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Background Methods Results and conclusion We aimed to prospectively evaluate the association between a diabetes risk reduction diet (DRRD) score and the risk of liver cancer development and chronic liver disease‐specific mortality.We included 98,786 postmenopausal women from the Women's Health Initiative‐Observational Study and the usual diet arm of the Diet Modification trial. The DRRD score was derived from eight factors: high intakes of dietary fiber, coffee, nuts, polyunsaturated fatty acids, low intakes of red and processed meat, foods with high glycemic index, sugar‐sweetened beverages (SSBs), and trans fat based on a validated Food‐Frequency Questionnaire administered at baseline (1993–1998). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for liver cancer incidence and chronic liver disease mortality were estimated using Cox proportional hazards regression models.After a median follow‐up of 22.0 years, 216 incident liver cancer cases and 153 chronic liver disease deaths were confirmed. A higher DRRD score was significantly associated with a reduced risk of developing liver cancer (HRTertile 3 vs. Tertile 1 = 0.69; 95% CI: 0.49–0.97; Ptrend = 0.03) and chronic liver disease mortality (HRT3 vs. T1 = 0.54; 95% CI: 0.35–0.82; Ptrend = 0.003). We further found inverse associations with dietary fiber and coffee, and positive associations with dietary glycemic index, SSBs, and trans fat. A higher DRRD score was associated with reduced risk of developing liver cancer and chronic liver disease mortality among postmenopausal women. [ABSTRACT FROM AUTHOR]

Automatic analysis of images is increasingly being used to generate color insights and this has led to various methods for generating palettes. Several studies have recently been published that explore methods to predict the visual similarity between pairs of palettes and these methods are often used to evaluate different generative methods. This work is concerned with being able to predict visual similarity between color palettes. Three data sets (two of which were previously published) are used to evaluate two methods for predicting visual similarity between palettes. A novel palette‐difference metric (based on the Hungarian algorithm) is compared to the previously published minimum color difference model (MICD) and was found to agree better with the visual data for two of the three data sets. Agreement between models and visual data was also better for CIEDE2000 (1, 2) than for CIELAB metrics. [ABSTRACT FROM AUTHOR]

The relationship between interfacial structure and thermal conductivity in epoxy resin/Al2O3 composite is important but is still elusive. Here, we illuminate this issue by investigating the role of four silane coupling agents in thermal conductivity for epoxy resin/Al2O3 composites. The results show that 3‐glycidoxypropyltrimethoxysilane (KH560) is the best silane coupling agent to modify Al2O3, resulting in the lowest viscosity and the highest thermal conductivity of the epoxy resin/Al2O3‐KH560 composite compared with alternative systems. This is attributed to the strong interfacial interaction between Al2O3‐KH560 and epoxy resin, as confirmed by the Fowkes model and broadband dielectric spectroscopy. The interfacial thermal resistance between the epoxy resin and Al2O3 is also quantitatively measured via a photothermal radiometry technique. The epoxy resin/Al2O3‐KH560 also has the lowest interfacial thermal resistance (1.50 ± 0.02 × 10−6 m2 K W−1), compared with the other three systems. This study advances the understanding of the relationship between interfacial structure and thermal conductivity in polymer composites. Highlights: The relationship between interfacial structure and thermal conductivity in epoxy resin/Al2O3 composite is understood.The interfacial structure is characterized by broadband dielectric spectroscopy.The interfacial thermal resistance is quantitatively measured via a photothermal radiometry technique. [ABSTRACT FROM AUTHOR]

The multifunctional derivatization of alcohols has been achieved by the bipyridinium‐based conjugated small molecule photocatalysts with redox center and Lewis acid site. Besides exhibiting high activity in the selective generation of aldehydes/ketones, acids from alcohols through solvent modulation, this system renders the first selective synthesis of esters via an attractive cross‐coupling pattern, whose reaction route is significantly different from the traditional condensation of alcohols and acids or esterification from hemiacetals. Following the oxidization of alcohol to aldehyde via bipyridinium‐mediated electron and energy transfer, the Lewis acid site of bipyridinium then activates the aldehyde and methanol to obtain the acetal, which further reacts with methanol to generate ester. This method not only demonstrates a clear advantage of bipyridinium in diverse catalytic activities, but also paves the way for designing efficient multifunctional small molecule photocatalysts. This metal‐ and additive‐free photocatalytic esterification reaction marks a significant advancement towards a more environmentally friendly, cost‐effective and green sustainable approach, attributed to the utilization of renewable substrate alcohol and the abundant, low‐cost air as the oxidant. The mildness of this esterification reaction condition provides a more suitable alternative for large‐scale industrial production of esters. [ABSTRACT FROM AUTHOR]

Exploring and taming the diffraction phenomena and divergence of light are foundational to enhancing comprehension of nature and developing photonic technologies. Despite the numerous types of nondiffraction beam generation technologies, the 3D deformation and intricate wavefront shaping of structures during propagation have yet to be studied through the lens of nanophotonic devices. Herein, the dynamic conversion of a circular Airy beam (CAB) to a Bessel beam with a single‐layer spin‐selective metasurface is demonstrated. This spatial transformation arises from the interplay of 1D local and 2D global phases, facilitating the 3D control of non‐diffractive light fields. An additional overall phase gradient and orbital angular momentum are introduced, which effectively altering the propagation direction and transverse fields of complex amplitude beams along the optical path. The manifested samples exhibit superior defect resistance, laying a crucial application in micro/nanolithography technologies. This approach expands the in‐plane spin‐selective mechanism and leverages the out‐of‐plane propagation dimension, allowing for integrated high‐resolution imaging, on‐chip optical micromanipulation, and micro/nanofabrication within a versatile nanophotonic platform. [ABSTRACT FROM AUTHOR]

Accurate monitoring of small molecules and precise characterization of the secretory ability of neurons are essential for effective diagnosis of neurological diseases. However, existing technologies for monitoring small molecules only provide approximate results. Plasmonic‐based biosensors are a potential solution in this biological application. Nevertheless, optical sensing nanoparticles require precise control of interparticle distance, particle shape and morphology, which can be challenging. This article discovers that the trapping of small molecules to aptamers induces a conformational change that alters the nanostructure of irregularly shaped Au nanoclusters (NCs) and aptamers due to the strong structure‐property relationships of Au NC‐aptamers. This change can be detected via resonance Rayleigh scattering (RRS) intensity in the dark‐field. This new technology overcomes the challenges of precise control of individual nanoparticles and the difficulty of small spectral peak shifts. The Au NC‐aptamers sensing device has a detection limit of 0.112 pm for dopamine, and this work detects 0.226 pm of dopamine surrounding a single epileptic neuron in polarization, which is more than those of healthy neurons. Overall, this easy‐to‐fabricate Au NC‐aptamers‐based technology has a high potential for monitoring small molecules and determining the secretory ability of single neurons, which is not possible using traditional technologies. [ABSTRACT FROM AUTHOR]

The necessity for precise determination of fruit storage durations is paramount in both industrial and domestic spheres, with hyperspectral imaging (HSI) technology emerging as a pivotal tool for prognosticating the physicochemical attributes indicative of mature fruit quality. This investigation employed hyperspectral imaging to conduct a noninvasive analysis of variations in soluble solids content (SSC), hardness, and moisture content (MC) in jujube fruit over the course of storage at divergent temperatures. Throughout the storage intervals (0, 7, 14, and 21 days) at varying temperatures (4 and 20°C), both physicochemical and spectral data were amassed. The raw spectral information underwent preprocessing through multiple scattering correction (MSC), standard normal variation (SNV), and Savitzky–Golay (SG) algorithms to refine the methodologies for SSC, hardness, and moisture content. Subsequently, the competitive adaptive reweighted sampling (CARS) algorithm facilitated the discernment and elimination of extraneous variables, thereby enhancing feature wavelength extraction. This process underpinned the development of partial least squares regression (PLSR), back propagation (BP), and genetic algorithm‐back propagation (GA‐BP) models predicated on CARS‐derived features, culminating in the selection of an optimal model. The findings underscore the capability of hyperspectral imaging technology to swiftly and nondestructively ascertain the SSC, hardness, and MC of jujube throughout the storage phase, thereby enabling the assessment of quality attributes over varying storage durations and facilitating the surveillance of jujube quality maintenance during storage. Practical Applications: The winter jujube garners appreciation from consumers owing to its exquisite flavor, yet its quality diminishes over time in storage due to various factors, thereby impacting its market value. Consequently, it is imperative to surveil the quality alterations of jujube throughout its storage to mitigate the degradation of its quality. Hyperspectral imaging technology offers a sophisticated means to forecast the physicochemical index changes indicative of the fruit's quality at maturity. This research delineates the development of predictive models for the soluble solids, hardness, and moisture content of jujube at divergent temperatures throughout the storage interval, selecting the paramount model through a holistic assessment, thereby fully harnessing the capabilities of hyperspectral imaging technology in monitoring jujube quality during storage. Moreover, the methodology employed herein is adaptable to other fruits in storage, harboring the potential for future application in the real‐time quality monitoring of fruits as they exit the storage facilities. [ABSTRACT FROM AUTHOR]

Aporphine alkaloids have diverse pharmacological activities; however, our understanding of their biosynthesis is relatively limited. Previous studies have classified aporphine alkaloids into two categories based on the configuration and number of substituents of the D‐ring and have proposed preliminary biosynthetic pathways for each category. In this study, we identified two specific cytochrome P450 enzymes (CYP80G6 and CYP80Q5) with distinct activities toward (S)‐configured and (R)‐configured substrates from the herbaceous perennial vine Stephania tetrandra, shedding light on the biosynthetic mechanisms and stereochemical features of these two aporphine alkaloid categories. Additionally, we characterized two CYP719C enzymes (CYP719C3 and CYP719C4) that catalyzed the formation of the methylenedioxy bridge, an essential pharmacophoric group, on the A‐ and D‐rings, respectively, of aporphine alkaloids. Leveraging the functional characterization of these crucial cytochrome P450 enzymes, we reconstructed the biosynthetic pathways for the two types of aporphine alkaloids in budding yeast (Saccharomyces cerevisiae) for the de novo production of compounds such as (R)‐glaziovine, (S)‐glaziovine, and magnoflorine. This study provides key insight into the biosynthesis of aporphine alkaloids and lays a foundation for producing these valuable compounds through synthetic biology. [ABSTRACT FROM AUTHOR]

Background: Bladder prolapse is a common clinical disorder of pelvic floor dysfunction in women, and early diagnosis and treatment can help them recover. Pelvic magnetic resonance imaging (MRI) is one of the most important methods used by physicians to diagnose bladder prolapse; however, it is highly subjective and largely dependent on the clinical experience of physicians. The application of computer‐aided diagnostic techniques to achieve a graded diagnosis of bladder prolapse can help improve its accuracy and shorten the learning curve. Purpose: The purpose of this study is to combine convolutional neural network (CNN) and vision transformer (ViT) for grading bladder prolapse in place of traditional neural networks, and to incorporate attention mechanisms into mobile vision transformer (MobileViT) for assisting in the grading of bladder prolapse. Methods: This study focuses on the grading of bladder prolapse in pelvic organs using a combination of a CNN and a ViT. First, this study used MobileNetV2 to extract the local features of the images. Next, a ViT was used to extract the global features by modeling the non‐local dependencies at a distance. Finally, a channel attention module (i.e., squeeze‐and‐excitation network) was used to improve the feature extraction network and enhance its feature representation capability. The final grading of the degree of bladder prolapse was thus achieved. Results: Using pelvic MRI images provided by a Huzhou Maternal and Child Health Care Hospital, this study used the proposed method to grade patients with bladder prolapse. The accuracy, Kappa value, sensitivity, specificity, precision, and area under the curve of our method were 86.34%, 78.27%, 83.75%, 95.43%, 85.70%, and 95.05%, respectively. In comparison with other CNN models, the proposed method performed better. Conclusions: Thus, the model based on attention mechanisms exhibits better classification performance than existing methods for grading bladder prolapse in pelvic organs, and it can effectively assist physicians in achieving a more accurate bladder prolapse diagnosis. [ABSTRACT FROM AUTHOR]

Wearable sensors hold immense potential for real‐time and non‐destructive sensing of volatile organic compounds (VOCs), requiring both efficient sensing performance and robust mechanical properties. However, conventional colorimetric sensor arrays, acting as artificial olfactory systems for highly selective VOC profiling, often fail to meet these requirements simultaneously. Here, a high‐performance wearable sensor array for VOC visual detection is proposed by extrusion printing of hybrid inks containing surface‐functionalized sensing materials. Surface‐modified hydrophobic polydimethylsiloxane (PDMS) improves the humidity resistance and VOC sensitivity of PDMS‐coated dye/metal‐organic frameworks (MOFs) composites. It also enhances their dispersion within liquid PDMS matrix, thereby promoting the hybrid liquid as high‐quality extrusion‐printing inks. The inks enable direct and precise printing on diverse substrates, forming a uniform and high particle‐loading (70 wt%) film. The printed film on a flexible PDMS substrate demonstrates satisfactory flexibility and stretchability while retaining excellent sensing performance from dye/MOFs@PDMS particles. Further, the printed sensor array exhibits enhanced sensitivity to sub‐ppm VOC levels, remarkable resistance to high relative humidity (RH) of 90%, and the differentiation ability for eight distinct VOCs. Finally, the wearable sensor proves practical by in situ monitoring of wheat scab‐related VOC biomarkers. This study presents a versatile strategy for designing effective wearable gas sensors with widespread applications. [ABSTRACT FROM AUTHOR]

The phosphatidylinositol‐3 kinase (PI3K) pathway is a crucial intracellular signaling pathway within living cells. The hyperactivation of PI3K signaling cascades is a common occurrence in human cancers, rendering PI3K a promising therapeutic target. Although several PI3K inhibitors are already available on the market, the adverse side effects of current therapies continue to highlight the necessity for the development of novel PI3K inhibitors. In this study, a virtual screening strategy employing naïve Bayesian classification (NBC) models, based on multicomplex‐based molecular docking and pharmacophore modeling, is developed. First, the docking accuracy and scoring reliability of four docking software are assessed, and Glide demonstrated higher predictability for PI3K inhibitors. Second, pharmacophore models are generated based on the current reported PI3K‐inhibitor interactions, and five pharmacophore hypotheses displayed significant capability in discriminating active PI3K molecules from inactive ones. Subsequently, three NBC models are constructed based on molecular docking and/or pharmacophore models, and the validation results showed that the NBC model, combining multicomplex‐based molecular docking and pharmacophore, significantly improved the hit rate of virtual screening against PI3K. Finally, the optimal NBC model is employed for virtual screening against the ChEMBL database, leading to the identification of multiple molecules with high potential as active PI3K inhibitors. [ABSTRACT FROM AUTHOR]

Imidacloprid and other neonicotinoid insecticides severely impact the performance and survival of honey bees and other pollinators. In the present study, we focused on the gene expression profile of newly emerged Apis mellifera queen bees after sublethal imidacloprid treatment during the larval stage. Royal jelly containing 1 ppb imidacloprid was provided to larvae for 3 consecutive days (2–4 days postemergence). Queen larvae treated with imidacloprid showed lower capping and emergence rates (35.5% and 24.22%, respectively) than did control larvae (61.68% and 52.95%, respectively), indicating a high failure rate of queen rearing associated with imidacloprid exposure during the larval stage. The molecular response to imidacloprid treatment was examined next. By comparing the gene expression profiles of imidacloprid‐treated queen larvae and those of control queen larvae using DESeq2, we identified 215 differentially expressed genes, with 105 and 111 up‐ and downregulated genes, respectively. Gene Ontology results indicated that chitin binding– and calcium ion binding–related genes were upregulated, while phototransduction‐ and visual perception–related genes were downregulated. The high mortality rate and altered gene expression profiles suggest that treatment with even 1 ppb imidacloprid can severely impact queen bee survival. Environ Toxicol Chem 2024;43:2232–2242. © 2024 SETAC [ABSTRACT FROM AUTHOR]

Background: Previous research has demonstrated heterogeneous adaptive outcomes across the autism spectrum; however, the current literature remains limited in elucidating turning points and associated factors for longitudinal variability (chronogeneity). To address these empirical gaps, we aimed to provide a finer‐grained characterization of trajectories of adaptive functioning from early childhood to adolescence in autism. Methods: Our sample (N = 406) was drawn from an inception cohort of children diagnosed Autistic at ages 2–5. Adaptive functioning was assessed with Vineland Adaptive Behavior Scales (VABS, 2nd Edition) across 6 visits from the time of diagnosis by age 18. Parallel‐process latent growth curve modeling were used to estimate domain‐level VABS trajectories, followed by latent class growth analysis to identify trajectory subgroups. Child characteristics at diagnosis, family demographics, and participation outcomes at adolescence were compared across subgroups. Results: Piecewise latent growth models best described VABS trajectories with two turning points identified at around ages 5‐6 and 9–10, respectively reflecting transitions into school age and early adolescence. We parsed four VABS trajectory subgroups that vary by level of functioning and change rate for certain domains and periods. Around 16% of the sample exhibited overall adequate functioning (standard score >85) with notable early growth and social adaptation during adolescence. About 21% showed low adaptive functioning (standard score ≤70), with decreasing slopes by age 6 followed by improvements in communication and daily‐living skills by age 10. The other two subgroups (63% in total) were characterized by adaptive functioning between low and adequate levels, with relatively stable trajectories entering school age. These subgroups differed most in their cognitive ability at diagnosis, household income, and social participation in adolescence. Conclusions: We identified key individual and family characteristics and time windows associated with distinct adaptive functioning trajectories, which have important implications for providing timely and tailored supports to Autistic people across developmental stages. [ABSTRACT FROM AUTHOR]

Background: Poor asthma control may adversely affect mental health. Our study investigates the correlation between inadequate asthma control, exhaled nitric oxide (FENO) levels, and anxiety and depression among pediatric asthma patients with COVID‐19. Methods: This prospective case–control study enrolled 520 asthmatic children (8–15 years), including 336 patients diagnosed with COVID‐19 after rapid antigen testing at home and 184 age‐matched asthmatic patients without COVID‐19 infection. FENO and spirometry were performed 1 month after COVID‐19 infection. Scores for Child Anxiety‐Related Disorders (SCARED) and depression screen derived from Patient Health Questionnaire‐9 (PHQ‐9) to assess their mental health status. Childhood asthma control test (C‐ACT), FENO levels, and spirometry were correlated with the SCARED and PHQ‐9 questionnaires. Results: SCARED subscales, including generalized anxiety disorder, social anxiety disorder, school avoidance, and depression scores from PHQ‐9, exhibited a significant increase in asthmatic patients diagnosed with COVID‐19 (p <.05). Among asthmatic children with SARS‐CoV‐2 infection, the poor asthma control group exhibited the highest SCARED and PHQ‐9 measurements (p <.01). Multiple linear regression analysis indicated that reduced C‐ACT scores and elevated FENO levels in asthmatic children with COVID‐19 were significant risk factors for both anxiety and depression scores (p <.05). Lower C‐ACT scales were associated with high scores of SCARED (r = −0.471) and PHQ‐9 (r = −0.329) in asthmatic children (p <.001). Conclusions: The current study emphasizes the need for healthcare professionals to closely monitor asthma control in asthmatic children to prevent heightened risks of depression and anxiety during the ongoing COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

A nano‐immunomodulator (R‐NPT NP) comprising a tumor microenvironment (TME) activable resiquimod (R848) and a π‐extended NIR‐absorbing naphthophenanthrolinetetraone (NPT) has been engineered for spatiotemporal controlled photothermal immunotherapy. R‐NPT NP demonstrated excellent photostability, while R848 promoted synergistic immunity as a toll‐like receptor 7/8 (TLR7/8) agonist. Upon accumulation at the tumor site, R‐NPT NP released R848 in response to redox metabolite glutathione (GSH), triggering dendritic cell (DC) activation. The photothermal effect endowed by R‐NPT NP can ablate tumors directly and trigger immunogenic cell death to augment immunity after photoirradiation. The synergistic effect of GSH‐liable TLR7/8 agonist and released immunogenic factors leads to a robust evocation of systematic immunity through promoted DC maturation and T cell infiltration. Thus, R‐NPT NP with photoirradiation achieved 99.3 % and 98.2 % growth inhibition against primary and distal tumors, respectively. [ABSTRACT FROM AUTHOR]

Homogeneous and heterogeneous reactions wherein the resulting products remain dissolved in solvents generally require complicated separation and purification process, despite the advantage of heterogeneous systems allowing retrieval of catalysts. Herein, we have developed an efficient approach for the one‐pot tandem synthesis of quinazolines, quinazolinones and benzothiadiazine 1,1‐dioxides from alcohols and amines utilizing a bifunctional bipyridinium photocatalyst with redox and Lewis acid sites using air as an oxidant. Through solvent‐modulation strategy, the photocatalytic system exhibits high performance and enables most products to separate spontaneously. Consequently, the homogeneous catalyst can be reused by direct centrifugation isolation of the products. Notably, the method is also applicable to the less active substrates, such as heterocyclic alcohols and aliphatic alcohols, and thus provides an efficient and environmentally friendly photocatalytic route with spontaneous separation of N‐heterocycles to reduce production costs and meet the needs of atomic economy and green chemistry. [ABSTRACT FROM AUTHOR]

Background: Dual transcranial direct current stimulation (tDCS) over the bilateral primary somatosensory cortex (PSC) has potential benefits in stroke. In addition, compared with traditional rehabilitation training, sensorimotor training can significantly improve the sensorimotor function of patients. However, the efficacy of dual‐tDCS combined with sensorimotor training in patients with subacute stroke is unknown. Objective: To assess whether dual‐tDCS may enhance the efficacy of sensorimotor training on the upper limb functions in patients with subacute stroke. In addition, this study aims to explore the potential clinical mechanism of this combination therapy. Methods: We randomized 52 individuals with first‐ever, unilateral subcortical stroke into the experimental group (n = 26) and the control group (n = 26). Patients in the experimental group received 20 min of dual‐tDCS over the PSC and 40 min of sensorimotor training each session, while patients in the control group received sham dual‐tDCS. The treatment cycle was a 1‐h session of therapy each day, 5 days per week for 4 weeks. The Fugl–Meyer Assessment of Upper Extremity (FMA–UE) subscale, Action Research Arm Test (ARAT), Box and Block test (BBT), Erasmus MC revised Nottingham sensory assessment scale (Em‐NSA), Neurometer sensory nerve quantitative detector (CPT), the Barthel index (BI), and Hospital Anxiety and Depression Scale (HADS) were used to assess upper limb function, activities of daily living (ADL), and mental health before and after the 4‐week treatment period. In addition, functional near‐infrared spectroscopy (fNIRS) was used to explore potential clinical brain mechanisms. Results: Both groups showed significant improvement in all clinical scales (All p < 0.05) after treatment. Compared with sham‐tDCS plus sensorimotor training, active dual‐tDCS coupled with sensorimotor training can significantly improve the FMA‐UE, ARAT, Em‐NSA‐Stereognosis, and CPT‐2K Hz. In addition, dual‐tDCS combined with sensorimotor training can significantly activate the left pre‐Motor and supplementary motor cortex (PM–SMC) and enhance the functional connection between the left somatosensory association cortex (SAC) and RPM–SMC. Furthermore, the difference of FMA–UE in the experimental group was positively correlated with the functional connectivity of RPM‐SMC‐LSAC (r = 0.815, p < 0.001). Conclusion: Dual‐tDCS over the PSC combined with sensorimotor training can improve upper limb sensory and motor dysfunction, enhance ADL, and alleviate depression and anxiety for subacute stroke patients. Our results indicated that RPM‐SMC‐LSAC may be potential therapeutic targets for dual‐tDCS in upper limb rehabilitation on stroke. [ABSTRACT FROM AUTHOR]

Summary: Eukaryotes have evolved sophisticated post‐translational modifications to regulate protein function and numerous biological processes, including ubiquitination controlled by the coordinated action of ubiquitin‐conjugating enzymes and deubiquitinating enzymes (Dubs). However, the function of deubiquitination in pathogenic fungi is largely unknown.Here, the distribution of Dubs in the fungal kingdom was surveyed and their functions were systematically characterized using the phytopathogen Fusarium graminearum as the model species, which causes devastating diseases of all cereal species world‐wide.Our findings demonstrate that Dubs are critical for fungal development and virulence, especially the ubiquitin‐specific protease 15 (Ubp15). Global ubiquitome analysis and subsequent experiments identified three important substrates of Ubp15, including the autophagy‐related protein Atg8, the mitogen‐activated protein kinase Gpmk1, and the mycotoxin deoxynivalenol (DON) biosynthetic protein Tri4. Ubp15 regulates the deubiquitination of the Atg8, thereby impacting its subcellular localization and the autophagy process. Moreover, Ubp15 also modulates the deubiquitination of Gpmk1 and Tri4. This modulation subsequently influences their protein stabilities and further affects the formation of penetration structures and the biosynthetic process of DON, respectively.Collectively, our findings reveal a previously unknown regulatory pathway of a deubiquitinating enzyme for fungal virulence and highlight the potential of Ubp15 as a target for combating fungal diseases. [ABSTRACT FROM AUTHOR]

Background: To evaluate the safety and efficacy of camrelizumab plus albumin paclitaxel and carboplatin in the neoadjuvant treatment of borderline resectable or unresectable locally advanced esophageal cancer. Methods: A retrospective analysis was conducted on 27 patients with borderline resectable or unresectable locally advanced esophageal cancer who received neoadjuvant treatment with camrelizumab plus albumin paclitaxel and carboplatin at Shanxi Cancer Hospital from January 2020 to March 2022. Of these, 20 patients underwent thoracoscopic esophagectomy after neoadjuvant treatment. Results: Overall, 88.9% (24/27) of patients completed neoadjuvant treatment. The objective response rate was 79.2% (19/24) according to the RECIST criteria. Of the 20 patients who underwent surgery, the R0 resection rate was 95%, and 35% (7/20) achieved pathological complete response (pCR). During neoadjuvant treatment, 30% (6/20) of patients experienced grade ≥3 treatment‐related adverse events (TRAEs), and 20% (4/20) had grade ≥3 postoperative complications. There were no cases of reoperation or perioperative mortality. Conclusion: Camrelizumab plus albumin paclitaxel and carboplatin were found to be safe and effective in the neoadjuvant treatment of borderline resectable or unresectable locally advanced esophageal cancer. It was observed to improve the rate of curative resection without increasing perioperative complications. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the efficacy and safety of induction immunochemotherapy followed by definitive chemoradiotherapy (CRT) for unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC). We identified unresectable stage III NSCLC patients who received induction immunochemotherapy. Overall survival (OS) and progression‐free survival (PFS) were the primary endpoints. From February 2019 to August 2022, 158 patients were enrolled. Following the completion of induction immunochemotherapy, the objective response rate (ORR) and disease control rate (DCR) were 52.5% and 83.5%, respectively. The ORR of CRT was 73.5%, representing 68.4% of the total cohort. The median PFS was 17.8 months, and the median OS was 41.9 months, significantly higher than in patients who received CRT alone (p < 0.001). Patients with concurrent CRT demonstrated markedly improved PFS (p = 0.012) and OS (p = 0.017) than those undergoing sequential CRT. Additionally, those with a programmed‐death ligand 1 (PD‐L1) expression of 50% or higher showed significantly elevated ORRs (72.2% vs. 47.2%, p = 0.011) and superior OS (median 44.8 vs. 28.6 months, p = 0.004) compared to patients with PD‐L1 expression below 50%. Hematologic toxicities were the primary severe adverse events (grade ≥ 3) encountered, with no unforeseen treatment‐related toxicities. Thus, induction immunochemotherapy followed by definitive CRT demonstrated encouraging efficacy and tolerable toxicities for unresectable LA‐NSCLC. [ABSTRACT FROM AUTHOR]

Background: The occurrence of gout is closely related to metabolism, but there is still a lack of evidence on the causal role of metabolites in promoting or preventing gout. Methods: We applied a two‐sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and gout using genome‐wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR‐Egger, weighted median, Cochran's Q test, Egger intercept test, and leave‐one‐out analysis, were performed to assess the stability and reliability of the results. We also performed a metabolic pathway analysis to identify potential metabolic pathways. Results: After screening, 486 metabolites were retained for MR analysis. After screening by IVW and sensitivity analysis, 14 metabolites were identified with causal effect on gout (P < 0.05), among which hexadecanedioate was the most significant candidate metabolite associated with a lower risk of gout (IVW OR = 0.50; 95% CI = 0.38–0.67; P = 1.65 × 10−6). Metabolic pathway analysis identified one pathway that may be associated with the disease. Conclusion: This MR study combining genomics with metabolomics provides a novel insight into the causal role of blood metabolites in the risk of gout, which implies that examination of certain blood metabolites would be a feasible strategy for screening populations with a higher risk of gout. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine BMI trajectories from birth throughout childhood, associations with health outcomes at age 13 years, and time frames during which early‐life BMI influenced adolescent health. Methods: Participants (1902, 44% male) reported perceived stress and psychosomatic symptoms and were examined for waist circumference (WC), systolic blood pressure (SBP), pulse wave velocity, and white blood cell counts (WBC). BMI trajectory was analyzed using group‐based trajectory modeling of retrospective data of weight/height from birth throughout childhood. The authors performed linear regression to assess associations between BMI trajectories and health outcomes at age 13 years, presented as estimated mean differences with 95% CI among trajectories. Results: Three BMI trajectories were identified: normal; moderate; and excessive gain. Adjusting for covariates, adolescents with excessive gain had higher WC (19.2 [95% CI: 18.4–20.0] cm), SBP (3.6 [95% CI: 2.4–4.4] mm Hg), WBC (0.7 [95% CI: 0.4–0.9] × 109/L), and stress (1.1 [95% CI: 0.2–1.9]) than adolescents with normal gain. Higher WC (6.4 [95% CI: 5.8–6.9] cm), SBP (1.8 [95% CI: 1.0–2.5] mm Hg), and stress (0.7 [95% CI: 0.1–1.2]) were found in adolescents with moderate versus normal gain. The association of early‐life BMI with SBP started around age 6 years with the excessive gain group, which was earlier than in the normal and moderate gain groups, in which it started at age 12 years. Conclusions: An excessive gain BMI trajectory from birth predicts cardiometabolic risk and stress in 13‐year‐old individuals. [ABSTRACT FROM AUTHOR]

The efficient filling of the multiple‐sized compound fillers can effectively increase the thermal conductivity of the polymer composite. However, determining the specific proportion of the compound fillers with different sizes is hard. This article proposes a random distribution model and the closest packing model to calculate the proportion of the compound fillers and prepare the epoxy composites with different compound fillers. By elaborately designing epoxy composites containing 75 wt% (48 vol%) ternary compound Al2O3 fillers, its thermal conductivity reached 1.640 W/(m·K). In addition, the volume resistivity for all prepared Al2O3/epoxy composites was higher than 1016 Ω cm. Besides, the electrical and dielectric properties of the epoxy composite with multiple‐sized compound fillers were comparable or superior to the composite with single‐sized fillers. Last but not least, the viscosity of the ternary compound Al2O3/epoxy mixture was significantly lower than the single‐sized Al2O3/epoxy mixture, which is beneficial for improving the processability of the epoxy composite. The results of this article will guide the development and utilization of epoxy composites with high thermal conductivities. Highlights: A random distribution model and the closest packing model were proposed.The thermal conductivity of the designed epoxy composites reached 1.640 W/(m·K).The compound filler can effectively improve the processability of the composite. [ABSTRACT FROM AUTHOR]

Summary: In potato, stolon swelling is a complex and highly regulated process, and much more work is needed to fully understand the underlying mechanisms.We identified a novel tuber‐specific basic helix–loop–helix (bHLH) transcription factor, StbHLH93, based on the high‐resolution transcriptome of potato tuber development.StbHLH93 is predominantly expressed in the subapical and perimedullary region of the stolon and developing tubers. Knockdown of StbHLH93 significantly decreased tuber number and size, resulting from suppression of stolon swelling. Furthermore, we found that StbHLH93 directly binds to the plastid protein import system gene TIC56 promoter, activates its expression, and is involved in proplastid‐to‐amyloplast development during the stolon‐to‐tuber transition. Knockdown of the target TIC56 gene resulted in similarly problematic amyloplast biogenesis and tuberization.Taken together, StbHLH93 functions in the differentiation of proplastids to regulate stolon swelling. This study highlights the critical role of proplastid‐to‐amyloplast interconversion during potato tuberization. [ABSTRACT FROM AUTHOR]

Aims: The effectiveness of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase‐4 inhibitors (DPP4i). Materials and Methods: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. Results: After up to 5 years of follow‐up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51–0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24–0.82). SGLT2i was related to reduced risks of AF‐related hospitalisation (HR: 0.72, 95% CI: 0.56–0.93), stroke (HR: 0.75, 95% CI: 0.60–0.94), and all‐cause death (HR: 0.33, 95% CI: 0.24–0.44). The protective effects were consistent irrespective of the concurrent use of non‐vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. Conclusions: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF‐related hospitalisation, stroke, and all‐cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i. [ABSTRACT FROM AUTHOR]

The treatment of bone defects remains a substantial clinical challenge due to the lack of spatiotemporal management of the immune microenvironment, revascularization, and osteogenic differentiation. Herein, deferoxamine (DFO)‐loaded black phosphorus nanosheets decorated by polydopamine layer are prepared (BPPD) and compounded into gelatin methacrylate/sodium alginate methacrylate (GA) hybrid hydrogel as a smart‐responsive therapeutic system (GA/BPPD) for accelerated bone regeneration. The BPPD nanocomposites served as bioactive components and near‐infrared (NIR) photothermal agents, which conferred the hydrogel with excellent NIR/pH dual‐responsive properties, realizing the stimuli‐responsive release of DFO and PO43 − during bone regeneration. Under the action of NIR‐triggered mild photothermal therapy, the GA/BPPD hydrogel exhibited a positive effect on promoting osteogenesis and angiogenesis, eliminating excessive reactive oxygen species, and inducing macrophage polarization to the M2 phenotype. More significantly, through macrophage M2 polarization‐induced osteoimmune microenvironment, this hydrogel platform could also drive functional cytokine secretion for enhanced angiogenesis and osteogenesis. In vivo experiments further demonstrated that the GA/BPPD system could facilitate bone healing by attenuating the local inflammatory response, increasing the secretion of pro‐healing factors, stimulating endogenous cell recruitment, and accelerating revascularization. Collectively, the proposed intelligent photothermal hydrogel platform provides a promising strategy to reshape the damaged tissue microenvironment for augmented bone regeneration. [ABSTRACT FROM AUTHOR]

The local structure and spin Hamiltonian parameters (SHPs) g factors (gx, gy, gz) and the hyperfine structure constants (Ax, Ay, Az) for Cu2+ doped in the LiTaO3 crystal are theoretically investigated by the perturbation formulas for a 3d9 ion under rhombically elongated octahedral based on the cluster approach. The impurity Cu2+ was assumed to occupy the host trigonally‐distorted octahedral Li+ site and experience the Jahn–Teller (JT) distortion from the host trigonal octahedral [TaO6]10− to the impurity rhombically elongated octahedral [CuO6]10−. Based on the calculations, the impurity‐ligand bond lengths parallel and perpendicular to the C2‐axis are found to be R||(≈ 2.305 Å) and R⊥ (≈ 2.112 Å) for the studied [CuO6]10− cluster, with the planar bond angle θ (≈ 78.2°). Meanwhile, the ground‐state wave function for Cu2+ center in LiTaO3 was also obtained. The calculated SHPs based on the above local lattice distortions agree well with the experimental data, and the results are discussed. [ABSTRACT FROM AUTHOR]

Patients with advanced liver cancer may benefit from 5‐fluorouracil (5‐FU) therapy. However, most of them eventually faced drug resistance, resulting in a poor prognosis. The present study aims to explore the potential mechanism of let‐7g/ABCC10 axis in the regulation of 5‐FU resistance in liver cancer cells. Huh‐7 cells were used to construct 5‐FU resistant Huh‐7/4X cells. CCK8, flow cytometry, and TUNEL staining were used to detect the characterization of Huh‐7 cells and Huh‐7/4X cells. Double luciferase report, PCR, and western blot analyses were used to detect the regulatory effects between let‐7g and ABCC10. The levels of biomarkers related to cell cycle progression and apoptosis were detected by western blot assays. The role of let‐7g in 5‐FU sensitivity of liver cancer cells was evaluated in nude mice. Compared with LX‐2 cells, the expression of let‐7g was decreased in Hep3B, HepG2, Huh‐7, and SK‐Hep1 cells, with the lowest expression in Huh‐7 cells. The sensitivity of Huh‐7 cell to 5‐FU was positively correlated with let‐7g expression. Transfection of let‐7g mimics inhibited the viability of Huh‐7/4X cells by prolonging the G1 phase, with the downregulation of ABCC10, PCNA, Cyclin D1, and CDK4. Meanwhile, let‐7g promoted apoptosis to increase 5‐FU sensitivity of Huh‐7/4X by downregulating ABCC10, Bcl‐XL as well as upregulating Bax, C‐caspase 3, and C‐PARP. Dual‐luciferase assay further confirmed that let‐7g inhibited ABCC10 expression by binding to the ABCC10 3'‐UTR region. Furthermore, let‐7g increased the sensitivity of Huh‐7/4X to 5‐FU in vitro and in vivo, which can be reversed by ABCC10 overexpression. In conclusion, let‐7g sensitized liver cancer cells to 5‐FU by downregulating ABCC10 expression. [ABSTRACT FROM AUTHOR]

Dynamic wave reflections would interfere with the laboratory observation of the soil arching under cyclic loading when a traditional trapdoor model with rigid boundaries was used. This problem would be prominent when investigating the soil arching in pile‐supported embankments where the stationary support (pile) would be small, making the rigid boundary close to the domain of interest affected by dynamic loads. To avoid dynamic wave reflections and narrow the calculation domain, soil arching within a pile‐supported embankment under cyclic loading is numerically investigated in a multi‐span segmented trapdoor model with flexible boundaries by the particle flow code (PFC). In addition, a pavement structure is included and the springs supporting the trapdoor follow a bi‐linear constitutive model. The energy‐absorbing flexible boundary at the bottom weakens the dynamic wave reflections and is in favor of passing vertical dynamic waves to compact the fill and weaken the influence of cyclic loading on the soil arching effect during the loading stage. Lateral flexible boundaries would facilitate realistically reproducing the effect of cyclic loading on the soil arching because they could consider the weakening of the plugging effect that occurs during the lateral expansion. The development of soil arches of mid‐span and side‐span are different when the load applied at the mid‐span is laterally transferred to adjacent spans by the arching effect. [ABSTRACT FROM AUTHOR]

Ecological stoichiometry facilitates the understanding of biogeochemical cycles by studying the balance among multiple elements in ecosystems. However, the spatial patterns of soil stoichiometry and their responses to land use in desertified land are unclear. In this study, we selected 525 sample points to collect topsoil (0–20 cm) samples throughout China's Horqin Sandy Land and measured soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP). We then calculated stoichiometric ratios (C:N:P). SOC (8.7 g kg−1), TN (0.9 g kg−1), and TP (0.3 g kg−1) were lower in this region than in Chinese and global terrestrial ecosystems due to aeolian desertification. SOC, TN, C:P, and N:P were significantly (p < 0.05) higher in grassland, followed by woodland, cropland, and sandy land. This sequence may result from the large number of dead roots that participate in the SOC turnover in grassland. TP was significantly higher in cropland due to fertilization. C:N did not differ significantly (p > 0.05) among grassland, woodland, and cropland because of the strong coupling relationship between SOC and TN. The values of SOC, TN, TP, C:P, and N:P in the Horqin Sandy Land were high in the north (dominated by mountain woodland and grassland) and were low in the south (dominated by desertified land). SOC, TN, and TP contents and C:N:P ratios were mainly affected by mean annual temperature (29.6%), land use (11.5%), and bulk density (11.4%) through their influence on soil microbial metabolism, litter and nutrient input, and soil structure, respectively. The results provide information on the overall changes in soil stoichiometry in the Horqin Sandy Land and its responses to land‐use changes, and can therefore guide ecological restoration in semiarid regions affected by desertification in the modern context of climate change. [ABSTRACT FROM AUTHOR]

Enterprise green human resource management (GHRM) strives to foster harmonious development among employees and the environment and among employees and the organization, as well as between employees and stakeholders, by stimulating individuals' green behavior, thereby enhancing the sustainable development performance of the enterprise. Based on the questionnaire data of 452 large enterprises in Beijing, Shanghai and Wuhan, China, from September 2021 to July 2022, and based on the optimal distinctiveness theory and stakeholder theory, this article examined the mediation mechanism and boundary conditions between GHRM and sustainable development performance of enterprises from the perspective of organizational ambidexterity. The results showed that 1) GHRM positively affected organizational ambidexterity and sustainable development performance; 2) organizational ambidexterity mediated the relationship between GHRM and sustainable development performance; 3) responsible leadership moderated the direct effect of GHRM on organizational ambidexterity; and 4) responsible leadership moderated the indirect effect of GHRM on sustainable development performance through organizational ambidexterity. At the organizational level, this study reveals the impact mechanism of GHRM on sustainable development performance and determines the boundary conditions of the impact. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes mellitus is one of the major chronic diseases, which enhances the risk of erectile dysfunction. However, the central pathological mechanisms of erectile dysfunction in diabetes mellitus patients are still unclear. Methods: Resting‐state functional magnetic resonance imaging data were acquired in 30 type‐2 diabetes mellitus, 31 type‐2 diabetes mellitus with erectile dysfunction patients, and 31 healthy controls. The measure of fractional amplitude of low‐frequency fluctuation was calculated and compared among groups. Results: Differences of fractional amplitude of low‐frequency fluctuation values were found in the left superior frontal gyrus (medial) and middle temporal gyrus among three groups. Compared with healthy controls group, type‐2 diabetes mellitus group exhibited lower fractional amplitude of low‐frequency fluctuation values in the left superior frontal gyrus (dorsolateral), anterior cingulate gyrus, calcarine fissure, and increased fractional amplitude of low‐frequency fluctuation values in the left post‐central gyrus. Compared with healthy controls group, erectile dysfunction with type‐2 diabetes mellitus group exhibited lower fractional amplitude of low‐frequency fluctuation values in the left superior frontal gyrus (medial), middle temporal gyrus, temporal middle (pole), and increased fractional amplitude of low‐frequency fluctuation values in the right post‐central gyrus. Compared with type‐2 diabetes mellitus group, erectile dysfunction with type‐2 diabetes mellitus group exhibited increased fractional amplitude of low‐frequency fluctuation values in the right median cingulum gyrus and left calcarine fissure. Conclusion: Erectile dysfunction with type‐2 diabetes mellitus patients showed functional changes in brain regions that were closely correlated with sexual dysfunction, which suggested that altered regional brain activity might be related to the pathophysiology of erectile dysfunction with type‐2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

In this case study, we focus on how hemispheric differences in the electric potential distribution in the auroral zones are related to hemispheric differences in the energetic particle precipitation that indicate the presence of field‐aligned potential drops. Utilizing data during the spring and fall equinox in 2013 and 2014 from the Defense Meteorological Satellite Program (DMSP) F16 and F17 satellites, we systematically examine simultaneous measurements of plasma drift velocity and particle precipitation in magnetically conjugate regions across the auroral zone in both hemispheres. This allows us to establish the degree to which the interhemispheric differences in ionospheric electric potential may be accounted for by field‐aligned potential drops. Thirty‐seven eligible cases examined show accelerated electron energy spectra at conjugate locations in the northern and/or southern hemispheres. Of these 37 cases, 23 show conjugate differences in electric potential that agree qualitatively with the observed electron acceleration and average energy of precipitating electrons in each hemisphere. This result suggests that the hemispheric differences in ionospheric electric potential in the auroral zone may be most frequently accounted for by field‐aligned potential drops along the magnetic flux tubes connecting conjugate points to the equatorial plane. The spatial and temporal variability of the potential distribution, electron precipitation, and magnetic field configuration could account for deviations from the normally observed situation in the remaining cases. More magnetically conjugate observations at various altitudes in both hemispheres are needed to investigate this hemispheric coupling in more detail. Key Points: 5 conjugate observations, having accelerated electrons in one hemisphere, show agreement in differences in potential and electron energy18 conjugate observations, having accelerated electrons in both hemispheres, show agreement in differences in potential and electron energyPotential drops along magnetic flux tubes connecting to the equatorial plane could account for the observed potential differences [ABSTRACT FROM AUTHOR]

Erectile Dysfunction (ED) is considered a physical and mental illness. A variety of potential associations between gut microbiota and health or disease have been found. By comparing the gut microbiota of healthy controls and ED patients, our study investigated the relationship between ED and gut microbiota. The results revealed that the ED group exhibited a significantly higher relative abundance of Bacteroides, Fusobacterium, Lachnoclostridium, Escherichia‐Shigella and Megamonas, while showing a significantly lower relative abundance of Bifidobacterium compared to the control group. The dysbiosis of gut microbiota played a role in the onset and progression of ED by influencing the gut barrier, cardiovascular system and mental health, which provided a novel perspective on understanding the pathophysiology of ED. What is more, we had identified several key gut microbiota. By combining 16S rRNA sequencing with machine learning techniques, we were able to uncover the significant value and impact of gut microbiota in the early detection of ED. [ABSTRACT FROM AUTHOR]

Summary: The conserved Spt‐Ada‐Gcn5‐Acetyltransferase (SAGA) complex controls eukaryotic transcription by modifying acetylation of histones. However, the mechanisms for this complex in regulating the transcription of target‐specific genes remain largely unknown in phytopathogenic fungi.A filamentous fungal‐specific transcription factor FgStuA was identified to interact with the SAGA complex physically. The coordinative mechanisms of FgStuA with the SAGA complex in regulating secondary metabolism and virulence were investigated in Fusarium graminearum with genetic, biochemical and molecular techniques.The transcription factor FgStuA binds to a 7‐bp cis‐element (BVTGCAK) of its target gene promoter. Under mycotoxin deoxynivalenol (DON) induction conditions, FgStuA recruits the SAGA complex into the promoter of TRI6, a core regulator of the DON biosynthesis gene cluster, leading to enhanced transcription of TRI6. During this process, we found that FgStuA is subject to acetylation by the SAGA complex, and acetylation of FgStuA plays a critical role for its enrichment in the TRI6 promoter. In addition, FgStuA together with the SAGA complex modulates fungal virulence.This study uncovers a novel regulatory mechanism of a transcription factor, which recruits and interacts with the SAGA complex to activate specific gene expression in pathogenic fungi. [ABSTRACT FROM AUTHOR]

Background and Objectives: Securing an adequate blood supply relies on accurate knowledge of blood donors and donation practices. As published evidence on Asian populations is sparse, this study aims to gather up‐to‐date information on blood donors and donation practices in Asia to assist planning and strategy development. Materials and Methods: Ten blood collection agencies (BCAs) provided 12 months' data on donors who met eligibility criteria or were deferred, as well as details of their donation practices. Body mass index and blood volumes were calculated and analysed. Results: Data on 9,599,613 donations and 154,834 deferrals from six national and four regional BCAs revealed varied donation eligibility and collection practices. Seven used haemoglobin (Hb) criteria below the World Health Organization anaemia threshold. Seven accepted donors weighing <50 kg. Data collection on the weight and height of donors and on deferrals was inconsistent, often not routine. Deferred donors appear to weigh less, with corresponding lower estimated blood volume. Conclusion: The diversity in eligibility criteria and donation practices reflects each BCA's strategy for balancing donor health with securing an adequate blood supply. Use of lower Hb criteria substantiate their appropriateness in Asia and indicate the need to define Hb reference intervals relevant to each population. We encourage routine gathering of donor weight and height data to enable blood volume estimation and local optimization of donation volumes. Blood volume estimation formulae specific for the Asian phenotype is needed. Information from this study would be useful for tailoring donation criteria of Asian donors around the world. [ABSTRACT FROM AUTHOR]

Amino acid transporters with different categories are highly expressed in intestinal epithelial cells for maintaining the essential metabolism of body. The zwitterionic property of amino acid with α‐amino and α‐carboxyl also has tremendous potential to conquer the mucus barrier. Therefore, Glu‐derived amphiphilic block polymers [i. e. poly(lactic acid)‐b‐poly(glutamine)25 (PPQ) and poly(lactic acid)‐b‐poly(glutamate)25 (PPD)] were rational designed and Glu‐derived zwitterionic micelles (PPQ‐M and PPD‐M) were further prepared toward oral delivery. In comparison with PEGylated micelles (PEG‐M), PPD‐M and PPQ‐M possessed superior mucus permeability. In addition, enhanced cellular internalization capacity was also detected in both zwitterionic micelles, which was mainly mediated by multiple amino acid transporters. The cellular uptake efficiency of PPQ‐M was obviously higher than that of PPD‐M due to the glutamine constitutional unit of PPQ‐M with higher affinity to amino acid transporters. Furthermore, the retrograde pathway played an important role in the intracellular transport (including transcytosis) of both zwitterionic micelles. Excellent villi absorption of zwitterionic micelles was observed in situ, which gave a convincing evidence for oral delivery application prospect. The results of this research demonstrated that Glu‐derived zwitterionic micelles with distinguished capacity of conquering intestinal mucosal barrier, have promising potential toward oral delivery. [ABSTRACT FROM AUTHOR]

Myosin heavy chain 16 (MYH16) may significantly affect cell cycle progression. Nevertheless, there is a lack of evidence about the clinical relevance of MYH16 upregulation in pan cancers, including lung adenocarcinoma (LUAD). MYH16 expression patterns were evaluated in various bioinformatics databases using The Cancer Genome Atlas data set. Clinical and pathological factor data were employed to risk‐stratify patients. The Kaplan–Meier plotter approach was used to estimate survival rates. Tumor immune infiltration was explored via the TIMER tool, and gene set enrichment analysis (GSEA) was used to identify the pathways involved in MYH16 upregulation. The results showed that MYH16 was abnormally upregulated in pan cancers, including LUAD. MYH16 expression induction in LUAD was found to be related to the tumor stage. Furthermore, MYH16 upregulation was correlated with LUAD development and worse overall survival, particularly in women. Notably, MYH16 overexpression in LUAD tissues corresponded to the amount of immune infiltration in the tumor. Additionally, univariate Cox hazard regression analysis revealed that MYH16 may be an independent prognostic indicator for LUAD. Furthermore, a nomogram was constructed according to MYH16 expression and clinical characteristics. BMP6 expression deficiency may be a key factor contributing to MYH16 upregulation in LUAD. Finally, GSEA demonstrated that MYH16 might mediate meiosis and gene silencing through RNA signaling pathways. This study, for the first time, showed that MYH16 upregulation in LUAD is associated with various risk factors, increased cancer aggressiveness, enhanced infiltration of tumor immune cells, and reduced survival rates. [ABSTRACT FROM AUTHOR]

Excess iodine will trigger the occurrence of autoimmune thyroiditis (AIT), and programmed death‐1 (PD‐1)/programmed death ligand (PD‐L) will also contribute to the development of AIT. The purpose of this study was to explore the role that negative regulatory signals mediated by PD‐1/PD‐L play in the development of spontaneous autoimmune thyroiditis (SAT) in NOD.H‐2h4 mice when they are exposed to iodine. Programmed death ligand 1 (PD‐L1) antibody was administered intraperitoneally to NOD.H‐2h4 mice. The relevant indicators were determined by flow cytometry, real‐time quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, immunohistochemistry, pathological hematoxylin and eosin staining, and arsenic–cerium catalytic spectrophotometry. Results showed that the level of urinary iodine, the level of thyroid lymphocyte infiltration, the level of thyroglobulin antibodies (TgAb) and interferon (IFN‐γ)/tumor necrosis factor (TNF‐α)/interleukin (IL‐2)/IL‐17, and the relative expression of PD‐1/PD‐L1/programmed death‐2 (PD‐L2) increased with the intervention of excess iodine. After the intervention of the PD‐L1 antibody, the expression of PD‐1/PD‐L1/PD‐L2 in different degrees was inhibited, but the level of thyroid lymphocyte infiltration and serum TgAb/IFN‐γ/TNF‐α/ IL‐2/IL‐17 did not decrease. Collectively, although PD‐1/PD‐L participates in the occurrence of SAT and induces inflammation, administration of the PD‐L1 antibody does not effectively improve the pathological process of SAT. More research is needed to determine whether PD‐1/PD‐L intervention can treat autoimmune thyroid disease. [ABSTRACT FROM AUTHOR]