Based on previous studies about microflora regulation and immunity enhancement activities of polysaccharides from
Nannf. var.
(Nannf.) L. T. Shen (CPP), there is little study on intestinal mucosal ...immunity, which is a possible medium for contacting microflora and immunity. In the present study, the BALB/c mice were divided into five groups (eight mice in each group), including a normal group (Con), a model control group (Model), and model groups that were administered CPP (50, 100, 200 mg/kg/d) orally each day for seven days after intraperitoneal injection of 60 mg/kg BW/d cyclophosphamide (CP) for three days. CPP recovered the spleen index and restored the levels of IFN-γ, IL-2, IL-10, as well as serum IgG. In addition, it elevated ileum secretory immunoglobulin A (sIgA), the number of
and acetic acid content in cecum. These results indicated that CPP plays an important role in the protection against immunosuppression, especially mucosa immune damage, and the inhibition of pathogenic bacteria colonization, which could be considered a potential natural source of immunoregulator.
In this study, an acidic polysaccharide from
Nannf. var.
(Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to ...consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-β-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of β-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4
/CD8
T lymphocyte ratio. These results suggest that β-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.
The discovery of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the outbreak of coronavirus disease 2019 (COVID‐19) are causing public health emergencies. A handful pieces of ...literature have summarized its clinical and radiologic features, whereas therapies for COVID‐19 are rather limited. To evaluate the efficacy of convalescent plasma therapy in COVID‐19 patients, we did this timely descriptive study. Six laboratory‐confirmed COVID‐19 patients were enrolled and received the transfusion of ABO‐compatible convalescent plasma. The efficacy of this intervention was determined by the alleviation of symptoms, changes in radiologic abnormalities and laboratory tests. No obvious adverse effect observed during the treatment. Transfusion of convalescent plasma led to a resolution of ground‐glass opacities and consolidation in patients #1, #2, #3, #4, and #6. In patients #1 and #5 who presented with SARS‐CoV‐2 in throat swab, convalescent plasma therapy elicited an elimination of the virus. Serologic analysis indicated an immediate increase in anti‐SARS‐CoV‐2 antibody titers in patients #2 and #3, but not in patient #1. This study indicates that convalescent plasma therapy is effective and specific for COVID‐19. This intervention has a special significance for eliminating SARS‐CoV‐2 and is believed to be a promising state‐of‐the‐art therapy during COVID‐19 pandemic crisis.
Highlights
Convalescent plasma is a specific therapy for COVID‐19.
Convalescent plasma therapy is safe and effective in COVID‐19 patients.
The SARS‐CoV‐2 neutralizing antibody in the convalescent plasma may directly lead to virus clearance.
Convalescent plasma therapy improves both clinical symptoms and radiologic abnormalities.
Despite great improvements in the diagnosis and treatment of neoplasms, metastatic disease is still the leading cause of death in cancer patients, with mortality rates still rising. Given this ...background, new ways to treat cancer will be important for development of improved cancer control strategies. Cdc42 is a member of the Rho GTPase family and plays an important role in cell-to-cell adhesion, formation of cytoskeletal structures, and cell cycle regulation. It thus influences cellular proliferation, transformation, and homeostasis, as well as the cellular migration and invasion processes underlying tumor formation. Cdc42 acts as a collection point for signal transduction and regulates multiple signaling pathways. Moreover, recent studies show that in most human cancers Cdc42 is abnormally expressed and promoting neoplastic growth and metastasis. Regarding possible new treatments for cancer, miRNA and small molecules targeting Cdc42 and related pathways have been recently found to be effective on cancer. In this review, we analyze the newly recognized regulation mechanisms for Cdc42 and Cdc42-related signal pathways, and particularly new treatments using small molecules and miRNAs to inhibit the abnormal overexpression of Cdc42 that may slow down the metastasis process, improve cancer therapy and lead to novel strategies for development of antineoplastic drugs.
Rice grain with excessive cadmium (Cd) is a major source of dietary Cd intake and a serious threat to health for people who consume rice as a staple food. The development of elite rice cultivars with ...consistently low Cd content is challenging for conventional breeding approaches, and new strategies urgently need to be developed. Here, we report the development of new indica rice lines with low Cd accumulation and no transgenes by knocking out the metal transporter gene OsNramp5 using CRISPR/Cas9 system. Hydroponic culture showed that Cd concentrations in shoots and roots of osnramp5 mutants were dramatically decreased, resulting in rescue of impaired growth in high Cd condition. Cd-contaminated paddy field trials demonstrated that Cd concentration in osnramp5 grains was consistently less than 0.05 mg/kg, in contrast to high Cd concentrations from 0.33 mg/kg to 2.90 mg/kg in grains of Huazhan (the wild-type indica rice). In particular, the plant yield was not significantly affected in osnramp5 mutants. Furthermore, we developed promising hybrid rice lines with extremely low Cd content in grains. Our work supplies a practical approach to developing Cd pollution-safe indica rice cultivars that minimizes Cd contamination risk in grains.
Bisphenol A (BPA) is a widespread environmental pollutant linked to detrimental effects on human health and reduced life expectancy following chronic exposure. This prospective cohort study aimed to ...examine the association between BPA exposure and mortality in American adults and to explore the potential mitigating effects of dietary quality on BPA-related mortality. This study utilized data from 8761 American adults in the 2003–2016 National Health and Nutrition Examination Survey (NHANES). Urinary BPA levels were employed to assess BPA exposure, and dietary quality was evaluated using the Healthy Eating Index-2015 (HEI-2015). All-cause, cardiovascular disease (CVD), and cancer mortality statuses were determined until December 31, 2019, resulting in a cumulative follow-up of 80,564 person-years. The results showed that the highest tertile of urinary BPA levels corresponded to a 36% increase in all-cause mortality and a 62% increase in CVD mortality compared to the lowest tertile. In contrast, the highest tertile of HEI-2015 scores was associated with a 29% reduction in all-cause mortality relative to the lowest tertile. Although no significant interaction was found between HEI-2015 scores and urinary BPA levels concerning mortality, the association between HEI-2015 scores and both all-cause and CVD mortality was statistically significant at low urinary BPA levels. Continuous monitoring of BPA exposure is crucial for evaluating its long-term adverse health effects. Improving dietary quality can lower all-cause mortality and decrease the risk of all-cause and CVD mortality at low BPA exposure levels. However, due to the limited protective effect of dietary quality against BPA exposure, minimizing BPA exposure remains a vital goal.
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•BPA exposure linked to increased all-cause and cardiovascular disease mortality.•High dietary quality, as assessed by HEI-2015 scores, reduces all-cause mortality.•Minimizing BPA exposure remains crucial because of dietary quality's limited protection.
Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in ...a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment.
•Integrated farms had a greater number/abundance of ARG and MGE subtypes.•Integrated farms had higher abundance of colistin/tigecycline resistance genes.•Relationships among ARGs, MGEs, and microbial ...taxa were more complex in integrated farms.
Cumulative research on resistomes and microbiomes from aquatic environments has revealed that both integrated freshwater and monoculture freshwater aquaculture systems can cause the development and dissemination of antibiotic resistance genes (ARGs) and associated mobile genetic elements (MGEs). However, few studies have examined differences in resistomes between the different aquaculture modes, and those that do have focused on antibiotic residues or individual resistance genes. In the current study, we collected 44 environmental samples from two monoculture freshwater aquaculture farms and four integrated farms (two duck and fish farms, two laying duck and fish farms) in Guangdong, China, in 2018. After measuring the concentrations of antibiotic residues in the samples, we characterized MGEs and ARGs and examined their association with potential bacterial hosts in the microbial communities using high-throughput sequencing-based metagenomic and network analyses. We then compared the resistome profiles of the different aquaculture models. We found that the number and total relative abundance of ARG and MGE subtypes in the integrated (fish and duck/laying duck) farm samples were significantly higher than those in samples from monoculture freshwater aquaculture farms. Specifically, both the mobile colistin resistance genes mcr variants and tigecycline resistance gene tet(X) variants in integrated farms exhibited higher total relative abundance than that in monoculture farms. Moreover, the interrelationships among ARGs and microbial taxa, ARGs and MGEs, and MGEs and microbial taxa in the integrated farm samples were also more complex than those observed in monoculture freshwater aquaculture farm samples. Meanwhile, the species of Acinetobacter and Escherichia were identified to be the possible host of tet(X) and ESBL gene blaCTX-M in aquaculture, respectively. To the best of our knowledge, this is the first metagenomic study to analyze differences in resistome profiles between integrated and monoculture ponds. Overall, integrated aquaculture systems exhibited a higher prevalence of resistance genes compared with monoculture freshwater aquaculture farms. Therefore, additional antimicrobial resistance surveillance should be focused on this type of freshwater aquaculture system.
High current density hydrogen evolution reaction (HER) in alkaline water electrolysis plays crucial role in renewable and sustainable energy systems, while posing a great challenge to the ...highly‐efficient electrocatalysts. Here, the synthesis of Ni/NiO@MoO3−x composite nanoarrays is reported by a moderate reduction strategy, combining Ni/NiO nanoparticles (≈20 nm) with amorphous MoO3−x nanoarrays. The Ni/NiO@MoO3−x composite nanoarrays possess enhanced hydrophilicity, optimize reaction energy barriers, accelerate reactant diffusion/bubble detachment, and therefore display an ultrahigh alkaline HER activity with a low η10 overpotential of 7 mV as well as Tafel slope of 34 mV dec−1. More significantly, the Ni/NiO@MoO3−x nanoarrays only demand low overpotentials of 75 and 112 mV to deliver 100 and 200 mA cm−2 hydrogen production current, and can steadily work at 100 mA cm−2 for 40 h, which is more efficient and stable than the Pt/C catalyst.
The synthesis of Ni/NiO@MoO3−x composite nanoarrays to accelerate reaction and diffusion kinetics for alkaline high current density hydrogen evolution reaction.
Schematic diagram showing that HIF-1α induces lncRNA-CBSLR to recruit YTHDF2 protein and CBS mRNA to form CBSLR/ YTHDF2/CBS complex, which in turn decreases CBS mRNA stability in an m6A dependent ...manner. The decreased CBS expression reduced methylation of ACSL4 protein, thus, the protein is degraded via the ubiquitination-proteasome pathway. It eventually protects GC from ferroptosis under a hypoxic tumor microenvironment.
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•1. The hypoxic microenvironment is a common hallmark of solid tumors and is strongly associated with therapy resistance and poor prognosis.•2. CBSLR, a long noncoding RNA transactivated by HIF-1α, is upregulated in GC and associated with poor prognosis.•3. CBSLR inhibition induces ferroptosis under hypoxic conditions and contributes to chemoresistance.•4. lncRNA-CBSLR recruits YTHDF2 protein and CBS mRNA to form CBSLR/ YTHDF2/CBS complex, which in turn decreases CBS mRNA stability in an m6A dependent manner.•5. CBSLR/CBS inhibits ferroptosis by modulating ACSL4 methylation to be polyubiquitinated.
Tumors are usually refractory to anti-cancer therapeutics under hypoxic conditions. However, the underlying molecular mechanism remains to be elucidated.
Our study intended to identify hypoxia inducible lncRNAs and their biological function in gastric cancer (GC).
Differentially expressed lncRNAs were determined by microarray analysis between GC cells exposed to hypoxia (1% O2) and normoxia (21% O2) for 24 h. The expression level of CBSLR was manipulated in several GC cell lines to perform molecular and biological analyses both in vitro and in vivo.
We identified a hypoxia-induced lncRNA-CBSLR that protected GC cells from ferroptosis, leading to chem-resistance. Mechanically, CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of CBS mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Furthermore, under decreased CBS levels, the methylation of the ACSL4 protein was reduced, leading to protein polyubiquitination and degradation of ACSL4. This, in turn, decreased the pro-ferroptosis phosphatidylethanolamine (PE) (18:0/20:4) and PE (18:0/22:4) content and contributed to ferroptosis resistance. Notably, CBSLR is upregulated, whereas CBS is downregulated in GC tissues compared to matched normal tissues; and GC patients with high CBSLR/low CBS levels have a worse clinical outcome and a poorer response to chemotherapy.
Our study reveals a novel mechanism in how HIF1α/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.
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