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Juan Du,1,* Li-Li Shi,2,* Wei-Wei Jiang,3 Xue-Ai Liu,3 Xin-Hong Wu,3 Xiang-Xiang Huang,3 Ming-Wei Huo,3 Ling-Zhi Shi,3 Jingjian Dong,2 Xiaohong Jiang,2 Renyu Huang,4 Qing-Ri Cao,3 Wenzhou Zhang1 1Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2College of Medicine, Jiaxing University, Jiaxing, People’s Republic of China; 3College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, People’s Republic of China; 4College of Social Science, Soochow University, Institute of Culture and Tourism Development, Soochow University, Suzhou, 215123, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenzhou Zhang, Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China, Email hnzzzwzx@sina.com Qing-Ri Cao, College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Jiangsu, 215123, People’s Republic of China, Email qrcao@suda.edu.cnBackground: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges.Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated.Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX.Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations. Keywords: DTX-BSA nanoparticles, thermal-driven self-assembly, microfluidic technology, in-vitro release, pharmacokinetics

Xin-Xin Huang,1 Quan Lin,2 Yun Li,2 Li Li2 1The Ministry of Health, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of ChinaCorrespondence: Li Li, Email cheditor@163.comPurpose: High hepatitis B infection rates in China are a major public health issue, and mother-to-child transmission (MTCT) is a significant risk factor.Patients and Methods: This study was conducted with a prospective multicentre design from January 2021 to December 2022 in 245 hospitals providing midwifery services in southeastern China. The participants were pregnant women who were positive for hepatitis B surface antigen (HBs Ag) and their children. The HBs Ag concentration was tested in children aged 8– 12 months. The odds ratio for each risk factor was calculated by logistic regression analysis, and the decision tree model was used.Results: A total of 5369 children born to hepatitis B-infected mothers between 8 and 12 months of age were enrolled, among whom 81 (1.51%) were positive for HBsAg. The risk factors for hepatitis B infection in 5369 children under one-year-old were a high intrauterine hepatitis B exposure level, a history of hepatitis B immunoglobulin (HBIG) delay beyond 12 hours after birth, and lack of full hepatitis B vaccine (HepB), with risks of 3.356 (1.223~9.209), 5.691 (1.931~16.773), and 5.137 (2.265~11.650), respectively. The discrimination accuracy of the decision tree was 98.5%. The risk factors for hepatitis B infection in 4542 children under one year old with high exposure risk were nonstandard treatment by the mother during pregnancy, HBIG delay beyond 12 hours after birth, and no complete HepB administration, with risks of 2.925 (1.063– 8.047), 5.354 (1.806– 15.871) and 5.147 (2.258– 11.733), respectively. The discrimination accuracy of the decision tree was 98.3%.Conclusion: To prevent mother-to-child transmission of hepatitis B, it is necessary to standardize the treatment of pregnant women with a high exposure risk of hepatitis B, implement combined vaccination within 12 hours of birth, and standardise the full course of HepB.Keywords: hepatitis B, prevention of mother-to-child transmission, risk factors, risk of exposure, decision tree

Yu-Qin Xu,1 YanHua Gou,1 Jin-Jun Yuan,1 Yan-Xian Zhu,1 Xiao-Ming Ma,1 Chen Chen,2 Xing-Xian Huang,1 Zhuo-Xin Yang,1 Yu-Mei Zhou1 1The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Zhuo-Xin Yang; Yu-Mei Zhou, Email 001188@gzucm.edu.cn; zym_star@163.comBackground: Increasing evidences demonstrate that immune dysregulation can result in depression, and it is reported that persistent inflammatory response is related to the unresponsiveness of antidepressant treatment.Purpose: This study aimed to explore the reason why some responded but some not responded to acupuncture in treating postpartum depression (PPD), and whether it related to the levels of inflammatory cytokines.Patients and Methods: Women diagnosed with PPD were recruited in to accept 8-week acupuncture. All subjects were assessed the 17-item Hamilton Depression Rating Scale (HDRS17) at baseline, week 1, week 2, week 4 and week 8 during the treatment. A panel of 9 cytokines was measured at baseline and 8 weeks.Results: Of the 121 participants, 96 completed the 8-week assessment and 46 completed the blood sample collection. HDRS17 scores of 96 subjects showed significant statistical reduction since the first week (P = 0.002) and reached to 5.31 (P < 0.000) at the end of therapy. And we divided the 46 subjects into responders and non-responders according to the response rate of HDRS17 scores. Responders and non-responders did not differ significantly between-group in changes in the 9 cytokines. In responders, IL-6, IL-10 and IFN-γ levels were statistically lower (P = 0.006; P = 0.033; P = 0.024), while TGF-β 1 was statistically higher after 8 weeks treatment (P < 0.000). In non-responders, the levels of IL-5, TNF-α and TGF-β 1 were statistically higher (P = 0.018; P < 0.000; P < 0.000), while IFN-γ was statistically lower (P = 0.005).Conclusion: Acupuncture could alleviate depressive symptoms of patients with PPD and might through adjusting peripheral inflammatory response by up-regulating anti-inflammatory cytokines and down-regulating pro-inflammatory cytokines.Keywords: acupuncture, postpartum depression, inflammatory cytokines

Run Dong,1,2,* Min Liu,3,* Xiao-Xi Huang,4 Zheng Liu,4 Ding-Yuan Jiang,5 Hui-Juan Xiao,1 Jing Geng,5 Yan-Hong Ren,5 Hua-Ping Dai5 1Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Respiratory Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory Medicine, Zhengzhou Central Hospital, Zhengzhou, People’s Republic of China; 3Department of Radiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 4Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Medical Research, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Clinical Research Center for Respiratory Diseases; Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua-Ping DaiDepartment of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of ChinaEmail daihuaping@ccmu.edu.cnBackground: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia. And, oxidation/antioxidant imbalance plays an important role in the progress of IPF. Fullerene is considered to be a novel “structural” antioxidant. This study aimed to explore if water-soluble C60 (C60(OH)22) can exhibit antifibrotic activity in its antioxidant role.Methods: Healthy C57BL/6J mice were randomly grouped and induced pulmonary fibrosis by intratracheal injection of bleomycin.Results: The survival rate of mice was observed and found that 10mg/kg was the optimal dose of water-soluble C60 for pulmonary fibrosis. We observed that water-soluble C60 can alleviate the severity of pulmonary fibrosis by observing the chest computed tomography, pulmonary pathology, and content of collagen, alpha smooth muscle actin and fibronectin in lung. Compared with bleomycin group, ROS, the content of TNF-α in BALF, and the number of fibroblasts was significantly decreased and the number of type Ⅱ alveolar epithelial cells was increased after treatment with C60.Conclusion: Therefore, thanks to its powerful antioxidant action, water-soluble C60 can reduce the severity of pulmonary fibrosis induced by bleomycin in mice.Keywords: pulmonary fibrosis, bleomycin, water-soluble C60, mice

Jianyuan Song,* Xiaoxue Huang,* Zhuhong Chen, Mingqiu Chen, Qingliang Lin, Anchuan Li, Yuangui Chen, Benhua Xu Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China *These authors contributed equally to this work Objective: To explore the value of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in predicting downstaging to stage 0–I cancer after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer.Materials and methods: We respectively investigated pretreatment CEA, pretreatment CA19-9, posttreatment CEA, posttreatment CA19-9, pre–post-CA19-9 ratio, and pre–post-CEA ratio in 674 patients with locally advanced rectal cancer receiving nCRT and determined the patients’ thresholds by using the receiver operating characteristic curve analysis. The association between downstaging (stage 0–I after nCRT), pathological complete response, and clinicopathological parameters was evaluated using the Pearson χ2 test. The clinicopathological parameters which were found to be significantly associated with downstaging were analyzed by logistic regression models and were incorporated into a scoring system.Results: Multivariate analysis showed that pretreatment CA19-9 level, posttreatment CEA level, pre–post-CEA ratio, and pre–post-CA19-9 ratio were significantly correlated with downstaging. Area under the curve of the scoring system was higher than that of parameters alone.Conclusion: The 4-factor scoring system with CA19-9 level, posttreatment CEA level, pre–post-CEA ratio, and pre–post-CA19-9 ratio is of more value in predicting downstaging to stage 0–I patients with locally advanced rectal cancer after nCRT than using the parameters alone. Keywords: CEA, CA19-9, neoadjuvant chemoradiotherapy, rectal cancer

We introduce several types of Levtin-Polyak well-posedness for a vector quasivariational inequality with functional constraints. Necessary and/or sufficient conditions are derived for them.

Abstract We apply the quadratic penalization technique to derive strong Lagrangian duality property for an inequality constrained invex program. Our results extend and improve the corresponding results in the literature.

This paper reports an investigation of dyeing processes of textiles made from a novel 100% bio-based and fully degradable polylactide/poly (hydroxybutyrate-co-hydroxyvalerate) (PLA/PHBV) fiber. The dye exhaustion, depth of shade and fastness, as well as bursting strength of dyed PLA/PHBV fabrics have been evaluated in terms of types and concentration of dyestuff, dyeing bath temperature, duration, liquor ratio and pH value. Finally, the energy cost of the whole dyeing process of the proposed material is calculated and compared with that of polyethylene terephthalate. The experimental results show that an excellent dyeing effect and bursting strength can be achieved by properly applied dyes (e.g. C.I. Disperse Orange 30, Red 74, and Blue 79) under optimal low-dyeing-temperature conditions (100°C, 10min, pH 5, LR 30:1). In addition, considering the low energy cost during the whole process, PLA/PHBV fibers can be regarded as a promising and environment-friendly material for the textile industry. [ABSTRACT FROM AUTHOR]

Background: In addition to attention and hyperactivity problems, children with attention deficit hyperactivity disorder (ADHD) have poorer organizational skills needed to manage time and materials. This study examines the improvement of organizational skills in children with ADHD by studying organizational skills training (OST)., Methods: This was a prospective, randomized controlled trial. Between September 2023 and January 2024, 70 children with a diagnosis of ADHD and at least one domain of executive dysfunction (EF) were divided into two groups. The conventional group was treated with medication, biofeedback, and behavioral interventions based on the children's actual condition. The OST group received OST in addition to the conventional group., Results: The mean age of the children was 8.33 ± 1.62 years. A total of 66 children completed the intervention and follow-up, 32 in the conventional group and 34 in the OST group. There were no differences between the two groups of children in terms of their preintervention scores on the BRIEF, SNAP-IV, or IVA-CPT. Postintervention scores on the behavioral scales decreased ( p  < .05), and IVA-CPT scores increased ( p  < .05) in both groups compared with those in the preintervention period. The OST group had a lower BRIEF ( p  = .019) and SNAP-IV Attention deficit subscale ( p  = .046) and a higher IVA-CPT Attention deficit Index ( p  = .032) than the conventional group after the intervention. The percentage of children with a normal BRIEF total score in the OST group was 79.41% (27/34) after the intervention, which was greater than the 37.50% (12/32) in the conventional group ( p  = .001). Compared with the OST group, children in the conventional group were at greater risk of having BRIEF scores that remained abnormal after the intervention. Analysis of covariance revealed a statistically significant effect of group ( p  = .008), preintervention BRIEF ( p  < .001), and participation score ( p  = .036) on postintervention BRIEF., Conclusion: OST can further improve organizational skills in daily life in children with ADHD while improving core symptoms of attention deficit in addition to conventional treatment. The effect of OST on BRIEF is also influenced by the child's BRIEF status at the baseline level and the level of cooperation during the intervention., Trial Registration: The randomized controlled trial registration number was ChiCTR2300075744., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Motivated by the pair-density-wave (PDW) state found in the one-dimensional Kondo-Heisenberg chain, we report on a determinant quantum Monte Carlo study of pair fields for a two-dimensional half-filled Hubbard layer coupled to an itinerant, noninteracting layer with one electron per site. In a specific range of interlayer hopping, the pairing vertex associated with PDW order becomes more attractive than that for uniform d-wave pairing, although both remain subdominant to the leading antiferromagnetic correlations at half filling. Our result sheds light on where one potentially may find a PDW state in such a model.

Resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) leads to ineffective chemotherapy and, consequently, delayed treatment, thereby contributing to poor prognosis. Glycolysis is an important intrinsic reason for gemcitabine resistance as it competitively inhibits gemcitabine activity by promoting deoxycytidine triphosphate accumulation in PDAC. However, biomarkers are lacking to determine which patients can benefit significantly from glycolysis inhibition under the treatment of gemcitabine activity, and a comprehensive understanding of the molecular mechanisms that promote glycolysis in PDAC will contribute to the development of a strategy to sensitize gemcitabine chemotherapy. In this study, we aimed to identify a biomarker that can robustly indicate the intrinsic resistance of PDAC to gemcitabine and guide chemotherapy sensitization strategies. After establishing gemcitabine-resistant cell lines in our laboratory and collecting pancreatic cancer and adjacent normal tissues from gemcitabine-treated patients, we observed that circRNA hsa&#95;circ&#95;0008383 (namely cNEK6) was highly expressed in the peripheral blood and tumor tissues of patients and xenografts with gemcitabine-resistant PDAC. cNEK6 enhanced resistance to gemcitabine by promoting glycolysis in PDAC. Specifically, cNEK6 prevented K48 ubiquitination of small ribonucleoprotein peptide A from the BTRC, a ubiquitin E3 ligase; thus, the accumulated SNRPA stopped PP2Ac translation by binding to its G-quadruplexes in 5' UTR of mRNA. mTORC1 pathway was aberrantly phosphorylated and activated owing to the absence of PP2Ac. The expression level of cNEK6 in the peripheral blood and tumor tissues correlated significantly and positively with the activation of the mTORC1 pathway and degree of glycolysis. Hence, the therapeutic effect of gemcitabine is limited in patients with high cNEK6 levels, and in combination with the mTORC1 inhibitor, rapamycin, can enhance sensitivity to gemcitabine chemotherapy., (© 2024. The Author(s).)

Aim: To explore the risk factors for low-birth-weight infants born to pregnant women with GDM to develop a prediction model and to construct a prediction nomogram for the risk of low birth weight infants born to pregnant women with GDM., Methods: The clinical data of singleton infants diagnosed with gestational diabetes mellitus in Southeast China in 2019 were retrospectively reviewed. Gestational conditions and neonatal weight were assessed., Results: A total of 386 diabetic mothers and infants were enrolled, including 193 in the low birth weight group and 193 in the normal birth weight group. The statistically significant factors were age over 36 years (OR = 1.916, 95% CI 1.048-3.505), junior high school education (OR = 4.454, 95% CI 1.882-10.543), history of fetal distress (OR = 0.120, 95% CI 0.016-0.925), gestational hypertension (OR = 3.681, 95% CI 1.357-9.986), preeclampsia (OR = 24.652, 95% CI 5.956-102.036), threatened preterm birth (OR = 18.393, 95% CI 8.457-39.999), triglycerides (OR = 0.642, 95% CI 0.485-0.850), and inadequate gestational weight gain (OR = 1.997, 95% CI 1.162-3.432). The area under the receiver operating characteristic curve (AUC) was 0.834 (95% CI: 0.794-0.874, p  < 0.001), and the sensitivity and specificity were 82.38 and 87.56%, respectively. The goodness-of-fit test likelihood ratio 2 was 2.089 ( p  = 0.978). The comprehensive nomogram model showed that the discrimination and mean absolute error were 0.834 and 0.015, respectively. The calibration curves showed acceptable agreement between the predictions of the column line plots and the observations. The DCA curves showed good positive net yields in the prediction model., Discussion: This study established a prediction model and risk score for low birth weight in pregnant women with GDM. It helps pregnancy clinics to identify the risk of low birth weight in newborns promptly, in addition to glycemic control and weight management for pregnant women with GDM, and should improve the appropriate treatment plan for pregnant women with higher risk, to provide personalized and precise treatment for pregnant women with GDM and improve infant outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pan, Huang and Jiang.)

Background: The World Health Organization advocates integrating neglected tropical diseases (NTDs) into common delivery platforms to combat them in resource-constrained settings. However, limited literature exists on the benefits of integration. This study examines the feasibility and impact of adding skin screening to a mass drug administration (MDA) campaign in Côte d'Ivoire., Methods: In June 2023, the Ministry of Health and Public Hygiene of Côte d'Ivoire piloted screening for skin-related NTDs alongside a national MDA campaign targeting soil-transmitted helminthiases and schistosomiasis. Two districts, Fresco and Koro, were selected for the pilot. The study applied both quantitative and qualitative assessments. The quantitative aspect focused on campaign costs and outputs, using an ingredient approach for costing. The qualitative evaluation employed an empirical phenomenological approach to analyze the campaign's operational feasibility and appreciation by stakeholders., Findings: MDA activities cost $0·66 per treated child and skin screening $0·62 per screened person, including medical products. The MDA campaign exceeded coverage targets in both districts, whereas skin screening coverage varied by locality and age group. Both the service delivery team and the beneficiaries expressed appreciation for the integrated campaign. However, opportunities for improvement were identified., Conclusion: Integrating MDA and skin NTD screening proved operationally feasible in this context but had not recorded cost-saving effects. The performance of the MDA campaign was not negatively affected by additional skin screening activities, but effective integration requires thorough joint planning, strengthened training, and proper supervision., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The Nab-paclitaxel combined with gemcitabine (AG) regimen is the main chemotherapy regimen for pancreatic cancer, but drug resistance often occurs. Currently, the ability to promote sensitization in drug-resistant cases is an important clinical issue, and the strategy of repurposing conventional drugs is a promising strategy. This study aimed to identify a classic drug that targets chemotherapy resistance's core signaling pathways and combine it with the AG regimen to enhance chemosensitivity. We also aimed to find reliable predictive biomarkers of drug combination sensitivity. Using RNA sequencing, we found that abnormal PI3K/Akt pathway activation plays a central role in mediating resistance to the AG regimen. Subsequently, through internal and external verification of randomly selected AG-resistant patient-derived organoid (PDO) and PDO xenograft models, we discovered for the first time that the classic anti-inflammatory drug sulindac K-80003, an inhibitor of the PI3K/Akt pathway that we focused on, promoted sensitization in half (14/28) of AG-resistant pancreatic ductal adenocarcinoma cases. Through RNA-sequencing, multiplex immunofluorescent staining, and immunohistochemistry experiments, we identified cFAM124A as a novel biomarker through which sulindac K-80003 promotes AG sensitization. Its role as a sensitization marker is explained via the following mechanism: cFAM124A enhances both the mRNA expression of cathepsin L and the activity of the cathepsin L enzyme. This dual effect stimulates the cleavage of RXRα, leading to large amounts of truncated RXRα, which serves as a direct target of K-80003. Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer., (© 2024. The Author(s).)

Pepper ( Piper nigrum L.) is a widely used spice plant known for its fruits and roots, which serve as flavor enhancers in culinary applications and hold significant economic value. Despite the popularity of pepper fruits, their roots remain relatively understudied, with limited research conducted on their bioactive components. This study focused on discovering and separating the primary bioactive amide alkaloids found in pepper roots. The process involved using the antioxidant activity of crude fractions and the Global Natural Products Social Molecular Networking analysis platform. The process led to the discovery of 23 previously unknown hydroxyl-amide alkaloids. Notably, compounds 11 , 12 , and 14 showed excellent antioxidant activity, while compound 11 exhibited significant inhibitory effects on mushroom tyrosinase. Theoretical exploration of enzyme-ligand interactions was conducted through molecular docking and molecular dynamics simulation. The findings of this study highlight the potential of hydroxyl-amide alkaloids as antioxidant products and natural food preservatives in the pharmaceutical and food cosmetic industries.

Objective: Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and serious manifestation of idiopathic inflammatory myopathy (IIM) associated with poor outcomes. Plasma exchange (PE) can quickly remove pathogenic substances from the blood. Therefore, PE may be efficacious in IIM patients who have elevated levels of autoantibodies, cytokines and chemokines, fighting for time for immunosuppressive therapy. However, the value of adding PE to immunosuppressants remains unclear. The purpose of this study was to determine the short-term outcomes, including the survival rate at 6 months and change of the laboratory data, of PE in combination with immunosuppressants and/or biologics in the treatment of IIM-RP-ILD., Methods: We searched PubMed, Embase and Cochrane Library to find reports of interest published from inception to March 4, 2024. STATA 15.1 was used for data analysis. A fixed or random-effects model with inverse-variance weighting was used to estimate the pooled risk ratio (RR) and 95% confidence interval (CI)., Results: Two hundred and thirty studies were identified. Eleven studies, including five retrospective cohort studies, four case-control studies and two case series, were included. PE was performed on 114 patients. The survival rate at 6 months was 80% (95%CI = 64%-92%), with moderate heterogeneity ( I 2 =63.45%, p  < 0.05). Moreover, the 6-month survival rate was significantly better in the PE group than in the non-PE group (RR, 1.34; 95% CI = 1.05-1.71, I 2 =30.7%; p  = 0.194). ILD-related serum markers, including ferritin, KL-6 and anti-MDA-5 antibody titres, were significantly suppressed by a series of PE treatments ( p  < 0.05)., Conclusion: The application of PE therapy plus treatment with corticosteroids, immunosuppressants and/or biologics was effective for patients with IIM-RP-ILD. PE may have additional supportive effect in intractable disease.

Aim: To analyze the changes in scientific output relating to Leber congenital amaurosis (LCA) and forecast the study trends in this field., Methods: All of the publications in the field of LCA from 2002 to 2022 were collected from Web of Science (WOS) database. We analyzed the quantity (number of publications), quality (citation and H-index) and development trends (relative research interest, RRI) of published LCA research over the last two decades. Moreover, VOSviewer software was applied to define the co-occurrence network of keywords in this field., Results: A total of 2158 publications were ultimately examined. We found that the focus on LCA kept rising and peaked in 2015 and 2018, which is consistent with the development trend of gene therapy. The USA has contributed most to this field with 1162 publications, 56 674 citations and the highest H-index value (116). The keywords analysis was divided into five clusters to show the hotspots in the field of LCA, namely mechanism-related, genotype-related, local phenotype-related, system phenotype-related, and therapy-related. We also identified gene therapy and anti-retinal degeneration therapy as a major focus in recent years., Conclusion: Our study illustrates historical research process and future development trends in LCA field. This may help to guide the orientation for further clinical diagnosis, treatment and scientific research., Competing Interests: Conflicts of Interest: Huang XX, None; Wang YM, None; Xie MY, None; Sun YQ, None; Zhao XH, None; Chen YH, None; Chen JQ, None; Han SY, None; Zhou MW, None; Sun XD, None., (International Journal of Ophthalmology Press.)

Objective: To analyze the correlation between drug-induced sleep endoscopy (DISE), results, polysomnography (PSG) indicators, and clinical parameters in patients with obstructive sleep apnea (OSA), and to establish and validate a predictive model for tongue base plane obstruction. Methods: This retrospective study analyzed 117 OSA patients diagnosed via PSG and treated at the Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, between October 2014 and March 2022. The cohort comprised of 114 males and 3 females, with an age range of 20 to 54 years (mean age 38.1±8.4 years). Data on DISE results, PSG results, and clinical indicators were collected for all 117 patients. Logistic regression analysis was performed to identify relevant indicators, and a predictive model for tongue base plane obstruction was constructed and internally validated using the R programming language. Results: Univariate logistic regression analysis identified four independent risk factors for predicting tongue root plane obstruction: tonsil grading, N2, N3, and rapid eye movement sleep(REM) stage [ OR :0.412(0.260~0.652),1.045(1.012~1.079),0.943(0.903~0.984),0.961(0.925~0.998), P <0.05]. Multivariate logistic regression analysis confirmed tonsil grading and N3 sleep stage (12.48±12.22%) as significant predictors. A nomogram model incorporating these factors demonstrated good predictive performance, with an area under curve(AUC) of 0.82 (95% CI : 0.548-1.000), an optimal cutoff of 0.519, a specificity of 80.0%, and a sensitivity of 86.7%. Internal validation of the model in the validation cohort yielded an AUC of 0.751 (95% CI : 0.625-0.876). Conclusions: Tongue base plane obstruction observed during DISE in OSA patients is associated with tonsil grading and N3 sleep stage duration. The predictive model developed for tongue base plane obstruction based on DISE demonstrates good efficacy, as evidenced by its internal validation.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery., (© 2024. The Author(s).)

Introduction: Lipid metabolism dysfunction is widely involved in the pathological process of acute ischemic stroke (AIS). The coordination of lipid metabolism between neurons and astrocytes is of great significance. However, the full scope of lipid dynamic changes and the function of key lipids during AIS remain unknown. Hence, identifying lipid alterations and characterizing their key roles in AIS is of great importance., Methods: Untargeted and targeted lipidomic analyses were applied to profile lipid changes in the ischemic penumbra and peripheral blood of transient middle cerebral artery occlusion (tMCAO) mice as well as the peripheral blood of AIS patients. Infarct volume and neurological deficits were assessed after tMCAO. The cell viability and dendritic complexity of primary neurons were evaluated by CCK8 assay and Sholl analysis. Seahorse, MitoTracker Green, tetramethyl rhodamine methyl ester (TMRM), 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX were used as markers of mitochondrial health. Fluorescent and isotopic free fatty acid (FFA) pulse-chase assays were used to track FFA flux in astrocytes., Results: Long-chain acylcarnitines (LCACs) were the lipids with the most dramatic changes in the ischemic penumbra and peripheral blood of tMCAO mice. LCACs were significantly elevated on admission in AIS patients and associated with poor outcomes in AIS patients. Increasing LCACs through a bolus administration of palmitoylcarnitine amplified stroke injury, while decreasing LCACs by overexpressing carnitine palmitoyltransferase 2 (CPT2) ameliorated stroke injury. Palmitoylcarnitine aggravated astrocytic mitochondrial damage after OGD/R, while CPT2 overexpression in astrocytes ameliorated cocultured neuron viability. Further study revealed that astrocytes stimulated by OGD/R liberated FFAs from lipid droplets into mitochondria to form LCACs, resulting in mitochondrial damage and lowered astrocytic metabolic support and thereby aggravated neuronal damage., Conclusion: LCACs could accumulate and damage neurons by inducing astrocytic mitochondrial dysfunction in AIS. LCACs play a crucial role in the pathology of AIS and are novel promising diagnostic and prognostic biomarkers for AIS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

A phytochemical study of the ethanol extract from Ailanthus altissima (Mill.) Swingle leaves resulted in the isolation of four new monoterpenoids (1-3, 5). The structures were elucidated using HRESIMS data, NMR spectroscopic data, quantum chemical calculations for NMR and ECD, and custom DP4+ probability analysis. Additionally, the absolute configuration of sugar was determined by acid hydrolysis. Compounds 1-4 are cyclogeraniane monocyclic monoterpenes, while compound 5 contains an acyclic mycrane monoterpenes skeleton. Anti-tyrosinase, anti-acetylcholinesterase, and anti-butyrylcholinesterase activities were tested. Compound 1 showed notable anti-acetylcholinesterase activity, and compound 3 exhibited significant inhibitory effects on anti-tyrosinase activity. Furthermore, the potential binding sites of compounds 1 and 3 were predicted by molecular docking., Competing Interests: Declaration of competing interest Qi Song, Zhi-Kang Duan, Ya-Nuo Tan, Zhi-Heng Gao, Dai Liu, Jin-Le Hao, Bin Lin, Xiao-Xiao Huang, and Shao-Jiang Song declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is a severe neurodegenerative disease associated with the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Although its pathogenesis remains unclear, microglia-mediated neuroinflammation significantly contributes to the development of PD. Here we showed that the sine oculis homeobox (SIX) homologue family transcription factors SIX2 exerted significant effects on neuroinflammation. The SIX2 protein, which is silenced during development, was reactivated in lipopolysaccharide (LPS)-treated microglia. The reactivated SIX2 in microglia mitigated the LPS induced inflammatory effects, and then reduced the toxic effect of conditioned media (CM) of microglia on co-cultured MES23.5 DA cells. Using the LPS-stimulated Cx3cr1-Cre ERT2 mouse model, we also demonstrated that the highly-expressed SIX2 in microglia obviously attenuated neuroinflammation and protected the DA neurons in SN. Further RNA-Seq analysis on the inflammatory activated microglia revealed that the SIX2 exerted these effects via up-regulating the FXYD domain containing ion transport regulator 2 (FXYD2). Taken together, our study demonstrated that SIX2 was an endogenous anti-inflammatory factor in microglia, and it exerted anti-neuroinflammatory effects by regulating the expression of FXYD2, which provides new ideas for anti-neuroinflammation in PD., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Reproducibility and scale-up production of microspheres through spray drying present significant challenges. In this study, biodegradable microspheres of Triamcinolone Acetonide Acetate (TAA) were prepared using a novel static mixing method by employing poly( lactic-co-glycolic acid) (PLGA) as the sustained-release carrier., Methods: TAA-loaded microspheres (TAA-MSs) were prepared using a static mixing technique. The PLGA concentration, polyvinyl alcohol concentration (PVA), phase ratio of oil/water, and phase ratio of water/solidification were optimized in terms of the particle size, drug loading (DL), and encapsulation efficiency (EE) of TAA-MSs. The morphology of TAA-MSs was examined using Scanning Electron Microscopy (SEM), while the physicochemical properties were evaluated through X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FT-IR). The in vitro release of TAA-MSs was compared to that of the pure drug (TAA) using a water-bath vibration method in the medium of pH 7.4 at 37°C., Results: The formulation composition and preparation condition for the preparation of TAA-MSs were optimized as follows: the PLGA concentration was 1%, the phase ratio of oil(dichloromethane) /water (PVA solution) was 1:3, the phase ratio of water (PVA solution)/solidification was 1:2. The optimized TAA-MSs displayed spherical particles with a size range of 30-70 μm, and DL and EE values of 27.09% and 98.67%, respectively. Moreover, the drug-loaded microspheres exhibited a significant, sustained release, with 20% of the drug released over a period of 28 days. The XRD result indicated that the crystalline form of TAA in microspheres had been partly converted into the amorphous form. DSC and FT-IR results revealed that some interactions between TAA and PLGA occurred, indicating that the drug was effectively encapsulated into PLGA microspheres., Conclusion: TAA-loaded PLGA microspheres have been successfully prepared via the static mixing technique with enhanced EE and sustained-release manner., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

1,2-diarylpropanes are a kind of abundant natural products formed by radical coupling. On account of molecular flexibility, it was challenged in the identifications of relative and absolute configurations of the 1,2-diarylpropanes. In this research, fourteen pairs of enantiomeric 1,2-diarylpropanes (1a/1b-14a/14b), comprising twelve previously undescribed pairs (1a/1b-4a/4b, 6a/6b-10a/10b, and 12a/12b-14a/14b), were isolated from the fruit of Crataegus pinnatifida. Their structures were determined through multiple NMR spectral analyses, empirical NMR rules, X-ray crystallography, and the comparison of experimental ECD spectra with calculated data. In addition, the analysis of ECD spectra revealed that substituent effects could generate an inverted chiroptical response, exhibiting in mirror-image ECD signals. This phenomenon was investigated by conformational analysis, molecular orbital analysis, the transition density matrix and hole/electron distributions. Moreover, a potential experimental rule was proposed for the rapid determination of the absolute configurations of the 1,2-diarylpropanes., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest to this work., (Copyright © 2024. Published by Elsevier Ltd.)

Demand for the exploration of botanical pesticides continues to increase due to the detrimental effects of synthetic chemicals on human health and the environment and the development of resistance by pests. Under the guidance of a bioactivity-guided approach and HSQC-based DeepSAT, 16 coumarin derivatives were discovered from the leaves of Ailanthus altissima (Mill.) Swingle, including seven undescribed monoterpenoid coumarins, three undescribed monoterpenoid phenylpropanoids, and two new coumarin derivatives. The structure and configurations of these compounds were established and validated via extensive spectroscopic analysis, acetonide analysis, and quantum chemical calculations. Biologically, 5 exhibited significant antifeedant activity toward the Plutella xylostella . Moreover, tyrosinase being closely related to the growth and development of larva, the inhibitory potentials of 5 against tyrosinase was evaluated in vitro and in silico . The bioactivity evaluation results highlight the prospect of 5 as a novel category of botanical insecticide.

Introduction: Neglected tropical diseases (NTDs) mainly affect underprivileged populations, potentially resulting in catastrophic health spending (CHS) and impoverishment from out-of-pocket (OOP) costs. This systematic review aimed to summarize the financial hardship caused by NTDs., Methods: We searched PubMed, EMBASE, EconLit, OpenGrey, and EBSCO Open Dissertations, for articles reporting financial hardship caused by NTDs from database inception to January 1, 2023. We summarized the study findings and methodological characteristics. Meta-analyses were performed to pool the prevalence of CHS. Heterogeneity was evaluated using the I2 statistic., Results: Ten out of 1,768 studies were included, assessing CHS (n = 10) and impoverishment (n = 1) among 2,761 patients with six NTDs (Buruli ulcer, chikungunya, dengue, visceral leishmaniasis, leprosy, and lymphatic filariasis). CHS was defined differently across studies. Prevalence of CHS due to OOP costs was relatively low among patients with leprosy (0.0-11.0%), dengue (12.5%), and lymphatic filariasis (0.0-23.0%), and relatively high among patients with Buruli ulcers (45.6%). Prevalence of CHS varied widely among patients with chikungunya (11.9-99.3%) and visceral leishmaniasis (24.6-91.8%). Meta-analysis showed that the pooled prevalence of CHS due to OOP costs of visceral leishmaniasis was 73% (95% CI; 65-80%, n = 2, I2 = 0.00%). Costs of visceral leishmaniasis impoverished 20-26% of the 61 households investigated, depending on the costs captured. The reported costs did not capture the financial burden hidden by the abandonment of seeking healthcare., Conclusion: NTDs lead to a substantial number of households facing financial hardship. However, financial hardship caused by NTDs was not comprehensively evaluated in the literature. To develop evidence-informed strategies to minimize the financial hardship caused by NTDs, studies should evaluate the factors contributing to financial hardship across household characteristics, disease stages, and treatment-seeking behaviors., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:XXH works for the World Health Organization. The author alone is responsible for the views expressed in this publication and does not necessarily represent the decisions, policies, or views of the World Health Organization., (Copyright: © 2024 Patikorn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients., (© 2024. The Author(s).)

Background: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear., Methods and Results: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1 GFP Ccr2 RFP mice and NLRP3 -deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3 -deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction., Conclusions: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Background: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used for acute ischemic stroke (AIS) patients. GBCAs or AIS alone may cause the adverse effects on kidney tissue, respectively. However, whether GBCAs and AIS would generate a synergistic negative effect remains undefined., Purpose: To evaluate synergistic negative effects of AIS and GBCAs on renal tissues in a mouse model of AIS, and to compare the differences of these negative effects between linear and macrocyclic GBCAs., Study Type: Animal study., Animal Model: Seventy-two healthy mice underwent transient middle cerebral artery occlusion (tMCAO) and sham operation to establish AIS and sham model (N = 36/model). 5.0 mmol/kg GBCAs (gadopentetate or gadobutrol) or 250 μL saline were performed at 4.5 hours and 1 day after model establishing (N = 12/group)., Assessment: Inductively coupled plasma mass spectrometry (ICP-MS) was performed to detect Gd concentrations. Serum biochemical analyzer was performed to measure the serum creatinine (Scr), uric acid (UA), and blood urea nitrogen (BUN). Pathological staining was performed to observe tubular injury, cell apoptosis, mesangial hyperplasia, and interstitial fibrosis., Statistical Tests: Two-way analysis of variances with post hoc Sidak's tests and independent-samples t-tests were performed. A P-value <0.05 was considered statistically significant., Results: AIS groups showed higher Gd concentration than sham group on day 1 p.i. regardless of gadopentetate or gadobutrol used. Increased total Gd concentration was also found in AIS + gadopentetate group compared with the sham group on day 28 p.i. Significantly higher rates for renal dysfunction, higher tubular injury scores, and higher numbers of apoptotic cells on days 1 or 28 p.i. were found for AIS mice injected with GBCA. AIS + gadopentetate group displayed more severe renal damage than the AIS + gadobutrol group., Data Conclusion: AIS and GBCAs may cause increased total Gd accumulation and nephrotoxicity in a mouse, especially linear GBCAs were used., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 4., (© 2023 International Society for Magnetic Resonance in Medicine.)

Agaricus is a species-rich genus with more than 600 species around the world. In this work, three new species, Agaricus cacainus, A. baiyunensis , and A. praeclarefibrillosus are described from the specimens collected at Baiyun Mountain, Guangzhou, China, a subtropical area with a monsoon maritime climate, based on phylogenetic analyses and morphological examinations of internal transcribed spacer (ITS1-5.8S-ITS2 = ITS), D1/D2 domains of the large subunit of ribosomal DNA (28S), and a part of translation elongation factor 1-alpha ( TEF1 ). Agaricus cacainus in A . sect. Amoeni is characterized by a parabolic to applanate, slightly depressed pileus covered with chocolate brown, appressed, triangular squamules against white background, a white, furfuraceous stipe, an unchanging context when cut, a fragile and evanescent annulus, usually 4- or 2-spored basidia, and mostly pyriform cheilocystidia. Agaricus baiyunensis in A . sect. Minores has a pileus with a slightly truncate top covered with light brown, downy-wooly fibrillose scales and a light yellowish stipe with membranous annulus. Agaricus praeclarefibrillosus in A . sect. Brunneopicti is characterized by a pileus surface with brownish, triangular, recurved scales and longitudinally splitting lines toward margin, a cottony stipe with white, tiny, recurved fibrils, a single annulus, and variously shaped cheilocystidia, with sparsely ornamented basidiospores. The detailed comparison of their morphological characteristics with closely related species is provided.

Introduction: Ischemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed., Methods: In this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case-control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments., Results: A total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis., Discussion: In conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hao, Liu, Lu, Zhao, Lin, Ma, Xue, Jin, Li, Zhou, Huang and Guan.)

Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum . Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro . Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.

Objective: Multicause-of-death methods were used to analyze mortality and leading causes of death associated with polymyalgia rheumatica (PMR) in the United States from 1999 to 2020., Materials and Methods: We analyzed mortality data from the Centers for Disease Control and Prevention (CDC) Data analysis system and selected death certificates that listed PMR as the cause of death based on the International Statistical Classification of Diseases and Related Health Problems (ICD-10) category code. Relevant mortality rates, number of deaths and historical trends were analyzed. The number of PMR-related deaths and age-standardized mortality rate (ASMR) trend charts were made using Excel 2010 version and trend lines were added., Results: Over the last 22 years, the total number of PMR-related deaths in the United States was 15,421 women (89.8%), a ratio of about 1:9 men to women. When PMR is listed as the underlying cause of death, the ASMR for women and men (per 100,000 people) is approximately 1.8-5.1:1, and when it is listed as the non-underlying cause of death, it is 1.8-3.3:1. PMR deaths are more frequent in individuals aged 70 years and above, with patients aged 80 years and above being most affected. Among different ethnicities, the highest number of deaths was found in Caucasians, followed by Black or African American. When it comes to causes of death, heart disease still ranks first, followed by cancer. In addition, we also found that when PMR combined with malignant tumors as a multiple cause of death, the number of female deaths was higher than that of male deaths, the overall number of deaths of both showed an upward trend, and the overall ASMR of both showed a downward trend., Conclusions: In the past 22 years, we have observed a low mortality rate of PMR in the United States. However, for patients with PMR, especially elderly women, medical workers should be vigilant and pay attention to whether they are combined with other complications, such as malignant neoplasms, and make timely diagnosis and treatment to further reduce the mortality rate of patients with PMR.

Seven undescribed neovibsane-type diterpenoids (1-7) were isolated from the leaves of Viburnum odoratissimum. Their planar structures and relative configurations were elucidated based on a combination of 1D and 2D NMR analysis. The absolute configurations were confirmed by Rh 2 (OCOCF 3 ) 4 -induced ECD analysis and comparison of experimental and TDDFT-calculated ECD spectrum. Based on the empirical results of the ECD of in situ formed Rh-complexes, rapid determination of the absolute configuration of C-14 within vibsane-type diterpenoids was proposed. In addition, 3 exhibited a high neuroblastoma cell protective effect of 81.8 % at 50 μM (the control group showed a neuroblastoma cell protective effect of 56.2 % at 50 μM)., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Eight structurally diverse components, including six undescribed ones, (±)-daphuarin A (1a/1b), daphuarin B (2), daphuarin D-E (4-6), together with a pair of new natural products (±)-daphuarin C (3a/3b) were isolated from the herb of Daphne bholua Buch.-Ham. ex D. Don. Their planar structures were elucidated by extensive spectroscopic analyses. The configurations were established with the assistance of quantum chemical calculations, together with the Custom DP4+ method. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To show the impact of Sjögren's syndrome (SS) on maternal and fetal outcomes following pregnancy., Methods: We performed a literature search based on PubMed, Web of science, Wan fang, China National Knowledge Infrastructure and ProQuest databases from 1 January 2007 to 6 November 2022. Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the certainty of the evidence. Systematic reviews and meta-analyses were performed using RevMan 5.3 software. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Trial sequential analyses were performed by TSA 0.9., Results: Nine studies with 2341 patients and 2472 pregnancies with SS were included in our analysis. This current analysis showed pregnancy hypertension and preeclampsia/eclampsia to be significantly higher in pregnant women with SS compared to pregnant women without SS (OR: 1.65, 95% CI: 1.04-2.63; P = 0.03), (OR: 2.06, 95% CI: 1.16-3.65; P = 0.01) respectively. Cesarean section, thromboembolic disease, premature rupture of membranes, and spontaneous abortion were also significantly higher in the SS women with OR: 2.07, 95% CI: 1.48-2.88; P < 0.0001, OR: 9.45, 95% CI: 1.99-44.87; P = 0.005, OR: 1.36, 95% CI: 1.13-1.64; P = 0.001, OR: 9.30, 95% CI: 4.13-20.93; P < 0.00001, respectively. Significantly higher premature births were observed with infants who were born from SS mothers (OR: 2.19, 95% CI: 1.54-3.12; P < 0.0001). Infants defined as 'small for gestational age/intrauterine growth restriction' and 'weighing < 2500 g' were also significantly higher in patients suffering from SS (OR: 2.26, 95% CI: 1.38-3.70; P = 0.001), (OR: 3.84, 95% CI: 1.39-10.61; P = 0.009) respectively. In addition, live birth significantly favored infants who were born from mothers without SS (OR: 21.53, 95% CI: 8.36-55.44; P < 0.00001). Subgroup analysis by sample size revealed that pregnancy hypertension risk has significantly increased in small cohort (OR: 2.74, 95%CI: 1.45-5.18), and a slight increase was found in population-based studies (OR: 1.14, 95%CI: 0.91-1.43). In both small cohorts and population-based researches, cesarean section was significantly higher in SS (OR: 2.13, 95% CI: 1.29, 3.52; OR: 1.85, 95% CI: 1.29-2.64, respectively). The number of infants with intrauterine growth restriction did not grow in the population-based researches (OR: 2.07, 95%CI: 0.92-4.66) although there has been an increase in small reports (OR: 2.53, 95%CI: 1.16-5.51). Subgroup analysis was conducted on the basis of study location (not Asian vs. Asian countries) indicated that cesarean section was significantly higher in SS in both countries (OR: 1.69, 95% CI: 1.31-2.18; OR: 3.37, 95% CI: 2.39-4.77, respectively)., Conclusion: This meta-analysis has shown SS to have a high impact on maternal and fetal outcomes following pregnancy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Guiding by LC-MS/MS analysis and the Global Natural Products Social (GNPS) Molecular Networking, three undescribed sesquiterpenoids, stedapgens A-C, and two known analogues were discovered in the barks of Daphne genkwa Sieb. et Zucc. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolated novel compounds were tested for their acetylcholinesterase inhibitory activities with IC 50 = 0.754 ± 0.059, 0.696 ± 0.026, and 0.337 ± 0.023  μ g/ml. Among them, stedapgen A displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

This paper reports lithium concentrations and isotopic compositions of olivines in the oceanized subcontinental lithospheric mantle (SCLM) peridotites of the Tibetan Yunzhug ophiolite. The results show systematic Li isotope changes with distance from the rim of olivine grains. δ 7 Li values of olivine in dunites decrease from + 10.46 to + 1.33‰ with increasing distance to olivine rim from 26.15 to 124.71 μm. A negative correlation of δ 7 Li and Li content in olivine from dunite and harzburgite indicates recent diffusive ingress of Li into the peridotites. The extremely heavy Li isotopic composition requires the seawater or seawater alteration endmember in the mixing model, and reveals Li diffusion from seawater into olivine. As in dunites, olivines in a harzburgite sample show similar variations in δ 7 Li as a function of distance from the grain rim (e.g., 6.01 to 1.73 in sample 14YZ13). We suggest that the behavior of Li in the oceanized SCLM peridotites may be controlled by Li diffusion from seawater, as Li activity in the liquid state is higher than the solid state in transporting Li through the olivines in the peridotites. This study supports that seawater Li diffusion is one of the important factors for the heterogeneity of mantle Li isotopes in ophiolites., (© 2024. The Author(s).)

A chemical investigation of leaves of Viburnum chingii afforded eleven compounds, including one undescribed lignan ( 1 ), a pair of known phenylpropanoid enantiomers ( 2a / 2b ), and eight known lignans ( 3 - 10 ). Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. The absolute configurations of compounds 1 was determined by comparing the experimental ECD data with the calculated values. The compounds 2a / 2b were separated successfully by a chiral chromatographic column. In addition, the acetylcholinesterase (AChE) inhibitory activities of described compounds were evaluated.

Eight structurally diverse rearranged sesquiterpenoids, including seven undescribed sesquiterpenoids (1a/1b and 3-8) were obtained from the aerial parts of Daphne penicillata. 1a/1b, 3, 5 and 6 possess rare rearranged guaiane skeletons and 4 represents the first example of rearranged carotene sesquiterpenoids. Their structures and absolute configurations were determined by extensive spectroscopic analyses, NMR and ECD calculations. Interestingly, 1a and 1b were a pair of magical interconverting epimers that may interconvert by retro-aldol condensation. The mechanism of interconversion has been demonstrated indirectly by 9-OH derivatization of 1a/1b and a hypothetical biogenetic pathway was proposed. All compounds were evaluated for anti-inflammatory and cytotoxic activities. Among them, 1a/1b and 2 exhibited potential inhibitory activities on the production of NO against LPS-induced BV2 microglial cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Four pairs of neolignan enantiomers (±)-1- (±)-4 with a distinctive isochroman moiety, including seven undescribed compounds, were isolated and identified from the fruits of Crataegus pinnatifida. Structural characterization of these compounds was established through comprehensive spectroscopic analyses, as well as quantum chemical calculations of ECD and NMR data. The preliminary bioassay displayed that compounds (+)-2 and (±)-3 exerted protective activities against H 2 O 2 -induced human neuroblastoma SH-SY5Y cells compared with the positive control. These bioactive compounds could be potential candidates for further pharmaceutical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No potential conflict of interest was reported by the authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)