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Abstract Copper mineralization in the Pulang (PL) porphyry deposit, Langdu (LD) porphyry-skarn deposit and Songnuo (SN) porphyry prospect in northwestern Yunnan, China, is closely related to the emplacement of quartz monzonite porphyries. The chemical compositions of biotite and apatite from those porphyries were analyzed to calculate the halogen fugacity and to constrain mineralized and barren porphyries. Our data show that biotites from the PL deposit have higher MgO, SiO2, TiO2 and F contents than those from the LD deposit or SN prospect. Compared to those in the LD deposit and SN prospect, the Mg (atoms per formula unit (apfu)) and AlVI (apfu) value in biotite is greater, and the F content is greater and the SO3 and Ce2O3/Y2O3 ratio in apatite are lower in the PL deposit. Ti-biotite thermometry and apatite-biotite geothermometry show that the crystallization temperature of biotite from the PL deposit is higher than that from the SN prospect or LD deposit. The results suggest that oxygen fugacity, magmatic sulfur, and H2O contents cannot be used to efficiently distinguish the PL deposit from the LD deposit and SN prospect. However, the halogen chemistry of biotite from the PL deposit is distinctly different from that of the LD deposit or SN prospect according to the lower IV (F), indicating that mineralized quartz monzonite porphyries in the PL deposit formed during the late magmatic stage, which is in contrast to those in the LD deposit and SN prospect. The mineralized porphyries display a remarkable negative linear relationship (r = − 0.96) with the log (f HF/f HCl) and log (f H2O/f HF) ratio, which can be used to distinguish the mineralized and barren porphyries. Compared with other typical porphyry Cu systems, there is a remarkable positive linear relationship between IV (Cl) and log (f H2O/f HCl). In addition, the linear slope and intercept for log (f H2O/f HCl) ratios and the IV (Cl) of biotite from the potassic and phyllic alteration zones are significantly greater than those from other porphyries.

Abstract To verify the novel method of achieving a true-triaxial stress path with the pseudo-triaxial apparatus, a series of drained and undrained tests were carried out for the identical scheme with pseudo-triaxial apparatus and true-triaxial apparatus respectively. The differences between the two types of tests were quantified. The results show that the novel method effectively achieved the true-triaxial stress path by controlling the loading ratio of the pseudo-triaxial apparatus. The relationships of q − ε 1 and η − ε s measured by the two apparatuses had a higher similarity which decreases slightly with the b increase. When 0 ≤ b

Abstract Background Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. Methods Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. Results After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI

Background Automatic cell type identification has been an urgent task for the rapid development of single-cell RNA-seq techniques. Generally, the current approach for cell type identification is to generate cell clusters by unsupervised clustering and later assign labels to each cell cluster with manual annotation. Methods Here, we introduce LIDER (celL embeddIng based Deep nEural netwoRk classifier), a deep supervised learning method that combines cell embedding and deep neural network classifier for automatic cell type identification. Based on a stacked denoising autoencoder with a tailored and reconstructed loss function, LIDER identifies cell embedding and predicts cell types with a deep neural network classifier. LIDER was developed upon a stacked denoising autoencoder to learn encoder-decoder structures for identifying cell embedding. Results LIDER accurately identifies cell types by using stacked denoising autoencoder. Benchmarking against state-of-the-art methods across eight types of single-cell data, LIDER achieves comparable or even superior enhancement performance. Moreover, LIDER suggests comparable robust to batch effects. Our results show a potential in deep supervised learning for automatic cell type identification of single-cell RNA-seq data. The LIDER codes are available at https://github.com/ShiMGLab/LIDER.

Abstract To study the function of LoHDZ2 in larch, we first constructed a VB191103-LoHDZ2::GUS overexpression vector. Through Agrobacterium-mediated infection, the expression vector was transferred into a larch embryogenic cell line. A stable resistant cell line was subsequently screened, and mature embryos were induced to grow until they developed into seedlings. Antagonistic cell lines were identified at both the DNA and RNA levels. The transgenic cell lines were then subjected to GUS staining, and transgenic cell lines were ultimately identified and obtained. These transgenic cell lines were sequenced to identify differentially expressed genes, and a cluster analysis was performed. The resistant cell lines were cultured under stress conditions involving 20% PEG6000 and 200 mM NaCl proliferation media (1/10-BM). After the stress treatment, the contents of peroxidase (POD), malondialdehyde (MDA) and superoxide dismutase (SOD) in both wild-type and transgenic cell lines were measured. The results are summarized below: (1) When the specific fragment of the target gene in the genome of the resistant cell line was amplified. At the RNA level, the expression of the fragment in four resistant lines increased. In addition, GUS staining showed a blue reaction, indicating that LoHDZ2 was successfully integrated into the larch embryonic cell lines. (2) To verify the accuracy and reliability of the transcriptome data, 10 differentially expressed genes (5 upregulated and 5 down regulated genes) were subjected to qRT-PCR verification. The results showed that the expression trend of the 10 differentially expressed genes was the same as that revealed by RNA-Seq, indicating that the transcriptome data were reliable. (3) The transcriptome sequencing showed that 176 genes were upregulated and that 140 genes were down regulated. Through GO enrichment analysis and KEGG metabolic pathway analysis, the screened differentially expressed genes were related to biological processes such as larch metabolism and response to stimuli, indicating that these genes may be closely involved in the regulation of the larch response to external stimuli, including heat stress, drought stress, metal ion stress and bacterial infection, and may participate in the growth process. (4) After 20% PEG6000 treatment, the POD enzyme activity of the transgenic cell line was greater than that of the wild-type; this activity could effectively remove the amount of peroxide produced. The MDA content of the transgenic cell lines was lower than that of the wild-type cell lines, and the accumulation degree of harmful substances was low, indicating that the degree of oxidative damage of the transgenic cell lines was lower than that of the wild-type cell lines. The SOD content of the transgenic cell lines was lower than that of the wild-type cell lines, indicating that the drought resistance of the transgenic cell lines was enhanced. After 200 mM NaCl treatment, although the increase in SOD content was not obvious, the same trend was detected, indicating that the resistance of the transgenic cell lines was indeed stronger than that of the wild-type cell lines. According to the results of previous experiments, after this gene was overexpressed in tobacco, the transformed plants showed obvious dwarfing, which may indicate that the stress resistance of the plant was enhanced. In conclusion, a transgenic larch cell line was successfully obtained, and transgenic larch seedlings were successfully induced. LoHDZ2 may participate in the response of plants to the external environment, and may participate in the growth and development of Larix olgensis by affecting plant metabolic pathways.

Poultry farming is one of the pillar industries of global animal husbandry. In order to guarantee production, poultry are frequently vaccinated from the moment they are hatched. Even so, the initial immunity of chicks is still very poor as they are in the “window period” of immune protection. In ovo vaccination pushes the initial immunization time forward to the incubation period, thereby providing earlier immune protection for chicks. In ovo vaccination is currently a research hotspot of poultry disease prevention and control, which is in line with the intensification of poultry production. However, the vaccines currently available for in ovo vaccination are limited and cannot meet the needs of industrial development, so how to efficiently activate the adaptive immune response of chicken embryos becomes the key to restrict product development and technological progress of in ovo vaccination. Its breakthrough, to a large extent, depends on systematic illustration of the mechanism underlying the adaptive immune response post immunization. Clarification of this issue will provide us with theoretical support and potential solutions for the development of novel vaccines for in ovo vaccination, the augmentation of efficacy of current vaccines and the optimization of immune programs.

Abstract Knowledge of the changes in the immune microenvironment during pulmonary bacterial acute and chronic infections is limited. The dissection of immune system may provide a basis for effective therapeutic strategies against bacterial infection. Here, we describe a single immune cell atlas of mouse lungs after acute and chronic Pseudomonas aeruginosa infection using single‐cell transcriptomics, multiplex immunohistochemistry, and flow cytometry. Our single‐cell transcriptomic analysis revealed large‐scale comprehensive changes in immune cell composition and high variation in cell–cell interactions after acute and chronic P. aeruginosa infection. Bacterial infection reprograms the genetic architecture of immune cell populations. We identified specific immune cell types, including Cxcl2+ B cells and interstitial macrophages, in response to acute and chronic infection, such as their proportions, distribution, and functional status. Importantly, the patterns of immune cell response are drastically different between acute and chronic infection models. The distinct molecular signatures highlight the importance of the highly dynamic cell–cell interaction process in different pathological conditions, which has not been completely revealed previously. These findings provide a comprehensive and unbiased immune cellular landscape for respiratory pathogenesis in mice, enabling further understanding of immunologic mechanisms in infection and inflammatory diseases.

Abstract Background There are over 16.8 million rare disease patients in China, representing a large community that should not be neglected. While the public lack the awareness of their existence and difficult status quo, for one reason that they exist as a rare and special group in our society, for another reason that all sectors of the community haven’t introduced and propagandized them suitably. However, as a special group with more difficulties in all aspects than normal healthy persons, they need enough care and love from us. To provide a basis for policy-makers to better understand the status quo of rare disease patients and care-givers in China and to devise some new policies to improve their quality of life, a comprehensive analysis of the status quo, unmet needs, difficulty caused by the rare disease is essential. Methods A questionnaire-based online study of patients and care-givers (usually family members) was performed. The questionnaire was composed of 116 questions, such as the diagnosis process, treatment access, financial burden, views on patients’ organizations, and a series of standardized tests to assess the quality of their life, including the SF-36, PHQ-9, PHQ-15, GAD-7, and PSQI. To examine the influence of age, disease type, and relationship to patients on the scores in these tests, statistical analysis with a general linear model was conducted. Findings A total of 1959 patients and care-givers participated in the survey, representing 104 rare diseases, such as lysosomal storage diseases, hemophilia, and muscular dystrophy diseases. The diagnosis was delayed for 1.4 ± 3.0 years, and patients experienced 1.6 ± 3.8 misdiagnoses between 3.2 ± 2.4 hospitals. The hospitals where diagnoses were made were highly concentrated in 10 large hospitals (43.8%) and 5 big cities (42.1%), indicating a significant inequality of medical resources. The disease often led to difficulty in social life, education, and employment, as well as financial burden that was seldom covered by medical insurance. A battery of standardized tests demonstrated poor health status, depression, somatization, anxiety, and sleeping issues among both patients and care-givers (p

Abstract Background It is estimated that there are over 16.8 million rare disease patients in China, representing a significant challenge for the healthcare system and society. Rare disease patients often experience delayed diagnosis, misdiagnosis, or improper treatment, which may be due to the lack of rare disease awareness among physicians. Materials and methods A total of 224 physicians from different hospitals in China participated in the questionnaire, and 9 rare disease experts were interviewed with open-ended questions. Results Most physicians (83.5%) were from Tertiary hospitals, which have over 500 beds. Only 5.3% of physicians were moderately or well aware of rare diseases. Most physicians (80.1%) had suspected their patients to have rare diseases less than 3 times. There was a strong support for special legislations for rare diseases and orphan drugs. Further, multinomial logistic regression (MLR) was used to determine whether hospitals, gender, and career length has an impact on perspectives and awareness. It was shown that male physicians were more likely to think newborn screening is important (p

Abstract Background Each rare disease only affects a small number of population. However, a total of 7000 rare diseases may affect 10% of the population. Due to the severity and lack of rare disease awareness, rare disease represents a huge challenge for the healthcare system. In Western countries, patient organizations have been playing an integral role in raising awareness, advocating legislation, and supporting drug development. This study aims to assess the unmet needs of rare disease patient organizations in China, and identify their unmet needs, providing essential information for the government and legislators. Results A total of 28 individuals representing 28 patient organizations in China were interviewed. Most organizations do not have official registration, employees, written standard operation protocol, or reliable financial resources. Misdiagnosis or delayed diagnosis is common, and treatment is often lacking. Due to the lack of financial resources, no organizations have been able to sponsor academic research, unlike their counterparts in Western countries. As to challenges, 71.4% of interviewees listed lack of rare disease awareness among the general public, while 67.9% selected lack of financial resources. Further, only 7.3% of these organizations received support from the government, and 28.6% received support from the general public. As to recommendations to the government, 82.1% of interviewees selected special insurance programs for rare diseases because rare diseases have been generally excluded from the national medical insurance programs. In addition, 78.6% of interviewees recommended to stimulate rare disease research, 75% recommended to import orphan drugs, and 71.4% recommended legislation of an orphan drug act, highlighting the urgent need of therapies. Conclusions Due to lack of support and rare disease awareness, patient organizations in China are still in the early phase. To empower these patient organizations, the interviewees’ recommendations, including legislating orphan drug act and releasing official definition of rare diseases, should be considered by the government and legislators.

Background As one of the most important vegetable crops, pepper has rich nutritional value and high economic value. Increasing heat stress due to the global warming has a negative impact on the growth and yield of pepper. Methods To understand the heat stress response mechanism of pepper, an iTRAQ-based quantitative proteomic analysis was employed to identify possible heat-responsive proteins and metabolic pathways in 17CL30 and 05S180 pepper seedlings under heat stress. Result In the present study, we investigated the changes of phenotype, physiology, and proteome in heat-tolerant (17CL30) and heat-sensitive (05S180) pepper cultivars in response to heat stress. Phenotypic and physiological changes showed that 17CL30 had a stronger ability to resist heat stress compared with 05S180. In proteomic analysis, a total of 3,874 proteins were identified, and 1,591 proteins were considered to participate in the process of heat stress response. According to bioinformatic analysis of heat-responsive proteins, the heat tolerance of 17CL30 might be related to a higher ROS scavenging, photosynthesis, signal transduction, carbohydrate metabolism, and stress defense, compared with 05S180.

With the emergence and rapid spread of new pandemic variants, especially variants of concern (VOCs), the development of next-generation vaccines with broad-spectrum neutralizing activities is of great importance. In this study, SCTV01C, a clinical stage bivalent vaccine based on trimeric spike extracellular domain (S-ECD) of SARS-CoV-2 variants Alpha (B.1.1.7) and Beta (B.1.351) with a squalene-based oil-in-water adjuvant was evaluated in comparison to its two corresponding (Alpha and Beta) monovalent vaccines in mouse immunogenicity studies. The two monovalent vaccines induced potent neutralizing antibody responses against the antigen-matched variants, but drastic reductions in neutralizing antibody titers against antigen-mismatched variants were observed. In comparison, the bivalent vaccine SCTV01C induced relatively higher and broad-spectrum cross-neutralizing activities against various SARS-CoV-2 variants, including the D614G variant, VOCs (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.1.529), variants of interest (VOIs) (C.37, B.1.621), variants under monitoring (VUMs) (B.1.526, B.1.617.1, B.1.429, C.36.3) and other variants (B.1.618, 20I/484Q). All three vaccines elicited potent Th1-biased T-cell immune responses. These results provide direct evidence that variant-based multivalent vaccines could play important roles in addressing the critical issue of reduced protective efficacy against the existing and emerging SARS-CoV-2 variants.

In recent years, China has made great efforts to resolve the health inequality caused by household registration restrictions, and the unequal allotment of health services faced by migrant workers has been effectively alleviated. However, inequality in health services may exist not only between migrant workers and local citizens but also among migrant workers. Thus, the unbalanced utilization of health services among migrant workers deserves attention. Using data from the 2017 China Migrants Dynamic Survey (CMDS), we examined the relationship between socioeconomic status (SES) and healthcare-seeking behavior through multivariate regression analysis. Then, from the perspective of SES, this study divided migrant workers into different groups to explore the characteristics of healthcare-seeking behavior in different groups. The results showed that SES had a significant relationship with healthcare-seeking behavior. Those with high SES were more likely to use high-quality health services. By subdividing the category of migrant workers, we found that the utilization of health services among migrant workers was unbalanced. Education and income had significant gradients in multiple measures of healthcare-seeking behavior, while occupation had no significant difference in the behavior. Migrant workers with higher income and education were more likely to use high-quality health services. Especially for migrant workers who had high incomes (above 15,000 CNY) or whose educational backgrounds were graduate level or above, their utilization of health resources was significantly higher than that of other groups. When designing particular policies to improve the healthcare-seeking behavior of different SES migrant workers, we should pay attention to the low-education groups and low-income groups. Policymakers can reduce the current health inequality of migrant workers by strengthening health education and increasing medical subsidies to achieve health equality among migrant workers and between migrant workers and local citizens.

Coronavirus disease (COVID-19) causes a serious threat to human health. Virus-like particles (VLPs) constitute a promising platform in SARS-CoV-2 vaccine development. In this study, the E, M, and S genes were cloned into multiple cloning sites of a new triple expression plasmid with one p10 promoter, two pPH promoters, and three multiple cloning sites. The plasmid was transformed into DH10 BacTMEscherichia coli competent cells to obtain recombinant bacmid. Then the recombinant bacmid was transfected in ExpiSf9TM insect cells to generate recombinant baculovirus. After ExpiSf9TM cells infection with the recombinant baculovirus, the E, M, and S proteins were expressed in insect cells. Finally, SARS-CoV-2 VLPs were self-assembled in insect cells after infection. The morphology and the size of SARS-CoV-2 VLPs are similar to the native virions.

WRKY proteins are a large group of plant transcription factors that are involved in various biological processes, including biotic and abiotic stress responses, hormone response, plant development, and metabolism. WRKY proteins have been identified in several plants, but only a few have been identified in Capsicum annuum. Here, we identified a total of 62 WRKY genes in the latest pepper genome. These genes were classified into three groups (Groups 1-3) based on the structural features of their proteins. The structures of the encoded proteins, evolution, and expression under normal growth conditions were analyzed and 35 putative miRNA target sites were predicted in 20 CaWRKY genes. Moreover, the response to cold or CMV treatments of selected WRKY genes were examined to validate the roles under stresses. And alternative splicing (AS) events of some CaWRKYs were also identified under CMV infection. Promoter analysis confirmed that CaWRKY genes are involved in growth, development, and biotic or abiotic stress responses in hot pepper. The comprehensive analysis provides fundamental information for better understanding of the signaling pathways involved in the WRKY-mediated regulation of developmental processes, as well as biotic and abiotic stress responses.

To study the strengthening mechanism and effect underlying the reinforcement of a fractured rock mass with grouting, compressive shear tests were conducted with an RMT-150B rock mechanics test system. Prefabricated structural surfaces were strengthened with a new inorganic dual-liquid grouting material at five water-cement ratios (0.6-1.5). The effects of these water-cement ratios of the grouting on the deformation, strength, and failure characteristics of the prefabricated structural surface were analyzed. The results show that reinforcement with grouting significantly influenced the bearing capacity of the structural surface. The shear strength of the structure was significantly improved and the deformation resistance of the structural surface was enhanced. The shear stress-displacement curves, generated in compressive shear tests of the grouting-reinforced structures, were all nonlinear. The shearing process comprised three stages: elasticity, yield, and failure. Decreasing the water-cement ratio of the grouting material weakened the plasticity of the grouted structural surface and enhanced its brittleness. The deformation type changed from plastic slip to brittle shear. The shear strength, cohesion, and angle of internal friction of the grouting-reinforced structural surface increased with decreasing water-cement ratio.

Cytochrome P450 2E1 (CYP2E1) plays an important role in both alcohol-induced and immune-mediated liver injury. However, the mechanism underlying CYP2E1 transcriptional regulation has not been clarified. This study focused on the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways in alcohol-induced and immune-mediated liver injury rat models. Male Sprague-Dawley rats were used in pharmacokinetic, molecular pharmacology, and morphology experiments. A rat model of alcohol-induced liver injury (AL) was established by feeding an ethanol-containing diet (42 g/kg/day) for 5 weeks as indicated. A rat immune-mediated liver injury (IM) model was established by the sequential injection of bacillus Calmette-Guérin (BCG, 125 mg/kg, once) via the tail vein after test day 21 and 10 μg/kg LPS 13 days later. HPLC, real-time PCR, western blot and ELISA analyses were performed. CYP2E1 expression was enhanced during the process of alcohol-induced liver injury (increased by 56%, P < 0.05) and significantly reduced during that of immune-mediated liver injury (reducedby52%, P < 0.05). NF-κB was activated in both the AL and IM groups (increased by 56% and76%, respectively, P < 0.05). Compared to those in the livers of AL model rats, the interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and iNOS levels in IM model rat livers were increased (increased by 26%, 21% and 101%, respectively, P < 0.05). The differential changes in CYP2E1 in the processes of alcohol-induced and immune-mediated liver injury may result from the differential expression of inflammatory cytokines and iNOS after NF-κB activation, leading to the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways.

BACKGROUND: Both kyphoplasty (KP) and vertebroplasty (VP) are effective for patients with osteoporotic vertebral compression fracture (OVCF), but which approach might be more effective remains unclear, so we decided to update earlier systematic reviews. OBJECTIVE: Review and analyze studies published as of August 2015 that compared clinical outcomes and complications of KP versus VP. DESIGN: Systematic review and meta-analysis. SEARCH METHOD: Published reports up to August 2015 were found in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). SELECTION CRITERIA: Randomized controlled trials (RCTs) and prospective and retrospective cohort studies comparing KP and VP in patients with OVCF. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies and extracted data. RESULTS: Thirty-two studies involving 3274 patients fulfilled the inclusion criteria. There were significant differences between the two groups in short- and long-term postoperative changes in measures of pain intensity and dysfunction (P

Diatoms constitute a major group of phytoplankton, accounting for ~20% of the world's primary production. It has been shown that iron (Fe) can be the limiting factor for phytoplankton growth, in particular, in the HNLC (High Nutrient Low Chlorophyll) regions. Iron plays thus an essential role in governing the marine primary productivity and the efficiency of biological carbon pump. Oceanic systems are undergoing continuous modifications at varying rates and magnitudes as a result of changing climate. The objective of our research is to evaluate how changing environmental conditions (dust deposition, ocean warming and acidification) can affect marine Fe biogeochemistry and diatom growth. Laboratory culture experiments using a marine diatom Chaetoceros socialis were conducted at two temperatures (13°C and 18°C) and under two pCO2 (carbon dioxide partial pressure) (400 μatm and 800 μatm) conditions. The present study clearly highlights the effect of ocean acidification on enhancing the release of Fe upon dust deposition. Our results also confirm that being a potential source of Fe, dust provides in addition a readily utilizable source of macronutrients such as dissolved phosphate (PO4) and silicate (DSi). However, elevated atmospheric CO2 concentrations may also have an adverse impact on diatom growth, causing a decrease in cell size and possible further changes in phytoplankton composition. Meanwhile, ocean warming may lead to the reduction of diatom production and cell size, inducing poleward shifts in the biogeographic distribution of diatoms. The changing climate has thus a significant implication for ocean phytoplankton growth, cell size and primary productivity, phytoplankton distribution and community composition, and carbon (C), nitrogen (N), phosphorus (P), silicon (Si) and Fe biogeochemical cycles in various ways.

This paper focuses on the impact of rainfall on the temporal and spatial distribution of taxi passengers. The main objective is to provide guidance for taxi scheduling on rainy days. To this end, we take the occupied and empty states of taxis as units of analysis. By matching a taxi's GPS data to its taximeter data, we can obtain the taxi's operational time and the taxi driver's income from every unit of analysis. The ratio of taxi operation time to taxi drivers' income is used to measure the quality of taxi passengers. The research results show that the spatio-temporal evolution of urban taxi service demand differs based on rainfall conditions and hours of operation. During non-rush hours, taxi demand in peripheral areas is significantly reduced under increasing precipitation conditions, whereas during rush hours, the demand for highly profitable taxi services steadily increases. Thus, as an intelligent response for taxi operations and dispatching, taxi services should guide cruising taxis to high-demand regions to increase their service time and ride opportunities.

Concanavalin A (ConA), a T-cell mitogen that induces acute autoimmune hepatitis, is widely used to model pathophysiological processes of human acute autoimmune liver disease. Although autophagy has been extensively studied in the past decade, little is known about its molecular mechanism underlying the regulation of ConA-induced acute hepatitis. In this study, we used a Cre-conditional atg7 KO mouse to investigate the effects of Atg7-associated autophagy on ConA-induced murine hepatitis. Our results demonstrated that atg7 deficiency in mice enhanced macrophage activation and increased pro-inflammatory cytokines upon ConA stimulation. Atg7 silencing resulted in accumulation of dysfunctional mitochondria, disruption of reactive oxygen species (ROS) degradation, and increase in pro-inflammatory cytokines in Raw264.7 cells. p38/MAPK and NF-κB levels were increased upon ConA induction due to Atg7 deficiency. Blocking ROS production inhibited ConA-induced p38/IκB phosphorylation and subsequent intracellular inflammatory responses. Hence, this study demonstrated that atg7 knockout in mice or Atg7 knockdown in cell culture augmented ConA-induced acute hepatitis and related cellular malfunction, indicating protective effects of Atg7 on regulating mitochondrial ROS via a p38/MAPK-mediated pathway. Collectively, our findings reveal that autophagy may attenuate macrophage-mediated inflammatory response to ConA and may be the potential therapeutic targets for acute liver injury.

Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1-25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level.

We and others have recently shown that soyasaponins abundant in soybeans can decrease inflammation by suppressing the nuclear factor kappa B (NF-kB)-mediated inflammation. However, the exact molecular mechanisms by which soyasaponins inhibit the NF-kB pathway have not been established. In this study in macrophages, soyasaponins (A1, A2 and I) inhibited the lipopolysaccharide (LPS)-induced release of inflammatory marker prostaglandin E2 (PGE2) to a similar extent as the NF-kB inhibitor (BAY117082). Soyasaponins (A1, A2 and I) also suppressed the LPS-induced expression of cyclooxygenase 2 (COX-2), another inflammatory marker, in a dose-dependent manner by inhibiting NF-kB activation. In defining the associated mechanisms, we found that soyasaponins (A1, A2 and I) blunted the LPS-induced IKKα/β phosphorylation, IkB phosphorylation and degradation, and NF-kB p65 phosphorylation and nuclear translocation. In studying the upstream targets of soyasaponins on the NF-kB pathway, we found that soyasaponins (A1, A2 and I) suppressed the LPS-induced activation of PI3K/Akt similarly as the PI3K inhibitor LY294002, which alone blocked the LPS-induced activation of NF-kB. Additionally, soyasaponins (A1, A2 and I) reduced the LPS-induced production of reactive oxygen species (ROS) to the same extent as the anti-oxidant N-acetyl-L-cysteine, which alone inhibited the LPS-induced phosphorylation of Akt, IKKα/β, IkBα, and p65, transactivity of NF-kB, PGE2 production, and malondialdehyde production. Finally, our results show that soyasaponins (A1, A2 and I) elevated SOD activity and the GSH/GSSG ratio. Together, these results show that soyasaponins (A1, A2 and I) can blunt inflammation by inhibiting the ROS-mediated activation of the PI3K/Akt/NF-kB pathway.

Glutathione conjugation reactions are one of the principal mechanisms that plants utilize to detoxify xenobiotics. The induction by four herbicides (2,4-D, atrazine, metolachlor and primisulfuron) and a herbicide safener (dichlormid) on the expression of three genes, ZmGST27, ZmGT1 and ZmMRP1, encoding respectively a glutathione-S-transferase, a glutathione transporter and an ATP-binding cassette (ABC) transporter was studied in maize. The results demonstrate that the inducing effect on gene expression varies with both chemicals and genes. The expression of ZmGST27 and ZmMRP1 was up-regulated by all five compounds, whereas that of ZmGT1 was increased by atrazine, metolachlor, primisulfuron and dichlormid, but not by 2,4-D. For all chemicals, the inducing effect was first detected on ZmGST27. The finding that ZmGT1 is activated alongside ZmGST27 and ZmMRP1 suggests that glutathione transporters are an important component in the xenobiotic detoxification system of plants.

The metabolism of chiral herbicides in plants remains poorly understood. Glutathione conjugation reactions are one of the principal mechanisms that plants utilize to detoxify xenobiotics. The induction by rac- and S-metolachlor of the expression of three genes, ZmGST27, ZmGT1 and ZmMRP1, encoding respectively a glutathione-S-transferase, a glutathione transporter and an ATP-binding cassette (ABC) transporter was studied in maize. The results demonstrate that the inducing effect of rac- and S-metolachlor on the expression of ZmGST27 and ZmGT1 is comparable. However, the inducing effect of rac-metolachlor on ZmMRP1 expression is more pronounced than that of S-metolachlor. Furthermore, vanadate, an ABC transporter inhibitor, could greatly reduce the difference in herbicidal activity between rac- and S-metolachlor. These results suggest that the ABC transporters may preferentially transport conjugates of rac-metolachlor, leading to a faster metabolism of the latter. Through comparing the expression of ZmGST27, ZmMRP1 and ZmGT1 after treatment by rac- and S-metolachlor, we provide novel insights into the metabolic processes of chiral herbicides in plants.

Men who have sex with men (MSM) are at a substantial risk of HIV, given rising HIV prevalence in urban China. Adolescent and adult students often take HIV-related risk as part of sexual exploration. We compared the risks of HIV and syphilis infections and risky sexual behaviors between student and non-student among urban MSM.Respondent driven sampling approach was used to recruit men who were self-identified as MSM in Chongqing Metropolitan City in southwestern China in 2009. Each participant completed a computer-assisted self-interview which collected demographic and behavioral data, and provided blood specimens for HIV and syphilis testing. Multivariable logistic regression analyses identified predictors for HIV and syphilis infections while comparing student and non-student MSM.Among 503 MSM participants, 36.4% were students, of whom 84.2% were in college. The adjusted prevalence of HIV infection was 5.5% (95% confidence interval [CI]: 2.1%-10.2%) in students and 20.9% (95% CI: 13.7%-27.5%) in non-students; the adjusted prevalence of syphilis was 4.4% (95% CI: 0.7%-9.0%) in students and 7.9% (95% CI: 3.6%-12.9%) in non-students (P = 0.12). Two groups had similar risky sexual behaviors such as number of sexual partners and exchanging sex for money. Multivariate analysis showed that students had lower HIV prevalence than non-students (adjusted odds ratio [AOR]: 0.3; 95% CI: 0.1-0.8) adjusting for age, ethnicity and other variables.Student MSM have lower HIV and similar syphilis prevalence compared with non-student MSM. However, due to a shorter duration of sexual experience and high prevalence of at-risk sexual behaviors among student MSM, HIV risk might be quite high in students as in non-students.

The Cucurbitaceae includes important crops such as cucumber, melon, watermelon, squash and pumpkin. However, few genetic and genomic resources are available for plant improvement. Some cucurbit species such as cucumber have a narrow genetic base, which impedes construction of saturated molecular linkage maps. We report herein the development of highly polymorphic simple sequence repeat (SSR) markers originated from whole genome shotgun sequencing and the subsequent construction of a high-density genetic linkage map. This map includes 995 SSRs in seven linkage groups which spans in total 573 cM, and defines approximately 680 recombination breakpoints with an average of 0.58 cM between two markers. These linkage groups were then assigned to seven corresponding chromosomes using fluorescent in situ hybridization (FISH). FISH assays also revealed a chromosomal inversion between Cucumis subspecies [C. sativus var. sativus L. and var. hardwickii (R.) Alef], which resulted in marker clustering on the genetic map. A quarter of the mapped markers showed relatively high polymorphism levels among 11 inbred lines of cucumber. Among the 995 markers, 49%, 26% and 22% were conserved in melon, watermelon and pumpkin, respectively. This map will facilitate whole genome sequencing, positional cloning, and molecular breeding in cucumber, and enable the integration of knowledge of gene and trait in cucurbits.

Abstract In the process of penicillin fermentation, there is a strong nonlinear relationship between the input eigenvector and multiple output vectors, which makes the prediction accuracy of the existing model difficult to meet the requirements of chemical production. Therefore, a local selective ensemble learning multi-objective soft sensing modeling strategy is proposed in this study. Firstly, a localization method based on transfer entropy and k-means is proposed to reconstruct the sample set. Then, based on the reconstructed local samples, the local soft sensing model is established by the multi-objective support vector regression method, and the selective ensemble of sub-models and the adaptive calculation of prediction weights are realized. At the same time, to reduce the adverse effects caused by improper selection of model parameters, the sparrow search algorithm is used to realize the tuning of the mentioned model parameters. Finally, the proposed modeling strategy is simulated. The results show that, compared with other methods, the proposed local selective ensemble learning multi-objective soft sensing modeling strategy has better prediction performance.

Objective To achieve supervision and management of the whole business process of blood center, raise productivity and ensure blood quality by enabling blood center managers comprehensively grasp the key business operation situation of the whole process at anytime and anywhere. Methods A whole business process supervision and management system was established covering background of preparation, business scope, content of position supervision and management, overall framework design, interface design of management and supervision management, physical database design, program development and online debugging, and was integrated with the blood bank management information system. The display and management were through a mobile APP to record key indicators of business process from blood collection to blood supply timely and comprehensively. Statistical analysis was conducted on total collection volume, total preparation volume and total supply volume, as well as discarding rate of test unqualified and of non-test unqualified (lipemic blood excluded) in 2023 and 2022. Results We established a mobile APP based on a blood bank management information system for business supervision and management of whole process, and achieved management by phones. After its implementation in 2023, the total collection volume, total preparation volume and total supply volume in 2023 were all higher than those in 2022, with growth rates of 5.88% (13 247/225 454 U), 4.73% (24 156/510 698 U), and 6.70% (34 814/519 914 U), respectively. The discarding rate in 2023 was lower than that in 2022 (0.54%, 2 868/534 854 U) vs (0.60%, 3 047/510 698 U) (P