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Objective: The possible enhancing effect of anlotinib on programmed death receptor ligand (PD-L1) antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium, including lymphatic endothelial cells (LECs) and blood endothelial cells (BECs), were determined to identify patients who would benefit from this treatment. Methods: PD-L1 positivity in LECs, BECs, and tumor cells (TCs) was assessed using paraffin sections with multicolor immunofluorescence in an investigator’s brochure clinical trial of TQB2450 (PD-L1 antibody) alone or in combination with anlotinib in patients with non-small cell lung cancer. Progression-free survival (PFS) with different levels of PD-L1 expression was compared between the two groups. Results: Among 75 patients, the median PFS (mPFS) was longer in patients who received TQB2450 with anlotinib [10 and 12 mg (161 and 194 days, respectively)] than patients receiving TQB2450 alone (61 days) [hazard ratio (HR) 10 mg = 0.390 (95% confidence interval {CI}, 0.201–0.756), P = 0.005; HR 12 mg = 0.397 (0.208–0.756), P = 0.005]. The results were similar among 58 patients with high PD-L1 expression in LECs and TCs [159 and 209 vs. 82 days, HR 10 mg = 0.445 (0.210–0.939), P = 0.034; HR 12 mg = 0.369 (0.174–0.784), P = 0.009], and 53 patients with high PD-L1 expression in BECs and TCs [161 and 209 vs. 41 days, HR 10 mg = 0.340 (0.156–0.742), P = 0.007; HR 12 mg = 0.340 (0.159–0.727), P = 0.005]. No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases. Conclusions: Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs. Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs, which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.

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.

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 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.;

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.

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.

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.

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.;

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.

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.

In recent years, physical layer security technology has provided a new way to solve the problem of secure transmissions in wireless communications from an information theory perspective by using physical layer security coding and the inherent characteristics of the channel. As a nonsystematic code, Luby transform (LT) code has the characteristics of random coding and rateless, therefore, eavesdroppers cannot directly obtain useful information from leaked code symbols. As a shifted LT (SLT) code, the SLT codes can efficiently recover information, with a smaller decoding overhead. Therefore, we propose an SLT-LT joint code anti-eavesdropping scheme based on random symbol sets. Based on the environment of the main channel, the sender selects a set of random symbols to send to legitimate receivers as known symbols and uses these random symbols and message symbols to form source symbols for the SLT-LT concatenated coding to increase the bit error rate (BER) of the eavesdroppers. The experimental results show that, compared with other anti-eavesdropping LT schemes, our proposed scheme only adds a small amount of decoding overhead but has a better security performance.

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.

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.

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.

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.

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.

To solve the problem that the existing YOLOv3 algorithm had more false detections and missed detections for traffic sign detection task with small target problems and complex background, based on the YOLOv3, a channel attention method for target detection and a spatial attention method based on semantic segmentation guidance were proposed to form the YOLOv3-A (attention) algorithm.The detection features in the channel and spatial dimensions were recalibrated, allowing the network to focus and enhance the effective features, and suppress interference features, which greatly improved the detection performance.Experiments on the TT100K traffic sign data set show that the algorithm improves the detection performance of small targets, and the accuracy and recall rate of the YOLOv3 are improved by 1.9% and 2.8% respectively.

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.

Lane changing behavior is one of the most important tasks in driving. Cooperative lane change based on vehicle-vehicle (V2V) communication technology is getting extensive attention due to its potential to improve traffic safety and increase efficiency. In order to explore the internal mechanism of cooperative lane change behavior, the cooperative car-following model considering the stimulatory effect of lane-changing types is proposed in this paper. We investigate three lane changing types (free lane change, forced lane change, and cooperative lane change) to impact cooperative lane changing behavior. Based on this analysis, cooperative level function is presented. By using linear stability theory, the stability criterion of the proposed model is obtained. Simulation scenarios are set in three typical situations (starting process, stopping process and perturbation process) to analyze FVD model, cooperative driving for non-lane mode and cooperative driving for lane-changing mode. Simulation results indicate that cooperative driving of lane-changing mode has larger stable region compared to FVD model, cooperative driving for non-lane mode. Furthermore, the higher the level of cooperation, the greater the area of stability. Meanwhile, the simulation experiment also shows that response capability and smoothness of cooperative driving for lane-changing mode is be effectively promoted to the acceleration, velocity evolution.

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.

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.

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.

Background: Cranial radiotherapy is clinically used in the treatment of brain tumours; however, the consequent cognitive and emotional dysfunctions seriously impair the life quality of patients. LW-AFC, an active fraction combination extracted from classical traditional Chinese medicine prescription Liuwei Dihuang decoction, can improve cognitive and emotional dysfunctions in many animal models; however, the protective effect of LW-AFC on cranial irradiation–induced cognitive and emotional dysfunctions has not been reported. Recent studies indicate that impairment of adult hippocampal neurogenesis (AHN) and alterations of the neurogenic microenvironment in the hippocampus constitute critical factors in cognitive and emotional dysfunctions following cranial irradiation. Here, our research further investigated the potential protective effects and mechanisms of LW-AFC on cranial irradiation–induced cognitive and emotional dysfunctions in mice.Methods: LW-AFC (1.6 g/kg) was intragastrically administered to mice for 14 days before cranial irradiation (7 Gy γ-ray). AHN was examined by quantifying the number of proliferative neural stem cells and immature neurons in the dorsal and ventral hippocampus. The contextual fear conditioning test, open field test, and tail suspension test were used to assess cognitive and emotional functions in mice. To detect the change of the neurogenic microenvironment, colorimetry and multiplex bead analysis were performed to measure the level of oxidative stress, neurotrophic and growth factors, and inflammation in the hippocampus.Results: LW-AFC exerted beneficial effects on the contextual fear memory, anxiety behaviour, and depression behaviour in irradiated mice. Moreover, LW-AFC increased the number of proliferative neural stem cells and immature neurons in the dorsal hippocampus, displaying a regional specificity of neurogenic response. For the neurogenic microenvironment, LW-AFC significantly increased the contents of superoxide dismutase, glutathione peroxidase, glutathione, and catalase and decreased the content of malondialdehyde in the hippocampus of irradiated mice, accompanied by the increase in brain-derived neurotrophic factor, insulin-like growth factor-1, and interleukin-4 content. Together, LW-AFC improved cognitive and emotional dysfunctions, promoted AHN preferentially in the dorsal hippocampus, and ameliorated disturbance in the neurogenic microenvironment in irradiated mice.Conclusion: LW-AFC ameliorates cranial irradiation–induced cognitive and emotional dysfunctions, and the underlying mechanisms are mediated by promoting AHN in the dorsal hippocampus and improving the neurogenic microenvironment. LW-AFC might be a promising therapeutic agent to treat cognitive and emotional dysfunctions in patients receiving cranial radiotherapy.

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 Rationale Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with “early” stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). Objectives To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. Methods Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. Results Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005–1.379], p = 0.043). Conclusions Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. Trial registration NCT01581229. Registered 19 April 2012

Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality all over the world. Acute exacerbation of COPD (AECOPD) not only accelerates the progression of disease, but also causes hospital administration and death events. Epidemiologic studies have shown air pollution is a high risk factor of AECOPD. However, there are rare technics or treatment strategies recommended to reduce severe air pollution related AECOPD. Methods This is a multi-center, prospective, randomized and standard treatment parallel control clinical trial. Seven hundred sixty-four stable COPD patients in group B, C and D according to GOLD 2017 will be recruited and equally divided into two parallel groups, salvational intervention (SI group) and control group (CT group). Original treatments for participants include tiotropium (18μg once q.d), budesonide/formoterol (160μg/4.5μg once or twice b.i.d) or budesonide/formoterol (160μg/4.5μg once or twice b.i.d) with tiotropium (18μg once q.d). The savational intervention for SI group is routine treatment plus budesonide/formoterol (160μg/4.5μg once b.i.d) from the first day after severe air pollution (air quality index, AQI ≥200) to the third day after AQI

Here, we described the generation of human induced pluripotent stem cells (iPSC) from peripheral blood mononuclear cells (PBMCs) of a 87-year-old female patient with sporadic Alzheimer's disease (sAD) having APOE3 (ε3/ε3) genotype. iPSC line were generated from PBMCs with four factors of OCT4, SOX2, c-MYC and KLF4 using episomal system. The pluripotency of the iPSC line was assessed by embryoid body (EB) formation. Flow cytometry analyses revealed >97% cells positive for the pluripotency markers NANOG, OCT4 and SSEA4. Furthermore, the iPSC line displayed a normal karyotype (46, XX). The iPSC line may provide valuable tools for the study of sAD pathogenesis.

The number of passengers in a high-speed railway line normally varies significantly by the time periods, such as the peak and nonpeak hours. A reasonable classification of railway operation time intervals is essential for an adaptive adjustment of the train schedule. However, the passenger flow intervals are usually classified manually based on experience, which is subjective and inaccurate. Based on the time samples of actual passenger demand data for 365 days, this paper proposes an affinity propagation (AP) algorithm to automatically classify the passenger flow intervals. Specifically, the AP algorithm first merges time samples into different categories together with the passenger transmit volume of the stations, which are used as descriptive variables. Furthermore, clustering validity indexes, such as Calinski–Harabasz, Hartigan, and In-Group Proportion, are employed to examine the clustering results, and reasonable passenger flow intervals are finally obtained. A case study of the Zhengzhou-Xi’an high-speed railway indicates that our proposed AP algorithm has the best performance. Moreover, based on the passenger flow interval classification results obtained using the AP algorithm, the train operation plan fits the passenger demand better. As a result, the indexes of passenger demand satisfaction rate, average train occupancy rate, and passenger flow rate are improved by 7.6%, 16.7%, and 14.1%, respectively, in 2014. In 2015, the above three indicators are improved by 5.7%, 18.4%, and 14.4%, respectively.

Various deconvolution algorithms for acoustic source are developed to improve spatial resolution and suppress sidelobe of the conventional beamforming. To improve the computational efficiency and solution convergence of deconvolution, this paper proposes a Fourier-based improved fast iterative shrinkage thresholding algorithm. Simulations and experiments show that Fourier-based improved fast iterative shrinkage thresholding algorithm can achieve excellent acoustic identification performance, with high computational efficiency and good convergence. For Fourier-based improved fast iterative shrinkage thresholding algorithm, the larger the weight coefficient, the narrower the mainlobe width, and the better the convergence, but the spurious source also increases. The recommended weight coefficient for the array described herein is 3. In addition, like other Fourier-based deconvolution algorithms, Fourier-based improved fast iterative shrinkage thresholding algorithm using irregular focus grid can obtain better acoustic source identification performance than using the conventional regular focus grid.

Objectives Cardiac rehabilitation (CR) improves outcomes after myocardial infarction (MI), but it is underused in China. The purpose of this study was to develop a set of quality indicators (QIs) to improve clinical practices and to confirm the measurability and performance of the developed QIs for CR in Chinese patients after MI.Design and setting The QIs were developed by a Chinese expert consensus panel during in-person meetings. The five QIs most in need of improvement were selected using a national questionnaire. Finally, the completion rate and feasibility of the QIs were verified in a group of MI survivors at university hospitals in China.Participants Seventeen professionals participated in the consensus panel, 89 personnel in the field of CR participated in the national questionnaire and 165 MI survivors participated in the practice test.Results A review of 17 eligible articles generated 26 potential QIs, among which 17 were selected by the consensus panel after careful evaluation. The 17 QIs were divided into two domains: (1) improving participation and adherence and (2) CR process standardisation. Nationwide telephone and WeChat surveys identified the five QIs most in need of improvement. A multicenter practice test (n=165) revealed that the mean performance value of the proposed QIs was 43.9% (9.9%–86.1%) according to patients with post-MI.Conclusions The consensus panel identified a comprehensive set of QIs for CR in patients with post-MI. A nationwide questionnaire survey was used to identify the QIs that need immediate attention to improve the quality of CR. Although practice tests confirmed the measurability of the proposed QIs in clinical practice, the implementation of the QIs needs to be improved.Trial registration number This study is part of a study registered in ClinicalTrials.gov (NCT03528382).

Evaluating the responses of net primary productivity (NPP) to climate change is essential for regional ecosystem management and adaptations to climate change. The Yangtze River Economic Belt (YREB) is a key ecological functional area and hotspot of carbon sequestration in China due to the high degree of forest coverage. We used a process-based ecosystem model to project terrestrial NPP and analyzed the response to climate change over the 21st century in the YREB under two representative concentration pathway (RCP) scenarios using the regional climate model. The results show that the projection of NPP generally increased by 13.5% under RCP4.5 and 16.4% under RCP8.5 in the middle of the century, by 23% under RCP4.5, and by 35% under RCP8.5 in the late term of the century compared with that from a reference period of current climate conditions (1985–2006). The rate of NPP change under the RCP8.5 scenario is higher than that under the RCP4.5 scenario. Similarly, the NPP is also projected to increase both with 1.5 and 2 °C global warming targets in the YREB. The magnitudes of NPP increment are approximately 14.7% with 1.5 °C and 21% with 2 °C warming targets compared with the current climate, which are higher than the average increments of China. Although NPP is projected to increase under the two scenarios, the tendency of NPP increasingly exhibits a slowdown after the 2060 s under the RCP4.5 scenario, and the growth rate of NPP is projected to drop in more than 31% of regional areas with the additional 0.5 °C warming. In contrast, under the RCP8.5 scenario, the trend in NPP keeps rising substantially, even above 2 °C global warming. However, the NPP in some provinces, including Jiangxi and Hunan, is projected to reduce at the end of the 21st century, probably because of temperature rises, precipitation decreases, and water demand increases. Generally, the NPP is projected to increase due to climate change, particularly temperature increase. However, temperature rising does not always show a positive effect on NPP increasing; the growth rate of NPP will slow down under the RCP4.5 scenario in the mid-late 21st century, and NPP will also reduce by the end of this century under the RCP8.5 scenario in some places, probably presenting some risks to terrestrial ecosystems in these areas, in terms of reduced functions and service decline, a weakened capacity of carbon sequestration, and reduced agricultural production.

Two healthy elderly donated their peripheral blood mononuclear cells (PBMCs). The induced pluripotent stem cell lines (IPTi005-A and IPTi007-A) were reprogrammed by episomal vector system with Yamanaka factors OCT4, SOX2, C-MYC and KLF4. Both the two iPSC lines can differentiate into three germ layers determined by embryoid bodies (EBs) differentiation. Flow cytometry analysis showed that more than 90% cells expressed NANOG, OCT4 and SSEA4. Besides, the iPSC lines of IPTi005-A and IPTi007-A were confirmed to exhibit a normal karyotype. In the studies of age-related disease, the iPSC lines can be used as controls.

Aging is a natural biological process associated with cognitive decline and neuroendocrine–immune system changes; the neuroendocrine–immune system plays crucial role in brain aging and neurodegeneration, and it is essential to discern beneficial attempts to delay the aging progress based on immunological aging. In this study, we have investigated the effects of Traditional Chinese Medicine (TCM)—Liuwei Dihuang decoction (LW)—and donepezil, memantine, and melatonin on cognitive decline in aging mice. The aged SAMR1 mice received oral administration of donepezil (1mg/kg), memantine (10 mg/kg), melatonin (10 mg/kg), and LW (10 g/kg) for 3 months. A shuttle box, Morris water maze, and elevated-zero maze were performed to assess cognitive function, and flowcytometry, Luminex, and radioimmunoassay were performed to measure the lymphocyte subsets, inflammatory factors, and hormones. We observed that survival days of mice was increased with melatonin and LW, the anxiety behavior was significantly improved by memantine, melatonin, and LW treatment, active avoidance responses significantly improved by LW, donepezil, and memantine, the spatial learning ability was significantly improved by donepezil, and LW and melatonin were beneficial to the spatial memory of old mice. For immune function, LW increased CD4+ and CD4+CD28+ cells and reduced TNF-α, IL-1β, and G-CSF in plasma, and it also promoted the secretion of anti-inflammatory factors IL-4, IL-5, and IL-10 by regulating the active of Th2 cells in spleen. Donepezil and memantine exerted protective effects against CD4+CD28+ cell decrease caused by aging and reduced the pro-inflammatory factors TNF-α, IL-1β, and G-CSF in plasma. Melatonin could reverse CD8+CD28+ cell imbalances and increased B cells. For endocrine factors, LW increased TSH levels in the pituitary, and melatonin increased the GH level in blood. Our findings indicated that LW improved the cognitive decline in aging mice, and this might be associated with modulation of the active T cells and HPG axis hormones as well as increasing anti-inflammatory factors. Meanwhile, donepezil and memantine have advantages in regulating adaptive immunity, melatonin has advantages in the regulation of B cells and pituitary hormones, and LW exhibits a better effect on neuroendocrine immune function compared with the others from a holistic point of view. LW might be a potential therapeutic strategy for anti-aging-related syndromes, and it can also provide a value on medication guidance about drug combinations or treatment in clinic.

It is vast significance to explore the spatial and temporal evolution characteristics and influencing factors of herbivorous animal husbandry industry based on the context of China's agriculture pursuing high-quality development. In this paper, we analyze the spatial and temporal evolution of the layout of China's herbivorous animal husbandry industry and its influencing factors based on the spatial autocorrelation analysis, standard deviation ellipse, and spatial Durbin model with data from 1980 to 2017. The results show that there are significant positive autocorrelation characteristics of "high-high" aggregation and "low-low" aggregation in the Chinese herbivorous animal husbandry industry. To be specific, in the past four decades, the spatial distribution center of China's herbivorous animal husbandry industry has moved towards the northeast, crossing the boundary between agriculture and animal husbandry in China, presenting a clear trend of moving from pastoral area to agricultural area; the gradual narrowing of the spatial distribution range indicates the gradually increased degree of aggregation within the industry; the east-west stretch of spatial distribution has been strengthened, and the azimuth angle shows clockwise change, suggesting that the industrial expansion in the northeast-southwest direction is prominent; the influencing factors of changes in the spatial distribution of the industry reveal that the quantity and production capacity of productive land, people's income and living standards, and the level of mechanization will promote the development of China's herbivorous animal husbandry industry, and are essential factors influencing industrial distribution and transfer, while policy factor has small or even not significant impact on industrial aggregation, reflecting that the policy has not played the expected role, and policy support needs to be further intensified.

Fracture to fifth metatarsal's base is one the most common injury experienced at the foot. Studies have for long debated the use of operative and non-operative interventions for the management of the fracture, especially owing to its peculiar vasculature. However, to date, no attempt has been made to synthesize the evidence comparing the efficacy of operative and non-operative interventions for managing the fifth metatarsal's base fracture. To meta-statistically compare the effects of operative and non-operative management of fifth metatarsal base fracture. A systematic identification of literature was performed according to PRISMA guidelines on four academic databases: MEDLINE, Scopus, EMBASE, and CENTRAL. A meta-analysis evaluated the influence of operative and non-operative interventions on rate of non-union, mean duration of union, duration of return to activity, duration of return to sport, visual analog scale, and the American orthopedic foot & ankle scale. Out of 1,170 records, 11 articles including 404 participants (mean age: 29.8 ± 7.4 years) were included in this review. This systematic review presents a 1b level of evidence supporting the use of operative interventions for enhancing fracture union as compared to non-operative interventions. The meta-analysis reveals beneficial effects for operative interventions by demonstrating medium to large effect reduction of rate of non-union (Hedge's g: -0.66), duration of union (-1.7), duration of return to activity (-2.07), visual analog scale (-0.86), and enhancement of the American orthopedic foot & ankle scale score (0.73) as compared to non-operative intervention. The current systematic review and meta-analysis recommend the use of operative interventions for managing the fifth metatarsal's base fracture. The review reports beneficial effects of operative interventions as compared to non-operative interventions for reducing the rate of non-union, duration of union, duration of return to activity, duration of return to sport, visual analog scale, and increasing the American orthopedic foot & ankle scale score.

In an urban rail transit line, train services are performed by the rolling stocks that are initially stored at depots. Before the start of the operation period, rolling stocks consecutively leave the depots and run without passengers (deadhead routing) to the origin station of their corresponding first departure train service in an operation day (first train service) using either direct or indirect routes. This paper investigates the rolling stock deadhead routing problem in an urban transit line with multiple circulation plans, depots, and rolling stock types. Given the rolling stock circulation plans, the problem is to identify a deadhead route for the rolling stock required by the train services to cover the initial operation. By pregenerating all direct and indirect candidate deadhead routes in a polynomial manner, the problem is then nicely formulated as a mixed integer linear programming (MILP) model to minimize the total deadhead mileages. A real-world case from the urban rail transit line 3 of Chongqing in China is adopted to test the proposed method. Computational results demonstrate that the problems of large-scale instances can be quickly solved to optimality by commercial optimization solvers on a personal computer. In addition, our optimization method is better than the empirical practices in terms of the solution quality. Meanwhile, alternative measures can further decrease the total deadhead mileages according to the proposed model, e.g., opening idle switch stations and prolonging the time that is used for the rolling stock departure. Finally, the model is further extended to consider operating costs, and more computation cases are tested for better adapting to the practical operating conditions.

Train platforming is critical for ensuring the safety and efficiency of train operations within the stations, especially when unexpected train delays occur. This paper studies the problem of reoptimization of train platforming in case of train delays, where the train station is modeled using the discretization of the platform track time-space resources. To solve the reoptimization problem, we propose a mixed integer linear programming (MILP) model, which minimizes the weighted sum of total train delays and the platform track assignment costs, subject to constraints defined by operational requirements. Moreover, we design an efficient heuristic algorithm to solve the MILP model such that it can speed up the reoptimization process with good solution precision. Furthermore, a real-world case is taken as an example to show the efficiency and effectiveness of the proposed model and algorithm. The computational results show that the MILP model established in this paper can describe the reoptimization of train platforming accurately, and it can be solved quickly by the proposed heuristic algorithm. In addition, the model and algorithm developed in this paper can provide an effective computer-aided decision-making tool for the train dispatchers in case of train delays.

The evaluation of the railway operation safety situation is important for managers to ensure transportation safety and make control decisions. In this study, first, six situation indicators are designed from a regional perspective based on the characteristics of railway operation accidents, and the quantitative methods of these indicators are determined. Second, an improved technique for order of preference by similarity to ideal solution (TOPSIS) method is developed to evaluate the railway operation safety situation against the situation indicators. Based on the set-pair analysis (SPA) theory and cosine similarity measure (CSM), the comprehensive evaluation values and rankings of the safety situation are first calculated from the distance and trend levels for each period. Game theory is then employed to determine a more reasonable combined weight, and the values of the parameters involved in the situation indicators are also estimated. The real-life statistical accident data in a regional area of China from 2016 to 2018 are chosen as a case study to verify the proposed method. A brief analysis is conducted, resulting in suggestions for the evaluation results. Two groups of comparative experiments are designed to demonstrate the feasibility and effectiveness of the method. Finally, the quality of the evaluation results is verified through actual conditions and expert scoring. Some extensions and potential practical applications of this work are discussed.

A 62-year old sporadic Alzheimer's disease (sAD) male patient with APOE3 (ε3/ε3) genotype donated his peripheral blood mononuclear cells (PBMCs). The induced pluripotent stem cell (iPSC) line was established by episomal vector system with the four factors OCT4, SOX2, C-MYC and KLF4. EB differentiation in vitro showed that iPSC line had a potential to differentiate into three germ layers. More than 90% cells expressed NANOG, OCT4 and SSEA4 detected by flow cytometry. In addition, the iPSC line was karyotypically normal. The iPSC line may provide new valuable tools for studying pathogenesis of sAD and screening candidate drugs for the disease.