ADAM9 drives the immunosuppressive microenvironment by cholesterol biosynthesis-mediated activation of IL6-STAT3 signaling for lung tumor progression.

Chronic inflammation associated with lung cancers contributes to immunosuppressive tumor microenvironments, reducing CD8+ T-cell function and leading to poor patient outcomes. A disintegrin and metalloprotease domain 9 (ADAM9) promotes cancer progression. Here, we aim to elucidate the role of ADAM9 in the immunosuppressive tumor microenvironment. A bioinformatic analysis of TIMER2.0 was used to investigate the correlation of ADAM9 and to infiltrate immune cells in the human lung cancer database and mouse lung tumor samples. Flow cytometry, immunohistochemistry, and RNA sequencing (RNA-seq) were performed to investigate the ADAM9-mediated immunosuppressive microenvironment. The coculture system of lung cancer cells with immune cells, cytokine array assays, and proteomic approach was used to investigate the mechanism. By analyzing the human LUAD database and the mouse lung cancer models, we showed that ADAM9 was associated with the immunosuppressive microenvironment. Additionally, ADAM9 released IL6 protein from cancer cells to inhibit IL12p40 secretion from dendritic cells, therefore leading to dendritic cell dysfunction and further affecting T-cell functions. Proteomic analysis indicated that ADAM9 promoted cholesterol biosynthesis and increased IL6-STAT3 signaling. Mechanistically, ADAM9 reduced the protein stability of LDLR, resulting in reduced cholesterol uptake and induced cholesterol biosynthesis. Moreover, LDLR reduction enhanced IL6-STAT3 activation. We reveal that ADAM9 has a novel biological function that drives the immunosuppressive tumor microenvironment by linking lung cancer's metabolic and signaling axes. Thus, by targeting ADAM9 an innovative and promising therapeutic opportunity was indicated for regulating the immunosuppression of lung cancer.

Itaconate protects ferroptotic neurons by alkylating GPx4 post stroke.

Neuronal ferroptosis plays a key role in neurologic deficits post intracerebral hemorrhage (ICH). However, the endogenous regulation of rescuing ferroptotic neurons is largely unexplored. Here, we analyzed the integrated alteration of metabolomic landscape after ICH using LC-MS and MALDI-TOF/TOF MS, and demonstrated that aconitate decarboxylase 1 (Irg1) and its product itaconate, a derivative of the tricarboxylic acid cycle, were protectively upregulated. Deficiency of Irg1 or depletion of neuronal Irg1 in striatal neurons was shown to exaggerate neuronal loss and behavioral dysfunction in an ICH mouse model using transgenic mice. Administration of 4-Octyl itaconate (4-OI), a cell-permeable itaconate derivative, and neuronal Irg1 overexpression protected neurons in vivo. In addition, itaconate inhibited ferroptosis in cortical neurons derived from mouse and human induced pluripotent stem cells in vitro. Mechanistically, we demonstrated that itaconate alkylated glutathione peroxidase 4 (GPx4) on its cysteine 66 and the modification allosterically enhanced GPx4's enzymatic activity by using a bioorthogonal probe, itaconate-alkyne (ITalk), and a GPx4 activity assay using phosphatidylcholine hydroperoxide. Altogether, our research suggested that Irg1/itaconate-GPx4 axis may be a future therapeutic strategy for protecting neurons from ferroptosis post ICH.

Cyclic guanosine monophosphate-adenosine monophosphate synthetase/stimulator of interferon genes signaling aggravated corneal allograft rejection through neutrophil extracellular traps.

The activation of innate immunity following transplantation has been identified as a crucial factor in allograft inflammation and rejection. However, the role of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling-mediated innate immunity in the pathogenesis of allograft rejection remains unclear. Utilizing a well-established murine model of corneal transplantation, we demonstrated increased expression of cGAS and STING in rejected-corneal allografts compared with syngeneic (Syn) and normal (Nor) corneas, along with significant activation of the cGAS/STING pathway, as evidenced by the enhanced phosphorylation of TANK-binding kinase 1and interferon regulatory factor 3. Pharmacological and genetic inhibition of cGAS/STING signaling markedly delayed corneal transplantation rejection, resulting in prolonged survival time and reduced inflammatory infiltration. Furthermore, we observed an increase in the formation of neutrophil extracellular traps (NETs) in rejected allografts, and the inhibition of NET formation through targeting peptidylarginine deiminase 4 and DNase I treatment significantly alleviated immune rejection and reduced cGAS/STING signaling activity. Conversely, subconjunctival injection of NETs accelerated corneal transplantation rejection and enhanced the activation of the cGAS/STING pathway. Collectively, these findings demonstrate that NETs contribute to the exacerbation of allograft rejection via cGAS/STING signaling, highlighting the targeting of the NETs/cGAS/STING signaling pathway as a potential strategy for prolonging allograft survival.

Precious Metal Free Hydrogen Evolution Catalyst Design and Application.

The quest to identify precious metal free hydrogen evolution reaction catalysts has received unprecedented attention in the past decade. In this Review, we focus our attention to recent developments in precious metal free hydrogen evolution reactions in acidic and alkaline electrolyte owing to their relevance to commercial and near-commercial low-temperature electrolyzers. We provide a detailed review and critical analysis of catalyst activity and stability performance measurements and metrics commonly deployed in the literature, as well as review best practices for experimental measurements (both in half-cell three-electrode configurations and in two-electrode device testing). In particular, we discuss the transition from laboratory-scale hydrogen evolution reaction (HER) catalyst measurements to those in single cells, which is a critical aspect crucial for scaling up from laboratory to industrial settings but often overlooked. Furthermore, we review the numerous catalyst design strategies deployed across the precious metal free HER literature. Subsequently, we showcase some of the most commonly investigated families of precious metal free HER catalysts; molybdenum disulfide-based, transition metal phosphides, and transition metal carbides for acidic electrolyte; nickel molybdenum and transition metal phosphides for alkaline. This includes a comprehensive analysis comparing the HER activity between several families of materials highlighting the recent stagnation with regards to enhancing the intrinsic activity of precious metal free hydrogen evolution reaction catalysts. Finally, we summarize future directions and provide recommendations for the field in this area of electrocatalysis.

Associations of Cognitive Impairment with All-Cause and Cardiovascular Mortality Among Individuals with Diabetes: A Prospective Cohort Study.

This study explored the association between diabetes, cognitive imFpairment (CI), and mortality in a cohort of 2931 individuals aged 60 and above from the 2011 to 2014 NHANES. Mortality data was gathered through 2019, and multivariable Cox proportional hazards models were used to determine the association between diabetes, CI, and mortality adjusting for sociodemographic characteristics, lifestyle factors, and comorbidity conditions. The study spanned up to 9.17 years, observing 579 deaths, with individuals having both diabetes and CI showing the highest all-cause mortality (23.6 events per 100 patient-years). Adjusted analysis revealed a 2.34-fold higher risk of all-cause mortality for this group, surpassing those with diabetes or CI alone. These results held after a series of stratified and sensitivity analyses. In conclusion, CI was linked to higher all-cause mortality in individuals with diabetes, emphasizing the need to address cognitive dysfunction in diabetic patients.

To corset or not to corset after lumbar spine fixation surgery?: A prospective randomized clinical trial and literature review.

PURPOSE: Orthosis after lumbar fusion surgery is common. However, the evidence for benefit remains to be determined, especially in tropical areas with heavy workers. To investigate postoperative orthosis and whether it affects pain improvement, quality of life, and fusion rate. METHOD: From May 2021 to May 2022, this single-center prospective randomized clinical trial enrolled 110 patients. We excluded 9 patients, and 101 people were analyzed finally. Corset group, in which participants used a corset for 3 months postoperatively; Non-corset group, in which participants didn't wear any orthosis. ODI and VAS scale were recorded before the surgery: 2 weeks, 1 month, 3 months, half a year, and 1 year postoperatively. The lumbar X-ray was done before the surgery, 6 months postoperatively. All complications in 1 year were recorded. RESULTS: Significant decrease in VAS score in the non-corset group since post-operation day 5 (corset group 3.44 ±â€…1.77, non-corset group 3.36 ±â€…1.75, P = .0093) during admission, and also a decrease in admission duration (corset group 11.08 ±â€…2.39, non-corset group 9.55 ±â€…1.75, P = .0004) were found. There was a significantly better ODI score in the non-corset group since post-operation 1 month, while in the corset group until post-operation 3 months. Both groups had no significant difference in satisfaction, complication rates, and X-ray results, such as fusion, angular rotation, sagittal transition, and slip in the neutral position. CONCLUSION: After the transpedicular screw fixation with posterolateral fusion surgery for degenerative spondylolisthesis, non-orthosis is a safe strategy. It can reduce the admission duration and has the trend for better functional outcomes.

Atomic-scale Ru anchored on chromium-shavings as a precursor for a pH-universal hydrogen evolution reaction electrocatalyst.

In the leather manufacturing industry, the management of substantial quantities of solid waste containing chrome shavings remains a formidable challenge. Concurrently, there is a pressing need for the development of pH-universal and economically viable electrocatalysts for the hydrogen evolution reaction (HER). In response to these intertwined challenges, this study proposes an innovative approach wherein the amino groups present on the surface of chrome shavings are utilized to immobilize single ruthenium atoms during pyrolysis, thereby facilitating the synthesis of hydrogen evolution electrocatalysts. The optimized sample, denoted as CN/Cr2O3/Ru-1, demonstrates exceptional electrocatalytic performance, exhibiting an ultra-low overpotential of -28 mV in 1.0 M KOH at a current density of 10 mA cm-2, and it also exhibits good performance in acidic and neutral electrolytes. Importantly, these overpotentials surpass those reported for many previous ruthenium-based catalysts. Density functional theory (DFT) calculations elucidate that both oxygen (O) and chromium (Cr) moieties within Cr2O3 can engage in favorable interactions with the coordination patterns of the ruthenium (Ru) atoms, thereby elucidating the synergistic enhancement conferred by the chromium element in CN/Cr2O3/Ru, which ultimately facilitates and promotes the catalytic activity of the ruthenium atoms serving as the catalytic center. This facile synthesis route not only presents a green solution for addressing waste chromium pollutants but also offers a promising avenue for the development of high-performance, cost-efficient electrocatalysts.

The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation.

CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood. In this study, we uncovered the PTM profiling of CTCF and demonstrated that CTCF can be O-GlcNAcylated and arginine methylated. Functionally, we demonstrated that O-GlcNAcylation inhibits CTCF binding to chromatin. Meanwhile, deficiency of CTCF O-GlcNAcylation results in the disruption of loop domains and the alteration of chromatin loops associated with cellular development. Furthermore, the deficiency of CTCF O-GlcNAcylation increases the expression of developmental genes and negatively regulates maintenance and establishment of stem cell pluripotency. In conclusion, these results provide key insights into the role of PTMs for the 3D chromatin structure.

Application of the Industrial Byproduct Gypsum in Building Materials: A Review.

The industrial byproduct gypsum is a general term for byproducts discharged from industrial production with calcium sulfate as the main ingredient. Due to the high number of impurities and production volume, the industrial byproduct gypsum is underutilized, leading to serious environmental problems. At present, only desulfurization gypsum and phosphogypsum have been partially utilized in cementitious materials, cement retarders, etc., while the prospects for the utilization of other byproduct gypsums remain worrying. This paper mainly focuses on the sources and physicochemical properties of various types of gypsum byproducts and summarizes the application scenarios of various gypsums in construction materials. Finally, some suggestions are proposed to solve the problem of the industrial byproduct gypsum. This review is informative for solving the environmental problems caused by gypsum accumulation.

Brain endothelial GSDMD activation mediates inflammatory BBB breakdown.

The blood-brain barrier (BBB) protects the central nervous system from infections or harmful substances1; its impairment can lead to or exacerbate various diseases of the central nervous system2-4. However, the mechanisms of BBB disruption during infection and inflammatory conditions5,6 remain poorly defined. Here we find that activation of the pore-forming protein GSDMD by the cytosolic lipopolysaccharide (LPS) sensor caspase-11 (refs. 7-9), but not by TLR4-induced cytokines, mediates BBB breakdown in response to circulating LPS or during LPS-induced sepsis. Mice deficient in the LBP-CD14 LPS transfer and internalization pathway10-12 resist BBB disruption. Single-cell RNA-sequencing analysis reveals that brain endothelial cells (bECs), which express high levels of GSDMD, have a prominent response to circulating LPS. LPS acting on bECs primes Casp11 and Cd14 expression and induces GSDMD-mediated plasma membrane permeabilization and pyroptosis in vitro and in mice. Electron microscopy shows that this features ultrastructural changes in the disrupted BBB, including pyroptotic endothelia, abnormal appearance of tight junctions and vasculature detachment from the basement membrane. Comprehensive mouse genetic analyses, combined with a bEC-targeting adeno-associated virus system, establish that GSDMD activation in bECs underlies BBB disruption by LPS. Delivery of active GSDMD into bECs bypasses LPS stimulation and opens the BBB. In CASP4-humanized mice, Gram-negative Klebsiella pneumoniae infection disrupts the BBB; this is blocked by expression of a GSDMD-neutralizing nanobody in bECs. Our findings outline a mechanism for inflammatory BBB breakdown, and suggest potential therapies for diseases of the central nervous system associated with BBB impairment.

In silico genome-wide analysis of homeodomain-leucine zipper transcription factors in Cannabis sativa L.

HD-Zip (Homeodomain-Leucine Zipper) is a family of transcription factors unique to higher plants and plays a vital role in plant growth and development. Increasing research results show that HD-Zip transcription factors are widely involved in many life processes in plants. However, the HD-Zip transcription factor for cannabis, a valuable crop, has not yet been identified. The sequence characteristics, chromosome localization, system evolution, conservative motif, gene structure, and gene expression of the HD-Zip transcription factor in the cannabis genome were systematically studied. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify its function. The results showed that cannabis contained 33 HD-Zip gene members. The number of amino acids is 136-849aa, the isoelectric point is 4.54-9.04, and the molecular weight is 23264.32-93147.87Da. Many cis-acting elements are corresponding to hormone and abiotic stress in the HD-Zip family promoter area of cannabis. Sequencing of the transcriptome at 5 tissue sites of hemp, stems, leaves, bracts, and seeds showed similar levels of expression of 33 members of the HD-Zip gene family at 5 tissue sites. Bioinformatics results show that HD-Zip expression is tissue-specific and may be influenced by hormones and environmental factors. This lays a foundation for further research on the gene function of HD-Zip.

Feasibility analysis of China's medical insurance coverage of assisted reproductive technology.

There are millions of patients experiencing infertility in China, but assisted reproductive technology (ART) is performed at the patient's expense and is difficult to afford. With the sharp decline in China's birth rate, there is a growing controversy over the inclusion of ART in medical insurance (MI). This study aims to explore the feasibility of ART coverage by MI for the first time. We obtained basic data such as the prevalence of infertility, the cost of ART, and the success rate in China with the method of meta-analysis and consulting the government bulletin. Then, we calculated the number of infertile couples in China and the total financial expenditure of MI covering ART. Finally, we discussed the feasibility of coverage, and analyzed the population growth and economic benefits after coverage. According to our research results, it was estimated that there were 4.102-11.792 million infertile couples in China, with an annual increase of 1.189-1.867 million. If MI covered ART, the fund would pay 72.313-207.878 billion yuan, accounting for 2-6% of the current fund balance, and the subsequent annual payment would be 20.961-32.913 billion yuan, accounting for 4-7% of the annual fund balance. This was assuming that all infertile couples would undergo ART, and the actual cost would be lower. The financial input‒output ratio would be 13.022. Benefiting from the inclusion of ART in MI coverage, there would be 3.348-9.624 million new live infants, and 8-13% newborns would be born every year thereafter, which means that by 2050, 37-65 million people would be born. Due to its affordable cost, high cost-effectiveness and favourable population growth, it may be feasible to include ART in MI.

Application of quality control circle in the management of early ambulation after cesarean section: An observational study.

BACKGROUND: The quality control circle (QCC) model has achieved good results in clinical applications in many hospitals in China and has gained popularity. This study aims to explore the application of QCC activities on early ambulation after cesarean section. METHODS: A QCC management group was established following standardized methods and techniques. The theme of the group was identified as "to enhance the implementation rate of the patient early ambulation after the cesarean section" through a matrix graph. The early ambulation rates after surgery of patients who received cesarean section were compared before and after QCC managements. RESULTS: Our data suggested that the early ambulation rates after cesarean section increased from 37.5% to 81.25% after applying QCC management. The biggest factor influencing the ambulation activities 24 ±â€…4 hours after the surgery was patients and family members do not cooperate. In addition, outstanding improvements in terms of nurses' sense of responsibility and self-confidence, communication and teamwork capacity in the problem-solving process were observed after the establishment of QCC. CONCLUSION: The application of QCC management had not only increase the early ambulation rates after cesarean section but also improved the quality of nursery care in general.

Single-Nuclei Characterization of Lacrimal Gland in Scopolamine-Induced Dry Eye Disease.

Purpose: The lacrimal gland (LG) is the main organ responsible for tear secretion and an important pathogenic site for dry eye disease (DED). This study aimed to comprehensively characterize LG cellular heterogeneity under normal and DED conditions using single-nucleus RNA sequencing (snRNA-seq). Methods: Single LG nuclei isolated from mice with or without DED induced by scopolamine (SCOP)/desiccating stress (DS) were subjected to snRNA-seq using the 10x Genomics platform. These cells were clustered and annotated using the t-distributed stochastic neighbor embedding (t-SNE) method and unbiased computational informatic analysis. Cluster identification and functional analysis were performed based on marker gene expression and bioinformatic data mining. Results: The snRNA-seq analysis of 30,351 nuclei identified eight major cell types, with acinar cells (∼72.6%) being the most abundant cell type in the LG. Subclustering analysis revealed that the LG mainly contained two acinar cell subtypes, two ductal cell subclusters, three myoepithelial cell (MECs) subtypes, and four immunocyte subclusters. In the SCOP-induced DED model, three major LG parenchymal cell types were significantly altered, characterized by a reduced proportion of acinar cells with a lowered secretion potential and an augmented proportion of ductal cells and MECs. LG immunocytes in DED scenarios showed an intensified inflammatory response and dysregulated intercellular communication with three major LG parenchymal cells. Conclusions: Overall, this study offers a systemic single-nucleus transcriptomic profile of LGs in both normal and DED conditions and an atlas of the complicated interactions of immunocytes with major LG parenchymal cells. The findings also facilitate understanding the pathogenesis of DED.

New plant polyphenol-derived tannic acid-based chromium-free tanning agent for sustainable and clean leather production.

This study aimed to prepare a new bio-based chromium-free tanning agent. The green epoxide monocase ethylene glycol diglycidyl ether (EGDE) was grafted with tannic acid (TA) derived from natural plant using the one-pot method to synthesize new plant polyphenol-derived tannic acid-based chromium-free tanning agents (TA-EGDE) with abundant terminal epoxides. FTIR, 1H NMR, XPS, GPC, SEM, and other analytical techniques were used to characterize tanning agents. These consequences manifested that EGDE was successfully grafted with the phenol hydroxyl group of TA. The epoxide value of TA-EGDE showed a tendency to increase and then decrease with increasing EGDE dosage, and the epoxide value of TA-EGDE-2 attained a maximum of 0.262 mol/100 g. GPC analysis showed that the formula weight of the prepared TA-EGDE was partially distributed above 5000 Da. The tanning experiment demonstrated that the shrinkage temperatures (Ts) of the TA-EGDE-tanned leathers were all higher than 81.5 °C. Compared with the traditional commercial chromium-free tanning agent (F-90, TWS), TA-EGDE-tanned leathers exhibited higher Ts and better mechanical properties. The TA-EGDE prepared in this study not only has ecological environmental protection but also provides finished leather with good moisture, heat resistance, and mechanical properties.

Transurethral surgical treatment for benign prostatic hyperplasia with detrusor underactivity: a systematic review and meta-analysis.

BACKGROUND: The efficacy of surgical treatment for benign prostatic hyperplasia (BPH) patients with detrusor underactivity (DU) remains controversial. METHODS: To summarize relevant evidence, three databases (PubMed, Embase, and Web of Science) were searched from database inception to May 1, 2023. Transurethral surgical treatment modalities include transurethral prostatectomy (TURP), photoselective vaporization of the prostate (PVP), and transurethral incision of the prostate (TUIP). The efficacy of the transurethral surgical treatment was assessed according to maximal flow rate on uroflowmetry (Qmax), International Prostate Symptom Score (IPSS), postvoid residual (PVR), quality of life (QoL), voided volume, bladder contractility index (BCI) and maximal detrusor pressure at maximal flow rate (PdetQmax). Pooled mean differences (MDs) were used as summary statistics for comparison. The quality of enrolled studies was evaluated by using the Newcastle-Ottawa Scale. Sensitivity analysis and funnel plots were applied to assess possible biases. RESULTS: In this study, 10 studies with a total of 1142 patients enrolled. In BPH patients with DU, within half a year, significant improvements in Qmax (pooled MD, 4.79; 95% CI, 2.43-7.16; P < 0.05), IPSS(pooled MD, - 14.29; 95%CI, - 16.67-11.90; P < 0.05), QoL (pooled MD, - 1.57; 95% CI, - 2.37-0.78; P < 0.05), voided volume (pooled MD, 62.19; 95% CI, 17.91-106.48; P < 0.05), BCI (pooled MD, 23.59; 95% CI, 8.15-39.04; P < 0.05), and PdetQmax (pooled MD, 28.62; 95% CI, 6.72-50.52; P < 0.05) were observed after surgery. In addition, after more than 1 year, significant improvements were observed in Qmax (pooled MD, 6.75; 95%CI, 4.35-9.15; P < 0.05), IPSS(pooled MD, - 13.76; 95%CI, - 15.17-12.35; P < 0.05), PVR (pooled MD, - 179.78; 95%CI, - 185.12-174.44; P < 0.05), QoL (pooled MD, - 2.61; 95%CI, - 3.12-2.09; P < 0.05), and PdetQmax (pooled MD, 27.94; 95%CI, 11.70-44.19; P < 0.05). Compared with DU patients who did not receive surgery, DU patients who received surgery showed better improvement in PVR (pooled MD, 137.00; 95%CI, 6.90-267.10; P < 0.05) and PdetQmax (pooled MD, - 8.00; 95%CI, - 14.68-1.32; P < 0.05). CONCLUSIONS: Our meta-analysis results showed that transurethral surgery can improve the symptoms of BPH patients with DU. Surgery also showed advantages over pharmacological treatment for BPH patients with DU. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023415188.

Characterization of an antimicrobial peptide family from the venom gland of Heteropoda venatoria.

Spider venom boasts extensive peptide diversity, constituting a natural biochemical arsenal for defense and predation. The new family HvAMPs, including 9 homologous members, were identified from the unnormalized cDNA library of Heteropoda venatoria venom gland by Sanger sequencing. The putative mature peptide is composed of 22 aliphatic amino acid residues. The mature peptides of HvAMP1 and HvAMP5, with 3 different amino acids, were synthesized and both were shown to adopt an amphipathic α-helical structure and amphipathicity in SDS buffer by CD spectroscopy. In comparison to HvAMP1, HvAMP5 exhibits higher antibacterial activity, particularly against Gram-positive bacteria, coupled with reduced hemolytic activity and cytotoxicity. Results from SYTO 9/PI staining indicate that HvAMP5 acts by disrupting bacterial cell membranes. Analysis of the relationships between structures and functions suggests that HvAMP5 enhances antibacterial activity and reduces mammalian cell toxicity by increasing positive charge and proline substitution. The three residues variation can augment the electrostatic attraction of antibacterial peptides to the bacterial phospholipid bilayer. The present study suggests that the HvAMPs may exert lytic action against cells of different origins to increase cellular and tissue barrier permeability to facilitate spider's defense or predation. Moreover, HvAMP5 holds promise as a novel antibacterial agent for treating Gram-positive bacterial infections. Simultaneously, the numerous diverse amino acid residue substitutions within the HvAMP family offer a template for future study.

Precise prediction of phase-separation key residues by machine learning.

Understanding intracellular phase separation is crucial for deciphering transcriptional control, cell fate transitions, and disease mechanisms. However, the key residues, which impact phase separation the most for protein phase separation function have remained elusive. We develop PSPHunter, which can precisely predict these key residues based on machine learning scheme. In vivo and in vitro validations demonstrate that truncating just 6 key residues in GATA3 disrupts phase separation, enhancing tumor cell migration and inhibiting growth. Glycine and its motifs are enriched in spacer and key residues, as revealed by our comprehensive analysis. PSPHunter identifies nearly 80% of disease-associated phase-separating proteins, with frequent mutated pathological residues like glycine and proline often residing in these key residues. PSPHunter thus emerges as a crucial tool to uncover key residues, facilitating insights into phase separation mechanisms governing transcriptional control, cell fate transitions, and disease development.

Probabilistic human health risk assessment of PCDD/Fs near municipal solid-waste incinerator using Monte Carlo analysis coupled with triangular fuzzy numbers.

PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016-2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.

Research on Lane-Changing Decision Making and Planning of Autonomous Vehicles Based on GCN and Multi-Segment Polynomial Curve Optimization.

This paper considers the interactive effects between the ego vehicle and other vehicles in a dynamic driving environment and proposes an autonomous vehicle lane-changing behavior decision-making and trajectory planning method based on graph convolutional networks (GCNs) and multi-segment polynomial curve optimization. Firstly, hierarchical modeling is applied to the dynamic driving environment, aggregating the dynamic interaction information of driving scenes in the form of graph-structured data. Graph convolutional neural networks are employed to process interaction information and generate ego vehicle's driving behavior decision commands. Subsequently, collision-free drivable areas are constructed based on the dynamic driving scene information. An optimization-based multi-segment polynomial curve trajectory planning method is employed to solve the optimization model, obtaining collision-free motion trajectories satisfying dynamic constraints and efficiently completing the lane-changing behavior of the vehicle. Finally, simulation and on-road vehicle experiments are conducted for the proposed method. The experimental results demonstrate that the proposed method outperforms traditional decision-making and planning methods, exhibiting good robustness, real-time performance, and strong scenario generalization capabilities.