Prevalence, characteristics, evaluation, and management of carotid body tumors: Systematic analysis based on available evidence.

OBJECTIVE: Although carotid body tumors (CBTs) are rare, they attract particular attention because of their propensity for malignant transformation and the high surgical risk. Because data are scarce and as it is difficult to achieve a large sample size, no study has yet comprehensively analyzed the characteristics, management, or operative complications of CBTs. Therefore, we collected and analyzed all currently available information on CBTs and used the pooled data to derive quantitative information on disease characteristics and management. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and the Web of Science up to December 1, 2022, for studies that investigated the characteristics and management of CBTs. The primary objective was to identify the prevalence of the various characteristics and the incidence of complications. The secondary objective was to compare patients who underwent preoperative embolization (PE) and those who did not (non-PE), as well as to compare patients with different Shamblin grades and those with and without succinate dehydrogenase (SDH) mutations in terms of CBT characteristics and complications. Two reviewers selected studies for inclusion and independently extracted data. All statistical analyses were performed using the standard statistical procedures of Review Manager 5.2 and Stata 12.0. RESULTS: A total of 155 studies with 9291 patients and 9862 tumors were identified. The pooled results indicated that the median age of patients with CBT was 45.72 years, and 65% were female. The proportion of patients with bilateral lesions was 13%. In addition, 16% of patients had relevant family histories, and the proportion of those with SDH gene mutations was 36%. Sixteen percent of patients experienced multiple paragangliomas, and 12% of CBTs had catecholamine function. The incidence of cranial nerve injury (CNI) was 27%, and 14% of patients suffered from permanent CNI. The incidence rates of operative mortality and stroke were both 1%, and 4% of patients developed transient ischemic attacks. Of all CBTs, 6% were malignant or associated with metastases or recurrences. The most common metastatic locations were the lymph nodes (3%) and bone (3%), followed by the lungs (2%). Compared with non-PE, PE reduced the estimated blood loss (standardized mean difference, -0.95; 95% confidence interval [CI], -1.70 to -0.20) and the operation time (standardized mean difference, -0.56; 95% CI, -1.03 to -0.09), but it increased the incidence of stroke (odds ratio, 2.44; 95% CI, 1.04-5.73). Higher Shamblin grade tumors were associated with more operative complications. Patients who were SDH gene mutation-positive were more likely to have a relevant family history and had more symptoms. CONCLUSIONS: CBT was most common in middle-aged females, and early surgical resection was feasible; there was a low incidence of serious operative complications. Routine PE is not recommended because this may increase the incidence of stroke, although PE somewhat reduced the estimated blood loss and operation time. Higher Shamblin grade tumors increased the incidence of operative complications. Patients who were SDH gene mutation-positive had the most relevant family histories and symptoms.

Isolation of two peptaibols with potent antimicrobial and cytotoxic activities from the mangrove endophytic fungus Trichoderma lentiforme ML-P8-2.

Trichorzin PA is a family of 18-residue peptaibols with linear and flexible peptide chains. The three-dimensional structures and biological activities of trichorzin PA peptaibols are largely uncharacterised. In this work, two previously identified peptaibols, trichorzin PA VI (1) and II (2), were isolated from Trichoderma lentiforme ML-P8-2. While for the first time, we report here the X-ray crystallographic structure of 1, antimicrobial activities against a panel of common pathogenic bacteria and fungi, and cytotoxicities of 1 and 2. In bioassays, 1 and 2 exhibited strong antimicrobial activities against the seven tested microbes, with MIC values in the range of 0.19-6.25 µM. Additionally, 1 and 2 displayed potent cytotoxicities against five human cancer cell lines, with IC50 values in the range of 0.01 ± 0.02-2.75 ± 0.17 µM. The bioassay results were generally better than those reported for other 18-residue peptaibols, including other trichorzin PA members.

STON2 variations are involved in synaptic dysfunction and schizophrenia-like behaviors by regulating Syt1 trafficking.

Synaptic dysfunction is a core component of the pathophysiology of schizophrenia. However, the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood. The Stonin 2 (STON2) gene encodes a major adaptor for clathrin-mediated endocytosis (CME) of synaptic vesicles. In this study, we showed that the C-C (307Pro-851Ala) haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME. We found that schizophrenia-related STON2 variations led to protein dephosphorylation, which affected its interaction with synaptotagmin 1 (Syt1), a calcium sensor protein located in the presynaptic membrane that is critical for CME. STON2307Pro851Ala knockin mice exhibited deficits in synaptic transmission, short-term plasticity, and schizophrenia-like behaviors. Moreover, among seven antipsychotic drugs, patients with the C-C (307Pro-851Ala) haplotype responded better to haloperidol than did the T-A (307Ser-851Ser) carriers. The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin mice. Our findings demonstrated the effect of schizophrenia-related STON2 variations on synaptic dysfunction through the regulation of CME, which might be attractive therapeutic targets for treating schizophrenia-like phenotypes.

Overlooked Role of Coexistent Hydrogen Peroxide in Activated Peracetic Acid by Cu(II) for Enhanced Oxidation of Organic Contaminants.

Cu(II)-catalyzed peracetic acid (PAA) processes have shown significant potential to remove contaminants in water treatment. Nevertheless, the role of coexistent H2O2 in the transformation from Cu(II) to Cu(I) remained contentious. Herein, with the Cu(II)/PAA process as an example, the respective roles of PAA and H2O2 on the Cu(II)/Cu(I) cycling were comprehensively investigated over the pH range of 7.0-10.5. Contrary to previous studies, it was surprisingly found that the coexistent deprotonated H2O2 (HO2-), instead of PAA, was crucial for accelerating the transformation from Cu(II) to Cu(I) (kHO2-/Cu(II) = (0.17-1) × 106 M-1 s-1, kPAA/Cu(II) < 2.33 ± 0.3 M-1 s-1). Subsequently, the formed Cu(I) preferentially reacted with PAA (kPAA/Cu(I) = (5.84 ± 0.17) × 102 M-1 s-1), rather than H2O2 (kH2O2/Cu(I) = (5.00 ± 0.2) × 101 M-1 s-1), generating reactive species to oxidize organic contaminants. With naproxen as the target pollutant, the proposed synergistic role of H2O2 and PAA was found to be highly dependent on the solution pH with weakly alkaline conditions being more conducive to naproxen degradation. Overall, this study systematically investigated the overlooked but crucial role of coexistent H2O2 in the Cu(II)/PAA process, which might provide valuable insights for better understanding the underlying mechanism in Cu-catalyzed PAA processes.

The Polyketides with Antimicrobial Activities from a Mangrove Endophytic Fungus Trichoderma lentiforme ML-P8-2.

Five new polyketides, including two chromones (1-2), two phenyl derivatives (4-5), and a tandyukusin derivative (6), along with five known polyketides (3 and 7-10) were isolated from mangrove endophytic fungus Trichoderma lentiforme ML-P8-2. The planar structures of compounds were elucidated via detailed 1D, 2D NMR, and HR-ESI-MS analysis. ECD spectra, optical rotation values calculation, and alkali hydrolysis were applied in the determination of the absolute configuration of the new compounds. In bioassays, 6 and 9 exhibited promising antifungal activities against Penicillium italicum, with an MIC value of 6.25 µM for both compounds. Moreover, 3 displayed moderate AChE inhibitory activity with an IC50 value of 20.6 ± 0.3 µM.

Dietary Restriction Delays But Cannot Heal Irradiation-Induced Hair Graying by Preserving Hair Follicle Stem Cells in Quiescence.

DNA damage represents one of the cell intrinsic causes of stem cell aging, which leads to differentiation-induced removal of damaged stem cells in skin and blood. Dietary restriction (DR) retards aging across various species, including several strains of laboratory mice. Whether, DR has the potential to ameliorate DNA damage-driven stem cell exhaustion remains incompletely understood. In this study, we show that DR strongly extends the time to hair graying in response to γ-irradiation (ionizing radiation [IR])-induced DNA damage of C57BL/6 J mice. The study shows that DR prolongs resting phase of hair follicles. DR-mediated prolongation of hair follicle stem cell (HFSC) quiescence blocks hair growth and prevents the depletion of HFSCs and ckit+ melanoblasts in response to IR. However, prolongation of HFSC quiescence also correlates with a suppression of DNA repair and cannot prevent melanoblast loss and hair graying in the long run, when hair cycling is reinitiated even after extended periods of time. Altogether, these results support a model indicating that nutrient deprivation can delay but not heal DNA damage-driven extinction of melanoblasts by stalling HFSCs in a prolonged state of quiescence coupled with inhibition of DNA repair. Disconnecting these two types of responses to DR could have the potential to delay stem cell aging.

Hydroxylamine enhanced the degradation of diclofenac in Cu(II)/peracetic acid system: Formation and contributions of CH3C(O)O•, CH3C(O)OO•, Cu(III) and •OH.

The slow reduction of Cu(II) into Cu(I) through peracetic acid (PAA) heavily limited the widespread application of Cu(II)/PAA system. Herein, hydroxylamine (HA) was proposed to boost the oxidative capacity of Cu(II)/PAA system by facilitating the redox cycle of Cu(I)/Cu(II). HA/Cu(II)/PAA system was quite rapid in the removal of diclofenac within a broad pH range of 4.5-9.5, with a 10-fold increase in the removal rate of diclofenac compared with the Cu(II)/PAA system at an optimal initial pH of 8.5. Results of UV-Vis spectra, electron paramagnetic resonance, and alcohol quenching experiments demonstrated that CH3C(O)O•, CH3C(O)OO•, Cu(III), and •OH were involved in HA/Cu(II)/PAA system, while CH3C(O)OO• was verified as the predominant reactive species of diclofenac elimination. Different from previously reported Cu-catalyzed PAA processes, CH3C(O)OO• mainly generated from the reaction of PAA with Cu(III) rather than CH3C(O)O• and •OH. Four possible elimination pathways for diclofenac were proposed, and the acute toxicity of treated diclofenac solution with HA/Cu(II)/PAA system significantly decreased. Moreover, HA/Cu(II)/PAA system possessed a strong anti-interference ability towards the commonly existent water matrix. This research proposed an effective strategy to boost the oxidative capacity of Cu(II)/PAA system and might promote its potential application, especially in copper-contained wastewater.

A non-Newtonian fluid quasi-solid electrolyte designed for long life and high safety Li-O2 batteries.

The Li dendrite growth and the liquid electrolyte volatilization under semi-open architecture are intrinsic issues for Li-O2 battery. In this work, we propose a non-Newtonian fluid quasi-solid electrolyte (NNFQSE) SiO2-SO3Li/PVDF-HFP, which has both shear-thinning and shear-thickening properties. The component interactions among the sulfonated silica nanoparticles, liquid electrolyte, and polymer network are beneficial for decent Li+ conductivity and high liquid electrolyte retention without volatilization. Furthermore, NNFQSE exhibits shear-thinning property to eliminate the stress of dendrite growth during repeated cycling. Meanwhile, when the force suddenly increases, such as a high current rate, the NNFQSE may dynamically turn shear-thickening to respond and mechanically stiffen to inhibit the lithium dendrite penetration. By coupling with the NNFQSE, the lithium symmetrical battery can run over 2000 h under 1 mA cm-2 at room temperature, and the quasi-solid Li-O2 battery actualizes long life above 5000 h at 100 mA g-1.

Exosomes in liver fibrosis: The role of modulating hepatic stellate cells and immune cells, and prospects for clinical applications.

Liver fibrosis is a global health problem caused by chronic liver injury resulting from various factors. Hepatic stellate cells (HSCs) have been found to play a major role in liver fibrosis, and pathological stimuli lead to their transdifferentiation into myofibroblasts. Complex multidirectional interactions between HSCs, immune cells, and cytokines are also critical for the progression of liver fibrosis. Despite the advances in treatments for liver fibrosis, they do not meet the current medical needs. Exosomes are extracellular vesicles of 30-150 nm in diameter and are capable of intercellular transport of molecules such as lipids, proteins and nucleic acids. As an essential mediator of intercellular communication, exosomes are involved in the physiological and pathological processes of many diseases. In liver fibrosis, exosomes are involved in the pathogenesis mainly by regulating the activation of HSCs and the interaction between HSCs and immune cells. Serum-derived exosomes are promising biomarkers of liver fibrosis. Exosomes also have promising therapeutic potential in liver fibrosis. Exosomes derived from mesenchymal stem cells and other cells exhibit anti-liver fibrosis effects. Moreover, exosomes may serve as potential therapeutic targets for liver fibrosis and hold promise in becoming drug carriers for liver fibrosis treatment.

Leakage Dynamics of Glass Bottles on Container Closure Integrity Testing: Influence of Different Laser-Drilled Microhole Geometries.

Container closure integrity testing (CCIT) is a critical step in ensuring package integrity and providing feedback on package designs. In practical applications, CCIT methods, namely physical and probabilistic methods, must be appropriately selected and validated to ensure their suitability for the intended use. However, the industry still lacks practical recommendations regarding the choice of CCIT methods and artificial leaks to set the acceptance criteria. The main reason is the lack of correlation between testing methods. Artificially introduced leak microholes are the only way to determine the sensitivity of a CCIT method and to implement the method correlation. However, the type of artificial leakage is a key factor because in most studies, leakage is described and valued using a single parameter, such as size. This can significantly affect the credibility of the relevant test results, especially in the case of microbial invasion, where the difference in test conditions and samples will severely affect the probability of microbial invasion. Therefore, it is vital to conduct a systematic study on the influence of leakage conditions on CCIT methods. In this study, the influence of the shapes of artificial leaks on the two kinds of testing methods was systematically studied based on a laser-drilled microhole-a highly potential and non-exogenous artificial leak manufacturing method that can fabricate different leakage geometries. The reason for the influence of the shape of an artificial leak on the CCIT is that the deterministic method takes defects as an idealized model and ignores the influence of the leak shape, wall thickness, and other factors on leakage and pollution risks. However, these factors seriously affect the dynamic process of leakage and microbial invasion. The pressure decay method is used to test the leakage flow rate of conical and straight holes. Microbial challenge tests are then used to verify the impact of leakage shapes on the pollution risk. The results of the tests indicated that the probability of microbial invasion in the conical holes is much higher than that in straight holes with the same flow test results and that the wall thickness can also affect microbial invasion. Thus, it can be proven that the risk of leakage and invasion or the sensitivity of different methods cannot only be compared through the leak diameter. Numerous influencing factors, including leakage geometry (e.g., shape and thickness), must be considered in practical applications.

Prognostic Significance of ANGPTL4 in Lung Adenocarcinoma: A Meta-Analysis Based on Integrated TCGA and GEO Databases.

Lung adenocarcinoma (LUAD) is a common malignant tumor with a poor prognosis. Recent studies have found that angiopoietin-like 4 (ANGPTL4) is abnormally expressed in many tumors, so it can serve as a potential prognostic marker and therapeutic target. However, its prognostic value in LUAD remains unclear. We downloaded RNA sequence data for LUAD from The Cancer Genome Atlas (TCGA) database, methylation data from the University of California Santa Cruz genome database, and clinical information. R software (version 4.1.1) was applied to analyze the ANGPTL4 expression in LUAD and nontumor samples, and the correlation with clinical characteristics to assess its prognostic and diagnostic value. In addition, we analyzed the relationship between the ANGPTL4 expression and methylation levels. Tumor IMmune Estimation Resource (TIMER) tool was taken for immune infiltration analysis, and two Gene Expression Omnibus (GEO) datasets were combined for meta-analysis. Finally, differentially expressed genes (DEGs) related to ANGPTL4 were analyzed to clarify its function. As shown in our results, ANGPTL4 was upregulated in LUAD and was an independent risk factor for the diagnosis and prognosis of LUAD. The general methylation level and eight ANGPTL4 methylation sites were significantly negatively correlated with the ANGPTL4 expression. Furthermore, we found that B cell infiltration was negatively correlated with ANGPTL4 expression and was an independent risk factor. Meta-analysis showed that the high expression of ANGPTL4 was closely associated with a poor prognosis. 153 DEGs, including the matrix metalloproteinase family, the chemokines subfamily, and the collagen family, were correlated with ANGPTL4. In this study, we found that ANGPTL4 was significantly elevated in LUAD and was closely associated with the development and poor prognosis of LUAD, suggesting that ANGPTL4 may be a prognostic biomarker and a potential therapeutic target for LUAD.

HCCANet: histopathological image grading of colorectal cancer using CNN based on multichannel fusion attention mechanism.

Histopathological image analysis is the gold standard for pathologists to grade colorectal cancers of different differentiation types. However, the diagnosis by pathologists is highly subjective and prone to misdiagnosis. In this study, we constructed a new attention mechanism named MCCBAM based on channel attention mechanism and spatial attention mechanism, and developed a computer-aided diagnosis (CAD) method based on CNN and MCCBAM, called HCCANet. In this study, 630 histopathology images processed with Gaussian filtering denoising were included and gradient-weighted class activation map (Grad-CAM) was used to visualize regions of interest in HCCANet to improve its interpretability. The experimental results show that the proposed HCCANet model outperforms four advanced deep learning (ResNet50, MobileNetV2, Xception, and DenseNet121) and four classical machine learning (KNN, NB, RF, and SVM) techniques, achieved 90.2%, 85%, and 86.7% classification accuracy for colorectal cancers with high, medium, and low differentiation levels, respectively, with an overall accuracy of 87.3% and an average AUC value of 0.9.In addition, the MCCBAM constructed in this study outperforms several commonly used attention mechanisms SAM, SENet, SKNet, Non_Local, CBAM, and BAM on the backbone network. In conclusion, the HCCANet model proposed in this study is feasible for postoperative adjuvant diagnosis and grading of colorectal cancer.

Rapid diagnosis of diabetes based on ResNet and Raman spectroscopy.

Diabetes mellitus is a global public health problem, and the epidemic situation in China is particularly serious. The prevalence of the disease has been increasing in recent years, and the number of patients is the highest in the world. Diabetes has become another chronic non-communicable disease that seriously endangers the health of our people after cardiovascular and cerebrovascular diseases and tumors. In this study, urine sample data were collected from 37 diabetic patients and 37 healthy volunteers using Raman spectroscopy. The collected data were preprocessed using an adaptive iterative reweighted penalized least squares (airPLS) algorithm and a polynomial Savitzky-Golay smoothing algorithm. After extracting features using principal component analysis (PCA) dimensionality reduction algorithm, ResNet, support vector machine (SVM) and linear discriminant analysis (LDA) classification models were selected to classify and identify diabetic patients and healthy controls. The results show that ResNet has the best discrimination effect, and the average accuracy, recall and F1-score can reach 84.28%, 86.20% and 84.02% respectively after five cross-validations, and the area under the subject working characteristic (ROC) curve is 0.93. The experimental results show that the model established in this paper is simple to operate, highly accurate and has good reference value for rapid screening of diabetes.

Role of CD4+T, CD8+T Cells, and CD4+T/CD8+T Cell Ratio in Gastric Cancer and Its Clinical Significance.

Objective: To study the expression and clinical importance of CD4+T, CD8+T cells, and CD4+T/CD8+T cell percentage in gastric cancer (GC) patients. Methods: The blood count of CD4+T and CD8+T lymphocytes was ascertained via flow cytometry before surgery in 93 GC patients undergoing gastrectomy. The CD4+T, CD8+T, and Foxp3+T lymphocytes in cancerous and normal adjacent tissues and the presence of PD-L1 in cancerous tissues were detected via immunohistochemistry. The link between the permeation of CD4+T, CD8+T lymphocytes in venous blood, and cancer and normal adjacent tissues was analyzed. Results: Lauren histotype, TNM stage, lymphatic/nervous invasion, and NLR level were all considerably associated with peripheral CD4+T and CD8+T cell levels, whereas CD8+T lymphocytes were also associated with vascular invasion (p < 0.05). The CD4+T lymphocyte counts, CD4+T, and CD8+T cell percentage in GC tissues were found to have been decreased when compared to normal adjacent tissues, whereas the CD8+T and Foxp3+T lymphocyte count was higher in GC tissues (p < 0.05). According to a Spearman analysis, the CD4+T and CD8+T cell counts in tumor tissues were positively related to the Foxp3+T lymphocyte count (p < 0.05). Greater peripheral CD4+T lymphocyte counts and increased level of CD4+T/CD8+T percentage corresponded with greater CD4+T cell levels and increased CD4+T/CD8+T quantity in normal adjacent tissues. Higher levels of peripheral CD8+T cells corresponded with higher quantities of CD8+T cells in cancer tissues. A reduced CD4+T lymphocyte count, together with a reduced CD4+T/CD8+T percentage in venous blood, was consistent with a diminished CD4+T cell count along with a reduced CD4+T/CD8+T lymphocyte ratio in cancer and normal adjacent tissues. Conclusion: The peripheral quantity of CD4+T and CD8+T lymphocytes in GC patients can partly reflect the infiltrating state of these lymphocytes in cancer and normal adjacent tissues and can preliminarily predict immunotherapy response to a certain extent.

Dietary Restriction Attenuates Inflammation and Protects Mouse Skin from High-Dose Ultraviolet B Irradiation.

Ultraviolet B (UVB) radiation may influence the occurrence or even worsen cutaneous disorders from inflammatory to neoplastic disorders. Dietary restriction (DR) is a well-known regimen that can retard aging-associated pathologies, and is shown by us and others that it can significantly inhibit inflammation under various conditions, including in both undisturbed and stressed settings. It is unknown whether DR could act as a nonpharmacological factor to protect skin against UVB-induced damage. In this study, we performed 30% DR to mice 1 week before UVB irradiation (798.6 mJ/cm2). Remarkably, continuous DR significantly ameliorated UVB-induced skin damage and histological changes, associated with a great reduction in the inflammatory responses in the skin. Intriguingly, refed DR mice with ad libitum diet even 24 hours postirradiation reinflamed the inflammatory responses and induced significantly strong damage to the skin. Together, this study provides the first experimental evidence that DR greatly protects mouse skin from high dose of UVB irradiation, which if translatable could have great implications in human beings.

The characteristics of carotid body tumors in high-altitude region: Analysis from a single center.

OBJECTIVES: Though carotid body tumors are rare, increasing attentions have been given because of malignant transformation and high surgical risk. However, at present, the characteristics and etiology still remain unclear. Our study was designed to describe the clinical features of carotid body tumors in our institution and to compare the results with previous reports. METHODS: We retrospectively reviewed carotid body tumor patients diagnosed in our institution from January 2015 to May 2020. The demographics, comorbidities, lesion location, anatomic characteristics, complications, and postoperative outcomes were evaluated. Carotid body tumor measurements were determined from computed tomography, magnetic resonance imaging, and carotid arteriography examination. We described and compared the clinical features of carotid body tumors in our institution and other reports. RESULTS: We totally identified 122 carotid body tumor cases for the present analysis. The mean age was 50.26 years, with the majority being female (82%). The commonest presentation was a painless neck mass (68%). For the distribution of nationality, most patients were the Han nationality (69.7%). The mean altitude of habitat of patients was 2689.4 km; 19.7% patients suffered bilateral lesions. The main blood supply of carotid body tumors was from external carotid artery (54.1%). For patients who received operation, 11 (11.2%) patients experienced cranial nerve injury. The maximal diameter of tumors was 3.99 ± 1.98 cm in male and 3.38 ± 1.36 cm in female. The volume of tumors was 31.49 ± 29.76 cm3 in male and 15.27 ± 13.06 cm3 in female. The distance to base of skull of tumors was 3.39 ± 1.07 cm (3.99 ± 1.98 cm in male vs 3.38 ± 1.36 cm, P < 0.05). Two patients (2.04%) were identified as having malignant carotid body tumor. CONCLUSIONS: Though carotid body tumor had a low morbidity and multitudinous clinicopathologic features, it was apt to middle-aged women and the main blood supply was from external carotid artery. The painless neck mass was the commonest presentation of carotid body tumors. There were significant difference between male and female patients regarding platelet, hemoglobin, distance to base of skull, tumor volume, altitude of habitat, carotid body tumor location, and hypertension.

Secondary Metabolites with α-Glucosidase Inhibitory Activity from Mangrove Endophytic Fungus Talaromyces sp. CY-3.

Eight new compounds, including two sambutoxin derivatives (1-2), two highly oxygenated cyclopentenones (7-8), four highly oxygenated cyclohexenones (9-12), together with four known sambutoxin derivatives (3-6), were isolated from semimangrove endophytic fungus Talaromyces sp. CY-3, under the guidance of molecular networking. The structures of new isolates were elucidated by analysis of detailed spectroscopic data, ECD spectra, chemical hydrolysis, 13C NMR calculation, and DP4+ analysis. In bioassays, compounds 1-5 displayed better α-glucosidase inhibitory activity than the positive control 1-deoxynojirimycin (IC50 = 80.8 ± 0.3 µM), and the IC50 value was in the range of 12.6 ± 0.9 to 57.3 ± 1.3 µM.

The noninferiority of transcatheter aortic valve implantation compared to surgical aortic valve replacement for severe aortic disease: Evidence based on 16 randomized controlled trials.

BACKGROUND: Currently, transcatheter aortic valve implantation (TAVI) as an effective and convenient intervention has been adopted extensively for patients with severe aortic disease. However, the efficacy and safety of TAVI have not yet been well evaluated and its noninferiority compared with traditional surgical aortic valve replacement (sAVR) still lack sufficient evidence. This meta-analysis was designed to comprehensively compare the noninferiority of TAVI with sAVR for patients with severe aortic disease. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to October 1, 2020 was conducted for relevant studies that comparing TAVI and sAVR in the treatment of severe aortic disease. The primary outcomes were early, midterm and long term mortality. The secondary outcomes included early complications and other late outcomes. Two reviewers assessed trial quality and extracted the data independently. All statistical analyzes were performed using the standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 16 studies including 14394 patients were identified. There was no difference in 30-day, 1-year, 2-year, and 5-year all-cause or cardiovascular mortality as well as stroke between TAVI and sAVR. Regarding to the 30-day outcomes, compared with sAVR, TAVI experienced a significantly lower incidence of myocardial infarction (risk ratio [RR] 0.62; 95% confidence interval [CI] 0.40-0.97; 5441 pts), cardiogenic shock (RR 0.34; 95% CI 0.19-0.59; 1936 pts), acute kidney injury (AKI) > stage 2 (RR 0.37; 95% CI 0.25-0.54; 5371 pts), and new-onset atrial fibrillation (NOAF) (RR 0.29; 95% CI 0.24-0.35; 5371 pts) respectively, but higher incidence of permanent pacemaker implantation (RR 3.16; 95% CI 1.61-6.21; 5441 pts) and major vascular complications (RR 2.22; 95% CI 1.14-4.32; 5371 pts). Regarding to the 1- and 2-year outcomes, compared with sAVR, TAVI experienced a significantly lower incidence of NOAF, but higher incidence of neurological events, transient ischemic attacks (TIA), permanent pacemaker and major vascular complications respectively. Regarding to the 5-year outcomes, compared with sAVR, TAVI experienced a significantly lower incidence of NOAF, but higher incidence of TIA and reintervention respectively. CONCLUSIONS: Our analysis shows that TAVI was equal to sAVR in early, midterm and long term mortality for patients with severe aortic disease. In addition, TAVI may be favorable in reducing the incidence of both early, midterm and long term NOAF. However, pooled results showed superiority of sAVR in reducing permanent pacemaker implantation, neurological events, TIA, major vascular complications and reintervention.

Strain Localization of Orthotropic Elasto-Plastic Cohesive-Frictional Materials: Analytical Results and Numerical Verification.

Strain localization analysis for orthotropic-associated plasticity in cohesive-frictional materials is addressed in this work. Specifically, the localization condition is derived from Maxwell's kinematics, the plastic flow rule and the boundedness of stress rates. The analysis is applicable to strong and regularized discontinuity settings. Expanding on previous works, the quadratic orthotropic Hoffman and Tsai-Wu models are investigated and compared to pressure insensitive and sensitive models such as von Mises, Hill and Drucker-Prager. Analytical localization angles are obtained in uniaxial tension and compression under plane stress and plane strain conditions. These are only dependent on the plastic potential adopted; ensuing, a geometrical interpretation in the stress space is offered. The analytical results are then validated by independent numerical simulations. The B-bar finite element is used to deal with the limiting incompressibility in the purely isochoric plastic flow. For a strip under vertical stretching in plane stress and plane strain as well as Prandtl's problem of indentation by a flat rigid die in plane strain, numerical results are presented for both isotropic and orthotropic plasticity models with or without tilting angle between the material axes and the applied loading. The influence of frictional behavior is studied. In all the investigated cases, the numerical results provide compelling support to the analytical prognosis.

Long-term mid-onset dietary restriction rejuvenates hematopoietic stem cells and improves regeneration capacity of total bone marrow from aged mice.

Currently, the world's aging population is expanding rapidly, leading to a rise in aged hematopoietic cell transplantation (HCT) recipients and aged donors. However, the age of donors is negatively related to the prognosis after transplantation due to functional decline in hematopoietic stem cells (HSCs) during aging. Previously, we showed that an early-onset dietary restriction (DR) significantly retards early aging of HSCs. However, the effects of a mid-onset DR on HSCs remain unknown. In the current study, we performed 30% DR in 15- to 18-month-old mice (equivalent to 50-60 human years) for short-term (4 months) and long-term (9 months). We show that DR reduces and rectifies the imbalance of the HSC pool in aged mice. Short-term DR improves hematopoietic reconstitution in purified HSC transplantations, but not in bone marrow transplantations. Intriguingly, long-term mid-onset DR improves the hematopoietic regeneration of aging HSCs with a particular enhancement of lymphoid outputs even in total bone marrow transplantation settings. Mechanistically, long-term DR rejuvenates the aberrantly regulated mitochondrial pathways in aging HSCs and is accompanied by increased quiescence and reduced DNA damage signaling in HSCs. Short-term DR showed a similar trend of rescuing these aging hallmarks but to a much lesser extent. Together, the current study suggests that mid-onset DR ameliorates the function of aging HSCs and long-term DR even improved hematopoietic reconstitution in bone marrow transplantation, which could potentially have considerable implications in HCT of humans when only old donors are available.