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Xichen Wan,1– 3 Tong Lin,1– 3 Yunzhen Luo,4 Jiaxu Hong,1– 3,5 Jingyi Cheng,1– 3,&ast; Keqing Zhao6,&ast; 1Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 2NHC Key Laboratory of Myopia and Related Eye Diseases, Shanghai, People’s Republic of China; 3Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, People’s Republic of China; 4Department of Otolaryngology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 5Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Zhao, Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email rhinoresearch@163.com Jingyi Cheng, Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email tippicjy@126.comPurpose: To evaluate the effect of vidian neurectomy (VN) on the ocular surface and the possibility of dry eye in the treatment of allergic rhinitis.Methods: Twelve participants were recruited in this prospective study. Prior to and after 1 and 6 months of VN, an ocular surface disease index (OSDI) questionnaire was obtained, and the Schirmer’s tear test (STT), break-up time (BUT), corneal fluorescence staining (CFS) score, and Keratograph 5M were used to evaluate the ocular surface condition.Results: Two patients (16.67%) met the dry eye diagnosis criteria one month after surgery; however, their symptoms were relieved after to 3– 4 months and none of them met the diagnostic criteria for dry eye after six months. Compared with the baseline values, the STT was significantly reduced (P=0.002), while the tear meniscus height (TMH) (P=0.262), break-up time (BUT) (P=0.916), first keratographic tear film break-up time (NK-BUTfirst) (P=0.791), and average keratographic break-up time (NK-BUTave) (P=0.970) did not change significantly 6 months after surgery. The degree of STT decreased from baseline to 6-month and was related to the basic STT (ρ= 0.837, P=0.001) and sex (ρ= − 0.584, P= 0.026) but not to age, OSDI score, BUT, NK-BUTfirst, NK-BUTave or CFS (all P> 0.05). Among these factors, STT at baseline was confirmed to be a predictor of a decline in tear secretion after surgery (B = 0.731, P< 0.001).Conclusion: In this 6-month prospective pilot study, decreased tearing was observed after VN, but this decrease did not increase the possibility of dry eyes.Keywords: vidian neurectomy, ocular surface, dry eye

Hao Zhang,1,&ast; Anqi Xu,2,&ast; Xiangxiang Li,3,&ast; Binbin Pan,1 Xin Wan1 1Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Quality Management, Nanjing Red Cross Blood Center, Nanjing, People’s Republic of China; 3Department of Nephrology, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Binbin Pan; Xin Wan, Department of Nephrology, Nanjing First Hospital, No. 68, Changle Road, Nanjing, Jiangsu, 210006, People’s Republic of China, Tel +86 025-87726209, Email panbinbin@njmu.edu.cn; wanxin@njmu.edu.cnBackground and Objectives: Loss of immunoglobulin G (IgG) is accompanied with proteinuria, especially macroproteinuria. The complement system participates kidney disease resulting in proteinuria. Whether the ratio of complement and IgG is associated with macroproteinuria remains unknown.Design, Setting, Participants and Measurements: A total of 1013 non-dialysis chronic kidney disease (CKD) patients were recruited according to the electrical case records system with 268 patients who endured kidney biopsy. Patients were grouped via the estimated glomerular filtration rate or the levels of proteinuria determination. Biomarkers in different CKD groups or proteinuria groups were compared by one-way ANOVA or independent samples t-test. Pearson or spearman analysis was employed to analyze correlation between clinical indexes. Further, influence factor of macroproteinuria was studied by using binary logistic regression. The ROC curve was performed to explore probable predictive biomarker for macroproteinuria.Results: No significant difference of complement C3 and C4 among CKD1 to CKD5 stages, while higher level of complement C4 in patients with macroproteinuria. Further, C4 had a positive correlation with proteinuria (r=0.255, p=0.006). After adjusted for age, IgA, IgM, triglyceride and HDL, a binary logistic regression model showed lnC4/IgG (OR=3.561, 95% CI 2.196– 5.773, p< 0.01), gender (OR=1.737, 95% CI 1.116– 2.702, p=0.014), age (OR=0.983, 95% CI 0.969– 0.997, p=0.014), and history of diabetes (OR=0.405, 95% CI 0.235– 0.699, p< 0.01) were independent influence factors of macroproteinuria. The area under the ROC curve was 0.77 (95% CI: 0.75– 0.82, p< 0.001) for C4/IgG. The analysis of ROC curves revealed a best cut-off for complement C4 was 0.024 and yielded a sensitivity of 71% and a specificity of 71%. The area under the ROC curve was 0.841 (95% CI: 0.735– 0.946, p < 0.001) for C4/IgG in IgA nephropathy patients. The analysis of ROC curves revealed a best cut-off for complement C4/IgG was 0.026 and yielded a sensitivity of 75% and a specificity of 81.2%. The area under the ROC curve for C4/IgG in CKD1-5 stages were 0.772, 0.811, 0.785, 0.835, 0.674.Conclusion: Complement C4/IgG could be used to predict macroproteinuria.Keywords: complement C4, immunoglobulin G, macroproteinuria, chronic kidney disease, kidney biopsy

Binbin Liu,1,&ast; Pan Su,1,&ast; Peilei Hu,1,&ast; Mi Yan,1 Wenbin Li,1 Songlin Yi,1 Zhenhua Chen,1 Xiaoping Zhang,1 Jingwei Guo,1 Xiaojie Wan,1 Jue Wang,1 Daofang Gong,1 Hua Bai,1 Kanglin Wan,2 Haican Liu,2 Guilian Li,2 Yunhong Tan1 1Clinical Laboratory, Hunan Chest Hospital, Changsha, People’s Republic of China; 2National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunhong Tan, Clinical Laboratory, Hunan Chest Hospital, Changsha, People’s Republic of China, Tel +86-13874947876, Email Tanyunhong@163.com Guilian Li, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China, Tel +86-18519886112, Email liguilian@icdc.cnBackground: China is a country with a burden of high rates of both TB and multidrug-resistant TB (MDR-TB). However, published data on pyrazinamide (PZA) resistance are still limited in Hunan province, China. This study investigated the prevalence, transmission, and genetic diversity of PZA resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Hunan province.Methods: Drug susceptibility testing (DST) with the Bactec MGIT 960 PZA kit and pyrazinamidase (PZase) testing were conducted on all 298 MDR clinical isolates. Moreover, 24-locus MIRU-VNTR and DNA sequencing of pncA, rpsA, and panD genes were conducted on 180 PZA-resistant (PZA-R) isolates.Results: The prevalence of PZA resistance among MDR-TB strains reached 60.4%. Newly diagnosed PZA-R TB patients and clustered isolates with identical pncA, rpsA, and panD mutations showed that transmission of PZA-R isolates played a significant role in the formation of PZA-R TB. Ninety-eight mutation patterns were observed in the pncA among 180 PZA-R isolates, and seventy-one (72.4%) were point mutations. Twenty-four of these mutations are new, including 2 base substitutions (V93G and T153S) and 22 nucleotide deletions or insertions. The W119C was found in PZA-S isolates, on the other hand, F94L and V155A mutations were found in both PZA resistant and susceptible isolates with positive PZase activity, indicating that they were not associated with PZA resistance. This is not entirely in line with the WHO catalogue. Ten novel rpsA mutations were found in 10 PZA-R isolates, which all combined with mutations in pncA. Thus, it is unpredictable whether these mutations in rpsA can impact PZA resistance. No panD mutation was found in all PZA-R isolates.Conclusion: DNA sequencing of pncA and PZase activity testing have great potential in predicting PZA resistance.Keywords: tuberculosis, pyrazinamide, transmission, pncA mutations, rpsA mutations, panD mutations, China

Xuan Yi,1 Xinxing Wan,1 Md Asaduzzaman Khan,2,3 Xiaoying Sun,1 Zhouqi Wang,1 Ke Chen,1 Lin Peng4 1Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Research Division, Nature Study Society of Bangladesh, Dhaka, 1000, Bangladesh; 3Pulmonary Department, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, 02118, USA; 4Department of Nephrology, The First Hospital of Changsha, Changsha, People’s Republic of ChinaCorrespondence: Lin Peng, Department of Nephrology, The First Hospital of Changsha, Changsha, People’s Republic of China, Tel +86-731-8466-7510, Email plin1018@163.com Ke Chen, Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8861-8239, Email chenke520@yeah.netPurpose: Adipogenesis is one of the major pathways for generating obesity or overweight that can cause a range of metabolic disorders. Circular RNAs (circRNAs), a specific type of RNAs, have a significant influence on metabolic disorders. This study aims to find differentially expressed circRNAs (DECs) during human subcutaneous adipose tissue (SATs) adipogenesis.Patients and Methods: The human adipose tissue-derived stromal cells (hADSCs) were isolated from human SATs (n = 3), and then induced into adipocytes. Total RNAs were extracted from hADSCs and adipocytes, and he DECs were detected using circRNA microarray. The GO and KEGG pathways of DECs were analyzed by bioinformatic methods, and partial DECs were further validated by quantitative polymerase chain reaction (qPCR).Results: Our study detected a total of 1987 DECs, among which, 1134 were found upregulated and 853 were downregulated. GO analysis showed that the upregulated DECs have catalytic activity in intracellular organelle and cytoplasms, whereas downregulated DECs are enriched in organelle lumen, and are involved in positive regulation of developmental process. In addition, pathway results demonstrated that upregulated DECs are involved in platinum drug resistance and cellular senescence, and downregulated DECs are enriched in proteoglycans in cancer and focal adhesion pathway. Two circRNAs, namely has_circ_0001600 and has_circ_0001947 were validated to be significantly upregulated in adipocytes compared to hADSCs.Conclusion: Our study explored DECs between hADSCs derived from SATs and adipocytes, and report that two circRNAs named has_circ_0001600 and has_circ_0001947 might be important factors involved in human adipogenesis, however, the molecular mechanism should be further explored.Keywords: circRNA microarray, subcutaneous adipose tissue, human adipose tissue-derived stromal cells, adipogenesis, SAT

The suspension smelting oxidation step has favourable conditions to generate chemical flue dust from the low-boiling elements of the feed mixture due to the high particle temperatures in the reaction shaft where combusting sulphide mineral particles reach temperatures above the melting point of magnetite. Arsenic, antimony, lead, and zinc are common impurity elements of high volatility in copper concentrates. They tend to accumulate in the flue dust due to the high volatility and closed mode of the flue dust circulation practiced in most industrial smelting-converting processes. Then, the only outlets for the volatile impurities are the anodes and the discard slag. A separate flue dust treatment for impurity removal is an option but it creates an additional step for the smelting plant and cost in the processing. When the concentrate grades decrease, and their impurity levels rise this outlet for the trace elements may become necessary. The arsenic condensation mechanisms in dust-free conditions in the copper flash smelting process gas train have been recently studied in SO2-air-N2 gas mixtures. It seems that the formation mechanism of arsenic-containing dust deposits is kinetically constrained, and their chemistries are influenced by the condensation temperature and atmosphere.

This paper introduces a novel Attention-based Bidirectional Long Short-Term Memory (BiLSTM) model for detecting stress in social media text, aiming to enhance mental health monitoring in the digital age. Utilizing the unique communicative nature of social media, this study employs user-generated content to analyze emotional and stress levels. The proposed model incorporates an attention mechanism with the Bi-LSTM architecture to improve the identification of temporal features and context relationships in text data, which is crucial for detecting stress indicators. This model stands out by dynamically focusing on text segments that significantly denote stress, thereby boosting the detection sensitivity and accuracy. Through rigorous testing against baseline models such as Text-CNN, LSTM, GRU, and standard Bi-LSTM, our method demonstrates superior performance, achieving the highest F1-score of 81.21%. These results underscore its potential for practical applications in mental health monitoring where accurate and timely detection of stress is essential. [ABSTRACT FROM AUTHOR]

Using observations from multi‐satellites at different altitudes, including the CHAllenging Minisatellite Payload (CHAMP), the Gravity Recovery and Climate Experiment, Swarm B, and Defense Meteorological Satellites Program F17, the ionospheric post‐midnight enhancement at mid‐latitudes and the associated inter‐hemispheric asymmetry during equinox are investigated in this study. During equinox months, the ionospheric electron density enhancement during post‐nighttime at mid‐latitudes is visible in both hemispheres, however, it is asymmetric between the Northern and Southern Hemispheres. At most longitudes, inter‐hemispheric asymmetry of Mid‐latitude Ionospheric Post‐midnight Enhancement (MIPE) reverses with altitudes, from a stronger electron density in the Northern Hemisphere at CHAMP altitude to a stronger electron density in the Southern Hemisphere at top ionosphere during equinox. The reversal altitude and reversal time have significant longitudinal differences. The effective ionospheric uplifting induced by the combination of neutral winds and geomagnetic field configuration is the main contribution to the asymmetry reversal of MIPE at lower altitudes, as shown in the simulations from the SAMI2 and HWM14 models. In comparison with that in the Southern Hemisphere, the stronger neutral winds in the Northern Hemisphere move the plasma along the geomagnetic field lines to a higher altitude with lower chemical recombination, resulting in the enhancement of electron density. Plain Language Summary: The mid‐latitude ionospheric post‐midnight enhancement is a phenomenon that the electron densities at mid‐latitudes are higher than that at low‐latitudes during post‐midnight. Recently, the mid‐latitude post‐midnight electron density bands during equinox months are found to have an inter‐hemispheric asymmetry and an altitudinal reversal at most longitudes. However, the potential physical mechanisms are poorly understood, which is key in the modeling and forecasting of near‐Earth space weather. Using simulation results from models, we found that neutral winds and geomagnetic field configuration are critical for the reversal of inter‐hemispheric asymmetry with altitude. Key Points: The mid‐latitude ionospheric post‐midnight enhancement exhibit significant inter‐hemispheric asymmetry during equinox months at various altitudes above F2‐peakAt most longitudes, the hemispheric asymmetry reversed with altitude and the reversal altitude shows significant longitudinal differencesThe effective ionospheric uplifting induced by neutral winds and geomagnetic field configuration is the key in the altitudinal reversal [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP) overdose is still a leading cause of drug-induced liver injury (DILI), accompanied with severe inflammatory response. However, the therapy for APAP-induced DILI is rather limited. The combined application of natural products to treat DILI induced by APAP may be a new direction of the research. This study was conducted to evaluate the dual anti-inflammatory activity of curcumin (CUR) combined with berberine (BBR) against APAP-mediated DILI. Network pharmacology found that PI3K-Akt and PPAR signaling pathways were primarily involved in anti-DILI of the combination of CUR and BBR. APAP injection enhanced the levels of ALT, AST, IL-1β, IL-6, and TNF-α in mice, while such phenomenon was significantly reversed by the cotreatment of CUR and BBR, which was more effective than either single treatment. The increase of p-NF-κB and p-IKKα/β protein expression and the decrease of p-PI3K, p-AKT, and PPARγ protein expression in APAP-treated mice were markedly inhibited by the coadministration of CUR and BBR. Molecular docking further demonstrated that both CUR and BBR could stably bind to PI3K, AKT, and PPARγ protein. In conclusion, the combination of CUR and BBR more effectively protected liver from APAP-triggered DILI than individual treatment. The mechanism is to alleviate hepatic inflammation by inhibiting NF-κB activation, which is possibly mediated by PI3K/Akt and PPARγ signaling pathways., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hypertrophic scar (HS) manifests as abnormal dermal myofibroblast proliferation and excessive collagen deposition, leading to raised scars and significant physical, psychological, and financial burdens for patients. HS is difficult to cure in the clinic and current therapies lead to recurrence, pain, and side effects. In this study, a natural amphiphilic polymer mucin is used to prepare a dissolving microneedle (muMN) that is loaded with oregano essential oil (OEO) for HS therapy. muMN exhibits sufficient skin/scar tissue penetration, quick skin recovery time after removal, good loading of natural essential oil, fast dissolution and detachment from the base layer, and good biocompatibility to applied skin. In the rabbit HS model, OEO@muMN shows a significant reduction in scar thickness, epidermal thickness index, and scar elevation index. OEO@muMN also attenuates the mean collagen area fraction and decreases the number of capillaries in scar tissues. Biochemical Assay reveals that OEO@muMN significantly inhibits the expression of transforming growth factor-β1 (TGF-β1) and hydroxyproline (HYP). In summary, this study demonstrates the feasibility and good efficacy of using the anti-proliferative and anti-oxidative OEO for HS treatment. OEO@muMN is an efficient formulation that holds the potential for clinical anti-HS application. muMN is an efficient platform to load and apply essential oils transdermally., 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.)

Ethnopharmacological Relevance: The plants in the genus Erigeron are known to exhibit antiviral activities, including those against the respiratory syncytial virus (RSV). In traditional medicine Erigeron annuus (L.) Pers (EA) has been used in the treatment of pulmonary diseases and acute infectious hepatitis., Aim of This Study: The aim of this study is to determine the optimum extraction method to produce the most potent anti-RSV extract, elucidate its mode and mechanisms of antiviral activity in both in vitro and in vivo models, and identify the chemical structures of the bioactive compounds., Materials and Methods: The whole plant of EA was extracted with ethyl acetate, methanol, ethanol, water, aqueous methanol (60, 80% and 100%) and aqueous ethanol (50, 75% and 95%) using maceration, reflux, and ultrasound-assisted extraction methods. The antiviral activities of the extracts were determined in vitro. The in vitro antiviral activities of the extracts were determined using Hep-2 cells. Four in vitro experiments were performed to determine the mode of antiviral activity of the most active extract, ethyl acetate fraction (EAE) of Erigeron annuus whole plant extract prepared by refluxing with 50% ethanol, by examining its ability to inactivate the virus directly, inhibit viral adsorption and penetration, inhibit viral replication and preventive effect. The effect of temperature and duration of treatment on these modes of action was also determined. The antiviral activity of the EAE was also assessed in vivo in a mouse model. The lung index, viral load, and lung tissue histology were measured. qRT-PCR and ELISA studies were performed to determine the expression of key genes (TLR-3 and TLR-4) and proteins (IL-2, IFN-γ, and TNF-α) related to RSV infection. The most active antiviral compound was isolated using chromatography techniques, and its chemical structure was identified through electrospray triple quadrupole mass spectroscopy and nuclear magnetic resonance spectroscopy., Results: The EAE was the most active on RSV. In vitro experiments showed that the antiviral activity of EAE is via direct inactivation, inhibition of entry, and inhibition of the proliferation of the virus. In vivo experiments showed that the EAE effectively inhibited the proliferation of RSV in the lungs and alleviated the lung tissue lesions in RSV-infected mice. The antiviral activity of the EAE is mediated by downregulating the expression of TLR3 and TLR4 in the lung, upregulating the expression of IL-2 and IFN-γ, and downregulating the expression of TNF-α. Apigenin 7-O-methylglucuronide was found to be a major bioactive compound in EAE., Conclusions: The results of this study confirmed the antiviral activity of EA by inactivating, inhibiting the entry, and inhibiting the proliferation of RSV. The activity is mediated by regulating the immunity and inflammatory mediators. Apigenin 7-O-methylglucuronide is the bioactive compound present in EA., 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.)

The proliferation of nitrile mixtures has significantly exacerbated environmental pollution. This study employed metagenomic analysis to investigate the short-term effects of nitrile mixtures on soil microbial communities and their metabolic functions. It also examined the responses of indigenous microorganisms and their functional metabolic genes across various land use types to different nitrile stressors. The nitrile compound treatments in this study resulted in an increase in the abundance of Proteobacteria, Actinobacteria, and Firmicutes, while simultaneously reducing overall microbial diversity. The key genes involved in the denitrification process, namely, nirK, nosZ, and hao, were down-regulated, and NO 3 - -N, NO 2 - -N, and NH 4 + -N concentrations decreased by 7.7%-12.3%, 11.1%-21.3%, and 11.3%-30.9%, respectively. Notably, pond sludge samples exhibited a significant increase in the abundance of nitrogen fixation-related genes nifH, vnfK, vnfH, and vnfG following exposure to nitrile compounds. Furthermore, the fumarase gene fumD, which is responsible for catalyzing fumaric acid into malic acid in the tricarboxylic acid cycle, showed a substantial increase of 7.2-10.6-fold upon nitrile addition. Enzyme genes associated with the catechol pathway, including benB-xylY, dmpB, dmpC, dmpH, and mhpD, displayed increased abundance, whereas genes related to the benzoyl-coenzyme A pathway, such as bcrA, dch, had, oah, and gcdA, were notably reduced. In summary, complex nitrile compounds were found to significantly reduce the species diversity of soil microorganisms. Nitrile-tolerant microorganisms demonstrated the ability to degrade and adapt to nitrile pollutants by enhancing functional enzymes involved in the catechol pathway and fenugreek conversion pathway. This study offers insights into the specific responses of microorganisms to compound nitrile contamination, as well as valuable information for screening nitrile-degrading microorganisms and identifying nitrile metabolic enzymes., 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 Inc.)

Groundwater recharge is a viable solution to groundwater overexploitation. However, the injection of recharge water may break the dissolution balance and induce the release of trace elements especially arsenic (As), which has been identified in river deltas. Only a few studies have been conducted in inland basins with high As concentration, high pH, and low Eh. Aiming to analyze As release with groundwater recharge in inland high-As regions and determine the effects of coexisting ions in recharge water, this study established PHase Equilibria Calculation (PHREEQC) models using rainwater and groundwater data from three inland sedimentary basins with slow groundwater flow in semi-arid regions. The simulations fitted with the batch experiments, achieving an R-squared (R 2 ) of 0.98. The coexisting ions in the recharge water significantly affected As release during recharge. Ca 2+ inhibited the release of total arsenic (Total-As) by increasing the surface charge of iron oxides. NO 3 - inhibited Total-As release by promoting the conversion of trivalent As into pentavalent As. Conversely, HCO 3 - facilitated As release by competing with arsenate for adsorption sites. On the basis of the modeling and batch experiment results, Total-As release with groundwater recharge was predicted. The results indicated that the high Ca 2+ concentration in the recharge water inhibited the As release by 83.5 %, which can be used as a strategy to control As release during groundwater recharge in high-As inland basins., 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.)

Acrylamide exposure has become an emerging environmental and food safety issue, and its toxicity poses a potential threat to public health worldwide. However, limited studies have paid attention to the detrimental effects of parental exposure to acrylamide on the neurodevelopment in zebrafish offspring. In this study, the embryos were life-cycle exposed to acrylamide (0.125 and 0.25 mM) for 180 days. Subsequently, these zebrafish (F0) were allowed to mate, and their offspring (F1) were collected to culture in clean water from embryos to adults. We employed developmental and morphological observations, behavioral profiles, metabolomics analyses, and transcriptional level examinations to investigate the transgenerational neurotoxicity with parental exposure to acrylamide. Our results showed that parental exposure to acrylamide harms the birth, development, and behavior characterization of the F1 zebrafish larvae, including poor egg quality, increased mortality rates, abnormal heart rates, slowed swimming activity, and heightened anxiety behavior, and continuously disturbs mental health in F1 adult zebrafish. The transcriptional analysis showed that parental chronic exposure to acrylamide deteriorates the neurodevelopment in F1 larvae. In addition, metabolomics analyses revealed that sphingolipid metabolism disruption may be associated with the observed abnormal development and behavioral response in unexposed F1 offspring. Overall, the present study provides pioneer evidence that acrylamide induces transgenerational neurotoxicity via targeting and disrupting sphingolipid metabolism, which reveals intergenerational transmission of acrylamide exposure and unravels its spatiotemporal toxicological effect on neurodevelopment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the value of 18 F-FDG PET/CT-based intratumoral and peritumoral radiomics in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer., Methods: 190 patients who met the inclusion and exclusion criteria from 2017 to 2022 were studied. Features were extracted from the PET/CT intratumoral and peritumoral regions, feature selection was performed through the correlation analysis, t-tests, and least absolute shrinkage and selection operator regression (LASSO). Four classifiers, support vector machine (SVM), k-nearest neighbor (KNN), logistic regression (LR), and naive bayes (NB) were used to build the prediction models. The receiver operating characteristic (ROC) curves were plotted to measure the predictive performance of the models. Concurrent stratified analysis was conducted to establish subtype-specific features for each molecular subtype., Results: Compared to intratumoral features alone, intratumoral + peritumoral features achieved higher AUC values in each classifier. The SVM model constructed with intratumoral + peritumoral features achieved the highest AUC values in both the train and test set (train set: 0.95 and test set: 0.83). Subtype-specific features improve performance in predicting the efficacy of NAC (luminal group: 0.90; HER2 + group: 0.86; triple negative group: 0.92)., Conclusion: Intratumoral and peritumoral radiomics models based on 18 F-FDG PET/CT can reliably forecast the efficacy of NAC, thereby assisting clinical decision-making., (© 2024. The Author(s).)

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are characterized by excessive triglyceride accumulation in the liver. However, due to an incomplete understanding of its pathogenesis, more efforts are needed to identify specific and effective treatments. N4-acetylcytidine (ac4C) is a newly discovered RNA modification to regulate mRNA. N-acetyltransferase 10 (NAT10) has not been fully explored in MASLD and MASH., Methods: The clinical relevance of NAT10 was evaluated based on its expression in various mouse and human models of MASLD and MASH. Acetylated RNA immunoprecipitation sequencing and mRNA stability assays were used to explore the role of NAT10 in regulating ac4C modification and expression of target genes. Genetically engineered mice were employed to investigate the role of NAT10 in MASLD and MASH progression., Results: Hepatic NAT10 expression was significantly increased in multiple mice and humans of MASLD and MASH. Genetic knockout of NAT10 protected mice from diet-induced hepatic steatosis and steatohepatitis, whereas overexpression of NAT10 exacerbated high-fat-diet-induced liver steatosis. Mechanistically, NAT10 binds to Srebp-1c mRNA, promoting its stability and expression, thereby upregulating lipogenic enzymes. Treatment with Remodelin, a NAT10-specific inhibitor, effectively ameliorates liver steatosis and dyslipidemia in a preclinical mouse model., Conclusions: Our findings indicate that NAT10 could regulate lipid metabolism in MASLD and MASH by stabilizing Srebp-1c mRNA and upregulating lipogenic enzymes. This study highlights the role of NAT10 and RNA acetylation in the pathogenesis of MASLD and MASH. Thus, our findings suggest a promising new therapeutic approach, such as the use of NAT10 inhibitor, for treating metabolic liver disease., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background and Objectives: Despite the fact that the parietal cortex is associated with consciousness, the underlying mechanisms of parietal repetitive transcranial magnetic stimulation (rTMS) have not yet been specifically investigated. The present study aims to examine the effects of parietal rTMS on patients with disorders of consciousness (DoC) and identify a novel potential target., Methods: Twenty minimally conscious state (MCS) patients were stochastically assigned to a real or sham rTMS group in a controlled trial. The real rTMS group was administered over the parietal cortex, with a frequency of 10 Hz and a rest motor threshold of 90 %. The sham rTMS group was identical to the real rTMS group without magnetic stimulation over the cortex. Pre- and post-treatment resting-state electrophysiological (EEG) data and coma recovery scale-revised (CRS-R) score were gathered. Microstate analyses were calculated to evaluate the brain activity dynamics., Results: The real rTMS treatment improved the CRS-R scores. There were notable alterations in the mean microstate duration (MMD) of microstate B in the real rTMS group. The sham rTMS group did not exhibit such changes in CRS-R score or EEG results, which were not statistically significant. Furthermore, the MMD and RTC of microstate E were found to be negatively correlated with baseline CRS-R scores., Conclusion: Parietal rTMS can induce behavioral improvement and brain activity dynamics in patients with MCS. EEG microstates can be used as a valuable method to study neurophysiological mechanisms behind MCS. And the parietal cortex represents an alternative for rTMS therapy protocols., 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: Association between mitochondrial dysfunction and osteoarthritis (OA) has been consistently investigated, yet their genetic association remains obscure. In this study, mitochondrial-related genes were used as instrumental variables to proxy for mitochondrial dysfunction, and summary data of knee OA (KOA) were used as outcome to examine their genetic association., Methods: We obtained 1136 mitochondrial-related genes from the human MitoCarta3.0 database. Genetic proxy instruments for mitochondrial-related genes from studies of corresponding gene expression (n = 31,684) and protein (n = 35,559) quantitative trait locus (eQTLs and pQTLs), respectively. Aggregated data for KOA (62,497 KOA cases and 333,557 controls) were extracted from the largest OA genome-wide association study (GWAS). We integrated QTL data with KOA GWAS data to estimate their genetic association using summary data-based Mendelian randomization analysis (SMR). Additionally, we implemented Bayesian colocalization analysis to reveal whether suggestive mitochondrial-related genes and KOA were driven by a same genetic variant. Finally, to validate the primary findings, replication study (24,955 cases and 378,169 controls) and multi-SNP-based SMR (SMR-multi) test was performed., Results: Through SMR analysis, we found that the expression levels of 2 mitochondrial-related genes were associated with KOA risk. Specifically, elevated gene expression levels of the IMMP2L (odds ratio [OR] = 1.056; 95% confidence interval [CI] = 1.030-1.082; P- FDR  = 0.004) increased the risk of KOA. Conversely, increased gene expression levels of AKAP10 decreased the risk of KOA (OR = 0.955; 95% CI, 0.934-0.977; P- FDR  = 0.019). Colocalization analysis demonstrated that AKAP10 (PP.H4 = 0.84) and IMMP2L (PP.H4 = 0.91) shared the same genetic variant with KOA. In addition, consistent results were found in replication study and SMR-multi test, further demonstrating the reliability of our findings., Conclusions: In summary, our analyses revealed the genetic association between mitochondrial dysfunction proxied by mitochondrial-related genes and KOA, providing new insight into potential pathogenesis of KOA. Furthermore, these identified candidate genes offer the possibility of clinical drug target development for KOA. Key points • This is the first SMR study to explore the genetic association between mitochondrial dysfunction proxied by mitochondrial-related genes and KOA. • Sufficient evidence to support genetic association between the expression levels of AKAP10 and IMMP2L, and KOA • Our MR analysis may provide novel new insight into potential pathogenesis of KOA. • These identified candidate genes offer the possibility of clinical drug target development for KOA., (© 2024. The Author(s).)

The tire antioxidant 6-PPD has been widely used to enhance tire performance and extend tire lifespan. 6-PPD quinone (6-PPDQ), a quinone derivative derived from 6-PPD in the presence of ozone, has been recognized an emerging environmental contaminant. In addition to causing acute lethality to coho salmon, 6-PPDQ exhibits toxic effects on other aquatic species and mammals. Based on the existing evidence, we provide a critical overview on the human internal exposure, potential adverse effects on health, and prediction of human health risk of 6-PPDQ. 6-PPDQ could be detected in human samples, including human urine, blood, and cerebrospinal fluid. Human exposure to 6-PPDQ in the environment is inevitable and may lead to adverse health effects, including hepatotoxicity, enterotoxicity, pulmonary toxicity, neurotoxicity, reproductive toxicity, and cardiotoxicity. Additionally, potential human health risk to 6-PPDQ through exposure routes and human samples were predicted. This review is helpful to identify the existing knowledge gaps and future research directions regarding the human health effects of 6-PPDQ., 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.)

Implant-associated infections (IAIs) are the main cause of prosthetic implant failure. Bacterial biofilms prevent antibiotic penetration, and the unique metabolic conditions in hypoxic biofilm microenvironment may limit the efficacy of conventional antibiotic treatment. Escaping survival bacteria may not be continually eradicated, resulting in the recurrence of IAIs. Herein, a sonosensitive metal-organic framework of Cu-TCPP (tetrakis(4-carboxyphenyl) porphyrin) nanosheets and tinidazole doped probiotic-derived membrane vesicles (OMVs) with high-penetration sonodynamic therapy (SDT), bacterial metabolic state interference, and bacterial cuproptosis-like death to eradicate IAIs is proposed. The Cu-TCPP can convert O 2 to toxic 1 O 2 through SDT in the normoxic conditions, enhancing the hypoxic microenvironment and activating the antibacterial activity of tinidazole. The released Cu(II) under ultrasound can be converted to Cu(I) by exogenous poly(tannic acid) (pTA) and endogenous glutathione. The disruption of the bacterial membrane by SDT can enhance the Cu(I) transporter activity. Transcriptomics indicate that the SDT-enhanced Cu(I) overload and hypoxia-activated therapy hinder the tricarboxylic acid cycle (TCA), leading to bacterial cuproptosis-like death. Moreover, the OMVs-activated therapy can polarize macrophages to a M2-like phenotype and facilitate bone repair. The sonodynamic biofilm microenvironment modulation strategy, whereby the hypoxia-enhanced microenvironment is potentiated to synergize SDT with OMVs-activated therapy, provides an effective strategy for antibacterial and osteogenesis performance., (© 2024 Wiley‐VCH GmbH.)

Probing influence by perioperative nursing mediated by 3D printing and mind mapping in gynecological tumor laparoscopy. 90 subjects divided into three groups: A (n=30), B (n=30) and C (n=30). Each group was given a different type of nursing intervention postoperative recovery (postoperative anal gas exhausting time, eating time, hospital stay, leaving bed-time, and drainage tube extraction time) were compared among the three groups. Hamilton Anxiety Scale (HAMA)/Hamilton Depression Scale (HAMD), strategies Used by People to Promote Health (SUPPH), Generic quality-of-life Inventory (GQOLI-74) scores and complication rates were compared among the three groups. The postoperative recovery of group A and B was better than group C, and group A was better than group B (P<0.05). Post-intervening, HAMA/HAMD scorings within groups A/B reduced compared with group C, with group A＞group B (P<0.05). The complication rate of group A and B was lower than that of group C (P<0.05). Perioperative nursing mediated by 3D printing and mind mapping works well.

Purpose: Envonalkib (TQ-B3139) is a novel, potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor used to treat ALK-positive non-small cell lung cancer. This phase I mass balance study investigated the pharmacokinetics, metabolism, and excretion of 14 C-radiolabeled envonalkib in healthy Chinese male subjects., Methods: A single oral dose of 600 mg (150 µCi) [ 14 C]envonalkib was administered to healthy male subjects under fasted state. Samples of blood, urine and feces were collected for quantitative determination of total radioactivity and unchanged envonalkib, and the metabolites identification., Results: After dosing, the median T max of radioactivity was 4 h and the mean t 1/2 was 65.2 h in plasma. The exposure of total radioactivity was much higher than that of unchanged envonalkib in plasma. The mean total recovery of the radiolabeled dose was 93.93% over 504 h post-dose, with 15.23% in urine and 78.71% in feces. Envonalkib underwent extensive metabolism and a total of 15 metabolites were identified in plasma, urine, and feces. Unchanged envonalkib and its major metabolite M315 were the main components in plasma, accounting for 20.37% and 33.33% of total plasma radioactivity. In urine, O-dealkylation metabolite M315 was the major component accounted for 7.98% of dose. In feces, 16.01% of dose was excreted as cysteine conjugate M434-1. Envonalkib was well tolerated and there were no serious adverse events observed in the study., Conclusion: Envonalkib was extensively metabolized prior to excretion and eliminated primarily as metabolites via feces., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this study, a nanozyme (ZIF-Co-Cys) with high oxidase-like catalytic activity was prepared, and a ratiometric fluorescent/photothermal dual-mode probe was constructed for organophosphorus pesticides (OPs) detection based on the competitive effect of ZIF-Co-Cys and the enzymatic reaction product of acid phosphatase (ACP) on o-phenylenediamine and the inhibition effect of OPs on ACP activity. Using dimethyl dichloroviny phosphate (DDVP) as the model, both the fluorescence intensity ratio and the temperature change of the probe solution exhibited an excellent correlation with OPs concentration. The detection limits were 1.64 ng/mL and 0.084 ng/mL, respectively. Additionally, the detection of DDVP residues in real samples verified the outstanding anti-interference and accuracy of the probe. This work not only provided a complementary dual-mode method for the accurate and rapid detection of OPs residues in complex samples, but also supplied a new insight into the design of a multi-mode sensing platform based on the cascade reaction of nanozyme., 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.)

Multi-view clustering (MVC), which effectively fuses information from multiple views for better performance, has received increasing attention. Most existing MVC methods assume that multi-view data are fully paired, which means that the mappings of all corresponding samples between views are predefined or given in advance. However, the data correspondence is often incomplete in real-world applications due to data corruption or sensor differences, referred to as the data-unpaired problem (DUP) in multi-view literature. Although several attempts have been made to address the DUP issue, they suffer from the following drawbacks: 1) most methods focus on the feature representation while ignoring the structural information of multi-view data, which is essential for clustering tasks; 2) existing methods for partially unpaired problems rely on pregiven cross-view alignment information, resulting in their inability to handle fully unpaired problems; and 3) their inevitable parameters degrade the efficiency and applicability of the models. To tackle these issues, we propose a novel parameter-free graph clustering framework termed unpaired multi-view graph clustering framework with cross-view structure matching (UPMGC-SM). Specifically, unlike the existing methods, UPMGC-SM effectively utilizes the structural information from each view to refine cross-view correspondences. Besides, our UPMGC-SM is a unified framework for both the fully and partially unpaired multi-view graph clustering. Moreover, existing graph clustering methods can adopt our UPMGC-SM to enhance their ability for unpaired scenarios. Extensive experiments demonstrate the effectiveness and generalization of our proposed framework for both paired and unpaired datasets.

Objective: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm., Methods: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models., Results: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort., Conclusions: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice., (© 2024. The Author(s).)

Cooking process for food significantly impacts household air and increases exposure to endocrine disruptors such as acrylamide, consequently affecting human health. In the past 30 years, the transformation of cooking methods to high-temperature thermal processing has occurred widely in China. Yet the transition of cooking methods on the onset of type 2 diabetes (T2D) remains unclear, which may hinder health-based Sustainable Development Goals. We aimed to estimate the associations between dietary intake with different cooking methods and T2D risk. We included 14,745 participants (>20 y) from the China Health and Nutrition Survey (1991-2015). Food consumption was calculated using three consecutive 24-h dietary recalls combined with both individual participant level and household food inventory. Cooking methods, including boiling, steaming, baking, griddling, stir-frying, deep-frying, and raw eating, were also recorded. The consumption of baked/griddled and deep-fried foods was positively associated with 39% and 35% higher of T2D risk by comparing the highest with the lowest category of food consumption, respectively. The use of unhealthy cooking methods for processing foods including baked/griddled and deep-fried foods was attributable for 15 million T2D cases of the total T2D burden in 2011, resulting in a medical cost of $2.7 billion and was expected to be attributable for 39 million T2D cases in 2030, producing a medical cost of $223.8 billion. Replacing one serving of deep-fried foods and baked/griddle foods with boiled/steamed foods was related to 50% and 20% lower risk of T2D, respectively. Our findings recommend healthy driven cooking methods for daily diet for nourishing sustainable T2D prevention in China., 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: Persistent lymphopenia can be regarded as an important index of acquired immune dysfunction in sepsis. Whether the specific immune factor changes in septic patients with lymphopenia and the correlation to gut microbiota and metabolites remain unclear., Methods: This single-center prospective observation conducted lymphocyte subgroup analysis of blood samples and 16S rRNA gene amplicons sequencing and untargeted metabolomics analysis of fecal samples from 36 subjects with the persistent (≥3d) (n=21) and non-persistent lymphopenia (<3d) (n=15)., Results: The persistent lymphopenia showed higher the 28d mortality and 90d mortality, while significantly lower CD3 + T/LY, CD3 + T cells, CD3 + CD4 + T cells, CD3 + CD8 + T cells, Th1 cells, Th2 cells, CD45RA + Treg cells. The 16S rRNA results showed that Staphylococcus, Peptostreptococcus, Bulleidia, Leuconostoc were significant enriched in the persistent lymphopenia. The metabolomics analysis showed that α-Ketoisovaleric acid was increased and 7-DHCA, α-MCA, β-MCA, HCA, LCA-3S, CA, UCA and Citramalic acid were decreased in the persistent lymphopenia., Conclusion: In the process of interaction between host receptors and gut microbiota in patients with persistent lymphopenia sepsis, with a significant reduction in gut microbiota diversity and bile acid metabolites. That can affect various inflammatory pathways of gut immune cells, causing immune dysfunction in the body, which may be one of the main causes of death., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Neonatal septic shock represents a critical and life-threatening condition that necessitates immediate and personalized interventions. Prior research endeavors have been undertaken to inform the optimization of neonatal septic shock management, yet substantial heterogeneity prevails in the selection, measurement, and reporting of outcomes across relevant studies. The heterogeneity in outcome selections and measures impedes the comparability of results and the synthesis of evidence, thus contributing to suboptimal utilization of research findings. This protocol presents the methodology for identifying and developing a Core Outcome Set for Neonatal Septic Shock Management (COS-NSS), intended for use in both research and routine clinical practice. A rigorous four-stage approach will be employed to develop the COS-NSS. In Stage 1, a scoping review will be conducted to compile a list of currently reported outcomes for neonatal septic shock management. Stage 2 will involve an expert stakeholder meeting using a semi-structured discussion approach to elucidate all identified outcomes and outcome domains, as well as to gather any additional outcomes. Moving to Stage 3, a two-round e-Delphi survey involving a wide variety of stakeholders will be undertaken to elicit diverse perspectives on the level of importance assigned to each proposed outcome. Finally, in Stage 4, the results of the Delphi study will be discussed in a consensus meeting to determine and agree on the final list of outcomes that will constitute the COS-NSS., Discussion: The stagewise approach integrates research evidence with multi-stakeholder perspectives to establish standardized outcomes that would improve consistency across neonatal septic shock trials. The development and uptake of the COS-NSS will facilitate effective comparison of studies, allowing for study synthesis and generation of high-quality evidence, thus ultimately fostering enhanced medical care for neonates suffering from septic shock., Trial Registration: Core Outcome Measures in Effectiveness Trials (COMET) Initiative database registration: 2766 . Registered on July 19th, 2023., (© 2024. The Author(s).)

Background: Nudge is an attempt to easily and cheaply influence an individual's health judgments, decisions, or behaviors in nuanced and predictable ways. To date, there are no published reviews of the evidence for or against nudges as health promotion strategies in older adults., Objective: This review aims to summarize what is known about the impact of various nudges that target different kinds of health behavior in older adults., Design: A scoping review., Review Methods: We conducted a comprehensive search across the PubMed, Web of Science, Embase, EBSCOhost, and the Cochrane Library databases from the earliest available date to March 2024. To gain a broad understanding of this field, we used relevant search terms related to 'nudge' and 'older adult'. All articles selected and data extracted were double-checked. Nudges were summarized and analyzed according to Thaler's dual-systems theory taxonomy., Results: Overall, 18 articles were selected. Nudges have been applied to reduce overuse in healthcare (n = 7), enhance vaccination uptake (n = 4), raise dietary intake (n = 3), increase physical activity (n = 1), improve lifestyle management (n = 1), improve hand hygiene (n = 1), and improve terminal treatment (n = 1). Twelve nudges were used to promote health for older adults. Type I nudges included environmental cues, reminders, default options, and feedback. Type II nudges were framing, social norms, social comparison, highlighted suggested choices, pre-commitment, accountability justification, expert authority, and gamification. Most, but not all, nudges have proven to be feasible and effective for health promotion among older adults., Conclusions: This encouraging evidence suggests there is potential for nudges to promote health among older adults. Future research should tailor nudges to individual and cultural characteristics, explore the most effective nudges and long-term effects, expand nudges to more health domains, implement age-friendly digital nudges, and analyze the nursing economics of nudges., Registration: Open Science Framework websites (OSF.IO/PGY25)., 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.)

Janus transition metal dichalcogenides (TMDs) are a novel class of 2D materials with unique mirror asymmetry. Plasma-assisted synthesis at room temperature is favored for producing Janus TMDs due to its energy efficiency and prevention of alloying. However, current methods require stringent control over growth conditions, risking defects or unintended materials. A robust plasma-assisted (RPA) synthesis strategy is introduced, incorporating a built-in tube with a suitable inner diameter into the plasma-assisted system. This innovation creates a mild, uniform plasma atmosphere, allowing for broader variations in growth parameters without significantly affecting Janus MoSSe's morphology and characteristics. This approach simplifies the synthesis process and enhances the success rate of Janus TMD production. Additionally, methods are explored to enhance the photoluminescence (PL) of Janus MoSSe. Releasing MoSSe from the growth substrate and annealing it removes strain and unintentional doping, improving PL performance. MoSSe on hexagonal boron nitride (h-BN) flakes after annealing shows a 32-fold increase in PL intensity. Bis(trifluoromethane) sulfonimide (TFSI) treatment of MoSSe results in a remarkable 70-fold increase in PL intensity, a 2.5-fold extension in exciton lifetime, and quantum yield (QY) reaching up to ≈31.2%. These findings provide critical insights for optimizing the luminescence properties of 2D Janus materials, advancing Janus optoelectronics., (© 2024 Wiley‐VCH GmbH.)

Protein phosphatases Mg 2+ /Mn 2+ dependent (PPMs), serine/threonine phosphatases, are widely distributed in apicomplexan parasites, and Toxoplasma gondii possesses the largest number of PPMs in the apicomplexan parasites. Though the function of some PPMs has been characterized in T. gondii, much less is known about two phosphatase 2C domain-containing proteins, PPM2A and PPM2B. PPM2A was identified as one of Toxoplasma Calmodulin's interacting proteins through proximity-based protein interaction BioID technology in the previous study, and PPM2B was the homolog of PPM2A in T. gondii. In this study, PPM2A was distributed in the whole tachyzoite of T. gondii, and PPM2B was mainly distributed in the cytoplasm by inserting a 10HA tag in the C-terminus of the two genes in the RH∆ku80 strain. PPM2A knockout (Δppm2a), PPM2B knockout (Δppm2b), and double knockout (ΔΔ) in RHΔhxgprt type I strain under CRISPR-Cas9 system did not result in intracellular replication defect. Besides, mouse experiments demonstrated that PPM2A, PPM2B, and double knockout did not reduce the pathogenicity of T. gondii compared with the RH∆hxgprt strain. However, the plaque size of these single knockout and double knockout strains were smaller than that in the control RH∆hxgprt strain. Our results provide new insight into the function of PPMs in the pathogenesis of T. gondii., 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. Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organization that can inappropriately influence our work. Besides, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be constructed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024. Published by Elsevier B.V.)

Automated polyp segmentation from colonoscopy images is crucial for colorectal cancer diagnosis. The accuracy of such segmentation, however, is challenged by two main factors. First, the variability in polyps' size, shape, and color, coupled with the scarcity of well-annotated data due to the need for specialized manual annotation, hampers the efficacy of existing deep learning methods. Second, concealed polyps often blend with adjacent intestinal tissues, leading to poor contrast that challenges segmentation models. Recently, diffusion models have been explored and adapted for polyp segmentation tasks. However, the significant domain gap between RGB-colonoscopy images and grayscale segmentation masks, along with the low efficiency of the diffusion generation process, hinders the practical implementation of these models. To mitigate these challenges, we introduce the Highlighted Diffusion Model Plus (HDM+), a two-stage polyp segmentation framework. This framework incorporates the Highlighted Diffusion Model (HDM) to provide explicit semantic guidance, thereby enhancing segmentation accuracy. In the initial stage, the HDM is trained using highlighted ground-truth data, which emphasizes polyp regions while suppressing the background in the images. This approach reduces the domain gap by focusing on the image itself rather than on the segmentation mask. In the subsequent second stage, we employ the highlighted features from the trained HDM's U-Net model as plug-in priors for polyp segmentation, rather than generating highlighted images, thereby increasing efficiency. Extensive experiments conducted on six polyp segmentation benchmarks demonstrate the effectiveness of our approach.

Epigallocatechin gallate (EGCG) has demonstrated potential effects on obesity-induced precocious puberty, but the underlying mechanisms remain unclear. Female mice were randomly assigned into control (CON), EGCG-treated (EGCG), high-fat diet (HFD), and HFD with EGCG treatment (HFDEGCG) groups. Key measurements included body weight, vaginal opening time, and serum sex hormone levels. The gut microbiota was analyzed through 16S rRNA sequencing, fecal metabolites were assessed via metabolomics, and the hypothalamic transcriptome was examined using RNA sequencing. EGCG mitigated weight gain and delayed vaginal opening in mice with obesity-induced precocious puberty. Additionally, it reduced serum estradiol levels and decreased the number of mature ovarian follicles in the HFDEGCG group compared to the HFD group. EGCG treatment partially reversed HFD-induced dysbiosis by increasing the abundance of beneficial bacteria such as Akkermansia . Metabolomic analysis revealed significant alterations in tryptophan metabolism, while transcriptome analysis identified genes involved in metabolic pathways. Correlation analyses underscored the importance of the gut-brain axis in mediating EGCG's effects. Overall, EGCG prevents obesity-induced precocious puberty by modulating the gut microbiota, altering metabolic pathways, and regulating hypothalamic gene expression.

Background: There is a growing interest in utilizing a combination of brain radiotherapy (RT) and tyrosine kinase inhibitors (TKIs) for patients diagnosed with brain metastases (BM) in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LAC). The current status of this treatment strategy remains a subject of debate., Methods: We initiated our study by conducting a comprehensive literature search using the SCI-expanded database of Web of Science Core Collection (WoSCC). We utilized the VOSPviewer software to analyze various aspects of the research, including the year of publication, authorship, keywords, and country.Subsequently, we performed an extensive and systematic literature search on popular online databases. Our primary outcome measures were overall survival (OS) and intracranial progression-free survival (iPFS), both quantified by hazard ratios (HRs). Additionally, for data verification, we included data from patients in non-small cell lung cancer with brain metastasis who underwent therapeutic intervention at the Cancer Prevention and Treatment Center of Sun Yat-sen University and the Radiotherapy Department of Hanzhong Central Hospital between August 2012 and November 2021., Results: The bibliometric analysis revealed an increasing trend in research focused on the combination of RT and TKIs for the management of lung cancer brain metastases over the previous decade. Then, nine studies consistent with the research direction were included for meta-analysis. The meta-analysis showed that the OS (HR = 0.81, 95% confidence interval: 0.69-0.94; P = 0.007) and iPFS (HR = 0.71, 95% confidence interval: 0.61-0.82; P < 0.001) of the combination therapy were significantly prolonged. Finally, 168 EGFR-mutated BM advanced LAC patients in the real world were verified, and the median iPFS of the combination therapy (n = 88 and EGFR-TKIs alone (n = 80) were 16.0 and 9.0 months, respectively, (P < 0.001). The median OS was 29.0 and 27.0 months, respectively, with no dramatic difference (P = 0.188)., Conclusions: Research on EGFR-mutant LAC brain metastasis has turned towards exploring optimal treatment strategies for this condition. Our meta-analysis and real-world data analysis consistently demonstrate that combination therapy offers a substantial improvement in patient survival compared to EGFR-TKI monotherapy. Notably, among patients undergoing salvage radiotherapy (RT), our subgroup analysis reveals that those initially treated with third-generation TKIs experience more significant benefits than those treated with first- or second-generation TKIs., (© 2024. The Author(s).)

Background: Remote programming enables physicians to adjust implantable pulse generators over the internet for patients with Parkinson disease who have undergone deep brain stimulation (DBS) surgery. Despite these technological advances, the demand for and attitudes toward remote programming compared with standard programming among patients with Parkinson disease are still not well understood., Objective: This study aims to investigate the preferences and perceptions associated with these 2 programming methods among patients with Parkinson disease through a web-based survey., Methods: A web-based survey was administered to 463 patients with Parkinson disease who have undergone DBS surgery. The survey aimed to assess the burdens associated with postoperative programming and to compare patients' attitudes toward the 2 different programming methods., Results: A total of 225 patients completed the survey, all of whom had undergone standard programming, while 132 patients had also experienced remote programming. Among those who received standard programming, 191 (85%) patients required the support of more than 1 caregiver, 129 (58%) patients experienced over 2 days of lost work time, 98 (42%) patients incurred expenses ranging from US $42 to US $146, and 14 (6%) patients spent over US $421. Of the 132 patients who had used remote programming, 81 (62%) patients indicated a preference for remote programming in the future. However, challenges with remote programming persisted, including difficulties in obtaining official prescriptions, a lack of medical insurance coverage, and limited medical resources., Conclusions: Postoperative programming of DBS imposes significant burdens on patients and their caregivers during standard programming sessions-burdens that could be mitigated through remote programming. While patient satisfaction with remote programming is high, it is imperative for clinicians to develop personalized programming strategies tailored to the needs of different patients., (© Xiaonan Wan, Zhengyu Lin, Chengcheng Duan, Zhitong Zeng, Chencheng Zhang, Dianyou Li. Originally published in JMIR Aging (https://aging.jmir.org).)

Background: The role of plant-based dietary patterns in preventing cardiovascular disease (CVD) among individuals with prediabetes and diabetes remains unclear. We aimed to evaluate the associations of plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) with cardiovascular disease (CVD) risk and explore potential contributing factors among people with prediabetes and diabetes., Methods: A total of 17,926 participants with prediabetes and 7798 with diabetes were enrolled from the UK Biobank between 2006 and 2010 and followed until the end of 2020. We calculated the PDI, hPDI, and uPDI based on 18 major food groups including plant-based foods and animal-based foods and applied Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD risk related to PDI, hPDI, and uPDI. Decomposition analysis was performed to assess the role of dietary components, and mediation analysis was performed to assess the potential mediating role of serum biomarkers underlying these associations., Results: A total of 2324 CVD events were documented among individuals with prediabetes, while 1461 events occurred among patients with diabetes. An inverse association was found between hPDI and CVD risk among individuals with prediabetes (HR T3 vs. T1 = 0.88, 95% CI = 0.79-0.98, P trend  = 0.025) but not those with diabetes. A positive association was found between uPDI and CVD risk among individuals with prediabetes (HR T3 vs. T1 = 1.17, 95% CI = 1.05-1.30, P trend  = 0.005) and those with diabetes (HR T3 vs. T1 = 1.14, 95% CI = 1.00-1.29, P trend  = 0.043). High-sugar-sweetened beverages (SSB) intake accounted for 35% of the hPDI-CVD association and 15% of the uPDI-CVD association among individuals with prediabetes, whereas low intake of whole grain accounted for 36% of the association among patients with diabetes. Elevated cystatin C levels explained the largest proportion of the association between uPDI and CVD risk among individuals with prediabetes (15%, 95% CI = 7-30%) and diabetes (44%, 95% CI = 9-86%)., Conclusions: Adherence to an unhealthy plant-based diet is associated with a higher CVD risk in people with prediabetes or diabetes, which may be partially attributed to low consumption of whole grains, high intake of SSB, and high blood cystatin C levels., (© 2024. The Author(s).)

Rationale: Previous research has demonstrated the applicability of Google Trends in predicting infectious diseases., Aims and Objectives: This study aimed to analyze public interest in other infectious diseases before and after the outbreak of COVID-19 via Google Trends data and to predict these trends via time series models., Method: Google Trends data for 12 common infectious diseases were obtained in this study, covering the period from 1 February 2018 to 5 May 2023. The ARIMA, TimeGPT, XGBoost, and LSTM algorithms were then utilized to establish time series prediction models., Results: Our study revealed a significant decrease in public interest in most infectious diseases at the beginning of the pandemic outbreak, followed by a rebound in the post-pandemic era, which is consistent with reported disease incidences. Furthermore, our prediction models demonstrated good accuracy, with TimeGPT showing unique advantages., Conclusions: Our study highlights the potential application value of Google Trends and large pre-trained models for infectious disease prediction., (© 2024 John Wiley & Sons Ltd.)

Background: Recurrent preimplantation embryo developmental arrest (RPEA) is the most common phenotype in assisted reproductive technology treatment failure associated with identified genetic abnormalities. Currently known maternal genetic variants explain only a limited number of cases. Variants of the β-tubulin subunit gene, TUBB8 , cause oocyte meiotic arrest and RPEA through a broad spectrum of spindle defects. In contrast, α-tubulin subunit genes are poorly studied in the context of preimplantation embryonic development., Methods: Whole exome sequencing was performed on the PREA cohort. Functional characterisations of the identified candidate disease-causing variants were validated using Sanger sequencing, bioinformatics, in vitro functional analyses and single-cell RNA-sequencing of arrested embryos., Results: Four homozygous variants were identified in the PREA cohort: two of TUBA1C (p.Gln358Ter and p.Asp444Metfs*42) and two of TUBA4A (p.Arg339Cys and p.Tyr440Ter). These variants cause varying degrees of spindle assembly defects. Additionally, we characterised changes in the human arrested embryo transcriptome carrying TUBA4A variants, with a particular focus on spindle organisation, chromosome segregation and mRNA decay., Conclusion: Our findings identified TUBA1C as a novel genetic marker and expanded the genetic and phenotypic spectrum of TUBA4A in female infertility and RPEA, which altogether highlighted the importance of α-tubulin isotypes in preimplantation embryonic development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fungi are prevalent pathogens that cause substantial yield losses of major crops. Ear rot (ER), which is primarily induced by Fusarium or Aspergillus species, poses a significant challenge to maize production worldwide. ER resistance is regulated by several small effect quantitative trait loci (QTLs). To date, only a few ER-related genes have been identified that impede molecular breeding efforts to breed ER-resistant maize varieties., Aim of Review: Our aim here is to explore the research progress and mine genic resources related to ER resistance, and to propose a regulatory model elucidating the ER-resistant mechanism in maize as well as a trade-off model illustrating how crops balance fungal resistance and grain yield. Key Scientific Concepts of Review: This review presents a comprehensive bibliometric analysis of the research history and current trends in the genetic and molecular regulation underlying ER resistance in maize. Moreover, we analyzed and discovered the genic resources by identifying 162 environmentally stable loci (ESLs) from various independent forward genetics studies as well as 1391 conservatively differentially expressed genes (DEGs) that respond to Fusarium or Aspergillus infection through multi-omics data analysis. Additionally, this review discusses the syntenies found among maize ER, wheat Fusariumhead blight (FHB), and rice Bakanaedisease (RBD) resistance-related loci, along with the significant overlap between fungal resistance loci and reported yield-related loci, thus providing valuable insights into the regulatory mechanisms underlying the trade-offs between yield and defense in crops., 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. Production and hosting by Elsevier B.V.)

The toxic effects of potentially toxic elements have been observed at low concentrations; however, many studies have focused on single-species toxicity testing. Consequently, it is imperative to quantify toxicity at the community level at environmental concentrations. A microcosm approach was employed in conjunction with the Lotka-Volterra model to ascertain the impact of environmentally relevant concentrations of cadmium (Cd) on plankton abundance, community function, and stability. The results demonstrated that Cd led to a reduction in the abundance of Daphnia magna, yet unexpectedly resulted in an increase in the abundance of Brachionus calyciflorus and Paramecium caudatum. Additionally, Cd was observed to impede primary productivity, metabolic capacity and the stability of the planktonic community. Further model analyses revealed that the environmental concentration of Cd directly reduced intrinsic growth rates and intraspecific interactions. In particular, we found that the predation effects of Daphnia magna on Brachionus calyciflorus were significantly weakened. The findings of this study offer quantitative evidence that Cd exposure exerts an indirect influence on the structure and functioning of plankton ecosystems, mediated by alterations in trophic interactions. The findings indicate that the impact of environmental concentrations of potentially toxic elements may be underestimated in single-species experiments., 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.)

M-N-C catalysts with nitrogen-coordinated metal single-atom active sites have demonstrated high activity for hydrogen storage materials, but their stability in this application remains uncertain. This study addresses this issue by using nickel phthalocyanine (NiPc) molecules on MgH₂ particles as a model system. It is found that the N-coordinated high-valence Ni single atoms in the NiN₄ active site are unstable in the reducing environment of hydrogen storage, spontaneously evolving into zero-valence Ni, forming a Ni₁-Mg single-atom alloy (SAA). The Ni₁-Mg SAA exhibits remarkable stability in catalyzing Mg hydrogen storage reactions. Furthermore, it demonstrates comprehensive catalytic activity for each step of hydrogen absorption and desorption from Mg, surpassing the efficiency of the NiN₄ active site, especially in the critical steps of hydrogenation and dehydrogenation. Overall, the catalytic performance of Ni₁-Mg SAA is superior to most known nickel-based catalysts. This evolutionary process is also observed in FePc, CoPc, and tetraphenylporphyrin nickel (Ni-TPP), suggesting that this reducing transformation is a universal phenomenon for MN₄-type active sites in hydrogen storage catalysis., (© 2024 Wiley‐VCH GmbH.)

The EFA6 protein family, originally identified as Sec7 guanine nucleotide exchange factors, has also been found to regulate cortical microtubule (MT) dynamics. Here, we find that in the mature C. elegans epidermal epithelium, EFA-6 forms punctate foci in specific regions of the apical cortex, dependent on its intrinsically disordered region (IDR). The EFA-6 IDR can form biomolecular condensates in vitro. In genetic screens for mutants with altered GFP::EFA-6 localization, we identified a gain-of-function (gf) mutation in α-tubulin tba-1 that induces ectopic EFA-6 foci in multiple cell types. Lethality of tba-1(gf) is partially suppressed by loss of function in efa-6. The ability of TBA-1(gf) to trigger ectopic EFA-6 foci requires β-tubulin TBB-2 and the chaperon EVL-20/Arl2. tba-1(gf)-induced EFA-6 foci display slower turnover, contain the MT-associated protein TAC-1/TACC, and require the EFA-6 MT elimination domain (MTED). Our results reveal functionally important crosstalk between cellular tubulins and cortical MT regulators in vivo., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Between 2013 and 2018, the novel A/Anhui/1/2013 (AH/13)-lineage H7N9 virus caused at least five waves of outbreaks in humans, totaling 1,567 confirmed human cases in China. Surveillance data indicated a disproportionate distribution of poultry infected with this AH/13-lineage virus, and laboratory experiments demonstrated that this virus can efficiently spread among chickens but not among Pekin ducks. The underlying mechanism of this selective transmission remains unclear. In this study, we demonstrated the absence of Neu5Gc expression in chickens across all respiratory and gastrointestinal tissues. However, Neu5Gc expression varied among different duck species and even within the tissues of the same species. The AH/13-lineage viruses exclusively bind to acetylneuraminic acid (Neu5Ac), in contrast to wild waterbird H7 viruses that bind both Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). The level of Neu5Gc expression influences H7 virus replication and facilitates adaptive mutations in these viruses. In summary, our findings highlight the critical role of Neu5Gc in affecting the host range and interspecies transmission dynamics of H7 viruses among avian species.IMPORTANCEMigratory waterfowl, gulls, and shorebirds are natural reservoirs for influenza A viruses (IAVs) that can occasionally spill over to domestic poultry, and ultimately humans. This study showed wild-type H7 IAVs from waterbirds initially bind to glycan receptors terminated with N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc). However, after enzootic transmission in chickens, the viruses exclusively bind to Neu5Ac. The absence of Neu5Gc expression in gallinaceous poultry, particularly chickens, exerts selective pressure, shaping IAV populations, and promoting the acquisition of adaptive amino acid substitutions in the hemagglutinin protein. This results in the loss of Neu5Gc binding and an increase in virus transmissibility in gallinaceous poultry, particularly chickens. Consequently, the transmission capability of these poultry-adapted H7 IAVs in wild water birds decreases. Timely intervention, such as stamping out, may help reduce virus adaptation to domestic chicken populations and lower the risk of enzootic outbreaks, including those caused by IAVs exhibiting high pathogenicity., Competing Interests: The authors declare no conflict of interest.

Substituted p-phenylenediamines (PPDs), a class of antioxidants, have been widely used to extend the lifespan of rubber products, such as tires and pipes. During use, PPDs will generate their quinone derivatives (PPD-Qs). In recent years, PPDs and PPD-Qs have been detected in the global environment. Among them, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q), the oxidation product of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), has been identified as highly toxic to coho salmon, with the lethal concentration of 50 % (LC50) being 95 ng/L, highlighting it as an emerging pollutant of great concern. This review summarizes the physicochemical properties, global environmental distribution, bioaccessibility, potential toxicity, human exposure risk, and green measures of PPDs and PPD-Qs. These chemicals exhibit lipophilicity, bioaccumulation potential, and poor aqueous stability. They have been found in water, air, dust, soil, and sediment worldwide, indicating their significance as emerging pollutants. Notably, current studies have identified electronic waste (e-waste), such as discarded wires and cables, as a non-negligible source of PPDs and PPD-Qs, in addition to tire wear. PPDs and PPD-Qs exhibit strong bioaccumulation in aquatic organisms and mammals, with a tendency for biomagnification within the food web, posing health threats to humans. Available toxicity data indicate that PPDs and PPD-Qs have negative effects on aquatic organisms, mammals, and invertebrates. Acute exposure leads to death and acute damage, and long-term exposure can cause a series of adverse effects, including growth and development toxicity, reproductive toxicity, neurotoxicity, intestinal toxicity, and multi-organ damage. This paper discusses current research gaps and offers recommendations to understand better the occurrence, behavior, toxicity, and environmental exposure risks of PPDs and PPD-Qs., 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.)