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A facile, fast and visible sensing platform for ascorbic acid (AA) detection has been developed based on self-assembled hydrangea-like europium metal-organic framework (HL-EuMOF). HL-EuMOF was synthesized through a simple one-step mixing process with Eu 3+ and 1, 10-phenanthroline-2, 9-dicarboxylic acid at room temperature, which exhibited excellent properties including strong red fluorescence, long decay lifetime (548.623 μs) and good luminescent stability. Based on the specific redox reaction between Fe 3+ and AA, the HL-EuMOF@Fe 3+ was fabricated with "turn-off" response for AA, where the resulting Fe 2+ displayed effective fluorescence quenching ability toward HL-EuMOF. The sensor demonstrated low detection limit (31.94 nM), rapid response time (30 s) and high selectivity. Integration of smartphone-assisted RGB analysis with HL-EuMOF@Fe 3+ permitted convenient and visible quantitative determination of AA level. This approach also presented good detection performances in complex human serum and beverage samples, which could provide a valuable tool for AA detection in biomedical research and food industry., 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. Published by Elsevier Ltd.)

Inspired by the structure characteristics of natural products, the size and morphology of particles are carefully controlled using a bottom-up approach to construct nanomaterials with specific spatial unit distribution. Animal polysaccharide nanomaterials, such as chitosan and chondroitin sulfate nanomaterials, exhibit excellent biocompatibility, degradability, customizable surface properties, and novel physical and chemical properties. These nanomaterials hold great potential for development in achieving a sustainable bio-economy. This paper provides a summary of the latest research results on the preparation of nanomaterials from animal polysaccharides. The mechanism for preparing nanomaterials through the bottom-up method from different sources of animal polysaccharides is introduced. Furthermore, this paper discusses the potential hazards posed by industrial applications to the environment and human health, as well as the challenges and future prospects associated with using animal polysaccharides in nanomaterials., 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 Ltd. All rights reserved.)

Background: Zellweger Syndrome (ZS), or cerebrohepatorenal syndrome, is a rare disorder due to PEX gene mutations affecting peroxisome function. While PEX6 coding mutations are known to cause ZS, the impact of noncoding mutations is less clear., Methods: A Chinese neonate and his family were subjected to whole exome sequencing (WES) and bioinformatics to assess variant pathogenicity. A minigene assay was also performed for detailed splicing variant analysis., Results: WES identified compound heterozygous PEX6 variants: c.315G>A (p. Trp105Ter) and c.2095-3 T>G. Minigene assays indicated that the latter variant led to abnormal mRNA splicing and the loss of exon 11 in PEX6 expression, potentially causing nonsense-mediated mRNA decay (NMD) or truncated protein structure., Conclusion: The study suggests that PEX6: c.2095-3 T>G might be a genetic contributor to the patient's condition, broadening the known mutation spectrum of PEX6. These insights lay groundwork for potential gene therapy for such variants., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

The reddish-orange color of Antarctic krill oil fades during storage, and the mechanism remains unclear. Model systems containing different combinations of astaxanthin (ASTA), phosphatidylethanolamine (PE), and tocopherol were subjected to accelerated storage. Among all groups containing ASTA, only the ones with added PE showed significant fading. Meanwhile, the specific UV-visible absorption (A 470 and A 495 ) showed a similar trend. Peroxide value and thiobarbituric acid reactive substances increased during storage, while ASTA and PE contents decreased. Correlation analysis suggested that oxidized PE promoted fading by accelerating the transformation of ASTA. PE content exceeded the critical micelle concentration (1μg/g) indicating the formation of reverse micelles. Molecular docking analysis indicated that PE also interacted with ASTA in an anchor-like manner. Therefore, it is speculated that amphiphilic ASTA is more readily distributed at the oil-water interface of reverse micelles and captured by oxidized PE, which facilitates oxidation transfer, leading to ASTA oxidation and color fading., 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 Ltd. All rights reserved.)

The gut microbiome plays a key role in regulating the gut-skin axis, and host genetics partially influence this regulation. The study investigated the role of gut microbiota and host genetics in the gut-skin axis, focusing on the unusual "coffee-like" color phenotype observed in TYRP1 mutant Oujiang Color Common Carp. We employed comparative high-throughput omics data from wild-type and mutant fish to quantify the influence of both genetics and gut microbes on skin transcriptomic expression and blood metabolites. We found 525 differential metabolites (DMs) and 45 distinct gut microbial genera in TYRP1 mutant fish compared to wild type. Interaction and causal mediation analyses revealed a complex interplay. The TYRP1 mutation likely triggers an inflammatory pathway involving Acinetobacter bacteria, Leukotrience-C4 and Spermine. This inflammatory response appears to be counterbalanced by an anti-inflammatory cardiovascular genetic network. The net effect is the upregulation of COMT, PLG, C2, C3, F10, TDO2, MHC1, and SERPINF2, leading to unusual coffee-like coloration. This study highlights the intricate interplay between gut microbiota, host genetics, and metabolic pathways in shaping complex phenotypes., 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 B.V.)

Selenium (Se)-enriched yeast is a good nutritional source for human being. Kazachstania unispora (K. unispora) has shown the positive physiological functionality for human health, whose potential for Se enrichment, however, remains elusive. This study demonstrated the ability of K. unispora to convert inorganic Se to organic Se, and then comprehensively investigated the accumulation and metabolism of Se in K. unispora. The results indicated that K. unispora can effectively accumulate organic Se, of which 95% of absorbed Se was converted to organic forms. Among these organic Se, 46.17% of them was bound to protein and 16.78% was combined with polysaccharides. In addition, some of the organic Se was metabolized to selenomethionine (30.26%) and selenocystine (3.02%), during which four low-molecular weight selenometabolites were identified in K. unispora. These findings expand the scope of Se-enriched yeast species, and provide useful knowledge for further investigation of Se enrichment mechanism in K. unispora., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Dent disease (DD) is a hereditary renal disorder characterized by low molecular weight (LMW) proteinuria and progressive renal failure. Inactivating mutations of the CLCN5 gene encoding the 2Cl - /H + exchanger ClC-5 have been identified in patients with DD type 1. ClC-5 is essentially expressed in proximal tubules (PT) where it is thought to play a role in maintaining an efficient endocytosis of LMW proteins. However, the exact pathological roles of ClC-5 in progressive dysfunctions observed in DD type 1 are still unclear. To address this issue, we designed a mouse model carrying the most representative type of ClC-5 missense mutations found in DD patients. These mice showed a characteristic DD type 1 phenotype accompanied by altered endo-lysosomal system and autophagy functions. With ageing, KI mice showed increased renal fibrosis, apoptosis and major changes in cell metabolic functions as already suggested in previous DD models. Furthermore, we made the interesting new discovery that the Lipocalin-2-24p3R pathway might be involved in the progression of the disease. These results suggest a crosstalk between the proximal and distal nephron in the pathogenesis mechanisms involved in DD with an initial PT impairment followed by the Lipocalin-2 internalisation and 24p3R overexpression in more distal segments of the nephron. This first animal model of DD carrying a pathogenic mutation of Clcn5 and our findings pave the way aimed at exploring therapeutic strategies to limit the consequences of ClC-5 disruption in patients with DD type 1 developing chronic kidney disease., 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 B.V. All rights reserved.)

A novel core-shell structured alginate-based hydrogel bead modified by co-gelatinizing with starch and protocatechuic acid (PA), was designed to modulate physical properties of beads, release behavior and antioxidant stability of encapsulated bioactives. Core was fabricated by ionotropic gelation, and its formulation (ratio of sodium alginate/starch) was determined by particle size/starch distribution, texture and bioactive encapsulation capacity of core. Then, coating core with shell-forming solution co-gelatinized with different doses of PA, and subsequently cross-linked with Ca 2+ to obtain core-shell structured beads. Surface microstructure, mechanical characteristics, and swelling ratio of beads were affected by concentrations of PA. Besides, core-shell structure containing PA could enhance delivery and sustained release of encapsulated phenolic bioactives during in vitro digestion, and improve their antioxidant potential stability. Furthermore, interaction between PA and polysaccharide components was elucidated by FTIR and TGA. The present information was beneficial for the advancement of functional food materials and bioactive delivery systems., 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. Published by Elsevier Ltd.)

The Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-child Transmission of Hepatitis B Virus , developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019, serves as a valuable reference for standardizing the prevention of mother-to-child transmission in China. As new evidence continues to emerge, it is essential to update these guidelines regularly to optimize clinical practice and research. To this end, the Infectious Disease Physician Branch of the Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of the Chinese Medical Association, in collaboration with multidisciplinary experts, have updated the guidelines based on the latest domestic and international research advancements and clinical practices, providing up-to-date guidance for clinicians and maternal and child healthcare workers., Competing Interests: All experts signed a conflict-of-interest declaration form before joining the 2024 Guidelines committee. No conflicts of interest related to the 2024 Guidelines exist. HR has been an Editor-in-Chief of Journal of Clinical and Translational Hepatology since 2013, FJ have been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2023. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

Brain metastasis is a major cause of poor prognosis and death in lung adenocarcinoma (LUAD); however, the understanding of therapeutic strategies and mechanisms for brain metastases from LUAD (BM-LUAD) remains notably limited, especially at the proteomics levels. To address this issue, we conducted integrated proteomic and glycoproteomic analyses on 49 BM-LUAD tumors, revealing two distinct subtypes of the disease: BM-S1 and BM-S2. Whole exome sequencing analysis revealed that somatic mutations in STK11 and KEAP1, as well as copy number deletions on chr19p13.3, such as STK11, UQCR11, and SLC25A23, were more frequently detected in BM-S2. In BM-S1 tumors, we observed significant infiltration of GFAP + astrocytes, as evidenced by elevated levels of GFAP, GABRA2, GABRG1 and GAP43 proteins and an enrichment of astrocytic signatures in both our proteomic data and external spatial transcriptomic data. Conversely, BM-S2 tumors demonstrated higher levels of PD-1 immune cell infiltration, supported by the upregulation of PD-1 and LAG-3 genes. These findings suggest distinct microenvironmental adaptations required by the different BM-LUAD subtypes. Additionally, we observed unique glycosylation patterns between the subtypes, with increased fucosylation in BM-S1 and enhanced sialylation in BM-S2, primarily affected by glycosylation enzymes such as FUT9, B4GALT1, and ST6GAL1. Specifically, in BM-S2, these sialylation modifications are predominantly localized to the lysosomes, underscoring the critical role of N-glycosylation in the tumor progression of BM-LUAD. Overall, our study not only provides a comprehensive multi-omic data resource but also offers valuable biological insights into BM-LUAD, highlighting potential mechanisms and therapeutic targets for further investigation., 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 B.V.)

Autophagy is an evolutionarily conserved degradation pathway for maintaining cellular homeostasis and its dysregulation leads to numerous human diseases such as cancer. As a core protein for autophagy, ATG16L1 (autophagy related 16 like 1) is heavily regulated by post-translational modifications, including phosphorylation, ubiquitination, and methylation, which is critical for autophagy regulation. In this study, we identify HDAC1 (histone deacetylase 1) as a regulator of ATG16L1 acetylation and hence autophagy. Specifically, HDAC1 colocalizes and interacts with ATG16L1, and reduces its acetylation, which is highly dependent on its enzymatic activity. By promoting ATG16L1 deacetylation, HDAC1 enhances ATG16L1 interaction with the ATG12-ATG5 conjugate, resulting in the activation of autophagic pathway. Consistently, the induction of basal autophagy by HDAC1 in colorectal cancer cells largely relies on its deacetylase activity as well as ATG16L1. Moreover, HDAC1 enhances the survival, proliferation, and transformation of colorectal cancer cells in an ATG16L-dependent manner, indicating the fundamental roles of autophagy in colorectal cancer. Together, our findings uncover a novel regulatory mechanism of autophagy and suggest both HDAC1 and ATG16L1 as therapeutic targets for colorectal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cerebral small vascular disease (CSVD) has a high incidence worldwide, but its pathological mechanisms remain poorly understood due to the lack of proper animal models. The current animal models of CSVD have several limitations such as high mortality rates and large-sized lesions, and thus it is urgent to develop new animal models of CSVD. Ultrasound can activate protoporphyrin to produce reactive oxygen species in a liquid environment. Here we delivered protoporphyrin into cerebral small vessels of rat brain through polystyrene microspheres with a diameter of 15 μm, and then performed transcranial ultrasound stimulation (TUS) on the model rats. We found that TUS did not affect the large vessels or cause large infarctions in the brain of model rats. The mortality rates were also comparable between the sham and model rats. Strikingly, TUS induced several CSVD-like phenotypes such as cerebral microinfarction, white matter injuries and impaired integrity of endothelial cells in the model rats. Additionally, these effects could be alleviated by antioxidant treatment with N-acetylcysteine (NAC). As control experiments, TUS did not lead to cerebral microinfarction in the rat brain when injected with the polystyrene microspheres not conjugated with protoporphyrin. In sum, we generated a rat model of CSVD that may be useful for the mechanistic study and drug development for CSVD., Competing Interests: Declaration of competing interest The authors declare that there is no competing interest., (Copyright © 2024. Published by Elsevier Inc.)

Recurrent epidemics of coronaviruses have posed significant threats to human life and health. The mortality rate of patients infected with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is 35 %. The main protease (M pro ) plays a crucial role in the MERS-CoV life cycle, and M pro exhibited a high degree of conservation among different coronaviruses. Therefore inhibition of M pro has become an effective strategy for the development of broad-spectrum anti-coronaviral drugs. The inhibition of SARS-CoV-2 M pro by the anti-tumor drug carmofur has been revealed, but structural studies of carmofur in complex with M pro from other types of coronavirus have not been reported. Hence, we revealed the structure of the MERS-CoV M pro -carmofur complex, analysed the structural basis for the binding of carmofur to MERS-CoV M pro in detail, and compared the binding patterns of carmofur to M pro s of two different coronaviruses, MERS-CoV and SARS-CoV-2. Considering the importance of M pro s for coronavirus therapy, structural understanding of M pro inhibition by carmofur could contribute to the design and development of novel antiviral drugs with safe and broad-spectrum efficacy., Competing Interests: Declaration of competing interest The authors declare that no conflicts of interest exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Shale gas has been extensively extracted in the Sichuan Basin in China in recent years. To gain insight into the potential impact of shale gas wastewater (SGW) discharge, sediment in a small river receiving treated SGW, as well as cultivated soil and paddy soil irrigated by the river water were collected. The occurrence and distribution of polycyclic aromatic compounds (PACs), including polycyclic aromatic hydrocarbons (PAHs) and their alkylated/oxygenated derivatives (APAHs/OPAHs), and thiophenes were investigated, the resultant potential ecological risks were assessed subsequently. The total concentration of PACs varied in the range of 1299.9-9286.4, 2069.4-11,512.3, and 475.7-2927.9 ng/g in sediment, cultivated soil and paddy soil, respectively, with thiophenes followed by APAHs being the abundant components in all the studied samples, demonstrating the potential impact of SGW discharge on sediment and surrounding soil environment. Based on the measured concentrations, potential ecological risks posed by PAHs and APAHs were calculated, and moderate to high ecological risks were observed in partial sampling sites, which mainly caused by 3-4 rings PAHs and APAHs., 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 B.V. All rights reserved.)

Nanoplastics are ubiquitous in marine environments, exhibiting high bioavailability and potential toxicity to marine organisms. However, the impacts of nanoplastics with various surface modifications on marine microalgae remain largely unexplored. This study explored the toxicity mechanisms of two nanoplastic types-polystyrene (PS) and polymethyl methacrylate (PMMA)-with distinct surface modifications on Skeletonema costatum at cellular and molecular levels. Results showed that nanoplastics significantly impaired the growth of microalgae, particularly PS-NH 2 , which caused the most pronounced growth inhibition, reaching 56.99 % after a 96-h exposure at 50 mg/L. Transcriptomic profiling revealed that nanoplastics disrupted the expression of genes predominantly involved in ribosome biogenesis, aminoacyl-tRNA biosynthesis, amino acid metabolism, and carbohydrate metabolism pathways. The integrated biochemical and transcriptomic evidence highlighted that PS-NH 2 nanoplastics had the most adverse impact on microalgae, affecting fundamental pathways such as ribosome biogenesis, energy metabolism, photosynthesis, and oxidative stress. Our findings underscore the influence of surface-modified nanoplastics on algal growth and contribute new understanding to the toxicity mechanisms of these nanoplastics in marine microalgae, offering critical information for assessing the risks of emerging pollutants., 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 B.V. All rights reserved.)

Background: Despite increasing evidence of a strong correlation between air pollution and otitis media (OM), the impact of early-life ozone (O 3 ) exposure on the development of OM in children remains uncertain., Objectives: To explore the connection between early-life O 3 exposure and OM, and to identify the critical time period(s) during which O 3 exposure significantly influences the development of OM in children., Methods: We conducted a study involving 8689 children living in Changsha, China. Information regarding personal factors, health conditions, and the indoor environment was gathered using questionnaires. Personal exposure to outdoor O 3 and other major pollutants at the place of residence during the periods before conception, prenatal periods, and after birth was calculated by applying the inverse distance weighted (IDW) method with data gathered from ten air quality monitoring stations. Multiple logistic regression analyses were employed to investigate the associations between O 3 exposure and children's OM., Results: After controlling for covariates and ambient temperature, exposure to O 3 during the year preceding pregnancy was correlated with childhood lifetime OM, showing ORs (95 % CI) of 1.28 (1.01-1.64). O 3 exposures in the 10th-12th, 7th-9th, and 4th-6th months before pregnancy were all linked to children's lifetime OM. Within the multi-window model, we detected that O 3 exposure in the 10th to 12th month prior to pregnancy was significantly related to lifetime OM, showing ORs (95 % CI) of 1.28 (1.05-1.55). A significant link was discovered between childhood OM and O 3 exposure after controlling for six other pollutants (SO 2 , PM 2.5 , NO 2 , PM 2.5 - 10 , CO, and PM 10 ) during the 10th to 12th month prior to conception. Exposure to O 3 during the 36th gestational week significantly raised the likelihood of childhood lifetime OM. There is a significant interaction between O 3 and temperature exposure during the first trimester of pregnancy and one year before pregnancy on childhood lifetime OM., Conclusions: Preconceptional O 3 exposure and its interaction with low temperature played critical roles in children's OM development, backing the hypothesis of "(pre) fetal origins of childhood OM"., 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 B.V. All rights reserved.)

As a novel pollutant, microplastic pollution has become a global environmental concern. Melatonin (MT) has a protective effect on the damage caused by pollutants. However, there is still a lack of research on the transgenerational toxicity of microplastics and the alleviation of microplastics toxicity by MT. In this study, the adult zebrafish was exposed to (0, 0.1 and 1 mg/L) polystyrene nanoplastics (PSNP) with or without (1 μM) MT for 14 days, and embryos (F1) were used for experiments. Our study found that long-term exposure of parents to 1 mg/L PSNP reduced fertilization rate and survival rate of offspring, increased the deformity rate and induced embryos to hatch in advance. The growth inhibition of offspring was related to the gene transcription of the growth hormone/insulin-like growth factor axis. Moreover, PSNP caused oxidative stress in offspring, damaged immune system, reduced antioxidant capacity and induced apoptosis. MT supplementation could effectively alleviate the developmental toxicity and oxidative damage of offspring, but the negative effects brought by PSNP could not be completely eliminated. Our research provided a new reference for the protective effect of MT on transgenerational toxicity induced by PSNP., 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 B.V. All rights reserved.)

This article delves into the principle, essence, definitions, classifications, fundamentals, and industrial applications of staged gasification for biomass, offering an insightful exploration into its multifaceted dimensions. By segmenting the gasification process based on its intricate reaction network into distinct sub-processes implemented in separate reactors or reaction zones, staged gasification facilitates nuanced reaction control and sub-process intensification. It aims to optimize the gasification process by minimizing inhibitory effects and maximizing promotional interactions among chemical reactions, intermediates, or targeted products. This approach has been extensively tested, yielding significant technical benefits such as in-situ tar component conversion and efficiency enhancements. A clear categorization of the diverse staged gasification processes documented in literature is presented, distinguishing them based on the nature of interactions among separated stages, namely, chemical interaction, thermal interaction, and sequential staging. Definitions are provided for key concepts such as decoupling gasification, dual-bed or twin-bed gasification, and gasification with in-situ tar removal. Core fundamentals discussed include the reaction characteristics and kinetics of sub-processes, in-situ conversion of heteroatomic components, reactor configuration, and reaction regulation strategies. The article also presents an analysis of several industrial applications to elucidate the technical characteristics of staged gasification. Concluding with a discussion on prospective research concerns, this review underscores the evolving landscape of staged gasification technology and its pivotal role in advancing biomass conversion efficiencies., 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 B.V. All rights reserved.)

Objective: To investigate the impact of the deep-learning-based CT fractional flow reserve (CT-FFR) on clinical decision-making and long-term prognosis in patients with obstructive coronary heart disease. Methods: In this single-center retrospective cohort study, consecutive patients with obstructive coronary heart disease (with at least one stenosis≥50%) on their first coronary computed tomography angiography (CCTA) in Beijing Anzhen Hospital from February 2017 to July 2018 were included. Baseline clinical and CT characteristics were collected. Deep-learning-based CT-FFR and Leiden CCTA risk score were calculated. All patients enrolled were followed up for at least 5 years. The study endpoint was major adverse cardiovascular events (MACE), defined as the composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and unplanned revascularization. Receiver operating characteristic (ROC) curves were drawn to define the optimal cut-off point of the Leiden score in predicting the 5-year MACE, and survival analysis and Cox regression were performed to explore the related factors of MACE. Results: A total of 622 patients, aged 61 (54, 66) years, with 407 (65.4%) males were included. Diagnostic coronary angiography was performed in 78 patients after their baseline CCTA, with 34 (43.6%) patients had CT-FFR>0.80. During a follow-up time of 2 181 (2 093, 2 355) days, 155 patients (24.9%) suffered from MACE. ROC derived optimal cut-off point of Leiden score for predicting MACE was 15.48. Survival analysis found that male patients, Leiden risk score>15 and CT-FFR≤0.80 had worse prognosis. Multivariate Cox regression analysis identified CT-FFR≤0.80 as an robust and independent predictor of MACE ( HR =4.98, 95% CI 3.15-7.86, P <0.001). Conclusion: Deep-learning-based CT-FFR aids in clinical decision-making and the evaluation of long-term prognosis in patients with obstructive coronary heart disease.

Objective: To develop and validate an artificial intelligence (AI) diagnostic model for coronary artery disease based on facial photos. Methods: This study was a cross-sectional study. Patients who were scheduled to undergo coronary angiography (CAG) at Beijing Anzhen Hospital and Beijing Daxing Hospital from August 2022 to November 2023 were included consecutively. Before CAG, facial photos were collected (including four angles: frontal view, left and right 60° profile, and top of the head). Photo datasets were randomly divided into a training set, a validation set (70%), and a testing set (30%). The model was constructed using Masked Autoencoder (MAE) and Vision Transformer (ViT) architectures. Firstly, the model base was pre-training using 2 million facial photos obtained from the publicly available VGGFace dataset, and fine-tuned by the training and validation sets; the model was validated in the test set. In addition, the ResNet architecture was used to process the dataset, and its outputs were compared with those of the models based on MAE and ViT. In the test set, the area under the operating characteristic curve ( AUC ) of the AI model was calculated using CAG results as the gold standard. Results: A total of 5 974 participants aged 61 (54, 67) years were included, including 4 179 males (70.0%), with a total of 84 964 facial photos. There were 79 140 facial photos in the training and validation sets, with 3 822 patients with coronary artery disease; there were 5 824 facial photos in the test set, with 239 patients with coronary artery disease. The AUC value of the MAE and ViT model initialized with pre-training model weights was 0.841 and 0.824, respectively. The AUC of the ResNet model initialized with random weights was 0.810, while the AUC of the ResNet model initialized with pre-training model weights was 0.816. Conclusion: The AI model based on facial photos showes good diagnostic performance for coronary artery disease and holds promise for further application in early diagnosis.

Background: Cell-surface proteins play key roles in the communication between external stimuli and internal signaling. As protein types and expression levels vary in different cells, in-situ visualization of the whole surface proteome (surfaceome) may facilitate the study of their functions in homeostasis maintenance or response to environmental changes (e.g., drug treatment). However, there lacks easily-prepared and universal labeling probes to visualize them in living cells., Results: We designed and synthesized a small-molecule fluorescent probe, SRB-NHS, for one-step labeling of surfaceome. Live-cell imaging results exhibited the plasma membrane localization of the fluorescent signal from SRB-NHS and SDS-PAGE/fluorescence scanning results confirmed the covalent labeling of proteins by SRB-NHS, indicating the suitability of SRB-NHS for surfaceome labeling towards different cell lines., Significance: Upon labeling by SRB-NHS, the cellular internalization of surfaceome was studied under different stimuli (e.g., nutritional deprivation, drug treatments). Intriguingly, specific monitoring of the interaction between antibody drugs and related cell-surface targets can be achieved when the probe is used in combination with fluorescently labeled antibodies and imaged via Förster resonance energy transfer (FRET), offering a new method compatible with various cell lines to monitor the surfaceome or a specific drug-target interaction in situ., 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 B.V. All rights reserved.)

Purpose: The mechanism underlying the upregulation of FLOT2 in tumors, especially its regulatory mechanism at the RNA level, remains unclear. The purpose of this study is to investigate the regulatory mechanism of FLOT2 upregulation in tumors, particularly at the RNA level, and its role in nasopharyngeal carcinoma (NPC) progression., Methods: We identified the role of HNRNPH1 in maintaining FLOT2 mRNA stability and its dependency on the m6A modification. We explored the interaction between HNRNPH1 and METTL14, a key enzyme in m6A modification, and its impact on FLOT2 mRNA stability. We also assessed the expression levels of HNRNPH1 and METTL14 in NPC and their correlation with patient malignancy and prognosis. Experimental approaches included in vitro and in vivo assays to study the effects of HNRNPH1 knockdown on NPC cell proliferation and invasion., Results: HNRNPH1 is highly expressed in NPC and stabilizes FLOT2 mRNA through an m6A-dependent mechanism. HNRNPH1 interacts with METTL14 to prevent its degradation by STUB1 E3 ligases, leading to increased m6A modification of FLOT2 by METTL14. Additionally, IGF2BP3 was shown to recognize the m6A modification on FLOT2 mRNA, further stabilizing it. High expression of HNRNPH1 and METTL14 were observed in NPC and were positively associated with increased malignancy and poorer patient outcomes. HNRNPH1 knockdown significantly reduced the proliferation and invasive capabilities of NPC cells. Restoration of METTL14 in HNRNPH1-depleted cells could rescue FLOT2 expression and the malignant phenotype, but this effect was negated by the knockdown of FLOT2., Conclusion: Our study elucidates a novel mechanism where HNRNPH1 and METTL14 work together to maintain the stability of FLOT2 mRNA, thereby promoting NPC progression. Targeting this pathway presents a promising therapeutic strategy for the treatment of NPC., Competing Interests: Declarations. Ethical approval: The study was conducted in accordance with the principles of the Declaration of Helsinki. The Informed consent forms were completed by patients before surgery, and the study was approved by the Ethical Committee of Jiangxi Cancer Hospital and the Institutional Animal Care and Use of Committee of Nanchang Royo Biotech Co,. Ltd). Consent for publication: All the authors have read the manuscript and agreed to submit the paper to the Journal. Competing interests: The authors declare no competing interests., (© 2024. Springer Nature Switzerland AG.)

Jieyu Anshen Granule is a traditional Chinese medicine prescription used for depression and primarily comprises five herbal medicines: Zhizi, Chaihu, Zhigancao, Danggui, and Yuanzhi. This study established a traditional Chinese herbal medicine-specific library using emerging ultra-high-performance liquid chromatography-quadrupole-orbitrap-tandem mass spectrometry analysis. Through library comparison, the study has fulfilled isomers distinction. As a result, 47 compounds were simultaneously and putatively identified from Jieyu Anshen Granule, including 12 unexpected compounds and 35 expected compounds. The unexpected compounds comprised cyclocommunol, 5-hydroxyflavone, tangeretin, 3,5,6,7,8,3',4'-heptemethoxyflavone, calycosin-7-O-β-D-glucoside, 7,4'-dihydroxyflavone, naringenin-7-O-β-D-glucoside, matrine, betaine, jervine, alantolactone, and hypericin. Among the 35 expected compounds, saikosaponin A, saikosaponin D, glycyrrhizic acid, geniposide, ligustilide, and polygalaxanthone III were further investigated using a quantum chemistry approach. Based on these, an effective quality assessment strategy is proposed for the Pharmacopeia, involving the simultaneous analysis of glycyrrhizic acid, geniposide, ligustilide, polygalaxanthone III, saikosaponins A and D through ultra-high-performance liquid chromatography-quadrupole-orbitrap-tandem mass spectrometry analysis. This strategy enables the detection of adulteration in relation to Zhizi, Chaihu, Zhigancao, Danggui, and Yuanzhi in Jieyu Anshen Granule. The findings of unexpected compounds will deepen the understanding of chemistry in Jieyu Anshen Granule., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

Purpose: Posttranslational modification significantly contributes to the transcriptional diversity of tumors. Adenosine deaminase acting on RNA 1 (ADAR1) and its mediated adenosine-to-inosine (A-to-I) editing have been reported to influence tumorigenesis across various cancer types. Nevertheless, the relationship between ADAR1 and radioresistence remains to be elucidated., Methods: The protein expression was detected by immunohistochemistry and Western Blot, while the mRNA expression was measured by RT-qPCR. The tumor growth was evaluated by CCK8, colony formation assays, EdU assay, and in-vivo mouse model. γ-H2AX foci formation, neutral comet tailing assay, and clonogenic cell survival assay were performed to determine the DNA damage and radiosensitivity. RNA-seq was conducted to identify the main downstream effector. The interaction between ADAR1 and Rad18 was examined by immunofluorescence and co-immunoprecipitation., Results: We reported that ADAR1 was upregulated and correlated with poor prognosis in non-small cell lung cancer (NSCLC). In addition, we demonstrated that silencing ADAR1 significantly impaired tumor growth and improved tumor sensitivity to radiotherapy in vitro and in vivo. Mechanistically, we found that Rad18, which has been established as a versatile modulator of DNA repair, was the major downstream effector of ADAR1. ADAR1 not only regulated Rad18 mRNA expression by E2F3 but also colocalized and interacted with Rad18. Finally, our rescue experiments demonstrated that ADAR1's protumorigenic functions were partially dependent on Rad18., Conclusion: Our results revealed the role of ADAR1 in cooperation with Rad18 in modulating oncogenesis and radioresistance in NSCLC for the first time, and suggested the therapeutic potential of targeting ADAR1 in overcoming radioresistance., Competing Interests: Declarations. Ethics approval and consent to participate: The present study was approved by the Ethics Committee of Union Hospital of Huazhong University of Science and Technology. Animal experiment was approved by the Animal Care and Use Committee at Tongji Medical College, Huazhong University of Science and Technology. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Inflammation is a complex physiological response involving various cellular and molecular events. Sulfur dioxide (SO 2 ), which is usually in the form of HSO 3 - and SO 3 2- under physiological conditions, plays a crucial role in the regulation of inflammation and diseases. Frequency upconversion luminescence (FUCL) can realize the unique anti-Stokes process of long-wavelength excitation to short-wavelength emission; thus, it is a highly promising optical method for in vivo imaging due to its deep tissue penetration, low photo-damage, etc . Therefore, we developed a near-infrared FUCL NIRX-1 probe for the detection of HSO 3 - . NIRX-1 had a fast response (80 s), a low detection limit (0.43 μM), and high selectivity towards HSO 3 - . In addition, NIRX-1 had deep light penetration ability due to the near-infrared excitation at 808 nm and was able to detect HSO 3 - in living cells and mice. Lastly, NIRX-1 was employed in the imaging of HSO 3 - in an inflammation mouse model through FUCL imaging techniques. All these features make NIRX-1 a good candidate for the investigation of SO 2 -associated physiological and pathological processes.

Electrochemical reduction is a promising way to make use of CO 2 as feedstock for generating renewable fuel and valuable chemicals. Several metals can be used as the electrocatalyst to generate CO and formic acid, but hydrogen formation is an unwanted side reaction that can even be dominant. The lack of selectivity is, in general, a significant problem, but silver-based electrocatalysts have been shown to be highly selective, with faradaic efficiency of CO production exceeding 90%, when the applied voltage is below -1 V vs RHE. In this voltage range, only a small amount of hydrogen and formate is formed. We present calculations of the activation free energy for the various elementary steps as a function of applied voltage at the three low index facets, Ag(111), Ag(100) and Ag(110), as well as experimental measurements on polycrystalline electrodes, to identify the reason for this high selectivity. The formation of formic acid is suppressed, even though it is thermodynamically favored, because of the low coverage of adsorbed hydrogen and kinetic hindrance to the formation of the HCOO* intermediate, while *COOH, a key intermediate in CO formation, is thermodynamically unstable until the applied voltage reaches -1 V vs RHE, at which point the kinetics for its formation are more favorable than for hydrogen. The calculated results are consistent with experimental measurements carried out for acidic conditions and provide an atomic scale insight into the high CO selectivity of silver-based electrocatalysts.

Throughout the course of the SARS-CoV-2 pandemic, genetic variation has contributed to the spread and persistence of the virus. For example, various mutations have allowed SARS-CoV-2 to escape antibody neutralization or to bind more strongly to the receptors that it uses to enter human cells. Here, we compared two methods that estimate the fitness effects of viral mutations using the abundant sequence data gathered over the course of the pandemic. Both approaches are grounded in population genetics theory but with different assumptions. One approach, tQLE, features an epistatic fitness landscape and assumes that alleles are nearly in linkage equilibrium. Another approach, MPL, assumes a simple, additive fitness landscape, but allows for any level of correlation between alleles. We characterized differences in the distributions of fitness values inferred by each approach and in the ranks of fitness values that they assign to sequences across time. We find that in a large fraction of weeks the two methods are in good agreement as to their top-ranked sequences, i.e. as to which sequences observed that week are most fit. We also find that agreement between the ranking of sequences varies with genetic unimodality in the population in a given week., (Creative Commons Attribution license.)

The thermal properties of interfaces in nanomaterials are critical for various technological applications, including thermal management in electronic and photonic devices, thermoelectric conversion and thermal insulation. Recent advancements in numerical simulation tools (the non-equilibrium Green's approach, the Boltzmann transport equation and the Monte Carlo method, molecular dynamics simulations) have significantly enhanced our understanding of phonon transport and scattering processes in nanomaterials. These advances have led to the discovery of new thermal interfacial materials and enabled precise modulation of phonon thermal conductance to achieve desired thermal performance. This review summarizes recent research progress in interface thermal transport, focusing on intriguing heat phenomena such as finite size effect and phonon coherent property. Additionally, it discusses strategies for modulating thermal conductance through disorder and roughness. Finally, the review proposes the opportunities and challenges associated with modulating interface thermal transport., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

This work investigates Jahn-Teller conical intersections (CoIns) and the pseudo-Jahn-Teller effect on the formations and transformations of the low-lying singlet metal-ligand charge transfer ( 1 MLCT) excited states during the ultrafast evolution process of photoexcited [Ru(tpy) 2 ] 2+* (tpy = 2,2':6',2″-terpyridine). Longuet-Higgins' geometric phase analyses indicate that the potential energy surface (PES) crossing between charge transfer states 1 MLCT 1 and 1 MLCT 2 is a CoIn, originating from the change in diabatic Hamiltonian matrix elements around the CoIn. Moreover, an E ⊗( b 1 + b 2 ) Jahn-Teller distortion can occur around the Franck-Condon and minimal energy CoIn (MECI) configurations, causing the molecule to distort spontaneously from the high-symmetry D 2 d configuration to C 2 v symmetry configurations that are close to it. Furthermore, the pseudo-Jahn-Teller effect can cause the molecule to distort further from C 2 v to C 1 geometries since the former is a second-order saddle point on the whole dimensional PES but the latter is a true minimum. Eight minima in total are symmetrically distributed around the MECI. These minima are connected by the interligand electron transfer, the charge transfer, and the butterfly-like conformational inversion reactions, all of which have extremely small energy barriers.

Bacillus cereus , a global threat, is one of the major causes of toxin-induced foodborne diseases. However, a comprehensive assessment of the prevalence and characteristics of B. cereus worldwide is still lacking. Here, we applied whole-genome sequence analysis to 191 B. cereus collected in Africa, America, Asia, Europe, and Oceania from the 1900s to 2022, finding that CC142 dominated the global B. cereus clonal complex. The results provided direct evidence that B. cereus could spread through the food chain and intercontinentally. B. cereus from different generations worldwide showed coherence in the antibiotic-resistant gene and virulence and biofilm gene profiles, although with high genomic heterogeneity. The BCI-BCII-vanZF-fosB profiles and virulence and biofilm genes were detected at high rates, and we emphasized that B. cereus would pose a serious challenge to global public health and clinical treatment.IMPORTANCEThis study first emphasized the prevalence, genetic characteristics, and pathogenicity of Bacillus cereus worldwide from the 1900s to 2022 using whole-genome sequence analysis. The CC142 dominated the global Bacillus cereus clonal complex. Moreover, we revealed a close evolutionary relationship between the isolates from different sources. B. cereus isolates from different generations worldwide showed coherence in potential pathogenicity, although with high genomic heterogeneity. The BCI-BCII-vanZF-fosB profiles and virulence and biofilm genes were detected at high rates, and we emphasized that B. cereus would pose a serious challenge to global public health and clinical treatment., Competing Interests: The authors declare no conflict of interest.

Human noroviruses (HuNoVs) are a significant cause of epidemic and sporadic acute gastroenteritis worldwide. The lack of a reproducible culture system hindered the study of HuNoV replication and pathogenesis for almost a half-century. This barrier was overcome with our successful cultivation of multiple HuNoV strains in human intestinal enteroids (HIEs), which has significantly advanced HuNoV research. We optimized culture media conditions and generated genetically modified HIE cultures to enhance HuNoV replication in HIEs. Building upon these achievements, we now present new insights into this culture system, which involve testing different media, unique HIE lines, and additional virus strains. HuNoV infectivity was evaluated and compared in new HIE models, including HIEs generated from different intestinal segments of individual adult organ donors, HIEs from human intestinal organoids produced from directed differentiation of human embryonic stem cells that were then transplanted and matured in mice before making enteroids (H9tHIEs), genetically engineered (J4 FUT2 knock-in [ KI ] , J2 STAT1 knockout [ KO ]) HIEs, as well as HIEs derived from a patient with common variable immunodeficiency (CVID) and from infants. Our findings reveal that small intestinal HIEs, but not colonoids, from adults, H9tHIEs, HIEs from a CVID patient, and HIEs from infants support HuNoV replication with segment and strain-specific differences in viral infection. J4 FUT2-KI HIEs exhibit the highest susceptibility to HuNoV infection, allowing the cultivation of a broader range of genogroup I and II HuNoV strains than previously reported. Overall, these results contribute to a deeper understanding of HuNoVs and highlight the transformative potential of HIE cultures in HuNoV research. IMPORTANCE Human noroviruses (HuNoVs) cause global diarrheal illness and chronic infections in immunocompromised patients. This paper reports approaches for cultivating HuNoVs in secretor positive human intestinal enteroids (HIEs). HuNoV infectivity was compared in new HIE models, including ones from (i) different intestinal segments of single donors, (ii) human embryonic stem cell-derived organoids transplanted into mice, (iii) genetically modified lines, and (iv) a patient with common variable immunodeficiency disease. HIEs from small intestine, but not colon, support HuNoV replication with donor, segment, and strain-specific variations. Unexpectedly, HIEs from one donor are resistant to GII.3 infection. The genetically modified J4 FUT2 knock-in ( KI ) HIEs enable cultivation of a broad range of GI and GII genotypes. New insights into strain-specific differences in HuNoV replication in HIEs support this platform for advancing understanding of HuNoV biology and developing potential therapeutics., Competing Interests: The authors declare no conflict of interest.

Background: From 2022 to 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused by Omicron variants spread rapidly in Guangdong Province, resulting in over 80% of the population being infected., Results: To investigate the levels of neutralizing antibodies (NAbs) in individuals following the rapid pandemic and to evaluate the cross-protection against currently circulating variants of SARS-CoV-2 in China, neutralization assay and magnetic particle chemiluminescence method were used to test the 117 serum samples from individuals who had recovered 4 weeks post-infection. The results indicated that the levels of NAbs against prototype and Omicron variants BA.5 were significantly higher than those against Omicron variants BQ.1, XBB.1.1, XBB.1.9, XBB.1.16 and EG.5, regardless of whether the infection was primary or secondary., Conclusions: The cross-protection provided by NAbs induced by prototype and Omicron BA.5 variants was limited when challenged by BQ.1, XBB.1.1, XBB.1.9, XBB.1.16 and EG.5 variants. This indicates that we should pay more attention to the risk of multiple infection from any novel Omicron variants that may emerge in the near future., Competing Interests: Declarations. Ethics approval and consent to participate: The authors have adhered to the ethical policies of the journal. No ethical approval was required since this study was performed on the remnants for the diagnosis of stored microbiological samples, human material was removed and no participant data has been handled. In addition, research has been performed in accordance with the Declaration of Helsinki and all experimental protocols were approved by the Research Ethics Review Committee of Guangdong Provincial Center for Disease Control and Prevention. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3), a plasma membrane-bound metabolic enzyme, converts extracellular nucleotides into nucleosides. ENTPD3 is involved in various pathophysiological processes, including cellular adhesion, metabolism, activation, and migration. However, its specific function in the uterus remains unclear. This study aimed to investigate the expression pattern and localization of Entpd3 in the mouse uterus throughout the estrous cycle using immunohistochemistry (IHC), quantitative real-time PCR, and western blot analysis. The effect of sex steroid hormones on Entpd3 expression was also examined in ovariectomized (OVX) mice treated with 17β-estradiol (E2)/progesterone (P4) and estrogen receptor antagonist (Fulvestrant)/progesterone receptor antagonist (Mifepristone). Results demonstrated that elevated levels of Entpd3 mRNA and protein were noted during estrus and metestrus, with a decline in diestrus and proestrus. IHC revealed abundant ENTPD3 in the cytoplasm of glandular and luminal epithelial cells during estrus and metestrus. Additionally, treatment with E2 or P4 in OVX mice downregulated the expression of Entpd3 in the mouse uterus, which was rescued by Fulvestrant or Mifepristone. This study demonstrated that the expression of Entpd3 in the mouse uterus varied dynamically throughout the estrous cycle and was steroid-dependent, suggesting a potential role for Entpd3 in female mice's reproductive function., Competing Interests: Declarations. Ethics Approval: The Helsinki Declaration’s ethical criteria were followed in the conduct of this investigation. The research protocol was approved by Ethics Committee of the First Affiliated Hospital of Guangxi Medical University for Medical Experimental Animals (No. 2024-D176-01). Consent to Participate: Not applicable. Consent for Publication: All listed authors have reviewed and approved the manuscript for publication. Conflict of Interest: The authors claim to have no conflicting interests., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification in 2012, extensive research has unveiled its involvement in the pathophysiology of numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious diseases, autoimmune conditions, metabolic disorders, and skin diseases. Oxidizable lipids, overload iron, and compromised antioxidant systems are known as critical prerequisites for driving overwhelming lipid peroxidation, ultimately leading to plasma membrane rupture and ferroptotic cell death. However, the precise regulatory networks governing ferroptosis and ferroptosis-targeted therapy in these diseases remain largely undefined, hindering the development of pharmacological agonists and antagonists. In this review, we first elucidate core mechanisms of ferroptosis and summarize its epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, and N6-methyladenosine modification) and nonepigenetic modifications (e.g., genetic mutations, transcriptional regulation, and posttranslational modifications). We then discuss the association between ferroptosis and disease pathogenesis and explore therapeutic approaches for targeting ferroptosis. We also introduce potential clinical monitoring strategies for ferroptosis. Finally, we put forward several unresolved issues in which progress is needed to better understand ferroptosis. We hope this review will offer promise for the clinical application of ferroptosis-targeted therapies in the context of human health and disease., Competing Interests: The authors have declared that no conflict of interest exists., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by mutations that decrease transforming growth factor-β signaling. LDS-causing mutations increase the risk of aneurysm throughout the arterial tree, yet the aortic root is a site of heightened susceptibility. Here we investigate the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1 M318R/+ LDS mice by single-cell transcriptomics to identify molecular determinants of this vulnerability. Reduced expression of components of the extracellular matrix-receptor apparatus and upregulation of stress and inflammatory pathways were observed in all LDS VSMCs. However, regardless of genotype, a subset of Gata4-expressing VSMCs predominantly located in the aortic root intrinsically displayed a less differentiated, proinflammatory profile. A similar population was also identified among aortic VSMCs in a human single-cell RNA sequencing dataset. Postnatal VSMC-specific Gata4 deletion reduced aortic root dilation in LDS mice, suggesting that this factor sensitizes the aortic root to the effects of impaired transforming growth factor-β signaling., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

TnpB proteins encoded in the IS200/IS605 family are RNA-guided endonuclease which can be harnessed in genome editing. However, the collateral nuclease activity of TnpB remains poorly understood, which limits the development of TnpB-based diagnostic tools. Here we showed that TnpB from a thermophilic archaeon exhibits enhanced collateral ssDNA cleavage activity (trans-cleavage) activated by high temperature. Mutations either in the TAM or seed sequences of the target DNA impair the trans-cleavage activity, which indicates its potential to be employed in molecular diagnostic. Importantly, by optimizing the length and the sequences of the collateral substrates, we have developed a new nucleic acid detection method based on TnpB with a sensitivity of 29 cp μl -1 in 30 min, which we name it TESD (TnpB Enable fast and Sensitive Detection). In summary, our findings illustrate the collateral nuclease activity of a TnpB from thermophiles and provide a novel platform for molecular diagnostics., Competing Interests: Competing interests: L.M., T.L., Y.X., F.W. and N.P. have an authorized Chinese patent (no. 202311201983.0). The other authors declare no competing interests., (© 2024. The Author(s).)

The welding workshop of metal structural parts is highly energy-consuming. To meet the national low-carbon green demand, this paper focus on the welding workshop scheduling problem in production process with considering the carbon footprints such as equipment energy consumption, welding material consumption and shielding gas consumption. Firstly, a bi-objective low-carbon welding scheduling mathematical model is established with minimizing makespan and carbon emission. Then, an improved Grey Wolf Optimizer (IGWO) with three strategies is designed to solve this multi-objective problem. The grey wolf multi-wandering strategy (first) is proposed to enhance the population diversity. The grey wolf coordinated hunting strategy (second) based on dynamic weights is introduced to improve the convergence of IGWO. A local optimization strategy(third) is designed to improve the post-optimal search performance by adjusting the machine assignment based on the critical path. A welding workshop green scheduling case is designed to verify the model and algorithm proposed in this paper. The minimum completion time and carbon emissions obtained by the IGWO algorithm are 842.14 and 3.85E + 05, respectively. This result is better than that obtained by NSGA-II and GWO.The results show that the model effectively reduce the carbon emissions of the workshop, and the algorithm can effectively solve the model., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The family of SQUAMOSA promoter binding protein-like (SPL) transcription factors is essential for regulating plant growth and development. While this SPL gene functional research has been limited in Rhododendron molle (R. molle)., Objective: To preliminarily explore the regulatory mechanism of the SPL gene in flower bud development of R. molle., Methods: In this study, for R. molle, the flower bud differentiation period was determined by observing the morphological anatomy of the flower bud. The SPL gene family members were identified based on the R. molle genome, Additionally, the expressions of RmSPL genes at five flower bud differentiation stages were analyzed via Quantitative reverse transcription PCR (RT-qPCR)., Results: We first characterized 20 SPL family members in the reference genome of R. molle. The phylogenetic analysis of plant SPL proteins separated them into eight subfamilies (G1-G8) according to conserved gene structures and protein motifs. Cis-elements of promoter region analysis showed that RmSPL genes were regulated by light, phytohormones, stress response, and plant growth and development and may play a critical role in the photoresponse, abasic acid, anaerobic induction, and meristematic expression. Gene expression analysis showed that 18 RmSPL genes were differentially expressed in different developing flower buds. In particular, RmSPL1/7/8/12/13 exhibited significantly different expressions, suggesting that they were likely essential genes for regulating the differentiation of flower buds., Conclusion: In conclusion, our analysis of RmSPL genes provides a theoretical basis and reference for future functional analysis of RmSPL genes in the flower bud differentiation of R. molle., Competing Interests: Declarations. Conflict of interest: The authors have no competing interests. Ethical approval: Not applicable. Informed consent: Not applicable., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Microfluidic-engineered hydrogel microspheres have emerged as a promising avenue for advancements in tissue engineering and regenerative medicine, particularly through the precise manipulation of fluids to achieve personalized composite biomaterials. In this study, we employed microfluidic technology to fabricate hydrogel microspheres (HMs) using Chinese herbal Bletilla striata polysaccharide (BSP) as the primary material. Concurrently, the natural active ingredient 20(S)-protopanaxadiol (PPD) was encapsulated within the HMs in the form of liposomes (PPD-Lipo), resulting in the formation of nanocomposite hydrogel microspheres (PPD-Lipo@HMs) intended for diabetic wound tissue repair. PPD-Lipo@HMs are characterized by the expansive specific surface area, adjustable mechanical properties, and exceptional biocompatibility. PPD-Lipo@HMs can stimulate the production of vascular endothelial factors, which in turn enhances the migration of endothelial cells, the creation of tubes, angiogenesis, and tissue repair. Moreover, the PPD-Lipo@HMs accumulation produces a microsphere scaffold that effectively covers damaged tissues, promoting the attachment, spread, and multiplication of fibroblast and endothelial cells. The polysaccharide material BSP within PPD-Lipo@HMs can modulate the immune microenvironment of the damaged tissue, reducing inflammation, encouraging re-epithelialization and granulation tissue formation, accelerating angiogenesis and collagen deposition, ultimately leading to tissue repair. The findings highlight the superior therapeutic efficacy of the microfluidic-engineered PPD-Lipo@HMs in addressing the complex challenges of diabetic wound tissue repair, thereby affirming the significant potential of microfluidic engineering technology in tissue repair applications., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine (SYXK2024-092). Consent for publication: All authors read and agreed to submit the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Ancient Chang'an in the Tang Dynasty (618-907 AD) was one of the world's largest and most populated cities and acted as the eastern end of the world-famous Silk Road. However, little is known about the genetics of Chang'an people and whether the Western Regions-related gene flows have been prevalent in this cosmopolitan city., Results: Here, we present seven genomes from Xingfulindai (XFLD) sites dating to the Tang Dynasty in Chang'an. We observed that four of seven XFLD individuals (XFLD&#95;1) were genetically homogenous with the Late Neolithic Wadian, Pingliangtai, and Haojiatai populations from the middle reaches of the Yellow River Basin (YR&#95;LN), with no genetic influence from the Western Eurasian or other non-Yellow River-related lineages. The remaining three XFLD individuals were a mixture of YR&#95;LN-related ancestry and ~ 3-15% Western Eurasian-related ancestry. Mixtures of XFLD&#95;1 and Western Eurasian-related ancestry drove the main gradient of genetic variation in northern and central Shaanxi Province today., Conclusions: Our study underlined the widespread distribution of the YR&#95;LN-related ancestry alongside the Silk Road within the territory of China during the historical era and provided direct evidence of trans-Eurasian communication in Chang'an from a genetic perspective., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study aimed to investigate the regulatory mechanisms that influenced autophagy in Steroid-induced necrosis of the femoral head (SONFH) by constructing a competing endogenous RNA (ceRNA) network. Blood sample data from the SONFH patients were obtained from the Gene Expression Omnibus (GEO) database under the accession number GSE123568. Autophagy-related genes were identified from the Human Autophagy Database (HADb). Differential analysis and weighted gene co-expression network analysis (WGCNA) were performed on the GSE123568 dataset to screen for core genes and validation was performed with the validation set. Based on the GEO dataset (GSE74089), we performed differential lncRNA analysis. Meanwhile, we utilized three databases, namely miRDB, TargetScan, and StarBase, to predict the miRNAs of target genes and corresponding lncRNAs. Cytoscape software was used to construct and visualize the ceRNA networks. We also employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to quantify their expression levels. A total of 1692 differentially expressed genes (DEGs) were identified in the GSE123568 dataset. By intersecting with the HADb database, 47 autophagy-related genes were identified from these DEGs. Furthermore, we found the significant correlation between RNF144B and 37 autophagy genes. Importantly, we established a regulatory axis involving TUG1, hsa-miR-31-5p, and RNF144B., and both TUG1 and RNF144B were upregulated, while hsa-miR-31-5p was downregulated in the SONFH cell model. A TUG1-hsa-miR-31-5p-RNF144B axis was related to autophagy genes, which potentially provided insights into the RNA interactions triggering autophagy in SONFH., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

SnO 2 prepared by chemical bath deposition (CBD) is among the most promising electron transport layers for enabling high efficiency, large area perovskite solar cells (PSCs). However, the uneven surface coverage of SnO 2 and the presence of defects in the film and/or at the SnO 2 /perovskite interface significantly affect the device performance. Herein, a multifunctional molecule of phosphorylcholine chloride (CP) is introduced to modulate the CBD growth of SnO 2 and suppress the generation of defects. The agglomeration of SnO 2 nanoparticles is hindered due to the electrostatic repulsion effect, leading to the formation of dense and conformal films with improved optical transmittance and electrical conductivity. Moreover, the defects both in SnO 2 and at the interface of SnO 2 /perovskite are successfully passivated and the energy band structure is well regulated, contributing to the suppression of nonradiative recombination and the improvement of electron transport. As a result, a remarkably high power conversion efficiency (PCE) of 24.04% is attained for PSCs processed in air ambient. The unencapsulated devices exhibit improved long-term stability, maintaining over 80% of their initial PCE after storing in air ambient for 1500 h or under one-sun illumination for 600 h., (© 2024 Wiley‐VCH GmbH.)

Objectives: The clinical decision-making regarding post hoc management of early colorectal cancer (CRC) patients who have undergone non-curative endoscopic resection (ER) remains a subject of debate. This systematic review and meta-analysis aims to compare the clinical outcomes between patients undergoing additional surgery and those receiving surveillance only., Methods: A comprehensive literature search was conducted across three major medical databases: PubMed, Embase, and the Cochrane Library. STATA software was utilized for pooling analysis. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Quality Scale., Results: A total of 15 eligible studies encompassing 3,508 early CRC patients were included in this meta-analysis (additional surgery group: 1,974 cases; surveillance-only group: 1,533 cases). All included studies demonstrated good methodological quality, with Newcastle-Ottawa scores no less than 6. The results of the meta-analysis indicated that compared to the surveillance-only group, patients in the additional surgery group exhibited significantly improved overall survival (OR = 2.95, 95% CI: 2.05-4.24, P < 0.05), enhanced recurrence-free survival (OR = 2.53, 95% CI = 1.38-4.62, P < 0.05), a reduced recurrence rate (OR = 1.96, 95% CI = 1.22-3.13, P < 0.05), and a lower local recurrence rate (OR = 2.35, 95% CI = 1.12-4.95, P < 0.05). No significant sources of heterogeneity were identified among the studies analyzed; publication bias was also deemed acceptable across these investigations. Furthermore, we performed subgroup analyses based on inclusion criteria and age stratification which revealed notable differences in effect sizes between groups (JSCCR subgroup: OR = 2.09; 95% CI = 1.32-3.30 versus Non-JSCCR subgroup: OR = 1 .54; 95% CI = 0.89 -2.65, indicating negative results). Pooling analysis showed no significant difference between subgroups when stratified by age using a cutoff value of 65 years old., Conclusions: Compared to patients who underwent surveillance only, those receiving additional surgical treatment demonstrated superior outcomes in terms of overall survival, recurrence-free survival, recurrence rates, and control of local recurrences. This suggests that such an approach may represent a more optimal clinical decision for early-stage colorectal cancer (CRC) patients who have received non-curative endoscopic resection (ER). Furthermore, this study indicates that the inclusion criteria significantly influence the reported outcomes. Notably, age did not affect the recurrence rate. Overall, this is the first meta-analysis aimed at exploring and clarifying this ongoing controversy., Competing Interests: Declarations. Ethics approval and consent to participate: The formal ethical review was waived by our institutional review board. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study investigates various microfluidic chip fabrication techniques, highlighting their applicability and limitations in the context of urgent diagnostic needs showcased by the COVID-19 pandemic. Through a detailed examination of methods such as computer numerical control milling of a polymethyl methacrylate, soft lithography for polydimethylsiloxane-based devices, xurography for glass-glass chips, and micromachining-based silicon-glass chips, we analyze each technique's strengths and trade-offs. Hence, we discuss the fabrication complexity and chip thermal properties, such as heating and cooling rates, which are essential features of chip utilization for a polymerase chain reaction. Our comparative analysis reveals critical insights into material challenges, design flexibility, and cost-efficiency, aiming to guide the development of robust and reliable microfluidic devices for healthcare and research. This work underscores the importance of selecting appropriate fabrication methods to optimize device functionality, durability, and production efficiency., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/aims: The study aims to evaluate choroidal vascular changes in younger patients with myopia using ultrawidefield swept-source optical coherence tomography angiography (SS-OCTA)., Methods: Overall, 724 eyes of 362 participants (177 males, 185 females, age: 32.43±6.20 years) underwent SS-OCTA imaging (24×20 mm). The eyes were divided into normal, low myopia (LM), moderate myopia (MM), high myopia and superhigh myopia groups according to the spherical equivalent refraction (SER). Changes in choroidal vascular thickness (ChVT) and density (ChVD) in nine grids of the fundus were analysed using the latest version of the built-in analysis software., Results: Axial length (AL) showed a negative correlation with SER ( r =0.822, p=0.000); ChVT and ChVD showed a negative correlation with AL (p≤0.001) in all nine grids. In group analysis, compared with normal eyes, myopia affects ChVT earlier than ChVD, as observed in the LM and MM groups, respectively. The decrease in ChVT was most evident in the macular grid ( β = -34.20, p=0.000), whereas the decrease in ChVD was most evident in the optic disc grid ( β = -2.19, p=0.001)., Conclusion: Myopia has a significant impact on choroidal vascular structure, resulting in spatiotemporal differences. Using SS-OCTA with a new version of the built-in analysis software and a study with a larger sample cohort may aid in providing more authentic information on choroidal vascular changes in eyes with myopia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A new indigotin alkaloid, named talarindigotin A ( 1 ), along with the analogue 5H, 6H-quinindolin-11-one ( 2 ) were isolated from the mangrove endophytic fungus Talaromyces amestolkiae SCNU-F0041. Their structures were assigned on the basis of NMR, HRMS, and single-crystal X-ray diffraction analysis. In the cytotoxic bioassay, compound 1 showed great cytotoxicity against HepG2, Hela, HCT116, and Huh7 human cancer cell lines with IC 50 values ranging from 2.08 to 4.58 μM.

Wide-bandgap perovskite sub-cells (WPSCs), one of the most crucial components of perovskite-based tandem solar cells (PTSCs), play a critical role in determining the performance of tandem devices. However, confined by the compromised crystallization properties of wide-bandgap perovskites, WPSCs exhibit significantly lower efficiency than their theoretical limit. In particular, for n-i-p structured all-inorganic WPSCs (AIWPSCs), severe nonradiative recombination due to the buried interface defects severely decreases the photovoltaic performance. Herein, an efficient propionate group (PA - ) based ionic liquid, methylamine propionate (MAPA), is introduced into the perovskite/electron-transport layer (ETL) interface to passivate the buried interface of AIWPSCs. The intense interaction between the PA - and Pb-Pb dimer effectively heals the defects at the buried interface and facilitates a more homogeneous elemental distribution in the perovskite film. As a result, CsPbI 2.2 Br 0.8 -based AIWPSCs with a high power conversion efficiency (PCE) of 18.29% and open-circuit voltage (V OC ) of 1.33 V are obtained, which illustrates the superiority of MAPA in optimizing the performance of AIWPSCs. Moreover, by integrating these AIWPSCs with small-bandgap organic solar cells (SOSCs), high performance n-i-p structured all-inorganic perovskite/organic tandem solar cells (AIPOTSCs) with a high PCE of 23.19% and V OC of 2.08 V are also achieved., (© 2024 Wiley‐VCH GmbH.)

Developing and fabricating a heterogeneous catalyst for efficient formic acid (FA) dehydrogenation coupled with CO 2 hydrogenation back to FA is a promising approach to constructing a complete CO 2 -mediated hydrogen release-storage system, which remains challenging. Herein, a facile two-step strategy involving high-temperature pyrolysis and wet chemical reduction processes can synthesize efficient pyridinic-nitrogen-modified carbon-loaded gold-palladium alloy nanodots (AuPd alloy NDs). These NDs exhibit a prominent electron synergistic effect between Au and Pd components and tunable alloy-support interactions. The pyridinic-N dosage in carbon substrate improves the surface electron density of the alloy catalyst, thus regulating the chemical adsorption of FA molecules. Specifically, the engineered Au 3 Pd 7 /CN 0.25 demonstrates an outstanding room-temperature FA dehydrogenation efficiency, achieving ≈100% conversion and an initial turnover frequency (TOF) of up to 9049 h -1 . The versatile AuPd alloy NDs also show the ability to convert CO 2 , one of the products of FA dehydrogenation, into FA (formate) with a 90.8% yield under mild conditions. Moreover, in-depth insights into the unique alloyed microstructure, structure-activity relationship, key intermediates, and the alloy-driven five-step reaction mechanism involving the rate-determining step of C─H bond cleavage from critical *HCOO species via D-labeled isotope, in situ infrared spectroscopy, and theoretical calculations are investigated., (© 2024 Wiley‐VCH GmbH.)