Efficacy of ganglion impar block combined with pudendal nerve pulsed radiofrequency for pudendal neuralgia management-a randomized clinical trial.

BACKGROUND: Pudendal neuralgia is a chronic and debilitating condition. Its prevalence ranges from 5 to 26%. Currently, therapeutic approaches to treat pudendal neuralgia include patient education, medication management, psychological and physical therapy, and procedural interventions, such as nerve block, trigger point injections, and surgery. Drug therapy has a limited effect on pain relief. A pudendal nerve block may cause a significant decrease in pain scores for a short time; however, its efficacy significantly decreases over time. In contrast, pudendal nerve pulsed radiofrequency can provide pain relief for 3 months, and ganglion impar block has been widely used for treating chronic perineal pain and chronic coccygodynia. This study aimed to determine the efficacy and safety of monotherapy (pudendal nerve pulsed radiofrequency) and combination therapy (pudendal nerve pulsed radiofrequency plus ganglion impar block) in patients with pudendal neuralgia. METHODS: This randomized, controlled clinical trial will include 84 patients with pudendal neuralgia who failed to respond to drug or physical therapy. Patients will be randomly assigned into one of the two groups: mono or combined treatment groups. The primary outcome will be a change in pain intensity measured using the visual analog scale. The secondary outcomes will include a Self-Rating Anxiety Scale score, Self-Rating Depression Scale score, the use of oral analgesics, the Medical Outcomes Study Health Survey Short Form-36 Item score, and the occurrence of adverse effects. The study results will be analyzed using intention-to-treat and per-protocol analyses. Primary and secondary outcomes will be evaluated between the mono and combined treatment groups. Subgroup analyses will be conducted based on the initial ailment, age, and baseline pain intensity. The safety of the treatment will be assessed by monitoring adverse events, which will be compared between the two groups. DISCUSSION: This study protocol describes a randomized, controlled clinical trial to determine the efficacy and safety of mono and combination therapies in patients with pudendal neuralgia. The study results will provide valuable information on the potential benefits of this combination therapy and contribute to the development of more effective and safer treatments for patients with pudendal neuralgia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200061800).

High-Performance W-Doped Bi0.5Sb1.5Te3 Flexible Thermoelectric Films and Generators.

Bi-Sb-Te-based thermoelectric materials have the best room-temperature thermoelectric properties, but their inherent brittleness and rigidity limit their application in the wearable field. In this study, W-doped p-type Bi0.5Sb1.5Te3 (W-BST) thin films were prepared using magnetron sputtering on polyimide substrates to create thermoelectric generators (TEGs). Bending tests showed that the thin film has excellent flexibility and mechanical durability, meeting the flexible requirements of wearable devices. W doping can significantly increase the carrier concentration, Seebeck coefficient, and electrical conductivity of BST thin films. At 300 K, the power factor of the W-BST film is 2.25 times higher than that of the undoped film, reaching 13.75 µW cm-1 K-2. First-principles calculations showed that W doping introduces significant impurity peaks in the bandgap, in which W d electrons remarkably hybridize with the Sb and Te p electrons, leading to an improved electrical conductivity of BST films. Furthermore, W doping significantly reduces the work function of BST films, thereby improving the carrier mobility. A TEG module fabricated from four layers of W-BST thin films achieved a maximum output power density of 6.91 mW cm-2 at a temperature difference of 60 K. Application tests showed that the flexible TEG module could power a portable clock using the temperature difference between body temperature and room temperature. At a medium temperature of 439 K, the assembled TEG module can provide a stable output voltage of 1.51 V to power a LED. This study demonstrates the feasibility of combining inorganic thermoelectric materials with flexible substrates to create high-performance flexible TEGs.

Simultaneous multiplex genome loci editing of Halomonas bluephagenesis using an engineered CRISPR-guided base editor.

Halomonas bluephagenesis TD serves as an exceptional chassis for next generation industrial biotechnology to produce various products. However, the simultaneous editing of multiple loci in H. bluephagenesis TD remains a significant challenge. Herein, we report the development of a multiple loci genome editing system, named CRISPR-deaminase-assisted base editor (CRISPR-BE) in H. bluephagenesis TD. This system comprises two components: a cytidine (CRISPR-cBE) and an adenosine (CRISPR-aBE) deaminase-based base editor. CRISPR-cBE can introduce a cytidine to thymidine mutation with an efficiency of up to 100 % within a 7-nt editing window in H. bluephagenesis TD. Similarly, CRISPR-aBE demonstrates an efficiency of up to 100 % in converting adenosine to guanosine mutation within a 7-nt editing window. CRISPR-cBE has been further validated and successfully employed for simultaneous multiplexed editing in H. bluephagenesis TD. Our findings reveal that CRISPR-cBE efficiently inactivated all six copies of the IS1086 gene simultaneously by introducing stop codon. This system achieved an editing efficiency of 100 % and 41.67 % in inactivating two genes and three genes, respectively. By substituting the Pcas promoter with the inducible promoter PMmp1, we optimized CRISPR-cBE system and ultimately achieved 100 % editing efficiency in inactivating three genes. In conclusion, our research offers a robust and efficient method for concurrently modifying multiple loci in H. bluephagenesis TD, opening up vast possibilities for industrial applications in the future.

Status and influencing factors of nurses' burnout: A cross-sectional study during COVID-19 regular prevention and control in Jiangsu Province, China.

Background: Chinese nurses working with immense stress may have issues with burnout during COVID-19 regular prevention and control. There were a few studies investigating status of burnout and associated factors among Chinese nurses. However, the relationships remained unclear. Objectives: To investigate status and associated factors of nurses' burnout during COVID-19 regular prevention and control. Methods: 784 nurses completed questionnaires including demographics, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Insomnia Severity Index, Impact of Event Scale-revised, Perceived Social Support Scale, Connor-Davidson Resilience Scale, General Self-efficacy Scale and Maslach Burnout Inventory. Results: 310 (39.5%), 393 (50.1%) and 576 (73.5%) of respondents were at high risk of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA). The risk of EE, DP and reduced PA were moderate, high and high. Nurses with intermediate and senior professional rank and title and worked >40 h every week had lower scores in EE. Those worked in low-risk department reported lower scores in PA. Anxiety, post-traumatic stress disorder (PTSD), self-efficacy and social support were influencing factors of EE and DP, while social support and resilience were associated factors of PA. Conclusion: Chinese nurses' burnout during COVID-19 regular prevention and control was serious. Professional rank and title, working unit, weekly working hours, anxiety, PTSD, self-efficacy, social support and resilience were associated factors of burnout.

Degradation of TRIM32 is induced by RTA for Kaposi's sarcoma-associated herpesvirus lytic replication.

TRIM32 is often aberrantly expressed in many types of cancers. Kaposi's sarcoma-associated herpesvirus (KSHV) is linked with several human malignancies, including Kaposi's sarcoma and primary effusion lymphomas (PELs). Increasing evidence has demonstrated the crucial role of KSHV lytic replication in viral tumorigenesis. However, the role of TRIM32 in herpesvirus lytic replication remains unclear. Here, we reveal that the expression of TRIM32 is upregulated by KSHV in latency, and reactivation of KSHV lytic replication leads to the inhibition of TRIM32 in PEL cells. Strikingly, RTA, the master regulator of lytic replication, interacts with TRIM32 and dramatically promotes TRIM32 for degradation via the proteasome systems. Inhibition of TRIM32 induces cell apoptosis and in turn inhibits the proliferation and colony formation of KSHV-infected PEL cells and facilitates the reactivation of KSHV lytic replication and virion production. Thus, our data imply that the degradation of TRIM32 is vital for the lytic activation of KSHV and is a potential therapeutic target for KSHV-associated cancers. IMPORTANCE: TRIM32 is associated with many cancers and viral infections; however, the role of TRIM32 in viral oncogenesis remains largely unknown. In this study, we found that the expression of TRIM32 is elevated by Kaposi's sarcoma-associated herpesvirus (KSHV) in latency, and RTA (the master regulator of lytic replication) induces TRIM32 for proteasome degradation upon viral lytic reactivation. This finding provides a potential therapeutic target for KSHV-associated cancers.

Loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing K1-ST23 hypervirulent Klebsiella pneumoniae.

OBJECTIVES: This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent Klebsiella pneumoniae (hvKp). METHODS: Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted. RESULTS: Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes blaCTX-M-15 and blaCTX-M-71, respectively, but KP30086 lost both. Cloning of gene blaCTX-M-71 and conjugation experiment of blaCTX-M-71-carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105. CONCLUSIONS: In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying blaCTX-M-71 and mutated OmpK36 had a synergetic effect on the resistance.

Strain rate-dependent failure mechanics of the intervertebral disc under tension/compression and constitutive analysis.

BACKGROUND: The intervertebral disc exhibits not only strain rate dependence (viscoelasticity), but also significant asymmetry under tensile and compressive loads, which is of great significance for understanding the mechanism of lumbar disc injury under physiological loads. OBJECTIVE: In this study, the strain rate sensitive and tension-compression asymmetry of the intervertebral disc were analyzed by experiments and constitutive equation. METHOD: The Sheep intervertebral disc samples were divided into three groups, in order to test the strain rate sensitive mechanical behavior, and the internal displacement as well as pressure distribution. RESULTS: The tensile stiffness is one order of magnitude smaller than the compression stiffness, and the logarithm of the elastic modulus is approximately linear with the logarithm of the strain rate, showing obvious tension-compression asymmetry and rate-related characteristics. In addition, the sensitivity to the strain rate is the same under these two loading conditions. The stress-strain curves of unloading and loading usually do not coincide, and form a Mullins effect hysteresis loop. The radial displacement distribution is opposite between the anterior and posterior region, which is consistent with the stress distribution. By introducing the damage factor into ZWT constitutive equation, the rate-dependent viscoelastic and weakening behavior of the intervertebral disc can be well described.

Genomic evidence for evolutionary history and local adaptation of two endemic apricots: Prunus hongpingensis and P. zhengheensis.

Apricot, belonging to the Armeniaca section of Rosaceae, is one of the economically important crop fruits that has been extensively cultivated. The natural wild apricots offer valuable genetic resources for crop improvement. However, some of them are endemic, with small populations, and are even at risk of extinction. In this study we unveil chromosome-level genome assemblies for two southern China endemic apricots, Prunus hongpingensis (PHP) and P. zhengheensis (PZH). We also characterize their evolutionary history and the genomic basis of their local adaptation using whole-genome resequencing data. Our findings reveal that PHP and PZH are closely related to Prunus armeniaca and form a distinct lineage. Both species experienced a decline in effective population size following the Last Glacial Maximum (LGM), which likely contributed to their current small population sizes. Despite the observed decrease in genetic diversity and heterozygosity, we do not observe an increased accumulation of deleterious mutations in these two endemic apricots. This is likely due to the combined effects of a low inbreeding coefficient and strong purifying selection. Furthermore, we identify a set of genes that have undergone positive selection and are associated with local environmental adaptation in PHP and PZH, respectively. These candidate genes can serve as valuable genetic resources for targeted breeding and improvement of cultivated apricots. Overall, our study not only enriches our comprehension of the evolutionary history of apricot species but also offers crucial insights for the conservation and future breeding of other endemic species amidst rapid climate changes.

Nitrogen removal and carbon reduction of mature landfill leachate under extremely low dissolved oxygen conditions by simultaneous partial nitrification anammox and denitrification.

In this study, a SNAD-SBBR process was implemented to achieve ammonia removal and carbon reduction of mature landfill leachate under extremely low dissolved oxygen conditions (0.051 mg/L) for a continuous operation of 266 days. The process demonstrated excellent removal performance, with ammonia nitrogen removal efficiency reaching 100 %, total nitrogen removal efficiency reaching 87.56 %, and an average removal rate of 0.180 kg/(m3·d). The recalcitrant organic compound removal efficiency reached 34.96 %. Nitrogen mass balance analysis revealed that the Anammox process contributed to approximately 98.1 % of the nitrogen removal. Candidatus Kuenenia achieved a relative abundance of 1.49 % in the inner layer of the carrier. In the SNAD-SBBR system, the extremely low DO environment created by the highly efficient partial nitrification stage enabled the coexistence of AnAOB, denitrifying bacteria, and Nitrosomonas, synergistically achieving ammonia removal and carbon reduction. Overall, the SNAD-SBBR process exhibits low-cost and high-efficiency characteristics, holding tremendous potential for landfill leachate treatment.

A Multifunctional Additive Based on the Cation-Anion Synergistic Effect for Highly Stable Zinc Metal Anodes.

The Zn dendrite and hydrogen evolution reaction have been a "stubborn illness" for the life span of zinc anodes, which significantly hinders the development of aqueous zinc batteries (AZBs). Herein, considering the ingenious molecular structure, a multifunctional additive based on the synergistic regulation of cations and anions at the interface is designed to promote a dendrite-free and stable Zn anode. Theoretical calculations and characterization results verified that the electrostatic shield effect of the cation, the solvation sheath structure, and the bilayer structural solid electrolyte film (SEI) jointly account for the uniform Zn deposition and side reaction suppression. Ultimately, a remarkably high average Coulombic efficiency (CE) of 99.4% is achieved in the Zn||Cu cell for 300 cycles, and a steady charge/discharge cycling over 3000 and 300 h at 1.0 mA cm-2/1.0 mAh cm-2 and 10 mA cm-2/10 mAh cm-2 is obtained in the Zn||Zn cell. Furthermore, the assembled full battery demonstrates a prolonged cycle life of 2000 cycles.

Identification of an immune-related signature as a prognostic classifier for patients with early-stage head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is the most common type and accounts for 90% of all head and neck cancer cases. Despite advances in early diagnosis and treatment strategies-chemotherapy, surgical resection, and radiotherapy-5-year survival remains grim. For patients with early-stage HNSCC, accurately predicting clinical outcomes is challenging. Considering the pivotal role of the immune system in HNSCC, we developed a reliable immune-related gene signature (IRGS) and explored its predictive accuracy in patients with early-stage HNSCC. Methods: We examined immune gene expression profiles and clinical information from 230 early-stage HNSCC specimens, including 100 cases from The Cancer Genome Atlas (TCGA), 49 cases from the Gene Expression Omnibus (GEO; GSE65858), and 81 cases from an independent clinical cohort. The prognostic signature was constructed using Kaplan-Meier analysis and the least absolute shrinkage and selection operator (LASSO) Cox algorithm. We also explored the IRGS-related biological pathways and immune landscape using bioinformatics analysis. Results: A nine-immune-gene signature was generated to significantly stratify patients into high and low-risk groups. High risk patients exhibited shorter survival time [hazard ratio (HR) =13.795, 95% confidence interval (CI): 3.275-58.109, P<0.001]. The signature demonstrated robust prognostic ability in the training and validation sets and could independently predict overall survival (OS) and relapse-free survival (RFS). Subsequently, the receiver operating characteristic (ROC) curve and C-index confirmed the signature's predictive accuracy compared to clinical parameters. Additionally, cases classified as low risk showed more immune cell infiltration than high-risk cases. Conclusions: Our novel IRGS is a reliable and robust classifier for accurate patient stratification and prognostic evaluation. Future studies will attempt to affirm the signature's clinical application to early-stage HNSCC.

BMP7-Loaded Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorate Liver Fibrosis by Targeting Activated Hepatic Stellate Cells.

Purpose: Human umbilical cord mesenchymal stem cell (hucMSC)-derived small extracellular vesicles (sEVs) are natural nanocarriers with promising potential in treating liver fibrosis and have widespread applications in the fields of nanomedicine and regenerative medicine. However, the therapeutic efficacy of natural hucMSC-sEVs is currently limited owing to their non-specific distribution in vivo and partial removal by mononuclear macrophages following systemic delivery. Thus, the therapeutic efficacy can be improved through the development of engineered hucMSC-sEVs capable to overcome these limitations. Patients and Methods: To improve the anti-liver fibrosis efficacy of hucMSC-sEVs, we genetically engineered hucMSC-sEVs to overexpress the anti-fibrotic gene bone morphogenic protein 7 (BMP7) in parental cells. This was achieved using lentiviral transfection, following which BMP7-loaded hucMSC-sEVs were isolated through ultracentrifugation. First, the liver fibrosis was induced in C57BL/6J mice by intraperitoneal injection of 50% carbon tetrachloride (CCL4) twice a week for 8 weeks. These mice were subsequently treated with BMP7+sEVs via tail vein injection, and the anti-liver fibrosis effect of BMP7+sEVs was validated using small animal in vivo imaging, immunohistochemistry (IHC), tissue immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). Finally, cell function studies were performed to confirm the in vivo results. Results: Liver imaging and liver histopathology confirmed that the engineered hucMSC-sEVs could reach the liver of mice and aggregate around activated hepatic stellate cells (aHSCs) with a significantly stronger anti-liver fibrosis effect of BMP7-loaded hucMSC-sEVs compared to those of blank or negative control-transfected hucMSC-sEVs. In vitro, BMP7-loaded hucMSC-sEVs promoted the phenotypic reversal of aHSCs and inhibited their proliferation to enhance the anti-fibrotic effects. Conclusion: These engineered BMP7-loaded hucMSC-sEVs offer a novel and promising strategy for the clinical treatment of liver fibrosis.

Response of plants and soils to inundation duration and construction of the plant‒soil association mode in the hydro‒fluctuation belt of the reservoir wetland.

Hydro-Fluctuation Belt (HFB), a periodically exposed bank area formed by changes in water level fluctuations, is critical for damaging the reservoir wetland landscape and ecological balance. Thus, it is important to explore the mechanism of hydrological conditions on the plant-soil system of the HFB for protection of the reservoir wetland and landscape restoration. Here, we investigated the response of plant community characteristics and soil environment of the HFB of Tonghui River National Wetland Park (China), is a typical reservoir wetland, to the duration of inundation, as well as the correlation between the distribution of dominant plants and soil pH, nutrient contents, and enzyme activity by linear regression and canonical correlation analyses. The results show that as the duration of inundation decreases, the vegetation within the HFB is successional from annual or biennial herbs to perennial herbs and shrubs, with dominant plant species prominent and uneven distribution of species. Soil nutrient contents and enzyme activities of HFB decreased with increasing inundation duration. Dominant species of HFB plant community are related to soil environment, with water content, pH, urease, and available potassium being principle soil environmental factors affecting their distribution. When HFB was inundated for 0-30 days, soil pH was strongly acidic, with available potassium content above 150 mg kg-1 and higher urease activity, distributed with Arundo donax L., Polygonum perfoliatum L., Alternanthera philoxeroides (Mart.) Griseb., and Daucus carota L. communities. When inundated for 30-80 days, soil pH was acidic, with lower available potassium content (50-150 mg kg-1) and urease activity, distributed with Beckmannia syzigachne (Steud.) Fern.+ Polygonum lapathifolium L., Polygonum lapathifolium L., Medicago lupulina L. + Dysphania ambrosioides L. and Leptochloa panicea (Retz.) Ohwi communities. Using the constructed HFB plant-soil correlation model, changes in the wetland soil environment can be quickly judged by the succession of plant dominant species, which provides a simpler method for the monitoring of the soil environment in the reservoir wetland, and is of great significance for the scientific management and reasonable protection of the reservoir-type wetland ecosystem.

Unveiling the diversity, composition, and dynamics of phyllosphere microbial communities in Alhagi sparsifolia across desert basins and seasons in Xinjiang, China.

Phyllosphere microbes residing on plant leaf surfaces for maintaining plant health have gained increasing recognition. However, in desert ecosystems, knowledge about the variety, composition, and coexistence patterns of microbial communities in the phyllosphere remains limited. This study, conducted across three basins (Turpan-TLF, Tarim-CL, and Dzungaria-MSW) and three seasons (spring, summer, and autumn) in Xinjiang, China, aimed to explore the diversity and composition of microbial communities in the phyllosphere, encompassing both bacteria and fungi in Alhagi sparsifolia. We also investigated the co-occurrence patterns, influencing factors, and underlying mechanisms driving these dynamics. Results indicate that phyllosphere bacteria exhibited lower diversity indices (ACE, Shannon, Simpson, Fisher phylogenetic diversity, and Richness) in spring compared to summer and autumn, while the Goods Coverage Index (GCI) was higher in spring. Conversely, diversity indices and GCI of phyllosphere fungi showed an opposite trend. Interestingly, the lowest level of multi-functionality and niche width in phyllosphere bacteria occurred in spring, while the highest level was observed in phyllosphere fungi. Furthermore, the study revealed that no significant differences in multi-functionality were found among the regions (CL, MSW, and TLF). Network analysis highlighted that during spring, phyllosphere bacteria exhibited the lowest number of nodes, edges, and average degree, while phyllosphere fungi had the highest. Surprisingly, the multi-functionality of both phyllosphere bacteria and fungi showed no significant correlation with climatic and environmental factors but displayed a significant association with the morphological characteristics and physicochemical properties of leaves. Structural Equation Model indicated that the morphological characteristics of leaves significantly influenced the multi-functionality of phyllosphere bacteria and fungi. However, the indirect and total effects of climate on multi-functionality were greater than the effects of physicochemical properties and morphological characteristics of leaves. These findings offer new insights into leaf phyllosphere microbial community structure, laying a theoretical foundation for vegetation restoration and rational plant resource utilization in desert ecosystems.

A Gradient Composite Structure Enables a Stable Microsized Silicon Suboxide-Based Anode for a High-Performance Lithium-Ion Battery.

The practical application of microsized anodes is hindered by severe volume changes and fast capacity fading. Herein, we propose a gradient composite strategy and fabricate a silicon suboxide-based composite anode (d-SiO@SiOx/C@C) consisting of a disproportionated microsized SiO inner core, a homogeneous composite SiOx/C interlayer (x ≈ 1.5), and a highly graphitized carbon outer layer. The robust SiOx/C interlayer can realize a gradient abatement of stress and simultaneously connect the inner SiO core and carbon outer layer through covalent bonds. As a result, d-SiO@SiOx/C@C delivers a specific capacity of 1023 mAh/g after 300 cycles at 1 A/g with a retention of >90% and an average Coulombic efficiency of >99.7%. A full cell assembled with a LiNi0.8Co0.15Al0.05O2 cathode displays a remarkable specific energy density of 569 Wh/kg based on total active materials as well as excellent cycling stability. Our strategy provides a promising alternative for designing structurally and electrochemically stable microsized anodes with high capacity.

Brain function abnormalities and neuroinflammation in people living with HIV-associated anxiety disorders.

Background: People living with HIV (PLWH) exhibits an increased susceptibility to anxiety disorders, concomitant with heightened vulnerability to aberrant immune activation and inflammatory responses, and endocrine dysfunction. There exists a dearth of scholarly investigations pertaining to the neurological, immune, and endocrine dimensions of HIV-associated anxiety disorders. Method: This study aimed to compare a group of 16 individuals diagnosed with HIV-associated anxiety disorders (HIV ANXs) according to the Diagnostic and statistical manual of mental disorders (5th ed.), with a HIV individual control group (HIV control) of 49 PLWH without mental disorders. Muti-modal magnetic resonance was employed to assess the brain function and structure of both groups. Seed-based functional connectivity (FC) was used to assess the regional intrinsic brain activity and the influence of regional disturbances on FC with other brain regions. Peripheral blood cytokines and chemokines concentrations were measured using liquid chip and ELISA. Results: Amplitude of low-frequency fluctuations in the right inferior temporal gyrus (ITG) was increased. There is a significant decreased regional homogeneity in HIV ANXs in the right superior occipital gyrus (SOG). The right ITG and the right SOG were separately set as the seed brain region of interest (ROI 1 and ROI 2) to be analyzed the FC. FC decreased in HIV ANXs between ROI1 and the right middle occipital gyrus, the right SOG, FC between ROI2 and left ITG increased in HIV ANXs. No significant structural difference was found between two groups. Pro-inflammatory chemokines showed higher levels in the HIV ANXs. Pro-inflammatory cytokines, neurotrophic factors, and endocrine factors were significantly correlated with alterations in brain function. Conclusion: This study suggests that patients with HIV-associated anxiety disorders may exhibit abnormalities in neurologic, immune, and endocrine functioning. Consequently, it is imperative to implement additional screening and intervention measures for anxiety disorders among PLWH.

Pathological proliferation: a potential mechanism for poor CD4+ T cell recovery in people living with HIV.

Background: People living with HIV (PLWH) fail to achieve normalization of CD4+ T cell counts and function, especially in immunological non-responders (INRs). The frequencies of Ki67+CD4+ T cells were inversely associated with CD4+ T cell counts in HIV infected patients. Early ART did not normalize CD4+ T cell proliferation. However, the features of the abnormal proliferation CD4+ T cell in INRs are far from known. Method: PLWH were divided into INRs (n= 16) and immunological responders (IRs, n= 53) groups. Mass cytometry was applied to peripheral blood T cells to profile the immune cells and liquid chip technique was used to measure plasma levels of cytokines and chemokines. Correlation analyses were conducted to evaluate associations between the degree of CD4+ T cell proliferation and immune function. Results: The percentage of Ki67+ CD4+ T cells were significant higher in INRs, and we defined these cells with significant higher level of Ki67, as over-proliferating cells. No significant difference of markers' expression (HLA-DR, CD38, CD57, PD-1, PD-L1, CD107a, perforin) was found between INRs and IRs. Compared with naïve CD4+ T cells in INRs, Ki67+ CD4+ T cells exhibited lower levels of CD57 and CD38. Whereas Ki67+ T cells exhibited higher levels of CD38 and CD57 and activation compared with differentiated mature central memory CD4+ T cells and effector memory CD4+ T cells. Ki67+ cells did not show higher levels of senescence and activation compared to certain Ki67- CD4+ central memory T cells in IRs. Furthermore, Ki67+ CD4+ Tcm cells exhibited positive correlations with pro-inflammatory cytokines. Conclusion: We proposed and validated the hypothesis of "pathological proliferation" in INRs: excessive proliferation of CD4+ T cells in INRs may be accompanied by aberrant activation, senescence and loss of immune function. Eventually, such over-proliferating but poor-quality cells in INRs result in incomplete recovery of both CD4+ T cell counts and function. An intervention that enhancing the proliferative capacity or functional ability or both of CD4+ T cell in INRs might therefore be beneficial.

Effects of community structure of Cunninghamia lanceolata sprouting forests with different densities on ecosystem carbon density at the early stage of succession.

To explore potential responses of ecosystem carbon density to changes of community structure during natural regeneration of woody plants, we analyzed the relationships between ecosystem carbon density and its components, tree species diversity, structural diversity (CVDBH) and spatial structure parameters (mingling, aggregation, dominance, crowding) of Cunninghamia lanceolata forests with different sprouting densities (1154, 847 and 465 individuals·hm-2) at the early stage of succession in Baishanzu National Park. The results showed that tree species diversity (species richness index and Shannon diversity index) increased with the decrease of sprouting density of C. lanceolata. Among the stand structural parameters, CVDBH, stand density, and mingling increased with the decrease of sprouting density of C. lanceolata. The stand distribution pattern of different C. lanceolata densities was uniform, with sub-dominant stand growth status and relatively dense status. The carbon density of tree layer under high, medium, and low sprouting densities of C. lanceolata were 57.56, 56.12 and 46.54 t·hm-2, soil carbon density were 104.35, 122.71 and 142.00 t·hm-2, and the total carbon density of ecosystem were 164.59, 182.41 and 190.13 t·hm-2, respectively. There was little variation in carbon density of understory layer and litter layer among different treatments. The carbon density distribution characteristics of different C. lanceolata densities were following the order of soil layer (63.4%-74.7%) > tree layer (24.5%-35.0%) > understory layer and litter layer (0.8%-2.0%). The results of variance partitioning analysis indicated that the change of tree layer carbon density was mainly influenced by stand structure diversity, soil layer carbon density was influenced by both tree species diversity and stand structure diversity, while ecosystem carbon density was mainly influenced by tree species diversity. Stand spatial structure parameters had a relatively little effect on ecosystem carbon density and its components. The sprouting density of C. lanceolata significantly affected ecosystem carbon accumulation during the conversion from C. lanceolata plantations to natural forests. A lower remaining density of C. lanceolata (about 500 individuals·hm-2) was more conducive to forest carbon sequestration.

NaClO Co-selects antibiotic and disinfectant resistance in Klebsiella pneumonia: Implications for the potential risk of extensive disinfectant use during COVID-19 pandemic.

The inappropriate use of antibiotics is widely recognized as the primary driver of bacterial antibiotic resistance. However, less attention has been given to the potential induction of multidrug-resistant bacteria through exposure to disinfectants. In this study, Klebsiella pneumonia, an opportunistic pathogen commonly associated with hospital and community-acquired infection, was experimentally exposed to NaClO at both minimum inhibitory concentration (MIC) and sub-MIC levels over a period of 60 days. The result demonstrated that NaClO exposure led to enhanced resistance of K. pneumonia to both NaClO itself and five antibiotics (erythromycin, polymyxin B, gentamicin, tetracycline, and ciprofloxacin). Concurrently, the evolved resistant strains exhibited fitness costs, as evidenced by decreased growth rates. Whole population sequencing revealed that both concentrations of NaClO exposure caused genetic mutations in the genome of K. pneumonia. Some of these mutations were known to be associated with antibiotic resistance, while others had not previously been identified as such. In addition, 11 identified mutations were located in the virulence factors, demonstrating that NaClO exposure may also impact the pathogenicity of K. pneumoniae. Overall, this study highlights the potential for the widespread use of NaClO-containing disinfectants during the COVID-19 pandemic to contribute to the emergence of antibiotic-resistant bacteria. ENVIRONMENTAL IMPLICATION: Considering the potential hazardous effects of disinfectant residues on environment, organisms and biodiversity, the sharp rise in use of disinfectants during COVID-19 pandemic has been considered highly likely to cause worldwide secondary disasters in ecosystems and human health. This study demonstrated that NaClO exposure enhanced the resistance of K. pneumonia to both NaClO and five antibiotics (erythromycin, polymyxin B, gentamicin, tetracycline, and ciprofloxacin), highlighting the widespread use of NaClO-containing disinfectants during the COVID-19 pandemic may increase the emergence of antibiotic-resistant bacteria in the environment.