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Mitochondria are the major cellular energy‐producing organelles and intracellular source of reactive oxygen species. These organelles are responsible for driving cell life and death through mitochondrial network structure homeostasis, which is determined by a balance of fission and fusion. Recent advances revealed that a number of components of the fission and fusion machinery, including dynamin‐related protein 1 (Drp1), mitofusin1/2 (Mfn1/2) and Optic atrophy 1 (OPA1), that have been implicated in mitochondrial shape changes are indispensible for autophagy, apoptosis and necroptosis. Drp1 is the main regulator of mitochondrial fission and has become a key point of contention. The controversy focuses on whether Drp1 is directly involved in the regulation of cell death and, if involved, whether is it a stimulator or a negative regulator of cell death. Here, we examine the relevance of the homeostasis of the mitochondrial network structure in 3 different types of cell death, including autophagy, apoptosis and necroptosis. Furthermore, a variety of cancers often exhibit a fragmented mitochondrial phenotype. Thus, the fragmented ratio can reflect tumor progression that predicts prognosis and therapeutic response. In addition, we investigate whether the targeting of the mitochondrial fission protein Drp1 could be a novel therapeutic approach. Here, we examine the relevance of the homeostasis of the mitochondrial network structure in 3 different types of cell death, including autophagy, apoptosis and necroptosis. Furthermore, a variety of cancers often exhibit a fragmented mitochondrial phenotype. Targeting the mitochondrial fission protein Drp1or other shaping proteins is becoming a topic of interest. Further studies are needed to understand the differential effects of oncogenic signaling pathways on mitochondrial dynamics and to identify additional new signaling axes that regulate mitochondrial network structure homeostasis.

Oral cancer (OC) poses a threat to human health and imposes a heavy burden on countries. We assessed the burden imposed by OC on Asian nations from 1990 to 2019 based on gender and age. We collected oral cancer data from the 2019 Global Burden of Disease study from 1990 to 2019 in 45 Asian countries and territories. Annual case data and age-standardised rates (ASRs) were used to investigate the incidence, mortality, and disability-adjusted life-years (DALYs) of OC based on age and gender from 1990 to 2019 in 45 Asian countries and territories. Estimated annual percentage changes (EAPCs) were used to assess incidence rate, mortality, and trends in DALYs. The age-standardised incidence rate (ASIR) of OC increased from 1990 to 2019 with an EAPC of 0.32 (95% CI, 0.19-0.46), and the age-standardised death rate of OC remained stable at an EAPC of 0.08 (95%CI, from -0.06 to 0.21). The age-standardised DALYs of OC decreased at an EAPC of -0.16 (95%CI, from -0.30 to -0.02). The proportion of patients older than 70 years increased yearly in terms of incidence, mortality, and DALYs from 1990 to 2019. Of the DALYs, smoking was the main contributor in the Asian regions, and the largest contributor to DALYs in most Asian regions. Other contributors were alcohol use and chewing tobacco. Although the burden of OC was declining in Asia, South Asia remained the region with the highest burden. OC caused the greatest burden in Pakistan, Taiwan China, and India. Therefore, measures should be taken to reduce the burden of oral cancer in high-risk regions and countries with attributable risk factors.

Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18–65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2–T3 vs T4), and recurrent nodal stage (N0 vs N1–N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3–53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference –23% [95% CI –39 to –7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.

In this paper, we demonstrate a synthesis of mesoporous carbon spheres via a self-assembly of resorcinol-formaldehyde polymer and surfactant F127 in aqueous phase in the presence of phytic acid as the catalyst and phosphorus source. The obtained mesoporous carbon spheres have high phosphorus content and excellent electrochemical performance. The enhancement of the electrochemical performance of the material is primarily attributed to the structural characteristics and chemical properties of phosphorus atoms being similar to those of nitrogen atoms, and the atomic radius being slightly larger than that of nitrogen atoms, with strong electron donating ability. After successful doping, rich active sites are formed. These carbon spheres are examined as electrode materials for supercapacitors. The structural characterization revealed that the mesoporous carbon spheres possessed an average pore diameter of 2.4 nm and a specific surface area of 1207 m 2 g − 1 . Electrochemical measurements demonstrated a specific capacitance of 257.5 F g − 1 at 0.5 A g − 1 in a three-electrode configuration. used as supercapacitor electrodes with a capacitance of 92.8 F g − 1 at a current density of 0.5 A g − 1 . Furthermore, the energy density is 4.64 Wh Kg − 1 at a power density of 150 W Kg − 1 and the capacitance retention rate is 98.99% After 5000 cycles at a current density of 2 A g − 1 , an extremely highly promising supercapacitor electrode material.

A delayed treatment effect is a commonly observed phenomenon in tumor immunotherapy clinical trials. It can cause a loss of statistical power and complicate the interpretation of the analytical findings. This phenomenon also poses challenges for interim analysis in the context of phase II/III seamless design or group sequential design. It shows potential to lead researchers to make incorrect go/no-go decisions. Despite its significance, rare research has explored the impact of delayed treatment effects on the decision success rate of the interim analysis and the methods to compensate for this loss. In this study, we propose an analysis procedure based on change points for improving the decision success rate at the interim analysis in the presence of delayed treatment effects. This procedure primarily involves three steps: I. detecting and testing the number and locations of change points; II. estimating treatment efficacy; and III. making go/no-go decisions. Simulation results demonstrate that when there is a delayed treatment effect with a single change point, using the proposed analysis procedure significantly improves the decision success rate while controlling the type I error rate. Moreover, the proposed method exhibits very little disparity compared to the unadjusted method when the proportional hazards assumption holds. Therefore, the proposed analysis procedure provides a feasible approach for decision-making at the interim analysis when delayed treatment effects are present.

The lithium fast ion conductor LiAlSiO 4 demonstrates exceptional lithium-ion transmission properties alongside remarkable chemical stability. Utilizing sol-gel techniques, we synthesized LiAlSiO 4 -coated cathode materials (LNCM@LASO) based on Li 1.2 Mn 0.54 Ni 0.13 Co 0.13 O 2 to enhance their electrochemical performance. Rm space groups were identified in all materials through high-intensity diffraction peaks, indicating the presence of hexagonal layered α-NaFeO 2 structures. Benefiting from the coating layer of LiAlSiO 4 , the conductivity and electrochemical performance of Li 1.2 Mn 0.54 Ni 0.13 Co 0.13 O 2 are significantly improved. Compared with the unmodified LASO-0 sample (42.27%), the LASO-3 sample exhibits a superior initial coulomb efficiency of 66.02%. At various charge/discharge rates (0.1, 0.2, 0.5, 1, and 2 C), the LASO-3 electrode exhibits specific discharge capacities of 210.6, 189.3, 168.1, 151.8, and 125.2 mAh·g −1 , correspondingly. Upon reverting the current density from 2 C to 0.1 C, the discharge capacity of the LASO-3 electrode rebounds to 206.4 mAh·g −1 . After 100 cycles at 0.1 C, the LASO-3 electrode achieves a peak capacity retention rate of 88.9%. The superior conductive properties and chemical stability of the LNCM@LASO enhance the electron and ion transfer, thereby preventing electrolyte attack and boosting the electrochemical performance. This research marks a crucial step towards developing high-capacity, low-cost lithium-ion batteries with wide-ranging implications across multiple disciplines and industries.

Background Sheep and goats have undergone domestication and improvement to produce similar phenotypes, which have been greatly impacted by structural variants (SVs). Here, we report a high-quality chromosome-level reference genome of Asiatic mouflon, and implement a comprehensive analysis of SVs in 897 genomes of worldwide wild and domestic populations of sheep and goats to reveal genetic signatures underlying convergent evolution. Results We characterize the SV landscapes in terms of genetic diversity, chromosomal distribution and their links with genes, QTLs and transposable elements, and examine their impacts on regulatory elements. We identify several novel SVs and annotate corresponding genes (e.g., BMPR1B , BMPR2 , RALYL , COL21A1 , and LRP1B ) associated with important production traits such as fertility, meat and milk production, and wool/hair fineness. We detect signatures of selection involving the parallel evolution of orthologous SV-associated genes during domestication, local environmental adaptation, and improvement. In particular, we find that fecundity traits experienced convergent selection targeting the gene BMPR1B , with the DEL00067921 deletion explaining ~10.4% of the phenotypic variation observed in goats. Conclusions Our results provide new insights into the convergent evolution of SVs and serve as a rich resource for the future improvement of sheep, goats, and related livestock.

A mild, efficient and practical protocol for the preparation of 2-sulfonylquinolines through CS2/Et2NH-induced deoxygenative C2-H sulfonylation of quinoline N-oxides with readily available RSO2Cl was developed. The reaction proceeded well under transition-metal-free conditions and exhibited a wide substrate scope and functional group tolerance. The preliminary studies suggested that the nucleophilic sulfonyl sources were generated in situ via the reaction of CS2, Et2NH and sulfonyl chlorides.

Receptor activity modifying protein 1 (RAMP1) facilitates the localization of the calcitonin-like receptor (CLR) to the plasma membrane, but its role in osteosarcoma (OS) remains unclear. We evaluated the RAMP1 expression and prognostic value across different cancers, studying tumor immune infiltration. The prognostic value was analyzed using the GSE39058 and TARGET datasets. Differential gene expression was evaluated. a protein-protein interaction network was constructed, and gene set enrichment analysis was performed. The function of RAMP1 in the tumor microenvironment was analyzed, and its expression in OS cell lines was validated using quantitative real-time PCR. High RAMP1 expression correlated with poor prognosis relative to low RAMP1 expression ( p < 0.05). Low RAMP1 expression correlated with an abundance of CD4+ memory-activated T cells. whereas a high expression level correlated with a high proportion of gamma-delta T cells (γδ T cells). Differentially expressed genes from TARGET was enriched in olfactory transduction pathways (normalized enrichment scores [NES] = 1.6998, p < 0.0001). RAMP1 expression negatively correlated with CD44 expression but positively correlated with TNFSF9 expression. The RAMP1 gene is substantially expressed in OS cells compared to the normal osteoblast cell line hFOB1.19. Thus, RAMP1 may be a prognostic biomarker and potential therapeutic target in OS.

Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB’s toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB’s active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.