Genetic characteristics of classical astroviruses in Shenzhen, China, 2016-2019.

Human astrovirus (HAstV) is a single-stranded, positive-sense RNA virus and is the leading cause of viral gastroenteritis. However, despite its prevalence, astroviruses still remain one of the least studied enteroviruses. In this study, we sequenced 11 classical astrovirus strains from clinical samples collected in Shenzhen, China from 2016 to 2019, analyzed their genetic characteristics, and deposited them into GenBank. We conducted phylogenetic analysis using IQ-TREE software, with references to astrovirus sequences worldwide. The phylogeographic analysis was performed using the Bayesian Evolutionary Analysis Sampling Trees program, through Bayesian Markov Chain Monte Carlo sampling. We also conducted recombination analysis with the Recombination Detection Program. The newly sequenced strains were categorized as HAstV genotype 1, which is the predominant genotype in Shenzhen. Phylogeographic reconstruction indicated that HAstV-1 may have migrated from the United States to China, followed by frequent transmission between China and Japan. The recombination analysis revealed recombination events within and across genotypes, and identified a recombination-prone region that produced relatively uniform recombination breakpoints and fragment lengths. The genetic analysis of HAstV strains in Shenzhen addresses the current lack of astrovirus data in the region of Shenzhen and provides key insights to the evolution and transmission of astroviruses worldwide. These findings highlight the importance of improving surveillance of astroviruses.

Patterns of gestational weight gain among women with obesity and its correlation with hypertensive disorders of pregnancy in Chinese women.

Gestational weight management in obese women is critical in clinical work. Adverse pregnancy outcomes are associated with improper gestational weight gain (GWG). However, the pattern of GWG (PGWG) and its correlation with hypertensive disorders of pregnancy (HDP) in obesity are still unclear in China. This retrospective cohort study evaluates clinical data from 799 women through multivariate analyses and trajectory analyses. All the participants are stratified per first trimester weight gain category into three groups (Inadequate-1st, <0.5 kg; Adequate-1st, 0.5-2.0 kg; Excessive-1st, >2.0 kg) and PGWG refers to the weekly weight gain during each gestational period. GWG is positively associated with first trimester weight gain. 78.4% of the Excessive-1st participants have excessive total GWG, in contrast to Inadequate-1st (32.7%) and Adequate-1st (48.2%). After 20 weeks, the weekly weight gain rapidly accelerates, and 77.3% have a weekly weight gain exceeding the Institute of Medicine recommendations. Trajectory analysis of weekly weight gain based on HDP shows two separate weight gain curves after 20 weeks in women with and without a high risk of HDP. Especially in Excessive-1st participants, weekly weight gain after 20 weeks over 0.32 kg/w is positively related to the risk of HDP (<0.32 kg/w vs. 0.32-0.61 kg/w, adjusted odds ratios [aOR]: 2.999, 95% confidence interval [CI]: 1.054-8.537; <0.32 kg/w vs. >0.61 kg/w, aOR: 5.362, 95% CI: 1.719-16.729). In summary, the first trimester is critical for gestational weight management in obesity. Excessive weight gain during the first trimester and after 20 weeks predicts a high risk of HDP, which should be noted in clinical practice.

Deltex E3 ubiquitin ligase 3 inhibits colorectal cancer cell growth and regulates cell cycle progression via upregulating E2F transcription factor 1.

BACKGROUND: The mortality rate of colorectal cancer (CRC) remains high in developing countries. Interventions that can inhibit the proliferation of tumor cells represent promising strategies in CRC treatment. Deltex E3 ubiquitin ligase 3 (DTX3) plays an essential role in tumor development and may predict the outcome of cancer patients. This study aimed to investigate the regulatory mechanisms of DTX3 in CRC progression. METHODS AND RESULTS: The expression of DTX3 was significantly downregulated in CRC tissues relative to normal colorectal tissues. DTX3 overexpression inhibited, while DTX3 knockout promoted the colony-forming capacity and proliferation of CRC cells. E2F transcription factor 1 (E2F1) is a key mediator of cell cycle progression that participates in the progression, metastasis, and chemoresistance of CRC. Further analysis revealed that DTX3 regulated the transcriptional activity of E2F1 in CRC cells. The transcription by E2F1 was significantly reduced with the increase in the cellular level of DTX3, while DTX3 knockout exerted an opposite effect. DTX3 knockout also increased the expression of E2F1 target genes involved in cell cycle progression, CDC2 and Cyclin D3, while PD 0332991, an inhibitor of E2F1 transcription, inhibited the expression of both proteins. CONCLUSIONS: In conclusion, DTX3 regulated CRC cell growth via regulating E2F1 and its downstream genes. These findings support further exploration of DTX3 as a potential therapeutic target for CRC.

Co-fermented cow milk protein by Lactobacillus helveticus KLDS 1.8701 and Lactobacillus plantarum KLDS 1.0386 attenuates its allergic immune response in Balb/c mice.

Milk protein is one of the major food allergens. As an effective processing method, fermentation may reduce the potential allergenicity of allergens. This study aimed to evaluate the therapeutic potential of co-fermented milk protein using Lactobacillus helveticus KLDS 1.8701 and Lactobacillus plantarum KLDS 1.0386 in cow milk protein allergy (CMPA) management. This study determined the secondary and tertiary structures of the fermented versus unfermented proteins by Fourier-transform infrared spectroscopy and surface hydrophobicity to evaluate its conformational changes. Our results showed that different fermentation methods have significantly altered the conformational structures of the cow milk protein, especially the tertiary structure. Further, the potential allergenicity of the fermented cow milk protein was assessed in Balb/c mice, and mice treated with the unfermented milk and phosphate-buffered saline were used as a control. We observed a significant reduction in allergenicity via the results of the spleen index, serum total IgE, specific IgE, histamine, and mouse mast cell protease 1 in the mice treated with the co-fermented milk protein. In addition, we analyzed the cytokines and transcription factors expression levels of spleen and jejunum and confirmed that co-fermentation could effectively reduce the sensitization of cow milk protein by regulating the imbalance of T helper (Th1/Th2 and Treg/Th17). This study suggested that changes of conformational structure could reduce the potential sensitization of cow milk protein; thus, fermentation may be a promising strategy for developing a method of hypoallergenic dairy products.

Infant formula supplemented with 1,3-olein-2-palmitin regulated the immunity, gut microbiota, and metabolites of mice colonized by feces from healthy infants.

Infant formula is currently an important food to cope with insufficient breastfeeding. Although 1,3-olein-2-palmitin (OPO) has been used in infant formula, its effects on the immune system, gut microbiota, and metabolites for infants remain unclear. This study constructed a mouse model of colonizing healthy infant feces using antibiotic treatment and fecal microbial transplantation. Thus, the gap between the infant formula supplemented with OPO and human milk in mouse serum biochemistry, immune system, intestinal microbiota, short-chain fatty acid production, and metabolites was evaluated. Our results showed that regarding IL-9, IL-10 levels, fecal secretory IgA, and endotoxin, formula supplemented with OPO and human milk types had comparable levels. Additionally, OPO slightly increased the content of short-chain fatty acids. The 16S rRNA gene sequence analysis and metabonomics analysis demonstrated that feeding different foods affects the gut microbiota of mice; in particular, supplementing formula feeding with OPO enriched the abundance of bifidobacteria. Furthermore, feeding different foods leads to unique intestinal content of metabolites, and the gut microbiota regulates the metabolites' differences. Our results reveal a brand new perspective of OPO regarding gut microbiota and metabolites.

Proteolytic activities of combined fermentation with Lactobacillus helveticus KLDS 1.8701 and Lactobacillus plantarum KLDS 1.0386 reduce antigenic response to cow milk proteins.

Cow milk protein is one of the leading food allergens. This study aimed to develop an effective method for reducing milk sensitization by evaluating antigenicity of fermented skim milk protein using Lactobacillus helveticus KLDS 1.8701, Lactobacillus plantarum KLDS 1.0386, and a combination of both strains. The proteolytic systems of strains in terms of genotype and phenotype are characterized by complete genome sequence, and evaluation the antigenicity of skim milk proteins was determined by ELISA and liquid chromatography with tandem mass spectrometry. Our results showed that the genomes encoded a variety of peptidase genes. For fermented skim milk, the degree of hydrolysis of the combined strains was higher than that of individual strain. Electrophoresis showed that the band color density of α-casein (α-CN) by fermentation of the combined strains was reduced when compared with control group. The fermentation process of the combined strains inhibited α-CN, ß-lactoglobulin, and α-lactalbumin antigenicity by 69.13, 36.10, and 20.92, respectively. Major allergic epitopes of α-CN and ß-lactoglobulin were cleaved by abundant proteases of combined strains. In all, this study showed that the fermentation process involving both L. helveticus and L. plantarum strains could reduce cow milk protein allergenicity through the combination of cell-envelope proteinase and peptidase on α-CN.

Large object distance and super-resolution graded-index photonic crystal flat lens.

In order to realize super-resolution imaging of point source at any positions within a large object distance range, a graded-index equivalent medium (GEM) flat lens, which can break through the object distance limit d (d is the lens thickness), is analyzed by negative refraction. Based on this analysis, graded-index photonic crystal (GPC) flat lens with a large object distance is designed. Its imaging resolution can reach up to 0.4λ at the maximum object distance of 5d, which breaks through the diffraction limit.

Rare Shewanella spp. associated with pulmonary and bloodstream infections of cancer patients, China: a case report.

BACKGROUND: Members of Shewanella species are opportunistic pathogens that are found in marine environments. Currently more than sixty species have been identified, whereas the most commonly clinical cases associated with Shewanella species have involved only two species, i.e., S. algae and S. putrefaciens. We present two cases of pulmonary and bloodstream infections caused by two rare Shewanella spp. strains from patients of gastrointestinal cancer. CASE PRESENTATION: Two male patients with a history of gastrointestinal cancer presented to hospital with pulmonary and bloodstream infections, respectively. The infective pathogens of both cases were primarily isolated and identified as Shewanella algae (case I) and Shewanella putrefaciens (case II) by phenotypic features and VITEK 2 system, but they were further confirmed as Shewanella haliotis and Shewanella upenei by 16S rRNA gene sequence analysis. The major bacterial composition of the bronchoalveolar lavage in case I was also identified as Shewanella by 16S rRNA amplicon sequencing analysis. Antimicrobial susceptibility testing showed that the two strains had broad susceptibility, but S. haliotis in the case I was resistant to ciprofloxacin and levofloxacin and S. upenei in the case II was intermediate to imipenem, piperacillin/tazobactam and ciprofloxacin. CONCLUSIONS: To the best of our knowledge, this is the first cases of the pulmonary and bloodstream infections caused by Shewanella spp. from clinical patients in mainland China. Shewanella as a potential pathogen in China should not be ignored.

Biological Activity of Lactic Acid Bacteria Exopolysaccharides and Their Applications in the Food and Pharmaceutical Industries.

Exopolysaccharides are natural macromolecular bioactive substances produced by lactic acid bacteria. With their unique physiological activity and structural characteristics, they are gradually showing broad application prospects in the food and pharmaceutical industries. Exopolysaccharides have various biological functions, such as exerting antioxidant and anti-tumor activities and regulating gut microbiota. Meanwhile, as a food additive, exopolysaccharides can significantly enhance the taste and quality of food, bringing consumers a better eating experience. In the field of medicine, exopolysaccharides have been widely used as drug carriers due to their non-toxic properties and good biocompatibility. This article summarizes the biological activities of exopolysaccharides produced by lactic acid bacteria, their synthesis, and their applications in food and pharmaceutical industries, aiming to promote further research and development in this field.

Exopolysaccharides of lactic acid bacteria: Structure, biological activity, structure-activity relationship, and application in the food industry: A review.

Over the past few decades, researchers have discovered that probiotics play an important role in our daily lives. With the further deepening of research, more and more evidence show that bacterial metabolites have an important role in food and human health, which opens up a new direction for the research of lactic acid bacteria (LAB) in the food and pharmaceutical industry. Many LAB have been widely studied because of the ability of exopolysaccharides (EPS). Lactic acid bacteria exopolysaccharides (LAB EPS) not only have great potential in the treatment of human diseases but also can become natural ingredients in the food industry to provide special qualitative structure and flavor. This paper has organized and summarized the biosynthesis, strain selection, production process parameters, structure, and biological activity of LAB EPS, filling in the monotony and incompleteness of previous articles' descriptions of LAB EPS. Therefore, this paper focuses on the general biosynthetic pathway, structural characterization, structure-activity relationship, biological activity of LAB EPS, and their application in the food industry, which will help to deepen people's understanding of LAB EPS and develop new active drugs from LAB EPS. Although the research results are relatively affluent, the low yield, complex structure, and few clinical trials of EPS are still the reasons that hinder its development. Therefore, future knowledge expansion should focus on the regulation of structure, physicochemical properties, function, higher production of EPS, and clinical trial applications, which can further increase the commercial significance and value of EPS. Furthermore, better understanding the structure-function relationship of EPS in food remains a challenge to date.

Characteristics of the oral glucose tolerance test in women with different pre-pregnancy body mass index and the effect of gestational diabetes mellitus on twin pregnancy outcomes.

OBJECTIVE: This study aimed to investigate the mid-pregnancy blood glucose levels of women with singleton or twin pregnancies. METHOD: The relationship between blood glucose levels and Gestational Diabetes Mellitus (GDM) was studied in women with different pre-pregnancy Body Mass Index (BMI), and the effect of GDM on twin pregnancy outcomes was analyzed. Women with twin (n = 1,985) and singleton (n = 1,985) pregnancies were categorized into underweight (BMI < 18.5 kg/m2, n = 597), normal weight (BMI: 18.5-23.9 kg/m2, n = 2,575), and overweight/obese (BMI ≥ 24 kg/m2, n = 798) groups. RESULTS: The incidence of GDM was 21.01% in women with twin pregnancies. Among the women with GDM in twin pregnancies, 38.37% had at least two abnormal blood glucose levels. The incidence of these parameters increased with preconception BMI, and the incidence of twin pregnancies was higher than that of singleton pregnancies (p < 0.001). In the normal weight and overweight/obese group, the oral glucose tolerance test glucose level and incidence of GDM were higher in women with twin than singleton pregnancies (p < 0.05). For twin pregnancies, the prevalence of selective fetal growth restriction was higher and anemia was lower in the GDM group than in the non-GDM group (all p < 0.05). CONCLUSION: Therefore, a greater emphasis should be placed on BMI before conception, and well-controlled GDM does not increase adverse pregnancy outcomes for twin pregnancies.

Type I Mirizzi syndrome treated by electrohydraulic lithotripsy under the direct view of SpyGlass: A case report.

BACKGROUND: Mirizzi syndrome is an uncommon clinical complication for which the available treatment options mainly include open surgery, laparoscopic surgery, endoscopic retrograde cholangiopancreatography (ERCP), electrohydraulic lithotripsy, and laser lithotripsy. Here, a patient diagnosed with type I Mirizzi syndrome was treated with electrohydraulic lithotripsy under SpyGlass direct visualization, which may provide a reference to explore new treatments for Mirizzi syndrome. CASE SUMMARY: This paper describes a middle-aged female patient with suspected choledocholithiasis who complained for over 1 mo of intermittent abdominal pain, dark yellow urine, jaundice, and was proposed to undergo ERCP lithotomy. Mirizzi syndrome was found during the operation and confirmed by SpyGlass. Electrohydraulic lithotripsy was performed under the direct vision of SpyGlass. After the lithotripsy, the stones were extracted using the stone extraction basket and balloon. After the operation, the patient developed transient hyperamylasemia. Through a series of symptomatic treatments (such as fasting, fluids and anti-inflammation medications), the symptoms of the patient improved. Finally, laparoscopic cholecystectomy or open cholecystectomy was performed after a half-year post-operatively. CONCLUSION: Direct visualization-guided laser or electrohydraulic lithotripsy with SpyGlass is feasible and minimally invasive for type I Mirizzi syndrome without apparent unsafe outcomes.

Dynamic changes of serum taurine and the association with gestational diabetes mellitus: A nested case-control study.

Objective: There is a lack of risk factors that can effectively identify gestational diabetes mellitus (GDM) in early pregnancy. It is unclear whether serum taurine in the first trimester and dynamic changes have different characteristics in GDM women. Whether these features are associated with the occurrence of GDM has not yet been elucidated. The main objective of this study was to observe the dynamic changes of serum taurine during pregnancy and investigate the relationship between serum taurine levels and GDM in the first and second trimesters. Methods: This was a nested case-control study in 47 women with GDM and 47 age-matched normoglycemic women. We examined serum taurine at 8-12 weeks' gestation and 24-28 weeks' gestation. The serum taurine of the two groups was compared. Multivariable logistic regression analysis was performed to investigate how serum taurine was associated with GDM. Results: The serum taurine concentration of GDM women was significantly lower than that of normoglycemic women in the first trimester(2.29 vs 3.94 µmol/L, P<0.001). As the pregnancy progressed, serum taurine concentration in normoglycaemic women decreased significantly(3.94 vs 2.47 µmol/L, P<0.001), but not in the GDM group(2.29 vs 2.37 µmol/L, P=0.249), resulting in the disappearance of differences between the two groups(2.47 vs 2.37 µmol/L, P=0.160). After adjustment for pre-pregnancy body mass index(BMI), fasting plasma glucose(FPG), and lipid profiles in the first trimester, the serum taurine concentration in the first trimester was negatively correlated with the risk of GDM(OR=0.017, 95% CI=0.003-0.107, P<0.001). Furthermore, dynamic change of serum taurine showed a significantly positive correlation with the risk of GDM(OR=9.909, 95% CI=3.556-27.610, P<0.001). Conclusion: Low serum taurine concentration in the first trimester was significantly associated with the development of GDM. As the pregnancy progressed, the association between serum taurine and GDM disappeared in the second trimester, which might be related to the inhibition of taurine transporter(TauT) activity by high glucose.

Increased intraocular inflammation in retinal vein occlusion is independent of circulating immune mediators and is involved in retinal oedema.

We aim to understand the link between systemic and intraocular levels of inflammatory mediators in treatment-naïve retinal vein occlusion (RVO) patients, and the relationship between inflammatory mediators and retinal pathologies. Twenty inflammatory mediators were measured in this study, including IL-17E, Flt-3 L, IL-3, IL-8, IL-33, MIP-3ß, MIP-1α, GRO ß, PD-L1, CD40L, IFN-ß, G-CSF, Granzyme B, TRAIL, EGF, PDGF-AA, PDGF-AB/BB, TGF-α, VEGF, and FGFß. RVO patients had significantly higher levels of Flt-3 L, IL-8, MIP-3ß, GROß, and VEGF, but lower levels of EGF in the aqueous humor than cataract controls. The levels of Flt-3 L, IL-3, IL-33, MIP-1α, PD-L1, CD40 L, G-CSF, TRAIL, PDGF-AB/BB, TGF-α, and VEGF were significantly higher in CRVO than in BRVO. KEGG pathway enrichment revealed that these mediators affected the PI3K-Akt, Ras, MAPK, and Jak/STAT signaling pathways. Protein-Protein Interaction (PPI) analysis showed that VEGF is the upstream cytokine that influences IL-8, G-CSF, and IL-33 in RVO. In the plasma, the level of GROß was lower in RVO than in controls and no alterations were observed in other mediators. Retinal thickness [including central retinal thickness (CRT) and inner limiting membrane to inner plexiform layer (ILM-IPL)] positively correlated with the intraocular levels of Flt-3 L, IL-33, GROß, PD-L1, G-CSF, and TGF-α. The size of the foveal avascular zone positively correlated with systemic factors, including the plasma levels of IL-17E, IL-33, INF-ß, GROß, Granzyme B, and FGFß and circulating high/low-density lipids and total cholesterols. Our results suggest that intraocular inflammation in RVO is driven primarily by local factors but not circulating immune mediators. Intraocular inflammation may promote macular oedema through the PI3K-Akt, Ras, MAPK, and Jak/STAT signaling pathways in RVO. Systemic factors, including cytokines and lipid levels may be involved in retinal microvascular remodeling.

Maternal weight, blood lipids, and the offspring weight trajectories during infancy and early childhood in twin pregnancies.

BACKGROUND: The intrauterine environment has a profound and long-lasting influence on the health of the offspring. However, its impact on the postnatal catch-up growth of twin children remains unclarified. Therefore, this study aimed to explore the maternal factors in pregnancy associated with twin offspring growth. METHODS: This study included 3142 live twin children born to 1571 mothers from the Beijing Birth Cohort Study conducted from 2016 to 2021 in Beijing, China. Original and corrected weight-for-age standard deviation scores of the twin offspring from birth to 36 months of age were calculated according to the World Health Organization Child Growth Standards. The corresponding weight trajectories were identified by the latent trajectory model. Maternal factors in pregnancy associated with the weight trajectories of the twin offspring were examined after adjustment for potential confounders. RESULTS: Five weight trajectories of the twin children were identified, with 4.9% (154/3142) exhibiting insufficient catch-up growth, 30.6% (961/3142), and 46.8% (1469/3142) showing adequate catch-up growth from different birth weights, and 15.0% (472/3142) and 2.7% (86/3142) showing various degrees of excessive catch-up growth. Maternal short stature [adjusted odds ratio (OR) = 0.691, 95% confidence interval (CI) = 0.563-0.848, P = 0.0004] and lower total gestational weight gain (GWG) (adjusted OR = 0.774, 95% CI = 0.616-0.972, P = 0.03) were associated with insufficient catch-up growth of the offspring. Maternal stature (adjusted OR = 1.331, 95% CI = 1.168-1.518, P < 0.001), higher pre-pregnancy body mass index (BMI) (adjusted OR = 1.230, 95% CI = 1.090-1.387, P < 0.001), total GWG (adjusted OR = 1.207, 95% CI = 1.068-1.364, P = 0.002), GWG rate (adjusted OR = 1.165, 95% CI = 1.027-1.321, P = 0.02), total cholesterol (TC) (adjusted OR = 1.150, 95% CI = 1.018-1.300, P = 0.03) and low-density lipoprotein-cholesterol (LDL-C) (adjusted OR = 1.177, 95% CI = 1.041-1.330) in early pregnancy were associated with excessive growth of the offspring. The pattern of weight trajectories was similar between monochorionic and dichorionic twins. Maternal height, pre-pregnancy BMI, GWG, TC and LDL-C in early pregnancy were positively associated with excess growth in dichorionic twins, yet a similar association was observed only between maternal height and postnatal growth in monochorionic twins. CONCLUSION: This study identified the effect of maternal stature, weight status, and blood lipid profiles during pregnancy on postnatal weight trajectories of the twin offspring, thereby providing a basis for twin pregnancy management to improve the long-term health of the offspring.

Weighted p-norm distance t kernel SVM classification algorithm based on improved polarization.

The kernel function in SVM enables linear segmentation in a feature space for a large number of linear inseparable data. The kernel function that is selected directly affects the classification performance of SVM. To improve the applicability and classification prediction effect of SVM in different areas, in this paper, we propose a weighted p-norm distance t kernel SVM classification algorithm based on improved polarization. A t-class kernel function is constructed according to the t distribution probability density function, and its theoretical proof is presented. To find a suitable mapping space, the t-class kernel function is extended to the p-norm distance kernel. The training samples are obtained by stratified sampling, and the affinity matrix is redefined. The improved local kernel polarization is established to obtain the optimal kernel weights and kernel parameters so that different kernel functions are weighted combinations. The cumulative optimal performance rate is constructed to evaluate the overall classification performance of different kernel SVM algorithms, and the significant effects of different p-norms on the classification performance of SVM are verified by 10 times fivefold cross-validation statistical comparison tests. In most cases, the results using 6 real datasets show that compared with the traditional kernel function, the proposed weighted p-norm distance t kernel can improve the classification prediction performance of SVM.

Bifidobacterium animalis subsp. lactis XLTG11 improves antibiotic-related diarrhea by alleviating inflammation, enhancing intestinal barrier function and regulating intestinal flora.

Antibiotic-associated diarrhea (AAD) is a common side effect during antibiotic treatment. In this study, we evaluated the regulatory effect of Bifidobacterium animalis subsp. lactis XLTG11 on mouse diarrhea caused by antibiotic-induced intestinal flora disturbance. Then, two strains of Bifidobacterium animalis subsp. lactis XLTG11 and Bifidobacterium animalis subsp. lactis BB-12 were administered to AAD mice. We found that the recovery effect of using B. lactis XLTG11 was better than that of B. lactis BB-12. B. lactis XLTG11 reduced the pathological characteristics of the intestinal tract, and significantly reduced the levels of lipopolysaccharide (LPS), D-lactic acid (D-LA) and diamine oxidase (DAO) to decrease intestinal permeability. In addition, these two strains significantly increased the expression of aquaporin and tight junction proteins, and inhibited toll-like receptor 4 (TLR4)/activation of the nuclear factor-κB (NF-κB) signaling pathway, significantly increased the levels of anti-inflammatory cytokines and decreased levels of pro-inflammatory cytokines. Moreover, after treatment with B. lactis XLTG11, the contents of acetic acid, propionic acid, butyric acid and total short-chain fatty acids were significantly increased. Compared with the MC group, B. lactis XLTG11 increased the abundance and diversity of the intestinal flora and changed the composition of the intestinal flora. We found that B. lactis XLTG11 can promote the recovery of intestinal flora and mucosal barrier function, thereby effectively improving AAD-related symptoms, providing a scientific basis for future clinical applications.

Dynamic changes and early predictive value of branched-chain amino acids in gestational diabetes mellitus during pregnancy.

Objective: Branched-chain amino acids (BCAAs) are closely associated with type 2 diabetes mellitus, but their roles in gestational diabetes mellitus (GDM) are still controversial. This study aims to explore the dynamic changes of BCAAs during pregnancy and identify potential early biomarkers for GDM. Methods: This study is a nested case-control study involved 49 women with GDM and 50 age- and body mass index (BMI)-matched healthy pregnant women. The dynamic changes of valine (Val), isoleucine (Ile), and leucine (Leu) were detected in the first (8-12 weeks) and second trimesters (24-28 weeks) by liquid chromatography-mass spectrometry. Results: Serum Val, Ile, and Leu were higher in GDM patients than in controls in the first trimester. Compared with the first trimester, the serum Val, Ile, and Leu in GDM patients were decreased in the second trimester. In addition, Val, Ile, and Leu in the first trimester were the risk factors for GDM, and Ile presented a high predictive value for GDM. Ile + age (≥ 35) + BMI (≥ 24) exhibited the highest predictive value for GDM (AUC = 0.902, sensitivity = 93.9%, specificity = 80%). Conclusion: Maternal serum Ile in the first trimester was a valuable biomarker for GDM. Ile combined with advanced maternal age and overweight may be used for the early prediction of GDM.

Distinct gut microbiota and metabolite profiles induced by delivery mode in healthy Chinese infants.

Delivery mode is recognized as an important determinant of gut microbiota composition. Vaginally delivered infants were colonized by maternal vaginal and fecal microbiota, while those delivered by cesarean section were colonized by environmental microorganisms. To reveal differences induced by delivery mode, we determined fecal microbiota and fecal metabolome from 60 infants in Northeast China region. Bacterial gene sequence analysis showed that the feces of vaginally delivered infants had the highest abundance of Bifidobacterium, Lactobacillus, Bacteroides and Parabacteroides, while the feces of cesarean section delivered infants were more enriched in Klebsiella. LC-MS-based metabolomics data demonstrated that the feces of vaginally delivered infants were associated with high abundance of DL-norvaline and DL-citrulline, while the feces of cesarean section delivered infants were abundant in trans-vaccenic acid and cis-aconitic acid. Moreover, the feces of vaginally delivered infants was significantly in positive correlation with tryptophan metabolism and pyruvate metabolism, however, the feces of cesarean section delivered infants was positively correlated with ABC transporters. Collectively, our study demonstrated that gut microbiota and metabolite profiles were significantly different between vaginally delivered and cesarean section delivered infants, and provided the theoretical basis for restoring the intestinal environment of cesarean section infants birthed in the study region. SIGNIFICANCE: The intestinal microbiota and metabolites play important roles in infant development. To validate whether delivery modes influence the gut environment, we performed a detailed analysis of the earliest microbial colonization of the infant gut using a combination of 16S rRNA gene amplicon sequencing and LC-MS-based metabolomics. We found that the gut microbiota and metabolite composition were significantly different between vaginally delivered infants and cesarean section delivered infants. Our findings establish a vital baseline for studies tracking the infant gut microbiota and metabolite development following different delivery modes, and their associated effects on infant health. This study provides preliminary evidence that the observed differences due to delivery modes highlight their importance in shaping the early intestinal microbiota and metabolites.

Systems pharmacology reveals the multi-level synergetic mechanism of action of Ginkgo biloba L. leaves for cardiomyopathy treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiomyopathy is a common cause of heart failure and may lead to increased risk of sudden cardiac death, lacking simple, safe and effective treatment strategies due to unclear pathogenesis. Ginkgo biloba L. leaves (GBLs), a traditional Chinese medicine (TCM), has been widely used in clinical medicine for improving blood circulation, and was demonstrated to be effective on cardiomyopathy in preclinical studies. However, because of the widely known holistic therapeutic philosophy via multi-target and multi-pathway effect for most TCMs, to explore its underlying molecular mechanisms of action (MoA) remains a great challenge. AIM OF STUDY: Decipher the underlying MoA of GBLs for cardiomyopathy treatment: Study design and methods: An integrated systems pharmacology framework was employed to screen potential active compounds, identify therapeutic targets, explore the action pathways and verify mechanisms of GBLs with in vitro experiments. RESULTS: We firstly confirmed the therapeutic effect of GBLs on cardiomyopathy and subsequently screened 27 active compounds from GBLs according to their pharmacokinetic properties. Then Probability Ensemble Approach was applied to identify the compound combinations that exert synergetic effect from GBLs. Network analysis and functional enrichment analysis demonstrated that these compounds exhibit synergistic therapeutic effect by acting on multiple targets and thereby regulating multiple pathways mainly involved in pro-survival, anti-apoptotic and anti-inflammatory processes. Finally, using a doxorubicin-induced myocardial injury model, therapeutic effect of ginkgolide A, ginkgolide B, isorhamnetin, as well as their synergistic effect on PI3K-AKT and NF-κB signaling pathways were validated in vitro. Importantly, we demonstrated that Ginkgo diterpene lactone meglumine injection (GDJ), an approved injection derived from GBLs, could be a promising agent for cardiomyopathy treatment. CONCLUSION: Collectively, the multi-level synergetic mechanism of GBLs on cardiomyopathy treatment was demonstrated with systems pharmacology approach, providing a paradigm for deciphering the complicated MoA of TCMs.