Erythromycin disrupts Acinetobacter baumannii biofilms through destruction of the quorum sensing system.

BACKGROUND: This study was conducted to explore the effects of erythromycin on biofilms comprising Acinetobacter baumannii (A baumannii). METHODS: To clarify the effect of erythromycin on the biofilms of A baumannii, we collected pure Ab strains isolated and identified from a variety of sample types extracted from patients in the microbiological laboratory of our hospital from April to August 2023, and divided them into an experimental group (treated with erythromycin) and a control group (without erythromycin). The morphology and quantity of A baumannii biofilm were observed at 24h, 48h, 72h, and 5d post-treatment, respectively, and the expression of quorum sensing (QS) system gene (abaI, abaR) mRNA was detected by fluorescence quantitative PCR. RESULTS: The results showed that A baumanniis are prone to form multiple drug-resistant (MDR) bacteria, against which the most commonly used clinical antibiotics are ineffective. Overall, we found that the number of bacteria, the number of bacteria in the biofilm, and the number of biofilms formed gradually increased over time, with a statistical difference (P < .05). After the addition of erythromycin, significant improvements in biofilm formation were achieved, indicating that erythromycin can destroy A baumannii biofilms, inhibiting bacterial growth to a certain extent. The expression levels of abaI and abaR gradually increased over time, indicating that the role of the QS system became more apparent over time. Biofilm formation is related to the QS system of A baumanniis. After erythromycin treatment, abaI and abaR mRNA expression was downregulated in the experimental group. CONCLUSION: Erythromycin disrupts A baumannii biofilms by destroying the quorum sensing system.

Transcriptome and metabolome analyses reveal the effects of formula and breast milk on the growth and development of human small intestinal organoids.

Breast milk is widely acknowledged as the ideal nutritional resource for infants and can well meet the nutritional requirements for baby's growth and development. Infant formula is a substitute for breast milk, designed to closely mimic its composition and function for breast milk. Most of the previous studies used tumor colorectal cancer cell lines to study the nutritional potency of formula and its components, so realistic data closer to the baby could not be obtained. Small intestinal organoids, derived from differentiated human embryonic stem cells, can be used to simulate nutrient absorption and metabolism in vitro. In this experiment, we used small intestinal organoids to compare the nutrient absorption and metabolism of three infant formulae for 0-6 months with breast milk samples. Transcriptome and metabolome sequencing methods were used to analyze the differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs). The pathways related to DEGs, DEMs were enriched using GO, KEGG, GSEA and other methods to investigate their biological characteristics. We have found that both formula and breast milk promote the development of the infant's immune system, nutrient absorption and intestinal development. In PMH1 we found that the addition of oligofructose to milk powder promoted lipid metabolism and absorption. In PMH2 we found that whey protein powder favours the development of the immune system in infants. In PMH3 we found that oligogalactans may act on the brain-gut axis by regulating the intestinal flora, thereby promoting axon formation and neural development. By linking these biological properties of the milk powder with its composition, we confirmed the effects of added ingredients on the growth and development of infants. Also, we demonstrated the validity of small intestine organoids as a model for absorption and digestion in vitro. Through the above analyses, the advantages and disadvantages of the roles of formula and breast milk in the growth and metabolism of infants were also compared.

Multi-Omics Profiles of Small Intestine Organoids in Reaction to Breast Milk and Different Infant Formula Preparations.

Ensuring optimal infant nutrition is crucial for the health and development of children. Many infants aged 0-6 months are fed with infant formula rather than breast milk. Research on cancer cell lines and animal models is limited to examining the nutrition effects of formula and breast milk, as it does not comprehensively consider absorption, metabolism, and the health and social determinants of the infant and its physiology. Our study utilized small intestine organoids induced from human embryo stem cell (ESC) to compare the nutritional effects of breast milk from five donors during their postpartum lactation period of 1-6 months and three types of Stage 1 infant formulae from regular retail stores. Using transcriptomics and untargeted metabolomics approaches, we focused on the differences such as cell growth and development, cell junctions, and extracellular matrix. We also analyzed the roles of pathways including AMPK, Hippo, and Wnt, and identified key genes such as ALPI, SMAD3, TJP1, and WWTR1 for small intestine development. Through observational and in-vitro analysis, our study demonstrates ESC-derived organoids might be a promising model for exploring nutritional effects and underlying mechanisms.

Clitocine enhances the drug sensitivity of colon cancer cells by promoting FBXW7-mediated MCL-1 degradation via inhibiting the A2B/cAMP/ERK axis.

Chemotherapy resistance to colon cancer is an unavoidable obstacle in the clinical management of the disease. Clitocine, an adenosine analog, played a significant role in the chemosensitivity of human colon cancer cells by promoting myeloid cell leukemia 1 (MCL-1) protein degradation. However, the detailed mechanism remains to be further elucidated. We found that clitocine upregulates the expression of F-box and WD repeat domain containing 7 (FBXW7), a ubiquitin ligase involved in the MCL-1 degradation. Transcriptome sequencing analysis revealed that clitocine significantly inhibits the cyclic adenosine monophosphate (cAMP) and extracellular regulated protein kinases (ERK) downstream signaling pathways in colon cancer cells, thereby enhancing FBXW7 expression and subsequently promoting the ubiquitination degradation of MCL-1 protein. We verified that clitocine regulated intracellular cAMP levels by competitive binding with the adenosine receptor A2B. A molecular docking assay also verified the binding relationship. By decreasing intracellular cAMP levels, clitocine blocks the activation of downstream signaling pathways, which ultimately enhances the drug sensitivity of colon cancer cells through increased FBXW7 expression due to the inhibition of its promoter DNA methylation. Both knockout of the adenosine receptor A2B and Br-cAMP treatment can effectively attenuate the function of clitocine in vitro and in vivo. This study clarified that clitocine enhanced the drug sensitivity of colon cancer cells by promoting FBXW7-mediated MCL-1 degradation via inhibiting the A2B/cAMP/ERK axis, providing further knowledge of the clinical application for clitocine.NEW & NOTEWORTHY Our study found that clitocine enhances the drug sensitivity of colon cancer cells by promoting FBXW7-mediated MCL-1 degradation via inhibiting the A2B/cAMP/ERK axis.

Using integrated transcriptomics and metabolomics to explore the effects of infant formula on the growth and development of small intestinal organoids.

Infant formulas are designed to provide sufficient energy and the necessary nutrients to support the growth and development of newborns. Currently, research on the functions of formula milk powder focuses on clinical research and cell experiments, and there were many cell experiments that investigated the effect of infant formulas on cellular growth. However, most of the cells used are tumor cell lines, which are unable to simulate the real digestion process of an infant. In this study, we innovatively proposed a method that integrates human small intestinal organoids (SIOs) with transcriptomics and metabolomics analysis. We induced directed differentiation of human embryonic stem cells into SIOs and simulated the intestinal environment of newborns with them. Then, three kinds of 1-stage infant formulas from the same brand were introduced to simulate the digestion, absorption, and metabolism of the infant intestine. The nutritional value of each formula milk powder was examined by multi-omics sequencing methods, including transcriptomics and metabolomics analysis. Results showed that there were significant alterations in gene expression and metabolites in the three groups of SIOs after absorbing different infant formulas. By analyzing transcriptome and metabolome data, combined with GO, KEGG, and GSEA analysis, we demonstrated the ability of SIOs to model the different aspects of the developing process of the intestine and discovered the correlation between formula components and their effects, including Lactobacillus lactis and lactoferrin. The study reveals the effect and mechanisms of formula milk powder on the growth and development of infant intestines and the formation of immune function. Furthermore, our method can help to construct a multi-level assessment model, detect the effects of nutrients, and evaluate the interactions between nutrients, which is helpful for future research and development of infant powders.

Pretreatment pulmonary tumor necrosis is a promising prognostic imaging biomarker for first-line anti-PD-1/PD-L1 therapy in advanced lung squamous cell carcinoma: a multi-institutional, propensity score-matching cohort analysis.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002-1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056-2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

Predicting anti-PD-1/PD-L1 inhibitor treatment outcomes: pulmonary tumor necrosis in lung squamous cell carcinoma Our study focused on lung squamous cell carcinoma (LSCC) patients receiving first-line anti-PD-1/PD-L1 therapy. We explored the impact of a feature called pretreatment pulmonary tumor necrosis (PTN) on their prognosis. PTN was identified in 39.6% of patients using baseline chest CT scans. Results revealed that patients with PTN had a shorter time without disease progression (median PFS of 6.5 months compared to 8.6 months) and a higher risk of unfavorable outcomes. This suggests that PTN may serve as a negative prognostic imaging marker for anti-PD-1/PD-L1 therapy in advanced LSCC. Further research is needed to confirm and understand these findings better.

In-Situ Polymerized High-Voltage Solid-State Lithium Metal Batteries with Dual-Reinforced Stable Interfaces.

Solid polymer electrolytes (SPEs) represent a pivotal advance toward high-energy solid-state lithium metal batteries. However, inadequate interfacial contact remains a significant bottleneck, impeding scalability and application. Inadequate interfacial contact remains a significant bottleneck, impeding scalability and application. Recent efforts have focused on transforming liquid/solid interfaces into solid/solid ones through in situ polymerization, which shows potential especially in reducing interface impedance. Here, we designed high-voltage SSLMBs with dual-reinforced stable interfaces by combining interface modification with an in situ polymerization technology inspired by targeted effects in medicine. Theoretical calculations and time-of-flight secondary ion mass spectrometry (TOF-SIMS) analysis demonstrate that tetramethylene sulfone (TMS) and bis(2,2,2-trifluoromethyl) carbonate (TFEC) exhibit selective adsorption at the interface of the LiNi0.8Co0.1Mn0.1O2 (NCM) cathode and Li anode, respectively. These compounds further decompose to form a stable cathode-electrolyte interface (CEI) film and a solid electrolyte interface (SEI) film, thereby simultaneously achieving a superior interface between the SPE and both the Li anode and NCM cathode. The developed Li||SPE||Li cell sustained cycling for more than 1000 h at 0.3 mA cm-2, and the NCM||SPE||Li cell also demonstrated an excellent capacity retention of 86.8% after 1000 cycles at 1 °C. This work will provide valuable insights for the rational design of high-voltage SSLMBs with stable interfaces, leveraging in situ polymerization as a cornerstone technology.

Sustained release of brimonidine from conjunctival sac insert to reduce intraocular pressure for glaucoma treatment.

BACKGROUND: Glaucoma is one of the major irreversible blinding eye diseases in the world. Reducing intraocular pressure (IOP) is the primary treatment option, and taking eye drops daily is the common method. However, short drug duration and poor bioavailability of eye drops may lead to unsatisfied therapeutic effects and inadequate patient compliance. METHODS: A brimonidine-loaded silicone rubber insert (BRI@SR@PT) was prepared by loading brimonidine into a surface-modified silicone rubber ring, followed by polydopamine/thermoplastic polyurethane coatings. The physical properties, in vitro cytocompatibility and drug release of BRI@SR@PT were investigated. The BRI@SR@PT was administrated in the conjunctival sac of rabbit eyes, and its in vivo drug release, IOP-lowering efficacy and biosafety were assessed. RESULTS: The BRI@SR@PT presented great thermal stability and excellent elasticity. The BRI@SR@PT was able to release BRI sustainably for 28 days with little toxicity in vitro. Compared to BRI eye drops, the BRI@SR@PT effectively lowered IOP for 21 days based on the sustained BRI release with great biosafety when administrated in conjunctival sac of rabbit eyes in a noninvasive fashion. CONCLUSIONS: The conjunctival sac insert (BRI@SR@PT), as a promising drug-delivery platform, may provide a sustained IOP-lowering treatment for patients with ocular hypertension or glaucoma, without the need for invasive procedures.

Disturbance of bile acids profile aggravates the diarrhea induced by capecitabine through inhibiting the Wnt/ß-catenin pathway.

INTRODUCTION: Diarrhea is the primary dose-limiting side effect of capecitabine(Cap) hindering its clinical application, but the mechanism is unclear. Clarifying this mechanism may enhance the patient compliance and improve the treatment outcome. OBJECTIVES: To assess if the endogenous metabolic profile could prodict the diarrhea induced by Cap and explore and validate underlying mechanisms. METHODS: Untargeted and targeted bile acids(BAs) metabolomics were performed to analyzed the metabolic profile of baseline samples from colorectal cancer(CRC) patients and the association with the diarrhea induced by Cap was assessed. The toxicity of BAs and Cap and its metabolites alone or their combinations to the human normal intestinal epithelial cell(HIEC) was assessed, and the key genes that mediated the BAs-enhanced toxicity of Cap were discovered by RNA-seq and then validated. A mouse model with high exposure levels of BAs was constructed and then treated with Cap to verify the Cap-induced diarrhea enhanced by BAs. RESULTS: The baseline endogenous metabolic profile showed obviously difference between diarrhea and non-diarrhea CRC patients, and the differential metabolites mainly enriched in BAs metabolism; the deoxycholic acid(DCA) and lithocholic acid(LCA) were selected to be the key BAs that enhanced the toxicity of Cap metabolite 5-FU to the HIEC cell; the DCA and LCA could inhibit the Wnt/ß-catenin signaling pathway, which then suppressed the P-glycoprotein and increased the exposure level of 5-FU in the HIEC cell. The results of animal experiment verified that the excessive DCA and LCA could aggravate the Cap-induced diarrhea through inhibiting Wnt/ß-catenin-P-glycoprotein pathway. CONCLUSIONS: The disordered BAs metabolic profile showed close relationship with diarrhea induced by Cap, and excessive DCA and LCA were proved to be the key BAs, which could aggravate the Cap-induced diarrhea through inhibiting Wnt/ß-catenin-P-glycoprotein pathway.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3). CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).

Ultra-Stable Sodium-Ion Battery Enabled by All-Solid-State Ferroelectric-Engineered Composite Electrolytes.

Symmetric Na-ion cells using the NASICON-structured electrodes could simplify the manufacturing process, reduce the cost, facilitate the recycling post-process, and thus attractive in the field of large-scale stationary energy storage. However, the long-term cycling performance of such batteries is usually poor. This investigation reveals the unavoidable side reactions between the NASICON-type Na3V2(PO4)3 (NVP) anode and the commercial liquid electrolyte, leading to serious capacity fading in the symmetric NVP//NVP cells. To resolve this issue, an all-solid-state composite electrolyte is used to replace the liquid electrolyte so that to overcome the side reaction and achieve high anode/electrolyte interfacial stability. The ferroelectric engineering could further improve the interfacial ion conduction, effectively reducing the electrode/electrolyte interfacial resistances. The NVP//NVP cell using the ferroelectric-engineered composite electrolyte can achieve a capacity retention of 86.4% after 650 cycles. Furthermore, the electrolyte can also be used to match the Prussian-blue cathode NaxFeyFe(CN)6-z·nH2O (NFFCN). Outstanding long-term cycling stability has been obtained in the all-solid-state NVP//NFFCN cell over 9000 cycles at a current density of 500 mA g-1, with a fading rate as low as 0.005% per cycle.

Dual-gradient Concentration Distribution in Sb-Cu Alloy Nanoarrays for Robust Sodium-ionStorage.

Alloy-type materials are attractive for anodes in sodium-ion batteries (SIBs) owing to their high theoretical capacities and overall performance. However, the accumulation of stress/strain during repeated cycling results in electrode pulverization, leading to rapid capacity decay and eventual disintegration, thus hindering their practical applications. Herein, we report a 3D coral-like Sb-Cu alloy nanoarray with gradient distribution of both elements. The array features a Sb-rich bottom and a Cu-rich top with increasing Sb and decreasing Cu concentrations from top to bottom. The former is the active component that provides the high capacity, whereas the latter serves as an inert additive that acts against volume variation. The gradual transition in composition within the electrode introduces a ladder-type volume expansion effect, facilitating a smooth distribution and effective release of stress, thereby ensuring the wanted mechanical stability and structural integrity. The as-developed nanoarray affords a high reversible capacity (460 mAh g-1 at 0.5 C), stable cycling (89% retention over 120 cycles at 1.0 C), and superior rate capability (354 mAh g-1 at 10 C). The concentration dual-gradient strategy paves a new pathway of designing alloy-type materials for SIBs.

Estimation of accelerated hazards models based on case K informatively interval-censored failure time data.

The accelerated hazards model is one of the most commonly used models for regression analysis of failure time data and this is especially the case when, for example, the hazard functions may have monotonicity property. Correspondingly a large literature has been established for its estimation or inference when right-censored data are observed. Although several methods have also been developed for its inference based on interval-censored data, they apply only to limited situations or rely on some assumptions such as independent censoring. In this paper, we consider the situation where one observes case K interval-censored data, the type of failure time data that occur most in, for example, medical research such as clinical trials or periodical follow-up studies. For inference, we propose a sieve borrow-strength method and in particular, it allows for informative censoring. The asymptotic properties of the proposed estimators are established. Simulation studies demonstrate that the proposed inference procedure performs well. The method is applied to a set of real data set arising from an AIDS clinical trial.

Pharmacokinetic assessment of tacrolimus in combination with deoxyschizandrin in rats.

Background: Tacrolimus (Tac) is commonly used for postoperative immunosuppressive therapy in transplant patients. However, problems, for example, low bioavailability and unstable plasma concentration, persist for a long time, Studies have reported that the deoxyschizandrin could effectively improve these problems, but the pharmacokinetic parameters (PKs) of Tac combined with deoxyschizandrin are still unknown. Method: In this study, an UHPLC-MS/MS method has been established for simultaneous quantitation of Tac and deoxyschizandrin. The PKs of Tac influenced by different doses of deoxyschizandrin after single and multiple administrations were analyzed, and the different impact of deoxyschizandrin and Wuzhi capsule on PKs of Tac were compared. Result: The modified UHPLC-MS/MS method could rapid quantification of Tac and deoxyschizandrin within 2 min using bifendatatum as the internal standard (IS). All items were successfully validated. The C max of deoxyschizandrin increased from 148.27 ± 23.20 to 229.13 ± 54.77 ng/mL in rats after multiple administrations for 12 days. After co-administration of 150 mg/mL deoxyschizandrin, Tac had an earlier T max and greater C max and AUC0-t, and the C max and AUC0-t of Tac increased from 14.26 ± 4.73 to 54.48 ± 14.37 ng/mL and from 95.10 ± 32.61 to 315.23 ± 92.22 h/ng/mL, respectively; this relationship was positively proportional to the dosage of deoxyschizandrin. In addition, compared with Wuzhi capsule, the same dose of deoxyschizandrin has a better effective on Tac along with more stable overall PKs. Conclusion: An UHPLC-MS/MS method was established and validated for simultaneous detection of deoxyschizandrin and Tac. Deoxyschizandrin could improve the in vivo exposure level and stability of Tac, besides, this effect is better than Wuzhi capsule in same dose.

One-pot assay using a target-driven split aptamer recognition and assembly strategy for convenient and rapid detection of gliotoxin.

An aptamer targeting gliotoxin (GTX) was optimized to increase the binding affinity by approximately 20 times and achieve higher structural stability and targeting specificity. Molecular dynamics simulations were used to explore the molecular mechanism and key action sites underlying the recognition of GTX by the optimized aptamer. Subsequently, the optimized aptamer was split into two fragments and a convenient and rapid one-pot assay for GTX detection was successfully established using a target-driven split aptamer recognition and assembly strategy. The method exhibited a good linear range of 0.128 nM to 2 µM, a low detection limit of 0.07 nM, and excellent selectivity for GTX. Furthermore, the method had good accuracy and stability in real sample analysis. Therefore, the developed one-pot method provides a reliable, convenient, and cost-effective approach for the widespread application of GTX detection.

A flexible time-varying coefficient rate model for panel count data.

Panel count regression is often required in recurrent event studies, where the interest is to model the event rate. Existing rate models are unable to handle time-varying covariate effects due to theoretical and computational difficulties. Mean models provide a viable alternative but are subject to the constraints of the monotonicity assumption, which tends to be violated when covariates fluctuate over time. In this paper, we present a new semiparametric rate model for panel count data along with related theoretical results. For model fitting, we present an efficient EM algorithm with three different methods for variance estimation. The algorithm allows us to sidestep the challenges of numerical integration and difficulties with the iterative convex minorant algorithm. We showed that the estimators are consistent and asymptotically normally distributed. Simulation studies confirmed an excellent finite sample performance. To illustrate, we analyzed data from a real clinical study of behavioral risk factors for sexually transmitted infections.

One-step hydrothermal synthesis of vanadium dioxide/carbon core-shell composite with improved ammonium ion storage for aqueous ammonium-ion battery.

Aqueous nonmetallic ion batteries have garnered significant interest due to their cost-effectiveness, environmental sustainability, and inherent safety features. Specifically, ammonium ion (NH4+) as a charge carrier has garnered more and more attention recently. However, one of the persistent challenges is enhancing the electrochemical properties of vanadium dioxide (VO2) with a tunnel structure, which serves as a highly efficient NH4+ (de)intercalation host material. Herein, a novel architecture, wherein carbon-coated VO2 nanobelts (VO2@C) with a core-shell structure are engineered to augment NH4+ storage capabilities of VO2. In detail, VO2@C is synthesized via the glucose reduction of vanadium pentoxide under hydrothermal conditions. Experimental results manifest that the introduction of the carbon layer on VO2 nanobelts can enhance mass transfer, ion transport and electrochemical kinetics, thereby culminating in the improved NH4+ storage efficiency. VO2@C core-shell composite exhibits a remarkable specific capacity of ∼300 mAh/g at 0.1 A/g, which is superior to that of VO2 (∼238 mAh/g) and various other electrode materials used for NH4+ storage. The NH4+ storage mechanism can be elucidated by the reversible NH4+ (de)intercalation within the tunnel of VO2, facilitated by the dynamic formation and dissociation of hydrogen bonds. Furthermore, when integrated into a full battery with polyaniline (PANI) cathode, the VO2@C//PANI full battery demonstrates robust electrochemical performances, including a specific capacity of ∼185 mAh·g-1 at 0.2 A·g-1, remarkable durability of 93 % retention after 1500 cycles, as well as high energy density of 58 Wh·kg-1 at 5354 W·kg-1. This work provides a pioneering approach to design and explore composite materials for efficient NH4+ storage, offering significant implications for future battery technology enhancements.

Lightweight, Strong, and Transparent Wood Films Produced by Capillary Driven Self-Densification.

Wood delignification and densification enable the production of high strength and/or transparent wood materials with exceptional properties. However, processing needs to be more sustainable and besides the chemical delignification treatments, energy intense hot-pressing calls for alternative approaches. Here, this study shows that additional softening of delignified wood via a mild swelling process using an ionic liquid-water mixture enables the densification of tube-line wood cells into layer-by-layer sheet structures without hot-pressing. The natural capillary force induces self-densification in a simple drying process resulting in a transparent wood film. The as-prepared films with ≈150 µm thickness possess an optical transmittance ≈70%, while maintaining optical haze >95%. Due to the densely packed sheet structure with a large interfacial area, the reassembled wood film is fivefold stronger and stiffer than the delignified wood in fiber direction. Owing to a low density, the specific tensile strength and elastic modulus are as high as 282 MPa cm3 g-1 and 31 GPa cm3 g-1. A facile and highly energy efficient wood nanotechnology approach are demonstrated toward more sustainable materials and processes by directly converting delignified wood into transparent wood omitting polymeric matrix infiltration or mechanical pressing.

Characterization of zinc finger protein 536, a neuroendocrine regulator, using pan-cancer analysis.

BACKGROUND: Previous studies suggested that zinc finger protein 536 (ZNF536) was abundant in the central brain and regulated neuronal differentiation. However, the role of ZNF536 in cancer has remained unclear. METHODS: ZNF536 mutation, copy number alteration, DNA methylation, and RNA expression were explored using public portals. Data from The Cancer Genome Atlas (TCGA) were utilized to analyze pathways and tumor microenvironment (TME), with a focus on prognosis in both TCGA and immunotherapy pan-cancer cohorts. Methylated ZNF536 from small cell lung cancer (SCLC) cell lines were utilized to train with probes for conducting enrichment analysis. Single-cell RNA profile demonstrated the sublocalization and co-expression of ZNF536, and validated its targets by qPCR. RESULTS: Genetic alterations in ZNF536 were found to be high-frequency and a single sample could harbor different variations. ZNF536 at chromosome 19q12 exerted a bypass effect on CCNE1, supported by CRISPR data. For lung cancer, ZNF536 mutation was associated with longer survival in primary lung adenocarcinoma (LUAD), but its prognosis was poor in metastatic LUAD and SCLC. Importantly, ZNF536 mutation and amplification had opposite prognoses in Stand Up To Cancer-Mark Foundation (SU2C-MARK) LUAD cohort. ZNF536 mutation altered the patterns of genomic alterations in tumors, and had distinct impacts on the signaling pathways and TME compared to ZNF536 amplification. Additionally, ZNF536 expression was predominantly in endocrine tumors and brain tissues. High-dimensional analysis supported this finding and further revealed regulators of ZNF536. Considering that the methylation of ZNF536 was involved in the synaptic pathway associated with neuroendocrine neoplasms, demonstrating both diagnostic and prognostic value. Moreover, we experimentally verified ZNF536 upregulated neuroendocrine markers. CONCLUSIONS: Our results showed that ZNF536 alterations in cancer, including variations in copy number, mutation, and methylation. We proved the involvement of ZNF536 in neuroendocrine regulation, and identified highly altered ZNF536 as a potential biomarker for immunotherapy.

Electrochemical Knocking-Down of Zn Metal Clusters into Single Atoms.

Single Atoms Catalysts (SACs) have emerged as a class of highly promising heterogeneous catalysts, where the traditional bottom-up synthesis approaches often encounter considerable challenges in relation to aggregation issues and poor stability. Consequently, achieving densely dispersed atomic species in a reliable and efficient manner remains a key focus in the field. Herein, we report a new facile electrochemical knock-down strategy for the formation of SACs, whereby the metal Zn clusters are transformed into single atoms. While a defect-rich substrate plays a pivotal role in capturing and stabilizing isolated Zn atoms, the feasibility of this novel strategy is demonstrated through a comprehensive investigation, combining experimental and theoretical studies. Furthermore, when studied in exploring for potential applications, the material prepared shows a remarkable improvement of 58.21% for the Li+ storage and delivers a capacity over 300 Wh kg-1 after 500 cycles upon the transformation of Zn clusters into single atoms.