Insulin resistance and dyslipidemia in low-birth-weight goat kids.

Low birth weight (LBW) impairs the development and health of livestock by affecting postnatal growth performance and metabolic health in adulthood. Previous studies on indigenous goats in southwest China showed that LBW goat kids had higher mortality and morbidity rates, including hepatic dyslipidemia and liver damage. However, the mechanism of insulin resistance affecting lipid metabolism under LBW conditions remains unclear. In this study, we conducted in vivo glucose-insulin metabolic studies, measured biochemical parameters, and analyzed related regulatory pathways. Both glucose tolerance tests and insulin tolerance tests indicated insulin resistance in LBW goat kids compared to controls (p < 0.05). The marker of insulin resistance, homeostasis model assessment (HOMA), was 2.85-fold higher in LBW than in control goats (p < 0.01). Additionally, elevated levels of free fatty acids in both plasma and skeletal muscle were observed in LBW goats compared to normal birth weight (NBW) goats (p < 0.05). Transcriptome analysis revealed impairments in lipid metabolism and insulin signaling in LBW goats. The observed lipid accumulation was associated with the upregulation of genes linked to fatty acid uptake and transport (FABP3), fatty acid oxidation (PPARA), triacylglycerol synthesis (LPIN1 and DGAT1), oxidative stress (ANKRD2), and insulin resistance (PGC1α). Furthermore, the insulin receptor substrate 2 (IRS2) was lower in the liver of LBW goat kids (p < 0.05). While there was no change in insulin function in skeletal muscle, LBW may lead to lipid accumulation in skeletal muscle by interfering with insulin function in the liver. These findings collectively impact the health and growth performance of livestock.

Pharmacological modulation of RB1 activity mitigates resistance to neoadjuvant chemotherapy in locally advanced rectal cancer.

Resistance to neoadjuvant chemotherapy leads to poor prognosis of locally advanced rectal cancer (LARC), representing an unmet clinical need that demands further exploration of therapeutic strategies to improve clinical outcomes. Here, we identified a noncanonical role of RB1 for modulating chromatin activity that contributes to oxaliplatin resistance in colorectal cancer (CRC). We demonstrate that oxaliplatin induces RB1 phosphorylation, which is associated with the resistance to neoadjuvant oxaliplatin-based chemotherapy in LARC. Inhibition of RB1 phosphorylation by CDK4/6 inhibitor results in vulnerability to oxaliplatin in both intrinsic and acquired chemoresistant CRC. Mechanistically, we show that RB1 modulates chromatin activity through the TEAD4/HDAC1 complex to epigenetically suppress the expression of DNA repair genes. Antagonizing RB1 phosphorylation through CDK4/6 inhibition enforces RB1/TEAD4/HDAC1 repressor activity, leading to DNA repair defects, thus sensitizing oxaliplatin treatment in LARC. Our study identifies a RB1 function in regulating chromatin activity through TEAD4/HDAC1. It also provides the combination of CDK4/6 inhibitor with oxaliplatin as a potential synthetic lethality strategy to mitigate oxaliplatin resistance in LARC, whereby phosphorylated RB1/TEAD4 can serve as potential biomarkers to guide the patient stratification.

Identification of novel molecular subtypes to improve the classification framework of nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) treatment is largely based on a 'one-drug-fits-all' strategy in patients with similar pathological characteristics. However, given its biological heterogeneity, patients at the same clinical stage or similar therapies exhibit significant clinical differences. Thus, novel molecular subgroups based on these characteristics may better therapeutic outcomes. METHODS: Herein, 192 treatment-naïve NPC samples with corresponding clinicopathological information were obtained from Fujian Cancer Hospital between January 2015 and January 2018. The gene expression profiles of the samples were obtained by RNA sequencing. Molecular subtypes were identified by consensus clustering. External NPC cohorts were used as the validation sets. RESULTS: Patients with NPC were classified into immune, metabolic, and proliferative molecular subtypes with distinct clinical features. Additionally, this classification was repeatable and predictable as validated by the external NPC cohorts. Metabolomics has shown that arachidonic acid metabolites were associated with NPC malignancy. We also identified several key genes in each subtype using a weighted correlation network analysis. Furthermore, a prognostic risk model based on these key genes was developed and was significantly associated with disease-free survival (hazard ratio, 1.11; 95% CI, 1.07-1.16; P < 0.0001), which was further validated by an external NPC cohort (hazard ratio, 7.71; 95% CI, 1.39-42.73; P < 0.0001). Moreover, the 1-, 3-, and 5-year areas under the curve were 0.84 (95% CI, 0.74-0.94), 0.81 (95% CI, 0.73-0.89), and 0.82 (95% CI, 0.73-0.90), respectively, demonstrating a high predictive value. CONCLUSIONS: Overall, we defined a novel classification of nasopharyngeal carcinoma (immune, metabolism, and proliferation subtypes). Among these subtypes, metabolism and proliferation subtypes were associated with advanced stage and poor prognosis of NPC patients, whereas the immune subtype was linked to early stage and favorable prognosis.

The mutual overlapping impact of stress and infection on mental health problems in adolescents and youths during and after COVID-19 pandemic in China.

BACKGROUND: It is unclear about the mutual impact of COVID-19 related psychological stress and infection on mental health of adolescent and youth students. This study aimed to explore the mutual impact of COVID-19 related psychological stress and infection on mental health problems among students. METHODS: This study was conducted from December 14, 2022 to February 28, 2023 in Sichuan, China. Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, PTSD Checklist for DSM-5, Insomnia Severity Index, and Internet Addiction Test were used. Participants were grouped by COVID-19 infection and psychological stress level. The differences among groups were compared, and logistic regression analysis was used to investigate risk factors for depression, anxiety, PTSD and insomnia among groups. RESULTS: Of 90,118 participants, 82,873 (92.0 %) finished the questionnaires and were included in the study. Of 82,873 participants, 33,314 (40.2 %) reported to be infected with COVID-19. Participants had depression symptoms (38.1 %), anxiety symptoms (31.8 %), PTSD (33.9 %), insomnia (34.0 %), and internet addiction (60.3 %). Compared with participants uninfected with low psychological stress level, the risk for symptoms of depression, anxiety, PTSD and insomnia increased by 9.6 %, 12.3 %, 6.6 %, and 12.0 % in participants infected with low psychological stress level (p < 0.001), 106.8 %, 125.9 %, 125.2 %, and 95.7 % in participants uninfected with high psychological stress level (p < 0.001), and 147.3 %, 161.1 %, 158.7 %, and 141.0 % in participants infected with high psychological stress level (p < 0.001). LIMITATION: This study is a cross-sectional design, and no causal associations should be inferred. Infection status was based on self-report of participants with infectious symptoms. CONCLUSION: COVID-19 related psychological stress and infection per se have mutually overlapping impacts on mental health problems among students. Further health policies and psychosocial interventions should be developed to reduce mutually overlapping impact and improve the long-term mental health among students.

Screening the optimal housekeeping genes (HKGs) of placenta tissues by RNA-sequence and qRT-PCR throughout gestation in goat (Capra Hircus).

Selection of stable housekeeping genes (HKGs) is very important for accurate calculation of relative expression levels of target genes by quantitative real-time polymerase chain reaction (qRT-PCR). At present, the appropriate HKGs have not been identified in placental tissues throughout the pregnancy of the goat. In our study, 20 HKGs were tentatively selected from RNA-seq data and previous reports. The cycle threshold (Ct) of HKGs was determined by qRT-PCR in trophoblast membrane and cotyledon villus collected from 38 Dazu Black goats on gestation days of 20, 25, 30, 45, 60, 90, 120, and 150 (birth). The expression stability of the HKGs was analyzed by geNorm, Normfinder, Bestkeeper and Delta Ct algorithms, and comprehensively evaluated by ReFinder and ComprFinder. In addition, the optimal HKGs were further verified by placenta-specific genes (SPP1, VEGFA and PAG6). The 16 candidate HKGs (except POP4, TBP, RNF10, UBC) showed a qualified Ct value, less than 28. Among them, YWHAZ, EIF3K and PPIB showed the most stable expression in placental tissues during early, mid-late pregnancy and postpartum, but the least stable expression was B2M at early and mid-late stage, and PPIB at postpartum. After comprehensive analysis, RPLP0, EIF3K and YWHAZ were found to be the most stable placental HKGs throughout pregnancy. The classical HKGs, ACTB, GAPDH and 18S RNA have unstable expressions and even ranked at the bottom of the list from comprehensive index, suggesting an inappropriate for target gene normalization. Taken together, our study confirmed that YWHAZ, EIF3K, HMBS and RPLP0 may be the optimal HKGs in goat placenta at different stage of pregnancy, which provided a valuable reference of HKGs on functional gene expression detection for further research on placenta development and growth in ruminants.

Engineering contact curved interface with high-electronic-state active sites for high-performance potassium-ion batteries.

Potassium-ion batteries (PIBs) have attracted ever-increasing interest due to the abundant potassium resources and low cost, which are considered a sustainable energy storage technology. However, the graphite anodes employed in PIBs suffer from low capacity and sluggish reaction kinetics caused by the large radius of potassium ions. Herein, we report nitrogen-doped, defect-rich hollow carbon nanospheres with contact curved interfaces (CCIs) on carbon nanotubes (CNTs), namely CCI-CNS/CNT, to boost both electron transfer and potassium-ion adsorption. Density functional theory calculations validate that engineering CCIs significantly augments the electronic state near the Fermi level, thus promoting electron transfer. In addition, the CCIs exhibit a pronounced affinity for potassium ions, promoting their adsorption and subsequently benefiting potassium storage. As a result, the rationally designed CCI-CNS/CNT anode shows remarkable cyclic stability and rate capability. This work provides a strategy for enhancing the potassium storage performance of carbonaceous materials through CCI engineering, which can be further extended to other battery systems.

IGSF6 is a novel biomarker to evaluate immune infiltration in mismatch repair-proficient colorectal cancer.

Immunotherapy has dramatically changed the landscape of treatment for colorectal cancer (CRC), but currently lack of effective predictive biomarker, especially for tumors with mismatch repair (MMR) proficiency. The response of immunotherapy is associated with the cell-cell interactions in tumor microenvironment, encompassing processes such as cell-cell recognition, binding, and adhesion. However, the function of immunoglobulin superfamily (IGSF) genes in tumor immune microenvironment remains uncharacterized. This study quantified the immune landscape by leveraging a gene expression matrix from publicly accessible databases. The associations between IGSF6 gene expression and immune cell infiltration were assessed. The expression levels of IGSF6, CD8+ T cells, CD4+ T cells and CD68+ macrophage cells in cancer tissues from CRC patients and CRC cell lines were evaluated. IGSF6 was more highly expressed in CRC tumor tissues than adjacent normal tissues. And IGSF6 was significantly correlated with immune cell infiltration in MMR-proficient patients. Remarkably, MMR-proficient patients with high IGSF6 expression showed more sensitive to immunotherapy and chemotherapy than those with low IGSF6 expression. In summary, IGSF6 could be a novel biomarker to evaluate immune infiltration and predict therapeutic effect for MMR-proficient CRC.

UBR4 deficiency causes male sterility and testis abnormal in Drosophila.

Introduction: It has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility with a Drosophila model. Methods: Different Ubr4 knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could induce male sterility and influent egg hatchability in Drosophila. Results: We found that Ubr4 deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of Ubr4 knockdown flies. Gene Ontology analysis revealed significant upregulation of CG11598 and Sfp65A, and downregulation of Pelota in Ubr4 knockdown flies. These proteins were involved in the biometabolic or reproductive process in Drosophila. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that UBR4 was low expressed in cryptorchidism patients, which further supported the important role of UBR4 in male fertility. Discussion: Overall, our findings suggest that UBR4 deficiency could promote male infertility and may be involved in the protein modification of UBR4 by upregulating Sfp65A and CG11598, whereas downregulating Pelota protein expression.

Integrated multi-omics analyses reveal Jorunnamycin A as a novel suppressor for muscle-invasive bladder cancer by targeting FASN and TOP1.

BACKGROUND: Bladder cancer is a urological carcinoma with high incidence, among which muscle invasive bladder cancer (MIBC) is a malignant carcinoma with high mortality. There is an urgent need to develop new drugs with low toxicity and high efficiency for MIBC because existing medication has defects, such as high toxicity, poor efficacy, and side effects. Jorunnamycin A (JorA), a natural marine compound, has been found to have a high efficiency anticancer effect, but its anticancer function and mechanism on bladder cancer have not been studied. METHODS: To examine the anticancer effect of JorA on MIBC, Cell Counting Kit 8, EdU staining, and colony formation analyses were performed. Moreover, a xenograft mouse model was used to verify the anticancer effect in vivo. To investigate the pharmacological mechanism of JorA, high-throughput quantitative proteomics, transcriptomics, RT-qPCR, western blotting, immunofluorescence staining, flow cytometry, pulldown assays, and molecular docking were performed. RESULTS: JorA inhibited the proliferation of MIBC cells, and the IC50 of T24 and UM-UC-3 was 0.054 and 0.084 µM, respectively. JorA-induced significantly changed proteins were enriched in "cancer-related pathways" and "EGFR-related signaling pathways", which mainly manifested by inhibiting cell proliferation and promoting cell apoptosis. Specifically, JorA dampened the DNA synthesis rate, induced phosphatidylserine eversion, and inhibited cell migration. Furthermore, it was discovered that fatty acid synthase (FASN) and topoisomerase 1 (TOP1) are the JorA interaction proteins. Using DockThor software, the 3D docking structures of JorA binding to FASN and TOP1 were obtained (the binding affinities were - 8.153 and - 7.264 kcal/mol, respectively). CONCLUSIONS: The marine compound JorA was discovered to have a specific inhibitory effect on MIBC, and its potential pharmacological mechanism was revealed for the first time. This discovery makes an important contribution to the development of new high efficiency and low toxicity drugs for bladder cancer therapy.

A Comprehensive Analysis of Prognostic Indicators in Serous Ovarian Cancer Based on Leukocyte Migration and Immune Microenvironment.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) treatment is facing clinical challenges. The tumor immune microenvironment (TME) has recently been shown to perform a critical function in the prediction of clinical outcomes as well as the effectiveness of treatment. Leukocyte migration is enhanced in malignant tumors and promotes immunity. However, its role in how to underlie the migration of immune cells into the TME remains to be further explained in HGSOC. METHODS: We built a prognostic multigene signature with leukocyte migration-related differentially expressed genes (LMDGs), which is associated with TME by single-sample gene set enrichment analysis (ssGSEA), in the The Cancer Genome Atlas (TCGA) cohort. Furthermore, we systematically correlated risk signature with immunological characteris-tics in TME, mutational profiles of HGSOC, and potential value in predicting efficacy of platinum-based chemotherapy and immunotherapy. Screening of the most important prognostic factor among risk signatures by Friends analysis, and immunofluorescence was employed to examine both the expression of CD2 as well as its relationship with CD8 and PD-1. RESULTS: LMDGs-related prognostic model showed good prediction performance. Patients who had high-risk scores exhibited significantly reduced progression-free survival (PFS) and overall survival (OS) than those with low-risk scores, according to the results of the survival analysis (p < 0.001). In the TCGA cohort, the risk signature was found to have independent prognostic sig-nificance for HGSOC (HR =1.829, 95% CI = 1.460-2.290, p < 0.001) and validated in the Gene Expression Omnibus (GEO) cohort. Samples with high-risk scores had lower levels of CD8+ T cells infiltration. The low-risk signature shapes an inflamed TME in HGSOC. Furthermore, immune therapy might be effective for the low-risk subtype of HGSOC patients (p < 0.001). Friends analysis revealed that CD2 was the most important prognostic gene among risk signatures. Real-time quantitative PCR analysis showed the expression of CD2 was greater in tumor cells as opposed to normal ovarian cells. CD8, PD-1, and CD2 were shown to be co-localized in HGSOC tissues, according to immunofluorescence analyses. CD2 was significantly correlated with CD8 (r = 0.47). CONCLUSIONS: Our study identified and validated a promising LMDGs signature associated with inflamed TME, which might offer some prospective clinical implications for the treatment of SOC. CD2 might be a novel biomarker to predict immune efficacy.

Comparison of stigmatizing views towards COVID-19 and mental disorders among adolescent and young adult students in China.

Objective: Infectious diseases including COVID-19 and mental disorders are two of the most common health conditions associated with stigma. However, the comparative stigma of these two conditions has received less attention in research. This study aimed to compare the prevalence of stigmatizing views toward people with COVID-19 and mental disorders and the factors associated with these views, among a large sample of adolescent and young adult students in China. Methods: A total of 9,749 adolescents and young adults aged 15-24 years completed a survey on stigmatizing attitudes toward COVID-19 and mental disorders, as well as mental health-related factors, including general mental health status and symptoms of depression, anxiety, insomnia, and post-traumatic stress disorder (PTSD). Multivariable linear regression analyses were conducted to identify factors associated with stigmatizing views. Findings: The prevalence of COVID-19 and mental disorders-related stigma was 17.2% and 40.7%, respectively. COVID-19-related stigma scores were significantly higher among male students (ß = 0.025, p < 0.05), those without quarantine experience (ß = 0.035, p < 0.001), those with lower educational level (p < 0.001), those with lower family income (p < 0.01), and those with higher PTSD symptoms (ß = 0.045, p < 0.05). Mental disorder-related stigma scores were significantly higher among individuals with average and lower-than-average levels of family income (p < 0.01), depression symptoms (ß = 0.056, p < 0.001), anxiety symptoms (ß = 0.051, p < 0.001), and mental health problems (ß = 0.027, p < 0.05). Conclusion: The stigma of mental disorders is higher in the youth population than the stigma of COVID-19. Factors associated with stigmatizing attitudes toward people with COVID-19 and mental disorders varied across the youth. Stigma-reduction interventions among the youth should be targeted specifically to COVID-19 or mental disorders conditions.

Formal Synthesis of Ecteinascidin 743 from N-Cbz-l-tyrosine.

A formal total synthesis of ecteinascidin 743 and lurbinectedin is achieved. Key features involve a Pictet-Spengler cyclization coupling of the tetrahydroisoquinoline and phenylalaninol moieties prepared by a common route with high yield and selectivity, a Parikh-Doering oxidation with good chemoselectivity and functionality tolerance, and a light-mediated A-ring elaboration of pentacyclic methoxyquinone substrates. By the approach, the known advanced intermediate (4-step conversion to Et-743) can be obtained conveniently in 21 total steps from N-Cbz-l-tyrosine.

In Situ Construction Channels of Lithium-Ion Fast Transport and Uniform Deposition to Ensure Safe High-Performance Solid Batteries.

Solid-state lithium-ion batteries (SLIBs) are the promising development direction for future power sources because of their high energy density and reliable safety. To optimize the ionic conductivity at room temperature (RT) and charge/discharge performance to obtain reusable polymer electrolytes (PEs), polyvinylidene fluoride (PVDF), and poly(vinylidene fluoride-hexafluoro propylene) (P(VDF-HFP)) copolymer combined with polymerized methyl methacrylate (MMA) monomers are used as substrates to prepare PE (LiTFSI/OMMT/PVDF/P(VDF-HFP)/PMMA [LOPPM]). LOPPM has interconnected lithium-ion 3D network channels. The organic-modified montmorillonite (OMMT) is rich in the Lewis acid centers, which promoted lithium salt dissociation. LOPPM PE possessed high ionic conductivity of 1.1 × 10-3 S cm-1 and a lithium-ion transference number of 0.54. The capacity retention of the battery remained 100% after 100 cycles at RT and 0.5 C. The initial capacity of one with the second-recycled LOPPM PE is 123.9 mAh g-1 . This work offered a feasible pathway for developing high-performance and reusable LIBs.

An immune-related prognostic model predicts neoplasm-immunity interactions for metastatic nasopharyngeal carcinoma.

Background: The prognosis of nasopharyngeal carcinoma (NPC) has been recognized to improve immensely owing to radiotherapy combined with chemotherapy. However, patients with metastatic NPC have a poor prognosis. Immunotherapy has dramatically prolonged the survival of patients with NPC. Hence, further research on immune-related biomarkers is imperative to establish the prognosis of metastatic NPC. Methods: 10 NPC RNA expression profiles were generated from patients with or without distant metastasis after chemoradiotherapy from the Fujian Cancer Hospital. The differential immune-related genes were identified and validated by immunohistochemistry analysis. The method of least absolute shrinkage and selection operator (LASSO)was used to further establish the immune-related prognostic model in an external GEO database (GSE102349, n=88). The immune microenvironment and signal pathways were evaluated in multiple dimensions at the transcriptome and single-cell levels. Results: 1328 differential genes were identified, out of which 520 were upregulated and 808 were downregulated. Notably, most of the immune genes and pathways were down-regulated in the metastasis group. A prognostic immune model involving nine hub genes. Patients in low-risk group were characterized by survival advantage, hot immune phenotype and benefit from immunotherapy. Compared with immune cells, malignant cell exhibited the most active levels of risk score by ssGSEA. Accordingly, intercellular communications including LT, CD70, CD40 and SPP1, and the like, between high-risk and low-risk were explored by the R package "Cellchat". Conclusion: We have constructed a model based on immunity of metastatic NPC and determined its prognostic value. The model identified the level of immune cell infiltration, cell-cell communication, along with potential immunotherapy for metastatic NPC.

The pluripotent factor OCT4A enhances the self-renewal of human dental pulp stem cells by targeting lncRNA FTX in an LPS-induced inflammatory microenvironment.

BACKGROUND: Regulating the pluripotency of human dental pulp stem cells (hDPSCs) is key for the self-repair of injured dental pulp. We previously found that OCT4A promotes the proliferation and odontogenic differentiation of human dental pulp cells (hDPCs). Recent studies have shown the interaction between OCT4A and lncRNAs in pluripotency maintenance of various stem cells. The aim of this study was to explore the underlying roles and mechanisms of OCT4A and its related lncRNAs in the proliferation and multidirectional differentiation of hDPSCs in an inflammatory microenvironment. METHODS: Human lncRNA microarrays were applied to screen out the differentially expressed lncRNAs in hDPSCs between the OCT4A-overexpressing and vector groups. Lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment. The effects of OCT4A and the lncRNA FTX on the proliferation and multidifferentiation of hDPSCs were observed by the CCK-8 assay, EdU staining, real-time PCR, western blotting, and Alizarin red and oil red O staining. Bioinformatics analysis and chromatin immunoprecipitation (ChIP) assays were performed to clarify the targeted mechanism of OCT4A on FTX. The regulation by FTX of the expression of OCT4A and its downstream pluripotent transcription factors SOX2 and c-MYC was further detected by real-time PCR and western blotting. RESULTS: The microarray results showed that 978 lncRNAs (250 of which were upregulated and 728 downregulated) were potentially differentially expressed genes (fold change ≥ 2, P < 0.05). LPS stimulation attenuated the self-renewal of hDPSCs. OCT4A enhanced the cell proliferation and multidifferentiation capacities of hDPSCs in an inflammatory microenvironment, while FTX exhibited the opposite effects. OCT4A negatively regulated FTX function by binding to specific regions on the FTX promoter, thereby inhibiting the transcription of FTX. Moreover, overexpression of FTX downregulated the expression of OCT4A, SOX2 and c-MYC, whereas knockdown of FTX facilitated their expression. CONCLUSIONS: OCT4A was found to be a crucial factor maintaining the self-renewal of hDPSCs by transcriptionally targeting FTX in an inflammatory microenvironment. Moreover, we proposed a novel function of FTX in negatively regulating the pluripotency and multilineage differentiation capacity of hDPSCs. The hierarchical organization between OCT4A and FTX expanded the understanding of the network between transcription factors and lncRNAs in fine-tuning the pluripotency/differentiation balance of adult stem cells, and provided prospective targets for optimizing dental-derived stem cell sources for regenerative endodontics.

Progressive activation of porous vanadium nitride microspheres with intercalation-conversion reactions toward high performance over a wide temperature range for zinc-ion batteries.

Rechargeable aqueous zinc-ion batteries have great promise for becoming next-generation storage systems, although the irreversible intercalation of Zn2+ and sluggish reaction kinetics impede their wide application. Therefore, it is urgent to develop highly reversible zinc-ion batteries. In this work, we modulate the morphology of vanadium nitride (VN) with different molar amounts of cetyltrimethylammonium bromide (CTAB). The optimal electrode has porous architecture and excellent electrical conductivity, which can alleviate volume expansion/contraction and allow for fast ion transmission during the Zn2+ storage process. Furthermore, the CTAB-modified VN cathode undergoes a phase transition that provides a better framework for vanadium oxide (VOx). With the same mass of VN and VOx, VN provides more active material after phase conversion due to the molar mass of the N atom being less than that of the O atom, thus increasing the capacity. As expected, the cathode displays an excellent electrochemical performance of 272 mAh g-1 at 5 A g-1, high cycling stability up to 7000 cycles, and excellent performance over a wide temperature range. This discovery creates new possibilities for the development of high-performance multivalent ion aqueous cathodes with rapid reaction mechanisms.

Enantioselective Total Synthesis of (+)-Penostatins A and C.

A stereoselective and column-economic approach to (+)-penostatins A and C has been developed. The multisubstituted A ring and B/C rings in their unique tricyclic framework are constructed through a Diels-Alder reaction/ozonolysis sequence and an exo intramolecular hetero-Diels-Alder reaction with high chemo-, regio-, and stereoselectivity. Using this route, (+)-penostatins A and C can be synthesized in 19 and 20 steps, respectively, with a good overall yield involving only five or six column chromatographic purifications.

Impact of Radiotherapy Combined With Chemotherapy on Long-Term Outcomes of Patients With Recurrent Nasopharyngeal Carcinoma.

Background: It remains controversial whether the application of chemotherapy has an impact on recurrent nasopharyngeal carcinoma (rNPC) patients with salvage radiotherapy. Here, we aimed to evaluate treatment outcomes of rNPC patients and derive a prognostic model to assess the benefit of chemotherapy in patients with re-radiotherapy. Methods: This study was conducted as a retrospective study. In total, 340 rNPC patients treated with salvage intensity-modulated radiotherapy (IMRT) or radiochemotherapy (RCT) from October 2006 to September 2019 were included in this study. Overall survival (OS) was the primary outcome. Kaplan-Meier method was employed to detect the prognostic difference with Log-rank tests. The Cox regression analysis was performed to explore the potential prognostic factors while the multivariate Cox analysis was used to identify candidate variables for the prognostic model of OS. Results: The 5-year actuarial rates of OS, progression-free survival, loco-regional progression-free survival, and distant metastases-free survival did not show significant difference between the IMRT and RCT groups (P > .05). Age at recurrence and rT category were found to be the independent prognostic factors for OS. We found that rNPC patients suffered poor OS in the high-risk group (patients with higher age at recurrence and advanced rT category) (high-risk vs low-risk, HR = 1.87, 95% CI: 1.36-2.57, P < .001). Salvage RT alone may be superior to RCT for patients in the low-risk group (RCT group vs RT group, HR = 1.89, 95% CI: 1.11-3.20, P = .038). Conclusion: Salvage RT combined with chemotherapy cannot improve survival outcomes for rNPC. More novel clinical trials should be explored to develop individualized strategies to improve survival and minimize toxicities.