Hyaluronic acid-coated porphyrin nanoplatform with oxygen sustained supplying and glutathione depletion for enhancing photodynamic/ion/chemo synergistic cancer treatment.

Hypoxia and high concentration of glutathione (GSH) in tumor seriously hinder the role of reactive oxygen species (ROS) and oxygen-dependence strategy in tumor treatment. In this work, a self-generating oxygen and self-consuming GSH hyaluronic acid (HA)-coated porphyrin nanoplatform (TAPPP@CaO2/Pt(IV)/HA) is established for enhancing photodynamic/ion/chemo targeting synergistic therapy of tumor. During the efforts of ROS production by nanosystems, a GSH consuming strategy is implemented for augmenting ROS-induced oxidative damage for synergetic cancer therapy. CaO2 in the nanosystems is decomposed into O2 and H2O2 in an acidic environment, which alleviates hypoxia and enhances the photodynamic therapy (PDT) effect. Calcium overload causes mitochondria dysfunction and induces apoptosis. Pt (IV) reacts with GSH to produce Pt (II) for chemotherapy and reduce the concentration of GSH, protecting ROS from scavenging for augmenting ROS-induced oxidative damage. In vitro and in vivo results demonstrated the self-generating oxygen and self-consuming GSH strategy can enhance ROS-dependent PDT coupled with ion/chemo synergistic therapy. The proposed strategy not only solves the long-term problem that hypoxia limits therapeutic effect of PDT, but also ameliorates the highly reducing environment of tumors. Thus the preparation of TAPPP@CaO2/Pt(IV)/HA provided a novel strategy for the effective combined therapy of cancers.

Association between endometriosis and arthritis: results from NHANES 1999-2006, genetic correlation analysis, and Mendelian randomization study.

Background: Previous studies reported that endometriosis may have a higher risk of arthritis. However, it remains unclear whether the association between endometriosis and arthritis has genetic correlations, or the relationship is causal. Linkage Disequilibrium Score (LDSC) and Mendelian Randomization (MR) analyses use genetic variation as a natural experiment to explore genetic correlations and causal inferences from observational data, reducing unmeasured confounding factors. Method: Participants (aged 20-54 years, n = 2,915) for the cross-sectional study were obtained from the National Health and Nutrition Examination Survey (NHANES). Endometriosis and arthritis were diagnosed based on self-reported by reproductive health and medical condition questionnaire. Weighted multivariable logistic regression was used to explore the relationship between endometriosis and arthritis. LDSC and MR analysis were performed using the genome-wide association study (GWAS) summary statistics to identify the causal association. Result: A significant positive association between endometriosis and arthritis was found after multivariable adjustment (OR = 1.89; 95% CI: 1.33, 2.67). When exploring different types of arthritis, a positive association was revealed with rheumatoid arthritis (RA), other types of arthritis, and cases that the arthritis type were unknown, with an OR of 2.07 (95% CI: 1.03, 4.17), 2.78 (95% CI: 1.30, 5.95), and 2.06 (95% CI: 1.36, 3.11), respectively. However, genetic correlation analysis between endometriosis and RA did not reveal any significant findings (all P values > 0.05). Moreover, MR analysis also failed to identify a causal relationship between endometriosis and RA (all P values > 0.05). Conclusion: Cross-sectional study identified a significant positive association between endometriosis and arthritis among US women, especially among RA, while findings based on LDSC and MR analysis did not support a genetic correlation or causal role. These findings suggest that clinicians should pay more attention to the coexistence of RA in endometriosis patients and explore the shared pathophysiological mechanisms of these two disorders, with a particular focus on extrinsic factors rather than intrinsic genetic inheritance.

A disproportionality analysis of low molecular weight heparin in the overall population and in pregnancy women using the FDA adverse event reporting system (FAERS) database.

Background: Low molecular weight heparin (LMWH) is extensively utilized as an anticoagulant for the prevention and management of various thrombotic conditions. However, despite the widespread use of LMWH in clinical indications, its adverse events (AEs) have not received substantial attention, and there is a lack of systematic and comprehensive AE studies. This study aims to evaluate AE signals associated with LMWH in the overall population and in pregnancy women from the FDA Adverse Event Reporting System database. Methods: We used the Standardized MedDRA Query to identify pregnancy-related AE reports. Disproportionality analyses were employed to identify LMWH-related AE by calculating the reporting odds ratios (ROR), proportional reporting ratios (PRR), bayesian confidence propagation neural network (BCPNN), and the empirical Bayesian geometric mean (EBGM). Results: For the overall population, the significantly reported adverse signals in SOCs were pregnancy, puerperium, and perinatal conditions, vascular disorders, blood and lymphatic system disorders, and product issues. The five strongest AEs signal of LMWH-related were anti factor X antibody positive (n = 6, ROR 506.70, PRR 506.65, IC 8.31, EBGM 317.03), heparin-induced thrombocytopenia test positive (n = 19, ROR 263.10, PRR 263.02, IC 7.65, EBGM 200.79), anti factor X activity increased (n = 10, ROR 255.93, PRR 255.89, IC 7.62, EBGM 196.61), heparin-induced thrombocytopenia test (n = 14, ROR 231.85, PRR 231.80, IC 7.51, EBGM 182.09), and spontaneous heparin-induced thrombocytopenia syndrome (n = 3, ROR 230.31, PRR 230.30, IC 7.50, EBGM 181.16). For pregnancy women, the five strongest AEs signals of LMWH-related included sternal fracture (n = 3, ROR 243.44, PRR 243.35, IC 6.61, EBGM 97.94), syringe issue (n = 12, ROR 97.49, PRR 97.34, IC 5.94, EBGM 61.21), bleeding time prolonged (n = 3, ROR 97.38, PRR 97.34, IC 5.94, EBGM 61.21), spinal compression fracture (n = 10, ROR 90.24, PRR 90.13, IC 5.87, EBGM 58.30), and injection site haematoma (n = 19, ROR 79.23, PRR 79.04, IC 5.74, EBGM 53.47). Additionally, unexpected AEs associated with LMWH in pregnancy women were observed, including premature baby death, placental necrosis, abortion, antiphospholipid syndrome, systolic dysfunction, compartment syndrome, body height decreased, rubella antibody positive, and ultrasound doppler abnormal. Conclusion: This study identified unexpected AE signals of LMWH-relate in pregnancy women. Our study could provide valuable evidence for the clinical practice of LMWH, especially for identifying AEs and ensuring safe usage in pregnancy women.

Combining Partial True Discovery Guarantee Procedures.

Closed testing has recently been shown to be optimal for simultaneous true discovery proportion control. It is, however, challenging to construct true discovery guarantee procedures in such a way that it focuses power on some feature sets chosen by users based on their specific interest or expertise. We propose a procedure that allows users to target power on prespecified feature sets, that is, "focus sets." Still, the method also allows inference for feature sets chosen post hoc, that is, "nonfocus sets," for which we deduce a true discovery lower confidence bound by interpolation. Our procedure is built from partial true discovery guarantee procedures combined with Holm's procedure and is a conservative shortcut to the closed testing procedure. A simulation study confirms that the statistical power of our method is relatively high for focus sets, at the cost of power for nonfocus sets, as desired. In addition, we investigate its power property for sets with specific structures, for example, trees and directed acyclic graphs. We also compare our method with AdaFilter in the context of replicability analysis. The application of our method is illustrated with a gene ontology analysis in gene expression data.

Genome-wide Cas9-mediated screening of essential non-coding regulatory elements via libraries of paired single-guide RNAs.

The functions of non-coding regulatory elements (NCREs), which constitute a major fraction of the human genome, have not been systematically studied. Here we report a method involving libraries of paired single-guide RNAs targeting both ends of an NCRE as a screening system for the Cas9-mediated deletion of thousands of NCREs genome-wide to study their functions in distinct biological contexts. By using K562 and 293T cell lines and human embryonic stem cells, we show that NCREs can have redundant functions, and that many ultra-conserved elements have silencer activity and play essential roles in cell growth and in cellular responses to drugs (notably, the ultra-conserved element PAX6_Tarzan may be critical for heart development, as removing it from human embryonic stem cells led to defects in cardiomyocyte differentiation). The high-throughput screen, which is compatible with single-cell sequencing, may allow for the identification of druggable NCREs.

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study.

Introduction: Studies have shown that the gut microbiota is associated with male infertility (MI). However, their causal relationship and potential mediators need more evidence to prove. We aimed to investigate the causal relationship between the gut microbiome and MI and the potential mediating role of inflammatory cytokines from a genetic perspective through a Mendelian randomization approach. Methods: This study used data from genome-wide association studies of gut microbes (Mibiogen, n = 18, 340), inflammatory cytokines (NFBC1966, FYPCRS, FINRISK 1997 and 2002, n=13, 365), and male infertility (Finngen, n=120, 706) to perform two-way Mendelian randomization (MR), mediated MR, and multivariate MR(MVMR) analyses. In this study, the inverse variance weighting method was used as the primary analysis method, and other methods were used as supplementary analysis methods. Results: In the present study, two gut microbes and two inflammatory cytokines were found to have a potential causal relationship with MI. Of the two gut microorganisms causally associated with male infertility, Anaerotruncus increased the risk of male infertility (odds ratio = 1.81, 95% confidence interval = 1.18-2.77, P = 0.0062), and Bacteroides decreased the risk of male infertility (odds ratio = 0.57, 95% confidence interval = 0.33-0.96, P = 0.0363). In addition, of the two inflammatory cytokines identified, hepatocyte growth factor(HGF) reduced the risk of male infertility (odds ratio = 0.50, 95% confidence interval = 0.35-0.71, P = 0.0001), Monocyte chemotactic protein 3 (MCP-3) increased the risk of male infertility (odds ratio = 1.28, 95% confidence interval = 1.03-1.61, P = 0.0039). Mediated MR analysis showed that HGF mediated the causal effect of Bacteroides on MI (mediated percentage 38.9%). Multivariate MR analyses suggest that HGF may be one of the pathways through which Bacteroides affects MI, with other unexplored pathways. Conclusion: The present study suggests a causal relationship between specific gut microbiota, inflammatory cytokines, and MI. In addition, HGF may mediate the relationship between Bacteroides and MI.

Novel Dual-Emission Emitters Featuring Phenothiazine-S-Oxide and Phenothiazine-S,S-Dioxide Motifs.

In this study, we have successfully designed and synthesized two novel dual-emission emitters featuring phenothiazine-5-oxide and phenothiazine-5,5-dioxide motifs, characterized by highly lopsided and asymmetric conformational states. Through rigorous spectral examinations and DFT calculations, the compounds exhibit distinctive ICT phenomena, coupled with efficient emission in solid states and AIEE characteristics under high water fractions in DMF/H2O mixtures. These non-planar luminogens exhibit vibrant green and blue solid-state luminescence, with fluorescence quantum yields of 24.1 % and 15.21 %, respectively. Additionally, they both emit green fluorescence in THF solution, with notable emission quantum yields (QYs) 36.4 % and 30.4 %. Comprehensive theoretical investigations unveil well-defined electron cloud density separation between the energies of HOMO/LUMO levels within the two luminogens. Notably, the targeted molecule harboring the phenothiazine-S,S-dioxide motif also demonstrates remarkable reversible mechanofluorochromic properties. Moreover, we testify their potential in applications such as solid-state rewritable information storage and live-cell imaging in solution states. Through theoretical calculations and comparative studies, we have explored the intrinsic relationship between molecular structure and performance, effectively screening and identifying new fluorescent molecules exhibiting outstanding luminescent attributes. These discoveries establish a robust theoretical and technical foundation for the synthesis and application of efficient DSE-based MFC materials, opening new avenues in the realm of advanced luminescent materials.

Interactions between nitrogen and phosphorus modulate the food quality of the marine crop Pyropia haitanensis (T. J. Chang & B. F. Zheng) N. Kikuchi & M. Miyata (Porphyra haitanensis).

The quality of Pyropia haitanensis (T. J. Chang & B. F. Zheng) N. Kikuchi & M. Miyata (Porphyra haitanensis) is directly affected by nutrient availability. However, the molecular mechanism underlying the synergistic regulatory effects of nitrogen (N) and phosphorus (P) availability on P. haitanensis quality is unknown. Here, we performed physiological and multi-omics analyses to reveal the combined effects of N and P on P. haitanensis quality. The pigments accumulated under high N because of increases in N metabolism and porphyrin metabolism, ultimately resulting in intensely colored thalli. High N also promoted amino acid metabolism and inosine 5'-mononucleotide (IMP) synthesis, but inhibited carbohydrates accumulation. This resulted in increased amino acid, IMP and decreased agaro-carrageenan and cellulose contents, thereby improving the nutritional value and taste. Furthermore, high P promoted carbon metabolism and amino acid metabolism.This study provided the basis for elucidating the mechanism behind N and P regulating the seaweed quality.

Inflammatory markers are associated with infertility prevalence: a cross-sectional analysis of the NHANES 2013-2020.

BACKGROUND: Inflammation exerts a critical role in the pathogenesis of infertility. The relationship between inflammatory parameters from peripheral blood and infertility remains unclear. Aim of this study was to investigate the association between inflammatory markers and infertility among women of reproductive age in the United States. METHODS: Women aged 20-45 were included from the National Health and Nutrition Examination Survey (NHANES) 2013-2020 for the present cross-sectional study. Data of reproductive status was collected from the Reproductive Health Questionnaire. Six inflammatory markers, systemic immune inflammation index (SII), lymphocyte count (LC), product of platelet and neutrophil count (PPN), platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) were calculated from complete blood counts in mobile examination center. Survey-weighted multivariable logistic regression was employed to assess the association between inflammatory markers and infertility in four different models, then restricted cubic spline (RCS) plot was used to explore non-linearity association between inflammatory markers and infertility. Subgroup analyses were performed to further clarify effects of other covariates on association between inflammatory markers and infertility. RESULTS: A total of 3,105 women aged 20-45 was included in the final analysis, with 431 (13.88%) self-reported infertility. A negative association was found between log2-SII, log2-PLR and infertility, with an OR of 0.95 (95% CI: 0.78,1.15; p = 0.60), 0.80 (95% CI:0.60,1.05; p = 0.10), respectively. The results were similar in model 1, model 2, and model 3. Compared with the lowest quartile (Q1), the third quartile (Q3) of log2-SII was negatively correlation with infertility, with an OR (95% CI) of 0.56 (95% CI: 0.37,0.85; p = 0.01) in model 3. Similarly, the third quartile (Q3) of log2-PLR was negatively correlation with infertility, with an OR (95% CI) of 0.61 (95% CI: 0.43,0.88; p = 0.01) in model 3. No significant association was observed between log2-LC, log2-PPN, log2-NLR, log2-LMR and infertility in model 3. A similar U-shaped relationship between log2-SII and infertility was found (p for non-linear < 0.05). The results of subgroup analyses revealed that associations between the third quartile (Q3) of log2-SII, log2-PLR and infertility were nearly consistent. CONCLUSION: The findings showed that SII and PLR were negatively associated with infertility. Further studies are needed to explore their association better and the underlying mechanisms.

Multifunctional polydopamine/hemin-cyclodextrin reinforced chitosan nanocomposite hydrogel: A synergistic platform for wound healing.

Chronic cutaneous wounds present a significant challenge for healthcare providers globally, with the risk of bacterial infections emerging as a particularly concerning issue. There is an increasing need to employ a combination of diverse antibacterial strategies to address infections comprehensively in chronic wounds. This study introduces a highly efficient antibacterial platform that encapsulates the NO precursor (BNN6) into ß-cyclodextrin-modified hemin-bearing polydopamine nanoparticles called NO/CHPDA. These nanoparticles are seamlessly integrated into a hydrogel composite comprised of L-arginine grafted chitosan (Arg-CS) and oxide dextrans (oDex). The amalgamation of photothermal therapy (PTT), chemodynamic therapy (CDT), and nitric oxide (NO) antibacterial strategies within the NO/CHPDA@Arg-CS/oDex nanocomposite hydrogel demonstrates a synergistic and highly effective capacity to eradicate bacteria and accelerate the wound healing process in vivo. Remarkably, this nanocomposite hydrogel maintains excellent biocompatibility and induces minimal side effects. The resulting nanocomposite hydrogel represents a promising therapeutic solution for treating bacterial infections in wound healing applications.

Allicin Protects Renal Function, Improves Oxidative Stress and Lipid Peroxidation in Rats with Chronic Renal Failure.

INTRODUCTION: The research was an attempt to explore the potential impact of allicin on lipid peroxidation and oxidative stress in rats diagnosed with chronic kidney disease (CKD), and to determine its underlying mechanism. METHODS: Sixty rats were randomly divided into sham-operated, modelling, and allicin low, medium, and high dose groups. The histopathological structure of the kidney was observed in each group. Biochemical measurements were conducted to assess kidney function, including serum creatinine (Scr) and blood urea nitrogen (BUN), and 24-hour urine protein quantification. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxidative species (ROS), and reduced glutathione (GSH) in kidney tissue were measured, and mitogen-activated protein kinase (MAPK) and NF (nuclear factor) -κB protein levels were detected by western blotting. RESULTS: They showed that allicin improved the pathological structure of renal tissue and protected renal function by reducing oxidative stress and lipid peroxidation via targeting the ROS/ MAPK/NF-κB pathway. Allicin increased SOD and GSH levels, while decreasing Scr, MDA, ROS, BUN, and the amount of protein excreted in urine over a 24-hour in medium and high dose groups. MAPK and NF-κB protein levels in medium and high dose allicin groups were lower than the modelling group. CONCLUSION: Based on the results, it can be inferred that allicin may safeguard renal function in rats with CKD and has the potential to serve as a treatment for kidney ailments.  DOI: 10.52547/ijkd.7496.

Clearance of intracellular bacterial infections by hyaluronic acid-based ROS responsive drug delivery micelles.

Pathogenic bacteria residing inside cells could cause disruption of cellular metabolic balance. Therefore, basing on high oxidative stress response of the intracellular bacteria infected micro-environment, a novel amphipathic micelle (HATAD-TCS) was developed consisting of hyaluronic acid-derivative and reactive oxygen species (ROS) - responsive group and antibacterial agent triclosan (TCS). ROS-generating cinnamaldehyde (CA) was incorporated into ROS-cleavable linkages which are future linked to the 1-decylamine to form hydrophobicity. The cinnamaldehyde released did not just killed bacteria however, also maintained intracellular ROS levels. In this study, the HATAD-TCS micelles have been characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The HATAD-TCS micelles could release drug gradually upon exposure to endogenous ROS being caused by infected intracellular bacteria. Furthermore, the more promising therapeutic effect of the HATAD-TCS micelles was observed in a mouse pneumonia model. These results might highlight a ROS-responsive hyaluronic acid-based nanoparticle, which could effectively treat intracellular bacterial infections.

Untargeted metabolomics of the cochleae from two laryngeally echolocating bats.

High-frequency hearing is regarded as one of the most functionally important traits in laryngeally echolocating bats. Abundant candidate hearing-related genes have been identified to be the important genetic bases underlying high-frequency hearing for laryngeally echolocating bats, however, extensive metabolites presented in the cochleae have not been studied. In this study, we identified 4,717 annotated metabolites in the cochleae of two typical laryngeally echolocating bats using the liquid chromatography-mass spectroscopy technology, metabolites classified as amino acids, peptides, and fatty acid esters were identified as the most abundant in the cochleae of these two echolocating bat species, Rhinolophus sinicus and Vespertilio sinensis. Furthermore, 357 metabolites were identified as significant differentially accumulated (adjusted p-value <0.05) in the cochleae of these two bat species with distinct echolocating dominant frequencies. Downstream KEGG enrichment analyses indicated that multiple biological processes, including signaling pathways, nervous system, and metabolic process, were putatively different in the cochleae of R. sinicus and V. sinensis. For the first time, this study investigated the extensive metabolites and associated biological pathways in the cochleae of two laryngeal echolocating bats and expanded our knowledge of the metabolic molecular bases underlying high-frequency hearing in the cochleae of echolocating bats.

The effect of dietary carbohydrate and calorie restriction on weight and metabolic health in overweight/obese individuals: a multi-center randomized controlled trial.

BACKGROUND: Both low-carbohydrate (LC) and calorie-restricted (CR) diets have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a 12-week randomized trial to compare the effects of these diets separately and in combination on both weight loss and metabolic risk factors in overweight/obese individuals. METHODS: A total of 302 participants were randomized to LC diet (n = 76), CR diet (n = 75), LC + CR diet (n = 76), or normal control (NC) diet (n = 75) using a computer-based random number generator. The primary outcome was the change in body mass index (BMI). The secondary outcomes included body weight, waist circumference, waist-to-hip ratio, body fat, and metabolic risk factors. All participants attended health education sessions during the trial. RESULTS: A total of 298 participants were analyzed. BMI change over 12 weeks was - 0.6 (95% CI, - 0.8 to - 0.3) kg/m2 in NC, - 1.3 (95% CI, - 1.5 to - 1.1) kg/m2 in CR, - 2.3 (95% CI, - 2.6 to - 2.1) kg/m2 in LC, and - 2.9 (95% CI, - 3.2 to - 2.6) kg/m2 in LC + CR. LC + CR diet was more effective than LC or CR diet alone at reducing BMI (P = 0.001 and P < 0.001, respectively). Furthermore, compared with the CR diet, the LC + CR diet and LC diet further reduced body weight, waist circumference, and body fat. Serum triglycerides were significantly reduced in the LC + CR diet group compared with the LC or CR diet alone. Plasma glucose, homeostasis model assessment of insulin resistance, and cholesterol concentrations (total, LDL, and HDL) did not change significantly between the groups during the 12-week intervention. CONCLUSIONS: The reduction of carbohydrate intake without restricting caloric intake is more potent to achieve weight loss over 12 weeks when compared to a calorie-restricted diet in overweight/obese adults. The combination of restricting carbohydrate and total calorie intake may augment the beneficial effects of reducing BMI, body weight, and metabolic risk factors among overweight/obese individuals. TRIAL REGISTRATION: The study was approved by the institutional review board of Zhujiang Hospital of Southern Medical University and registered at the China Clinical Trial Registration Center (registration number: ChiCTR1800015156).

(n, m) Distribution of Single-Walled Carbon Nanotubes Grown from a Non-Magnetic Palladium Catalyst.

Non-magnetic metal nanoparticles have been previously applied for the growth of single-walled carbon nanotubes (SWNTs). However, the activation mechanisms of non-magnetic metal catalysts and chirality distribution of synthesized SWNTs remain unclear. In this work, the activation mechanisms of non-magnetic metal palladium (Pd) particles supported by the magnesia carrier and thermodynamic stabilities of nucleated SWNTs with different (n, m) are evaluated by theoretical simulations. The electronic metal-support interaction between Pd and magnesia upshifts the d-band center of Pd, which promotes the chemisorption and dissociation of carbon precursor molecules on the Pd surface, making the activation of magnesia-supported non-magnetic Pd catalysts for SWNT growth possible. To verify the theoretical results, a porous magnesia supported Pd catalyst is developed for the bulk synthesis of SWNTs by chemical vapor deposition. The chirality distribution of Pd-grown SWNTs is understood by operating both Pd-SWNT interfacial formation energy and SWNT growth kinetics. This work not only helps to gain new insights into the activation of catalysts for growing SWNTs, but also extends the use of non-magnetic metal catalysts for bulk synthesis of SWNTs.

Closed testing with Globaltest, with application in metabolomics.

The Globaltest is a powerful test for the global null hypothesis that there is no association between a group of features and a response of interest, which is popular in pathway testing in metabolomics. Evaluating multiple feature sets, however, requires multiple testing correction. In this paper, we propose a multiple testing method, based on closed testing, specifically designed for the Globaltest. The proposed method controls the familywise error rate simultaneously over all possible feature sets, and therefore allows post hoc inference, that is, the researcher may choose feature sets of interest after seeing the data without jeopardizing error control. To circumvent the exponential computation time of closed testing, we derive a novel shortcut that allows exact closed testing to be performed on the scale of metabolomics data. An R package ctgt is available on comprehensive R archive network for the implementation of the shortcut procedure, with applications on several real metabolomics data examples.

Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis.

Background: Insulin secretory agents are commonly used to treat type 2 diabetes. However, traditional insulin secretory agents such as sulfonylureas and glinides have side effects of hypoglycemia. In recent years, researchers have discovered that berberine can inhibit the voltage-gated k+ channels of pancreatic ß cell membrane and promote insulin secretion without causing hypoglycemia, because the glucose-lowering effects of berberine are only under hyperglycemic conditions or in a high-glucose-dependent manner. In order to shed light on the glucose-lowing effects of berberine in type 2 diabetes with different baseline fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), we conducted a meta-analysis of randomized controlled trials. Methods: We searched eight databases, which included PubMed, EMBASE, Web of Science, the Cochrane Library, and the Chinese databases such as Sino-Med, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database for Chinese Technical Periodicals, for randomized controlled trials, with berberine as the intervention and patients with type 2 diabetes mellitus as subjects, published up until November 2021. We analyzed the glucose-lowing effects of berberine, including its effects on FPG, HbA1c and 2-h plasma blood glucose (2hPBG), by calculating weighted mean differences (WMD) and 95% confidence interval (CI). To assess the safety of berberine, we analyzed the incidence of total adverse events and hypoglycemia by calculating relative risk (RR) and 95% CI. Results: Thirty-seven studies involving 3,048 patients were included in the meta-analysis. The results showed that berberine could reduce FPG (WMD = -0.82 mmol/L, 95% CI (-0.95, -0.70)), HbA1c (WMD = -0.63%, 95% CI (-0.72, -0.53)), and 2hPBG (WMD = -1.16 mmol/L, 95% CI (-1.36, -0.96)), with all results being statistically significant. Subgroup analyses revealed that the glucose-lowering effect of berberine was associated with baseline mean FPG and HbA1c in type 2 diabetes. In addition, berberine alone or in combination with oral hypoglycemic agents (OHAs) in the treatment of T2DM did not significantly increase the incidence of total adverse events (RR = 0.73, 95% CI (0.55, 0.97), p = 0.03) and the risk of hypoglycemia (RR = 0.48, 95% CI (0.21, 1.08), p = 0.08). Conclusion: Berberine has a glucose-lowering effect, which is related to the baseline FPG and HbA1c levels of patients. Treatment with berberine may be safe since it does not increase the incidence of total adverse events and the risk of hypoglycemia. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=292975, identifier CRD42021292975.

Cultivation of different seaweed species and seasonal changes cause divergence of the microbial community in coastal seawaters.

Although the effects of certain species of seaweed on the microbial community structure have long been a research focus in marine ecology, the response of the microbial community to seasons and different seaweed species is poorly understood. In the present study, a total of 39 seawater samples were collected during 3 months from three zones: Neoporphyra haitanensis cultivation zones (P), Gracilaria lemaneiformis-Saccharina japonica mixed cultivation zones (G), and control zones (C). These samples were then analyzed using 18S and 16S rRNA gene sequencing to ascertain the fungal and bacterial communities, respectively, along with the determination of environmental factors. Our results showed that increased dissolved oxygen (DO), decreased inorganic nutrients, and released dissolved organic matter (DOM) in seaweed cultivation zone predominantly altered the variability of eukaryotic and prokaryotic microbial communities. Certain microbial groups such as Aurantivirga, Pseudomonas, and Woeseia were stimulated and enriched in response to seaweed cultivation, and the enriched microorganisms varied across seaweed cultivation zones due to differences in the composition of released DOM. In addition, seasonal changes in salinity and temperature were strongly correlated with microbial community composition and structure. Our study provides new insights into the interactions between seaweed and microbial communities.

Visualizing germination of microbiota endospores in the mammalian gut.

Transmission of bacterial endospores between the environment and people and the following germination in vivo play critical roles in both the deadly infections of some bacterial pathogens and the stabilization of the commensal microbiotas in humans. Our knowledge about the germination process of different bacteria in the mammalian gut, however, is still very limited due to the lack of suitable tools to visually monitor this process. We proposed a two-step labeling strategy that can image and quantify the endospores' germination in the recipient's intestines. Endospores collected from donor's gut microbiota were first labeled with fluorescein isothiocyanate and transplanted to mice via gavage. The recipient mice were then administered with Cyanine5-tagged D-amino acid to label all the viable bacteria, including the germinated endospores, in their intestines in situ. The germinated donor endospores could be distinguished by presenting two types of fluorescent signals simultaneously. The integrative use of cell-sorting, 16S rDNA sequencing, and fluorescence in situ hybridization (FISH) staining of the two-colored bacteria unveiled the taxonomic information of the donor endospores that germinated in the recipient's gut. Using this strategy, we investigated effects of different germinants and pre-treatment interventions on their germination, and found that germination of different commensal bacterial genera was distinctly affected by various types of germinants. This two-color labeling strategy shows its potential as a versatile tool for visually monitoring endospore germination in the hosts and screening for new interventions to improve endospore-based therapeutics.

Gut microbiota diversity in middle-aged and elderly patients with end-stage diabetic kidney disease.

Background: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD), but the mechanism between DKD and ESRD remains unclear. Some experts have put forward the "microbial-centered ESRD development theory", believing that the bacterial load caused by gut microecological imbalance and uremia toxin transfer are the core pathogenic links. The purpose of this study was to analyze the genomic characteristics of gut microbiota in patients with ESRD, specifically DKD or non-diabetic kidney disease (NDKD). Methods: In this cross-sectional study, patients with ESRD were recruited in a community, including 22 DKD patients and 22 NDKD patients matched using gender and age. Fecal samples of patients were collected for 16S rDNA sequencing and gut microbiota analysis. The distribution structure, diversity, and abundance of microflora in DKD patients were analyzed by constructing species evolutionary trees and analyzing alpha diversity, beta diversity, and linear discriminant analysis effect size (LEfSe). Results: The results of our study showed that there were statistically significant differences in the richness and species of gut microbiota at the total level between DKD patients and NDKD patients. The analysis of genus level between the two groups showed significant differences in 16 bacterial genera. Among them, Oscillibacter, Bilophila, UBA1819, Ruminococcaceae UCG-004, Anaerotruncus, Ruminococcaceae, and Ruminococcaceae NK4A214 bacteria in DKD patients were higher than those in NDKD patients. Conclusions: 16S rDNA sequencing technology was used in this study to analyze the characteristics of intestinal flora in ESRD patients with or without diabetes. We found that there was a significant difference in the intestinal flora of ESRD patients caused by DKD and NDKD, suggesting that these may be potential causative bacteria for the development of ERSD in DKD patients.