Comparison of the effectiveness of probiotic supplementation in glucose metabolism, lipid profile, inflammation and oxidative stress in pregnant women.

Objective: The optimal probiotic supplementation in pregnant women has not been thoroughly evaluated. By employing a network meta-analysis (NMA) approach, we compared the effectiveness of different probiotic supplementation strategies for pregnant women. Methods: A comprehensive search across multiple databases was performed to identify studies comparing the efficacy of probiotic supplements with each other or the control (placebo) among pregnant women. Results: This NMA, including 32 studies, systematically evaluated 6 probiotic supplement strategies: Lactobacillus, Lacticaseibacillus rhamnosus and Bifidobacterium (LRB), Lactobacillus acidophilus and Bifidobacterium (LABB), Lactobacillus acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum (LLB), multi-combination of four probiotics (MP1), and multi-combination of six or more probiotics (MP2). Among these strategies, LLB, MP1, and MP2 all contain LABB. The NMA findings showed that MP1 was the most effective in reducing fasting blood sugar (FBS) (surface under the cumulative ranking curve [SUCRA]: 80.5%). In addition, MP2 was the most efficacious in lowering the homeostasis model assessment of insulin resistance (HOMA-IR) (SUCRA: 89.1%). LABB was ranked as the most effective in decreasing low-density lipoprotein cholesterol (LDLC) (SUCRA: 95.5%), total cholesterol (TC) (SUCRA: 95.5%), and high-sensitivity C-reactive protein (hs-CRP) (SUCRA: 94.8%). Moreover, LLB was ranked as the most effective in raising total antioxidant capacity (TAC) (SUCRA: 98.5%). Conclusion: Multi-combination of probiotic strains, especially those strategies containing LABB, may be more effective than a single probiotic strain in glycolipid metabolism, inflammation, and oxidative stress of pregnant women.

Blood Group Antigen A Carriers Exhibit an Extended Progression-Free Survival with no more Immune-Related Adverse Events.

Extensive investigations have been conducted regarding the potential correlation between blood type and the immune system, as well as cancer risk in the Southern Chinese population. However, the prognostic value of the blood group and its genetic determinants in the context of immune checkpoint inhibitor (ICI) treatment remains unclear. Therefore, the associations between the ABO blood group and its single nucleotide polymorphisms (SNPs) were examined in relation to ICI treatment outcomes in 370 eligible patients with cancer. This approach allowed us to derive the blood group from the SNPs responsible for blood group determination. In the discovery cohort (N = 168), antigen A carriers (blood types A and AB) exhibited an extended progression-free survival (PFS; hazard ratio (HR) = 0.58, 95% confidence interval (CI) = 0.34-0.98). The association results from the SNP-derived blood were consistent with those from the measured blood group. In the validation cohort (N = 202), Cox regression analysis revealed that the antigen A carriers (rs507666 AA+GA genotype carriers) experienced significantly extended PFS compared with the non-antigen A carriers (HR = 0.61, 95% CI = 0.40-0.93). Therefore, a longer PFS was observed in antigen A carriers (P value = 0.003, HR = 0.60, 95% CI = 0.44-0.84). Furthermore, haplotype 2 carriers (rs507666 GA and rs659104 GG) demonstrated both extended PFS and improved overall survival. Notably, the presence of antigen A was not associated with the occurrence of overall immune-related adverse events (irAEs) or organ-specific toxicity. In summary, our findings revealed that antigen A carriers did not experience a higher incidence of irAEs while exhibiting better immunotherapy efficacy.

Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19.

Background: COVID-19 could develop severe respiratory symptoms in certain infected patients, especially in the patients with immune disorders. Gut microbiome and plasma metabolome act important immunological modulators in the human body and could contribute to the immune responses impacting the progression of COVID-19. However, the causal relationship between specific intestinal bacteria, metabolites and severe COVID-19 remains not clear. Methods: Based on two-sample Mendelian randomization (MR) framework, the causal effects of 131 intestinal taxa and 452 plasma metabolites on severe COVID-19 were evaluated. Single nucleotide polymorphisms (SNPs) strongly associated with the abundance of intestinal taxa and the concentration of plasma metabolites had been utilized as the instrument variables to infer whether they were causal factors of severe COVID-19. In addition, mediation analysis was conducted to find the potential association between the taxon and metabolite, and further colocalization analysis had been performed to validate the causal relationships. Results: MR analysis identified 13 taxa and 53 metabolites, which were significantly associated with severe COVID-19 as causal factors. Mediation analysis revealed 11 mediated relationships. Myo-inositol, 2-stearoylglycerophosphocholine, and alpha-glutamyltyrosine, potentially contributed to the association of Howardella and Ruminiclostridium 6 with severe COVID-19, respectively. Butyrivibrio and Ruminococcus gnavus could mediate the association of myo-inositol and N-acetylalanine, respectively. In addition, Ruminococcus torques abundance was colocalized with severe COVID-19 (PP.H4 = 0.77) and the colon expression of permeability related protein RASIP1 (PP.H4 = 0.95). Conclusions: Our study highlights the potential causal relationships between gut microbiome, plasma metabolome and severe COVID-19, which potentially serve as clinical biomarkers for risk stratification and prognostication and benefit the mechanism mechanistic investigation of severe COVID-19.

Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization.

Hydrochlorothiazide (HCTZ) is reported to impair glucose tolerance and may induce new onset of diabetes, but the pharmacomicrobiomics of the adverse effect for HCTZ remains unknown. Mice-fed HCTZ exhibited insulin resistance and impaired glucose tolerance. By using FMT and antibiotic cocktail models, we found that HCTZ-induced metabolic disorder was mediated by commensal microbiota. HCTZ consumption disturbed the structure of the intestinal microbiota, causing abnormal elevation of Gram-negative Enterobacteriaceae and lipopolysaccharide (LPS) then leading to intestinal barrier dysfunction. Additionally, HCTZ activated TLR4 signaling and induced macrophage polarization and inflammation in the liver. Furthermore, HCTZ-induced macrophage polarization and metabolic disorder were abrogated by blocking TLR4 signaling. HCTZ consumption caused a significant increase in Gram-negative Enterobacteriaceae, which elevated the levels of LPS, thereby activating LPS/TLR4 pathway, promoting inflammation and macrophage polarization, and resulting in metabolic disorders. These findings revealed that the gut microbiome is the key medium underlying HCTZ-induced metabolic disorder.

High-solids enzymatic saccharification of starch-rich raw herbal biomass residues for producing high titers of glucose.

The bioresource utilization of herbal biomass residues (HBRs) has been receiving more attention. Herein, three different HBRs from Isatidis Radix (IR) and Sophorae Flavescentis Radix (SFR) and Ginseng Radix (GR) were subjected to batch and fed-batch enzymatic hydrolysis to produce high-concentration glucose. Compositional analysis showed the three HBRs had substantial starch content (26.36-63.29%) and relatively low cellulose contents (7.85-21.02%). Due to their high starch content, the combined action of cellulolytic and amylolytic enzymes resulted in greater release of glucose from the raw HBRs compared to using the individual enzyme alone. Batch enzymatic hydrolysis of 10% (w/v) raw HBRs with low loadings of cellulase (≤ 10 FPU/g substrate) and amylolytic enzymes (≤ 5.0 mg/g substrate) led to a high glucan conversion of ≥ 70%. The addition of PEG 6000 and Tween 20 did not contribute to glucose production. Furthermore, to achieve higher glucose concentrations, fed-batch enzymatic hydrolysis was conducted using a total solid loading of 30% (w/v). After 48-h of hydrolysis, glucose concentrations of 125 g/L and 92 g/L were obtained for IR and SFR residues, respectively. GR residue yielded an 83 g/L glucose concentration after 96 h of digestion. The high glucose concentrations produced from these raw HBRs indicate their potential as ideal substrate for a profitable biorefinery. Notably, the obvious advantage of using these HBRs is the elimination of the pretreatment step, which is typically required for agricultural and woody biomass in similar studies.

Integrated analysis of clinical and genetic factors on the interindividual variation of warfarin anticoagulation efficacy in clinical practice.

AIM: The anticoagulation effect of warfarin is usually evaluated by percentage of time in therapeutic range (PTTR), which is negatively correlated with the risk of warfarin adverse reactions. This study aimed to explore the effects of genetic and nongenetic factors on anticoagulation efficacy of warfarin during different therapeutic range. METHODS: We conducted an observational retrospective study aiming at evaluating the impact of clinical and genetic factors on PTTR from initial to more than six months treatment. This analysis included patients with heart valve replace (HVR) surgery who underwent long-term or life-long time treatment with standard-dose warfarin for anticoagulation control in Second Xiangya Hospital. All patients were followed for at least 6 months. We genotyped single nucleotide polymorphisms in VKORC1 and CYP2C9 associated with altered warfarin dose requirements and tested their associations with PTTR. RESULTS: A total of 629 patients with intact clinical data and available genotype data were enrolled in this study, and only 38.63% patients achieved good anticoagulation control (PTTR > 0.6). Clinical factors, including male gender, older age, overweight, AVR surgery and stroke history, were associated with higher PTTR. Patients with VKORC1 -1639AA genotype had significantly higher PTTR level compared with GA/GG genotype carriers only in the first month of treatment. Patients with CYP2C9*3 allele had higher PTTR compared with CYP2C9*1*1 carriers. Moreover, compared with VKORC1 -1639 AG/GG carriers, INR > 4 was more likely to be present in patients with AA genotype. The frequency of CYP2C9*1*3 in patients with INR > 4 was significantly higher than these without INR > 4. CONCLUSION: We confirmed the relevant factors of warfarin anticoagulation control, including genetic factors (VKORC1 -1639G > A and CYP2C9*3 polymorphisms) and clinical factors (male gender, older age, overweight, AVR surgery and stroke history), which could be helpful to individualize warfarin dosage and improve warfarin anticoagulation control during different treatment period.

Cellulose esterification with carboxylic acid in deep eutectic solvent pretreatment inhibits enzymatic hydrolysis.

Avicel cellulose was pretreated using two commonly used carboxylic acid-based deep eutectic solvents, i.e., choline chloride-lactic acid and choline chloride-formic acid. The pretreatment process resulted in the formation of cellulose esters with lactic acid and formic acid, which was confirmed by infrared and nuclear magnetic resonance spectra. Surprisingly, the esterified cellulose led to a significant decrease in the 48-h enzymatic glucose yield (≥75%) compared to raw Avicel cellulose. Analysis of changes in cellulose properties caused by pretreatment, including crystallinity, degree of polymerization, particle size and cellulose accessibility, contradicted the observed decline in enzymatic cellulose hydrolysis. However, removing the ester groups through saponification largely recovered the reduction in cellulose conversion. The decreased enzymatic cellulose hydrolysis by esterification may be attributed to changes in the interaction between cellulose-binding domain of cellulase and cellulose. These findings provide valuable insights into improving the saccharification of lignocellulosic biomass pretreated by carboxylic acid-based DESs.

Multidimensional evaluation of teaching strategies for pharmacology based on a comprehensive analysis involving 21,269 students.

Background: Given the limitations of traditional pharmacology pedagogical method, diverse novel teaching methods have been widely explored. In this study, we performed a network meta-analysis (NMA) to evaluate the effects of different strategies in pharmacology education. Methods: Literature databases were searched from their inception to November 2022, and the studies were screened according to predefined inclusion and exclusion criteria to extract important information. Outcomes, including theoretical test scores, experimental test scores, subjective test scores, satisfaction scores, and the proportion of satisfaction, were analyzed using R software (version 3.6.1) and STATA (version 15). The NMA was conducted with a random-effects model under the Bayesian framework to calculate odds ratios (ORs) or mean differences (MDs) with associated 95% credible intervals (95% CIs). Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the teaching methods examined. Results: A total of 150 studies involving 21,269 students were included. This NMA systematically evaluated 24 teaching strategies, such as problem-based learning (PBL), team-based learning (TBL), case-based learning (CBL) and flipped classrooms (FC), etc., The results of the NMA showed that, PBL combined with CBL was most likely to improve students' theoretical and subjective test scores (SUCRA = 75.49 and 98.19%, respectively), TBL was most likely to improve the experimental test score (SUCRA = 92.38%) and the satisfaction score (SUCRA = 88.37%), while FC had the highest probability of being the best option for improving the proportion of satisfaction (SUCRA = 84.45%). Conclusion: The current evidence indicates that TBL, PBL combined with CBL, and FC might be optimal strategies for pharmacology education since they have a more beneficial effect on students.

Planting Anion Channels in a Negatively Charged Polyamide Layer for Highly Selective Nanofiltration Separation.

A nanofiltration (NF) membrane with high salt permeation and high retention of small organics is appealing for the treatment of high-salinity organic wastewater. However, the conventional negatively charged NF membranes commonly show high retention of divalent anions (e.g., SO42-), and the reported positively charged NF membranes normally suffer super low selectivity for small organics/Na2SO4 and high fouling potential. In this work, we propose a novel "etching-swelling-planting" strategy assisted by interfacial polymerization and mussel-inspired catecholamine chemistry to prepare a mix-charged NF membrane. By X-ray photoelectron spectroscopy depth profiling and pore size distribution analysis, it was found that such a strategy could not only deepen the positive charge distribution but also narrow the pore size. Molecular dynamics confirm that the planted polyethyleneimine chains play an important role to relay SO42- ions to facilitate their transport across the membrane, thus reversing the retention of Na2SO4 and glucose (43 vs 71%). Meanwhile, due to the high surface hydrophilicity and smoothness as well as the preservation of abundant negatively charged groups (-OH and -COOH) inside the separation layer, the obtained membrane exhibited excellent antifouling performance, even for the coking wastewater. This study advances the importance of vertical charge distribution of NF membranes in separation selectivity and antifouling performance.

Highly efficient glucose production from raw non-pretreated Chinese medicinal herbal residues via the synergism of cellulase and amylolytic enzymes.

Available literature on Chinese medicinal herbal residues (CMHRs) bioconversion highlights pretreatment prior to saccharification with cellulase without considering the presence of starch constituent. Herein, four commonly found CMHRs were tested for starch content, and it was found they all contained starch with content ranging from 4.74% to 16.78%. Hydrolysis of raw CMHRs with combined cellulase and amylolytic enzymes yielded increments of 16.85% to 26.51% in 48-h glucan conversion compared to cellulase alone. Further study showed 48-h glucan conversion of raw CMHRs outperformed that pretreated by water-ethanol successive extraction, ultrasound and acid, but underperformed alkali-pretreated CMHRs. Although increasing 48-h glucan conversion in the range of 7.40% to 24.10% compared to raw CMHRs, alkaline pretreatment demonstrated low glucose recovery and incurred additional cost, making it unfavorable. Saccharification of the four raw CMHRs with combined enzymes seems like a preferred option considering the elimination of high-cost pretreatment step.

Magnesium Isoglycyrrhizinate Attenuates Anti-Tuberculosis Drug-Induced Liver Injury by Enhancing Intestinal Barrier Function and Inhibiting the LPS/TLRs/NF-κB Signaling Pathway in Mice.

Liver injury caused by first-line anti-tuberculosis (anti-TB) drugs accounts for a high proportion of drug-induced liver injury (DILI), and gut microbiota and intestinal barrier integrity have been shown to be involved in the development of DILI. Magnesium isoglycyrrhizinate (MgIG) is the fourth-generation glycyrrhizic acid preparation, which is well documented to be effective against anti-TB DILI, but the underlying mechanism is largely unclear. In the present study, we established a BALB/c mice animal model of the HRZE regimen (39 mg/kg isoniazid (H), 77 mg/kg rifampicin (R), 195 mg/kg pyrazinamide (Z), and 156 mg/kg ethambutol (E))-induced liver injury to investigate the protective effect of MgIG against anti-TB DILI and underlying mechanisms. The results demonstrated that intraperitoneal injection of MgIG (40 mg/kg) significantly ameliorated HRZE-induced liver injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and malondialdehyde (MDA) levels and improved liver pathological changes. Species composition analysis of gut microbiota showed that Lactobacillus was the only probiotic that was down-regulated by HRZE and recovered by MgIG. In addition, MgIG attenuated HRZE-induced intestinal pathology, significantly decreased HRZE-induced intestinal permeability by increasing the protein expression of tight junction protein 1 (ZO-1) and occludin, decreased HRZE-induced high lipopolysaccharide (LPS) levels, and further markedly attenuated mRNA expression levels of TNF-α, IL-6, TLR2, TLR4, and NF-κB. Supplementation with Lactobacillus rhamnosus JYLR-005 (>109 CFU/day/mouse) alleviated HRZE-induced liver injury and inflammation in mice. In summary, MgIG effectively ameliorated HRZE-induced liver injury by restoring the abundance of Lactobacillus, enhancing intestinal barrier function, and further inhibiting the activation of the LPS/TLRs/NF-κB signaling pathway. Regulating gut microbiota and promoting the integrity of intestinal barrier function may become a new direction for the prevention and treatment of anti-TB DILI.

Vitamin D metabolism pathway polymorphisms are associated with efficacy and safety in patients under anti-PD-1 inhibitor therapy.

Aim: Vitamin D (VitD) signaling has been increasingly investigated for its role in stimulating the innate and adaptive immune systems and suppressing inflammatory responses. Therefore, we examined the associations between VitD-related genetic polymorphisms, plasma 25-hydroxyvitamin D (25(OH)D), and the efficacy and safety of immune checkpoint inhibitors (ICIs). Patients and methods: A total of 13 single-nucleotide polymorphisms (SNPs) in VitD metabolic pathway genes were genotyped in 343 cancer patients receiving ICI treatment using the MassARRAY platform. In 65 patients, the associations between plasma 25(OH)D levels and ICI treatment outcomes were investigated further. Results: We found that the CYP24A1 rs6068816TT and rs2296241AA genotypes were significantly higher in patients who responded to ICIs. Furthermore, patients with higher plasma 25(OH)D levels had a better treatment response. The distribution of allele and genotype frequencies showed that three SNPs (rs10877012, rs2762934, and rs8018720) differed significantly between patients who had immune-related adverse events (irAEs) and those who did not. There was no statistically significant relationship between plasma 25(OH)D levels and the risk of irAEs. Conclusion: In summary, our findings showed that genetic variations in the VitD metabolism pathway were associated with ICI treatment outcomes, and VitD supplementation may be useful in improving ICI treatment efficacy.

Enhancing the Antifouling Ability of a Polyamide Nanofiltration Membrane by Narrowing the Pore Size Distribution via One-Step Multiple Interfacial Polymerization.

Application of nanofiltration membranes in industries still has to contend with membrane fouling that causes a significant loss of separation performance. Herein, an innovative approach to design antifouling membranes with a narrowed pore size distribution by interfacial polymerization (IP) assisted by silane coupling agents is reported. An aqueous solution of piperazine anhydrous (PIP) and γ-(2,3-epoxypropoxy) propytrimethoxysilane (KH560) is employed to perform IP with an organic solution of trimesoyl chloride and tetraethyl orthosilicate (TEOS) on a porous support. In accordance with the results of molecular dynamics and dissipative particle dynamics simulations, the reactive additive KH560 accelerates the diffusion rate of PIP to enrich at the reaction boundary. Moreover, the hydrolysis/condensation of KH560 and TEOS at the aqueous/organic interface forms an interpenetrating network with the polyamide network, which regulates the separation layer structure. The characterization results indicate that the polyamide-silica membrane has a denser, thicker, and uniform separation layer. The mean pore size of the polyamide-silica membrane and the traditional polyamide membrane is 0.62 and 0.74 nm, respectively, and these correspond to the geometric standard deviation (namely, pore size distribution) of 1.39 and 1.97, respectively. It is proved that the narrower pore size distribution endows the polyamide-silica membrane with stronger antifouling performance (flux decay ratio decreases from 18.4 to 3.8%). Such a membrane also has impressive long-term antifouling stability during cane molasses decolorization at a high temperature (50 °C). The outcomes of this study not only provide a novel one-step multiple IP strategy to prepare antifouling nanofiltration membranes but also emphasize the importance of pore size distribution in fouling control for various industrial liquid separations.

Acid-Sensitive Nanoparticles Based on Molybdenum Disulfide for Photothermal-Chemo Therapy.

The combination of multiple treatments has recently been investigated for tumor treatment. In this study, molybdenum disulfide (MoS2) with excellent photothermal conversion performance was used as the core, and manganese dioxide (MnO2), which responds to the tumor microenvironment, was loaded on its surface by liquid deposition to form a mesoporous core-shell structure. Then, the chemotherapeutic drug Adriamycin (DOX) was loaded into the hole. To further enhance its water solubility and stability, the surface of MnO2 was modified with mPEG-NH2 to prepare the combined antitumor nanocomposite MoS2@DOX/MnO2-PEG (MDMP). The results showed that MDMP had a diameter of about 236 nm, its photothermal conversion efficiency was 33.7%, and the loading and release rates of DOX were 13 and 65%, respectively. During in vivo and in vitro studies, MDMP showed excellent antitumor activity. Under the combined treatment, the tumor cell viability rate was only 11.8%. This nanocomposite exhibits considerable potential for chemo-photothermal combined antitumor therapy.

Chemoenzymatic Cascade Reaction for Green Cleaning of Polyamide Nanofiltration Membrane.

Chemical cleaning is indispensable for the sustainable operation of nanofiltration (NF) in wastewater treatment. However, the common chemical cleaning methods are plagued by low cleaning efficiency, high chemical consumption, and separation performance deterioration. In this work, a chemoenzymatic cascade reaction is proposed for pollutant degradation and polyamide NF membrane cleaning. Glucose oxidase (GOD) enzymatic reaction in this cascade system produces hydrogen peroxide (H2O2) and gluconic acid to trigger the oxidation of foulants by Fe3O4-catalyzed Fenton reaction. By virtue of the microenvironment (pH and H2O2 concentration) engineering and substrate enrichments, this chemoenzymatic cascade reaction (GOD-Fe3O4) exhibits a favorable degradation efficiency for bisphenol A and methyl blue (MB). Thanks to the strong oxidizing degradation, the water flux of the NF10 membrane fouled by MB is almost completely recovered (∼95.8%) after a 3-cycle fouling/cleaning experiment. Meanwhile, the chemoenzymatic cascade reaction improves the applicability of the Fenton reaction in polyamide NF membrane cleaning because it prevents the membrane from damaging by high concentration of H2O2 and inhibits the secondary fouling caused by ferric hydroxide precipitates. By immobilizing GOD on the aminated Fe3O4 nanoparticles, a reusable cleaning agent is prepared for highly efficient membrane cleaning. This chemoenzymatic cascade reaction without the addition of an acid/base/oxidant provides a promising candidate for sustainable and cost-effective cleaning for the polyamide NF membrane.

Comparative effectiveness of glycyrrhizic acid preparations aimed at preventing and treating anti-tuberculosis drug-induced liver injury: A network meta-analysis of 97 randomized controlled trials.

BACKGROUND AND OBJECTIVES: Clinical guidelines and expert consensus do not yet recommend glycyrrhizic acid (GA) preparations, such as compound glycyrrhizin, diammonium glycyrrhizin, magnesium isoglycyrrhizinate (MGIG), et al., for the prevention of anti-tuberculosis(anti-TB) drug-induced liver injury (DILI) due to insufficient evidence. Although these GA preparations are recommended for the treatment of anti-TB DILI, which one performs best is unclear. Previous conventional meta-analyses did not summarize the results of simultaneous comparisons of different glycyrrhizinate preparations. Therefore, we aimed to compare and rank different GA preparations on preventing and treating the anti-TB DILI by network meta-analysis (NMA). METHODS: A systematic search on PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure, SinoMed, Chongqing VIP and, the Wanfang Database was performed up to December 19, 2020. The literature was screened according to predefined inclusion and exclusion criteria to extract important information. The outcomes were the incidence of liver injury (prevention section) and treatment response rate (treatment section). The NMA was conducted with a random-effects model under the Bayesian framework to calculate risk ratios (RRs) with 95% credible intervals (95% CrIs) using R software (version 3.6.1). RESULTS: From 1,411 publications, we included 97 relevant randomized clinical trials (RCTs) (10,923 participants). In terms of preventing anti-TB DILI (33 RCTs, comprising 5,762 patients), CGC, DGC, DGEC, and DGI, but not CGI, significantly reduced the incidence of liver injury than control group (RRs ranged from 0.26 to 0.58); CGC and DGEC were superior to DGC (RRs = 0.50 and 0.58, respectively). In terms of treating anti-TB DILI (64 RCTs, comprising 5,161 patients), MGIG was most effective among all regimens (RRs ranged from 1.15 to 1.72) while DGC ranked last (RRs ranged from 0.58 to 0.83). CONCLUSIONS: All GA preparations except for CGI were effective in preventing the incidence of anti-TB DILI and CGC was superior to DGC. MGIG seems to be the best choice among all GA preparations for the treatment of anti-TB DILI. Future clinical practice guidelines should factor in these novel findings to improve patient outcomes; however, further high-quality trials are needed to validate these results.

Regenerable temperature-responsive biocatalytic nanofiltration membrane for organic micropollutants removal.

Biocatalytic nanofiltration membranes (BNMs) exhibit great potentials in organic micropollutants removal attributed to its synergistic effect between enzyme catalysis and membrane separation. However, the difficulties in regeneration of the BNMs halted their economic practicality. Inspired by cell membranes with stimuli-responsive channels, we have developed the temperature-responsive BNMs with nanogating function by poly(N-isopropyl acrylamide) (PNIPAM) modification. PNIPAM modification increases the geometric confinement of the support layer to enzymes, thus improving enzyme loading, inhibiting enzyme leakage, and preventing membrane permeability decline caused by enzyme excess migration and aggregation. By optimizing the concentration of reaction monomers, modification time, and strategies, the PNIPAM-based BNMs show high bisphenol A (BPA) removal efficiency and long-term stability. Furthermore, the PNIPAM-polyethyleneimine-based BNMs can be easily regenerated at 38°C, and the laccase activity and BPA removal efficiency are fully recovered. This work would promote the real application of BNMs in bioconversion, drug delivery, and biosensors.

An enzymatic membrane reactor for oligodextran production: Effects of enzyme immobilization strategies on dextranase activity.

An enzymatic membrane reactor (EMR) with immobilized dextranase provides an excellent opportunity for tailoring the molecular weight (Mw) of oligodextran to significantly improve product quality. However, a highly efficient EMR for oligodextran production is still lacking and the effect of enzyme immobilization strategy on dextranase hydrolysis behavior has not been studied yet. In this work, a functional layer of polydopamine (PDA) or nanoparticles made of tannic acid (TA) and hydrolysable 3-amino-propyltriethoxysilane (APTES) was first coated on commercial membranes. Then cross-linked dextranase or non-cross-linked dextranase was loaded onto the modified membranes using incubation mode or fouling-induced mode. The fouling-induced mode was a promising enzyme immobilization strategy on the membrane surface due to its higher enzyme loading and activity. Moreover, unlike the non-cross-linked dextranase that exhibited a normal endo-hydrolysis pattern, we surprisingly found that the cross-linked dextranase loaded on the PDA modified surface exerted an exo-hydrolysis pattern, possibly due to mass transfer limitations. Such alteration of hydrolysis pattern has rarely been reported before. Based on the hydrolysis behavior of the immobilized dextranase in different EMRs, we propose potential applications for the oligodextran products. This study presents a unique perspective on the relation between the enzyme immobilization process and the immobilized enzyme hydrolysis behavior, and thus opens up a variety of possibilities for the design of a high-performance EMR.