Ts2O mediated deoxygenative C2-dithiocarbamation of quinoline N-oxides with CS2 and amines.

A general, efficient and practical protocol for Ts2O promoted deoxygenative dithiocarbamation of quinoline N-oxides with in situ generated dithiocarbamic acids from CS2 and amines is reported. The reaction proceeded well under transition-metal free conditions to obtain a variety of novel quinoline-dithiocarbamate compounds with wide functional group tolerance and good to high yields.

Protective Effect of Mesenchymal Stem Cell Active Factor Combined with Alhagi maurorum Extract on Ulcerative Colitis and the Underlying Mechanism.

Ulcerative colitis (UC) is a relapsing and reoccurring inflammatory bowel disease. The treatment effect of Alhagi maurorum and stem cell extracts on UC remains unclear. The aim of the present study was to investigate the protective role of Alhagi maurorum combined with stem cell extract on the intestinal mucosal barrier in an intestinal inflammation mouse model. Sixty mice were randomly divided into a control group, model group, Alhagi group, MSC group, and MSC/Alhagi group. MSC and Alhagi extract were found to reduce the disease activity index (DAI) scores in mice with colitis, alleviate weight loss, improve intestinal inflammation in mice (p < 0.05), preserve the integrity of the ileal wall and increase the number of goblet cells and mucin in colon tissues. Little inflammatory cell infiltration was observed in the Alhagi, MSC, or MSC/Alhagi groups, and the degree of inflammation was significantly alleviated compared with that in the model group. The distribution of PCNA and TNF-alpha in the colonic tissues of the model group was more disperse than that in the normal group (p < 0.05), and the fluorescence intensity was lower. After MSC/Alhagi intervention, PCNA and TNF-alpha were distributed along the cellular membrane in the MSC/Alhagi group (p < 0.05). Compared with that in the normal control group, the intensity was slightly reduced, but it was still stronger than that in the model group. In conclusion, MSC/Alhagi can alleviate inflammatory reactions in mouse colonic tissue, possibly by strengthening the protective effect of the intestinal mucosal barrier.

Ts2O Promoted Deoxygenative C-H Dithiocarbonation of Quinoline N-Oxides with Potassium O-Alkyl Xanthates.

A simple, efficient, and practical method for the synthesis of S-quinolyl xanthates was developed via Ts2O-promoted deoxygenative C-H dithiocarbonation of quinoline N-oxides with various potassium O-alkyl xanthates. The reaction performed well under transition-metal-free, base-free, and room-temperature conditions with wide substrate tolerance. Employing potassium O-tert-butyl xanthate (tBuOCS2K) as a nucleophile, some valuable quinoline-2-thiones were unexpectedly obtained in a one-pot reaction without any additional base.

Intermittent fasting improves the oocyte quality of obese mice through the regulation of maternal mRNA storage and translation by LSM14B.

Obesity has significant repercussions for female reproductive health, including adverse effects on oocyte quality, fertility, embryo development and offspring health. Here, we showed that intermittent fasting (IF) has several notable effects on follicular development, oocyte development and maturation and offspring health in obese mice. IF treatment prevents obesity-associated germline-soma communication defects, mitochondrial dysfunction, oxidative damage, apoptosis, and spindle/chromosomal disruption. RNA-sequencing analysis of oocytes from normal diet (ND), high-fat diet (HFD), and HFD + IF mice indicated that IF treatment improved mitochondrial oxidative phosphorylation function and mRNA storage and translation, which was potentially mediated by the Smith-like family member 14 B (LSM14B). Knockdown of LSM14B by siRNA injection in oocytes from ND mice recapitulates all the translation, mitochondrial dysfunction and meiotic defect phenotypes of oocytes from HFD mice. Remarkably, the injection of Lsm14b mRNA into oocytes from HFD mice rescued the translation, mitochondrial dysfunction and meiotic defect phenotypes. These results demonstrated that dysfunction in the oocyte translation program is associated with obesity-induced meiotic defects, while IF treatment increased LSM14B expression and maternal mRNA translation and restored oocyte quality. This research has important implications for understanding the effects of obesity on female reproductive health and offers a potential nonpharmacological intervention to improve oocyte quality and fertility in obese individuals.

Intern-Nursing Students' Knowledge of Vascular Catheter-Associated Infections and Its Associated Factors: A Cross-Sectional Survey in China.

Background: Medical personnel contact with the patient closely, and their knowledge of vascular catheter-associated infections (VCAIs) is closely related to the prevention of VCAIs. Researchers mainly pay attention to the VCAIs knowledge of doctors and nurses but rarely pay attention to the nursing students in the hospital internship stage. Purpose: To investigate the current situation of knowledge of intern-nursing students in VCAIs, and analyze its influencing factors. Patients and Methods: 843 intern-nursing students were selected from 10 hospitals in five regions of eastern, western, southern, northern, and central China from June 26 to July 31, 2023, using a two-stage random sampling method. A self-designed questionnaire with good reliability and validity was used to investigate their knowledge of VCAIs, and t-test, multiple linear regression analysis, and Welch t-test were used to analyze the collected data by using SPSS Statistics 26.0 (IBM Corp., Armonk, NY). Results: Intern nursing students' mean score of VCAIs knowledge was 48.66 (SD=15.77), with a score below 60 (unqualified) accounting for 75.4%, a score of 60-79 (qualified) accounting for 19.7%, a score of 80-89 (good) accounting for 3.6%, and a score of above 90 accounting for 1.3%. Students who attended VCAIs training three or more times had higher scores than those who did not attend training (B: 4.706, p=0.001), knowledge scores of students with a bachelor's degree or above were higher than those with junior college degree or below (B: 8.479, p<0.001), students who interned in tertiary hospitals had higher scores than those practicing in secondary hospitals (B:12.381, p<0.001) and scores of students in hospital training were significantly higher than study independently (B:4.116, p=0.007). Conclusion: Intern-nursing students have a relatively low level of knowledge about VCAIs. It is recommended to strengthen clinical systematic and standardized training, improve the knowledge mastery level of intern-nursing students, and enhance their ability to handle VCAIs.

TsCl promoted deoxygenative phosphorothiolation of quinoline N-oxides towards S-quinolyl phosphorothioates.

A convenient, efficient and practical approach for the synthesis of S-quinolyl phosphorothioates via cheap TsCl promoted deoxygenative C2-H phosphorothiolation of quinoline N-oxides with readily available triethylammonium O,O-dialkylphosphorothioates was developed. The reaction performed well under transition-metal-free conditions at room temperature with a very short reaction time (10-20 min). Preliminary studies showed that the current transformation underwent a nucleophilic substitution process.

Growth differentiation factor 9 regulates the expression of estrogen receptors via Smad2/3 signaling in goat cumulus cells.

Both oocyte secretory factors (OSFs) and estrogen are essential for the development and function of mammalian ovarian follicles, playing synergistic role in regulating oocyte growth. OSFs can significantly affect the biological processes regulated by estrogen in cumulus cells (CCs). It is a scientific question worth investigating whether oocyte secretory factors can influence the expression of estrogen receptors in CCs. In our study, we observed a significant increase in the mRNA and protein expressions of estrogen receptor ß (Esr2/ERß) and G-protein-coupled estrogen receptor (GPER) in cumulus cells of goat cumulus-oocyte complexes (COCs) cultured in vitro for 6 h. Furthermore, the addition of 10 ng/mL growth-differentiation factor 9 (GDF9) and 5 ng/mL bone morphogenetic protein 15 (BMP15) to the culture medium of goat COCs resulted in a significant increase in the expressions of ERß and GPER in cumulus cells. To explore the mechanism further, we performed micromanipulation to remove oocyte contents and co-cultured the oocytectomized complexes (OOXs) with denuded oocytes (DOs) or GDF9/BMP15. The expressions of ERß and GPER in the co-culture groups were significantly higher than those in the OOXs group, but there was no difference compared to the COCs group. Mechanistically, we found that SB431542 (inhibitor of GDF9 bioactivity), but not LDN193189 (inhibitor of BMP15 bioactivity), abolished the upregulation of ERß and GPER in cumulus cells and the activation of Smad2/3 signaling. In conclusion, our results demonstrate that the oocyte secretory factor GDF9 promotes the activation of Smad2/3 signaling in cumulus cells during goat COCs culture in vitro, and the phosphorylation of Smad2/3 induces the expression of estrogen receptors ERß and GPER in cumulus cells.

PLZF protein forms a complex with protein TET1 to target TCF7L2 in undifferentiated spermatogonia.

The transcription factor promyelocytic leukemia zinc finger (PLZF, also known as ZBTB16) is critical for the self-renewal of spermatogonial stem cells (SSCs). However, the function of PLZF in SSCs is not clear. Here, we found that PLZF acted as an epigenetic regulator of stem cell maintenance and self-renewal of germ cells. The PLZF protein interacts with the ten-eleven translocation 1 (TET1) protein and subsequently acts as a modulator to regulate the expression of self-renewal-related genes. Furthermore, Transcription Factor 7-like 2 (TCF7L2) is promoted by the coordination of PLZF and Tri-methylation of lysine 4 on histone H3 (H3K4me3). In addition, testicular single-cell sequencing indicated that TCF7L2 is commonly expressed in the PLZF cluster. We demonstrated that PLZF directly targets TCF7L2 and alters the landscape of histone methylation in the SSCs nucleus. Meanwhile, the RD domain and Zn finger domain of PLZF synergize with H3K4me3 and directly upregulate TCF7L2 expression at the transcriptional level. Additionally, we identified a new association between PLZF and the histone methyltransferase EZH2 at the genomic level. Our study identified a new association between PLZF and H3K4me3, established the novel PLZF&TET1-H3K4me3-TCF7L2 axis at the genomic level which regulates undifferentiated spermatogonia, and provided a platform for studying germ cell development in male domestic animals.

UCHL1 maintains microenvironmental homeostasis in goat germline stem cells.

Spermatogonial stem cells (SSCs) play a crucial role in mammalian spermatogenesis and maintain the stable inheritance of the germline in livestock. However, stress and bacterial or viral infections can disrupt immune homeostasis of the testes, thereby leading to spermatogenesis destruction and infertility, which severely affects the health and productivity of mammals. This study aimed to explore the effect of ubiquitin C-terminal hydrolase L1 (UCHL1) knockdown (KD) in goat SSCs and mouse testes and investigate the potential anti-inflammatory function of UCHL1 in a poly(I:C)-induced inflammation model to maintain microenvironmental homeostasis. In vitro, the downregulation of UCHL1 (UCHL1 KD) in goat SSCs increased the expression levels of apoptosis and inflammatory factors and inhibited the self-renewal and proliferation of SSCs. In vivo, the structure of seminiferous tubules and spermatogenic cells was disrupted after UCHL1 KD, and the expression levels of apoptosis- and inflammation-related proteins were significantly upregulated. Furthermore, UCHL1 inhibited the TLR3/TBK1/IRF3 pathway to resist poly(I:C)-induced inflammation in SSCs by antagonizing HSPA8 and thus maintaining SSC autoimmune homeostasis. Most importantly, the results of this study showed that UCHL1 maintained immune homeostasis of SSCs and spermatogenesis. UCHL1 KD not only inhibited the self-renewal and proliferation of goat SSCs and spermatogenesis but was also involved in the inflammatory response of goat SSCs. Additionally, UCHL1 has an antiviral function in SSCs by antagonizing HSPA8, which provides an important basis for exploring the specific mechanisms of UCHL1 in goat spermatogenesis.

Ball milling synthesis of S-quinolyl xanthates via coupling of haloquinolines with potassium O-alkyl xanthates.

An environmentally benign protocol that provides various S-quinolyl xanthates via a ball milling enabled cross coupling reaction of haloquinolines and readily available potassium O-alkyl xanthates is first reported. The reaction proceeded well under mild, transition metal- and solvent-free conditions, making it an attractive method for the introduction of xanthates into the quinoline scaffold.

Risk Factors and Predictive Models for Peripherally Inserted Central Catheter Unplanned Extubation in Patients With Cancer: Prospective, Machine Learning Study.

BACKGROUND: Cancer indeed represents a significant public health challenge, and unplanned extubation of peripherally inserted central catheter (PICC-UE) is a critical concern in patient safety. Identifying independent risk factors and implementing high-quality assessment tools for early detection in high-risk populations can play a crucial role in reducing the incidence of PICC-UE among patients with cancer. Precise prevention and treatment strategies are essential to improve patient outcomes and safety in clinical settings. OBJECTIVE: This study aims to identify the independent risk factors associated with PICC-UE in patients with cancer and to construct a predictive model tailored to this group, offering a theoretical framework for anticipating and preventing PICC-UE in these patients. METHODS: Prospective data were gathered from January to December 2022, encompassing patients with cancer with PICC at Xiangya Hospital, Central South University. Each patient underwent continuous monitoring until the catheter's removal. The patients were categorized into 2 groups: the UE group (n=3107) and the non-UE group (n=284). Independent risk factors were identified through univariate analysis, the least absolute shrinkage and selection operator (LASSO) algorithm, and multivariate analysis. Subsequently, the 3391 patients were classified into a train set and a test set in a 7:3 ratio. Utilizing the identified predictors, 3 predictive models were constructed using the logistic regression, support vector machine, and random forest algorithms. The ultimate model was selected based on the receiver operating characteristic (ROC) curve and TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) synthesis analysis. To further validate the model, we gathered prospective data from 600 patients with cancer at the Affiliated Hospital of Qinghai University and Hainan Provincial People's Hospital from June to December 2022. We assessed the model's performance using the area under the curve of the ROC to evaluate differentiation, the calibration curve for calibration capability, and decision curve analysis (DCA) to gauge the model's clinical applicability. RESULTS: Independent risk factors for PICC-UE in patients with cancer were identified, including impaired physical mobility (odds ratio [OR] 2.775, 95% CI 1.951-3.946), diabetes (OR 1.754, 95% CI 1.134-2.712), surgical history (OR 1.734, 95% CI 1.313-2.290), elevated D-dimer concentration (OR 2.376, 95% CI 1.778-3.176), targeted therapy (OR 1.441, 95% CI 1.104-1.881), surgical treatment (OR 1.543, 95% CI 1.152-2.066), and more than 1 catheter puncture (OR 1.715, 95% CI 1.121-2.624). Protective factors were normal BMI (OR 0.449, 95% CI 0.342-0.590), polyurethane catheter material (OR 0.305, 95% CI 0.228-0.408), and valved catheter (OR 0.639, 95% CI 0.480-0.851). The TOPSIS synthesis analysis results showed that in the train set, the composite index (Ci) values were 0.00 for the logistic model, 0.82 for the support vector machine model, and 0.85 for the random forest model. In the test set, the Ci values were 0.00 for the logistic model, 1.00 for the support vector machine model, and 0.81 for the random forest model. The optimal model, constructed based on the support vector machine, was obtained and validated externally. The ROC curve, calibration curve, and DCA curve demonstrated that the model exhibited excellent accuracy, stability, generalizability, and clinical applicability. CONCLUSIONS: In summary, this study identified 10 independent risk factors for PICC-UE in patients with cancer. The predictive model developed using the support vector machine algorithm demonstrated excellent clinical applicability and was validated externally, providing valuable support for the early prediction of PICC-UE in patients with cancer.

Experience of postpartum depression among Chinese women: A meta-synthesis of qualitative research.

Postpartum depression (PPD) is associated with various adverse health outcomes among mothers and babies. Meta-synthesis can improve our understanding of postpartum women's experiences. However, the meta-analysis of PPD among Chinese women is limited. Therefore, a meta-analysis was conducted to evaluate the prevalence of PPD among Chinese women and if and how traditional culture may exacerbate PPD. Qualitative studies on the experiences of Chinese women with PPD were searched from database establishment until May 2022 in ten databases. The meta-ethnography reporting guidelines and framework was applied to the writing and reporting of this review. The protocol for this systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42022323388). 2321 studies were retrieved, and 11 studies qualified for the meta-synthesis. The final five themes extracted and re-conceptualized from these studies were as follows: the gap between expectation and reality, conflicts with family, physical and mental frustrations, critical needs for coping with changes, and measures against PPD. Chinese women with PPD frequently feel vulnerable physically, mentally, or both after childbirth and often have conflicts with their families due to the influence of traditional Chinese culture. Family relationships and social support often are factors preventing women from seeking help.

Nurses' Willingness and Demand for Internet+Home Care Services and the Associated Factors in Municipal Hospitals in China: Cross-Sectional Survey.

BACKGROUND: Developing Internet+home care (IHC) services is a promising way to address the problems related to population aging, which is an important global issue. However, IHC services are in their infancy in China. Limited studies have investigated the willingness and demand of nurses in municipal hospitals to provide IHC services. OBJECTIVE: This study aims to investigate the willingness and demand of nurses in municipal hospitals in China to provide IHC services and analyze the factors to promote IHC development in China. METHODS: This cross-sectional study used multistage sampling to recruit 9405 nurses from 10 hospitals in 5 regions of China. A self-designed questionnaire with good reliability and validity was used to measure nurses' willingness and demand for providing IHC services. Data analysis used the chi-square test, Welch t test, binary logistic regression analysis, and multiple linear regression analysis. RESULTS: Nurses were highly willing to provide IHC services and preferred service distances of <5 km and times from 8 AM to 6 PM. An individual share >60% was the expected service pay sharing. Job title, educational level, monthly income, and marital status were associated with nurses' willingness to provide IHC services in binary logistic regression analysis. Supervising nurses were 1.177 times more likely to express a willingness to provide IHC services than senior nurses. Nurses with a bachelor's degree had a 1.167 times higher likelihood of expressing willingness to provide IHC services than those with a junior college education or lower. Married nurses were 1.075 times more likely to express a willingness than unmarried nurses. A monthly income >¥10,000 increased the likelihood of nurses' willingness to provide IHC services, by 1.187 times, compared with an income <¥5000. Nurses' total mean demand score for IHC services was 17.38 (SD 3.67), with the highest demand being privacy protection. Multiple linear regression analysis showed that job title, monthly income, and educational level were associated with nurses' demand for IHC services. Supervising nurses (B=1.058, P<.001) and co-chief nurses or those with higher positions (B=2.574, P<.001) reported higher demand scores than senior nurses. Monthly incomes of ¥5000 to ¥10,000 (B=0.894, P<.001) and >¥10,000 (B=1.335, P<.001), as well as a bachelor's degree (B=0.484, P=.002) and at least a master's degree (B=1.224, P=.02), were associated with higher demand scores compared with a monthly income <¥5000 and junior college education or lower, respectively. CONCLUSIONS: Nurses in municipal hospitals showed a high willingness and demand to provide IHC services, with differences in willingness and demand by demographic characteristics. Accordingly, government and hospitals should regulate the service period, service distance, and other characteristics according to nurses' willingness and demand and establish relevant laws and regulations to ensure the steady and orderly development of IHC services.

Development and Optimal Immune Strategy of an Alum-Stabilized Pickering emulsion for Cancer Vaccines.

Therapeutic cancer vaccines are considered as one of the most cost-effective ways to eliminate cancer cells. Although many efforts have been invested into improving their therapeutic effect, transient maturation and activations of dendritic cells (DCs) cause weak responses and hamper the subsequent T cell responses. Here, we report on an alum-stabilized Pickering emulsion (APE) that can load a high number of antigens and continue to release them for extensive maturation and activations of antigen-presenting cells (APCs). After two vaccinations, APE/OVA induced both IFN-γ-secreting T cells (Th1) and IL-4-secreting T cells (Th2), generating effector CD8+ T cells against tumor growth. Additionally, although they boosted the cellular immune responses in the spleen, we found that multiple administrations of cancer vaccines (three or four times in 3-day intervals) may increase the immunosuppression with more PD-1+ CD8+ and LAG-3+ CD8+ T cells within the tumor environment, leading to the diminished overall anti-tumor efficacy. Combining this with anti-PD-1 antibodies evidently hindered the suppressive effect of multiple vaccine administrations, leading to the amplified tumor regression in B16-OVA-bearing mice.

Remodeling of Gut Microbiota by Probiotics Alleviated Heat Stroke-Induced Necroptosis in Male Germ Cells.

SCOPE: Systemic heat stress (or heatstroke; HS) induces germ cell death and spermatogenesis disorders in men and male mammals. Also, it affects the immune environment of the circulatory system promoting gut inflammation and intestinal permeability, leading to pathogenic infection. In this study, the crosstalk between the gut and testis (gut-testis axis) under HS is explored, by examining the effects of intestinal immune status on the health of the male reproductive system in mice. METHODS AND RESULTS: A mouse model of systemic heat stress is established to investigate the effect of probiotics on testis health. The results reveal that pro-inflammatory factor receptor activation pathway and pathogen infection response pathway are significantly upregulated in HS testes, leading to necroptosis, while pro-inflammatory factor and endotoxin are detected locally in the intestine and then entered the blood. The study then uses probiotics to intervene in gut microbiota, which results in milder gut microbial changes, lower inflammatory responses in the HS gut, and less necroptosis in the HS testes. CONCLUSION: Probiotics-based remodeling of gut microbiota (GM) reduces the proliferation of abnormal bacteria and decreases the spread of gut-derived inflammatory mediators into the blood circulation under long-term systemic heat stress, which relieves inflammation on germ cells.

Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.

HIV-related neuropathic pain (HRNP) is a neurodegeneration that gradually develops during the long-term course of acquired immune deficiency syndrome (AIDS) and manifests as abnormal sock/sleeve-like symmetrical pain and nociceptive hyperalgesia in the extremities, which seriously reduces patient quality of life. To date, the pathogenesis of HRNP is not completely clear. There is a lack of effective clinical treatment for HRNP and it is becoming a challenge and hot spot for medical research. In this study, we conducted a systematic review of the progress of HRNP research in recent years including (1) the etiology, classification and clinical symptoms of HRNP, (2) the establishment of HRNP pathological models, (3) the pathological mechanisms underlying HRNP from three aspects: molecules, signaling pathways and cells, (4) the therapeutic strategies for HRNP, and (5) the limitations of recent HRNP research and the future research directions and prospects of HRNP. This detailed review provides new and systematic insight into the pathological mechanism of HRNP, which establishes a theoretical basis for the future exploitation of novel target drugs. HIV infection, antiretroviral therapy and opioid abuse contribute to the etiology of HRNP with symmetrical pain in both hands and feet, allodynia and hyperalgesia. The pathogenesis involves changes in cytokine expression, activation of signaling pathways and neuronal cell states. The therapy for HRNP should be patient-centered, integrating pharmacologic and nonpharmacologic treatments into multimodal intervention.

Mesenchymal Stem Cells Pretreated with Collagen Promote Skin Wound-Healing.

The existing treatment modalities for skin injuries mainly include dressings, negative-pressure wound treatment, autologous skin grafting, and high-pressure wound treatment. All of these therapies have limitations such as high time cost, the inability to remove inactivated tissue in a timely manner, surgical debridement, and oxygen toxicity. Mesenchymal stem cells have a unique self-renewal ability and wide differentiation potential, and they are one of the most promising stem cell types in cell therapy and have great application prospects in the field of regenerative medicine. Collagen exerts structural roles by promoting the molecular structure, shape, and mechanical properties of cells, and adding it to cell cultures can also promote cell proliferation and shorten the cell doubling time. The effects of collagen on MSCs were examined using Giemsa staining, EdU staining, and growth curves. Mice were subjected to allogeneic experiments and autologous experiments to reduce individual differences; all animals were separated into four groups. Neonatal skin sections were detected by HE staining, Masson staining, immunohistochemical staining, and immunofluorescence staining. We found that the MSCs pretreated with collagen accelerated the healing of skin wounds in mice and canines by promoting epidermal layer repair, collagen deposition, hair follicle angiogenesis, and an inflammatory response. Collagen promotes the secretion of the chemokines and growth factors associated with skin healing by MSCs, which positively influences skin healing. This study supports the treatment of skin injuries with MSCs cultured in medium with collagen added.

A visible-light-mediated cascade reaction of quinoxalin-2(1H)-ones, alkenes, and sulfinic acids.

A photocatalytic three-component cascade reaction of quinoxalin-2(1H)-ones, alkenes, and sulfinic acids under metal-, strong oxidant-, and external photocatalyst-free conditions was developed. The reaction was performed at room temperature using air as a green oxidant. Various sulfonated quinoxalin-2(1H)-ones were obtained in satisfactory yields with good functional group compatibility. The preliminary study showed that the current transformation was enabled by the formation of an electron donor-acceptor (EDA) complex between quinoxalin-2(1H)-ones and sulfinic acids.