Trends in the mobility of primary healthcare human resources in underdeveloped regions of western China from 2000 to 2021: Evidence from Nanning.

OBJECTIVE: This research aimed to identify the fundamental and geographic characteristics of the primary healthcare personnel mobility in Nanning from 2000 to 2021 and clarify the determinants that affect their transition to non-primary healthcare institutions. METHODS: Through utilizing the Primary Healthcare Personnel Database (PHPD) for 2000-2021, the study conducts descriptive statistical analysis on demographic, economic, and professional aspects of healthcare personnel mobility across healthcare reform phases. Geographic Information Systems (QGIS) were used to map mobility patterns, and R software was employed to calculate spatial autocorrelation (Moran's I). Logistic regression identified factors that influenced the transition to non-primary institutions. RESULTS: Primary healthcare personnel mobility is divided into four phases: initial (2000-2008), turning point (2009-2011), rapid development (2012-2020), and decline (2021). The rapid development stage saw increased mobility with no spatial clustering in inflow and outflow. From 2016 to 2020, primary healthcare worker mobility reached its peak, in which the most significant movement occurred between township health centers and other institutions. Aside from their transition to primary medical institutions, the primary movement of grassroots health personnel predominantly directs towards secondary general hospitals, tertiary general hospitals, and secondary specialized hospitals. Since 2012, the number and mobility distance of primary healthcare workers have become noticeably larger and remained at a higher level from 2016 to 2020. The main migration of primary healthcare personnel occurred in their districts (counties). Key transition factors include gender, education, ethnicity, professional category, general practice registration, and administrative division. CONCLUSIONS: This study provides evidence of the features of primary healthcare personnel mobility in the less developed western regions of China, in which Nanning was taken as a case study. It uncovers the factors that impact the flow of primary healthcare personnel to non-primary healthcare institutions. These findings are helpful to policy refinement and support the retention of primary healthcare workers.

Safety of a 90-min duration of intravenous infusion of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma in a tertiary hospital in China: a prospective, open-label, exploratory clinical trial.

This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P<0.001). For the subsequent cycles with 90-min SDI, only two (0.25%) IRRs occurred among 814 infusions (one grade 1 hand numbness and one grade 2 chill/fever). The 90-min obinutuzumab SDI might be safe and feasible in patients with B-cell NHL in China.

Nickel-catalyzed oxidative thiolation of α-amino carbonyl compounds with thiols.

An efficient oxidative thiolation of α-amino carbonyl compounds with thiols by the catalysis of an Earth-abundant nickel salt is disclosed for the first time. A variety of alkyl thiols and (hetero)aryl thiols underwent the reaction well with α-amino ketones and an α-amino ester to produce the desired α,α-aminothiocarbonyl compounds in good to excellent yields under ligand- and base-free conditions.

Safety of a 90-min duration of intravenous infusion of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma in a tertiary hospital in China: a prospective, open-label, exploratory clinical trial

This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P<0.001). For the subsequent cycles with 90-min SDI, only two (0.25%) IRRs occurred among 814 infusions (one grade 1 hand numbness and one grade 2 chill/fever). The 90-min obinutuzumab SDI might be safe and feasible in patients with B-cell NHL in China.

Comprehensive analysis revealed the immunoinflammatory targets of rheumatoid arthritis based on intestinal flora, miRNA, transcription factors, and RNA-binding proteins databases, GSEA and GSVA pathway observations, and immunoinfiltration typing.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. This study aimed to identify potential biomarkers and possible pathogenesis of RA using various bioinformatics analysis tools. METHODS: The GMrepo database provided a visual representation of the analysis of intestinal flora. We selected the GSE55235 and GSE55457 datasets from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) separately. With the intersection of these DEGs with the target genes associated with RA found in the GeneCards database, we obtained the DEGs targeted by RA (DERATGs). Subsequently, Disease Ontology, Gene Ontology, and the Kyoto Encyclopedia of Genes and Genomes were used to analyze DERATGs functionally. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed on the data from the gene expression matrix. Additionally, the protein-protein interaction network, transcription factor (TF)-targets, target-drug, microRNA (miRNA)-mRNA networks, and RNA-binding proteins (RBPs)-DERATGs correlation analyses were built. The CIBERSORT was used to evaluate the inflammatory immune state. The single-sample GSEA (ssGSEA) algorithm and differential analysis of DERATGs were used among the infiltration degree subtypes. RESULTS: There were some correlations between the abundance of gut flora and the prevalence of RA. A total of 54 DERATGs were identified, mainly related to immune and inflammatory responses and immunodeficiency diseases. Through GSEA and GSVA analysis, we found pathway alterations related to metabolic regulations, autoimmune diseases, and immunodeficiency-related disorders. We obtained 20 hub genes and 2 subnetworks. Additionally, we found that 39 TFs, 174 drugs, 2310 miRNAs, and several RBPs were related to DERATGs. Mast, plasma, and naive B cells differed during immune infiltration. We discovered DERATGs' differences among subtypes using the ssGSEA algorithm and subtype grouping. CONCLUSIONS: The findings of this study could help with RA diagnosis, prognosis, and targeted molecular treatment.

Nerolidol, Bioactive Compound Suppress Growth of HCT-116 Colorectal Cancer Cells Through Cell Cycle Arrest and Induction of Apoptosis.

Colon cancer is the most prevalent cancer and causes the highest cancer-associated mortality in both men and women globally. It has a high incidence and fatality rate, which places a significant burden on the healthcare system. The current work was performed to understand the beneficial roles of nerolidol on the viability and cytotoxic mechanisms in the colon cancer HCT-116 cells. The MTT cytotoxicity assay was done to investigate the effect of nerolidol at different doses (5-100 µM) on the HCT-116 cell viability. The impacts of nerolidol on ROS accumulation and apoptosis were investigated using DCFH-DA, DAPI, and dual staining assays, respectively. The flow cytometry analysis was performed to study the influence of nerolidol on the cell cycle arrest in the HCT-116 cells. The outcomes of the MTT assay demonstrated that nerolidol at different doses (5-100 µM) substantially inhibited the HCT-116 cell viability with an IC50 level of 25 µM. The treatment with nerolidol appreciably boosted the ROS level in the HCT-116 cells. The findings of DAPI and dual staining revealed higher apoptotic incidences in the nerolidol-exposed HCT-116 cells, which supports its ability to stimulate apoptosis. The flow cytometry analysis demonstrated the considerable inhibition in cell cycle at the G0/G1 phase in the nerolidol-exposed HCT-116 cells. Our research showed that nerolidol can inhibit the cell cycle, increase ROS accumulation, and activate apoptosis in HCT-116 cells. In light of this, it may prove to be a potent and salutary candidate to treat colon cancer.

IL-22-Induced Ubiquitin-Specific Protease 15 Promotes Proliferation and Inflammation of Keratinocytes through Stabilization of Squamous Cell Carcinoma Antigen 2.

Ubiquitin-specific protease 15 (USP15) plays a significant role in regulating various biological processes in several autoimmune diseases and cancers. However, its role in psoriatic keratinocytes (KCs) has not been extensively studied. In this study, we described that USP15 promotes proliferation and inflammation in KCs by stabilizing squamous cell carcinoma antigen 2. We discovered that the expression of USP15 and squamous cell carcinoma antigen 2 was elevated in lesions from patients with clinical psoriasis and an imiquimod-induced psoriatic dermatitis mouse model. USP15 was able to bind, deubiquitinate, and stabilize squamous cell carcinoma antigen 2. Knocking down USP15 resulted in reduced KC inflammation and impaired KC viability and clonogenicity. Topically applying USP15 small interfering RNA significantly ameliorated imiquimod-induced psoriatic dermatitis and reduced the infiltration of T cells and neutrophils. In addition, we determined that IL-22 was a key cytokine that upregulated the expression of USP15. These findings provide insights regarding the mechanisms involved in the proliferation and inflammation of KCs mediated by IL-22, suggesting a potential IL-22-USP15-squamous cell carcinoma antigen 2 axis in the pathogenesis of psoriatic KCs.

Prospective, multi-center post-marketing surveillance cohort study to monitor the safety of the human papillomavirus-16/18 AS04-adjuvanted vaccine in Chinese girls and women aged 9 to 45 years, 2018-2020.

Following the approval of Cervarix for the immunization of girls and women in China against high-risk human papillomavirus types 16 and 18, a non-interventional post-authorization safety study was performed. A multi-center prospective cohort study assessed safety following Cervarix vaccination of Chinese girls and women aged 9-45 years between 31 May 2018 and 3 December 2020. Adverse events following immunization (AEFIs), potential immune-mediated diseases (pIMDs), and pregnancy-related outcomes were collected up to 12 months from the third immunization or 24 months from the first immunization, whichever came first. Among 3,013 women who received 8,839 Cervarix doses, 167 (5.5%) reported ≥ 1 any AEFI, and 22 (0.7%) reported 40 serious AEFIs. During the 30 days after each dose, 147 women (4.9%) reported 211 medically attended AEFIs, including 3 serious AEFIs reported by 1 woman (0.03%). One woman reported a pIMD. Cervarix was inadvertently administered to 65 women (2.2%) within 60 days before conception or during pregnancy. Of these women, 34 (52.3%) gave birth to live infant(s) with no apparent congenital anomalies, and 1 (1.5%) woman gave birth to a live infant with a congenital anomaly. No serious AEFIs or pIMDs were considered to be related to the vaccination. In Chinese women aged 9-45 years, immunization with the Cervarix three-dose schedule was well tolerated. Overall, no safety concerns were identified, although rare adverse events may have been missed due to the study sample size.Clinical trial registration: NCT03438006.

Infection with high-risk human papillomavirus is a prerequisite for cervical cancerCervarix is a human papillomavirus-16/18 AS04-adjuvanted vaccineMulti-centre prospective cohort study to monitor safety of Cervarix immunisationSafety was monitored in 3,013 girls/women aged 9­45 years in China (8,839 doses)Cervarix was well tolerated, and no safety concerns were identified.

The relationship between skeletal muscle mass to visceral fat area ratio and metabolic dysfunction-associated fatty liver disease subtypes in middle-aged and elderly population: a single-center retrospective study.

Background: It has been reported that decreased muscle mass combined with excessive visceral adipose tissue are significantly correlated with the risk of non-alcoholic fatty liver disease (NAFLD). However, it has not been explored among populations with metabolic dysfunction-associated fatty liver disease (MAFLD) subtypes. We aimed to investigate whether appendicular skeletal muscle mass to visceral fat area ratio (SVR), an indicator of sarcopenic obesity, influences on the risk of MAFLD subtypes and its hepatic condition in middle-aged and elderly population. Methods: A total of 4,003 middle-aged and elderly subjects were finally enrolled in this single-center retrospective study. Abdominal ultrasonography was employed for hepatic steatosis diagnosis. Participants were divided into four groups: diabetes-MAFLD, overweight/obese-MAFLD, lean-MAFLD and no MAFLD. Appendicular skeletal muscle mass as well as visceral fat area (VAF) was estimated by bioimpedance analysis measurements. Liver fibrosis was defined as a Fibrosis-4 index (FIB-4) and the NAFLD Fibrosis Score (NFS). Multivariate logistic regression analysis was performed to estimate the odds ratio and 95% confidence interval between SVR and MAFLD subtypes/hepatic condition stratified by sex. Results: Participants with MAFLD subtypes had a significant lower value of SVR compared with those without MAFLD (P<0.001), while high quartiles of FIB-4 and NFS also showed a decreasing value of SVR in comparison with its lower quartiles (Pfor trend<0.001). The lowest quartile of SVR increased the prevalence of MAFLD subtypes [adjusted OR (95%CI): 2.96 (1.48 ~ 5.93) male /3.30(1.46 ~ 7.46) female for diabetes-MAFLD, 1.91(1.26 ~ 2.88) male /4.48(1.91 ~ 10.49) female for overweight/obese-MAFLD and 4.01(1.46 ~ 10.98) male/2.53(1.19 ~ 5.37) female for lean-MAFLD groups] compared with the highest quartile of SVR (all Pfor trend<0.001). Besides, the interaction effect of gender on the relationship between SVR and MAFLD subtypes was statistically significant (all Pfor interaction<0.001).Restricted cubic spline indicated an inverse association between SVR and the risk of MAFLD subtypes with linearity (all P for non-linearity>0.05). The lowest quartile of SVR also increases the risk of MAFLD fibrosis in both males and females. Conclusion: Our study concluded that a decrease in SVR (appendicular skeletal muscle mass divided by visceral fat area) is significantly associated with an increased prevalence of developing MAFLD subtypes and liver fibrosis in middle-aged and older persons of both genders.

Electrochemical deoxygenative homo-couplings of aromatic aldehydes.

An electrochemical deoxygenative homo-coupling of aromatic aldehydes is achieved to selectively access bibenzyl and stilbene derivatives. The protocol allows the homo-coupling of aldehydes to occur after single-electron-reduction at the cathode. Taking advantage of the oxophilicity of triphenylphosphine, the electrochemical deoxygenation proceeds smoothly to give reductive homo-coupling products.

Perioperative Administration of Pregabalin and Esketamine to Prevent Chronic Pain After Breast Cancer Surgery: A Randomized Controlled Trial.

Background: Perioperative multimodal analgesia can prevent chronic pain after breast cancer surgery. This study aimed to investigate the efficacy of combined perioperative oral pregabalin and postoperative esketamine in preventing chronic pain after breast cancer surgery. Methods: Ninety patients undergoing elective breast cancer surgery were randomized into the combined pregabalin and esketamine group (EP group) and the general anesthesia alone group (Control group). The EP group received 150 mg of oral pregabalin 1 h before surgery and twice daily for seven days postoperatively, and a patient-controlled analgesia pump after surgery that delivered 100 µg sufentanil + 1.25 mg/kg esketamine + 4 mg tropisetron in 100 mL saline solution intravenously. The Control group received placebo capsules before and after the surgery and routine postoperative analgesia (100 µg sufentanil + 4 mg tropisetron in 100 mL saline solution). The primary outcome was the incidence of chronic pain three and six months after surgery. Secondary outcomes included acute postoperative pain, postoperative opioid consumption, and incidence of adverse events. Results: The incidence of chronic pain in the EP group was significantly lower than in the Control group three (14.3% vs 46.3%, P = 0.005) and six (7.1% vs 31.7%, P = 0.009) months postoperatively. The rest numerical rating scale (NRS) pain scores 1-3 days postoperatively and coughing NRS pain scores 1-7 days postoperatively in the EP group were significantly lower than in the Control group (all P ˂ 0.05). The cumulative sufentanil consumption in the EP group during postoperative 0-12, 12-24, and 24-48, 0-24, and 0-48 hours were significantly lower than in the Control group (all P ˂ 0.05). Conclusion: Combined perioperative oral pregabalin and postoperative esketamine effectively prevented chronic pain after breast cancer surgery, improved acute postoperative pain, and reduced postoperative opioid consumption.

Prediction of dose deposition matrix using voxel features driven machine learning approach.

OBJECTIVES: A dose deposition matrix (DDM) prediction method using several voxel features and a machine learning (ML) approach is proposed for plan optimization in radiation therapy. METHODS: Head and lung cases with the inhomogeneous medium are used as training and testing data. The prediction model is a cascade forward backprop neural network where the input is the features of the voxel, including 1) voxel to body surface distance along the beamlet axis, 2) voxel to beamlet axis distance, 3) voxel density, 4) heterogeneity corrected voxel to body surface distance, 5) heterogeneity corrected voxel to beamlet axis, and (6) the dose of voxel obtained from the pencil beam (PB) algorithm. The output is the predicted voxel dose corresponding to a beamlet. The predicted DDM was used for plan optimization (ML method) and compared with the dose of MC-based plan optimization (MC method) and the dose of pencil beam-based plan optimization (PB method). The mean absolute error (MAE) value was calculated for full volume relative to the dose of the MC method to evaluate the overall dose performance of the final plan. RESULTS: For patient with head tumor, the ML method achieves MAE value 0.49 × 10-4 and PB has MAE 1.86 × 10-4. For patient with lung tumor, the ML method has MAE 1.42 × 10-4 and PB has MAE 3.72 × 10-4. The maximum percentage difference in PTV dose coverage (D98) between ML and MC methods is no more than 1.2% for patient with head tumor, while the difference is larger than 10% using the PB method. For patient with lung tumor, the maximum percentage difference in PTV dose coverage (D98) between ML and MC methods is no more than 2.1%, while the difference is larger than 16% using the PB method. CONCLUSIONS: In this work, a reliable DDM prediction method is established for plan optimization by applying several voxel features and the ML approach. The results show that the ML method based on voxel features can obtain plans comparable to the MC method and is better than the PB method in achieving accurate dose to the patient, which is helpful for rapid plan optimization and accurate dose calculation. ADVANCES IN KNOWLEDGE: Establishment of a new machine learning method based on the relationship between the voxel and beamlet features for dose deposition matrix prediction in radiation therapy.

Predicting PD-L1 expression status in patients with non-small cell lung cancer using [18F]FDG PET/CT radiomics.

BACKGROUND: In recent years, immune checkpoint inhibitor (ICI) therapy has greatly changed the treatment prospects of patients with non-small cell lung cancer (NSCLC). Among the available ICI therapy strategies, programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors are the most widely used worldwide. At present, immunohistochemistry (IHC) is the main method to detect PD-L1 expression levels in clinical practice. However, given that IHC is invasive and cannot reflect the expression of PD-L1 dynamically and in real time, it is of great clinical significance to develop a new noninvasive, accurate radiomics method to evaluate PD-L1 expression levels and predict and filter patients who will benefit from immunotherapy. Therefore, the aim of our study was to assess the predictive power of pretherapy [18F]-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT)-based radiomics features for PD-L1 expression status in patients with NSCLC. METHODS: A total of 334 patients with NSCLC who underwent [18F]FDG PET/CT imaging prior to treatment were analyzed retrospectively from September 2016 to July 2021. The LIFEx7.0.0 package was applied to extract 63 PET and 61 CT radiomics features. In the training group, the least absolute shrinkage and selection operator (LASSO) regression model was employed to select the most predictive radiomics features. We constructed and validated a radiomics model, clinical model and combined model. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to evaluate the predictive performance of the three models in the training group and validation group. In addition, a radiomics nomogram to predict PD-L1 expression status was established based on the optimal predictive model. RESULTS: Patients were randomly assigned to a training group (n = 233) and a validation group (n = 101). Two radiomics features were selected to construct the radiomics signature model. Multivariate analysis showed that the clinical stage (odds ratio [OR] 1.579, 95% confidence interval [CI] 0.220-0.703, P < 0.001) was a significant predictor of different PD-L1 expression statuses. The AUC of the radiomics model was higher than that of the clinical model in the training group (0.706 vs. 0.638) and the validation group (0.761 vs. 0.640). The AUCs in the training group and validation group of the combined model were 0.718 and 0.769, respectively. CONCLUSION: PET/CT-based radiomics features demonstrated strong potential in predicting PD-L1 expression status and thus could be used to preselect patients who may benefit from PD-1/PD-L1-based immunotherapy.

Virulence Variability and Genetic Diversity in Blumeria graminis f. sp. hordei in Southeastern and Southwestern China.

Powdery mildew is a key airborne foliar disease of barley in southeastern and southwestern China. Barley varieties usually partially or wholly lose resistance to the pathogen Blumeria graminis (DC.) f. sp. hordei 3 to 5 years after release due to the frequent acquirements of new virulences in the pathogen population. However, no B. graminis f. sp. hordei virulence detection has been carried out in the recent decade and, thus, no information is available on the present virulence components and major pathotypes in epidemic regions. Twenty-one near-isogenic lines of Pallas were selected to detect B. graminis f. sp. hordei virulence variation, with 97 pathotypes identified from the isolates collected from 2015 to 2019. The virulence complexities ranged from 1 to 12, with 1.5 isolates on average assigned per pathotype, suggesting a natural trait of high pathotype diversity and low virulence complexity in the Chinese B. graminis f. sp. hordei populations. Eleven high-virulence pathotypes were detected in the traditional barley-growing regions in Yunnan and Zhejiang. Six virulent pathotypes to resistance gene mlo-5 were detected only in the two traditional epidemic regions, with a virulence frequency (VF) of 4.8% (7 of 147). Compared with the results from a decade ago, VFs for resistance alleles Mla3, mlo-5, Mla6 + Mla14, Mla7 + Mlk, Mlg + MlCP, and Mla13 + MlRu3 + MlaRu4 increased from 0 to 0.7 to 25.8%. Isolates from Yunnan and Zhejiang had similar virulence profiles, which differed from those identified in Tibet. In addition, genetic diversities differed in the isolate groups collected from Tibet, Yunnan, and Zhejiang.

The association of dietary glutamine supplementation with the development of high salt-induced hypertension in rats.

Glutamine supplementation has been reported to affect blood pressure (BP). However, its role in the progression of hypertension induced by high salt diet (HSD) has not been elucidated. Male normotensive Wistar rats were exposed to high salt diet and treated with different doses of glutamine supplementation. Rats aged 6 weeks were assigned to five groups: (1) Normal-salt diet (0.3% NaCl, NSD); (2) High-salt diet (8% NaCl, HSD); (3) High-salt + low-dose diet (8% NaCl, 0.5 g of L-glutamine/kg body weight, HSLGD); (4) High-salt + middle-dose diet (8% NaCl, 1.5 g of L-glutamine/kg body weight, HSMGD); and (5) High-salt + high-dose diet (8% NaCl, 2.5 g of L-glutamine/kg body weight, HSHGD). After supplementing different doses of glutamine to male Wistar 6-week-old rats fed with HSD for 7 weeks, we found no difference in body weight among groups. Importantly, we showed that dietary L-glutamine supplementation could prevent the development of hypertension in a dose-dependent manner [dramatically lowering systolic blood pressure (SBP) and slightly reducing diastolic blood pressure (DBP) of hypertensive rats, while the differences of DBP between groups did not reach statistical significance]. Our data further elucidated that dietary glutamine supplementation mildly alleviated the degree of left ventricular hypertrophy, including interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in hypertensive rats. Together, our results offer evidence that the dietary uptake of glutamine may be associated with attenuating the development of high salt-induced hypertension and slightly alleviating the degree of left ventricular hypertrophy in hypertensive rats. Therefore, glutamine supplementation may act as a prospective dietary intervention for the treatment of hypertension.

Dehydroxylative Arylation of Alcohols via Paired Electrolysis.

Nonactivated alcohols along with arene compounds are used in electrochemical dehydroxylative arylation for constructing C(sp3)-C(sp2) bonds. The PIII reagent undergoes single-electron anodic oxidation to form its radical cation, which reacts with the alcohol to produce an alkoxytriphenylphosphine radical. Through spontaneous ß-scission of the phosphoranyl radical, the C-O bond is cleaved to form an alkyl radical species, which couples with the radical anion generated by cathodic reduction of the electron-poor arene to afford the dehydroxylative arylated product.

Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a common age-related neurodegenerative disease that leads to memory loss and cognitive function damage due to intracerebral neurofibrillary tangles (NFTs) and amyloid-ß (Aß) protein deposition. The phosphoinositide-dependent protein kinase (PDK1)/protein kinase B (Akt) signaling pathway plays a significant role in neuronal differentiation, synaptic plasticity, neuronal survival, and neurotransmission via the axon-dendrite axis. The phosphorylation of PDK1 and Akt rises in the brain, resulting in phosphorylation of the TNF-α-converting enzyme (TACE) at its cytoplasmic tail (the C-terminal end), changing its internalization as well as its trafficking. The current review aimed to explain the mechanisms of the PDK1/Akt/TACE signaling axis that exerts its modulatory effect on AD physiopathology. We provide an overview of the neuropathological features, genetics, Aß aggregation, Tau protein hyperphosphorylation, neuroinflammation, and aging in the AD brain. Additionally, we summarized the phosphoinositide 3-kinase (PI3K)/PDK1/Akt pathway-related features and its molecular mechanism that is dependent on TACE in the pathogenesis of AD. This study reviewed the relationship between the PDK1/Akt signaling pathway and AD, and discussed the role of PDK1/Akt in resisting neuronal toxicity by suppressing TACE expression in the cell membrane. This work also provides a perspective for developing new therapeutics targeting PDK1/Akt and TACE for the treatment of AD.

Emerging functions of neuronostatin in physiology, pathology, and potential therapeutics.

Neuronostatin, a bioactive peptide hormone, was encoded by pro-somatostatin and discovered using a bioinformatic method in 2008. Neuronostatin is widely expressed in the central nervous system (CNS) and peripheral tissues, it is also highly conserved among humans, rodents, and even goldfish. The 13 and 19 amino acids and the C-terminal amidation type play important roles in physiological and pathological functions. The present study reviews the roles of neuronostatin in food intake and drinking of water, as well as in the neuroendocrine processes, pain regulation, cardiovascular and circulation function, memory and studies, depression-like effect, and energy metabolism in animals. However, the information on the physiology and pathology of neuronostatin, especially the molecular mechanism, remains scarce. Considering the broad functions of neuronostatin, this endogenous neuropeptide could be a promising therapeutic target for future research and drug design if the exact receptor could be found in humans.

Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation.

Alzheimer's disease (AD) is associated with the accumulation and aggregation of amyloid in the brain. The cation channel TRPV2 may mediate the pathological changes in mild cognitive impairment. A high-affinity agonist of TRPV2 named cannabidiol is one of the candidate drugs for AD. However, the molecular mechanism of cannabidiol via TRPV2 in AD remains unknown. The present study investigated whether cannabidiol enhances the phagocytosis and clearance of microglial Aß via the TRPV2 channel. We used a human dataset, mouse primary neuron and microglia cultures, and AD model mice to evaluate TRPV2 expression and the ability of microglial amyloid-ß phagocytosis in vivo and in vitro. The results revealed that TRPV2 expression was reduced in the cortex and hippocampus of AD model mice and AD patients. Cannabidiol enhanced microglial amyloid-ß phagocytosis through TRPV2 activation, which increased the mRNA expression of the phagocytosis-related receptors, but knockdown of TRPV2 or Trem2 rescued the expression. TRPV2-mediated effects were also dependent on PDK1/Akt signaling, a pathway in which autophagy was indispensable. Furthermore, cannabidiol treatment successfully attenuated neuroinflammation while simultaneously improving mitochondrial function and ATP production via TRPV2 activation. Therefore, TRPV2 is proposed as a potential therapeutic target in AD, while CBD is a promising drug candidate for AD.

Associations between constipation, overeating, and depression: A survey of Chinese oldest-old and centenarians.

Objectives: Depression is a common disease of elderly population, with a global prevalence of more than 20%. Few studies have involved the associations of constipation and overeating with depression, especially in the elderly population. We aimed to address these associations in Chinese oldest-old and centenarians. Methods: A total of 1863 elderly individuals from 18 regions of Hainan, China, were investigated from July 2014 to December 2016. Health survey, physical examination, and blood analyses were performed through structured questionnaires and standard procedures. The Geriatric Depression Scale (GDS-15) was used to measure depression. Results: The proportions of elderly individuals with depression, constipation, and overeating were 20.80% (349), 15.14% (254), and 26.52% (445), respectively. The prevalence of constipation and overeating was significantly higher in the elderly group with depression than in those without depression (P < 0.05, all). In the multiple linear regression analyses, higher prevalence of constipation and overeating had positive and significant associations with the GDS-15 (P < 0.05, all). In the multiple logistic regression analyses, constipation (odds ratio [OR]: 2.328; 95% confidence interval [CI]: 1.540-3.521) and overeating (OR: 2.735; 95% CI: 1.920-3.898) had positive and significant associations with depression (P < 0.05, in all). Conclusions and Implications: This study provides epidemiological evidence that constipation and overeating have positive associations with depression in Chinese oldest-old and centenarians. The interventions for constipation and overeating should be improved to promote prevention and treatment for depression and achieve successful aging and healthy longevity.