Breadth and polyfunctionality of T cell responses to human cytomegalovirus in men who have sex with men: relationship with HIV infection and frailty.

Cytomegalovirus (CMV)-seropositive adults have large T cell responses to a wide range of CMV proteins; these responses have been associated with chronic inflammation and frailty in people with or without HIV infection. We analyzed the relationships between chronic HIV infection, frailty, and the breadth and polyfunctionality of CD4 and CD8 T cell responses to CMV. Peripheral blood mononuclear cells from 42 men (20 without HIV and 22 with virologically suppressed HIV) in the Multicenter AIDS Cohort Study (MACS) were stimulated with peptide pools spanning 19 CMV open reading frames (ORFs). As measured by flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α, and IL-2, CD8 T cells from men with HIV responded to significantly more CMV ORFs than those from men without HIV. This was primarily due to a broader response to ORFs that are expressed during the late phase of CMV replication. The number of ORFs to which a participant's T cells responded was positively correlated with the sum of all that individual's T cell responses; these correlations were weaker in men with than without HIV. Polyfunctional CMV-specific CD4 responses (production of more than one cytokine) were significantly lower in men with than without HIV. Frailty status did not substantially affect the breadth or magnitude of the CMV-specific T cell responses. These results suggest that immune control of CMV infection is affected more by chronic HIV infection than by frailty. The differences between men with and without HIV were similar to those reported between young and older adults without HIV. IMPORTANCE: T cell responses to chronic cytomegalovirus (CMV) infection have significant biological and clinical implications in HIV infection and aging. Here, we systematically analyzed the breadth, magnitude, and polyfunctionality of T cell responses to multiple CMV antigens in men with and without HIV in the Multicenter AIDS Cohort Study (MACS), a longstanding study of the natural and treated history of HIV-1 infection in men who have sex with men. We found that the breadth and polyfunctionality of T cell responses to CMV were different between men with chronic, treated HIV and those without HIV. The reason for these differences is unknown, but these findings suggest that people with treated HIV may have more frequent CMV reactivation than people without HIV. Differences between people with and without HIV also resembled differences reported between young and older adults without HIV, supporting a role for the immune responses to CMV in the aging process.

MISP-mediated enhancement of pancreatic cancer growth through the Wnt/ß-catenin signaling pathway is suppressed by Fisetin.

Pancreatic cancer is a highly malignant tumor characterized by high mortality and low survival rates. The mitotic interactor and substrate of Plk1 (MISP) is a cancer-associated protein that regulates mitotic spindle localization and is highly expressed in several malignant tumors, contributing to tumor development. However, the function and regulatory mechanisms of MISP in pancreatic cancer remain unclear. In this study, we analyzed RNA sequencing data related to pancreatic cancer from the TCGA and GEO databases, identifying MISP as a potential prognostic marker for the disease. MISP was significantly upregulated in pancreatic cancer cells and tissues compared to normal pancreatic cells and tissues. Notably, in pancreatic cancer cells, high MISP protein expression promoted cell proliferation and growth. Mechanistically, the upregulation of MISP facilitated the nuclear accumulation of ß-catenin, thereby activating the Wnt/ß-catenin signaling pathway and promoting pancreatic cancer growth. In search of effective inhibitors of MISP expression, we screened an FDA-approved drug library and identified Fisetin as a potential suppressor of MISP expression. Fisetin was found to downregulate the transcription factor MYB, thereby reducing MISP expression. Further experiments demonstrated that Fisetin effectively inhibited the in vitro and in vivo growth of pancreatic cancer by suppressing the MISP/Wnt/ß-catenin signaling axis. In summary, our research has identified MISP as a novel therapeutic target in pancreatic cancer and uncovered its associated regulatory mechanisms.

Metal organic framework-assisted copper-modified titania (Cu/TiO2) with abundant exposed active sites and highly accessible pore channels for an enhanced photo-generation of hydrogen.

Metal-doping is a common strategy for establishing active sites on photocatalyst, but appropriately exposing them for maximized atomic utilization remains a great challenge in photocatalytic research. Herein, we propose a metal organic framework (MOF)-assisted approach to synthesis copper-modified titania (Cu-TiO2/Cu) photocatalyst with homogenously distributed and highly accessible active sites in its matrix. Significantly, an MOF precursor, namely NH2-MIL-125, with co-chelation of titania (Ti) and copper (Cu) was subjected to mild calcination, subsequently results in Cu-modified TiO2 with highly accessible channels to its inner surface. These channels provide not only a large reactive surface (>400 m2 g-1); they also enable facile modifying route for the pre-deposited Cu in prior to photoreaction. Specifically, NH3 treatment was applied to partially reduce deposited Cu ions (Cu+ and Cu2+) into Cu nanoparticles, where their interplays realize improved optical properties and charge separation during photoreactions. Furthermore, the NH3-induced Cu nanoparticles could also serve as the adsorptive site for H+, thereby enabling 5629 µmol h-1 g-1 H2 generation over the optimum photocatalyst of Cu20/TiO2/Cu500. Such performance is associated to 35.44 and 1.71-fold improvements compared to pure TiO2 (Cu0/TiO2) and untreated Cu-ion modified TiO2 (Cu20/TiO2), respectively. This work offers a new synthetic strategy for obtaining photocatalyst with evenly distributed and highly accessible active sites, thus improving the commensurability of photocatalytic H2 generation from the industrial perspective.

Relationship between nausea and vomiting and physical activity in patients with lung cancer undergoing first chemotherapy.

Objective: Nausea and vomiting are the distressing and debilitating side effects of chemotherapy. This study explores the relationship between the degree of nausea and vomiting and physical activity in patients with lung cancer during the first chemotherapy cycle. Design: A total of 107 patients with lung cancer who received platinum drugs during chemotherapy in a hospital in Shanghai, China, in 2023 were involved in this study. Data were collected with medical record system and self-reported questionnaires.Questionnaires included the International Physical Activity Questionnaire (IPAQ) and Index of Nausea, Vomiting, and Retching (INVR). IPAQ was used before chemotherapy; INVR was used on the second and sixth day of chemotherapy, followed by the analysis of the correlation between physical activity status and degree of nausea and vomiting during chemotherapy. The influencing factors of nausea and vomiting during chemotherapy in patients with lung cancer were analyzed using logistic regression analysis. Results: More than half of the patients experienced nausea, vomiting or retching related symptoms after chemotherapy, and the proportion of moderate to high physical activity was 50.5%. Univariate analysis showed that the degree of nausea and vomiting was influenced by factors such as age, gender, and history of drinking (P < 0.05). The degree of nausea and vomiting was negatively correlated with physical activity (P < 0.05). The multivariate linear analysis showed that gender, history of drinking, and moderate and high physical activity are contributing factors to nausea and vomiting during chemotherapy (P < 0.05). Conclusion: Moderate and high physical activity before chemotherapy is a protective factor for nausea and vomiting in patients with lung cancer. Physical activity can not only improve the degree of nausea and vomiting in patients with lung cancer but also reduce the incidence in these patients during the first chemotherapy cycle.

Mesoporous Silicon with Strontium-Powered Poly(Lactic-Co-Glycolic acid)/Gelatin-Based Dressings Facilitate Skin Tissue Repair.

Purpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management. Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats. Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.). Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.

Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

HBXIP induces PARP1 via WTAP-mediated m6A modification and CEBPA-activated transcription in cisplatin resistance to hepatoma.

Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m6A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAP promoter and further facilitating the promotion of the m6A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1 promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma.

Interfacial Engineering of MoS2@CoS2 Heterostructure Electrocatalysts for Effective pH-Universal Hydrogen Evolution Reaction.

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

Target NF-κB p65 for preventing posttraumatic joint contracture in rats.

RelA/p65 is as a crucial component of the nuclear factor κB (NF-κB) signaling pathway that has a significant impact on various fibrotic diseases. However, its role in the fibrosis of tissues surrounding the joint after traumatic injury remains unclear. In this study, rats were divided into three groups: non-operated control (NC) group, p65-siRNA treated (siRNA-p65) group, and negative siRNA treated (siRNA-neg) group. Then, 10 µL (10 nmol) of p65-siRNA was injected into the joint of the siRNA-p65 group. Meanwhile, 10 µL of negative siRNA was administered to the knee joint of the operated siRNA-neg group for comparison. The rats in the NC group did not receive surgery or drug intervention. After 4 weeks of right knee fixation in each group, X-ray measurements revealed significantly reduced degree of knee flexion contracture following p65-siRNA treatment (siRNA-neg: 77.73° ± 2.799°; siRNA-p65: 105.7° ± 2.629°, p < 0.0001). Histopathological examination revealed that the number of dense fibrous connective tissues decreased following p65-siRNA inhibition. Western blot analysis revealed significantly different expression levels of fibrosis-related proteins between the siRNA-p65 and siRNA-neg groups. Immunohistochemical analysis revealed a reduction in the average number of myofibroblasts in the siRNA-p65 group compared with that in the siRNA-neg group. Thus, intra-articular p65-siRNA injection could attenuate fibroblast activation and fibrosis-related protein production, suppress periarticular tissue fibrosis, and prevent joint contracture by downregulating the NF-κB p65 pathway. Statement of clinical significance: Intra-articular injection of p65-siRNA could reduce myofibroblast proliferation and fibrosis-related protein expression by downregulating the NF-κB p65 pathway, inhibit periarticular tissue fibrosis, and prevent joint adhesion, which represents a potential therapy in the prevention of joint fibrosis following traumatic injury.

Research on the Effectiveness of the Training of Nosocomial Infection Control Specialist Nurses under the Background of the New Crown Epidemic Based on Competence-based Theory.

Background: Coronavirus disease 2019 is highly contagious and has the potential to cause nosocomial infections, has placed a strong pressure on worldwide healthcare systems over the last years. Nosocomial infection has many influencing factors, among which the unreasonable operation of nurses accounts for 30.0%-50.0%. Therefore, strengthening the professional skill training of nurses is of great significance in reducing the nosocomial infection rate. Objective: This research aimed to explore the effectiveness of the training of nosocomial infection control on the competencies of specialist nurses under the background of the new crown epidemic based on competency-based theory. Design: This was a retrospective study. Setting: This study was performed in Dongfang Hospital, Affiliated to Tongji University. Participants: A total of 84 key nurses, each of them recommended by one department from June 2020 to June 2021, were chosen as study subjects, and they could actively participate in the training. Interventions: Nurses received systematic and standardized training based on competency-based theory under the background of coronavirus disease 2019, including focus group meeting, training of core emergency capability, teaching training and contingency plan for COVID-19 infection. Primary Outcome Measures: (1) core competence (2) job fit (3) core emergency response for major infectious diseases, and (4) nurses' satisfaction. All these primary outcomes can reflect the competencies of specialist nurses after training. Results: The scores in critical thinking and scientific research, clinical nursing, ethics and legal practice, professional development, education consulting and professional knowledge, professional skills, comprehensive quality, and professional ability of nurses training were higher than those before (P = .000). After training, the scores in relevant matters needing attention (international rescue, bioterrorist attacks, and infectious disease emergencies after natural disasters), filling in the People's Republic of China Infectious Disease Report Card, and the scope of reporting infectious disease emergencies were all higher than before (P = .000). All nurses had relatively high satisfaction with the curriculum setting and assessment form, with satisfaction of 100.0%, followed by training duration, with satisfaction of 92.86%. Conclusion: Under the background of coronavirus disease 2019, based on competence-based theory, training of nosocomial infection control specialist nurses could improve their core competence, job fit, and core emergency response capabilities, with high satisfaction. Under the background of the normalization of the prevention and control of the novel coronavirus pneumonia epidemic, the training model based on competence-based theory of nurses is worth promoting.

Exosomes derived from M2 macrophages prevent steroid-induced osteonecrosis of the femoral head by modulating inflammation, promoting bone formation and inhibiting bone resorption.

Inflammatory reactions are involved in the development of steroid-induced osteonecrosis of the femoral head(ONFH). Studies have explored the therapeutic efficacy of inhibiting inflammatory reactions in steroid-induced ONFH and revealed that inhibiting inflammation may be a new strategy for preventing the development of steroid-induced ONFH. Exosomes derived from M2 macrophages(M2-Exos) display anti-inflammatory properties. This study aimed to examine the preventive effect of M2-Exos on early-stage steroid-induced ONFH and explore the underlying mechanisms involved. In vitro, we explored the effect of M2-Exos on the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells(BMMSCs). In vivo, we investigated the role of M2-Exos on inflammation, osteoclastogenesis, osteogenesis and angiogenesis in an early-stage rat model of steroid-induced ONFH. We found that M2-Exos promoted the proliferation and osteogenic differentiation of BMMSCs. Additionally, M2-Exos effectively attenuated the osteonecrotic changes, inhibited the expression of proinflammatory mediators, promoted osteogenesis and angiogenesis, reduced osteoclastogenesis, and regulated the polarization of M1/M2 macrophages in steroid-induced ONFH. Taken together, our data suggest that M2-Exos are effective at preventing steroid-induced ONFH. These findings may be helpful for providing a potential strategy to prevent the development of steroid-induced ONFH.

KRAS/PI3K axis driven GTF3C6 expression and promotes LUAD via FAK pathway.

INTRODUCTION: Effective targeting drugs for KRAS mutation-mediated Lung Adenocarcinoma (LUAD) are currently are limited. OBJECTIVES: Investigating and intervening in the downstream key target genes of KRAS is crucial for clinically managing KRAS mutant-driven LUAD. GTF3C6, a newly identified member of the general transcription factor III (GTF3) family, plays a role in the transcription of RNA polymerase III (pol III)-dependent genes. However, its involvement in cancer remains unexplored. METHODS: This study examined the expression, roles, and potential molecular mechanisms of GTF3C6 in LUAD tissues, LSL-KrasG12D/+;LSL-p53-/- LUAD mouse models, and LUAD patients-derived organoid using Western blot, qRT-PCR, immunofluorescence, immunohistochemistry, and gene manipulation assays. RESULTS: We present the first evidence that GTF3C6 is highly expressed in LUAD tissues, LSL-KrasG12D/+;LSL-p53-/- LUAD mouse models, and LUAD organoids, correlating with poor clinical prognosis. Furthermore, GTF3C6 was found to promote anchorage-independent proliferation, migration, and invasion of LUAD cells. Mechanistically, KRAS mutation drives GTF3C6 expression through the PI3K pathway, and GTF3C6 knockdown reverses the malignant phenotype of KRAS mutation-driven LUAD cells. Additionally, the FAK pathway emerged as a crucial downstream signaling pathway through which GTF3C6 mediates the malignant phenotype of LUAD. Finally, GTF3C6 knockdown suppresses LUAD organoid formation and inhibits tumor growth in vivo. CONCLUSION: Our findings demonstrate that GTF3C6, driven by KRAS mutation, promotes LUAD development by regulating FAK phosphorylation, suggesting its potential as a biomarker and therapeutic target in KRAS mutant-driven LUAD.

The experiences of family resilience in patients with permanent colostomy and their spouses: A dyadic qualitative study.

PURPOSE: With the prolonged survival time of patients with permanent colostomy for colorectal cancer, they and their spouses face tremendous pressure and development dilemmas that can easily lead to family adaptation crises. This qualitative study amid to explore the dyadic experiences of family resilience among Chinese patients with permanent colostomy and their spouses. METHODS: A phenomenological research method was adopted. Semi-structured, in-depth, face-to-face interviews with 10 dyads of patients with permanent colostomy and their spouses were recruited through purposive sampling from a public tertiary hospital in China from March 2023 to July 2023.The Dyadic interview analysis and Colaizzi methods were used to analyze the interview data. RESULTS: Three themes and nine subthemes were developed. (1) family crisis and dichotomous coping with stress-family crisis and coping pressure caused by enterostomy; (2) Adjustment and adaptation within the family-Joint adjustment and adaptation within the couple's family; and (3) integration and utilization of multi-dimensional social external resources (micro-level, meso-level, and macro-level). CONCLUSIONS: Couples living with permanent colostomy often undergo a complex emotional journey, experiencing varied levels of individual stress as they navigate social interactions and daily activities, which can contribute to a decline in family adaptation. With the help of the perspective of family advantage, health practitioners should pay attention to the evaluation of individual factors and family environmental resources, to fully mobilize advantage resources and give effective interventions to improve the family and social adaptation level of patients and their spouses.

Heparin versus normal saline for the care of peripheral intravenous catheters in children: A meta-analysis.

AIM: To conduct a meta-analysis to evaluate the role of heparin versus normal saline lock in the care of peripheral intravenous catheters. DESIGN: A meta-analysis. METHODS: This meta-analysis searched nine databases for randomized controlled trials (RCTs) on heparin versus normal saline for the care of peripheral intravenous catheters in children up to April 5, 2023. The quality of included RCTs was evaluated using the risk of bias tool of Cochrane library. RevMan5.3 software was used for data analysis. RESULTS: Ten RCTs with a total of 1255 children were involved. Meta-analysis indicated that heparin lock reduced the incidence of blockage of peripheral intravenous catheter [OR = 2.01, 95% CI (1.42,2.84), p < 0.001], prolonged the duration of peripheral intravenous catheter indwelling[MD = -0.43, 95% CI (-0.75, -0.11), p = 0.008]. There were no statistical differences in the incidence of phlebitis [OR = 1.02, 95% CI (0.59, 1.74), p = 0.95 W]. PUBLIC CONTRIBUTION: Heparin may have more benefits in the nursing care of peripheral intravenous catheters compared with normal saline.

Roflumilast: Modulating neuroinflammation and improving motor function and depressive symptoms in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease causing central nervous system demyelination, often associated with depression. Current treatments for MS do not effectively address both physical disability and depression. Roflumilast, a phosphodiesterase-4 inhibitor with anti-inflammatory properties, has shown promise for autoimmune diseases. METHODS: We used an experimental autoimmune encephalomyelitis (EAE) rat model to study roflumilast's effects. Motor dysfunction and depression symptoms were assessed, and histopathological analysis evaluated its anti-inflammatory properties. Flow cytometry examined the drug's impact on brain microglia. TNF-α, IL-1ß, and IL-6 levels in hippocampal tissue were assessed using ELISA kits. RESULTS: Roflumilast improved motor dysfunction and depression symptoms in EAE rats. Histopathological analysis revealed reduced inflammation, demyelination, and axonal loss in the spinal cord. Roflumilast suppressed microglial cell activation and conversion to pro-inflammatory M1-type cells. Flow cytometry showed roflumilast inhibited inflammatory marker expression in microglia and their activation in the hippocampus. IL-6 was identified as a roflumilast target for suppressing hippocampal inflammation. LIMITATIONS: This study used an animal model and did not assess long-term or potential side effects of roflumilast treatment. CONCLUSIONS: Roflumilast holds promise as a treatment for depression and motor impairment in MS. Its anti-inflammatory properties, reducing inflammation and inhibiting microglial activation, suggest its potential for MS therapy. However, further research is needed to evaluate long-term effects and safety in MS patients.

Application of direct observation of operational skills in nursing skill evaluation of pressure injury: A randomized clinical trial.

This was a non-blinded, single-centre, randomized, controlled clinical trial that compared the effectiveness of direct observation of procedural skills (DOPSs)with traditional assessment methods in pressure injury (PI) care skills. The study population included 82 nursing professionals randomly assigned to the study group (n = 41) and the control group (n = 41). Both groups of nurses underwent a 6-month training in PI care skills and were subsequently evaluated. The main outcome variables were the PI skill operation scores and theoretical scores. Secondary outcome variables included satisfaction and critical thinking abilities. Independent sample t-tests and chi-square tests were used to assess differences between the two groups of nurses. The results showed no statistically significant difference in PI skill operation scores between the two groups of nurses (p > 0.05). When comparing the PI theoretical scores, the study group scored higher than the control group, and this difference was statistically significant (p < 0.05). In terms of satisfaction assessment, the study group and the control group showed differences in improving self-directed learning, enhancing communication skills with patients, improving learning outcomes and increasing flexibility in clinical application (p < 0.05). When comparing critical thinking abilities between the two groups of nurses, there was no statistically significant difference at the beginning of the training, but after 3 months following the training, there was a statistically significant difference between the two groups (p < 0.01).The results indicated that the DOPS was effective in improving PI theoretical scores, increasing nurse satisfaction with the training and enhancing critical thinking abilities among nurses.

[A novel method for detecting circulating tumor cells immunity based on micro-nano technique].

This study was to develop a new method for detecting circulating tumor cells (CTCs) with high sensitivity and specificity, therefore to detect the colorectal cancer as early as possible for improving the detection rate of the disease. To this end, we prepared some micro-column structure microchips modified with graphite oxide-streptavidin (GO-SA) on the surface of microchips, further coupled with a broad-spectrum primary antibody (antibody1, Ab1), anti-epithelial cell adhesion molecule (anti-EpCAM) monoclonal antibody to capture CTCs. Besides, carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) were coupled with colorectal cancer related antibody as specific antibody 2 (Ab2) to prepare complex. The sandwich structure consisting of Ab1-CTCs-Ab2 was constructed by the microchip for capturing CTCs. And the electrochemical workstation was used to detect and verify its high sensitivity and specificity. Results showed that the combination of immunosensor and micro-nano technology has greatly improved the detection sensitivity and specificity of the immunosensor. And we also verified the feasibility of the immunosensor for clinical blood sample detection, and successfully recognitized detection and quantization of CTCs in peripheral blood of colorectal cancer patients by this immunosensor. In conclusion, the super sandwich immunosensor based on micro-nano technology provides a new way for the detection of CTCs, which has potential application value in clinical diagnosis and real-time monitoring of disease.

Risk factors for adverse pregnancy outcomes in Chinese women: a meta-analysis.

Objective: This study examined the associated risk factors of adverse pregnancy outcomes among Chinese females and furnished some fundamental principles and recommendations for enhanced prevention of adverse pregnancy and preservation of women's well-being. Methods: A systematic review was conducted by retrieving the MEDLINE (The National Library of Medicine), Embase, PubMed, and Cochrane databases. The relevant risk factors for adverse pregnancy in Chinese women were retrieved from May 2017 to April 2023. Use Review Manager for data analysis. Calculate the merge effect based on data attributes using mean difference (MD) or odds ratio (or) and 95% confidence interval (CI). The meta-analysis was registered at INPLASY (International Platform of Registered Systematic Review and Meta-analysis Protocols, 202340090). Results: A total of 15 articles were included, with a total of 946,818 Chinese pregnant women. Moreover, all the literature was scored by the NOS (Newcastle-Ottawa Scale), and all literatures were ≥7 points, which were evaluated as high quality. There are seven risk factors related to adverse pregnancy in Chinese women: parity, pregnancy frequency, education level, smoking, gestational diabetes, gestational weeks, and age. Moreover, the main risk factors for adverse pregnancy are pregnancy frequency, education level, gestational diabetes mellitus, and age. Conclusion: The pregnancy frequency, education level, gestational diabetes mellitus, and age were significantly associated with the adverse pregnancy in Chinese women, whereas gestational weeks, smoking, and parity had no significant effect on adverse pregnancy.

Ab Initio Time-Domain Study of Charge Relaxation and Recombination in N-Doped Cu2O.

Cu2O is a good photoelectric material with excellent performance, and its crystal structure, electronic structure, and optical properties have been extensively studied. To further illustrate the charge distribution and the carrier transport in this system, the e-h recombination dynamics was studied. It is found that N doping induced a shallower impurity band above the VBM, leading to significant charge localization around the impurity atom. NAMD simulation reveals that the N doping system possesses a longer e-h nonradiative recombination time scale. Therefore, we demonstrate that the formation of the impurity band and charge localization play an essential role in suppressing e-h recombination in N doping systems. This work is conducive for understanding the carrier transport mechanism in N-doped Cu2O.

CUL3 induces mitochondrial dysfunction via MRPL12 ubiquitination in renal tubular epithelial cells.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease worldwide and the strongest predictor of mortality in patients with diabetes. Despite its significance, the pathological mechanism underlying the onset and progression of DKD remains incompletely understood. In this study, we have shown that mitochondrial ribosomal protein L12 (MRPL12) plays a significant role in DKD by modulating mitochondrial function. We demonstrated that MRPL12 was mainly ubiquitinated at K150 in renal tubular epithelial cells. We have found that Cullin3 (CUL3), an E3 ubiquitin ligase, directly interacts with MRPL12 and induces the K63-linked ubiquitination of MRPL12, resulting in mitochondrial biosynthesis dysfunction. Moreover, under high-glucose (HG) conditions in renal tubular epithelial cells, we observed up-regulation of CUL3 expression, significant increase in CUL3-mediated ubiquitination of MRPL12 and dysregulation of mitochondrial biosynthesis. Notably, CUL3 knockdown stabilised the MRPL12 protein and protected mitochondrial biosynthesis under HG conditions. Our findings provide novel insight into how CUL3 affects mitochondrial biosynthesis in renal tubular epithelial cells through MRPL12 ubiquitination and suggest a potential therapeutic strategy for DKD in the future.