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AIM: To explore the optimal concentration of endoplasmic reticulum stress immunohistochemical(IHC)staining antibody in mouse retinitis pigmentosa(RP)model, which provides the corresponding index detection method for studying the pathogenesis and intervention measures of RP.METHODS: Clean male C57BL/6J mice were intraperitoneally injected with N-methyl-N-nitrosourea(MNU, 60mg/kg)to prepare RP mouse model. Electroretinogram(ERG)and hematoxylin-eosin(HE)staining were performed on 7d after modeling to verify the successful modeling. The expression of endoplasmic reticulum stress-related proteins(IRE1, ATF6, PERK, GRP78, Caspase-12)was detected by IHC staining.RESULTS: The following proteins, including IRE1, ATF6, PERK, GRP78 and Caspase-12, were positively expressed in retina of RP mouse. The optimal concentrations of the above proteins were as follows: IRE1 antibody concentration was 1:1000, ATF6 antibody concentration was 1:500 and 1:1000(with no difference in positive expression, P>0.05), PERK antibody concentration was 1:1500, GRP78 antibody concentration was 1:200 and Caspase-12 antibody concentration was 1:100, the proteins were well expressed at the above concentrations, and the positive expressions of corresponding proteins were different from those of other antibody concentrations(P

Hypoxia has been reported to be an important factor leading to male infertility, and it has been reported that hypoxia can induce the apoptosis of mouse spermatogenic cells. Sirtuin 3 (SIRT3) has been reported to promote the degradation of hypoxia‐inducible factor 1α (HIF‐1α), and thus, we hypothesized that SIRT3 may influence hypoxia‐induced apoptosis of spermatogonia. In this study, we overexpressed or inhibited SIRT3 in mouse type B spermatogonia GC‐2 cells and then subjected the cells to hypoxia or normoxia, before examining hypoxia‐responsive gene expression and cell viability. We report that SIRT3 stabilizes hypoxia‐inducible factor 1α (HIF‐1α) and activates its downstream target gene expression in GC‐2 cells. We also show that the SIRT3 inhibitor 3‐TYP suppresses HIF‐1α target gene expression and alleviates hypoxia‐induced apoptosis of GC‐2 cells. Our study reveals the critical role and underlying mechanisms of SIRT3 in hypoxia‐induced apoptosis of mouse type B spermatogonia GC‐2 cells.

Abstract Background Ornamental trees with seasonally-dependent leaf color, such as Acer palmatum, have gained worldwide popularity. Leaf color is a main determinant of the ornamental and economic value of A. palmatum. However, the molecular mechanisms responsible for leaf color changes remain unclear. Results We chose A. palmatum cultivars with yellow (‘Jinling Huangfeng’) and red (‘Jinling Danfeng’) leaves as the ideal material for studying the complex metabolic networks responsible for variations in leaf coloration. The 24 libraries obtained from four different time points in the growth of ‘Jinling Huangfeng’ and ‘Jinling Danfeng’ was subjected to Illumina high-throughput sequencing. We observed that the difference in cyanidin and delphinidin content is the primary reason behind the varying coloration of the leaves. Transcriptomic analyses revealed 225,684 unigenes, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes (DEGs) confirmed that they were involved in ‘anthocyanin biosynthesis.’ Eighteen structural genes involved in anthocyanin biosynthesis were thought to be related to anthocyanin accumulation, whereas 46 MYBs, 33 basic helix-loop-helixs (bHLHs), and 29 WD40s were presumed to be involved in regulating anthocyanin biosynthesis. Based on weighted gene co-expression network analysis (WGCNA), three candidate genes (ApRHOMBOID, ApMAPK, and ApUNE10) were screened in the significant association module with a correlation coefficient (r 2 ) of 0.86. Conclusion In this study, the leaf color changes of two A. palmatum genotypes were analyzed. These findings provide novel insights into variations in leaf coloration and suggest pathways for targeted genetic improvements in A. palmatum.

Abstract Introduction With the spread of the epidemic worldwide, an increasing number of doctors abroad have observed the following atypical symptoms of coronavirus disease 2019 (COVID‐19): olfactory or taste disorders. Therefore, clarifying the incidence and clinical characteristics of olfactory and taste disorders in Chinese COVID‐19 patients is of great significance and urgency. Materials and Methods A retrospective study was conducted, which included 229 severe acute respiratory syndrome coronavirus 2 confirmed patients, through face‐to‐face interviews and telephone follow‐up. Following the completion of questionnaires, the patients participating in the study, were categorized according to the degree of olfactory and taste disorders experienced, and the proportion of each clinical type of patient with olfactory and taste disorders and the time when symptoms appeared were recorded. Results Among the 229 patients, 31 (13.54%) had olfactory dysfunction, and 44 (19.21%) had gustatory dysfunction. For the patients with olfactory dysfunction, 6 (19.35%) developed severe disease and became critically ill. Olfactory dysfunction appeared before the other symptoms in 21.43% of cases. The proportion of females with olfactory and gustatory dysfunction was higher than that of males (P

Abstract Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.

Soundscape quality in green spaces of residential areas directly contributes to residents’ quality of life. It has close relationships with landscape characteristics, which should be considered in landscape planning and design processes in residential areas. Accordingly, this study proposed a new perspective on the interrelationships between soundscape perception and landscape pattern on multi-scale, based on a case study of 30 residential green spaces in Fuzhou, China. Percentage of Landscape (PLAND), Patch Density (PD), Landscape Shape Index (LSI), and Patch cohesion index (COHESION) were utilized to represent the landscape pattern of vegetation, buildings, and roads in the residential areas. Soundscape perception was interpreted using the sound dominant degree (SDD) of sound sources and overall soundscape quality. The examined spatial scales range from 20 m to 180 m, with concentric circles spaced 20 m apart for each sampling point. Correlation analyses indicated that most landscape indices of vegetation and buildings were correlated with these soundscape perception indicators, while limited landscape indices of roads were associated with them. Based on the multi-scale landscape indices, multiple linear regression models for the SDD of sound sources and overall soundscape quality were established, confirming that the scale effect of landscape patterns can affect soundscape perception. Expressly, results indicated that these models were chiefly influenced by the landscape indices at a scale less than 120 m, but the scale effect of landscape pattern on the SDD of birdsong, pleasantness, and quietness was not so evident. Furthermore, we found that the number of explanatory variables may somewhat affect the model performance. The overall interpretability of these landscape indices for the SDD of sound sources was better than that of overall soundscape quality, implying the complexity of the latter. This study offers a fresh insight into the relationship between landscapes and soundscapes at varying scales. The findings can provide useful information for the promotion strategies of landscapes and soundscapes, especially in residential green spaces.

Strobilomyces, one of the most noticeable genera of Boletaceae (Boletales), is both ecologically and economically important. Although many studies have focused on Strobilomyces in China, the diversity still remains incompletely understood. In the present study, several collections of Strobilomyces from Hainan Island, tropical China were studied based on morphology and molecular phylogenetic analyses. Four species are described as new, viz. S. baozhengii, S. conicus, S. hainanensis, and S. pachycystidiatus. Detailed descriptions, color photos of fresh basidiomata, and line drawings of microstructures of the four species are presented.

Ectothermic fish exposure to hypothermal stress requires adjusting their metabolic molecular machinery, which was investigated using Indian medaka (Oryzias dancena; 10 weeks old, 2.5 ± 0.5 cm) cultured in fresh water (FW) and seawater (SW; 35‰) at room temperature (28 ± 1 °C). The fish were fed twice a day, once in the morning and once in the evening, and the photoperiod was 12 h:12 h light: dark. In this study, we applied two hypothermal treatments to reveal the mechanisms of energy metabolism via pgc-1α regulation in the gills of Indian medaka; cold-stress (18 °C) and cold-tolerance (extreme cold; 15 °C). The branchial ATP content was significantly higher in the cold-stress group, but not in the cold-tolerance group. In FW- and SW-acclimated medaka, the expression of genes related to mitochondrial energy metabolism, including pgc-1α, prc, Nrf2, tfam, and nd5, was analyzed to illustrate differential responses of mitochondrial energy metabolism to cold-stress and cold-tolerance environments. When exposed to cold-stress, the relative mRNA expression of pgc-1α, prc, and Nrf2 increased from 2 h, whereas that of tfam and nd5 increased significantly from 168 h. When exposed to a cold-tolerant environment, prc was significantly upregulated at 2 h post-cooling in the FW and SW groups, and pgc-1α was significantly upregulated at 2 and 12 h post-cooling in the FW group, while tfam and nd5 were downregulated in both FW and SW fish. Hierarchical clustering revealed gene interactions in the cold-stress group, which promoted diverse mitochondrial energy adaptations, causing an increase in ATP production. However, the cold-tolerant group demonstrated limitations in enhancing ATP levels through mitochondrial regulation via the PGC-1α energy metabolism pathway. These findings suggest that ectothermic fish may develop varying degrees of thermal tolerance over time in response to climate change. This study provides insights into the complex ways in which fish adjust their metabolism when exposed to cold stress, contributing to our knowledge of how they adapt.

Internal combustion engines, during their operation, subject the piston to high-temperature and high-pressure conditions, requiring it to endure intense, continuous reciprocating motion. This strenuous process leads to significant wear and tear. Among the engine’s crucial components, the piston ring plays a pivotal role but is particularly susceptible to wear. Therefore, extensive research has been devoted to investigating the wear of piston rings, a critical sealing component within internal combustion engines. To address the high cost of existing coating methods, which hinders widespread application, we propose a bionic design approach inspired by groove structures observed on earthworm bodies, aimed at enhancing the wear resistance of piston rings. Bionic piston rings featuring optimally designed groove structures inspired by the earthworm’s anatomy were designed. These rings exhibited varying groove depths (1 mm, 2 mm, and 3 mm), groove widths (0.1 mm, 0.3 mm, and 0.5 mm), and groove spacings (0.1 mm, 0.2 mm, and 0.3 mm). We conducted thermal–structural coupling analyses on both standard piston rings and these bionic counterparts. The results revealed that the maximum stress was concentrated at the first piston ring, precisely at the opposing region of the end gap. Thus, the initial piston ring endured the primary frictional losses. Moreover, a comparison of stress levels between bionic rings and the standard ring revealed that the bionic groove structure substantially reduced stress and minimized stress concentration, thus enhancing wear resistance. Groove width had the most notable influence on wear performance, followed by groove depth and groove spacing. Optimal wear resistance was achieved when the groove depth was 3 mm, groove width was 0.1 mm, and groove spacing was 0.1 mm. Subsequently, we constructed a piston ring friction test bench to validate the wear resistance of the most effective piston ring. The results indicated that the wear resistance of the bionic piston ring exceeded that of the standard piston ring by up to 19.627%. Therefore, incorporating a bionic groove structure within the piston ring can effectively reduce surface friction and enhance wear resistance. This, in turn, can enhance the operational lifespan of internal combustion engines under favorable working conditions.

An efficient and direct approach to pyrroles was successfully developed by employing 3-formylchromones as decarboxylative coupling partners, and facilitated by microwave irradiation. The protocol utilizes easily accessible feedstocks, a catalytic amount of DBU without any metals, resulting in high efficiency and regioselectivity. Notably, all synthesized products were evaluated against five different cancer cell lines and compound 3l selectively inhibited the proliferation of HCT116 cells with an IC50 value of 10.65 μM.

A facile and efficient visible-light-mediated method for directly converting 1,4-naphthoquinones into dihydrocyclo-buta[b]naphthalene-3,8-diones (DHCBNDOs) under mild and clean conditions without using any photocatalysts is reported. This approach exhibited favorable compatibility with functional groups and afforded a series of DHCBNDOs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

ObjectiveTo explore the mediating role of depression in the relationship between family functioning and suicidal ideation (SI) in college students, and to explore whether acceptance (It is one of the core components of psychological flexibility) plays a moderating role in this mediating model.MethodsIn a cross-sectional study, questionnaires were distributed to college students during November and December 2022. The sample of Chinese college students (n = 592, 43.07% male, 56.93% female, mean age 19.40 years, SD = 1.24 years) completed the Family Adaptability and Cohesion Evaluation Scale (FACES III), the Center for Epidemiological Depression Scale (CES-D), the Positive and Negative Suicide Ideation Inventory (PANSI), and the Acceptance and Action Questionnaire-Second Edition (AAQ II). SPSS 25.0 for Windows and PROCESS 2.15 macros were used for data analysis.ResultsThere was a significant negative correlation between family functioning and SI, and depression played a mediating role in this relationship. Acceptance moderated the indirect effects of depression and SI in college students. In college students with a lower acceptance level (i.e., higher experiential avoidance level), depression had more influence on SI, while the influence of depression on SI was less in college students with a higher acceptance level (i.e., lower experiential avoidance level). Family functioning indirectly influenced SI through the moderation of acceptance.ConclusionMental health educators in colleges and universities should pay more attention to identifying and relieving depression in college students, thereby dealing with suicide risk more effectively. At the same time, college students should be discouraged from excessive use of experiential avoidance strategies, and instead taught to master effective emotional regulation strategies such as mindfulness, distress tolerance, and radical acceptance skills to improve their acceptance level and alleviate the influence of depression on SI.

The morbidity and mortality of colorectal cancer (CRC) have been increasing in recent years, and early detection of CRC can improve the survival rate of patients. RNA methylation plays crucial roles in many biological processes and has been implicated in the initiation of various diseases, including cancer. Serum contains a variety of biomolecules and is an important clinical sample for biomarker discovery. In this study, we developed a targeted metabolomics method for the quantitative analysis of nucleosides in human serum samples by using liquid chromatography with tandem mass spectrometry (LC-MS/MS). We successfully quantified the concentrations of nucleosides in serum samples from 51 healthy controls, 37 patients with colorectal adenomas, and 55 patients with CRC. The results showed that the concentrations of N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 3-methyluridine (m3U) were increased in patients with CRC, whereas the concentrations of N2-methylguanosine (m2G), 2′-O-methyluridine (Um), and 2′-O-methylguanosine (Gm) were decreased in patients with CRC, compared with the healthy controls and patients with colorectal adenomas. Moreover, the levels of 2′-O-methyluridine and 2′-O-methylguanosine were lower in patients with colorectal adenomas than those in healthy controls. Interestingly, the levels of Um and Gm gradually decreased in the following order: healthy controls to colorectal adenoma patients to CRC patients. These results revealed that the aberrations of these nucleosides were tightly correlated to colorectal adenomas and CRC. In addition, the present work will stimulate future investigations about the regulatory roles of these nucleosides in the initiation and development of CRC.

Non-coding RNAs are crucial for cancer progression, among which miR-34c-3p has been demonstrated to be a tumor suppressor in non-small cell lung cancer (NSCLC). In this study, we attempt to identify flavonoids that can up-regulate miR-34c-3p expression, evaluate the anticancer activity of the flavonoids and explore its underlying mechanism in NSCLC cells. Six flavonoids were screened by RT-qPCR and we found that jaceosidin significantly increased miR-34c-3p expression in A549 cells. We found that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner, indicated by cell counting kit (CCK-8) assay, wound healing assay, transwell assay and EdU assay, we observed that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner. Further research suggested that miR-34c-3p bound to the transcriptome of integrin α2β1 and then inhibited its expression, leading to the inhibitory effect on the migration and invasion of NSCLC. Our study sheds some light on anti-tumor of jaceosidin and provides a potential lead compound for NSCLC therapy.

IntroductionArsenic trioxide (ATO) is a promising anticancer drug for hematological malignancy. Given the dramatic efficacy of acute promyelocytic leukemia (APL), ATO has been utilized in other types of cancers, including solid tumors. Unfortunately, the results were not comparable with the effects on APL, and the resistance mechanism has not been clarified yet. This study intends to identify relevant genes and pathways affecting ATO drug sensitivity through genome-wide CRISPR-Cas9 knockdown screening to provide a panoramic view for further study of ATO targets and improved clinical outcomes.MethodsA genome-wide CRISPR-Cas9 knockdown screening system was constructed for ATO screening. The screening results were processed with MAGeCK, and the results were subjected to pathway enrichment analysis using WebGestalt and KOBAS. We also performed protein-protein interaction (PPI) network analysis using String and Cytoscape, followed by expression profiling and survival curve analysis of critical genes. Virtual screening was used to recognize drugs that may interact with the hub gene.ResultsWe applied enrichment analysis and identified vital ATO-related pathways such as metabolism, chemokines and cytokines production and signaling, and immune system responses. In addition, we identified KEAP1 as the top gene relating to ATO resistance. We found that KEAP1 expression was higher in the pan-cancer, including ALL, than in normal tissue. Patients with acute myeloid leukemia (AML) with higher KEAP1 expression had worse overall survival (OS). A virtual screen showed that etoposide and eltrombopag could bind to KEAP1 and potentially interact with ATO.DiscussionATO is a multi-target anticancer drug, and the key pathways regulating its sensitivity include oxidative stress, metabolism, chemokines and cytokines, and the immune system. KEAP1 is the most critical gene regulating ATO drug sensitivity, which is related to AML prognosis and may bind to some clinical drugs leading to an interaction with ATO. These integrated results provided new insights into the pharmacological mechanism of ATO and potentiate for further applications in cancer treatments.

BackgroundDiabetic peripheral neuropathy (DPN) is a serious complication in Diabetes Mellitus (DM) patients and the underlying mechanism is yet unclear. Ferroptosis has been recently intensively researched as a key process in the pathogenesis of diabetes but there yet has been no related bioinformatics-based studies in the context of DPNMethodsWe used data mining and data analysis techniques to screen differentially expressed genes (DEGs) and immune cell content in patients with DPN, DM patients and healthy participants (dataset GSE95849). These DEGs were then intersected with the ferroptosis dataset (FerrDb) to obtain ferroptosis DEGs and the associated key molecules and miRNAs interactions were predicted.ResultsA total of 33 ferroptosis DEGs were obtained. Functional pathway enrichment analysis revealed 127 significantly related biological processes, 10 cellular components, 3 molecular functions and 30 KEGG signal pathways. The biological processes that were significantly enriched were in response to extracellular stimulus and oxidative stress. Key modules constructed by the protein–protein interaction network analysis led to the confirmation of the following genes of interest: DCAF7, GABARAPL1, ACSL4, SESN2 and RB1. Further miRNA interaction prediction revealed the possible involvement of miRNAs such as miR108b-8p, miR34a-5p, mir15b-5p, miR-5838-5p, miR-192-5p, miR-222-3p and miR-23c. Immune-environment content of samples between DM and DPN patients revealed significant difference in the levels of endothelial cells and fibroblasts, which further speculates their possible involvement in the pathogenesis of DPN.ConclusionOur findings could provide insight for investigations about the role of ferroptosis in the development of DPN.

Conducting on-site surveys to assess tourists' spatial visitation patterns and preferences is both time and labor intensive. However, an assessment of regional visitation patterns based on social media data can be an important decision-making tool for tourism management. In this study, an assessment of the visitation patterns of Chinese mainland tourists in Sabah is conducted to identify high-visitation hotspots and their changes, as well as large-scale and small-scale temporal characteristics. The data is sourced from the Sina Weibo platform using web crawler technology. In this work, a spatial overlay analysis was used to identify the hotspots of Chinese tourists' visits and the spatial and temporal variations. The results of the study revealed that the hotspots visited by Chinese tourists prior to 2016 have shifted from the southeast coast of Sabah, to the west coast of Sabah. At a small scale, Chinese tourists' visitation hotspots were mainly concentrated in the urban area along the southwest coast of Kota Kinabalu, shifting to the southeast of the urban area in 2018. This study provides insights into the applicability of social media big data in regional tourism management and its potential to enhance fieldwork.