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Background: Currently, there is a lack of global or even country/regional level data on adolescent non-alcoholic fatty liver disease (NAFLD) prevalence. However, an evidenced dose-dependent relationship exists between body mass index (BMI) and the risk of NAFLD. We aim to estimate the global and regional prevalence of adolescent NAFLD and related non-alcoholic steatohepatitis (NASH) based on BMI., Methods: Sigmoidal fitting curves were generated between BMI and the risk of NAFLD/NASH using the data extracted from the NHANES database. With global and regional BMI data from the NCD-RisC database, adolescent NAFLD/NASH prevalence was estimated at the international, regional, and country levels from 1975 to 2016. The prevalence of adolescent NAFLD/NASH from 2017 to 2030 was also forecasted., Results: The mean NAFLD prevalence was 15.31, and 12.68%, while the mean NASH prevalence was 2.50, and 2.47%, in boys, and girls aged 12-18, respectively. For both boys and girls, NAFLD/NASH prevalence increased with increasing BMI, and age. The global prevalence of adolescent NAFLD/NASH has gradually increased in the period from 1975 to 2016 and will maintain a similar trend between 2017 and 2030. High-income Western Countries had higher adolescent NAFLD/NASH whereas South Asia and Sub-Saharan Africa exhibited relatively lower adolescent NAFLD/NASH prevalence. The estimated annual percentage change (EAPC) of NAFLD prevalence in boys ranged from 0.72% (age 18) to 1.16% (age 12) while that in girls ranged from 0.69% (age 18) to 0.92% (age 12). EAPC of NASH prevalence in boys ranged from 1.65% (age 18) to 1.77% (age 12), and in girls from 1.48% (age 18) to 1.68% (age 12)., Conclusion: The adolescent NAFLD/NASH prevalence increases year by year, and its burden varies significantly among different countries and regions. BMI is a precise predictor of NAFLD/NASH prevalence., 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 Lin, Li, Huang, Lin, Hong, Weng and Pan.)

Background: Dental informatics is an emerging discipline. Although the accreditation agency governing dental education programs asserts the importance of informatics as foundational knowledge, no well-defined dental informatics courses currently exist within the standard predoctoral dental curriculum. There is a nationwide lack of dental informatics academic programs. This training gap is due to a lack of qualified dental informaticians to impart knowledge on dental informatics., Objectives: This paper aims to introduce a novel conceptual framework for an interdisciplinary dental informatics program in preparing students to become dental informaticians., Methods: In 2023, we developed a standalone graduate certificate program in dental informatics at Indiana University (IU) School of Dentistry in collaboration with IU Luddy School of Informatics, Computing, and Engineering and IU Fairbanks School of Public Health. Feedback was collected through online surveys to assess course quality from students who took Introduction to Health Information in Dentistry. Feedback was analyzed qualitatively, utilizing a thematic analysis approach. Common responses relevant to dental informatics education were grouped into themes., Results: Five major themes emerged during our analysis of the students' feedback: foundational knowledge and skills; experiential learning: learning by doing; access to resources and working on clinical information systems; health promotion through team-based learning; and retention of knowledge assessment and application. A conceptual framework was formulated through these themes as a guideline for future program improvement. This interdisciplinary educational program framework showed how students and faculty from various disciplines could collaborate, learn from each other, and bring in expertise from different domains. The collaboration happens in clinical, laboratory, and virtual settings to acquire hands on learning through practice and research projects., Conclusions: The developed conceptual framework aligned with the interdisciplinary nature of dental informatics. It can potentially be adopted by other interdisciplinary informatics programs in health and non-health care disciplines., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Enhancing the electrochemiluminescence (ECL) properties of polycyclic aromatic hydrocarbons (PAHs) is a significant topic in the ECL field. Herein, we elaborately chose PAH derivative luminophore 1,3,6,8-tetrakis( p -benzoic acid)pyrene (H 4 TBAPy) as the organic ligand to synthesize a new Ru-complex-free ECL-active metal-organic framework Dy-TBAPy. Interestingly, Dy-TBAPy exhibited a more brilliant ECL emission and higher ECL efficiency than H 4 TBAPy aggregates. On the one hand, TBAPy luminophores were assembled into rigid MOF skeleton via coordination bonds, which not only enlarged the distance between pyrene cores to eliminate the aggregation-caused quenching (ACQ) effect but also obstructed the intramolecular motions of TBAPy to diminish the nonradiative relaxation, thus realizing a remarkable coordination-enhanced ECL. On the other hand, the ultrahigh porosity of Dy-TBAPy was beneficial to the diffusion of electrons, ions, and coreactant (S 2 O 8 2- ) in the skeleton, which efficiently boosted the excitation of interior TBAPy luminophores and led to a high utilization ratio of TBAPy, further improving ECL properties. More intriguingly, the ECL intensity of the Dy-TBAPy/S 2 O 8 2- system was about 4.1, 87.0-fold higher than those of classic Ru(bpy) 3 2+ /TPrA and Ru(bpy) 3 2+ /S 2 O 8 2- systems. Considering the aforementioned fabulous ECL performance, Dy-TBAPy was used as an ECL probe to construct a supersensitive ECL biosensor for microRNA-21 detection, which showed an ultralow detection limit of 7.55 aM. Overall, our study manifests that coordinatively assembling PAHs into MOFs is a simple and practicable way to improve ECL properties, which solves the ACQ issue of PAHs and proposes new ideas for developing highly efficient Ru-complex-free ECL materials, therefore providing promising opportunities to fabricate high-sensitivity ECL biosensors.

Motivation: Exploring the association between drugs and targets is essential for drug discovery and repurposing. Comparing with the traditional methods that regard the exploration as a binary classification task, predicting the drug-target binding affinity can provide more specific information. Many studies work based on the assumption that similar drugs may interact with the same target. These methods constructed a symmetric graph according to the undirected drug similarity or target similarity. Although these similarities can measure the difference between two molecules, it is unable to analyze the inclusion relationship of their substructure. For example, if drug A contains all the substructures of drug B, then in the message-passing mechanism of the graph neural network, drug A should acquire all the properties of drug B, while drug B should only obtain some of the properties of A., Results: To this end, we proposed a structure-inclusive similarity (SIS) which measures the similarity of two drugs by considering the inclusion relationship of their substructures. Based on SIS, we constructed a drug graph and a target graph, respectively, and predicted the binding affinities between drugs and targets by a graph convolutional network-based model. Experimental results show that considering the inclusion relationship of the substructure of two molecules can effectively improve the accuracy of the prediction model. The performance of our SIS-based prediction method outperforms several state-of-the-art methods for drug-target binding affinity prediction. The case studies demonstrate that our model is a practical tool to predict the binding affinity between drugs and targets., Availability and Implementation: Source codes and data are available at https://github.com/HuangStomach/SISDTA., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Huntington's disease (HD) is a hereditary neurodegenerative disorder that primarily affects the striatum, a brain region responsible for movement control. The disease is characterized by the mutant huntingtin (mHtt) proteins with an extended polyQ stretch, which are prone to aggregation. These mHtt aggregates accumulate in neurons and are the primary cause of the neuropathology associated with HD. To date, no effective cure for HD has been developed., Methods: The immortalized ST Hdh Q111/Q111 striatal cell line, the mHtt-transfected wild-type ST Hdh Q7/Q7 striatal cell line, and N2a cells were used as Huntington's disease cell models. Flow cytometry was used to assess cellular reactive oxygen species and transfection efficiency. The CCK-8 assay was used to measure cell viability, while fluorescence microscopy was used to quantify aggregates. Immunoblotting analyses were used to evaluate the effects on protein expression., Results: Polyphenols are natural antioxidants that offer neuroprotection in neurological disorders. In this study, we provide evidence that oleuropein, the primary polyphenol in olive leaves and olive oil, enhances cell viability in HD cell models, including. ST Hdh Q7/Q7 ST Hdh Q7/Q7 striatal cells, N2a cells ectopically expressing the truncated mHtt, and ST Hdh Q111/Q111 striatal cells expressing the full-length mHtt. Oleuropein effectively reduced both soluble and aggregated forms of mHtt protein in these HD model cells. Notably, the reduction of mHtt aggregates associated with oleuropein was linked to increased proteasome activity rather than changes in autophagic flux. Oleuropein seems to modulate proteasome activity through an unidentified pathway, as it did not affect the 20S proteasome catalytic β subunits, the proteasome regulator PA28γ, or multiple MAPK pathways., Discussion: We demonstrated that oleuropein enhances the degradation of mHtt by increasing proteasomal protease activities and alleviates mHtt-induced cytotoxicity. Hence, we propose that oleuropein and potentially other polyphenols hold promise as a candidate for alleviating Huntington's disease., 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 Huang, Lee, Chen, Huang and Her.)

Immune checkpoint inhibitors (ICIs) activate anti-cancer immunity by blocking T cell checkpoint molecules such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Although ICIs induce some durable responses in various cancer patients, they also have disadvantages, including low response rates, the potential for severe side effects, and high treatment costs. Therefore, selection of patients who can benefit from ICI treatment is critical, and identification of biomarkers is essential to improve the efficiency of ICIs. In this review, we provide updated information on established predictive biomarkers (tumor programmed death-ligand 1 [PD-L1] expression, DNA mismatch repair deficiency, microsatellite instability high, and tumor mutational burden) and potential biomarkers currently under investigation such as tumor-infiltrated and peripheral lymphocytes, gut microbiome, and signaling pathways related to DNA damage and antigen presentation. In particular, this review aims to summarize the current knowledge of biomarkers, discuss issues, and further explore future biomarkers., Competing Interests: Declaration of interests M.-C.H. is a co-inventor on the methodology for de-glycosylation staining., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: At present, there is a dearth of comprehensive data at the global, national, and regional levels regarding the adult non-alcoholic fatty liver disease (NAFLD) prevalence. This cross-sectional study aims at ascertaining the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH), utilizing body mass index (BMI) as a determining factor., Methods: Based on the NHANES database, sigmoidal fitting curves were generated to establish the relationship between BMI and the risk of NAFLD/NASH. Utilizing BMI data from the NCD Risk Factor Collaboration (NCD-RisC) database at both global and regional levels, the prevalence of NAFLD/NASH among adults was estimated from 1975 to 2016, encompassing global, regional, and national perspectives. Additionally, projections were made to forecast the prevalence of adult NAFLD/NASH from 2017 to 2030., Results: In 2016, the global prevalence of NAFLD was 41.12% for males and 37.32% for females, while the global prevalence of NASH was 15.79% for males and 16.48% for females. The prevalence of NAFLD/NASH increased with higher BMI in both genders. Over the period from 1975 to 2016, there has been a gradual increase in the global prevalence of NAFLD/NASH in adults, and this trend is expected to continue between 2017 and 2030. In males, the prevalence of adult NAFLD/NASH was found to be highest in High-income Western countries, while it was highest in Central Asia, Middle East, and North African countries after 1995., Conclusions: The prevalence of adult NAFLD/NASH has been observed to increase annually, with significant variations in burden across different countries and regions., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-118/coif). M.Z.H. reports the funding from the Natural Science Foundation of Fujian Province of China (No. 2020J011218). J.S.P. reports the funding from the National Natural Science Foundation of China (No. 82372318), Natural Science Foundation of Fujian Province of China (No. 2022J02030), and Major Research Project for Young and Middle-aged People of the Health Commission of Fujian Province (No. 2022ZQNZD004). The other authors have no conflicts of interest to declare., (2024 Translational Gastroenterology and Hepatology. All rights reserved.)

Two new triarylamine-based diamine monomers, namely, N , N '-bis(4-methoxyphenyl)- N , N '-bis(4-(4-aminophenyl-4'-methoxyphenylamino)phenyl)- p -phenylenediamine ( 3 ) and N , N '-bis(4-methoxyphenyl)- N , N '-bis(4-((4-aminophenyl-1-naphthyl)amino)phenyl)- p -phenylenediamine ( 7 ), were successfully synthesized and led to two series of electroactive polyamides by polycondensation reactions with common aromatic dicarboxylic acids. The polymers demonstrated multicolored electrochromism, high optical contrast, and remarkable enhancements in redox and electrochromic stability. Compared to other triarylamine-based polymers, the studied polyamides exhibited enhanced electrochromic stability (only 3~6% decay of its coloration efficiency at 445 nm after 14,000 switching cycles) at the first oxidation stage. The polyamides also showed strong absorption in the near-infrared region upon oxidation. Polymers with multicolored electrochromism and high redox stability can be developed by incorporation of four triarylamine cores in each repeat unit and electron-donating methoxy groups on the active sites of the triphenylamine units.

Photocatalytic reduction of CO 2 is a promising strategy to mitigate the effects of global warming by converting CO 2 into valuable energy-dense products. Silver bismuth iodide (SBI) is an attractive material owing to its tunable bandgap and favorable band-edge positions for efficient CO 2 photoreduction. In this study, SBI materials, including AgBi 2 I 7 , AgBiI 4 , Ag 2 BiI 5 , and Ag 3 BiI 6 are first synthesized, through gas-solid reaction by controlling the stoichiometric ratio of reactants. The X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) results revealed that the distance between Ag-I is proportional to the degree of Ag ions delocalization, which occupies the vacant sites. That greatly retards the charge recombination at vacant sites. In addition, the surface potential via photo-assisted Kelvin probe force measurements of various SBI catalysts shows that Ag 3 BiI 6 exhibits the highest surface potential change due to the rich delocalized Ag ions. This results in effective charge carrier transport and prevention of charge recombination at vacant sites. Taking the above advantages, the averaged CO and CH 4 production rates for Ag 3 BiI 6 achieved 0.23 and 0.10 µmol g -1  h -1 , respectively. The findings suggest that Ag 3 BiI 6 has a high potential as a novel photocatalyst for CO 2 reduction and sheds light on the possibility of solving environmental contamination and sustainable energy crises., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Magnesium is one of the essential nutrients for plant growth, and plays a pivotal role in plant development and metabolism. Soil magnesium deficiency is evident in citrus production, which ultimately leads to failure of normal plant growth and development, as well as decreased productivity. Citrus is mainly propagated by grafting, so it is necessary to fully understand the different regulatory mechanisms of rootstock and scion response to magnesium deficiency. Here, we characterized the differences in morphological alterations, physiological metabolism and differential gene expression between trifoliate orange rootstocks and lemon scions under normal and magnesium-deficient conditions, revealing the different responses of rootstocks and scions to magnesium deficiency. The transcriptomic data showed that differentially expressed genes were enriched in 14 and 4 metabolic pathways in leaves and roots, respectively, after magnesium deficiency treatment. And the magnesium transport-related genes MHX and MRS2 may respond to magnesium deficiency stress. In addition, magnesium deficiency may affect plant growth by affecting POD, SOD, and CAT enzyme activity, as well as altering the levels of hormones such as IAA, ABA, GA 3 , JA, and SA, and the expression of related responsive genes. In conclusion, our research suggests that the leaves of lemon grafted onto trifoliate orange were more significantly affected than the roots under magnesium-deficient conditions, further indicating that the metabolic imbalance of scion lemon leaves was more severe., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Glioblastoma (GBM) is notorious for the aggressive behaviors and easily results in chemo-resistance. Studies have shown that the use of herbal medicines as treatments for GBM as limited by the blood-brain barrier (BBB) and glioma stem cells., Purpose: The aim of this study was to investigate the relationship between GBM suppression and α-terpineol, the monoterpenoid alcohol derived from Eucalyptus glubulus and Pinus merkusii., Study Design: Using serial in-vitro and in-vivo studies to confirm the mechanism of α-terpineol on down-regulating GBM development., Methods: The 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate IC50 of α-terpineol to inhibit GBM cell survival. In order to evaluate the impact of GBM aggressive behaviors by α-terpineol, the analysis of cell migration, invasion and colony formation were implemented. In addition, the ability of tumor spheres and WB of CD44 and OCT3/4 were evaluated under the impression of α-terpineol decreased GBM stemness. The regulation of neoangiogenesis by α-terpineol via the WB of angiogenic factors and human umbilical vein endothelial cells (HUVEC) tube assay. To survey the decided factors of α-terpineol downregulating GBM chemoresistance depended on the impact of O6-methylguanine-DNA methyltransferase (MGMT) expression and autophagy-related factors activation. Additionally, WB and quantitative real-time polymerase chain reaction (qRT/PCR) of KDEL (Lys-Asp-Glu-Leu) containing 2 (KDELC2), endoplasmic reticulum (ER) stress, phosphoinositide 3-kinase (PI3k), mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) cascade signaling factors were examined to explore the mechanism of α-terpineol inhibiting GBM viability. Finally, the orthotopic GBM mouse model was applied to prove the efficacy and toxicity of α-terpineol on regulating GBM survival., Results: α-terpineol significantly suppressed GBM growth, migration, invasion, angiogenesis and temozolomide (TMZ) resistance. Furthermore, α-terpineol specifically targeted KDELC2 to downregulate Notch and PI3k/mTOR/MAPK signaling pathway. Finally, we also demonstrated that α-terpineol could penetrate the BBB to inhibit GBM proliferation, which resulted in reduced cytotoxicity to vital organs., Conclusion: Compared to published literatures, we firstly proved α-terpineol possessed the capability to inhibit GBM through various mechanisms and potentially decreased the occurrence of chemoresistance, making it a promising alternative therapeutic option for GBM in the future., Competing Interests: Declaration of competing interest This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. The study design was approved by the appropriate ethics review board. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. All authors declare that there is no conflict of interest in this study., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Presently, the exposure of plasticizers to humans and animals occurs daily, which pose a potential threat to reproductive health. In the present study, a pregnant mouse model exposed to di(2-ethylhexyl) phthalate (DEHP, one of the most common plasticizers) and melatonin was established, and the single-cell transcriptome technology was applied to investigate the effects of melatonin in ovarian cells against DEHP. Results showed that DEHP markedly altered the gene expression pattern of ovarian cells, and severely weakened the histone methylation modification of oocytes. The administration of melatonin recovered the expression of LHX8 and SOHLH1 proteins that essential for primordial follicle formation, and increased the expression of CEBPB, as well as key genes of histone methylation modification (such as Smyd3 and Kdm5a). In addition, the ovarian damage caused by DEHP was also relieved after the overexpression of CEBPB, which suggested melatonin could improve primordial follicle formation progress via enhancing CEBPB expression in mice. Besides, the apoptosis of ovarian cells induced by DEHP also was diminished by melatonin. The study provides evidence of melatonin preventing the damage mediated by plasticizers on the reproductive system in females and CEBPB may serve as a downstream target factor of melatonin in the process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: To investigate the frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students., Methods: Totally 158 student volunteers underwent routine vision examination in the optometry clinic of Guangxi Medical University. Their data were used to identify the different types of accommodation and non-strabismic binocular vision dysfunction and to determine their frequency. Correlation analysis and logistic regression were used to examine the factors associated with these abnormalities., Results: The results showed that 36.71% of the subjects had accommodation and non-strabismic binocular vision issues, with 8.86% being attributed to accommodation dysfunction and 27.85% to binocular abnormalities. Convergence insufficiency (CI) was the most common abnormality, accounting for 13.29%. Those with these abnormalities experienced higher levels of eyestrain ( χ 2 =69.518, P <0.001). The linear correlations were observed between the difference of binocular spherical equivalent (SE) and the index of horizontal esotropia at a distance ( r =0.231, P =0.004) and the asthenopia survey scale (ASS) score ( r =0.346, P <0.001). Furthermore, the right eye's SE was inversely correlated with the convergence of positive and negative fusion images at close range ( r =-0.321, P <0.001), the convergence of negative fusion images at close range ( r =-0.294, P <0.001), the vergence facility (VF; r =-0.234, P =0.003), and the set of negative fusion images at far range ( r =-0.237, P =0.003). Logistic regression analysis indicated that gender, age, and the difference in right and binocular SE did not influence the emergence of these abnormalities., Conclusion: Binocular vision abnormalities are more prevalent than accommodation dysfunction, with CI being the most frequent type. Greater binocular refractive disparity leads to more severe eyestrain symptoms., Competing Interests: Conflicts of Interest: Cai J, None; Fan WW, None; Zhong YH, None; Wen CL, None; Wei XD, None; Wei WC, None; Xiang WY, None; Chen JM, None., (International Journal of Ophthalmology Press.)

Pathway analysis, including nontopology-based (non-TB) and topology-based (TB) methods, is widely used to interpret the biological phenomena underlying differences in expression data between two phenotypes. By considering dependencies and interactions between genes, TB methods usually perform better than non-TB methods in identifying pathways that include closely relevant or directly causative genes for a given phenotype. However, most TB methods may be limited by incomplete pathway data used as the reference network or by difficulties in selecting appropriate reference networks for different research topics. Here, we propose a gene set correlation enrichment analysis method, Gscore, based on an expression dataset-derived coexpression network to examine whether a differentially expressed gene (DEG) list (or each of its DEGs) is associated with a known gene set. Gscore is better able to identify target pathways in 89 human disease expression datasets than eight other state-of-the-art methods and offers insight into how disease-wide and pathway-wide associations reflect clinical outcomes. When applied to RNA-seq data from COVID-19-related cells and patient samples, Gscore provided a means for studying how DEGs are implicated in COVID-19-related pathways. In summary, Gscore offers a powerful analytical approach for annotating individual DEGs, DEG lists, and genome-wide expression profiles based on existing biological knowledge., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objectives: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) on intestinal mucosal damage, intestinal mucosal oxidative stress injury and apoptosis induced by 5-fluorouraeil (5-FU) chemotherapy in colorectal cancer-bearing mice., Methods: Thirty male BALB/c mice were randomly divided into normal control, colorectal cancer (CT26), 5-FU, non-acupoint and ST36 groups, with 6 mice in each group. Except for those of the normal control group, mice of the remaining 4 groups received subcutaneous implantation of colorectal CT26 cell suspension (0.1 mL) in the right armpit for establishing colorectal cancer model. Rats of the 5-FU group, non-acupoint group and ST36 group were given with 5 mg/mL 5-FU solution once every 3 days for a total of 21 days. For mice of the non-acupoint group and ST36 group, EA (2 Hz, 1-2 mA) was applied to bilateral ST36 or non-acupoints (the bilateral sunken spots about 3 mm to the midpoint between the tail root and the anus) for 5 min after each intraperitoneal infusion of 5-FU, once every 3 days, for a total of 21 days. After the intervention, the diarrhea index was assessed. The length of colon (from the endpoint of cecum to the anal orifice) was measured. Histopathological changes of colonic mucosa were observed by H.E. staining, and the length of colonic villi was measured. The content of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of colonic tissue were detected by thibabituric acid, xanthine oxidase and colorimetric method, respectively. The rate of cell apoptosis in the colonic tissue was measured by TUNEL assay. The positive expressions of Bax and Bcl-2 in colonic tissue were determined by immunohistochemistry., Results: The CT26 model group didn't show any significant changes in the diarrhea index, colon length, colon villus length, MDA content, SOD and GSH-Px activities, colonic cell apoptosis rate, and Bax and Bcl-2 expression levels when compared with the normal group . Compared with the CT26 group, the 5-FU group had a remarkable increase in the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level ( P <0.01, P <0.05), and a marked decrease in the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level ( P <0.01), suggesting the side effects of administration of 5-FU. Compared with the 5-FU group, the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level were markedly decreased ( P <0.05, P <0.01) and those of the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level were obviously increased ( P <0.01) in the ST36 group. Compared with the 5-FU group, the non-acupoint group also had an increase in the colon villus length, SOD and GSH-Px activities ( P <0.01, P <0.05) and a decrease in the cell apoptosis rate ( P <0.01)., Conclusions: EA at ST36 has a positive effect in reducing intestinal mucosal damage induced by 5-FU chemotherapy in cancer-bearing mice, which may be related to its function in relieving oxidative stress injury and inhibiting apoptosis of colonic tissue.

Aim: To explore the risk factors for acute acquired comitant esotropia (AACE)., Methods: A retrospective cohort study was conducted by analyzing 83 patients (case group) with AACE who underwent strabismus correction surgery from January 1, 2021 to June 30, 2022. Totally 73 outpatient volunteers were recruited during the same period as the normal control group. The case group's binocular vision time, near and distance esotropia angle, and near stereo vision function were recorded, and the age, gender, refractive status, and best-corrected visual acuity (BCVA) of both groups were analyzed. Additionally, multiple logistic regression analysis was conducted using an eye usage condition questionnaire to determine the independent risk factors for AACE., Results: In the case group, 61 patients (73.49%) had myopia, with a mean equivalent spherical power (SE) of -3.35±3.31 D (range: +2.75 to -10.62 D) of the right eye and -2.87±3.35 D (range: +2.75 to -11.12 D) of the left eye. The average duration of diplopia in the case group was 29.83±35.72mo, of which 80 patients (96.39%) were primarily with distance diplopia. The near and distance esotropia angle after wearing glasses were 52.36±20.95 prism degree (PD) and 56.71±19.54 PD, respectively, and there was no statistically significant difference between the two ( t =1.38, P =0.169). The incidence of improper glasses wearing and unhealthy eye habits in the case group was significantly higher than those in the control group ( P <0.05). Close-up work without glasses [ β =2.30, odds ratio (OR)=10, 95% confidence interval (CI) 2.35-42.51, P =0.002] and near work in supine position ( β =1.80, OR=6.02, 95%CI 3.29-11.02, P <0.001) were independent risk factors for AACE., Conclusion: Patients with AACE mainly present with distance diplopia, and there is a high degree of variation in myopia. Near work without wearing glasses and in supine position are independent risk factors for AACE., (International Journal of Ophthalmology Press.)

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS), 64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital (Beijing, China) between January 2016 and December 2017 were included in the study. Data on medical history, physical examination and laboratory examination results, and micro-TESE outcomes were collected. Patients were divided into two groups according to micro-TESE outcomes. The following factors were compared between the two groups by the Mann‒Whitney U test or Student's t-test based on the distribution (nonnormal or normal) of the factors: age, testicular size, follicle-stimulating hormone level, luteinizing hormone level, testosterone level, and anti-Müllerian hormone level. The overall success rate of sperm retrieval was 50.0%. Correlation analysis showed that testicular volume was positively correlated with testosterone level. Using a logistic regression model, age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters., (Copyright © 2023 Copyright: © The Author(s)(2023).)

The identification of gasdermin as the executor of pyroptosis has opened new avenues for the study of this process. Although pyroptosis research has mainly focused on immune cells since it was discovered three decades ago, accumulating evidence suggests that pyroptosis plays crucial roles in many biological processes. One example is the discovery of gasdermin-mediated cancer cell pyroptosis (CCP) which has become an important and frontier field in oncology. Recent studies have shown that CCP induction can heat tumor microenvironment (TME) and thereby elicit the robust anti-tumor immunity to suppress tumor growth. As a newly discovered form of tumor cell death, CCP offers promising opportunities for improving tumor treatment and developing new drugs. Nevertheless, the research on CCP is still in its infancy, and the molecular mechanisms underlying the expression, regulation and activation of gasdermins are not yet fully understood. In this review, we summarize the recent progress of gasdermin research in cancer area, and propose that the anti-tumor effect of immune cell pyroptosis (ICP) and CCP depends on their duration, intensity, and the type of cells undergoing pyroptosis within TME., Competing Interests: Declaration of Competing Interest All authors report no declarations of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Zearalenone (ZEN) is a widespread and transgenerational toxicant that can cause serious reproductive health risks, which poses a potential threat to global agricultural production and human health; its estrogenic activity can lead to reproductive toxicity through the induction of granulosa cell apoptosis. Herein, comparative transcriptome analysis, single-cell transcriptome analysis, and weighted gene co-expression network analysis (WGCNA) combined with gene knockout in vivo and RNA interference in vitro were used to comprehensively describe the damage caused by ZEN exposure on ovarian granulosa cells. Comparative transcriptome analysis and WGCNA suggested that the tumor necrosis factor (TNF)-α-mediated mitogen-activated protein kinase 7 (MAP2K7)/ AKT serine/threonine kinase 2 (AKT2) axis was disordered after ZEN exposure in porcine granulosa cells (pGCs) and mouse granulosa cells (mGCs). In vivo gene knockout and in vitro RNA interference verified that TNF-α-mediated MAP2K7/AKT2 was the guiding signal in ZEN-induced apoptosis in pGCs and mGCs. Moreover, single-cell transcriptome analysis showed that ZEN exposure could induce changes in the TNF signaling pathway in offspring. Overall, we concluded that the TNF-α-mediated MAP2K7/AKT2 axis was the main signaling pathway of ZEN-induced apoptosis in pGCs and mGCs. This work provides new insights into the mechanism of ZEN toxicity and provides new potential therapeutic targets for the loss of livestock and human reproductive health caused by ZEN., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Microdissection testicular sperm extraction (micro-TESE) is widely used to treat nonobstructive azoospermia. However, a good prediction model is required to anticipate a successful sperm retrieval rate before performing micro-TESE. This retrospective study analyzed the clinical records of 200 nonobstructive azoospermia patients between January 2021 and December 2021. The backward method was used to perform binary logistic regression analysis and identify factors that predicted a successful micro-TESE sperm retrieval. The prediction model was constructed using acquired regression coefficients, and its predictive performance was assessed using the receiver operating characteristic curve. In all, 67 patients (sperm retrieval rate: 33.5%) underwent successful micro-TESE. Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels varied significantly between patients who underwent successful and unsuccessful micro-TESE. Binary logistic regression analysis yielded the following six predictors: anti-Müllerian hormone (odds ratio [OR] = 0.902, 95% confidence interval [CI]: 0.821-0.990), inhibin B (OR = 1.012, 95% CI: 1.001-1.024), Klinefelter's syndrome (OR = 0.022, 95% CI: 0.002-0.243), Y chromosome microdeletion (OR = 0.050, 95% CI: 0.005-0.504), cryptorchidism with orchiopexy (OR = 0.085, 95% CI: 0.008-0.929), and idiopathic nonobstructive azoospermia (OR = 0.031, 95% CI: 0.003-0.277). The prediction model had an area under the curve of 0.720 (95% CI: 0.645-0.794), sensitivity of 65.7%, specificity of 72.2%, Youden index of 0.379, and cut-off value of 0.305 overall, indicating good predictive value and accuracy. This model can assist clinicians and nonobstructive azoospermia patients in decision-making and avoiding negative micro-TESE results., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Anthracyclines are a class of conventionally and routinely used first-line chemotherapy drugs for cancer treatment. In addition to the direct cytotoxic effects, increasing evidence indicates that the efficacy of the drugs also depends on immunomodulatory effects with unknown mechanisms. Galectin-9 (Gal-9), a member of the β-galactoside-binding protein family, has been demonstrated to induce T-cell death and promote immunosuppression in the tumor microenvironment. Here, we asked whether anthracycline-mediated immunomodulatory activity might be related to Gal-9. We found that combining doxorubicin with anti-Gal-9 therapy significantly inhibited tumor growth and prolonged overall survival in immune-competent syngeneic mouse models. Moreover, Gal-9 expression was increased in response to doxorubicin in various human and murine cancer cell lines. Mechanistically, doxorubicin induced tumoral Gal-9 by activating the STING/interferon β pathway. Clinically, Gal-9 and p-STING levels were elevated in the tumor tissues of breast cancer patients treated with anthracyclines. Our study demonstrates Gal-9 upregulation in response to anthracyclines as a novel mechanism mediating immune escape and suggests targeting Gal-9 in combination with anthracyclines as a promising therapeutic strategy for cancer treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Zhu, Wu, Li, Tong, Huang, Gong, Gong and Zhong.)

Exploring drug-protein interactions (DPIs) through computational methods can effectively reduce the workload and the cost of DPI identification. Previous works try to predict DPIs by integrating and analyzing the unique features of drugs and proteins. They cannot adequately analyze the consistency between the drug features and the protein features due to their different semantics. However, the consistency of their features, such as the correlation originating from their sharing diseases, may reveal some potential DPIs. Here we propose a deep neural network-based co-coding method (DNNCC for short) to predict novel DPIs. DNNCC projects the original features of drugs and proteins to a common embedding space through a co-coding strategy. In this way, the embedding features of drugs and proteins have the same semantics. Therefore, the prediction module can discover the unknown DPIs by exploring the feature consistency between drugs and proteins. The experimental results indicate that the performance of DNNCC is significantly superior to five state-of-the-art DPI prediction methods under several evaluation metrics. The superiority of integrating and analyzing the common features of drugs and proteins is proved by the ablation experiments. The novel DPIs predicted by DNNCC verify that DNNCC is a powerful prior tool that can effectively discover potential DPIs.

Nuclear epidermal growth factor receptor (EGFR) has been shown to be correlated with drug resistance and a poor prognosis in patients with cancer. Previously, we have identified a tripartite nuclear localization signal (NLS) within EGFR. To comprehensively determine the functions and underlying mechanism of nuclear EGFR and its clinical implications, we aimed to explore the nuclear export signal (NES) sequence of EGFR that is responsible for interacting with the exportins. We combined in silico prediction with site-directed mutagenesis approaches and identified a putative NES motif of EGFR, which is located in amino acid residues 736-749. Mutation at leucine 747 (L747) in the EGFR NES led to increased nuclear accumulation of the protein via a less efficient release of the exportin CRM1. Interestingly, L747 with serine (L747S) and with proline (L747P) mutations were found in both tyrosine kinase inhibitor (TKI)-treated and -naïve patients with lung cancer who had acquired or de novo TKI resistance and a poor outcome. Reconstituted expression of the single NES mutant EGFR L747P or EGFR L747S , but not the dual mutant along with the internalization-defective or NLS mutation, in lung cancer cells promoted malignant phenotypes, including cell migration, invasiveness, TKI resistance, and tumor initiation, supporting an oncogenic role of nuclear EGFR. Intriguingly, cells with germline expression of the NES L747 mutant developed into B cell lymphoma. Mechanistically, nuclear EGFR signaling is required for sustaining nuclear activated STAT3, but not for Erk. These findings suggest that EGFR functions are compartmentalized and that nuclear EGFR signaling plays a crucial role in tumor malignant phenotypes, leading to tumorigenesis in human cancer., Competing Interests: None., (AJCR Copyright © 2023.)

Water transport is vital for the durability of ultra-high performance concrete (UHPC) in engineering, but its absorption behavior requires further comprehension. This study investigates the impact of silica fume (SF) and metakaolin (MK) on water absorption in UHPC matrix with a high volume of limestone powder (LS) under two curing temperatures, and the variation in water transport with pore size obtained by low field nuclear magnetic resonance (LF-NMR). Relations between cumulative water absorption with other properties were discussed, and the pore size distribution (PSD) measured by Mercury intrusion porosimetry (MIP) was compared with that determined by LF-NMR. Results showed that MK outperformed SF in reducing water absorption in UHPC matrix, containing 30% LS under steam curing due to the synergistic effect between MK and LS. The incorporation of LS greatly affected the water absorption process of UHPC matrix. In samples without LS, capillary and gel pores absorbed water rapidly within the first 6 h and slowly from 6 h to 48 h simultaneously. However, in samples with 30% LS, gel pore water decreased during water absorption process due to the coarsening of gel pores. MK was able to suppress gel pore deterioration caused by the addition of a large amount of LS. Compared with PSD measured by MIP, NMR performed better in detecting micropores (<10 nm).

The thermoresponsive drug-loaded hydrogels have attracted widespread interest in the field of medical applications due to their ease of delivery to structurally complex tissue defects. However, drug-resistant infections remain a challenge, which has prompted the development of new non-antibiotic hydrogels. To this end, we prepared chitosan-methacrylate (CTSMA)/gelatin (GEL) thermoresponsive hydrogels and added natural phenolic compounds, including tannic acid, gallic acid, and pyrogallol, to improve the efficacy of hydrogels. This hybrid hydrogel imparted initial crosslinking at physiological temperature, followed by photocuring to further provide a mechanically robust structure. Rheological analysis, tensile strength, antibacterial activity against E. coli , S. aureus , P. gingivalis, and S. mutans , and L929 cytotoxicity were evaluated. The experimental results showed that the hybrid hydrogel with CTSMA/GEL ratio of 5/1 and tannic acid additive had a promising gelation temperature of about 37 °C. The presence of phenolic compounds not only significantly ( p < 0.05) enhanced cell viability, but also increased the tensile strength of CTSMA/GEL hybrid hydrogels. Moreover, the hydrogel containing tannic acid revealed potent antibacterial efficacy against four microorganisms. It was concluded that the hybrid hydrogel containing tannic acid could be a potential composite material for medical applications.

Background: Non-alcoholic fatty liver disease (NAFLD) is usually accompanied by metabolic syndrome, which is associated with increased risk of cancer. To inform a tailored cancer screen in patients at higher risks, we estimated the global burden of cancer attributable to metabolic risks., Methods: Data of common metabolism-related neoplasms (MRNs) were derived from the Global Burden of Disease (GBD) 2019 database. Age-standardized, disability-adjusted life year (DALY) rates and death rates of patients with MRNs were extracted from the GBD 2019 database and stratified by metabolic risk, sex, age, and level of socio-demographic index (SDI). The annual percentage changes of age-standardized DALYs and death rates were calculated., Findings: Metabolic risks, consisting of high body mass index and fasting plasma glucose, contributed substantially to the burden of neoplasms, including colorectal cancer (CRC), tracheal, bronchus, and lung cancer (TBLC), etc. Globally, in 2019, there was an estimated age-standardized DALY rate (ASDR) of 234 (95% confidence interval [CI] 124-376) per 100,000 person years for neoplasms attributable to metabolic risks. ASDRs of MRNs were higher for CRC, TBLC, men, patients aged ≥50 years, and patients with high or high-middle SDI., Conclusions: The findings of this study further underpin the correlation between NAFLD and intrahepatic and extrahepatic cancers and highlight the possibility of tailored cancer screening for the NAFLD population at higher risks., Funding: This work was supported by the National Natural Science Foundation of China and Natural Science Foundation of Fujian Province of China., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Male reproductive health has become a serious public health concern, and semen quality is essential to male reproduction. We aimed to investigate geographical differences in the semen quality of sperm donors from northern and southern China by enrolling donors across the country., Methods: A total of 1,012 sperm donors were enrolled in this study between 2015 and 2019. Donors were first divided into two parts based on their birthplace according to the "Qinling-Huaihe" line, and secondly, by their residential latitude. Finally, donors were re-classified into two groups (typically north and south) which contained 667 samples., Results: Statistically significant differences in sperm concentration were observed among men from different latitudes in China (P=0.04). The sperm concentrations of males from 18° to 27° north latitude were significantly lower than those from 36° to 45° and 45° to 54° [median 131, 134, and 146, respectively, P=0.021 (18° to 27° vs. 36° to 45°) and P=0.01 (18° to 27° vs. 45° to 54°)]., Conclusion: We hypothesize environmental pollution and mental stress due to the increased population size may be the main factors underlying differences in the sperm quality of men in northern and southern China., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-578/coif). The authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

In order to reveal the complex mechanism governing the mitotic/meiotic switch in female germ cells at epigenomic and genomic levels, we examined the chromatin accessibility (scATAC-seq) and the transcriptional dynamics (scRNA-seq) in germ cells of mouse embryonic ovary between E11.5 to 13.5 at single-cell resolution. Adopting a strict transcription factors (TFs) screening framework that makes it easier to understand the single-cell chromatin signature and a TF interaction algorithm that integrates the transcript levels, chromatin accessibility, and motif scores, we identified 14 TFs potentially regulating the mitotic/meiotic switch, including TCFL5, E2F1, E2F2, E2F6, E2F8, BATF3, SP1, FOS, FOXN3, VEZF1, GBX2, CEBPG, JUND, and TFDP1. Focusing on TCFL5, we constructed Tcfl5 +/- mice which showed significantly reduced fertility and found that decreasing TCFL5 expression in cultured E12.5 ovaries by RNAi impaired meiotic progression from leptotene to zygotene. Bioinformatics analysis of published results of the embryonic germ cell transcriptome and the finding that in these cells central meiotic genes (Stra8, Tcfl5, Sycp3, and E2f2) possess open chromatin status already at the mitotic stage together with other features of TCFL5 (potential capability to interact with core TFs and activate meiotic genes, its progressive activation after preleptotene, binding sites in the promoter region of E2f2 and Sycp3), indicated extensive amplification of transcriptional programs associated to mitotic/meiotic switch with an important contribution of TCFL5. We conclude that the identified TFs, are involved in various stages of the mitotic/meiotic switch in female germ cells, TCFL5 primarily in meiotic progression. Further investigation on these factors might give a significant contribution to unravel the molecular mechanisms of this fundamental process of oogenesis and provide clues about pathologies in women such as primary ovarian insufficiency (POI) due at least in part to meiotic defects., (© 2023. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) outbreak has had a widespread and profound impact on people's mental health. The factors associated with mental symptoms among men diagnosed with infertility, a disease closely related to psychological conditions, remain unclear. The aim of this study is to investigate the risk factors associated with mental symptoms among infertile Chinese men during the pandemic., Results: A total of 4,098 eligible participants were recruited in this cross-sectional, nationwide study, including 2,034 (49.6%) with primary infertility and 2,064 (50.4%) with secondary infertility. The prevalence of mental health conditions was 36.3%, 39.6%, and 6.7% for anxiety, depression, and post-pandemic stress, respectively. Sexual dysfunction is associated with a higher risk with adjusted odds ratios (ORs) of 1.40 for anxiety, 1.38 for depression, and 2.32 for stress. Men receiving infertility drug therapy displayed a higher risk for anxiety (adjusted OR, 1.31) and depression (adjusted OR, 1.28) symptoms, while those receiving intrauterine insemination had a lower risk of anxiety (adjusted OR, 0.56) and depression (adjusted OR, 0.55) symptoms., Conclusion: The COVID-19 pandemic has had a significant psychological impact on infertile men. Several psychologically vulnerable populations were identified, including individuals with sexual dysfunction, respondents receiving infertility drug therapy, and those experiencing control measures for COVID-19. The findings provide a comprehensive profile of the mental health status of infertile Chinese men during the COVID-19 outbreak and provide potential psychological intervention strategies., (© 2023. The Author(s).)

This study examines the effects of a COVID-19 outbreak on levels of social capital on a college campus, drawing on survey data collected from students at two colleges-one that experienced an outbreak and one that did not. Social capital is examined as an individual level resource and as a campus level normative tool used to fight collective action problems. We test the hypothesis that the outbreak, as a "shock" to the campus, diminished social capital. We also test hypotheses on gender, race, and ethnicity and social capital, informed by prior research. Our findings suggest that the outbreak did reduce social capital at both the individual and campus levels, though individual social capital had a mitigating effect that increased campus social capital. We find also that gender was significantly linked to campus social capital, while race was predictive of individual level social capital., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Atmospheric black carbon (BC), primary and secondary brown carbon (BrC pri and BrC sec ) are the light-absorbing carbonaceous aerosol components. The vertical changes in the BC and BrC distributions are not generally known. Here, we presented a study of the spectral light absorption properties, direct solar absorption, and potential source areas of BC and BrC at the foothill (375 m a.s.l.) and summit (2060 m a.s.l.) of Mt. Hua, China. More than tripled BC and BrC light absorption coefficient were observed at the foothill compared to the summit. The dominant carbonaceous light-absorbing was attributed to BC with the percentages of 77 % (foothill) and 79 % (summit), respectively. The light absorption coefficient and direct solar absorption of BrC pri were much higher than those of BrC sec at foothill, especially in winter. The enhancing contributions of BrC sec light absorption coefficient and direct solar absorption were observed with high RH and visibility at the summit. The light absorption properties of BC, BrC pri , and BrC sec may be attributed to the emissions, meteorological conditions, and photochemical oxidation. The inferred potential source spatial distributions of BC and BrC pri showed different patterns at the foothill and summit. The results underlined the primary emission effects (including BC and BrC pri ) at the foothill and the importance of BrC sec at the summit, respectively., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Motivation: Large-scale heterogeneous data provide diverse perspectives for predicting drug-protein interactions (DPIs). However, the available information on molecular interactions and clinical associations related to drugs or proteins is incomplete because there may be unproven interactions and associations. This incomplete information in the available data is presented in the form of non-interaction and non-correlation, which may mislead the prediction model. Existing methods fuse incomplete and complete information without considering their integrity, so the negative effects of incomplete information still exist., Results: We develop a network-based DPI prediction method named BRWCP, which uses the complete information network to correct the prediction results acquired by the incomplete information network. By integrating relevant heterogeneous information that may be incomplete, the feature similarities of drugs and proteins are obtained. Combining the feature similarities and known DPIs, an incomplete information-based drug-protein heterogeneous network is constructed. Then, a bidirectional random walk with pruning algorithm is adopted in this heterogeneous network to predict potential DPIs. Next, the predicted DPIs are combined with the chemical fingerprint similarity of drugs and amino acid sequence similarity of proteins to construct the complete information network. The bidirectional random walk with pruning algorithm is applied in the new network to obtain the final prediction results until it converges. Experimental results show that BRWCP is superior to several state-of-the-art DPI prediction methods, and case studies further confirm its ability to tap potential DPIs., Availability and Implementation: The code and data used in BRWCP are available at https://github.com/lyfdomain/BRWCP., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Circular RNAs (circRNAs) are highly conserved and ubiquitously expressed noncoding RNAs that participate in multiple reproduction-related diseases. However, the expression pattern and potential functions of circRNAs in the testes of patients with non-obstructive azoospermia (NOA) remain elusive. In this study, according to a circRNA array, a total of 37 881 circRNAs were identified that were differentially expressed in the testes of NOA patients compared with normal controls, including 19 874 upregulated circRNAs and 18 007 downregulated circRNAs. Using quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we confirmed that the change tendency of some specific circRNAs, including hsa&#95;circ&#95;0137890, hsa&#95;circ&#95;0136298, and hsa&#95;circ&#95;0007273, was consistent with the microarray data in another larger sample. The structures and characteristics of these circRNAs were confirmed by Sanger sequencing, and fluorescence in situ hybridization revealed that these circRNAs were primarily expressed in the cytoplasm. Bioinformatics analysis was used to construct the competing endogenous RNA (ceRNA) network, and numerous miRNAs that could be paired with circRNAs validated in this study were reported to be vital for spermatogenesis regulation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that genes involved in axoneme assembly, microtubule-based processes, and cell proliferation were significantly enriched. Our data suggest that there are aberrantly expressed circRNA profiles in patients with NOA and that these circRNAs may help identify key diagnostic and therapeutic molecular biomarkers for NOA patients., Competing Interests: None

Objective: To evaluate the protective function of Babao Dan (BBD) on 5-flurouracil (5-FU)-induced intestinal mucositis (IM) and uncover the underlying mechanism., Methods: A total of 18 male mice were randomly divided into 3 groups by a random number table, including control, 5-FU and 5-FU combined BBD groups, 6 mice in each group. A single intraperitoneal injection of 5-FU (150 mg/kg) was performed in 5-FU and 5-FU combined BBD groups on day 0. Mice in 5-FU combined BBD group were gavaged with BBD (250 mg/kg) daily from day 1 to 6. Mice in the control group were gavaged with saline solution for 6 days. The body weight and diarrhea index of mice were recorded daily. On the 7th day, the blood from the heart of mice was collected to analyze the proportional changes of immunological cells, and the mice were subsequently euthanized by mild anesthesia with 2% pentobarbital sodium. Colorectal lengths and villus heights were measured. Intestinal-cellular apoptosis and proliferation were evaluated by Tunel assay and immunohistochemical staining of proliferating cell nuclear antigen, respectively. Immunohistochemistry and Western blot were performed to investigate the expressions of components in Wnt/β-catenin pathway (Wnt3, LRP5, β-catenin, c-Myc, LRG5 and CD44)., Results: BBD obviously alleviated 5-FU-induced body weight loss and diarrhea, and reversed the decrease in the number of white blood cells, including monocyte, granulocyte and lymphocyte, and platelet (P<0.01). The shortening of colon caused by 5-FU was also reversed by BBD (P<0.01). Moreover, BBD inhibited apoptosis and promoted proliferation in jejunum tissues so as to reduce the intestinal mucosal damage and improve the integrity of villus and crypts. Mechanically, the expression levels of Wnt/β -catenin mediators such as Wnt3, LRP5, β-catenin were upregulated by BBD, activating the transcription of c-Myc, LRG5 and CD44 (P<0.01)., Conclusions: BBD attenuates the adverse effects induced by 5-FU via Wnt/β-catenin pathway, suggesting it may act as a potential agent against chemotherapy-induced intestinal mucositis., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To understand the impact of common cancers of the gastrointestinal tract and help to formulate evidence-based policy, we evaluate the relationship between the burden of GI tract cancers and socioeconomics., Methods: Data on GI tract cancer burden were obtained from the Global Burden of Disease (GBD) 2019 including mortality and incidence rates. According to the Socio-demographic Index (SDI) level, country and territory, and sex, etc. , the data were further stratified. The association between the burden of GI tract cancer and socioeconomics, indicated by SDI, was described. Uncertainty analysis was estimated using bootstrap draw., Results: In 2019, five major cancers of the gastrointestinal tract led to an age-standardized incidence rate (ASIR) of 61.9 (95% CI 56.1-67.6) per 100 000 person-years. From 1990 to 2019, five common tumors of the gastrointestinal tract related age-standardized death rates (ASDRs) decreased by -22.7% (-31.1 to -13.5). For the five common tumors, ASIRs and ASDRs were both higher in males than those in females. Globally, Mongolia, and several East Asia countries exhibited the highest ASIRs in 2019. The high SDI, and high-middle SDI locations recorded the highest incidence rate and death rate of colon and rectum cancer and pancreatic cancer. On the contrary, the low-middle SDI, and low SDI locations possessed the highest incidence rate and death rate of stomach cancer and esophageal cancer., Conclusion: There is a profound association between socioeconomics and burden of common cancers of the gastrointestinal tract. It would be helpful for the high SDI, and high-middle SDI locations to pay special attention to the screening of colon and rectum cancer and pancreatic cancer while the low-middle SDI, and low SDI locations should pay more attention to the screening of stomach cancer and esophageal cancer., 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 © 2022 Hong, Li, Chen, Lin, Pan and Gong.)

Since the COVID-19 pandemic, the tourism economy has been seriously affected. China has implemented a direct traveling management mechanism and recovered from the pandemic faster than the rest of the world. However, the COVID-19 situation is complicated and uncontrollable because of the available unclear information including difficult medical terminologies. This study attempts to find the determinants of the travel intention of China's tourists in the post-COVID-19 epidemic. Along with information overload and perception risk, an expanded research model of the Theory of Planned Behavior (TPB) was employed to propose the theoretical framework of this study. A survey was conducted among 518 tourists who spend their holiday in Hainan, which is a popular tourist destination in China. The empirical results show that information overload positively and significantly impacted perceived risk. Furthermore, perceived risk negatively affects the intention to travel. Perceived risk also negatively affected the attitude toward traveling. However, response self-efficacy did not have a significant effect on the intention to travel. Finally, based on the analysis results, this study proposes relevant research contributions and practical recommendations with management implications for the travel industries., 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., (Copyright © 2022 Wu, Cao, Mao and Hu.)

N-linked glycosylation of proteins is one of the post-translational modifications (PTMs) that shield tumor antigens from immune attack. Signaling lymphocytic activation molecule family 7 (SLAMF7) suppresses cancer cell phagocytosis and is an ideal target under clinical development. PTM of SLAMF7, however, remains less understood. In this study, we investigated the role of N-glycans on SLAMF7 in breast cancer progression. We identified seven N-linked glycosylation motifs on SLAMF7, which are majorly occupied by complex structures. Evolutionally conserved N98 residue is enriched with high mannose and sialylated glycans. Hyperglycosylated SLAMF7 was associated with STT3A expression in breast cancer cells. Inhibition of STT3A by a small molecule inhibitor, N-linked glycosylation inhibitor-1 (NGI-1), reduced glycosylation of SLAMF7, resulting in enhancing antibody affinity and phagocytosis. To provide an on-target effect, we developed an antibody-drug conjugate (ADC) by coupling the anti-SLAMF7 antibody with NGI-1. Deglycosylation of SLAMF7 increases antibody recognition and promotes macrophage engulfment of breast cancer cells. Our work suggests deglycosylation by ADC is a potential strategy to enhance the response of immunotherapeutic agents., Competing Interests: H.-C.H. and C.-W.L. are inventors listed on patent applications in the filing., (AJCR Copyright © 2022.)

Background: The aim of this study was to translate and cross-culturally adapt the international prostate symptom score (IPSS) and benign prostatic hyperplasia impact index (BII) into simplified Chinese for mainland Chinese patients with benign prostatic hyperplasia (BPH)., Methods: The original English IPSS and BII were translated into simplified Chinese versions based on cross-cultural adaptation guidelines. Internal consistency was evaluated with Cronbach's α, then test-retest reliability with intraclass correlation coefficients (ICCs) in stable patients. The validity of these two adaptations was tested by the correlation between the IPSS and BII with visual prostate symptom score (VPSS) and 36 items Short Form Health Survey (SF-36). The floor and ceiling effects were calculated by the proportion of participants who obtained the highest and lowest possible score., Results: A total of 105 native Chinese-speaking patients with BPH were enrolled. Cronbach's α was over 0.75 for the simplified Chinese IPSS (IPSS 0.815; IPSS-symptom 0.782) and 0.709 for the simplified Chinese BII, indicating acceptable internal consistency. The ICCs for the test-retest reliability were over 0.75 (IPSS, r  = 0.836; IPSS-symptom, r  = 0.801; IPSS-quality of life, r  = 0.794; BII, r  = 0.758), indicating excellent test-retest reliability. There were very good positive correlations between IPSS and BII ( r  = 0.605), as well as VPSS ( r  = 0.634), and very good or good negative correlations between IPSS-Qol and SF-36 physical functioning ( r  = -0.621), and vitality ( r  = -0.659), and between BII and SF-36 physical functioning ( r  = -0.421). No floor or ceiling effect was detected in the simplified Chinese IPSS and BII., Conclusions: This study indicates that the simplified Chinese IPSS and BII are reliable and valid measurements of the symptom and quality of life among Chinese patients with BPH, which is likely to be widely used in this population., Competing Interests: The authors declare that they have no competing interests., (© 2022 Asian Pacific Prostate Society. Publishing services by Elsevier B.V.)

Pepper is an important and widely cultivated economic vegetable in the world (Yin et al., 2021). In June 2021, approximately 25% to 33.3% of the pepper plants had rot disease symptoms in Zhuanghang Comprehensive Experimental Base (30.894829 °N, 121.391374 °E), Fengxian district, Shanghai city, China. Water-soaked spots appeared on fruits that increased in size and leading to smelly fruit decay. To isolate the pathogen, three pepper samples with severe symptoms were collected. The samples were surface disinfected with 70% ethanol for 30 sec, 10% chlorine bleach for 10 min, rinsing with sterile water for three times and the rot tissues were cut and dried on sterile filter paper. The dried paper was later placed on potato dextrose agar (PDA) medium and incubated at 28°C (Tang et al., 2021). After 2-3 days, four types of colonies with different colony appearances were observed, in which only one can induce fruit rot phenotype (data not shown). Four isolates were cultured for molecular identification in each type. ITS1/ITS4, T1/βt-2b and EF1-526F/EF1-1567R primers were used to amplify the internal transcribed spacer region (ITS), the beta-tubulin (TUB2) and the translation elongation factor I alpha (EF1-α) genes, respectively (Chen et al., 2018) and corresponding sequences from the isolates were analyzed with BLAST. Sequences of the isolate which can induce pepper decay were submitted to GenBank under the accession numbers of OM663701 (ITS), OM720127 (TUB2) and OM720128 (EF1-α). The results showed that the pathogen had 99% sequence homology to most strains of Botryosphaeria dothidea (B. dothidea) and displayed the highest sequence similarity to strain LBSX-1 (ITS: KF55123), strain JGT01 (TUB2: MW202404) and isolate CZA (EF1-α: MN025271). Based on molecular characterization, the isolate was identified as B. dothidea isolate SH01. A phylogenetic tree was constructed using Maximum Parsimony (MP) methods by MEGA7, and showed that SH01 was closely related to isolate CMW9075. To confirm the pathogenicity, five healthy pepper fruits were surface sterilized, 500μl of conidial suspension (1×103 conidia/ml) were injected into pepper (sterilized distilled water as control). Six days post inoculation (dpi), fruit rot symptoms appeared and the pepper decayed at 12 dpi. Four days post inoculation with mycelium plugs (from a 4-day-old culture on PDA, PDA plugs as control), hyphae were observed in the inoculation site and B. dothidea was re-isolated from the symptomatic areas, thus fulfilling Koch's postulates (Back et al., 2021, Chen et al., 2020). The pepper rotted severely at 7 dpi. The colonies of SH01 were pale to white and gradually turned into gray in 4-6 days. Conidia of the pathogen were unicellular, aseptate, hyaline and fusiform to fusoid, with dimensions of 19.7-23.5 μm × 3.8-5.2 μm (average = 21.9 μm × 4.8 μm, n = 50). Hyphae were transparent, branched and composed of multiple cells. The characteristic was consistent with the descriptions of B. dothidea (Vasic et al., 2013). B. dothidea belongs to Botryosphaeriaceae, causing widespread diseases in many plant species, commonly associated with cankers and dieback of woody plants and economic crops, such as plumcot trees (Back et al., 2021), eucalyptus (Yu et al., 2009) and soybeans (Chen et al., 2020) in China and Korea. Our findings reported for the first time that B. dothidea (SH01) can induce the pepper rot disease and future work on its pathogenesis may provide strategies for disease control against this fungus.

Although several traditional Chinese medicine (TCM)-related databases have emerged, they focus on researching single medicinal materials, which is far from sufficient for clinical research and application. In comparison, compound prescriptions are more informative and meaningful in TCM, for they embody the information on the compatibility of TCM besides the relatively isolated information about single medicinal materials. The compatibility information is essential in TCM because it conveys not only what components are involved to treat special diseases but also how to combine these single medical materials. We established a database of Chinese patent medicine and compound prescription (CPMCP). It demonstrates the prescription information of Chinese patent medicines (CPMs) and ancient Chinese medicine prescriptions (CMPs). CPMCP reports their comprehensive and standardized information such as the components, indications and contraindications. It is worth mentioning that we organized relevant experts and spent lots of time manually mapping the functions of compound prescriptions in ancient Chinese to the standardized TCM symptom vocabularies, obtaining a total of 71 414 associations between compound prescriptions and TCM symptoms. In this way, CPMCP established the associations between TCM and modern medicine (MM) according to the associations between TCM symptoms and MM symptoms. In addition, to further exhibit the compatibility mechanism of compound prescriptions, CPMCP summarizes a set of common drug combination principles by analyzing the existing prescriptions. We believe that CPMCP can promote the modernization of TCM and make greater contributions to MM. Database URL http://cpmcp.top., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Primary liver cancer (PLC) is a major contributor to cancer-related deaths. Data on global and country-specific levels and trends of PLC are essential for understanding the effects of this disease and helping policymakers to allocate resources., Aim: To investigate the association between the burden of PLC and socioeconomic development status., Methods: Cancer mortality and incidence rates were obtained from the Global Burden of Disease (GBD) 2019, and the data were stratified by country and territory, sex, and the Socio-demographic Index (SDI) level. The association between the attributable etiology of PLC and socioeconomic development status, represented using the SDI, was described. The attributable etiology of PLC included hepatitis B, hepatitis C, alcohol use, and nonalcoholic steatohepatitis. The association between the attributable etiology of PLC and SDI was further stratified by sex and geographical location. A confidence analysis was also performed based on bootstrap draw., Results: The age-standardized incidence rate of PLC was 6.5 [95% confidence intervals (CI): 5.9-7.2] per 100000 person-years, which decreased by -27.5% (-37.0 to -16.6) from 1990 to 2019. Several countries located in East Asia, South Asia, West Africa, and North Africa shouldered the heaviest burden of PLC in 2019. In terms of incidence rates, the first leading underlying cause of PLC identified was hepatitis B, followed by hepatitis C, alcohol use, and nonalcoholic steatohepatitis. Regarding stratification using the SDI, the incidence rate of PLC was the highest for high and middle SDI locations. Further, the leading attributable etiologies of PLC were hepatitis B for the middle and high middle SDI locations while hepatitis C and nonalcoholic steatohepatitis for the high SDI locations., Conclusion: The pronounced association between socioeconomic development status and PLC burden indicates socioeconomic development status affects attributable etiologies for PLC. GBD 2019 data are valuable for policymakers implementing PLC cost-effective interventions., Competing Interests: Conflict-of-interest statement: All authors report no conflicts interests., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Targeting immune checkpoints such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has transformed cancer treatment, with durable clinical responses across a wide range of tumor types. However, a high percentage of patients fail to respond to anti-PD-1/PD-L1 treatment. A greater understanding of PD-L1 regulation is critical to improving the clinical response rate of PD-1/PD-L1 blockade. Here, we demonstrate that PD-L1 is phosphorylated and stabilized by casein kinase 2 (CK2) in cancer and dendritic cells (DC). Phosphorylation of PD-L1 at Thr285 and Thr290 by CK2 disrupted PD-L1 binding with speckle-type POZ protein, an adaptor protein of the cullin 3 (CUL3) ubiquitin E3 ligase complex, protecting PD-L1 from CUL3-mediated proteasomal degradation. Inhibition of CK2 decreased PD-L1 protein levels by promoting its degradation and resulted in the release of CD80 from DC to reactivate T-cell function. In a syngeneic mouse model, combined treatment with a CK2 inhibitor and an antibody against T-cell immunoglobulin mucin-3 (Tim-3) suppressed tumor growth and prolonged survival. These findings uncover a mechanism by which PD-L1 is regulated and suggest a potential antitumor treatment option to activate DC function by blocking the CK2-PD-L1 pathway and inhibiting Tim-3., Significance: This work identifies a role for CK2 in immunosuppression by phosphorylation and stabilization of PD-L1, identifying CK2 inhibition as an immunotherapeutic approach for treating cancer., (©2022 American Association for Cancer Research.)