Sennoside A(SA),a typical prodrug,exerts its laxative effect only after its transformation into rhei-nanthrone catalyzed by gut microbial hydrolases and reductases.Hydrolases have been identified,but reductases remain unknown.By linking a photoreactive group to the SA scaffold,we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling(ABPP).From lysates of an active strain,Bifidobacterium pseudocatenulatum(B.pseu-docatenulatum),397 proteins were enriched and subsequently identified using mass spectrometry(MS).Among these proteins,chromate reductase/nicotinamide adenine dinucleotide(NADH)phosphate(NADPH)-dependent flavin mononucleotide(FMN)reductase/oxygen-insensitive NADPH nitroreductase(nfrA)was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource(UniProt)database screening.We also determined that recombinant nfrA could reduce SA.Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Objective:To explore the relationship between gallbladder polyps and colorectal polyps, providing insights into whether the presence of gallbladder polyps can serve as an indicator for colonoscopy screening.Methods:Clinical data from 2 542 patients who underwent colonoscopy and abdominal ultrasound at the First Affiliated Hospital of Shihezi University between January and December 2022 were retrospectively analyzed. Patients were divided into colorectal polyp group ( n=1 266) and non-colorectal polyp group ( n=1 276) based on colonoscopy findings. Univariate and multivariate Logistic regression models were used to analyze the relationship between gallbladder polyps and colorectal polyps. Results:The prevalence rates of gallbladder polyp in colorectal polyp group and non-colorectal polyp group were 16.67% (211/1 266) and 11.21% (143/1 276). Multivariate Logistic regression analysis showed a lower risk of colorectal polyps in women ( P<0.001, OR=0.523, 95% CI: 0.440-0.622). Age ( P<0.001, OR=1.059, 95% CI: 1.050-1.068), and hypertriglyceridemia ( P=0.013, OR=1.350, 95% CI: 1.066-1.709), low level of high-density lipoprotein ( P<0.001, OR=1.588, 95% CI: 1.280-1.969), and gallbladder polyp ( P<0.001, OR=1.712, 95% CI: 1.344-2.180) were independent risk factors for colorectal polyp. There was no significant difference in hypercholesterolemia, elevated low-density lipoprotein, hyperuricemia, or cholecystectomy between colorectal polyp group and non-colorectal polyp group ( P>0.05). Conclusion:The identification of gallbladder polyps via abdominal ultrasound may indicate a higher likelihood of colorectal polyps in patients, underscoring the need for further colonoscopy screening in individuals with gallbladder polyps.

Objective:To explore the relationship between gallbladder polyps and colorectal polyps, providing insights into whether the presence of gallbladder polyps can serve as an indicator for colonoscopy screening.Methods:Clinical data from 2 542 patients who underwent colonoscopy and abdominal ultrasound at the First Affiliated Hospital of Shihezi University between January and December 2022 were retrospectively analyzed. Patients were divided into colorectal polyp group ( n=1 266) and non-colorectal polyp group ( n=1 276) based on colonoscopy findings. Univariate and multivariate Logistic regression models were used to analyze the relationship between gallbladder polyps and colorectal polyps. Results:The prevalence rates of gallbladder polyp in colorectal polyp group and non-colorectal polyp group were 16.67% (211/1 266) and 11.21% (143/1 276). Multivariate Logistic regression analysis showed a lower risk of colorectal polyps in women ( P<0.001, OR=0.523, 95% CI: 0.440-0.622). Age ( P<0.001, OR=1.059, 95% CI: 1.050-1.068), and hypertriglyceridemia ( P=0.013, OR=1.350, 95% CI: 1.066-1.709), low level of high-density lipoprotein ( P<0.001, OR=1.588, 95% CI: 1.280-1.969), and gallbladder polyp ( P<0.001, OR=1.712, 95% CI: 1.344-2.180) were independent risk factors for colorectal polyp. There was no significant difference in hypercholesterolemia, elevated low-density lipoprotein, hyperuricemia, or cholecystectomy between colorectal polyp group and non-colorectal polyp group ( P>0.05). Conclusion:The identification of gallbladder polyps via abdominal ultrasound may indicate a higher likelihood of colorectal polyps in patients, underscoring the need for further colonoscopy screening in individuals with gallbladder polyps.

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge.Liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analytical platform for the exploration of novel active compounds from complex matrices.However,the LC-HRMS-based analysis workflow suffers from several bottleneck issues,such as trace content of target compounds,limited acquisition for fragment information,and uncertainty in interpreting relevant MS2 spectra.Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus,while the reported structures are merely focused on dicaffeoylspermidines due to their low content.To comprehensively detect the new structures of lycibarbarspermidine derivatives,a"depict"strategy was developed in this study.First,potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway,and a comprehensive database was established,which enlarged the coverage of lycibarbarspermidine derivatives.Second,the polarity-oriented sample prep-aration of potential new compounds increased the concentration of the target compounds.Third,the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification.Finally,the weak response signals were captured by data-dependent scanning(DDA)followed by parallel reaction monitoring(PRM),and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved.Based on the integrated strategy above,210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus,and in particular,170 potential new compounds were structurally characterized.The integrated strategy improved the sensitivity of detection and the coverage of low-response components,and it is expected to be a promising pipeline for discovering new compounds.

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1 N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(1FN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degra-dation,as a promising candidate for antiviral therapy.

Objective: To establish the norm of the Physical Activity afterschool Questionnaire for Preschooler(P-PAQ) in urban areas of China, so as to provide a basis for graded guidance from the family perspective and to improve children s physical activity levels. Methods: From October 2020 to January 2021, 6 267 children aged 3-6 years old were recruited from 40 kindergartens in eight cities across six major administrative regions by stratified cluster sampling, and the P-PAQ initially developed by the researchers of this study were completed by the primary caregivers. The questionnaire was administered to collect data relating to the amount of physical activity undertaken by the preschoolers, and the norm was determined by quartiles. Data relating to parental concepts of sports and parental behavior were assessed by calculating mean scores in order to establish the norm. Results: Among preschoolers in urban areas, the M(P 25 ，P 75 ) of total physical activity time (min/day), moderate-to-vigorous physical activity time (min/day), outdoor time (min/day) and screen time (min/day) on school days outside kindergarten and on weekends were 84 (54,120), 22 (8,40), 12 (0,24) and 18 (6,30), and 170 (115,240), 60 (30,95), 90 (35,120) and 30 (20,60), respectively. When the score of parents sports concept and behavior (total score of 40) were≥34, 29-<34, 24-<29, <24, it was defined as four levels about above medium, medium, lower medium and lower, respectively. And for two dimensions，when the score of parental sports concept were ≥19, 17-<19, 15-<17, <15，and the score of parental behaviors were ≥16, 12-<16, 8-<12, <8, it was defined as four levels about upper medium, medium, lower medium and lower, respectively. Conclusion The norm of extracurricular activities among preschool children in Chinese cities has good representativeness and appropriate threshold values, which could provide a valuable reference for early assessment, as well as guidance in relation to out-of-school physical activity behaviors among children aged 3-6 years old.

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the Bact state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration.
Spliceosomes/metabolism* ; Introns/genetics* ; RNA Splicing ; RNA, Messenger/genetics* ; Cell Nucleus/metabolism*

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

OBJECTIVE To standardize the English translations of the current Chinese patent medicine （CPM） instructions in order to increase its English translation quality and improve its readability. METHODS In an attempt to standardize its English translation， 64 CPM instructions were collected as samples for translation projects in Trados， using its two core functions of translation memory and terminology， combined with pre-editing （PRE） and post-editing （PE） skills. RESULTS The results showed that translation projects had up to 21.65% perfect match. Based on translation project practice， it is proposed to use the free translation or transcreation plus transliteration method to translate product names of CPM， and apply two human-computer interaction translation modes：“ machine translation （MT）+computer-assisted translation （CAT）+PE” and “PRE+MT+CAT+PE”， which are adopted in the translation of weak literary sections and strong literary sections， respectively. CONCLUSIONS The application of CAT not only improves the translation quality and the translation mode， reduces the translation cost， and maintains the consistency and style of the translation， but also accumulates language assets for future use， providing a novel reference for translating traditional Chinese medicine literature.