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Background: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes., Methods: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests., Results: We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX., Conclusion: These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis., (© 2024. The Author(s).)

Energy status is linked to the production of reactive oxygen species (ROS) in macrophages, which is elevated in obesity. However, it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of obesity. Here, we show that the Rab-GTPase activating protein (RabGAP) TBC1D1, a substrate of the energy sensor AMP-activated protein kinase (AMPK), is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity development. TBC1D1 deletion decreases, whereas an energy overload-mimetic non-phosphorylatable TBC1D1 S231A mutation increases, ROS production and M1-like polarization in macrophages. Mechanistically, TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS generation. Transplantation of TBC1D1 S231A bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable TtSOD for removal of ROS selectively in macrophages alleviates both TBC1D1 S231A mutation- and diet-induced obesity. Our findings therefore have implications for drug discovery to combat obesity., (© 2024. Science China Press.)

Objective: Dietary medium-chain fatty acids (MCFAs), characterized by chain lengths of 8-12 carbon atoms, have been proposed to have beneficial effects on glucose and lipid metabolism, yet the underlying mechanisms remain elusive. We hypothesized that MCFA intake benefits metabolic health by inducing the release of hormone-like factors., Methods: The effects of chow diet, high-fat diet rich in long-chain fatty acids (LCFA HFD) fed ad libitum or pair-fed to a high-fat diet rich in MCFA (MCFA HFD) on glycemia, hepatic gene expression, circulating fibroblast growth factor 21 (FGF21), and liver fat content in both wildtype and Fgf21 knockout mice were investigated. The impact of a single oral dose of an MCFA-rich oil on circulating FGF21 and hepatic Fgf21 mRNA expression was assessed. In flag-tagged Crebh knockin mice and liver-specific Crebh knockout mice, fed LCFA HFD or MCFA HFD, active hepatic CREBH and hepatic Fgf21 mRNA abundance were determined, respectively., Results: MCFA HFD improves glucose tolerance, enhances glucose clearance into brown adipose tissue, and prevents high-fat diet-induced hepatic steatosis in wildtype mice. These benefits are associated with increased liver expression of CREBH target genes (Apoa4 and Apoc2), including Fgf21. Both acute and chronic intake of dietary MCFAs elevate circulating FGF21. Augmented hepatic Fgf21 mRNA following MCFA HFD intake is accompanied by higher levels of active hepatic CREBH; and MCFA-induced hepatic Fgf21 expression is blocked in mice lacking Crebh. Notably, while feeding male and female Fgf21 wildtype mice MCFA HFD results in reduced liver triacylglycerol (TG) levels, this liver TG-lowering effect is blunted in Fgf21 knockout mice fed MCFA HFD. The reduction in liver TG levels observed with MCFA HFD was independent of weight loss., Conclusions: Dietary MCFAs reduce liver fat accumulation via activation of a CREBH-FGF21 signaling axis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C.C. is co-founder of Ousia Pharma ApS, a biotech company developing therapeutics for obesity. C.C. is also on the editorial board of Molecular Metabolism. The remaining authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Breast cancer (BC) is one of the most frequently diagnosed cancers in women. Chemotherapy continues to be the treatment of choice for clinically combating it. Nevertheless, the chemotherapy process is frequently hindered by multidrug resistance, thereby impacting the effectiveness of the treatment. Multidrug resistance (MDR) refers to the phenomenon in which malignant tumour cells develop resistance to anticancer drugs after one single exposure. It can occur with a broad range of chemotherapeutic drugs with distinct chemical structures and mechanisms of action, and it is one of the major causes of treatment failure and disease relapse. Research has long been focused on overcoming MDR by using multiple drug combinations, but this approach is often associated with serious side effects. Therefore, there is a pressing need for in-depth research into the mechanisms of MDR, as well as the development of new drugs to reverse MDR and improve the efficacy of breast cancer chemotherapy. This article reviews the mechanisms of multidrug resistance and explores the application of nano-drug delivery system (NDDS) to overcome MDR in breast cancer. The aim is to offer a valuable reference for further research endeavours., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background and Aims: Evidence is increasingly suggesting that shift work is a risk factor for cardiometabolic disease. However, the causal relationship between shift work and cardiometabolic disease is not yet fully understood. In this study, we employed two-sample Mendelian randomization (MR) to investigate the causal relationship between shift work and the risk of cardiometabolic outcomes., Methods and Results: Genome-wide association study (GWAS) statistics for shift work were obtained from the UK Biobank. Mendelian randomization analyses were conducted to explore the causal effects of shift work on cardiometabolic outcomes, using single-nucleotide polymorphisms (SNPs) as instrumental variables. The results suggested a causal effect between shift work and body mass index, body fat percentage, triglycerides, high-density lipoprotein, type 2 diabetes, hypertension, and cardiorespiratory fitness. After correcting for multiple tests, only body mass index and high-density lipoprotein showed significant associations. No causal effects were found between shift work and overweight, obesity, total cholesterol, low-density lipoprotein, fasting glucose, 2-h glucose, fasting insulin, coronary artery disease, myocardial infarction, heart failure, atrial fibrillation, or ischemic stroke., Conclusion: This MR study provides genetic evidence for a suggestive causal link between shift work and certain cardiometabolic outcomes. Our research may have the significance of providing insight into public hygiene to improve the understanding of shift work and cardiometabolic disease risk. Further experimental studies are needed to confirm our findings., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The correlation between socio-economic status (SES) and bone-related diseases garners increasing attention, prompting a bidirectional Mendelian randomization (MR) analysis in this study. Genetic data on SES indicators (average total household income before tax, years of schooling completed, and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fractures (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses and multivariable MR were performed to enhance the robustness of our findings. Higher educational attainment exhibited associations with increased eBMD (β: .06, 95% confidence interval [CI]: 0.01-0.10, P = 7.24 × 10-3), and reduced risks of osteoporosis (OR: 0.78, 95% CI: 0.65-0.94, P = 8.49 × 10-3), spine fracture (OR: 0.76, 95% CI: 0.66-0.88, P = 2.94 × 10-4), femur fracture (OR: 0.78, 95% CI: 0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR: 0.79, 95% CI: 0.70-0.88, P = 2.05 × 10-5), foot fracture (OR: 0.78, 95% CI: 0.66-0.93, P = 5.92 × 10-3), and wrist-hand fracture (OR: 0.83, 95% CI: 0.73-0.95, P = 7.15 × 10-3). Material deprivation appeared to increase the risk of spine fracture (OR: 2.63, 95% CI: 1.43-4.85, P = 1.91 × 10-3). A higher FN-BMD level positively affected increased household income (β: .03, 95% CI: 0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index, type 2 diabetes, smoking initiation, and frequency of alcohol intake. The MR analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings provide valuable insights for health guideline formulation and policy development., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ultra-instantaneous UHT (UI-UHT, >155°C, <0.1 s) treated milk exhibits higher retention of active protein than regular UHT milk. However, UI-UHT products demonstrate increased susceptibility to destabilization during storage. This study aimed at monitoring the destabilizing process of UI-UHT milk across different storage temperatures and uncovering its potential mechanisms. Compared with regular UHT treatment, ultra-instantaneous treatment markedly accelerated the milk's destabilization process. Aged gel formation occurred after 45 d of storage at 25°C, whereas creaming and sedimentation were observed after 15 d at 37°C. To elucidate the instability mechanism, measurements of plasmin activity, protein hydrolysis levels, and proteomics of the aged gel were conducted. In UI-UHT milk, plasmin activity, and protein hydrolysis levels significantly increased during storage. Excessive protein hydrolysis at 37°C resulted in sedimentation, whereas moderate hydrolysis and an increase in protein particle size at 25°C resulted in aged gel formation. Proteomics analysis results indicated that the aged gel from UI-UHT milk contained intact caseins, major whey proteins, and their derived peptides. Furthermore, specific whey proteins including albumin, lactotransferrin, enterotoxin-binding glycoprotein PP20K, and MFGM proteins were identified in the gel. Additionally, MFGM proteins in UI-UHT milk experienced considerable hydrolysis during storage, contributing to fat instability. This study lays a theoretical foundation for optimizing UI-UHT milk storage conditions to enhance the quality of liquid milk products., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Cell surface marker expression is one of the criteria for defining human mesenchymal stem or stromal cells (MSC) in vitro. However, it is unclear if expression of markers including CD73 and CD90 reflects the in vivo origin of cultured cells. We evaluated expression of 15 putative MSC markers in primary cultured cells from periosteum and cartilage to determine whether expression of these markers reflects either the differentiation state of cultured cells or the self-renewal of in vivo populations. Cultured cells had universal and consistent expression of various putative stem cell markers including > 95% expression CD73, CD90 and PDPN in both periosteal and cartilage cultures. Altering the culture surface with extracellular matrix coatings had minimal effect on cell surface marker expression. Osteogenic differentiation led to loss of CD106 and CD146 expression, however CD73 and CD90 were retained in > 90% of cells. We sorted freshly isolated periosteal populations capable of CFU-F formation on the basis of CD90 expression in combination with CD34, CD73 and CD26. All primary cultures universally expressed CD73 and CD90 and lacked CD34, irrespective of the expression of these markers ex vivo indicating phenotypic convergence in vitro. We conclude that markers including CD73 and CD90 are acquired in vitro in most 'mesenchymal' cells capable of expansion. Overall, we demonstrate that in vitro expression of many cell surface markers in plastic-adherent cultures is unrelated to their expression prior to culture., (© 2024. The Author(s).)

This paper is concerned with the secure output consensus problem for the heterogeneous multi-agent systems under the event-triggered scheme in the presence of the denial-of-service attack. Without detecting the attack, the hold-input controller update strategy is adopted when some transmission data may be lost due to the effect of the attack. Based on the tolerable duration of the attack, a novel edge-based event-triggered scheme is developed. The scheme can avoid continuous communication and exclude Zeno behavior. With the aid of the switched system theory, output consensus is preserved. An example shows the effectiveness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 ISA. Published by Elsevier Ltd. All rights reserved.)

Uranium is considered as a very important nuclear energy material because of the huge amount of energy it releases. As the main product of the spontaneous decay of uranium, it is difficult for helium to react with uranium because of its chemical inertness. Therefore, bubbles will be formed inside uranium, which could greatly reduce the performance of uranium or cause safety problems. Additionally, nuclear materials are usually operated in an environment of high-temperature and high-pressure, so it is necessary to figure out the exact state of helium inside uranium under extreme conditions. Here, we explored the structural stability of the U-He system under high pressure and high temperature by using density functional theory calculations. Two metastable phases are found between 50 and 400 GPa: U 4 He with space group Fmmm and U 6 He with space group P 1̄. Both are metallic and adopt layered structures. Electron localization function calculation combined with charge density difference analysis indicates that there are covalent bonds between U and U atoms in both Fmmm -U 4 He and P 1̄-U 6 He. Regarding the elastic modulus of α-U, the addition of helium has certain influence on the mechanical properties of uranium. Besides, first-principles molecular dynamics simulations were carried out to study the dynamical behavior of Fmmm -U 4 He and P 1̄-U 6 He at high-temperature. It was found that Fmmm -U 4 He and P 1̄-U 6 He undergo one-dimensional superionic phase transitions at 150 GPa. Our study revealed the exotic structure of U-He compounds beyond the formation of bubbles under high-pressure and high-temperature, which might be relevant to the performance and safety issues of nuclear materials under extreme conditions.

Objective: T cells contribute to tissue injury in systemic sclerosis (SSc), yet the specific T cell subsets expanded in patients with SSc remain incompletely defined. Here we evaluated specific phenotypes and functions of peripheral helper T (Tph) and follicular helper T (Tfh) cells, which have been implicated in autoantibody production, and assessed their associations with clinical features in a well-characterized cohort of patients with SSc., Methods: Mass cytometry of T cells from peripheral blood mononuclear cells of patients with SSc and controls were evaluated using t-distributed stochastic neighbor embedding visualization, biaxial gating, and marker expression levels. Findings were validated with flow cytometry and in vitro assays., Results: The frequencies of PD-1 high CXCR5 + Tfh cells and PD-1 high CXCR5 - Tph cells were similar in patients with SSc and controls. t-distributed stochastic neighbor embedding visualization (tSNE) revealed distinct populations within the PD-1 high CXCR5 - cells distinguished by expression of HLA-DR and inducible costimulator (ICOS). Among PD-1 high CXCR5 - cells, only the HLA-DR + ICOS - cell population was expanded in patients with SSc. Cytometric and RNA sequencing analyses indicated that these cells expressed cytotoxic rather than B cell helper features. HLA-DR + ICOS - PD-1 high CXCR5 - cells were less potent in inducing B cell plasmablast differentiation and antibody production than comparator T helper cell populations. HLA-DR + ICOS - PD-1 high CXCR5 - cells were significantly associated with the presence and severity of interstitial lung disease among patients with SSc., Conclusion: Among PD-1 high CXCR5 - T cells, a subset of HLA-DR + ICOS - cells with cytotoxic features is specifically expanded in patients with SSc and is significantly associated with interstitial lung disease severity. This potential cytotoxicity appearing in the CD4 T cell population can be evaluated as a prognostic disease biomarker in patients with SSc., (© 2024 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions 1,2 . Expansion of T follicular helper (T FH ) and T peripheral helper (T PH ) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE 3,4 . Human T FH and T PH cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs.  5,6 ), yet regulation of T cell CXCL13 production and the relationship between CXCL13 + T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4 + T cell phenotypes in patients with SLE, with expansion of PD-1 + /ICOS + CXCL13 + T cells and reduction of CD96 hi IL-22 + T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 + T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13 + T PH /T FH cell differentiation and promote an IL-22 + phenotype. Type I interferon, a pathogenic driver of SLE 7 , opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13 + T PH /T FH cells on a polarization axis opposite from T helper 22 (T H 22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Clinical validity of genome sequencing (GS) (>30×) has been preliminarily verified in the post-natal setting. This study is to investigate the potential utility of trio-GS as a prenatal test for diagnosis of central nervous system (CNS) anomalies., Methods: We performed trio-based GS on a prospective cohort of 17 foetuses with CNS abnormalities. Single nucleotide variation (SNV), small insertion and deletion (Indel), copy number variation (CNV), structural variant (SV), and regions with absence of heterozygosity (AOH) were analyzed and classified according to ACMG guidelines., Results: Trio-GS identified diagnostic findings in 29.4% (5/17) of foetuses, with pathogenic variants found in SON , L1CAM , KMT2D, and ASPM . Corpus callosum (CC) and cavum septum pellucidum (CSP) abnormalities were the most frequent CNS abnormalities (47.1%, 8/17) with a diagnostic yield of 50%. A total of 29.4% (5/17) foetuses had variants of uncertain significance (VUS). Particularly, maternal uniparental disomy 16 and a de novo mosaic 4p12p11 duplication were simultaneously detected in one foetus with abnormal sulcus development. In addition, parentally inherited chromosomal inversions were identified in two foetuses., Conclusion: GS demonstrates its feasibility in providing genetic diagnosis for foetal CNS abnormalities and shows the potential to expand the application to foetuses with other ultrasound anomalies in prenatal diagnosis.

Radiotherapy (RT) is a highly valuable method in cancer therapy, but its therapeutic efficacy is limited by its side effects and tumour radiation resistance. The resistance is mainly induced by hypoxia in the tumour microenvironment (TME). As a nano-oxygen carrier, Haemoglobin-based oxygen carriers (HBOCs) administration is a promising strategy to alleviate tumour hypoxia which may remodel TME to ameliorate radiation resistance and enable RT more effective. In this study, we administered fractionated RT combined with HBOC to treat Miapaca-2 cell and Hela cell xenografts on nude mice. The study found that HBOC relieved hypoxic environment and down-regulate expression of hypoxia-inducible factor-1α (Hif-1α) both in regular (100 mm 3 ) and large (360/400 mm 3 ) tumours. The proliferation and metastasis of tumour tissue also decreased after HBOC application. Nevertheless, in vivo RT combined with HBOC performed more effectively to suppress tumour growth in large tumours than in regular tumours. This is due to more severe hypoxic regions exist in the large solid tumours compared to the regular counterparts, and HBOC administration may be more effective in alleviating hypoxia in large tumours. Thus, HBOC sensitization therapy is more suitable for large solid tumours.

Recently, the solar-driven interfacial evaporation desalination has attracted more and more attentions due to the advantages of low cost, zero energy consumption, and high water purification rate, etc. One of the bottlenecks of this emerging technique lies in a lack of simple and low-cost ways to construct three-dimensional (3D) hierarchical microstructures for photothermal membranes. To this end, a two-step strategy is carried out by combining surface functionalization with substrate engineering. Firstly, a silane coupling agent 3-aminopropyltriethoxysilane (APTES) is grafted onto an ideal photothermal material of Ti 3 C 2 T x MXene, to improve the nanochannel sizes and hydrophilicity, which are attributed to enlarged interspaces of MXene and introduced hydrophilic group e.g., -NH 2 and -OH, respectively. Secondly, a low-cost and robust nonwoven fiber (NWF) substrate, which has a 3D micron-sized mesh structure with interlaced fiber stacks, is employed as the skeleton to load enough APTES-grafted MXene by a simple soaking method. Benefited from above design, the Ti 3 C 2 T x -APTES/NWF composite membrane with a 3D hierarchical structure shows enhanced light scattering and utilization, water transport and vapor escape. A remarkable evaporation rate of 1.457 kg m -2  h -1 and an evaporation efficiency of 91.48 % are attained for a large-area (5 × 5 cm 2 ) evaporator, and the evaporation rate is further increased to 1.672 kg m -2  h -1 for a small-area (2 × 2 cm 2 ) device. The rejection rates of salt ions and heavy metal ions are higher than 99 % and 99.99 %, respectively, and the removal rates of organic dye molecules are nearly to 100 %. Besides, the composite photothermal membrane exhibits great stabilities in harsh conditions such as high salinities, long cycling, large light intensities, strong acid/alkali environments, and mechanical bending. Most importantly, the photothermal membrane shows a considerable cost-effectiveness of 89.4 g h -1 /$. Hence, this study might promote the commercialization of solar-driven interfacial evaporation desalination by collaboratively considering surface modification and substrate engineering for MXene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass., (© 2024. The Author(s).)

Phase heterogeneity of bromine-iodine (Br-I) mixed wide-bandgap (WBG) perovskites has detrimental effects on solar cell performance and stability. Here, we report a heterointerface anchoring strategy to homogenize the Br-I distribution and mitigate the segregation of Br-rich WBG-perovskite phases. We find that methoxy-substituted phenyl ethylammonium ( x -MeOPEA + ) ligands not only contribute to the crystal growth with vertical orientation but also promote halide homogenization and defect passivation near the buried perovskite/hole transport layer (HTL) interface as well as reduce trap-mediated recombination. Based on improvements in WBG-perovskite homogeneity and heterointerface contacts, NiO x -based opaque WBG-perovskite solar cells (WBG-PSCs) achieved impressive open-circuit voltage ( V oc ) and fill factor (FF) values of 1.22 V and 83%, respectively. Moreover, semitransparent WBG-PSCs exhibit a PCE of 18.5% (15.4% for the IZO front side) and a high FF of 80.7% (79.4% for the IZO front side) for a designated illumination area (da) of 0.12 cm 2 . Such a strategy further enables 24.3%-efficient two-terminal perovskite/silicon (double-polished) tandem solar cells (da of 1.159 cm 2 ) with a high V oc of over 1.90 V. The tandem devices also show high operational stability over 1000 h during T 90 lifetime measurements.

Background: Patients with cleft lip and palate (CLP) have an oronasal communication differed from the closed state in healthy individuals, leading to a unique oral microbiome. This study aimed to determine if variances in the oral microbiota persist among CLP patients who have received treatments for the closure of these fistulas compared to the microbiota of healthy individuals., Methods: Saliva samples were collected from a cohort comprising 28 CLP patients (CLP group) and 30 healthy controls (HC group). Utilizing 16S rRNA sequencing on the Illumina NovaSeq platform, we conducted a comprehensive analysis of the diversity and composition of the oral microbiota., Results: The analysis of the microbiota in the saliva samples revealed a total of 23 microbial phyla, 38 classes, 111 orders, 184 families, 327 genera and 612 species. The alpha diversity with microbial abundance and evenness indicated the significant difference between the CLP and HC groups. Principal coordinate analysis (PCoA) and the ADONIS test further supported the presence of distinct microorganisms between the two groups. The CLP group displayed elevated abundances of Neisseria, Haemophilus, Porphyromonas, and Granulicatella, as indicated by LefSe analysis. Conversely, Rothia, Veillonella, and Pauljensenia exhibited significant reductions in abundance in the CLP group. The results of the PICRUSt analysis indicated significant differences in the relative abundance of 25 KEGG pathways within the CLP group. Through Spearman correlation analysis, strong associations between Rothia, Veillonella, and Pauljensenia and 25 functional pathways linked to CLP were identified., Conclusion: Findings of this study offer a thorough comprehension of the microbiome profiles of CLP patients after the restoration of oronasal structure and are anticipated to present innovative concepts for the treatment of CLP., (© 2024. The Author(s).)

Background: Acute myocardial infarction (AMI) and diabetic nephropathy (DN) are common clinical co-morbidities, but they are challenging to manage and have poor prognoses. There is no research on the bioinformatics mechanisms of comorbidity, and this study aims to investigate such mechanisms., Methods: We downloaded the AMI data (GSE66360) and DN datasets (GSE30528 and GSE30529) from the Gene Expression Omnibus (GEO) platform. The GSE66360 dataset was divided into two parts: the training set and the validation set, and GSE30529 was used as the training set and GSE30528 as the validation set. After identifying the common differentially expressed genes (DEGs) in AMI and DN in the training set, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and protein-protein interaction (PPI) network construction were performed. A sub-network graph was constructed by MCODE, and 15 hub genes were screened by the Cytohubba plugin. The screened hub genes were validated, and the 15 screened hub genes were subjected to GO, KEGG, Gene MANIA analysis, and transcription factor (TF) prediction. Finally, we performed TF differential analysis, enrichment analysis, and TF and gene regulatory network construction., Results: A total of 46 genes (43 up-regulated and 3 down-regulated) were identified for subsequent analysis. GO functional analysis emphasized the presence of genes mainly in the vesicle membrane and secretory granule membrane involved in antigen processing and presentation, lipopeptide binding, NAD + nucleosidase activity, and Toll-like receptor binding. The KEGG pathways analyzed were mainly in the phagosome, neutrophil extracellular trap formation, natural killer cell-mediated cytotoxicity, apoptosis, Fc gamma R-mediated phagocytosis, and Toll-like receptor signaling pathways. Eight co-expressed hub genes were identified and validated, namely TLR2, FCER1G, CD163, CTSS, CLEC4A, IGSF6, NCF2, and MS4A6A. Three transcription factors were identified and validated in AMI, namely NFKB1, HIF1A, and SPI1., Conclusions: Our study reveals the common pathogenesis of AMI and DN. These common pathways and hub genes may provide new ideas for further mechanistic studies., (© 2024. The Author(s).)

Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy., Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4)., Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects., Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: The retina is a highly metabolically active tissue, and there is a lack of clarity about the relationship between metabolites and diabetic retinopathy (DR). This study used two-sample bidirectional Mendelian randomization (MR) analyses to identify causal relationships between metabolites and DR., Methods: Genetic variants were selected from the open-access Genome-Wide Association Studies (GWAS) summary database as proxies for the 1400 most recently published metabolites. MR analysis was performed to examine associations between these metabolite traits and DR. Single nucleotide polymorphism (SNP) data that were significantly associated with exposure were screened through association analysis. Validated instrumental variables (IVs) were obtained by removing SNPs with linkage disequilibrium (LD) and F-statistic values below 10. MR analyses were performed using the inverse variance weighted (IVW) method as the primary approach. The robustness of the results was verified by sensitivity analyses, including assessments of heterogeneity, horizontal pleiotropy, and the leave-one-out method., Results: In the IVW approach and in the primary analysis of several sensitivity analyses, genetically determined glycolithocholate sulfate levels, androstenediol (3 beta, 17 beta) monosulfate (1) levels, 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4) levels, 1-oleoyl-2-arachidonoyl-GPE (18:1/20:4) levels, 1-oleoyl-2-linoleoyl-GPE (18:1/18:2) levels, X-26109 levels, N6-methyllysine levels, (N6,N6-dimethyllysine levels), and (N2-acetyl,N6,N6-dimethyllysine levels) were negatively associated with the risk of DR. 5-hydroxymethyl-2-furoylcarnitine levels and the glutamate-to-alanine ratio were positively associated with the risk of DR. No reverse causal association was found between DR and metabolites., Discussion: This MR study suggests that nine metabolites may have a protective effect in DR, while two metabolites may be associated with an increased risk of DR. However, further research is needed to confirm these findings. Supplementation with beneficial metabolites may reduce DR risk and could potentially be a novel therapeutic approach to DR treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Zhao, Xie, Hong, Cao, Ding and Zhang.)

Objective: This study aimed to assess the effects of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs) in chronic periodontitis and explore the underlying mechanism involved., Methods: In vitro, Pg-OMVs were incubated with Ea.hy926 (vessel endothelial cells, ECs) to evaluate their effects on endothelial functions and to investigate the underlying mechanism. The effects of endothelial dysfunction on MG63 osteoblast-like cells were verified using an indirect co-culture method. For in vivo studies, micro-CT was conducted to identify alveolar bone mass. Immunofluorescence staining was conducted to confirm the levels of stimulator of interferon genes (STING) in the blood vessel and the number of Runx2 + cells around the alveolar bone., Results: Pg-OMVs were endocytosed by ECs, leading to endothelial dysfunction. The cGAS-STING-TBK1 pathway was activated in ECs, which subsequently inhibited MG63 migration and early osteogenesis differentiation. In vivo, Pg-OMVs promoted alveolar bone resorption, increased STING levels in the blood vessel, and decreased Runx2 + cells around the alveolar bone., Conclusions: Pg-OMVs caused endothelial dysfunction and activated the cGAS-STING-TBK1 signal cascade in ECs, thereby impairing ECs-mediated osteogenesis. Furthermore, Pg-OMVs aggregated alveolar bone loss and altered the blood vessel-mediated osteogenesis with elevated STING., (© 2024 Wiley Periodicals LLC.)

Rationale: Respiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction of interferon-stimulated genes ( ISGs ). How asthma-susceptibility genes modulate cellular response upon viral infection by fine-tuning ISG induction and subsequent airway inflammation in genetically susceptible asthma patients remains largely unknown., Objectives: To decipher the functions of gasdermin B (encoded by GSDMB ) in respiratory virus-induced lung inflammation., Methods: In two independent cohorts, we analysed expression correlation between GSDMB and ISG s . In human bronchial epithelial cell line or primary bronchial epithelial cells, we generated GSDMB -overexpressing and GSDMB -deficient cells. A series of quantitative PCR, ELISA and co-immunoprecipitation assays were performed to determine the function and mechanism of GSDMB for ISG induction. We also generated a novel transgenic mouse line with inducible expression of human unique GSDMB gene in airway epithelial cells and infected the mice with respiratory syncytial virus to determine the role of GSDMB in respiratory syncytial virus-induced lung inflammation in vivo ., Results: GSDMB is one of the most significant asthma-susceptibility genes at 17q21 and acts as a novel RNA sensor, promoting mitochondrial antiviral-signalling protein (MAVS)-TANK binding kinase 1 (TBK1) signalling and subsequent inflammation. In airway epithelium, GSDMB is induced by respiratory viral infections. Expression of GSDMB and ISGs significantly correlated in respiratory epithelium from two independent asthma cohorts. Notably, inducible expression of human GSDMB in mouse airway epithelium led to enhanced ISGs induction and increased airway inflammation with mucus hypersecretion upon respiratory syncytial virus infection., Conclusions: GSDMB promotes ISGs expression and airway inflammation upon respiratory virus infection, thereby conferring asthma risk in risk allele carriers., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Constructing an artificial solid electrolyte interphase (SEI) on lithium metal electrodes is a promising approach to address the rampant growth of dangerous lithium morphologies (dendritic and dead Li 0 ) and low Coulombic efficiency that plague development of lithium metal batteries, but how Li + transport behavior in the SEI is coupled with mechanical properties remains unknown. We demonstrate here a facile and scalable solution-processed approach to form a Li 3 N-rich SEI with a phase-pure crystalline structure that minimizes the diffusion energy barrier of Li + across the SEI. Compared with a polycrystalline Li 3 N SEI obtained from conventional practice, the phase-pure/single crystalline Li 3 N-rich SEI constitutes an interphase of high mechanical strength and low Li + diffusion barrier. We elucidate the correlation among Li + transference number, diffusion behavior, concentration gradient, and the stability of the lithium metal electrode by integrating phase field simulations with experiments. We demonstrate improved reversibility and charge/discharge cycling behaviors for both symmetric cells and full lithium-metal batteries constructed with this Li 3 N-rich SEI. These studies may cast new insight into the design and engineering of an ideal artificial SEI for stable and high-performance lithium metal batteries., (© 2024. The Author(s).)

Background: According to epidemiological studies, particulate matter 2.5 (PM2.5) is a significant contributor to cardiovascular disease (CVD). However, making causal inferences is difficult due to the methodological constraints of observational studies. In this study, we used two-sample Mendelian randomization (MR) to examine the causal relationship between PM 2.5 and the risk of CVD., Methods: Genome-wide association study (GWAS) statistics for PM2.5 and CVD were collected from the FinnGen and UK Biobanks. Mendelian randomization analyses were applied to explore the causal effects of PM2.5 on CVD by selecting single-nucleotide polymorphisms(SNP) as instrumental variables., Results: The results revealed that a causal effect was observed between PM2.5 and coronary artery disease(IVW: OR 2.06, 95% CI 1.35, 3.14), and hypertension(IVW: OR 1.07, 95% CI 1.03, 1.12). On the contrary, no causal effect was observed between PM2.5 and myocardial infarction(IVW: OR 0.73, 95% CI 0.44, 1.22), heart failure(IVW: OR 1.54, 95% CI 0.96, 2.47), atrial fibrillation(IVW: OR 1.03, 95% CI 0.71, 1.48), and ischemic stroke (IS)(IVW: OR 0.98, 95% CI 0.54, 1.77)., Conclusion: We discovered that there is a causal link between PM2.5 and coronary artery disease and hypertension in the European population, using MR methods. Our discovery may have the significance of public hygiene to improve the understanding of air quality and CVD risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Alcoholic fatty liver disease (FALD) and non-alcoholic fatty liver disease (NAFLD) have similar pathological spectra, both of which are associated with a series of symptoms, including steatosis, inflammation, and fibrosis. These clinical manifestations are caused by hepatic lipid synthesis and metabolism dysregulation and affect human health. Despite having been studied extensively, targeted therapies remain elusive. The Cytochrome P450 (CYP450) family is the most important drug-metabolising enzyme in the body, primarily in the liver. It is responsible for the metabolism of endogenous and exogenous compounds, completing biological transformation. This process is relevant to the occurrence and development of AFLD and NAFLD. In this review, the correlation between CYP450 and liver lipid metabolic diseases is summarised, providing new insights for the treatment of AFLD and NAFLD., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Jiang et al.)

Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the rabbit hemorrhagic disease virus (RHDV). Since the first outbreaks of type 2 RHDV (RHDV2) in April 2020 in China, the persistence of this virus in the rabbit population has caused substantial economic losses in rabbit husbandry. Previous failures in preventing RHDV2 prompted us to further investigate the immune mechanisms underlying the virus's pathogenicity, particularly concerning the spleen, a vital component of the mononuclear phagocyte system (MPS). For this, a previous RHDV2 isolate, CHN/SC2020, was utilized to challenge naive adult rabbits. Then, the splenic transcriptome was determined by RNA-Seq. This study showed that the infected adult rabbits had 3148 differentially expressed genes (DEGs), which were associated with disease, signal transduction, cellular processes, and cytokine signaling categories. Of these, 100 upregulated DEGs were involved in inflammatory factors such as IL1α, IL-6, and IL-8. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were significantly enriched in the cytokine-cytokine receptor interaction signaling pathway, which may play a vital role in CHN/SC2020 infection. At the same time, proinflammatory cytokines and chemokines were significantly increased in the spleen at the late stages of infection. These findings suggested that RHDV2 (CHN/SC2020) might induce dysregulation of the cytokine network and compromise splenic immunity against viral infection, which expanded our understanding of RHDV2 pathogenicity.

Rechargeable garnet-based solid-state Li batteries hold immense promise as nonflammable, nontoxic, and high energy density energy storage systems, employing Li 7 La 3 Zr 2 O 12 (LLZO) with a garnet-type structure as the solid-state electrolyte. Despite substantial progress in this field, the advancement and eventual commercialization of garnet-based solid-state Li batteries are impeded by void formation at the LLZO/Li interface at practical current densities and areal capacities beyond 1 mA cm -2 and 1 mAh cm -2 , respectively, resulting in limited cycling stability and the emergence of Li dendrites. Additionally, developing a fabrication approach for thin LLZO electrolytes to achieve high energy density remains paramount. To address these critical challenges, herein, we present a facile methodology for fabricating self-standing, 50 μm thick, porous LLZO membranes with a small pore size of ca. 2.3 μm and an average porosity of 51%, resulting in a specific surface area of 1.3 μm -1 , the highest reported to date. The use of such LLZO membranes significantly increases the Li/LLZO contact area, effectively mitigating void formation. This methodology combines two key elements: (i) the use of small pore formers of ca. 1.5 μm and (ii) the use of ultrafast sintering, which circumvents ceramics overdensification using rapid heating/cooling rates of ca. 50 °C per second. The fabricated porous LLZO membranes demonstrate exceptional cycling stability in a symmetrical Li/LLZO/Li cell configuration, exceeding 600 h of continuous operation at a current density of 0.1 mA cm -2 .

Objective: To evaluate the local incidence of orofacial cleft (OFC) encountered in fetal morphology scan and prenatal diagnosis, genetic etiology of fetuses with or without other structural abnormalities, and their pregnancy outcomes., Design: Retrospective cohort study., Setting: Two maternal fetal medicine units, tertiary hospitals, Hong Kong., Participants: All pregnant women with antenatal diagnosis of fetal OFC between January 2016 and December 2020 (N = 66)., Results: OFC has an incidence of 0.13% among pregnancies in Hong Kong and 28.8% (19/66) were syndromic cleft that exhibited other fetal structural anomalies. There were 55 cases (84.6%) who opted for invasive prenatal diagnostic testing. Genetic defects were identified in 25.8% (17/66) of this cohort, including 14 pathogenic variants. The detection rate in the syndromic cases is 68.4% (13/19) which was significantly higher than 8.5% (4/47) among non-syndromic cases. Aneuploidies would be the most common cause, accounting for 9.1% (6/66). Chromosomal microarray analysis (CMA) provided an incremental diagnostic yield of 6.1% compared to conventional karyotyping. A total of 29 live births including 3 cases of a variant of uncertain significance and 26 cases without genetic abnormalities detected have continued pregnancy to birth. There were 87.5% (21/24) without detectable pathogenic genetic abnormality reported good long-term outcomes. The chance of OFC fetuses having a good long-term outcome was significantly higher if no genomic variant was detected ( P  < .001)., Conclusions: Invasive prenatal tests with CMA should be offered to pregnancies with OFC regardless of the type. It has provided incremental diagnostic yield over conventional karyotyping and helped in prenatal and genetic counseling. A negative result in non-syndromic OFC favors couples to keep the pregnancy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The conventional therapeutic treatment of triple-negative breast cancer (TNBC) is negatively influenced by the development of tumor cell drug resistant, and systemic toxicity of therapeutic agents due to off-target activity. In accordance with research findings, nanoparticles (NPs) responsive to the tumor microenvironment (TME) have been discovered for providing opportunities to selectively target tumor cells via active targeting or Enhanced Permeability and Retention (EPR) effect. The combination of the TME control and therapeutic NPs offers promising solutions for improving the prognosis of the TNBC because the TME actively participates in tumor growth, metastasis, and drug resistance. The NP-based systems leverage stimulus-responsive mechanisms, such as low pH value, hypoxic, excessive secretion enzyme, concentration of glutathione (GSH)/reactive oxygen species (ROS), and high concentration of Adenosine triphosphate (ATP) to combat TNBC progression. Concurrently, NP-based stimulus-responsive introduces a novel approach for drug dosage design, administration, and modification of the pharmacokinetics of conventional chemotherapy and immunotherapy drugs. This review provides a comprehensive examination of the strengths, limitations, applications, perspectives, and future expectations of both novel and traditional stimulus-responsive NP-based drug delivery systems for improving outcomes in the medical practice of TNBC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2024 Wiley Periodicals LLC.)

Chronic craniofacial pain is intractable and its mechanisms remain unclarified. The rostral ventromedial medulla (RVM) plays a crucial role in descending pain facilitation and inhibition. It is unclear how the descending circuits from the RVM to spinal trigeminal nucleus (Sp5) are organized to bidirectionally modulate craniofacial nociception. We used viral tracing, in vivo optogenetics, calcium signaling recording, and chemogenetic manipulations to investigate the structure and function of RVM-Sp5 circuits. We found that most RVM neurons projecting to Sp5 were GABAergic or glutamatergic and facilitated or inhibited craniofacial nociception, respectively. Both GABAergic interneurons and glutamatergic projection neurons in Sp5 received RVM inputs: the former were antinociceptive, whereas the latter were pronociceptive. Furthermore, we demonstrated activation of both GABAergic and glutamatergic Sp5 neurons receiving RVM inputs in inflammation- or dysfunction-induced masseter hyperalgesia. Activating GABAergic Sp5 neurons or inhibiting glutamatergic Sp5 neurons that receive RVM projections reversed masseter hyperalgesia. Our study identifies specific cell types and projections of RVM-Sp5 circuits involved in facilitating or inhibiting craniofacial nociception respectively. Selective manipulation of RVM-Sp5 circuits can be used as potential treatment strategy to relieve chronic craniofacial muscle pain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The periosteum plays a crucial role in bone healing and is an important source of skeletal stem and progenitor cells. Recent studies in mice indicate that diverse populations of skeletal progenitors contribute to growth, homeostasis and healing. Information about the in vivo identity and diversity of skeletal stem and progenitor cells in different compartments of the adult human skeleton is limited. In this study, we compared non-hematopoietic populations in matched tissues from the femoral head and neck of 21 human participants using spectral flow cytometry of freshly isolated cells. High-dimensional clustering analysis indicated significant differences in marker distribution between periosteum, articular cartilage, endosteum and bone marrow populations, and identified populations that were highly enriched or unique to specific tissues. Periosteum-enriched markers included CD90 and CD34. Articular cartilage, which has very poor regenerative potential, showed enrichment of multiple markers, including the PDPN + CD73 + CD164 + CD146 - population previously reported to represent human skeletal stem cells. We further characterized periosteal populations by combining CD90 with other strongly expressed markers. CD90 + CD34 + cells sorted directly from periosteum showed significant colony-forming unit fibroblasts (CFU-F) enrichment, rapid expansion, and consistent multi-lineage differentiation of clonal populations in vitro. In situ, CD90 + CD34 + cells include a perivascular population in the outer layer of the periosteum and non-perivascular cells closer to the bone surface. CD90 + cells are also highly enriched for CFU-F in bone marrow and endosteum, but not articular cartilage. In conclusion, our study indicates considerable diversity in the non-hematopoietic cell populations in different tissue compartments within the adult human skeleton, and suggests that periosteal progenitor cells reside within the CD90 + CD34 + population., Competing Interests: Declaration of competing interest The authors do not have any competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Streptococcosis is a highly contagious aquatic bacterial disease that poses a significant threat to tilapia. Vaccination is a well-known effective measure to prevent and control fish bacterial diseases. Among the various immunization methods, immersion vaccination is simple and can be widely used in aquaculture. Besides, nanocarrier delivery technology has been reported as an effective solution to improve the immune effect of immersion vaccine. In this study, the surface immunogenic protein (Sip) was proved to be conserved and potential to provide cross-immunoprotection for both Streptococcus agalactiae (S. agalactiae) and Streptococcus iniae (S. iniae) by multiple sequences alignment and Western blotting analysis. On this basis, we expressed and obtained the recombinant protein rSip and connected it with functionalized carbon nanotubes (CNT) to construct the nanocarrier vaccine system CNT-rSip. After immersion immunization, the immune effect of CNT-rSip against above two streptococcus infections was evaluated in tilapia based on some aspects including the serum specific antibody level, non-specific enzyme activities, immune-related genes expression and relative percent survival (RPS) after bacteria challenge. The results showed that compared with control group, CNT-rSip significantly (P < 0.05) increased the serum antibody levels, related enzyme activities including acid phosphatase, alkaline phosphatase, lysozyme and total antioxidant capacity activities, as well as the expression levels of immune-related genes from 2 to 4 weeks post immunization (wpi), and all these indexes peaked at 3 wpi. Besides, the above indexes of CNT-rSip were higher than those of rSip group with different extend during the experiment. Furthermore, the challenge test indicated that CNT-rSip provided cross-immunoprotection against S. agalactiae and S. iniae infection with RPS of 75 % and 72.41 %, respectively, which were much higher than those of other groups. Our study indicated that the nanocarrier immersion vaccine CNT-rSip could significantly improve the antibody titer and confer cross-immuneprotection against S. agalactiae and S. iniae infection in tilapia., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Streptococcal disease has severely restricted the development of global tilapia industry, which is mainly caused by Streptococcus agalactiae (S. agalactiae) and Streptococcus iniae (S. iniae). Vaccination has been proved to be a potential strategy to control it. In this study, a multi-epitope subunit vaccine Sip-Srr (SS) was prepared based on the B-cell antigenic epitopes prediction and multiple sequence alignment analysis of Sip and Srr sequences. Furthermore, the BNC-rSS nanocarrier vaccine system was constructed by connecting the rSS protein with modified bacterial nanocellulose (BNCs) and characterized by Fourier Transform Infrared Spectroscopy and Scanning Electron Microscope, the immersion immune effect against S. agalactiae and S. iniae infection was evaluated. The results showed that compared with the control group, BNC-rSS significantly enhanced serum antibody production, related enzyme activities and immune-related genes expression. It was noteworthy that BNC-rSS vaccine improved immune protection of tilapia, with survival rates of 66.67 % (S. agalactiae) and 60.00 % (S. iniae), respectively, compared with those of rSS vaccine (30 % and 33.33 %, respectively). Our study indicated that the BNC-rSS nanovaccine could elicit robust immune responses in tilapia by immersion immunization, and had the potential to offer cross-protection against S. agalactiae and S. iniae infection in tilapia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Metallic zinc (Zn) has been considered one of the most promising anode materials for next-generation aqueous Zn batteries due to its low redox potential and high storage capacity. However, excessive dendrite formation in Zn metal, corrosion, the evolution of hydrogen gas during the cycling process, and the poor Zn-ion (Zn 2+ ) transport from the electrolyte to the electrode limit its practical application. One of the most effective strategies to suppress Zn dendrite growth and promote Zn 2+ transport is to introduce suitable protective layers between the Zn metal electrode and the electrolyte. Herein, we mathematically simulated the dynamic interactions between the Zn deposition on the anode and the resulting displacement of a protective layer that covers the anode, the latter of which can simultaneously inhibit Zn dendrite growth and enhance the Zn 2+ transport through the interface between the Zn anode and the protective layer. Our simulation results indicate that a protective layer of high Zn 2+ diffusivity not only improves the deposition rate of the Zn metal but also prevents dendrite growth by homogenizing the Zn 2+ concentration at the anode surface. In addition, it is revealed that the anisotropic Zn 2+ diffusivity in the protective layer influences the 2D diffusion of Zn 2+ . Higher Zn 2+ diffusivity perpendicular to the Zn metal surface inhibits dendrite growth, while higher diffusivity parallel to the Zn metal surface promotes dendrite growth. Our work thus provides a fundamental understanding and a design principle for controlling anisotropic Zn 2+ diffusion in the protective layer for better suppression of dendrite growth in Zn metal batteries.

Objective: To explore the efficacy and safety of ultrasound-guided injection acupotomy as a minimally invasive intervention treatment of cervical spondylotic radiculopathy (CSR)., Methods: 160 CSR subjects were recruited who met the inclusion criteria in our hospital from October 2019 to December 2021. The subjects were randomly divided into the experimental and control group, with 80 cases in each. The experimental group received ultrasound-guided injection acupotomy as a minimally invasive intervention therapy. The control group received ultrasound-guided selective nerve root block (SNRB). The Odom's criteria clinical curative effect, visual analogue scale (VAS), neck disability index (NDI), and 36-Item Short Form Health Survey questionnaire (SF-36) were used to evaluate the outcome of subjects at several different points in time., Results: At 30 min and 1 month after the end of treatment, there was no significant difference in any scores. However, after six months, the excellent and good rate was better in the experimental group compared to the control (RD = 0.175; 95% CI, 0.044-0.300, p  = 0.009). The total effective rate was also better in the experimental group (RD = 0.126; 95% CI, 0.021-0.232, p  = 0.018). In contrast, the VAS score (MD = -0.500; 95% CI, -1.000-0.000, p  = 0.030) and NDI score (MD = -6.460; 95% CI, -11.067 to -1.852, p  = 0.006) were lower in the experimental group compared to the control. The total SF-36 score was higher in the experimental group (MD = 7.568; 95% CI, 2.459-12.677, p  = 0.004)., Conclusion: Ultrasound-guided injection acupotomy minimally invasive interventional treatment of CSR has no significant difference in short-term curative effect compared with ultrasound-guided SNRB, but the data indicators are significantly better than the latter at 6 months after the end of the course of treatment, showing better long-term efficacy.

Thromboembolism, arising from the utilization of cardiovascular medical devices, remains a prevalent issue entailing substantial morbidity and mortality. Despite the proposal of various surface modification strategies, each approach possesses inherent limitations and drawbacks. Herein, we propose a novel approach for the in situ growth of nanocoatings on various material surfaces through the cooperative assembly of silk fibroin (SF) and lysozyme. The intrinsic in situ growth characteristic enables the nanocoatings to achieve stable and uniform adherence to diverse substrate surfaces, including the inner surface of intravascular catheters, to redefine the surface properties of the material. The features of the hydrophilic and negatively charged nanocoating contribute to its antithrombotic properties, as evidenced by the reduced likelihood of platelet adhesion upon modification of the ultrathin and mechanically robust coating. In vitro assessment confirms a significant reduction in blood clot formation along with the promotion of anticoagulation. Such a SF/Ly nanocoating holds substantial promise as a surface modification strategy to enhance the hemocompatibility of medical devices and other materials that come into contact with blood, particularly in situations where medical-grade materials are temporarily unavailable, thus providing a feasible alternative.

Van der Waals (vdW) ferroelectrics have attracted significant attention for their potential in next-generation nano-electronics. Two-dimensional (2D) group-IV monochalcogenides have emerged as a promising candidate due to their strong room temperature in-plane polarization down to a monolayer limit. However, their polarization is strongly coupled with the lattice strain and stacking orders, which impact their electronic properties. Here, we utilize four-dimensional scanning transmission electron microscopy (4D-STEM) to simultaneously probe the in-plane strain and out-of-plane stacking in vdW SnSe. Specifically, we observe large lattice strain up to 4% with a gradient across ~50 nm to compensate lattice mismatch at domain walls, mitigating defects initiation. Additionally, we discover the unusual ferroelectric-to-antiferroelectric domain walls stabilized by vdW force and may lead to anisotropic nonlinear optical responses. Our findings provide a comprehensive understanding of in-plane and out-of-plane structures affecting domain properties in vdW SnSe, laying the foundation for domain wall engineering in vdW ferroelectrics., (© 2023. The Author(s).)

Background: Currently, the mechanism(s) underlying corticogenesis is still under characterization. Methods: We curated the most comprehensive single-cell RNA-seq (scRNA-seq) datasets from mouse and human fetal cortexes for data analysis and confirmed the findings with co-immunostaining experiments. Results: By analyzing the developmental trajectories with scRNA-seq datasets in mice, we identified a specific developmental sub-path contributed by a cell-population expressing both deep- and upper-layer neurons (DLNs and ULNs) specific markers, which occurred on E13.5 but was absent in adults. In this cell-population, the percentages of cells expressing DLN and ULN markers decreased and increased, respectively, during the development suggesting direct neuronal transition (namely D-T-U). Whilst genes significantly highly/uniquely expressed in D-T-U cell population were significantly enriched in PTN/MDK signaling pathways related to cell migration. Both findings were further confirmed by co-immunostaining with DLNs, ULNs and D-T-U specific markers across different timepoints. Furthermore, six genes (co-expressed with D-T-U specific markers in mice) showing a potential opposite temporal expression between human and mouse during fetal cortical development were associated with neuronal migration and cognitive functions. In adult prefrontal cortexes (PFC), D-T-U specific genes were expressed in neurons from different layers between humans and mice. Conclusion: Our study characterizes a specific cell population D-T-U showing direct DLNs to ULNs neuronal transition and migration during fetal cortical development in mice. It is potentially associated with the difference of cortical development in humans and mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Pan, Zhou, Wang, Zhang, Cao, Jiang, Li, Zhu, Zhao, Gu, Lin, Dong and Sun.)

Pyridinic nitrogen has been recognized as the primary active site in nitrogen-doped carbon electrocatalysts for the oxygen reduction reaction (ORR), which is a critical process in many renewable energy devices. However, the preparation of nitrogen-doped carbon catalysts comprised of exclusively pyridinic nitrogen remains challenging, as well as understanding the precise ORR mechanisms on the catalyst. Herein, a novel process is developed using pyridyne reactive intermediates to functionalize carbon nanotubes (CNTs) exclusively with pyridine rings for ORR electrocatalysis. The relationship between the structure and ORR performance of the prepared materials is studied in combination with density functional theory calculations to probe the ORR mechanism on the catalyst. Pyridinic nitrogen can contribute to a more efficient 4-electron reaction pathway, while high level of pyridyne functionalization result in negative structural effects, such as poor electrical conductivity, reduced surface area, and small pore diameters, that suppressed the ORR performance. This study provides insights into pyridine-doped CNTs-functionalized for the first time via pyridyne intermediates-as applied in the ORR and is expected to serve as valuable inspiration in designing high-performance electrocatalysts for energy applications., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

As China's rapid urbanization continues, uneven urban population spatial distribution (UPSD) has a profound impact on its CO 2 emissions. To understand how UPSD shapes CO 2 emissions in China, this study employs geographic detectors to analyze the spatial stratified heterogeneity patterns of urban CO 2 emissions and explore the spatial individual and interactive effects of UPSD in 2005 and 2015. Results show that CO 2 emissions increased significantly from 2005 to 2015, especially in developed cities and resource-based cities. The spatial individual effect of UPSD on spatial stratified heterogeneity pattern of CO 2 emissions has gradually increased in the North Coast, South Coast, the Middle Yellow River, and the Middle Yangtze River. The interaction of UPSD and urban transportation infrastructure, urban economic development, and urban industrial structure plays a more important role on the North Coast and East Coast than in other city groups in 2005. In 2015, the interaction between UPSD and urban research and development was the traction of mitigating CO 2 emissions in developed city groups, especially on the North Coast and East Coast. Moreover, the spatial interaction between the UPSD and urban industrial structure has gradually weakened in developed city groups, which means UPSD drives the prosperity of the service industry, thus contributing to the low-carbon development of Chinese cities., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Accurate prediction of protein-ligand binding affinities can significantly advance the development of drug discovery. Several graph neural network (GNN)-based methods learn representations of protein-ligand complexes via modeling intermolecule interactions and spatial structures (e.g., distances and angles) of complexes. However, these methods fail to emphasize the importance of bonds and learn hierarchical structures of complexes, which are significant for binding affinity prediction. In this article, we propose the structure-aware graph attention diffusion network (SGADN) to incorporate both distance and angle information for efficient spatial structure learning. We model complexes as line graphs with distance and angle information, focusing on bonds as nodes. Then we perform line graph attention diffusion layers (LGADLs) on line graphs to explore long-range bond node interactions and enhance spatial structure learning. Furthermore, we propose an attentive pooling layer (APL) to refine the hierarchical structures in complexes. Extensive experimental studies on two benchmarks demonstrate the superiority of SGADN for binding affinity prediction.