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To clarify differences in the aroma components and characteristics between traditional and wild Dianhong Congou black teas, five traditional and five wild Dianhong Congou black teas were investigated using headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to measure and analyze the aroma characteristics of the two types of tea. A total of 180 aroma components were detected in the 10 tea samples, including 31 alcohols, 19 ketones, 33 aldehydes, 32 esters, 11 acids, 35 hydrocarbons, and 19 other categories. Thirty-six components with odor activity values greater than 1 were identified in traditional Dianhong Congou and wild Dianhong Congou black teas, with nine components common to both. Linalool was found to be the major contributor to aroma in traditional Dianhong Congou black tea, which was characterized by a floral and sweet aroma, while linalool, hexanal, and nonanal were the most significant aroma components in wild Dianhong Congou black tea, which had floral, sweet, woody, and fruity aromas. The results of this study provide a data reference for understanding the aroma characteristics of traditional and wild Dianhong Congou black teas.

The increase of oxidative stress level is one of the vital mechanisms of liver toxicity induced by arsenic (As). Ellagic acid (EA) is widely known due to its excellent antioxidation. Nevertheless, whether EA could alleviate As-induced oxidative stress and the underlying mechanisms remain unknown. Herein, As (2 and 4 μM) and EA (25 and 50 μM) were selected for alone and combined exposure of HepG2 cells to investigate the effects of EA on As-induced oxidative stress. Results indicated that EA could alleviate the oxidative stress caused by As via decreasing intracellular ROS level and MDA content, as well as improving SOD, CAT and GSH-PX activities. qRT-PCR showed that EA might enhance the expression levels of antioxidant enzymes NQO1, CAT and GPX1 by activating MAPK (JNK, p38 and ERK)/keap1-Nrf2 signaling pathway. EA was found to promote dissociation from keap1 and nuclear translocation of Nrf2 by competing with Nrf2 at ARG-380 and ARG-415 sites on keap1 to exert antioxidation using molecular docking. Moreover, metabolomics revealed that EA might maintain the redox balance of HepG2 cells by modulating or reversing disorders of carbon, amino acid, lipid and other metabolisms caused by As. This study provides diversified new insights for the removal of liver toxicity of As and the application of EA.

Establishing a sustainable industrial structure system is imperative for transforming the society to high-quality development and achieve the ''carbon peak'' and ''carbon neutrality'' goals. In this study, we explored a low-carbon pathway of regional industrial structure optimization to achieve a balance among economic growth, social security, and environmental conservation. A multi-objective optimization model of industrial structure of economic-social-environmental system was constructed by minimizing carbon emissions and maximizing economic benefits and social employment. In this study, we explored the scientific allocation path for industrial structure and set various scenarios to meet the diverse preferences and development requirements of decision-makers. Southwest China was used as a practical case to validate the model's efficacy, offering a decision-making framework for the sustainable development of the regional economy. After optimization, carbon emissions reduced by 0.9 %∼3.2 %, economic benefits increased by 2.5 %∼4.8 %, and employment levels nearly doubled. The proportion of the transportation industry in southwest China decreased by 11.58 %. The raw coal was the energy source with the highest contribution to carbon emissions, 2494.2 × 108 kgCO2eq.

Interfacial engineering is important for ferroelectric thin-film heterostructures because of the modulation of boundary conditions of the spontaneous polarizations and their switching behaviors, which are essential for ferroelectric electronics. In this work, we study the effects of interfacial buffering layer, 5-nm-thick SrTiO3 (STO), on the imprint and domain switching of epitaxial Pt/Pb(Zr,Ti)O3/SrRuO3 (SRO) thin-film heterostructures and capacitors. By buffering the ultrathin SrTiO3 layer at the Pb(Zr,Ti)O3 surface, the imprint effect can be dramatically alleviated as observed in the piezoresponse force microscopy (PFM)-measured domain structures and polarization–electric field hysteresis loops in thin-film capacitors. However, when the SrTiO3 layer is buffered at the Pb(Zr,Ti)O3/SrRuO3 interface, the imprint effect is slightly increased. These phenomena are explained based on the band alignments among the Pt and SrRuO3 electrodes and the Pb(Zr,Ti)O3 layer associated with the existence of oxygen vacancies in the SrTiO3 layer. With the reduction of imprint effect, the domain switching dynamics are also improved in the SrTiO3-buffered Pb(Zr,Ti)O3 capacitor, in which the switching activation field is decreased by about 45.3% in comparison with that of the pristine capacitor. These results facilitate the design and optimization of ferroelectric devices with the improvements in domain configurations, switching behaviors and band alignments.

PurposePeak Expiratory Flow (PEF) is associated with a variety of adverse health outcomes in older adults; however, the relationship between PEF and frailty remains uncertain, and this study investigated the relationship between PEF and frailty within an olderly Asian demographic.MethodsData were sourced from the Chinese Health and Retirement Longitudinal Study (CHARLS). Individuals in the study, all 60 years or older, underwent baseline PEF assessments quantified as standardized residual (SR) percentile values. The evaluation of frailty was conducted based on the criteria established by Fried. Participants without frailty at the outset were tracked over a four-year period, during which the relationships between PEF and frailty were examined through logistic regression and discrete-time Cox regression analyses.ResultsAmong 5,060 participants, cross-sectional analysis revealed that the prevalence of frailty was 2–3 times higher in the lower 10–49th and

Tea (Camellia sinensis) falls into the family Theaceae, is a valuable commercial crop, and tea products made from its buds and young leaves are favored by consumers all over the world. The more common Thea plant is Camellia sinensis (C. sinensis), but its most important relative, Camellia taliensis (C. taliensis), is also utilized by locals in the area of cultivation to manufacture tea. In this investigation, C. taliensis (DL) and C. sinensis (QJZ) were characterized in terms of their agronomic traits, physicochemical indices, metabolomics, and transcriptomics. The leaf area of DL is larger than that of QJZ; the color of DL’s buds and leaves is yellowish-green, while that of QJZ’s is green. DL’s buds and leaves are more densely velvety than those of QJZ. The HPLC results indicated that the physicochemical contents varied considerably between the two samples, with DL having greater concentrations of EGCG and GABA than QJZ, while QJZ had remarkably higher concentrations of C, CA, and EGC than DL. A total of 2269 metabolites and 362,190,414 genes were positively identified, with the number of DAMs and DEGs being 1001 and 34,026, respectively. The flavonoids, phenolic acids, and alkaloid metabolites were dramatically different between the two tea group plants. Bioinformatics profiling revealed that the DAMs and DEGs of the two tea group plants interacted with each other and were involved in metabolic pathways, including “biosynthesis of secondary metabolites”, “biosynthesis of amino acids”, “biosynthesis of cofactors”, “phenylpropanoid biosynthesis”, and “flavonoid biosynthesis”. Overall, these results provide statistical support for germplasm conservation and production for both C. taliensis and C. sinensis.

To expand the development of characteristic extension products of Yunnan tea and improve the utilization rate of Yunnan tea resources, in this study, we compared the metabolite composition among raw Pu-erh tea, ripe Pu-erh tea prepared with glutinous rice (according to tea to glutinous rice ratio of 1:3), and ripe Pu-erh tea prepared with a mixture of sorghum, rice, glutinous rice, wheat, and corn as raw materials (according to a tea to glutinous rice ratio of 1:3). Rice flavor liquor prepared with 100% glutinous rice served as a control. The raw Pu-erh tea liquor (RAWJ), ripe Pu-erh tea liquor (RIPEJ), ripe Pu-erh tea mixed grain liquor (HHLSJ), and rice-flavor liquor (MJ) were all brewed by semi-solid fermentation. The non-volatile components of the liquor samples were analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry as a broadly targeted metabolomics technique. A total of 691 metabolites were identified from the four samples. Among them, 674, 671, 633, and 667 species were detected in RAWJ, RIPEJ, HHLSJ, and MJ samples, respectively. Venn diagram analysis demonstrated 19, 21, and 14 unique metabolites in RAWJ, RIPEJ, and HHLSJ, respectively, compared with the metabolite composition of MJ. Flavonoids are the most important differential metabolite between tea liquor and rice-flavor liquor. This study provides a theoretical basis for the development of tea liquor products and offers insight into the difference in non-volatile components between tea liquor and rice-flavor liquor.

Abstract Background and aims Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) predicts a poor prognosis. The aim of the present study was to evaluate the efficacy and safety of using lenvatinib and camrelizumab combined with transarterial chemoembolization (TACE) to treat HCC with PVTT. Methods This was a single‐arm, open‐label, multicenter, and prospective study. Eligible patients with advanced HCC accompanied by PVTT were enrolled to receive TACE combined with lenvatinib and camrelizumab. The primary endpoint was progression‐free survival (PFS), while the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results Between April 2020 and April 2022, 69 patients were successfully enrolled. With a median follow‐up time of 17.3 months, the median age of the patient cohort was 57 years (range: 49–64 years). According to modified Response Evaluation Criteria in Solid Tumors, the ORR was 26.1% (18 partial responses [PRs]) and the DCR was 78.3% (18 PRs, 36 stable diseases [SDs]). The median PFS (mPFS) and median OS (mOS) were 9.3 and 18.2 months, respectively. And tumor number >3 was identified as an adverse risk factor for both PFS and OS. The most common adverse events across all grades included fatigue (50.7%), hypertension (46.4%), and diarrhea (43.5%). Twenty‐four patients (34.8%) experienced Grade 3 toxicity that was relieved by dose adjustment and symptomatic treatment. No treatment‐related deaths occurred. Conclusions TACE combined with lenvatinib and camrelizumab is a well‐tolerated modality treatment with promising efficacy for advanced HCC with PVTT.

ObjectiveAlthough several acupuncture and moxibustion therapies have been tested in managing breast cancer-related lymphedema (BCRL), there is little consensus regarding the best options for treating this condition. This systematic review and network meta-analysis compared the efficacy of various acupuncture and/or moxibustion therapies for BCRL.MethodsSeven databases and two clinical registration centers were searched from their inception to December 1st, 2023. The Cochrane Collaboration risk-of-bias assessment tool evaluated the quality of included RCTs. A pairwise meta-analysis was performed in STATA 16.0, while a network meta-analysis was performed in R 4.2.2.Results18 studies were included in this analysis. Our results showed that acupuncture and moxibustion methods had great advantages in improving BCRL of patients with breast cancer. In particular, needle-warming moxibustion (NWM) could be the optimal acupuncture and moxibustion method for improving clinical effectiveness and reducing the degree of swelling of affected limbs.ConclusionOur findings suggest that NWM has great potential in treating BCRL. It may reduce arm circumference, lower swelling levels, and improve clinical effectiveness. Nevertheless, more multi-center, high-quality, and large sample RCTs will be needed in the future.

Repairing damaged tissue caused by bacterial infection poses a significant challenge. Traditional antibacterial hydrogels typically incorporate various components such as metal antimicrobials, inorganic antimicrobials, organic antimicrobials, and more. However, drawbacks such as the emergence of multi-drug resistance to antibiotics, the low antibacterial efficacy of natural agents, and the potential cytotoxicity associated with metal antibacterial nanoparticles in hydrogels hindered their broader clinical application. In this study, we successfully developed imidazolium poly(ionic liquids) (PILs) polymer microspheres (APMs) through emulsion polymerization. These APMs exhibited notable antibacterial effectiveness and demonstrated minimal cell toxicity. Subsequently, we integrated the APMs into a gelatin methacryloyl (GelMA)—polyethylene glycol (PEG) hydrogel. This composite hydrogel not only showcased strong antibacterial and anti-inflammatory properties but also facilitated the migration of human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) and promoted osteogenic differentiation in vitro.

To reveal the difference of quality between traditional and wild Yunnan Congou black tea, five traditional and wild Yunnan Congou black tea were collected, respectively. Sensory qualities and biochemical components were compared. Sensory evaluation results showed that the shape, infusion color and infused leaves of the samples collected in this paper conform to the characteristics of Yunnan Congou black tea, that was, color of the dry tea leaves were dark with oily gloss, the infusion were red or orange red and bright, and the infused leaves were tender and uniformity. However, traditional Yunnan Congou black tea had a strong taste, while the wild Yunnan Congou black tea had a mellow and fresh taste. The contents of water extract, total catechins and caffeine in traditional Yunnan Congou black tea were 41.07%, 18.53 and 14.60 mg/g, respectively, which were significantly higher than those of wild Yunnan Congou black tea with 38.42%, 10.58 and 9.54 mg/g, respectively. While the average content of free amino acid in traditional Yunnan Congou black tea (3.92%) was lower than that of wild Yunnan Congou black tea (5.01%). The average contents of tea polyphenols were 16.61% and 16.56%, respectively, with no significant difference. The average contents of theaflavin, thearubigins and theabrownin in traditional Yunnan Congou black tea were 0.64%, 6.75%, 10.93%, and 0.61%, 2.70%, 11.80% in wild Yunnan Congou black tea respectively, among them, the content of thearubigins were significantly different. The average contents of quercetin, rutin, kaempferol and myricetin were 0.09, 0.67, 0.01 and 0.07 mg/g in traditional Yunnan Congou black tea, while 0.14, 0.27, 0.16 and 0.15 mg/g in wild Yunnan Congou black tea, respectively, which showed significant differences. Principal component analysis (PCA) and clustering analysis (CA) based on contents of 19 biochemical components showed that traditional and wild Yunnan Congou black tea divided into two clusters, indicating that contents of biochemical component between these two type black tea were significantly different. In general, the contents of water extract, catechins, caffeine and flavonols in traditional Yunnan Congou black tea were higher, which resulting the strong taste. However, the content of free amino acids in wild Yunnan Congou black tea were higher, resulting in fresh and mellow taste.

ABSTRACT In the situation of mass vaccination against COVID-19, few studies have reported on the early kinetics of specific antibodies (IgG/IgM/IgA) of vaccine breakthrough cases. There is still a lack of epidemiological evidence about the value of serological indicators in the auxiliary diagnosis of COVID-19 infection, especially when the nucleic acid results were undetectable. Omicron breakthrough cases post-inactivated vaccination (n = 456) and COVID-19-naive individuals with two doses of inactivated vaccination (n = 693) were enrolled. Blood samples were collected and tested for SARS-CoV-2 antibody levels based on the magnetic chemiluminescence enzyme immunoassay. Among Omicron breakthrough cases, the serum IgG antibody level was 36.34 Sample/CutOff (S/CO) (95% confidence interval [CI], 31.89 to 40.79) in the acute phase and 88.45 S/CO (95% CI, 82.79 to 94.12) in the recovery phase. Serum IgA can be detected in the first week post-symptom onset (PSO) and showed an almost linear increase within 5 weeks PSO. Compared with those of breakthrough cases, IgG and IgA titers of the postimmune group were much lower (4.70 S/CO and 0.46 S/CO, respectively). Multivariate regression showed that serum IgG and IgA levels in Omicron breakthrough cases were mainly affected by the weeks PSO (P

Background and purposeCorpus callosum (CC) infarction is an extremely rare subtype of cerebral ischemic stroke, however, the symptoms of cognitive impairment often fail to attract early attention of patients, which seriously affects the long-term prognosis, such as high mortality, personality changes, mood disorders, psychotic reactions, financial burden and so on. This study seeks to develop and validate models for early predicting the risk of subjective cognitive decline (SCD) after CC infarction by machine learning (ML) algorithms.MethodsThis is a prospective study that enrolled 213 (only 3.7%) CC infarction patients from a nine-year cohort comprising 8,555 patients with acute ischemic stroke. Telephone follow-up surveys were carried out for the patients with definite diagnosis of CC infarction one-year after disease onset, and SCD was identified by Behavioral Risk Factor Surveillance System (BRFSS) questionnaire. Based on the significant features selected by the least absolute shrinkage and selection operator (LASSO), seven ML models including Extreme Gradient Boosting (XGBoost), Logistic Regression (LR), Light Gradient Boosting Machine (LightGBM), Adaptive Boosting (AdaBoost), Gaussian Naïve Bayes (GNB), Complement Naïve Bayes (CNB), and Support vector machine (SVM) were established and their predictive performances were compared by different metrics. Importantly, the SHapley Additive exPlanations (SHAP) was also utilized to examine internal behavior of the highest-performance ML classifier.ResultsThe Logistic Regression (LR)-model performed better than other six ML-models in SCD predictability after the CC infarction, with the area under the receiver characteristic operator curve (AUC) of 77.1% in the validation set. Using LASSO and SHAP analysis, we found that infarction subregions of CC infarction, female, 3-month modified Rankin Scale (mRS) score, age, homocysteine, location of angiostenosis, neutrophil to lymphocyte ratio, pure CC infarction, and number of angiostenosis were the top-nine significant predictors in the order of importance for the output of LR-model. Meanwhile, we identified that infarction subregion of CC, female, 3-month mRS score and pure CC infarction were the factors which independently associated with the cognitive outcome.ConclusionOur study firstly demonstrated that the LR-model with 9 common variables has the best-performance to predict the risk of post-stroke SCD due to CC infarcton. Particularly, the combination of LR-model and SHAP-explainer could aid in achieving personalized risk prediction and be served as a decision-making tool for early intervention since its poor long-term outcome.

Cultivar identification plays an important role in ensuring the quality of oat production and the interests of producers. However, the traditional methods for discrimination of oat cultivars are generally destructive, time-consuming and complex. In this study, the feasibility of a rapid and nondestructive determination of cultivars of oat seeds was examined by using multispectral imaging combined with multivariate analysis. The principal component analysis (PCA), linear discrimination analysis (LDA) and support vector machines (SVM) were applied to classify seeds of 16 oat cultivars according to their morphological features, spectral traits or a combination thereof. The results demonstrate that clear differences among cultivars of oat seeds could be easily visualized using the multispectral imaging technique and an excellent discrimination could be achieved by combining data of the morphological and spectral features. The average classification accuracy of the testing sets was 89.69% for LDA, and 92.71% for SVM model. Therefore, the potential of a new method for rapid and nondestructive identification of oat cultivars was provided by multispectral imaging combined with multivariate analysis.

Background: Lenvatinib is recommended as a first-line tyrosine kinase inhibitor for advanced hepatocellular carcinoma (HCC) since 2017. The aim of this study was to compare the clinical action of lenvatinib in hepatitis B virus (HBV)-related HCC and hepatitis C virus (HCV)-related HCC.Methods: A continuous cohort of advanced HCC was retrospectively enrolled. And the patients were divided into HBV-related HCC and HCV-related HCC based on previous history of hepatitis virus infection. Then propensity score matching (PSM) was conducted to compare objective response rate (ORR),disease control rate (DCR),progression-free survival (PFS),overall survival (OS) and safety between the two groups.Results: A total of 203 eligible patients were included, with 72 HBV-related HCC and 36 HCV-related HCC after PSM. Both ORR (20.8% vs. 5.6%, P = .0759) and DCR (76.4% vs. 52.8%, P = .0232) were significantly higher in the HBV-related HCC than in the HCV-related HCC. Although no statistical differences in PFS (6.1 months vs. 3.3 months, P = .17) and OS (14.9 months vs. 17.7 months, P = .96) were observed between the two groups, there was a trend of difference in the PFS survival curve. On multivariate regression analysis of PFS, both HBV infection (HR, .54; 95% CI, .31–.95; P = .0332) and antiviral time >5 years (HR, .49; 95% CI, .26–.9; P = .0219) were identified as independent favorable factors, and AFP >200 ng/mL (HR, 1.88; 95% CI, 1.1–3.22; P = .0216) were found to be an independent adverse factor. In addition, compared with HCC who received the first dose of antiviral drugs less than 5 years, the patients who were administered those drugs over 5 years had a significantly favorable PFS (11.27 months vs. 3.87 months, P = .0011). Lenvatinib was well tolerated in all patients and the adverse events (AEs) were similar between the two groups.Conclusion: It seemed that lenvatinib benefited more in HBV-related advanced HCC in delaying disease progression, compared to those with HCV-related advanced HCC.

BackgroundBoth inflammation and cerebral white matter injury are closely associated with vascular cognitive impairment (VCI). The aim of this study was to analyze the correlation between peripheral serological markers, white matter injury, and cognitive function in patients with non-disabling ischemic cerebrovascular events (NICE); to identify potential biological markers for the diagnosis and prediction of VCI; and to provide a basis for the early diagnosis and intervention of VCI.MethodsWe collected clinical data, along with demographic and medical history data, from 151 NICE patients. Fasting venous blood samples were collected. Based on the Montreal Cognitive Assessment (MoCA) after admission, we divided the patients into normal cognitive function (NCF) and VCI groups, and then classified them into mild white matter hyperintensity (mWMH) and severe white matter hyperintensity (sWMH) based on Fazekas scores. The differences in serological marker levels were compared between the cognitive function groups and the white matter hyperintensity groups. Binary logistic regression models and receiver operating characteristic curves were used to analyze the diagnostic predictive value of serological markers for VCI in patients with NICE and in the white matter hyperintensity subgroups.ResultsAmong 151 patients with NICE, 95 were male and 56 were female. Lymphocyte count (OR = 0.405, p = 0.010, 95% CI [0.201, 0.806]), red blood cell count (OR = 0.433, p = 0.010, 95% CI [0.228, 0.821]), and hemoglobin level (OR = 0.979, p = 0.046, 95% CI [0.958, 0.999]) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age, granulocyte/lymphoid ratio (NLR), and neutrophil percentage but a lower MoCA score, hemoglobin level, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.713, p = 0.003, 95% CI [0.593, 0.833]) had an acceptable predictive value for the diagnosis of VCI, whereas white blood cell count (AUC = 0.672, p = 0.011, 95% CI [0.545, 0.799]), red blood cell count (AUC = 0.665, p = 0.014, 95% CI [0.545, 0.784]), and hemoglobin level (AUC = 0.634, p = 0.047, 95% CI [0.502, 0.765]) had marginal predictive value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups.ConclusionLymphocyte count, red blood cell count, and hemoglobin level were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.

Abstract Background Interleukin-10 (IL-10) is an independent factor for predicting adverse outcomes in pediatric patients with hemophagocytic lymphohistiocytosis (HLH). However, little is known about its prognostic value in adult patients. Methods This single center retrospective study was conducted to explore the prognostic value of IL-10 in 101 adults newly diagnosed with HLH. The serum interleukin levels were quantitatively determined by chemiluminescence using cytokine profiling kits. Results Serum IL-10 levels were significantly increased in adult HLH patients. Elevated IL-10 levels was correlated with lower concentrations of hemoglobin (r = − 0.279, P = 0.005). IL-10 levels were significantly lower in patients with macrophage activation syndrome (MAS) than in those with infection-associated HLH (IAHS) and malignancy-associated HLH (MAHS) (P = 0.033, P = 0.012). Patients with MAS had relatively longer survival than those with IAHS and MAHS (P 1050 µg/L and IL-10 ≥ 129 pg/mL were poor prognostic factors for survival. However, multivariate analysis revealed that only high serum IL-10 levels (≥ 129 pg/mL) at diagnosis and high post-treatment ferritin levels (> 1050 µg/L) were independent risk factors for poor overall survival in adult HLH patients (HR: 4.087, 95% CI 2.064–8.090, P

BackgroundPatients with advanced intrahepatic cholangiocarcinoma (iCCA) have a poor prognosis and a substantial unmet clinical need. The study was aimed to investigate the efficacy and safety of sintilimab combined with lenvatinib for advanced iCCA in second-line setting.MethodsThe patients at multiple centers, who progressed after the first-line chemotherapy or could not tolerate chemotherapy, were treated with the combination of sintilimab plus lenvatinib. The primary endpoint was time to progression (TTP), and the secondary endpoints included tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Prognostic factors were analyzed using Cox regression analysis.ResultsA total of 41 patients with advanced iCCA were enrolled for this multi-center observational study. Under a median follow-up of 12.1 months, the median age was 59 years (range, 33–75 years). Sixteen patients died of disease progression, with a median TTP of 6.6 months (95% CI, 4.9–8.3). ORR and DCR were 46.3% and 70.3%, respectively. The patients with PD-L1 TPS ≥10% reported a significantly higher ORR compared to those with PD-L1 TPS

Purpose: To assess the correlation between admission body temperature and delayed cerebral infarction in elderly patients with ruptured intracranial aneurysm (IA).Methods: Patients with ruptured IA diagnosed between 2012 and 2020 were retrospectively analyzed. Patients were divided into a non-infarction and an infarction group based on the presence of cerebral infarction after treatment. The demographic and clinical information of the patients was gathered. Outcomes at the 3-month follow-up were assessed using the modified Rankin Scale. Correlation between admission body temperature and cerebral infarction was assessed using Spearman's rank correlation coefficient. A receiver operating characteristic (ROC) curve was used to assess the specificity and sensitivity of admission body temperature to predict cerebral infarction.Results: A total of 426 patients (142 men and 284 women) with ruptured IA were enrolled. Elderly patients with cerebral infarction (12.4%) had a lower body temperature at admission (p < 0.001), higher prevalence of hypertension and diabetes (p = 0.051 and p = 0.092, respectively), and higher rate of poor outcomes (p < 0.001). Admission body temperature was independently associated with cerebral infarction (odds ratio [OR] = 5.469, p < 0.001); however, hypertension (OR = 0.542, p = 0.056), diabetes (OR = 0.750, p = 0.465), and aneurysm size (OR = 0.959, p = 0.060) showed no association. An inverse correlation between admission body temperature and the incidence of cerebral infarction was observed (Spearman's r =−0.195, p < 0.001). An admission body temperature of 36.6°C was able to distinguish infarction and non-infarction patients. The area under the ROC curve was 0.669 (specificity, 64.15%; sensitivity, 81.50%; p < 0.001).Conclusions: Lower body temperature at admission (≤36.6°C) is an independent predictor of delayed cerebral infarction in elderly patients who have undergone treatment for ruptured IA. Therefore, it could be a risk factor for adverse outcomes of IA.

Background: Recently, both trivalent chromium Cr (III) and hexavalent chromium Cr (VI) have been reported to produce neurotoxicity. However, the underlying mechanisms of the neurotoxicity caused by different chemical valence of chromium remain unclear. Objective: The purpose of this study was to investigate the mechanism of neurotoxicity induced by exposure to chromium with different valence states based on metabolic disturbance in zebrafish larvae. Methods: Zebrafish embryos were exposed to 1 mg/L Cr (III) and 1 mg/L Cr (VI) for 120 hpf respectively. The related indexes of neural development were observed by stereoscope and behavior analysis system. 8OH-dG were detected using enzyme-linked immunosorbent assay. The generation of reactive oxygen species was detected using an oxidant-sensing probe 2',7'-dichlorodihydrofluorescein diacetate. AChE activity was determined by a colorimetric assay based on hydrolysis of acetylcholine. The expression levels of neurodevelopmental genes and methyltransferase genes in juvenile zebrafish was analyzed by real-time PCR. The methylation status of neurogenin1 and neurod1 genes was detected by bisulfite sequencing PCR. The binding of H3K27me3 was detected by chromatin immunoprecipitation-qPCR. Metabolic profiles and one carbon metabolic analysis were performed by UPLC-MS. Results: There were no significant differences in survival rate, hatching rate and spontaneous movement of zebrafish in both Cr-exposed groups compared to the control. The malformation rate in Cr (VI) -exposed group was obviously increased compared to the control and Cr (III) -exposed group. At 48hpf and 72hpf of exposure, the embryonic heart rate in Cr (III)-exposed group was significantly higher than that of Cr (VI)-exposed group and the control. At 120hpf, zebrafish in both Cr-exposed groups exhibited decreasing changes in swimming distance and disturbance of sensitivity to light and dark. 8OH-dG in Cr (VI)-exposed group were significantly higher than that in the control. The generation of ROS in both Cr -exposed groups was significantly higher than that in the control. The activity of AchE was significantly decreased in both Cr-exposed groups compared to the control. Most of early neurogenesis related genes, such as α-tubulin, elavl3, gap43, sox19b, neurogenin1 and neurod1 in Cr-exposed groups were significantly up-regulated compared to those in the control. The expression of dnmt1 and dnmt3 genes was significantly down-regulated in both Cr-exposed groups. BSP-PCR results showed that genic sequences in the neurogenin1 and neurod1 genes have lower levels of DNA methylation in both Cr-exposed groups, especial in Cr (VI)-exposed group. ChIP analysis showed that there was a decrease in H3K27me3 binding within the corresponding region of neurogenin1 in both Cr-exposed groups and that of neurod1 in Cr (III)-exposed group. Untargeted metabolomic analysis showed that significant changes in metabolites induced by Cr exposure were associated with differences in primary bile acid biosynthesis, phospholipid biosynthesis (phosphatidylcholine biosynthesis and phosphatidylethanolamine biosynthesis), linoleic acid metabolism, arachidonic acid metabolism, amino acid metabolism, purine metabolism, betaine metabolism, spermidine and spermine biosynthesis, and folate metabolism, the last four of which are related to one carbon metabolism. Targeted analysis of one carbon metabolites (5-MT, Gly, Met, SAH and Hcy) related with folate cycle and methionine metabolism were significantly decreased upon Cr exposure. The elevated SAM to SAH ratio in both Cr- exposed group indicated the decreasing capacity for methylation reaction. Conclusion: Cr (III) and Cr (VI) can induce neurotoxicity by interfering with one carbon metabolism and affecting DNA methylation and histone methylation to regulate the expression of neuro-related genes. Cr exposure also influenced primary bile acid biosynthesis and phospholipid biosynthesis, which are associated with neuroprotective effects and need to be further validated.

We propose a non-parametric method to cluster mixed data containing both continuous and discrete random variables. The product space of the continuous and discrete sample space is transformed into a new product space based on adaptive quantization on the continuous part. Detection of cluster patterns on the product space is determined locally by using a weighted modified chi-squared test. Our algorithm does not require any user input since the number of clusters is determined automatically by data. Simulation studies and real data analysis results show that our proposed method outperforms the benchmark method, AutoClass, in various settings.

Abstract Background Understanding the prevalence and evolution of HIV-1 drug resistance (DR) and associated mutation patterns is critical to implementing free antiretroviral therapy in Yunnan, the first antiretroviral treatment location in China. Here We provide a basis for understanding the occurrence and development of HIV-1 resistance in Yunnan and a theoretical foundational for strategy to delay HIV-1 drug resistance and achieve successful individualized treatment. Methods Plasma samples from different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to September 2016, and those from drug-resistant individuals were genotyped using in-house assays, 88 patients were selected for the study who had been on treatment for ≥6 months (and for whom drug resistance was then measured), and each patient had at least 3 genotype resistance tests and who were enrolled to analyze mutation and evolution of HIV resistance. Results 264 Pol sequences of 88 patients were obtained. Drug resistance levels to eight drugs increased to varying degrees with prolonged treatment. Resistance to efavirenz (EFV) and etravirine (ETR) showed the highest change, comparisons of resistant changes to second and first and to third and second agents showed altered level of drug resistance were 25 and 20 cases, 28 and 18 cases, respectively. The smallest change was Lopinavir/Ritonavir (LPV/r) present 2 and 3 cases; Resistance to lamivudine (3TC) and lopinavir/ritonavir (LPV/r) was high among patients detected thrice, whereas other drugs were distributed in all resistance levels. M184 V/I (26.14%), T69S (11.36%), and T215Y/I (10.23%) mutations were the most common in nucleoside reverse transcriptase inhibitors (NRTIs), and K103 N/R/S (21.59%), V179D/E (20.45%) in Non-NRTIs (NNRTIs). Furthermore, L10 V/F/I (6.82%), A71V (4.55%), and I54V (4.55%) mutations were common in protease inhibitors (PIs). Conclusions We found dynamic genotypic changes in HIV-1 drug-resistance in Yunnan, with prolonged treatment, and drug resistance was inevitable. However, resistance to different drugs occurred at varying times, and mutation site emergence was the main cause. These findings enhance our understanding of evolution and regulation, and are valuable for developing HIV-1 DR prevention strategies in Yunnan.

This paper reveals the contemporary Chinese state’s active role in shaping the country’s religion-related intangible cultural heritage (ICH) safeguarding, through a systematic review of China’s official inventories of national representative ICH projects and extensive investigations of relevant local practices and initiatives. Although China is ruled by a political party officially embracing an atheist ideology, various elements of the contemporary Chinese state have been proactively involved in safeguarding religion-related ICH. The Chinese state’s involvement in de facto religion-related ICH safeguarding predates its adoption of explicit ICH safeguarding narratives. Still, the Chinese state’s practices and initiatives in safeguarding religion-related ICH flourished after ratifying the UNESCO Convention for the Safeguarding of the Intangible Cultural Heritage in 2004. Since then, China’s central government has established a nationwide framework to recognise representative ICH items, including religion-related ones. Beyond Beijing, various local state agencies have also developed noticeable enthusiasm for supporting the safeguarding of religion-related ICH. In addition to engaging directly with ICH safeguarding, the contemporary Chinese state has also shaped China’s religion-related ICH by working closely with some academics and religious groups.

The tissue engineering of cartilage represents a promising approach for cartilage repair, and the process includes cells, growth factors, and a scaffold. The scaffold is important for supporting, reinforcing, and organizing the regenerating tissue. Currently, Wharton's jelly (WJ) is considered an ideal scaffold material for cartilage tissue engineering because it has a similar composition, structure, and function as cartilage tissue. Here, we fabricated electrospun nanofibers composed of a decellularized WJ matrix reinforced by poly(ε-caprolactone) (PCL) and investigated the feasibility of a nanofibrous WJ/PCL scaffold with adipose-derived stem cells (ASCs) for use in cartilage regeneration. WJ was decellularized and then electrospun with PCL to form a WJ/PCL scaffold. The results indicated that the WJ/PCL scaffold possessed appropriate mechanical properties, suitable biodegradation, excellent hydrophilicity, increased adherence rate, low immunological reactivity, and good biocompatibility when compared with pure WJ or pure PCL scaffolds. Importantly, the WJ/PCL scaffold showed chondroconductive capabilities with ASC in vitro culture for 4 weeks. Our findings demonstrated that electrospun nanofibrous WJ/PCL is an appropriate scaffold for cartilage tissue engineering. Keywords: Wharton's jelly, Electrospun, Cartilage, Scaffold, Adipose-derived stem cells

Objective: According to the EAU Guidelines, transurethral resection of the prostate (TURP) has so far still been considered as the gold standard for surgical treatment for patients with obstructing clinical benign prostate hyperplasia (BPH). However, its relatively high rate of complications and postoperative recurrence necessitates further modification and innovation on the surgery technique. We reported the patient outcomes with our technique. Methods: We retrospectively analyzed 52 patients with obstructing clinical BPH who underwent bipolar transurethral enucleation and resection of the prostate (B-TUERP) between March 2015 and September 2015. Pre- and perioperative parameters were obtained from medical charts. Postoperative follow-ups were administrated at 1, 3, 6, 12 and 24 month(s) after surgery, respectively. Results: All the operations were performed successfully with a mean operative time of 43.1 min and an average tissue removal rate of 74.7%. Qmax was significantly improved immediately after surgery, followed by a continuous improvement throughout the follow-ups. Following a steep decrease in mean prostate specific antigen (PSA) and post void residual (PVR) observed within the first half year after surgery, the serum PSA was then maintained at a constant level of 0.61 ng/mL. Temporary urinary retention was found in four cases (7.7%). Stress urinary incontinence occurred in five patients (9.6%), with the condition resolved in 1–2 weeks without extra treatment. Urethral strictures and bladder neck contractures, as the most commonly observed long-term complications, developed in four patients (7.7%). No recurrence was found during 2 years of follow-ups. An improvement in International Index of Erectile Function (IIEF-5) scores was witnessed in 17 patients preoperatively with normal sexual function during the first 6 months after surgery, and sustained throughout the 24-month period. Conclusions: Enucleation reflects an improvement on surgical technique in many ways with a need for surgical equipment that can be broadly accessible in clinical practice. Currently, bipolar resection is a commonly employed procedure in clinical settings, and its similarity shared with bipolar enucleation technique warrants a quick learning of B-TUERP by urologists. Based on these findings, we believe that the substitution of TURP by TUERP as the gold standard for prostate endoscopic procedure can be expected in the future.

The research on tidal-current energy-capture technology mainly focuses on the conditions of high flow velocity, focusing on the use of differential pressure lift, while the average flow velocity in most sea areas of China is less than 1.5 m/s, especially in the marine aquaculture area, where tidal-current energy is needed to provide green energy locally. Due to the low flow velocity of this type of sea area, it seriously affects the effect of differential pressure lift, which is conducive to exerting the effect of impact resistance. In this regard, the coupling effect of the differential pressure lift and the impact resistance on the blade torque is comprehensively considered, this research puts forward the design method of the lift-–drag-composite thin-plate arc turbine blade. Based on the blade element momentum (BEM) theory and Bernoulli’s principle, the turbine dynamic model was established, and the nonlinear optimization method was used to solve the shape parameters of the turbine blades, and the thin-plate arc and NACA airfoil blade turbines were trial-produced under the same conditions. A model experiment was carried out in the experimental pool, and the Xiangshan sea area in Ningbo, East China Sea was taken as the experimental sea area. The results of the two experiments showed the same trend, indicating that the energy-harvesting performance of the lift–drag-composite blade was significantly better than that of the lift blade under the conditions of low flow velocity and small radius, which verified the correctness of the blade design method, and can promote the research and development of tidal energy under the conditions of low flow velocity and small radius.