Selenobacteria-mediated Se transformation and uptake involving the unique genetic code.

Selenium (Se) is a crucial micronutrient for human health. Plants are the primary source of Se for humans. Selenium in the soil serves as the primary source of Se for plants. The soil contains high total Se content in large areas in Guangxi, China. However, the available Se is low, hindering Se uptake by plants. Microorganisms play a pivotal role in the activation of Se in the soil, thereby enhancing its uptake by plants. In this study, selenobacteria were isolated from Se-rich soils in Guangxi. Then two selenobacteria strains, YLB1-6 and YLB2-1, representing the highest (30,000 µg/mL) and lowest (10,000 µg/mL) Se tolerance levels among the Se-tolerant bacteria, were selected for subsequent analysis. Although the two selenobacteria exhibited distinct effects, they can significantly transform Se species, resulting in a decrease in the soil residual Se (RES-Se) content while concurrently increasing the available Se (AVA-Se) content. Selenobacteria also enhance the transformation of Se valencies, with a significant increase observed in soluble Se6+ (SOL-Se6+). Additionally, selenobacteria can elevate the pH of acidic soil. Selenobacteria also promote the uptake of Se into plants. After treatment with YLB1-6 and YLB2-1, the Se content in the aboveground part of Chinese flowering cabbage increased by 1.96 times and 1.77 times, respectively, while the Se accumulation in the aboveground part of the plant significantly increased by 104.36% and 81.69%, respectively, compared to the control. Further whole-genome sequencing revealed the genetic difference between the two selenobacteria. Additionally, 46 and 38 candidate genes related to selenium utilization were identified from YLB1-6 and YLB2-1, respectively. This work accelerates our understanding of the potential molecular mechanism of Se biofortification by selenobacteria. It also provides microorganisms and gene targets for improving crop varieties or microorganisms to exploit the rich Se source in soil.

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.

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.

Constraint-Induced Movement Therapy Modulates Neuron Recruitment and Neurotransmission Homeostasis of the Contralesional Cortex to Enhance Function Recovery after Ischemic Stroke.

Stroke often results in long-term and severe limb dysfunction for a majority of patients, significantly limiting their activities and social participation. Constraint-induced movement therapy (CIMT) is a rehabilitation approach aimed explicitly at enhancing upper limb motor function following a stroke. However, the precise mechanism remains unknown. This study explores how CIMT may alleviate forelimb paralysis in ischemic mice, potentially through structural and functional remodeling of brain regions beyond the infarct area, especially the contralateral cortex. We demonstrated that CIMT recruits neurons from the contralesional cortex into the network that innervates the affected forelimb, as evidenced by PRV retrograde nerve tracing. Additionally, we investigated how CIMT influences synaptic plasticity in the contralateral cortex by evaluating synaptic growth marker levels and neurotransmission's homeostatic regulation. Our findings uncover a rehabilitative mechanism by which CIMT treats ischemic stroke, characterized by increased recruitment of neurons from the contralateral cortex into the network that innervates the affected forelimb, facilitated by homeostatic regulation of neurotransmission.

Effect of emotional stimulus on response inhibition in people with mild cognitive impairment: an event-related potential study.

Background: A few studies are emerging to explore the issue of how aging promotes emotional response inhibition. However, there is a lack of empirical study concerning the impact of pathological cognitive impairment on emotional response inhibition. The present study investigated the effect of emotion on response inhibition in people with mild cognitive impairment, the stage of cognitive impairment before dementia. Methods: We used two emotional stop-signal tasks to explore whether the dual competition framework considering limited cognitive resources could explain the relationship between emotion and response inhibition in mild cognitive impairment. Results: The results showed that negative emotions prolonged N2 latency. The Go trial accuracy was reduced in the high-arousal negative conditions and the stop-signal reaction time was prolonged under high-arousal conditions. This study also verified impaired response inhibition in mild cognitive impairment and found that negative emotions prolonged P3 latency in mild cognitive impairment. Conclusion: Emotional information interferes with response inhibition in mild cognitive impairment populations, possibly because emotional information captures more attentional resources, thus interfering with response inhibition that relies on common-pool resources.

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.

Inhibition of METTL3 in macrophages provides protection against intestinal inflammation.

Inflammatory bowel disease (IBD) is prevalent, and no satisfactory therapeutic options are available because the mechanisms underlying its development are poorly understood. In this study, we discovered that increased expression of methyltransferase-like 3 (METTL3) in macrophages was correlated with the development of colitis and that depletion of METTL3 in macrophages protected mice against dextran sodium sulfate (DSS)-induced colitis. Mechanistic characterization indicated that METTL3 depletion increased the YTHDF3-mediated expression of phosphoglycolate phosphatase (PGP), which resulted in glucose metabolism reprogramming and the suppression of CD4+ T helper 1 (Th1) cell differentiation. Further analysis revealed that glucose metabolism contributed to the ability of METTL3 depletion to ameliorate colitis symptoms. In addition, we developed two potent small molecule METTL3 inhibitors, namely, F039-0002 and 7460-0250, that strongly ameliorated DSS-induced colitis. Overall, our study suggests that METTL3 plays crucial roles in the progression of colitis and highlights the potential of targeting METTL3 to attenuate intestinal inflammation for the treatment of colitis.

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.

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.

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.

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.

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.

Core competence of midwives in township hospitals and its influencing factors-A cross-sectional study.

Objective: This study aimed to assess the core competence of midwives in township hospitals through a self-assessment questionnaire. The relationship between professional identity and core competence and the factors influencing midwives' core competence was also investigated. Method: Convenience sampling was conducted in 77 township hospitals in Ganzhou, Jiangxi Province, China, with 150 participants. The questionnaires were distributed online in November 2021. We conducted a descriptive data analysis, a correlation analysis of the two variables of professional identity and core competencies, and multivariate linear regression to analyse the influencing factors, including the sociodemographic information, the Midwife Core Competence Scale, and the Nurses' Professional Identity Scale scores. Results: The mean score for the core competence was 206.43 (±37.45) out of 270. The highest score was for pregnancy care (3.97 ± 0.70) and the lowest was for newborn care (3.72 ± 0.78). The independent sample t-test results and one-way analysis of variance showed that qualifications, midwifery training situation, and midwifery working years had differential effects on midwives' core competencies (P < 0.05). Multiple linear regression showed that qualifications, midwifery working years, and level of professional identity were influencing factors (P < 0.05). Conclusions: The core competencies of midwives in township hospitals were lower than those reported in other studies. Advancements in education, midwifery working years, and professional identity may increase midwives' core competencies.

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.

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.

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.

Performance of the digital cell morphology analyzer MC-100i in a multicenter study in tertiary hospitals in China.

BACKGROUND: This study investigated the performance of the MC-100i, a pre-commercial digital morphology analyzer utilizing a convolutional neural network algorithm, in a multicentric setting involving up to 11 tertiary hospitals in China. METHODS: Blood smears were analyzed by MC-100i, verified by morphologists, and manually differentiated. The classification performance on WBCs and RBCs was evaluated by comparing the classification results using different methods. The PLT and PLT clump counting performance was also assessed. The total assay time including hands-on time was evaluated. RESULTS: The agreements between pre- and post-classification were high for normal WBCs (κ > 0.96) and lower for overall abnormal WBCs (κ = 0.90). The post-classification results correlated well with manual differentials for both normal and abnormal WBCs (r > 0.93), except for basophils (r = 0.8480) and atypical lymphocytes (r = 0.8211). The clinical sensitivity and specificity of each RBC abnormality after verification were above 90 % using microscopy reviews as the reference. The PLTs counted by the MC-100i before and after verification correlated well with those measured by the PLT-O mode (r = 0.98). Moreover, PLT clumps were successfully classified by the analyzer in EDTA-dependent pseudothrombocytopenia blood samples. CONCLUSIONS: The MC-100i is an accurate and reliable digital cell morphology analyzer, offering another intelligent option for hematology laboratories.

Upregulation of SEMP1 Contributes to Improving the Biological Functions of Trophoblast via the PI3K/AKT Pathway in Preeclampsia.

Disturbance of extravillous trophoblast infiltration is associated with preeclampsia (PE), a severe condition of pregnancy characterized by hypertension and proteinuria. Senescence-associated epithelial membrane protein 1 (SEMP1), an integral membrane protein, is a vital component of tight junction strands in epithelial or endothelial cells, with no clear function reported in PE. Gene Expression Omnibus (GEO) datasets showed that SEMP1 expression was downregulated in the placental tissues of PE patients, which was confirmed by assessing SEMP1 levels in placental samples collected in our hospital. Furthermore, less SEMP1 was detected in cytokeratin 7 positive trophoblast cells in the spiral arteries of rat placentas post L-arginine methyl ester hydrochloride (L-NAME) treatment. Trophoblast cells acquired robust ability of proliferation, migration, and invasion when SEMP1 was overexpressed. Such capability was weakened in SEMP1-silenced cells. Trophoblast cells overexpressing SEMP1 secreted more vascular endothelial growth factor A (VEGFA), which facilitated the tube formation of human umbilical vein endothelial cells. Blockade of PI3K/AKT signaling transduction with LY294002 dampened the effects of SEMP1 on trophoblast cells. Collectively, we firstly indicated that SEMP1 inhibition is a potential driver for PE, which may be associated with the deactivation of the PI3K/AKT pathway.