Evolution and function analysis of auxin response factors reveal the molecular basis of the developed root system of Zygophyllum xanthoxylum.

BACKGROUND: As a xerophytic shrub, forming developed root system dominated with lateral roots is one of the effective strategies for Zygophyllum xanthoxylum to adapt to desert habitat. However, the molecular mechanism of lateral root formation in Z. xanthoxylum is still unclear. Auxin response factors (ARFs) are a master family of transcription factors (TFs) in auxin-mediated biological processes including root growth and development. RESULTS: Here, to determine the relationship between ARFs and root system formation in Z. xanthoxylum, a total of 30 potential ZxARF genes were first identified, and their classifications, evolutionary relationships, duplication events and conserved domains were characterized. 107 ARF protein sequences from alga to higher plant species including Z. xanthoxylum are split into A, B, and C 3 Clades, consisting with previous studies. The comparative analysis of ARFs between xerophytes and mesophytes showed that A-ARFs of xerophytes expanded considerably more than that of mesophytes. Furthermore, in this Clade, ZxARF5b and ZxARF8b have lost the important B3 DNA-binding domain partly and completely, suggesting both two proteins may be more functional in activating transcription by dimerization with AUX/IAA repressors. qRT-PCR results showed that all A-ZxARFs are high expressed in the roots of Z. xanthoxylum, and they were significantly induced by drought stress. Among these A-ZxARFs, the over-expression assay showed that ZxARF7c and ZxARF7d play positive roles in lateral root formation. CONCLUSION: This study provided the first comprehensive overview of ZxARFs and highlighted the importance of A-ZxARFs in the lateral root development.

Ventral tegmental area dopaminergic circuits participates in stress-induced chronic postsurgical pain in male mice.

BACKGROUND: Chronic postsurgical pain (CPP) markedly impairs patients' quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established. It remains uncertain whether the dopamine signals in the rostral anterior cingulate cortex (rACC), which regulate pain, derive from the VTA. This study aims to explore the role of VTA-rACC dopaminergic circuits in a mouse model of CPP induced by CSDS. METHODS: We conducted CSDS on C57BL/6 J wild-type male mice (n = 12-16 mice/group) and DAT-cre male mice (n = 10-12 mice/group). After 10 days of CSDS, a left posterior plantar incision was made to establish a mouse model of CPP. Paw withdrawal thresholds (PWTs) were evaluated using Von-Frey fibre stimulation. The open field test (OFT) and elevated plus maze test (EPM) were used to assess pain-related negative emotions. We used immunofluorescence staining and Western Blot to analyse D1, D2, c-Fos, and TH expression. DAergic fibre projections in the VTA-rACC neural pathway were traced using retrograde tracing and immunofluorescence staining. Optogenetics and Chemogenetics were employed to manipulate DAergic neurons in the VTA and their axons in the rACC. RESULTS: The ipsilateral PWTs in male C57BL/6 J mice significantly decreased after surgery, returning to baseline after seven days. Conversely, in CSDS mice, ipsilateral PWTs remained reduced for at least 30 days post-incision. A significant reduction in TH-positive neurons expressing c-Fos in the VTA of CPP mice was observed 15 days post-incision. Activating DAergic neurons significantly improved ipsilateral PWTs and locomotor performance in the OFT and EPM in CPP mice post-incision. Additionally, D1 expression in the rACC was found to decrease in CPP mice, and this reduction counteracted the increase in PWTs caused by activating DAergic neuron axon terminals in the rACC. CONCLUSION: CSDS results in chronicity of postsurgical nociception and anxiety-like negative emotions, with alterations in DA transmission playing a role in CPP. Specific activation of DAergic neurons mitigates nociceptive responses and anxiety-like bahaviors, possibly mediated by D1 receptors in the rACC.

DUSP5 regulated by YTHDF1-mediated m6A modification promotes epithelial-mesenchymal transition and EGFR-TKI resistance via the TGF-ß/Smad signaling pathway in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) patients have a dismal survival rate because of cancer metastasis and drug resistance. The study aims to identify the genes that concurrently modulate EMT, metastasis and EGFR-TKI resistance, and to investigate the underlying regulatory mechanisms. METHODS: Cox regression and Kaplan-Meier analyses were applied to identify prognostic oncogenes in LUAD. Gene set enrichment analysis (GSEA) was used to indicate the biological functions of the gene. Wound-healing and Transwell assays were used to detect migratory and invasive ability. EGFR-TKI sensitivity was evaluated by assessing the proliferation, clonogenic survival and metastatic capability of cancer cells with treatment with gefitinib. Methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) analyses established the level of m6A modification present on the target gene and the protein's capability to interact with RNA, respectively. Single-sample gene set enrichment (ssGSEA) algorithm used to investigate levels of immune cell infiltration. RESULTS: Our study identified dual-specificity phosphatase 5 (DUSP5) as a novel and powerful predictor of adverse outcomes for LUAD by using public datasets. Functional enrichment analysis found that DUSP5 was positively enriched in EMT and transforming growth factor-beta (TGF-ß) signaling pathway, a prevailing pathway involved in the induction of EMT. As expected, DUSP5 knockdown suppressed EMT via inhibiting the canonical TGF-ß/Smad signaling pathway in in vitro experiments. Consistently, knockdown of DUSP5 was first found to inhibit migratory ability and invasiveness of LUAD cells in in vitro and prevent lung metastasis in in vivo. DUSP5 knockdown re-sensitized gefitinib-resistant LUAD cells to gefitinib, accompanying reversion of EMT progress. In LUAD tissue samples, we found 14 cytosine-phosphate-guanine (CpG) sites of DUSP5 that were negatively associated with DUSP5 gene expression. Importantly, 5'Azacytidine (AZA), an FDA-approved DNA methyltransferase inhibitor, restored DUSP5 expression. Moreover, RIP experiments confirmed that YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), a m6A reader protein, could bind DUSP5 mRNA. YTHDF1 promoted DUSP5 expression and the malignant phenotype of LUAD cells. In addition, the DUSP5-derived genomic model revealed the two clusters with distinguishable immune features and tumor mutational burden (TMB). CONCLUSIONS: Briefly, our study discovered DUSP5 which was regulated by epigenetic modification, might be a potential therapeutic target, especially in LUAD patients with acquired EGFR-TKI resistance.

Liraglutide Reduces Alcohol Consumption, Anxiety, Memory Impairment, and Synapse Loss in Alcohol Dependent Mice.

Glucagon-like peptide 1 (GLP-1) analogues have been commercialized for the management of type 2 diabetes. Recent studies have underscored GLP-1's role as a modulator of alcohol-related behavior. However, the role of the GLP-1 analogue liraglutide on alcohol-withdrawal responses have not been fully elucidated. Liraglutide binds to the G-protein-coupled receptor and activates an adenylyl cyclase and the associated classic growth factor signaling pathway, which acts growth factor-like and neuroprotective properties. The underlying neurobiological mechanisms of liraglutide on alcohol withdrawal remains unknown. This study endeavored to explore the effects of liraglutide on the emotion and memory ability of alcohol-withdrawal mice, and synaptic morphology in the medial prefrontal cortex (mPFC) and the hippocampus (HP), and thus affects the relapse-like drinking of alcohol-withdrawal mice. The alcohol-withdrawal group was reintroduced to a 20% v/v alcohol and water through the two-bottle choice for four consecutive days, a period referred to as alcohol re-drinking. Male C57BL/6J mice were exposed to a regimen of 20% alcohol and water for a duration of 6 weeks. This regimen established the two-bottle choice model of alcohol exposure. Learning capabilities, memory proficiency, and anxiety-like behavior were evaluated using the Morris water maze, open field, and elevated plus maze paradigms. Furthermore, synaptic morphology and the levels of synaptic transport-related proteins were assessed via Golgi staining and Western Blot analysis after a two-week alcohol deprivation period. Alcohol re-drinking of alcohol-withdrawal mice was also evaluated using a two-bottle choice paradigm. Our findings indicate that liraglutide can substantially decrease alcohol consumption and preference (p < 0.05) in the alcohol group and enhance learning and memory performance (p < 0.01), as well as alleviate anxiety-like behavior (p < 0.01) of alcohol-withdrawal mice. Alcohol consumption led to a reduction in dendritic spine density in the mPFC and HP, which was restored to normal levels by liraglutide (p < 0.001). Furthermore, liraglutide was found to augment the levels of synaptic transport-related proteins in mice subjected to alcohol withdrawal (p < 0.01). The study findings corroborate that liraglutide has the potential to mitigate alcohol consumption and ameliorate the memory impairments and anxiety induced by alcohol withdrawal. The therapeutic efficacy of liraglutide might be attributed to its role in counteracting synapse loss in the mPFC and HP regions and thus prevented relapse-like drinking in alcohol-withdrawal mice.

Policy implementation deviation of government purchase of old age care services in Jiangsu, China: based on empirical and policy analysis.

BACKGROUND: Government purchase of social forces to participate in old age care services can release the burden of social care. Current research on performance evaluation in this field mainly focussed on the establishment of appropriate evaluation indices. However, discussion on the policy implementation deviation is scarce. This study aimed to evaluate the performance of China's local government purchase of old age care services, analyse the characteristics of related policies and explore their deviation. METHODS: The persons who participated in the Training of the Trainer (ToT) organized by the Red Cross Society were enrolled. The policy documents were obtained from the official websites. The K-means cluster was used to determine the project performance grades. We compared the project performance grades between service objects and undertakers with different characteristics utilizing the non-parametric test. Based on the framework of 'Collaborative Participation - Project Performance Objective', we analysed the content of relevant policy aiding by NVivo 12. RESULTS: Data of project performance were collected from 306 participants. The standardized mean score of the efficiency dimension was the lowest (0.70 ± 0.24). The projects were divided into four grades: poor (17.0%), average (27.5%), good (12.4%) and excellent (43.1%). There were statistically significant differences in project performance grades only between advanced ageing groups (Z = 2.429, P = 0.015). As well, the policy also mentioned that the services focus should be tilted towards the oldest old. The purchasers mainly involved the Ministry of Civil Affairs and Health management departments in the policy. Respite services were less mentioned in the responsibilities of the undertakers. The requirement for efficiency and effectiveness was mentioned in less than half of the policy documents. CONCLUSION: Policy attention is needed for the responsibilities and functions of the intermediate purchasing force, as well as more precise directions and responsibilities of undertakers. The purchasers and undertakers should improve management abilities and capacity of old age care services and focus on associated factors to achieve the best marginal benefit. In addition, the embedded performance evaluation needs to be updated periodically to bridge the deviation between policy implementation and policy formulation.

A multi-stakeholder collaboration model of dementia-friendly communities: Experiences from Nanjing, China.

The care for people with dementia (PwD) in low- and middle-income countries (LMICs) is dominated by home care and supplemented sporadically by public care provided using public resources. In the context of community resources cannot meet the demand for high-quality services for PwD, dementia-friendly communities (DFCs) provide ideas for alleviating this situation by integrating resources from multiple stakeholders. However, there is still a considerable gap between the capacity of services and the demand of PwD. Based on the experience of elderly services and DFCs construction in Nanjing, China, this study developed a stakeholder collaboration model and clarified the collaborative relationship among stakeholders such as the government, communities, and medical institutions in meeting the needs of PwD. This work summarizes the partnerships and specific actions of stakeholders and highlights the importance of facilitating resource integration to provide comprehensive services.

Epidemiology and risk factors of oral frailty among older people: an observational study from China.

OBJECTIVES: This study aimed to compare the prevalence of oral frailty among community-dwelling older people in Nanjing, China with the usage of different measurements, and to investigate the potential risk factors of oral frailty. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 338 community-dwelling older people in Nanjing, China were recruited. METHODS: Oral frailty was measured based on the Oral Frailty Index-8 (OFI-8) scale and other measurement methods including the number of natural teeth (TN), repetitive saliva-swallowing test (RSST), and oral diadochokinesis (ODK). The chi-square test and the binary logistic regression analysis were performed to identify potential risk factors for oral frailty. RESULTS: There were 310 participants included in the analysis. Prevalence of oral frailty by using the OFI-8, OFI-8 + TN, OFI-8 + ODK, OFI-8 + TN + ODK and RSST measurement methods were 69.0%, 27.4%, 51.9%, 21.0% and 2.9%, respectively. Passive smoking (OR = 2.04; 95%CI 1.03-4.03), being widowed/unmarried (OR1 = 2.53; 95%CI 1.25-5.10; OR2 = 2.94; 95%CI 1.12-7.77), pre-frailty (OR = 1.76; 95%CI 1.03-3.01), frailty (OR = 3.01; 95%CI 1.39-6.54), and aged 80 years and above (OR = 3.99; 95%CI 1.35-11.81) were found to be risk factors of oral frailty by the usage of the four kinds of measurement methods. CONCLUSIONS AND IMPLICATIONS: The definition and diagnostic criteria of oral frailty are strongly needed to be unified in future research. Only subjective assessment is not enough for assessing oral frailty. Among objective indicators, RSST is not suitable as a screening method for oral frailty. In addition, objective indicators including TN and ODK should be valued for early screening and preventive interventions. The risk factors of oral frailty include physical frailty, passive smoking, and being widowed.

Jianpi Huayu Decoction suppresses cellular senescence in colorectal cancer via p53-p21-Rb pathway: Network pharmacology and in vivo validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Huayu Decoction (JHD) is an herbal prescription in traditional Chinese medicine based on Sijunzi Decoction to treat patients with colorectal cancer (CRC). Its effects on the inhibition of CRC cell proliferation and tumor growth are promising; however, its multicomponent nature makes a complete understanding of its mechanism challenging. AIM OF THE STUDY: To explore the therapeutic targets and underlying molecular pathways of JHD in CRC treatment using network pharmacology techniques and in vivo validation. MATERIALS AND METHODS: The active ingredients and targets of JHD were identified, compound-target interactions were mapped, and enrichment analyses were conducted. We identified the hub targets of JHD-induced cellular senescence in CRC. The binding affinities between compounds and targets were evaluated through molecular docking. Subsequently, we conducted bioinformatic analyses to compare the expression of hub targets between colorectal tissue and normal tissue. Finally, in vivo experiments were carried out utilizing a xenograft model to assess the effects of JHD on cellular senescence biomarkers. RESULTS: Network pharmacology revealed 129 active ingredients in JHD that were associated with 678 targets, leading to the construction of compound-target and target-pathway networks. Enrichment analyses highlighted key pathways including cellular senescence. Based on this, hub targets associated with cellular senescence were determined and validated. Molecular docking indicated favorable interactions between the active components and hub targets. Gene expression and survival analysis in CRC tissue were consistent with the potential roles of hub genes. Animal experiments showed that JHD triggered cellular senescence and suppressed the growth of CRC by regulating the p53-p21-Rb signaling pathway. CONCLUSIONS: This research adopted network pharmacology, bioinformatics, and animal experiments to unveil that JHD induces cellular senescence in CRC by influencing the p53-p21-Rb pathway and senescence-associated secretory phenotypes, highlighting its potential as a CRC treatment.

Neuroimage Analysis Methods and Artificial Intelligence Techniques for Reliable Biomarkers and Accurate Diagnosis of Schizophrenia: Achievements Made by Chinese Scholars Around the Past Decade.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) is characterized by significant cognitive and behavioral disruptions. Neuroimaging techniques, particularly magnetic resonance imaging (MRI), have been widely utilized to investigate biomarkers of SZ, distinguish SZ from healthy conditions or other mental disorders, and explore biotypes within SZ or across SZ and other mental disorders, which aim to promote the accurate diagnosis of SZ. In China, research on SZ using MRI has grown considerably in recent years. STUDY DESIGN: The article reviews advanced neuroimaging and artificial intelligence (AI) methods using single-modal or multimodal MRI to reveal the mechanism of SZ and promote accurate diagnosis of SZ, with a particular emphasis on the achievements made by Chinese scholars around the past decade. STUDY RESULTS: Our article focuses on the methods for capturing subtle brain functional and structural properties from the high-dimensional MRI data, the multimodal fusion and feature selection methods for obtaining important and sparse neuroimaging features, the supervised statistical analysis and classification for distinguishing disorders, and the unsupervised clustering and semi-supervised learning methods for identifying neuroimage-based biotypes. Crucially, our article highlights the characteristics of each method and underscores the interconnections among various approaches regarding biomarker extraction and neuroimage-based diagnosis, which is beneficial not only for comprehending SZ but also for exploring other mental disorders. CONCLUSIONS: We offer a valuable review of advanced neuroimage analysis and AI methods primarily focused on SZ research by Chinese scholars, aiming to promote the diagnosis, treatment, and prevention of SZ, as well as other mental disorders, both within China and internationally.

ZBTB20 suppresses tumor growth in glioblastoma through activating the TET1/FAS/caspase­3 pathway.

Zinc finger and BTB domain containing 20 (ZBTB20) is a key transcription repressor that regulates multiple physiological and pathophysiological processes. Thus far, the role of ZBTB20 in glioblastoma (GBM), a World Health Organization grade IV glioma, remains unclear. In the present study, the expression profile data of ZBTB20 in GBM tissues from public databases was analyzed. It was found that ZBTB20 expression in GBM tissues was significantly lower than that measured in lower grade glioma tissues. Furthermore, patients with GBM with lower ZBTB20 expression were associated with a shorter overall survival time. Gain- and loss-of-function experiments in GBM cells were also performed. The results demonstrated that ZBTB20 overexpression decreased GBM cell proliferation, while ZBTB20 knockdown significantly enhanced it. Cell cycle analysis showed the ZBTB20 overexpression may have inhibited proliferation through cell cycle arrest at the G2/M phase, while ZBTB20 knockdown increased the percentages of cells in both the S phase and G2/M phase. Ten-eleven translocation 1 (TET1) is an important tumor suppressor involved in the formation of various types of tumor, and it was upregulated in ZBTB20-overexpressing GBM cells. It was further demonstrated that ZBTB20 activated the TET1/FAS/caspase-3 pathway. The results of the present study therefore indicated the potential role of ZBTB20 as a tumor suppressor and therapeutic target for GBM.

Field-aged rice hull biochar stimulated the methylation of mercury and altered the microbial community in a paddy soil under controlled redox condition changes.

Mercury (Hg) contaminated paddy soils are hot spots for methylmercury (MeHg) which can enter the food chain via rice plants causing high risks for human health. Biochar can immobilize Hg and reduce plant uptake of MeHg. However, the effects of biochar on the microbial community and Hg (de)methylation under dynamic redox conditions in paddy soils are unclear. Therefore, we determined the microbial community in an Hg contaminated paddy soil non-treated and treated with rice hull biochar under controlled redox conditions (< 0 mV to 600 mV) using a biogeochemical microcosm system. Hg methylation exceeded demethylation in the biochar-treated soil. The aromatic hydrocarbon degraders Phenylobacterium and Novosphingobium provided electron donors stimulating Hg methylation. MeHg demethylation exceeded methylation in the non-treated soil and was associated with lower available organic matter. Actinobacteria were involved in MeHg demethylation and interlinked with nitrifying bacteria and nitrogen-fixing genus Hyphomicrobium. Microbial assemblages seem more important than single species in Hg transformation. For future directions, the demethylation potential of Hyphomicrobium assemblages and other nitrogen-fixing bacteria should be elucidated. Additionally, different organic matter inputs on paddy soils under constant and dynamic redox conditions could unravel the relationship between Hg (de)methylation, microbial carbon utilization and nitrogen cycling.

Tectorigenin Inhibits Glycolysis-induced Cell Growth and Proliferation by Modulating LncRNA CCAT2/miR-145 Pathway in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) places a heavy burden on global health. Tectorigenin (Tec) is a type of flavonoid-based compound obtained from the Chinese medical herb Leopard Lily Rhizome. It was found to exhibit remarkable anti-tumor properties in previous studies. However, the effect and molecular mechanisms of Tec in colorectal cancer have not been reported. OBJECTIVE: The objective of this study was to explore the action of Tec in proliferation and glycolysis in CRC and the potential mechanism with regard to the long non-coding RNA (lncRNA) CCAT2/micro RNA-145(miR-145) pathway in vitro and in vivo . METHODS: The anti-tumor effect of Tec in CRC was examined in cell and animal studies, applying Cell Counting Kit-8 (CCK-8) assay as well as xenograft model experiments. Assay kits were utilized to detect glucose consumption and lactate production in the supernatant of cells and animal serum. The expression of the glycolysis-related proteins was assessed by Western Blotting, and levels of lncRNA CCAT2 and miR-145 in CRC tissue specimens and cells were assessed by realtime quantitative PCR (RT-qPCR). RESULTS: Tec significantly suppressed cell glycolysis and proliferative rate in CRC cells. It could decrease lncRNA CCAT2 in CRC cells but increase the expression of miR-145. LncRNA CCAT2 overexpression or inhibition of miR-145 could abolish the inhibitive effects of Tec on the proliferation and glycolysis of CRC cells. The miR-145 mimic rescued the increased cell viability and glycolysis levels caused by lncRNA CCAT2 overexpression. Tec significantly inhibited the growth and glycolysis of CRC xenograft tumor. The expression of lncRNA CCAT2 decreased while the expression of miR-145 increased after Tec treatment in vivo. CONCLUSION: Tec can inhibit the proliferation and glycolysis of CRC cells through the lncRNA CCAT2/miR-145 axis. Altogether, the potential targets discovered in this research are of great significance for CRC treatment and new drug development.

Characteristics and duties of clinical research nurses: a scoping review.

Introduction: The characteristics and duties of clinical research nurses (CRNs) are constantly developing and changing with the progress of medical technology and increasing needs in patient care. With the continuous deepening and standardization of clinical trials, the importance and status of CRNs during the whole process of clinical trials are also increasingly valued. Methods: A scoping review of studies related to the characteristics and duties of CRNs was conducted to clarify relevant roles and concepts. An electronic search was conducted on three English databases (PubMed, Web of Science, Embase) and two Chinese databases (CNKI and Wanfang database) in December 2023. Two authors independently screened the literature, extracted information from the included literature, and summarized and reported the findings. Results: A total of 26 articles published between 1991 and 2023 were analyzed, and four characteristics of CRNs were identified as participants and managers of clinical trials, caregivers and protectors of subjects, coordinators of research teams, and educators. Basic knowledge, skills and literacy, communication and coordination ability, and advanced research ability are the competencies required for CRNs. Conclusion: Further studies should focus on the importance of various characteristics of CRNs, so as to improve the quality of clinical trials and promote clinical evidence-based practice.

Natural hair color and skin cancers: A two-sample Mendelian randomization study.

Previous observational studies have indicated an association between hair color and the risk of melanoma and keratinocyte skin cancer (KSC); however, different hair colors show inconsistent effects on skin cancers. Here, we conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between natural hair color and skin cancers by using 211 single nucleotide polymorphisms as genetic instruments from a genome-wide meta-analysis of 360,270 individuals of European ancestry. Light hair colors (red, blonde, and light brown) were associated with high levels of cutaneous melanoma (CM) and KSC (CM-inverse variance weighted [IVW] odds ratio [OR]-red: 1.034, 95% confidence interval [CI]: 1.025-1.044, P < 0.001; OR-blonde: 1.008, 95% CI: 1.003-1.014, P = 0.003; OR-light brown: 1.006, 95% CI: 1.002-1.011, P = 0.009; KSC-IVW OR-red: 1.078, 95% CI: 1.053-1.103, P < 0.001; OR-blonde: 1.024, 95% CI: 1.009-1.040, P = 0.002; OR-light brown: 1.018, 95% CI: 1.004-1.033, P = 0.01). However, dark brown hair showed an inverse causal relationship with skin cancers (CM IVW OR: 0.987, 95% CI: 0.984-0.990, P < 0.001; KSC IVW OR: 0.979, 95% CI: 0.970-0.988, P < 0.001). Black hair was associated with a decreased risk of KSC (IVW OR: 0.954, 95% CI: 0.913-0.997, P = 0.036) but showed no causal relationship with CM. The present study provides strong MR evidence of a causal association between hair color and skin cancer. Secondary MR analyses enhances result robustness by replicating findings, exploring gender-specific effects, and providing a more comprehensive understanding of the complex relationship between hair color and skin cancers. More large-scale MR studies or randomized controlled trials are required to further investigate the mechanisms of the association between hair color and skin cancers.

Abnormal methylation mediated upregulation of LINC00857 boosts malignant progression of lung adenocarcinoma by modulating the miR-486-5p/NEK2 axis.

LINC00857 is frequently dysregulated in varying cancers, which in turn exerts carcinogenic effects; however, its DNA methylation status in promoter region and molecular mechanisms underlying the progression of lung adenocarcinoma (LUAD) remain rarely understood. Through bioinformatics analysis, we examined the expression state and methylation site of LINC00857 in LUAD and further investigated the properties of LINC00857 as a competitive endogenous RNA in the cancer progression. The current study revealed that the overexpression of LINC00857 in LUAD tissue and cells was mainly caused by the hypomethylation of the promoter region. LINC00857 knockdown prominently reduced cell proliferation, impeded cell migration and invasion, and restrained lymph node metastasis, with enhancing radiosensitivity. The effects of LINC00857 on tumor growth were also investigated in nude mice models. Subsequently, the downstream factors, miR-486-5p and NEK2, were screened, and the putative regulatory axis was examined. Overall, the regulatory effect of methylation-mediated LINC00857 overexpression on miR-486-5p/NEK2 axis may be a new mechanism for LUAD progression.

Efficacy and safety of percutaneous transhepatic biliary radiofrequency ablation in patients with malignant obstructive jaundice.

BACKGROUND: Percutaneous transhepatic cholangiodrainage (PTCD) and endoscopic retrograde cholangiopancreatography/endoscopic nasobiliary drainage are the most common clinical procedures for jaundice control in patients with unresectable malignant obstructive jaundice, yet the safety and effect of endobiliary radiofrequency ablation (EB-RFA) combined PTCD is rarely reported, in this article, we report our experience of EB-RFA combined PTCD in such patients. AIM: To retrospectively study the efficacy and safety of EB-RFA combined PTCD in patients with unresectable malignant obstructive jaundice. METHODS: Patients with unresectable malignant obstructive jaundice treated with EB-RFA under PTCD were selected, the bile ducts of the right posterior lobe was selected as the target bile ducts in all cases. The general conditions of all patients, preoperative tumour markers, total bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB), alkaline phosphatase (ALP), and glutamyl transferase (GGT) before and on the 7th day after the procedure, as well as perioperative complications, stent patency time and patient survival were recorded. RESULTS: All patients successfully completed the operation, TBIL and DBIL decreased significantly in all patients at the 7th postoperative day (P = 0.009 and 0.006, respectively); the values of ALB, ALP and GGT also decreased compared with the preoperative period, but the difference was not statistically significant. Perioperative biliary bleeding occurred in 2 patients, which was improved after transfusion of blood and other conservative treatments, pancreatitis appeared in 1 patient after the operation, no serious complication and death happened after operation. Except for 3 patients with loss of visits, the stent patency rate of the remaining 14 patients was 100% 71% and 29% at the 1st, 3rd, and 6th postoperative months respectively, with a median survival of 4 months. CONCLUSION: EB-RFA under PTCD in patients with unresectable malignant obstructive jaundice has a satisfactory therapeutic effect and high safety, which is worthy of further clinical practice.

Observational study on stability of within-day glycemic variability of type 2 diabetes inpatients treated with decoctions of traditional Chinese medicine.

Background: Within-day glycemic variability (GV), characterized by frequent and significant fluctuations in blood glucose levels, is a growing concern in hospitalized patients with type 2 diabetes mellitus (T2DM). It is associated with an increased risk of hypoglycemia and potentially higher long-term mortality rates. Robust clinical evidence is needed to determine whether traditional Chinese medicine (TCM) decoctions can be a beneficial addition to the management of within-day GV in this patient population. Methods: This retrospective cohort study utilized data from adult inpatients diagnosed with T2DM admitted to the Traditional Chinese Medicine Hospital of Kaifeng. The primary outcome investigated was the association between the use of TCM decoctions and improved stability of within-day GV. Blood glucose variability was assessed using the standard deviation of blood glucose values (SDBG). For each patient, the total number of hospitalization days with SDBG below 2 mmol/L was calculated to represent within-day GV stability. Hospitalization duration served as the secondary outcome, compared between patients receiving TCM decoctions and those who did not. The primary analysis employed a multivariable logistic regression model, with propensity score matching to account for potential confounding variables. Results: A total of 1,360 patients were included in the final analysis. The use of TCM decoctions was significantly associated with enhanced stability of within-day GV (OR = 1.77, 95% CI: 1.34-2.33, P < 0.01). This association was most prominent in patients with a diagnosis of deficiency syndrome (predominantly qi-yin deficiency, accounting for 74.8% of cases) and a disease duration of less than 5 years (OR = 2.28, 95% CI: 1.21-4.29, P = 0.03). However, TCM decoctions did not exert a statistically significant effect on hospitalization duration among patients with T2DM (OR = 0.96, 95% CI: 0.91-1.01, P = 0.22). Conclusion: This study suggests that TCM decoctions may be effective in improving within-day GV stability in hospitalized patients with T2DM. This effect appears to be most pronounced in patients diagnosed with deficiency syndrome, particularly those with qi-yin deficiency and a shorter disease course. Further investigation is warranted to confirm these findings and elucidate the underlying mechanisms.

Ultrasound pretreatment enhances moisture migration and drying quality of mulberry via microstructure and cell-wall polysaccharides nanostructure modification.

The effects of ultrasound pretreatment (20 kHz, 30 W/L) on mulberries' texture, microstructure, characteristics of cell-wall polysaccharides, moisture migration, and drying quality were investigated over exposure times ranging from 15 to 45 min. Ultrasound induced softening of mulberry tissue, accompanied by an increase in water-soluble pectin and a decrease in chelate-soluble pectin and Na2CO3-soluble pectin concentrations. Noticeable depolymerization of the pectin nanostructure was observed in the pretreated mulberries, along with a decrease in molecular weight, attributed to side-chain structure cleavage. Ultrasound loosened the cell wall structure, increased free water content and freedom, thereby reducing water diffusion resistance. Ultrasound pretreatment reduced drying time by 11.2 % to 23.3 % at various processing times compared to controls. Due to significantly enhanced drying efficiency, the optimal pretreatment time (30 min) yielded dried mulberries with higher levels of total phenolics and total anthocyanins, along with an increased antioxidant capacity. The results of this study provide insights into the mechanisms by which ultrasound pretreatment can effectively enhance the mulberry drying process.

Assessing the temporal within-day glycemic variability during hospitalization in patients with type 2 diabetes patients using continuous glucose monitoring: a retrospective observational study.

AIMS: Frequent and extensive within-day glycemic variability (GV) in blood glucose levels may increase the risk of hypoglycemia and long-term mortality in hospitalized patients with diabetes. We aimed to assess the amplitude and frequency of within-day GV in inpatients with type 2 diabetes and to explore the factors influencing within-day GV. METHODS: We conducted a single-center, retrospective observational study by analyzing hospital records and 10-day real-time continuous glucose monitoring data. Within-day GV was assessed using the coefficient of variation (%CV). The primary outcome was the amplitude and frequency of within-day GV. The frequency of within-day GV was assessed by the consecutive days (CD) of maintaining within the target %CV range after first reaching it (CD after first reaching the target) and the maximum consecutive days of maintaining within the target %CV range (Max-CD). The target %CV range was less than 24.4%. We evaluated the factors influencing within-day GV using COX regression and Poisson regression models. RESULTS: A total of 1050 cases were analyzed, of whom 86.57% reduced the amplitude of within-day GV before the sixth day of hospitalization. Of the 1050 hospitalized patients, 66.57% stayed within the target %CV range for less than two days after first reaching the target and 69.71% experienced a Max-CD of fewer than four days. Reducing the average postprandial glucose excursion (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.77-0.85; incidence rate ratios [IRR]: 0.72, 95% CI: 0.69-0.74) and the use of α-glucosidase inhibitors (IRR: 1.1, 95% CI: 1.01-1.18) and glucagon-like peptide-1 agonist (IRR: 1.30, 95% CI: 1.02-1.65) contributed to reducing the amplitude and decreasing the frequency of within-day GV. However, the use of insulin (HR: 0.64, 95% CI: 0.55-0.75; IRR: 0.86, 95% CI: 0.79-0.93) and glinide (HR: 0.47, 95% CI: 0.31-0.73; IRR: 0.84, 95% CI: 0.73-0.97) may lead to an increased frequency of within-day GV. CONCLUSIONS: An increasing frequency of within-day GV was observed during the hospitalization in patients with type 2 diabetes, despite the effective reduction in the amplitude of within-day GV. Using medications designed to lower postprandial blood glucose could contribute to minimize the risk of frequent within-day GV.

More reliable biomarkers and more accurate prediction for mental disorders using a label-noise filtering-based dimensional prediction method.

The integration of neuroimaging with artificial intelligence is crucial for advancing the diagnosis of mental disorders. However, challenges arise from incomplete matching between diagnostic labels and neuroimaging. Here, we propose a label-noise filtering-based dimensional prediction (LAMP) method to identify reliable biomarkers and achieve accurate prediction for mental disorders. Our method proposes to utilize a label-noise filtering model to automatically filter out unclear cases from a neuroimaging perspective, and then the typical subjects whose diagnostic labels align with neuroimaging measures are used to construct a dimensional prediction model to score independent subjects. Using fMRI data of schizophrenia patients and healthy controls (n = 1,245), our method yields consistent scores to independent subjects, leading to more distinguishable relabeled groups with an enhanced classification accuracy of 31.89%. Additionally, it enables the exploration of stable abnormalities in schizophrenia. In summary, our LAMP method facilitates the identification of reliable biomarkers and accurate diagnosis of mental disorders using neuroimages.