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Chemical short-range-order has been widely noticed to dictate the electrochemical properties of Li-excess cation-disordered rocksalt oxides, a class of cathode based on earth abundant elements for next-generation high-energy-density batteries. Existence of short-range-order is normally evidenced by a diffused intensity pattern in reciprocal space, however, derivation of local atomic arrangements of short-range-order in real space is hardly possible. Here, by a combination of aberration-corrected scanning transmission electron microscopy, electron diffraction, and cluster-expansion Monte Carlo simulations, we reveal the short-range-order is a convolution of three basic types: tetrahedron, octahedron, and cube. We discover that short-range-order directly correlates with Li percolation channels, which correspondingly affects Li transport behavior. We further demonstrate that short-range-order can be effectively manipulated by anion doping or post-synthesis thermal treatment, creating new avenues for tailoring the electrochemical properties. Our results provide fundamental insights for decoding the complex relationship between local chemical ordering and properties of crystalline compounds.

Abstract Liver fibrosis, a chronic and long-term disease, can develop into hepatocellular carcinoma (HCC) and ultimately lead to liver failure. Early diagnosis and effective treatment still face significant challenges. Liver inflammation leads to liver fibrosis through continuous activation of hepatic stellate cells (HSCs) and the accumulation of immune cells. Intracellular communication among various immune cells is important for mediating the inflammatory response during fibrogenesis. Extracellular vesicles (EVs), which are lipid bilayer membrane-enclosed particles naturally secreted by cells, make great contributions to cell-cell communication and the transport of bioactive molecules. Nearly all the cells that participate in liver fibrosis release EVs loaded with lipids, proteins, and nucleic acids. EVs from hepatocytes, immune cells and stem cells are involved in mediating the inflammatory microenvironment of liver fibrosis. Recently, an increasing number of extracellular vesicle-based clinical applications have emerged, providing promising cell-free diagnostic and therapeutic tools for liver fibrosis because of their crucial role in immunomodulation during pathogenesis. The advantages of extracellular vesicle-based therapies include stability, biocompatibility, low cytotoxicity, and minimal immunogenicity, which highlight their great potential for drug delivery and specific treatments for liver fibrosis. In this review, we summarize the complex biological functions of EVs in the inflammatory response in the pathogenesis of liver fibrosis and evaluate the potential of EVs in the diagnosis and treatment of liver fibrosis.

Abstract Hexagonal boron nitride (hBN), as one of the few two-dimensional insulators, holds strategic importance for advancing post-silicon electronic devices and circuits. Achieving wafer-scale, high-quality monolayer hBN is essential for its integration into the semiconductor industry. However, the physical mechanisms behind the chemical vapor deposition (CVD) synthesis of hBN are not yet well understood. Investigating morphology engineering is critical for developing scalable synthetic techniques for the large-scale production of high-quality hBN. In this study, we explored the underlying mechanisms of the CVD growth process of hBN and found that the involvement of a small amount of oxygen effectively modulates the shape of the single-crystal hBN islands. By tuning the oxygen content in the CVD system, we synthesized well-aligned hexagonal hBN islands and achieved a continuous, high-quality single-crystal monolayer hBN film through the merging of these hexagonal islands on conventional single-crystal metal-foil substrates. Density functional theory was used to study the edges of hBN monolayers grown in an oxygen-assisted environment, providing insights into the formation mechanism. This study opens new pathways for controlling the island shape of 2D materials and establishes a foundation for the industrial-scale production of high-quality, large-area, single-crystal hBN.

Abstract Background X-prolyl aminopeptidase 3 (XPNPEP3) mutations are known to cause nephronophthisis-like nephropathy-1 (NPHPL1), a rare autosomal-recessive kidney disease characterized by progressive kidney failure and cystic kidney disease in childhood. The full phenotypic spectrum associated with mutations in XPNPEP3 is not fully elucidated. Case presentation A 13-year-old Chinese female patient with intellectual disability presented with a 2-year history of convulsions and fatigue, with a recent episode of swelling, breathlessness, and nocturnal dyspnea lasting 10 days. The patient was diagnosed with heart failure and kidney failure. Whole exome sequencing revealed a homozygous c.970–2 A > G mutation in XPNPEP3 associated with severe cardiac dysfunction and neurological symptoms, including epilepsy and intellectual disability. Notably, kidney ultrasound did not reveal the typical changes of NPHPL1, and kidney failure was hypothesized to be secondary to cardiac dysfunction rather than primary kidney pathology. Conclusions This case suggests the possible association of additional phenotypic features associated with XPNPEP3 mutations, emphasizing the need for further investigation into the heterogeneous clinical presentations associated with XPNPEP3 mutations. The findings highlight the importance of considering alternative phenotypes in patients with genetic mutations traditionally associated with specific diseases. Segregation and functional analyses are necessary to determine causality between the c.970–2 A > G XPNPEP3 mutation and disease.

Abstract Background Driving after cannabis use (DACU) is associated with increased risk of motor vehicle collisions. As cannabis legalization expands, DACU is emerging as a major public safety concern. Attitudes have a significant impact on behavioural decision making. As such, understanding the degree to which people have favorable or unfavorable evaluations of DACU is an important first step for informing prevention efforts. This systematic review summarizes existing evidence on attitudes toward DACU, their association with actual or intended DACU, and changes in attitudes following legalization of recreational cannabis. Methods Four electronic databases (MEDLINE, EMBASE, PsycINFO, and TRID) were searched for studies that reported attitudes or changes in attitudes toward DACU published between their inception dates and February 26 2024. A total of 1,099 records were retrieved. Studies were analyzed using an inductive thematic synthesis approach. Results Seventy studies from seven countries originating predominantly from the United States and Canada met inclusion criteria. Thematic analysis identified six themes. (I) Attitudes toward the safety and acceptability of DACU are mixed; participants in 35 studies predominantly expressed negative attitudes toward DACU (e.g., DACU is dangerous, affects driving ability, and increases crash risk). However, 20 studies reported opposing views. (II) Attitudes toward DACU vary by age, sex/gender, and cannabis use frequency; youth, men, and frequent cannabis users tended to view DACU more favorably than older participants, women, and occasional or non-users. (III) Attitudes toward DACU are associated with past DACU and intention to DACU. (IV) DACU is viewed more favorably than driving after drinking alcohol. (V) The relationship between legal status of recreational cannabis and attitudes toward DACU is unclear. (VI) Perceived risk of apprehension for DACU is low to moderate. Conclusions This review found that perceptions of DACU are primarily negative but mixed. Findings suggest that attitudes toward DACU are important targets for interventions to reduce this behaviour.

The issue of opacity within data-driven artificial intelligence (AI) algorithms has become an impediment to these algorithms’ extensive utilization, especially within sensitive domains concerning health, safety, and high profitability, such as chemical engineering (CE). In order to promote reliable AI utilization in CE, this review discusses the concept of transparency within AI utilizations, which is defined based on both explainable AI (XAI) concepts and key features from within the CE field. This review also highlights the requirements of reliable AI from the aspects of causality (i.e., the correlations between the predictions and inputs of an AI), explainability (i.e., the operational rationales of the workflows), and informativeness (i.e., the mechanistic insights of the investigating systems). Related techniques are evaluated together with state-of-the-art applications to highlight the significance of establishing reliable AI applications in CE. Furthermore, a comprehensive transparency analysis case study is provided as an example to enhance understanding. Overall, this work provides a thorough discussion of this subject matter in a way that—for the first time—is particularly geared toward chemical engineers in order to raise awareness of responsible AI utilization. With this vital missing link, AI is anticipated to serve as a novel and powerful tool that can tremendously aid chemical engineers in solving bottleneck challenges in CE.

Ulcerative colitis is a chronic inflammatory bowel disease, and its incidence is increasing year by year in China. Current drug treatments have side effects, so the use of probiotics to regulate intestinal microbiota is emerging as an intervention method. Numerous studies have shown that bifidobacteria have a good clinical effect in alleviating symptoms of ulcerative colitis. However, the underlying mechanism has not been systematically elucidated. In recent years, with continuous breakthroughs in research on multi-omics, the gut microbiota, the gut-brain axis, and the gut-liver axis, significant progress has been made in understanding the action mechanism of bifidobacteria in alleviating ulcerative colitis. This article reviews the latest progress that has been made in the research and application of bifidobacteria in alleviating ulcerative colitis in the past decade, and introduces bifidobacteria alleviating ulcerative colitis, with a focus on the underlying mechanism. This review reports that bifidobacteria alleviates ulcerative colitis mainly by regulating the structure of the intestinal microbiota, restoring intestinal barrier function, improving intestinal immune response, regulating intestinal purine metabolism, inhibiting oxidative stress, and providing energy for the intestinal epithelium. It is our hope that this review will provide a reference for further elucidating the regulatory mechanism of bifidobacteria on life and health as well as for furthering the application and promotion of probiotic preparation.

Abstract Safe and effective vaccines against COVID-19 for children and adolescents are needed. This international multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial assessed the efficacy, immunogenicity, and safety of CoronaVac® in children and adolescents (NCT04992260). The study was carried out in Chile, South Africa, Malaysia, and the Philippines. The enrollment ran from September 10, 2021 to March 25, 2022. For efficacy assessment, the median follow-up duration from 14 days after the second dose was 169 days. A total of 11,349 subjects were enrolled. Two 3-μg injections of CoronaVac® or placebo were given 28 days apart. The primary endpoint was the efficacy of the CoronaVac®. The secondary endpoints were the immunogenicity and safety. The vaccine efficacy was 21.02% (95% CI: 1.65, 36.67). The level of neutralizing antibody in the vaccine group was significantly higher than that in the placebo group (GMT: 390.80 vs. 62.20, P

Abstract Objective In this study, we investigated the efficacy of percutaneous poking reduction and Kirschner wire fixation in older children with irreducible supracondylar flexion-type fractures of the humerus. Methods This retrospective investigation included 27 children, comprising 15 males and 12 females, aged between 10 years and 3 months to 14 years and 11 months, all diagnosed with a flexion-type supracondylar fracture of the humerus within one week of trauma. All patients underwent surgery under general anesthesia. Following unsuccessful manual reduction, percutaneous poking reduction with Kirschner wires was performed under C-arm fluoroscopy to achieve fracture reduction. Following successful reduction, three 2.0 mm Kirschner wires were inserted in a cross pattern to secure the fracture ends. Postoperatively, the elbow joint was immobilized in a functional position with a plaster cast for four weeks. Results Follow-up in the outpatient department ranged from 9 to 36 months. Clinical functional assessment using Flynn’s criteria rated 24 cases as excellent, 2 as good, and 1 as fair, yielding an overall efficacy of 96.3%. No cases of fracture re-displacement, fracture fragment necrosis, or other complications such as nonunion, iatrogenic nerve injury, myositis ossificans, or long-term elbow joint dysfunction were observed during the postoperative follow-up. Conclusion The percutaneous poking reduction and Kirschner wire fixation technique is a simple and reliable procedure for treating irreducible flexion-type supracondylar fractures of the humerus in older children, with minimal trauma. This technique offers substantial stability for the fracture and results in excellent long-term recovery of joint function.

Abstract Mild sleep deprivation is widespread in many societies worldwide. Electroencephalography (EEG) microstate analysis provides information on spatial and temporal characteristics of resting brain network, serving as an indicator of neurophysiological activities at rest. This study seeks to investigate potential neural markers in EEG following mild sleep deprivation of a single night using EEG microstate analysis. Six-minute resting EEG was conducted on thirty healthy adults within 6 hours of waking in the morning and after at least 18 h of sleep deprivation. Translated and validated Malay language Karolinska Sleepiness Scale was used to assess the participants’ degree of sleepiness. Microstate characteristics analysis was conducted on the final 24 subjects based on four standard microstate maps. Microstate C shows a significant increase in mean duration, coverage and occurrence, while microstate D has significantly higher occurrence after sleep deprivation. This study demonstrates notable changes in resting state EEG microstates following mild sleep deprivation. Present findings deepen our understanding of the brain's spatiotemporal dynamics under this condition and suggest the potential utility of neural markers in this domain as components of composite markers for sleep deprivation.

Abstract Benefiting from the complex system composed of various constituents, medicament portions, species, and places of origin, traditional Chinese medicine (TCM) possesses numerous customizable and adaptable efficacies in clinical practice guided by its theories. However, these unique features are also present challenges in areas such as quality control, screening active ingredients, studying cell and organ pharmacology, and characterizing the compatibility between different Chinese medicines. Drawing inspiration from the holistic concept, an integrated strategy and pattern more aligned with TCM research emerges, necessitating the integration of novel technology into TCM modernization. The microfluidic chip serves as a powerful platform for integrating technologies in chemistry, biology, and biophysics. Microfluidics has given rise to innovative patterns like lab-on-a-chip and organoids-on-a-chip, effectively challenging the conventional research paradigms of TCM. This review provides a systematic summary of the nature and advanced utilization of microfluidic chips in TCM, focusing on quality control, active ingredient screening/separation, pharmaceutical analysis, and pharmacological/toxicological assays. Drawing on these remarkable references, the challenges, opportunities, and future trends of microfluidic chips in TCM are also comprehensively discussed, providing valuable insights into the development of TCM.

Abstract Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9+CD55low APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9+CD55low APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male.

Abstract The semiconductors industry has put its eyes on two-dimensional (2D) materials produced by chemical vapour deposition (CVD) because they can be grown at the wafer level with small thickness fluctuations, which is necessary to build electronic devices and circuits. However, CVD-grown 2D materials can contain significant amounts of lattice distortions, which degrades the performance at the device level and increases device-to-device variability. Here we statistically analyse the quality of commercially available CVD-grown hexagonal boron nitride (h-BN) from the most popular suppliers. h-BN is of strategic importance because it is one of the few insulating 2D materials, and can be used as anti-scattering substrate and gate dielectric. We find that the leakage current and electrical homogeneity of all commercially available CVD h-BN samples are significantly worse than those of mechanically exfoliated h-BN of similar thickness. Moreover, in most cases the properties of the CVD h-BN samples analysed don’t match the technical specifications given by the suppliers, and the sample-to-sample variability is unsuitable for the reproducible fabrication of capacitors, transistors or memristors in different batches. In the short term, suppliers should try to provide accurate sample specifications matching the properties of the commercialized materials, and researchers should keep such inaccuracies in mind; and in the middle term suppliers should try to reduce the density of defects to enable the fabrication of high-performance devices with high reliability and reproducibility.

Trace metals play a vital role in a variety of biological processes, but excessive amounts can be toxic and are receiving increasing attention. Trace metals in the environment are released from natural sources, such as rock weathering, volcanic eruptions, and other human activities, such as industrial emissions, mineral extraction, and vehicle exhaust. Lifestyle, dietary habits and environmental quality are the main sources of human exposure to trace metals, which play an important role in inducing human reproductive infertility. The purpose of this review is to summarize the distribution of various trace metals in oocyte and to identify the trace metals that may cause oocyte used in the design and execution of toxicological studies.

Abstract The prosperous evolution of conductive hydrogel‐based skin sensors is attracting tremendous attention nowadays. Nevertheless, it remains a great challenge to simultaneously integrate excellent mechanical strength, desirable electrical conductivity, admirable sensing performance, and brilliant healability in hydrogel‐based skin sensors for high‐performance diagnostic healthcare sensing and wearable human‐machine interface, as well as robust photothermal performance for promptly intelligent photothermal therapy followed by the medical diagnosis and superior electromagnetic interference (EMI) shielding performance for personal protection. Herein, a flexible healable MXene hydrogel‐based skin sensor is prepared through a delicate combination of MXene (Ti3C2Tx) nanosheets network with the polymeric network. The as‐prepared skin sensor is featured with significantly enhanced mechanical, conducting, and sensing performances, along with robust self‐healability, good biocompatibility, and reliable injectability, enabling ultrasensitive human motion monitoring and teeny electrophysiological signals sensing. As a frontier technology in artificial intelligence, machine learning can facilitate to efficiently and precisely identify the electromyography signals produced by various human motions (such as variable finger gestures) with up to 99.5% accuracy, affirming the reliability of the machine learning‐assisted gesture identification with great potential in smart personalized healthcare and human‐machine interaction. Moreover, the MXene hydrogel‐based skin sensor displays prominent EMI shielding performance, demonstrating the great promise of effective personal protection.

ObjectiveWeight-control compensatory behaviors appear to be a commonly utilized strategy for health management. Individuals engaging in such behaviors believe that the negative consequences from unhealthy behaviors will be neutralized by the positive consequences of healthy behaviors. Existing research has not reached a consensus on whether such behaviors are beneficial to health. This review aims to (1) summarize the patterns of weight-control compensatory health behaviors in different populations, (2) highlight correlates, predictors, and consequences of compensatory health behaviors, and (3) identify gaps for future research.MethodThis review identified existing literature using online databases, CINAHL and PubMed. Primary research articles published after 2000 with non-clinical participants of 12 years or older who engaged in compensatory behaviors for weight control purposes were selected. Descriptive statistics were extracted from 35 studies.ResultsDifferent patterns for weight-control compensatory behaviors emerged between the female and male sexes. Meanwhile, no clear association of such behaviors was found across weight status. Studies reviewed also highlighted three main areas of compensatory behaviors for weight management, namely dietary behaviors, physical activity, and alcohol consumption. Weight-control compensatory behaviors had significant negative correlations with mental health indicators, such as psychosocial functioning, emotional differentiation ability, and body esteem.ConclusionWeight-control compensatory behaviors may be a widely used weight management strategy and can be presented in diverse ways. Although believed to be promoting health, such behaviors appear to be associated with poor psychological well-being. This emerging topic warrants more in-depth investigation to establish the direction of causation. Future research may investigate the relationship between weight-control compensatory behaviors and various aspects of health over longer time periods, examine the engagement of multiple weight-control compensatory behaviors, and focus on high-risk populations.

BackgroundVaricella is a common infectious disease and a growing public health concern in China, with increasing outbreaks in Wuxi. Analyzing the correlation between climate factors and varicella incidence in Wuxi is crucial for guiding public health prevention efforts. ObjectiveThis study examines the impact of meteorological variables on varicella incidence in Wuxi, eastern China, from 2010 to 2019, offering insights for public health interventions. MethodsWe collected daily meteorological data and varicella case records from January 1, 2010, to December 31, 2019, in Wuxi, China. Generalized cross-validation identified optimal lag days by selecting those with the lowest score. The relationship between meteorological factors and varicella incidence was analyzed using Poisson generalized additive models and segmented linear regression. Subgroup analyses were conducted by gender and age. ResultsThe study encompassed 64,086 varicella cases. Varicella incidence in Wuxi city displayed a bimodal annual pattern, with peak occurrences from November to January of the following year and lower peaks from May to June. Several meteorological factors influencing varicella risk were identified. A decrease of 1°C when temperatures were ≤20°C corresponded to a 1.99% increase in varicella risk (95% CI 1.57-2.42, P

Abstract Background Various epigenetic regulations systematically govern gene expression in cells involving various biological processes. Dysregulation of the epigenome leads to aberrant transcriptional programs and subsequently results in diseases, such as cancer. Therefore, comprehensive profiling epigenomics is essential for exploring the mechanisms underlying gene expression regulation during development and disease. Methods In this study, we developed single‐cell chromatin proteins and accessibility tagmentation (scCPA‐Tag), a multi‐modal single‐cell epigenetic profile capturing technique based on barcoded Tn5 transposases and a droplet microfluidics platform. scCPA‐Tag enables the simultaneous capture of DNA profiles of histone modification and chromatin accessibility in the same cell. Results By applying scCPA‐Tag to K562 cells and a hepatocellular carcinoma (HCC) sample, we found that the silence of several chromatin‐accessible genes can be attributed to lysine‐27‐trimethylation of the histone H3 tail (H3K27me3) modification. We characterized the epigenetic features of the tumour cells and different immune cell types in the HCC tumour tissue by scCPA‐Tag. Besides, a tumour cell subtype (C2) with more aggressive features was identified and characterized by high chromatin accessibility and a lower abundance of H3K27me3 on tumour‐promoting genes. Conclusions Our multi‐modal scCPA‐Tag provides a comprehensive approach for exploring the epigenetic landscapes of heterogeneous cell types and revealing the mechanisms of gene expression regulation during developmental and pathological processes at the single‐cell level. Highlights scCPA‐Tag offers a highly efficient and high throughput technique to simultaneously profile histone modification and chromatin accessibility within a single cell. scCPA‐Tag enables to uncover multiple epigenetic modification features of cellular compositions within tumor tissues. scCPA‐Tag facilitates the exploration of the epigenetic landscapes of heterogeneous cell types and provides the mechanisms governing gene expression regulation.

BackgroundPolycystic ovary syndrome (PCOS) can lead to infertility and increase the risk of endometrial cancer. Analyzing the macrophage polarization characteristics in ovarian tissues of PCOS is crucial for clinical treatment.MethodsWe obtained 13 PCOS and nine control ovarian samples from the CEO database and analyzed differentially expressed genes (DEGs). Macrophage polarization-related genes (MPRGs) were sourced from the GeneCards and MSigDB databases. Intersection of DEGs with MPRGs identified DEGs associated with macrophage polarization (MPRDEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein–protein interaction (PPI) Network analysis were conducted on MPRDEGs. Moreover, the top 10 genes from three algorithms were identified as the hub genes of MPRGs. In addition, miRNAs, transcription factors (TFs), and drugs were retrieved from relevant databases for regulatory network analysis of mRNA-miRNA, mRNA-TF, and mRNA-Drug interactions. Immune cell composition analysis between the PCOS and control groups was performed using the CIBERSORT algorithm to calculate correlations across 22 immune cell types.ResultsA total of 13 PCOS samples and nine control ovarian samples were obtained in this study. We identified 714 DEGs between the two groups, with 394 up-regulated and 320 down-regulated. Additionally, we identified 774 MPRGs, from which we derived 30 MPRDEGs by intersecting with DEGs, among which 21 exhibited interaction relationships. GO and KEGG analyses revealed the enrichment of MPRDEGs in five biological processes, five cell components, five molecular functions, and three biological pathways. Immune infiltration analysis indicated a strong positive correlation between activated nature killer (NK) cells and memory B cells, while neutrophils and monocytes showed the strongest negative correlation. Further investigation of MPRDEGs identified nine hub genes associated with 41 TFs, 82 miRNAs, and 44 drugs or molecular compounds. Additionally, qRT-PCR results demonstrated overexpression of the CD163, TREM1, and TREM2 genes in ovarian tissues from the PCOS group.ConclusionThis study elucidated the polarization status and regulatory characteristics of macrophages in ovarian tissues of the PCOS subjects, confirming significant overexpression of CD163, TREM1, and TREM2. These findings contribute to a deeper understanding of the pathogenesis of PCOS.

IntroductionElectrical stimulation of the brain has shown promising prospects in treating various brain diseases. Although biphasic pulse stimulation remains the predominant clinical approach, there has been increasing interest in exploring alternative stimulation waveforms, such as sinusoidal stimulation, to improve the effectiveness of brain stimulation and to expand its application to a wider range of brain disorders. Despite this growing attention, the effects of sinusoidal stimulation on neurons, especially on their nonlinear firing characteristics, remains unclear.MethodsTo address the question, 50 Hz sinusoidal stimulation was applied on Schaffer collaterals of the rat hippocampal CA1 region in vivo. Single unit activity of both pyramidal cells and interneurons in the downstream CA1 region was recorded and analyzed. Two fractal indexes, namely the Fano factor and Hurst exponent, were used to evaluate changes in the long-range correlations, a manifestation of nonlinear dynamics, in spike sequences of neuronal firing.ResultsThe results demonstrate that sinusoidal electrical stimulation increased the firing rates of both pyramidal cells and interneurons, as well as altered their firing to stimulation-related patterns. Importantly, the sinusoidal stimulation increased, rather than decreased the scaling exponents of both Fano factor and Hurst exponent, indicating an increase in the long-range correlations of both pyramidal cells and interneurons.DiscussionThe results firstly reported that periodic sinusoidal stimulation without long-range correlations can increase the long-range correlations of neurons in the downstream post-synaptic area. These results provide new nonlinear mechanisms of brain sinusoidal stimulation and facilitate the development of new stimulation modes.

Abstract Tremendous popularity is observed for multifunctional flexible electronics with appealing applications in intelligent electronic skins, human–machine interfaces, and healthcare sensing. However, the reported sensing electronics, mostly can hardly provide ultrasensitive sensing sensitivity, wider sensing range, and robust cycling stability simultaneously, and are limited of efficient heat conduction out from the contacted skin interface after wearing flexible electronics on human skin to satisfy thermal comfort of human skin. Inspired from the ultrasensitive tactile perception microstructure (epidermis/spinosum/signal transmission) of human skin, a flexible comfortably wearable ultrasensitive electronics is hereby prepared from thermal conductive boron nitride nanosheets‐incorporated polyurethane elastomer matrix with MXene nanosheets‐coated surface microdomes as epidermis/spinosum layers assembled with interdigitated electrode as sensing signal transmission layer. It demonstrates appealing sensing performance with ultrasensitive sensitivity (≈288.95 kPa−1), up to 300 kPa sensing range, and up to 20 000 sensing cycles from obvious contact area variation between microdome microstructures and the contact electrode under external compression. Furthermore, the bioinspired electronics present advanced thermal management by timely efficient thermal dissipation out from the contacted skin surface to meet human skin thermal comfort with the incorporated thermal conductive boron nitride nanosheets. Thus, it is vitally promising in wearable artificial electronic skins, intelligent human‐interactive sensing, and personal health management.

Summary: Background: Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30–70 years with an office blood pressure (BP) of

Lithium-excess, cation-disordered rocksalt (DRX) materials have been subject to intense scrutiny and development in recent years as potential cathode materials for Li-ion batteries. Despite their compositional flexibility and high initial capacity, they suffer from poorly understood parasitic degradation reactions at the cathode-electrolyte interface. These interfacial degradation reactions deteriorate both the DRX material and electrolyte, ultimately leading to capacity fade and voltage hysteresis during cycling. In this work, differential electrochemical mass spectrometry (DEMS) and titration mass spectrometry are combined to quantify the extent of bulk redox and surface degradation reactions for a set of Mn2+/4+-based DRX oxyfluorides during initial cycling with a high-voltage charging cutoff (4.8 V vs Li/Li+). Increasing the fluorine content from 7.5 to 33.75% is shown to diminish oxygen redox and suppresses high-voltage O2 evolution from the DRX surface. Additionally, electrolyte degradation processes resulting in the formation of both gaseous species and electrolyte-soluble protic species are observed. Subsequently, DEMS is paired with a fluoride-scavenging additive to demonstrate that increasing fluorine content leads to increased dissolution of fluorine from the DRX material into the electrolyte. Finally, a suite of ex situ spectroscopy techniques (X-ray photoelectron spectroscopy, inductively coupled plasma optical emission spectroscopy, and solid-state nuclear magnetic resonance spectroscopy) are employed to study the change in DRX composition during charging, revealing the dissolution of manganese and fluorine from the DRX material at high voltages. This work provides insight into the degradation processes occurring at the DRX-electrolyte interface and points toward potential routes of interfacial stabilization.

Introduction This study aimed to investigate the effects of nicotine on the activation of pancreatic stellate cells (PSCs) and pancreatic fibrosis in chronic pancreatitis (CP), along with its underlying molecular mechanisms. Methods This was an in vivo and in vitro study. In vitro, PSCs were cultured to study the effects of nicotine on their activation and oxidative stress. Transcriptome sequencing was performed to identify potential signaling pathways involved in nicotine action. And the impact of nicotine on mitochondrial Ca2+ levels and Ca2+ transport-related proteins in PSCs was analyzed. The changes in nicotine effects were observed after the knockdown of the mitochondrial calcium uniporter (MCU) in PSCs. In vivo experiments were conducted using a mouse model of CP to assess the effects of nicotine on pancreatic fibrosis and oxidative stress in mice. The alterations in nicotine effects were observed after treatment with the MCU inhibitor Ru360. Results In vitro experiments demonstrated that nicotine promoted PSCs activation, characterized by increased cell proliferation, elevated α-SMA and collagen expression. Nicotine also increased the production of reactive oxygen species (ROS) and cellular malondialdehyde (MDA), exacerbating oxidative stress damage. Transcriptome sequencing revealed that nicotine may exert its effects through the calcium signaling pathway, and it was verified that nicotine elevated mitochondrial Ca2+ levels and upregulated MCU expression. Knockdown of MCU reversed the effects of nicotine on mitochondrial calcium homeostasis, improved mitochondrial oxidative stress damage and structural dysfunction, thereby alleviating the activation of PSCs. In vivo validation experiments showed that nicotine significantly aggravated pancreatic fibrosis in CP mice, promoted PSCs activation, exacerbated pancreatic tissue oxidative stress, and increased MCU expression. However, treatment with Ru360 significantly mitigated these effects. Conclusions This study confirms that nicotine upregulates the expression of MCU, leading to mitochondrial calcium overload and exacerbating oxidative stress in PSCs, and ultimately promoting PSCs activation and exacerbating pancreatic fibrosis in CP.

Abstract Background Zhu-Tokita-Takenouchi-Kim syndrome (ZTTK syndrome) is a severe multi-systemic developmental disorder, caused by variants in the SON gene. A patient diagnosed with ZTTK syndrome who carried a de novo SON mutation and exhibited recurrent myocardial injury was described in this case. Case presentation A 7-year-old girl was admitted to the Cardiology Department of Beijing Children’s Hospital in November 2019 due to myocardial injury following respiratory infection. She displayed elevated myocardial enzymes and severe T-wave changes on electrocardiogram. Over the past three years, she had experienced myocardial injury on three occasions. Additionally, she exhibited intellectual disability, congenital amblyopia, and dysmorphic facial features. Genetic analysis revealed a de novo heterozygous mutation c.3852_3856delGGTAT in the SON gene, which was confirmed by Sanger sequencing of her parents. She received anti-infection treatment and was administered metoprolol orally. Her condition was stable at the time of discharge. Over a 42-month follow-up period at the outpatient clinic, she complained intermittent fatigue and palpitation. Conclusions The identified SON mutation, which plays a crucial role in heart development and mitochondrial function, may be associated with an increased susceptibility to myocardial injury or cardiomyopathy. This case report contributes novel insights into this rare condition and suggests the expansion of the ZTTK syndrome phenotype.

A 57-year-old lady presented with symptoms of intestinal obstruction preceded by a 2-day history of lower abdomen pain. Clinically, she had a distended abdomen with tenderness in her lower abdomen. Laboratory investigations were unremarkable. An abdominal radiograph showed a dilated small bowel with no extensive bowel gas. A computed tomography (CT) scan showed suspected intestinal obstruction secondary to herniation into the right broad ligament. The decision was made to proceed with surgery, and the intraoperative results confirmed the CT results. The literature review is outlined here, and this instance illustrates a surprising discovery.

From 2003 to 2009, China, Japan, North Korea, Russia, South Korea, and the United States engaged in a series of multilateral negotiations to address North Korea’s nuclear program. On September 19, 2005, the six participants achieved a “gold standard” agreement on denuclearization. North Korea agreed to relinquish all nuclear weapons, abstain from deploying nuclear weapons, and rejoin the Treaty on the Non-Proliferation of Nuclear Weapons (NPT), as well as adhere to International Atomic Energy Agency (IAEA) safeguards. The United States affirmed its lack of nuclear weapons on the Korean Peninsula and expressed no intention of attacking or invading the Democratic People’s Republic of Korea (DPRK) with nuclear or conventional weapons. China, Japan, Russia, South Korea, and the United States concurred to provide energy assistance to the DPRK. Furthermore, the agreement established the principle of “commitment for commitment, action for action,” which holds significance for the spirit of future engagement. The prevailing impasse in resolving the nuclear issue on the Korean Peninsula prompts the inquiry of a possible negotiation model. This paper uses the Harvard negotiation method to examine a zone of possible agreement (ZOPA) between China, North Korea, Russia, and the United States, which culminated in the September 19, 2005 Six Party Talks agreement addressing the nuclear issue on the Korean Peninsula. The first section of the article is devoted to scrutinizing the Zone of Possible Agreement (ZOPA), which facilitated the 2005 agreement. Based on the acquired insights, the second section assesses the prospects for implementing the 2005 Joint Statement in the current context. This section also concentrates on identifying a ZOPA under current conditions, taking into account past experiences and lessons learned from past negotiations.

Abstract Homology Directed Repair (HDR) enables precise genome editing, but the implementation of HDR-based therapies is hindered by limited efficiency in comparison to methods that exploit alternative DNA repair routes, such as Non-Homologous End Joining (NHEJ). In this study, we develop a functional, pooled screening platform to identify protein-based reagents that improve HDR in human hematopoietic stem and progenitor cells (HSPCs). We leverage this screening platform to explore sequence diversity at the binding interface of the NHEJ inhibitor i53 and its target, 53BP1, identifying optimized variants that enable new intermolecular bonds and robustly increase HDR. We show that these variants specifically reduce insertion-deletion outcomes without increasing off-target editing, synergize with a DNAPK inhibitor molecule, and can be applied at manufacturing scale to increase the fraction of cells bearing repaired alleles. This screening platform can enable the discovery of future gene editing reagents that improve HDR outcomes.

Abstract All-polymer solar cells (all-PSCs) offer improved morphological and mechanical stability compared with those containing small-molecule-acceptors (SMAs). They can be processed with a broader range of conditions, making them desirable for printing techniques. In this study, we report a high-performance polymer acceptor design based on bithiazole linker (PY-BTz) that are on par with SMAs. We demonstrate that bithiazole induces a more coplanar and ordered conformation compared to bithiophene due to the synergistic effect of non-covalent backbone planarization and reduced steric encumbrances. As a result, PY-BTz shows a significantly higher efficiency of 16.4% in comparison to the polymer acceptors based on commonly used thiophene-based linkers (i.e., PY-2T, 9.8%). Detailed analyses reveal that this improvement is associated with enhanced conjugation along the backbone and closer interchain π-stacking, resulting in higher charge mobilities, suppressed charge recombination, and reduced energetic disorder. Remarkably, an efficiency of 14.7% is realized for all-PSCs that are solution-sheared in ambient conditions, which is among the highest for devices prepared under conditions relevant to scalable printing techniques. This work uncovers a strategy for promoting backbone conjugation and planarization in emerging polymer acceptors that can lead to superior all-PSCs.

Surface damage and fuel retention are one of the major threats to the performance of plasma-facing materials (PFMs) in ITER and future fusion reactors. This work aims to investigate the influence of suppressed blistering by heavy ion pre-damage on deuterium (D) retention in tungsten (W). Recrystallized W samples were irradiated with 3.5 MeV iron (Fe13+) ions at room temperature to create displacement damage with a peak damage level of 0.1 dpa. Afterwards, a series of low-energy (38 eV) D plasma exposures were performed at 500 K. Three exposure fluences below and above the blistering threshold (5 × 1024 ∼ 3 × 1025 D m−2) of the pre-damaged W are selected to decouple and couple the damage-induced defects and blistering-induced defects, respectively. Surface observations show that no blisters are formed in un-damaged W after low-fluence D exposure (5 × 1024 D m−2), whereas severe blistering (surface coverage ratio: 34.2 %) occurs in the high-fluence case (3 × 1025 D m−2). In contrast, only a small number of blisters (4.2 %) are formed in Fe-damaged W when D fluence reaches 3 × 1025 D m−2. Moreover, Fe pre-damage increases D retention by a factor of 3.33 and 1.20 at the low-fluence (5 × 1024 D m−2) and medium-fluence (1 × 1025 D m−2) D exposure, respectively. While in the high-fluence case (3 × 1025 D m−2), the enhancement effect of D retention in Fe-damaged W is significantly weakened, such that retention is lower for damaged W, probably due to the significant suppression effect on surface blistering and its accompanying defect formation. This work highlights the suppressed blistering-induced D retention by pre-existing damage in W.

Enhancing photosynthesis is a pivotal strategy for achieving sustainable plant production. Blue and red light facilitate plant growth since these wavelengths are readily absorbed by chlorophyll pigments and power crucial photosynthetic processes. In this investigation, double light conversion films were prepared by incorporating biomass-derived carbon dots into a polyvinyl alcohol matrix (CDs@PVAs). The study conclusively demonstrated that CDs@PVAs can convert ultraviolet and green light from sunlight into blue and red light. Using 2-week-old Athaliana plants as the model organism, the Athaliana plants were covered with CDs@PVAs and then exposed to simulated sunlight (0.57 mW cm−2) for 1 hour. The Fv/Fm value in the presence of the CDs@PVAs was approximately 12% higher than without the film, indicating a significant boost in photosynthesis. Analysis of gene expression showed that the CDs@PVAs cause significant upregulation of genes associated with photosynthesis. These double light conversion films thus emerge as promising contenders for eco-friendly plant cultivation methods that circumvent reliance on electric power. Their potential applications in agriculture are substantial, underscoring their significance in promoting sustainable practices.

ABSTRACTBackground The atherogenic index of plasma (AIP) is a novel metabolic biomarker of atherosclerosis. Nevertheless, the association between the AIP and new-onset hypertension has not been elucidated in the Chinese population.Methods Prospective data were obtained from 3150 participants aged ≥ 18 years in the China Health and Nutrition Survey from 2009 to 2015. The AIP is a logarithmically transformed ratio of triglycerides to high-density lipoprotein cholesterol in molar concentration. Cox regression analysis was used to determine the association of AIP index with new-onset hypertension.Results After the six-year follow-up, 1054 (33.4%) participants developed new-onset hypertension. The participants were divided into AIP quartile groups (Q1-Q4). Compared with those in Q1, subjects in Q3–4 had nearly 1.35 times the risk of new-onset hypertension after full adjustment [Q3: hazard ratio (HR): 1.35, 95% confidence interval (CI): 1.13–1.62; Q4: HR: 1.35, 95% CI: 1.13–1.64]. The risks of new-onset hypertension were nearly 1.30 times higher in subjects in Q2–4 than in subjects in Q1 (p

Bimetallic metal–organic frameworks (BMOFs) are a class of functional porous materials constructed by coordination between nodes containing two different metal ions and organic ligands. Studies have shown that the catalytic activity of BMOFs is greatly improved owing to the adjustment of charge distribution and the increase of active sites as well as the synergistic effect between the bimetals, and the advantages of their large specific surface area, high porosity, unique structure and dispersed active centres make them available as important organic materials applied in the field of wastewater treatment. In this review, the preparation and construction methods for BMOFs in recent years are summarized, and we focus on their removal of different types of pollutants in the aqueous environment, including ions, dyes, pharmaceuticals or personal care products, phenolic compounds and microorganisms, as well as their corresponding removal mechanisms. In addition, we provide an outlook on their future opportunities and challenges in wastewater treatment.

BackgroundSince common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea.Methods and findingsWe developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy.ConclusionsChanging the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.

Background and aimsCoffee contains many bioactive compounds, and its inconsistent association with subclinical atherosclerosis has been reported in observational studies. In this Mendelian randomization study, we investigated whether genetically predicted coffee consumption is associated with subclinical atherosclerosis, as well as the role of potential mediators.MethodsWe first conducted a two-sample Mendelian randomization analysis to examine the causal effect of coffee and its subtypes on subclinical atherosclerosis inferred from coronary artery calcification (CAC). Next, the significant results were validated using another independent dataset. Two-step Mendelian randomization analyses were utilized to evaluate the causal pathway from coffee to subclinical atherosclerosis through potential mediators, including blood pressure, blood lipids, body mass index, and glycated hemoglobin. Mendelian randomization analyses were performed using the multiplicative random effects inverse-variance weighted method as the main approach, followed by a series of complementary methods and sensitivity analyses.ResultsCoffee, filtered coffee, and instant coffee were associated with the risk of CAC (β = 0.79, 95% CI: 0.12 to 1.47, p = 0.022; β = 0.66, 95% CI: 0.17 to 1.15, p = 0.008; β = 0.66, 95% CI: 0.20 to 1.13, p = 0.005; respectively). While no significant causal relationship was found between decaffeinated coffee and CAC (β = −1.32, 95% CI: −2.67 to 0.04, p = 0.056). The association between coffee and CAC was validated in the replication analysis (β = 0.27, 95% CI: 0.07 to 0.48, p = 0.009). Body mass index mediated 39.98% of the effect of coffee on CAC (95% CI: 9.78 to 70.19%, p = 0.009), and 5.79% of the effect of instant coffee on CAC (95% CI: 0.54 to 11.04%, p = 0.030).ConclusionOur study suggests that coffee other than decaffeinated coffee increases the risk of subclinical atherosclerosis inferred from CAC. Body mass index mediated 39.98 and 5.79% of the causal effects of coffee and instant coffee on CAC, respectively. Coffee should be consumed with caution, especially in individuals with established cardiovascular risk factors, and decaffeinated coffee appears to be a safer choice.