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Background and Objective. Tuberculosis (TB) is a major threat to human health, especially in developing countries. Its susceptibility and progression depend on interactions between mycobacterium tuberculosis, host immune system, and genetic and environmental factors. Up to now, many studies have presented the association between TB susceptibility and host genetic polymorphisms, but never regarding CD59 gene, which is an essential complement regulator. This study investigated the relationship between multiple CD59 single nucleotide polymorphisms (SNPs) and susceptibility to TB among Chinese patients. Methods. A case–control study was conducted to investigate the SNPs at CD59 rs1047581, rs7046, rs2231460, rs184251026, rs41275164, rs831633, rs704700, rs41275166, and rs10768024 by sequence-specific primer-polymerase chain reaction (SSP-PCR) in 900 tuberculosis patients and 1,534 controls. Results. The minor allele frequencies at rs2231460, rs184251026, rs41275164, and rs41275166 were extremely low both in the Cases (0.00%–0.61%) and in the Controls (0.07%–0.43%), comparatively at rs1047581, rs7046, rs831633, rs704700, and rs10768024 were notably higher both in the Cases (8.23%–48.39%) and in the Controls (8.57%–47.16%). Among the nine SNPs, only homozygous CC genotype at rs10768024 showed a significant protective effect against TB than homozygous TT genotype (OR(95% CI) = 0.59(0.38, 0.91), χ2 = 5.779, P = 0.016 ), and homozygous TT and heterozygous CT genotypes showed a significant risk of TB infection in the recessive model (OR(95% CI) = 1.68(1.10, 2.56), χ2 = 5.769, P = 0.016 ). Further analysis verified that rs10768024 CC genotype independently related to TB susceptibility (OR(95% CI) = 0.60(0.39, 0.91), Wald χ2 = 5.664, P = 0.017 ) in multivariate logistic regression analysis, and its genetic mutation was independent of the other SNPs (r2 = 0.00–0.20) in haplotype analysis. Conclusions. The first investigation of the CD59 gene and susceptibility to TB suggests a significant risk with homozygous TT and heterozygous CT genotypes at rs10768024 loci. The homozygous CC mutation at rs10768024 loci showed a significant protection against TB susceptibility.

Relationship between d-metal active species (Co, Ni, & Cu) in Prussian blue analogue derived metal oxide/hydroxide films and the activation energy needed for full conversion of 5-HMF to 2,5-FDCA in alkaline solution.

Proton exchange membrane (PEM) is one of the most popular fuel cells for renewable energy production, and this paper presents a DC/DC boost converter structure to improve energy efficiency. To achieve high output power as well as constant output voltage, a combined method consisting of proportional-integral controller and adaptive sliding mode technique is designed. Also, due to the use of adaptive technique, the proposed technique has the ability to cover the effects of uncertainty with an unknown high limit and in addition to improving the quality of output power and voltage of PEM, it eliminates permanent tracking error and guarantees closed loop system stability. To show the operational implementation capability and flexibility of the method, FPGA has been used, which in addition to showing real-time performance, provides the ability to execute the controller at high speeds. Operationality and the possibility of practical implementation of the planned scheme on the existing systems provide the possibility of increasing the efficiency of energy extraction without further investment. The stability of the closed-loop system is achieved using Lyapunov technique and the results of simulation and comparison indicate the optimal performance of the system under the planned scheme and high efficiency in comparison with existing approaches.

Although ultra-small nanoclusters (USNCs,2 nm) have immense application capabilities in biomedicine, the investigation on body-wide organ responses towards USNCs is scant. Here, applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues, we systematically evaluate the interactions between the host and calcium phosphate (CaP) USNCs at the organism level. Combining single-cell mass cytometry, and magnetic luminex assay results, we identify dynamic immune responses to CaP USNCs at the single cell resolution. The innate immune is initially activated and followed by adaptive immune activation, as evidenced by dynamic immune cells proportions. Furthermore, using Nano Genome Atlas of multi-tissues, we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney. Moreover, based on the immunological response profiles, histological evaluation of major organs and local tissue, and a body-wide transcriptomics, we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection. Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.

The complex etiopathology of retained placenta (RP) and hazards associated with it has made it crucial for researchers and clinical veterinarians to study pathogenesis, early-warning diagnosis, and treatment. This study aimed to screen the potential prognostic markers of RP in dairy cows using plasma metabolomics coupled with clinical laboratory indicators. Blood samples were collected from 260 dairy cows at 21, 14, 7, and 0 days before parturition and 7, 14, and 21 days after parturition. Consequently, 10 healthy cows and 10 cows with RP with similar parity, body condition score, and age were included in the study. The changes in clinical laboratory indicators of the enrolled cows from 21 before parturition to 21 days after parturition were assessed. After initial overview of the multivariate statistical data using PCA analysis, the data were subjected to orthogonal partial least-squares discriminant analysis. Compared with cows with RP at 7 days before parturition, the levels of endothelin and 6-keto-prostaglandin F1α were increased in healthy cows, while the level of estradiol and progesterone decreased. Adenine dinucleotide phosphate, hypoxanthine, guanine dinucleotide phosphate, inosine monophosphate, and L-arginine were revealed as potential prognostic markers of cows with RP at 7 days before parturition involved in the regulation of taste transduction, purine and glutathione metabolism, and autophagy. The best period for the early-warning diagnosis of RP in dairy cows is 7 days before parturition, and purine metabolism and autophagy may play a vital role in the occurrence and development of RP in dairy cows.

Existing dynamic bus lanes (DBLs) typically use a fixed and long blocking space to guarantee bus priority, leading to a conflict between bus priority and traffic capacity. This study proposes an innovative approach in a connected-vehicle (CV) environment, called dynamic bus lane with moving block (DBLMB). The length of the moving block can be adjusted with the bus speed in real time, aiming to ensure bus priority with fewer road resources, thus improving traffic capacity. A three-lane cellular automata model is established to evaluate DBLMB in comparison with two other strategies, bus lane without priority and bus lane with intermittent priority (BLIP). First, the benefits of DBLMB over the established DBLs are analyzed qualitatively by the macroscopic fundamental diagram. Next, simulation experiments are conducted to compare the coordination between bus priority and capacity under different strategies. Then, the impact of DBLMB on microscopic traffic flow is investigated through evaluation indicators including lane density, lane speed, lane-changing frequency, and travel speed. Finally, the sensitivity of bus delay and traffic capacity to CV penetration is discussed. The results show that: (1) the capacity of a three-lane road adopting DBLMB strategy can be stabilized above 5200 passenger car units per hour (pcu/h) when the bus departure interval is higher than 60 s and the expected level of service is below B. (2) With 100%, 80%, 60%, 40%, and 20% of CV penetration, DBLMB improves the average capacity of the road by 523 pcu/h compared with BLIP, with only an incremental bus delay of 6.43 s per vehicle.

Creating a wide range of new compounds that not only have ideal pharmacological properties but also easily pass long-term toxicity evaluation is still a challenging task in current drug discovery. In this study, we developed a conditional generative model by combining a semisupervised variational autoencoder (SSVAE) with an MGA toxicity predictor. Our aim is to generate molecules with low toxicity, good drug-like properties, and structural diversity. For multiobjective optimization, we have developed a method with hierarchical constraints on the toxicity space of small molecules to generate drug-like small molecules, which can also minimize the effect on the diversity of generated results. The evaluation results of the metrics indicate that the developed model has good effectiveness, novelty, and diversity. The generated molecules by this model are mainly distributed in low-toxicity regions, which suggests that our model can efficiently constrain the generation of toxic structures. In contrast to simply filtering toxic ones after generation, the low-toxicity molecular generative model can generate molecules with structural diversity. Our strategy can be used in target-based drug discovery to improve the quality of generated molecules with low-toxicity, drug-like, and highly active properties.

SWEET (Sugars will eventually be exported transporter) proteins are a group of sugar transporters that are involved in sugar efflux, phloem loading, reproductive development, plant senescence, and stress responses. In this study, 23 SWEET transporter members were identified in the Medicago polymorpha genome, heterogeneously distributed on seven chromosomes. These MpSWEET genes were divided into four subfamilies, which showed similar gene structure and motif composition within the same subfamily. Seventeen MpSWEET genes encode seven transmembrane helices (TMHs), and all MpSWEET proteins possess conserved membrane domains and putative serine phosphorylation sites. Four and three pairs of MpSWEET genes were predicted to be segmentally and tandemly duplicated, respectively, which may have contributed to their evolution of M. polymorpha. The results of microarray and RNA-Seq data showed that some MpSWEET genes were specifically expressed in disparate developmental stages (including seedling stage, early flowering stage, and late flowering stage) or tissues such as flower and large pod. Based on protein network interaction and expression patterns of MpSWEET genes, six MpSWEET genes were selected for further quantitative real-time PCR validation in different stress treatments. qRT-PCR results showed that MpSWEET05, MpSWEET07, MpSWEET12, MpSWEET15, and MpSWEET21 were significantly upregulated for at least two of the three abiotic stress treatments. These findings provide new insights into the complex transcriptional regulation of MpSWEET genes, which facilitates future research to elucidate the function of MpSWEET genes in M. polymorpha and other legume crops.

The stellar optoelectronic properties of metal halide perovskites provide enormous promise for next-generation optical devices with excellent conversion efficiencies and lower manufacturing costs. However, there is a long-standing ambiguity as to whether the perovskite surface/interface (e.g. structure, charge transfer or source of off-target recombination) or bulk properties are the more determining factor in device performance. We fabricated an array of CsPbI3 crystal and hybrid glass composites by sintering and globally visualised the property-performance landscape. Our findings reveal that the interface is the primary determinant of the crystal phases, optoelectronic quality, and stability of CsPbI3. In particular, the presence of a diffusion "alloying" layer is discovered to be critical for passivating surface traps, and beneficially altering the energy landscape of crystal phases. However, high-temperature sintering results in the promotion of a non-stoichiometric perovskite and excess traps at the interface, despite the short-range structure of halide is retained within the alloying layer. By shedding light on functional hetero-interfaces, our research offers the key factors for engineering high-performance perovskite devices.

In recent years, the emergence and development of single-cell sequencing technologies have provided unprecedented opportunities to analyze deoxyribonucleic acid, ribonucleic acid and proteins at single-cell resolution. The advancements and reduced costs of high-throughput technologies allow for parallel sequencing of multiple molecular layers from a single cell, providing a comprehensive insight into the biological state and behavioral mechanisms of cells through the integration of genomics, transcriptomics, epigenomics and proteomics information. Researchers are actively working to further improve the cost-effectiveness, stability and high-throughput capabilities of single-cell multi-omics sequencing technologies and exploring their potential in precision medicine through clinical diagnostics. This review aims to survey the cutting-edge advancements in single-cell multi-omics sequencing, summarizing the representative technologies and their applications in profiling complex diseases, with a particular focus on tumors.

One of the promising technologies in the field of clean and renewable energy is the microbial fuel cells, which in addition to generating electrical energy from the metabolism of microorganisms, can also be used to improve the environment in wastewater treatment. In fact, this paper designs an integrated control model that in the presence of uncertainty and unknown parameters can consider the effect of input variables for two-population in a chamber. In addition to maintaining closed loop stability, it has acceptable behavior in terms of time to reach steady state and reduce system error and provide satisfactory performance in terms of output energy. Lyapunov analysis ensures system stability and system control functions are demonstrated by MATLAB / Simulink simulations.

Tuberculosis is an ancient disease of mankind, and its causative bacterium is Mycobacterium tuberculosis. Isoniazid is one of the most effective first-line antituberculosis drugs. As prodrugs, it and its derivative ethionamide act on enoyl-acyl carrier protein reductase (InhA) after being oxidized in bacteria, and kill the bacteria by inhibiting the formation of M. tuberculosis cell walls. However, the S94A mutation of InhA causes M. tuberculosis to develop cross-resistance to isoniazid and ethionamide. This work is dedicated to studying the cross-resistance mechanism of isoniazid and ethionamide through theoretical calculations. First, thermodynamic integral simulations are used to accurately calculate the relative binding energy of two drugs in the mutant and wild-type system. Furthermore, through classic molecular dynamic simulations and molecular mechanics generalized-Born surface area calculation, some key residues are identified and the binding affinity of isoniazid and ethionamide reduced by 9-13 kcal/mol due to S94A mutation. The hydrogen bond between Ala94 and isoniazid (ethionamide) disappeared and the energy contribution of Ala94 decreased after the mutation. In addition, the dynamic network analysis indicated that the mutation of Ser94 also indirectly affected the conformation of key residues such as Met147, Thr196, and Leu97, resulting in a reduction in the energy contribution of these residues. Finally, the binding conformation of isoniazid and ethionamide has also undergone major changes. The obtained results could provide valuable information for the future molecular design to overcome the drug resistance.

The membrane (M) protein is the most abundant structural protein of coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2, and plays a central role in virus assembly through its interaction with various partner proteins. However, mechanistic details about how M protein interacts with others remain elusive due to lack of high-resolution structures. Here, we present the first crystal structure of a betacoronavirus M protein from Pipistrellus bat coronavirus HKU5 (batCOV5-M), which is closely related to MERS-CoV, SARS-CoV, and SARS-CoV-2 M proteins. Furthermore, an interaction analysis indicates that the carboxy-terminus of the batCOV5 nucleocapsid (N) protein mediates its interaction with batCOV5-M. Combined with a computational docking analysis an M–N interaction model is proposed, providing insight into the mechanism of M protein–mediated protein interactions.

SPATS2L (Spermatogenesis-associated serine-rich 2-like) is anintranucleolar stress-response protein involved in chromosomal organization, ribosomal biogenesis, and translational control. Although there is mounting evidence that SPATS2L was involved in the carcinogenesis of some cancers, no thorough pan-cancer investigation of SPATS2L is available so far. Based on multiple databases, including TCGA, GTEx, CCLE, cBioPortal, TIMER2, ImmuCellAI, GDSC, and Reactome, we analyzed the expression, prognosis, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), immune cell infiltration, drug sensitivity, and clinicopathological and prognostic relevance of SPATS2L in pan-cancer including 33 types of cancers. SPATS2L expression was dramatically increased in a variety of malignancies, while it was low in ACC, KICH, and LAML as indicated by multiple databases and confirmed by immunohistochemistry assays. Importantly, SPATS2L has been found to have prognostic and clinicopathological importance in several malignancies. SPATS2L expression was also linked to TMB and MSI in 9 types of cancers, and there was a link between SPATS2L expression and DNA methylation in 28 types of cancers. SPATS2L was also found to be highly linked with immune cell infiltration, ICP expression, stromal score, immune score, and ESTIMATE score in various malignancies, demonstrating their regulatory roles on the TME. Consistently, the results of GSEA and GSVA analyses revealed a substantial link between SPATS2L and certain cellular immunological responses. Finally, SPATS2L was found to be strongly linked to 173 anti-tumor drugs. This study indicated that SPATS2L might be a potential cancer biomarker for the prognosis and immunotherapeutic response. SPATS2L expression in cancers may be involved in the regulation of the tumor immune microenvironment and drug sensitivity, which may be a new-targeted molecule for developing anti-tumor drugs and immunotherapy.

ObjectiveThis study evaluated the diagnostic value of different combinations of five commonly used tumour markers and screened the best combination of tumour markers.MethodsRegression analysis was used to evaluate 185 patients with suspected breast cancer admitted to Mianyang Central Hospital from January 2020 to December 2021. The differences of five tumour markers between a breast cancer group and a benign lesion group were analysed. The sensitivity and specificity of five tumour markers were compared.ResultsOf 185 patients with suspected breast cancer, 108 patients had breast cancer and 77 patients had benign breast tumours. The detection results of carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199) and carbohydrate antigen 153 (CA153) in patients with breast cancer were significantly higher than those in patients with benign breast tumours. In the analysis of the single-detection results of tumour markers, CEA had the highest sensitivity (23.94%), CA153 had the highest specificity (96.43%), AFP had the highest accuracy (47.66%) and CA153 had the highest area under the curve (AUC) value (0.727). With the increase of parallel indicators, the sensitivity, accuracy and AUC value increased in turn, and the increase was obvious in the front. The increase began to slow down after the three parallel indicators. Among the different combinations of three parallel detections of breast cancer tumour markers, the highest sensitivity was AFP + CEA + CA153 (83.46%), the highest accuracy was AFP + CEA + CA153 and AFP + CA153 + CA125 (80.25%), and the highest AUC was CEA + CA125 + CA199 (0.922).ConclusionAFP, CA153 and CA199 are recommended for clinical diagnosis of breast cancer. In routine physical examination and early breast cancer screening, the optimal combination of AFP + CEA + CA153 three parallel tests is recommended.

Serum 25-hydroxyvitamin D [25(OH)D] concentration represents the body's reserves of vitamin D, which is mostly used by clinicians to evaluate the storage status of vitamin D in the body. The present study aimed to investigate the serum vitamin D components in different health status of minors to correctly evaluate the vitamin D storage in vivo. A total of 2,270 minors were included in the study, which was divided into healthy group (1,204 cases) and disease group (1,066 cases, including 270 short stature, 433 respiratory infections, 175 malnutrition and 188 tic disorder subjects). The levels of 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] were measured by UHPLC-MS/MS in all subjects, and the 25(OH)D3 activity equivalents [25(OH)D3-AE] and 25(OH)D were calculated. In addition, the 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3] concentrations of 278 subjects (including 147 healthy and 131 disease subjects) were measured by random sampling. 25(OH)D2, 25(OH)D3, 25(OH)D and 25(OH)D3-AE levels in disease group were significantly lower than those in healthy group (p

The high cost of feed and nitrogen pollution caused by high protein diets, which have become major challenges restricting sustainable development in China’s animal husbandry. Properly reducing the protein level and improving protein utilization in feed are a promising approach in solving this problem. To determine the optimal dose of methionine hydroxyl analog chelated zinc (MHA-Zn) in reduced 1.5% protein diets of broilers, total 216 1-day-old broilers were randomly allotted into 4 treatments and assess the index of growth and development at 42-days. Results showed no significant difference was observed for edible part between low protein (LP) diet group (90 mg/kg MHA-Zn) and normal diet group (P > 0.05), and adding 90 mg/kg MHA-Zn in LP diet significantly improved ileum morphology and apparent total tract digestibility (ATTD) of nutrients (P Lactobacillus, Butyricoccus, Oscillospira et al.) (P

This study investigated the effects of CCHMA on growth performance, slaughter performance, serum biochemical indicators, intestinal morphology and microbiota of Zi goose. Initially, it was determined the optimal addition concentration of CCHMA to be 3 g/kg by the first feeding experiment. Then, 78 Zi geese were divided into control and CCHMA supplemented groups. The results showed that the body weight (BW) and average daily gain (ADG) of the CCHMA supplemented group was significantly increased (p < 0.05), and the feed/gain (F/G) of the CCHMA supplemented group was significantly decreased (p < 0.05) compared with the control group. The dressed yield percentage in the CCHMA supplemented group significantly increased by 0.78% (p < 0.05). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly lower in the CCHMA fed birds than in the control group (p < 0.05). Further, 16S rDNA gene sequencing conducted for cecal flora composition found that 3 g/kg CCHMA significantly increased the abundance of beneficial bacteria (CHKCI001, Colidextribacter and Subdoligranulum) (p < 0.05; p < 0.01) and suppressing harmful bacteria (Bacteroidetes and Methanobrevibacter) (p < 0.05) in the cecum of Zi goose. In conclusion, adding 3 g/kg of CCHMA in the diet can improve the growth performance, slaughter performance of Zi goose, and optimize the cecum microflora.

This meta-analysis was performed to evaluate the effect of Seprafilm® on postoperative small bowel obstruction.A literature search was conducted in the PubMed and EMBASE databases through August 2020. The pooled risk ratios as well as the corresponding 95% confidence intervals were calculated using RevMan 5.3 software.A total of 9 clinical control trials involving 4,351 patients (2,123 in the Seprafilm® group and 2,228 in the control group) were included. The overall analysis showed that the pooled risk ratio was 0.45 (95% confidence interval = 0.34-0.60; P.00001), indicating that the risk of postoperative small bowel obstruction can be significantly decreased by the application of Seprafilm®. Similarly, an obvious effect of Seprafilm® on reducing the rate of postoperative small bowel obstruction was also shown in the subgroup analyses by population (adult participants), study design (randomized control study or nonrandomized control study), region (Japan or Korea), follow-up duration (2 years or 5 years), and sheet number of Seprafilm® (1 sheet or1 sheet).In conclusion, the use of Seprafilm® is beneficial for decreasing the rate of postoperative small bowel obstruction.

Radiation exposure can immediately trigger a burst of reactive oxygen species (ROS), which can induce severe cell death and long-term tissue damage. Therefore, instantaneous release of sufficient radioprotective drugs is vital to neutralize those accumulated ROS in IR-exposed areas. To achieve this goal, we designed, synthesized, and evaluated a novel oral ROS-responsive radioprotective compound (M1) with high biocompatibility and efficient ROS-scavenging ability to act as a promising oral drug for radiation protection. The compound is stably present in acidic environments and is hydrolyzed in the intestine to form active molecules rich in thiols. M1 can significantly remove cellular ROS and reduce DNA damage induced by γ-ray radiation. An in vivo experiment showed that oral administration of M1 effectively alleviates acute radiation-induced intestinal injury. Immunohistochemical staining showed that M1 improved cell proliferation, reduced cell apoptosis, and enhanced the epithelial integrity of intestinal crypts. This study provides a promising oral ROS-sensitive agent for acute intestinal radiation syndrome.

This article proposes a two-layer collaborative stochastic optimization model of a hybrid combined heat and power system to determine the optimal capacities and operational strategies of components for minimizing the total cost, which includes investment, operation, and CO2 emission costs. Hybrid optimization algorithms, in genetic algorithm and particle swarm optimization, are employed to solve the two-layer optimization, respectively. Typical scenarios with probability distributions are generated in Monte Carlo simulations and a clustering approach, which demonstrate the influences of the uncertainties of renewable energies and electrical and thermal loads. The simulation results validate the effectiveness of the proposed optimization model. When considering the CO2 emission cost, the renewable energy penetration resulting from the larger capacities of renewable power technologies reaches 30%, which is 11.5% higher than the optimal case without considering the emission cost. This optimal integration increases the fossil energy utilization efficiency by 2.5% and the revenue from excess electricity sales by 2.7 times. The levelized capital cost, however, increases by 33.0%, and the utility grid integration and the net interaction also increase by 1.1% and 21.5%, respectively.

Diabetic nephropathy (DN) is the leading cause of end‑stage renal disease. Although Ginkgo biloba extract has a protective effect on DN, the protective effect and mechanism of its active ingredient Ginkgolide B (GB) on DN remain unclear. The aim of the present study was to investigate whether GB improves DN via alleviating oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination in PA-G-induced mouse podocytes and DN mice. The study in vitro showed that GB effectively reduced serum total cholesterol, triglyceride concentrations and lipid accumulation in PA-G-induced MPC5 cells. In addition, GB promoted the expression of ferroptosis markers GPX4 and FTH1, while inhibited the expression of TfR1, fibrosis markers α-SMA and Collagen α1, as well as intracellular iron content and ROS levels. Interference of GPX4 expression with siRNA counteracted the effect of GB. And GB inhibited GPX4 ubiquitination in a dose-dependent manner. In vivo the experimental results showed that GB effectively reduced hyperglycemia, serum total cholesterol and triglyceride concentrations, reduced urinary albumin excretion and the number of renal lipid droplets, and improved changes in renal structure in DN mice. GB inhibited the expression of ferroptosis marker TfR1 and fibrosis markers α-SMA and Collagen α1, while promoted the expression of ferroptosis markers GPX4 and FTH1. In conclusion, the results suggested that GB may improve DN via protecting the kidney from ferroptosis and oxidative stress damage by inhibiting the ubiquitination of GPX4. These findings suggested that GB, a natural medicine, may be an effective therapeutic option for DN.

Goose meat is consumed by consumers because it contains a relatively high proportion of polyunsaturated fatty acids (PUFAs). This study was conducted to explore the main differences in production performance, breast meat quality traits, and cecal microbiota compositions between the Zi goose (ZG) and Xianghai flying goose (FG). The production performance and breast meat quality trait analyses showed that compared with the ZG, the FG had a higher right breast muscle index, ileum villi height/crypt depth ratio (VH/CD), and cecum fermentation rate (higher short-chain fatty acid (SFCA) concentration); a lower abdominal fat index; a higher proportion of PUFAs; and a lower shear force. Spearman’s correlation coefficients between the cecal microbiota composition and production performance indexes suggested that the genus Faecalibacterium was positively associated with production performance; in contrast, the genus Candidatus Saccharimonas was negatively correlated with production performance; moreover, the Ruminococcus torques group, Parasutterella, and Methanobrevibacter were negatively related to the VH/CD. Taken together, in this particular trial, FG had better production performance, healthier meat quality traits, and better intestinal digestion and absorption capacities than ZG. These results not only provide a useful data reference for the production of healthy geese for human consumption but can also help guide the utilization of goose breed resources.

Adult tendons heal via fibrovascular scarring with inferior biomechanical properties. Mohawk (Mkx) emerged as a pivotal actor in tenolineage commitment. However, its precise function in tendinopathy remains poorly understood. This study investigates the cellular and molecular mechanisms underlying Mkx’ role in fibrovascular healing. Human samples were collected to test fibrovascular markers. We then performed RNAseq on Mkx−/− mice compared to their wild type littermates to decipher Mkx regulome. We therefore sought to reproduce TSPCs transition to myofibroblasts in-vitro by over-expressing MyoD and followed by phenotypic and experimental cells’ characterization using microscopy, qRT-PCR, flow cytometry sorting, presto-blue cell viability assay and immunofluorescence. Two different in vivo models were used to assess the effect of the MyoD-expressing myofibroblasts: transplantation in the dorsal area of immunodeficient mice and in an adult Achilles tendon injury model. To prevent angiofibrosis, we tested the molecule Xav939 and proceeded with histological stainings, q-RT PCR transcriptional quantification of angifibrotic markers, mechanical tests, and immunofluorescence. Tendinopathy samples showed fibrovascular healing with decreased tenolineage phenotype. Transcriptomic analysis of Mkx−/− tendons revealed myofibroblast-associated biological processes. Over-expression of MyoD in WT tendon stem progenitor cells (TSPCs) gave rise to myofibroblasts reprogramming in-vitro and fibrovascular scarring in-vivo. MKX directly binds to MyoD promoter and underlies global regulative processes related to angiogenesis and Wnt signaling pathway. Blocking Wnt signaling with the small molecule Xav393 resulted in higher histological and biomechanical properties. Taken together, our data provide the first in vivo and in-vitro evidence of tendon stem progenitor cells to myofibroblasts transition and show improved tendon healing via angiofibrosis modulation, thus opening potential therapeutic avenues to treat tendinopathy patients.

Bailemian capsule (BLMC) is a Chinese patent drug for treating insomnia with excellent curative effects. But there are few researches on it. In this research, a rapid separation and identification method using UPLC-QE-Orbitrap-MS was established, and 228 identified compounds were separated within 18 min. The structures of compounds were preliminarily determined by comparing the retention time and fragmentation law. Furthermore, multiple databases were used to integrate the compound targets of BLMC and the disease targets related to insomnia. After the intersection of the two sets of targets, a protein-protein interaction network and a drug-target-disease pharmacological network were established, then using the DAVID database to perform GO analysis and KEGG analysis on the common targets to find related pathways. Finally, a total of 289 common targets and 136 pathways were found to participate in the mechanism.

The investigation of nanoscale complex hydrides for hydrogen storage application has gained the spotlight in the past decade. Herein, the thermodynamic behavior of complex borohydrides confined in ...

Objective: This retrospective study analyzed the factors affecting recurrence in patients after surgery with borderline ovarian tumors and postoperative recurrence and pregnancy after fertility-sparing surgery (FSS), to provide guidance for clinical treatment of borderline ovarian tumors and propose a therapeutic strategy for fertility protection. Methods: A total of 415 patients with borderline ovarian tumors were initially operated on in the gynecology ward of Shengjing Hospital Affiliated with China Medical University from September 1, 2013, to September 1, 2019. Central pathology review and prospective follow-up were carried out. The clinical and pathological data were consulted through the medical record query system of our hospital. The recurrence and pregnancy of the patients were investigated through telephone follow-up and outpatient and inpatient medical records. The influence of clinical and pathological variables on recurrence and pregnancy were evaluated using univariate/multivariate analyses. Results: In this study, 415 patients were collected, of which 21 lost follow-up, and a total of 394 eligible patients were included in the analysis. Among these patients, 25 patients relapsed with a recurrence rate of 6.3% and there were 196 patients with fertility-sparing surgery, of the 63 patients attempting to conceive, 35 were able to attain pregnancy with a pregnancy rate of 55.6%. All patients survived until the follow-up deadline. In univariate and multivariate analyses, FSS, FIGO stage, and micropapillary pattern were independent risk factors for recurrence of BOTs. FIGO stage, micropapillary pattern were independent risk factors for recurrence of BOTs with FSS. The risk of recurrence was not related to omentectomy nor postoperative chemotherapy. While omentectomy and chemotherapy had an impact on the pregnancy rate (P

Prussian Blue Analogues (PBAs) are promising electrocatalysts for oxidation reactions due to their binary metal composition and tuneable redox properties. Herein, we report the generation of coordinative unsaturated metal sites in pulse electrodeposited (PED) CoFe PBAs for the oxidation of 5-hydroxymethylfurfural (HMF). The high reactivity by unsaturated metal sites, thoroughly characterized by a suite of spectroscopic techniques, results in a catalyst with superior activity towards the oxidation of HMF to 2,5 furandicarboxylic acid (FDCA).

Effectively learning and extracting the feature representations of 3D point clouds is an important yet challenging task. Most of existing works achieve reasonable performance in 3D vision tasks by modeling the relationships among points appropriately. However, the feature representations are only learned with a specific transform through these methods, which are easy to overlap and thus limit the representation ability of the model. To address these issues, we propose a novel Multi-Transform Learning framework for point clouds (PointMTL), which can extract diverse features from multiple mapping transform to obtain richer representations. Specifically, we build a module named Multi-Transform Encoder (MTE), which encodes and aggregates local features from multiple non-linear transforms. To further explore global context representations, a module named Global Spatial Fusion (GSF) is proposed to capture global information and selectively fuse with local representations. Moreover, to guarantee the richness and diversity of learned representations, we further propose a Spatial Independence Criterion (SIC) strategy to enlarge the differences between the transforms and reduce information redundancies. In contrast to previous works, our approach fully exploits representations from multiple transforms, thus having strong expressiveness and good robustness for point clouds related tasks. The experiments on three typical tasks (i.e., semantic segmentation on S3DIS and ScanNet, part segmentation on ShapeNet and shape classification on ModelNet40) demonstrates the effectiveness of our method.

ADP-mediated platelet aggregation is signaled through G protein-coupled receptors P2Y1 and P2Y12 on the platelet. The clinical effectiveness of inhibiting P2Y12 has been well established, and preclinical studies indicated that the inhibition of P2Y1 could provide equivalent antithrombotic efficacy as P2Y12 antagonists and reduce bleeding risks. On the basis of the 2-phenyl-1H-imidazole scaffold of our previously reported xanthine oxidase inhibitor WSJ-557, we first achieved the transition from the xanthine oxidase inhibitors to dual-target antagonists against P2Y1 and P2Y12. We described the structure-activity relationships of the 2-phenyl-1H-imidazole compounds, which led to the identification of the most potent antiplatelet agents, 24w and 25w, both showing a rapid onset of action in pharmacokinetic study. Furthermore, the rat model suggested that 24w demonstrated a wider therapeutic window than ticagrelor, displaying equivalent and dose-dependent antithrombotic efficacy with lower blood loss compared to ticagrelor at same oral dose. These results supported that 24w and 25w could be promising drug candidates.

Background and Aims. Radix Rehmanniae and Corni Fructus (RC) have been widely applied to treat diabetic nephropathy (DN) for centuries. But the mechanism of how RC plays the therapeutic role against DN is unclear as yet. Methods. The information about RC was obtained from a public database. The active compounds of RC were screened by oral bioavailability (OB) and drug-likeness (DL). Gene ontology (GO) analysis was performed to realize the key targets of RC, and an active compound-potential target network was created. The therapeutic effects of RC active compounds and their key signal pathways were preliminarily probed via network pharmacology analysis and animal experiments. Results. In this study, 29 active compounds from RC and 64 key targets related to DN were collected using the network pharmacology method. The pathway enrichment analysis showed that RC regulated advanced glycosylation end product (AGE-) RAGE and IL-17 signaling pathways to treat DN. The animal experiments revealed that RC significantly improved metabolic parameters, inflammation renal structure, and function to protect the kidney against DN. Conclusions. The results revealed the relationship between multicomponents and multitargets of RC. The administratiom of RC might remit the DM-induced renal damage through the AGE-RAGE signaling pathway to improve metabolic parameters and protect renal structure and function.