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The increasing global frequency and severity of coral bleaching events, driven by the loss of endosymbiotic algae, pose a significant threat to these vital ecosystems. However, gene expression plasticity offers a potential mechanism for rapid and effective acclimatization to environmental changes. We employed dual transcriptomics to examine the gene expression profile of Seriatopora hystrix, an ecologically important scleractinian coral, across healthy, mildly bleached, and severely bleached colonies collected from the waters of Likupang, North Sulawesi, Indonesia. Our analysis revealed that coral bleaching is associated with gene plasticity in calcium signaling and focal adhesion within coral hosts, as well as with endoplasmic reticulum stress in symbionts. Notably, we identified specific genes associated with innate immunity that were predominantly overexpressed in mildly bleached coral hosts. This overexpression implies that high expression plasticity of these key genes might contribute to bleaching resistance and the preservation of the host-symbiont relationship. Our findings offer a detailed insight into the dynamics of bleaching resistance in S. hystrix, shedding light on the variability of bleaching risks in Indonesian reefs and underscoring the coral's ability to utilize gene expression plasticity for immediate survival and potential long-term adaptation to climate changes., 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.)

Covalent organic frameworks (COFs) have been demonstrated as promising photocatalysts for hydrogen peroxide (H 2 O 2 ) production. However, the construction of COFs with new active sites, high photoactivity, and wide-range light absorption for efficient H 2 O 2 production remains challenging. Herein, we present the synthesis of a novel azobenzene-bridged 2D COF (COF-TPT-Azo) with excellent performance on photocatalytic H 2 O 2 production under alkaline conditions. Notably, although COF-TPT-Azo differs by only one atom (-N=N- vs. -C=N-) from its corresponding imine-linked counterpart (COF-TPT-TPA), COF-TPT-Azo exhibits a significantly narrower band gap, enhanced charge transport, and prompted photoactivity. Remarkably, when employed as a metal-free photocatalyst, COF-TPT-Azo achieves a high photocatalytic H 2 O 2 production rate up to 1498 μmol g -1  h -1 at pH = 11, which is 7.9 times higher than that of COF-TPT-TPA. Further density functional theory (DFT) calculations reveal that the -N=N- linkages are the active sites for photocatalysis. This work provides new prospects for developing high-performance COF-based photocatalysts., (© 2024 Wiley-VCH GmbH.)

Strigolactones (SLs) are known to regulate plant architecture formation, nitrogen (N) and phosphorus (P) responses, and secondary metabolism, but their effects in tea plants remain unclear. We demonstrated that the application of a bioactive SL analogue GR24 either to tea roots or leaves initially stimulated but later inhibited catechins, theanine, and caffeine biosynthesis. GR24 treatment also promoted the accumulation of flavonols and insoluble proanthocyanidins in a time- and dose-dependent manner. GR24 influenced flavonoid and theanine biosynthesis genes, such as up-regulating CsTT2c, CsMYB12 , and CsbZIP1 , modulating N-responsive and assimilation genes ( CsNRT1,1 , CsGSI/TS1 , CsHRS1 , CsPHR1 , CsNLA1 , and CsLBD37/38/39 ), and repressing N/P transport and signaling genes ( CsPHO2 , CsPHT1 s, CsNRT2,2 , CsHHO1 , and CsWRKY38 ). GR24-induced changes in secondary metabolites were also observed in the leaves of tea plants. GR24-regulated CsLBD37a interacted with CsTT8a and CsTT2c, repressing catechins biosynthesis by interrupting MBW complex formation. GR24 regulated caffeine biosynthesis and regulator genes CsS40 and CsNAC7 and may thereby suppress caffeine production. GR24 altered the transcriptomic profiles of multiple hormone biosynthesis and signaling genes that potentially regulate tea characteristic metabolism and N/P signaling. This study provides new insights into SL-induced transcriptional reprogramming that leads to changes in N/P nutrition, secondary metabolism, and hormone signaling in tea plants.

Introduction: Here, we report the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of a multi-kinase inhibitor (TG02 capsule) as a new therapy for patients with recurrent high-grade gliomas in China., Methods: This is a single-center, dose-escalation, open-label phase I study, which enrolled patients with recurrent high-grade gliomas who failed to temozolomide. Patients were assigned sequentially into different dose groups and received TG02 every 4 weeks. The dose was increased in a traditional 3+3 design. Primary endpoints were the dose-limited toxicity (DLT) and the maximum tolerated dose (MTD)., Results: Twelve patients (8 glioblastomas, 4 diffuse astrocytoma) were enrolled between May 2019 and November 2021. Three patients received 100 mg and 9 received 150 mg TG02 twice a week. The plasma concentration of TG02 reached the maximum at 2 hours after administration, and the elimination half-life was about 7 hours. No DLT occurred and MTD was not defined in this study. Eleven patients had one or more investigator-assessed treatment-related adverse events (TRAEs). The most frequent TRAEs were vomiting (91.7%) and diarrhea (75.0%), and 50% of the patients had grade 3 or 4 adverse events. There were no treatment-related deaths. The median progression-free survival and overall survival were 1.77 (95% confidence interval [CI]: 0.82-4.24) and 9.63 (95%CI: 2.66-not estimated) months, respectively., Conclusions: TG02 capsule 150mg twice a week is safe and tolerable in Chinese patients with recurrent high-grade gliomas. Patients who failed to temozolomide showed obvious tumor reduction when switching to TG02 capsule. The efficacy for recurrent gliomas warrant further investigation., (S. Karger AG, Basel.)

In situ gelling eye drops of tacrolimus (FK506 Gel) were developed to address the formulation challenge of tacrolimus for anterior ocular inflammatory diseases. Both in silico and in vitro investigations were conducted to screen a suitable cyclodextrin species to increase the drug solubility. Guanosine was employed as the gelator and combined with inclusion complexes of tacrolimus in the presence of borate anions to obtain FK506 Gel, which gelated when came into contact with cations in tear fluid and led to the formation of a nanofibrous hydrogel. The versatility of our design to improve the solubility and ocular retention of the hydrophobic drug was demonstrated in vivo with coumarin 6 as a model drug. A mouse dry eye model was used to evaluate the therapeutic effects of FK506 Gel, which, in combination with the biocompatibility study, suggested that FK506 Gel served as a superior treatment for anterior ocular inflammatory diseases.

HECT-type E3 ubiquitin ligases (HECT E3s) participate in the progression of cardiovascular diseases. HERC2 has been reported to play critical roles in many pathological processes, but its role in cardiac hypertrophy remains unclear. In this study, we observed that the expression and activity of HERC2 was significantly upregulated in hypertrophic hearts and angiotensin II (Ang II)-stimulated primary cardiomyocytes. Knockdown of HERC2 in cardiomyocytes significantly alleviated the myocardial hypertrophy induced by Ang II. Conversely, cardiac specific overexpression of HERC2 aggravated Ang II-induced cardiac hypertrophy in vitro and in vivo. Furthermore, we demonstrated that HERC2 promoted cardiac hypertrophy via increasing the expression of lin-28 homologue A (Lin28a), an RNA-binding protein that regulates pathological cardiac hypertrophic. Knocking down Lin28a attenuated Ang II-induced myocardial hypertrophy and abolished the increase in myocardial hypertrophy by overexpression of HERC2. Further investigation indicated that HERC2 promoted the expression level of Lin28a by reducing MeCP2, a transcriptional suppressor of Lin28a. We also showed that the pro-hypertrophic effect of HERC2 was partially dependent on MeCP2 inhibition. Mechanistically, HERC2 directly bound with MeCP2, and promoting its K48-linked polyubiquitination and degradation. Combined, these findings demonstrate HERC2 plays a crucial role in pathological cardiac hypertrophy, thereby indicating that targeting the HERC2/MeCP2/Lin28a axis is a potential strategy for heart failure therapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We show that the rates of single base substitutions, additions, and deletions across the nuclear genome are strongly increased in a strain harboring a mutator variant of DNA polymerase α combined with a mutation that inactivates the 3´-5´ exonuclease activity of DNA polymerase δ. Moreover, tetrad dissections attempting to produce a haploid triple mutant lacking Msh6, which is essential for DNA mismatch repair (MMR) of base•base mismatches made during replication, result in tiny colonies that grow very slowly and appear to be aneuploid and/or defective in oxidative metabolism. These observations are consistent with the hypothesis that during initiation of nuclear DNA replication, single-base mismatches made by naturally exonuclease-deficient DNA polymerase α are extrinsically proofread by DNA polymerase δ, such that in the absence of this proofreading, the mutation rate is strongly elevated. Several implications of these data are discussed, including that the mutational signature of defective extrinsic proofreading in yeast could appear in human tumors., 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.)

Objective: To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism., Methods: 1. Patients with CKD stage 2-5 were selected to analyze the effect of lanthanum-containing preparations on CKD. 2. Sixty healthy male Wistar rats were randomly divided into control group, model group, lanthanum chloride groups (0.03 ng/kg, 0.1 ng/kg, 0.3 ng/kg, q.3d., i.v.), and lanthanum carbonate group (0.3 g/kg, q.d., p.o.). The model group was given 2 % adenine suspension (200 mg/kg, q.d., p.o.) for the first two weeks, followed by adenine (200 mg/kg, b.i.d., p.o.) for 2 weeks, and all animals were sacrificed after eight weeks of administration. 3. The serum and kidneys of rats in each group were collected to detect the oxidative stress indicators and the expressions of LC3B-Ⅱ/Ⅰ, p62, Bcl-2, Bax, Caspase-3 and Cleaved Caspase-3. 4. Human renal tubular epithelial cells (HK-2 cells) were divided into control group, model group, lanthanum chloride group, pyrophosphate (PPI) group, chloroquine (CQ) group, rapamycin group, doxorubicin (DOX) group and N-acetyl-L-cysteine (NAC) group. The mitochondrial status, mitophagy and apoptosis levels were detected., Results: 1.Lanthanum-containing preparations can significantly reduce the biochemical indexes of kidney injury in patients with CKD. 2. In the model group, the glomerular and renal tubular edema, the mitochondria were short and round, and the expression of LC3B-Ⅱ/Ⅰ and Bax increased, while the expression of P62, Bcl-2 and Caspase-3 decreased, and there was a significant improvement in the administration group, especially the 0.1 ng/kg group and lanthanum carbonate group. 3. In the HK-2 cell model group, mitochondrial membrane potential decreased, morphology changed and the results were reversed by lanthanum chloride., Conclusion: Lanthanum chloride may alter the morphology of nano-hydroxyapatite, thereby inhibiting its induced mitophagy and mitochondria-mediated apoptosis, and ultimately improve CKD renal injury effectively., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Human parechovirus (HPeV) is a common virus that can cause severe infections in newborns. Due to the limited knowledge of the prevalence of HPeV in different cities in China and the unknown association between HPeV infection and clinical characteristics of newborns, this research investigated the epidemiological and clinical characteristics of HPeV infection in hospitalized neonates in Changsha. From August to October 2023, 145 anal swab samples from 96 newborns and 38 pharyngeal swab samples from 33 newborns in the neonatal intensive care unit (NICU) were collected. The prevalence of HPeV was detected by reverse transcription-polymerase chain reaction (RT-PCR). The genomes of HPeV were sequenced and the viral protein 1 (VP1) region was used for genotyping. Phylogenetic analysis and recombination analysis of HPeV genome were performed. Finally, HPeV was detected in 10 out of 44 patients in October, all of them were HPeV-1. The sequenced 4 genomes of HPeV showed high genetic diversity with known strains. Additionally, a HPeV-1 recombinant strain was detected. Compared with HPeV negative patients, HPeV patients had higher prevalence of abdominal pain and diarrhea, intracranial hemorrhage, and purulent meningitis. Compared with HPeV negative patients, HPeV patients had higher peripheral blood lymphocytes, albumin, globulin, pH and lower peripheral blood neutrophils and hemoglobin. HPeV is an important viral cause of newborn infections and appears to be increasing in prevalence in recent years. Characteristic clinical pictures exist in HPeV infections, and further research is needed to accumulate more cases to obtain a comprehensive understanding of HPeV infections., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, author- ship, and publication of this article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In Chinese criminal law, the ages of 12, 14, 16, and 18 years old play a significant role in the determination of criminal responsibility. In this study, we developed an epiphyseal grading system based on magnetic resonance image (MRI) of the hand and wrist for the Chinese Han population and explored the feasibility of employing deep learning techniques for bone age assessment based on MRI of the hand and wrist. This study selected 282 Chinese Han Chinese males aged 6.0-21.0 years old. In the course of our study, we proposed a novel deep learning model for extracting and enhancing MRI hand and wrist bone features to enhance the prediction of target MRI hand and wrist bone age and achieve precise classification of the target MRI and regression of bone age. The evaluation metric for the classification model including precision, specificity, sensitivity, and accuracy, while the evaluation metrics chosen for the regression model are MAE. The epiphyseal grading was used as a supervised method, which effectively solved the problem of unbalanced sample distribution, and the two experts showed strong consistency in the epiphyseal plate grading process. In the classification results, the accuracy in distinguishing between adults and minors was 91.1%, and the lowest accuracy in the three minor classifications (12, 14, and 16 years of age) was 94.6%, 91.1% and 96.4%, respectively. The MAE of the regression results was 1.24 years. In conclusion, the deep learning model proposed enabled the age assessment of hand and wrist bones based on MRI., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Epicardial adipose tissue (EAT) significantly contributes to the progression of cardiovascular diseases (CVDs). However, manually quantifying EAT volume is labor-intensive and susceptible to human error. Although there have been some deep learning-based methods for automatic quantification of EAT, they are mostly uninterpretable and fail to harness the complete anatomical characteristics. In this study, we proposed an enhanced deep learning method designed for EAT quantification on coronary computed tomography angiography (CCTA) scan, which integrated both data-driven method and specific morphological information. A total of 108 patients who underwent routine CCTA examinations were included in this study. They were randomly assigned to training set (n = 60), validation set (n = 8), and test set (n = 40). We quantified and calculated the EAT volume based on the CT attenuation values within the predicted pericardium. The automatic method demonstrated strong agreement with expert manual quantification, yielding a median Dice score coefficients (DSC) of 0.916 (Interquartile Range (IQR): 0.846-0.948) for 2D slices. Meanwhile, the median DSC for the 3D volume was 0.896 (IQR: 0.874-0.908) between these two measures, with an excellent correlation of 0.980 (p < 0.001) for EAT volumes. Additionally, our model's Bland-Altman analysis revealed a low bias of -2.39 cm³. The incorporation of pericardial anatomical structures into deep learning methods can effectively enhance the automatic quantification of EAT. The promising results demonstrate its potential for clinical application., (© 2024. The Author(s).)

Neurodegenerative disorders are multiple chronic neurological diseases that pose a serious public health risk to our society, especially among the aging population [...].

Background: Coffee and tea consumption account for most caffeine intake and 2-3 billion cups are taken daily around the world. Caffeine dependence is a widespread but under recognized problem., Objectives: To conduct a systematic review on the genetic susceptibility factors affecting caffeine metabolism and caffeine reward and their association with caffeine intake., Methodology: We conducted PubMed and Embase searches using the terms "caffeine", "reward", "gene", "polymorphism", "addiction", "dependence" and "habit" from inception till 2024. The demographics, genetic and clinical data from included studies were extracted and analyzed. Only case-control studies on habitual caffeine drinkers with at least 100 in each arm were included., Results: A total of 2552 studies were screened and 26 studies involving 1,851,428 individuals were included. Several genes that were involved with caffeine metabolism such as CYP1A2, ADORA2A, AHR, POR, ABCG2, CYP2A6, PDSS2 and HECTD4 rs2074356 (A allele specific to East Asians and monomorphic in Europeans, Africans and Americans) were associated with habitual caffeine consumption with effect size difference of 3% to 32% in number of cups of caffeinated drink per day per effect allele. In addition, ALDH2 was linked to the Japanese population. Genes associated with caffeine reward included BDNF, SLC6A4, GCKR, MLXIPL and dopaminergic genes such as DRD2 and DAT1 which had around 2-5% effect size difference in number of cups of caffeinated drink for each allele per day., Conclusion: Several genes that were involved in caffeine metabolism and reward were associated with up to 30% effect size difference in number of cups of caffeinated drink per day, and some associations were specific to certain ethnicities. Identification of at-risk caffeine dependence individuals can lead to early diagnosis and stratification of at-risk vulnerable individuals such as pregnant women and children, and can potentially lead to development of drug targets for dependence to caffeine., (© 2024. The Author(s).)

Introduction: People who smoke are at higher risk of Coronavirus Disease-2019 (COVID-19) hospitalizations and deaths and might benefit greatly from high COVID-19 vaccination coverage. Studies on tobacco use and COVID-19 vaccine uptake in the general population are lacking., Aims and Methods: We conducted a cohort study utilizing linked data from 42 935 participants from two national surveys in Finland (FinSote 2018 and 2020). Exposures were smoking and smokeless tobacco (snus) use. The primary outcome was the uptake of two COVID-19 vaccine doses. Secondary outcomes were the uptake of one COVID-19 vaccine dose; three COVID-19 vaccine doses; time between the first and second dose; and time between the second and third dose. We examined the association between tobacco use and COVID-19 vaccine uptake and between-dose spacing in Finland., Results: People who smoke had a 7% lower risk of receiving two COVID-19 vaccine doses (95% confidence interval [CI] = 0.91; 0.96) and a 14% lower risk of receiving three doses (95% CI = 0.78; 0.94) compared to never smokers. People who smoked occasionally had a lower risk of receiving three vaccine doses. People who currently used snus had a 28% lower uptake of three doses (95% CI = 0.56; 0.93) compared to never users but we did not find evidence of an association for one or two doses. We did not find evidence of an association between tobacco use and spacing between COVID-19 vaccine doses., Conclusions: People who smoke tobacco products daily, occasionally, and use snus had a lower uptake of COVID-19 vaccines. Our findings support a growing body of literature on lower vaccination uptake among people who use tobacco products., Implications: People who smoke or use snus might be a crucial target group of public health efforts to increase COVID-19 vaccinations and plan future vaccination campaigns., Clinical Trials Registration Number: NCT05479383., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This study demonstrated that metal-organic frameworks (MOFs)-derived Fe-NC cathode improved both methane yield and methane content in a microbial electrolysis cell-coupled anaerobic digestion (MEC-AD) system treating waste activated sludge (WAS) fermentation liquor. Results revealed that Fe-NC maintained a meso‑macroporous structure with a large specific surface area of 1381 m 2 /g and superior electrochemical properties. Its calculated specific capacitance and electron transfer resistance were 5.7 and 0.4 times of the carbon felt (CF) group. The bacterial and archaeal gene loads of Fe-NC biofilm after multiple acclimation cycles were 5.69E+10 and 1.86E+9 copies/cm 2 and Proteiniphilum and Methanobacterium were the most enriched syntrophs from stage Ⅰ to stage Ⅱ acclimation. Corresponding maximum methane yield and content achieved were 0.31 m 3 CH 4 /kg COD and 92.8 %, and its CO 2 -dependent methane production was improved by 107.6 %. Mechanistic investigations showed that Fe-NC biofilm improved enzyme-associated CO 2 reduction pathway companying by promoting the intra- and extracellular electron transfer as well as ATP synthesis, therefore favoring methanogenic energetic metabolism. More importantly, an enhanced proton-coupled electron transfer (PCET) process was proposed within Fe-NC biofilm, providing a synergistic advantage over unbalanced conventional sole electron/proton transfer. This work provides an effective strategy to strengthen the waste-to-energy and biogas upgrading technology, potentially bringing economic benefits to wastewater treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential 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. Additionally, Yan Zhou serves as Editor for Water Research. The editorial handling and review of this manuscript are managed by a different independent Editor., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis., (© 2024. The Author(s).)

Background: Polycystic ovary syndrome (PCOS) represents a prevalent endocrine disorder affecting numerous females worldwide. Dysbiosis of gut microbiota has been linked to the occurrence of PCOS; however, research into the characteristics of gut microbiota in PCOS patients, especially those from different regions and with different testosterone level, remains limited. Additionally, it is still unclear whether gut microbiota helps to distinguish different PCOS subtypes., Methods: We searched four electronic databases (PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov) from Jan 1, 2010 to May 1, 2024. This combined analysis included studies providing the raw data of gut microbiota in PCOS patients. We reanalyzed the characteristics of gut microbiota in PCOS patients from different regions and with different testosterone level., Findings: Fourteen publications satisfying the inclusion criteria were included in the combined analysis. Based on data from 948 individuals, we found alpha-diversity was not significantly different between PCOS and healthy control (HC) groups. However, gut microbiota composition was distinct in PCOS patients compared with healthy individuals. Specifically, Fusobacterium , Ruminococcus&#95;gnavus&#95;group , and Escherichia-Shigella increased, while Dysosmobacter, Schaedlerella , Merdimonas , Clostridiisalibacter , Flintibacter et al. decreased in PCOS women. Regionally, Alistipes was enriched in primarily European patients, while Blautia and Roseburia were more abundant in Chinese patients. Subtype analysis revealed that the gut microbiota of PCOS patients with higher testosterone level (PCOS-HT) differed significantly from those with lower testosterone level (PCOS-LT). Prevotella , Blautia , Dialister , Ruminococcus&#95;torques&#95;group and UCG-002 were enhanced in PCOS-HT patients, while Alistipes , Dysosmobacter , Phocaeicola and Faecalibacterium were diminished. Importantly, a set of eight genera effectively differentiated PCOS-HT patients from PCOS-LT patients with an AUC of 0.95., Interpretation: This systematic anatomization of gut microbiota revealed the microbial characteristics of PCOS patients, particularly those with different testosterone level, thus laying the foundations for further research into pathogenesis of PCOS, and the development of effective diagnostic, treatment, and intervention strategies., Funding: This work was supported by the National Natural Science Foundation of China (No. 81973217, 82260304), the Hainan Province Clinical Medical Center (QWYH202175), and the Specific Research Fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202311)., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Objective: A shared decision-making (SDM) model-based intervention programme was implemented for a population at high risk for diabetes to explore its effectiveness in intervening with blood glucose levels in this population., Methods: One hundred residents were selected according to the principle of voluntary participation and divided into the intervention group (n = 50) and the control group (n = 50) by using multistage cluster sampling. The control group received only brief diabetes knowledge education through a disease brochure issued by the hospital; the intervention group implemented a SDM model based on large classroom and individualised education for 4 months. Univariate analysis and generalised estimating equation fitting model were used to analyse the effect of intervention on blood glucose parameters in the study subjects., Results: Univariate analysis showed that after 4 months of intervention, fasting blood glucose was lower in the intervention group than in the control group (5.57 ± 0.56 vs. 6.07 ± 0.77, F = 45.721, p < 0.001); glycosylated hemoglobin was lower in the intervention group than in the control group (5.91 ± 0.28 vs. 6.02 ± 0.24, F = 25.998, p < 0.001), decreased by 0.26% in the intervention group and increased by 0.01% in the control group. One-way analysis of variance (ANOVA) showed that fasting blood glucose and glycosylated hemoglobin in the intervention group decreased to different extents from baseline. The generalised estimation equation was fitted with the intervention programme, gender, hypertension, smoking, alcohol consumption, physical activity, age, waist circumference, body mass index, baseline fasting blood glucose, and baseline glycosylated hemoglobin as independent variables, and fasting blood glucose and baseline glycosylated hemoglobin as dependent variables. Results showed that compared with the control group, fasting blood glucose and glycosylated hemoglobin levels were significantly different between the two groups (p < 0.001)., Conclusion: Applying an intervention programme based on SDM model to people at high risk of diabetes can improve patients' adherence to self-management and establish a good lifestyle, thus contributing to their good glycemic control., (© 2024 John Wiley & Sons Ltd.)

Thiazolidinediones (TZDs) including rosiglitazone and pioglitazone function as peroxisome proliferator-activated receptor gamma (PPARγ) full agonists, which have been known as a class to be among the most effective drugs for the treatment of type 2 diabetes mellitus (T2DM). However, side effects of TZDs such as fluid retention and weight gain are associated with their full agonistic activities toward PPARγ induced by the AF-2 helix-involved "locked" mechanism. Thereby, this study aimed to obtain novel PPARγ partial agonists without direct interaction with the AF-2 helix. Through performing virtual screening of the Targetmol L6000 Natural Product Library and utilizing molecular dynamics (MD) simulation, as well as molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis, four compounds including tubuloside b, podophyllotoxone, endomorphin 1 and paliperidone were identified as potential PPARγ partial agonists. An in vitro TR-FRET competitive binding assay showed podophyllotoxone displayed the optimal binding affinity toward PPARγ among the screened compounds, exhibiting IC 50 and ki values of 27.43 µM and 9.86 µM, respectively. Further cell-based transcription assays were conducted and demonstrated podophyllotoxone's weak agonistic activity against PPARγ compared to that of the PPARγ full agonist rosiglitazone. These results collectively demonstrated that podophyllotoxone could serve as a PPARγ partial agonist and might provide a novel candidate for the treatment of various diseases such as T2DM.

Hexavalent chromium [Cr(VI)] exposure increases the risk of cancer occurrence. This study found that the levels of an atypical methyltransferase, METTL16 were greatly upregulated in the cells, and mouse tissues with Cr(VI) exposure, and played a critical role in cell proliferation and tumor growth induced by Cr(VI). Similarly, we found METTL16 was upregulated in various human cancer tissues. To understand mechanism of METTL16 in inducing carcinogenesis and cancer development, we identified that glutamate-ammonia ligase (GLUL) as the METTL16 functional target for regulating glutamine metabolism and tumorigenesis induced by Cr(VI) exposure. We demonstrated that METTL16 promoted GLUL expression in a m6A-dependent manner. Furthermore, METTL16 methylated the specific stem-loop structure of GLUL transcript, thereby increased the recognition and splicing of pre-GLUL RNA modified site by m6A reader YTHDC1, which ultimately accelerated the production of mature GLUL mRNA. Animal model of Cr(VI) exposure further confirmed that the expression levels of METTL16 and GLUL were both significantly induced in vivo, and there had a significant positive correlation between METTL16 and GLUL levels. Furthermore, we found that YTHDC1 was also important in inducing GLUL expression, and MYC was the upstream mediator of METTL16 to increase its transcriptional activation. Our study revealed new mechanism of metal carcinogenesis and cancer development., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: WuHuTang (WHT) is a traditional Chinese medicine compound for treating asthma, and the evidence supports that it has a good effect on acute asthma attacks in children and adults. Respiratory syncytial virus (RSV) is an important factor in the pathogenesis of acute asthma attacks, and the effect on dendritic cells is the key to its pathogenesis. Previous studies have confirmed that the pathogenesis of viruses is related to exosomes. However, there are few studies on the exosomes induced by RSV. Whether WHT can improve the changes caused by RSV-induced exosomes or not is worthy of further exploration., Aim of the Study: We aim to study the effects of RSV-induced exosomes on the function and autophagy of dendritic cells, and to observe the intervention effect of WHT serum on the above effects., Methods: The co-culture model of exosomes derived from bone marrow mesenchymal stem cells induced by RSV (BMSCs-Exo-RSV) and dendritic cells was established, and then WHT serum was used to intervene. After 24 h of intervention, the CCK-8 method, flow cytometry, Elisa, RT-qCPR, and Western blot were used to detect the above-mentioned culture model., Results: RSV-induced exosomes had certain effects on viability, apoptosis, and costimulatory molecules generation of dendritic cells. At the same time, the levels of IL-6, IL-12, TNF-α, and autophagy increased, while the levels of IL-4, IL-10, and TGF-β decreased, and the AKT/TSC/mTOR pathway was inhibited. WHT serum could activate this pathway and reverse the above changes in dendritic cells., Conclusion: This study reveals that the pathogenic effect of RSV is related to the exosomes induced by RSV. The exosomes induced by RSV affect the function of dendritic cells by inhibiting the AKT/TSC/mTOR pathway, which can be activated by WHT to reverse the effects caused by RSV-induced exosomes., 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.)

In consideration of several serious side effects induced by the classical AF-2 involved "lock" mechanism, recently disclosed PPARγ-Ser273 phosphorylation mode of action has become an alternative and mainstream mechanism for currently PPARγ-based drug discovery and development with an improved therapeutic index. In this study, by virtue of structure-based virtual high throughput screening (SB-VHTS), structurally chemical optimization by targeting the inhibition of the PPARγ-Ser273 phosphorylation as well as in vitro biological evaluation, which led to the final identification of a chrysin-based potential hit (YGT-31) as a novel selective PPARγ modulator with potent binding affinity and partial agonism. Further in vivo evaluation demonstrated that YGT-31 possessed potent glucose-lowering and relieved hepatic steatosis effects without involving the TZD-associated side effects. Mechanistically, YGT-31 presented such desired therapeutic index, mainly because it effectively inhibited the CDK5-mediated PPARγ-Ser273 phosphorylation, selectively elevated the level of insulin sensitivity-related Glut4 and adiponectin but decreased the expression of insulin-resistance-associated genes PTP1B and SOCS3 as well as inflammation-linked genes IL-6, IL-1β and TNFα. Finally, the molecular docking study was also conducted to uncover an interesting hydrogen-bonding network of YGT-31 with PPARγ-Ser273 phosphorylation-related key residues Ser342 and Glu343, which not only gave a clear verification for our targeting modification but also provided a proof of concept for the abovementioned molecular mechanism., 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 Masson SAS. All rights reserved.)

Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with lung cancer, but roles and mechanisms of Cr(VI)-induced epigenetic dysregulations in carcinogenesis remain to be investigated. In this study, we identified that RNA m5C methyltransferase NSUN2 was significantly upregulated in Cr(VI)-transformed cells and lung tissues of Cr(VI)-exposed mice. Inhibition of NSUN2 reduced cell proliferation, migration, colony formation and tube formation abilities. We found NSUN2-mediated m5C modification induced metabolic reprogramming and cell cycle by promoting the mRNA stabilities of ME1, GLUT3 and CDK2. In addition, knockdown of NSUN2 attenuated tumorigenesis and angiogenesis in vivo. RNA m5C reader ALYREF was identified to be involved in NSUN2-mediated m5C modification in Cr (VI)-induced carcinogenesis. Further study showed that EP300 induced NSUN2 upregulation through transcriptional activation by inducing histone modification at H3K27ac site for regulating Cr(VI) carcinogenesis. Our findings demonstrated novel role and mechanism of NSUN2 and epigenetic changes by increasing the RNA m5C modification that are important for Cr (VI)-induced carcinogenesis through NSUN2/ALYREF pathway. NSUN2, ALYREF, ME1, GLUT3 or/and CDK2 may be used as potential new biomarkers or/and therapeutic target(s) in the future., 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 Ltd.. All rights reserved.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition worldwide, demanding further investigation into its pathogenesis. Circular RNAs (circRNAs) are emerging as pivotal regulators in MASLD processes, yet their pathological implications in MASLD remain poorly understood. This study focused on elucidating the role of circular RNA ribonucleotide reductase subunit M2 (circRRM2) in MASLD progression. In this study, we used both in vitro and in vivo MASLD models using long-chain-free fatty acid (FFA)-treated hepatocytes and high-fat diet (HFD)-induced MASLD in mice, respectively. We determined the expression patterns of circRRM2, microRNA-142-5p (miR-142-5p), and neuregulin 1 (NRG1) in livers of MASLD-afflicted mice and MASLD hepatocytes by RT-qPCR. Dual-luciferase reporter assays verified the binding relationships among circRRM2, miR-142-5p, and NRG1. We conducted further analyses of their roles in MASLD hepatocytes and modulated circRRM2, miR-142-5p, and NRG1 expression in vitro by transfection. Our findings were validated in vivo. The results demonstrated reduced levels of circRRM2 and NRG1, along with elevated miR-142-5p expression in MASLD livers and hepatocytes. Overexpression of circRRM2 downregulated lipogenesis-related genes and decreased triglycerides accumulation in livers of MASLD mice. MiR-142-5p, which interacts with circRRM2, effectively counteracted the effects of circRRM2 in MASLD hepatocytes. Furthermore, NRG1 was identified as a miR-142-5p target, and its overexpression mitigated the regulatory impact of miR-142-5p on MASLD hepatocytes. In conclusion, circRRM2, via its role as a miR-142-5p sponge, upregulating NRG1, possibly influenced triglycerides accumulation in both in vitro and in vivo MASLD models. NEW & NOTEWORTHY CircRRM2 expression was downregulated in free fatty acid (FFA)-challenged hepatocytes and high-fat diet (HFD) fed mice. Overexpressed circular RNA ribonucleotide reductase subunit M2 (circRRM2) attenuated metabolic dysfunction-associated steatotic liver disease (MASLD) development by suppressing FFA-induced triglycerides accumulation. CircRRM2 targeted microRNA-142-5p (miR-142-5p), which served as an upstream inhibitor of neuregulin 1 (NRG1) and collaboratively regulated MASLD progression.

Activated carbon (AC) systems and reverse osmosis (RO) systems are commonly used point-of-use (POU) water filtration systems for removing trace-level contaminants in tap water to protect human health. However, limited research has been done to evaluate their effectiveness in removing heavy metals like manganese (Mn) and uranium (U), or to assess the potential for undesired microbial growth within POU systems, which can reduce their treatment efficiency. This study aimed to systematically evaluate the removal of metals and assimilable organic carbon (AOC) in POU systems. AC systems were operated to 200% of their designed treatment capacities and RO systems were run for three weeks. The results showed that AC systems were generally ineffective at removing metals from drinking water, while RO systems effectively removed them. Both Mn and U were poorly removed by AC systems. Calcium (Ca) and magnesium (Mg) were poorly removed by AC systems, with efficiencies of less than 1%. Iron (Fe) removal by AC systems varied between 61% and 84%. Copper (Fe), likely due to its low influent concentration (<30 μg L -1 ), was effectively removed by AC systems with efficiencies over 95%. In contrast, RO systems consistently removed all metals effectively. Mn and U removal in RO systems exceeded 95%, while Ca, Mn, Fe, and Cu were all removed with efficiencies greater than 98%. AOC was effectively removed from all AC and RO systems, but with high variability in removal efficiency, which is likely attributed to the heterogeneity of biofilm and microbial growth within the POU systems. The new knowledge generated from this study can improve our understanding of chemical contaminant removal in POU systems and inform the development of better strategies for designing and operating POU systems to remove chemical contaminants in drinking water and mitigate their associated health risks., 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.)

In the context of the growing importance of heterocyclic compounds across various disciplines, numerous strategies for their construction have emerged. Exploiting the distinctive properties of cyclopropenes, this study introduces an innovative approach for the synthesis of benzo-fused five-membered oxa- and aza-heterocycles through a formal [4+1] cyclization and subsequent acid-catalyzed intramolecular O- to N- rearrangement. These transformations exhibit mild reaction conditions and a wide substrate scope. The applications in the late-stage modification of complex molecules and in the synthesis of a potential PD-L1 gene down-regulator, make this method highly appealing in related fields. Combined experimental mechanistic studies and DFT calculations demonstrate Rh(III)-mediated sequential C─H coupling/π-allylation/dynamically favorable O-attack route., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m 6 A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage., Competing Interests: Declaration of competing interest The authors declare no competing financial and/or non-financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chitosan oligosaccharides (COS), derived from chitin, have garnered considerable attention owing to their diverse biological activities and potential applications. Previous investigations into the bioactivity of COS often encountered challenges, primarily stemming from the use of COS mixtures, making it difficult to discern specific effects linked to distinct degrees of polymerization (DP). Recent progress underscores the significant variation in the biological activities of COS corresponding to different DPs, prompting dedicated research towards synthesizing COS with well-defined polymerization. Among the available methods, enzymatic preparation stands out as a viable and environmentally friendly approach for COS synthesis. This article provides a comprehensive overview of emerging strategies for the enzymatic preparation of single COS, encompassing protein engineering, enzymatic membrane bioreactors, and transglycosylation reactions. Furthermore, the bioactivities of single COS, including anti-tumor, antioxidant, antibacterial, anti-inflammatory, and plant defense inducer properties, exhibit close associations with DP values. The potential applications of single COS, such as in functional food, food preservation, and crop planting, are also elucidated., Competing Interests: Declarations Ethics Approval This is a review study. Consent to Participate Informed consent was obtained from all individual participants included in the study. Consent for Publication The authors provided informed consent for publication. Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Distinctive gut microbial profiles have been observed between patients with Wilson disease (WD) and healthy individuals. Despite this, the exact relationship and influence of gut microbiota on the advancement of WD-related liver damage remain ambiguous. This research seeks to clarify the gut microbiota characteristics in both human patients and mouse models of WD, as well as their impact on liver injury., Methods: Gut microbial features in healthy individuals, patients with WD, healthy mice and mice with early- and late-stage WD were analysed using 16S rRNA gene sequencing. Additionally, WD-afflicted mice underwent treatment with either an antibiotic cocktail (with normal saline as a control) or healthy microbiota (using disease microbiota as a control). The study assessed gut microbiota composition, hepatic transcriptome profiles, liver copper concentrations and hepatic pathological injuries., Results: Patients with hepatic WD and mice with WD-related liver injury displayed altered gut microbiota composition, notably with a significant reduction in Lactobacillus abundance. Additionally, the abundances of several gut genera, including Lactobacillus, Veillonella and Eubacterium coprostanoligenes, showed significant correlations with the severity of liver injury in patients with WD. In WD mice, antibiotic treatment or transplantation of healthy microbiota altered the gut microbial structure, increased Lactobacillus abundance and modified the hepatic transcriptional profile. These interventions resulted in reduced hepatic copper concentration and alleviation of WD-related liver injury., Conclusions: Individuals and mice with pronounced WD-related liver injury exhibited shifts in gut microbial composition. Regulating gut microbiota through healthy microbiota transplantation emerges as a promising therapeutic approach for treating WD-related liver injury., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Wernekinck commissure syndrome (WCS) is an extremely rare midbrain syndrome, which selectively destroys the decussation of the superior cerebellar peduncle and the central tegmental tract, which commonly presents with bilateral cerebellar ataxia, dysarthria, and internuclear ophthalmoplegia. Palatal myoclonus in Wernekinck commissure syndrome is uncommon and often occurs as a late phenomenon due to hypertrophic degeneration of bilateral inferior olivary nuclei., Material and Method: A patient with WCS, admitted to our hospital from December 2023, was chosen for this study, and the syndrome's clinical manifestations, imaging features, and etiology were retrospectively analyzed based on the literature. A 68-year-old right-handed East Asian man presented with dizziness, slurred speech, difficulty with swallowing and walking, and rhythmic contractions of the soft palate. He had several risk factors for ischemic cerebrovascular diseases (age, sex, dyslipidemia, hypertension and smoking history). Brain magnetic resonance imaging showed hyperintensity of DWI and hypointensity of ADC at the caudal midbrain which was around the paramedian mesencephalic tegmentum anterior to the aqueduct of midbrain., Results: He was diagnosed with Wernekinck commissure syndrome (WCS) secondary to caudal paramedian midbrain infarction. He was started on dual antiplatelet therapy (aspirin and clopidogrel) and intensive statin therapy. Blood pressure and glucose were also adjusted. His symptoms improved rapidly, and he walked steadily and speak clearly after 7 days of treatment., Conclusions: Palatal myoclonus is known to occur as a late phenomenon due to hypertrophic degeneration of bilateral inferior olivary nuclei. However, Our case suggests that palatal myoclonus can occur in the early stages in WCS., 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.)

PANoptosis is manifested with simultaneous activation of biomarkers for both pyroptotic, apoptotic and necroptotic signaling via the molecular platform PANoptosome and it is involved in pathologies of various inflammatory diseases including hemophagocytic lymphohistiocytosis (HLH). Scutellarin is a flavonoid isolated from herbal Erigeron breviscapus (Vant.) Hand.-Mazz. and has been shown to possess multiple pharmacological effects, but it is unknown whether scutellarin has any effects on PANoptosis and related inflammatory diseases. In this study, we found that scutellarin inhibited cell death in bone marrow-derived macrophages (BMDMs) and J774A.1 cells treated with TGF-β-activated kinase 1 (TAK1) inhibitor 5Z-7-oxozeaenol (OXO) plus lipopolysaccharide (LPS), which has been commonly used to induce PANoptosis. Western blotting showed that scutellarin dose-dependently inhibited the activation biomarkers for pyroptotic (Caspase-1p10 and GSDMD-NT), apoptotic (cleaved Casp3/8/9 and GSDME-NT), and necroptotic (phosphorylated MLKL) signaling. The inhibitory effect of scutellarin was unaffected by NLRP3 or Caspase-1 deletion. Interestingly, scutellarin blocked the assembly of PANoptosome that encompasses ASC, RIPK3, Caspase-8 and ZBP1, suggesting its action on upstream signaling. Consistent with this, scutellarin inhibited mitochondrial damage and mitochondrial reactive oxygen species (mtROS) generation in cells treated with OXO+LPS. Further, mito-TEMPO that can scavenge mtROS significantly inhibited OXO+LPS-induced PANoptotic cell death. In line with the in vitro results, scutellarin markedly alleviated systemic inflammation, multiple organ injury, and activation of PANoptotic biomarkers in mice with HLH. Collectively, our data suggest that scutellarin can inhibit PANoptosis by suppressing mitochondrial damage and mtROS generation and thereby mitigating multiple organ injury in mice with inflammatory disorders., 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.)

Most studies currently focus on traditional illuminant regulating plant growth, while less attention has been given to the LED internal luminescence. This study examined how polarized and vortex light affect the growth and photosynthetic traits of pepper plants, with LED light used as the control. The findings indicated that circular polarized light significantly increased the aboveground biomass of pepper. Additionally, both polarized and vortex light treatment significantly influenced the root development of pepper. In comparison to the control group, the chlorophyll content was highest under circular polarized light, while the Pn, Sc, Tr, and Ci values were highest under linear polarized light, and the enzyme activity of Rubisco was increased. Circular polarized light notably increased the activities of POD, CAT, and SOD, the activity of SOD reached its peak under the left vortex light. Moreover, the content of MDA was observed to be the lowest under linear and right vortex light treatments. The expressions of key genes for chlorophyll synthesis (CaHEMA1 and CaCAO) and antioxidant enzyme synthesis (CaPOD, CaSOD, and CaMDHAR) were significantly altered under varying polarized light conditions, The latter genes, which play crucial roles in antioxidant enzyme activity, also showed significant variations in response to different polarized light treatments. In conclusion, polarized light significantly impacts the growth of pepper and is anticipated to be utilized for plant growth, setting the stage for future research in this area., 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 GmbH. All rights reserved.)

Introduction: Heme-oxidized iron regulatory protein 2 (IRP2) ubiquitin ligase-1 (HOIL-1) is believed to contribute to the ubiquitination of IRP2, which facilitates the transcription of transferrin receptor 1 (TfR1) while preventing the transcription of ferroportin-1 (FPN-1). Bioinformatics analysis predicts that nadolol (a β-blocker) interacts with the HOIL-1., Method: The present study is intended to explore whether nadolol suppresses ferroptosis in the brains of rats suffering from ischemic stroke via targeting the HOIL-1/IRP2 pathway. A rat model of ischemic stroke was established by blocking the middle cerebral artery for 2 h plus 24 h reperfusion, and nadolol (2.5 or 5 mg/kg) was given at 1h after reperfusion. HT22 cells were subjected to 12 h of hypoxia, followed by 24 h of reoxygenation for simulating ischemic stroke, and nadolol (0.1 or 0.25 μM) was administered to the culture medium before reoxygenation., Results: The stroke rats showed evident brain injury (increases in neurological deficit score and infarct volume) and ferroptosis, along with up-regulation of IRP2 and TfR1 while downregulation of HOIL-1 and FPN-1; these phenomena were reversed in the presence of nadolol. In the cultured HT22 cells, hypoxia/reoxygenation-induced LDH release, ferroptosis, and changes in the levels of relevant proteins (IRP2, TfR1, HOIL-1, and FPN-1) were also reversed by nadolol., Conclusion: In terms of these findings, it is concluded that nadolol can protect the ischemic rats' brains against ferroptosis by targeting the HOIL-1/IRP2 pathway, thereby preventing intracellular iron overload. Thus, nadolol may be a novel indication for treating patients with ischemic stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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).)

To study the recharge source, hydrochemical characteristics, and evolution process of karst underground water and surface water in the Xianghualing Mining area, we collected 32 groups of samples from karst underground water and surface water sources in and around the mining area. Based on multivariate statistical analysis, the Piper three-line diagram, Gibbs diagram, and ion ratio coefficient, this study analyzed the hydrogeochemical characteristics of karst underground water and surface water in the Xianghualing Mining area. The study systematically revealed the recharge source, recharge age, and hydrochemical evolution law of both water sources. The results showed that the karst underground water and surface water in the Xianghualing Mining area were weakly alkaline, with the main anions being HCO 3 - and the main cations being Ca 2+ . The hydrochemical types mainly included HCO 3 -Ca, HCO 3 -Ca·Mg, and HCO 3 ·SO 4 -Ca·Mg types. Atmospheric precipitation was the primary source of recharge for karst underground water and surface water, and it was also influenced by evaporation during the runoff process. However, the evaporation effect of karst groundwater was relatively small, which was closely related to modern hydrology, and the cycle replacement process was more rapid. The hydrochemical evolution characteristics of karst underground water and surface water were mainly affected by rock weathering, cation exchange adsorption, mineral dissolution, and human activities （such as agricultural and mining activities）. Ca 2+ , Mg 2+ , and HCO 3 - were primarily derived from the dissolution of carbonate minerals, with a small portion also originating from the weathering and dissolution of silicate minerals. Na + and Cl - were primarily derived from the dissolution of rock salts. Among them, Cl - , NO 3 - , and SO 4 2- were greatly affected by external inputs from agricultural activities, domestic sewage discharge, and mining activities. The research results are of great significance to the cyclical evolution process of karst underground water and surface water, as well as the protection and utilization of water resources in the Xianghualing Mining area.

In recent decades, with the intensification of human activities, atmospheric nitrogen （N） deposition has been increasing. N deposition affects carbon （C） cycling in terrestrial ecosystems, especially in fragile karst ecosystems. Karst ecosystems are considered to be an important C pool. To evaluate the impact of N deposition on soil organic C （SOC） and its fractions in karst ecosystems of China, we collected and collated 14 English literature published through the end of March 2023, yielding a total of 460 sets of experimental data. The meta-analysis examined the effect of N addition levels [low N: ≤50 kg·（hm 2 ·a） -1 , medium N: 50-100 kg·（hm 2 ·a） -1 , and high N: &gt;100 kg·（hm 2 ·a） -1 , in terms of N] on SOC and its fractions [particular organic C （POC）, readily oxidized organic C （ROC）, microbial biomass C （MBC）, and dissolved organic C （DOC）]. The results showed that N addition levels significantly affected the responses of farmland and forest soil SOC and their active fractions to N addition. Specifically, low and high N additions significantly increased SOC concentration in farmland ecosystems, whereas medium N addition significantly increased SOC concentration in forest ecosystems. In addition, soil active C fraction concentrations increased under high N addition in farmland ecosystems and under low and medium N addition in forest ecosystems. Without considering the level of N addition, N addition significantly enhanced soil organic matter （SOM） mineralization in both farmland and forest ecosystems and increased the SOC concentration in farmland ecosystems but not forest ecosystems. The responses of different active C fractions to N addition were diverse. In farmland ecosystems, the POC and ROC concentrations increased, but DOC did not change with N addition. In forest ecosystems, the DOC and POC concentrations increased, but there was no significant effect on MBC. Moreover, the response ratios （RR） of SOC and its fractions in different ecosystems to N addition were influenced by different environmental factors. In farmland ecosystems, the response ratio of SOC was related to the annual average temperature and soil pH. The response ratio of DOC was affected by the annual average temperature, mean annual precipitation, and N addition rate. The POC response ratio was related to the N addition rate. In forest ecosystems, the effects of N addition on the SOC response ratio were significantly altered by the annual average temperature, mean annual precipitation, and soil pH. However, the response ratios of DOC, POC, and MBC were not affected by the annual average temperature, mean annual precipitation, soil pH, and N addition rate. Consequently, these findings indicate that N addition could enhance soil SOC concentration and promote soil C sequestration in farmland and forest ecosystems in karst regions, but this effect relies on the level of N addition. This provides a scientific basis for predicting the soil C sink function in karst ecosystems under climate change scenarios.

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 μM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon-γ (IFN-γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine-2,3-dioxygenase (IDO)- kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV-positive GC continuously secreted IFN-γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV-positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV-positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti-tumor immunotherapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Constructing well-defined active multisites is an effective strategy to break linear scaling relationships to develop high-efficiency catalysts toward multiple-intermediate reactions. Here, dual-intermetallic heterostructure composed of tungsten-bridged Co 3 W and WNi 4 intermetallic compounds seamlessly integrated on hierarchical nanoporous nickel skeleton is reported as a high-performance nonprecious electrocatalyst for alkaline hydrogen evolution and oxidation reactions. By virtue of interfacial tungsten atoms configuring contiguous multisites with proper adsorptions of hydrogen and hydroxyl intermediates to accelerate water dissociation/combination and column-nanostructured nickel skeleton facilitating electron and ion/molecule transportations, nanoporous nickel-supported Co 3 W-WNi 4 heterostructure exhibits exceptional hydrogen electrocatalysis in alkaline media, with outstanding durability and impressive catalytic activities for hydrogen oxidation reaction (geometric exchange current density of ≈6.62 mA cm -2 ) and hydrogen evolution reaction (current density of ≈1.45 A cm -2 at overpotential of 200 mV). Such atom-ordered intermetallic heterostructure alternative to platinum group metals shows genuine potential for hydrogen production and utilization in hydroxide-exchange-membrane water electrolyzers and fuel cells., (© 2024 Wiley‐VCH GmbH.)

Increased patient advocacy has resulted in a shift toward more active patient engagement in the research. A scoping review was conducted to explore the literature on healthcare research priority settings wherein children, youths, or their families were involved in the priority-setting process. Six databases including MEDLINE, CINAHL, PsycINFO, Embase, Web of Science, and Global Health and the James Lind Alliance website were searched up until September 2019. All primary studies involving children (<18 years of age) or families in developing research priorities in health care were included. All retrieved references were uploaded into Covidence, and two independent reviewers screened the search results. Descriptive thematic analysis was used to identify common themes. A total of 30 studies with 4247 participants were included. Less than half of the participants ( n = 1237, (33%) were pediatric patients and their families. A total of 455 research priorities were identified. Three common themes emerged: (i) quality of care delivery, (ii) self-efficacy in health behaviors, and (iii) community engagement in care. This scoping review revealed priority research health topics from the perspectives of children, youths, or their families. The findings may be used as a foundation for future research to improve the health outcomes of children, youths, or their families according to their identified priorities., 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.

Previous studies showed that serum amyloid A (SAA) and macrophages were associated with allergic airway inflammation. However, the interaction between SAA1 and macrophages in allergic airway inflammation remains to be further elucidated. In this study, the levels of SAA1 were measured in nasal tissues from patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), house dust mite (HDM)-treated BEAS-2B cells and the tissues of mice of HDM-induced allergic airway inflammation. Human monocytes-derived macrophages and mouse bone marrow-derived macrophages (BMDMs) were exposed to SAA1, and CCL17 and the other M1/M2-related factors were evaluated using RT-PCR and/or ELISA. To test the effects of SAA1-treated BMDMs on chemotaxis and differentiation of CD4 + T cells, number of migrated cells and the levels of Th1 and Th2 were measured using flow cytometry. SAA1 receptors were examined in BMDMs and lung macrophages of model mice. CD36 neutralizing antibody was applied to explore the mechanisms of SAA1 in regulating BMDMs using RT-PCR and/or ELISA. We found that SAA1 was expressed in epithelial cells, and was increased in the nasal tissues of patients with eosinophilic CRSwNP and HDM-treated BEAS-2B- cells as well as the bronchoalveolar lavage fluid and lung tissues of mice exposed to HDM. We also found that the level of CCL17 was increased in M2 macrophages, more CD4 + T cells were recruited and proportion of Th2 was increased after the treatment of SAA1. The treatment of CD36 neutralizing antibody decreased CCL17 level in SAA1-treated M2 BMDMs. In summary, our results showed that SAA1 was increased in allergic airway inflammation, and the administration of SAA1 upregulated the expression of CCL17 in M2 macrophages via CD36 and promoted the chemotaxis of CD4 + T cells and differentiation of Th2. It may provide a new therapeutic strategy that could mediate allergic airway inflammation via suppressing SAA1 to reduce recruitment of CD4 + T cells and activation of Th2., (Copyright © 2024. Published by Elsevier B.V.)

Boiling heat transfer has become increasingly importance in a variety of industrial fields, but it involves chaotic nature phenomena that remain experimentally challenging. From the perspective of nucleation, bubble embryos emerge at the early stage on extremely small time and length scales. Therefore, molecular dynamics (MD) simulation is a popular and useful tool to uncover the distinctive boiling mechanisms at microscale. Recently, such method has yielded meaningful achievements, but there is still elusive on the current status and bottlenecks behind complex boiling processes. In this work, the state-of-the-art studies on bubble nucleation and boiling heat transfer that covers 129 papers up to 2024 have been comprehensively reviewed. Meanwhile, fundamental concepts of MD are briefly introduced, including MD principles, force fields, and determination of nucleation-related parameters. In contrast to microscopic boiling, bubble nucleation stems from the competition between potential and kinetic energies on micro/nano scale. Then, the key factors such as interfacial wettability and mixture component are thoroughly elucidated for bubble nucleation. In addition, both passive and active techniques are systematically discussed to unveil the underlaying mechanisms for boiling heat transfer enhancement. Finally, the ongoing trials needed for MD simulation are identified, together with an outlook for how to address these challenges. This review aims to offer an up-to-date summary of boiling mechanisms and draw more attention to the development of advanced MD techniques., 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.)

Vegetable waste, rich in bioactive compounds, offers a promising resource for producing value-added products. This study explored the use of tomato waste, containing glucose (40 mg/g), lycopene (95.12 μg/g), and β-carotene (24.31 μg/g), for cultivating fucoxanthin-rich Isochrysis galbana. Water-soluble lycopene (2.0 μg/mL) and β-carotene (0.4 μg/mL) effectively upregulated key carotenoid synthesis genes and boosted cell growth and fucoxanthin production (3.64 and 3.60 pg/cell, respectively) within 10 days in a mixotrophic culture. Optimized tomato waste hydrolysate achieved a high cell density of 1.21 × 10 7 cells/mL, 2.13 g/L biomass, and 21.02 mg/g fucoxanthin. This study highlights the potential of combining tomato waste with microalgae for a novel and innovative approach towards waste management and resource utilization., 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 integration of polymers, supramolecular macrocycles and aggregation-induced emission (AIE) molecules provides numerous possibilities for constructing various functional supramolecular systems. Herein, we constructed supramolecular assembled systems based on discrete macrocyclic polymer hosts via the cooperation of hydra-headed macrocycles containing two or three pillar[5]arene units (defined as P2, P3), the block polymer F127 and AIE molecules (alkyl-cyano modified tetraphenylethene, alkyl-triazole-cyano modified 9,10-distyrylanthracene, defined as TPE-(CN) 4 and DSA-(TACN) 2 ). Compared with the binary assembly between hydra-headed hosts or F127 and AIE molecules, cascaded supramolecular assembly-induced emission enhancement (SAIEE) in aqueous solution was achieved in discrete macrocyclic polymer-based supramolecular assembled systems. Considering the cascaded SAIEE performance, we have successfully applied discrete macrocyclic polymer-based supramolecular assembled systems to bioimaging and constructed an artificial light-harvesting system (LHs) to explore more potential applications. The supramolecular assembly form of discrete macrocyclic polymers hosts and AIE molecules proposed in this work provides new inspiration for the construction and application of high-performance supramolecular luminescent systems., (© 2024 Wiley-VCH GmbH.)

Vascular calcification and vascular ageing are "silent" diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N 6 -methyladenosine (m 6 A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m 6 A methylation., (© 2024 The Authors.)