Built-in electric field mediated S-scheme charge migration and Co-N4(II) sites in cobalt phthalocyanine/MIL-68(In)-NH2 heterojunction for boosting photocatalytic nitric oxide oxidation.

The efficiency of photocatalytic Nitric Oxide(NO) oxidation is limited by the lack of oxygen(O2) active sites and poor charge carrier separation. To address this challenge, we developed a molecular Cobalt Phthalocyanine modified MIL-68(In)-NH2 photocatalyst with a robust Built-in electric field(BIEF). In the 2 % CoPc-MIN sample, the BIEF strength is increased by 3.54 times and 5.83 times compared to pristine CoPc and MIL-68(In)-NH2, respectively. This BIEF facilitates the efficient S-scheme charge transfer, thereby enhancing photogenerated carrier separation. Additionally, the Co-N4(II) sites in CoPc can effectively trap the separated photoexcited electrons in the S-scheme system. In addition, the Co-N4(II) sites can also serve as active sites for O2 adsorption and activation, promoting the generation of superoxide radical (O2-), thereby driving the direct conversion of NO to nitrate(NO3-). Consequently, the 2 % CoPc-MIN sample exhibits a remarkable photocatalytic NO removal efficiency of 79.37 % while effectively suppressing the formation of harmful by-product nitrogen dioxide(NO2) to below 3.5 ppb. This study provides a feasible strategy for designing high-efficiency O2 activation photocatalysts for NO oxidation.

Ginseng extract improves pancreatic islet injury and promotes ß-cell regeneration in T2DM mice.

Introduction: Panax ginseng C. A. Mey. (Araliaceae; Ginseng Radix et Rhizoma), a traditional plant commonly utilized in Eastern Asia, has demonstrated efficacy in treating neuro-damaging diseases and diabetes mellitus. However, its precise roles and mechanism in alleviating type 2 diabetes mellitus (T2DM) need further study. The objective of this study is to explore the pharmacological effects of ginseng extract and elucidate its potential mechanisms in protecting islets and promoting ß-cell regeneration. Methods: The T2DM mouse model was induced through streptozotocin combined with a high-fat diet. Two batches of mice were sacrificed on the 7th and 28th days following ginseng extract administration. Body weight, fasting blood glucose levels, and glucose tolerance were detected. Morphological changes in the pancreatic islets were examined via H & E staining. Levels of serum insulin, glucagon, GLP-1, and inflammatory factors were measured using ELISA. The ability of ginseng extract to promote pancreatic islet ß-cell regeneration was evaluated through insulin & PCNA double immunofluorescence staining. Furthermore, the mechanism behind ß-cells regeneration was explored through insulin & glucagon double immunofluorescence staining, accompanied by immunohistochemical staining and western blot analyses. Results and Discussion: The present research revealed that ginseng extract alleviates symptoms of T2DM in mice, including decreased blood glucose levels and improved glucose tolerance. Serum levels of insulin, GLP-1, and IL-10 increased following the administration of ginseng extract, while levels of glucagon, TNF-α, and IL-1ß decreased. Ginseng extract preserved normal islet morphology, increased nascent ß-cell population, and inhibited inflammatory infiltration within the islets, moreover, it decreased α-cell proportion while increasing ß-cell proportion. Mechanistically, ginseng extract might inhibit ARX and MAFB expressions, increase MAFA level to aid in α-cell to ß-cell transformation, and activate AKT-FOXM1/cyclin D2 to enhance ß-cell proliferation. Our study suggests that ginseng extract may be a promising therapy in treating T2DM, especially in those with islet injury.

Innovative Delivery System Combining CRISPR-Cas12f for Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Antimicrobial resistance poses a significant global challenge, demanding innovative approaches, such as the CRISPR-Cas-mediated resistance plasmid or gene-curing system, to effectively combat this urgent crisis. To enable successful curing of antimicrobial genes or plasmids through CRISPR-Cas technology, the development of an efficient broad-host-range delivery system is paramount. In this study, we have successfully designed and constructed a novel functional gene delivery plasmid, pQ-mini, utilizing the backbone of a broad-host-range Inc.Q plasmid. Moreover, we have integrated the CRISPR-Cas12f system into the pQ-mini plasmid to enable gene-curing in broad-host of bacteria. Our findings demonstrate that pQ-mini facilitates the highly efficient transfer of genetic elements to diverse bacteria, particularly in various species in the order of Enterobacterales, exhibiting a broader host range and superior conjugation efficiency compared to the commonly used pMB1-like plasmid. Notably, pQ-mini effectively delivers the CRISPR-Cas12f system to antimicrobial-resistant strains, resulting in remarkable curing efficiencies for plasmid-borne mcr-1 or blaKPC genes that are comparable to those achieved by the previously reported pCasCure system. In conclusion, our study successfully establishes and optimizes pQ-mini as a broad-host-range functional gene delivery vector. Furthermore, in combination with the CRISPR-Cas system, pQ-mini demonstrates its potential for broad-host delivery, highlighting its promising role as a novel antimicrobial tool against the growing threat of antimicrobial resistance.

Dysfunction of neurovascular coupling in patients with cerebral small vessel disease: A combined resting-state fMRI and arterial spin labeling study.

BACKGROUND: Cerebral small vessel disease (CSVD) closely correlates to cognitive impairment, but its pathophysiology and the neurovascular mechanisms of cognitive deficits were unclear. We aimed to explore the dysfunctional patterns of neurovascular coupling (NVC) in patients with CSVD and further investigate the neurovascular mechanisms of CSVD-related cognitive impairment. METHODS: Forty-three patients with CSVD and twenty-four healthy controls were recruited. We adopted resting-state functional magnetic resonance imaging combined with arterial spin labeling to investigate the NVC dysfunctional patterns in patients with CSVD. The Human Brain Atlas with 246 brain regions was applied to extract the NVC coefficients for each brain region. Partial correlation analysis and mediation analysis were used to explore the relationship between CSVD pathological features, NVC dysfunctional patterns, and cognitive decline. RESULTS: 8 brain regions with NVC dysfunction were found in patients with CSVD (p < 0.025, Bonferroni correction). The NVC dysfunctional patterns in regions of the default mode network and subcortical nuclei were negatively associated with lacunes, white matter hyperintensities burden, and the severity of CSVD (FDR correction, q < 0.05). The NVC decoupling in regions located in the default mode network positively correlated with delayed recall deficits (FDR correction, q < 0.05). Mediation analysis suggested that the decreased NVC pattern of the left superior frontal gyrus partially mediated the impact of white matter hyperintensities on delayed recall (Mediation effect: -0.119; 95%CI: -11.604,-0.458; p < 0.05). CONCLUSION: The findings of this study reveal the NVC dysfunctional pattern in patients with CSVD and illustrate the neurovascular mechanism of CSVD-related cognitive impairment. The NVC function in the left superior frontal gyrus may serve as a promising biomarker and therapeutic target for memory deficits in patients with CSVD.

The role of zyxin in signal transduction and its relationship with diseases.

This review highlighted the pivotal role of zyxin, an essential cell focal adhesions protein, in cellular biology and various diseases. Zyxin can orchestrate the restructuring and dynamic alterations of the cellular cytoskeleton, which is involved in cell proliferation, adhesion, motility, and gene transcription. Aberrant zyxin expression is closely correlated with tumor cell activity and cardiac function in both tumorigenesis and cardiovascular diseases. Moreover, in fibrotic and inflammatory conditions, zyxin can modulate cellular functions and inflammatory responses. Therefore, a comprehensive understanding of zyxin is crucial for deciphering signal transduction networks and disease pathogenesis. Investigating its role in diseases holds promise for novel avenues in early diagnosis and therapeutic strategies. Nevertheless, targeting zyxin as a therapeutic focal point presents challenges in terms of specificity, safety, drug delivery, and resistance. Nonetheless, in-depth studies on zyxin and the application of precision medicine could offer new possibilities for personalized treatment modalities.

Regulation of FSP1 myristoylation by NADPH: A novel mechanism for ferroptosis inhibition.

Excitotoxicity is a prevalent pathological event in neurodegenerative diseases. The involvement of ferroptosis in the pathogenesis of excitotoxicity remains elusive. Transcriptome analysis has revealed that cytoplasmic reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels are associated with susceptibility to ferroptosis-inducing compounds. Here we show that exogenous NADPH, besides being reductant, interacts with N-myristoyltransferase 2 (NMT2) and upregulates the N-myristoylated ferroptosis suppressor protein 1 (FSP1). NADPH increases membrane-localized FSP1 and strengthens resistance to ferroptosis. Arg-291 of NMT2 is critical for the NADPH-NMT2-FSP1 axis-mediated suppression of ferroptosis. This study suggests that NMT2 plays a pivotal role by bridging NADPH levels and neuronal susceptibility to ferroptosis. We propose a mechanism by which the NADPH regulates N-myristoylation, which has important implications for ferroptosis and disease treatment.

Mucosa-associated lymphoid tissue lymphoma of the lacrimal gland: A case report and literature review.

RATIONALE: The most common subtype of primary lymphoma of the ocular adnexa is the mucosa-associated lymphoid tissue (MALT) subtype. MALT lymphoma of the lacrimal gland is relatively rare among the lacrimal gland tumors, and the early clinical symptoms are atypical, which can easily lead to misdiagnosis and missed diagnosis. Here, we report a case of MALT lymphoma of the lacrimal gland and explore its clinical manifestations, pathological characteristics, management, and pathogenesis, with the aim of helping clinicians gain an in-depth understanding of ocular adnexal MALT lymphoma. PATIENT CONCERNS: A 60-year-old man presented to our hospital with proptosis and diplopia. The right eye deviated and shifted toward the lower part of the nose. DIAGNOSIS: Orbital enhanced magnetic resonance imaging suggested a mass with a maximum cross-section of 3.2 × 2.1 cm. T1 weighted image was isointense, and the enhancement was more uniform and obvious. INTERVENTIONS: The right orbital mass was treated surgically, and the final pathology report was MALT lymphoma. After the pathological report was released, the patient was transferred to the hematology department for further diagnosis and no further treatment was given eventually. OUTCOMES: Seven months later, the patient did not complain of discomfort. Whole-body positron emission tomography-computed tomography, superficial lymph node examination and orbital magnetic resonance imaging revealed no abnormal changes. LESSONS: The clinical manifestations of MALT lymphoma are heterogeneous. Imaging examination is important for assessing the size of the tumor and its relationship with adjacent tissues. Postoperative pathological examination may provide further evidence for the evaluation of the patient's surgical efficacy and prognosis. Management of MALT lymphoma of the lacrimal gland requires a multidisciplinary approach involving ophthalmologists, hematologists, and radiotherapists.

Copper-Bearing Metal-Organic Framework with Mucus-Penetrating Function for the Multi-Effective Clearance of Mucosal Colonized Helicobacter pylori.

Helicobacter pylori colonizes over 50% of people worldwide. Biofilm formation through penetrating gastric mucus and resistance acquired by H. pylori markedly reduces the efficacy of traditional antibiotics. The present triple therapy and bismuth-based quadruple therapy inevitably causes intestinal flora disturbance and fails to address the excessive H. pylori-triggered inflammatory response. Herein, a mucus-permeable therapeutic platform (Cu-MOF@NF) that consists of copper-bearing metal-organic framework (Cu-MOF) loaded with nitrogen-doped carbon dots and naturally active polysaccharide fucoidan is developed. The experimental results demonstrate that Cu-MOF@NF can penetrate the mucus layer and hinder H. pylori from adhering on gastric epithelial cells of the stomach. Notably, released Cu2+ can degrade the polysaccharides in the biofilm and interfere with the cyclic growing mode of "bacterioplankton ↔ biofilm", thereby preventing recurrent and persistent infection. Compared with traditional triple therapy, the Cu-MOF@NF not only possesses impressive antibacterial effect (even include multidrug-resistant strains), but also improves the inflammatory microenvironment without disrupting the balance of intestinal flora, providing a more efficient, safe, and antibiotic-free new approach to eradicating H. pylori.

Acquisition of 2C-like totipotency through defined maternal-effect factors.

Fully grown oocytes have the natural ability to transform 2 terminally differentiated gametes into a totipotent zygote representing the acquisition of totipotency. This process wholly depends on maternal-effect factors (MFs). MFs stored in the eggs are therefore likely to be able to induce cellular reprogramming to a totipotency state. Here we report the generation of totipotent-like stem cells from mESCs using 4MFs Hsf1, Zar1, Padi6, and Npm2, designated as MFiTLSCs. MFiTLSCs exhibited a unique and inherent capability to differentiate into embryonic and extraembryonic derivatives. Transcriptomic analysis revealed that MFiTLSCs are enriched with 2-cell-specific genes that appear to synergistically induce a transcriptional repressive state, in that parental genomes are remodeled to a poised transcriptional repression state while totipotency is established following fertilization. This method to derive MFiTLSCs could help advance the understanding of fate determinations of totipotent stem cells in a physiological context and establish a foundation for the development of oocyte biology-based reprogramming technology.

Endocrine disrupting chemical Bisphenol A and its association with cancer mortality: a prospective cohort study of NHANES.

Introduction: There is evidence suggesting that Bisphenol A (BPA) is associated with increased all-cause mortality in adults. However, the specific nature of the relationship between BPA exposure and cancer mortality remains relatively unexplored. Methods: The National Health and Nutrition Examination Survey (NHANES) dataset was used to recruit participants. Urinary BPA was assessed using liquid chromatography-mass spectrum (LC-MS). Through the use of multivariable Cox proportional hazard regressions and constrained cubic splines, the relationships between urine BPA and death from all causes and cancer were investigated. Results: This study has a total of 8,035 participants, and 137 died from cancers after a 7.5-year follow-up. The median level of BPA was 2.0 g/mL. Urinary BPA levels were not independently associated with all-cause mortality. For cancer mortality, the second quartile's multivariable-adjusted hazard ratio was 0.51 (95% confidence interval: 0.30 to 0.86; p = 0.011) compared to the lowest quartile. The restricted cubic splines showed that the association was nonlinear (p for nonlinearity = 0.028) and the inflection point was 1.99 ng/mL. Conclusion: Urinary BPA exposure was U-shaped associated with the risk of cancer mortality, and a lower level of BPA less than 1.99 ng/mL was associated with a higher risk of cancer mortality.

Effect of vanadium and tungsten loading order on the denitration performance of F-doped V2O5-WO3/TiO2 catalysts.

F-doped V2O5-WO3/TiO2 catalyst has been confirmed to have excellent denitration activity at low temperatures. Since the V2O5-WO3/TiO2 catalyst is a structure-sensitive catalyst, the loading order of V2O5 and WO3 may affect its denitration performance. In this paper, a series of F-doped V2O5-WO3/TiO2 catalysts with different V2O5 and WO3 loading orders were synthesized to investigate the effect of denitration performance at low temperatures. It was found that the loading orders led to significant gaps in denitration performance in the range of 120-240 °C. The results indicated loading WO3 first better utilized the oxygen vacancies on the TiF carrier promoting the generation of reduced vanadium species. In addition, loading WO3 first facilitated the dispersion of V2O5 thus enhanced the NH3 adsorption capacity of VWTiF. In situ DRIFT verified the rapid reaction between NO2, nitrate, and nitrite species and adsorbed NH3 over the VWTiF, confirming that the NH3 selective catalytic reduction (NH3-SCR) reaction over VWTiF at 240 °C proceeded by the Langmuir-Hinshelwood (L-H) mechanism. This research established the constitutive relationship between the loading order of V2O5 and WO3 and the denitration performance of the F-doped VWTi catalyst providing insights into the catalyst design process.

Decorating of 2D indium oxide onto 2D bismuth oxybromide to enhance internal electric field and stimulate artificial photosynthesis.

CO2 photocatalytic reduction is an excellent strategy for promoting solar-to-chemical energy conversion and alleviating the severe environmental crisis. In this study, 2D indium oxide (IO) is decorated on 2D bismuth oxybromide (BOB) nanosheets to gain BOB/IO (BxIy) heterojunction. The optimal B3I1 composite affords a CO production rate of 54.2 µmol⋅g-1, about 2.2 times and 11.3 times higher than those of the pristine BOB and IO, respectively. The introduction of IO significantly enhances the internal electric field (IEF), leading to accelerated charge transfer and prolonged lifetime of the photogenerated carriers. In the BxIy composite, the BOB and IO serve as the electron acceptor and donor, respectively, facilitating the reduction of CO2 and oxidation of H2O. In-situ DRIFTs spectra are used to confirm the catalytic active sites and provide insights into the mechanism of CO2 photoreduction. The results suggest *COOH and *CO2- species played a crucial role in the formation of CO. This work presents a valuable perspective on understanding the charge transfer route and developing highly efficient photocatalysts for CO2 photoreduction.

The Associations of Two Novel Inflammation Biomarkers, SIRI and SII, with Mortality Risk in Patients with Chronic Heart Failure.

Background: The associations of two novel inflammation biomarkers, systemic inflammation response index (SIRI) and systemic immune inflammation index (SII), with mortality risk in patients with chronic heart failure (CHF) are not well-characterized. Methods: This retrospective cohort study included patients with CHF in two medical centers of Chinese People's Liberation Army General Hospital, Beijing, China. The outcomes of this study included in-hospital mortality and long-term mortality. Associations of SIRI and SII with mortality were assessed using multivariable regressions and receiver operating characteristic (ROC) analyses. Results: A total of 6232 patients with CHF were included in the present study. We documented 97 cases of in-hospital mortality and 1738 cases of long-term mortality during an average 5.01-year follow-up. Compared with patients in the lowest quartile of SIRI, those in the highest quartile exhibited 134% higher risk of in-hospital mortality (adjusted odds ratio, 2.34; 95% confidence interval [CI], 1.16-4.72) and 45% higher risk of long-term mortality (adjusted hazard ratio, 1.45; 95% CI, 1.25-1.67). Compared with patients in the lowest quartile of SII, those in the highest quartile exhibited 27% higher risk of long-term mortality (adjusted hazard ratio, 1.27; 95% CI, 1.11-1.46). In ROC analyses, SIRI showed better prognostic discrimination than C-reactive protein (area under the curve: 69.39 vs 60.91, P = 0.01, for in-hospital mortality; 61.82 vs 58.67, P = 0.03, for 3-year mortality), whereas SII showed similar prognostic value with C-reactive protein. Conclusion: SIRI and SII were significantly associated with mortality risk in patients with CHF. SIRI may provide better prognostic discrimination than C-reactive protein.

Purine Metabolism and Hexosamine Biosynthetic Pathway Abnormalities in Diarrheal Weaned Piglets Identified Using Metabolomics.

Post-weaning diarrhea significantly contributes to the high mortality in pig production, but the metabolic changes in weaned piglets with diarrhea remain unclear. This study aimed to identify the differential metabolites in the urine of diarrheal weaned piglets and those of healthy weaned piglets to reveal the metabolic changes associated with diarrhea in weaned piglets. Nine 25-day-old piglets with diarrhea scores above 16 and an average body weight of 5.41 ± 0.18 kg were selected for the diarrhea group. Corresponding to the body weight and sex of the diarrhea group, nine 25-month-old healthy piglets with similar sex and body weights of 5.49 ± 0.21 kg were selected as the control group. Results showed that the serum C-reactive protein and cortisol of piglets in the diarrhea group were higher than those in the control group (p < 0.05). The mRNA expression of TNF-α, IFN-γ in the jejunum and colon, and IL-1ß in the jejunum were increased in diarrhea piglets (p < 0.05), accompanied by a reduction in the mRNA expression of ZO-1, ZO-2, and CLDN1 in the jejunum and colon (p < 0.05); mRNA expression of OCLN in the colon also occurred (p < 0.05). Metabolomic analysis of urine revealed increased levels of inosine, hypoxanthine, guanosine, deoxyinosin, glucosamine, glucosamine-1-p, N-Acetylmannosamine, chitobiose, and uric acid, identified as differential metabolites in diarrhea piglets compared to the controls. In summary, elevated weaning stress and inflammatory disease were associated with the abnormalities of purine metabolism and the hexosamine biosynthetic pathway of weaned piglets. This study additionally indicated the presence of energy metabolism-related diseases in diarrheal weaned piglets.

Impact of body mass index on long-term outcomes in patients undergoing percutaneous coronary intervention stratified by diabetes mellitus: a retrospective cohort study.

BACKGROUND: Patients with diabetes mellitus (DM) caused by obesity have increased in recent years. The impact of obesity on long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) with or without DM remains unclear. METHODS: We retrospectively analysed data from 1918 patients who underwent PCI. Patients were categorized into four groups based on body mass index (BMI, normal weight: BMI < 25 kg/m2; overweight and obese: BMI ≥ 25 kg/m2) and DM status (presence or absence). The primary endpoint was the occurrence of major adverse cardiac and cerebrovascular events (MACCE; defined as all-cause death, myocardial infarction, stroke, and unplanned repeat revascularization). RESULTS: During a median follow-up of 7.0 years, no significant differences in MACCE, myocardial infarction, or stroke were observed among the four groups. Overweight and obese individuals exhibited lower all-cause mortality rates compared with normal-weight patients (without DM: hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.37 to 0.78; with DM: HR: 0.57, 95% CI: 0.38 to 0.86). In non-diabetic patients, the overweight and obese group demonstrated a higher risk of unplanned repeat revascularization than the normal-weight group (HR:1.23, 95% CI:1.03 to 1.46). After multivariable adjustment, overweight and obesity were not significantly associated with MACCE, all-cause death, myocardial infarction, stroke, or unplanned repeat revascularization in patients with and without diabetes undergoing PCI. CONCLUSION: Overweight and obesity did not demonstrate a significant protective effect on long-term outcomes in patients with and without diabetes undergoing PCI.

Equisetin inhibits adiposity through AMPK-dependent regulation of brown adipocyte differentiation.

Obesity has a significant impact on endocrine function, which leads to metabolic diseases including diabetes, insulin resistance, and other complications associated with obesity. Development of effective and safe anti-obesity drugs is imperative and necessary. Equisetin (EQST), a tetramate-containing marine fungal product, was reported to inhibit bacterial fatty acid synthesis and affect mitochondrial metabolism. It is tempting to speculate that EQST might have anti-obesity effects. This study was designed to explore anti-obesity effects and underlying mechanism of EQST on 3T3-L1 adipocytes differentiated from 3T3-L1 cells. Oil Red O staining showed that EQST reduced lipid accumulation in 3T3-L1 adipocytes. Quantitative real-time polymerase chain reaction and Western blot analysis revealed that EQST significantly inhibited expression of adipogenesis/lipogenesis-related genes C/ebp-α, Ppar-γ, Srebp1c, Fas, and reduced protein levels. There was also increased expression of key genes and protein levels involved in lipolysis (Perilipin, Atgl, Hsl), brown adipocyte differentiation (Prdm16, Ucp1), mitochondrial biogenesis (Pgc1α, Tfam) and ß-oxidation Acsl1, Cpt1. Moreover, mitochondrial content, their membrane potential ΔΨM, and respiratory chain genes Mt-Co1, Cox7a1, Cox8b, and Cox4 (and protein) exhibited marked increase in expression upon EQST treatment, along with increased protein levels. Importantly, EQST induced expression and activation of AMPK, which was compromised by the AMPK inhibitor dorsomorphin, leading to rescue of EQST-downregulated Fas expression and a reduction of the EQST-increased expression of Pgc1α, Ucp1, and Cox4. Together, EQST robustly promotes fat clearance through the AMPK pathway, these results supporting EQST as a strong candidate for the development into an anti-obesity therapeutic agent.

Traditional Herb (Moxa) Modified Zinc Oxide Nanosheets for Quick, Efficient and High Tissue Penetration Therapy of Fungal Infection.

Fungal infection possesses the characteristics of high invasion depth and easy formation of a biofilm under the skin, which greatly hinders the treatment process. Here, traditional Chinese medicine moxa is carbonized and modified with zinc oxide (ZnO) nanosheets to synthesize carbonized moxa@ZnO (CMZ) with the dual response properties of yellow light (YL) and ultrasound (US) for synergistic antifungal therapy. CMZ with narrow bandgap can respond to long-wavelength YL that is highly safe and helpful for skin repair. Simultaneously, CMZ with a piezoelectric effect can further enhance the photocatalytic efficiency under the stimulation of US with high tissue penetration. Gene mechanism investigation indicates that when exposed to US and YL irradiation, CMZ-based therapy can adjust the expression of genes associated with fungal virulence, metabolic activity, mycelial growth and biofilm development, thus efficaciously eradicating planktonic Candida albicans (C. albicans) and mature biofilm. Importantly, despite the 1.00 cm thick tissue barrier, CMZ can rapidly eliminate 99.9% of C. albicans within 4 min, showing a satisfactory deep fungicidal efficacy. The in vivo therapeutic effect of this strategy is demonstrated in both open wound and deep cutaneous infection tests, speaking of dramatically better efficacy than the traditional fungicide ketoconazole (KTZ).

The disruptor of telomeric silencing 1-like (DOT1L) promotes peritoneal fibrosis through the upregulation and activation of protein tyrosine kinases.

The disruptor of telomeric silencing 1-like (DOT1L), a specific histone methyltransferase that catalyzed methylation of histone H3 on lysine 79, was associated with the pathogenesis of many diseases, but its role in peritoneal fibrosis remained unexplored. Here, we examined the role of DOT1L in the expression and activation of protein tyrosine kinases and development of peritoneal fibrosis. We found that a significant rise of DOT1L expression in the fibrotic peritoneum tissues from long-term PD patients and mice. Inhibition of DOT1L significantly attenuated the profibrotic phenotypic differentiation of mesothelial cells and macrophages, and alleviated peritoneal fibrosis. Mechanistically, RNA sequencing and proteomic analysis indicated that DOT1L was mainly involved in the processes of protein tyrosine kinase binding and extracellular matrix structural constituent in the peritoneum. Chromatin immunoprecipitation (ChIP) showed that intranuclear DOT1L guided H3K79me2 to upregulate EGFR in mesothelial cells and JAK3 in macrophages. Immunoprecipitation and immunofluorescence showed that extranuclear DOT1L could interact with EGFR and JAK3, and maintain the activated signaling pathways. In summary, DOT1L promoted the expression and activation of tyrosine kinases (EGFR in mesothelial cells and JAK3 in macrophages), promoting cells differentiate into profibrotic phenotype and thus peritoneal fibrosis. We provide the novel mechanism of dialysis-related peritoneal fibrosis (PF) and the new targets for clinical drug development. DOT1L inhibitor had the PF therapeutic potential.

Intermittent investigations on attenuation mechanism of rechargeable zinc-air batteries during charge/discharge cycles.

Rechargeable zinc-air batteries (RZABs) are an ideal substitute for energy storage, but the short cycle longevity during long-term charge/discharge operation is one of the bottleneck factors that seriously restrict commercial application. Herein, the FeCo alloy/N, S co-doped carbon aerogel (NSCA/FeCo) were prepared as catalysts of cathode for RZABs. We investigated the polarization and impedance on long-term cycles during the battery operation to explore the attenuation mechanism. The results indicated that the roundtrip efficiency of batteries during charge/discharge cycles reduced fast initially and then slow. Besides, the comparative experiment was tested through the replacement of a new electrolyte and a zinc sheet. It is manifested that the failure of the battery is mainly due to the attenuation of the air cathode performance. Therefore, to further disclose the influencing factors and internal mechanisms of air cathode performance degradation, we conducted a series of characterization and testing, including the hydrophilicity, surface morphology, elemental composition, and electrochemical performance of three-electrode systems at different cycle times. This work not only provides a theoretical basis for deeply comprehending the attenuation mechanism of the cathode but also serves a reference for the material design and operating condition optimization of RZABs.

In-situ construction defect-rich CuNiCoS4 /1T-MoS2 heterostructures as superior electrocatalysts for water splitting.

Rational design and construction of bifunctional heterostructure electrocatalysts with high-conductivity and more active sites is imperative for water splitting. Herein, based on the tunable property of layered double hydroxide laminates cations, topological transformation technology and template confine method, a series of high-performance bifunctional catalysts composed of transition metal doping NiCo2S4 (MNiCoS4, M = Cu, Fe, Zn, Mn) and 1T-MoS2 were in-situ fabricated on nickel foam. In particular, CuNiCoS4/1T-MoS2 exhibits an ultralow overpotential of 163 mV at 50 mA cm-2 for oxygen evolution reaction (OER) and favorable hydrogen evolution reaction activity. The two-electrode system requires only 1.52 V to attain a current density of 10 mA cm-2. To the best of our knowledge, its OER electrocatalytic activity far exceed state-of-art catalysts reported. The outstanding performance of this series of catalysts can be attributed to two aspects. First, the highly conductive 1T-MoS2 can facilitate electron transfer, and second, the defect-rich heterostructure can effectively regulate the electronic structure of the active metal and expose abundant active sites. This work provides a valuable strategy for developing high activity electrocatalysts for efficient water splitting.