A cuproptosis-based nanomedicine suppresses triple negative breast cancers by regulating tumor microenvironment and eliminating cancer stem cells.

Cuproptosis is a new kind of cell death that depends on delivering copper ions into mitochondria to trigger the aggradation of tricarboxylic acid (TCA) cycle proteins and has been observed in various cancer cells. However, whether cuproptosis occurs in cancer stem cells (CSCs) is unexplored thus far, and CSCs often reside in a hypoxic tumor microenvironment (TME) of triple negative breast cancers (TNBC), which suppresses the expression of the cuproptosis protein FDX1, thereby diminishing anticancer efficacy of cuproptosis. Herein, a ROS-responsive active targeting cuproptosis-based nanomedicine CuET@PHF is developed by stabilizing copper ionophores CuET nanocrystals with polydopamine and hydroxyethyl starch to eradicate CSCs. By taking advantage of the photothermal effects of CuET@PHF, tumor hypoxia is overcome via tumor mechanics normalization, thereby leading to enhanced cuproptosis and immunogenic cell death in 4T1 CSCs. As a result, the integration of CuET@PHF and mild photothermal therapy not only significantly suppresses tumor growth but also effectively inhibits tumor recurrence and distant metastasis by eliminating CSCs and augmenting antitumor immune responses. This study presents the first evidence of cuproptosis in CSCs, reveals that disrupting hypoxia augments cuproptosis cancer therapy, and establishes a paradigm for potent cancer therapy by simultaneously eliminating CSCs and boosting antitumor immunity.

Advancements in precision nanomedicine design targeting the anoikis-platelet interface of circulating tumor cells.

Tumor metastasis, the apex of cancer progression, poses a formidable challenge in therapeutic endeavors. Circulating tumor cells (CTCs), resilient entities originating from primary tumors or their metastases, significantly contribute to this process by demonstrating remarkable adaptability. They survive shear stress, resist anoikis, evade immune surveillance, and thwart chemotherapy. This comprehensive review aims to elucidate the intricate landscape of CTC formation, metastatic mechanisms, and the myriad factors influencing their behavior. Integral signaling pathways, such as integrin-related signaling, cellular autophagy, epithelial-mesenchymal transition, and interactions with platelets, are examined in detail. Furthermore, we explore the realm of precision nanomedicine design, with a specific emphasis on the anoikis‒platelet interface. This innovative approach strategically targets CTC survival mechanisms, offering promising avenues for combatting metastatic cancer with unprecedented precision and efficacy. The review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis.

The clinical symptoms and psychological status of biofeedback electrical stimulation combined with pelvic floor muscle training during the treatment of mild stress urinary incontinence after holmium laser enucleation of the prostate.

Introduction：To study the clinical symptoms and psychological status of biofeedback electrical stimulation combined with pelvic floor muscle training during the treatment of mild stress urinary incontinence (SUI) after holmium laser enucleation of the prostate (HoLEP). Methods：Group A was treated by biofeedback and electrical stimulation; Group B was treated by pelvic floor muscle training; and Group C was treated by biofeedback and electrical stimulation combined with pelvic floor muscle training. Patients in the 3 groups had follow-up evaluations every 8, 16, and 24 weeks. Clinical symptoms of urinary incontinence were assessed using the 24-hour urinary pad test, the Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF); and psychological status was evaluated using the modified Hospital Anxiety Depression Scale (HADS). Results：The results of ICIQ-UI-SF showed that there were differences within and between the three groups at 8 weeks, 16 weeks, and 24 weeks (P<0.05). The results of the 24-hour pad tests were similar (P<0.05), except for no difference between Group B and Group C at 8 weeks(P＞0.05). In the study with the score of HADS > 35, the differences among the three groups were statistically significant(P<0.05). There was no significant difference among the three groups at 0 and 8 weeks (P>0.05). There were differences in the results between Group C and the other two groups at 16 and 24 weeks of treatment (P<0.05) .For patients with HADS < 35 at week 0, the results were basically the same except for the difference between groups at week 8. HADS of all patients were no statistical difference (P > 0.05). Conclusions：Biofeedback electrical stimulation combined with pelvic floor muscle training is an efficient non-surgical combination therapy for the symptoms of SUI after HoLEP for BPH. In addition, the recovery of the patient's psychological state does not coincide with the recovery of urinary incontinence; therefore, we propose that patients still need additional psychological treatment after SUI disappears.

The Asymmetrical Fe-O-Se Bonds in Fe2O(SeO3)2 Boosting Bifunctional Oxygen Electrocatalytic Performance for Zinc-Air Battery.

Here Fe2O(SeO3)2/Fe3C@NC catalysts with high performance were fabricated for zinc-air batteries (ZABs). The experimental results confirmed that the existence of Fe-O-Se bonds in Fe2O(SeO3)2 crystal phase, and the Fe-O-Se bonds could obviously enhance ORR and OER catalytic performance of Fe2O(SeO3)2/Fe3C@NC. Density functional theoretical calculations (DFT) confirmed that the Fe2O(SeO3)2 in Fe2O(SeO3)2/Fe3C@NC had a higher d-band center of Fe atom and a lower p-orbital coupling degree with its own lattice O atom than Fe2O3, which leads to Fe site of Fe2O(SeO3)2 being more likely to adsorb external oxygen intermediates. The Fe-O-Se bonds in Fe2O(SeO3)2 results in the modification of coordination environment of Fe atoms and optimizes the adsorption energy of Fe site for oxygen intermediates. Compared with Fe2O3/Fe3C@NC, the Fe2O(SeO3)2/Fe3C@NC showed obvious enhancements of ORR/OER catalytic activities with a half-wave potential of 0.91 V for ORR in 0.1 M KOH electrolyte and a low overpotential of 345 mV for OER at 10 mA cm-2 in a 1.0 M KOH electrolyte. The peak power density and specific capacity of Fe2O(SeO3)2/Fe3C@NC-based ZABs are higher than those of Pt/C+RuO2-ZABs. The above results demonstrate that the asymmetrical Fe-O-Se bonds in Fe2O(SeO3)2 plays a key role in improving the bifunctional catalytic activities of ORR/OER for ZABs.

The correlation between social support, coping style, advance care planning readiness, and quality of life in patients with amyotrophic lateral sclerosis: a cross-sectional study.

OBJECTIVE: The primary goal for clinical healthcare professionals is to enhance the quality of life (QOL) of patients with amyotrophic lateral sclerosis (ALS). This study aimed to explore the correlation between social support, coping style, advance care planning (ACP) readiness, and QOL in patients with ALS. We also sought to analyze the mediating effect of coping style and ACP readiness between social support and QOL, and to provide insights for developing targeted interventions to improve patients' QOL. METHODS: A cross-sectional design was used, with participants recruited through convenience sampling in Tianjin, China. Statistical analysis included the t-test, analysis of variance, correlation analysis, and mediating effect analysis. RESULTS: The study included 215 participants. The QOL of patients with ALS was at a medium level, with significant correlations between social support, coping style, ACP readiness, and QOL (all p < 0.01). The direct effect of social support on QOL was 0.403 (p = 0.018), accounting for 41.85% of the total effect. The total indirect effect of social support on QOL through coping style and ACP readiness was 0.560 (p < 0.001), accounting for 58.15% of the total effect. The chain mediating effect involving facing, avoiding, and ACP readiness accounted for 16.72%. CONCLUSION: Social support directly influenced QOL and had an indirect impact through coping style and ACP readiness. Healthcare professionals can improve the QOL of patients with ALS by enhancing social support, disease-coping ability, and ACP readiness in clinical practice.

2D/2D Co3O4/BiOCl nanocomposite with enhanced antibacterial activity under full spectrum: Synergism of mesoporous structure, photothermal effect and photocatalytic reactive oxygen species.

The overuse of antibiotics has caused the emergence of drug-resistant bacteria and even superbugs, which makes it imperative to develop promising antibiotic-free alternatives. Herein, a multimodal antibacterial nanoplatform of two dimensional/two dimensional (2D/2D) mesoporous Co3O4/BiOCl nanocomposite is constructed, which possesses the effect of "kill three birds with one stone": (1) the use of mesoporous Co3O4 can enlarge the surface area of the nanocomposite and promote the adsorption of bacteria; (2) Co3O4 displays remarkable full-spectrum absorption and photo-induced self-heating effect, which can raise the temperature of Co3O4/BiOCl and help to kill bacteria; (3) the p-type Co3O4 and n-type BiOCl form a p-n heterojunction, which promotes the separation of photoelectrons and holes, thus producing more reactive oxygen species (ROS) for killing bacteria. The synergism of mesoporous structure, photothermal effect and photocatalytic ROS makes the developed Co3O4/BiOCl a promising antibacterial material, which shows outstanding antibacterial activity with an inhibition rate of nearly 100 % against Escherichia coli (E. coli) within 8 min. This work provides inspiration for designing multimodal synergistic nanoplatform for antibacterial applications.

The impact of vitamin E, vitamin B6, and niacin intake on cataract incidence based on NHANES 2005-2008 data.

Objective: This investigation aims to elucidate the correlations between dietary intakes of vitamin E, B6, and niacin and the incidence of cataracts, utilizing the comprehensive NHANES 2005-2008 dataset to affirm the prophylactic roles of these nutrients against cataract formation. Methods: Using data from the NHANES 2005-2008 cycles, this analysis concentrated on 7,247 subjects after exclusion based on incomplete dietary or cataract data. The identification of cataracts was determined through participants' self-reported ophthalmic surgical history. Nutritional intake was gauged using the automated multiple pass method, and the data were analyzed using logistic and quantile regression analyses to investigate the relationship between vitamin consumption and cataract prevalence. Results: Our analysis identified significant inverse associations between the intake of vitamins E, B6, and niacin and the risk of cataract development. Specifically, higher intakes of vitamin B6 (OR = 0.85, 95% CI = 0.76-0.96, p = 0.0073) and niacin (OR = 0.98, 95% CI = 0.97-1.00, p = 0.0067) in the top quartile were significantly associated with a reduced likelihood of cataract occurrence. Vitamin E intake showed a consistent reduction in cataract risk across different intake levels (OR = 0.96, 95% CI = 0.94-0.99, p = 0.0087), demonstrating a nonlinear inverse correlation. Conclusion: The outcomes indicate that elevated consumption of vitamin B6 and niacin, in conjunction with regular vitamin E intake, may have the potential to delay or prevent cataract genesis. These results suggest a novel nutritional strategy for cataract prevention and management, advocating that focused nutrient supplementation could be instrumental in preserving eye health and reducing the risk of cataracts. Further research is recommended to validate these findings and establish optimal dosages for maximum benefit.

Neonicotinoid insecticides in waters of Hongze lake, the largest impounded lake on the South-to-North water diversion project, China: Implications for environmental and public health.

Contamination by neonicotinoid (NEO) insecticides in surface waters is a global problem. Nevertheless, the occurrence of NEOs in lakes is not well known. Hongze Lake, the largest impounded lake on the Eastern Route of the South-to-North Water Diversion Project, was selected to investigate the distribution, ecological risks, and health risks of NEOs. Water samples from the lake and nearby rivers were collected and analyzed for 8 widely used NEOs in three seasons. The results indicated the average total NEO concentration in summer, winter, and spring was 222, 211, and 244 ng L-1 for the river water, and 265, 213, and 181 ng L-1 for the lake water, respectively, with no statistical seasonal difference. For the river water, the highest total NEO concentration in the three seasons was observed in the Andong River. For the lake water, the total NEO concentrations in summer were relatively high in sites near the inflow river estuaries due to the high riverine inputs during the flood period. The spatial difference in NEO concentration was relatively low in winter, which may be related to the wind-driven lake current. The seasonal variation in NEO compositions in the lake was generally similar to that in the river, indicating riverine input was the important source for the lake. Huai River was the largest contributor to the NEO inputs to the lake, and Sanhe Gate was the major output pathway. Clothianidin and imidacloprid in the river and lake water would produce moderate acute ecological risks in summer. Thus, the usage of the above two NEOs should be decreased or restricted. For integral NEO risks, 53% and 58% of the river and lake water sites exceeded the acute ecological threshold, respectively. Health risk assessment suggested drinking the water obtained from the lake would not produce a negative impact on public health.

Selective Lithium Recovery from Spent Lithium Manganate Batteries Using Oxidative Stabilization Technique.

Using oxidizing compounds to handle the recycling of discarded lithium batteries has advanced significantly in recent years. One of the most prominent methods is the sintered electrode powder treatment using pre-used additives, with an aqueous solution of the oxidizing agent fueling highly selective lithium extraction and transition metals retention in the refractory material. Herein, phosphoric acid (H3PO4) was used as the exchanger and hydrogen ions provider, the oxidant (K2S2O8) activity was driven by heating, the raw material structure was deformed and adjusted by the oxidizing drive, and lithium was exhausted, while manganese was converted into manganese(III) phosphate hydrate and manganese dioxide insoluble material. The optimized conditions resulted in a lithium leaching rate of 94.16% and a separation factor of 95.74%, while the corresponding manganese leaching rate was limited to less than 5%. The X-ray diffraction, X-ray spectroscopy, scanning electron microscopy, and inductively coupled plasma mass spectrometry measurements were used to investigate the influence of oxidation driving force and lithium leaching. Finally, the lithium leach solution was continuously stirred with sodium carbonate in boiling water to obtain the precipitate, which was separated and washed several times to obtain high-purity lithium carbonate.

Identification and validation of CCL5 as a key gene in HIV infection and pulmonary arterial hypertension.

Background: The relationship between human immunodeficiency virus (HIV) infection and pulmonary arterial hypertension (PAH) has garnered significant scrutiny. Individuals with HIV infection have a higher risk of developing PAH. However, the specific mechanism of HIV-associated PAH remains unclear. Our study aims at investigating the shared biomarkers in HIV infection and PAH and predicting the potential therapeutic target for HIV-associated PAH. Methods: Data for HIV infection and PAH were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis was performed to detect shared genes in HIV infection and PAH. Enrichment analysis was conducted to identify the function of common DEGs. Protein-protein interaction (PPI) analysis was used to detect key genes. These crucial genes were subsequently verified by RT-qPCR. Finally, candidate drugs were identified by using the Drug Signatures Database (DSigDB). Results: Nineteen common DEGs were identified in HIV infection and PAH. Enrichment analysis exhibited that the functions of these genes were mainly enriched in inflammatory responses, mainly including cellular immunity and interaction between viral proteins and cytokines. By constructing PPI networks, we identified the key gene CC-type chemokine ligand 5 (CCL5), and we verified that CCL5 was highly expressed in hypoxia induced human pulmonary artery endothelial cells (hPAECs) and human pulmonary artery smooth muscle cells (hPASMCs). In addition, we predicted 10 potential drugs targeting CCL5 by Autodock Vina. Conclusion: This study revealed that CCL5 might be a common biomarker of HIV infection and PAH and provided a new therapeutic target for HIV-associated PAH. However, further clinical validation is still indispensable.

Incorporating glacier processes into hydrological simulations in the headwaters of the Yangtze and yellow Rivers.

Contemporary hydrological models often oversimplify or neglect the effects of glacier ablation on watershed hydrological processes, leading to inaccurate simulations. To address this issue, we introduce a glacier ablation module that incorporates glacier ablation, sublimation, meltwater refreezing, and snow accumulation, integrated with the fully distributed hydrological model ESSI-3, forming the Glacier-ESSI-3 model. Application of the Glacier-ESSI-3 model in the headwaters of the Yangtze River (HYaR) and Yellow River (HYeR) demonstrates superior accuracy compared to the ESSI-3 model, effectively capturing the impact of glacier ablation on hydrological dynamics. Validation with remotely sensed data of snow cover and glacier dynamics confirms the model's efficacy in reproducing actual conditions in both watersheds. The results indicate that snow meltwater contributes more significantly to runoff than glacier meltwater, and the HYaR exhibiting a larger glacier meltwater contribution than the HYeR. Over time, the contribution rate of snow+glacier meltwater to runoff in the HYaR shows a fluctuating upward trend (10.04 % ± 1.13 % to 25.02 % ± 2.80 %), while it remains relatively stable in the HYeR (6.83 % ± 1.13 % to 10.19 % ± 0.89 %). This study highlights the critical role of glacier ablation in hydrological processes within glacierized watersheds. The Glacier-ESSI-3 model proves to be a robust tool for enhancing hydrological simulations in cold plateau regions, providing valuable insights into the intricate interactions between glaciers and hydrological dynamics.

PBAT/lignin-ZnO composite film for food packaging: Photo-stability, better barrier and antibacterial properties.

When PBAT used as film, stability deteriorates under sunlight exposure, the poor barrier and antibacterial properties are also limiting its application. In this work, lignin-ZnO nanoparticles were prepared by hydrothermal method, as additives to fill the PBAT matrix. In addition, PBAT-lignin-ZnO composite films were successfully prepared by melting and hot-pressing method. It is found that lignin could well dispersed the ZnO when its implantation into PBAT films, and lignin-ZnO not only maintaining tensile strength and thermal stability, but also could prompt PBAT's crystallinity. Especially, P-L-ZnO-2 composite films have good photostability. After 60 h aging, it can still maintain good molecular weight, chemical structure and mechanical properties. Besides, these composite films have improved hydrophobicity, barrier and antibacterial properties, could prevent mildew and significantly reduce the weight loss rate, color difference and hardness changes of strawberries during storage. This work provides a potential film material for outdoor applications and food packaging.

Amorphous P-CoOX Promotes the Formation of Hypervalent Ni Species in NiFe LDHs by Amorphous/Crystalline Interfaces for Excellent Catalytic Performance of Oxygen Evolution Reaction.

Water electrolysis has become an attractive hydrogen production method. Oxygen evolution reaction (OER) is a bottleneck of water splitting as its four-electron transfer procedure presents sluggish reaction kinetics. Designing composite catalysts with high performance for efficient OER still remains a huge challenge. Here, the P-doped cobalt oxide/NiFe layered double hydroxides (P-CoOX/NiFe LDHs) composite catalysts with amorphous/crystalline interfaces are successfully prepared for OER by hydrothermal-electrodeposition combined method. The results of electrochemical characterizations, operando Raman spectra, and DFT theoretical calculations have demonstrated the electrons in the P-CoOX/NiFe LDHs heterointerfaces are easily transferred from Ni2+ to Co3+ because that the amorphous configuration of P-CoOX can well induce Ni-O-Co orbital coupling. The electron transfer of Ni2+ to the surrounding Fe3+ and Co3+ will lead to the unoccupied eg orbitals of Ni3+ that can promote water dissociation and accelerate *OOH migration to improve OER catalytic performance. The optimized P-CoOX/NiFe LDHs exhibit superior catalytic performance for OER with a very low overpotential of 265 mV at 300 mA cm-2 and excellent long-term stability of 500 h with almost no attenuation at 100 mA cm-2. This work will provide a new method to design high-performance NiFe LDHs-based catalysts for OER.

Physicochemical properties dominating the behaviors of short/medium chain chlorinated paraffins in the atmosphere.

Chlorinated paraffins (CPs) are chlorinated alkane mixtures widely used as flame retardants and plasticizers in multiple industrial products. Systematic research on how homolog-specific properties affect their atmospheric behaviors is limited. Herein, we investigated the levels of short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) in long-timescale, seasonal, and size-fractioned particles in the urban area of Dalian, a coastal city in northern China. The average SCCP and MCCP concentrations in particles with diameters ≤ 10 µm were 3.36 and 4.89 ng/m3, respectively, and a general increase in the SCCP concentration was observed from 2.59 ng/m3 in 2018 - 2019 to 7.84 ng/m3 in 2021 - 2023. CP levels and patterns showed significant seasonal variation, with a higher abundance of C11-13Cl7-9 in winter and C10-12Cl5 in summer. Elevated particle levels in winter and high temperatures in summer contributed to the seasonal variations. SCCPs and MCCPs were concentrated on particles with diameters of < 1 µm and their geometric mean diameter increased with the increasing carbon and chlorine numbers. Total Daily intake of SCCP and MCCP was calculated to be 0.15 and 0.22 ng/kg bw/day for adults. 53.1 %, 8.5 %, and 38.4 % of inhaled SCCPs, and 60.6 %, 7.6 %, and 31.8 % of inhaled MCCPs deposited into the head airway, tracheobronchial region, and alveolar region, respectively. This study reports on how homolog-specific physicochemical properties alter the temporal variations, size distributions, and inhaled fractions of CPs.

The shell formation mechanism of Turbo argyrostomus based on ultrastructure and transcriptome analysis.

The gold inner shell of Turbo argyrostomus is an important morphological classification characteristic in Gastropoda. However, the gene sets responsible for shell formation in gastropods remain poorly explored. In this study, we investigated the microstructure using scanning electron microscopy (SEM), hematoxylin-eosin (HE) and Alcian blue staining-periodic acid-Schiff (AB-PAS) staining. The SEM results illustrated that the T. argyrostomus shell exhibited a special "sandwich" microstructure. The results of histological observation demonstrated two major cell types: adipocytes and mucin cells. A total of 318 differentially expressed genes were identified between edge mantle and central mantle, among which whey acidic protein, N66, and nacre-like proteins, and Lam G and EGF domains may be related to shell microstructure. 22.39% - 25.20% of the mucin genes had biomineralization related domains, which supported for the relationship between mucins and shell formation. Moreover, this study revealed energy distribution differences between the edge mantle and central mantle. These results provide insights for further understanding of the biomineralization mechanism in Gastropoda.

Pb(II) Adsorption Properties of a Three-Dimensional Porous Bacterial Cellulose/Graphene Oxide Composite Hydrogel Subjected to Ultrasonic Treatment.

A three-dimensional porous bacterial cellulose/graphene oxide (BC/GO) composite hydrogel (BC/GO) was synthesized with multi-layer graphene oxide (GO) as the modifier and bacterial cellulose as the skeleton via an ultrasonic shaking process to absorb lead ions effectively. The characteristics of BC/GO were investigated through TEM, SEM, FT-IR, NMR and Zeta potential experiments. Compared to bacterial cellulose, the ultrasonic method and the carboxyl groups stemming from GO helped to enhance the availability of O(3)H of BC, in addition to the looser three-dimensional structure and enriched oxygen-containing groups, leading to a significantly higher adsorption capacity for Pb(II). In this paper, the adsorption behavior of BC/GO is influenced by the GO concentration, adsorption time, and initial concentration. The highest adsorption capacity for Pb(II) on BC/GO found in this study was 224.5 mg/g. The findings implied that the pseudo-second-order model explained the BC/GO adsorption dynamics and that the data of its adsorption isotherm fit the Freundlich model. Because of the looser three-dimensional structure, the complexation of carboxyl groups, and the enhanced availability of O(3)H, bacterial cellulose exhibited a much better adsorption capacity.

High-Performance Bifunctional Electrocatalysts for Flexible and Rechargeable Zn-Air Batteries: Recent Advances.

Flexible rechargeable Zn-air batteries (FZABs) exhibit high energy density, ultra-thin, lightweight, green, and safe features, and are considered as one of the ideal power sources for flexible wearable electronics. However, the slow and high overpotential oxygen reaction at the air cathode has become one of the key factors restricting the development of FZABs. The improvement of activity and stability of bifunctional catalysts has become a top priority. At the same time, FZABs should maintain the battery performance under different bending and twisting conditions, and the design of the overall structure of FZABs is also important. Based on the understanding of the three typical configurations and working principles of FZABs, this work highlights two common strategies for applying bifunctional catalysts to FZABs: 1) powder-based flexible air cathode and 2) flexible self-supported air cathode. It summarizes the recent advances in bifunctional oxygen electrocatalysts and explores the various types of catalyst structures as well as the related mechanistic understanding. Based on the latest catalyst research advances, this paper introduces and discusses various structure modulation strategies and expects to guide the synthesis and preparation of efficient bifunctional catalysts. Finally, the current status and challenges of bifunctional catalyst research in FZABs are summarized.

Selenium-induced anion vacancy and active site migration stimulating remarkable sulfide Na-Ion storage.

Heterojunctions and controllable anionic vacancies are perceived to be powerful means of ameliorating the performance of sodium-ion batteries assignable to their unique physical and chemical properties. However, the mechanism by which heterojunction and vacancy structures affect sodium-ion battery storage remains to be systemically explored. In this study, the Se doped CoS2@CoS1.035@Carbon (Se-CoS2@CoS1.035@C) heterostructure with anion vacancy was synthesized by a one-step calcination. These heterostructures with lower metal oxidation states and anionic vacancies exhibit exceptional Na+ storage performance (554.3 mA h g-1 after 1500 cycles at 5.0 A g-1). Both electrochemical tests and theoretical calculations demonstrate excellent pseudocapacitive behavior and enhanced Na+ adsorption during discharge because of anionic vacancies and Se doping. Additionally, introducing weaker Co-Se bonds and extending Co-S and Co-Se bonds reduce binding energies, which effectively accelerates the conversion reaction. Our findings provide a feasible way to rationally design and facilely prepare heterostructured anode materials with rich anionic vacancies for sodium-ion batteries.

Sirtulin-Ypk1 regulation axis governs the TOR signaling pathway and fungal pathogenicity in Cryptococcus neoformans.

Cryptococcus neoformans is a life-threatening fungal pathogen that is a causative agent for pulmonary infection and meningoencephalitis in both immunocompetent and immunodeficient individuals. Recent studies have elucidated the important function of the target of rapamycin (TOR) signaling pathway in the modulation of C. neoformans virulence factor production and pathogenicity in animal infection models. Herein, we discovered that Ypk1, a critical component of the TOR signaling pathway, acts as a critical modulator in fungal pathogenicity through post-translational modifications (PTMs). Mass spectrometry analysis revealed that Ypk1 is subject to protein acetylation at lysines 315 and 502, and both sites are located within kinase functional domains. Inhibition of the C. neoformans TOR pathway by rapamycin activates the deacetylation process for Ypk1. The YPK1Q strain, a hyper-acetylation of Ypk1, exhibited increased sensitivity to rapamycin, decreased capsule formation ability, reduced starvation tolerance, and diminished fungal pathogenicity, indicating that deacetylation of Ypk1 is crucial for responding to stress. Deacetylase inhibition assays have shown that sirtuin family proteins are critical to the Ypk1 deacetylation mechanism. After screening deacetylase mutants, we found that Dac1 and Dac7 directly interact with Ypk1 to facilitate the deacetylation modification process via a protein-protein interaction. These findings provide new insights into the molecular basis for regulating the TORC-Ypk1 axis and demonstrate an important function of protein acetylation in modulating fungal pathogenicity. IMPORTANCE: Cryptococcus neoformans is an important opportunistic fungal pathogen in humans. While there are currently few effective antifungal treatments, the absence of novel molecular targets in fungal pathogenicity hinders the development of new drugs. There is increasing evidence that protein post-translational modifications (PTMs) can modulate the pathogenicity of fungi. In this study, we discovered that the pathogenicity of C. neoformans was significantly impacted by the dynamic acetylation changes of Ypk1, the immediate downstream target of the TOR complex. We discovered that Ypk1 is acetylated at lysines 315 and 502, both of which are within kinase functional domains. Deacetylation of Ypk1 is necessary for formation of the capsule structure, the response to the TOR pathway inhibitor rapamycin, nutrient utilization, and host infection. We also demonstrate that the sirtuin protein family is involved in the Ypk1 deacetylation mechanism. We anticipate that the sirtuin-Ypk1 regulation axis could be used as a potential target for the development of antifungal medications.

Organo-photoredox catalyzed gem-difluoroallylation of ketone-derived dihydroquinazolinones via C(sp3)-C bond and C(sp3)-F bond cleavage.

An organo-photoredox catalyzed gem-difluoroallylation of both acyclic and cyclic ketone derivatives with α-trifluoromethyl alkenes has been demonstrated, thus giving access to a diverse set of gem-difluoroalkenes in moderate to high yields. Pro-aromatic dihydroquinazolinones can be either pre-formed or in situ generated for ketone activation. This reaction is characterized by readily available starting materials, mild reaction conditions, and broad substrate scope. The feasibility of this reaction has been highlighted by the late-stage modification of several natural products and drug-like molecules as well as the in vitro antifungal activity.