Deciphering Microbiome, Transcriptome, and Metabolic Interactions in the Presence of Probiotic Lactobacillus acidophilus against Salmonella Typhimurium in a Murine Model.

Salmonella enterica serovar Typhimurium (S. Typhimurium), a foodborne pathogen that poses significant public health risks to humans and animals, presents a formidable challenge due to its antibiotic resistance. This study explores the potential of Lactobacillus acidophilus (L. acidophilus 1.3251) probiotics as an alternative strategy to combat antibiotic resistance associated with S. Typhimurium infection. In this investigation, twenty-four BALB/c mice were assigned to four groups: a non-infected, non-treated group (CNG); an infected, non-treated group (CPG); a group fed with L. acidophilus but not infected (LAG); and a group fed with L. acidophilus and challenged with Salmonella (LAST). The results revealed a reduction in Salmonella levels in the feces of mice, along with restored weight and improved overall health in the LAST compared to the CPG. The feeding of L. acidophilus was found to downregulate pro-inflammatory cytokine mRNA induced by Salmonella while upregulating anti-inflammatory cytokines. Additionally, it influenced the expression of mRNA transcript, encoding tight junction protein, oxidative stress-induced enzymes, and apoptosis-related mRNA expression. Furthermore, the LEfSe analysis demonstrated a significant shift in the abundance of critical commensal genera in the LAST, essential for maintaining gut homeostasis, metabolic reactions, anti-inflammatory responses, and butyrate production. Transcriptomic analysis revealed 2173 upregulated and 506 downregulated differentially expressed genes (DEGs) in the LAST vs. the CPG. Functional analysis of these DEGs highlighted their involvement in immunity, metabolism, and cellular development. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis indicated their role in tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), chemokine, Forkhead box O (FOXO), and transforming growth factor (TGF-ß) signaling pathway. Moreover, the fecal metabolomic analysis identified 929 differential metabolites, with enrichment observed in valine, leucine, isoleucine, taurine, glycine, and other metabolites. These findings suggest that supplementation with L. acidophilus promotes the growth of beneficial commensal genera while mitigating Salmonella-induced intestinal disruption by modulating immunity, gut homeostasis, gut barrier integrity, and metabolism.

Novel Synergistic Probiotic Intervention: Transcriptomic and Metabolomic Analysis Reveals Ameliorative Effects on Immunity, Gut Barrier, and Metabolism of Mice during Salmonella typhimurium Infection.

Salmonella typhimurium (S. typhimurium), a prevalent cause of foodborne infection, induces significant changes in the host transcriptome and metabolome. The lack of therapeutics with minimal or no side effects prompts the scientific community to explore alternative therapies. This study investigates the therapeutic potential of a probiotic mixture comprising Lactobacillus acidophilus (L. acidophilus 1.3251) and Lactobacillus plantarum (L. plantarum 9513) against S. typhimurium, utilizing transcriptome and metabolomic analyses, a novel approach that has not been previously documented. Twenty-four SPF-BALB/c mice were divided into four groups: control negative group (CNG); positive control group (CPG); probiotic-supplemented non-challenged group (LAPG); and probiotic-supplemented Salmonella-challenged group (LAPST). An RNA-sequencing analysis of small intestinal (ileum) tissue revealed 2907 upregulated and 394 downregulated DEGs in the LAPST vs. CPG group. A functional analysis of DEGs highlighted their significantly altered gene ontology (GO) terms related to metabolism, gut integrity, cellular development, and immunity (p ≤ 0.05). The KEGG analysis showed that differentially expressed genes (DEGs) in the LAPST group were primarily involved in pathways related to gut integrity, immunity, and metabolism, such as MAPK, PI3K-Akt, AMPK, the tryptophan metabolism, the glycine, serine, and threonine metabolism, ECM-receptor interaction, and others. Additionally, the fecal metabolic analysis identified 1215 upregulated and 305 downregulated metabolites in the LAPST vs. CPG group, implying their involvement in KEGG pathways including bile secretion, propanoate metabolism, arginine and proline metabolism, amino acid biosynthesis, and protein digestion and absorption, which are vital for maintaining barrier integrity, immunity, and metabolism. In conclusion, these findings suggest that the administration of a probiotic mixture improves immunity, maintains gut homeostasis and barrier integrity, and enhances metabolism in Salmonella infection.

Investigation of synthetic MRI with quantitative parameters for discriminating axillary lymph nodes status in invasive breast cancer.

OBJECTIVE: To investigate the potential value of quantitative parameters derived from synthetic magnetic resonance imaging (syMRI) for discriminating axillary lymph nodes metastasis (ALNM) in breast cancer patients. MATERIALS AND METHODS: A total of 56 females with histopathologically proven invasive breast cancer who underwent both conventional breast MRI and additional syMRI examinations were enrolled in this study, including 30 patients with ALNM and 26 with non-ALNM. SyMRI has enabled quantification of T1 relaxation time (T1), T2 relaxation time (T2) and proton density (PD). The syMRI quantitative parameters of breast primary tumors before (T1tumor, T2tumor, PDtumor) and after (T1+tumor, T2+tumor, PD+tumor) contrast agent injection were obtained. Similarly, measurements were taken for axillary lymph nodes before (T1LN, T2LN, PDLN) and after (T1+LN, T2+LN, PD+LN) the injection, then theΔT1 (T1-T1+), ΔT2 (T2-T2+), ΔPD (PD-PD+), T1/T2 and T1+/T2+ were calculated. All parameters were compared between ANLM and non-ALNM group. Intraclass correlation coefficient for assessing interobserver agreement. The independent Student's t test or Mann-Whitney U test to determine the relationship between the mean quantitative values and the ALNM. Multivariate logistic regression analyses followed by receiver operating characteristics (ROC) analysis for discriminating ALN status. A P value < 0.05 was considered statistically significant. RESULTS: The short-diameter of lymph nodes (DLN) in ALNM group was significantly longer than that in the non-ALNM group (10.22 ± 3.58 mm vs. 5.28 ± 1.39 mm, P < 0.001). The optimal cutoff value was determined to be 5.78 mm, with an AUC of 0.894 (95 % CI: 0.838-0.939), a sensitivity of 86.7 %, and a specificity of 90.2 %. In syMRI quantitative parameters of breast tumors, T2tumor, ΔT2tumor and ΔPDtumor values showed statistically significant differences between the two groups (P < 0.05). T2tumor value had the best performance in discriminating ALN status (AUC = 0.712), and the optimal cutoff was 90.12 ms, the sensitivity and specificity were 65.0 % and 83.6 % respectively. In terms of syMRI quantitative parameters of lymph nodes, T1LN, T2LN, T1LN/T2LN, T2+LN and ΔT1LN values were significantly different between the two groups (P < 0.05), and their AUCs were 0.785, 0.840, 0.886, 0.702 and 0.754, respectively. Multivariate analyses indicated that the T1LN value was the only independent predictor of ALNM (OR=1.426, 95 % CI: 1.130-1.798, P = 0.039). The diagnostic sensitivity and specificity of T1LN was 86.7 % and 69.4 % respectively at the best cutoff point of 1371.00 ms. The combination of T1LN, T2LN, T1LN/T2LN, ΔT1LN and DLN had better performance for differentiating ALNM and non-ALNM, with AUCs of 0.905, 0.957, 0.964 and 0.897, respectively. CONCLUSION: The quantitative parameters derived from syMRI have certain value for discriminating ALN status in invasive breast cancer, with T2tumor showing the highest diagnostic efficiency among breast lesions parameters. Moreover, T1LN acted as an independent predictor of ALNM.

Pirin Promotes the Progression of Non-Small-Cell Lung Cancer by Increasing ODC1 to Suppress Autophagy.

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer.

Small cell lung cancers (SCLC) are comprised of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLC, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes, including non-canonical BAF (ncBAF) complexes, as top dependencies specific to POU2F3-positive SCLC. Notably, clinical-grade pharmacologic mSWI/SNF inhibition attenuates proliferation of all POU2F3-positive SCLCs, while disruption of ncBAF via BRD9 degradation is uniquely effective in pure non-neuroendocrine POU2F3-SCLCs. mSWI/SNF maintains accessibility over gene loci central to POU2F3-mediated gene regulatory networks. Finally, chemical targeting of SMARCA4/2 mSWI/SNF ATPases and BRD9 decrease POU2F3-SCLC tumor growth and increase survival in vivo . Taken together, these results characterize mSWI/SNF-mediated global governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy for SCLC.

Effect of white jade snail secretion on antioxidant capacity and intestinal microbial diversity in mouse model of acute gastric ulcer.

BACKGROUND: In the present work, acute gastric ulcer models were constructed by administering hydrochloric acid/ethanol. The mice ingested white jade snail secretion (WJSS) through gastric infusion. Ulcer areas in gastric tissue were recorded, and malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. Notably, high-throughput 16S rDNA analysis of intestinal flora and determination of amino acid composition in feces were performed to understand the effect of WJSS on model mice. RESULTS: Compared with the control group, the ulcer area in the WJSS low-, medium- and high-concentration groups declined by 28.02%, 39.57% and 77.85%, respectively. MDA content decreased by 24.71%, 49.58% and 64.25%, and SOD relative enzyme activity fell by 28.19%, 43.37% and 9.60%, respectively. The amounts of amino acids in the low-, medium- and high-concentration groups were slightly lower, and probiotic bacteria such as Bacteroidetes and Lactobacillales increased in different-concentration WJSS groups. Adding WJSS contributes to the establishment of beneficial intestinal flora and the absorption of amino acids. CONCLUSION: Our results showed that WJSS has a beneficial effect on inhibiting hydrochloric acid-ethanolic gastric ulcers, suggesting that WJSS has excellent potential as a novel anti-ulcer agent. Combined with ulcer area, MDA content, SOD content, gut probiotics and other indicators, a high concentration of WJSS had the best protective effect on acute gastric ulcer. © 2023 Society of Chemical Industry.

A review of metal-organic framework (MOF) materials as an effective photocatalyst for degradation of organic pollutants.

Water plays a vital role in all aspects of life. Recently, water pollution has increased exponentially due to various organic and inorganic pollutants. Organic pollutants are hard to degrade; therefore, cost-effective and sustainable approaches are needed to degrade these pollutants. Organic dyes are the major source of organic pollutants from coloring industries. The photoactive metal-organic frameworks (MOFs) offer an ultimate strategy for constructing photocatalysts to degrade pollutants present in wastewater. Therefore, tuning the metal ions/clusters and organic ligands for the better photocatalytic activity of MOFs is a tremendous approach for wastewater treatment. This review comprehensively reports various MOFs and their composites, especially POM-based MOF composites, for the enhanced photocatalytic degradation of organic pollutants in the aqueous phase. A brief discussion on various theoretical aspects such as density functional theory (DFT) and machine learning (ML) related to MOF and MOF composite-based photocatalysts has been presented. Thus, this article may eventually pave the way for applying different structural features to modulate novel porous materials for enhanced photodegradation properties toward organic pollutants.

Aurora A kinase inhibition induces accumulation of SCLC tumor cells in mitosis with restored interferon signaling to increase response to PD-L1.

Despite small cell lung cancers (SCLCs) having a high mutational burden, programmed death-ligand 1 (PD-L1) immunotherapy only modestly increases survival. A subset of SCLCs that lose their ASCL1 neuroendocrine phenotype and restore innate immune signaling (termed the "inflammatory" subtype) have durable responses to PD-L1. Some SCLCs are highly sensitive to Aurora kinase inhibitors, but early-phase trials show short-lived responses, suggesting effective therapeutic combinations are needed to increase their durability. Using immunocompetent SCLC genetically engineered mouse models (GEMMs) and syngeneic xenografts, we show durable efficacy with the combination of a highly specific Aurora A kinase inhibitor (LSN3321213) and PD-L1. LSN3321213 causes accumulation of tumor cells in mitosis with lower ASCL1 expression and higher expression of interferon target genes and antigen-presentation genes mimicking the inflammatory subtype in a cell-cycle-dependent manner. These data demonstrate that inflammatory gene expression is restored in mitosis in SCLC, which can be exploited by Aurora A kinase inhibition.

Xuanfei Baidu decoction in the treatment of coronavirus disease 2019 (COVID-19): Efficacy and potential mechanisms.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide and become a major global public health concern. Although novel investigational COVID-19 antiviral candidates such as the Pfizer agent PAXLOVID™, molnupiravir, baricitinib, remdesivir, and favipiravir are currently used to treat patients with COVID-19, there is still a critical need for the development of additional treatments, as the recommended therapeutic options are frequently ineffective against SARS-CoV-2. The efficacy and safety of vaccines remain uncertain, particularly with the emergence of several variants. All 10 versions of the National Health Commission's diagnosis and treatment guidelines for COVID-19 recommend using traditional Chinese medicine. Xuanfei Baidu Decoction (XFBD) is one of the "three Chinese medicines and three Chinese prescriptions" recommended for COVID-19. This review summarizes the clinical evidence and potential mechanisms of action of XFBD for COVID-19 treatment. With XFBD, patients with COVID-19 experience improved clinical symptoms, shorter hospital stay, prevention of the progression of their symptoms from mild to moderate and severe symptoms, and reduced mortality in critically ill patients. The mechanisms of action may be associated with its direct antiviral, anti-inflammatory, immunomodulatory, antioxidative, and antimicrobial properties. High-quality clinical and experimental studies are needed to further explore the clinical efficacy and underlying mechanisms of XFBD in COVID-19 treatment.

KDM6A epigenetically regulates subtype plasticity in small cell lung cancer.

Small cell lung cancer (SCLC) exists broadly in four molecular subtypes: ASCL1, NEUROD1, POU2F3 and Inflammatory. Initially, SCLC subtypes were thought to be mutually exclusive, but recent evidence shows intra-tumoural subtype heterogeneity and plasticity between subtypes. Here, using a CRISPR-based autochthonous SCLC genetically engineered mouse model to study the consequences of KDM6A/UTX inactivation, we show that KDM6A inactivation induced plasticity from ASCL1 to NEUROD1 resulting in SCLC tumours that express both ASCL1 and NEUROD1. Mechanistically, KDM6A normally maintains an active chromatin state that favours the ASCL1 subtype with its loss decreasing H3K4me1 and increasing H3K27me3 at enhancers of neuroendocrine genes leading to a cell state that is primed for ASCL1-to-NEUROD1 subtype switching. This work identifies KDM6A as an epigenetic regulator that controls ASCL1 to NEUROD1 subtype plasticity and provides an autochthonous SCLC genetically engineered mouse model to model ASCL1 and NEUROD1 subtype heterogeneity and plasticity, which is found in 35-40% of human SCLCs.

Construction of electrochemical biosensors based on MoSe2@1T-MoS2 heterojunction for the sensitive and rapid detection of miRNA-155 biomarker in breast cancer.

MiRNA-155 is a typical biomarker for breast cancer. Since its low concentration in the physiological environment and the limitations of conventional miRNA detection methods like Northern imprinting and RT-qPCR, convenient, real-time, and rapid detection methods are urgently needed. In this work, an electrochemical biosensor was constructed based on the flower-like MoSe2@1T-MoS2 heterojunction electrode material and specific RNA recognition probes, which can realize the rapid determination of miRNA-155 content with a wide detection range from 1 fM to 1 nM and a limit of detection (LOD) as low as 0.34 fM. Furthermore, the contents of miRNA-155 in blood samples of tumor-bearing mice and normal mice were measured as 724.93 pM and 21.42 pM, respectively by this biosensor, demonstrating its strong identification ability and miRNA-155 can be regarded as an ideal diagnostic marker. On this basis, a portable sensor platform was designed for on-site detection simulation and showed good recovery efficiency from 95.80% to 98.69%. Meanwhile, compared with the standard detection method RT-qPCR, the accuracy and reliability of the biosensor were verified, indicating that the biosensor has the potential to provide point-of-care testing (POCT) for the early diagnosis of breast cancer.

The corporate path to green innovation: does the digital economy matter?

As China's digital transformation accelerates, there is growing interest in whether the digital economy can effectively boost green innovation in industrial enterprises and enable China's development to break through the constraints of resources and environment. Therefore, this study analyzes the data of A-share industrial listed enterprises (2011-2020). Results indicate that the digital economy promotes green innovation. The impact of the digital economy on green innovation varies significantly among different types of enterprises, with stronger effects on state-owned enterprises. Digital economy enhances green innovation via boosting public attention and optimizing energy structure. Therefore, playing the role of monitoring public attention, and optimizing energy use are key strategies to promote corporate green innovation.

Modulation of tumour hypoxia by ultrasound-responsive microbubbles to enhance the sono-photodynamic therapy effect on triple-negative breast cancer.

Sono-photodynamic therapy (SPDT) is an oxidative stress-dependant antitumour treatment modality. Due to the hypoxic tumour microenvironment, the antitumour effect of SPDT is limited. In this study, we developed lipid vesicles to transport a photosensitizer (chlorin e6, Ce6) and oxygen into tumours to promote SPDT efficiency on triple-negative breast cancer in vitro and in vivo. The results showed that compared with the same concentration of free Ce6, Lipo-Ce6 produced a higher singlet oxygen level under light irradiation. Cellular Lipo-Ce6 accumulation was 4-fold higher than that of free Ce6. The cytotoxicity on 4T1 cells caused by Lipo-Ce6-SPDT was significantly stronger than that caused by free Ce6-SPDT, and oxygen microbubbles (O2MB) further enhanced the cytotoxicity of Lipo-Ce6-SPDT under hypoxic conditions. Cellular ROS production in the Lipo-Ce6-SPDT+O2MB group was approximately 2.5-fold higher than that in the Lipo-Ce6-SPDT+C3F8MB group. Furthermore, O2MB rapidly relieved 4T1 subcutaneous xenograft hypoxia conditions under ultrasound exposure and significantly improved the antitumour activity of SPDT in vivo. These results indicate that the combination of O2MB and a high-activity liposome photosensitizer can significantly enhance the antitumour efficiency of SPDT for hypoxic tumours.

Ursane-Type Triterpenes with a Phenylpropanoid Unit from Camellia ptilosperma and Evaluation of Their Cytotoxic Activities.

Six new ursane-type triterpenes with a phenylpropanoid unit and five known oleanane-type triterpenes were isolated from the leaves of Camellia ptilosperma. The undescribed compounds were identified by analysis of 1D and 2D NMR and HRESIMS spectroscopic data as ptilospermanols A-F. The cytotoxicity of new compounds against six human cancer cell lines and three mouse tumor cell lines was evaluated by MTT assay.

Prohexadione-calcium alleviates the leaf and root damage caused by salt stress in rice (Oryza sativa L.) at the tillering stage.

Salt stress, as a principal abiotic stress, harms the growth and metabolism of rice, thus affecting its yield and quality. The tillering stage is the key growth period that controls rice yield. Prohexadione-calcium (Pro-Ca) can increase the lodging resistance of plants by reducing plant height, but its effects on rice leaves and roots at the tillering stage under salt stress are still unclear. This study aimed to evaluate the ability of foliar spraying of Pro-Ca to regulate growth quality at the rice tillering stage under salt stress. The results showed that salt stress reduced the tillering ability of the rice and the antioxidant enzyme activity in the roots. Salt stress also reduced the net photosynthetic rate (Pn), stomatal conductance (Gs) and intercellular CO2 concentration (Ci) of the rice leaves and increased the contents of osmotic regulatory substances in the leaves and roots. The application of exogenous Pro-Ca onto the leaves increased the tiller number of the rice under salt stress and significantly increased the photosynthetic capacity of the leaves. Additionally, it increased the activities of antioxidant enzymes and the AsA content. The contents of an osmotic regulation substance, malondialdehyde (MDA), and H2O2 in the leaves and roots also decreased. These results suggested that Pro-Ca can increase the tillering ability, photosynthetic capacity, osmotic adjustment substance content levels and antioxidant enzyme activity levels in rice and reduce membrane lipid peroxidation, thus improving the salt tolerance of rice at the tillering stage.

Prohexadione calcium enhances rice growth and tillering under NaCl stress.

Salt stress affects crop quality and reduces crop yields, and growth regulators enhance salt tolerance of crop plants. In this report, we examined the effects of prohexadione-calcium (Pro-Ca) on improving rice (Oryza sativa L.) growth and tillering under salt stress. We found that NaCl stress inhibited the growth of two rice varieties and increased malondialdehyde (MDA) levels, electrolyte leakage, and the activities of the antioxidant enzymes. Foliar application of Pro-Ca reduced seedling height and increased stem base width and lodging resistance of rice. Further analyses showed that Pro-Ca application reduced MDA content, electrolyte leakage, and membrane damage in rice leaves under NaCl stress. Pro-Ca enhanced the net photosynthetic rate (Pn), stomatal conductance (Gs), and intercellular CO2 concentration (Ci) of rice seedlings, while increasing the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbic acid peroxidase (APX) at the tillering stage under salt stress. Overall, Pro-Ca improves salt tolerance of rice seedlings at the tillering stage by enhancing lodging resistance, reducing membrane damages, and enhancing photosynthesis and antioxidant capacities of rice seedlings.

Synergistic adsorption and oxidation of trivalent antimony from groundwater using biochar supported magnesium ferrite: Performances and mechanisms.

Antimony (Sb) pollution is considered an environmental problem, since Sb is toxic and carcinogenic to humans. Here, a novel biochar supported magnesium ferrite (BC@MF) was adopted for Sb(III) removal from groundwater. The maximum adsorption capacity was 77.44 mg g-1. Together with characterization, batch experiments, kinetics, isotherms, and thermodynamic analyses suggested that inner-sphere complexation, H-bonding, and electrostatic interactions were the primary mechanisms. C-C/CC, C-O, and O-CO groups and Fe/Mg oxides might have acted as adsorption sites. The adsorbed Sb(III) was oxidized to Sb(V). The generation of reactive oxygen species, iron redox reaction, and oxidizing functional groups all contributed to Sb(III) oxidation. Furthermore, the fixed-bed column system demonstrated a satisfactory Sb removal performance; BC@MF could treat ∼6060 BV of simulated Sb-polluted groundwater. This research provides a promising approach to sufficiently remove Sb(III) from contaminated groundwater, providing new insights for the development of innovative strategies for heavy metal removal.

Metal-organic frameworks for high performance desalination through thickness control and structural fine-tuning.

Two-dimensional nanoporous membranes hold great promise for the design of state-of-the-art desalination architectures to alleviate the increasing global water scarcity. Herein, by employing molecular dynamics simulations, we demonstrate the great potential of two recently reported metal-organic frameworks (MOF) membranes, namely NiIT and NiAT, as efficient desalination membranes that reach super high water flux and high salt rejection. The desalination performance of the MOF membrane is highly tunable through controlling the membrane thickness from one layer to five layers. Double layer NiIT membrane exhibits excellent salt rejection of 100% for NaCl, and meanwhile achieving high water permeability of ∼45 L/cm2/MPa/day. While for the convertible double-layer NiAT, it effectively rejects ∼96% ions with an improved water permeation of over 70 L/cm2/MPa/day. Quantitative analysis of water distribution reveals a denser water solvation shell around NiAT membrane than NiIT and a higher water velocity through the nanopore of NiAT than that of NiIT, contributing to the enhanced water permeability. Through calculating free energy for water/ions translocating through two membranes, a clear energy barrier is observed for ions to penetrate through the sub-nanosized pores in both membranes, leading to the high salt rejection. The present study suggests that these two MOF membranes can serve as a promising semipermeable membrane for energy-efficient desalination which is highly prospective in industrial applications.

Brown adipose tissue-derived Nrg4 alleviates endothelial inflammation and atherosclerosis in male mice.

Brown adipose tissue (BAT) activity contributes to cardiovascular health by its energy-dissipating capacity but how BAT modulates vascular function and atherosclerosis through endocrine mechanisms remains poorly understood. Here we show that BAT-derived neuregulin-4 (Nrg4) ameliorates atherosclerosis in mice. BAT-specific Nrg4 deficiency accelerates vascular inflammation and adhesion responses, endothelial dysfunction and apoptosis and atherosclerosis in male mice. BAT-specific Nrg4 restoration alleviates vascular inflammation and adhesion responses, attenuates leukocyte homing and reduces endothelial injury and atherosclerosis in male mice. In endothelial cells, Nrg4 decreases apoptosis, inflammation and adhesion responses induced by oxidized low-density lipoprotein. Mechanistically, protein kinase B (Akt)-nuclear factor-κB signaling is involved in the beneficial effects of Nrg4 on the endothelium. Taken together, the results reveal Nrg4 as a potential cross-talk factor between BAT and arteries that may serve as a target for atherosclerosis.