with changes in the gut microbiota.DiscussionThis research provides support for the application of heat-killed MN68 and IN in the treatment of obesity, and highlights the combination of heat-killed BBMN68 and IN as functional food ingredients.

Cryptosporidiosis is considered a crucial zoonotic disease caused by widely distributing parasitic protozoa called Cryptosporidium spp. Nitazoxanide is the only FDA-approved drug but is only effective with a good immune response of the host. In addressing this unmet medical need, we previously identified a compound, namely, LN002, as a potent alternative oxidase inhibitor against cryptosporidiosis. To illustrate the pharmacokinetics, absolute bioavailability, and tissue distribution of LN002 in rats, rapid and sensitive high-performance liquid chromatography was developed and validated for the separation and detection of LN002 in plasma, tissue samples, and intestinal contents. In this study, a single dose of oral administration and intravenous injection of LN002 was used to determine the levels of LN002 in plasma, tissue samples, and intestinal contents by UHLC. Results of the study indicated that after intravenous administration of 1 mg/kg LN002, the AUC0–24 h, T1/2,Vd, and Cl were 7024.86 h·ng/mL, 10.91 h, 1.69 L/kg, and 0.11 L/h/kg, respectively. After oral administration of a single dosage of 100, 200, and 400 mg/kg LN002, the Tmax, Cmax, AUC0–24 h, T1/2, F, Vd, and Cl/F in plasma of rats were 1 h, 849.88–4033.21 ng/mL, 2280.41–7498.10 h·ng/mL, 17.96–18.83 h, 0.27%–0.32%, 581.54–869.21 L/kg, and 25.97–39.00 L/h/kg, respectively. After oral administration of 200 mg/kg, LN002 was extensively distributed in the main tissues of rats, and massive amounts of LN002 were distributed in the intestine and intestinal contents, indicating its potential as an effective anti-Cryptosporidium compound. After oral administration of a single dosage of 200 mg/kg, LN002 has a low bioavailability and high levels in the intestine, which is crucial for the safe and effective treatment of cryptosporidiosis. Overall, the results of this study provide valuable data support for the future study of LN002.

Abstract Generally, when optimizing a rolling stock schedule, the locations of the depots, or places in the network where the composition changes and maintenance occurs, are assumed known. The locations where maintenance is performed naturally influence the quality of any resulting rolling stock schedules. In this paper, the problem of selecting new depot locations and their corresponding capacities is considered. A two-stage mixed integer programming approach for rolling stock scheduling with maintenance requirements is extended to account for depot selection. First, a conventional flow-based model is solved, ignoring maintenance requirements, to obtain a variety of rolling stock schedules with multiple depot locations and capacity options. Then, a maintenance feasible rolling stock schedule can be obtained by solving a series of assignment problems by using the schedules found in the first stage. The proposed methodology is tested on real-life instances, and the numerical experiments of different operational scenarios are discussed.

Abstract Background It is controversial whether antibiotic should be used prophylactically 48 h after pancreatic surgery. Hence, the association of antibiotic prophylaxis (AP) after 48 h postoperatively with the incidence of surgical site infections (SSIs) and other healthcare-associated infections (HAIs) in patients receiving pancreatic surgery was evaluated. Methods A retrospective cohort analysis was performed on 1073 patients who underwent pancreatic surgery. These patients were categorized into the non-AP after 48 h postoperatively group (n = 963) and the AP after 48 h postoperatively group (n = 110) based on whether or not they obtained AP from 48 h to 30 days after surgery. Outcomes included SSIs and other HAIs. Results The incidence of SSIs in the non-AP after 48 h postoperatively group (98/963, 10.2%) was notably lower than that in the AP after 48 h postoperatively group (22/110, 20.0%) (P = 0.002). Other HAIs incidence was not significantly different between the non-AP after 48 h postoperatively group (77/963, 8.0%) and the AP after 48 h postoperatively group (11/110, 10.0%) (P = 0.468). Multiple regression analysis demonstrated that AP after 48 h postoperatively was a risk factor for SSIs (OR = 2.14, 95% CI 1.28–3.59) but not for other HAIs (OR = 1.24, 95% CI 0.63–2.42) after adjustment for age, gender, and diabetes. Subsequent to adjustment for all confounding factors, AP after 48 h postoperatively was not a influence factor for SSIs (OR = 2.13, 95% CI 0.76–5.99) and other HAIs (OR = 3.69, 95% CI 0.99–13.81). Conclusions AP after 48 h postoperatively following pancreatic surgery was not associated with the lower morbidity rate of SSIs and other HAIs. Nonetheless, this study may facilitate further development of strategies towards standardization of the duration of AP management of pancreatic surgery.

The fate of resource recovery is significantly influenced by the standards of water quality and bio-dried excess sludge for various applications. These standards must be practically attainable while ensuring public and environmental health, safety, and economic advantages. The present study investigates a reclaimed wastewater treatment plant (WWTP) in Beijing that incorporates both reclaimed water utilization facility and bio-dried excess sludge treatment. The study elucidates the standards for reclaimed water quality and bio-dried excess sludge for diverse applications. Notably, reclaimed water demonstrates substantial market demand in terms of economic benefits. However, bio-dried excess faces challenges due to higher operational costs and lower TP content. The heat power of the WWTP effluent water source can not only be harnessed for the bio-drying process blowers but also be elevated air temperatures to expedite the bio-drying process. HIGHLIGHTS The H-reclaimed wastewater treatment plant successfully adheres to the limits of reclaimed water quality and bio-dried excess sludge.; In contrast with the excess sludge, reclaimed water enjoys market demand, owing to its reduced operational cost.; Using the heat power of the effluent water source could accelerate the bio-drying process of excess sludge.;

Beijing Plain is a very active part of Beijing city regarding the socio-economic and human activities of the region. Over the past four decades, Beijing’s economic development and the continuous drought for nearly 10 years in the 2000s have negatively impacted the groundwater quantity and quality. Therefore, it is necessary to investigate the present situation of groundwater chemistry in this region to develop a comprehensive database and orientation for future research on groundwater quality evaluation. Mathematical statistics, Piper’s trilinear diagram, Gibbs plots, the ion ratio method and PHREEQC software 3.7.3 were used to analyze the groundwater hydrogeochemical characteristics and formation mechanisms of the quaternary aquifers of the Beijing Plain area. Hydrogeochemical results indicated that the groundwater is slightly alkaline, with pH values ranging from 6.76 to 8.65 and an average value of 7.92. The order of major cations in groundwater was Ca2+ > Na+ > Mg2+ > K+ with average values of 66.54 mg/L, 50.58 mg/L, 23.78 mg/L, and 1.81 mg/L, respectively, while the order of major anions was HCO3− > SO42− > Cl− with average values of 284.89 mg/L, 52.1 mg/L and 35.5 mg/L, respectively. The groundwater chemical types are Mg-Ca-Cl-HCO3, Na-Ca-HCO3, Mg-Ca-HCO3 and Mg-Na-HCO3. Research on the main influencing factors and PHREEQC hydrogeochemical inverse simulations results along the four pathways selected confirmed that rock weathering with sulfate, silicate and carbonate rock mineral dissolution and Na+, Mg2+ and Ca2+ ion reaction exchange influenced groundwater hydrogeochemical characteristics of the quaternary aquifers of the Beijing Plain area. Understanding the formation mechanisms of hydrogeochemistry in quaternary plains provides guidance for future studies and, through suggestions and case studies, facilitates decision-making by policy-makers on the sustainable management of groundwater resources.

Abstract Cellular transitions hold great promise in translational medicine research. However, therapeutic applications are limited by the low efficiency and safety concerns of using transcription factors. Small molecules provide a temporal and highly tunable approach to overcome these issues. Here, we present PC3T, a computational framework to enrich molecules that induce desired cellular transitions, and PC3T was able to consistently enrich small molecules that had been experimentally validated in both bulk and single-cell datasets. We then predicted small molecule reprogramming of fibroblasts into hepatic progenitor-like cells (HPLCs). The converted cells exhibited epithelial cell-like morphology and HPLC-like gene expression pattern. Hepatic functions were also observed, such as glycogen storage and lipid accumulation. Finally, we collected and manually curated a cell state transition resource containing 224 time-course gene expression datasets and 153 cell types. Our framework, together with the data resource, is freely available at http://pc3t.idrug.net.cn/ . We believe that PC3T is a powerful tool to promote chemical-induced cell state transitions.

Abstract The rapid increase of photovoltaic (PV) penetration in active distribution networks (ADN) is posing great challenges to traditional voltage control schemes. A two‐stage voltage control strategy of ADN is proposed by the authors based on the alternating direction method of multipliers (ADMM) with refined power to hydrogen (P2H) model, considering multiple types of PV forms such as residential photovoltaic cluster (RPVC) and small‐scale PV power stations. In the day‐ahead stage, the optimal power flow is performed to determine the optimal scheduling results of on‐load tap changers and capacitor banks etc. In the intra‐day stage, the real‐time voltage control strategy is implemented at the distribution network layer to regulate the power of each type of PV, energy storage systems and P2H to further reduce the voltage deviation. At the customer layer, the residential photovoltaic (RPV) within the RPVC is precisely controlled based on the ADMM algorithm to achieve the minimum voltage deviation at each RPV access point. The proposed strategy is tested on the modified IEEE 33‐bus and IEEE 69‐bus distribution systems, and the simulation results verify its effectiveness in mitigating voltage violations.

The phenylpyrazole derivative 5-amino-3-[1-cyano-2-(3-phenyl-1H-pyrazol-4-yl) vinyl]-1-phenyl-1H-pyrazole-4-carbonitrile (LN002), which was screened out through high-throughput molecular docking for the AOX target, exhibits promising efficacy against Cryptosporidium. However, its poor water solubility limits its oral bioavailability and therapeutic utility. In this study, solid dispersion agents were prepared by using HP-β-CD and Soluplus® and characterized through differential scanning calorimetry, Fourier transform infrared, powder X-ray diffraction, and scanning electron microscopy. Physical and chemical characterization showed that the crystal morphology of LN002 transformed into an amorphous state, thus forming a solid dispersion of LN002. The solid dispersion prepared with an LN002/HP-β-CD/Soluplus® mass ratio of 1:3:9 (w/w/w) exhibited significantly increased solubility and cumulative dissolution. Meanwhile, LN002 SDs showed good preservation stability under accelerated conditions of 25 °C and 75% relative humidity. The complexation of LN002 with HP-β-CD and Soluplus® significantly improved water solubility, pharmacological properties, absorption, and bioavailability.

Abstract Predicting future land system changes driven by anthropogenic and climactic impacts can help to explore adaptation and mitigation pathways for regional and global sustainable development. Here, we project land cover changes in China from 2030 to 2100 at a resolution of 1 km × 1 km under eight scenarios based on the Scenario Model Intercomparison Project (ScenraioMIP), which are extracted from Land Use Harmonization version 2 (LUH2). We use a rule‐based method to classify and map 9 land cover dynamic trajectories at patch scale to present land system changes. At the provincial scale we used hierarchical clustering to identify archetypes of land cover change, which can predict ecological risks for future management in western provinces. Our results reveal that anthropogenic mitigation policies under high mitigation pressure do not result in positive impacts on the land system, but rising temperatures will provide a great opportunity for ecological restoration in some regions.

Over the past 30 years, water security issue in Chinese cities has become increasingly serious, largely due to rapid urbanization, population growth and disproportionate investment in water infrastructure. Urban rainwater harvesting (URWH), a household and community-level rainwater management measure, has been widely used during this period. This study provides a critical review of the policies, methods, technology, construction, implementation and benefits related to URWH in China. We show that URWH in China has gone through three phases over the past 30 years: an initial development phase, a rapid development phase and a sponge city construction phase. URWH research has focused mainly on rainwater harvesting, storage, utilization, management and other technologies, with limited attention to policy and benefit analysis. However, the scale of URWH construction and implementation in China remains small and needs further development. Currently, while URWH assessments cover social, ecological and environmental benefits, the economic benefits need to be further strengthened. The next step in URWH implementation should be to strengthen research and development of policy, legal and design standards. This study provides guidance for the implementation of URWH in Chinese cities and other cities alike in developing countries. HIGHLIGHTS Urban rainwater harvesting (URWH) in China has been divided into three stages.; The construction and development of laws and regulations should be emphasized in China in the future.; The construction of URWH projects in China has been uneven.; China's URWH construction constitutes government-led investment projects embodying positive social and ecological benefits.;

IntroductionCognitive dysfunction has frequently been found in patients with migraine. The so-called contingent negative variation (CNV) and EEG power spectral densities may be the best choices to explore the underlining pathophysiology, such as cortical inhibition and habituation.MethodsThirty migraine patients without aura and healthy controls matched for sex, age, and education were recruited separately for CNV recording. The amplitudes, latencies, and squares of different CNV components, such as oCNV, iCNV, tCNV, and PINV, were selected and analyzed. Behavioral data, such as manual reaction time (RT), were analyzed. We used the Person correlation coefficient R to analyze different ERP components in relation to clinical characteristics. A multiple regression analysis was conducted for the migraine group. Spectral analysis of EEG data from all channels using the fast Fourier transform (FFT).ResultsThe migraine group had longer A-latency, C-latency, and iCNV-latency than the control group. The migraine group had higher iCNV-amplitude, oCNV-amplitude, and tCNV-amplitude than the control group, especially those located in the occipital area. The iCNV-square, oCNV-square, tCNV-square, or PINV-square in the migraine group was significantly larger than the control group. Different correlations were found between clinical characteristics and ERP components. The delta or theta activity in the migraine group was statistically lower than in the control group.DiscussionOur study has revealed that migraine attacks may influence responsivity, pre-activation, habituation, and cortical inhibition not only on the behavioral level but also on the electrophysiological level. Abnormal changes in cortical habituation and inhibition can be interpreted as CNV components. Additionally, analyses have revealed correlations between CNV components and various factors, including age, the clinical course of the condition, attack frequency, pain intensity, and duration. Thus, repetitive migraine attacks can lead to a reduction in cortical inhibition and subsequent impairment in executive function.

With the progress of economic development and increase in income, there have been significant transformations in the food consumption patterns among Chinese residents. Grain consumption has declined while the consumption of livestock products such as meat, poultry, eggs, and milk has gradually risen. Moreover, noteworthy adjustments have been observed in the meat consumption structure itself, with a substantial increase in poultry consumption and a significant decrease in pork consumption as representative of red meat. This study collects data mainly from the “Brick Agricultural Database” and “China National Grain & Oils Information Center”. And then, we employ the China Agricultural Industry Model (CASM) to simulate the economic and ecological consequences of augmenting poultry consumption as a substitute for red meat intake. The research findings demonstrate that ensuring an adequate intake of livestock products for residents without any decline will stimulate the doubling of China’s poultry meat demand by 2035 compared to 2020 while replacing pork. This would reduce feed grain requirements by 50 million tons and achieve carbon emission reductions amounting to 82 million tons. If we consider the consumption of poultry consumption growth in conjunction with its substitution for other red meats such as pork, beef, and mutton, this will save approximately 20 million tons of feed grains and lead to a reduction of around 103 million tons in carbon emissions. In conclusion, promoting future increases in poultry consumption as a substitute for pork and other red meat will yield extensive economic andecological benefits contributing toward international food security goals, as well as global carbon reduction targets. Additionally, advocating for increasing poultry consumption will also reduce the risk of chronic diseases and malignant tumors; this will significantly improve the national health states.

Bovine mastitis caused by infectious pathogens can lead to a decline in production performance and an increase in elimination rate, resulting in huge losses to the dairy industry. This study aims to prepare a novel dairy cow teat disinfectant with polyhexamethylene biguanide (PHMB) as the main bactericidal component and to evaluate its bactericidal activity in vitro and its disinfection effect in dairy cow teats. PHMB disinfectant with a concentration of 3 g/L was prepared with PVA-1788, propylene glycol and glycerol as excipients. When the dilution ratio is 1:4800 and the action time is 5 min, the PHMB teat disinfectant can reduce the four types of bacteria (S. agalactiae ATCC 12386, S. dysgalactiae ATCC 35666, S. aureus ATCC 6538, and E. coli ATCC 8099) by 99.99%. PHMB teat disinfectant applied on the skin of rabbits with four bacteria types achieved an average log10 reduction greater than 4. After 30 s of PHMB teat disinfectant dipping, the bacteria of cow teats were counted prior to disinfection. The mean log10 reduction in bacteria on the skin surface of 12 cows ranged from 0.99 to 3.52 after applying the PHMB teat disinfectant for 10 min. After 12 h, the PHMB teat disinfectant achieved an average log10 reduction in bacteria from 0.27 to 0.68 (compared with that prior to disinfection). These results suggested that PHMB teat disinfection has the potential to prevent and treat mastitis-causing bacteria in dairy herds.

Cell-based regenerative therapy utilizes the differentiation potential of stem cells to rejuvenate tissues. But the dynamic fate of stem cells is calling for precise control to optimize their therapeutic efficiency. Stem cell fate is regulated by specific conditions called “microenvironments.” Among the various factors in the microenvironment, the cell-surface glycan acts as a mediator of cell-matrix and cell-cell interactions and manipulates the behavior of cells. Herein, metabolic glycoengineering (MGE) is an easy but powerful technology for remodeling the structure of glycan. By presenting unnatural glycans on the surface, MGE provides us an opportunity to reshape the microenvironment and evoke desired cellular responses. In this review, we firstly focused on the determining role of glycans on cellular activity; then, we introduced how MGE influences glycosylation and subsequently affects cell fate; at last, we outlined the application of MGE in regenerative therapy, especially in the musculoskeletal system, and the future direction of MGE is discussed.

Abstract Background No studies have yet reported the effect of prevention and control measures, which were implemented to combat COVID-19, on the prevention and control of common HAIs. We aimed to examine the effect of the “Normalized Epidemic Prevention and Control Requirements” (implemented in May 2020) by comparison of hospital-acquired infections (HAIs) and community-acquired infections (CAIs) in China during 2018, 2019, and 2020. Methods Data of inpatients before and after implementation of new requirements were retrospectively analyzed, including infection rate, use of alcohol-based hand cleaner, anatomical sites of infections, pathogen species, infection by multi-drug resistant species, and use of different antibiotics. Results The HAI rate was significantly higher in 2020 than in 2018 and 2019 (P

Abstract Urbanization has resulted in dry/wet island effects in built-up areas. Compared to the limited number of observational datasets, simulations can provide data with richer spatial distribution, thereby proving to be more helpful for revealing the spatial distribution of dry/wet islands. This study simulated dry/wet island effects during typical summer and winter conditions in Beijing by coupling the Artificial Water Dissipation Urban Canopy Model with the Weather Research and Forecasting model. Observations of relative humidity, absolute humidity, and temperature from weather stations in Beijing were used to verify the model. The results showed that in 2020, Beijing was prone to be a dry island during summer, with the relative humidity approximately 5–10% lower than the surrounding suburbs. The dry island effect was not obvious in winter, and Beijing tended to be a wet island. The influence of artificial water dissipation on dry/wet islands is higher in winter than in summer. By considering the water vapor from artificial water dissipation, humidity in urban areas can be simulated more accurately.

Memory accuracy involves two major processes: pattern separation and pattern completion. Pattern separation refers to the ability to reduce overlap among similar inputs to avoid interference, and pattern completion refers to the ability to retrieve the whole information from partial or degraded cues. Impairments in pattern separation/pattern completion contribute to cognitive deficits in several diseases of the nervous system. Therefore, it is better to evaluate both pattern separation and pattern completion in one apparatus. However, few tools are available to assess pattern separation and pattern completion within the same apparatus for rodents. In this study, we designed a series of images with varying degrees of similarity to the correct image to evaluate pattern separation and pattern completion. First, mice were trained to discriminate between two totally different images, and once the correct percentage reached above 77% for two consecutive days, the images with different degrees of similarity were used to measure pattern separation and pattern completion. The results showed the mice performed progressively worse from S0 to S4 (increasing similarity) when discriminating similar images in pattern separation, and the mice performed progressively worse from C0 to C4 (decreasing cues information) when recalling the correct image according to partial cues in pattern completion, implying a good image similarity-dependent manner for memory accuracy evaluation. In sum, we designed a convenient, effective paradigm to evaluate pattern separation and pattern completion based on a touchscreen pairwise discrimination task, which may provide a new method for the studies of the effects and mechanisms of memory accuracy enhancing drugs.

Isopropoxy benzene guanidine (IBG) is a guanidine derivative with antibacterial activity against multidrug-resistant bacteria. A few studies have revealed the metabolism of IBG in animals. The aim of the current study was to identify potential metabolic pathways and metabolites of IBG. The detection and characterization of metabolites were performed with high-performance liquid chromatography tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). Seven metabolites were identified from the microsomal incubated samples by using the UHPLC-Q-TOF-MS/MS system. The metabolic pathways of IBG in the rat liver microsomes involved O-dealkylation, oxygenation, cyclization, and hydrolysis. Hydroxylation was the main metabolic pathway of IBG in the liver microsomes. This research investigated the in vitro metabolism of IBG to provide a basis for the further pharmacology and toxicology of this compound.

The compilation of technology lists addressing climate change has a guiding effect on promoting technological research and development, demonstration, and popularization. It is also crucial for China to strengthen ecological civilization construction, achieve the carbon emission peak and carbon neutrality target, and enhance global climate governance capabilities. This study first proposes the existing classification outline of the technology promotion lists, technology demand lists, and future technology lists. Then, different methodologies are integrated on the basis of the existing outline of four technology lists: China’s existing technological promotion list for addressing climate change, China’s demand list for climate change mitigation technology, China’s key technology list for addressing climate change, and China’s future technology list for addressing climate change. What’s more, core technologies are analyzed in the aspects of technology maturity, carbon reduction cost, carbon reduction potential, economic benefits, social influence, uncertainty, etc. The results show that: key industries and sectors in China already have relatively mature mitigation/adaptation technologies to support the achievement of climate change targets. The multi-sectoral system of promoting climate-friendly technologies has been established, which has played an active role in tackling climate change. Currently, climate technology needs are concentrated in the traditional technology and equipment upgrading, renewable energy technology, and management decision-making support technology. The key technologies are concentrated in 3 major areas and 12 technological directions that urgently need a breakthrough. For carbon emmission peak and nentrality, carbon depth reduction and zero carbon emissions and geoengineering technology (CDR and SRM) have played an important role in forming the structure of global emissions and achieving carbon neutrality in the future. Thus, the uncertainty assessment for the comprehensive technology cost-effectiveness, technology integration direction, technical maturity, ethics and ecological impacts is supportive to the national technology strategy. Finally, the presented study proposes several policy implications for medium- and long-term technology deployment, improving technology conversion rate, promoting the research and development of core technologies, and forming a technology list collaborative update and release mechanism.

Analysis of drug-induced expression profiles facilitated comprehensive understanding of drug properties. However, many compounds exhibit weak transcription responses though they mostly possess definite pharmacological effects. Actually, as a representative example, over 66.4% of 312,438 molecular signatures in the Library of Integrated Cellular Signatures (LINCS) database exhibit low-transcriptional activities (i.e. TAS-low signatures). When computing the association between TAS-low signatures with shared mechanism of actions (MOAs), commonly used algorithms showed inadequate performance with an average area under receiver operating characteristic curve (AUROC) of 0.55, but the computation accuracy of the same task can be improved by our developed tool Genetic profile activity relationship (GPAR) with an average AUROC of 0.68. Up to 36 out of 74 TAS-low MOAs were well trained with AUROC ≥ 0.7 by GPAR, higher than those by other approaches. Further studies showed that GPAR benefited from the size of training samples more significantly than other approaches. Lastly, in biological validation of the MOA prediction for a TAS-low drug Tropisetron, we found an unreported mechanism that Tropisetron can bind to the glucocorticoid receptor. This study indicated that GPAR can serve as an effective approach for the accurate identification of low-transcriptional activity drugs and their MOAs, thus providing a good tool for drug repurposing with both TAS-low and TAS-high signatures.

Gender equality is a yardstick for measuring the progress of social civilization and an important goal for mankind to achieve sustainable development. The importance of women in the global governance of climate change is self-evident. During the global climate change governance, it is very crucial to focus on achieving gender equality. Under the United Nations Framework Convention on Climate Change, which is the main channel of global climate change governance, the gender-specific climate change agenda started later than other topics and the progress is limited. This article summarized the progress, deficiencies and future directions of gender issues under the main channels of global climate governance, analyzed the current status of gender equality in Chinese climate response actions, and pointed out the progress and deficiencies of women in the fundamental scientific research and the participation in global governance and decision-making. Our research finds that in the current process of international climate change governance, gender issues have received adequate attention. While in China, despite the attention paid to gender issues, the practical action on gender equality is still out of the mainstream agenda. In the past few decades, Chinese women have made gratifying progress in basic scientific research on climate change and global climate governance, but there are still great insufficiencies in the field of decision-making. In the future, China needs to pay more attention to emphasize gender equality at the strategic level, and promote the formulation of policies and regulations in the field of gender and climate change. Increasing the proportion of women participating in decision-making and management in the field of climate change and disaster prevention and mitigation is also important. China also needs to focus on enabling a gender friendly environment and strengthening research on gender and climate change, support women's participation in relevant work, strengthen capacity-building, and enhance women's access to resources, funds, knowledge and information related to climate adaptation or mitigation.

Abstract Background Querying drug-induced gene expression profiles with machine learning method is an effective way for revealing drug mechanism of actions (MOAs), which is strongly supported by the growth of large scale and high-throughput gene expression databases. However, due to the lack of code-free and user friendly applications, it is not easy for biologists and pharmacologists to model MOAs with state-of-art deep learning approach. Results In this work, a newly developed online collaborative tool, Genetic profile-activity relationship (GPAR) was built to help modeling and predicting MOAs easily via deep learning. The users can use GPAR to customize their training sets to train self-defined MOA prediction models, to evaluate the model performances and to make further predictions automatically. Cross-validation tests show GPAR outperforms Gene set enrichment analysis in predicting MOAs. Conclusion GPAR can serve as a better approach in MOAs prediction, which may facilitate researchers to generate more reliable MOA hypothesis.

Maintaining optimum temperature during freeze-drying is crucial to ensuring the viability of strains. In this study, we evaluated the effect of pre-freezing, sublimation and desorption temperatures on the viability of Bifidobacterium longum BB68S (BB68S). Moreover, we examined the water content, water activity, enzyme activities, and scanning electron microscope of BB68S to explore mechanisms underpinning the effect of temperature on viability. Our analyses revealed the highest survival rates of BB68S collected after pre-freezing and sublimation drying at −40 °C (94.9 ± 2.2%) and −10 °C (65.4 ± 3.8%), respectively. Additionally, response surface methodology demonstrated that the optimum conditions for freeze-drying of BB68S were pre-freezing temperature at −45.52 °C and sublimation temperature at −6.58 °C, and the verification test showed that survival rates of BB68S could reach 69.2 ± 3.8%. Most of the vitality loss occurred during the sublimation drying phase. Further studies showed that different sublimation temperatures affected water content and activity, β-galactosidase, lactate dehydrogenase, Na+-K+-ATP and Ca2+-Mg2+-ATP activities. In conclusion, the temperature during freeze-drying, especially sublimation temperature, is a key factor affecting the survival rate of BB68S, and the vitality loss during freeze-drying process might be due to compromised cell membrane integrity and permeability.

In the research, sulfide nanoscale zero-valent iron (S-nZVI) was synthesized, characterized and further applied to remove hexavalent chromium Cr(VI) from water. The results showed that a maximum adsorption (81 mg/g) and repeatability was reached at a sulfur/iron molar ratio of 0.1. Sulfide modification could form amorphous FeS on the surface of nZVI, which enhanced the antioxidant activity and hydrophobicity of S-nZVI0.1. The removal of Cr (VI) by S-nZVI0.1 was in accordance with the pseudo-second-order and Langmuir model with the theoretical removal capacity of 83.51 mg/g. After aging 45 d, 60 mg/g of Cr(VI) still was adsorbed by S-nZVI0.1, suggesting that S-nZVI0.1 exhibited a better stability. 84.1 % of Cr(VI) was reduced to Cr(III) on the surface of S-nZVI0.1, Fe0, FeS, Fe2+ and S2- were involved in the reduction reaction. This study provided guidance for synthesizing well stability and high reaction of S-nZVI to remove Cr(VI). [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the efficacy and safety of aerosol inhalation of recombinant human interferon α1b (IFNα1b) injection for noninfluenza viral pneumonia. Methods One hundred sixty-four patients with noninfluenza viral pneumonia were divided into IFNα1b and control groups. The IFNα1b group received routine treatment + aerosol inhalation of recombinant human IFNα1b injection (50 μg × 2 injections, bid). The control group received routine treatment + IFN analog (two injections, bid). Overall response rate (ORR) of five kinds clinical symptoms. Further outcomes were daily average score and the response rate of each of the symptoms above. Results A total of 163 patients were included in the full analysis set (FAS) and 151 patients were included in the per-protocol set (PPS). After 7 days of treatment, ORR of clinical symptoms was higher in IFNα1b group than that in control group for both the FAS and PPS. Moreover, after 7 days of treatment, the daily score of three efficacy indexes including expectoration, respiratory rate, and pulmonary rales were improved. The ORRs for expectoration and pulmonary rales were higher in the IFNα1b group than in the control group (P 0.05). The incidence of adverse events was 6.5% (n = 5) in IFNα1b group and 3.5% (n = 3) in control group (P > 0.05). Conclusion Aerosol inhalation of recombinant human IFNα1b is safe and it can improve the clinical symptoms of noninfluenza viral pneumonia.

Climate change endangers food security worldwide, especially in developing countries. Livestock husbandry is one of the essential livelihoods for farmers and herders in remote arid and semiarid regions. However, it remains unclear how climate change will impact livestock husbandry in the future. This study collected sheep and goat distributions from the “gridded livestock of the world” (GLW) dataset for 1943 counties in Mainland China. Current climate data include precipitation and temperature from the National Meteorological Information Center (NMIC). We disentangled the effects of precipitation and temperature on current distributions of sheep and goats with the Bayesian Hierarchical Model by Integrated Nest Laplace Approximation (INLA). Further, we forecasted the potential sheep and goat distributions in 2030 and 2050 under Coupled Model Intercomparison Project (CMIP) scenarios. Our result showed that sheep distribution is significantly correlated with elevation, slope, market density, and highway distance, with absolute correlation coefficients ranging from 0.019 to 0.411. In addition to elevation, slope, and market density, goat distribution is also affected by gain production, with a correlation coefficient of 0.055. There is a dynamic correlation of temperature and precipitation with sheep and goat density. The sheep density distribution is predicted to increase in Northwest China, while the goat density distribution might increase in farming areas under climate change. Finally, this study suggests for the sheep and goat breeding industry to respond to climate change.

Nosocomial infection caused by carbapenem-resistant Klebsiella pneumonia (CRKP) infection has become a global public health problem. Human NK and NKT cells in peripheral immune responses are recognized as occupying a critical role in anti-bacterial immunity. Through performed scRNA-seq on serial peripheral blood samples from 3 patients with CRKP undergoing colonization, infection, and recovery conditions, we were able to described the immune responses of NK and NKT cells during CRKP infection and identified a mechanism that could contribute to CRKP clearance. The central player of CRKP infection process appears to be the NKT subset and CD56hiNKT subset which maintained immune competence during CRKP colonization. With time, CRKP leads to the loss of NK and CD160hiNKT cells in peripheral blood, resulting in suppressed immune responses and increased susceptibility to opportunistic infection. In summary, our study identified a possible mechanism for the CRKP invasion and to decipher the clues behind the host immune response that influences CRKP infection pathogenesis.