Type 2 diabetes mellitus(T2DM) is a prevalent metabolic and endocrine disorder. Long-term hyperglycemia can lead to severe chronic complications, imposing substantial economic burdens on both society and patients. Despite the availability of various hypoglycemic agents for clinical use, these agents often fail to meet the therapeutic needs of T2DM and its complications. Consequently, there is an urgent need for novel therapeutic strategies and drugs. Lithocarpus litseifolius(L. litseifolius), commonly referred to as "cordyceps on trees", has a long history of use in traditional medicine and can be applied in tea, sugar, and medicine. Research indicates that L. litseifolius extracts are rich in dihydrochalcones, including trilobatin, phloridzin, and phloretin, which exhibit a range of pharmacological activities, such as anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, hepatoprotective, and cardioprotective effects. These properties suggest potential applications in the treatment of T2DM and its complications. This review systematically compiled and organized the relevant literature from the past decade on dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts. It highlighted recent research progress regarding their role in treating T2DM and its complications through mechanisms such as reducing insulin resistance, regulating glucose transport, improving glucose and lipid metabolism, modulating enzyme activity, regulating gut microbiota, and alleviating inflammation and oxidative damage. The purpose of this review is to provide a reference and basis for future research on the prevention and treatment of T2DM and its complications using dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts.
Chalcones/chemistry* ; Diabetes Mellitus, Type 2/metabolism* ; Humans ; Animals ; Elaeocarpaceae/chemistry* ; Drugs, Chinese Herbal/therapeutic use* ; Hypoglycemic Agents/chemistry* ; Plant Extracts/chemistry*

To study the differences in transcript levels among different organs of Spatholobus suberectus and to explore the genes encoding enzymes related to the catechin biosynthesis pathway, this study utilized the genome and full-length transcriptome data of S. suberectus as references. Transcriptome sequencing and bioinformatics analysis were performed on five different organs of S. suberectus-roots, stems, leaves, flowers, and fruits-using the Illumina NovaSeq 6000 platform. A total of 115.28 Gb of clean data were obtained, with GC content values ranging from 45.19% to 47.54%, Q20 bases at 94.17% and above, and an overall comparison rate with the reference genome around 90%. In comparisons between the stem and root, stem and leaf, stem and flower, and stem and fruit, 10 666, 9 674, 9 320, and 5 896 differentially expressed genes(DEGs) were identified, respectively. The lowest number of DEGs was found in the stem and root comparison group. KEGG enrichment analysis revealed that the DEGs were mainly concentrated in the pathways of phytohormone signaling, phenylalanine biosynthesis, etc. A total of 39 genes were annotated in the catechin biosynthesis pathway, with at least one highly expressed gene found in all organs. Among these, PAL1, PAL2, C4H1, C4H3, 4CL1, 4CL2, and DFR2 showed high expression in the stems, suggesting that they may play important roles in the biosynthesis of flavonoids in S. suberectus. This study aims to provide important information for the in-depth exploration of the regulation of catechin biosynthesis in S. suberectus through transcriptome analysis of its different organs and to provide a reference for the further realization of S. suberectus varietal improvement and molecular breeding.
Catechin/biosynthesis* ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Fabaceae/metabolism* ; Transcriptome ; Flowers/metabolism* ; Plant Stems/metabolism* ; Plant Leaves/metabolism* ; Plant Roots/metabolism* ; Fruit/metabolism*

OBJECTIVE: To investigate the relationship between angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) and semen parameters. Methods： The semen samples of 820 male patients who were treated in the Reproductive Medicine Center of Taiyuan Central Hospital from August 2022 to August 2023 were retrospectively analyzed. The levels of AT1-AA and Ang Ⅱ of semen were detected by ELISA, and the function of AT1-AA was detected by cardiomyocyte beating assay in suckling rats. The patients were divided into low group, median group and high group according to the OD values of AT1-AA. The differences in general data and semen parameters between different groups were analyzed. And the correlation between AT1-AA level and semen parameters in semen of all study subjects was analyzed by the method of Spearman analysis. And the relationships between AT1-AA OD value, Ang Ⅱ level and semen parameters in the AT1-AA high value group were analyzed as well. RESULTS: AT1-AA was present in semen with good function. There was no significant difference in the general data of patients in different AT1-AA levels (P>0.05). In the comparison of semen parameters among the groups with different levels of AT1-AA, there were differences in sperm concentration, PR concentration, NP％, and ALH among the three groups (P<0.05). And AT1-AA OD value was positively correlated with total sperm count, sperm concentration, PR concentration, and NP％, and negatively correlated with semen volume (P<0.05). In the AT1-AA high value group, the OD value of AT1-AA in semen was negatively correlated with inactive sperm, and positively correlated with total motility (［PR+NP］％), curve rate, mean path rate, and ALH. However, there was no correlation between the level of Ang Ⅱ in semen and semen parameters (P>0.05). CONCLUSION The presence of AT1-AA in semen may be associated with the promotion of sperm motility.
Male ; Humans ; Autoantibodies ; Sperm Motility ; Semen ; Retrospective Studies ; Receptor, Angiotensin, Type 1/immunology* ; Animals ; Rats ; Angiotensin II ; Adult ; Sperm Count ; Semen Analysis ; Receptor, Angiotensin, Type 2/immunology*

OBJECTIVE: To investigate the effect of acupuncture on advanced cancer patients by meta-analysis. METHODS: Nine databases (the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure, the Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and WanFang Data) were searched for randomized controlled trials (RCTs) on acupuncture in advanced cancer patients published from inception to February 13, 2023 and updated to June 1, 2023. Primary outcomes were quality of life (QOL), while secondary outcomes were pain, fatigue, and adverse events (side effects). Data synthesis was performed using RevMan V.5.3 to calculate pooled effect sizes. RoB-2 was used for the risk of bias, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. RESULTS: Totally 17 RCTs involving 1,178 participants were included, 15 of which were pooled for meta-analysis. Most studies demonstrated some concern for the overall risk of bias. The pooled data indicated that acupuncture was associated with improved QOL [mean difference (MD)=6.67, 95% confidence interval (CI): 5.09 to 8.26], pain (MD=-1.18, 95% CI -2.28 to -0.08), and adverse events (risk ratio=0.30, 95% CI: 0.26 to 0.57) compared with control groups. Fatigue outcome was not included. Heterogeneity was substantial, and GRADE evidence was very low for both QOL and pain. CONCLUSIONS Acupuncture could benefit patients with advanced cancer and is considered safe compared with usual care. However, the evidence regarding QOL and pain outcomes requires further validation. It is crucial to encourage the development of high-quality studies to strengthen this evidence. (Registry No. CRD42023423539).
Humans ; Acupuncture Therapy ; Neoplasms/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome

Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People

Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

ObjectiveTo investigate a suspected outbreak of carbapenem-resistant Acinetobacter baumannii （CRAB） nosocomial infection in an intensive care unit （ICU） and provide scientific evidence for prevention and control of multi-drug resistant nosocomial infection. MethodsClinical and epidemiological data of 4 patients with CRAB infection were retrospectively investigated in the ICU of Renji Hospital in November 2021. Environmental hygiene monitoring and multilocus sequence typing （MLST） were conducted and intervention measures were taken. ResultsA total of 4 cases with CRAB infection were identified， among which 1 case was determined to be community-acquired and3 cases were hospital-acquired. The isolated strains shared the same drug resistance， and were all classified into ST368 type. In the surface and hand samples （n=40）， 2 CRAB strains were detected in the air filter beside the bed of the first case， with a detection rate of 5%. After adopting comprehensive prevention and control strategies， including environmental cleaning and disinfection， hand hygiene， staff management and training， and supervision， no similar case with CRAB infection was found. ConclusionThis suspected outbreak of CRAB nosocomial infection may be induced by inadequate environmental cleaning and disinfection， and inadequate implementation of hand hygiene. Timely identification， investigation， and targeted measures remain crucial to effective control of possible nosocomial infection.