Adenovirus type 5-expressing Gn induces better protective immunity than Gc against SFTSV infection in mice.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by the SFTS virus (SFTSV) with high morbidity and mortality. The major immunodominant region of SFTSV surface glycoprotein (G) remains unclear. In this study, we constructed adenovirus type 5 (Ad5) vectored vaccine candidates expressing different regions of SFTSV G (Gn, Gc and Gn-Gc) and evaluated their immunogenicity and protective efficacy in mice. In wild-type mice, compared with Ad5-Gc or Ad5-Gn-Gc, Ad5-Gn recruited/activated more dendritic cells and B cells in lymph nodes or peripheral blood, causing Th1-/Th2-mediated responses in splenocytes and triggered a greater level of SFTSV-neutralizing antibodies. In IFNAR Ab-treated mice, immunization of Ad5-Gn exhibited better protection against SFTSV challenge than Ad5-Gc or Ad5-Gn-Gc. Furthermore, passive immunization revealed complete protective immunity of Gn-specific serum rather than Gc. Collectively, our data demonstrated that Gn is the immunodominant fragment of SFTSV G and could be a potential candidate for SFTSV vaccine development.

Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China.

BACKGROUND: Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. METHODS: In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. FINDINGS: 445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. INTERPRETATION: The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. FUNDING: Akeso Biopharma.

Potential cardiac-derived exosomal miRNAs involved in cardiac healing and remodeling after myocardial ischemia-reperfusion injury.

Migratory cells exist in the heart, such as immune cells, fibroblasts, endothelial cells, etc. During myocardium injury, such as ischemia-reperfusion (MIRI), cells migrate to the site of injury to perform repair functions. However, excessive aggregation of these cells may exacerbate damage to the structure and function of the heart, such as acute myocarditis and myocardial fibrosis. Myocardial injury releases exosomes, which are a type of vesicle with signal transduction function and the miRNA carried by exosomes can control cell migration function. Therefore, regulating this migratory cell population through cardiac-derived exosomal miRNA is crucial for protecting and maintaining cardiac function. Through whole transcriptome RNA sequencing, exosomal miRNA sequencing and single-cell dataset analysis, we (1) determined the potential molecular regulatory role of the lncRNA‒miRNA‒mRNA axis in MIRI, (2) screened four important exosomal miRNAs that could be released by cardiac tissue, and (3) screened seven genes related to cell locomotion that are regulated by four miRNAs, among which Tradd and Ephb6 may be specific for promoting migration of different cells of myocardial tissue in myocardial infarct. We generated a core miRNA‒mRNA network based on the functions of the target genes, which may be not only a target for cardiac repair but also a potential diagnostic marker for interactions between the heart and other tissues or organs. In conclusion, we elucidated the potential mechanism of MIRI in cardiac remodeling from the perspective of cell migration, and inhibition of cellular overmigration based on this network may provide new therapeutic targets for MIRI and to prevent MIRI from developing into other diseases.

Sini San ameliorates lipid metabolism in hyperprolactinemia rat with liver-depression.

Sini San (SNS) is used to treat liver depression and is applied in both food and herbal medicine. Hyperprolactinemia (HPRL) is a common endocrine disorder, and patients with HPRL are usually associated with depressive symptoms. However, whether SNS is effective in treating HPRL combined with liver depression and its underlying mechanisms are unknown. We applied network pharmacology and molecular docking to predict the mechanism of SNS for the treatment of liver-depressed HPRL. Therapeutic effects were validated in animal models and cells. Metabolomics was also used to evaluate the effect of SNS on liver-depressed HPRL. Network pharmacology and molecular docking analysis showed that AKT1, TNF and IL6 were the key targets, and SNS improved depressive behaviors, regulated sex hormone levels, and improved ovarian morphology. Combined network pharmacology and metabolomics analyses showed that SNS could act by regulating lipid metabolism. In addition, SNS significantly reduced the release of prolactin (PRL) in rat pituitary tumor MMQ cells. Overall, SNS can significantly treat HPRL liver depression at both animal and cellular levels, and effectively alleviate the related symptoms by regulating lipid metabolism. AKT1, TNF and IL6 may be key targets.

Oral propranolol for the treatment of hemangiomas in high-risk infants: safety and cost analysis of outpatient-initiated therapy.

Objectives: To investigate the safety and cost analysis of oral propranolol treatment for high-risk infantile hemangiomas starting from the outpatient setting. Methods: A total of 41 high-risk infantile hemangioma patients from outpatient settings and 43 from inpatient settings were selected for the study. After routine pre-treatment examinations, patients were administered propranolol in a stepwise incremental dosing regimen over three consecutive days in the outpatient clinic. Changes in heart rate, blood pressure and PR interval before and after medication were compared. On the 10th day post-medication, liver and kidney functions, fasting blood glucose, tumor ultrasonography, and electrocardiogram were re-evaluated. The costs of treatment starting from the outpatient clinic (including pre-treatment examinations and the first three days of treatment) were calculated and compared with those of similarly managed inpatient cases. Results: The majority of patients exhibited a reduction in heart rate and blood pressure, as well as an extended PR interval after treatment of medication (P < 0.05), which remained within normal limits without clinical symptoms. On the 10th day post-medication, statistical differences in blood biochemistry and electrocardiograms were observed when compared to pre-treatment values (P < 0.05), but all values remained within normal ranges. No severe adverse reactions such as hypoglycemia occurred. Additionally, the cost of treatment from the outpatient clinic was significantly lower than that of inpatient care. Conclusion: Oral propranolol treatment for high-risk infantile hemangiomas starting from the outpatient setting is associated with few adverse reactions and significantly reduced treatment costs. It is worthy of broader application in hospitals without dermatology wards.

[Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on metabolomics].

In this study, a mouse model of premature ovarian failure(POF) was constructed by injecting D-galactose(200 mg·kg~(-1)) into the back of the neck for 6 weeks. The mice were randomly divided into a normal group(group N), a model group(group M), and a Qiwei Guibao Granules group(group A, 12.87 g·kg~(-1)). Starting from the 11th day of modeling, group A was treated with Qiwei Guibao Granules by gavage for 32 days, while group M and group N were given equal volume of saline. Metabolomics analysis was used to explore the mechanism of action of Qiwei Guibao Granules in the treatment of POF. The results showed that compared with group N, the group M exhibited decreased wet weight of bilateral ovaries, increased levels of LH and FSH in serum, and significantly decreased levels of E_2 and PROG. After treatment with Qiwei Guibao Granules, compared with the group M, the group A showed a significant increase in the wet weight of bilateral ovaries, a significant decrease in the levels of FSH and LH in serum, and a significant increase in the level of E_2. Metabolomics analysis revealed 55 differential metabolites identified between group N and group M(14 upregulated and 41 downregulated compared with group N) and 82 differential metabolites identified between group M and group A(56 upregulated and 26 downregulated compared with group M), with 5 metabolites showing consistent changes between the group N vs group M. After excluding these 5 metabolites, 77 metabolites that changed after intervention with Qiwei Guibao Granules were focused on. These mainly involved histidine metabolism, glycine, serine, and threonine metabolism, and glycerophospholipid metabolism. Among them, carnosine, 1-methyl-L-histidine, imidazoleacetic acid, choline, L-threonine, beta-hydroxypyruvic acid, phosphatidylcholine, and glycerol-3-phosphate were the major differential metabolites in these three metabolic pathways. Therefore, Qiwei Guibao Granules may exert therapeutic effects on POF mice by regulating amino acid metabolism and lipid metabolism in the mouse body.

Risks of bleeding and thromboembolic events in patients undergoing colonoscopy on uninterrupted and interrupted anticoagulant therapy in real-world setting.

BACKGROUND: Although anticoagulants may potentially increase the risk of post-colonoscopy bleeding events, temporary discontinuation of medications could elevate the risk of thromboembolism (TE). There is a paucity of data regarding the incidence of bleeding and TE events in patients undergoing colonoscopy while on uninterrupted or interrupted anticoagulant therapy. Therefore, we aimed to ascertain the risks of post-colonoscopy TE and bleeding in patients with continuous or interrupted use of anticoagulant agents. METHODS: The electronic databases of PubMed, Embase, and the Cochrane library were comprehensively searched from inception to March 15, 2024. We identified studies reporting the incidence of bleeding and TE events in patients undergoing colonoscopy with uninterrupted or interrupted anticoagulant therapy. The pooled incidence rate of bleeding and TE events was estimated using a random-effects model. RESULTS: This study included a total of 15 studies involving 63, 017 patients. Overall, the incidence of post-procedural bleeding for uninterrupted and interrupted direct oral anticoagulants (DOACs) was found to be 3.60 % (95 % CI: 1.60 %-5.60 %), and 0.90 % (95 % CI: 0.10 %-10.30 %), respectively. Subgroup analysis revealed that older age patients (≥65 years) had a significantly higher rate of bleeding with uninterrupted DOACs therapy compared to younger age patients (< 65 years) (7.20 % vs. 2.00 %). The highest rate of bleeding was observed in Asia (7.20 %, 95 % CI: 2.20 %-12.10 %). Similarly, the risk of bleeding was significantly increased among patients interrupting DOACs therapy in Asia compared to North America (1.40 % vs. 0.26 %). For patients on uninterrupted and interrupted warfarin, a higher rate of bleeding events was observed in older age patients than younger age patients (4.90 % vs. 0.80 %, and 2.20 % vs. 1.70 %, respectively). Uninterrupted warfarin showed a more significant risk of bleeding in Asia (4.20 %, 95%CI: 1.90 %-6.60 %) compared to North America (1.00 %, 95%CI: 0.50 %-1.50 %). Among those who did not interrupt DOACs therapy, the incidence of TE was the lowest (0.08 %, 95%CI: 0.04 %-0.11 %). CONCLUSION: This study provides a comprehensive assessment of bleeding and TE risks in patients undergoing colonoscopy while receiving uninterrupted or interrupted anticoagulant therapy in the real-world setting. The overall incidence of post-colonoscopy bleeding and TE events is relatively low. However, the uninterrupted DOACs and warfarin are associated with an elevated risk of bleeding, particularly among elderly patients and the Asian population.

Clinical and immunoserological characteristics of anti-p200 pemphigoid: Comparisons of patients with epitope spreading and non-epitope spreading.

BACKGROUND: Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease. Although the phenomenon of epitope spreading has been reported to be common in anti-p200 pemphigoid, the association between its clinical and immunoserological features has yet to be elucidated. OBJECTIVES: Our aim was to compare the clinical and immunoserological characteristics of anti-p200 pemphigoid patients with and without epitope spreading. METHODS: We performed a retrospective cohort study encompassing 30 patients with anti-p200 pemphigoid between January 2015 and December 2022. The clinical and immunoserological characteristics of anti-p200 pemphigoid were analyzed using combined immunoserological assays. RESULTS: Epitope spreading was observed in 11 of 30 patients (36.7%) with anti-p200 pemphigoid. Compared with patients in the non-epitope spreading group, patients in the epitope spreading group showed more heterogeneous clinical presentations (P = 0.018), a higher proportion of mucosal involvement (P = 0.003), higher Bullous Pemphigoid Disease Area Index (BPDAI) scores for skin erosions/blisters (P = 0.018), mucosal erosions/blisters (P = 0.001), activity (P = 0.017) and total scores (P = 0.022), and required a higher initial dose of prednisone for disease control (P = 0.040). CONCLUSIONS: This study supported the idea that anti-p200 pemphigoid was prone to epitope spreading. Anti-p200 pemphigoid patients with epitope spreading are more likely to present heterogeneous clinical phenotypes, frequent mucosal involvement, and a more severe and recalcitrant disease course.

Covalent Organic Frameworks-Based Fluorescence Sensor Array and QSAR Study for Identification of Energetic Heterocyclic Compounds.

The accurate identification of energetic heterocyclic compounds (EHCs) is of great significance in munition assessment, environmental monitoring, and biosafety but remains largely underexplored. Herein, a covalent organic frameworks-based fluorescence sensor array (COFx sensor array) for efficient screening of EHCs is reported. The topologies of the COFs were rationally designed by modulating the pore sizes and linkage strategies to achieve the simplified sensor array. Eighteen EHC representatives, including single-, dual-, and three-ring EHCs with multivariate substructures, were successfully discriminated ranging from 10 µM to 1 mM. The sensor array showed robust selectivity against a wide range of interferences. The quantitative structure-activity relationship (QSAR) analysis has been conducted for the mechanistic study of the sensor array. Three multiple linear regression models have been established using molecular descriptors to evaluate and predict Stern-Volmer coefficient values, achieving explicit correlation between EHC structures and the signal outputs of the sensor array. Five molecular descriptors are retained to reveal the governing factors of the sensor array resolution. The QSAR analysis facilitates the design and development of the COFx sensor array, offering a new approach for customized multivariate analysis.

A kinase fusion protein from Aegilops longissima confers resistance to wheat powdery mildew.

Many disease resistance genes have been introgressed into wheat from its wild relatives. However, reduced recombination within the introgressed segments hinders the cloning of the introgressed genes. Here, we have cloned the powdery mildew resistance gene Pm13, which is introgressed into wheat from Aegilops longissima, using a method that combines physical mapping with radiation-induced chromosomal aberrations and transcriptome sequencing analysis of ethyl methanesulfonate (EMS)-induced loss-of-function mutants. Pm13 encodes a kinase fusion protein, designated MLKL-K, with an N-terminal domain of mixed lineage kinase domain-like protein (MLKL_NTD domain) and a C-terminal serine/threonine kinase domain bridged by a brace. The resistance function of Pm13 is validated through transient and stable transgenic complementation assays. Transient over-expression analyses in Nicotiana benthamiana leaves and wheat protoplasts reveal that the fragment Brace-Kinase122-476 of MLKL-K is capable of inducing cell death, which is dependent on a functional kinase domain and the three α-helices in the brace region close to the N-terminus of the kinase domain.

Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

Spatiotemporal distribution of oxidative potential in PM2.5 and its key components across six Chinese cities.

Increasing evidence has supported that oxidative potential (OP) serves as a crucial indicator of health risk of exposure to PM2.5 over mass concentration. However, there is a lack of comparative studies across multiple cities, particularly on a fine temporal scale. In this study, we aim to investigate daily variation of ambient PM2.5 OP through simultaneous samplings in six Chinese cities for one year. Results showed that more than 60 % of the sampling days exhibited non-zero ranking difference between volume-normalized oxidative potential (OPv) and mass concentration among the six cities. Key components contributing to OPv inculde Mn, NO3-, and K+, followed by Ca2+, Al, SO42-, Cl-, Fe, and NH4+. Based on these chemical components, we developed a stepwise multivariable linear regression model (R2: 0.71) for OPv prediction. The performance of the model is comparable to both species- and sources-based ones in the literature. These findings suggest that a relatively lower daily-averaged mass concentration of PM2.5 does not necessarily indicate a lower oxidative risk. Future studies and policy developments on health benefits should also consider OPv rather than mass concentration alone. Priority could be given to sources/species that contribute significantly to oxidative potential of ambient PM2.5. SYNOPSIS: This study highlights inclusion of oxidative potential as a complementary metric for air pollution assessment and control.

Preliminary Screening and Study of Key Gene Expression in Endometrial Window Period.

Background: Implantation is a highly coordinated event involving both embryonic and endometrial participation. The endometrium expresses a complex array of proteins during the menstrual cycle many of which help to define a period of receptivity collectively known as the "window of implantation." Objective: Using high-throughput RNA sequencing technology analysis to find differentially expressed genes before and after the endometrial window, and search for key marker genes of the membrane implantation window. Design: This was a retrospective study. Setting: This study was performed in the Department of Obstetrics and Gynecology, Taizhou People's Hospital. Participants: Fifty patients with repeated implantation failure in in vitro fertilization were selected and were divided into (1) the normal window group (36 cases); (2) the window forward group (8 cases); and (3) the window backward group (6 cases) based on endometrial biopsy findings. Interventions: Using RNA sequencing technology combined with biological information analysis tools to analyze the differentially-expressed genes in 9 samples. Gene Ontology databases were used for the functional annotation of these differentially-expressed genes. Kyoto Encyclopedia of Genes and Genomes analysis was used to draw a signal path diagram. Primary Outcome Measures: (1) Screening of differentially-expressed genes and (2) functional analysis of the differential genes. Results: A total of 22 differentially-expressed genes related to endometrial receptivity were obtained by transcriptome sequencing. Seven of the 22 differentially-expressed genes have been shown to have a close relationship with the endometrial receptive window period. Further, it was proved that the Wnt signaling pathway and mitogen-activated protein kinase signaling pathway were closely related to endometrial receptivity. Conclusions: The present study identified a series of key genes and pathways that may be involved in the endometrial window period, providing an experimental and theoretical basis for exploring the personalized embryo transfer program.

Comparative Analysis of Micrometer-Sized Particle Deposition in the Olfactory Regions of Adult and Pediatric Nasal Cavities: A Computational Study.

Direct nose-to-brain drug delivery, a promising approach for treating neurological disorders, faces challenges due to anatomical variations between adults and children. This study aims to investigate the spatial particle deposition of micron-sized particles in the nasal cavity among adult and pediatric subjects. This study focuses on the olfactory region considering the effect of intrasubject parameters and particle properties. Two child and two adult nose models were developed based on computed tomography (CT) images, in which the olfactory region of the four nasal cavity models comprises 7% to 10% of the total nasal cavity area. Computational Fluid Dynamics (CFD) coupled with a discrete phase model (DPM) was implemented to simulate the particle transport and deposition. To study the deposition of micrometer-sized drugs in the human nasal cavity during a seated posture, particles with diameters ranging from 1 to 100 µm were considered under a flow rate of 15 LPM. The nasal cavity area of adults is approximately 1.2 to 2 times larger than that of children. The results show that the regional deposition fraction of the olfactory region in all subjects was meager for 1-100 µm particles, with the highest deposition fraction of 5.7%. The deposition fraction of the whole nasal cavity increased with the increasing particle size. Crucially, we identified a correlation between regional deposition distribution and nasal cavity geometry, offering valuable insights for optimizing intranasal drug delivery.

Evaluation of the inflammatory parameters as potential biomarkers of systemic inflammation extent and the disease severity in psoriasis patients.

The disease severity of psoriasis is mainly assessed subjectively via  psoriasis area and severity index (PASI) and body surface area (BSA), while an optimal measure of cutaneous response, may overlook systemic inflammation in psoriasis patients. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), monocyte to high density lipoprotein ratio (MHR), and systemic immune-inflammation index (SII) exhibit notable associations with the inflammation severity in multiple diseases. The aim of this retrospective study was to explore the associations between inflammatory parameters and the skin lesions' severity of psoriasis. After analysis, we found that patients with psoriasis had higher NLR, MLR, PLR, MHR, and SII levels compared to the control group. At baseline, the parameters of NLR (r = 0.124, P = 0.003), MLR (r = 0.153, P < 0.001), MHR (r = 0.217, P < 0.001) and SII (r = 0.141, P = 0.001) had a positive correlation with PASI in psoriasis patients. At the same time, we analyzed the patients who received different systemic therapy. We observed a significant decrease in NLR, PLR, MLR, and SII in psoriasis patients after treatment. Notably, TNF-α inhibitors and IL-17A inhibitors subgroups showed a more significant reduction than IL-23/IL-12/23 inhibitors and MTX medication. Additionally, we found the change of NLR (r = 0.194, P < 0.001), PLR (r = 0.104, P = 0.014), MLR (r = 0.191, P < 0.001), MHR (r = 0.106, P = 0.012), and SII (r = 0.228, P < 0.001) had a positive correlation with the change of PASI in psoriasis patients. In conclusion, this study suggests that NLR, MLR, and SII may serve as useful biomarkers for assessing systemic inflammation extent and disease severity in psoriasis patients.

The Investigation of the Subtle Structural Discrepancies between Oryza Sativa Recombinant and Plasma-Derived Human Serum Albumins to Design a Novel Nanoparticle as a Taxane Delivery System.

To solve the large size faultiness of Oryza sativa recombinant human serum albumin nanoparticle (OsrHSA NP), the structural discrepancies between OsrHSA and plasma-derived human serum albumin (pdHSA) were analyzed deeply in this research. It demonstrated that there were some subtle structural discrepancies located in subdomain IA and IIA between OsrHSA and pdHSA, which included peptide backbone, disulphide bridge and some amino acids. Firstly, the structural discrepancies were investigated through literature comparison, it inferred that the structural discrepancies resulted from the fatty acid (FA) binding to OsrHSA at site 2 of subdomain IA and IIA. To form a cavity for accommodation of FA molecule in OsrHSA, the peptide backbone structure of subdomain IA and IIA would change, accompanied by the conformational transition of disulphide bridges and side chain structure change of some amino acids in subdomain IA and IIA. These alterations induced the exposure of tryptophan (Trp) and tyrosine (Tyr) residues in subdomain IA and IIA and the decrease of net negative charges of molecular surface. The former would promote more OsrHSA molecules aggregate, and the latter would weaken the electrostatic repulsion. As a result, the size of OsrHSA NP was more extensive than that of pdHSA NP (175.84 ± 15.63 nm vs. 31.67 ± 1.31 nm) when the concentration of Dimethyl Sulphoxide (DMSO) was 30% (v/v). In this study, the experimental scheme of OsrHSA NP preparation was improved. There were two changes in the enhanced preparation scheme: pH 8.2 PBS buffer and 63% DMSO. It indicated that the improved OsrHSA NP carrier was comparable to the pdHSA NP carrier. The size and drug loading of paclitaxel-loaded improved OsrHSA NP were 53.57 ± 3.63 nm and 7.25 ± 0.46% (w/w), and those of docetaxel-loaded improved OsrHSA NP were 44.75 ± 2.26 nm and 8.43 ± 0.74% (w/w). Moreover, both NPs exhibited good stability for 168 h at 7.4 pH values. It is established that the improved OsrHSA NP is comparable to the pdHSA NP as a taxane delivery system.

Clinical Characteristics and Pathogen Spectrum of Male Genital Fungal Infections in Nanchang Area, South China.

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.

Dependence of evolution of Cyanobacteria superiority on temperature and nutrient use efficiency in a meso-eutrophic plateau lake.

Algal blooms in lakes have been a challenging environmental issue globally under the dual influence of human activity and climate change. Considerable progress has been made in the study of phytoplankton dynamics in lakes; The long-term in situ evolution of dominant bloom-forming cyanobacteria in meso-eutrophic plateau lakes, however, lacks systematic research. Here, the monthly parameters from 12 sampling sites during the period of 1997-2022 were utilized to investigate the underlying mechanisms driving the superiority of bloom-forming cyanobacteria in Erhai, a representative meso-eutrophic plateau lake. The findings indicate that global warming will intensify the risk of cynaobacteria blooms, prolong Microcystis blooms in autumn to winter or even into the following year, and increase the superiority of filamentous Planktothrix and Cylindrospermum in summer and autumn. High RUETN (1.52 Biomass/TN, 0.95-3.04 times higher than other species) under N limitation (TN < 0.5 mg/L, TN/TP < 22.6) in the meso-eutrophic Lake Erhai facilitates the superiority of Dolichospermum. High RUETP (43.8 Biomass/TP, 2.1-10.2 times higher than others) in TP of 0.03-0.05 mg/L promotes the superiority of Planktothrix and Cylindrospermum. We provided a novel insight into the formation of Planktothrix and Cylindrospermum superiority in meso-eutrophic plateau lake with low TP (0.005-0.07 mg/L), which is mainly influenced by warming, high RUETP and their vertical migration characteristics. Therefore, we posit that although the obvious improvement of lake water quality is not directly proportional to the control efficacy of cyanobacterial blooms, the evolutionary shift in cyanobacteria population structure from Microcystis, which thrives under high nitrogen and phosphorus conditions, to filamentous cyanobacteria adapted to low nitrogen and phosphorus levels may serve as a significant indicator of water quality amelioration. Therefore, we suggest that the risk of filamentous cyanobacteria blooms in the meso-eutrophic plateau lake should be given attention, particularly in light of improving water quality and global warming, to ensure drinking water safety.