NIR Activated Multimodal Therapeutics Based on Metal-Phenolic Networks-Functionalized Nanoplatform for Combating against Multidrug Resistance and Metastasis.

Multidrug resistance (MDR) and metastasis in cancer have become increasingly serious problems since antitumor efficiency is greatly restricted by a single therapeutic modality and the insensitive tumor microenvironment (TME). Herein, metal-phenolic network-functionalized nanoparticles (t-P@TFP NPs) are designed to realize multiple therapeutic modalities and reshape the TME from insensitive to sensitive under multimodal imaging monitoring. After a single irradiation, a near-infrared laser-activated multistage reaction occurs. t-P@TFP NPs trigger the phase transition of perfluoropentane (PFP) to release tannic acid (TA)/ferric ion (Fe3+ )-coated paclitaxel (PTX) and cause hyperthermia in the tumor region to efficiently kill cancer cells. Additionally, PTX is released after the disassembly of the TA-Fe3+ film by the abundant adenosine triphosphate (ATP) in the malignant tumor, which concurrently inhibits ATP-dependent drug efflux to improve sensitivity to chemotherapeutic agents. Furthermore, hyperthermia-induced immunogenic cell death (ICD) transforms "cold" tumors into "hot" tumors with the assistance of PD-1/PD-L1 blockade to evoke antitumor immunogenicity. This work carefully reveals the mechanisms underlying the abilities of these multifunctional NPs, providing new insights into combating the proliferation and metastasis of multidrug-resistant tumors.

Intranasal administration of ß-1, 3-galactosyltransferase 2 confers neuroprotection against ischemic stroke by likely inhibiting oxidative stress and NLRP3 inflammasome activation.

Ischemic stroke is one of the major causes of morbidity and mortality. The ß-1, 3-galactosyltransferase 2 (B3galt2), a member of ß-1, 3-galactosyltransferase family, is playing a vital role in the pathological process of cerebral ischemic injury, but its underlying mechanisms remain unclear. In the present study, we examined the involvement of oxidative stress and NLRP3 inflammasome activation in the neuroprotective effect of B3galt2. Cerebral ischemia/reperfusion (I/R) injury was simulated in a mouse middle cerebral artery occlusion (MCAO) model. Recombinant human B3galt2 (rh-B3galt2) was administered intranasally 1 h post MCAO, and TGF-ß1-siRNA was administered intracerebroventricularly 24 h before MCAO. Outcome measures included brain infarct volume, neurological function, blood-brain barrier (BBB) permeability, neuronal apoptosis, oxidative stress, and the inflammatory response. First, we found that rh-B3galt2 significantly alleviated brain infarct volume and BBB permeability, improved neurological function, and attenuated I/R-induced neuron apoptosis and oxidative stress. Furthermore, rh-B3galt2 attenuated pro-inflammatory cytokines, NF-κB, IL-6, TNF-α, and IL-1ß, and inhibited NLRP3 inflammasome activation. Finally, inhibition of TGF-ß1 by TGF-ß1-siRNA abolished the anti-oxidative and anti-inflammatory effects of rh-B3galt2 in mice after I/R. Collectively, our study demonstrated that rh-B3galt2 exerts neuroprotective effects by regulating cerebral ischemia-induced oxidative stress and NLRP3 inflammasome, which is mainly dependent on the heightening of the TGF-ß1 pathway. Thus, B3galt2 might be considered a new therapeutic target for ischemic stroke treatment.

Association between healthy lifestyle factors and health-related quality of life among Chinese adolescents: the moderating role of gender.

BACKGROUND: To examine the associations of the independent and combined healthy lifestyle factors with health-related quality of life (HRQOL) in adolescents, and to test the moderating role of gender. METHODS: This cross-sectional study included 5125 adolescents aged between 11 and 20 years. They provided self-reported data on six healthy lifestyle factors, including never smoking, never drinking, good sleep quality, sufficient sleep duration, appropriate Internet use, and adequate physical activity. Adolescents' HRQOL was evaluated using the Pediatric Quality of Life Inventory version 4.0. Linear regression models were conducted to explore the association of individual and combined healthy lifestyle factors with adolescents' HRQOL. We further performed stratified analyses and likelihood ratio test to explore the moderating role of gender in these associations. RESULTS: Of the included adolescents, the proportions with 0-2, 3, 4, and 5-6 healthy lifestyle factors were 13.6%, 26.4%, 44.3%, and 15.7%, respectively. Compared to adolescents with composite healthy lifestyle scores of 0-2, those with scores of 3, 4, or 5-6 had significantly higher HRQOL scores across all dimensions, summary scales, and total scale in both unadjusted and adjusted models. Specifically, adolescents with 5-6 healthy lifestyle factors had a total scale score that was 19.03 (95%CI: 17.76 to 20.30) points higher than their counterparts who only had 0-2 healthy lifestyle factors. Significant dose-response patterns were also observed in aforementioned associations. Gender was a significant moderator in the associations between composite healthy lifestyle groups and HRQOL scores, except for the social functioning dimension. CONCLUSIONS: Our results confirmed that combined healthy lifestyle factors were associated with improved HRQOL among adolescents, with a stronger association observed in girls. These findings underscore the necessity for education and healthcare authorities to design health-promoting strategies that encourage multiple healthy lifestyle factors in adolescents, with the objective of enhancing their overall health outcomes.

Diagnostic value of circulating microRNAs for esophageal cancer: a meta-analysis based on Asian data.

BACKGROUND AND OBJECTIVE: esophageal cancer (EC) is one of the most common gastrointestinal malignant diseases. We conducted a comprehensive meta-analysis to explore the clinical applicability of circulating microRNA for the diagnosis of EC. METHODS: as of September 10, 2021, a comprehensive literature search was conducted on PubMed, Embase, Web of Science, Cochrane Library, Wanfang Database, and China National Knowledge Infrastructure (CNKI) to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled to evaluate the test performance. The potential sources of heterogeneity were analyzed by subgroup analysis. Deeks' funnel plot was used to assess publication bias. RESULTS: 85 studies from 50 articles were included in the current meta-analysis. The overall pooled sensitivity was 0.82 (95 % CI, 0.79-0.84), specificity was 0.84 (95 % CI, 0.81-0.86), PLR was 4.9 (95 % CI, 4.2-5.9), NLR was 0.22 (95 % CI, 0.19-0.25), DOR was 22 (95 % CI, 17-29) and AUC was 0.89 (95 % CI, 0.86-0.92), respectively. Subgroup analysis suggested that miRNA clusters with a large sample size showed better diagnostic accuracy. Publication bias was not found. CONCLUSIONS: circulating miRNAs can be used as a potential non-invasive biomarker for the diagnosis of EC in Asian populations.

Siderophore Synthesis Ability of the Nitrogen-Fixing Bacterium (NFB) GXGL-4A is Regulated at the Transcriptional Level by a Transcriptional Factor (trX) and an Aminomethyltransferase-Encoding Gene (amt).

Kosakonia radicincitans GXGL-4A, a gram-negative nitrogen-fixing (NF) bacterial strain is coated with a thick capsulatus on the surface of cell wall, which becomes a physical barrier for exogenous DNA to enter the cell, so the operation of genetic transformation is difficult. In this study, an optimized Tn5 transposon mutagenesis system was established by using a high osmotic HO-1 medium combined with the electroporation transformation. Eventually, a mutant library containing a total of 1633 Tn5 insertional mutants were established. Of these mutants, the mutants M81 and M107 were found to have an enhanced capability to synthesize siderophore through the CAS agar plate assay and the spectrophotometric determination. The bacterial cells of two mutants were applied in cucumber growth-promoting experiment. Cucumber seedlings treated with M81 and M107 cells had a significant increase in biomass including seedling height, seedling fresh weight, root fresh weight, and root length. The whole genome sequencing of the mutants M81 and M107 showed that the integration sites of Tn5 transposon element were located in MmyB-like helix-turn-helix transcription regulator (locus tag: A3780_19720, trX) and aminomethyltransferase-encoding genes (locus tag: A3780_01680, amt) in the genome of GXGL-4A, respectively. The ability of siderophore synthesis of the target mutants was improved by Tn5 insertion mutagenesis, and the mutants obtained showed a good plant growth-promoting effect when applied to the cucumber seedlings. The results suggest that the identified functional genes regulates the biosynthesis of siderophore in azotobacter GXGL-4A, and the specific mechanism needs to be further investigated.

[Progress in replicative senescence of mesenchymal stem cells regulated by microenvironment].

Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can self-renew and differentiate. Numerous studies have shown that MSCs have important roles in areas such as regenerative medicine and tissue engineering. However, it is worth noting that MSCs will gradually age during long-term in vitro expansion with decreased stemness such as weakened migration ability, slowed proliferation rate and decreased differentiation potential, which greatly hinders the application of MSCs. Currently, the microenvironment for cell growth is recognized as one of the factors causing senescence in MSCs. Recent studies point out that the latest technologies such as exogenous administration, oxygen concentration regulation and extracellular matrix (ECM) construction can delay stem cell senescence by simulating or regulating the microenvironment. Here, we review the current knowledge of the characteristics and molecular mechanisms of senescent MSCs and microenvironment strategies to maintain MSCs stemness, which can provide a reference for future large-scale application of MSCs preparations in tissue engineering and clinical studies.

Regulating Exposed Facets of Metal-Organic Frameworks for High-rate Alkaline Aqueous Zinc Batteries.

Metal-organic frameworks (MOFs) have drawn growing attention as promising electrode candidates for rechargeable batteries. However, most studies focus on the direct use of MOF electrodes without any modification. Post-synthetic modification, a judicious tool to modify targeted properties of MOFs, has been long-neglected in the field of batteries. Herein, crystal-facet engineering is proposed to design MOF-based electrodes with high capacity and fast electrochemical kinetics. We found that a thermally-modified strategy can regulate the dominant exposed facet of Ni-based MOF (PFC-8). With the optimally exposed facets, the battery exhibited admirable rate capability (139.4 mAh g-1 at 2.5 A g-1 and 110.0 mAh g-1 at 30 A g-1 ) and long-term stability. Furthermore, density functional theory calculations demonstrate that stronger OH- adsorption behaviors and optimized electronic structures induced by the regulated exposed facets boost the electrochemical performance.

Rechargeable Aqueous Mn-Metal Battery Enabled by Inorganic-Organic Interfaces.

Aqueous batteries that use metal anodes exhibit maximum anodic capacity, whereas the energy density is still unsatisfactory partially due to the high redox potential of the metal anode. Current metal anodes are plagued by the dilemma that the redox potential of Zn is not low enough, whereas Al, Mg, and others with excessively low redox potential cannot work properly in aqueous electrolytes. Mn metal with a suitably low redox potential is a promising candidate, which was rarely explored before. Here, we report a rechargeable aqueous Mn-metal battery enabled by a well-designed electrolyte and robust inorganic-organic interfaces. The inorganic Sn-based interface with a bottom-up microstructure was constructed to preliminarily suppress water decomposition. With this bubble-free interface, the organic interface can be formed via an esterification reaction of sucrose triggered by acyl chloride in the electrolyte, generating a dense physical shield that isolates water while permitting Mn2+ diffusion. Hence, a Mn symmetric cell achieves a superior plating/stripping stability for 200 hours, and a Mn||V2 O5 battery maintains approximately 100 % capacity after 200 cycles. Moreover, the Mn||V2 O5 battery realizes a much higher output voltage than that of the Zn||V2 O5 battery, evidencing the possibility of increasing the energy density through using a Mn anode. This work develops a systematic strategy to stabilize a Mn-metal anode for Mn-metal batteries, opening a new door towards enhanced voltage of aqueous batteries.

Subtype-selective mechanisms of negative allosteric modulators binding to group I metabotropic glutamate receptors.

Group I metabotropic glutamate receptors (mGlu1 and mGlu5) are promising targets for multiple psychiatric and neurodegenerative disorders. Understanding the subtype selectivity of mGlu1 and mGlu5 allosteric sites is essential for the rational design of novel modulators with single- or dual-target mechanism of action. In this study, starting from the deposited mGlu1 and mGlu5 crystal structures, we utilized computational modeling approaches integrating docking, molecular dynamics simulation, and efficient post-trajectory analysis to reveal the subtype-selective mechanism of mGlu1 and mGlu5 to 10 diverse drug scaffolds representing known negative allosteric modulators (NAMs) in the literature. The results of modeling identified six pairs of non-conserved residues and four pairs of conserved ones as critical features to distinguish the selective NAMs binding to the corresponding receptors. In addition, nine pairs of residues are beneficial to the development of novel dual-target NAMs of group I metabotropic glutamate receptors. Furthermore, the binding modes of a reported dual-target NAM (VU0467558) in mGlu1 and mGlu5 were predicted to verify the identified residues that play key roles in the receptor selectivity and the dual-target binding. The results of this study can guide rational structure-based design of novel NAMs, and the approach can be generally applicable to characterize the features of selectivity for other G-protein-coupled receptors.

Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based "combo" nanoagent together with PD-L1 blockade in reversing multidrug resistance.

BACKGROUND: Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. RESULTS: In this study, we fabricated a "combo" nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. CONCLUSION: This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel.

High dose of dietary vitamin D3 modulated the yellow catfish (Pelteobagrus fulvidraco) splenic innate immune response after Edwardsiella ictaluri infection.

Vitamin D3 (VD3) has been shown to modulate the innate immune response in mammals but this has been rarely reported in fish. The current study found that increasing dietary VD3 content can reduce the density of yellow to dark brown pigmented macrophage aggregates (PMAs) in the spleens of yellow catfish infected with Edwardsiella ictaluri. The results of next-generation sequencing showed that a high dose of dietary VD3 (16,600 IU/kg) mainly affected the splenic immune response during Edwardsiella ictaluri infection via negative regulation of 'NF-κΒ transcription factor activity', 'NIK/NF-κΒ signaling' and the 'i-kappab kinase/NF-κΒ signaling' pathways. Follow-up qPCR showed that dietary VD3 increased the expression of NF-κΒ inhibitor iκb-α, decreased the expression of nf-κb p65, il-6, il1-ß and tnf-α, and down-regulated the expression of nik, ikks and nf-κb p52 in the NIK/NF-kappaB signaling pathway. The above results indicate that dietary VD3 can modulate the splenic innate immune response of yellow catfish after Edwardsiella ictaluri infection by inhibiting the NF-κB activation signaling pathways.

A novel deep-sea bacteriophage possesses features of Wbeta-like viruses and prophages.

As the most abundant biological entities, viruses are major players in marine ecosystems. However, our knowledge about virus-host interactions and viral ecology in the deep sea remains very limited. In this study, a novel bacteriophage (designated as phage BVE2) infecting Bacillus cereus group bacteria, was isolated from deep-sea sediments. Phage BVE2 caused host lysis within 1.5 h after infection. However, the presence of two integrase-encoding genes in the BVE2 genome suggested that BVE2 may also follow a temperate strategy. The genome of phage BVE2 is approximately 20 kb in length and is predicted to encode 28 proteins. Genomic and phylogenetic analysis suggested that BVE2 is a highly mosaic phage that has inherited genetic features from Wbeta-like viruses, B. cereus prophages, and its host, suggesting that frequent horizontal gene transfer events occurred during its evolution. This study will help to reveal the evolutionary history of Wbeta-like viruses and improve our understanding of viral diversity and virus-host interactions in the deep sea.

HP-NAP ameliorates OXA-induced atopic dermatitis symptoms in mice.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin inflammatory disease characterized by disequilibrium between Th1/Th2 lymphocytes. Helicobacter pylori neutrophil-activating protein (HP-NAP) has been reported that it has the potential immunomodulatory effect able to regulate the Th1/Th2 balance. OBJECTIVE: This study aimed to investigate the therapeutic effect of HP-NAP in AD mice model. METHODS: The model of AD was built with oxazolone (OXA) in BALB/c mice, then HP-NAP was used to treat AD by intraperitoneal injection. Ear thickness was measured by a digital thickness gauge. The ears tissues were collected and subjected to hematoxylin-eosin (H&E) and toluidine blue (TB) staining. The mRNA expression levels of inflammatory cytokines (IL-1ß, IL-5, IL-6, and TNF-α) in ear tissue were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The secretion of IgE, IL-4, and IFN-γ was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Treatment with HP-NAP successfully alleviated the symptoms of AD, such as erythema, horny substance, and swelling. The infiltration of lymphocytes and mast cells were significantly reduced following HP-NAP therapy. The secretion of IgE and IL-4 was significantly attenuated following treatment with HP-NAP. Additionally, HP-NAP observably downregulated inflammatory cytokine expression (e.g. IL-1ß, IL-5, IL-6, and TNF-α) in ear tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Taken together, our results showed that HP-NAP possessed the potential to be a novel immunomodulatory candidate drug against AD.

[Twin girls infected with SARS-CoV-2].

This article reports the diagnosis and treatment of twin girls who were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Hunan Province, China. The twin girls, aged 1 year and 2 months, were admitted on January 29, 2020 due to fever for one day and cough and sneezing for two days respectively. Both recovered after symptomatic treatment. The two girls had mild symptoms and rapid recovery, suggesting that children with SARS-CoV-2 infection may be mild and have a good prognosis. There were differences in the clinical symptoms and imaging findings between the twin girls, suggesting that SARS-CoV-2 infection has diverse clinical features in children.

Long non-coding RNA LINC00152 promotes cell growth and invasion of papillary thyroid carcinoma by regulating the miR-497/BDNF axis.

Long intergenic non-coding RNA 152 (LINC00152) was reported to be tightly linked to tumorigenesis and progression in multiple cancers. However, its biological role and modulatory mechanism in papillary thyroid carcinoma (PTC) has not been elucidated. In this study, we determined the expression levels of LINC00152 in PTC tissues and cell lines by quantitative real time polymerase chain reaction (qRT-PCR). Cell proliferation, colony formation, migration, and invasion were measured by a Cell Counting Kit-8 assay, colony formation analysis, wound healing, and transwell invasion assay, respectively. A luciferase reporter assay and qRT-PCR were used to determine whether LINC00152 interacts with miR-497 directly. We established a xenograft mouse model to examine the underlying molecular mechanism and effect of LINC00152 on tumor growth in vivo. We found that LINC00152 expression was significantly increased in PTC tissues and derived cell lines. LINC00152 knockdown significantly inhibited proliferation, colony formation, migration, and invasion in vitro, and impaired tumor growth in vivo. We revealed that LINC00152 functioned as a competing endogenous RNA to the miR-497 sponge, downregulating its downstream target brain-derived neurotrophic factor (BDNF), which is an oncogene in thyroid cancer. These findings suggest that LINC00152 is responsible for PTC cell proliferation and invasion and exerts its function by regulating the miR-497/BDNF axis.

BAP31 regulates IRAK1-dependent neuroinflammation in microglia.

BACKGROUND: Microglia, the mononuclear immune cells of the central nervous system (CNS), are essential for the maintenance of CNS homeostasis. BAP31, a resident and ubiquitously expressed protein of the endoplasmic reticulum, serves as a sorting factor for its client proteins, mediating the subsequent export, retention, and degradation or survival. Recently, BAP31 has been defined as a regulatory molecule in the CNS, but the function of BAP31 in microglia has yet to be determined. In the present study, we investigated whether BAP31 is involved in the inflammatory response of microglia. METHODS: This study used the BV2 cell line and BAP31 conditional knockdown mice generated via the Cre/LoxP system. A BAP31 knockdown experiment was performed to elucidate the role of BAP31 in the endogenous inflammatory cytokine production by microglial BV2 cells. A mouse model of lipopolysaccharide (LPS)-induced cognitive impairment was established to evaluate the neuroprotective effect of BAP31 against neuroinflammation-induced memory deficits. Behavioral alterations were assessed with the open field test (OFT), Y maze, and Morris water maze. The activation of microglia in the hippocampus of mice was observed by immunohistochemistry. Western blot, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and reverse transcription quantitative real-time polymerase chain reaction (RT-PCR) were used to clarify the mechanisms. RESULTS: BAP31 deficiency upregulates LPS-induced proinflammatory cytokines in BV2 cells and mice by upregulating the protein level of IRAK1, which in turn increases the translocation and transcriptional activity of NF-κB p65 and c-Jun, and moreover, knockdown of IRAK1 or use of an IRAK1 inhibitor reverses these functions. In the cognitive impairment animal model, the BAP31 knockdown mice displayed increased severity in memory deficiency accompanied by an increased expression of proinflammatory factors in the hippocampus. CONCLUSIONS: These findings indicate that BAP31 may modulate inflammatory cytokines and cognitive impairment induced by neuroinflammation through IRAK1, which demonstrates that BAP31 plays an essential role in microglial inflammation and prevention of memory deficits caused by neuroinflammation.

Properties and Applications of Extremozymes from Deep-Sea Extremophilic Microorganisms: A Mini Review.

The deep sea, which is defined as sea water below a depth of 1000 m, is one of the largest biomes on the Earth, and is recognised as an extreme environment due to its range of challenging physical parameters, such as pressure, salinity, temperature, chemicals and metals (such as hydrogen sulphide, copper and arsenic). For surviving in such extreme conditions, deep-sea extremophilic microorganisms employ a variety of adaptive strategies, such as the production of extremozymes, which exhibit outstanding thermal or cold adaptability, salt tolerance and/or pressure tolerance. Owing to their great stability, deep-sea extremozymes have numerous potential applications in a wide range of industries, such as the agricultural, food, chemical, pharmaceutical and biotechnological sectors. This enormous economic potential combined with recent advances in sampling and molecular and omics technologies has led to the emergence of research regarding deep-sea extremozymes and their primary applications in recent decades. In the present review, we introduced recent advances in research regarding deep-sea extremophiles and the enzymes they produce and discussed their potential industrial applications, with special emphasis on thermophilic, psychrophilic, halophilic and piezophilic enzymes.

[Meta-analysis of efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine in treatment of chronic urticarial].

To analyze the efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine as well as desloratadine alone in the treatment of chronic urticaria by Meta-analysis,in order to provide evidence-based reference for clinical treatment.PubMed,CBM,Wan Fang,VIP database and CNKI database were retrieved to collect randomized controlled trials( RCT) about Tripterygium Glycosides Tablets combined with desloratadine( test group) as well as desloratadine alone( control group) in the treatment of chronic urticaria. Meta-analysis was performed by using Rev Man 5. 3 software after data extraction and quality evaluation( a total of 15 RCTs were included,involving 1 411 patients). Meta-analysis showed that the total effective rate( RR = 1. 28,95%CI[1. 22,1. 35],P<0. 000 01) and the quality of life improvement rate( RR = 1. 49,95% CI[1. 33,1. 66],P< 0. 000 01) of the test group were better than those of the control group,and the recurrence rate( RR = 0. 29,95%CI[0. 21,0. 40],P<0. 000 01) was significantly lower than that of the control group,with statistically significant differences; there was no statistically significant difference in the incidence of adverse reactions( RR = 1. 02,95%CI[0. 68,1. 53],P = 0. 92) compared with the control group. Based on the included RCTs,the efficacy of Tripterygium Glycosides Tablets combined with desloratadine in the treatment of chronic urticaria were superior to those of desloratadine alone,with similarity in safety. However,due to the low quality of RCTs and the lack of large-scale multi-center studies,the results shall not be further verified by clinical trials.

PokMT1 from the Polyketomycin Biosynthetic Machinery of Streptomyces diastatochromogenes Tü6028 Belongs to the Emerging Family of C-Methyltransferases That Act on CoA-Activated Aromatic Substrates.

Recent biochemical characterizations of the MdpB2 CoA ligase and MdpB1 C-methyltransferase (C-MT) from the maduropeptin (MDP, 2) biosynthetic machinery revealed unusual pathway logic involving C-methylation occurring on a CoA-activated aromatic substrate. Here we confirmed this pathway logic for the biosynthesis of polyketomycin (POK, 3). Biochemical characterization unambiguously established that PokM3 and PokMT1 catalyze the sequential conversion of 6-methylsalicylic acid (6-MSA, 4) to form 3,6-dimethylsalicylyl-CoA (3,6-DMSA-CoA, 6), which serves as the direct precursor for the 3,6-dimethylsalicylic acid (3,6-DMSA) moiety in the biosynthesis of 3. PokMT1 catalyzes the C-methylation of 6-methylsalicylyl-CoA (6-MSA-CoA, 5) with a kcat of 1.9 min-1 and a Km of 2.2 ± 0.1 µM, representing the most proficient C-MT characterized to date. Bioinformatics analysis of MTs from natural product biosynthetic machineries demonstrated that PokMT1 and MdpB1 belong to a phylogenetic clade of C-MTs that preferably act on aromatic acids. Significantly, this clade includes the structurally characterized enzyme SibL, which catalyzes C-methylation of 3-hydroxykynurenine in its free acid form, using two conserved tyrosine residues for catalysis. A homology model and site-directed mutagenesis suggested that PokMT1 also employs this unusual arrangement of tyrosine residues to coordinate C-methylation but revealed a large cavity capable of accommodating the CoA moiety tethered to 5. CoA activation of the aromatic acid substrate may represent a general strategy that could be exploited to improve catalytic efficiency. This study sets the stage to further investigate and exploit the catalytic utility of this emerging family of C-MTs in biocatalysis and synthetic biology.

High-Throughput Design of Biocompatible Enzyme-Based Hydrogel Microparticles with Autonomous Movement.

Micro- and nanomotors and their use for biomedical applications have recently received increased attention. However, most designs use top-down methods to construct inorganic motors, which are labour-intensive and not suitable for biomedical use. Herein, we report a high-throughput design of an asymmetric hydrogel microparticle with autonomous movement by using a microfluidic chip to generate asymmetric, aqueous, two-phase-separating droplets consisting of poly(ethylene glycol) diacrylate (PEGDA) and dextran, with the biocatalyst placed in the PEGDA phase. The motor is propelled by enzyme-mediated decomposition of fuel. The speed of the motors is influenced by the roughness of the PEGDA surface after diffusion of dextran and was tuned by using higher molecular weight dextran. This roughness allows for easier pinning of oxygen bubbles and thus higher speeds of the motors. Pinning of bubbles occurs repeatedly at the same location, thereby resulting in constant circular or linear motion.