Targeting CD43 optimizes cancer immunotherapy through reinvigorating antitumor immune response in colorectal cancer.

PURPOSE: Colorectal cancer (CRC) is one of the most common malignancies worldwide, with dramatically increasing incidence and mortality for decades. However, current therapeutic strategies for CRC, including chemotherapies and immunotherapies, have only demonstrated limited efficacy. Here, we report a novel immune molecule, CD43, that can regulate the tumor immune microenvironment (TIME) and serves as a promising target for CRC immunotherapy. METHODS: The correlation of CD43 expression with CRC patient prognosis was revealed by public data analysis. CD43 knockout (KO) CRC cell lines were generated by CRISPR-Cas9 technology, and a syngenetic murine CRC model was established to investigate the in vivo function of CD43. The TIME was analyzed via immunohistochemical staining, flow cytometry and RNA-seq. Immune functions were investigated by depletion of immune subsets in vivo and T-cell functional assays in vitro, including T-cell priming, cytotoxicity, and chemotaxis experiments. RESULTS: In this study, we found that high expression of CD43 was correlated with poor survival of CRC patients and the limited infiltration of CD8+ T cells in human CRC tissues. Importantly, CD43 expressed on tumor cells, rather than host cells, promoted tumor progression in a syngeneic tumor model. Loss of CD43 facilitated the infiltration of immune cells and immunological memory in the TIME of CRC tumors. Mechanistically, the protumor effect of CD43 depends on T cells, thereby attenuating T-cell-mediated cytotoxicity and cDC1-mediated antigen-specific T-cell activation. Moreover, targeting CD43 synergistically improved PD-L1 blockade immunotherapy for CRC. CONCLUSION: Our findings revealed that targeting tumor-intrinsic CD43 could activate the antitumor immune response and provide particular value for optimized cancer immunotherapy by regulating the TIME in CRC patients.

Dietary supplementation with probiotics increases growth performance, improves the intestinal mucosal barrier and activates the Wnt/ß-catenin pathway activity in chicks.

BACKGROUND: Probiotics are effective feed additives that can replace antibiotics in animal livestock production. However, mono-strain probiotics appear less effective due to their instability. Therefore, the present study aimed to investigate dietary supplementation with compound probiotics on growth performance, diarrhea rate, intestinal mucosal barrier and its possible molecular mechanism in chicks. A total of 360 1-day-old chicks of the Hy-Line Brown Chicks were randomly divided into the control group (CON, basal diet), chlortetracycline group (500 mg/kg CTC) and compound probiotics group (1,000 mg/kg CPP, consisting of Bacillus subtilis, Bacillus licheniformis, Enterococcus faecium, and yeast). The experiment period was 56 days. RESULTS: The results showed that compared to the CON group, CPP significantly increased the average daily feed intake and average daily gain of chicks and reduce diarrhea (P< 0.05). The probiotic group exhibited increased immune organ (i.e., spleen and thymus) mass and increased levels of serum Ig A, IgM, and IgG (P < 0.05) compared to the CTC group. In addition, the jejunal mass and morphology were improved in the probiotic group (P < 0.05). Moreover, CPP reinforced jejunal barrier function, as indicated by increased transepithelial electrical resistance, protein expression of occludin and claudin-1, diamine oxidase levels in the jejunum (P < 0.05). Likewise, enhanced fluorescence signals of PCNA-labeled mitotic cells and villin-labeled absorptive cells in the jejunum (P < 0.05) suggested that CPP promoted intestinal stem cells activity. Mechanistically, the Wnt/ß-catenin signaling pathway, including ß-catenin, TCF4, c-Myc, cyclin D1, and Lgr5, was amplified in the jejunum by CPP addition (P < 0.05). CONCLUSION: This study demonstrated that dietary supplementation with CPP reinforced the jejunal epithelial integrity by activating Wnt/ß-catenin signaling and enhanced immune function in chicks. This article is protected by copyright. All rights reserved.

Succinate metabolism and its regulation of host-microbe interactions.

Succinate is a circulating metabolite, and the relationship between abnormal changes in the physiological concentration of succinate and inflammatory diseases caused by the overreaction of certain immune cells has become a research focus. Recent investigations have shown that succinate produced by the gut microbiota has the potential to regulate host homeostasis and treat diseases such as inflammation. Gut microbes are important for maintaining intestinal homeostasis. Microbial metabolites serve as nutrients in energy metabolism, and act as signal molecules that stimulate host cell and organ function and affect the structural balance between symbiotic gut microorganisms. This review focuses on succinate as a metabolite of both host cells and gut microbes and its involvement in regulating the gut - immune tissue axis by activating intestinal mucosal cells, including macrophages, dendritic cells, and intestinal epithelial cells. We also examined its role as the mediator of microbiota - host crosstalk and its potential function in regulating intestinal microbiota homeostasis. This review explores feasible ways to moderate succinate levels and provides new insights into succinate as a potential target for microbial therapeutics for humans.

Vanadium Oxide Nanozymes with Multiple Enzyme-Mimic Activities for Tumor Catalytic Therapy.

Using tumors containing high concentrations of hydrogen peroxide to design nanozymes is a new and effective strategy, and vanadium-based nanomaterials receive increasing attention. In this paper, four kinds of vanadium oxide nanozymes with different valences of vanadium are synthesized by a simple method to verify the effect of valence on enzyme activity. Vanadium oxide nanozyme-III (Vnps-III) with a low valence of vanadium (V4+) exhibits good peroxidase (POD) and oxidase (OXD) activities, which can effectively produce reactive oxygen species (ROS) in the tumor microenvironment for tumor treatment. In addition, Vnps-III can also consume glutathione (GSH) to reduce ROS consumption. Vanadium oxide nanozyme-I (Vnps-I) containing a high valence of vanadium (V5+) has catalase (CAT) activity, which can catalyze hydrogen peroxide (H2O2) into oxygen (O2), which is beneficial to alleviate the hypoxic environment of solid tumors. Finally, a vanadium oxide nanozyme with both trienzyme simulation activity and GSH consumption ability was screened out by adjusting the ratio of V4+ to V5+ in vanadium oxide nanozymes. In cell and animal experiments, we successfully demonstrate that vanadium oxide nanozymes have excellent antitumor ability and high safety, which may bring great potential for clinical cancer treatment.

Deoxynivalenol induces intestinal injury: insights from oxidative stress and intestinal stem cells.

Mycotoxins are fungal secondary metabolites that frequently occur in human and animal diets. Deoxynivalenol (DON) is one of the most widely occurring mycotoxins globally and poses significant harm to the animal husbandry industry and human health. People are increasingly aware of the adverse effects of DON on vulnerable structures and functions in the intestine, especially in the field of intestinal stem cells (ISCs). In this review, we present insights into DON that induces oxidative stress and affects the expansion of ISCs. Related studies of strategies for reducing its harm are summarized. We also discussed promising approaches such as regulation of microbiota, molecular docking, and modulation of the redox status via reducing the expression of Keap1 protein and single-cell sequencing, which may be critical for further revealing the mechanism of DON that induces oxidative stress and affects the expansion of ISCs.

Phytopathogenic bacteria utilize host glucose as a signal to stimulate virulence through LuxR homologues.

Chemical signal-mediated biological communication is common within bacteria and between bacteria and their hosts. Many plant-associated bacteria respond to unknown plant compounds to regulate bacterial gene expression. However, the nature of the plant compounds that mediate such interkingdom communication and the underlying mechanisms remain poorly characterized. Xanthomonas campestris pv. campestris (Xcc) causes black rot disease on brassica vegetables. Xcc contains an orphan LuxR regulator (XccR) which senses a plant signal that was validated to be glucose by HPLC-MS. The glucose concentration increases in apoplast fluid after Xcc infection, which is caused by the enhanced activity of plant sugar transporters translocating sugar and cell-wall invertases releasing glucose from sucrose. XccR recruits glucose, but not fructose, sucrose, glucose 6-phosphate, and UDP-glucose, to activate pip expression. Deletion of the bacterial glucose transporter gene sglT impaired pathogen virulence and pip expression. Structural prediction showed that the N-terminal domain of XccR forms an alternative pocket neighbouring the AHL-binding pocket for glucose docking. Substitution of three residues affecting structural stability abolished the ability of XccR to bind to the luxXc box in the pip promoter. Several other XccR homologues from plant-associated bacteria can also form stable complexes with glucose, indicating that glucose may function as a common signal molecule for pathogen-plant interactions. The conservation of a glucose/XccR/pip-like system in plant-associated bacteria suggests that some phytopathogens have evolved the ability to utilize host compounds as virulence signals, indicating that LuxRs mediate an interkingdom signalling circuit.

Comprehensive analysis of circular RNA-associated competing endogenous RNA networks and immune infiltration in gastric cancer.

BACKGROUND: Circular RNA (circRNA) has been proved to be an important regulator of gastric cancer (GC). However, the role and regulatory mechanism of circrna related competitive endogenous RNA (ceRNA) in GC have not been established. METHODS: CircRNA data and clinical data were obtained from the GEO and TCGA databases. The ceRNA networks were constructed and a function enrichment analysis was completed. Additionally, correlations between hub genes expression, immune cell infiltration, and clinical phenotypes were determined. The differentially expressed circRNAs and their downstream microRNAs (miRNAs) were validated by quantitative real-time polymerase chain reaction, and the hub genes were validated by western blot analysis. The migration and invasion ability of overexpressed hsa_circ_0002504 was determined by a transwell assay. RESULTS: The ceRNA network contained 2 circRNAs, 3 miRNAs, and 55 messenger RNAs (mRNAs). 323 biological processes terms, 53 cellular components terms, 51 molecular functions terms, and 4 signaling pathways were revealed by the function enrichment analysis. The GSEA analysis revealed that the hub genes were positively correlated with the axon guidance and adhesion molecules pathways. The correlation analysis revealed that overexpressed EPHA4 and KCNA1 indicated poor tissue differentiation and were associated with clinically advanced stages of GC. The in vitro experiments showed that hsa_circ_0002504 was significantly down-regulated in GC cell lines. In addition, the overexpression of hsa_circ_0002504 led to a significant downregulation of hsa-miR-615-5p and hsa-miR-767-5p, as well as an upregulation of EPHA4, KCNA1, and NCAM1. Furthermore, it suppressed the migration and invasion ability of GC cells. CONCLUSIONS: Hsa_circ_0002504 is a potential diagnostic biomarker for GC. High expression of EPHA4 and KCNA1 may indicate poor prognosis.

AaSEPALLATA1 integrates JA and light-regulated glandular secretory trichome initiation in Artemisia annua.

Glandular secretory trichomes (GSTs) can secrete and store a variety of specific metabolites. By increasing GST density, valuable metabolites can be enhanced in terms of productivity. However, the comprehensive and detailed regulatory network of GST initiation still needs further investigation. By screening a complementary DNA (cDNA) library derived from young leaves of Artemisia annua, we identified a MADS-box transcription factor, AaSEPALLATA1 (AaSEP1), positively regulates GST initiation. Overexpression of AaSEP1 in A. annua substantially increased GST density and artemisinin content. The HOMEODOMAIN PROTEIN 1 (AaHD1)-AaMYB16 regulatory network regulates GST initiation via the JA signaling pathway. In this study, AaSEP1 enhanced the function of AaHD1 activation on downstream GST initiation gene GLANDULAR TRICHOME-SPECIFIC WRKY 2 (AaGSW2) through interaction with AaMYB16. Moreover, AaSEP1 interacted with the jasmonate ZIM-domain 8 (AaJAZ8) and served as an important factor in JA-mediated GST initiation. We also found that AaSEP1 interacted with CONSTITUTIVE PHOTOMORPHOGENIC 1 (AaCOP1), a major repressor of light signaling. In this study, we identified a MADS-box transcription factor that is induced by JA and light signaling and that promotes the initiation of GST in A. annua.

Alu antisense RNA ameliorates methylglyoxal-induced human lens epithelial cell apoptosis by enhancing antioxidant defense.

AIM: To determine whether an antisense RNA corresponding to the human Alu transposable element (Aluas RNA) can protect human lens epithelial cells (HLECs) from methylglyoxal-induced apoptosis. METHODS: Cell counting kit-8 (CCK-8) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to assess HLEC viability. HLEC viability/death was detected using a Calcein-AM/PI double staining kit; the annexin V-FITC method was used to detect HLEC apoptosis. The cytosolic reactive oxygen species (ROS) levels in HLECs were determined using a reactive species assay kit. The levels of malondialdehyde (MDA) and the antioxidant activities of total-superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were assessed in HLECs using their respective kits. RT-qPCR and Western blotting were used to measure mRNA and protein expression levels of the genes. RESULTS: Aluas RNA rescued methylglyoxal-induced apoptosis in HLECs and ameliorated both the methylglyoxal-induced decrease in Bcl-2 mRNA and the methylglyoxal-induced increase in Bax mRNA. In addition, Aluas RNA inhibited the methylglyoxal-induced increase in Alu sense RNA expression. Aluas RNA inhibited the production of ROS induced by methylglyoxal, restored T-SOD and GSH-Px activity, and moderated the increase in MDA content after treatment with methylglyoxal. Aluas RNA significantly restored the methylglyoxal-induced down-regulation of Nrf2 gene and antioxidant defense genes, including glutathione peroxidase, heme oxygenase 1, γ-glutamylcysteine synthetase and quinone oxidoreductase 1. Aluas RNA ameliorated methylglyoxal-induced increases of the mRNA and protein expression of Keap1 that is the negative regulator of Nrf2. CONCLUSION: Aluas RNA reduces apoptosis induced by methylglyoxal by enhancing antioxidant defense.

Simultaneous, Label-Free and High-throughput SERS Detection of Multiple Pesticides on Ag@Three-Dimensional Silica Photonic Microsphere Array.

Rapid identification and quantitative simultaneous analysis for multiple pesticide in real samples based on surface-enhanced Raman spectroscopy (SERS) is still a challenge because of sample complexity, reproducibility, and stability of SERS substrate. With use of colloidal silver nanoparticles loaded three-dimensional (3D) silica photonic microspheres (SPMs) array as the analytical platform, a SERS-based array assay for multiple pesticides was developed in this work. The silver nanoparticles were fixed into the gaps formed by the self-assembled nanospheres of the 3D SPMs to produce "hot spots", on which the Raman enhanced effect was up to 9.86 × 107 and the maximum electric field enhancement effect reached to 9.75 times, ensuring the target pesticides on the surface of the SERS-substrate integrated SPM can be detected sensitively. Using 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate, and imidacloprid as the testing pesticides, the label-free and high-throughput SERS assay for simultaneous detection of the pesticides was established, giving good linear detection ranges (0.1-204.8 µg/mL for 2,4-D, 0.3-247.9 µg/mL for glyphosate, and 0.2-204.8 µg/mL for imidacloprid) and low detection limits (3.03 ng/mL for 2,4-D, 3.14 ng/mL for glyphosate, and 8.82 ng/mL for imidacloprid). The spiked recovery rates in the real samples were measured in the range of 82-112%, which was consistent with that of the classical standard methods. The label-free 3D SERS array analytical platform provides a powerful tool for high-throughput and low-cost screening of multiple pesticide residues in real samples.

Differential renal proteomics analysis in a novel rat model of iodinated contrast-induced acute kidney injury.

Contrast-induced acute kidney injury (CI-AKI), which occurs after the use of iodinated contrast media, has become the third leading cause of hospital-acquired acute kidney injury (AKI). It is associated with prolonged hospitalization and increased risks of end-stage renal disease and mortality. The pathogenesis of CI-AKI is unclear and effective treatments are lacking. By comparing different post-nephrectomy times and dehydration times, we constructed a new, short-course CI-AKI model using dehydration for 24 h two weeks after unilateral nephrectomy. We found that the low-osmolality contrast media iohexol caused more severe renal function decline, renal morphological damage, and mitochondrial ultrastructural alterations compared to the iso-osmolality contrast media iodixanol. The shotgun proteomics based on Tandem Mass Tag (TMT) was used to conduct proteomics research on renal tissue in the new CI-AKI model, and 604 distinct proteins were identified, mainly involving complement and coagulation cascade, COVID-19, PPAR signalling pathway, mineral absorption, cholesterol metabolism, ferroptosis, staphylococcus aureus infection, systemic lupus erythematosus, folate biosynthesis, and proximal tubule bicarbonate reclamation. Then, using parallel reaction monitoring (PRM), we validate 16 candidate proteins, of which five were novel candidates (Serpina1, Apoa1, F2, Plg, Hrg) previously unrelated to AKI and associated with an acute response as well as fibrinolysis. The pathway analysis and 16 candidate proteins may help to discover new mechanisms in the pathogenesis of CI-AKI, allowing for early diagnosis and outcome prediction.

Cytochalasans with Inhibitory Activity against NPC1L1 from the Endophytic Fungus Chaetomium nigricolor F5.

Mass spectrometry (MS)-based metabolic profiling of the endophytic fungus Chaetomium nigricolor F5 guided the isolation of five novel cytochalasans, chamisides B-F (1-5), and two known ones, chaetoconvosins C and D (6 and 7). Their structures including stereochemistry were unambiguously determined by MS, nuclear magnetic resonance, and single-crystal X-ray diffraction analyses. Compounds 1-3 share a new 5/6/5/5/7-fused pentacyclic skeleton in cytochalasans and are appropriately proposed to be the key biosynthetic precursors of co-isolated cytochalasans with a 6/6/5/7/5, 6/6/5/5/7, or 6/6/5 ring system. Remarkably, compound 5 with a relatively flexible side chain showed promising inhibition activity against the cholesterol transporter protein Niemann-Pick C1-like 1 (NPC1L1), expanding the function of cytochalasans.

Anti-aging Effects of Alu Antisense RNA on Human Fibroblast Senescence Through the MEK-ERK Pathway Mediated by KIF15.

OBJECTIVE: To investigate whether human short interspersed nuclear element antisense RNA (Alu antisense RNA; Alu asRNA) could delay human fibroblast senescence and explore the underlying mechanisms. METHODS: We transfected Alu asRNA into senescent human fibroblasts and used cell counting kit-8 (CCK-8), reactive oxygen species (ROS), and senescence-associated beta-galactosidase (SA-ß-gal) staining methods to analyze the anti-aging effects of Alu asRNA on the fibroblasts. We also used an RNA-sequencing (RNA-seq) method to investigate the Alu asRNA-specific mechanisms of anti-aging. We examined the effects of KIF15 on the anti-aging role induced by Alu asRNA. We also investigated the mechanisms underlying a KIF15-induced proliferation of senescent human fibroblasts. RESULTS: The CCK-8, ROS and SA-ß-gal results showed that Alu asRNA could delay fibroblast aging. RNA-seq showed 183 differentially expressed genes (DEGs) in Alu asRNA transfected fibroblasts compared with fibroblasts transfected with the calcium phosphate transfection (CPT) reagent. The KEGG analysis showed that the cell cycle pathway was significantly enriched in the DEGs in fibroblasts transfected with Alu asRNA compared with fibroblasts transfected with the CPT reagent. Notably, Alu asRNA promoted the KIF15 expression and activated the MEK-ERK signaling pathway. CONCLUSION: Our results suggest that Alu asRNA could promote senescent fibroblast proliferation via activation of the KIF15-mediated MEK-ERK signaling pathway.

[Distribution Characteristics and Health Effects of Bioaerosols in Spring over Xi'an City].

A large amount of fluffy caktins appears in spring in Xi'an that may cause air pollution and lead to health risks such as asthma. In this study, bioaerosol, PM2.5, and fluffy catkins were collected from different sample points (traffic site and campus site) in Xi'an in spring. The variations in bioaerosol, fluffy catkins, and the bacterial community structure were investigated using culture-dependent and high-throughput sequencing methods. The results showed that the concentration of culturable bacteria was significantly higher (P=0.027) at the traffic site. The concentration of culturable bacteria at the traffic site was 2.7 times that of fungi, whereas the concentration of culturable fungi at the campus site was 1.4 times higher than that of bacteria. The peak concentrations of culturable bacteria and fungi appeared at 08:00 a.m. The size distribution of culturable bacteria showed a bimodal pattern, whereas that of culturable fungi showed a unimodal distribution. Soil and vegetation were the main sources of atmospheric microorganisms (85.9%), and Proteobacteria was the most abundant phylum in both fluffy catkins and PM2.5, accounting for 91.3% (traffic site) and 99.1% (campus site) of the fluffy catkins. Actinobacteria, Firmicutes, Bacteroidetes, Cyanobacteria, and Deinococcus-Thermus were the dominant phyla in PM2.5. Some genera were opportunistic pathogen bacteria in the fluffy catkins, such as Enterobacter and Pseudomonas, which can lead to infection and diarrhea risks. These results could provide fundamental data on potential health risks of spring-borne bioaerosols.

Heat stress disrupts intestinal stem cell migration and differentiation along the crypt-villus axis through FAK signaling.

During heat stress (HS), the intestinal epithelium suffers damage due to imbalance of tissue homeostasis. However, the specific mechanism by which intestinal stem cells (ISCs) migrate and differentiate along the crypt-villus axis to heal lesions upon insult is unclear. In our study, C57BL/6 mice and IPEC-J2 cells were subjected to normal ambient conditions (25 °C for 7 days in vivo and 37 °C for 18 h in vitro) or 41 °C. The results showed that HS impaired intestinal morphology and barrier function. The numbers of ISCs (SOX9+ cells), mitotic cells (PCNA+ cells), and differentiated cells (Paneth cells marked by lysozyme, absorptive cells marked by Villin, goblet cells marked by Mucin2, enteroendocrine cells marked by Chromogranin A, and tuft cells marked by DCAMKL1) were reduced under high temperature. Importantly, BrdU incorporation confirmed the decreased migration ability of jejunal epithelial cells exposed to 41 °C. Furthermore, intestinal organoids (IOs) expanded from jejunal crypt cells in the HS group exhibited greater growth disadvantages. Mechanistically, the occurrence of these phenotypes was accompanied by FAK/paxillin/F-actin signaling disruption in the jejunum. The fact that the FAK agonist ZINC40099027 reversed the HS-triggered inhibition of IPEC-J2 cell differentiation and migration further confirmed the dominant role of FAK in response to high-temperature conditions. Overall, the present investigation is the first to reveal a major role of FAK/paxillin/F-actin signaling in HS-induced ISC migration and differentiation along the crypt-villus axis, which indicates a new therapeutic target for intestinal epithelial regeneration after heat injuries.

Microstructured Optical Fiber-Enhanced Light-Matter Interaction Enables Highly Sensitive Exosome-Based Liquid Biopsy of Breast Cancer.

Exosome-based liquid biopsies highlight potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. However, the existing techniques are severely limited for practical applications due to the complications of high cost, low sensitivity, tedious procedures, and large sample consumption. Herein, we report a microstructured optical fiber sensor for fast, sensitive, and accurate quantification of exosomes in blood samples of breast cancer patients. Numerical simulations are applied to demonstrate that hollow-core microstructured antiresonant fibers (HARFs) can stringently confine light in the fiber core, ensuring strong light-matter interaction and thus maximumly amplifying the signal. Taking this advantage, a AuNPs-dsDNA assembly containing gold nanoparticles, a recognizing DNA aptamer, and a fluorescent reporter DNA sequence is fabricated followed by immobilization on the fiber wall to form a AuNPs-dsDNA-HARF sensor. Cancer-derived exosomes can be recognized and captured in the fiber channel and generate dose-dependent fluorescent signals for quantification. The microfiber sensor demonstrates enhanced sensitivity and specificity, enabling the detection of single digits of exosome particles at the nanoliter sample level. In addition, by tracking exosome phenotypic changes, the proposed fiber sensor can facilitate precise drug treatment monitoring. This work provides a robust platform for exosome-based biopsy for cancer diagnosis and prediction of therapeutic outcomes.

Leaf sodium homeostasis controlled by salt gland is associated with salt tolerance in mangrove plant Avicennia marina.

Avicennia marina, a mangrove plant growing in coastal wetland habitats, is frequently affected by tidal salinity. To understand its salinity tolerance, the seedlings of A. marina were treated with 0, 200, 400 and 600 mM NaCl. We found the whole plant dry weight, photosynthetic parameters increased at 200 mM NaCl but decreased over 400 mM NaCl. The maximum quantum yield of primary photochemistry (Fv/Fm) significantly decreased at 600 mM NaCl. Transmission electron microscopy observations showed high salinity caused the reduction in starch grain size, swelling of the thylakoids and separation of the granal stacks and even destruction of the envelope. In addition, the dense protoplasm and abundant mitochondria in the secretory and stalk cells, and abundant plasmodesmata between salt gland cells were observed in the salt glands of the adaxial epidermis. At all salinities, Na+ content was higher in leaves than in stems and roots, however, Na+ content increased in the roots while it remained constant level in the leaves over 400 mM NaCl treatment, due to salt secretion from the salt glands. As a result, salt crystals on the leaf adaxial surface increased with salinity. On the other hand, salt treatment increased Na+ and K+ efflux and decreased H+ efflux from the salt glands by the non-invasive micro-test technology, although Na+ efflux reached the maximum at 400 mM NaCl. Further RT-qPCR analysis indicated that the expression of Na+/H+ antiporter (SOS1 and NHX1), H+-ATPase (AHA1 and VHA-c1), K+ channel (AKT1, HAK5 and GORK) were up-regulated, only Na+ inward transporter (HKT1) was down-regulated in the salt glands enriched adaxial epidermis of the leaves under 400 mM NaCl treatment. In conclusion, salinity below 200 mM NaCl was beneficial to the growth of A. marina, and below 400 mM, the salt glands could excrete Na+ effectively, thus improving its salt tolerance.

Qing Fei Hua Xian Decoction ameliorates bleomycin-induced pulmonary fibrosis by suppressing oxidative stress through balancing ACE-AngII-AT1R/ACE2-Ang-(1-7)-Mas axis.

Objectives: We aimed to investigate the preventative effect of Qing Fei Hua Xian Decoction (QFHXD) against pulmonary fibrosis (PF) and its potential mechanisms. Materials and Methods: Bleomycin (BLM)-induced rats were respectively treated with 413.3, 826.6, and 1239.9 mg/kg of QFHXD and prednisone for 28 days. The lung tissues of rats were collected on day 28 for histological and western blotting analysis. Results: QFHXD significantly reduced alveolus inflammation, collagen accumulation, and fibrosis deposition in BLM-induced PF rats (P<0.05). Collagen I and III, vimentin, and α-smooth muscle actin(α-SMA) expression levels were likewise decreased in PF rats treated with QFHXD (P<0.05). Additionally, QFHXD increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while decreasing NADPH oxidase 4 (NOX4) expression (P<0.05). Furthermore, QFHXD suppressed the PF progression by down-regulating Angiotensin-Converting Enzyme (ACE) -Angiotensin II (AngII) -Angiotensin II Type 1 Receptor (AT1R) axis (P<0.01) and up-regulating Angiotensin-Converting Enzyme 2 (ACE2) -Angiotensin-(1-7) (Ang-(1-7)) -Mas axis (P<0.05). Conclusion: QFHXD suppressed inflammatory infiltration and PF brought on by BLM in lung tissues through reducing oxidative stress by maintaining the equilibrium of ACE-AngII-AT1R and ACE2-Ang-(1-7) -Mas axes. This study may provide a novel clinical therapy option for PF.

Bavachin protects against diet-induced hepatic steatosis and obesity in mice.

Non-alcoholic fatty liver disease (NAFLD) is a major health concern worldwide, and the incidence of metabolic disorders associated with NAFLD is rapidly increasing because of the obesity epidemic. There are currently no approved drugs that prevent or treat NAFLD. Recent evidence shows that bavachin, a flavonoid isolated from the seeds and fruits of Psoralea corylifolia L., increases the transcriptional activity of PPARγ and insulin sensitivity during preadipocyte differentiation, but the effect of bavachin on glucose and lipid metabolism remains unclear. In the current study we investigated the effects of bavachin on obesity-associated NAFLD in vivo and in vitro. In mouse primary hepatocytes and Huh7 cells, treatment with bavachin (20 µM) significantly suppressed PA/OA or high glucose/high insulin-induced increases in the expression of fatty acid synthesis-related genes and the number and size of lipid droplets. Furthermore, bavachin treatment markedly elevated the phosphorylation levels of AKT and GSK-3ß, improving the insulin signaling activity in the cells. In HFD-induced obese mice, administration of bavachin (30 mg/kg, i.p. every other day for 8 weeks) efficiently attenuated the increases in body weight, liver weight, blood glucose, and liver and serum triglyceride contents. Moreover, bavachin administration significantly alleviated hepatic inflammation and ameliorated HFD-induced glucose intolerance and insulin resistance. We demonstrated that bavachin protected against HFD-induced obesity by inducing fat thermogenesis and browning subcutaneous white adipose tissue (subWAT). We revealed that bavachin repressed the expression of lipid synthesis genes in the liver of obese mice, while promoting the expression of thermogenesis, browning, and mitochondrial respiration-related genes in subWAT and brown adipose tissue (BAT) in the mice. In conclusion, bavachin attenuates hepatic steatosis and obesity by repressing de novo lipogenesis, inducing fat thermogenesis and browning subWAT, suggesting that bavachin is a potential drug for NAFLD therapy.

Electrochemically Reconstructed Vanadic Oxide-Doped Cobalt Pyrophosphate as an Electrocatalyst for the Oxygen Evolution Reaction.

More and more attention has been paid to the development of the efficient electrocatalysts for the oxygen evolution reaction (OER). Herein, a porous vanadic oxide-doped cobalt pyrophosphate electrocatalyst, namely V2O5-Co2P2O7, was exploited by using the electrochemical reconstruction method in the alkaline electrolyte and selecting a cobalt vanadium phosphate Co(H2O)4(VOPO4)2 as a precursor. The reconstructed vanadic oxide-doped cobalt pyrophosphate catalyst V2O5-Co2P2O7 exhibited efficient electrocatalytic activity for the OER in 1.0 M KOH, requiring a low overpotential of 199 mV at 10 mA cm-2, compared to the reported pyrophosphate electrocatalysts. The porous morphology and doping of vanadic oxide after electrochemical reconstruction were beneficial to enhance the electrocatalytic performance for the OER, through improving the surface area to bring in more accessibly active sites and regulating the electronic structures. The results provided a promising strategy to prepare the pyrophosphate electrocatalysts and improve the performance of the OER catalyst.