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Antibiotics are widely used in the breeding production of Bamei pigs, affecting the quality and safety of pork and causing enormous harm to human health, the environment, and public health. The use of probiotic fermented feed to replace antibiotic feed is one of the solutions, which has the potential to improve the intestinal microbiota, promote animal growth, and enhance immunity. The purpose of this study was to evaluate the effect of fermented feed with Lactiplantibacillus (L.) plantarum QP28-1a or Bacillus (B.) subtilis QB8a on feed, growth performance, gut microbiota, and immunity of weaned piglets. A total of 60 freshly weaned piglets from the Tibetan Plateau were randomly divided into five groups and fed basal feed, L. plantarum fermented feed, B. subtilis fermented feed, mixed fermented feed, and antibiotic fermented feed for 60 days, respectively. The results showed fermented feed supplemented with L. plantarum QP28-1a or B. subtilis QB8a significantly lowered the pH of the feed (P < 0.05), produced lactic acid and acetic acid, inhibited the growth of harmful bacteria in the feed, and reduced the feed conversion rate in the group fed mixed fermented feed (P < 0.05). The fermented feed increased the α-diversity and prominently altered the β-diversity of the intestinal microbiota, increasing the relative abundance of beneficial bacteria such as Lactobacillus and Turicibacter and decreasing the relative abundance of conditional pathogens such as Streptococcus and Clostridium, improving the intestinal microbiota of the Bamei piglets. Notably, the mixed fermented feed improved the immunity of Bamei piglets by modulating the production of pro-inflammatory cytokines, anti-inflammatory cytokines, and inflammatory-related signaling pathways. Spearman’s correlation analysis revealed that the increased expression of immune-related cytokines may be associated with a significant enrichment of Lactobacillus, Prevotellaceae, Erysipelotrichaceae, and Ruminococcaceae in the gut. In conclusion, the probiotic fermented feed maintained an acidic environment conducive to suppressing pathogens, reduced the feed conversion ratio, optimized the intestinal microbiota, improved immunity, and alleviated intestinal inflammation that may be caused by weaning, demonstrating the excellent application prospects of L. plantarum QP28-1a and B. subtilis QB8a fermented feed in the feeding of Bamei piglets.

BackgroundChinese patent medicines are specialty preparations in China that are produced using traditional prescriptions processed by modern pharmaceutical technology. They contain complex ingredients and much attention is paid to their clinical safety. Demonstrating the clinical safety of Chinese patent medicines containing toxic ingredients in modern pharmacological studies has become one of the urgent issues to be solved for the safe use of clinical medicines.ObjectivesThe aim of this research is to evaluate the safety of Chinese patent medicines containing toxic ingredients by applying the risk-benefit assessment method. Additionally, a database of ‘toxic ingredients–toxic Chinese herbal medicines-adverse reactions’ will be established to explore the relationship between toxic ingredients and adverse reactions. This will lay the foundation for the rational clinical use of Chinese patent medicines containing toxic ingredients.Methods1) Establish a database of ‘toxic Chinese herbal medicines–toxic ingredients–toxic Chinese patent medicines’ to count the Chinese patent medicines containing toxic ingredients in the 2020 edition of Chinese Pharmacopoeia. 2) Filtered the clinical studies, extracted the drug-related ADEs, and analyzed the characteristics and correlations of these ADEs. 3) Finally, this section summarizes the causes of ADEs related to Chinese patent medicines containing toxic ingredients and extracts the main risk factors to provide a reference for further study.Outcomes1) There are four main types of Chinese patent medicines containing toxic ingredients. These include medicines with diester aconitine metabolites, mineral composition, Araceae metabolites, and hydrogen cyanide. 2) Digestive system, skin and its appendages, and allergic reactions were the main types of ADEs related to four types of Chinese patent medicines containing toxic ingredients. 3) There are four primary risk factors associated with the clinical use of Chinese patent medicines containing toxic ingredients: medicine, medication, individual and regulatory factors.

IntroductionSeveral studies indicated that depression is associated with liver injury. The role of probiotics in alleviating depression is focused on improving the abnormalities of the central nervous system through the gut-brain axis, while the effect on liver injury is still unclear. The aim of this study was to elucidate the potential link between the antidepressant effect of a potential probiotic strain Bifidobacterium pseudocatenulatum W112 and its effect on alleviating liver injury.MethodsThe 4-week-old Kunming mice were exposed to chronic stress for 4 weeks to establish a depression model.ResultsThe depression-like behavior and related biomakers in chronic unpredictable mild stress (CUMS) mice were altered by supplemented with W112 for 2 weeks. Meanwhile, the modulation effect of W112 the gut microbiota in CUMS mice also result in an increase in the abundance of beneficial bacteria and a decrease in the abundance of harmful bacteria. Significantly, liver injury was observed in CUMS model mice. W112 improved liver injury by reducing AST/ALT in serum. Quantitative PCR results indicated that the mechanism of action of W112 in ameliorating liver injury was that the altered gut microbiota affected hepatic phospholipid metabolism and bile acid metabolism.DiscussionIn short, W112 could significantly improve the depressive and liver injury symptoms caused by CUMS. The gut-liver-brain axis is a potential connecting pathway between the antidepressant effects of W112 and its alleviation of liver injury.

Neurological injury, as a major pathogenic mechanism in depression, holds significant importance in the research and development of antidepressant drugs. Hemerocallis citrina Baroni (H. citrina), referred to as “Forgetting Sadness Grass,” has been confirmed to possess remarkable neuroprotective effects. Studies have identified that the total phenolics in H. citrina Baroni leaves (HLTP) consist of flavonoids and phenolic acids and numerous studies have substantiated the neuroprotective effects of them. Based on this, we propose that HLTP may possess neuroprotective properties. To confirm this hypothesis, we initially employed network pharmacology techniques to predict potential targets for the neuroprotective effects of HLTP based on the Swiss Target Prediction database. GO and KEGG analyses were conducted to predict potential pathways, and a component-target-pathway network was constructed. Molecular docking experiments were then performed to analyze the binding abilities of the selected active components with the main targets. Furthermore, we validated the neuroprotective effects of HLTP and key targets selected through network pharmacology using a corticosterone-induced PC12 neuronal cell damage model. Network pharmacology research has identified that in the HLTP, Quercetin, Rutin, Apigenin, and Isoquercitrin are potential active components that may exert neuroprotective effects by modulating key targets such as AKT1, TNF, TP53, and CASP3 through crucial pathways including PI3K/AKT and apoptosis. Molecular docking revealed that 4-O-Caffeoylquinic acid, 5-O-Caffeoylshikimic acid, 4-p-Coumaroylquinic acid, and 5-O-Feruloylquinic acid exhibit low binding energies with key targets. Particularly, 4-O-Caffeoylquinic acid forms stable binding through hydrogen bonding with residues such as LYS389, GLU49, GLN47, LYS30, ASP44, and GLU40 in AKT1. PC12 cells were stimulated with 200 μmol/L Corticosterone (Cort) for 24 h, and then treated with 50, 100 and 200 μg/mL of HLTP for 24 h. The cell viability of damaged cells were significantly increased in a dose-dependent manner by 9.50%, 10.42% and 21.25%, respectively (P < 0.01). Western blot analysis confirmed that HLTP significantly (P < 0.01) increased the protein expression of PI3K and AKT by 15.24%, 30.44%, 41.03%, and 21.78%, 43.63%, 12.86%, respectively. In addition, through biochemical method, flow cytometry and WB analysis, we found that different concentrations of HLTP can all improve cell damage by reducing ROS, MDA, Ca2+, Cyt-C, Caspase-3, TNF-α and IL-1β, and increasing SOD, CAT, MMP, Bcl-2/Bax and IL-10. In particular, the HLTP at 200 μg/mL, compared with the Model group, decreased by 140.2%, 54.66%, 51.34%, 65.26%, 40.32%, 63.87%, and 55.38%, and increased by 39.65%, 35.45%, 38.38%, 28.54%, and 39.98%, respectively. Through the above experiments, we verified that HLTP may exert neuroprotective effects by mediating the PI3K/AKT signaling pathway to counteract oxidative stress damage, improve mitochondrial dysfunction, and alleviate inflammatory injury.

Mulberry has also been regarded as a valuable source of forage for ruminants. This study was developed to investigate the impact of four additives and combinations thereof on fermentation quality and bacterial communities associated with whole-plant mulberry silage. Control fresh material (FM) was left untreated, while other groups were treated with glucose (G, 20 g/kg FM), a mixture of Lactobacillus plantarum and L. buchneri (L, 106 CFU/g FM), formic acid (A, 5 mL/kg FM), salts including sodium benzoate and potassium sorbate (S, 1.5 g/kg FM), a combination of G and L (GL), a combination of G and A (GA), or a combination of G and S (GS), followed by ensiling for 90 days. Dry matter content in the A, S, GA, and GS groups was elevated relative to the other groups (p

Neuronopathy, distal hereditary motor, type VIII is an exceedingly rare autosomal dominant genetic disorder, also known as congenital non-progressive distal spinal muscular atrophy. It is characterized by progressive weakness in distal motor function and atrophy of muscles, without accompanying sensory impairment. Presently, there is limited literature on this condition, and accurate epidemiological data regarding its incidence remains unavailable. We report a paediatric case of distal hereditary motor, type VIII that is caused by a heterozygous missense mutation in the TRPV4 gene (NM_021625): c.805C>T. The proband is a 7-year-old male child. During pregnancy, his mother had prenatal ultrasound revealing “inward turning of the feet”, a condition persisting after birth. The proband is currently unable to stand independently, exhibiting bilateral clubfoot deformity. Although possessing normal cognitive function, he cannot walk unaided. Computed radiography findings reveal pelvic tilt, bilateral knee joint valgus, and bilateral clubfoot. The patient underwent familial exome sequencing, revealing a mutation in the TRPV4 gene (NM_021625): c.805C>T (p.Arg269Cys). Considering the patient’s medical history, clinical manifestations, imaging studies, and genetic test results, the diagnosis for this individual is Neuronopathy, distal hereditary motor, type VIII. This report documents a case involving the TRPV4 gene mutation associated with Neuronopathy, distal hereditary motor, type VIII, contributing valuable case reference for the early diagnosis of this condition.

Objective: To systematically review the efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD).Methods: We systematically searched six databases to identify randomized controlled trials (RCTs) about nonsteroidal MRAs for CKD, from inception to 22 August 2023. Two reviewers independently screened the retrieved articles, extracted data, and assessed the risk of bias of included RCTs using the Cochrane risk of bias tool. We then conducted meta-analysis of the data using Stata 17.0 software.Results: 11 RCTs (n = 15,817) were included in this meta-analysis. Compared with placebo, nonsteroidal MRAs significantly reduced the proportion of patients with ≥40% decline in estimated glomerular filtration rate (eGFR) from baseline [RR = 0.85, 95% CI (0.78, 0.92), p < 0.001], although the magnitude of eGFR reduction was greater [WMD = −2.83, 95% CI (−3.95, −1.72), p < 0.001]. The experimental group also had lower incidence of composite renal outcome [RR = 0.86, 95% CI (0.79, 0.93), p < 0.001] and greater reduction in urine albumin-to-creatinine ratio (UACR) from baseline [WMD = −0.41, 95% CI (−0.49, −0.32), p < 0.001], as well as reduced cardiovascular events [RR = 0.88, 95% CI (0.80, 0.95), p = 0.003]. MRAs did not increase any adverse events compared to placebo [RR = 1.00, 95% CI (0.99, 1.01), p = 0.909], but had higher incidence of hyperkalemia [RR = 2.05, 95% CI (1.85, 2.280), p < 0.001]. Compared with eplerenone, there was no significant difference in the proportion of patients with ≥40% decline in eGFR [RR = 0.57, 95% CI (0.18, 1.79), p = 0.335] or hyperkalemia [RR = 0.95, 95%CI (0.48, 1.88), p = 0.875].Conclusion: Nonsteroidal MRAs can reduce the incidence of end-stage renal disease and cardiovascular adverse events in patients. Although there was still a risk of hyperkalemia compared to placebo, there was no significant difference in any adverse events compared to either placebo or eplerenone. It has become a new option for drug treatment of CKD patients, but more clinical trials are still needed to verify its efficacy and safety. Especially further direct comparison of the nonsteroidal MRAs to eplerenone in view of the relatively small number of patients reviewed are needed.

Introduction: Shizao decoction (SZD) is a traditional Chinese medicine decoction that has therapeutic effects on cirrhotic ascites (CAS). Because of the unclear treatment mechanism, in the current study, the anti-CAS activity of SZD and molecular mechanisms were analyzed by network analysis combined with pharmacokinetics and metabolomics.Methods: Firstly, we assessed the anti-CAS efficacy of SZD by hematoxylin-eosin (H&E), liver function tests, NO and ET-1 levels, and portal venous pressure. Secondly, network analysis was applied to dig out the metabolites, targets, and pathways related to SZD and CAS. Then, the pharmacokinetics of the pharmacokinetically relevant metabolites (PRM) were analyzed. Thirdly, the serum and urine metabolic biomarkers of rats with CAS were identified using metabolomics by comparing them with the SZD treatment group. In addition, MetaboAnalyst was utilized to conduct metabolic pathway analysis. Finally, the correlation analysis established a dynamic connection between absorbed PRM from SZD and CAS-associated endogenous metabolites.Results: Pharmacodynamic analysis indicated that SZD effectively mitigated liver injury symptoms by ameliorating inflammatory cell infiltration in CAS rats. The network analysis results indicated that twelve RPM contribute to the therapeutic efficacy of SZD against CAS; the key signaling pathways involved might be hepatitis B and PI3K-Akt. Pharmacokinetics results showed that the 12 RPM were efficiently absorbed into rat plasma, ensuring desirable bioavailability. The metabolomic analysis yielded 21 and 23 significantly distinct metabolites from the serum and urine, respectively. The 12 bioavailable SZD-PRM, such as luteolin, apigenin, and rutin, may be associated with various CAS-altered metabolites related to tryptophan metabolism, alpha-linolenic acid metabolism, glycine metabolism, etc.Discussion: A novel paradigm was provided in this study to identify the potential mechanisms of pharmacological effects derived from a traditional Chinese medicine decoction.

ObjectiveExcessive obesity can lead to dysfunction in adipose tissue, which contributes to the development of comorbidities associated with obesity, such as type 2 diabetes (T2D), cardiovascular and cerebrovascular disease, among others. Previous research has mainly focused on the Vanin family in systemic inflammatory diseases or predicting its role in tumor prognosis, while neglecting its role as a secretory protein in adipose tissue inflammation and metabolism. The objective of this study was to compare the changes in Vanin-2 levels in the circulating blood of normal and obese individuals, and to assess its correlation with inflammatory factors in vivo. Furthermore, the study aimed to systematically evaluate its effectiveness in human weight loss surgery.MethodsSerum concentrations of Vanin-2 and inflammatory indicators were measured in 518 volunteers. Furthermore, the concentrations of Vanin-2 were measured both before and after weight loss through a dietetic program or laparoscopic sleeve gastrectomy (LSG). Additionally, we assessed the levels of insulin, adiponectin, and inflammation-related factors. The hormonal profile and changes in body weight were evaluated at baseline and 3 months after surgery.ResultsSerum levels of Vanin-2 were found to be significantly increased in individuals with overweight/obesity (OW/OB) group (controls 438.98 ± 72.44, OW/OB 530.89 ± 79.39 ug/L; p

IntroductionThe macromolecular polysaccharide Inonotus obliquus polysaccharide (IOP) is composed of various monosaccharides, and it could modulate the composition and diversity of intestinal flora. However, its impact on the intestinal flora in rats of different genders remains unclear. Therefore, this study aims to investigate the structural changes of IOP and its effects on the intestinal flora after administration in male and female rats.MethodsIn this study, the molecular weight and purity of IOP were analyzed by high-performance gel permeation chromatography (HPGPC) and phenol sulfuric acid method, and NMR was used to confirm the chemical structure of IOP. Sex hormone [testosterone (T) and estradiol (E2)] levels and intestinal microbial changes were detected by enzyme-linked immunosorbent assay (ELISA) and 16S rRNA, respectively, after gavage of IOP (100 mg/kg) in male and female Sprague Dawley (SD) rats.ResultsHPGPC analysis showed that the average molecular weight (Mw) of IOP was 4,828 Da, and the total sugar content of the purified IOP was 96.2%, indicating that the polysaccharide is of high purity. NMR revealed that IOP is a linear macromolecule with an α-D-type glucose backbone. The results of ELISA and 16S rRNA showed that the IOP increased the abundance of beneficial bacteria, such as Clostridia_UCG-014 and Prevotellaceae_NK3B31, and reduced that of harmful bacteria, such as Colidextribacter and Desulfobacterota in the intestine of both male and female rats, and IOP changed the levels of sex hormones in male and female rats. Further analyses revealed that the increase in alpha diversity was higher in male than female rats. α diversity and β diversity revealed a significant difference in the composition of cecal microbiota between male and female rats in the control group, but IOP intake reduced this difference. Meanwhile, α analysis revealed a change in the composition of bacterial flora was more stable in male than female rats.ConclusionsThis study enhances our comprehension of the IOP structure and elucidates the alterations in intestinal flora following IOP administration in rats of varying genders. Nonetheless, further investigation is warranted to explore the specific underlying reasons for these discrepancies.

With the development of new energy industries such as photovoltaics, microgrids, or distributed energy sources require many DC-AC grid-connected interfaces. Reducing the switching loss of the inverter is important to improve the transmission efficiency of the inverter, reduce the heat generation of the inverter, promote the high frequency and miniaturization of the inverter, and efficiently use the distributed energy. Therefore, considering the wide application of DC-AC power electronic interfaces in microgrid and distributed energy, and to make up for existing deficiencies in traditional hard-switching inverters, an optimal control strategy and topology for an optimal-auxiliary resonant commutated pole (O-ARCP) inverter is proposed in this article. Firstly, this paper introduces the proposed inverter topology and analyzes the operation mode of the circuit with the control strategy. Then simulation experiments in islanding mode are carried out to verify the rationality of the content, and finally simplified experimental verification is carried out based on the simulation results. Simulation and experimental testing reveal that all switches of the proposed topology are in soft-switching mode, which proves the effectiveness of the proposed control strategy and analysis. The analysis and validation of this paper provide assistance in the development of control strategies and structures for soft-switching inverters.

IntroductionExcess copper induces cell death by binding to lipoylated components of the tricarboxylic acid cycle. Although a few studies have examined the relationship between cuproptosis-related genes (CRGs) and breast cancer prognosis, reports on estrogen receptor-positive (ER+) breast cancer are lacking. Herein, we aimed to analyze the relationship between CRGs and outcomes in patients with ER+ early breast cancer (EBC).MethodsWe conducted a case-control study among patients with ER+ EBC presenting poor and favorable invasive disease-free survival (iDFS) at West China Hospital. Logistic regression analysis was performed to establish the association between CRG expression and iDFS. A cohort study was performed using pooled data from three publicly available microarray datasets in the Gene Expression Omnibus database. Subsequently, we constructed a CRG score model and a nomogram to predict relapse-free survival (RFS). Finally, the prediction performance of the two models was verified using training and validation sets.ResultsIn this case-control study, high expression of LIAS, LIPT1, and ATP7B and low CDKN2A expression were associated with favorable iDFS. In the cohort study, high expression of FDX1, LIAS, LIPT1, DLD, PDHB, and ATP7B and low CDKN2A expression were associated with favorable RFS. Using LASSO-Cox analysis, a CRG score was developed using the seven identified CRGs. Patients in the low CRG score group had a reduced risk of relapse in both training and validation sets. The nomogram included the CRG score, lymph node status, and age. The area under the receiver operating characteristic (ROC) curve (AUC) of the nomogram was significantly higher than the AUC of the CRG score at 7 years.ConclusionsThe CRG score, combined with other clinical features, could afford a practical long-term outcome predictor in patients with ER+ EBC.

ObjectiveWe admitted a female patient with infantile onset epilepsy ( C, p.K156N) in the patient. In comparison with wildtype, electrophysiology revealed that SCN2A-K156N variant in transfected cells demonstrated reduced sodium current density, delayed activation and accelerated inactivation process of Na+ channel, all of which suggested a loss-of-function (LOF) of Nav1.2 channel.ConclusionWe showed the importance of functional analysis for a SCN2A variant with unknown significance to determine pathogenicity, drug reactions, and genotype–phenotype correlations. For patients suffering from early infantile epilepsies, the use of oxcarbazepine in some SCN2A-related epilepsies requires vigilance to assess the possibility of epilepsy worsening.

Interconnecting microgrids with similar geographical environment and related characteristics electrically and communicatively, this constitutes a microgrid cluster, which is a higher-level distributed power structure and an effective way to improve the utilization rate of distributed energy and local absorption level. However, the stable operation of microgrid clusters is determined by the cluster structure and its control strategy, which is also the focus and difficulty of current research. To address this challenge, this paper proposes a ring-based multi-agent microgrid cluster energy management strategy, which realizes the centerless coordinated autonomous operation of microgrid clusters with high stability. In addition, based on the multi-agent control strategy, this paper designs a variety of control strategies that can be switched autonomously for different control objectives of the microgrid cluster to realize smooth grid connection and off-grid of the microgrid cluster. Finally, based on Matlab platform simulation, the experimental results show that the control structure and energy management strategy proposed in this paper can realize the centerless coordination and autonomy of the microgrid cluster on the basis of stable operation, minimize the energy interaction between the cluster and the distribution network, and greatly improve the utilization rate and local absorption level of distributed energy.

IntroductionThe ongoing 2019 coronavirus disease pandemic (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, is a global public health threat. Early diagnosis and identification of SARS-CoV-2 and its variants plays a critical role in COVID-19 prevention and control. Currently, the most widely used technique to detect SARS-CoV-2 is quantitative reverse transcription real-time quantitative PCR (RT-qPCR), which takes nearly 1 hour and should be performed by experienced personnel to ensure the accuracy of results. Therefore, the development of a nucleic acid detection kit with higher sensitivity, faster detection and greater accuracy is important.MethodsHere, we optimized the system components and reaction conditions of our previous detection approach by using RT-RAA and Cas12b.ResultsWe developed a Cas12b-assisted one-pot detection platform (CDetection.v2) that allows rapid detection of SARS-CoV-2 in 30 minutes. This platform was able to detect up to 5,000 copies/ml of SARS-CoV-2 without cross-reactivity with other viruses. Moreover, the sensitivity of this CRISPR system was comparable to that of RT-qPCR when tested on 120 clinical samples.DiscussionThe CDetection.v2 provides a novel one-pot detection approach based on the integration of RT-RAA and CRISPR/Cas12b for detecting SARS-CoV-2 and screening of large-scale clinical samples, offering a more efficient strategy for detecting various types of viruses.

ObjectiveWe explored the DNA methylation and messenger RNA (mRNA) co-expression network and hub genes in first-episode, drug-naive adolescents with major depressive disorder (MDD). To preliminarily explore whether adolescent MDD has unique mechanisms compared with adult MDD.MethodsWe compared DNA methylation and mRNA profiles of peripheral blood mononuclear cells from four first-episode and drug-naive adolescents with MDD and five healthy adolescent controls (HCs). We performed differential expression analysis, constructed co-expression network, and screened the hub genes. And enrichment analysis was performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We also downloaded DNA methylation and mRNA datasets of adults with MDD (GSE113725/GSE38206) from the GEO database, and performed differential expression and enrichment analysis.ResultsOur clinical data showed that 3034 methylation sites and 4190 mRNAs were differentially expressed in first-episode, drug-naive adolescents MDD patients compared with HCs. 19 hub genes were screened out according to the high degree value in the co-expression network. The results from the GEO database showed that compared with adult HCs, there were 290 methylation sites and 127 mRNAs were differentially expressed in adult MDD patients.ConclusionCompared with adolescent HCs and adult MDD patients, the DNA methylation and mRNA expression patterns of first-episode, drug-naive adolescent MDD patients were different. The co-expression network of DNA methylation and mRNA and the screened hub genes may play an important role in the pathogenesis of MDD in first-episode, drug-naive adolescents. Compared with adult MDD, adolescent MDD is more enriched in metabolism in terms of function and pathways.

14-3-3 proteins (regulatory protein family) are phosphate serine-binding proteins. A number of transcription factors and signaling proteins have been shown to bind to the 14-3-3 protein in plants, which plays a role in regulating their growth (seed dormancy, cell elongation and division, vegetative and reproduction growth and stress response (salt stress, drought stress, cold stress). Therefore, the 14-3-3 genes are crucial in controlling how plants respond to stress and develop. However, little is known about the function of 14-3-3 gene families in gramineae. In this study, 49 14-3-3 genes were identified from four gramineae, including maize, rice, sorghum and brachypodium, and their phylogeny, structure, collinearity and expression patterns of these genes were systematically analyzed. Genome synchronization analysis showed large-scale replication events of 14-3-3 genes in these gramineae plants. Moreover, gene expression revealed that the 14-3-3 genes respond to biotic and abiotic stresses differently in different tissues. Upon arbuscular mycorrhizal (AM) symbiosis, the expression level of 14-3-3 genes in maize significantly increased, suggesting the important role of 14-3-3 genes in maize-AM symbiosis. Our results provide a better understanding on the occurrence of 14-3-3 genes in Gramineae plants, and several important candidate genes were found for futher study on AMF symbiotic regulation in maize.

Bone implant-associated infection is one of the most challenging problems encountered by orthopedic surgeons. There is considerable interest in the development of drug-loaded antibacterial coatings for the surfaces of metal implants. However, it is difficult to achieve the stable local release of an effective drug dose for many antibacterial coatings. In the present study, analyses of the thickness and water contact angle of multiple layers confirmed the successful assembly of multilamellar membrane structures. Measurement of the zone of bacterial inhibition indicated gradual degradation of the (montmorillonite [MMT]/hyaluronic acid [HA])10 multilamellar film structure with concentration-dependent degradation during incubation with hyaluronidase solution and Staphylococcus aureus. In vivo results resembled the in vitro results. Overall, the findings confirm that the (MMT/HA-rifampicin)10 multilamellar film structure exhibits good antibacterial properties and excellent biocompatibility. Further studies of the clinical potential of the antibacterial coating prepared in this experiment are warranted.

ObjectiveGPHB5 has been found to be associated with glucose and lipid metabolism in animal studies. However, the association of GPHB5 with IR and metabolic disorders remains unknown, and there is a lack of research in humans. Our aim in this study was to investigate the relationship between circulating GPHB5 and metabolic disorders in humans.MethodsBioinformatics analysis was performed to understand the relationship between GPHB5 and metabolic disorders. GPHB5 mRNA expression in mice and rats was determined using RT-qPCR. Circulating GPHB5 concentrations were measured with an ELISA kit. EHC and OGTT were performed in humans.ResultsBioinformatics analysis shows that GPHB5 is associated with metabolic disorders and PCOS. GPHB5 mRNA expression levels in the metabolic-related tissues of HFD-fed mice, db/db and ob/ob mice, and PCOS rats were significantly higher than those of WT mice or rats. In human studies, we find that circulating GPHB5 levels were significantly higher in women with IR and PCOS. GPHB5 levels were positively correlated with age, BMI, WHR, BP, FBG, 2 h-BG, FIns, 2 h-Ins, TC, LDL-C, HbA1c, and FFA, but negatively correlated with adiponectin. Furthermore, GPHB5 was positively correlated with DHEAS and FAI, while negatively correlated with SHBG, FSH, SHBG and FSH. The increased GPHB5 concentration was related to IR and PCOS. After the treatment of metformin, GLP-1RA (Lira), and TZDs, circulating GPHB5 levels were decreased.ConclusionsOur results reveal that circulating GPHB5 could be a biomarker and potential therapeutic target for IR and PCOS in women.

Submesoscale motions are ubiquitous in the ocean, playing a significant role in energy transfer, mass transport, and biogeochemical processes. However, little attention has been drawn to the submesoscale dynamics in shallow coastal waters. In the present study, submesoscale motions in the Bohai Sea, a typical shallow sea with mean depth of about 18 m, are studied using a validated high-resolution (~ 500 m) model based on Regional Oceanic Modeling System (ROMS). The results show that submesoscale structures in the Bohai Sea are mainly located in the shallow coastal regions, the Bohai Strait, the areas around islands and headlands, and mostly tend to be parallel to the isobaths. The periodic variations of submesoscale motions are closely related to the tidal, spring-neap, and seasonal cycles in the Bohai Sea. The spring-neap variations of submesoscale motions are mainly attributed to the curl of vertical mixing, which is stronger during spring tides than neap tides. Compared with winter, the stronger background horizontal and vertical density variance in summer are conducive to frontogenesis, resulting in more active submesoscale motions. The results in this study are expected to contribute to enriching our knowledge about submesoscale dynamics in shallow coastal seas.

Whole-crop wheat silage (WCWS) is an excellent feed material for ruminants. However, microbial fermentation during silage production consumes valuable nutrients, decreasing the quality of silage. The main objective of this study was to assess how the addition of increasing amounts of Artemisia argyi (AA) affected fermentation quality, microbial composition, and mycotoxin production in whole-crop wheat at dough stage (WCWD) silage during ensiling to aerobic exposure compared with Lactiplantibacillus buchneri (LB). The addition of 20% AA, resulted in a lower pH and higher lactic acid content, was found in silage treated with 20% AA, and an obvious increase in the relative abundance of Lactobacillus was detected in silages treated with LB and 20% AA, respectively. Meanwhile, inoculation with 20% AA decreased the abundance of harmful microorganisms, including Acinetobacter, Enterobacter, and Aspergillus. It also reduced the contents of mycotoxins, Aflatoxin B1 (AFB1), and deoxynivalenol (DON) during ensiling and aerobic exposure. These results confirmed that WCWD treated with 20% AA could improve the fermentation quality and enhance the aerobic stability of silage.

Although numerous adverse effects of alcohol addiction on health, behavior, and brain function were widely reported, the neurobiological mechanism of alcohol dependence remains largely unknown. In this study, a total of twenty-nine patients with alcohol dependence and twenty-nine status-matched normal controls (NCs) were recruited. Percent amplitude of fluctuation (PerAF) was applied to identify alcohol-related brain activity deficits. We found that alcohol dependence was associated with widespread differences in the left orbitofrontal cortex, right higher visual cortex, right supramarginal gyrus, right postcentral gyrus, and bilateral cerebellum posterior lobe with decreased PerAF, but no brain areas with increased PerAF differences were found. ROC curve showed that decreased PerAF revealed extremely high discriminatory power with a high AUC value of 0.953, as well as a high degree of sensitivity (96.6%) and specificity (86.2%), in distinguishing patients with alcohol dependence from NCs. In the alcohol dependence group, the amount of daily alcohol consumption showed significant negative correlations with the right cerebellum posterior lobe and right higher visual cortex. These findings suggest that the cerebellar-visual-orbitofrontal circuit was disturbed by alcohol dependence. The proposed new method of PerAF may be served as a potential biomarker to identify the regional brain activity deficits of alcohol dependence.

Obesity is a leading worldwide health threat with ever-growing prevalence, it promotes the incidence of various diseases, particularly cardiovascular disease, metabolic syndrome, diabetes, hypertension, and certain cancers. Traditional Chinese Medicine (TCM) has been used to control body weight and treat obesity for thousands of years, Chinese medicinal herbs provide a rich natural source of effective agents against obesity. However, some problems such as complex active ingredients, poor quality control, and unclear therapeutic mechanisms still need to be investigated and resolved. Prodrugs provide a path forward to overcome TCM deficiencies such as absorption, distribution, metabolism, excretion (ADME) properties, and toxicity. This article aimed to review the possible prodrugs from various medicinal plants that demonstrate beneficial effects on obesity and seek to offer insights on prodrug design as well as a solution to the global obesity issues.

BackgroundAllelochemicals secreted by allelopathic rice roots are transmitted to the receptor rhizosphere through the soil medium to inhibit the growth of the surrounding weeds. This research aimed to explore the relationships between the spatial-temporal distribution of rice roots in soil and weed-suppression ability at its seedling stage.ResultsThis study first examined the root distribution of three rice cultivars in paddy soil in both vertical and horizontal directions at 3–6 leaf stage. Then, an experiment using rice–barnyardgrass mixed culture was conducted to analyze the allelopathic potential and allelochemical content secreted by rice roots in different lateral soil layers. The results showed that allelopathic rice had a smaller root diameter and larger root length density, root surface area density, and root dry weight density than those of non-allelopathic rice, in the top 5 cm at 5- and 6-leaf stages. In particular, there were significant differences in root distribution at the horizontal distance of 6–12 cm. Besides, allelopathic rice significantly inhibited the above-ground growth of barnyardgrass co-cultured at 12 cm lateral distance in situ, and the content of benzoic acid derivatives in allelopathic rice in a 6–12 cm soil circle was higher than that observed at 0–6 cm distance. Moreover, correlation analysis confirmed that the distribution of roots in the horizontal distance was significantly correlated with weed inhibition effect and allelochemical content.ConclusionThese results implied that spatial distribution of allelopathic rice roots in paddy soil, particularly at the lateral distance, appears to have important impact on its weed-suppressive activity at the seedling stage, suggesting that modifying root distribution in soil may be a novel method to strengthen the ability of rice seedlings to resist paddy weeds.

Northeast China is a major soybean production region in China. A representative sample of the Northeast China soybean germplasm population (NECSGP) composed of 361 accessions was evaluated for their seed protein content (SPC) in Tieling, Northeast China. This SPC varied greatly, with a mean SPC of 40.77%, ranging from 36.60 to 46.07%, but it was lower than that of the Chinese soybean landrace population (43.10%, ranging from 37.51 to 50.46%). The SPC increased slightly from 40.32–40.97% in the old maturity groups (MG, MGIII + II + I) to 40.93–41.58% in the new MGs (MG0 + 00 + 000). The restricted two-stage multi-locus genome-wide association study (RTM-GWAS) with 15,501 SNP linkage-disequilibrium block (SNPLDB) markers identified 73 SPC quantitative trait loci (QTLs) with 273 alleles, explaining 71.70% of the phenotypic variation, wherein 28 QTLs were new ones. The evolutionary changes of QTL-allele structures from old MGs to new MGs were analyzed, and 97.79% of the alleles in new MGs were inherited from the old MGs and 2.21% were new. The small amount of new positive allele emergence and possible recombination between alleles might explain the slight SPC increase in the new MGs. The prediction of recombination potentials in the SPC of all the possible crosses indicated that the mean of SPC overall crosses was 43.29% (+2.52%) and the maximum was 50.00% (+9.23%) in the SPC, and the maximum transgressive potential was 3.93%, suggesting that SPC breeding potentials do exist in the NECSGP. A total of 120 candidate genes were annotated and functionally classified into 13 categories, indicating that SPC is a complex trait conferred by a gene network.

Background: Qingfei Paidu decoction (QFPDD) has been widely used in treating coronavirus disease 2019 (COVID-19) in China. However, studies on the treatment effect of COVID-19 patients and other respiratory diseases have not been well demonstrated. Our study aims to determine the treatment effect of QFPDD in combination with conventional treatment on COVID-19 patients and other respiratory diseases.Methods: This retrospective study recruited COVID-19 patients who were treated with QFPDD for at least two courses (6 days) from seven hospitals in five provinces from January 21 to March 18 2020. Demographic, epidemiological, clinical, laboratory, computed tomography characteristics, treatment, and outcome data were collected and analyzed. The improvements in clinical symptoms before and after QFPDD treatment were compared.Results: Eight COVID-19 patients were included in this study. Of them, six were males (75.0%). The median age of the patients was 66 (60–82) years. Four patients were classified as mild and moderate cases (50.0%); there were two severe cases (25.0%) and critical cases (25.0%). The most common symptom was cough (7 [87.5%]), followed by fever (6 [75.0%]), fatigue (4 [50.0%]), asthma (4 [50.0%]), and anorexia (3 [37.5%]). Abnormal findings included decrease in neutrophils (3 [37.5%]), lymphocytes (2 [25.0%]), alkaline phosphatase (3 [37.5%]), lactic dehydrogenase (4 [50.0%]), erythrocyte sedimentation rate (2 [25.0%]), and C-reactive protein (5 [83.3%]) at admission. After one course (3 days) of QFPDD, nasal obstruction and sore throat completely disappeared, and fever (5 [83.3%]), fatigue (2 [50.0%]), and cough (2 [28.6%]) were improved. After two courses (6 days), the fever disappeared completely in all patients, and the other symptoms showed a tendency to improve. In non-severe patients, 87.5% baseline symptoms completely disappeared. In severe patients, 61.1% of the baseline symptoms completely disappeared after patients were administered QFPDD for two courses. Of the abnormal indicators, 55.6% returned to normal levels. The median duration to complete fever recovery was 1.0 day. The median durations of viral shedding and hospitalization were 10.5 and 21.5 days, respectively. None of the patients worsened and died, and no serious adverse events occurred related to QFPDD during hospitalization.Conclusion: QFPDD combined with conventional treatment improved clinical symptoms in COVID-19 patients with other respiratory diseases, and no serious adverse reactions associated with QFPDD were observed. Larger sample studies confirm our findings in the future.

A centrifugal pump is an important solid–liquid mixture conveying machinery, which is widely used in mineral mining, water conservancy engineering, and other fields. Solid particles will wear the impeller of the centrifugal pump in the process of transportation, resulting in lower service life of the impeller, especially in the transportation of a high concentration of solid particles. Many scholars use numerical simulation to study the wear of centrifugal pumps, but few efforts have been made in the wear experiment. In this study, the effect of three factors, namely, diameter of solid particles, mass concentration of particles, and material of impellers on the wear of a solid–liquid two-phase centrifugal pump was studied by the wear experiment. The solid particles are SiO2 with irregular shapes, and the diameter ranges are 0.125–0.212 mm, 0.212–0.425 mm, and 0.425–0.710 mm. The mass concentration of solid particles is 15%, 20%, and 30%. The material of impellers is carbon structural steel (Q235), gray cast iron (HT200), and low-alloy high-strength steel (16 Mn). The amount of wear is determined by measuring the thickness of the impeller material before and after wear experiments. The wear morphology of the impeller was observed by using a digital microscope. The results showed that the wear mainly concentrated on the middle and trailing edges of the blade. Impellers of different materials suffer different wear forms, among which the impeller made of HT200 has the best erosion resistance. The increase of solid mass concentration will aggravate the wear of the impeller. The change of particle diameters also has a great influence on impeller wear.

ObjectivesThis study aims to explore the benefits and harms of Chinese Herbal Medicine (CHM) for mild cognitive impairment (MCI).MethodsElectronic searching was conducted in two English and four Chinese databases till 2021 December. Randomized clinical trials on CHM compared to no intervention, placebo or other therapies for MCI were included.ResultsForty-nine RCTs (48 finished trials and 1 protocol) were identified. The overall methodological quality of included trials was relatively low. This review found that compared to no intervention or placebo, CHM can significantly decrease the number of patients who progressed to dementia (RR 0.36, 95% CI 0.22–0.58) and increase the cognitive function assessed by MMSE (MD 1.96, 95% CI 1.41–2.50) and MoCA (MD 2.44, 95% CI 1.57–3.31). The subgroup analysis of different CHM showed that Ginko leaf tablets can significantly improve the cognitive function compared to no intervention or placebo when assessed by MMSE (MD 2.03, 95% CI 1.18–2.88) and MoCA (MD 3.11, 95% CI 1.90–4.33). Compared to western medicine, CHM can significantly increase the score of MMSE (MD 0.88 95% CI 0.46–1.30) and MoCA (MD 0.87, 95% CI 0.33–1.41), but there was no significant difference on the score of ADL (SMD −0.61, 95% CI −1.49 to 0.27). None of the RCTs reported on the quality of life. Of 22 RCTs that reported adverse events, there was no statistical difference between the CHM and the control group.ConclusionsCHM, Ginko leaf extracts in particular, could help to prevent progression into dementia and to improve cognitive function and ability of daily living activities. More qualified RCTs were needed to confirm the conclusion due to the low quality of current trials.Systematic Review RegistrationUnique Identifier: CRD42020157148.

ObjectTo investigate the distribution characteristics of gut microbiota in children with tic disorder (TD) and the possible role of these characteristics in the pathogenesis of TD.MethodsThe medical records of 28 children with TD treated at Wuxi Children's Hospital from January 1 to October 31, 2020, and 21 age-matched healthy children (controls) were included. The relative quantification of bacterial taxa was performed using 16S ribosomal RNA gene amplicon sequencing.ResultsThere was no significant difference in the alpha diversity of gut microbiota between the TD and control groups. Analyses of beta diversity were able to differentiate the TD patients from the healthy controls based on their gut microbiota. At the phylum level, the two groups were mainly composed of four phyla, Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria. There were significant differences in Firmicutes and Actinobacteria between the two groups (P

Temperature changes have a great impact on fish feeding, intestinal microorganisms, metabolism, and immune function. Therefore, it is necessary to develop effective methods to enhance the survival rates and growth of fish under water temperature changes. Lactic acid bacteria (LAB) are promising immunostimulatory feed additive, as demonstrated by their beneficial effects in several fish species. This study investigated the short-term effects of dietary LAB on intestinal microbiota composition and immune responses of crucian carp (Carassius auratus) when water temperature decreased from 30 ± 1°C to 18 ± 1°C. Lactococcus (L.) lactis 1,209 and L. lactis 1,242 with potential probiotics isolated from the intestine of Qinghai naked carp (Gymnocypris przewalskii) were selected as feed additives for the crucian carp feeding experiment. A total of 225 commercially available healthy crucian carp (250 ± 10 g) of similar age were kept in 30°C water for a week and then immediately transferred to 18 ± 1°C water, assigned to three dietary treatments for a 16-day feeding trial randomly: (1) HC, diets without additives (the control group); (2) HT, diets with 106 CFU/ml L. lactis 1,209; and (3) HL, with 106 CFU/ml L. lactis 1,242. Each group was set up with 3 replicates and each with 25 fish. The results showed that the mortality rate of crucian carp in HC, HT, and HL group was 50, 27, and 33%, respectively. High-throughput sequencing results displayed that the composition of the intestinal microorganism varied dynamically in response to different treatments and water temperature decrease. Among them, compared with the HC group, a higher abundance of Firmicutes and Proteobacteria, and a lower of Actinobacteria appeared in HT and HL. The cytokines heat shock protein 70 (HSP-70) in crucian carp intestinal tract significantly decreased when water temperature decreased (p < 0.05).

PurposeOlder adults aged 60 years and above are classified as being of high-risk for infection during the COVID-19 pandemic. This study aimed to investigate the associations of psychological factors (motivational factors: risk perception, health knowledge, attitude, subjective norm, motivational self-efficacy, and intention; volitional factors: volitional self-efficacy, planning, and action control) of preventive behaviors with three preventive behaviors (hand washing, facemask wearing, and social distancing) among Chinese older adults during the COVID-19 pandemic.MethodsA cross-sectional questionnaire survey was administered via SOJUMP, a widely used online survey platform in China. A total of 928 older adults (mean = 67.24 years, age range: 60–90 years, SD = 6.43, 55.9% females) were recruited using a snowball sampling approach from Hubei Province (n = 667) and outside Hubei Province (n = 261) in China during May 18, 2020 to June 7, 2020. Multiple hierarchical regressions were conducted with four models to examine the association between demographic, past behavior, psychological factors and each preventive behavior.Principal FindingsAll three preventive behaviors in older adults increased dramatically during the pandemic of COVID-19. Gender, living status, educational level, past behavior, health knowledge, intention and planning significantly predicted hand washing behavior, R2 = 0.395, F(10, 927) = 54.372, p

CuSbS2, as a direct bandgap semiconductor, is a promising candidate for fabricating flexible thin-film solar cells due to its low grain growth temperature (300°C–450°C). Uniform and highly crystalline CuSbS2 thin films are crucial to improving device performance. However, uniform CuSbS2 is difficult to obtain during electrodeposition and post-sulfurization due to the “dendritic” deposition of Cu on Mo substrates. In this study, Sb/Cu layers were sequentially pulse electrodeposited on Mo substrates. By adjusting the pulse parameters, smooth and uniform Sb layers were prepared on Mo, and a flat Cu layer was obtained on Sb without any dendritic clusters. A two-step annealing process was employed to fabricate CuSbS2 thin films. The effects of temperature on phases and morphologies were investigated. CuSbS2 thin films with good crystallinity were obtained at 360°C. As the annealing temperature increased, the crystallinity of the films decreased. The CuSbS2 phase transformed into a Cu3SbS4 phase with the temperature increase to 400°C. Finally, a 0.90% efficient solar cell was obtained using the CuSbS2 thin films annealed at 360°C.

The aim of this study was to investigate effects of wilting and Lactobacillus plantarum inoculation on the dynamics of the fermentation products, residual non-structural carbohydrates, and bacterial communities in alfalfa silage. Fresh and wilted alfalfa were ensiled with and without L. plantarum for 10, 30, 60, and 90 days. A high-throughput sequencing method for absolute quantification of 16S rRNA was adopted to determine the bacterial community composition at different ensiling periods. For the wilted silage, the bacterial community, pH value, and ammonia nitrogen concentration remained stable in the silage at 30 days. L. plantarum inoculation accelerated lactic acid fermentation and altered the predominant genus in the wilted silage as compared with the non-inoculated group. For the non-wilted group, fast consumption of water-soluble carbohydrates (WSCs) was observed at 10 days in the non-inoculated silage along with rapid growth of undesirable Hafnia. L. plantarum inoculation inhibited growth of Hafnia at 10 days in the non-wilted silage. Clostridia fermentation occurred in the non-wilted silage at 90 days, as indicated by an increased pH, formation of butyric acid (BA), and apparent abundance of genera belonging to Clostridia. L. plantarum inoculation inhibited BA accumulation and growth of Garciella in the non-wilted silage at 90 days as compared with the non-wilted silage without inoculation, but had little effect on the growth of Clostridium sensu stricto. Overall, the high moisture content of the non-wilted alfalfa silage led to rapid consumption of WSCs and growth of harmful microorganisms at the early stage of ensiling, resulting in poor fermentation quality. Wilting and L. plantarum inoculation both improved fermentation quality and inhibited the growth of spoilage microorganisms in alfalfa silage, while L. plantarum inoculation alone failed to achieve optimum fermentation quality of non-wilted alfalfa silage.

BackgroundThe T cell receptor (TCR) diversity is essential for effective T cell immunity. Previous studies showed that TCR diversity in Wiskott–Aldrich Syndrome (WAS) patients was severely impaired, especially in the memory T cell populations. Whether this defect was caused by intrinsic WASp deficiency or extrinsic reasons is still unclear.MethodsWe sorted different T cell subsets from the bone marrow chimeric mice model using both magnetic beads and flow cytometry. TCR repertoires of memory T cells, especially CD4+ effector memory T (TEM) cells and CD8+ central memory T (TCM) cells, were analyzed using the UMI quantitative high-throughput sequencing (HTS).ResultsAn average of 5.51 million sequencing reads of 32 samples was obtained from the Illumina sequencing platform. Bioinformatic analyses showed that compared with wild type (WT), WAS knock out (KO)-CD4+ TEM cells exhibited increased Simpson index and decreased D50 index (P

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a major global public health burden and lacks effective risk stratification. We aimed to assess a multi-biomarker model in improving risk prediction in HFpEF.Methods: We analyzed 18 biomarkers from the main pathophysiological domains of HF in 380 patients hospitalized for HFpEF from a prospective cohort. The association between these biomarkers and 2-year risk of all-cause death was assessed by Cox proportional hazards model. Support vector machine (SVM), a supervised machine learning method, was used to develop a prediction model of 2-year all-cause and cardiovascular death using a combination of 18 biomarkers and clinical indicators. The improvement of this model was evaluated by c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: The median age of patients was 71-years, and 50.5% were female. Multiple biomarkers independently predicted the 2-year risk of death in Cox regression model, including N-terminal pro B-type brain-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), tumor necrosis factor-α (TNFα), endoglin, and 3 biomarkers of extracellular matrix turnover [tissue inhibitor of metalloproteinases (TIMP)-1, matrix metalloproteinase (MMP)-2, and MMP-9) (FDR < 0.05). The SVM model effectively predicted the 2-year risk of all-cause death in patients with acute HFpEF in training set (AUC 0.834, 95% CI: 0.771–0.895) and validation set (AUC 0.798, 95% CI: 0.719–0.877). The NRI and IDI indicated that the SVM model significantly improved patient classification compared to the reference model in both sets (p < 0.05).Conclusions: Multiple circulating biomarkers coupled with an appropriate machine-learning method could effectively predict the risk of long-term mortality in patients with acute HFpEF. It is a promising strategy for improving risk stratification in HFpEF.

Lactic acid bacteria are a kind of microorganisms that can ferment carbohydrates to produce lactic acid, and are currently widely used in the fermented food industry. In recent years, with the excellent role of lactic acid bacteria in the food industry and probiotic functions, their microbial metabolic characteristics have also attracted more attention. Lactic acid bacteria can decompose macromolecular substances in food, including degradation of indigestible polysaccharides and transformation of undesirable flavor substances. Meanwhile, they can also produce a variety of products including short-chain fatty acids, amines, bacteriocins, vitamins and exopolysaccharides during metabolism. Based on the above-mentioned metabolic characteristics, lactic acid bacteria have shown a variety of expanded applications in the food industry. On the one hand, they are used to improve the flavor of fermented foods, increase the nutrition of foods, reduce harmful substances, increase shelf life, and so on. On the other hand, they can be used as probiotics to promote health in the body. This article reviews and prospects the important metabolites in the expanded application of lactic acid bacteria from the perspective of bioengineering and biotechnology.

Relative quantification 16S-seq (RQS) has drawn deeper insights into bacterial community compositions in silage. However, it provides no information on dynamics of the total amount of bacterial DNA through the ensiling process and across different treatments. In this study, bacterial compositions in alfalfa silage with and without Lactobacillus plantarum inoculation after 10 and 60days of ensiling were investigated using absolute quantification 16S-seq (AQS), and bacterial composition and its interaction with fermentation properties of silage indicated by AQS and RQS were compared. Variation in total bacterial DNA amounts across different treatments and ensiling periods was illustrated by AQS. AQS indicated higher bacterial richness indices and closer correlations of these indices with fermentation properties than RQS via spearman’s correlation analyses, as well as more taxa with significance on bacterial abundance via lefse analyses. In conclusion, AQS effectively illustrated the dynamics of bacterial communities during the ensiling process.

Objective: This research aims to analyze the application regularity of Chinese patent medicine during the COVID-19 epidemic by collecting the names of the top three Chinese patent medicines used by 24 hospitals in 14 provinces of China in four time periods (January 20–22, February 16–18, March 01–03, April 01–03, 2020), and explore its contribution to combating the disease.Methods: 1) We built a database of the top three Chinese patent medicines used by 24 hospitals. 2) The frequency and efficacy distribution of Chinese patent medicine were analyzed with risk areas, regions, and hospitals of different properties as three factors. 3) Finally, we analyzed the differences in the use of heat-clearing and non-heat-clearing medicines among the three factors (χ2 test) and the correlation between the Chinese patent medicine and COVID-19 epidemic (correlation analysis) with SPSS 23.0 statistical software.Results: 1) The heat-clearing medicine was the main use category nationwide during January 20–22, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas (p < 0.01). 2) The variety of Chinese patent medicine was increased nationwide during February 16–18, 2020, mainly including tonics, blood-activating and resolving-stasis, and heat-clearing medicines. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in the southern and northern regions (p < 0.05). 3) Tonics, and blood-activating and resolving-stasis medicines became the primary use categories nationwide during March 01–03, 2020. 4) The tonics class, and blood-activating and resolving-stasis medicine were still the primary categories nationwide during April 01–03, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas (p < 0.01).Conclusion: Chinese patent medicine has a certain degree of participation in fighting against the COVID-19. The efficacy distribution is related to the risk area, region, and hospital of different properties, among which the risk area is the main influencing factor. It is hoped that future research can further collect the application amount of Chinese patent medicine used in hospitals all over the country, so as to perfectly reflect the relationship between Chinese patent medicine and the epidemic situation.

BackgroundS100A8 plays a key role in many cellular processes and is highly expressed in various solid cancers. However, the prognostic role of S100A8 has not been well defined. Therefore, we conducted a quantitative meta-analysis to investigate whether or not S100A8 could be used as a prognostic biomarker in solid tumors.MethodsPubMed, Web of Science, Embase, and Cochrane library were searched to acquire relevant studies that evaluated the association between expression of S100A8 and prognosis of cancer patients. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were extracted to evaluate the association between S100A8 overexpression and Overall Survival (OS), Disease-Free Survival (DFS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS). The expression of S100A8 was also validated by Flow cytometry, immunohistochemistry (IHC), and western blot.ResultsA total of 2,817 patients from 13 independent studies, ranging from 43 to 1,117 patients in size, were statistically analyzed. Our results indicated that a high level of S100A8 expression was significantly associated with poor OS, poor DFS, and poor PFS/RFS. In term of clinical pathological characteristics, a high expression level of S100A8 was significantly associated with differentiation grades, lymphatic metastasis, ER statue, and PR statue. The validation studies showed that the expression of S100A8 was at high levels in MDA-MB-231 (79.7%), MDA-MB-453 (89.2%), HTB-9 (70.2%), and T24 (53.3%) cells and it was higher in breast cancer tissue and bladder cancer tissue than their corresponding para-carcinoma tissue.ConclusionsS100A8 overexpression was significantly associated with poor clinical prognosis in cancer patients. S100A8 is potential a prognostic biomarker in breast cancer and bladder cancer. More well-designed studies with adequate prognostic data are needed to confirm the prognostic role of S100A8 revealed in this study.

The objective of this study was to investigate the mechanism of Lactobacillus plantarum (L. plantarum) involved in improving fermentation quality of naturally ensiled alfalfa under poor conditions. High-moisture wilted alfalfa was ensiled without inoculants (CK) or with inoculation of two L. plantarum additives (LPI and LPII). The pH and fermentation products of silage were determined after 30 and 90 days of ensiling. Additionally, the bacterial community compositions were analyzed. The L. plantarum inoculants significantly promoted lactic acid accumulation, and Lactobacillus abundance for both periods. At 90 days, silage in CK exhibited a high pH, a loss in dry matter, and a high concentration of ammoniacal nitrogen. The inoculations of L. plantarum significantly inhibited the growth of Clostridia, and reduced ammoniacal nitrogen concentration in silage (P < 0.05). Thus, inoculation with L. plantarum improved the fermentation quality of alfalfa silage and inhibited the growth of spoilage microorganisms, and further delayed spoilage of alfalfa silage under adverse ensiling conditions.

Intramuscular fat (IMF) content plays an essential role in meat quality. For identifying potential candidate genes and pathways regulating IMF content, the IMF content and the longissimus dorsi transcriptomes of 28 purebred Duroc pigs were measured. As a result, the transcriptome analysis of four high- and four low-IMF individuals revealed a total of 309 differentially expressed genes (DEGs) using edgeR and DESeq2 (p < 0.05, |log2(fold change)| ≥ 1). Functional enrichment analysis of the DEGs revealed 19 hub genes significantly enriched in the Gene Ontology (GO) terms and pathways (q < 0.05) related to lipid metabolism and fat cell differentiation. The weighted gene coexpression network analysis (WGCNA) of the 28 pigs identified the most relevant module with 43 hub genes. The combined results of DEGs, WGCNA, and protein–protein interactions revealed ADIPOQ, PPARG, LIPE, CIDEC, PLIN1, CIDEA, and FABP4 to be potential candidate genes affecting IMF. Furthermore, the regulation of lipolysis in adipocytes and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were significantly enriched for both the DEGs and genes in the most relevant module. Some DEGs and pathways detected in our study play essential roles and are potential candidate genes and pathways that affect IMF content in pigs. This study provides crucial information for understanding the molecular mechanism of IMF content and would be helpful in improving pork quality.

Dl-3-n-butylphthalide (dl-NBP) was approved by the FDA of China for the treatment of acute ischemic stroke. Dl-NBP has been shown to promote neurological functional recovery and enhance white matter integrity using an endothelin-1-induced focal permanent cerebral ischemia model, which could mimic those patients who have no opportunity to receive either tissue plasminogen activator (tPA) thrombolysis or endovascular therapy. However, it is not clear whether dl-NBP could promote neurological functional recovery in a focal transient cerebral ischemia model, which could mimic those patients who have the opportunity to receive either tPA thrombolysis or endovascular therapy. In this study, using a model of middle cerebral artery occlusion in mice, we aim to explore the effect of two-week dl-NBP treatment on neurological functional recovery after ischemic stroke as well as its underlying mechanism. Our results showed that dl-NBP treatment promoted functional recovery assessed by neurological scores and an adhesive remove test, and this improved the integrity of white matter after 60-min ischemia and 14-day reperfusion. In addition, dl-NBP increased the number of RECA-1 positive vessels and enhanced the expression of the tight junction protein occludin. More importantly, dl-NBP also promoted the expression of hypoxia-induced factor-1α, the vascular endothelial growth factor, Notch, and delta-like ligand 4. In conclusion, our study provides evidence that dl-NBP treatment could also promote functional recovery after focal transient ischemia stroke, and this recovery is associated with upregulated white matter integrity, microvessels, and the tight junction protein occludin. Our results suggested that, in future, dl-NBP may also be applied in clinic to promote functional recovery during the later phase of focal transient ischemic stroke.

Purpose: We investigated the effects of Traditional Chinese Medicine (TCM) on the occurrence and progression of albuminuria in patients with type 2 diabetes.Methods: In this randomized, double-blind, multicenter, controlled trial, we enrolled 600 type 2 diabetes without diabetic nephropathy (DN) or with early-stage DN. Patients were randomly assigned (1:1) to receive Liuwei Dihuang Pills (LWDH) (1.5 g daily) and Ginkgo biloba Tablets (24 mg daily) orally or matching placebos for 24 months. The primary endpoint was the change in urinary albumin/creatinine ratio (UACR) from baseline to 24 months.Results: There were 431 patients having UACR data at baseline and 24 months following-up in both groups. Changes of UACR from baseline to follow-up were not affected in both groups: −1.61(−10.24, 7.17) mg/g in the TCM group and −0.73(−7.47, 6.75) mg/g in the control group. For patients with UACR ≥30 mg/g at baseline, LWDH and Ginkgo biloba significantly reduced the UACR value at 24 months [46.21(34.96, 58.96) vs. 20.78(9.62, 38.85), P < 0.05]. Moreover, the change of UACR from baseline to follow-up in the TCM group was significant higher than that in the control group [−25.50(−42.30, −9.56] vs. −20.61(−36.79, 4.31), P < 0.05].Conclusion: LWDH and Ginkgo biloba may attenuate deterioration of albuminuria in type 2 diabetes patients. These results suggest that TCM is a promising option of renoprotective agents for early stage of DN.Trial registration: The study was registered in the Chinese Clinical Trial Registry. (no. ChiCTR-TRC-07000037, chictr.org)

Plant organ shape is determined by the spatial-temporal expression of genes that control the direction and rate of cell division and expansion, as well as the mechanical constraints provided by the rigid cell walls and surrounding cells. Despite the importance of organ morphology during the plant life cycle, the interplay of patterning genes with these mechanical constraints and the cytoskeleton is poorly understood. Shapes of harvestable plant organs such as fruits, leaves, seeds and tubers vary dramatically among, and within crop plants. Years of selection have led to the accumulation of mutations in genes regulating organ shapes, allowing us to identify new genetic and molecular components controlling morphology as well as the interactions among the proteins. Using tomato as a model, we discuss the interaction of Ovate Family Proteins (OFPs) with a subset of TONNEAU1-recruiting motif family of proteins (TRMs) as a part of the protein network that appears to be required for interactions with the microtubules leading to coordinated multicellular growth in plants. In addition, SUN and other members of the IQD family also exert their effects on organ shape by interacting with microtubules. In this review, we aim to illuminate the probable mechanistic aspects of organ growth mediated by OFP-TRM and SUN/IQD via their interactions with the cytoskeleton.

Increase of blood brain barrier (BBB) permeability after acute ischemia stroke is a predictor to intracerebral hemorrhage transformation (HT) for tissue plasminogen activator (tPA) thrombolysis and post-endovascular treatment. Previous studies showed that 2-h ischemia induced damage of BBB integrity and matrix metalloproteinase-2 (MMP-2) made major contribution to this disruption. A recent study showed that blocking β2-adrenergic receptor (β2-AR) alleviated ischemia-induced BBB injury by reducing hypoxia-inducible factor-1 alpha (HIF-1α) level. In this study, we sought to investigate the interaction of HIF-1α with MMP-2 and vascular endothelial growth factor (VEGF) in BBB injury after acute ischemia stroke. Rat suture middle cerebral artery occlusion (MCAO) model was used to mimic ischemia condition. Our results showed that ischemia produced BBB damage and MMP-2/9 upregulation was colocalized with Rhodamine-dextran leakage. Pretreatment with YC-1, a HIF-1α inhibitor, alleviated 2-h ischemia-induced BBB injury significantly accompanied by decrease of MMP-2 upregulation. In addition, YC-1 also prevented VEGF-induced BBB damage. Of note, VEGF was shown to be colocalized with neurons but not astrocytes. Taken together, BBB damage was reduced by inhibition of interaction of HIF-1α with MMP-2 and VEGF during acute cerebral ischemia. These findings provide mechanisms underlying BBB damage after acute ischemia stroke and may help reduce thrombolysis- and post-endovascular treatment-related cerebral hemorrhage.

Soybean (Glycine max L.) is a major legume crop that is mainly distributed in temperate regions. The adaptability of soybean to grow at relatively high latitudes is attributed to natural variations in major genes and quantitative trait loci (QTLs) that control flowering time and maturity. Identification of new QTLs and map-based cloning of candidate genes are the fundamental approaches in elucidating the mechanism underlying soybean flowering and adaptation. To identify novel QTLs/genes, we developed two F8:10 recombinant inbred lines (RILs) and evaluated the traits of time to flowering (R1), maturity (R8), and reproductive period (RP) in the field. To rapidly and efficiently identify QTLs that control these traits, next-generation sequencing (NGS)-based QTL analysis was performed. This study demonstrates that only one major QTL on chromosome 4 simultaneously controls R1, R8, and RP traits in the Dongnong 50 × Williams 82 (DW) RIL population. Furthermore, three QTLs were mapped to chromosomes 6, 11, and 16 in the Suinong 14 × Enrei (SE) RIL population. Two major pleiotropic QTLs on chromosomes 4 and 6 were shown to affect flowering time, maturity, and RP. A QTL influencing RP was identified on chromosome 11, and QTL on chromosome 16 was associated with time to flowering responses. All these QTLs contributed to soybean maturation. The QTLs identified in this study may be utilized in fine mapping and map-based cloning of candidate genes to elucidate the mechanisms underlying flowering and soybean adaptation to different latitudes and to breed novel soybean cultivars with optimal yield-related traits.

Bermudagrass (Cynodon dactylon) is one of tolerant grass species to drought and salt. The comparative analyses of bermudagrass in response to drought and salt stresses at the physiological, proteomic and metabolomic levels were performed in this study. The physiological results indicated that osmolytes accumulation, ROS level and antioxidant enzyme activities were extensively changed by drought and salt stresses. Through comparative proteomic analyses, we successfully identified a total of 77 proteins involved in photosynthesis, oxidative pentose phosphate, glycolysis, and redox metabolic pathways when exposed to drought and salt stresses. Among them, 36 proteins were commonly regulated by both treatments, while other 40 and 13 proteins were specifically regulated by drought and salt, respectively. Totally 15 proteins were involved in carbon metabolic pathway. Moreover, contents of 37 metabolites including amino acids, organic acids, sugars, and sugar alcohols were regulated by drought and salt treatments. Among them, 18 commonly modulated metabolites were involved in carbon and amino acid metabolic pathways. Drought treatment for 21 days caused less accumulation of sugars and sugar alcohols and increased ROS level in bermudagrass which led to relatively more severe cell membrane reflected by high EL value and lower survival rate when compared to 400mM salt treatment for 21 days. These results suggested that drought and 400mM NaCl stresses for 21 days treatment affected common and specific changes in bermudagrass, which would provide new insights to understand the underlying molecular mechanisms and metabolic homeostasis of bermudagrass in responses to abiotic stresses.

Fusarium verticillioides is the most commonly reported fungal species responsible for ear rot of maize which substantially reduces grain yield. It also results in a substantial accumulation of mycotoxins that give rise to toxic response when ingested by animals and humans. For inefficient control by chemical and agronomic measures, it thus becomes more desirable to select more resistant varieties. However, the molecular mechanisms underlying the infection process remain poorly understood, which hampers the application of quantitative resistance in breeding programs. Here, we reveal the disease-resistance mechanism of the maize inbred line of BT-1 which displays high resistance to ear rot using RNA high throughput sequencing. By analyzing RNA-seq data from the BT-1 kernels before and after F. verticillioides inoculation, we found that transcript levels of genes associated with key pathways are dramatically changed compared with the control treatment. Differential gene expression in ear rot resistant and susceptible maize was confirmed by RNA microarray and qRT-PCR analyses. Further investigation suggests that the small heat shock protein family, some secondary metabolites, and the signaling pathways of abscisic acid (ABA), jasmonic acid (JA) or salicylic acids (SA) may be involved in the pathogen-associated molecular pattern-triggered immunity against F. verticillioides. These data will not only provide new insights into the molecular resistant mechanisms against fungi invading, but may also result in the identification of key molecular factors associated with ear rot resistance in maize.