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Abstract Background Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH), including neuroinflammation, glymphatic–lymphatic system dysfunction, brain edema, BBB disruption, and cell death. Astrocytes transform into two new reactive phenotypes with changed morphology, altered gene expression, and secretion profiles, termed detrimental A1 and beneficial A2. This study investigates the effect of 67LR activation by PEDF-34, a PEDF peptide, on neuroinflammation and astrocyte polarization after the experimental SAH. Methods A total of 318 male adult Sprague-Dawley rats were used in experiments in vivo, of which 272 rats were subjected to the endovascular perforation model of SAH and 46 rats underwent sham surgery. 67LR agonist (PEDF-34) was administrated intranasally 1 h after SAH. 67LR-specific inhibitor (NSC-47924) and STAT1 transcriptional activator (2-NP) were injected intracerebroventricularly 48 h before SAH. Short- and long-term neurological tests, brain water content, immunostaining, Nissl staining, western blot, and ELISA assay were performed. In experiments in vitro, primary astrocyte culture with hemoglobin (Hb) stimulation was used to mimic SAH. The expression of the PEDF-34/67LR signaling pathway and neuro-inflammatory cytokines were assessed using Western blot, ELISA, and immunohistochemistry assays both in vivo and in vitro. Results Endogenous PEDF and 67LR expressions were significantly reduced at 6 h after SAH. 67LR was expressed in astrocytes and neurons. Intranasal administration of PEDF-34 significantly reduced brain water content, pro-inflammatory cytokines, and short-term and long-term neurological deficits after SAH. The ratio of p-JNK/JNK and p-STAT1/STAT1 and the expression of CFB and C3 (A1 astrocytes marker), significantly decreased after PEDF-34 treatment, along with fewer expression of TNF-α and IL-1β at 24 h after SAH. However, 2-NP (STAT1 transcriptional activator) and NSC-47924 (67LR inhibitor) reversed the protective effects of PEDF-34 in vivo and in vitro by promoting A1 astrocyte polarization with increased inflammatory cytokines. Conclusion PEDF-34 activated 67LR, attenuating neuroinflammation and inhibiting astrocyte A1 polarization partly via the JNK/STAT1 pathway, suggesting that PEDF-34 might be a potential treatment for SAH patients. Graphical Abstract

Abstract Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical β-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

Abstract Background Superficial soft tissue metastasis (S-STM) of malignant tumors is uncommon and often brings great pain to patients. However, current treatment options are limited. The purpose of this study was to explore the clinical efficacy and prognostic factors of CT-guided radioactive iodine-125 (125I) seed implantation (RISI) for the treatment of S-STM. Methods We retrospectively evaluated 132 patients with S-STM who received RISI between June 2010 and July 2022. Local tumor progression-free survival (ltPFS), tumor response, pain control and complication were analyzed. The independent factors affecting ltPFS were screened out using a layered Cox proportional hazards model. Results The median follow-up time was 8.3 months (interquartile range [IQR], 4.5–15.3 months). The objective response rate (ORR) was 81.8%. The median ltPFS was 9.1 (95% CI: 6.6, 11.6) months. The Cox proportional hazard regression model revealed that the independent factors influencing ltPFS included KPS score, primary tumor, metastases, boundary, density and postoperative D90 (All P

Abstract Lung cancer stands as the leading cause of mortality among all types of tumors, with over 40% of cases being lung adenocarcinoma (LUAD). Family with sequence similarity 83 member A (FAM83A) emerges as a notable focus due to its frequent overexpression in LUAD. Despite this, the precise role of FAM83A remains elusive. This study addresses this gap by unveiling the crucial involvement of FAM83A in maintaining the cancer stem cell-like (CSC-like) phenotype of LUAD. Through a global proteomics analysis, the study identifies human epidermal growth factor receptor 2 (HER2 or ErbB2) as a crucial target of FAM83A. Mechanistically, FAM83A facilitated ErbB2 expression at the posttranslational modification level via the E3 ubiquitin ligase STUB1 (STIP1-homologous U-Box containing protein 1). More importantly, the interaction between FAM83A and ErbB2 at Arg241 promotes calcineurin (CALN)-mediated dephosphorylation of ErbB2, followed by inhibition of STUB1-mediated ubiquitin-proteasomal ErbB2 degradation. The maintenance of the CSC-like phenotype by FAM83A, achieved through the posttranslational regulation of ErbB2, offers valuable insights for identifying potential therapeutic targets for LUAD.

Abstract Background Inherited retinal dystrophies (IRDs) are a group of debilitating visual disorders characterized by the progressive degeneration of photoreceptors, which ultimately lead to blindness. Among the causes of this condition, mutations in the PCYT1A gene, which encodes the rate-limiting enzyme responsible for phosphatidylcholine (PC) de novo synthesis via the Kennedy pathway, have been identified. However, the precise mechanisms underlying the association between PCYT1A mutations and IRDs remain unclear. To address this knowledge gap, we focused on elucidating the functions of PCYT1A in the retina. Results We found that PCYT1A is highly expressed in Müller glial (MG) cells in the inner nuclear layer (INL) of the retina. Subsequently, we generated a retina-specific knockout mouse model in which the Pcyt1a gene was targeted (Pcyt1a-RKO or RKO mice) to investigate the molecular mechanisms underlying IRDs caused by PCYT1A mutations. Our findings revealed that the deletion of Pcyt1a resulted in retinal degenerative phenotypes, including reduced scotopic electroretinogram (ERG) responses and progressive degeneration of photoreceptor cells, accompanied by loss of cells in the INL. Furthermore, through proteomic and bioinformatic analyses, we identified dysregulated retinal fatty acid metabolism and activation of the ferroptosis signalling pathway in RKO mice. Importantly, we found that PCYT1A deficiency did not lead to an overall reduction in PC synthesis within the retina. Instead, this deficiency appeared to disrupt free fatty acid metabolism and ultimately trigger ferroptosis. Conclusions This study reveals a novel mechanism by which mutations in PCYT1A contribute to the development of IRDs, shedding light on the interplay between fatty acid metabolism and retinal degenerative diseases, and provides new insights into the treatment of IRDs.

Hierarchical networks are frequently encountered in animal groups, gene networks, and artificial engineering systems such as multiple robots, unmanned vehicle systems, smart grids, wind farm networks, and so forth. The structure of a large directed hierarchical network is often strongly influenced by reverse edges from lower- to higher-level nodes, such as lagging birds’ howl in a flock or the opinions of lower-level individuals feeding back to higher-level ones in a social group. This study reveals that, for most large-scale real hierarchical networks, the majority of the reverse edges do not affect the synchronization process of the entire network; the synchronization process is influenced only by a small part of these reverse edges along specific paths. More surprisingly, a single effective reverse edge can slow down the synchronization of a huge hierarchical network by over 60%. The effect of such edges depends not on the network size but only on the average in-degree of the involved subnetwork. The overwhelming majority of active reverse edges turn out to have some kind of “bunching” effect on the information flows of hierarchical networks, which slows down synchronization processes. This finding refines the current understanding of the role of reverse edges in many natural, social, and engineering hierarchical networks, which might be beneficial for precisely tuning the synchronization rhythms of these networks. Our study also proposes an effective way to attack a hierarchical network by adding a malicious reverse edge to it and provides some guidance for protecting a network by screening out the specific small proportion of vulnerable nodes.

Abstract The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs). While target genes of FOXP3 have been identified, its upstream regulatory machinery still remains elusive. Our methodology selected five top-ranked candidates that were tested via proof-of-concept experiments. Following knockdown, three out of five candidates showed significant effects on the mRNA expression of FOXP3 across multiple donors. This provides insights into the regulatory mechanisms modulating FOXP3 transcriptional expression in Tregs. Overall, at the genome level this represents a high level of accuracy in predicting upstream regulatory genes of key genes of interest.

Abstract Background Emerging evidences have demonstrated that gut microbiota composition is associated with pulmonary arterial hypertension (PAH). However, the underlying causality between intestinal dysbiosis and PAH remains unresolved. Method An analysis using the two-sample Mendelian randomization (MR) approach was conducted to examine the potential causal relationship between gut microbiota and PAH. To assess exposure data, genetic variants associated with 196 bacterial traits were extracted from the MiBioGen consortium, which included a sample size of 18,340 individuals. As for the outcomes, summary statistics for PAH were obtained from the NHGRI-EBI GWAS Catalog, which conducted a meta-analysis of four independent studies comprising a total of 11,744 samples. Causal effects were estimated employing various methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weight mode and simple mode, with sensitivity analyses also being implemented with Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots. Results Following false discovery rate (FDR) correction, the genetically predicted genus Eubacterium fissicatena group (odds ratio (OR) 1.471, 95% confidence interval (CI) 1.178–1.837, q = 0.076) exhibited a causal association with PAH. In addition, the genus LachnospiraceaeUCG004 (OR 1.511, 95% CI 1.048–2.177) and genus RuminococcaceaeUCG002 (OR 1.407, 95% CI 1.040–1.905) showed a suggestive increased risk of PAH, while genus Eubacterium eligens group (OR 0.563, 95% CI 0.344–0.922), genus Phascolarctobacterium (OR 0.692, 95% CI 0.487–0.982), genus Erysipelatoclostridium (OR 0.757, 95% CI 0.579–0.989) and genus T–yzzerella3 (OR 0.768, 95% CI 0.624–0.945) were found to have nominal protective effect against PAH. Conclusion The findings from our MR study have revealed a potential causal relationship between gut microbiota and PAH. Specifically, we have identified four types of gut microbiota that exhibit a protective effect on PAH, as well as three types that have a detrimental impact on PAH, thereby offering valuable insights for future mechanistic and clinical investigations in the field of PAH.

Abstract When unperturbed, granular materials form stable structures that resemble the ones of other amorphous solids like metallic or colloidal glasses. Whether or not granular materials under shear have an elastic response is not known, and also the influence of particle surface roughness on the yielding transition has so far remained elusive. Here we use X-ray tomography to determine the three-dimensional microscopic dynamics of two granular systems that have different roughness and that are driven by cyclic shear. Both systems, and for all shear amplitudes Γ considered, show a cross-over from creep to diffusive dynamics, indicating that rough granular materials have no elastic response and always yield, in stark contrast to simple glasses. For the system with small roughness, we observe a clear dynamic change at Γ ≈ 0.1, accompanied by a pronounced slowing down and dynamical heterogeneity. For the large roughness system, the dynamics evolves instead continuously as a function of Γ. We rationalize this roughness dependence using the potential energy landscape of the systems: The roughness induces to this landscape a micro-corrugation with a new length scale, whose ratio over the particle size is the relevant parameter. Our results reveal the unexpected richness in relaxation mechanisms for real granular materials.

Abstract. Background:. Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease. Methods:. Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA. Results:. A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain (COL1A1) and synaptotagmin like 2 (SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8+ T cells. In addition, single-cell analysis indicated that fibroblasts and CD8+ T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions:. COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

STFE(structural, transparent, fluorinated, envelope) membrane material is a new type of transparent architecture membrane material. Compared with general architecture membrane materials, which have the disadvantage of cannot balance strength and transparency, STFE has both high transparency and certain tensile strength. In this study, tensile strength tests were conducted on this new type of membrane material, and data obtained from different test methods, such as clamping test, winding test, and dumbbell-shaped test, were compared, and the mechanism for the differences was analyzed. The results showed that the winding-type test with smooth surface contact yielded the highest and most accurate strength data, clamping tests due to the tendency of the specimen to slip out of the clamping end, dumbbell tests due to the stress concentration effect, and winding tests with rough surface contact due to material damage caused by pressure, all reduce the measured tensile strength values. The measured tensile strength of STFE membrane material was 4241N/5 cm in the warp direction and 4335N/5 cm in the weft direction. This indicates that STFE membrane material has sufficient strength to be used in tensile membrane structures.

Abstract Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones. Using site-specific antibodies, we find that HBO1 may preferentially catalyze histone H3K9la and scaffold proteins including JADE1 and BRPF2 can promote the enzymatic activity for histone Kla. Notably, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on transcription start sites (TSSs). Besides, the regulated Kla can promote key signaling pathways and tumorigenesis, which is further supported by evaluating the malignant behaviors of HBO1- knockout (KO) tumor cells, as well as the level of histone H3K9la in clinical tissues. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription.

Abstract The rational design of carbon-supported transition-metal single-atom catalysts requires the precise arrangement of heteroatoms within the single-atom catalysts. However, achieving this design is challenging due to the collapse of the structure during the pyrolysis. Here, we introduce a topological heteroatom-transfer strategy to prevent the collapse and accurately control the P coordination in carbon-supported single-atom catalysts. As an illustration, we have prepared self-assembled helical fibers with encapsulated cavities. Within these cavities, adjustable functional groups can chelate metal ions (Nx···Mn+···Oy), facilitating the preservation of the structure during the pyrolysis based phosphidation. This process allows for the transfer of heteroatoms from the assembly into single-atom catalysts, resulting in the precise coordination tailoring. Notably, the Co–P2N2–C catalyst exhibits electrocatalytic performance as a non-noble metal single-atom catalyst for alkaline hydrogen evolution, attaining a current density of 100 mA cm−2 with an overpotential of only 131 mV.

Introduction: Refractory lupus nephritis (LN) causes kidney disease progression and increases the risk of loss of renal function. Due to the high specificity and few side effects of biological agents, they are recommended for the treatment of systemic lupus erythematosus. There are few data on telitacicept for the treatment of refractory LN. Case Presentation: Here, we report the efficacy and safety of telitacicept in the treatment of refractory LN in a 25-year-old female patient. This patient with refractory lupus developed Pneumocystis jirovecii pneumonia while using multitargeted therapy, and the patient’s urine protein was rapidly relieved after telitacicept combination with low-dose mycophenolate mofetil (MMF). Conclusion: This result suggests that telitacicept has a positive effect on refractory LN with no significant side effects. Further reports and a registry are necessary to confirm that telitacicept with low-dose MMF should be preferred in refractory LN.

Abstract Background This study aimed to investigate the impact of self-consciousness on depression of college students, and mainly focus on confirming the mediator role of life meaningful and self-efficacy, as well as the moderator role of social support. Methods In the present study, convenient sampling method was adopted, 583 college students were recruited from Harbin city and Wenzhou city in China. All students were assessed using self-assessment scales, including self-consciousness scale, life meaningful scale, self-efficacy scale, social support scale, and self-rating depression scale. Descriptive statistical analysis and correlation analysis, structural equation model analysis were conducted by SPSS 25.0 and M-plus. Results Results showed that self-consciousness was negatively related to depression, life meaningful and self-efficacy partially mediated the relation between self-consciousness and depression. Moderated mediation analysis further indicated that the relation between self-efficacy and depression were moderated bu social support. Compare with college students who had high social support, depression in those with low social support was more susceptible to the effect of self-efficacy. Conclusion These findings imply that college students with low levels of self-consciousness are more easy to be depressive, enhancing their sense of life meaning and self-efficacy can effectively alleviate depression, and college student with high social support can benefit more from self-efficacy. Therefore we should pay more attention to the mental health problems of low levels self-consciousness college students in university.

Abstract Yutu-2 rover conducted an exciting expedition on the 41st lunar day to investigate a fin-shaped rock at Longji site (45.44°S, 177.56°E) by extending its locomotion margin on perilous peaks. The varied locomotion encountered, especially multi-form wheel slippage, during the journey to the target rock, established unique conditions for a fin-grained lunar regolith analysis regarding bearing, shear and lateral properties based on terramechanics. Here, we show a tri-aspect characterization of lunar regolith and infer the rock’s origin using a digital twin. We estimate internal friction angle within 21.5°−42.0° and associated cohesion of 520-3154 Pa in the Chang’E-4 operational site. These findings suggest shear characteristics similar to Apollo 12 mission samples but notably higher cohesion compared to regolith investigated on most nearside lunar missions. We estimate external friction angle in lateral properties to be within 8.3°−16.5°, which fills the gaps of the lateral property estimation of the lunar farside regolith and serves as a foundational parameter for subsequent engineering verifications. Our in-situ spectral investigations of the target rock unveil its composition of iron/magnesium-rich low-calcium pyroxene, linking it to the Zhinyu crater (45.34°S, 176.15°E) ejecta. Our results indicate that the combination of in-situ measurements with robotics technology in planetary exploration reveal the possibility of additional source regions contributing to the local materials at the Chang’E-4 site, implying a more complicated geological history in the vicinity.

Abstract Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1‐catalyzed RNA N7‐methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non‐ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac‐specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC‐ or Mettl1‐induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF.

Summary: Background: The long-term survival and perioperative outcomes of robotic-assisted lobectomy (RAL) and video-assisted lobectomy (VAL) in resectable non-small-cell lung cancer (NSCLC) were found to be comparable in retrospective studies, but they have not been investigated in a randomized trial setting. We conducted the RVlob trial to investigate if RAL was non-inferior to VAL in patients with resectable NSCLC. Methods: In this single-center, open-label, and parallel-arm randomized controlled trial conducted in Ruijin Hospital (Shanghai, China) between May 2017 and May 2020, we randomly assigned patients with resectable NSCLC in a 1:1 ratio to receive either RAL or VAL. One of the primary endpoints was 3-year overall survival. Secondary endpoints included 3-year disease-free survival. The Kaplan–Meier approach was used to calculate overall survival and disease-free survival at 3 years. This study was registered with ClinicalTrials.gov, NCT03134534. Findings: A total of 320 patients were randomized to receive RAL (n = 157) or VAL (n = 163). The baseline characteristics of patients were well balanced between the two groups. After a median follow-up of 58.0 months, the 3-year overall survival was 94.6% (95% confidence interval [CI], 91.0–98.3) in the RAL group and 91.5% (95% CI, 87.2–96.0) in the VAL group (hazard ratio [HR] for death, 0.65; 95% CI, 0.33–1.28; P = 0.21); noninferiority of RAL was confirmed according to the predefined margin of −5% (absolute difference, 2.96%; a one-sided 90% CI, −1.39% to ∞; P = 0.0029 for noninferiority). The 3-year disease-free survival was 88.7% (95% CI, 83.6–94.1) in the RAL group and 85.4% (95% CI, 80.0–91.2) in the VAL group (HR for disease recurrence or death, 0.87; 95% CI, 0.50–1.52; P = 0.62). Interpretation: This study is the first randomized trial to show that RAL resulted in non-inferior overall survival compared with VAL in patients with resectable NSCLC. Based on our results, RAL is an equally oncologically effective treatment and can be considered as an alternative to VAL for resectable NSCLC. Funding: National Natural Science Foundation of China (82072557), National Key Research and Development Program of China (2021YFC2500900), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20172005, the 2nd round of disbursement), program of Shanghai Academic Research Leader from Science and Technology Commission of Shanghai Municipality (20XD1402300), Novel Interdisciplinary Research Project from Shanghai Municipal Health Commission (2022JC023), and Interdisciplinary Program of Shanghai Jiao Tong University (YG2023ZD04).

In this paper, the GSP655060Fe soft pack lithium-ion battery with a capacity of 1600 mAh is utilized, employing lithium iron phosphate as the positive electrode and graphite as the negative electrode. In order to comprehensively evaluate the performance of lithium batteries under the conditions of multi-application scenarios, the operating conditions of the battery were simulated under various external confinement pressures of 300 N, 400 N, 500 N, and 600 N, respectively, and the ambient temperatures of 10 ℃, 25 ℃, and 40 ℃, respectively, were controlled to thoroughly test the battery. One charge/discharge test was conducted on six batteries of the same model at multiplicities of 0.5 C, 1 C, 1.5 C, and 2 C, respectively. To ensure the accuracy and reliability of the experimental data, a Battery comprehensive tester Neware BTS-5V12A was utilized, which possesses high-precision voltage and current measurement capabilities with an error rate of only 0.05 %. This data plays an important role in battery research and development, new energy vehicles, electronic products, and other fields.

Inflammasomes play pivotal roles in inflammation by processing and promoting the secretion of IL-1β. Caspase-1 is involved in the maturation of IL-1β and IL-18, while human caspase-4 specifically processes IL-18. Recent structural studies of caspase-4 bound to Pro-IL-18 reveal the molecular basis of Pro-IL-18 activation by caspase-4. However, the mechanism of caspase-1 processing of pro-IL-1β and other IL-1β-converting enzymes remains elusive. Here, we observed that swine Pro-IL-1β (sPro-IL-1β) exists as an oligomeric precursor unlike monomeric human Pro-IL-1β (hPro-IL-1β). Interestingly, Seneca Valley Virus (SVV) 3C protease cleaves sPro-IL-1β to produce mature IL-1β, while it cleaves hPro-IL-1β but does not produce mature IL-1β in a specific manner. When the inflammasome is blocked, SVV 3C continues to activate IL-1β through direct cleavage in porcine alveolar macrophages (PAMs). Through molecular modeling and mutagenesis studies, we discovered that the pro-domain of sPro-IL-1β serves as an 'exosite' with its hydrophobic residues docking into a positively charged 3C protease pocket, thereby directing the substrate to the active site. The cleavage of sPro-IL-1β generates a monomeric and active form of IL-1β, initiating the downstream signaling. Thus, these studies provide IL-1β is an inflammatory sensor that directly detects viral protease through an independent pathway operating in parallel with host inflammasomes.

Importance: Abnormal blood pressure pattern is an independent risk factor for vascular events. Blood pressure variability can predict cardiovascular and cerebrovascular disease outcomes and is closely associated with the risk of cognitive impairment. However, the relationship between blood pressure variability and cerebral small vessel disease neuroimaging markers remains unclear. This study aimed to evaluate the relationship between blood pressure variability and cerebral small vessel disease neuroimaging markers. Data sources: We searched multiple databases, including Embase, Web of Science, PubMed, Cochrane Library, UpToDate, and World of Science, from their inception until November 27, 2023.Main Outcomes and Measures: A meta-analysis of 19 observational studies involving 14519 participants was performed. Findings: ①Systolic blood pressure variability was correlated with the cerebral small vessel disease total burden, white matter hyperintensities and lacunar infarction; ② Diastolic blood pressure variability was correlated with the cerebral small vessel disease total burden, white matter hyperintensities and cerebral microbleeds; ③ Non-dipping patterns were correlated with white matter hyperintensities and lacunar infarction. ④ Reverse-dipping patterns were significantly correlated with white matter hyperintensities and cerebral microbleeds. Conclusions: and Relevance: Blood pressure variability correlates with neuroimaging markers of cerebral small vessel disease and its burden. Hence, early monitoring and intervention of blood pressure variability may be essential for the early diagnosis, prevention and treatment of cerebral small vessel disease.

Abstract RNA velocity is closely related with cell fate and is an important indicator for the prediction of cell states with elegant physical explanation derived from single-cell RNA-seq data. Most existing RNA velocity models aim to extract dynamics from the phase delay between unspliced and spliced mRNA for each individual gene. However, unspliced/spliced mRNA abundance may not provide sufficient signal for dynamic modeling, leading to poor fit in phase portraits. Motivated by the idea that RNA velocity could be driven by the transcriptional regulation, we propose TFvelo, which expands RNA velocity concept to various single-cell datasets without relying on splicing information, by introducing gene regulatory information. Our experiments on synthetic data and multiple scRNA-Seq datasets show that TFvelo can accurately fit genes dynamics on phase portraits, and effectively infer cell pseudo-time and trajectory from RNA abundance data. TFvelo opens a robust and accurate avenue for modeling RNA velocity for single cell data.

Abstract Hypoxia-inducible factor 1 (HIF1) is critically important for driving angiogenesis and tumorigenesis. Linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin ligase capable of catalyzing protein linear ubiquitination to date, is implicated in cell signaling and associated with cancers. However, the role and mechanism of LUBAC in regulating the expression and function of HIF1α, the labile subunit of HIF1, remain to be elucidated. Herein we showed that LUBAC increases HIF1α protein expression in cultured cells and tissues of human lung cancer and enhances HIF1α DNA-binding and transcriptional activities, which are dependent upon LUBAC enzymatic activity. Mechanistically, LUBAC increases HIF1α stability through antagonizing HIF1α decay by the chaperone-mediated autophagy (CMA)-lysosome pathway, thereby potentiating HIF1α activity. We further demonstrated that HIF1α selectively interacts with HOIP (the catalytic subunit of LUBAC) primarily in the cytoplasm. LUBAC catalyzes linear ubiquitination of HIF1α at lysine 362. Linear ubiquitination shields HIF1α from interacting with heat-shock cognate protein of 70 kDa and lysosome-associated membrane protein type 2 A, two components of CMA. Consequently, linear ubiquitination confers protection against CMA-mediated destruction of HIF1α, increasing HIF1α stability and activity. We found that prolyl hydroxylation is not a perquisite for LUBAC’s effects on HIF1α. Functionally, LUBAC facilitates proliferation, clonogenic formation, invasion and migration of lung cancer cells. LUBAC also boosts angiogenesis and exacerbates lung cancer growth in mice, which are greatly compromised by inhibition of HIF1α. This work provides novel mechanistic insights into the role of LUBAC in regulating HIF1α homeostasis, tumor angiogenesis and tumorigenesis of lung cancer, making LUBAC an attractive therapeutic target for cancers.

Synthetic aperture radar (SAR) images are often affected by a type of multiplicative noise known as “speckle” due to their active imaging characteristics. This property complicates the processing and interpretation of SAR images. While deep learning techniques have demonstrated success in despeckling, many models are tailored to specific noise levels. This specificity can limit a model's ability to generalize to real SAR images with varying noise levels, potentially leading to oversmoothing or overfocusing on specific details. To address these challenges, we present the Adaptive Noise Estimation and Despeckling Network (ANED-Net). This network consists of a noise-level estimation phase and a noise-level-guided nonblind denoising phase. During the nonblind denoising phase, we develop a noise-feature-guided denoising network. This network integrates a hierarchical encoder–decoder denoising module based on the Transformer block (T-unet) and a denoising enhancement control block. Together, they skillfully capture both local and global dependencies inherent in SAR images, facilitating effective noise removal. Furthermore, we also introduce a deep-attention mechanism to counteract the attentional collapse observed when the Transformer is extended in depth, enhancing the network's feature extraction capability and strengthening the model's denoising performance. Extensive tests on synthetic and real images show that ANED-Net is robust to different noise scenarios. It effectively mitigates speckle noise even at unspecified levels and outperforms many established methods.

Abstract The dynamic changes of RNA N6-methyladenosine (m6A) during cancer progression participate in various cellular processes. However, less is known about a possible direct connection between upstream regulator and m6A modification, and therefore affects oncogenic progression. Here, we have identified that a key enzyme in N4-acetylcytidine (ac4C) acetylation NAT10 is highly expressed in human osteosarcoma tissues, and its knockdown enhanced m6A contents and significantly suppressed osteosarcoma cell growth, migration and invasion. Further results revealed that NAT10 silence inhibits mRNA stability and translation of m6A reader protein YTHDC1, and displayed an increase in glucose uptake, a decrease in lactate production and pyruvate content. YTHDC1 recognizes differential m6A sites on key enzymes of glycolysis phosphofructokinase (PFKM) and lactate dehydrogenase A (LDHA) mRNAs, which suppress glycolysis pathway by increasing mRNA stability of them in an m6A methylation-dependent manner. YTHDC1 partially abrogated the inhibitory effect caused by NAT10 knockdown in tumor models in vivo, lentiviral overexpression of YTHDC1 partially restored the reduced stability of YTHDC1 caused by lentiviral depleting NAT10 at the cellular level. Altogether, we found ac4C driven RNA m6A modification can positively regulate the glycolysis of cancer cells and reveals a previously unrecognized signaling axis of NAT10/ac4C-YTHDC1/m6A-LDHA/PFKM in osteosarcoma. Video Abstract

Abstract The association between pandemic experience and immediate mental health risks, such as depression, is well-documented, yet the long-term effects remain unclear. This study examines the impact of early childhood exposure to the 2003 SARS pandemic on adulthood mental health after 17 years in China, using data from the 2020 China Family Panel Studies (CFPS). The analysis included 6289 participants, aged 3 to 30 years during the SARS outbreak, with an average age of 35.3 years at the time of survey. Adulthood mental health was assessed using Center for Epidemiologic Studies Depression Scale (CESD) and an indicator of clinical depression. The severity of local SARS outbreaks was assessed by cumulative cases per 10,000 population. Results show that each additional case per 10,000 population was linked to a 1.617-fold (95% confidence interval (CI): 1.425–1.836) increase in odds of depression after 17 years for younger children (aged 3–12 years in 2003) relative to older cohorts (aged 13-30). This risk was higher in children from rural areas (adjusted odds ratio (aOR) 3.64; 95% CI 2.92–4.55), with poor physical health (1.98; 1.59–2.48), and from low-income families (2.87; 2.03–4.05). The childhood pandemic experience elevated the probability of developing depression-prone personality traits, which contributes to the enduring impact of childhood pandemic experiences on adulthood mental health. These findings highlight the long-lasting psychological impact of early-childhood pandemic exposure, underscoring the need for targeted interventions to mitigate its effects on the younger generation and emphasizing the importance of monitoring long-term mental health and personality development in children post-pandemics, particularly in light of COVID-19.

The refinement of embryo culture media is essential in improving embryo viability and in vitro production efficiency. Our previous work demonstrated that the nutrients (carbohydrates, amino acids, and vitamins) in traditional culture media far exceed the need for an embryo and producing developmentally competent embryos in a reduced nutrient environment is feasible. Here, we aim to evaluate the impact of exogenous lipid and l-carnitine supplementation on bovine blastocyst development and refine our RN condition further. Zygotes were cultured in the control medium (100% nutrients) and reduced nutrient media containing 6.25% of the standard nutrient concentrations supplemented with l-carnitine and lipid-free or lipid-rich BSA. Increased blastocyst development was observed in the reduced nutrient lipid-rich medium compared to the other two groups. However, in both reduced nutrient conditions, blastocyst cell numbers were lower than those obtained in the control condition. We then examined the expression level of 18 transcripts correlated with lipid metabolism, glucose metabolism, redox balance, and embryo quality, along with mitochondrial DNA copy numbers, ATP productions, and lipid profile. The results indicated that lipid metabolism, embryo quality, and redox enzyme-related genes were upregulated while the glucose-related gene was downregulated in embryos derived from reduced nutrient lipid-rich condition. Finally, we identified that the lipid-rich BSA has enriched linoleic, stearic, oleic, palmitic, and alpha-linoleic fatty acids, a lipid profile that may contribute to the increased lipid metabolism and improved blastocyst development of the bovine embryos under the reduced nutrient condition.

The initial investment for a buried pipe system using soil as a seasonal thermal storage medium is costly and not suitable for small rural buildings. To promote the cost-effective heating in rural areas, this study proposes a novel seasonal thermal storage system utilizing water and soil as thermal storage medium with copper rods to enhance thermal transfer between water tank and the surrounding soil. An experimental platform was established to discuss the temperature variation characteristics and investigate the thermal performance under different operating modes and experimental parameters. The results show that the temperature of the soil without copper rods is linearly related to the depth, while the highest temperature at the end of the copper rods occurs at the middle depth. The soil with short copper rods exhibits the most rapid thermal storage response and a relatively shorter thermal extraction response time. Intermittent operation can significantly enhance the thermal extraction rate and outlet temperature of the thermal storage unit, whereas the energy storage efficiency decreases with the extension of the downtime. The soil contribution rate of the thermal storage unit is influenced by the operational duration, initial temperature of the water tank and outdoor ambient temperature.

A novel combined cooling, heating and power (CCHP) system is proposed based on mixture consisting of CO2 and organic fluids to meet the seasonal energy demand in buildings. Thermodynamic model was constructed based on the laws of thermodynamics, and seasonal operation modes were also established. Techno-economic performance was analyzed and the performance of mixture consisting of CO2 and organic fluids compared with CO2 and pure organic fluids. Results show that the temperature of the turbine inlet in trans-critical power cycle should be 10 °C lower than the heat source temperature, with the turbine inlet pressure being approximately 1.4 times as large as critical pressure. Turbine inlet temperature is negatively correlated to the payback period and levelized energy cost while turbine inlet pressure is positively correlated to the system economic performance. The carbon dioxide content is negatively correlated to net power output, thermal efficiency and exergy efficiency, while coefficient of performance will hit the bottom with the carbon dioxide content, except CO2/Propane. For the carbon dioxide content is between 5 % and 10 %, the system overall performance is also close to optimal value. In general, CO2/R134a (0.10/0.90) and CO2/R1234ze(E) (0.10/0.90) is recommendable.

Triple-negative breast cancer (TNBC) is labeled as an aggressive type of breast cancer and still has limited therapeutic targets despite the advanced development of cancer therapy. Neutrophils, representing the conventional inflammatory response, significantly influence the malignant phenotype of tumors, supported by abundant evidence. As a vital function of neutrophils, NETs are the extracellular fibrous networks including the depolymerized chromatin DNA frames with several antimicrobial proteins. They are produced by activated neutrophils and are involved in host defence or immunological reactions. This review focuses more on the interactions between neutrophils and TNBC, focusing on how neutrophils modulate the immune response within the tumor milieu. Specifically, we delve into the role of NETs, which are involved in promoting tumor growth and metastasis, inhibiting anti-tumor immunity, and promoting tumor-associated thrombosis. Furthermore, we discuss recent advancements in therapeutic strategies aimed at targeting NETs to enhance the efficacy of TNBC treatment. The advances in the knowledge of the dynamics between neutrophils and TNBC may lead to the opportunity to devise new immunotherapeutic strategies targeted to fight this hostile type of breast cancer.

Climate change is reshaping the seasonal distribution of precipitation patterns across Central Asia, affecting not only the total accumulation but also the timing of precipitation events. However, how seasonal precipitation timing (i.e., precipitation seasonality) shift and may influence dryland ecosystem responses have rarely been considered. Here we utilized gross primary productivity (GPP) data derived from satellite observations over 2001–2022 and a proxy of precipitation timing (precipitation center time index, PCT) to elucidate changes in precipitation timing and assess its impact on vegetation productivity along bioclimate gradients in Central Asia. Our findings revealed that, from southwest to northeast, the precipitation season gradually extended from spring (PCT ≤ 5.0) to summer (PCT ≥ 6.0). Notably, approximately 74.4 % of the study area exhibited a trend of advanced precipitation, particularly evident in regions characterized by earlier precipitation onset. Changes in precipitation timing were found to induce variations in vegetation productivity, albeit with spatial heterogeneity. About 82.0 % of the vegetated areas showed positive GPP anomalies with advanced precipitation, especially in the eastern drylands, while delayed precipitation depressed productivity, leading to negative GPP anomalies in nearly 65.9 % of the vegetation zones. Vegetation in arid regions demonstrated heightened susceptibility to altered precipitation timing, whereas this sensitivity diminished in humid regions characterized by greater moisture availability. More precipitation distributed in early growing season would be more favorable to increase GPP, especially in xeric sparse vegetation, grassland, rained cropland, and shrubland. Our study highlight that it is necessary to pay more attention to the effects of altered precipitation timing on changes in terrestrial ecosystem productivity related to carbon cycle, especially in dryland.

In this work, we performed a systematic investigation on the comparison of magnetic anisotropy between three III-Mn-V dilute ferromagnetic semiconductors (Ga,Mn)As, (In,Mn)As and (Ga,Mn)P prepared by ion implantation and pulsed laser melting. Compressive strain induces in-plane magnetic anisotropy in (Ga,Mn)As and (Ga,Mn)P, while out-of-plane magnetic anisotropy is present in (In,Mn)As due to tensile strain introduced by Mn substitution. Interestingly, all materials prepared herein does not present strong in-plane uniaxial anisotropy, between [110] and [11¯0] directions, which always exhibits in low temperature molecular beam epitaxy (LT-MBE) grown (Ga,Mn)As samples. The reason is ascribed to the fact that the ultra-fast recrystallization induced by pulsed laser melting weakens the formation of Mn-Mn dimers along the [11¯0] direction which presents in LT-MBE grown (Ga,Mn)As.

PurposeThe aim of this study was to establish a validated nomogram to predict risk factors for major post-operative complications in patients with rectal cancer (RC) by analyzing the factors contributing to major post-operative complications in RC patients.MethodsWe retrospectively collected baseline and surgical information on patients who underwent RC surgery between December 2012 and December 2022 at a single-center teaching hospital. The entire cohort was randomly divided into two subsets (60% of the data for development, 40% for validation). Independent risk factors for major post-operative complications were identified using multivariate logistic regression analyses, and predictive models were developed. Area under the curve (AUC) was calculated using receiver operating characteristic curve (ROC) to assess predictive probability, calibration curves were plotted to compare the predicted probability of the nomogram with the actual probability, and the clinical efficacy of the nomogram was assessed using decision curve analysis (DCA).ResultsOur study included 3151 patients who underwent radical surgery for RC, including 1892 in the development set and 1259 in the validation set. Forty (2.1%) patients in the development set and 26 (2.1%) patients in the validation set experienced major post-operative complications. Through multivariate logistic regression analysis, age (p

ObjectiveTo evaluate intracerebral hemorrhage (ICH) risk in patients with ischemic stroke (IS) and cerebral microbleeds (CMBs) undergoing anticoagulation therapy for non-valvular atrial fibrillation (AF).MethodsWe conducted a comprehensive search across multiple databases, including Embase, PubMed, Cochrane, UpToDate, Scopus, WOS, and SinoMed. The search covered observational literature published from each database inception until February 1, 2023. We analyzed the prevalence of CMBs during the follow-up period, compared future ICH risk between patients with and without baseline CMBs (CMBs presence/absence, ≧5 CMBs), and examined factors influencing ICH occurrence in patients with CMBs. Also studied recurrent stroke during anticoagulation therapy, the risk of future ICH when white matter hyperintensity (WMH) and CMBs coexist, and the effects of anticoagulants vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on future ICH.ResultsWe included 7 articles involving 5,134 participants. The incidence of CMBs was 24%; baseline CMBs were associated with an increased ICH risk compared to patients without CMBs. ICH—risk was more significant in patients with baseline ≥5 CMBs. After anticoagulant therapy, ICH risk was higher than that of recurrent IS. The risk of future ICH was significantly increased with anticoagulant VKAs compared with NOAC.ConclusionAnticoagulant therapy for ischemic stroke patients with non-valvular AF and CMBs increases future ICH risk. Discontinuing anticoagulation due to ICH risk should be avoided. NOACs are safe and effective for patients with CMBs and IS.

Mixed matrix composite membranes (MMCMs) are considered as one of the potential directions for the development of CO2 capture membranes. Nevertheless, the high cost and the challenging nature of improving separation performance are significant obstacles that prevent MMCMs from being widely applied in practice. In this study, we developed a cost-effective modified pore-optimized MOF-808 (MOF-808@PVAm) and utilized it to fabricate high-performance CO2 capture MMCMs. Specifically, MOF-808 and polyvinylamine (PVAm) were cross-linked by γ-(2,3-epoxypropoxy) propytrimethoxysilane (KH-560), which improved the pore structure characteristics of MOF-808 and led to high-performance MMCMs. For 2 bar feed gas (CO2/N2, 15/85), the MMCM with 33.33 wt.% MOF-808@PVAm loading displayed remarkable CO2 permeance of 2753 GPU and selectivity of 181. The prepared MMCM demonstrated good operational stability in simulated flue gas and exhibited potential for application in various gas purification fields (CO2/CH4, CO2/H2) through gas permeation tests.

This work aims to estimate the Curie temperature and critical exponents in the critical regime of III-V ferromagnetic semiconductor (FS) (Ga,Mn)P film using various methods, including Arrott and Kouvel-Fisher plots, as well as electrical transport measurements. The (Ga,Mn)P film was prepared by implanting Mn ions into an intrinsic (001) GaP wafer, followed by pulsed laser melting (PLM). The magnetic properties of the (Ga,Mn)P layer were systematically investigated. The study investigated the accuracy of four different methods in determining the critical behaviors for the magnetic properties close to TC. The results suggest that the critical exponents are similar to those of the mean-field model, as indicated by the modified Arrot plots and temperature dependent effective critical exponents. However, the accuracy of the temperature-dependent resistance Rxx(T) method and Kouvel-Fisher (K-F) analysis is limited due to the Gaussian distribution of Mn ions in the film.

Abstract Existing drug-target interaction (DTI) prediction methods generally fail to generalize well to novel (unseen) proteins and drugs. In this study, we propose a protein-specific meta-learning framework ZeroBind with subgraph matching for predicting protein-drug interactions from their structures. During the meta-training process, ZeroBind formulates training a protein-specific model, which is also considered a learning task, and each task uses graph neural networks (GNNs) to learn the protein graph embedding and the molecular graph embedding. Inspired by the fact that molecules bind to a binding pocket in proteins instead of the whole protein, ZeroBind introduces a weakly supervised subgraph information bottleneck (SIB) module to recognize the maximally informative and compressive subgraphs in protein graphs as potential binding pockets. In addition, ZeroBind trains the models of individual proteins as multiple tasks, whose importance is automatically learned with a task adaptive self-attention module to make final predictions. The results show that ZeroBind achieves superior performance on DTI prediction over existing methods, especially for those unseen proteins and drugs, and performs well after fine-tuning for those proteins or drugs with a few known binding partners.

Abstract Background Antibody-mediated immune responses play a crucial role in the immune defense of human body. The evolution of bioengineering has led the progress of antibody-derived drugs, showing promising efficacy in cancer and autoimmune disease therapy. A critical step of this development process is obtaining the affinity between antibodies and their binding antigens. Results In this study, we introduce a novel sequence-based antigen–antibody affinity prediction method, named DG-Affinity. DG-Affinity uses deep neural networks to efficiently and accurately predict the affinity between antibodies and antigens from sequences, without the need for structural information. The sequences of both the antigen and the antibody are first transformed into embedding vectors by two pre-trained language models, then these embeddings are concatenated into an ConvNeXt framework with a regression task. The results demonstrate the superiority of DG-Affinity over the existing structure-based prediction methods and the sequence-based tools, achieving a Pearson’s correlation of over 0.65 on an independent test dataset. Conclusions Compared to the baseline methods, DG-Affinity achieves the best performance and can advance the development of antibody design. It is freely available as an easy-to-use web server at https://www.digitalgeneai.tech/solution/affinity .

Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance. Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia. Ginsenoside is a natural active component in Panax ginseng C.A. Meyer, and some of them enhance thermogenesis. However, there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis. Using thermogenic protein uncoupling protein 1 (UCP1)-luciferase reporter assay, we identified ginsenoside F1 as a novel UCP1 activator in the ginsenosides library. Using pull down assay and inhibitor interference, we found F1 binds to β3-adrenergic receptors (β3-AR) to enhance UCP1 expression via cAMP/PKA/CREB pathway. We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice, including body weight, body composition and energy expenditure. The results of proteomics showed that F1 significantly up-regulated thermogenesis proteins and lipolytic proteins, but down-regulated fatty acid synthesis proteins. Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifically by promoting the browning of white adipose tissue in obese mice. Additionally, ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes, and shows a stronger mitochondria respiration ability than norepinephrine. These findings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.

Abstract The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its relationship with genomic features, clinicopathological characteristics and prognosis in lung cancer is poorly understood, which could lead to population bias in prospective studies. We retrospectively analyzed 1011 lung cancer patients whose tumor samples were successfully profiled by high-throughput sequencing panel including GI/HRD score. Alterations of many cancer suppressor genes were associated with higher GI/HRD scores, biallelic inactivation of TP53 was correlated with a high GI/HRD score. A combination of two gene alterations exhibited a higher GI/HRD scores than single gene alterations. The GI/HRD score was associated with advanced stages in lung adenocarcinoma but not in lung squamous cell carcinoma. Furthermore, patients with higher GI/HRD scores had significantly shorter overall survival and progression-free survival than patients with lower GI/HRD scores. Finally, patients with a combination of a higher GI/HRD scores and TP53 alteration exhibited an extremely poor prognosis compared with patients with a lower GI/HRD scores and wild-type TP53 (overall survival, training cohort, hazard ratio (HR) = 8.56, P

Abstract Amyloid-like assembly is not only associated with pathological events, but also leads to the development of novel nanomaterials with unique properties. Herein, using Fmoc diphenylalanine peptide (Fmoc–F–F) as a minimalistic model, we found that histidine can modulate the assembly behavior of Fmoc–F–F and induce enzyme-like catalysis. Specifically, the presence of histidine rearranges the β structure of Fmoc–F–F to assemble nanofilaments, resulting in the formation of active site to mimic peroxidase-like activity that catalyzes ROS generation. A similar catalytic property is also observed in Aβ assembled filaments, which is correlated with the spatial proximity between intermolecular histidine and F-F. Notably, the assembled Aβ filaments are able to induce cellular ROS elevation and damage neuron cells, providing an insight into the pathological relationship between Aβ aggregation and Alzheimer’s disease. These findings highlight the potential of histidine as a modulator in amyloid-like assembly of peptide nanomaterials exerting enzyme-like catalysis.

Abstract Recently, the optoelectronic memory is capturing growing attention due to its integrated function of sense and memory as well as multilevel storage ability. Although tens of states have been reported in literature, there are still three obvious deficiencies in most of the optoelectronic memories: large programming voltage (>20 V), high optical power density (>1 mW cm−2), and poor compatibility originating from the over-reliance on channel materials. Here, we firstly propose an optoelectronic memory based on a new photosensitive dielectric (PSD) architecture. Data writing and erasing are realized by using an optical pulse to switch on the PSD. The unique design enables the memory to work with a programming voltage and optical power density as low as 4 V and 160 µW cm−2, respectively. Meanwhile, this device may be extended to different kinds of transistors for specific applications. Our discovery offers a brand-new direction for non-volatile optoelectronic memories with low energy consumption.

Boron(B)element is often utilized to enhance mechanical properties of stainless steel due to its excellent performance. In this study, selective laser melting (SLM) was used to print 316L/B stainless steel with varying boron weight content. The effects of boron content on microstructure, nanoindentation, and mechanical properties of the printed 316L stainless steel were discussed. Fine cell dendrites and columnar crystals were found in the SLM printed stainless steel due to the rapid solidification in SLM. It was found that boron has a higher growth limiting factor in the iron system and the boron solute can provide a high component supercooling. By adding boron element to stainless steel during printing, the honeycomb and grain size after solidification are significantly reduced due to interactions between the boron element and the 316L. Tensile testing results show that the ultimate tensile strength of the SLM fabricated parts with 0.5 wt% and 1 wt% boron element addition can be increased significantly to 1071 MPa and 1174 MPa, respectively.

Nafion membranes are widely used as proton exchange membranes, but their proton conductivity deteriorates in high-temperature environments due to the loss of water molecules. To address this challenge, we propose the utilization of porous aromatic frameworks (PAFs) as a potential solution. PAFs exhibit remarkable characteristics, such as a high specific surface area and porosity, and their porous channels can be post-synthesized. Here, a novel approach was employed to synthesize a PAF material, designated as PAF-45D, which exhibits a specific surface area of 1571.9 m2·g−1 and possesses the added benefits of facile synthesis and a low cost. Subsequently, sulfonation treatment was applied to PAF-45D in order to introduce sulfonic acid groups into its pores, resulting in the formation of PAF-45DS. The successful incorporation of sulfonic groups was confirmed through TG, IR, and EDS analyses. Furthermore, a novel Nafion composite membrane was prepared by incorporating PAF-45DS. The Nyquist plot of the composite membranes demonstrates that the sulfonated PAF-45DS material can enhance the proton conductivity of Nafion membranes at high temperatures. Specifically, under identical film formation conditions, doping with a 4% mass fraction of PAF-45DS, the conductivity of the Nafion composite membrane increased remarkably from 2.25 × 10−3 S·cm−1 to 5.67 × 10−3 S·cm−1, nearly 2.5 times higher. Such promising and cost-effective materials could be envisioned for application in the field of Nafion composite membranes.

Liquid-liquid phase separation is vital in the formation of many biomolecular condensates, including cellular membraneless organelles. When semiflexible macromolecules are involved, the process switches from mostly enthalpy- to dominantly entropy-driven, changing the intrinsic nature of the interfaces and bringing new physical traits. Here, we present a concept to address the complexity of entropic interfaces where laser trapping and microscopy are combined to capture the behavior of probe colloidal particles onto liquid crystalline droplet surfaces. Hertz-Frank-Oseen contact theory is extended to calculate the elasticity of the droplet based on particle trajectories. We show that this method is sensitive enough to resolve the anisotropic elasticity originating from the collective molecular orientation of constitutive semiflexible mesogens, introducing a possible tool to assess biomechanics of cellular and molecular condensates.

The river valley forests of the Irtysh River Basin are a germplasm bank of Salicaceae species and rare plant resources in China, and the distribution varies with the river and is highly distinctive. However, there is a dearth of systematic research on the characteristics of plant resources. In this study, a comprehensive investigation was conducted in the trunk stream and six tributaries with valley forest distribution in the Irtysh River Basin, and 244 quadrats were set up. The analysis focused on the composition of the flora and resource characteristics. The results reveal the following: (1) The valley forests of the Irtysh River Basin contain 256 species of plants belonging to 57 families and 178 genera, among which 19 species of trees, 23 species of shrubs, and 214 species of herbs were investigated. (2) Among the identified species, 226 (88.67%) were recognized as resource plants, with medicinal plants being the most abundant (176 species, 68.75% of the total). (3) The distribution patterns of trees, shrubs, and herbs of each resource type vary across rivers. Elevation drop, river length, and river distance all significantly affect the number of specie. This study elucidated the current status and distributional characteristics of plant resources in the valley forests of the Irtysh River Basin, which is essential for both biodiversity conservation and sustainable resource utilization.

Symmetry in traffic patterns is a fundamental aspect of intelligent transportation systems, aiming to precisely predict traffic flow in real time despite the complex interplay of spatial and temporal factors. This paper presents a novel method of traffic forecasting that incorporates parameters related to road symmetry into a Graph Convolution Network model. Our model is crafted to dynamically adjust to real-time changes in road conditions, including the presence of symmetric and asymmetric road layouts, which substantially influence traffic flow. We have developed a GCN model that not only accounts for standard traffic flow metrics but also integrates a matrix representing road symmetry. The model undergoes training and validation on the METR-LA dataset, showcasing a significant enhancement in prediction accuracy. In the comparative analysis of state-of-the-art methods, our model demonstrated a significant enhancement in performance, achieving 30.68% improvement in Mean Squared Error (MSE) and a 24.28% improvement in Mean Absolute Error (MAE) over the best-performing method. The implications of our research are profound for urban planners, traffic management systems, and navigation service providers, as it offers a more dependable tool for forecasting traffic conditions, aiding in road design, and refining route planning strategies based on the symmetry of road networks.

The Irtysh River, which stretches for 633 km, is the second longest river in Xinjiang. The valley forests within its basin are unique forest resources that exhibit crucial ecological functions and form an integral part of China’s “Three North” Shelterbelt Forest Project. However, previous studies mainly focused on individual tributaries or main streams, lacking comprehensive research on the overall river and valley forest resources and their ecological functions. To address this research gap based on comprehensive investigations, this study analyzed the dominant species composition, spatial distribution patterns, and influencing factors of valley forests across various branches of the Irtysh River basin plain. The results revealed the presence of 10 local tree species in the area, with Populus laurifolia, Populus alba, Salix alba, and Betula pendula as the dominant species. However, seedling regeneration was relatively weak. P. laurifolia, P. alba, and S. alba were widely distributed across tributaries and main streams, whereas B. pendula was primarily found in the tributaries. The four dominant species exhibited distinct clustering patterns. The concentration intensity of these dominant species in the main stream of the Irtysh River basin was significantly higher than those in other tributaries, with P. laurifolia showing a lower concentration intensity across the entire basin than the other dominant species. Negative density dependence was the primary biological factor influencing species aggregation intensity, with significant positive effects on P. alba and S. alba and significant negative effects on B. pendula. Among the abiotic factors, elevation had a significant positive effect on the aggregation intensities of P. alba, S. alba, and B. pendula, indicating that these species tend to aggregate more densely at higher elevations. Conversely, slope had a significant negative impact on the aggregation intensities of P. laurifolia, P. alba, and S. alba, suggesting that increasing slope steepness leads to a decrease in the clustering of these species. Similarly, the distance from the river channel had a significant negative effect on the aggregation intensities of S. alba and B. pendula, implying that as the distance from the river increases, the clustering patterns of these species become less pronounced. This study aimed to detail the current state of valley forest resources and their ecological functions, thereby laying a foundation for their effective protection.

(1) Background: One method of eradicating brucellosis is to cull cattle that test positive for antibodies 12 months after being vaccinated with the 19-strain vaccine. Variations in immunization regimens and feeding practices may contribute to differences in the rate of persistent antibodies. We conducted this study to investigate the real positive rate of Brucella antibody in field strains of Brucella spp. after immunization over 12 months in dairy cows. This research aims to provide data to support the development of strategies for preventing, controlling, and eradicating brucellosis. (2) Method: We employed the baseline sampling method to collect samples from cows immunized with the A19 vaccine for over 12 months in Lingwu City from 2021 to 2023. Serological detection was conducted using the RBPT method. An established PCR method that could distinguish between 19 and non-19 strains of Brucella was utilized to investigate the field strains of Brucella on 10 dairy farms based on six samples mixed into one using the Mathematical Expectation strategy. (3) Results: We analyzed the rates of individual seropositivity and herd seropositive rates in dairy cattle in Lingwu City from 2021 to 2023 and revealed that antibodies induced by the Brucella abortus strain A19 vaccine persist in dairy herds for more than 12 months. We established a PCR method for identifying both Brucella A19 and non-A19 strains, resulting in the detection of 10 field strains of Brucella abortus from 1537 dairy cows. By employing a Mathematical Expectation strategy, we completed testing of 1537 samples after conducting only 306 tests, thereby reducing the workload by 80.1%. (4) Conclusions: There was a certain proportion of cows with a persistent antibody titer, but there was no evidence that all of these cattle were naturally infected with Brucella. The established PCR method for distinguishing between Brucella abortus strain 19 and non-19 strains can be specifically utilized for detecting natural Brucella infection in immunized cattle. We propose that relying solely on the detection of antibodies in cattle immunized with the A19 vaccine more than 12 months previously should not be solely relied upon as a diagnostic basis for brucellosis, and it is essential to complement this approach with PCR analysis to specifically identify field Brucella spp. Brucella abortus was the predominant strain identified in the field during this study. Detection based on the Mathematical Expectation strategy can significantly enhance detection efficiency.