N-Doped Carbon Nanonecklaces with Encapsulated BiOCl Nanoparticles as High-Rate Anodes for Lithium-Ion Batteries.

The unique two-dimensional layered structure of BiOCl makes it highly promising for energy storage applications. In this study, we successfully synthesized BiOCl nanoparticles encapsulated in N-doped carbon nanonecklaces (BiOCl NPs/N-CNNs) using well-established electrospinning and solvothermal substitution. As an anode material for lithium-ion batteries, BiOCl NPs/N-CNNs exhibited enhanced rate performance, delivering a capacity of 220.2 mA h g-1 at 8 A g-1. Furthermore, it demonstrated remarkable long cycle stability, retaining a capacity of 200.5 mA h g-1 after 9000 cycles with a discharge rate of 8.0 A g-1. The superior electrochemical performance can be attributed to the stacked layered structure of BiOCl, facilitated by van der Waals force, as well as the ingenious nanonecklace structures. These structures not only provide fast ion diffusion pathways but also enhance electrolyte penetration and offer more active sites for Li+ insertion and extraction. Additionally, the nanonecklace structure prevents the aggregation of nanopolyhedra, promoting the complete reaction of BiOCl with Li+. Moreover, the unique nanopolyhedron structure alleviates the stress caused by the volume expansion of Bi nanoparticles during cycling and reduces the internal resistance of the electrode.

Arsenic removal from coal by ferric chloride enhanced leaching under ultraviolet irradiation during flue gas desulphurization with coal slurry.

During coal combustion, the harmful element arsenic can be released into environment and cause potential significant harm to human beings. Therefore, it is very important to study the removal of arsenic from coal before combustion. In this work, simulated SO2-containing flue gas was used to leach arsenic from coal in a 1 L UV photoreactor. The effects of FeCl3, ultraviolet (UV), pH and the Cl-/Fe3+ molar ratio on arsenic leaching and SO2 removal were experimentally investigated and the enhancing mechanism was analysed. Experimental results demonstrated that FeCl3 and UV could efficiently increase iron and arsenic leaching percentages and SO2 removal efficiency. UV irradiation could induce the oxidation of most trivalent arsenic. The arsenic leaching percentage was significantly larger than that of iron. Low pH was favourable for iron and arsenic leaching. The optimal Cl-/Fe3+ molar ratio was determined to be 3:1. The introduced ferric chloride could not only increase the concentrations of free radicals and ferric iron oxidants, the chloride ion might also impede the formation of passive coatings, thus increasing the arsenic leaching percentage, intensifying the oxidation of trivalent arsenic and enhancing the removal of SO2.

3-Trifluoromethyl Pyrrole Synthesis Based on ß-CF3-1,3-Enynamides.

A new metal-free method for the rapid, productive, and scalable preparation of 3-trifluoromethyl pyrroles has been developed. It is based on the electrophilic nature of the double bond of ß-CF3-1,3-enynamides due to the electron-withdrawing characteristics of the trifluoromethyl groups and the strong nucleophilic nature of alkyl primary amines. Evidence for the highly regioselective 1,4-hydroamination was observed after the isolation and characterization of the allenamide intermediate.

Combined exposure to PM2.5 and PM10 in reductions of physiological development among preterm birth: a retrospective study from 2014 to 2017 in China.

Background: Preterm birth (PTB) has been linked with ambient particulate matter (PM) exposure. However, data are limited between physiological development of PTB and PM exposure. Methods: Trimester and season-specific PM exposure including PM2.5 and PM10 was collected from Jiaxing between January 2014 and December 2017. Information about parents and 3,054 PTB (gestational age < 37 weeks) outcomes such as weight (g), head circumference (cm), chest circumference (cm), height (cm) and Apgar 5 score were obtained from birth records. We used generalized linear models to assess the relationship between PTB physiological developmental indices and PM2.5, PM10 and their combined exposures. A binary logistic regression model was performed to assess the association between exposures and low birth weight (LBW, < 2,500 g). Results: Results showed that there were 75.5% of low birth weight (LBW) infants in PTB. Decreased PM2.5 and PM10 levels were found in Jiaxing from 2014 to 2017, with a higher PM10 level than PM2.5 each year. During the entire pregnancy, the highest median concentration of PM2.5 and PM10 was in winter (61.65 ± 0.24 vs. 91.65 ± 0.29 µg/m3) followed by autumn, spring and summer, with statistical differences in trimester-specific stages. After adjusting for several potential factors, we found a 10 µg/m3 increase in joint exposure of PM2.5 and PM10 during the entire pregnancy associated with reduced 0.02 week (95%CI: -0.05, -0.01) in gestational age, 7.9 g (95%CI: -13.71, -2.28) in birth weight, 0.8 cm in height (95%CI: -0.16, -0.02), 0.05 cm (95%CI: -0.08, - 0.01) in head circumference, and 0.3 (95%CI: -0.04, -0.02) in Apgar 5 score, except for the chest circumference. Trimester-specific exposure of PM2.5 and PM10 sometimes showed an opposite effect on Additionally, PM2.5 (OR = 1.37, 95%CI: 1.11, 1.68) was correlated with LBW. Conclusion: Findings in this study suggest a combined impact of fine particulate matter exposure on neonatal development, which adds to the current understanding of PTB risk and health.

A Novel One-Step Reactive Extrusion Process for High-Performance Rigid Crosslinked PVC Composite Fabrication Using Triazine Crosslinking Agent@Melamine-Formaldehyde Microcapsules.

In this work, we propose, for the first time, a simple, fast, and efficient strategy to fabricate high-performance rigid crosslinked PVC composites by continuous extrusion. This strategy improves the poor processing fluidity of composites and solves the impossibility of conducting extrusion in one step via using microcapsule-type crosslinking agents prepared by in situ polymerization to co-extrude with PVC blends. The results demonstrate that the PVC/microcapsule composites were successfully prepared. Within the studied parameters, the properties of crosslinked PVC gradually increased with the addition of microcapsules, and its Vicat softening temperature increased from 79.3 °C to 86.2 °C compared with pure PVC. This study shows the possibility for the industrial scale-up of the extrusion process for rigid crosslinked PVC.

Safety, pharmacokinetics, and pharmacodynamics of TG103, a novel long-acting GLP-1/Fc fusion protein after a single ascending dose in Chinese healthy subjects.

BACKGROUND AND OBJECTIVE: TG103 is a novel GLP-1/Fc fusion protein, developed for the treatment of type 2 diabetes and obesity. This trial was designed to assess the safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) profiles after single ascending dose of TG103 in healthy Chinese subjects. METHOD: In this double-blind, randomized, placebo-controlled phase I study, Chinese healthy subjects were admitted consecutively to TG103 3 mg, 7.5 mg, 15 mg, and 22.5 mg group with 8 subjects per group and randomized in a 3:1 ratio to receive TG103 treatment or placebo. Following a single subcutaneous(s.c.) injections of TG103, safety and tolerability were evaluated and blood samples were collected for PK and PD analysis at the specified time-points. RESULT: Overall, 32 healthy subjects were enrolled and completed the study. During the study, a total of 84 adverse effects (AEs) were reported in 25 subjects, all were mild or moderate and resolved spontaneously without intervention. The most common treatment related AEs in TG103 group were decreased appetite (41.7%), nausea, flatulence, elevated urinary ß2-microglobulin, increased serum total bile acid (20.8% each), decreased high-density lipoprotein (16.7%), abdominal distension (12.5%). After a single s.c. administration of TG103 3-22.5 mg, the median Tmax was 36∼48 h, and mean t1/2 was about 147.16∼184.72 h. The mean Cmax for each group was 94.35±52.19, 337.67±56.71, 757.67±206.99, 1236.33±666.25 ng/mL, with AUC0-t of 14.93±7.67, 59.15±7.39, 91.79±20.41, 163.61±55.99 µg·h/mL, respectively. It showed a linear pharmacokinetic profile in the single dose of TG103 3 mg to 22.5 mg. Compared with placebo, fasting blood glucose decreased in all dose groups, most notably in the 15 mg group, which was consistent with the changes in blood glucose during OGTT, while 2-hour postprandial glucose decreased in all dose groups except 3 mg group. CONCLUSION: TG103 offers a potential option for hypoglycemic therapy with good tolerability and safety. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03990090; registered 18 June 2019.

Inhibiting virus replication and excessive inflammatory response: Mechanism of combined prescription of Ma-Xing-Shi-Gan decoction and Xiao-Chai-Hu decoction against influenza virus.

ETHNOPHARMACOLOGICAL RELEVANCE: The combined prescription of two classical decoctions (Ma-Xing-Shi-Gan decoction with Xiao-Chai-Hu decoction), named as San-Yang-He-Zhi (SYHZ) decoction, has been widely used for the treatment of influenza virus (IFV) infections for decades. AIM OF THE STUDY: This study aimed to evaluate the anti-influenza effect of SYHZ decoction and explore the underlying mechanism. MATERIALS AND METHODS: The ingredients of SYHZ decoction were analyzed by mass spectrometry. An animal model of IFV infection was established by challenging C57BL/6J mice with PR8 virus. Three groups of mice were infected with lethal or non-lethal doses of IFV, then followed by oral administration of phosphate-buffered saline (PBS), or SYHZ, or oseltamir; blank control mice (without IFV infection) were treated with PBS. Survival rate, Lung index, colon length, body weight loss and IFV viral load were measured 7 days post infection; histology and electron-microscopy examinations of lung tissue were performed; cytokine and chemokine levels in lung and serum were measured; and the intestinal metagenome, the cecum metabolome, and the lung transcriptome were analyzed. RESULTS: SYHZ treatment significantly improved survival rate compared with PBS (40% vs 0%); improved lung index, colon length, and body weight loss; and alleviated lung histological damage and viral load. SYHZ-treated mice had significantly lower levels of IL-1ß, TNF-α, IL-6, CCL2, CXCL10 in lung and serum, and increased levels of multiple bioactive components in cecum. Pro-inflammatory cytokines, Toll- and NOD-like receptors, pro-apoptosis molecules, and lung-injury-related proteins were downregulated in SYHZ mice, whereas surfactant protein and mucin were upregulated. The NOD-like receptor pathway, Toll-like receptor pathway, and NF-κB pathway were downregulated by SYHZ treatment. CONCLUSIONS: SYHZ decoction alleviated IFV infection in a mouse model. Multiple bioactive ingredients of SYHZ may inhibit replication of IFV and suppress excessive immune response.

Automatic comprehensive aspects reports in clinical acute stroke MRIs.

The Alberta Stroke Program Early CT Score (ASPECTS) is a simple visual system to assess the extent and location of ischemic stroke core. The capability of ASPECTS for selecting patients' treatment, however, is affected by the variability in human evaluation. In this study, we developed a fully automatic system to calculate ASPECTS comparable with consensus expert readings. Our system was trained in 400 clinical diffusion weighted images of patients with acute infarcts and evaluated with an external testing set of 100 cases. The models are interpretable, and the results are comprehensive, evidencing the features that lead to the classification. This system adds to our automated pipeline for acute stroke detection, segmentation, and quantification in MRIs (ADS), which outputs digital infarct masks and the proportion of diverse brain regions injured, in addition to the predicted ASPECTS, the prediction probability and the explanatory features. ADS is public, free, accessible to non-experts, has very few computational requirements, and run in real time in local CPUs with a single command line, fulfilling the conditions to perform large-scale, reproducible clinical and translational research.

Lactiplantibacillus pentosus P2020 protects the hyperuricemia and renal inflammation in mice.

Introduction: Hyperuricemia (HUA) is a common metabolic disease, and its prevalence has been increasing worldwide. Pharmaceutical drugs have been used for controlling HUA but they all have certain side effects, which thus calls for discovering alternative options including using treatment of probiotics to prevent the development of HUA. Methods: We established HUA mice model induced by potassium oxonate and adenine and performed in vivo experiments to verify the ability to lower serum uric acid of Lactiplantibacillus pentosus P2020 (LPP), a probiotics stain extracted from Chinese pickle. We also tried to discussed the underlying mechanisms. Results: Oral administration with LPP significantly decreased serum uric acid and reduced renal inflammatory response by downregulating multiple inflammation pathways including NK-kB, MAPK, and TNFα. We also found that LPP administration significantly promoted uric acid excretion by regulating expression of transporters in the kidney and ileum. In addition, LPP intake improved intestinal barrier function and modulated the composition of gut microbiota. Discussion: These results suggest that probiotics LPP may have a promising potential to protect against development of HUA and HUA-related renal damage, and its working mechanisms involve regulation of inflammation pathways and expression of transporters in the kidney and ileum.

Synthesis of Acrylate Dual-Tone Resists and the Effect of Their Molecular Weight on Lithography Performance and Mechanism: An Investigation.

Acrylate photoresists have gained considerable attention in recent years owing to their high resolution, high sensitivity, and versality. In this work, a series of thermally stable copolymers are synthesized by introducing an isobornyl group, and well characterized using Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectra (1H-NMR). The effects of polymerization conditions on the molecular weight and their further influence on lithography are explored. By analyzing the thermal properties, film-forming capabilities, and the patterning behavior of these copolymers, a direct correlation between lithography performance and polymerization conditions is established via the molecular weight. In addition, the baking temperature of lithography is also optimized by atomic force microscopy (AFM), after which a line resolution of 0.1 µm is observed under the exposure of a 248 nm UV light and electron beam. Notably, our synthesized photoresist displays dual-tone resist characteristics when different developers are applied, and the reaction mechanism of acid-catalyzed hydrolysis is finally proposed by comparing the structural changes before and after exposure.

A Single-center, Open-label, Parallel Control Study Comparing the Pharmacokinetics and Safety of a Single Oral Dose of Roflumilast and Its Active Metabolite Roflumilast N-oxide in Healthy Chinese and Caucasian Volunteers.

Roflumilast is a phosphodiesterase-4 inhibitor which treats chronic obstructive pulmonary disease (COPD). Roflumilast N-oxide is the major metabolite of roflumilast with a similar mechanism of action to roflumilast. Although racial differences in roflumilast drug disposition have been observed, the necessity of dose adjustment is subject to debate. This study compares the pharmacokinetics of a single 500 µg dose of roflumilast in healthy Chinese and Caucasian subjects under uniform conditions. Chinese subjects were found to have longer t1/2 and higher AUC0-t and Cmax than Caucasian subjects. The point estimates on the geometric mean of AUC0-t in Chinese subjects were 22% higher for roflumilast and 46% higher for roflumilast N-oxide. Point estimates on the geometric mean of Cmax were 9% and 24% higher for roflumilast and roflumilast N-oxide, respectively. Total phosphodiesterase-4 (PDE4) inhibitory (tPDE4i) activity, a theoretical parameter that describes the combined contribution to PDE4 inhibitory activity of roflumilast and roflumilast N-oxide, was 44% higher in Chinese subjects than in Caucasian subjects. With about a 10-fold higher plasma AUC compared to the parent roflumilast and a much longer observed half-life, roflumilast N-oxide has been estimated to contribute about 90% of tPDE4i, with 10% attributed to the parent compound roflumilast. Following body weight normalization, these figures were lower but remained significant. Safety analysis showed signs of reduced tolerance or different pharmacodynamic response to roflumilast in Chinese recipients than in Caucasians. Our results suggest that Chinese patients should receive a dose of roflumilast lower than 500 µg daily during future clinical trials.

Differentiation therapy: Unlocking phenotypic plasticity of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The current treatment of HCC mainly includes surgery, chemotherapy, and liver transplantation. HCC differentiation therapy aims to restore tumor cells' normal liver characteristics and unlock their phenotypic plasticity. Understanding the molecular and signaling pathways that control HCC differentiation can help identify new targets for inducing differentiation and provide ideas for drug design. Downregulation of liver enriched transcription factors, imbalanced signal pathway, and dysregulated microRNA play essential roles in regulating the differentiation state of HCC. Restoring normal expression levels of these molecules could induce the tumor cells to differentiate into hepatocyte-like cells (HLCs) and suppress the malignant tumor phenotype. The strategies for inducing HLCs from induced pluripotent stem cells, fibroblasts, and other somatic cells provide a reference for the induced differentiation of liver cancer. The differentiation therapy is expected to be a promising and effective treatment for HCC.

Identification of Medicinal Compounds of Fagopyri Dibotryis Rhizome from Different Origins and Its Varieties Using UPLC-MS/MS-Based Metabolomics.

Fagopyrum dibotrys, being native to southwest China, is widely distributed in Yunnan, Guizhou Provinces and Chongqing City. However, the quality of medicinal materials growing in different origins varies greatly, and cannot meet the market demand for high-quality F. dibotrys. In this study, 648 metabolites were identified, and phenolic compounds of F. dibotrys from different origins were clearly separated by principal component analysis (PCA). Our results suggested that the medicinal differences of F. dibotrys from different origins can be elucidated via the variations in the abundance of the phenolic and flavonoid compounds. We found that the epicatechin, total flavonoids and total tannin content in Yunnan Qujing (YQ) and Yunnan Kunming (YK) were higher than those in Chongqing Shizhu (CS), Chongqing Fuling (CF) and Guizhou Bijie (GB), suggesting that Yunnan Province can be considered as one of the areas that produce high-quality medicinal materials. Additionally, 1,6-di-O-galloyl-ß-D-glucose, 2,3-di-O-galloyl-D-glucose and gallic acid could be used as ideal marker compounds for the quality control of F. dibotrys from different origins caused by metabolites, and the F. dibotrys planted in Yunnan Province is well worth exploiting.

Design and Optimization of a BAW Magnetic Sensor Based on Magnetoelectric Coupling.

Magnetic sensors actuated by bulk acoustic wave (BAW) have attracted extensive attention due to the fact of their high sensitivity, GHz-level high frequency, and small size. Different from previous studies, suppression of energy loss and improvement in energy conversion efficiency of the BAW magnetoelectric (ME) sensor were systematically considered during the device design in this work. Finite element analysis models of material (magnetic composite), structure (ME heterostructure), and device (BAW ME magnetic sensor) were established and analyzed in COMSOL software. Additionally, the magnetic composite was prepared by radio frequency magnetron sputtering, and its soft magnetism was characterized by magnetic hysteresis loop and surface roughness. The research results demonstrate that after inserting four layers of 5 nm Al2O3 films, a performance of 86.7% eddy current loss suppression rate, a less than 1.1% magnetostriction degradation rate, and better soft magnetism were achieved in 600 nm FeGaB. Furthermore, compared with other structures, the two-layer piezomagnetic/piezoelectric heterostructure had a better ME coupling performance. Eventually, the design of the BAW ME magnetic sensor was optimized by the resonance-enhanced ME coupling to match the resonance frequency between the magnetic composite and the BAW resonator. When a 54,500 A/m direct current bias magnetic field was applied, the sensor worked at the first-order resonance frequency and showed good performance. Its linearity was better than 1.30%, the sensitivity was as high as 2.33 µmV/A, and the measurement range covered 0-5000 A/m.

Pharmacokinetics, metabolite profiling, safety, and tolerability of inhalation aerosol of 101BHG-D01, a novel, long-acting and selective muscarinic receptor antagonist, in healthy Chinese subjects.

101BHG-D01 is a novel, long-acting, selective muscarinic receptor antagonist for the treatment of chronic obstructive pulmonary disease (COPD). A single-site, randomized, double-blind, placebo-controlled and dose-escalation study of 101BHG-D01 inhalation aerosol was conducted to evaluate its pharmacokinetics, metabolite profiling, safety and tolerability following the single inhaled doses ranged from 20 to 900 µg in healthy Chinese subjects. After inhalation, 101BHG-D01 was absorbed rapidly into plasma with the time to maximum concentration about 5 min, and eliminated slowly with the terminal phase half-life about 30 h. The cumulative excretion rates of 101BHG-D01 in feces and urine were about 30% and 2%, respectively, which showed the study drug was mainly excreted in feces. The maximum drug concentration and area under the plasma concentration-time curve increased with dose escalation in the range of 20-600 µg, but their values increased out of proportion to the whole studied doses. The main metabolic pathways were loss of phenyl group and hydroxylation. No metabolite that presented at greater than 10 percent of total drug-related exposure was observed. 101BHG-D01 was safe and well tolerated after administration. The study results indicate that 101BHG-D01 is a good candidate for the treatment of COPD and enable further clinical development in subsequent studies in patients. Clinical Trial Registration: http://www.chinadrugtrials.org.cn; Identifier: CTR20192058.

Association between YKL-40 and asthma: a systematic meta-analysis.

PURPOSE: Many studies have shown that chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is associated with asthma. The purpose of this meta-analysis was to evaluate the role of serum YKL-40 in the diagnosis and differential diagnosis of asthma, severity grading, and determination of disease state. METHODS: The PubMed, Ovid, and Cochrane databases were searched. A total of 17 articles involving 5696 subjects were included in this meta-analysis. RESULTS: The results showed that the level of YKL-40 was significantly higher in asthmatic patients than in the normal group regardless of age and residential location, and increased with severity and acute exacerbation (p < 0.05). YKL-40 levels were significantly different between chronic obstructive pulmonary disease (COPD) and asthma, and also between asthma-COPD overlap syndrome (ACO) and asthma (p < 0.05). CONCLUSION: YKL-40 may act as a potential serological marker for the diagnosis of asthma, assessment of severity, indicator of the disease state, and differential diagnosis of COPD, ACO, and asthma.

Detection and Segmentation of Breast Masses Based on Multi-Layer Feature Fusion.

In breast mass detection, there are many different sizes of masses in the image. However, when the existing target detection model is directly used to detect the breast mass, it is easy to appear the phenomenon of misdetection and missed detection. Therefore, in order to improve the detection accuracy of breast masses, this paper proposed a target detection model D-Mask R-CNN based on Mask R-CNN, which is suitable for breast masses detection. Firstly, this paper improved the internal structure of FPN, and modified the lateral connection mode in the original FPN structure to dense connection. Secondly, modified the size of the anchor of RPN to improve the location accuracy of breast masses. Finally, Soft-NMS was used to replace the NMS in the original model to reduce the possibility that the correct prediction results may be eliminated during the NMS process. This paper used the CBIS-DDSM dataset for all experiments. The results showed that the mAP value of the improved model for detecting breast masses reached 0.66 in the test set, which was 0.05 higher than that of the original Mask R-CNN.

Antibacterial Activity Prediction Model of Traditional Chinese Medicine Based on Combined Data-Driven Approach and Machine Learning Algorithm: Constructed and Validated.

Traditional Chinese medicines (TCMs), as a unique natural medicine resource, were used to prevent and treat bacterial diseases in China with a long history. To provide a prediction model of screening antibacterial TCMs for the design and discovery of novel antibacterial agents, the literature about antibacterial TCMs in the China National Knowledge Infrastructure (CNKI) and Web of Science database was retrieved. The data were extracted and standardized. A total of 28,786 pieces of data from 904 antibacterial TCMs were collected. The data of plant medicine were the most numerous. The result of association rules mining showed a high correlation between antibacterial activity with cold nature, bitter and sour tastes, hemostatic, and purging fire efficacies. Moreover, TCMs with antibacterial activity showed a specific aggregation in the phylogenetic tree; 92% of them came from Tracheophyta, of which 74% were mainly concentrated in rosids, asterids, Liliopsida, and Ranunculales. The prediction models of anti-Escherichia coli and anti-Staphylococcus aureus activity, with AUC values (the area under the ROC curve) of 77.5 and 80.0%, respectively, were constructed by the Neural Networks (NN) algorithm after Bagged Classification and Regression Tree (Bagged CART) and Linear Discriminant Analysis (LDA) selection. The in vitro experimental results showed the prediction accuracy of these two models was 75 and 60%, respectively. Four TCMs (Cirsii Japonici Herba Carbonisata, Changii Radix, Swertiae Herba, Callicarpae Formosanae Folium) were proposed for the first time to show antibacterial activity against E. coli and/or S. aureus. The results implied that the prediction model of antibacterial activity of TCMs based on properties and families showed certain prediction ability, which was of great significance to the screening of antibacterial TCMs and can be used to discover novel antibacterial agents.

Changes in clinical trials of endocrine disorder and metabolism and nutrition disorder drugs in mainland China over 2010-2019.

With the improvements in relevant policies, laws, and regulations regarding drug clinical trials in China, the quantity and quality of drug clinical trials have gradually improved, and the development prospects of drug clinical trials for endocrine disorders and metabolism and nutrition disorders are promising. Based on information from the clinical trials from the online drug clinical trial registration platform of the National Medical Products Administration, we aimed to review and evaluate the development of clinical trials of drugs for endocrine disorders and metabolism and nutrition disorders in mainland China from 2010 to 2019, as well as the trends over time. A total of 861 trials were carried out on 254 types of drugs for endocrine disorders and metabolism and nutrition disorders, among which 531 (61.67%) involved endocrine disorders, and 330 (38.33%) addressed metabolism and nutrition disorders. The annual number of clinical trials has been increasing gradually, with a significant increase in 2017. Among them, the proportion of clinical trials with Chinese epidemiological characteristics was relatively large (Wu, Annual Report on Development Health Management and Health Industry in China, 2018). The largest number of trials were for diabetes drugs (55.63%), followed by trials of drugs for hyperlipidemia (19.4%) and those for hyperuricemia (7.9%). It was found that the geographical area of the leading units also showed obvious unevenness according to the analysis of the test unit data. Based on the statistics and evaluation of the data, comprehensive information is provided to support the cooperation of global pharmaceutical R&D companies and research units in China and the development of international multicenter clinical trials in China. This work additionally provides clinical trial units with a self-evaluation of scientific research competitiveness and hospital development strategies. At the same time, it provides a reference with basic data for sponsors and stakeholders in these trials to determine their development strategy goals.

A Novel Immunobiotics Bacteroides dorei Ameliorates Influenza Virus Infection in Mice.

Objective: Probiotics can modulate immune responses to resist influenza infection. This study aims to evaluate the anti-viral efficacy of B. dorei. Methods: C57BL/6J mice were infected with influenza virus together with treatment of PBS vehicle, B. dorei, or oseltamivir respectively. Anti-influenza potency of B. dorei and the underlying mechanism were determined by measuring survival rate, lung viral load and pathology, gene expression and production of cytokines and chemokines, and analysis of gut microbiota. Results: Administration of B. dorei increased (by 30%) the survival of influenza-infected mice, and improved their weight loss, lung pathology, lung index, and colon length compared to the vehicle control group. B. dorei treatment reduced (by 61%) the viral load of lung tissue and increased expression of type 1 interferon more rapidly at day 3 postinfection. At day 7 postinfection, B. dorei-treated mice showed lower local (lung) and systemic (serum) levels of interferon and several proinflammatory cytokines or chemokines (IL-1ß, IL-6, TNF-α, IL-10, MCP-1 and IP-10) with a efficacy comparable to oseltamivi treatment. B. dorei treatment also altered gut microbiota as indicated by increased levels of Bacteroides, Prevotella, and Lactobacillus and decreased levels of Escherichia, Shigella, and Parabacteroides. Conclusion: B. dorei has anti-influenza effect. Its working mechanisms involve promoting earlier interferon expression and down-regulating both local and systemic inflammatory response. B. dorei changes the composition of gut microbiota, which may also contribute to its beneficial effects.