Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

BACKGROUND:Bibliometrics and visual analyses based on thematic literature are particularly important for understanding the foundation and frontiers of postmenopausal osteoporosis research. OBJECTIVE:To perform bibliometric,citation,and visualization analyses of highly cited SCI papers in postmenopausal osteoporosis research over the last 20 years. METHODS:The top 100 highly cited papers on postmenopausal osteoporosis published between 2003 and 2022 included in SCI-EXPANDED catalog of the Web of Science database were obtained for bibliometric measure and visual analysis using CiteSpace software. RESULTS AND CONCLUSION:The top 100 highly cited papers have a total of 67 377 citations in the Web of Science Core Collection,with an annual average of 49.17 citations per paper.Postmenopausal osteoporosis research primarily involves medical,engineering,biological,and multidisciplinary fields.The subcategories are dominated by endocrinology and metabolism,and medicine:internal medicine.Stable and close cooperative network relationships have been formed globally.United States,University of California System,Cummings,and Steven R are the country,research institution,and author,respectively,with the most highly-cited publications.The frontiers of postmenopausal osteoporosis research mainly include calcium and vitamin D supplementation and fracture risk,clinical studies of bisphosphonates in the treatment of postmenopausal osteoporosis,atypical femur fracture,clinical studies of new drugs and sequential treatment of postmenopausal osteoporosis,predictors of fracture risk,mid-and long-term follow-up of osteoporotic vertebral compression fractures,genetic polymorphisms and hereditary factors,formulation and updating of clinical practice guidelines for postmenopausal osteoporosis.Large cohort studies,high-quality randomized controlled trials,systematic reviews,meta-analyses,and clinical practice guidelines are the great engines that drive the development of clinical research in postmenopausal osteoporosis.We should make efforts in the above areas to improve China's international influence in the field of osteoporosis.

BackgroundPrevention and intervention of procrastination in college students are of great practical significance， and studies have illustrated a pairwise correlation among mindfulness， self-control， insecure attachment and procrastination， whereas the mechanism by which insecure attachment leads to procrastination remains unclear， and the related mediation path is quite understudied. ObjectiveTo investigate the effect of insecure attachment on procrastination among college students and the pathway of mindfulness and self-control， so as to inform the design of interventions for procrastination among college students. MethodsRandom and cluster sampling method were utilized to enroll 514 college students from 4 colleges in Guangdong Province From February to April 2023. Subjects were assessed using Irrational Procrastination Scale （IPS）， Adult Attachment Scale （AAS）， Mindful Attention Awareness Scale （MAAS） and Brief Self-Control Scale （BSCS）. Pearson correlation analysis were adopted to identify the correlation among above scales， and the mediation effect was examined via Bootstrap procedure. ResultsAAS score was positively correlated with IPS score （r=0.382， P<0.01）， and negatively correlated with MAAS and BSCS scores （r=-0.242， -0.353， P<0.01）. IPS score was negatively correlated with MAAS and BSCS scores （r=-0.314， -0.682， P<0.01）. MAAS score was positively correlated with BSCS score （r=0.439， P<0.01）. Insecure attachment positively predicted procrastination （β=0.377， P<0.01）， and the prediction of procrastination by insecure attachment was mediated by self-control， with an indirect effect value of 0.163 （95% CI： 0.105~0.223）， accounting for 43.24% of the total effect value. The mindfulness and self-control exerted a chained mediation effect on the relationship between insecure attachment and procrastination， and the indirect effect value was 0.056 （95% CI： 0.028~0.089）， accounting for 14.85% of the total effect value. ConclusionInsecure attachment can influence procrastination among college students both directly and indirectly through the single mediation of self-control or the chained mediation of mindfulness and self-control. ［Funded by 2023 National College Student Innovation and Entrepreneurship Training Program （number， 202310570023）］

Objective To study the effect and mechanism of paeonol(PAE)on renal interstitial fibrosis in rats.Methods The rats were randomly divided into sham operation(Sham)group,unilateral ureteral obstruction(UUO)group,PAE low dose(PAE-L)group,PAE medium dose(PAE-M)group,PAE high dose(PAE-H)group and irbesartan(IRB)group.Except for the Sham group,the UUO model was established in other groups.Each group was given a corresponding intervention for two weeks.Serum creatinine(Scr),blood urea nitrogen(BUN),serum 8-hydroxydeoxyguanosine(8-OHdG)levels,renal tissue superoxide dismutase(SOD),glutathione peroxidase(GPX)activities,α-smooth muscle actin(α-SMA),type Ⅰ collagen(Col-Ⅰ),fibronectin(FN),silent information regulator 1(SIRT1),nuclear factor E2-related factor 2(Nrf2)protein expression were detected;observe pathological changes of kidney tissue and calculate collagen volume fraction(CVF).Results Compared with the UUO group,the serum levels of Scr,BUN,and 8-OHdG in each dose group of PAE were decreased,the activities of SOD and GPX in kidney tissue were increased,the positive expressions of α-SMA,Col-Ⅰ and FN in kidney tissue were decreased,and the protein expressions of SIRT1 and Nrf2 were increased.Masson staining showed a decrease of CVF in renal tissue(all P<0.05),and HE staining showed a different degree of improvement in pathological changes such as inflammatory cell infiltration and tubular dilatation in renal tissue;PAE improves renal interstitial fibrosis in rats in a dose-dependent manner(P<0.05),and the effect of large dose PAE on renal interstitial fibrosis in rats was similar to that of IRB.Conclusion PAE can alleviate UUO-induced rat renal interstitial fibrosis and oxidative stress,and improve rat renal function.And this mechanism may be related to the activation of the SIRT1/Nrf2 signaling pathway.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Objective:To explore any effect of upper limb swing training guided by rhythmic auditory stimulation (RAS) on the walking ability of stroke survivors.Methods:Eighty stroke survivors were randomly divided into an observation group and a control group. Both groups received conventional rehabilitation treatment, including neuromuscular facilitation, muscle strength training, balance training and gait training, but the observation group was additionally provided with RAS-guided upper limb swing training for 20min once a day, 5d per week for 6 weeks. Before and after the intervention, balance and lower limb function were quantified in both groups using Holden′s walking function classification, the Fugl-Meyer lower extremity motor function scale (FMA-LE), the Berg Balance Scale (BBS) and the 10m walk test (10MWT). Limits of stability were also quantified.Results:After the treatment, the average Holden, FMA-LE and BBS scores, as well as the average 10MWT time were significantly better in the observation group than in the control group. The average stability limits and their maintenance were also superior.Conclusion:RAS-guided upper limb swing training can improve the gait, walking ability, walking stability, walking speed and balance of stroke survivors.

Objective:To document any effect of clinical rehabilitation pathway management on intubation time, dysfunction and medical expenditure associated with tracheotomy after a stroke.Methods:A total of 154 stroke survivors undergoing tracheotomy were randomly divided into an observation group and a control group, each of 77. Both groups were given routine rehabilitation, while the observation group was additionally provided with clinical rehabilitation pathway management during the rehabilitation intervention. Kaplan-Meier analysis was performed before the experiment and after 2, 4 and 6 weeks of treatment. Clinical pulmonary infection scores (CPISs), scores on the Chelsea Physical Function Assessment Scale (CPAx) and hospitalization cost were compared between the two groups.Results:The median extubation time of the observation group (2d) was significantly shorter than that of the control group (10d). After 2, 4 and 6 weeks of treatment, the average CPIS scores of the observation group were in each case significantly lower than those before treatment and the control group′s averages at the same time points, even though after 4 and 6 weeks of treatment the control group′s average CPIS scores had improved significantly. After 2, 4 and 6 weeks of treatment, the average CPAx scores of the observation group were significantly higher than those before treatment and better than the control group′s averages, even though the control group too had improved significantly compared with before the treatment. Hospitalization days, total hospitalization cost, antibiotic cost and laboratory examination cost of the observation group were, on average, significantly lower than those of the control group.Conclusion:Rehabilitation path management can shorten the period of intubation, prevent pulmonary infections, relieve dysfunction, and reduce medical expenses for stroke survivors after a tracheotomy. It is worthy of clinical promotion.

Objective:To identify the differentially expressed long-chain non-coding RNA(lncRNA) and mRNA using ribonucleic acid sequencing(RNA-seq), and construct a competing endogenous RNA(ceRNA) regulatory network in mice with sepsis-associated encephalopathy.Methods:Ten clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups( n=5 each) using a random number table method: sham operation group(group Sham) and sepsis group(group Sepsis). Sepsis was induced by cecal ligation and puncture(CLP) in group Sepsis, while group Sham only underwent laparotomy without CLP. Morris water maze test and contextual fear conditioning test were performed to detect the cognitive function on 1 day before CLP and 3 days after CLP. Three mice were randomly sacrificed in group Sham, and 3 mice with the worst results in the cognitive function test were sacrificed in group Sepsis. The hippocampal tissues were obtained for RNA-seq via the BGISEQ-500 platform, and the differentially expressed mRNA and lncRNA were identified. The differentially expressed mRNAs and lncRNAs were visualized and analyzed by Dr. Tom platform provided by Shenzhen BGI Technology Service Co., Ltd., and the ceRNA regulatory network was constructed using the online visualization tool Cytoscape software. Results:Compared with group Sham, the escape latency was significantly prolonged, and the percentage of time of staying at the target quadrants and percentage of time spent freezing were decreased in group Sepsis( P<0.05). A total of 62 differentially expressed lncRNAs were obtained from RNA-seq, of which the expression of 45 lncRNAs was up-regulated and the expression of 17 lncRNAs was down-regulated.There were 282 differentially expressed mRNAs identified from RNA-seq, of which the expression of 173 mRNAs was up-regulated, and the expression of 109 mRNAs was down-regulated.Gene Ontology enrichment analysis revealed that the differentially expressed mRNAs were involved in biological processes such as memory, learning or memory, inflammatory responses, regulation of aging-related behavioral decline, and regulation of synaptic plasticity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that differentially expressed mRNAs were enriched in IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway and etc. KDA analysis was performed on the differentially expressed mRNAs to identify the key driver genes, and the results showed that Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 were the key SAE genes.A competing endogenous RNA regulatory network was successfully constructed based on 9 lncRNAs, 28 mRNAs and 134 miRNAs in the hippocampus of mice with SAE. Conclusions:The results of RNA-seq find that 10 mRNAs including Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 and lncRNAs such as Rian, Gm35874 and Gm34347 are key genes regulating SAE in mice. Meanwhile, a ceRNA regulatory network based on lncRNA-miRNA-mRNA is successfully constructed in the hippocampus of mice with SAE.

The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.
Humans ; Cell Cycle/physiology* ; Cell Division ; Cyclin-Dependent Kinases/metabolism* ; Cyclins/metabolism*