Implementation of an Enhanced Crayfish Optimization Algorithm.

This paper presents an enhanced crayfish optimization algorithm (ECOA). The ECOA includes four improvement strategies. Firstly, the Halton sequence was used to improve the population initialization of the crayfish optimization algorithm. Furthermore, the quasi opposition-based learning strategy is introduced to generate the opposite solution of the population, increasing the algorithm's searching ability. Thirdly, the elite factor guides the predation stage to avoid blindness in this stage. Finally, the fish aggregation device effect is introduced to increase the ability of the algorithm to jump out of the local optimal. This paper performed tests on the widely used IEEE CEC2019 test function set to verify the validity of the proposed ECOA method. The experimental results show that the proposed ECOA has a faster convergence speed, greater performance stability, and a stronger ability to jump out of local optimal compared with other popular algorithms. Finally, the ECOA was applied to two real-world engineering optimization problems, verifying its ability to solve practical optimization problems and its superiority compared to other algorithms.

Potential mechanisms of cancer prevention and treatment by sulforaphane, a natural small molecule compound of plant-derived.

Despite recent advances in tumor diagnosis and treatment technologies, the number of cancer cases and deaths worldwide continues to increase yearly, creating an urgent need to find new methods to prevent or treat cancer. Sulforaphane (SFN), as a member of the isothiocyanates (ITCs) family, which is the hydrolysis product of glucosinolates (GLs), has been shown to have significant preventive and therapeutic cancer effects in different human cancers. Early studies have shown that SFN scavenges oxygen radicals by increasing cellular defenses against oxidative damage, mainly through the induction of phase II detoxification enzymes by nuclear factor erythroid 2-related factor 2 (Nrf2). More and more studies have shown that the anticancer mechanism of SFN also includes induction of apoptotic pathway in tumor cells, inhibition of cell cycle progression, and suppression of tumor stem cells. Therefore, the application of SFN is expected to be a necessary new approach to treating cancer. In this paper, we review the multiple molecular mechanisms of SFN in cancer prevention and treatment in recent years, which can provide a new vision for cancer treatment.

Metal ion stimulation-related gene signatures correlate with clinical and immunologic characteristics of glioma.

Background: Environmental factors serve as one of the important pathogenic factors for gliomas. Yet people focus only on the effect of electromagnetic radiation on its pathogenicity, while metals in the environment are neglected. This study aimed to investigate the relationship between metal ion stimulation and the clinical characteristics and immune status of GM patients. Methods: Firstly, mRNA expression profiles of GM patients and normal subjects were obtained from Chinese GM Genome Atlas (CGGA) and Gene Expression Omnibus (GEO) to identify differentially expressed metal ion stimulation-related genes(DEMISGs). Secondly, two molecular subtypes were identified and validated based on these DEMISGs using consensus clustering. Diagnostic and prognostic models for GM were constructed after screening these features based on machine learning. Finally, supervised classification and unsupervised clustering were combined to classify and predict the grade of GM based on SHAP values. Results: GM patients are divided into two different response states to metal ion stimulation, M1 and M2, which are related to the grade and IDH status of the GM. Six genes with diagnostic value were obtained: SLC30A3, CRHBP, SYT13, DLG2, CDK1, and WNT5A. The AUC in the external validation set was higher than 0.90. The SHAP value improves the performance of classification prediction. Conclusion: The gene features associated with metal ion stimulation are related to the clinical and immune characteristics of transgenic patients. XGboost/LightGBM Kmeans has a higher classification prediction accuracy in predicting glioma grades compared to using purely supervised classification techniques.

Long-term intake of sulforaphene alleviates D-galactose-induced skin senescence by activating AMPK-Sirt 1 pathway.

D-Galactose (D-gal) accumulation triggers the generation of oxygen free radicals, resulting in skin aging. Sulforaphene (SFE), an isothiocyanate compound derived from radish seeds, possesses diverse biological activities, including protective effects against inflammation and oxidative damage. This investigation delves into the antioxidant impact of SFE on age-related skin injury. In vivo experiments demonstrate that SFE treatment significantly improves the macro- and micro-morphology of dorsal skin. It effectively diminishes the elevation of oxidative stress biomarkers in mice skin tissue treated with D-gal, concurrently enhancing the activity of antioxidant enzymes. Additionally, SFE mitigates collagen mRNA degradation, lowers pro-inflammatory cytokine levels, and downregulates MAPK-related protein expression in the skin. Moreover, SFE supplementation reduces lipid metabolite levels and elevates amino acid metabolites, such as L-cysteine and L-histidine. These findings suggest that SFE holds promise as a natural remedy to mitigate aging induced by oxidative stress.

Regulation of hippocampal mossy fiber-CA3 synapse function by a Bcl11b/C1ql2/Nrxn3(25b+) pathway.

The transcription factor Bcl11b has been linked to neurodevelopmental and neuropsychiatric disorders associated with synaptic dysfunction. Bcl11b is highly expressed in dentate gyrus granule neurons and is required for the structural and functional integrity of mossy fiber-CA3 synapses. The underlying molecular mechanisms, however, remained unclear. We show in mice that the synaptic organizer molecule C1ql2 is a direct functional target of Bcl11b that regulates synaptic vesicle recruitment and long-term potentiation at mossy fiber-CA3 synapses in vivo and in vitro. Furthermore, we demonstrate C1ql2 to exert its functions through direct interaction with a specific splice variant of neurexin-3, Nrxn3(25b+). Interruption of C1ql2-Nrxn3(25b+) interaction by expression of a non-binding C1ql2 mutant or by deletion of Nrxn3 in the dentate gyrus granule neurons recapitulates major parts of the Bcl11b as well as C1ql2 mutant phenotype. Together, this study identifies a novel C1ql2-Nrxn3(25b+)-dependent signaling pathway through which Bcl11b controls mossy fiber-CA3 synapse function. Thus, our findings contribute to the mechanistic understanding of neurodevelopmental disorders accompanied by synaptic dysfunction.

The human brain contains billions of neurons working together to process the vast array of information we receive from our environment. These neurons communicate at junctions known as synapses, where chemical packages called vesicles released from one neuron stimulate a response in another. This synaptic communication is crucial for our ability to think, learn and remember. However, this activity depends on a complex interplay of proteins, whose balance and location within the neuron are tightly controlled. Any disruption to this delicate equilibrium can cause significant problems, including neurodevelopmental and neuropsychiatric disorders, such as schizophrenia and intellectual disability. One key regulator of activity at the synapse is a protein called Bcl11b, which has been linked to conditions affected by synaptic dysfunction. It plays a critical role in maintaining specific junctions known as mossy fibre synapses, which are important for learning and memory. One of the genes regulated by Bcl11b is C1ql2, which encodes for a synaptic protein. However, it is unclear what molecular mechanisms Bcl11b uses to carry out this role. To address this, Koumoundourou et al. explored the role of C1ql2 in mossy fibre synapses of adult mice. Experiments to manipulate the production of C1ql2 independently of Bcl11b revealed that C1ql2 is vital for recruiting vesicles to the synapse and strengthening synaptic connections between neurons. Further investigation showed that C1ql2's role in this process relies on interacting with another synaptic protein called neurexin-3. Disrupting this interaction reduced the amount of C1ql2 at the synapse and, consequently, impaired vesicle recruitment. These findings will help our understanding of how neurodevelopmental and neuropsychiatric disorders develop. Bcl11b, C1ql2 and neurexin-3 have been independently associated with these conditions, and the now-revealed interactions between these proteins offer new insights into the molecular basis of synaptic faults. This research opens the door to further study of how these proteins interact and their roles in brain health and disease.

Increased long-distance and homo-trans interactions related to H3K27me3 in Arabidopsis hybrids.

In plants, the genome structure of hybrids changes compared with their parents, but the effects of these changes in hybrids remain elusive. Comparing reciprocal crosses between Col × C24 and C24 × Col in Arabidopsis using high-throughput chromosome conformation capture assay (Hi-C) analysis, we found that hybrid three-dimensional (3D) chromatin organization had more long-distance interactions relative to parents, and this was mainly located in promoter regions and enriched in genes with heterosis-related pathways. The interactions between euchromatin and heterochromatin were increased, and the compartment strength decreased in hybrids. In compartment domain (CD) boundaries, the distal interactions were more in hybrids than their parents. In the hybrids of CURLY LEAF (clf) mutants clfCol × clfC24 and clfC24 × clfCol , the heterosis phenotype was damaged, and the long-distance interactions in hybrids were fewer than in their parents with lower H3K27me3. ChIP-seq data revealed higher levels of H3K27me3 in the region adjacent to the CD boundary and the same interactional homo-trans sites in the wild-type (WT) hybrids, which may have led to more long-distance interactions. In addition, the differentially expressed genes (DEGs) located in the boundaries of CDs and loop regions changed obviously in WT, and the functional enrichment for DEGs was different between WT and clf in the long-distance interactions and loop regions. Our findings may therefore propose a new epigenetic explanation of heterosis in the Arabidopsis hybrids and provide new insights into crop breeding and yield increase.

Analysis of early clinical signs and risk factors for severe hemorrhagic cystitis after stem cell transplantation in children.

INTRODUCTION: To analyze the characteristics of early clinical symptoms of hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) and the risk factors of severe HC. METHODS: We retrospectively analyzed 77 children with post-HSCT HC treated at our hospital between June 2013 and June 2021. Clinical characteristics were collected and catalogued. RESULTS: Among the children with urinary tract irritation symptoms (UTIS) as the first symptom, symptoms appeared earlier than hematuria symptoms (28 day vs. 31 day, p = 0.027), and the time progressing to severe HC was significantly longer in these children (12 day vs. 7 day, p = 0.038), but there was no significant difference in the number of participants (57.8% vs. 59.4%, p = 0.889). BK polyomavirus (BKV) infection was an independent risk factor (hazard ratio [HR] = 2.782, p = 0.035) for severe HC, which was also positively associated with multi-viral infection (HR = 2.215, p = 0.020). CONCLUSIONS: In HC children, when the first urinary tract symptom was UTIS, it appeared earlier than hematuria, and the time of progression to severe HC was significantly longer, suggesting that we still need more aggressive treatment for these children to prevent the worsening of symptoms. The severity of HC was positively correlated with BKV infection and multiple infections.

Exploring the relationship between immune heterogeneity characteristic genes of rheumatoid arthritis and acute myeloid leukemia.

BACKGROUND: People with autoimmune diseases are prone to cancer, and there is a close relationship between rheumatoid arthritis (RA) and acute myeloid leukemia (AML). The bone marrow (BM) is affected throughout the course of RA, with a variety of hematologic involvement. Hopes are pinned on rheumatoid arthritis research to obtain BM biomarkers for AML. METHODS: Synovial transcriptome sequencing data for RA and osteoarthritis (OA), and single-cell sequencing data for RA and controls were obtained from the GEO database.Bone marrow sequencing data for AML patients and normal subjects were obtained from the UCSC Xena database. The final immune heterogeneity characteristics of RA were determined through ssGSEA analysis, gene differential expression analysis, fuzzy c-means clustering algorithm, and XGboost algorithm. Random Ferns classifiers (RFs) are used to identify new bone marrow markers for AML. RESULTS: SELL, PTPRC, IL7R, CCR7, and KLRB1 were able to distinguish leukemia cells from normal cells well, with AUC values higher than 0.970. CONCLUSION: Genes characterizing the immune heterogeneity of RA are associated with AML, and KLRBA may be a potential target for AML treatment.

Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia.

Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.

New Insight into the Potential Protective Function of Sulforaphene against ROS-Mediated Oxidative Stress Damage In Vitro and In Vivo.

Sulforaphene (SFE) is a kind of isothiocyanate isolated from radish seeds that can prevent free-radical-induced diseases. In this study, we investigated the protective effect of SFE on oxidative-stress-induced damage and its molecular mechanism in vitro and in vivo. The results of cell experiments show that SFE can alleviate D-gal-induced cytotoxicity, promote cell cycle transformation by inhibiting the production of reactive oxygen species (ROS) and cell apoptosis, and show a protective effect on cells with H2O2-induced oxidative damage. Furthermore, the results of mice experiments show that SFE can alleviate D-galactose-induced kidney damage by inhibiting ROS, malondialdehyde (MDA), and 4-hydroxyalkenals (4-HNE) production; protect the kidney against oxidative stress-induced damage by increasing antioxidant enzyme activity and upregulating the Nrf2 signaling pathway; and inhibit the activity of pro-inflammatory factors by downregulating the expression of Toll-like receptor 4 (TLR4)-mediated inflammatory response. In conclusion, this research shows that SFE has antioxidant effects, providing a new perspective for studying the anti-aging properties of natural compounds.

NDUFC2 deficiency exacerbates endothelial mesenchymal transformation during ischemia-reperfusion via NLRP3.

Ischemic stroke is the main type of cerebrovascular disease. Emergency thrombectomy combined with medication therapy is currently the primary treatment for stroke. Inflammation and oxidative stress induced by ischemia-reperfusion cause secondary damage to blood vessels, especially endothelial mesenchymal transformation (EndoMT). However, much is still unclear about the role of EndoMT in ischemia-reperfusion. In this study, an in vivo ischemia-reperfusion model was established by transient middle cerebral artery occlusion (tMCAO) in wild-type (WT) C57BL/6 mice and NLRP3 (NOD-like receptor thermal protein domain associated protein 3) knockout (KO) C57BL/6 mice. An in vitro ischemia-reperfusion model was established by oxygen glucose deprivation and reoxygenation (OGD/R) of human brain microvascular endothelial cells (HBMECs). α-SMA (alpha smooth muscle actin), CD31 (platelet endothelial cell adhesion molecule-1, PECAM-1/CD31), NDUFC2 (NADH: ubiquinone oxidoreductase subunit C2), and NLRP3 were used to evaluate EndoMT and inflammation. Real-time PCR measured superoxide dismutase 1 (SOD1) and catalase (CAT) mRNA expression to evaluate oxidative stress levels. NLRP3 was activated by ischemia-reperfusion injury and NLRP3 inactivation inhibited the EndoMT in tMCAO mice. Further experiments demonstrated that OGD/R treatment induced NLRP3 activation and EndoMT in HBMECs, which resulted in NDUFC2 deficiency. NDUFC2 overexpression suppressed NLRP3 activation and EndoMT in HBMECs induced by OGD/R. Moreover, NDUFC2 overexpression rescued SOD1 and CAT mRNA expression. These results demonstrated that NDUFC2 deficiency decreased the antioxidant levels, leading to NLRP3 activation and EndoMT during ischemia-reperfusion injury and suggesting that NDUFC2 is a potential drug target for the treatment of ischemic stroke.

Derivation of trophoblast stem cells from human expanded potential stem cells.

Human trophoblast development study has long been limited by the lack of suitable materials. Here we present a detailed protocol for the differentiation of human expanded potential stem cells (hEPSCs) into human trophoblast stem cells (TSCs) and for the subsequent establishment of TSC lines. The hEPSC-derived TSC lines can be continuously passaged and are functional in further differentiation into syncytiotrophoblasts and extravillous trophoblasts. The hEPSC-TSC system offers a valuable cell source for studying human trophoblast development in pregnancy. For complete details on the use and execution of this protocol, please refer to Gao et al. (2019)1 and Ruan et al. (2022).2.

Expanded Potential Stem Cells from Human Embryos Have an Open Chromatin Configuration with Enhanced Trophoblast Differentiation Ability.

Human expanded potential stem cells (hEPSC) have been derived from human embryonic stem cells and induced pluripotent stem cells. Here direct derivation of hEPSC from human pre-implantation embryos is reported. Like the reported hEPSC, the embryo-derived hEPSC (hEPSC-em) exhibit a transcriptome similar to morula, comparable differentiation potency, and high genome editing efficiency. Interestingly, the hEPSC-em show a unique H3 lysine-4 trimethylation (H3K4me3) open chromatin conformation; they possess a higher proportion of H3K4me3 bound broad domain (>5 kb) than the reported hEPSC, naive, and primed embryonic stem cells. The open conformation is associated with enhanced trophoblast differentiation potency with increased trophoblast gene expression upon induction of differentiation and success in derivation of trophoblast stem cells with bona fide characteristics. Hippo signaling is specifically enriched in the H3K4me3 broad domains of the hEPSC-. Knockout of the Hippo signaling gene, YAP1 abolishes the ability of the embryo-derived EPSC to form trophoblast stem cells.

Study on Surface Integrity and Fatigue Properties of TC4 Titanium Alloy by Surface Ultrasonic Rolling.

In this paper, the influence of a surface ultrasonic rolling process on the surface integrity of TC4 titanium alloy and its influence on the fatigue properties were studied. By comparing and analyzing the surface roughness, microhardness, residual stress, microstructure, and fatigue fracture, the surface strengthening and modification mechanism of TC4 titanium alloy is discussed. The results show that the surface roughness of titanium alloy is observably decreased after the suitable surface ultrasonic rolling process, and the maximum Ra value can be reduced to 0.052 µm. The axial residual stress on the specimen surface can be increased to -685 MPa. The hardening rate of the surface hardness of the sample was 35%. The residual compressive stress and hardness of the sample surface increased with the increase of static pressure. However, the increase of feed rate and rational speed was less. After surface ultrasonic rolling, the sample surface exhibited obvious grain refinement, the number of high-angle boundaries increased to include the formation of nano-equiaxed grains. The fatigue strength increased by 52% from 280 MPa to 425 MPa. Under 450 MPa, the fatigue life of samples with SUR 2 was the highest, at about 7.7 times that of the original samples. The surface integrity of titanium alloy samples after surface ultrasonic rolling treatment is greatly improved, which is the reason for the significant increase in fatigue life of the samples.

Effect of grazing and climatic factors on biodiversity-ecosystem functioning relationships in grassland ecosystems - a case study of typical steppe in Inner Mongolia, China.

Biodiversity underpins grassland ecological functions and productive capacities. By studying the mechanisms for the maintenance of species diversity in animal communities, we can provide important theoretical guidance for the optimization of grazing management and biodiversity protection. The typical grassland of Xilingol in Inner Mongolia, China, was used as the experimental area, and a grazing intensity experiment was set up. This consisted of four gradient levels that were grazed by sheep, which were available for continuous monitoring, namely control standard sheep unit·day·hectare-1·year-1 (CK, 0 SSU·d·hm-2y-1), light grazing (LG, 170 SSU·d·hm-2·y-1), moderate grazing (MG, 340 SSU·d·hm-2·y-1), and high grazing (HG, 510 SSU·d·hm-2·y-1). Nine consecutive years of multi-indicator monitoring of vegetation was carried out from 2014-2022, using monitoring data coupled with time series and inter-annual climatic (relative moisture index, RMI) fluctuations. This was done to analyze the impacts of disturbances, such as grazing use and climatic fluctuations, on the diversity of species and above-ground productivity of the community, thereby exploring the relationship between diversity and productivity, and provide possible explanations for the emergence of a range of ecological responses. The statistical analysis methods used were One-way Analysis of Variance (ANOVA), general linear regression and mixed-effects models. The main conclusions of this study are as follows: (1) The grassland in the experimental area under CK had the highest diversity and productivity and the ecosystem was better able to buffer the negative impacts of climatic drought. Furthermore, the effect of climate on productivity and diversity weakened as the intensity of grazing increased. (2) LG to MG had a constant diversity. (3) Grazing utilization changed the relationship between community species diversity and aboveground productivity by releasing spatial community resources, altering the structure of plant communities, weakening competitive exclusion, and strengthening complementary effects. However, under all of the conditions there is a brief stage in the time series when diversity is stimulated to increase, and the higher the grazing intensity, the earlier this occurs.

Effective degradation of tetracycline via recyclable cellulose nanofibrils/polyvinyl alcohol/Fe3O4 hybrid hydrogel as a photo-Fenton catalyst.

In this work, the method of in-situ co-precipitation was used to prepare PVA/CNF/Fe3O4 hybrid hydrogel, and the relationship between its structure and performance was explored. The Fe3O4NPs prepared by this method were dispersed on the carrier PVA/CNF hydrogel and were easy to recover. The catalytic degradation of tetracycline was investigated using PVA/CNF/Fe3O4 hybrid hydrogel as photo-Fenton catalysts. The results showed that light and hydrogel carriers were pivotal factors in promoting Fe2+ and Fe3+ cycling and that the PVA/CNF/Fe3O4 hybrid hydrogel as catalysts were able to activate H2O2 to generate a large amount of oxygen radical •OH, resulting in efficient removal of tetracycline. The tetracycline degradation followed a proposed first-order kinetic model and achieved a removal rate of about 98% in 120 min at an optimum pH of 3, H2O2 100 mM, catalyst 0.3 g/L, and a temperature of 25 °C.

Characterization of antibacterial aerogel based on ɛ-poly-l-lysine/nanocellulose by using citric acid as crosslinker.

In this paper, based on the TEMPO oxidated Cellulose Nanofiber (TOCNF)/ɛ-poly-l-lysine (ɛ-PL) cross-linking network and citric acid as the cross-linking agent, aerogel material was designed. Citric acid (CA) can be used as a multifunctional cross-linking agent with TOCNF esterification cross-linking, and with TOCNF and ɛ-PL hydrogen bond cross-linking, but also as a reinforcing agent to improve mechanical and antibacterial properties. When the ɛ-PL content reached 0.8%, the tensile strength of the aerogel increased from 12.03 MPa to 26.44 MPa, while the elongation at break decreased to 29.33%. As the amount of ɛ-PL increased, the thermal decomposition temperature of aerogel rose to 215 °C. Aerogels had a high antibacterial efficiency (above 99.9%). After 28 days, aerogels can be biodegraded in the soil. More importantly, the aerogel had a hemolysis rate of less than 5%, indicating that the prepared degradable cellulose aerogel was a material with good blood compatibility. It had huge application potential in medical environment and food packaging.

Impact of low-level viremia with drug resistance on CD4 cell counts among people living with HIV on antiretroviral treatment in China.

BACKGROUND: Maintaining plasma HIV RNA suppression below the limit of quantification is the goal of antiretroviral therapy (ART). When viral loads (VL) remain in low-level viremia (LLV), or between 201 and 999 copies/mL, the clinical consequences are still not clear. We investigated the occurrence of LLV with drug resistance and its effect on CD4 cell counts in a large Chinese cohort. METHODS: We analysed data of 6,530 ART-experienced patients (42.1 ± 10.9 years; 37.3% female) from the China's national HIV drug resistance (HIVDR) surveillance database. Participants were followed up for 32.9 (IQR 16.7-50.5) months. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50-200 copies/mL during ART. Outcomes were drug resistance associated mutations (DRAM) and CD4 cell counts levels. RESULTS: Among 6530 patients, 58.0% patients achieved VL less than 50 copies/mL, 27.8% with VL between 50 and 999 copies/mL (8.6% experienced LLV), and 14.2% had a VL ≥ 1000 copies/mL. Of 1818 patients with VL 50-999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/µL (AOR 3.8, 95% CI 2.6-5.5, p < 0.01) comparing with those without HIVDR. Of 925 patients with VL ≥ 1000 copies/mL, 495 (53.5%) acquired HIVDR, the most common DRAM were K103N 43.8%, M184I/V 43.2%, M41L 19.0%, D67N/G 16.4%, V181C/I/V 14.5%, G190A/S 13.9% and K101E 13.7% (multidrug resistance: 75.8%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/µL (AOR 5.8, 95% CI 4.6-7.4, p < 0.01) comparing with those without HIVDR. CONCLUSION: Persistent with VL 50-999 copies/mL on ART is associated with emerging DRAM for all drug classes, and patients in this setting were at increased risk of CD4 cell counts < 200 cells/µL, which suggest resistance monitoring and ART optimization be earlier considered.

Single-cell genomics identifies distinct B1 cell developmental pathways and reveals aging-related changes in the B-cell receptor repertoire.

BACKGROUND: B1 cells are self-renewing innate-like B lymphocytes that provide the first line of defense against pathogens. B1 cells primarily reside in the peritoneal cavity and are known to originate from various fetal tissues, yet their developmental pathways and the mechanisms underlying maintenance of B1 cells throughout adulthood remain unclear. RESULTS: We performed high-throughput single-cell analysis of the transcriptomes and B-cell receptor repertoires of peritoneal B cells of neonates, young adults, and elderly mice. Gene expression analysis of 31,718 peritoneal B cells showed that the neonate peritoneal cavity contained many B1 progenitors, and neonate B cell specific clustering revealed two trajectories of peritoneal B1 cell development, including pre-BCR dependent and pre-BCR independent pathways. We also detected profound age-related changes in B1 cell transcriptomes: clear difference in senescence genetic program was evident in differentially aged B1 cells, and we found an example that a B1 subset only present in the oldest mice was marked by expression of the fatty-acid receptor CD36. We also performed antibody gene sequencing of 15,967 peritoneal B cells from the three age groups and discovered that B1 cell aging was associated with clonal expansion and two B1 cell clones expanded in the aged mice had the same CDR-H3 sequence (AGDYDGYWYFDV) as a pathogenically linked cell type from a recent study of an atherosclerosis mouse model. CONCLUSIONS: Beyond offering an unprecedent data resource to explore the cell-to-cell variation in B cells, our study has revealed that B1 precursor subsets are present in the neonate peritoneal cavity and dissected the developmental pathway of the precursor cells. Besides, this study has found the expression of CD36 on the B1 cells in the aged mice. And the single-cell B-cell receptor sequencing reveals B1 cell aging is associated with clonal expansion.

Cellulose nanofibers aerogels functionalized with AgO: Preparation, characterization and antibacterial activity.

In the experiment, a chemical oxidation method was used to prepare nano-divalent silver oxide powder with a particle size of about 10 nm. Compared with silver nanoparticles and monovalent silver compounds, nano­silver oxide has better antibacterial properties. The cellulose antibacterial aerogel was prepared by combining it with cellulose nanofibrils and using freeze-thaw cycles and freeze-drying methods. The microscopic morphology, mechanical properties, in vitro release of silver ions, antibacterial properties and biodegradability of composite aerogels were studied. The porosity of the cellulose antibacterial aerogel can reach 94%, the swelling rate was greater than 1000%, and the pore size was between 13 and 15 nm, which showed a larger storage space and attachment site for the aerogel. The diameter of the inhibition zone of the aerogel against Escherichia coli and Staphylococcus aureus was 23 mm and 20 mm respectively, and the aerogels still exhibited significant antibacterial activities with more than 99.5% reductions in Escherichia coli and Staphylococcus aureus, which shows highly effective antibacterial properties. This research proposes an economical and novel preparation method of antibacterial cellulose aerogel, making it a candidate material with high efficiency, broad-spectrum antibacterial and more suitable for life needs.