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Abstract Background Hemifacial spasm (HFS) is a neuromuscular disorder characterized by unilateral facial muscle spasms, negatively impacts quality of life due to social embarrassment. Botulinum Neurotoxin (BoNT) injections have emerged as a viable therapeutic approach. This systematic review evaluated the efficacy and safety of BoNT injections for HFS management, along with effects on patients’ quality of life and mental health. Materials and methods A systematic search for studies on BoNT treatment for HFS published between January 1, 2000, and May 1, 2024, was performed across major databases. Study quality was evaluated using Cochrane and Joanna Briggs Institute (JBI) tools, with data management handled by EndNote X9 and statistical analyses conducted via Review Manager (RevMan 5.4) and STATA 14.0. Results Thirty-five studies met the inclusion criteria: 2 RCTs comprising 83 HFS patients compared the efficacy of perioral injections of botulinum toxin and placebo, while 33 single-arm studies reported outcomes for 2786 patients post-BoNT injection. The selection of 17 single-arm studies focused on the effectiveness rate as the key outcome metric. Pooled estimate signified a remarkably high effectiveness (ES: 0.882, 95% CI: 0.830, 0.926, P

Abstract The identification of predictors for immunotherapy is often hampered by the absence of control groups in many studies, making it difficult to distinguish between prognostic and predictive biomarkers. This study presents biomarker analyses from the phase 3 CONTINUUM trial (NCT03700476), the first to show that adding anti-PD-1 (aPD1) to chemoradiotherapy (CRT) improves event-free survival (EFS) in patients with locoregionally advanced nasopharyngeal carcinoma. A dynamic single-cell atlas was profiled using mass cytometry on peripheral blood mononuclear cell samples from 12 pairs of matched relapsing and non-relapsing patients in the aPD1-CRT arm. Using a supervised representation learning algorithm, we identified a Ki67+ proliferating regulatory T cells (Tregs) population expressing high levels of activated and immunosuppressive molecules including FOXP3, CD38, HLA-DR, CD39, and PD-1, whose abundance correlated with treatment outcome. The frequency of these Ki67+ Tregs was significantly higher at baseline and increased during treatment in patients who relapsed compared to non-relapsers. Further validation through flow cytometry (n = 120) confirmed the predictive value of this Treg subset. Multiplex immunohistochemistry (n = 249) demonstrated that Ki67+ Tregs in tumors could predict immunotherapy benefit, with aPD1 improving EFS only in patients with low baseline levels of Ki67+ Tregs. These findings were further validated in the multicenter phase 3 DIPPER trial (n = 262, NCT03427827) and the phase 3 OAK trial of anti-PD-L1 immunotherapy in NSCLC, underscoring the predictive value of Ki67+ Treg frequency in identifying the beneficiaries of immunotherapy and potentially guiding personalized treatment strategies.

Abstract Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases. Latent features were transformed into principal components (PC) and correlated with known radiographic findings. PCs were combined with physiological data to classify clinical outcomes: (1) recipient time to extubation of

In this study, we introduced an innovative and robust semi-supervised learning strategy tailored for high-dimensional data categorization. This strategy encompasses several pivotal symmetry elements. To begin, we implemented a risk regularization factor to gauge the uncertainty and possible hazards linked to unlabeled samples within semi-supervised learning. Additionally, we defined a unique non-second-order statistical indicator, termed $ C_{p} $-Loss, within the kernel domain. This $ C_{p} $-Loss feature is characterized by symmetry and bounded non-negativity, efficiently minimizing the influence of noise points and anomalies on the model's efficacy. Furthermore, we developed a robust safe semi-supervised extreme learning machine (RS3ELM), grounded on this educational framework. We derived the generalization boundary of RS3ELM utilizing Rademacher complexity. The optimization of the output weight matrix in RS3ELM is executed via a fixed point iteration technique, with our theoretical exposition encompassing RS3ELM's convergence and computational complexity. Through empirical analysis on various benchmark datasets, we demonstrated RS3ELM's proficiency and compared it against multiple leading-edge semi-supervised learning models.

Abstract Porcine pasteurellosis is an infectious disease caused by Pasteurella multocida (P. multocida), which seriously endangers the healthy development of pig breeding industry. Early detection of disease transmission in animals is a crucial early warning for humans. Therefore, predicting risk areas for disease is essential for public health authorities to adopt preventive measures and control strategies against diseases. In this study, we developed a predictive model based on multi-criteria decision analysis (MCDA) and assessed risk areas for porcine pasteurellosis in the Chinese mainland. By using principal component analysis, the weights of seven spatial risk factors were determined. Fuzzy membership function was used to standardize all risk factors, and weight linear combination was used to create a risk map. The sensitivity of the risk map was analyzed by calculating the mean of absolute change rates of risk factors, as well as calculating an uncertainty map. The results showed that risk areas for porcine pasteurellosis were predicted to be locate in the south-central of the Chinese mainland, including Sichuan, Chongqing, Guangdong, and Guangxi. The maximum standard deviation of the uncertain map was less than 0.01and the ROC results showed that the prediction model has moderate predictive performance with the area under the curve (AUC) value of 0.80 (95% CI 0.75–0.84). Based on the above process, MCDA was combined with WebGIS technology to construct a system for predicting risk areas of porcine pasteurellosis. Risk factor data was directly linked to the developed model, providing decision support for disease prevention and control through monthly updates.

Abstract Nowadays, human activities intensified the combined pollution of fluoride and lead in acidic tea garden soil. The key to eliminating this combined pollution is to immobilize pollutants simultaneously, thus preventing their migration from tea garden soil to tea trees. In this paper, the natural product bayberry tannin was employed as raw material to fabricate functional materials (TF-Zr) for simultaneous adsorption of fluorine (F) and lead (Pb) in water and soil by the reactivity of tannin with Pb2+ and the affinity of Zr with F. SEM-Mapping, EDS, FT-IR, XPS were utilized to probe the immobilization mechanisms. The results showed that TF-Zr could simultaneously and efficiently adsorb F– and Pb2+ from water with the adsorption capacity of 5.02 mg/g (Pb) and 4.55 mg/g (F). The adsorption processes were both in accordance with the proposed secondary kinetic adsorption model. Besides, the presence of F– promoted the adsorption of Pb2+ by TF-Zr. The materials were applied into tea garden soil to explore its effect on the variation of F and Pb forms in the soil. It was found that the proportion of water-soluble fluorine, exchangeable fluorine and exchangeable lead in the tea garden soil decreased significantly, while the proportion of residual fluorine and lead increased evidently, illustrating TF-Zr possessed eximious fixation effect on the highly reactive fluorine and lead in the soil and facilitated their conversion to the more stable residue state. Therefore, TF-Zr can be used for the efficient and simultaneous immobilization of fluorine and lead in water and tea garden soil.

Course-based Undergraduate Research Experiences (CUREs) integrate active, discovery-based learning into undergraduate curricula, adding tremendous value to Biochemistry and Molecular Biology (BMB) education. There are multiple challenges in transforming a research project into a CURE, such as the readiness of students, the time commitment of the instructor, and the productivity of the research. In this article, we report a CURE course developed and offered in the University of Massachusetts Amherst BMB Department since 2018 that addresses these challenges. Our CURE focuses on fungal effectors which are proteins secreted by a destructive pathogenic fungus Fusarium oxysporum, one of the top five most devastating plant pathogens. By studying this group of proteins, students are connected to real-world problems and participate in the search for potential solutions. A 3-week "standard Boot Camp" is implemented to help students familiarize themselves with all basic techniques and boost their confidence. Next, molecular cloning, a versatile technique with modularity and repeatability, is used as the bedrock of the course. Our past 5 years of experience have confirmed that we have developed a novel and feasible CURE protocol. Measurable progress documented by students who took this course includes stimulated active learning and increased career trajectory to pursue hypothesis-based research to address societal needs. In addition, data generated through the course advance ongoing lab research. Collectively, we encourage the implementation of CURE among research-intensive faculty to provide a more inclusive research experience to undergraduate students, an important element in predicting career success.

Abstract Current concepts of corticothalamic organization in the mammalian brain are mainly based on sensory systems, with less focus on circuits for higher-order cognitive functions. In sensory systems, first-order thalamic relays are driven by subcortical inputs and modulated by cortical feedback, while higher-order relays receive strong excitatory cortical inputs. The applicability of these principles beyond sensory systems is uncertain. We investigated mouse prefronto-thalamic projections to the midline thalamus, revealing distinct top-down control. Unlike sensory systems, this pathway relies on indirect modulation via the thalamic reticular nucleus (TRN). Specifically, the prelimbic area, which influences emotional and motivated behaviors, impacts instrumental avoidance responses through direct and indirect projections to the paraventricular thalamus. Both pathways promote defensive states, but the indirect pathway via the TRN is essential for organizing avoidance decisions through disinhibition. Our findings highlight intra-thalamic circuit dynamics that integrate cortical cognitive signals and their role in shaping complex behaviors.

Spinal cord injury (SCI) is a traumatic condition that results in impaired motor and sensory function. Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord, and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI. Although human umbilical cord mesenchymal stem cells (Huc-MSCs) can ameliorate inflammatory microenvironments and promote neural regeneration in SCI, their efficacy is greatly limited by the local microenvironment after SCI. Therefore, in this study, we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor, in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence, and combined with the reactive oxygen species (ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair. Meanwhile, we also modified the classic ferroptosis inhibitor Ferrostatin-1 (Fer-1) and synthesized a new prodrug Feborastatin-1 (Feb-1). The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI, and promoted the recovery of neurological function in rats with SCI. This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.

Abstract The recent Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic highlights the significant threat coronaviruses (CoVs) pose to public health. With their extensive cross-continental movements, migratory birds have the potential to serve as reservoirs and vectors for CoVs. This study aimed to investigate the prevalence of CoVs in birds in densely populated areas of Guangdong Province, China. Of the 128 samples collected from birds, six tested positive for CoVs (4.7%, 95% CI: 1.7–9.9%), and three complete viral genomes were obtained through viral metagenomics and PCR. Phylogenetic analysis revealed that two CoVs (MD_XN18 and SG_DWY40) belonged to the Gammacoronavirus genus, while one (CP_XN11) belonged to the Deltacoronavirus genus. Homology analysis revealed that the MD_XN18 strain discovered in mallards shares 95.6–97.4% sequence similarity with chicken infectious bronchitis viruses (IBVs), providing direct evidence that migratory mallards can transmit avian IBVs. Recombination analysis suggested that two genomic regions of SG_DWY40 could originate from unknown sources through recombination, potentially leading to the expression of a novel viral protein, provisionally named NS3.5. These findings underscore the ongoing transmission and evolution of CoVs among birds in cities near Guangdong Province, emphasizing the need for continued monitoring and research.

Abstract Background The purpose of this study was to improve the deep learning (DL) model performance in predicting and classifying IMRT gamma passing rate (GPR) by using input features related to machine parameters and a class balancing technique. Methods A total of 2348 fields from 204 IMRT plans for patients with nasopharyngeal carcinoma were retrospectively collected to form a dataset. Input feature maps, including fluence, leaf gap, leaf speed of both banks, and corresponding errors, were constructed from the dynamic log files. The SHAP framework was employed to compute the impact of each feature on the model output for recursive feature elimination. A series of UNet++ based models were trained on the obtained eight feature sets with three fine-tuning methods including the standard mean squared error (MSE) loss, a re-sampling technique, and a proposed weighted MSE loss (WMSE). Differences in mean absolute error, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared between the different models. Results The models trained with feature sets including leaf speed and leaf gap features predicted GPR for failed fields more accurately than the other models (F(7, 147) = 5.378, p

Abstract Employing machine learning methods for mapping surface ocean pCO2 has reduced the uncertainty in estimating sea-air CO2 flux. However, a general discrepancy exists between the Southern Ocean carbon sinks derived from pCO2 products and those from biogeochemistry models. Here, by performing a boosting ensemble learning feed-forward neural networks method, we have identified an underestimation of the surface Southern Ocean pCO2 due to notably uneven density of pCO2 measurements between summer and winter, which resulted in about 16% overestimating of Southern Ocean carbon sink over the past three decades. In particular, the Southern Ocean carbon sink since 2010 was notably overestimated by approximately 29%. This overestimation can be mitigated by a winter correction in algorithms, with the average Southern Ocean carbon sink during 1992-2021 corrected to −0.87 PgC yr−1 from the original −1.01 PgC yr−1. Furthermore, the most notable underestimation of surface ocean pCO2 mainly occurred in regions south of 60°S and was hiding under ice cover. As the surface ocean pCO2 under sea ice coverage in the winter is much higher than the atmosphere, if sea ice melts completely, there could be a further reduction of about 0.14 PgC yr−1 in the Southern Ocean carbon sink.

Abstract Background Laparoscopic Total Extra-peritoneal Inguinal Hernia Repair(TEP) presents escalated risks of surgical complications, notably bleeding, particularly in European Hernia Society (EHS) types 3 and recurrent inguinal hernia. In this study, we introduced an innovative technique using indocyanine green-labeled fluorescence laparoscopy to mitigate intraoperative complications, including bleeding and rupture of the hernial sac. Methods This retrospective study reviewed records of 17 patients who underwent TEP repair at Anqing Municipal Hospital between July and August 2023. Intraoperatively, fluorescence imaging was utilized to trace the pathway of the spermatic vessels and outline the boundaries of the hernia sac to facilitate a thorough dissection. Results The procedure was successfully completed in all 17 patients, with a median operation time of 42 min (range: 30–51 min). Median intraoperative blood loss was 5 ml (range: 3–8 ml). Complete dissection of the hernia sac was achieved in each case without any incidents of sac rupture. Hemodynamic parameters of blood flow within the spermatic artery on postoperative day 1 showed no statistically significant deviations from the preoperative values. Furthermore, during the 7-month follow-up period, there were no cases of seroma formation or hernia recurrence. Conclusion Our findings suggest that employing indocyanine green-labeled fluorescence technology in TEP repair significantly reduces intraoperative complications, notably bleeding and rupture of the hernial sac. This technique demonstrated a negligible impact on the hemodynamic parameters of the spermatic artery and reduced the overall surgical time.

Abstract Electrocatalytic alkynes semi-hydrogenation to produce alkenes with high yield and Faradaic efficiency remains technically challenging because of kinetically favorable hydrogen evolution reaction and over-hydrogenation. Here, we propose a hierarchically nanoporous Cu50Au50 alloy to improve electrocatalytic performance toward semi-hydrogenation of alkynes. Using Operando X-ray absorption spectroscopy and density functional theory calculations, we find that Au modulate the electronic structure of Cu, which could intrinsically inhibit the combination of H* to form H2 and weaken alkene adsorption, thus promoting alkyne semi-hydrogenation and hampering alkene over-hydrogenation. Finite element method simulations and experimental results unveil that hierarchically nanoporous catalysts induce a local microenvironment with abundant K+ cations by enhancing the electric field within the nanopore, accelerating water electrolysis to form more H*, thereby promoting the conversion of alkynes. As a result, the nanoporous Cu50Au50 electrocatalyst achieves highly efficient electrocatalytic semi-hydrogenation of alkynes with 94% conversion, 100% selectivity, and a 92% Faradaic efficiency over wide potential window. This work provides a general guidance of the rational design for high-performance electrocatalytic transfer semi-hydrogenation catalysts.

Abstract Background The National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m2, and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin. Methods Our institutional database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m2) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m2. Survival outcomes were evaluated using Kaplan–Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event. Results Among 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8–65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58–5.47, p

Abstract Background Several studies have demonstrated the population-level effectiveness of oral PrEP in reducing the risk of HIV infection. However, oral PrEP utilization among MSM in China remains below 1%. While existing literature has primarily focused on oral PrEP preference and willingness, there is limited exploration of the underlying factors contributing to oral PrEP cessation in China. This study aims to fill this gap by investigating the factors associated with oral PrEP cessation among MSM in China. Methods Assisted by MSM community organizations, we collected 6,535 electronic questionnaires from 31 regions across China, excluding Taiwan, Hong Kong, and Macau. The questionnaire focused on investigating MSM's awareness, willingness, usage, and cessation of oral PrEP. Additionally, 40 participants were randomly chosen for key informant interviews. These qualitative interviews aimed to explore the reasons influencing MSM discontinuing oral PrEP. Results We eventually enrolled 6535 participants. Among the 685 participants who had used oral PrEP, 19.70% (135/685) ceased oral PrEP. The results indicated that individuals spending > ¥1000 on a bottle of PrEP (aOR = 2.999, 95% CI: 1.886–4.771) were more likely to cease oral PrEP compared to those spending ≤ ¥1000. Conversely, individuals opting for on-demand PrEP (aOR = 0.307, 95% CI: 0.194–0.485) and those using both daily and on-demand PrEP (aOR = 0.114, 95% CI: 0.058–0.226) were less likely to cease PrEP compared to those using daily PrEP. The qualitative analysis uncovered eight themes influencing oral PrEP cessation: (i) High cost and low adherence; (ii) Sexual inactivity; (iii) Lack of knowledge about PrEP; (iv) Trust in current prevention strategies; (v) Poor quality of medical service and counseling; (vi) PrEP stigma; (vii) Partner and relationship factors; (viii) Access challenges. Conclusions The cessation of oral PrEP among MSM in China is associated with various factors, including the cost of oral PrEP medication, regimens, individual perception of HIV risk, stigma, and the quality of medical services. It is recommended to provide appropriate regimens for eligible MSM and develop tailored combinations of strategies to enhance PrEP awareness and acceptance among individuals, medical staff, and the MSM community. The findings from this study can support the refinement of HIV interventions among MSM in China, contributing to efforts to reduce the burden of HIV in this population.

There are numerous instabilities present in charged particle beams that undergo exponential growth and reach saturation. In various applications, such as free-electron lasers or micro-bunching light sources, achieving saturation is desirable. Conversely, there are applications where these instabilities are utilized as linear broad-band amplifiers for signals embedded in the charged beam. In the latter scenario, the saturation of an instability induces non-linear distortions in the imprinted signal, thereby limiting the useful range of such amplifiers. Accurate evaluation of these instabilities necessitates a complete and comprehensive modeling approach that includes shot noise within the beam. Unfortunately, such modeling is not always feasible or practical. In this paper, we introduce a methodology utilizing the frequency and bandwidth of the instability as key parameters. Through this, we derive an estimation for the range of linear instability growth. Our derivation is conducted in a model-independent manner, making it applicable to a broad spectrum of instabilities. To validate our approach, we employ established and thoroughly benchmarked simulations with a free electron laser (FEL) code as well as self-consistent 3-dimensional simulation of plasma-cascade instability using code SPACE.

Abstract Aims Surveys and research on the applications of the hepatic venous pressure gradient (HVPG) are important for understanding the current status and future development of this technology in China. This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022. Methods We investigated the overall status of HVPG technology in China—including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications, and current challenges by using online questionnaire. By counting the number and percentages of cases of these results, we hope to clarify the current status of HVPG measurements in China. Results According to the survey, 85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces. A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022, of which 2813 cases (56.4%) were measured alone. The average cost of HVPG measurement was 5646.8 ± 2327.9 CNY. Of the clinical teams who performed the measurements (sometimes multiple per hospital), 94.3% (82/87) used the balloon method, and the majority of the teams (72.4%, 63/87) used embolectomy catheters. Conclusions This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology. It is still necessary to continue promoting and popularizing this technology in the future.

Abstract Background Conflicting findings regarding the impact of High protein intake during the early phase in critically ill patients have been reported. Therefore, we aimed to assess the influence of higher early protein intake on the prognosis of critically ill patients. Methods This randomized controlled trial involved 173 critically ill patients who stayed in the Intensive Care Unit/Emergency ICU (ICU/EICU) for at least 7 days. The Low group (n = 87) and High group (n = 86) received protein supplementation of 0.8 g/kg.d and 1.5 g/kg.d, respectively, within 1–3 days of enteral nutrition (EN) initiation, with both groups transitioning to 1.5 g/kg.d on the 4th day. The serum prealbumin (PA), blood urea nitrogen/creatinine, and rectus femoris muscle thickness and cross-sectional area of all patients was measured on the 1th, 3rd, 5th, 7th day, and the day of ICU/EICU discharge. Results Patients in both Low and High groups showed no significant differences in age, APACHE II scores, or other demographic and baseline characteristics. There were also no significant differences in the primary outcome (28-day mortality rate) and secondary outcomes (incidence rate of refeeding syndrome and EN tolerance score) between the two groups. However, the Low group exhibited a significantly higher 28-day mortality rate (HR = 2.462, 95% CI: 1.021–5.936, P = 0.045) compared to High group, as determined by Cox proportional hazards models incorporating the time factor. The High group exhibited significantly shorter durations of mechanical ventilation and ICU stay compared to the Low group. Serum PA levels were higher, and rectus femoris muscle atrophy rates were lower in the High group. Furthermore, for septic patients, high protein intake significantly reduced the 28-day mortality rate despite a small sample size (n = 34). Conclusions Our study indicates that increasing early protein intake to 1.5 g/kg.d may be safe and help improve the nutritional status and prognosis of critically ill patients. Trial registration This study was registered with the Chinese Clinical Trial Registry (ChiCTR2000039997, https://www.chictr.org.cn/ ).

Abstract Background Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis. Methods The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout. Results We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout: ADH1B, BMP1, and HIST1H3A. Conclusion According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition.

Abstract Background Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects. Methods In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats. Results Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration. Conclusions The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair. Graphical Abstract

IntroductionThe present study aimed to evaluate the effects of substituting fish meal with pork meal in feed on the growth performance, feed utilization, intestinal morphology, and immune function of Penaeus monodon.MethodsA total of 600 uniformly sized juvenile shrimp with an initial weight of 1.20 ± 0.03 g were randomly assigned to four groups, with each group consisting of six replicates of 25 shrimp each. Fish meal protein was replaced with 0%, 5%, 10%, and 15% pork meal, and crystalline amino acids and fish oil were supplemented accordingly. The groups were designated as P0, P5, P10, and P15, and the study duration was 70 days.ResultsResults indicated no significant difference in specific growth rate (SGR) between the P5 and P10 groups compared to the P0 group. However, the SGR in the P15 group was significantly lower than that in the P5 and P10 groups. Feed conversion rates (FCRs) for the P5 and P10 groups were comparable to the P0 group, whereas the P15 group showed a significantly higher FCR than the other groups. There were no significant differences in whole body composition among all the groups. Apart from alanine, the amino acid composition of muscles did not differ significantly among all the groups. Results of enzyme activity in plasma revealed that the replacement of fish meal with pork meal reduced levels of aspartate aminotransferase (AST) and superoxide dismutase (SOD). Specifically, levels of AST in the P5 and P15 groups were significantly lower compared to the P0 and P10 groups. Histological examination of midgut tissues showed that villus height initially increased and then decreased with higher replacement ratios. The P5 group had the highest villus height, while the P15 group had the lowest villus height. Analysis of gene expression related to liver immune functions indicated that genes in TLR signaling pathway were significantly elevated in the P15 group compared to the other groups.DiscussionIn conclusion, even with the supplementation of crystalline amino acids and fish oil, pork meal should not replace more than 10% of fish meal in the feed of P. monodon to maintain optimal growth and feed efficiency.

One of the pharmacological approaches to neoplastic disease aims to target the metastatic capacity of tumor cells to reduce their aggressive behavior. In this study, we analyzed the antimigratory capacity of the compound SEMBL, (S)-β-salicyloylamino-a-exo-methylene-ƴ-butyrolactone, a new analog of (-)-Dehydroxymethylepoxyquinomicin ((-)-DHMEQ), in three different breast cancer cell lines: MCF-7, MCF-7R and MDA-MB-231. This molecule is characterized by intense antiproliferative activity, evaluated by MTS assay, showing greater potency than DHMEQ. SEMBL was able to inhibit nuclear factor κappa B (NF-κB) activation observed through TransAM™ assay, while cell invasion and wound healing assays revealed a strong reduction in invasive capacity mediated by metalloproteinase 2 (MMP-2) and Vimentin decrease. These results, obtained in vitro, were corroborated on 3D systems made up of Poly-L-Lactic Acid (PLLA) scaffolds. In summary, SEMBL exerts interesting anti-tumor activities in preclinical breast cancer models and therefore it could be a promising new molecule to be studied also in other types of neoplastic disease.

PurposeThe overall survival of patients with pancreatic cancer is extremely low. We aimed to establish machine learning (ML) based model to accurately predict three-year survival and prognosis of pancreatic cancer patients.MethodsWe analyzed pancreatic cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2021. Univariate and multivariate logistic analysis were employed to select variables. Recursive Feature Elimination (RFE) method based on 6 ML algorithms was utilized in feature selection. To construct predictive model, 13 ML algorithms were evaluated by area under the curve (AUC), area under precision-recall curve (PRAUC), accuracy, sensitivity, specificity, precision, cross-entropy, Brier scores and Balanced Accuracy (bacc) and F Beta Score (fbeta). An optimal ML model was constructed to predict three-year survival, and the predictive results were explained by SHapley Additive exPlanations (SHAP) framework. Meanwhile, 101 ML algorithm combinations were developed to select the best model with highest C-index to predict prognosis of pancreatic cancer patients.ResultsA total of 20,064 pancreatic cancer patients from SEER database was consecutively enrolled. We utilized eight clinical variables to establish prediction model for three-year survival. CatBoost model was selected as the best prediction model, and AUC was 0.932 [0.924, 0.939], 0.899 [0.873, 0.934] and 0.826 [0.735, 0.919] in training, internal test and external test sets, with 0.839 [0.831, 0.847] accuracy, 0.872 [0.858, 0.887] sensitivity, 0.803 [0.784, 0.825] specificity and 0.832 [0.821, 0.853] precision. Surgery type had the greatest effects on three-year survival according to SHAP results. For prognosis prediction, “RSF+GBM” algorithm was the best prognostic model with C-index of 0.774, 0.722 and 0.674 in training, internal test and external test sets.ConclusionsOur ML models demonstrate excellent accuracy and reliability, offering more precise personalized prognostic prediction to pancreatic cancer patients.

Both ambient fine particulate matter (PM2.5) and aging are important urban concerns. However, the associations between PM2.5 constituents and the acceleration of aging (AA) remain unclear. We included 16,051 adults (aged 25–80 years) with 19,252 medical observations in Taiwan during 2008−2017. 2-year average PM2.5 and its five major constituents were assessed using a two-stage machine learning model at a resolution of 1 km2. AA was determined by the difference between the Klemera–Doubal biological age and chronological age. A linear mixed model (LMM) with inverse probability weights was used to examine the associations between AA and air pollution. In a semi-randomized study design, we applied a post-matching LMM to assess the impacts of changes in air pollution exposure on AA. Each interquartile range increase in ambient PM2.5, SO4-2, NO3–, NH4+, organic matters (OM), and black carbon (BC) was associated with a 0.20 (95 %confidence interval [CI]: 0.17–0.24), 0.19 (0.15–0.23), 0.14 (0.11–0.18), 0.21 (0.17–0.24), 0.22 (0.19–0.26) and 0.25 (0.21–0.28) year increase in AA, respectively. BC was generally associated with the greatest increase in AA as compared to other constituents. We did not find evident thresholds in their concentration–response associations. Participants exposed to increased levels of PM2.5, SO4-2, NO3–, NH4+, OM, and BC experienced an increase in AA of 0.11 (−0.07–0.29), 0.20 (0.02–0.39), 0.15 (−0.02–0.33), 0.12 (−0.07–0.31), 0.24 (0.07–0.41), and 0.30 (0.07–0.52) years, respectively, compared to those exposed to decreased/unchanged levels. Long-term exposure to ambient PM2.5 and its constituents may accelerate biological aging among Chinese adults. Exposed to increased levels may further aggregate the aging process. This study suggests that reducing exposure to air pollution is beneficial, even for residents within moderately-to-highly polluted regions, such as Taiwan. Rigorous regulation of PM2.5 and its constituents may prevent the acceleration of biological age.

Ecological vulnerability (EV) assessment is an important means of reflecting the evolutionary process of the local ecological environment, which is crucial for ecological security. The current EV assessment still faces challenges in comprehensively revealing its spatio-temporal change characteristics due to diversity, multi-scale complexity and non-linearity of ecosystems. In this study, we comprehensively revealed the spatio-temporal change features and driver mechanisms of EV in Yunnan Province (YP) using methods such as breaks for additive seasonal and trend (BFAST) and Geodetector. According to the findings, (1) the ecological vulnerability index (EVI) in YP decreased by 0.0265 on the raster scale between 2000 and 2018, and the ecological vulnerability level (EVL) was mainly dominated by level III. At the city scale, EVL in YP was dominated by level IV. At the basin scale, the average EV of the Jinsha River basin was much greater other basins. (2) The linear trend of EV in the YP mainly showed an insignificant decrease, mostly concentrated in the YP’s eastern region. The non-linear trend mainly showed a monotonous decrease, with the mutation time concentrated in 2009. The future persistence trend of EV under different coupling modes was dominated by anti-persistence decrease (Sen-MK + Hurst) and anti-persistence monotonous decrease (BFAST + Hurst), with an area percentage of 40.19 % and 25.13 %, respectively. (3) Gross primary productivity was the priority factor influencing YP’s EV (q = 0.4137). This study not only enriches the cases of EV assessment studies in the high mountain valley area but also bridges the gap of analysing the multi-spatial scale characteristics and change trends of regional EV.

BackgroundSigmoid Ventricular Septum (SVS) is a type of hypertrophic cardiomyopathy characterized by a reduced angle between the basal interventricular septum and the ascending aorta, and SVS can lead to dynamic Left Ventricular Outflow Tract obstruction (LVOTO) during hypercontractile states. Patients experiencing LVOTO may manifest symptoms such as angina, syncope, etc. Radiofrequency ablation (RFA) has been utilized to treat patients with hypertrophic obstructive cardiomyopathy, but there is no reports on its use in treating LVOTO resulting from SVS. Our report describes two cases of SVS treated with endocardial ablation to improve LVOTO.Case reportCase 1: A 74-year-old female patient with angina and syncope was admitted to the hospital and diagnosed with SVS by transthoracic echocardiogram. The patient exhibited LVOTO and Systolic Anterior Motion (SAM) phenomena during the administration of the dobutamine stress test. After RFA was performed, the patient's symptoms significantly improved. Additionally, septum decreased from 16 to 13 mm after ten months, and the morphological changes associated with SVS also disappeared. Case 2: A 57-year-old female was admitted to the hospital due to recurrent chest pain after physical activity for more than four years. The transthoracic echocardiogram indicated that the patient met the diagnostic criteria for SVS, and LVOTO and SAM phenomenaoccurred following dobutamine stress test. The patient had significant improvement in symptoms after undergoing RFA treatment.ConclusionsThese two cases represent the first documented instances where dynamic LVOTO caused by SVS could be effectively managed through endocardial RFA.

Trisomy 21, characterized by the presence of an additional chromosome 21, leads to a set of clinical features commonly referred to as Down syndrome (DS). The pathological phenotypes observed in DS are caused by a combination of factors, such as mitochondrial dysfunction, neuroinflammation, oxidative stress, disrupted metabolic patterns, and changes in protein homeostasis and signal transduction, and these factors collectively induce neurological alterations. In DS, the triplication of chromosome 21 and the micronuclei arising from the missegregation of chromosomes are closely associated with inflammation and the development of redox imbalance. Autophagy, an essential biological process that affects cellular homeostasis, is a powerful tool to facilitate the degradation of redundant or dysfunctional cytoplasmic components, thereby enabling the recycling of their constituents. Targeting the autophagy process has been suggested as a promising method to balance intracellular inflammation and oxidative stress and improve mitochondrial dysfunction. In this review, we summarize the role of autophagy in regulating inflammation and redox homeostasis in DS and discuss their crosslinks. A comprehensive elucidation of the roles of autophagy in DS offers novel insights for the development of therapeutic strategies aimed at aneuploidy-associated diseases.

The APOE 4 allele remains the primary genetic risk factor for sporadic Alzheimer’s disease, whereas the APOE 2 allele emerges as a protective factor. Therapeutic approaches in murine models with human APOE alleles, such as modulating APOE levels and converting isoforms, show efficacy. However, there is a lack of in vitro APOE2-mutant human neuronal models. Hence, in this study, we generated human induced pluripotent stem cells (hiPSCs) from the peripheral blood mononuclear blood cells (PMBC) of a 42-year-old female donor carrying the APOE-ε2/ε2 allele. The newly generated hiPSC displayed normal karyotype and could differentiate into three germ layers. Besides, they retained their original genotype and expressed pluripotency markers.

Objectives: This study examined whether changes in late-life physical performance are associated with contemporaneous changes in blood pressure (BP) in older men. Design: prospective cohort study over 7 years. Setting and Participants: Physical performance (gait speed, grip strength, chair stand performance) and clinic-measured BP at baseline and at least one follow-up (year 7 or 9) were assessed in 3,135 men aged ≥65 y enrolled in the Osteoporotic Fractures in Men Study (MrOS). Methods: Generalized estimating equation analysis of multivariable models with standardized point estimates (β [95% CI]) described longitudinal associations between physical performance and BP changes in participants overall, and stratified by baseline cardiovascular disease (CVD), antihypertensive medication use (none, ≥1), and enrollment age (

Abstract Background This study aimed to evaluate the global burden of lung cancer due to ambient particulate matter (PM) pollution in women of childbearing age from 1990 to 2021. Methods This was a secondary analysis utilizing data from the Global Burden of Disease (GBD) 2021, with a focus on the temporal trends of the lung cancer burden attributable to ambient PM2.5 among women of childbearing age. Results In 2021, the global mortality and disability‐adjusted life years (DALYs) number of lung cancer burden attributable to ambient PM2.5 among women of childbearing age were approximately 5205 and 247,211, respectively. The rate of lung cancer attributable to ambient PM2.5 among women of childbearing age increased between 1990 and 2021, with the age‐standardized mortality rate (ASMR) increasing from 0.22 (95% uncertainty interval [UI]; 0.13 to 0.33) to 0.25 (95% UI; 0.14 to 0.37; average annual percent change [AAPC] = 0.40) and the age‐standardized DALYs rate (ASDR) increasing from 10.39 (95% UI; 5.96 to 15.72) to 12.06 (95% UI; 6.83 to 17.51; AAPC = 0.41). The middle sociodemographic index (SDI) region, East Asia, and China had the heaviest burden, while the high SDI region showed the highest decrease. ASMR and ASDR exhibited an inverted U‐shaped relationship with the SDI. Conclusions From 1990 to 2021, the lung cancer burden attributable to ambient PM2.5 among women of childbearing age exhibited an increasing trend. Furthermore, increasing attention should be paid to the middle SDI region, East Asia, and China, as ambient PM pollution remains a critical target for intervention.

Abstract Despite docetaxel combined with cisplatin and 5‐fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48‐linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)‐like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG‐like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7‐USP10‐G3BP1 axis contains potential targets and biomarkers for NPC treatment.

BackgroundInflammation is associated with the pathophysiology of schizophrenia. The blood markers for systemic inflammation include neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), lymphocyte-monocyte ratio (LMR), system inflammation response index (SIRI), and platelet-lymphocyte ratio (PLR). However, these inflammation markers and their relationships with clinical phenotypes among Han Chinese patients with first-episode adolescent-onset schizophrenia (AOS) is unclear. This investigation aimed to elucidate the impact of inflammation on Han Chinese AOS patients as well as the association of blood-based inflammation markers with clinical symptoms.MethodsAltogether, 203 Han Chinese individuals participated in this study, 102 first-episode AOS patients and 101 healthy controls. The assessment of inflammatory indices was based on complete blood cell count. Furthermore, schizophrenia-related clinical symptoms were evaluated using the five-factor model of the Positive and Negative Syndrome Scale (PANSS).ResultsIn Han Chinese first-episode AOS patients, levels of SIRI, PLR, SII, and NLR were significantly increased (p < 0.001), while LMR decreased (p < 0.001) compared to healthy controls. Furthermore, multivariate logistic regression showed that LMR, NLR, SII, and SIRI (all p < 0.05) were independently associated with AOS. Moreover, Receiver operating characteristics assessment indicated that NLR, SIRI, LMR, and SII could effectively distinguish AOS patients from healthy controls. Their areas under the curves were 0.734, 0.701, 0.715, and 0.730 (all p < 0.001). In addition, Correlation analysis revealed that LMR was negatively correlated with the PANSS total, negative, and cognitive factor scores (all p < 0.05); NLR was positively correlated with the cognitive factor score (p < 0.01); SII was negatively correlated with the positive factor score and positively with the negative and cognitive factor scores (all p < 0.05); SIRI was positively correlated with the PANSS total and cognitive factor scores (all p < 0.01).ConclusionsThis research established the involvement of peripheral blood inflammatory markers (LMR, NLR, SII, and SIRI) with the clinical manifestations and pathophysiology of schizophrenia, and these can serve as screening tools or potential indices of the inflammatory state and AOS symptoms severity.

Urbanization affects vegetation distribution by changing land cover. However, it also significantly changes urban water and heat conditions, affecting vegetation growth and development. Vegetation coverage is an effective indicator of vegetation growth. This study analyzed trends in vegetation coverage over the past 35 years, taking the Yunnan Central Urban Economic Circle as the study area. The study was based on applying the pixel dichotomy model and correlation statistical analysis on joint Landsat 5, 7, and 8 long- term remote sensing data, meteorological, and land use data. The direct and indirect effects of urbanization on vegetation coverage were also further explored by constructing an urbanization impact framework. The results revealed that: (1) The urban area during urbanization from 1986 to 2021 increased by 720.29 km2. There was a continuous decline in vegetation cover in and around urban areas, which intensified with accelerating urbanization, with the effect being more pronounced in suburban areas. (2) There were consistent increasing trends in urbanization’s direct and indirect effects on vegetation over the last 35 years, with average negative and positive effects of − 0.41 and 1.59, respectively. (3) Direct effects could mainly be attributed to the expansion of impervious surfaces, whereas the main indirect effect during the late urbanization period (2011–2020) was increasing average temperature. The average temperature showed a correlation coefficient with urbanization of 0.7767, and this relationship showed seasonal heterogeneity due to the significant growth of urban vegetation in summer and winter. (4) Cities that developed faster showed better environmental planning and construction. The direct and indirect effects of urbanization on vegetation during the early and middle stages were higher in cities developing at slow and moderate rates, with this trend reversing only in the later stages of urbanization. The results of this study can increase understanding of the effect of urbanization on vegetation coverage in the Yunnan Central Urban Economic Circle. They can assist in improving urban green spaces and urban ecological resilience.

Recent research has highlighted the beneficial effects of urban green spaces on physical and mental health. This study focused on the hospital population and innovatively subdivided the population into four groups: doctors, caregivers, patients and nurses. A total of 96 volunteers participated in this virtual reality experiment to assess the restoration of a linear canopy landscape and a landscape with different levels of hydrodynamics through interactive audiovisual immersion. We utilized pre-research method, brainwave monitoring technique, psychological scales, observation and interviews in this experiment. The research identified five key findings. First, both linear canopy landscapes and those with low to medium hydrodynamic forces significantly enhance physiological and psychological restoration for all groups, with the most substantial physiological benefits observed in doctors and patients, and the greatest psychological relief noted in caregivers. Second, landscapes with medium hydrodynamic forces yield higher restorative effects than those with low forces in hospital settings. Third, green landscapes with medium and low-density canopies prove more conducive to patient recovery compared to those with high-density canopies. Fourth, the inclusion of bird songs does not markedly affect physiological restoration across the hospital groups. Finally, landscapes that incorporate elements of water dynamics, open skies, and lightly foliated canopies draw significant interest from all groups involved. This study advocates for the integration of natural blue and green elements into hospital environments as complementary therapeutic interventions, aiming to alleviate stress and promote health recovery among hospital communities.

Phthalates (PAEs) are synthetic compounds extensively employed in consumer products. Blood pressure (BP) in children can vary, the degree of visit-to-visit BP variability (VVV) is at least partially independent of BP. The interactions between PAEs exposure, pubertal-related genetic susceptibility and lifestyles on childhood VVV are not investigated. This study utilized data from a cohort collected from Oct 2017–2020 in Xiamen, China. Seven urine PAE metabolites were measured. The long-term VVV was characterized employing the standard deviation (SD) and average real variability. We constructed a genetic risk score (GRS) of pubertal-related genes and healthy lifestyle scores. Exposed to high levels of mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (OR=1.43, 95 %CI=1.07, 1.92) and mono-2-ethyl-5-oxohexyl phthalate (OR=1.36, 95 % CI=1.01, 1.83) was related to increased SBP-SD, and the OR for high SBP-SD related to high GRS was 1.38 (95 % CI=1.02, 1.85). Compared to participants who had low GRS and low MEHHP exposure, participants exhibiting high GRS and MEHHP levels were more likely to experience high SBP-SD (OR=2.00, P

Extensive research has shown that PR domain 16 (PRDM16) plays a critical role in adipose tissue metabolism, including processes such as browning and thermogenesis of adipocytes, beigeing of adipocytes, and adipogenic differentiation of myoblasts. These functions have been associated with diseases such as obesity and diabetes. Additionally, PRDM16 has been correlated with various other conditions, including migraines, heterochromatin abnormalities, metabolic syndrome, cardiomyopathy, sarcopenia, nonsyndromic cleft lip, and essential hypertension, among others. However, there is currently no systematic or comprehensive conclusion regarding the mechanism of PRDM16 in human tumours, including haematologic and solid tumours. The aim of this review is to provide an overview of the research progress on PRDM16 in haematologic and solid tumours by incorporating recent literature findings. Furthermore, we explore the prospects of PRDM16 in the precise diagnosis and treatment of human haematologic and solid tumours.

Residues of herbicides with the extensive applications may impact the soil ecosystem and ultimately threaten agricultural sustainability. However, the effects of long-term herbicide residues on soil multifunctionality and the soil microbial community remain poorly understood. Here, we evaluated relationships between soil multifunctionality and soil microbial communities with residual herbicide concentrations by surveying and analyzing 62 black soil samples collected from an agricultural area in northeastern China. Total residual herbicide concentrations varied from 35 to 568 μg/kg in the soil samples. The response of soil multifunctionality to increasing residual herbicide concentrations exhibited an inverted U-shaped relationship with a peak at approximately 310 μg/kg, with net mineralized organic nitrogen (Nm) and total nitrogen (TN) exhibiting the same trend. Microbial community richness was significantly lower in soil samples with high residual herbicide concentrations (> 310 μg/kg, HG) compared to low residual herbicide concentrations (< 310 μg/kg, LG). In addition, the relative abundances of specific keystone microbial genera differed significantly between LG and HG: norank_f_Acetobacteraceae, norank_f_Caldilineaceae, Candidatus_Alysiosphaera, and Gonytrichum. The relative abundances of these genera were also significantly correlated with soil multifunctionality. Structural equation models (SEMs) further showed that herbicide residues influenced soil multifunctionality by affecting these specific keystone genera. Our study demonstrates that long-term herbicide residues significantly impact the multifunctionality of agricultural black soil, where low concentrations stimulate while high concentrations inhibit, underscoring the need for reasonable application of herbicides to maintain soil ecosystem health.

Research efforts on permanganate (Mn(VII)) combined with redox-mediator (RM), have received increasing attention due to their significant performance for bisphenol-A (BPA) removal. However, the mechanisms underpinning BPA degradation remain underexplored. Here we show the overlooked interactions between RM and BPA during permanganate oxidation by introducing an RM—N-hydroxyphthalimide (NHPI). We discovered that the concurrent generation of MnO2 and phthalimide-N-oxyl (PINO) radical significantly enhances BPA oxidation within the pH range of 5.0–6.0. The detection of radical cross-coupling products between PINO radicals and BPA or its derivatives corroborates the pivotal role of radical cross-coupling in BPA oxidation. Intriguingly, we observed the formation of an NHPI-BPA complex, which undergoes preferential oxidation by Mn(VII), marked by the emergence of an electron-rich domain in NHPI. These findings unveil the underlying mechanisms in the Mn(VII)/RM system and bridge the knowledge gap concerning BPA transformation via complexation. This research paves the way for further exploration into optimizing complexation sites and RM dosage, significantly enhancing the system's efficiency in water treatment applications.

Abstract Background Major depressive disorder (MDD) is a severe mental illness with high relapse rates and high mortality. Depression not only severely limits psychosocial functioning but also reduces quality of life. It can also negatively affect patients’ clinical parameters, including lipid metabolism markers. This study aimed to investigate the prevalence and risk factors of hyperlipidemia (HL) in patients with MDD who were hospitalized for the first time. Methods In this study, we enrolled 981 patients with MDD who were hospitalized for the first time, collected their demographic data and biochemical indicators, and evaluated their clinical symptoms. We divided the patients into HL and non-HL subgroups based on whether they had co-morbid HL. We compared whether there were significant differences between the two groups regarding demographics and general clinical information. Results A total of 708 of 981 MDD patients were described as being in the hyperlipidemic group, with an incidence of 72.17%. Clinical Global Impression Scale-Severity of Illness (CGI-SI) score and Hamilton Depression Scale (HAMD) score are risk factors for co-morbid HL in patients with MDD. The area under the ROC curve for the CGI-SI and HAMD score and their combined discriminatory ability was approximately 63%, 67%, and 68%, respectively. Conclusion The prevalence of HL was high in patients with MDD who were first hospitalized; Higher HAMD score and CGI-SI score were risk factors for the development of HL in MDD; The HAMD score and the CGI-SI score are predictive of the severity of HL.

Abstract Background Abdominal perineal resection (APR) of rectal cancer, also known as Mile’s procedure, is a classic procedure for the treatment of rectal cancer. Through the improvement of surgical skills and neoadjuvant therapy, the sphincter-preserving rate in rectal cancer patients has improved, even in patients with ultralow rectal cancer who underwent APR in the past. However, APR cannot be completely replaced by low anterior resection (LAR) in reality. APR still has its indications, when the tumor affects the external sphincter, etc. Good perineal exposure in APR is difficult and can seriously affect surgical safety and the long-term prognosis. Methods We reviewed the records of 16 consecutive patients with rectal cancer who underwent APR at Anqing Municipal Hospital from January 2022 to April 2023, including 11 males and 5 females, with an average age of 64.8 ± 10.3 years. The perineal operation was completed with the Lone-Star® retractor-assisted (LSRA) exposure method. After incising the skin and subcutaneous tissue, a Lone-Star® retractor was placed, and the incision was retracted in surrounding directions with 8 small retractors, which facilitated the freeing of deep tissues. We dynamically adjusted the retractor according to the plane to fully expose the surgical field. Results All 16 patients underwent laparoscopic-assisted APR successfully. Thirteen procedures were performed independently by a single person, and the others were completed by two persons due to intraoperative arterial hemostasis. All specimens were free of perforation and had a negative circumferential resection margin (CRM). Postoperative complications occurred in 4 patients, including urinary retention in 1 patient, pulmonary infection in 1 patient, intestinal adhesion in 1 patient and peristomal dermatitis in 1 patient, and were graded as ClavienDindo grade 3 or lower and cured. No distant metastasis or local recurrence was found for any of the patients in the postoperative follow-up. Conclusions The application of the LSRA exposure method might be helpful for perineal exposure during APR for rectal cancer, which could improve intraoperative safety and surgical efficiency, achieve one-person operation, and increase the comfort of operators.

Abstract Uncontrollable zinc (Zn) plating and hydrogen evolution greatly undermine Zn anode reversibility. Previous electrolyte designs focus on suppressing H2O reactivity, however, the accumulation of alkaline byproducts during battery calendar aging and cycling still deteriorates the battery performance. Here, we present a direct strategy to tackle such problems using a strong Brønsted acid, bis(trifluoromethanesulfonyl)imide (HTFSI), as the electrolyte additive. This approach reformulates battery interfacial chemistry on both electrodes, suppresses continuous corrosion reactions and promotes uniform Zn deposition. The enrichment of hydrophobic TFSI– anions at the Zn|electrolyte interface creates an H2O-deficient micro-environment, thus inhibiting Zn corrosion reactions and inducing a ZnS-rich interphase. This highly acidic electrolyte demonstrates high Zn plating/stripping Coulombic efficiency up to 99.7% at 1 mA cm–2 ( > 99.8% under higher current density and areal capacity). Additionally, Zn | |ZnV6O9 full cells exhibit a high capacity retention of 76.8% after 2000 cycles.

Abstract To solve the problems of high sampling requirements and low predictive accuracy resulting from the complexity, uniqueness, and randomness of predicting the risk of the CO2 and N2 injection to enhance coal seam gas drainage (CO2/N2–ECGD) technology. The principal component analysis (PCA) method to reduce the dimensionality of the factor data that contribute to the effect risk of the technology was adopted. And the particle swarm optimization (PSO) method was implemented to search for optimal hyperparameters in support vector machine (SVM) by particle search, as a solution to the traditional SVM hyperparameters optimization problem. A novel risk prediction model using machine learning algorithms for gas injection displacement technology was constructed. The prediction results were tested and compared with those of backpropagation (BP), Random Forest (RF), and Decision Tree (DT) models using data from 29 gas injection displacement field projects in China. The results demonstrated that the SVM model had greater accuracy in prediction than the other three models. Additionally, after PSO optimization and dimensionality reduction, the PCA–PSO–SVM model reached 100% prediction accuracy, while requiring less modeling and operation time. The study provided a reliable and reasonable model for predicting technical effects, along with a theoretical basis for risk management and prevention. First, the technology's influencing indicators were analyzed by examining its mechanisms. Second, we utilized the PCA method to reduce the dimensionality of the factor data that contribute to the risk of the technology's effects. Third, we implemented the PSO method to search for optimal hyperparameters in the SVM through particle search, as a solution to the traditional SVM hyperparameters optimization problem. Finally, the prediction results were tested and compared with those of BP, RF, and DT models using data from 29 gas injection displacement field projects in China. The SVM model was found to have greater accuracy in prediction than the other three models. After PSO optimization and dimensionality reduction, the PCA–PSO–SVM model achieved 100% prediction accuracy while requiring less modeling and operation time. The study presents a valid and reasonable model for predicting technical effects and a theoretical basis for risk management and prevention.

Abstract Background The utilization of liposomes in drug delivery has garnered significant attention due to their efficient drug loading capacity and excellent biocompatibility, rendering them a promising platform for tumor therapy. However, the average size of liposomes ~ 100 nm leads to liposomes being susceptible to hepatic and renal metabolism to excretion outside the body leading to poor drug delivery efficiency with a total utilization rate of less than 0.7%, resulting in unfavorable treatment outcomes. Results We have developed a novel liposome platform equipped with tumor surface nucleolin-targeting capacity to enhance drug accumulation at the tumor in vivo. The encapsulation of doxorubicin through thin film hydration has resulted in the formation of D@L-AS1411. Through in vivo experiments, we have demonstrated the effective accumulation of D@L-AS1411 at the tumor site and its ability to improve doxorubicin utilization rates by 40%. Additionally, D@L-AS1411 induces immunogenic death of tumor cells, release of tumor-associated antigens, upregulation of calreticulin expression, and recruitment of active T cell infiltration, and ultimately improves the therapeutic efficacy against tumors (70%). Conclusions Based on the nucleic acid aptamer AS1411, D@L-1411 is developed to specifically enhance the accumulation of Dox at tumor sites, thereby inhibiting and enhancing the anti-tumor effect. In summary, this study not only provides an efficient tumor-targeting delivery platform but also contributes to the improvement of chemotherapy–immunotherapy combination for tumor treatment strategy in the clinic.

Abstract Background Diabetic wounds are one of the long-term complications of diabetes, with a disordered microenvironment, diabetic wounds can easily develop into chronic non-healing wounds, which can impose a significant burden on healthcare. In diabetic condition, senescent cells accumulate in the wound area and suppress the wound healing process. AMPK, as a molecule related to metabolism, has a close relationship with aging and diabetes. The purpose of this study was to investigate the effects of AMPK activation on wound healing and explore the underlying mechanisms. Methods AMPK activator A769662 was topically applied in wound models of diabetic mice. Alterations in the wound site were observed and analyzed by immunohistochemistry. The markers related to autophagy and ferritinophagy were analyzed by western blotting and immunofluorescence staining. The role of AMPK activation and ferritinophagy were also analyzed by western blotting. Results Our results show that AMPK activation improved diabetic wound healing and reduced the accumulation of senescent cells. Intriguingly, we found that AMPK activation-induced ferroptosis is autophagy-dependent. We detected that the level of ferritin had deceased and NCOA4 was markedly increased after AMPK activation treatment. We further investigated that NCOA4-mediated ferritinophagy was involved in ferroptosis triggered by AMPK activation. Most importantly, AMPK activation can reverse the ferroptosis-insensitive of senescent fibroblast cells in diabetic mice wound area and promote wound healing. Conclusions These results suggest that activating AMPK can promote diabetic wound healing by reversing the ferroptosis-insensitive of senescent fibroblast cells. AMPK may serve as a regulatory factor in senescent cells in the diabetic wound area, therefore AMPK activation can become a promising therapeutic method for diabetic non-healing wounds.

Abstract Sustainable battery recycling is essential for achieving resource conservation and alleviating environmental issues. Many open/closed-loop strategies for critical metal recycling or direct recovery aim at a single component, and the reuse of mixed cathode materials is a significant challenge. To address this barrier, here we propose an upcycling strategy for spent LiFePO4 and Mn-rich cathodes by structural design and transition metal replacement, for which uses a green deep eutectic solvent to regenerate a high-voltage polyanionic cathode material. This process ensures the complete recycling of all the elements in mixed cathodes and the deep eutectic solvent can be reused. The regenerated LiFe0.5Mn0.5PO4 has an increased mean voltage (3.68 V versus Li/Li+) and energy density (559 Wh kg–1) compared with a commercial LiFePO4 (3.38 V and 524 Wh kg–1). The proposed upcycling strategy can expand at a gram-grade scale and was also applicable for LiFe0.5Mn0.5PO4 recovery, thus achieving a closed-loop recycling between the mixed spent cathodes and the next generation cathode materials. Techno-economic analysis shows that this strategy has potentially high environmental and economic benefits, while providing a sustainable approach for the value-added utilization of waste battery materials.

Ti and its alloys have been widely applied in various fields of national economy due to their excellent combinations of specific mechanical properties and outstanding corrosion behavior. Among Ti alloys, Ti–1Al–8V–5Fe (Ti-185) alloy is a metastable and low-cost β-Ti alloy, and owns extremely outstanding mechanical performance. In the paper, to overcome the issue of β flecks associated with Fe segregation in conventional ingot metallurgy process, Ti-185 alloy was prepared by electrostatic levitation (ESL) technique at various supercoolings, and its solidification behavior and dendrite growth were systematically analyzed. Moreover, the thermophysical parameters of liquid Ti-185 alloy were tested, and the microstructure, hardness and compressive property were compared to that of cast ingot. Results shown that the maximum supercooling of 311 K in the liquid Ti-185 alloy can be achieved, and a noticeable recalescence phenomenon appears during ESL process. The density and the ratio of specific heat to emissivity of liquid Ti-185 alloy increases linearly with temperature decreasing. Once the crystal nucleus is formed, the nonfacted interface will advance promptly. Moreover, the dendritic growth velocity (v) exhibits an exponential relationship with the supercooling (ΔT), and can be depicted as the equation of v = 1.59·ΔT1.65 mm s−1. Additionally, at a supercooling of 229 K or above, single crystal can be formed using ESL technique. Furthermore, the microhardness, elastic modulus and compressive strength of as-levitated Ti-185 alloy are hardly affected by the supercooling, but the plasticity of as-levitated sample is obviously higher than that of as-cast one.

Powdery mildew (PM), caused by Blumeria graminis f. sp. tritici (Bgt), is one of the destructive wheat diseases worldwide. Wild emmer wheat (Triticum turgidum ssp. dicoccoides, WEW), a tetraploid progenitor of common wheat, is a valuable genetic resource for wheat disease resistance breeding programs. We developed three hexaploid pre-breeding lines with PM resistance genes derived from three WEW accessions. These resistant pre-breeding lines were crossed with susceptible common wheat accessions. Segregations in the F2 populations were 3 resistant : 1 susceptible, suggesting a single dominant allele in each resistant parent. Mapping of the resistance gene in each line indicated a single locus on the long arm of chromosome 7A, at the approximate location of previously cloned Pm60 from T. urartu. Sanger sequencing revealed three different Pm60 haplotypes (Hap 3, Hap 5, and Hap 6). Co-segregating diagnostic markers were developed for identification and selection of each haplotype. The resistance function of each haplotype was verified by the virus-induced gene silencing (VIGS). Common wheat lines carrying each of these Pm60 haplotypes were resistant to most Bgt isolates and differences in the response arrays suggested allelic variation in response.

Abstract Background Diabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators. Methods A male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators. Results Saline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1β) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks. Conclusion Intravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators.