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Zhile Li, Han Gan, Siyuan Li, Yuchen Xue, Kai Luo, Kai Huang, Yunqian Zhang, Yan Wang, Lai Jiang, Hui Zhang Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Lai Jiang; Hui Zhang, Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People’s Republic of China, Email jianglai@xinhuamed.com.cn; zhanghui22002@xinhuamed.com.cnBackground: Septic lung injury (SLI) is a severe condition with high mortality, and ferroptosis, a form of programmed cell death, is implicated in its pathogenesis. However, the explicit mechanisms underlying this condition remain unclear. This study aimed to elucidate and validate key ferroptosis-related genes involved in the pathogenesis of SLI through bioinformatics analysis and experimental validation.Methods: Microarray data related to SLI from the GSE130936 dataset were downloaded from the Gene Expression Omnibus (GEO) database. These data were then intersected with the FerrDb database to obtain ferroptosis-related differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks and functional enrichment analysis were employed to identify key ferroptosis-related DEGs. The Connectivity Map (c-MAP) tool was used to search for potential compounds or drugs that may inhibit ferroptosis-related DEGs. The transcriptional levels of the key genes and potential therapeutic compounds were verified in an LPS-induced mouse model of lung injury. The expression of these key genes was further verified using the GSE60088 and GSE137342 datasets.Results: 38 ferroptosis-related DEGs were identified between the septic and control mice. PPI network analysis revealed four modules, the most significant of which included eight ferroptosis-related DEGs. Functional enrichment analysis showed that these genes were enriched in the HIF-1 signaling pathway, including IL-6 (Interleukin-6), TIMP1 (Tissue Inhibitor of Metalloproteinase 1), HIF-1α (Hypoxia-Inducible Factor-1α), and HMOX1 (Heme Oxygenase-1). Phloretin, a natural compound, was identified as a potential inhibitor of these genes. Treatment with phloretin significantly reduced the expression of these genes (p < 0.05), mitigated lung injury, improved inflammatory profiles by approximately 50%, and ferroptosis profiles by nearly 30% in the SLI models.Conclusion: This study elucidates the significant role of ferroptosis in SLI and identifies phloretin as a potential therapeutic agent. However, further research, particularly involving human clinical trials, is necessary to validate these findings for clinical use.Keywords: sepsis, SLI, ferroptosis, bioinformatics, HIF-1α, phloretin

Baojun Guo,1,2 Hui Gan,1 Mingshan Xue,1,3 Zhifeng Huang,1 Zhiwei Lin,1 Shiyun Li,1 Peiyan Zheng,1 Baoqing Sun1 1Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China; 2School of Medicine, Henan University, Kaifeng, 475004, People’s Republic of China; 3Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Baoqing Sun; Peiyan Zheng, Email sunbaoqing@vip.163.com; gdmcslxx@126.comBackground: This study analyzed the burden of chronic obstructive pulmonary disease (COPD) in China, the United States, and India from 1990 to 2019 and projected the trends for the next decade.Methods: This study utilized the GBD 2019 to compare the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate, and the proportion attributed to different risk factors in China, the United States, and India. Joinpoint models and autoregressive integrated moving average (ARIMA) models were employed to capture the changing trends in disease burden and forecast outcomes.Results: From 1990 to 2019, China’s age-standardized COPD incidence and mortality rates decreased by 29% and 70%, respectively. In the same period, India’s rates decreased by 8% and 33%, while the United States saw an increase of 9% in COPD incidence and a 22% rise in mortality rates. Smoking and ambient particulate matter pollution are the two most significant risk factors for COPD, while household air pollution from solid fuels and low temperatures are the least impactful factors in the United States and India, respectively. The proportion of risk from household air pollution from solid fuels is higher in India than in China and the United States. Predictions for 2030 suggest that the age-standardized DALY rates, ASIR, and ASMR in the United States and India are expected to remain stable or decrease, while China’s age-standardized incidence rate is projected to rise.Conclusion: Over the past three decades, the incidence of COPD has been decreasing in China and India, while showing a slight increase in the United States. Smoking and ambient particulate matter pollution are the primary risk factors for men and women, respectively. The risk of household air pollution from solid fuels in India needs attention.Keywords: COPD, global burden of disease, risk factors, DALYs

BACKGROUND This study aimed to investigate the expression of RSPO3 and ß-catenin in preeclampsia and the relationship between RSPO3 and b-catenin levels and maternal-fetal outcomes. MATERIAL AND METHODS We enrolled 60 pregnant women with preeclampsia and 60 pregnant women without preeclampsia. We collected peripheral blood from the patients upon admission; placenta and cord blood were collected after delivery. The expression of RSPO3 and ß-catenin in maternal blood, cord blood, and placenta was measured. We used the Spearman method to examine the correlations between clinical characteristics and RSPO3. Logistic regression modeling was used to identify the independent risk factors for preeclampsia. RESULTS RSPO3 and ß-catenin levels were decreased in the peripheral blood, cord blood, and placentas of women with preeclampsia, with significant differences (P<0.05). The preeclampsia group had more adverse pregnancy outcomes. RSPO3 level of the preeclampsia group was negatively correlated with systolic blood pressure (r=-0.4654, P<0.001) and diastolic blood pressure (r=-0.4617, P<0.001) in cord blood, and systolic blood pressure (r=-0.5373, P<0.05) and diastolic blood pressure (r=-0.4898, P<0.05) in maternal blood. CONCLUSIONS RSPO3 and ß-catenin were decreased in preeclampsia, RSPO3 was negatively correlated with blood pressure, and RSPO3 could be a risk factor for the development of preeclampsia.

Objective: Hemodialysis catheter-related right atrial thrombus (CRAT) is a rare and fatal complication related with catheter. Treatment recommendations are controversial. We reported our institution's recent three cases in managing CRAT and review and analyze the reported cases of CRAT in hemodialysis patients., Methods: A systematic search of the PubMed, Embase and Web of Science databases was conducted to identify the therapy and outcome data in hemodialysis CRAT patients., Results: From 1975 to November 2023, a total of previous 144 cases which reported in the literatures and three new cases in our institution of CRAT in hemodialysis were included and analyzed. Overall mortality was 18.1% (26/144). Most of cases can be detected by echocardiography. Thirty-three patients had no treatment, except for catheter removal, replacement or antibiotics, but eleven of them have died. Thrombolytic therapy was adopted in 14 cases but only nine cases was successful, the remaining cases need to further therapy. Eventually, 71 cases have been treated by anticoagulation and 34 cases received thrombectomy., Conclusions: We recommend that the replacement of the catheter and anticoagulation combined with thrombolysis is a preferred therapy. Thrombectomy should be considered when other methods fail or new complication happened. Thrombolysis alone has a low success rate but may be useful in combination with anticoagulant therapy., Competing Interests: Declarations Ethics approval and consent to participate The case was approved by the Human Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (Number:2023 − 315). Consent for publication The patient provided written informed consent. Clinical trial number Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

As an emerging therapeutic method, the application of sonodynamic therapy (SDT) is hindered by its intrinsic unsatisfactory efficiency, the tumor hypoxia and low tumor specificity. Here, we reported the design of a tumor-targeting multifunctional nanodrug for O 2 -generation/O 2 -economization dually enhanced SDT/chemodynamic therapy (CDT) combination therapy. After the co-encapsulation of sonosensitizer indocyanine green (ICG) and oxidative phosphorylation inhibitor metformin (Met) into hollow MnO 2 (H-MnO 2 ) nanoparticles, ICG/Met@H-MnO 2 @MPN-FA (IMMMF) was conveniently prepared through the formation of metal-phenolic networks (MPNs) between Fe 3+ and folic acid (FA) immobilized tannic acid (TA, TA-FA) onto its surface. In vitro experiments indicated its selective uptake by 4T1 cells via the specific folate receptors-FA interactions. Responding to glutathione (GSH) and the acidic environment, the decomposition of IMMMF led to the release of Mn 2+ and Fe 2+ for enhanced CDT, and ICG for SDT. Furthermore, Met was continuously released to reduce O 2 consumption for enhanced SDT. More importantly, IMMMF catalyzed the endogenous H 2 O 2 into O 2 for further enhanced SDT. Expectedly, both in vitro and in vivo antitumor assays confirmed its satisfactory therapeutic efficiency via CDT/SDT synergistic therapy. Hence, this intelligent sonocatalytic nanoagent emerges as a promising candidate for CDT-enhanced SDT, which also provides a novel strategy for dually alleviating tumor hypoxia with better therapy., 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.)

The increasing role of environmental pollutants and nutrients in the development of myopia. Further longitudinal evidence is needed to elucidate the effects of early-life environmental pollutants on myopia and nutrients to protect against pollutant-induced myopia. We used mother-child dyads from the Ma'anshan Birth Cohort (n = 2028) to explore the modifying effects of maternal vitamin D status of prenatal and childhood arsenic exposure with refractive parameters and myopia. We measured serum or plasma arsenic concentrations during three trimesters, in cord blood, in childhood (5-year-old), and performed cycloplegic refraction in children aged 7-9 years (n = 1616). Primary outcomes were myopia and refractive parameters including axial length (AL), corneal radius of curvature, and spherical equivalent refraction error. Linear regression, logistic regression, and multiple informant models were performed for the association of prenatal and childhood arsenic exposure with vision health. Sex- and vitamin D status stratification analyses were also conducted. Cord serum arsenic was positively associated with AL (β = 0.15, 95%CI: 0.01, 0.29) and the risk of developing myopia (OR = 1.72, 95%CI: 1.07,， 2.75). Among boys, a 1 ng/L increase in cord serum log 10 -transformed arsenic resulted in larger AL and a higher risk of myopia. In the vitamin D deficient group (<20 ng/mL), cord serum arsenic showed positive associations with AL (0.26 [0.06, 0.46]) and the risk of myopia (1.99 [1.01, 3.90]). Late pregnancy arsenic exposure likely affects offspring development of myopia, especially in boys. Maternal sufficient vitamin D may confer protective effects against the development of myopia., 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.)

Backgrounds: Evidence concerning the short-term acute effect of air pollution on sleep health is quite limited. This study aims to examine the association between short-term exposure to ambient criteria air pollutants (CAPs) and sleep disturbance among young adults., Methods: A nationwide retrospective study was conducted across 261 Chinese cities from 2023 to 2024. Participants' sleep quality was assessed by the Pittsburgh Sleep Quality Index, and air pollutant concentrations were collected during the study period. Distributed lag nonlinear models were utilized to assess the effect of CAPs on sleep disturbance and seven sleep quality components over the seven days preceding the survey (lag 0-7). Stratification analyses involving gender, cigarette smoking, and hazardous drinking behavior were performed., Results: Of 12,279 young adults, 39% were identified as having sleep disturbances. Increases of 10 μg/m 3 in PM 2.5 , PM 10 , O 3 , and NO 2 exposure were linked to a heightened risk of sleep disturbance, with the maximum single-day percentage changes being 8.3% (95% confidence intervals: 1.9-15.2%), 10.0% (1.2-19.6%), 6.0% (2.3-9.8%), and 23.6% (4.5-46.0%), respectively. A 10 μg/m 3 elevation in PM 2.5 , PM 10 , and O 3 were associated with 18.4%-34.8% of cumulative increase in sleep disturbance risk. Additionally, a 10 μg/m 3 increase in PM 2.5 and PM 10 concentrations prolonged sleep latency by 3 and 4.8 min, respectively. Each 10 μg/m 3 increase in PM 10 and O 3 shortened sleep duration by 5.4 and 5.7 min. NO 2 exposure increased scores on the daytime dysfunction component of the PSQI, resulting in a percentage change of 23.9%. The association between PM 2.5 , O 3 , and NO 2 exposure and sleep disturbance was stronger in subpopulations with cigarette smoking behavior., Conclusion: Short-term exposure to PM 2.5 , PM 10 , O 3 , and NO 2 is significantly associated with sleep disturbance among young adults. Sustained improvements in air quality may help improve sleep health., 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.)

Oropharyngeal carcinomas linked to high-risk types of human papillomavirus (HPV + OPC) as a distinct tumor entity, have a better prognosis than HPV - OPC. Current treatment approaches do not differentiate between HPV-positive and negative disease, but ongoing studies are exploring de-escalation strategies, aiming to reduce therapy-related morbidity and improve patient quality of life, particularly focusing on reducing late effects from radiotherapy.We performed a literature search for both published and ongoing clinical trials and critically discussed the presented concepts and results. Those include reduction in radiotherapy dose or volume, omission or modification of concomitant chemotherapy/immunotherapy, usage of induction chemotherapy and utilization of advanced molecular and imaging biomarkers and radiomics for selected subgroups of HPV + OPC patients. While promising data have been reported from various Phase II trials, evidence from Phase III de-escalation trials has failed to demonstrate improved outcomes. Therefore, further data and an improved risk stratification are required before de-escalated radiation treatments can be recommended outside of clinical trials.The review aims to outline current de-escalation strategies and future possibilities for enhancing patient outcomes in HPV + OPC., 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: Allergen component resolved diagnosis (CRD) is a method for identifying specific protein molecules that cause hypersensitivity. Unlike traditional methods that use crude allergen extracts containing multiple component species, CRD focuses on individual allergen protein molecules for more precise diagnosis. The World Allergy Organization (WAO) recommends CRD as a supplement to clinical history and allergen extract testing, and in some cases, it can replace crude extract tests., Methods: CRD involves the use of natural or recombinant proteins to detect specific IgE antibodies directed at individual allergenic components. This method allows for a more detailed analysis of a patient's allergic response compared to the use of whole allergen extracts. The Allergy Prevention and Control Specialty Committee of the Chinese Preventive Medicine Association, in collaboration with multidisciplinary experts, developed an expert consensus that incorporates the consensus of the European Academy of Allergy and Clinical Immunology (EAACI), WAO, and important domestic literature on CRD in recent years., Results: The consensus aims to standardize the algorithm of allergen diagnosis and provides a reference for clinical practice. It also offers guidance for clinicians on the common protein families identified by CRD, the scenarios where CRD is applicable, and the significance of detecting common allergen components., Conclusions: Despite its potential, CRD is not widely used in clinical practice in China due to the lack of allergen component reagents and a general unawareness among clinicians about CRD's application and interpretation of test results. The expert consensus developed by the Chinese Preventive Medicine Association aims to address this gap and enhance the clinical application of CRD in China., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Due to the soliton-like electronic structural characteristics, cyanine dyes typically exhibit spectral behaviors such as large molar extinction coefficients, narrow spectra, and high fluorescence efficiency. However, their extensive applications as emitters in electroluminescence are largely ignored due to their serious emission quenching in the aggregation state. Herein, it is reported a squaraine dye (a type of cyanine) SQPhEt. At different solution concentrations, the unusual decrease in full-width at half-maxima (FWHM) with increasing Stokes shift indicates the fluorescence quenching of SQPhEt in the aggregated state is because of the strong self-absorption effect. A sensitized device structure can help to reduce the doping concentration of dye, which can effectively suppress self-absorption. Benefitting from the large molar extinction coefficient of SQPhEt, even at low doping concentrations of 0.1 wt%, efficient Förster energy transfer can be achieved. The corresponding spin-coating sensitized device based on SQPhEt as the dopant exhibits favorable deep-red emission at 668 nm with a small FWHM of 0.10 eV., (© 2024 Wiley‐VCH GmbH.)

Background: The current analgesics often prevent patients from getting effective treatment due to their adverse effects. Cannabidiol (CBD) is well tolerated, has few side effects and has been extensively investigated in analgesia. However, its oral bioavailability is extremely low. In order to solve this problem, we developed the cannabidiol nanocrystals (CBD-NC) in the earlier stage., Methods: In this study, we evaluated the nociceptive behaviours associated with neuropathic pain (NP) induced by the spared nerve injury (SNI) model. Assessment of pain threshold was evaluated by paw withdraw threshold (PWT) and paw withdrawal latency (PWL). The improving effect on the motor dysfunction was determined by rota-rod testing. To assess the neuroprotective effect, nerve demyelination and expression of peripheral myelin protein PMP22 were measured with myelin sheath staining and western blotting. Protein expressions in microglia of spinal cord were tested by western blot to explore the underlying mechanism., Results: Compared with the CBD oil solution, CBD-NC significantly reduced mechanical allodynia and thermal hyperalgesia in rats. CBD-NC could improve motor dysfunction induced by SNI in rats, significantly reverse the demyelination and increase the expression of the marker protein of peripheral myelin. Underlying spinal analgesic mechanism of microglia and related factors were preliminarily confirmed., Conclusions: CBD-NC administration is an effective treatment for NP associated with SNI, and the analgesic effect of CBD-NC was significantly better than that of CBD oil sol. By contrast, CBD-NC has a fast-acting and long-term effect in the treatment of NP. Our study further supports the potential therapeutic effect of CBD-NC on NP., Significance: The absolute bioavailability of the CBD-NC intramuscular injection formulation can reach 203.31%, which can solve the problem of low oral bioavailability. This research evaluated the therapeutic effect of CBD-NC on NP associated with the SNI model for the first time. All available date showed that whatever the analgesic or neuroprotective effect of CBD-NC, it was significantly better than that of CBD oil sol., which was consistent with the results of the pharmacokinetic. This research supports the initiation of more trials testing the efficacy of CBD-NC for treating NP., (© 2024 European Pain Federation ‐ EFIC®.)

Objective: To prepare chitosan-loaded nanoparticles (NPs) that enhance the oral bioavailability of puerarin (Pur) and render it responsive to reactive oxygen species (ROS)., Significance: This research makes substantial progress towards the theory of intelligent drug delivery, offering a new reference for combining Pur with other natural medicinal active ingredients., Methods: The acylation reaction between chitosan and ROS-sensitive 3-carboxyphenylboronic acid (PBA) was used to synthesise ROS-sensitive phenylboronylated chitosan (PBACS). Subsequently, PBACS-PBA-Pur-NPs and PBACS-TPP-Pur-NPs were prepared via ion gelation after the addition of PBA and sodium tripolyphosphate(TPP), respectively. The physicochemical and functional properties of both NPs were compared, and their differences were preliminarily studied through molecular docking., Results: Reactive oxygen species-sensitive PBACS was successfully synthesised. Of the two NPs prepared, PBACS-TPP-Pur-NPs had a size of 127.2 ± 0.80 nm, polydispersity index (PDI) of 0.129 ± 0.0008, and an encapsulation rate of 95.75 ± 0.387 %, whereas PBACS-PBA-Pur-NPs had a size of 149.8 ± 0.1414 nm, PDI of 0.389 ± 0.0012, and an encapsulation rate of 91.77 ± 0.279 %. The micromorphology of the PBACS-TPP-Pur-NPs exhibited better physical properties. However, PBACS-PBA-Pur-NPs demonstrated a faster in vitro release and more significant in vitro anti-inflammatory effects. Pharmacokinetically, the AUC 0-24 , T max , and C max of PBACS-PBA-Pur-NPs were 3.485, 2.117, and 3.339 times higher, respectively, than those of Pur. The AUC 0-24 , T max , and C max of PBACS-TPP-Pur-NPs were 2.41, 1.33, and 2.03 times higher, respectively, than those of Pur. Molecular simulation revealed that the binding energy of PBACS-PBA-Pur -NPs was approximately -4.34 kcal/mol and that of PBACS-TPP-Pur-NPs was even lower, approximately -5.93 kcal/mol, suggesting that the NPs prepared with TPP are more densely packed than those designed with PBA, resulting in slower and reduced drug release., Conclusion: The NPs constructed in this study effectively reduced inflammatory factors at the disease site, providing a theoretical and experimental basis for the application of nano drugs in inflammatory disease models. In addition, the molecular docking study of the two NPs offered insights into the relationship between the release and structure of subsequent nano drugs., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Over the past decade, there has been a rapid increase in the incidence of inflammatory bowel disease. It has been suggested that multifactorial interactions of environmental factors, genetic factors, immune response and intestinal microbiota are involved in the pathogenesis of inflammatory bowel disease. It is widely recognized that the intestinal microbiota are essential for human metabolism, the immune system and pathogen resistance, and are integral to human health. Therefore, the dysbiosis of the microbiota is a critical step leading to intestinal mucosal damage and a key factor in the pathogenesis of inflammatory bowel disease. Regulating the microbiota through interventions such as enteral nutrition, fecal microbiota transplantation, and probiotic supplementation has the potential to prevent or even reverse intestinal dysbiosis, opening up new perspectives for the treatment of inflammatory bowel disease.

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, β4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both T cell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Organophosphate esters (OPEs) are a class of environmental chemicals with endocrine-disrupting properties. Epidemiologic studies have demonstrated that prenatal OPEs exposure is associated with neurodevelopmental disorders in offspring. However, studies assessing the effects of prenatal OPEs exposure on the dynamic changes in attention deficit hyperactivity disorder (ADHD) symptoms in preschoolers are scarce. Since vitamin D has been demonstrated to have a "neuroprotective" effect, the modifying effects of maternal vitamin D were estimated., Methods: The present study included 2410 pregnant women from the Ma'anshan Birth Cohort. The levels of OPEs in the mothers' urine were examined in the three trimesters. The Chinese version of the Conners Abbreviated Symptom Questionnaire was used to examine preschoolers' ADHD symptoms at 3, 5, and 6 years of age. ADHD symptom trajectories were fitted via group-based trajectory modeling. We used multinomial logistic regression, Bayesian kernel machine regression, quantile-based g-computation, and generalized linear models to assess individual and mixed relationships between OPEs during pregnancy and preschoolers' ADHD symptoms and trajectories., Results: Preschoolers' ADHD symptom scores were fitted to 3 trajectories, including the low-score, moderate-score, and high-score groups. First-trimester dibutyl phosphate (DBP), second-trimester bis(2-butoxyethyl) phosphate (BBOEP), and third-trimester diphenyl phosphate (DPHP) were associated with an increased risk in the high-score group (p < 0.05). BBOEP in the third trimester was associated with decreased risk in the moderate-score group (OR = 0.89, 95% CI: 0.79, 1.00). For mothers with 25(OH)D deficiency, a positive relationship was observed between OPEs during pregnancy and symptom trajectories. Our results did not reveal any mixed effects of OPEs on ADHD symptom trajectories., Conclusion: Prenatal exposure to OPEs had heterogeneous associations with ADHD symptom trajectories in preschoolers. Additionally, the effect of individual OPEs on symptom trajectories was intensified by vitamin D deficiency., 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.)

Evidence on the link of long-term exposure to ozone (O 3 ) with childhood asthma, rhinitis, conjunctivitis and eczema is inconclusive. We did a population-based cross-sectional survey, including 177,888 children from 173 primary and middle schools in 14 Chinese cities. A satellite-based spatiotemporal model was employed to assess four-year average O 3 exposure at both residential and school locations. Information on asthma, allergic rhinitis, eczema and conjunctivitis was collected by a standard questionnaire developed by the American Thoracic Society. We used generalized non-linear and linear mixed models to test the associations. We observed linear exposure-response associations between O 3 and all outcomes. The odds ratios of doctor-diagnosed asthma, rhinitis, eczema, and conjunctivitis associated with per interquartile increment in home-school O 3 concentration were 1.31 (95 % confidence interval [CI]: 1.28, 1.34), 1.25 (95 %CI: 1.23, 1.28), 1.19 (95 %CI: 1.16, 1.21), and 1.28 (95 %CI: 1.21, 1.34), respectively. Similar associations were observed for asthma-related outcomes including current asthma, wheeze, current wheeze, persistent phlegm, and persistent cough. Moreover, stronger associations were observed among children who were aged > 12 years, physically inactive, and exposed to higher temperature. In conclusion, long-term O 3 exposure was associated with higher risks of asthma, allergic rhinitis, conjunctivitis and eczema in children., 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 evaluate the effect of malnutrition assessed by the Geriatric Nutritional Risk Index (GNRI) on major adverse cardiac and cerebrovascular events (MACCE) in the elderly patients after endovascular aortic aneurysm repair (EVAR)., Materials and Methods: This was a retrospective cohort study of elderly patients who underwent EVAR in a tertiary hospital. Malnutrition status was assessed by the GNRI. The primary outcome was MACCE. The predictive ability of the GNRI was compared with both the Revised Cardiac Risk Index (RCRI) and the modified Frailty Index (mFI) using Receiver operating characteristic (ROC) curve., Result: A total of 453 patients underwent EVAR November 2015 and January 2020 was retrospectively analyzed, equally divided into three (low/medium/high) groups according to GNRI values which ranked from low to high. Five (1.10%) patients were lost in follow-up after surgery, and the median length of follow-up was 28.00 (15.00-47.00) months. The high GNRI values reduced length of hospital stay following EVAR in comparison to patients in low GNRI values group (β 9.67, 95% CI 4.01-23.32, p  = 0.0113; adjusted β -1.96, 95% CI -3.88, -0.05, p  = 0.0454). GNRI status was associated with a significantly increased risk of long-term mortality after EVAR (Medium GNRI, unadjusted HR 0.40, 95%CI 0.23-0.70, p  = 0.0014; adjusted HR 0.47, 95%CI 0.26-0.84, p  = 0.0107; high GNRI, 0.27 95%CI 0.14-0.55; p  = 0.0003; adjusted HR 0.32 95%CI 0.15-0.68, p  = 0.0029). Both medium and high GNRI values were linked to significantly reduced risks of MACCE compared to low GNRI score patients (Medium GNRI, unadjusted HR 0.34, 95%CI 0.13-0.88, p  = 0.00265; adjusted HR 0.37, 95%CI 0.14-0.96, p  = 0.0408; High GNRI, 0.26 95%CI 0.09-0.78; p  = 0.0168; adjusted HR 0.21 95%CI 0.06-0.73, p  = 0.0029). Compared with the RCRI and mFI, the GNRI had better discrimination in predicting long-term MACCE. An area under the curve (AUC) for GNRI mFI, and RCRI is 0.707, 0.614 and 0.588, respectively. (Z statistic, GNRI vs. mFI, p  = 0.0475; GNRI vs. RCRI, p  = 0.0017)., Conclusion: Malnutrition assessed by the GNRI may serve as a useful predictor of long-term MACCE in elderly patients after EVAR, with preferable discrimination abilities compared with both RCRI and mFI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Zou, Wang, Zhao, Ma, Huang, Yuan, Liu, Han, Gan and Yang.)

All-solid-state lithium metal batteries (ASSLMBs) have been regarded as promising candidates to settle the safety issues of liquid electrolytes for rechargeable lithium batteries. However, the currently reported gel polymer electrolytes still have flammable liquid solvents, thus leading to the potential safety hazard. Here, solvent-free deep eutectic solid polymer electrolytes (SPEs) are designed and fabricated via an in situ polymerization, which are composed of a poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) electrospun membrane, succinonitrile (SN), poly(ethylene glycol) diacrylate (PEGDA200, M n = 200 g mol -1 ), lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), and lithium difluoro(oxalato)borate (LiDFOB). The deep eutectic solvent (DES) with SN/LiTFSI provides a superior room-temperature ionic conductivity, while the PEGDA200 precursor acts as cross-linking network to form SPEs under thermal initiation for free radical polymerization, and LiDFOB can form a stable solid electrolyte interface (SEI) layer. The PVDF-HFP electrospun membrane with a three-dimensional nanofibrous network structure for SN/PEGDA200/LiTFSI/LiDFOB SPEs exhibits a wide electrochemical stability window, high lithium-ion transference number, and good compatibility with the lithium metal anode. Furthermore, the obtained SPEs assembled with Li//LiMn 0.6 Fe 0.4 PO 4 , Li//LiFePO 4 , and Li//LiNi 0.8 Co 0.1 Mn 0.1 O 2 asymmetric cells show excellent cycling performance and rate capability at a wide temperature. This strategy provides a promising path in designing high-energy-density ASSLMBs for practical application.

Focal cortical dysplasia (FCD) is a structural lesion that is the most common anatomical lesion identified in children, and the second most common in adults with drug-resistant focal-onset epilepsy. These lesions vary in size, location, and histopathological manifestations. FCDs are classified into three subtypes associated with loss-of-function mutations in PI3K/AKT, TSC1/TSC2, RHEB, and DEPDC/NPRL2/NPRL3. During the decades of research into FCD, experimental models have played an irreplaceable role in the research design of studies investigating disease pathogenesis, pathophysiology, and treatment. Further, the establishment of FCD experimental models has moved the field forward by (1) revealing the cellular processes and signaling pathways underlying FCD pathogenesis and (2) varying the methods and materials to study the function of FCD proteins. Currently, FCD experimental models are predominantly murine, with each model providing unique insights into FCD lesions. This review briefly summarizes the pathology and molecular functions of FCD, further comparing the available modeling methods and indexes, as well as the utilization of models, followed by an analysis of the similarities, advantages, and disadvantages between these models and human FCD., Competing Interests: Declaration of interest None., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

This paper conducts quasi-experiment design with Chinese listed companies microdata to investigate the effect and mechanism of corporate participation in carbon emission trading market on firm financial performance by using the staggered difference-in-differences method. We show that: a) corporate participation in carbon emission trading market can enhance firm financial performance; b) an increase in green innovation ability and a decrease in strategic choice variance both partially mediate the relationship between carbon emission trading and firm performance; c) executive background heterogeneity and external environmental uncertainty moderate the relationship between carbon emission trading and firm performance in different directions; d) our further study indicates that carbon emission trading pilot policy has a spatial spillover effect on firm financial performance in the neighboring provinces. Therefore, we recommend that the government and enterprises make an effort to further stimulate the vitality of corporate participation in carbon emission trading market., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic kidney disease (CKD), stemming from varied nephric impairments, manifests a steadily escalating global incidence. As a progressive pathological condition, CKD is typified by an intensification in the gravity of renal interstitium fibrotic transformations. Nonetheless, the intrinsic mechanisms underpinning nephric fibrosis remain elusive. In this context, we elucidated a marked augmentation in aerobic glycolysis within proximal tubular epithelial cells (TECs) of CKD patients, alongside unilateral ureteral obstruction (UUO) and ischemia-reperfusion injury (IRI) murine models, concomitant with deficiency of Trim21. Experimental investigations, both in vivo and in vitro, revealed that Trim21 deficiency aggravates the aberrantly heightened aerobic glycolysis, thereby exacerbating fibrotic reaction progression. Concomitantly, enhancive glycolytic flux paralleled an elevation in ATP genesis and reconstitution of cytoskeletal architecture. Mechanistically, we uncovered that Trim21 modulates aerobic glycolysis in TECs via ubiquitin-facilitated degradation of phosphofructokinase platelet (PFKP), thus attenuating nephric fibrosis. Collectively, our insights posit Trim21 as a prospective therapeutic target in the amelioration of renal fibrosis., (© 2024 Wiley Periodicals LLC.)

Background: Emerging observational studies indicated an association between hyperthyroidism and gastrointestinal disorders. However, it remains unclear whether this association is causal, particularly in the case of gastroesophageal reflux (GERD) and esophageal cancer., Methods: To assess the potential causal relationship between hyperthyroidism and GERD or esophageal cancer, we conducted a bidirectional 2-sample Mendelian randomization study. Independent genetic instruments for hyperthyroidism from the UK Biobank (N case=3,545 and N control=459,388) and public genome-wide association study (GWAS) dataset (N case=3,731 and N control=480,867) were used to investigate the association with esophageal cancer in the UK Biobank study (N case=740 and N control=372,016) and GERD in the public GWAS database (N case=20,381 and N control=464,217). Four different approaches (inverse variance weighted (IVW), weighted mode, MR-Egger, and weighted median regression) were used to ensure that our results more reliable. Additional sensitivity analyses were also performed to validate our results., Results: When hyperthyroidism was considered as the exposure factor, it appeared to act as a protective factor for GERD (OR IVW = 0.88, 95% CI, 0.79-0.99, P = 0.039), while as a risk factor for esophageal cancer (OR IVW = 1.03, 95% CI, 1.01-1.06, P = 0.003). However, there is no evidence supporting a reverse causal relationship between genetic susceptibility to hyperthyroidism and GERD or esophageal cancer., Conclusion: Our findings provided genetic evidence supporting bidirectional causal relationships between hyperthyroidism and GERD or esophageal cancer. These results substantiate certain discoveries from previous observational studies on a causal level and provide insight into relevant genetic susceptibility factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Li, Gan and Guo.)

Rice cadmium (Cd) and microplastics are prevalent contaminants, posing a co-exposure threat to humans by means of dietary intake. To assess whether co-exposure of microplastics affects the bioavailability of rice Cd, mice were exposed to Cd-contaminated rice with microplastic co-exposure. We found that polyethylene (PE), polystyrene (PS), polypropylene (PP), and polyamide (PA) microplastic co-exposure via diet consumption (2 μg g -1 ) caused 1.17-1.38-fold higher Cd accumulation in tissue of mice fed by Cd-rice. For mice with co-exposure of PE microplastics, the higher rice-Cd bioavailability corresponded to colonization of Lactobacillus reuteri (38.9 % vs 17.5 %) in the gut compared to control mice, which caused higher production of gut metabolites particularly peptides, likely causing a 'side effect' of elevating Cd solubility in the intestinal lumen. In addition, abundance of sphingosine 1-phosphate in the gut of mice was reduced under PE microplastic exposure, which may reduce intracellular calcium ions (Ca 2+ ) in enterocytes and form a weaker competition in pumping of intracellular Ca 2+ and Cd 2+ across the basolateral membrane of enterocytes, leading to higher Cd 2+ transport efficiency. The results suggest elevated Cd exposure risk from rice consumption with microplastic co-exposure at environmentally relevant low concentrations., 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.)

The epidermal growth factor receptor (EGFR) protein is highly expressed in a range of malignancies. Although therapeutic interventions directed toward EGFR have yielded therapeutic responses in cancer patients, side effects are common because of normal-tissue expression of wild-type EGFR. We developed a novel tumor-specific anti-EGFR chimeric antibody ch806 labeled with 225 Ac and evaluated its in vitro properties and therapeutic efficacy in murine models of glioblastoma and colorectal cancer. Methods: 225 Ac-ch806 was prepared using different chelators, yielding [ 225 Ac]Ac-macropa-tzPEG 3 Sq-ch806 and [ 225 Ac]Ac-DOTA-dhPzPEG 4 -ch806. Radiochemical yield, purity, apparent specific activity, and serum stability of 225 Ac-ch806 were quantified. In vitro cell killing effect was examined. The biodistribution and therapeutic efficacy of 225 Ac-ch806 were investigated in mice with U87MG.de2-7 and DiFi tumors. Pharmacodynamic analysis of tumors after therapy was performed, including DNA double-strand break immunofluorescence of γH2AX, as well as immunohistochemistry for proliferation, cell cycle arrest, and apoptosis. Results: [ 225 Ac]Ac-macropa-tzPEG 3 Sq-ch806 surpassed [ 225 Ac]Ac-DOTA-dhPzPEG 4 -ch806 in radiochemical yield, purity, apparent specific activity, and serum stability. [ 225 Ac]Ac-macropa-tzPEG 3 Sq-ch806 was therefore used for both in vitro and in vivo studies. It displayed a significant, specific, and dose-dependent in vitro cell-killing effect in U87MG.de2-7 cells. 225 Ac-ch806 also displayed high tumor uptake and minimal uptake in normal tissues. 225 Ac-ch806 significantly inhibited tumor growth and prolonged survival in both U87MG.de2-7 and DiFi models. Enhanced γH2AX staining was observed in 225 Ac-ch806-treated tumors compared with controls. Reduced Ki-67 expression was evident in all 225 Ac-ch806-treated tumors. Increased expression of p21 and cleaved caspase 3 was shown in U87MG.de2-7 and DiFi tumors treated with 225 Ac-ch806. Conclusion: In glioblastoma and colorectal tumor models, 225 Ac-ch806 significantly inhibited tumor growth via induction of double-strand breaks, thereby constraining cancer cell proliferation while inducing cell cycle arrest and apoptosis. These findings underscore the potential clinical applicability of 225 Ac-ch806 as a potential therapy for EGFR-expressing solid tumors., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The nodule mass is an important indicator for evaluating the invasiveness of neoplastic ground-glass nodules (GGNs); however, the efficacy of nodule mass acquired by artificial intelligence (AI) has not been validated. This study thus aimed to determine the efficacy of nodule mass measured by AI in predicting the invasiveness of neoplastic GGNs., Methods: From May 2019 to September 2023, a retrospective study was conducted on 755 consecutive patients comprising 788 pathologically confirmed neoplastic GGNs, among which 259 were adenocarcinoma in situ (AIS), 282 minimally invasive adenocarcinoma (MIA), and 247 invasive adenocarcinoma (IAC). Nodule mass was quantified using AI software, and other computed tomography (CT) features were concurrently evaluated. Clinical data and CT features were compared using the Kruskal-Wallis test or Pearson chi-square test. The predictive efficacy of mass and CT features for evaluating invasive lesions (ILs) (MIAs and IACs) and IACs was analyzed and compared via receiver operating characteristic (ROC) analysis and the Delong test., Results: ROC curve analysis revealed that the optimal cutoff value of mass for distinguishing ILs and AISs was 225.25 mg [area under the curve (AUC) 0.821; 95% confidence interval 0.792-0.847; sensitivity 64.27%; specificity 89.19%; P<0.001], and for differentiating IACs from AISs and MIAs, it was 390.4 mg (AUC 0.883; 95% confidence interval 0.858-0.904; sensitivity 80.57%; specificity 86.32%; P<0.001). The efficacy of nodule mass in distinguishing ILs and AISs was comparable to that of size (P=0.2162) and significantly superior to other CT features (each P value <0.001). Additionally, the ability of nodule mass to differentiate IACs from AISs and MIAs was significantly better than that of CT features (each P value <0.001)., Conclusions: AI-based nodule mass analysis is an effective indicator for determining the invasiveness of neoplastic GGNs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-665/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Renal tubular epithelial cells (TECs) undergo an energy-related metabolic shift from fatty acid oxidation to glycolysis during chronic kidney disease (CKD) progression. However, the mechanisms underlying this burst of glycolysis remain unclear. Herein, a new critical glycolysis regulator, the transcription factor forkhead box protein K1 (FOXK1) that is expressed in TECs during renal fibrosis and exhibits fibrogenic and metabolism-rewiring capacities is reported. Genetic modification of the Foxk1 locus in TECs alters glycolytic metabolism and fibrotic lesions. A surge in the expression of a set of glycolysis-related genes following FOXK1 protein activation contributes to the energy-related metabolic shift. Nuclear-translocated FOXK1 forms condensate through liquid-liquid phase separation (LLPS) to drive the transcription of target genes. Core intrinsically disordered regions within FOXK1 protein are mapped and validated. A therapeutic strategy is explored by targeting the Foxk1 locus in a murine model of CKD by the renal subcapsular injection of a recombinant adeno-associated virus 9 vector encoding Foxk1-short hairpin RNA. In summary, the mechanism of a FOXK1-mediated glycolytic burst in TECs, which involves the LLPS to enhance FOXK1 transcriptional activity is elucidated., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes 29 proteins including four structural, 16 nonstructural (nsps), and nine accessory proteins (https://epimedlab.org/sars-cov-2-proteome/). Many of these proteins contain potential targetable sites for the development of antivirals. Despite the widespread use of vaccinations, the emergence of variants necessitates the investigation of new therapeutics and antivirals. Here, the EpiMed Coronabank Chemical Collection (https://epimedlab.org/crl/) was utilized to investigate potential antivirals against the nsp14 exoribonuclease (ExoN) domain. Molecular docking was performed to evaluate the binding characteristics of our chemical library against the nsp14 ExoN site. Based on the initial screen, trisjuglone, ararobinol, corilagin, and naphthofluorescein were identified as potential lead compounds. Molecular dynamics (MD) simulations were subsequently performed, with the results highlighting the stability of the lead compounds in the nsp14 ExoN site. Protein-RNA docking revealed the potential for the lead compounds to disrupt the interaction with RNA when bound to the ExoN site. Moreover, hypericin, cyanidin-3-O-glucoside, and rutin were previously identified as lead compounds targeting the papain-like protease (PL pro ) naphthalene binding site. Through performing MD simulations, the stability and interactions of lead compounds with PL pro were further examined. Overall, given the critical role of the exonuclease activity of nsp14 in ensuring viral fidelity and the multifunctional role of PL pro in viral pathobiology and replication, these nsps represent important targets for antiviral drug development. Our databases can be utilized for in silico studies, such as the ones performed here, and this approach can be applied to other potentially druggable SARS-CoV-2 protein targets., 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 Inc. All rights reserved.)

Image compressed sensing (ICS) has been extensively applied in various imaging domains due to its capability to sample and reconstruct images at subNyquist sampling rates. The current predominant approaches in ICS, specifically pure convolutional networks (ConvNets)-based ICS methods, have demonstrated their effectiveness in capturing local features for image recovery. Simultaneously, the Transformer architecture has gained significant attention due to its capability to model global correlations among image features. Motivated by these insights, we propose a novel hybrid network for ICS, named MTC-CSNet, which effectively combines the strengths of both ConvNets and Transformer architectures in capturing local and global image features to achieve high-quality image recovery. Particularly, MTC-CSNet is a dual-path framework that consists of a ConvNets-based recovery branch and a Transformer-based recovery branch. Along the ConvNets-based recovery branch, we design a lightweight scheme to capture the local features in natural images. Meanwhile, we implement a Transformer-based recovery branch to iteratively model the global dependencies among image patches. Ultimately, the ConvNets-based and Transformer-based recovery branches collaborate through a bridging unit, facilitating the adaptive transmission and fusion of informative features for image reconstruction. Extensive experimental results demonstrate that our proposed MTC-CSNet surpasses the state-of-the-art methods on various public datasets. The code and models are publicly available at MTC-CSNet.

Background: The purpose of this study is to investigate the prevalence and risk factor of cognitive frailty in patients undergoing maintenance hemodialysis., Methods: Systematically searched PubMed, EmBase, Web of Science, Cochrane Library, SinoMed, China Knowledge Resource Integrated Database, Wanfang Database, and Weipu Database from inception until January 1, 2024. Two researchers were independently screened and cross-checked. Stata 15.1 software was used to perform the meta-analysis., Results: A total of 15 articles were included, including 5398 patients. The results showed that the prevalence of cognitive frailty in patients undergoing maintenance hemodialysis was 24%. Among them, age (odds ratio [OR] = 1.33, 95% CI [1.16, 1.53]), waist circumference (OR = 1.05, 95% CI [1.03, 1.08]), malnutrition (OR = 2.91, 95% CI [1.94, 4.35]), comorbidities (OR = 1.93, 95% CI [1.47, 2.54]), stroke history (OR = 2.94, 95% CI [1.72, 5.03]), and depression (OR = 3.26, 95% CI [1.91, 5.57]) were the main risk factors for cognitive frailty in patients undergoing maintenance hemodialysis. Education level (OR = 0.48, 95% CI [0.31, 0.73]) was protective factors for cognitive frailty in patients undergoing maintenance hemodialysis., Conclusions: Current evidence showed that the prevalence of cognitive frailty in patients undergoing maintenance hemodialysis was high, and there were many risk factors. Therefore, early identification and intervention of cognitive frailty in maintenance hemodialysis patients should be carried out, which may be helpful to reduce the prevalence rate and occurrence of adverse events and improve the prognosis of patients., (© 2024 Wiley Periodicals LLC.)

Background: TP53 mutations are associated with prostate cancer (PCa) prognosis and therapy., Purpose: To develop TP53 mutation classification models for PCa using MRI radiomics and clinicopathological features., Study Type: Retrospective., Population: 388 patients with PCa from two centers (Center 1: 281 patients; Center 2: 107 patients). Cases from Center 1 were randomly divided into training and internal validation sets (7:3). Cases from Center 2 were used for external validation., Field Strength/sequence: 3.0T/T2-weighted imaging, dynamic contrast-enhanced imaging, diffusion-weighted imaging., Assessment: Each patient's index tumor lesion was manually delineated on the above MRI images. Five clinicopathological and 428 radiomics features were obtained from each lesion. Radiomics features were selected by least absolute shrinkage and selection operator and binary logistic regression (LR) analysis, while clinicopathological features were selected using Mann-Whitney U test. Radiomics models were constructed using LR, support vector machine (SVM), and random forest (RF) classifiers. Clinicopathological-radiomics combined models were constructed using the selected radiomics and clinicopathological features with the aforementioned classifiers., Statistical Tests: Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC). P value <0.05 indicates statistically significant., Results: In the internal validation set, the radiomics model had an AUC of 0.74 with the RF classifier, which was significantly higher than LR (AUC = 0.61), but similar to SVM (AUC = 0.69; P = 0.422). For the combined model, the AUC of RF model was 0.84, which was significantly higher than LR (0.64), but similar to SVM (0.80; P = 0.548). Both the combined RF and combined SVM models showed significantly higher AUCs than the radiomics models. In the external validation set, the combined RF and combined SVM models showed AUCs of 0.83 and 0.82., Data Conclusion: Pathological-radiomics combined models with RF, SVM show the association of TP53 mutations and pathological-radiomics features of PCa., Evidence Level: 3 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

The development of intracerebral hemorrhage (ICH) is a dynamic process and intervention during the acute phase of ICH is critical for subsequent recovery. Therefore, it is crucial to screen potential signature genes and therapeutic target genes in the acute phase of ICH. In this study, based on the results of mRNA sequencing in mouse ICH and mRNA sequencing of human ICH from online databases, top five potential signature genes after ICH, Tyrobp, Itgb2, Tlr2, Ptprc and Itgam, were screened. Quantitative PCR results showed higher mRNA expression of Tyrobp, Itgb2, Tlr2, Ptprc, and Itgam in the 1-, 3- and 5-day mouse ICH groups compared to the sham-operated group. Immune infiltration correlation analysis shows that the top-ranked signature gene, Tyrobp, is negatively correlated with M2 macrophages and plasma cells, and Western blot analysis shows higher expression of the Tyrobp protein in the 1-, 3-, and 5-day mouse ICH groups compared to the sham-operated group. Furthermore, immunohistochemistry revealed that TYROBP protein expression was significantly higher in human ICH tissues than in normal brain tissues. Our results suggest that Tyrobp is a signature gene in the acute phase of ICH and may be a potential target for the treatment of the acute phase of ICH., (© 2024. The Author(s).)

Background: Human hexokinase 2 (HK2) plays an important role in regulating Warburg effect, which metabolizes glucose to lactate acid even in the presence of ample oxygen and provides intermediate metabolites to support cancer cell proliferation and tumor growth. HK2 overexpression has been observed in various types of cancers and targeting HK2-driven Warburg effect has been suggested as a potential cancer therapeutic strategy. Given that epigenetic enzymes utilize metabolic intermediates as substrates or co-factors to carry out post-translational modification of histones and nucleic acids modifications in cells, we hypothesized that altering HK2 expression could impact the epigenome and, consequently, chromatin stability in yeast. To test this hypothesis, we established genetic models with different yeast hexokinase 2 (HXK2) expression in Saccharomyces cerevisiae yeast cells and investigated the effect of HXK2-dependent metabolism on parental nucleosome transfer, a key DNA replication-coupled epigenetic inheritance process, and chromatin stability., Results: By comparing the growth of mutant yeast cells carrying single deletion of hxk1Δ, hxk2Δ, or double-loss of hxk1Δ hxk2Δ to wild-type cells, we firstly confirmed that HXK2 is the dominant HXK in yeast cell growth. Surprisingly, manipulating HXK2 expression in yeast, whether through overexpression or deletion, had only a marginal impact on parental nucleosome assembly, but a noticeable trend with decrease chromatin instability. However, targeting yeast cells with 2-deoxy-D-glucose (2-DG), a clinical glycolysis inhibitor that has been proposed as an anti-cancer treatment, significantly increased chromatin instability., Conclusion: Our findings suggest that in yeast cells lacking HXK2, alternative HXKs such as HXK1 or glucokinase 1 (GLK1) play a role in supporting glycolysis at a level that adequately maintains epigenomic stability. While our study demonstrated an increase in epigenetic instability with 2-DG treatment, the observed effect seemed to occur dependent on non-glycolytic function of Hxk2. Thus, additional research is needed to identify the molecular mechanism through which 2-DG influences chromatin stability., (© 2024. The Author(s).)

Background: Water, sanitation, and hygiene (WaSH) are crucial determinants of human health. However, the spatio-temporal trends in the global burden of disease attributable to unsafe WaSH remain poorly understood. This study aimed to estimate the disease burden attributable to unsafe WaSH from 1990 to 2019 using data from the Global Burden of Disease (GBD) Study 2019, providing new insights into the associated health conditions., Methods: We extracted data on deaths and disability-adjusted life years (DALYs) attributable to unsafe WaSH from 1990 to 2019 from the GBD 2019. The disease burden was evaluated by region, sociodemographic index (SDI), sex, age, risk factor, and specific disease., Results: Globally, unsafe WaSH was responsible for 1 656 887.37 (95% uncertainty interval (UI) = 1 198 864.94, 2 312 688.33) deaths in 2019, a 49% decrease from 1990. The global age-standardised DALY rate due to unsafe WaSH was 1244.29 (95% UI = 993.20, 1544.13) per 100 000 in 2019, a 66% reduction since 1990. Western sub-Saharan Africa had the highest age-standardised death rate (ASDR) and age-standardised DALY rate in both 1990 and 2019. Among the 21 regions studied, only high-income North America witnessed an increasing ASDR from 1990 to 2019. Countries and territories in low SDI regions had higher ASDRs and age-standardised DALY rates. U-shaped associations were observed between the estimated annual percentage change (EAPC) of ASDR, EAPC of age-standardised DALY rate, and SDI. Both rates were slightly lower in females, with the burden concentrated in those under five and over 80 years old. In 2019, unsafe water source and diarrhoeal diseases remained the leading risk factor and cause of unsafe WaSH-related disease burden, respectively., Conclusions: Despite substantial improvements in hygiene awareness and health education, unsafe WaSH persists as a significant global health risk and a major contributor to the burden of diarrhoeal diseases. Disparities across regions and age groups remain evident. Increased efforts are needed to raise awareness and strengthen water and sanitation infrastructure, particularly in low SDI settings, to mitigate the health risks associated with unsafe WaSH., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Childhood leukemia is a prevalent form of pediatric cancer, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the primary manifestations. Timely treatment has significantly enhanced survival rates for children with acute leukemia. This study aimed to develop an early and comprehensive predictor for hematologic malignancies in children by analyzing nutritional biomarkers, key leukemia indicators, and granulocytes in their blood. Using a machine learning algorithm and ten indices, the blood samples of 826 children with ALL and 255 children with AML were compared to a control group of 200 healthy children. The study revealed notable differences, including higher indicators in boys compared to girls and significant variations in most biochemical indicators between leukemia patients and healthy children. Employing a random forest model resulted in an area under the curve (AUC) of 0.950 for predicting leukemia subtypes and an AUC of 0.909 for forecasting AML. This research introduces an efficient diagnostic tool for early screening of childhood blood cancers and underscores the potential of artificial intelligence in modern healthcare., (© 2024. The Author(s).)

Following the coronavirus disease-2019 outbreak caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an ongoing need to seek drugs that target COVID-19. First off, novel drugs have a long development cycle, high investment cost, and are high risk. Second, novel drugs must be evaluated for activity, efficacy, safety, and metabolic performance, contributing to the development cycle, investment cost, and risk. We searched the Cochrane COVID-19 Study Register (including PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and WHO COVID-19 Coronaviral Disease Global Literature to identify completed and ongoing studies as of February 20, 2024. We evaluated the pharmacological effects, in vivo and in vitro data of the 16 candidates in the paper. The difficulty of studying these candidates in clinical trials involving COVID-19 patients, dosage of repurposed drugs, etc. is discussed in detail. Ultimately, Metformin is more suitable for prophylactic administration or mildly ill patients; the combination of Oseltamivir, Tamoxifen, and Dexamethasone is suitable for moderately and severely ill patients; and more clinical trials are needed for Azvudine, Ribavirin, Colchicine, and Cepharanthine to demonstrate efficacy., Competing Interests: I also certify that I have disclosed any financial or non-financial relationships that may be interpreted as constituting a conflict of interest about this manuscript. I understand that this information will be subject to peer review, and I am willing to provide further information or clarification if required. I confirm that I have no known conflicts of interest that would influence the results or interpretation of the data presented in this manuscript, and I understand that failure to disclose a conflict of interest is unethical and may result in sanctioning imposed on me., (© 2024 The Authors. Published by Elsevier Ltd.)