Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis.

Dynamin 1 mediates fission of endocytic synaptic vesicles in the brain and has two major splice variants, Dyn1xA and Dyn1xB, which are nearly identical apart from the extended C-terminal region of Dyn1xA. Despite a similar set of binding partners, only Dyn1xA is enriched at endocytic zones and accelerates vesicle fission during ultrafast endocytosis. Here, we report that Dyn1xA achieves this localization by preferentially binding to Endophilin A1 through a newly defined binding site within its long C-terminal tail extension. Endophilin A1 binds this site at higher affinity than the previously reported site, and the affinity is determined by amino acids within the Dyn1xA tail but outside the binding site. This interaction is regulated by the phosphorylation state of two serine residues specific to the Dyn1xA variant. Dyn1xA and Endophilin A1 colocalize in patches near the active zone, and mutations disrupting Endophilin A binding to the long tail cause Dyn1xA mislocalization and stalled endocytic pits on the plasma membrane during ultrafast endocytosis. Together, these data suggest that the specificity for ultrafast endocytosis is defined by the phosphorylation-regulated interaction of Endophilin A1 with the C-terminal extension of Dyn1xA.

ALS/FTLD-Linked Mutations in FUS Glycine Residues Cause Accelerated Gelation and Reduced Interactions with Wild-Type FUS.

The RNA-binding protein fused in sarcoma (FUS) can form pathogenic inclusions in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). Over 70 mutations in Fus are linked to ALS/FTLD. In patients, all Fus mutations are heterozygous, indicating that the mutant drives disease progression despite the presence of wild-type (WT) FUS. Here, we demonstrate that ALS/FTLD-linked FUS mutations in glycine (G) strikingly drive formation of droplets that do not readily interact with WT FUS, whereas arginine (R) mutants form mixed condensates with WT FUS. Remarkably, interactions between WT and G mutants are disfavored at the earliest stages of FUS nucleation. In contrast, R mutants physically interact with the WT FUS such that WT FUS recovers the mutant defects by reducing droplet size and increasing dynamic interactions with RNA. This result suggests disparate molecular mechanisms underlying ALS/FTLD pathogenesis and differing recovery potential depending on the type of mutation.

Precursor Engineering of Solution-Processed Sb2 S3 Solar Cells.

Antimony-based chalcogenides have emerged as promising candidates for next-generation thin film photovoltaics. Particularly, binary Sb2 S3 thin films have exhibited great potential for optoelectronic applications, due to the facile and low-cost fabrication, simple composition, decent charge transport and superior stability. However, most of the reported efficient Sb2 S3 solar cells are realized based on chemical bath deposition and hydrothermal methods, which require large amount of solution and are normally very time-consuming. In this work, Ag ions are introduced within the Sb2 S3 sol-gel precursors, and effectively modulated the crystallization and charge transport properties of Sb2 S3 . The crystallinity of the Sb2 S3 crystal grains are enhanced and the charge carrier mobility is increased, which resulted improved charge collection efficiency and reduced charge recombination losses, reflected by the greatly improved fill factor and open-circuit voltage of the Ag incorporated Sb2 S3 solar cells. The champion devices reached a record high power conversion efficiency of 7.73% (with antireflection coating), which is comparable with the best photovoltaic performance of Sb2 S3 solar cells achieved based on chemical bath deposition and hydrothermal techniques, and pave the great avenue for next-generation solution-processed photovoltaics.

Surface Plasmon Resonance-Enhanced CdS/FTO Heterojunction for Cu2+ Detection.

Copper ion (Cu2+) pollution poses a serious threat to marine ecology and fisheries. However, the complexity of seawater and its interference factors make the online detection of Cu2+ quite challenging. To address this issue, we introduce the concept of the photo-assisted adjustment barrier effect into electrochemical detection, using it as a driving force to generate electrochemical responses. The Schottky barrier demonstrates a remarkable regulatory influence on the electrochemical response under photoexcitation, facilitating the response through Cu2+ adsorption. We developed a 4-MBA-AuNPs/CdS/FTO composite that serves as a sensitive platform for Cu2+ detection, achieving a detection limit of 70 nM. Notably, the photo-assisted adjustment of the barrier effect effectively counters the interference posed by ions in seawater, ensuring accurate detection. Furthermore, the sensor exhibits a promising recovery rate (99.62-104.9%) in real seawater samples, highlighting its practical applications. This innovative approach utilizing the photo-assisted adjustment barrier effect offers a promising path for developing electrochemical sensors that can withstand interference.

Using the Photo-Piezoelectric Effect of AuPt@BaTiO3 Oxidase Mimetics for Colorimetric Detection of GSH in Serum.

Nanozymes possess major advantages in catalysis and biosensing compared with natural nanozymes. In this study, the AuPt@BaTiO3 bimetallic alloy Schottky junction is prepared to act as oxidase mimetics, and its photo-piezoelectric effect is investigated. The synergy between the photo-piezoelectric effect and the local surface plasmon resonance enhances the directional migration and separation of photogenerated electrons, as well as hot electrons induced by the AuPt bimetallic alloy. This synergy significantly improves the oxidase-like activity. A GSH colorimetric detection platform is developed based on this fading principle. Leveraging the photo-piezoelectric effect allows for highly sensitive detection with a low detection limit (0.225 µM) and reduces the detection time from 10 min to 3 min. The high recovery rate (ranging from 99.91% to 101.8%) in actual serum detection suggests promising potential for practical applications. The development of bimetallic alloy heterojunctions presents new opportunities for creating efficient nanozymes.

Facial expression recognition ability and its neuropsychological mechanisms in children with attention deficit and hyperactive disorder. / æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢æ‚£å„¿é¢éƒ¨è¡¨æƒ è¯†åˆ«èƒ½åŠ›åŠå ¶ç¥žç»å¿ƒç†æœºåˆ¶.

Attention deficit and hyperactive disorder (ADHD) is a chronic neurodevelopmental disorder characterized by inattention, hyperactivity-impulsivity, and working memory deficits. Social dysfunction is one of the major challenges faced by children with ADHD. It has been found that children with ADHD can't perform as well as typically developing children on facial expression recognition (FER) tasks. Generally, children with ADHD have some difficulties in FER, while some studies suggest that they have no significant differences in accuracy of specific emotion recognition compared with typically developing children. The neuropsychological mechanisms underlying these difficulties are as follows. First, neuroanatomically. Compared to typically developing children, children with ADHD show smaller gray matter volume and surface area in the amygdala and medial prefrontal cortex regions, as well as reduced density and volume of axons/cells in certain frontal white matter fiber tracts. Second, neurophysiologically. Children with ADHD exhibit increased slow-wave activity in their electroencephalogram, and event-related potential studies reveal abnormalities in emotional regulation and responses to angry faces when facing facial stimuli. Third, psychologically. Psychosocial stressors may influence FER abilities in children with ADHD, and sleep deprivation in ADHD children may significantly increase their recognition threshold for negative expressions such as sadness and anger. This article reviews research progress over the past three years on FER abilities of children with ADHD, analyzing the FER deficit in children with ADHD from three dimensions: neuroanatomy, neurophysiology and psychology, aiming to provide new perspectives for further research and clinical treatment of ADHD.

Exploring the mechanism of artificial selection signature in Chinese indigenous pigs by leveraging multiple bioinformatics database tools.

BACKGROUND: Chinese indigenous pigs in Yunnan exhibit considerable phenotypic diversity, but their population structure and the biological interpretation of signatures of artificial selection require further investigation. To uncover population genetic diversity, migration events, and artificial selection signatures in Chinese domestic pigs, we sampled 111 Yunnan pigs from four breeds in Yunnan which is considered to be one of the centres of livestock domestication in China, and genotyped them using Illumina Porcine SNP60K BeadChip. We then leveraged multiple bioinformatics database tools to further investigate the signatures and associated complex traits. RESULTS: Population structure and migration analyses showed that Diannanxiaoer pigs had different genetic backgrounds from other Yunnan pigs, and Gaoligongshan may undergone the migration events from Baoshan and Saba pigs. Intriguingly, we identified a possible common target of sharing artificial selection on a 265.09 kb region on chromosome 5 in Yunnan indigenous pigs, and the genes on this region were associated with cardiovascular and immune systems. We also detected several candidate genes correlated with dietary adaptation, body size (e.g., PASCIN1, GRM4, ITPR2), and reproductive performance. In addition, the breed-sharing gene MMP16 was identified to be a human-mediated gene. Multiple lines of evidence at the mammalian genome, transcriptome, and phenome levels further supported the evidence for the causality between MMP16 variants and the metabolic diseases, brain development, and cartilage tissues in Chinese pigs. Our results suggested that the suppression of MMP16 would directly lead to inactivity and insensitivity of neuronal activity and skeletal development in Chinese indigenous pigs. CONCLUSION: In this study, the population genetic analyses and identification of artificial selection signatures of Yunnan indigenous pigs help to build an understanding of the effect of human-mediated selection mechanisms on phenotypic traits in Chinese indigenous pigs. Further studies are needed to fully characterize the process of human-mediated genes and biological mechanisms.

Design of an Organic Template for Synthesizing ITR Zeolites under Ge-Free Conditions.

Germanosilicate zeolites with various structures have been extensively synthesized, but the syntheses of corresponding zeolite structures in the absence of germanium species remain a challenge. One such example is an ITR zeolite structure, which is a twin of the ITH zeolite structure. Through the modification of a classic organic template for synthesizing ITH zeolites and thus designing a new organic template with high compatibility to ITR zeolite assisted by theoretical simulation, we, for the first time, show the Ge-free synthesis of an ITR structure including pure silica, aluminosilicate, and borosilicate ITR zeolites. These materials have high crystallinity, corresponding to an ITR content of more than 95%. In the methanol-to-propylene (MTP) reaction, the obtained aluminosilicate ITR zeolite exhibits excellent propylene selectivity and a long lifetime compared with conventional aluminosilicate ZSM-5 zeolite. The strategy for the design of organic templates might offer a new opportunity for rational syntheses of novel zeolites and, thus, the development of highly efficient zeolite catalysts in the future.

Plasmonic Array at the Liquid-Liquid Interface: A Dual-Mode Optical Sensing Platform for Multianalytes.

Analyte-triggered nanoparticle (NP) assemblies in bulk colloidal suspension have been extensively utilized in various optical sensors. Nevertheless, the assembling process is still limited by the slow diffusion dynamics of NPs and the low concentration of analytes in trace detections, which hinders further improvement of the sensitivity and repeatability of the sensors. In this work, by functionalizing the gold NPs with specific ligands, we constructed a dual-mode optical sensing platform for multianalytes based on the plasmonic NP array at the liquid-liquid interface. Through emulsification, the NP diffusion kinetics are boosted for several orders, and the NPs are condensed from the bulk aqueous phase to the liquid-liquid interface as a plasmonic array. The as-formed metasurface generates major reflectance and surface-enhanced Raman scattering changes in response to analytes, providing two optical sensing modes. As prototypes, cysteine and glucose are selected as the target molecules, achieving the limit of detection as 193 ± 2 and 297 ± 12 pM, respectively.

Sirt3 restricts tumor initiation via promoting LONP1 deacetylation and K63 ubiquitination.

BACKGROUND: Sirtuin 3 (Sirt3) is a controversial regulator of carcinogenesis. It residents in the mitochondria and gradually decays during aging. In this study, we tried to investigate the role of Sirt3 in carcinogenesis and to explore its involvement in metabolic alteration. METHODS: We generated conditional intestinal epithelium Sirt3-knockout mice by crossing ApcMin/+; Villin-Cre with Sirt3fl/fl (AVS) mice. The deacetylation site of Lon protease-1 (LONP1) was identified with Mass spectrometry. The metabolic flux phenotype was determined by Seahorse bioanalyzer. RESULTS: We found that intestinal epithelial cell-specific ablation of Sirt3 promotes primary tumor growth via stabilizing mitochondrial LONP1. Notably, we newly identified that Sirt3 deacetylates human oncogene LONP1 at N terminal residue lysine 145 (K145). The LONP1 hyperacetylation-mutant K145Q enhances oxidative phosphorylation to accelerate tumor growth, whereas the deacetylation-mutant K145R produces calorie-restriction like phenotype to restrain tumorigenesis. Sirt3 deacetylates LONP1 at K145 and subsequently facilitates the ESCRT0 complex sorting and K63-ubiquitination that resulted in the degradation of LONP1. Our results sustain the notion that Sirt3 is a tumor-suppressor to maintain the appropriate ubiquitination and degradation of oncogene LONP1. CONCLUSION: Sirt3 represents a targetable metabolic checkpoint of oncogenesis, which produces energy restriction effects via maintaining LONP1 K145 deacetylation and subsequent K63 ubiquitination.

Vav1-dependent Rac1 activation mediates hypoxia-induced gemcitabine resistance in pancreatic ductal adenocarcinoma cells through upregulation of HIF-1α expression.

Hypoxia has been shown to induce gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC) cells, however, the underlying mechanisms remain to be clarified. In the present study, we investigated whether activation of Vav1/Rac1/HIF-1α axis is responsible for hypoxia-induced GEM resistance in PDAC cells. Our results showed that Rac1 activation contributed to hypoxia-induced GEM resistance in PANC-1 cells. Hypoxia treatment led to an increased expression level of Vav1, which was responsible for Rac1 activation and GEM resistance in PDAC cells. Furthermore, Rac1 mediated hypoxia-induced GEM resistance by upregulating HIF-1α in PDAC cells. Taken together, these findings suggest that hypoxia induces GEM resistance in PDAC cells by activating the Vav1/Rac1/HIF-1α signaling pathway.

Primary Care Physicians' and Patients' Perspectives on Equity and Health Security of Infectious Disease Digital Surveillance.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic facilitated the rapid development of digital detection surveillance (DDS) for outbreaks. This qualitative study examined how DDS for infectious diseases (ID) was perceived and experienced by primary care physicians and patients in order to highlight ethical considerations for promoting patients' autonomy and health care rights. METHODS: In-depth interviews were conducted with a purposefully selected group of 16 primary care physicians and 24 of their patients. The group was reflective of a range of ages, educational attainment, and clinical experiences from urban areas in northern and southern China. Interviews were audio recorded, transcribed, and translated. Two researchers coded data and organized it into themes. A third researcher reviewed 15% of the data and discussed findings with the other researchers to assure accuracy. RESULTS: Five themes were identified: ambiguity around the need for informed consent with usage of DDS; importance of autonomous decision making; potential for discrimination against vulnerable users of DDS for ID; risk of social inequity and disparate care outcomes; and authoritarian institutions' responsibility for maintaining health data security. The adoption of DDS meant some patients would be reluctant to go to the hospital for fear of either being discriminated against or forced into quarantine. Certain groups (older people and children) were thought to be vulnerable to DDS misappropriation. CONCLUSIONS: These findings indicate the paramount importance of establishing national and international ethical frameworks for DDS implementation. Frameworks should guide all aspects of ID surveillance, addressing privacy protection and health security, and underscored by principles of social equity and accountability.Annals "Online First" article.

Prognostic factors for the efficacy of infliximab in patients with luminal fistulizing Crohn's disease.

BACKGROUND: Enteric fistula is one of the penetrating features in Crohn's disease (CD). This study aimed to clarify the prognostic factors for the efficacy of infliximab (IFX) treatment in luminal fistulizing CD patients. METHODS: We retrospectively included 26 cases diagnosed with luminal fistulizing CD hospitalized in our medical center from 2013 to 2021. The primary outcome of our research was defined as death from all causes and undergoing of any relevant abdominal surgery. Kaplan-Meier survival curves were used to describe overall survival. Univariate and multivariate analyses were used to identify prognostic factors. A predictive model was constructed using Cox proportional hazard model. RESULTS: The median follow-up time was 17.5 months (range 6-124 months). The 1- and 2-year surgery-free survival rates were 68.1% and 63.2%, respectively. In the univariate analysis, the efficacy of IFX treatment at 6 months after initiation (P < 0.001, HR 0.23, 95% CI 0.01-0.72) and the existence of complex fistula (P = 0.047, HR 4.11, 95% CI 1.01-16.71) was found significantly related to the overall surgery-free survival, while disease activity at baseline (P = 0.099) also showed predictive potential. The multivariate analysis showed that efficacy at 6 months (P = 0.010) was an independent prognostic factor. The C-index of the model for surgery-free survival was 0.923 (P < 0.001), indicating an acceptable predictive effect. CONCLUSION: Prognostic model including the existence of complex fistula, disease activity at baseline and efficacy of IFX at 6 months may be useful to predict long-term outcome of luminal fistulizing CD patients.

The burden of anemia among Chinese HIV-infected patients following the initiation of antiretroviral therapy in the treat-all era: a nationwide cohort study.

BACKGROUND: To assess the prevalence of anemia before and after antiretroviral therapy (ART) initiation and to identify impact of anemia on mortality among HIV-infected patients in China during the Treat-All era. METHODS: All HIV-infected patients who newly initiated ART between January 1, 2017 and December 31, 2020 were enrolled and followed up to December 31, 2021 in China. We analyzed the prevalence of anemia before and after ART initiation. Generalized estimating equations were fitted to determine factors associated with anemia after ART. Time-dependent cox proportional hazards models were performed to estimate the effect of anemia on death. RESULTS: Of 436,658 patients at the baseline of ART initiation, the overall prevalence of anemia was 28.6%. During a median 2.65 (IQR: 1.80-3.51) years of follow-up after ART initiation, 376,325 (86.2%) patients had at least one Hb measurement (a total of 955,300 hemoglobin measurements). The annual prevalence of anemia after ART was 17.0%, 14.1%, 13.4%, 12.6% and 12.7%, respectively. Being anemic at the baseline of ART initiation (adjusted odds ratio, aOR = 6.80, 95% confidence interval (CI): 6.67-6.92) was the strongest factor associated with anemia after ART. Anemia status after ART showed a strong association with death after multivariable adjustment (mild anemia: adjusted hazard ratio (aHR) = 2.65, 95% CI: 2.55-2.76; moderate anemia: aHR = 4.60; 95% CI:4.40-4.81; severe anemia: aHR = 6.41; 95% CI:5.94-6.91). CONCLUSIONS: In the era of ART universal access, pre-ART anemia was common among HIV-infected patients. Notably, a certain proportion of anemia still persisted after ART, and was significantly associated with death. We recommend strengthening the monitoring of patients at risk of anemia, especially in patients with baseline anemia or during the first year of ART, and timely treatment for correcting anemia.

Zeolite nanosheets for catalysis.

Zeolites with well-defined micropores have been widely used as heterogeneous catalysts in the fields of petroleum refining, fine chemicals, and environment protection. However, the sole micropores in the zeolite structures usually impose diffusion constraints, which would greatly influence their catalytic performances. Therefore, it is highly desirable to shorten the diffusion pathway of zeolites and thus eliminate the diffusion constraints. One of the efficient methods is to synthesize zeolite nanosheets, which has become a hot topic in the past decades. In this tutorial review, the recent progresses in the synthesis of zeolite nanosheets and their relevant catalysis are briefly discussed. Various strategies for the synthesis of zeolite nanosheets are summarized including delamination, templated crystallization, additive-assisted synthesis, seed-directed synthesis, and gaseous expansion synthesis. In addition, the catalytic reactions of zeolite nanosheets with acidic and metal sites are also outlined. This tutorial review should be significant for the design and preparation of highly efficient zeolite catalysts.

New Monoterpenoid Indole Alkaloids from Tabernaemontana crassa Inhibit ß-Amyloid42 Production and Phospho-Tau (Thr217).

Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A-C (1-3), were isolated from the seeds of Tabernaemontana crassa. Tabercrassine A (1) is an ibogan-ibogan-type bisindole alkaloid which is formed by the polymerization of two classic ibogan-type monomers through a C3 unit aliphatic chain. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Cellular assays showed that alkaloids 1-3 all reduce Aß42 production and inhibit phospho-tau (Thr217), a new biomarker of Alzheimer's disease [AD] associated with BACE1-, NCSTN-, GSK3ß-, and CDK5-mediated pathways, suggesting these alkaloids' potential against AD.

Expressions with Aspectual Verbs Elicit Slower Reading Times than Those with Psychological Verbs: An Eye-Tracking Study in Mandarin Chinese.

Research over the last 20 years has investigated the processing costs for sentences such as John began the book. Much of this work has conflated sentences with aspectual verbs, like start or finish, with psychological verbs, like enjoy or tolerate. However, recent studies have reported greater costs for aspectual verbs compared to psychological verbs (e.g., Katsika et al. in Ment Lex 7:58-76, 2012; Lai et al. in Compositionality and concepts in linguistics and psychology, 2017). The present paper reports an eye-tracking study that examined the costs of processing both verb types in Mandarin Chinese. The results revealed greater costs both for aspectual verbs compared to controls (John read the book) and for aspectual verbs compared to psychological verbs, reinforcing the claims of the Structured Individual Hypothesis (Piñango and Deo in J Semant 33:359-408, 2016). Strikingly, there was an early effect at the verb for aspectual verbs but not for psychological verbs. We argue that this result, together with previous findings and other conceptual issues, necessitates a conservative modification of the SIH: aspectual verbs are semantically more complex than psychological verbs. This modification retains the core analysis underlying the SIH, but reconciles the SIH with experimental findings by bringing it in line with the view that lexical semantic complexity has immediate consequences in processing (e.g., Brennan and Pylkkänen in Lang Cogn Process 25:777-807, 2010).

Effects of straw addition on the physicochemical and microbial features of black soldier fly larvae frass derived from fish meat and bone meal.

Black soldier fly larvae (BSFL) hold great promise for sustainable management of meat and bone meal (MBM), a kind of organic waste. Harvested BSFL frass can be used as soil amendment or organic fertilizer. This study evaluated the quality and microbial profile in the frass of BSFL, fed with fish MBM containing 0% (CK), 1% (T1), 2% (T2) and 3% (T3) of rice straw. Results suggested straw addition into fish MBM had no significant impacts on BSFL weight; however, straw addition remarkably affected waste reduction and conversion efficiency, as well as physicochemical properties including electric conductivity, organic matter (OM) and total phosphorus contents in frass. Fourier transform infrared analysis indicated that increasing levels of cellulose and lignin might not be fully degraded or transformed by BSFL when more straw was introduced into substrates. Straw addition had hardly significant influences on microbial richness or evenness in BSFL frass, only T3 treatment remarkably elevated the phylogenetic diversity value more than the control. Bacteroidetes, Proteobacteria, Actinobacteria and Firmicutes were the most dominant phyla. Genera Myroides, Acinetobacter and Paenochrobactrum maintained high abundances in all frass samples. Elements including OM, pH and Na were key factors in shaping the microbiological characteristics of BSFL frass. Our findings helped to understand the effects of fish MBM waste manipulation on BSFL frass qualities and contributed to the further application of BSFL frass.

Design of a Small Organic Template for the Synthesis of Self-Pillared Pentasil Zeolite Nanosheets.

Zeolite nanosheets with excellent mass transfer are attractive, but their successful syntheses are normally resulted from a huge number of experiments. Here, we show the design of a small organic template for the synthesis of self-pillared pentasil (SPP) zeolite nanosheets from theoretical calculations in interaction energies between organic templates and pentasil zeolite skeletons. As expected, the SPP zeolite nanosheets with the thickness at 10-20 nm have been synthesized successfully. Characterizations show that the SPP zeolite nanosheets with about 90% MFI and 10% MEL structures have good crystallinity, the house-of-card morphology, large surface area, and fully four-coordinated aluminum species. More importantly, methanol-to-propylene tests show that the SPP zeolite nanosheets exhibit much higher propylene selectivity and longer reaction lifetime than conventional ZSM-5 zeolite. These results offer a good opportunity to develop highly efficient zeolite catalysts in the future.