Search

Abstract Background The study aims to investigate the demographic characteristics, the variations in their immune status, and mortality risk among HIV-1 infection long-term non-progressors (LTNP). Methods Eligible LTNP and typical progressors (TP) were recruited in Guangxi by December 2018. Participants were followed up until December 2022, monitoring ART status, CD4+ T cell counts, and survival/death outcomes. Multivariate logistic, Cox regression, and Kaplan-Meier method were employed to scrutinize associated factors and mortality risk of LTNP. Results A total of 212 LTNP and 390 TP were included. LTNP cohort predominantly comprised males (84.43%), those diagnosed with HIV at age ≤ 40 years (93.87%), and those infected through injection drug use (59.91%). The mortality rate of LTNP were lower than TP (12.74% vs. 27.18%). TP had a higher mortality risk compared to LTNP (adjusted hazard ratio [aHR] = 4.051, 95% CI: 2.284–7.186, P

Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g., $$n\rightarrow 3 \nu $$ n → 3 ν or $$nn \rightarrow 2 \nu $$ n n → 2 ν ), which do not produce an observable signal. The invisible decay includes two decay modes: $$ n \rightarrow { inv} $$ n → inv and $$ nn \rightarrow { inv} $$ n n → inv . The invisible decays of s-shell neutrons in $$^{12}\textrm{C}$$ 12 C will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $${\bar{\nu }}_e$$ ν ¯ e , natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ τ / B ( n → inv ) > 5.0 × 10 31 years and $$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ τ / B ( n n → inv ) > 1.4 × 10 32 years .

A series of flexible and self-standing coal-derived carbon fibers (CCFs) were fabricated through electrospinning coupled with carbonization using bituminous coal and polyacrylonitrile (PAN) as the carbon precursors. These CCFs were utilized as free-standing lithium-ion battery (LIB) anodes. Optimizing carbonization temperature reveals that the CCFs exhibit a one-dimensional solid linear structure with a uniform distribution of graphite-like microcrystals. These fibers possess a dense structure and smooth surface, with averaging diameter from approximately 125.0 to 210.0 nm at carbonization temperatures ranging from 600 to 900 °C. During electrospinning and carbonization, the aromatic rings enriched in bituminous coal crosslink with PAN chains, forming a robust three-dimensional (3D) framework. This 3D microstructure significantly enhances the flexibility and tensile strength of CCFs, while increasing the graphite-like sp2 microcrystalline carbon content, thus improving electrical conductivity. The CCFs carbonized at 700 °C demonstrate an optimal balance of sp3 amorphous and sp2 graphite-like carbons. The average diameter of CCFs-700 is 177 nm and the specific surface area (SSA) is 7.2 m2·g−1. Additionally, the fibers contain oxygen-containing functional groups, as well as nitrogen-containing functional groups, including pyridinic nitrogen and pyrrolic nitrogen. Owing to its characteristics, the CCFs-700 showcases remarkable electrochemical performance, delivering a high reversible capacity of 631.4 mAh·g−1. CCFs-700 also exhibit outstanding cycle stability, which retains approximately all of their first capacity (400.1 mAh·g−1) after 120 cycles. This research offers an economical yet scalable approach for producing flexible and self-supporting anodes for LIBs that do not require current collectors, binders and conductive additives, thereby simplifying the electrode fabrication process.

Abstract Diabetes Mellitus combined with Mild Cognitive Impairment (DM-MCI) is a high incidence disease among the elderly. Patients with DM-MCI have considerably higher risk of dementia, whose daily self-care and life management (i.e. self-management) have a significant impact on the development of their condition. Thus, the inclusion and discrimination of subsequent interventions according to their self-management is an urgent issue. A Sparse-representation-based Discriminative Classification model (SDC) is proposed in this paper to correctly classify MCI-DM patients based on their self-management ability. Specifically, an L1-minimization sparse representation model, an efficient machine learning model, is used to obtain the sparse histogram that encodes the identity of the test sample. Then, the coefficient of determination $$\:{R}^{2}$$ is adopted to determine the category based on the sparse histogram of the test sample. Extensive experiments on the self-management data of DM-MCI are conducted to verify the effectiveness of SDC. The experimental results show that the accuracy $$\:\mathcal{A}$$ , precision $$\:\mathcal{P}$$ , recall $$\:\mathcal{R}$$ , and F1-score $$\:\mathcal{F}$$ are 94.3%, 95.0%, 94.3%, and 94.5%, respectively, demonstrating the excellent performance of SDC. The model used in this study has high accuracy and can be used for subgroup discrimination. The use of the sparse representation model in this study has supportive implications for the inclusion of research subjects in clinical intervention strategies.

Abstract Ulcerative colitis (UC) is characterised notably by an imbalance in intestinal mucosal homeostasis. Although mitochondrial dysfunction has been identified as a potential contributor to this imbalance, it remains an incomplete understanding. Consequently, further investigation into the role of mitochondria in UC is warranted. The study focusing on the GSE87466 dataset for differential gene expression analysis. Mitochondria-related genes were sourced from the MitoCart3.0 database. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify hub genes. The intersection of DEGs, hub genes, and mitochondria-related genes facilitated the identification of 14 mitochondria-related differentially expressed genes (MitoDEGs). Three machine learning algorithms were then applied to select signature MitoDEGs specific to UC: HMGCS2 and AMACR. They have decreased expression in UC patients and have a high diagnostic value for UC. In the inflammatory environment, knockout of both HMGCS2 and AMACR showed disruption of mitochondrial structure and function. Among them, the AMACR knockdown group had an increased number of damaged mitochondria and a significant reduction in the length, area and circumference of MAMs. Therefore, the study identified two new signature MitoDEGs in UC. HMGCS2 and AMACR provide insights into the interplay between mitochondrial dysfunction and UC intestinal mucosal homeostasis.

Abstract. Nanomedicine is an interdisciplinary area that utilizes nanoscience and technology in the realm of medicine. Rapid advances in science and technology have propelled the medical sector into a new era. The most commonly used nanotechnology in the field of medicine is nanoparticles. Due to their unique physicochemical properties, nanoparticles offer significant benefits of precision medicine for diseases such as inflammatory bowel disease that cannot be effectively treated by existing approaches. Nanomedicine has emerged as a highly active research field, with extensive scientific and technological studies being carried out, as well as growing international competition in the commercialization of this field. The accumulation of expertise in the key technologies relating to nanomedicine would provide strategic advantages in the development of cutting-edge medical techniques. This review presented a comprehensive analysis of the primary uses of nanoparticles in medicine, including recent advances in their application for the diagnosis and treatment of inflammatory bowel disease. Furthermore, we discussed the challenges and possibilities associated with the application of nanoparticles in clinical settings.

Abstract This study investigates the precision measurement of the CKM matrix element |V cb | through semileptonic WW events at future Higgs factories, i.e., FCC-ee, ILC, C3, and CEPC. We use full detector simulation to generate the WW → ℓνcb signal events and various backgrounds at s $$ \sqrt{s} $$ = 240 GeV with unpolarized beams. The relative statistical uncertainties of |V cb | are projected to be 0.91% for the muon channel and 1.2% for the electron channel, assuming a baseline integrated luminosity of 5 ab−1. The sensitivities at other Higgs factory scenarios are also projected. Possible contributors to systematic uncertainties are discussed, with the most prominent one being the systematics of flavor-tagging and mistagging rates. Combining with WW threshold runs, the relative systematic uncertainty can be further reduced.

Abstract Connectivity between qubits plays an irreplaceable role in quantum computation. An urgent task of quantum computation based on atomic arrays is to generate effective coupling between two distant qubits, thereby enhancing connectivity. In this paper, we investigate the realization of two-qubit gates utilizing buffer-atomic configuration, where the non-coding atoms serve as quantum buses to connect the computational qubits. Geometric control is achieved through globally-shined laser pulses in the Rydberg blockade region. It is found that acceleration based on shortcut to adiabaticity can be realized by reshaping the original control waveforms. The proposed distant two-qubit gate demonstrates robustness against systematic errors and random noise. Further numerical simulations indicate that high-fidelity control is maintained even when considering next-nearest-neighbor coupling among the atoms. Thus, our proposal provides a fast and experimentally feasible method for realizing distant two-qubit gates in atomic arrays, which may contribute to improving the scalability of quantum computations.

Introduction Previous research suggests a potential association between physical activity (PA) and breast cancer (BC), but the causal relationship remains uncertain. The aim of this study was to explore the causal relationship between PA and BC through Mendelian randomization (MR) analysis. Material and methods Genome-wide association studies utilizing data from the UK Biobank baseline were employed to analyze PA phenotypes, encompassing 460,376 participants. Summary data for BC, comprising 122,977 cases and 105,974 controls, were obtained from the BC Association Consortium. The cases were further categorized based on estrogen receptor status into estrogen receptor-positive breast cancer (ER+ BC) and estrogen receptor-negative breast cancer (ER– BC). The inverse variance weighted method was employed as the primary approach for two-sample MR. Additionally, the MR-PRESSO (MR-Pleiotropy RESidual Sum and Outlier) method was utilized to eliminate outliers. Tests for heterogeneity and pleiotropy were conducted to enhance result accuracy. Furthermore, multivariable Mendelian randomization was performed, adjusting for potential confounders to ensure result stability. Results MR analysis was employed to assess the causal link between PA and BC. Two-sample MR analysis revealed a genetic prediction indicating that walking for pleasure was associated with decreased risk of ER+ BC (odds ratio (OR) = 0.302, 95% CI = 0.105–0.872, p = 0.027), while other physical activities were not significantly correlated with BC, ER+ BC and ER– BC. These findings remained reliable and consistent in the sensitivity analysis, including Cochran’s Q and MR-Egger regression. Furthermore, reverse MR analysis suggested that BC did not exert a notable impact on PA. Conclusions Our findings suggest that engaging in leisure walking is associated with a reduced risk of ER+ BC. Nevertheless, additional research is warranted to comprehensively elucidate the underlying mechanisms and strengthen the causal relationship.

The screening of novel antiviral agents from marine microorganisms is an important strategy for new drug development. Our previous study found that polyether K-41A and its analog K-41Am, derived from a marine Streptomyces strain, exhibit anti-HIV activity by suppressing the activities of HIV-1 reverse transcriptase (RT) and its integrase (IN). Among the K-41A derivatives, two disaccharide-bearing polyethers—K-41B and K-41Bm—were found to have potent anti-HIV-1IIIB activity in vitro. This study aimed to clarify whether K-41B and K-41Bm have inhibitory effects on different HIV-1 strains or whether these two derivatives have mechanisms of action different from that of their precursor, K-41A. An anti-HIV-1 assay indicated that K-41B and K-41Bm have potent anti-HIV-1BaL activity, with low 50% inhibitory concentrations (IC50s) (0.076 and 0.208 μM, respectively) and high selective indexes (SIs) (58.829 and 31.938, respectively) in the peripheral blood mononuclear cell (PBMC)-HIV-1BaL system. The time-of-addition (TOA) assay indicated that K-41B and K-41Bm may exert antiviral effects by activating multiple stages of HIV-1 replication. A cell protection assay indicated that the pretreatment of cells with K-41B or K-41Bm has almost no inhibitory effect on HIV-1 infection. A virus inactivation assay indicated that pretreatment of the virus with K-41B or K-41Bm inhibits HIV-1 infection by 60%. A cell–cell fusion assay showed that K-41B and K-41Bm blocked the cell fusion mediated by viral envelope proteins. The HIV-1 key enzyme experiment also indicated that both compounds have certain inhibitory effects on HIV-1 IN. Furthermore, molecular docking showed that K-41B and K-41Bm interact with several viral and host proteins, including HIV-1 IN, an envelope protein (gp120), a transmembrane protein (gp41), and cell surface receptors (CD4, CCR5, and CXCR4). Overall, in addition to having a similar anti-HIV-1 mechanism of inhibiting HIV-1 IN like the precursor polyether K-41A, the disaccharide-bearing polyether derivatives K-41B and K-41Bm may also inhibit viral entry. This suggests that they display anti-HIV-1 mechanisms that are different from those of their precursor polyethers.

Abstract Urinary incontinence (UI) in females is a prevailing condition that affects individuals across various age groups and is not limited to older females. The presence of serum alpha-Klotho (α-klotho) serves as a reliable biomarker to indicate the effects of antiaging. Nevertheless, the scientific research on the association between α-klotho and UI remains limited. Therefore, the purpose of this study is to investigate and evaluate the connection between α-klotho levels and the UI among females in the US. We utilized data from the National Health and Nutrition Examination Survey 2007–2016 to investigate the potential connection between α-klotho levels and the UI among females aged 40 to 79. Weighted linear regression models and sensitivity tests were conducted to explore the correlation. 2628 females were involved in this study, representing 22,492,348 non-institutionalized residents in the US. The mean age was 53.9 ± 0.2 years and the mean level of α-klotho was 873.0 ± 8.9 pg/mL. After adjusting for relevant covariables, weighted linear regression models revealed that individuals with severe UI exhibited significantly lower serum α-klotho levels (β = − 100.66; 95% CI: − 156.31, − 45.01; P

Abstract Background There are various frailty assessment tools in the world, and the application choice of frailty assessment tools for the elderly perioperative population varies. It remains unclear which frailty assessment tool is more suitable for the perioperative population in China. To validate the Perioperative Frailty Index (FI-32) derived from the Chinese Hospital Information System by investigating the impact of preoperative frailty on postoperative outcomes, and ascertain the diagnostic value of FI-32 for predicting postoperative complications through comparing with the FRAIL scale and the modified Frailty Index (mFI-11). Methods A prospective cohort study was conducted in a tertiary hospital. Elderly patients who were 60 years or older and underwent selective operation were included. The FI-32, FRAIL scale, and mFI-11 were assessed. Demographic, surgical variables and outcome variables were extracted from medical records. The data of readmission and mortality within 30 days and 90 days of surgery were ascertained by Telephone follow-up by professionally trained researchers. Multiple logistic regression was used to examine the association between frailty and complications. Receiver operating characteristic curves(ROC) were used to compare FI-32 with mFI-11 and FRAIL, to explore the predictive ability of frailty. Results 335 patients qualified for the inclusion criteria and were enrolled in the study, and among them, 201 (60.0%) were females, and the Median(P 25, P 75)age at surgery was 69 (65,74) years. The prevalence of frailty in the study population was 16.4% (assessed by FI-32). After adjusting for concomitant variables including demographic characteristics (such as gender, BMI, smoking, drinking, average monthly income and educational level) and surgical factors (such as surgical approach, surgical site, anesthesia method, operation time, intraoperative bleeding, and intraoperative fluid intake), there was a statistically significant association between frailty and the development of postoperative complication after surgery (OR = 3.051, 95% CI:1.460–6.378, P = 0.003). There were also significant differences in mortality within 30 days of surgery, the length of hospital stay (LOS) and the hospitalization costs. FI-32, FRAIL and mFI-11 showed a moderate predictive ability for postoperative complications, the Area Under Curves (AUCs) were 0.582, 0.566 and 0.531, respectively. With adjusting concomitant variables associated with postoperative complications, the AUCs of FI-32, FRAIL and mFI-11 in the adjusted prediction models were 0.824, 0.827 and 0.820 respectively. Conclusions The FI-32 has a predictive effect on postoperative adverse outcomes in elderly Chinese patients. Compared to FRAIL and mFI-11, the FI-32 had the same ability to predict postoperative complications, and FI-32 can be extracted directly from HIS, which greatly saves the time for clinical medical staff to evaluate perioperative frailty.

Abstract Pancreas segmentation has great significance in computer‐aided diagnosis of pancreatic diseases. The small size of the pancreas, high variability in shape, and blurred edges make the task of pancreas segmentation challenging. A new model called SEY‐Net is proposed to solve the above problems, which is a one‐stage model with multi‐inputs. SEY‐Net is composed of three main components. Firstly, the edge information extraction (EIE) module is designed to improve the segmentation accuracy of the pancreas boundary. Then, the SE_ResNet50 is selected as the encoder's backbone to fit the size of the pancreas. Finally, the dual cross‐attention is integrated into the skip connection to better focus on the variable shape of the pancreas. The experimental results shows that the proposed method has better performance and outperforms the other existing state‐of‐the‐art pancreas segmentation methods.

AIM: To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy (DR) utilizing a two-sample Mendelian randomization (MR) analysis. METHODS: The research data were obtained from summary statistics of genome-wide association studies (GWAS). Genetic loci closely related to cheese intake were extracted as instrumental variables (IVs), and DR was the outcome variable. The data were extracted from individuals of European ethnicity. The data of cheese intake consisted of 451 486 samples with 9 851 867 single nucleotide polymorphisms (SNPs), while the DR data consisted of 206 234 samples with 16 380 446 SNPs. Sixty-one genetic loci closely related to cheese intake were selected as IVs. MR analysis was performed by inverse-variance weighted (IVW) method and MR-Egger regression respectively. The causal relationship between cheese intake and DR was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs). Egger-intercept test was used to test horizontal pleiotropy and sensitivity analysis was performed by leave-one-out test. RESULTS: The P value of the IVW method was less than 0.05, indicating a significant negative correlation between cheese intake and DR. MR-Egger regression showed that the intercept was 0.01 with a standard error of 0.022, and a P-value of 0.634, indicating no evidence of horizontal pleiotropy affecting the IVs related to the exposure factors. Besides, heterogeneity tests confirmed the absence of heterogeneity, and the “leave-one-out” sensitivity analysis demonstrated that the results were stable. CONCLUSION: Cheese intake is causally negatively correlated with the occurrence of DR, and cheese intake could reduce the risk of DR.

Abstract SHP-1, a nonreceptor protein tyrosine phosphatase encoded by ptpn6, has been regarded as a regulatory protein of hematopoietic cell biology for years. However, there is now increasing evidence to support its role in tumors. Thus, the role of ptpn6 for prognosis and immune regulation across 33 tumors was investigated, aiming to explore its functional heterogeneity and clinical significance in pan-cancer. Differential expression of ptpn6 was found between cancer and adjacent normal tissues, and its expression was significantly correlated with the prognosis of tumor patients. In most cancers, ptpn6 expression was significantly associated with immune infiltration. This was further confirmed by ptpn6-related genes/proteins enrichment analysis. Additionally, genetic alterations in ptpn6 was observed in most cancers. As for epigenetic changes, it’s phosphorylation levels significantly altered in 6 tumors, while methylation levels significantly altered in 12 tumors. Notably, the methylation levels of ptpn6 were significantly decreased in 11 tumors, accompanied by its increased expression in 8 of them, suggesting that the hypomethylation may be related to its increased expression. Our results show that ptpn6 plays a specific role in tumor immunity and exerts a pleiotropic effect in a variety of tumors. It can serve as a prognostic factor for some cancers. Especially in LGG, KIRC, UCS and TGCT, the increased expression of ptpn6 is associated with poor prognosis and high immune infiltration. This aids in understanding the role of ptpn6 in tumor biology, and can provide insight into presenting a potential biomarker for poor prognosis and immune infiltration in cancers.

Intertrochanteric femur fracture is the most common hip fracture in elderly people, and the academic community has reached a consensus that early surgery is imperative. Proximal femoral nail anti‐rotation (PFNA) and InterTan are the preferred internal fixation devices for intertrochanteric femur fractures in elderly individuals due to their advantages, such as a short lever arm, minimal stress shielding, and resistance to rotation. However, PFNA is associated with complications such as nail back‐out and helical blade cut‐out due to stress concentration. As a new internal fixation device for intertrochanteric femur fractures, the proximal femoral biodegradable nail (PFBN) addresses the issue of nail back‐out and offers more stable fracture fixation, a shorter lever arm, and stress distribution compared to PFNA and InterTan. Clinical studies have shown that compared to PFNA, PFBNs lead to faster recovery of hip joint function, shorter non‐weight‐bearing time, and faster fracture healing. This article provides a literature review of the structural characteristics, biomechanical analysis, and clinical studies of PFBNs, aiming to provide a theoretical basis for the selection of internal fixation devices for the treatment of intertrochanteric femur fractures in elderly patients and to improve the quality of life of patients during the postoperative period.

Abstract Objective To develop and validate a machine learning model for predicting mortality-associated prognostic factors in order to reduce in-hospital mortality rates among HIV/AIDS patients with Cryptococcus infection in Guangxi, China. Methods This retrospective prognostic study included HIV/AIDS patients with cryptococcosis in the Fourth People’s Hospital of Nanning from October 2011 to June 2019. Clinical features were extracted and used to train ten machine learning models, including Logistic Regression, KNN, DT, RF, Adaboost, Xgboost, LightGBM, Catboost, SVM, and NBM, to predict the outcome of HIV patients with cryptococcosis infection. The sensitivity, specificity, AUC, and F1 value were applied to assess model performance in both the testing and training sets. The optimal model was selected and interpreted. Results A total of 396 patients were included in the study. The average in-hospital mortality of HIV/AIDS patients with cryptococcosis was 12.9% from 2012 to 2019. After feature screening, 20 clinical features were selected for model construction, accounting for 93.8%, including ART, Electrolyte disorder, Anemia, and 17 laboratory tests. The RF model (AUC 0.9787, Sensitivity 0.9535, Specificity 0.8889, F1 0.7455) and the SVM model (AUC 0.9286, Sensitivity 0.7907, Specificity 0.9786, F1 0.8293) had excellent performance. The SHAP analysis showed that the primary risk factors for prognosis prediction were identified as BUN/CREA, Electrolyte disorder, NEUT%, Urea, and IBIL. Conclusions RF and SVM machine learning models have shown promising predictive abilities for the prognosis of hospitalized HIV/AIDS patients with cryptococcosis, which can aid clinical assessment and treatment decisions for patient prognosis.

Abstract Background Cognitive frailty (CF) is characterized by the coexistence of physical frailty and cognitive impairment, and it is associated with adverse health outcomes. Older adults are particularly vulnerable to CF due to factors such as age-related brain changes and the presence of comorbidities. Objective To investigate the effect of preoperative CF on postoperative complications in older patients. Methods This prospective cohort study was conducted among 253 patients aged 60–85 years, who underwent elective orthopedic and abdominal surgery (with a postoperative hospital stay of ≥ 3 days) at the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2023 to November 2023. CF was assessed using the Montreal Cognitive Assessment (MoCA) for the cognitive status and the Fried criteria for five frailty scales. Participants were split into four groups: Group A (neither frailty nor cognitive impairment), Group B (frailty without cognitive impairment), Group C (cognitive impairment without frailty), and Group D (cognitive frailty). The primary outcome was postoperative complications, while secondary outcomes included mobility disability, prolonged hospital stay (PLOS), re-operation and 90-day readmission. Results The median age (interquartile range) of participants was 69 (65–73) years, of which 40.3% were male. The prevalence of CF was 17.8%. The incidence of postoperative complications was 18.2% in Group A, 50.0% in Group B, 37.4% in Group C, and 75.6% in Group D. Multivariate analysis revealed that, compared to the control group (without cognitive impairment or frailty), patients with CF had a significantly higher risk of postoperative complications (OR, 12.86; 95%CI, 4.23–39.08). “Patients with frailty without cognitive impairment” had an increased risk (OR, 6.53; 95%CI, 2.04–20.9), while “those with cognitive impairment without frailty” also showed a higher risk (OR, 3.46; 95%CI, 1.57–7.64). Conclusions Cognitive frailty is significantly associated with an increased risk of postoperative adverse outcomes in older patients undergoing orthopedic and abdominal surgeries with general anesthesia. It indicates that clinicians should pay much attention to these older adults with CF.

Thermally resistant peptides were obtained from enzymatical hydrolysis of Hongqu rice distiller’s grains and evaluated for its effect on resistance to thermally induced oxidative stress in Saccharomyces cerevisiae. Various proteases were screened for the survival rate of S. cerevisiae under heat stress. The enzymatic hydrolysis conditions were optimized based on the yield of thermally resistant peptides, and the peptides were identified by mass spectroscopy and its antioxidant activity was investigated. The expression of genes in the pentose phosphate pathway and the contents of intracellular coenzyme, glutathione (GSH) and reactive oxygen species (ROS) were analyzed to explore the protective effects of the peptides on S. cerevisiae from heat-induced oxidative stress. The results indicated that the optimal enzymatic hydrolysis conditions were as follows: Hongqu rice distiller’s grains/water ratio 1:10, hydrolysis temperature 50 ℃, hydrolysis time 3 h, protamex dosage 3 000 U/g, and pH 8.5. Under these conditions, the yield of thermally resistant peptides was 62.44%, and the survival rate of S. cerevisiae in the presence of the prepared peptides under heat stress was 73.97%, which was 22.76% higher than that of the control group (pure water). Sequence identification showed that 16 out of the top 20 most abundant peptides had hydrophobic amino acid contents of over 50%. The peptides exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) cation radical scavenging activity with a half-maximal effective concentration (EC50) of 4.53 and 1.82 mg/mL, respectively, indicating good antioxidant activity. Besides, the thermally resistant peptides upregulated gene expression in the pentose phosphate pathway, elevated NADH kinase activity, increased GSH content by 5.74 times, and restored intracellular ROS to almost the same level as before heat stress treatment, thus enhancing resistance to heat-induced oxidative stress in S. cerevisiae.

Abstract Background Microecological equilibrium is essential for human health. Previous research has demonstrated that Streptococcus strain A, the main bacterial group in the respiratory tract, can suppress harmful microbes and protect the body. In this study, Streptococcus strain D19T was isolated from the oral and pharyngeal cavities of healthy children. Its antibacterial mechanism against Acinetobacter baumannii was examined, as well as its potential to prevent inflammatory damage to cells. We evaluated the effect of the fermentation conditions of D19T on inhibition of Acinetobacter baumannii growth; Isolation and purification of antibacterial active components of strain D19T and molecular mechanism of inhibition of Acinetobacter baumannii; Molecular mechanism of D19T antibacterial protein reversing cellular inflammatory injury induced by Acinetobacter baumannii. Results The supernatant of fermentation broth of Streptococcus D19T was the active component against Acinetobacter baumannii, but the bacteria had no antibacterial activity. The supernatant of D19T fermentation broth was precipitated by (NH4)2SO4 solution, and the protein was the active antibacterial component. After gel filtration chromatography and anion gel filtration chromatography, the molecular weight of antibacterial protein was 53kD. D19T antibacterial protein can improve cell membrane permeability, limit extracellular soluble protein release, inhibit Acinetobacter baumannii biofilm formation, and prevent Acinetobacter baumannii adhesion. Acinetobacter baumannii induces inflammatory damage to respiratory cells via ferroptosis, and the D19T antibacterial protein can counteract this damage, protecting the respiratory tract. Conclusion Streptococcus strain D19T, as a potential probiotic, inhibits the growth of Acinetobacter baumannii and the inflammatory damage of respiratory cells, playing a protective role in human respiratory health.

As a “cold tumor”, triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an “in situ nanovaccine” Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an “in situ nanovaccine” to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid‐derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, “cold tumor” was transformed into a “hot tumor”, not only implementing a “turning foes to friends” therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.

Abstract Background HIV/AIDS has emerged as a nationwide epidemic and has taken the forefront position as the primary infectious killer of adults in China. The control and prevention of the disease have been hampered by a weak link in the form of heterosexual transmission. However, conventional intervention measures have demonstrated suboptimal efficacy in reducing the incidence of new HIV infections. In light of the current epidemiological characteristics, we have developed and executed an innovative intervention model known as the Joint Prevention and Control Mechanism of the ‘CDC-Public Security Bureau-NGO’. The purpose of this research is to assess the impact of this model on the AIDS awareness, HIV infection rates, sexual behavior, and associated factors among female sex workers and elderly clients. Through the provision of robust evidence of the efficacy of this innovative model, we seek to advocate for its implementation in future interventions. Methods The research design of this study incorporates both a serial cross-sectional study and time-series analysis from 2014 to 2021, including a 4-year traditional intervention (2014–2017) and the 4-year ‘CDC-Public Security Bureau-NGO’ innovative intervention (2018–2021), was conducted to evaluate the effects of the new intervention. The GM(1, 1) model was performed to predict the proportion of HIV infection without implementing the innovative intervention in 2018–2021; P and C values were used to evaluate the performance of the model. Mann-Kendall test and descriptive methods were used to analyzed the trend of traditional and innovative interventions models on HIV positive detection rate in FSWs and elderly clients. Results The condom usage rates during the last commercial sexual encounter for FSWs and elderly clients improved from 74.9% and 9.1%, respectively, to 96.9% and 28.1%. (P

Abstract Background Phosphofructokinase P (PFKP) is a key rate-limiting enzyme in glycolysis, playing a crucial role in various pathophysiological processes. However, its specific function in tumors remains unclear. This study aims to evaluate the expression and specific role of PFKP across multiple tumor types (Pan-cancer) and to explore its potential clinical significance as a therapeutic target in cancer treatment. Methods We analyzed the expression of PFKP, immune cell infiltration, and patient prognosis across various cancers using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we conducted a series of experiments in lung cancer cells, including Western blot, CCK-8 assay, colony formation assay, transwell migration assay, scratch wound healing assay, LDH release assay, and flow cytometry, to evaluate the impact of PFKP on tumor cells. Results PFKP was found to be highly expressed in most cancers and identified as a prognostic risk factor. Elevated PFKP expression is associated with poorer clinical outcomes, particularly in lung adenocarcinoma (LUAD). Receiver operating characteristic (ROC) curve analysis indicated that PFKP can effectively differentiate between cancerous and normal tissues. The expression of PFKP in most tumors showed significant correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune score, and immune cell infiltration. In vitro experiments demonstrated that PFKP overexpression promotes lung cancer cell proliferation and migration while inhibiting apoptosis, whereas PFKP deficiency results in the opposite effects. Conclusion PFKP acts as an oncogene involved in tumorigenesis and may influence the immune microenvironment within the tumor. Our findings suggest that PFKP could serve as a potential biomarker for predicting prognosis and the efficacy of immunotherapy in tumors.

Based on the closed-loop frequency domain model of permanent magnet synchronous generator–based wind power generation system (PMSG-WPGS), the stability domain of the control parameters is constructed through the D-partition method in this paper to acquire the range of machine-side converter (MSC) and grid-side converter (GSC) parameters. First, the basic stability domain of the controller parameters is established according to the control structure and transfer function of the back-to-back converter. Then, based on the frequency domain performance indexes, amplitude margin and phase angle margin, the obtained basic stability domain is adjusted to further gain the control parameter values that meet the frequency domain index. Furthermore, the rationality of the stability domain range is verified by drawing root locus curves of variable controller parameters on the machine side and grid side. Finally, the low-power scale experimental platform of PMSG-WPGS is built in the lab to validate the feasibility of the proposed stability domain construction method.

Bladder cancer (BLCA) remains a significant health risk despite advancements in medical science that have led to reduced incidence and death rates. While the molecular regulatory mechanisms of BLCA are not yet fully understood, HSPE1, a member of the heat shock protein family, is regarded as a reliable prognostic target for BLCA. Using data from The Cancer Genome Atlas (TCGA) database, the differential expression levels of HSPE1 and its relationship to GPX4 were examined. Gene Set Enrichment Analysis was used to carry out HSPE1 pathway enrichment analysis. HSPE1 and GPX4 expressions in cells were assessed using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting. Cell cycle alternations and apoptosis were evaluated using flow cytometry. Cell proliferation was assessed using EdU and colony formation assays. The lactate dehydrogenase (LDH) test, glutathione (GSH) measurement, and Liperfluo assay were utilized to evaluate the presence of ferroptosis in cells. BLCA tissues and cells had significantly elevated levels of HSPE1. In BLCA, high expression of HSPE1 inhibited apoptosis while promoting cell proliferation and cell cycle progression. Significant enrichment of HSPE1 was found in the GSH metabolism and ferroptosis pathways, according to pathway enrichment analysis. In cancer cells, HSPE1 promoted GSH accumulation, decreased lipid peroxidation, and inhibited cell ferroptosis, as demonstrated in a rescue experiment with the ferroptosis inhibitor Fer-1. Pearson correlation analysis unveiled a substantial positive correlation between HSPE1 and the ferroptosis regulator GPX4. According to the results of rescue experiments, HSPE1 regulated GPX4 to affect cell lipid peroxidation levels and GSH accumulation. HSPE1 plays a crucial role in regulating GPX4 to prevent BLCA cells from undergoing ferroptosis, with this control mechanism dependent on GSH.

Rare earth polishing powder has gained widespread usage in the surface polishing of high-precision materials, exhibiting an annual growth rate exceeding 10 %. However, a significant portion of this powder is discarded due to impurities and the need for particle size refinement. The waste generated from polishing powder contains 10.31 %–86.93 % rare earth elements, making secondary recycling economically viable. This work critically analyses and verifies existing methods for recovering rare earths(REs)from rare earth polishing powder waste (REPPW). It concludes that the acid roasting, water leaching, and reduction, coordination acid-leaching methods can achieve rare earth recovery rates exceeding 98 %, offering a relatively simple and environmentally friendly process. We highlight various rare earth recovery processes from REPPW, including alkaline roasting with acid-leaching, acid roasting with water-leaching, acid-leaching with alkali dissolution and washing, and acid-leaching with the aid of reducing agents. It is found that the acid-leaching-water leaching process and the acid-leaching-reducing agent synergy process demonstrate high recovery rates, ease of operation, reduced environmental impact, and stable product quality. It is recommended that researchers focus on refining leaching theories, optimizing process conditions and determining key parameters to further advance the production of rare earth recovery from REPPW. The findings of this study contribute to the development of sustainable practices for the recovery of valuable REs from industrial waste streams.

Identifying the prevalence and risk factors of secondary human immunodeficiency virus (HIV) transmission from people living with HIV (PLWH) to other people is crucial for ending the HIV epidemic. However, the data among antiretroviral therapy (ART) patients is limited. This study aims to assess the prevalence and risk factors of secondary HIV transmission among PLWH receiving ART by longitudinal molecular networks in China. In this study, the prevalence of secondary HIV transmission was 10.8%. The R0 was greater than 1 from 2017 to 2021 and peaked in 2019. PLWHs who were male sex, older age, engaged in condomless sex, experienced higher ART follow-up viral load, experienced ART medical omissions, infected with non-CRF01_AE subtype, and self-reported sexually transmitted infections (STIs) at HIV diagnosis increased the risk of secondary HIV transmission. However, those participants with higher education were less likely to be involved in secondary HIV transmission. The diagnostic age of the participants was nonlinearly associated with the risk of secondary HIV transmission, with a cutoff value of 43.13 years indicating a higher risk of secondary HIV transmission for patients diagnosed at or above this age. This study revealed substantial secondary HIV transmission and persistent HIV expansion among local PLWH, highlighting the necessity of enhancing viral load monitor, promoting adherence to ART, and promoting safe sex practices, particularly among older adults with HIV, to mitigate secondary HIV transmission.