Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

Coffee Leaf Tea Extracts Improve Hyperuricemia Nephropathy and Its Associated Negative Effect in Gut Microbiota and Amino Acid Metabolism in Rats.

Hyperuricemia nephropathy (HN) is a metabolic disease characterized by tubular damage, tubulointerstitial fibrosis, and uric acid kidney stones and has been demonstrated to be associated with hyperuricemia. Coffee leaf tea is drunk as a functional beverage. However, its prevention effects on HN remain to be explored. This study showed that coffee leaf tea extracts (TE) contain 19 polyphenols, with a total content of 550.15 ± 27.58 mg GAE/g. TE decreased serum uric acid levels via inhibiting XOD activities and modulating the expression of urate transporters (GLUT9, OAT3, and ABCG2) in HN rats. TE prevented HN-induced liver and kidney damage and attenuated renal fibrosis. Moreover, it upregulated the abundance of SCFA-producing bacteria (Phascolarctobacterium, Alloprevotella, and Butyricicoccus) in the gut and reversed the amino acid-related metabolism disorder caused by HN. TE also decreased the circulating LPS and d-lactate levels and increased the fecal SCFA levels. This study supported the preliminary and indicative effect of coffee leaf tea in the prevention of hyperuricemia and HN.

Research on the experience of National Master of Traditional Chinese Medicine Professor Lu ZhiZheng in treating chronic atrophic gastritis based on data mining technology.

BACKGROUND: The purpose of this research is to summarize the academic expertise of Professor Lu Zhizheng in the treatment of Chronic Atrophic Gastritis, and to explain his clinical reasoning and common prescriptions in the treatment of CAG. METHODS: Professor Lu's outpatient cases of CAG from January 2008 to December 2021 were selected, and the PageRank algorithm was applied on the FangNet platform to analyze the usage frequencies of herbs, their four natures and five flavors according to Traditional Chinese Medicine, core herbs, and herb clustering patterns, with the goal of summarizing the distinguishing features of Professor Lu's academic and clinical approach to CAG. A total of 170 patients from 252 consultations were included in this study. The prescriptions involved a total of 239 herbs, which occurred a cumulative 4339 times. The herb natures were mainly warm, neutral, and slightly cold, and the herb flavors were predominantly sweet, bitter, and pungent. The channel tropism of the selected herbs primarily targeted the spleen, stomach, and lung meridians. Herb rank analysis showed that 34 herbs, including Gancao, Taizishen, Banxia, Huanglian, Shengjiang, Baizhu, Yiyiren, Maiya, Cangzhu, and Kuxingren, were the driver herbs used by Professor Lu for the treatment of CAG. RESULTS: Herb-herb co-occurrence/exclusivity analysis revealed 10 sets of frequently used herb pairs; herb cluster analysis yielded 10 herb clusters. These results reflected the emphasis Professor Lu placed on protecting Qi and Yin while clearing damp-heat. Professor Lu Zhizheng utilized dialectics reinforced with flexible thinking in the treatment of CAG, and emphasized that identifying the pathogenesis and addressing the syndrome should be prioritized. CONCLUSIONS: The characteristic treatment strategy aimed to replenish Qi and nourish Yin, clear away damp-heat, and treat CAG patients comprehensively under the guidance of established principles.

Case report: Acrodermatitis enteropathica result from a novel SLC39A4 gene mutation.

The clinical data and gene sequencing results in a child with acrodermatitis enteropathica were retrospectively reported, and the related literature was reviewed. A girl aged 9 years and 4 months presented with a repeated skin rash, mainly distributed in the perioral, anogenital, and acral areas, accompanied with alopecia, and a low blood zinc level was found many times. A significant improvement was seen after continuous zinc supplementation. The genetic sequencing test demonstrated that the patient had compound heterozygous for two SLC39A4 mutations: c.1466dupT (p.S490Efs*155) and c.295G > A (p.A99T), and her parents were heterozygous carriers of these two mutations. An improvement was achieved after continuous zinc supplementation. This case report might guide further research on this aspect.

The Dual Dose-Dependent Effects of Corticosterone on Hippocampal Cell Apoptosis After Traumatic Brain Injury Depend on the Activation Ratio of Mineralocorticoid Receptors to Glucocorticoid Receptors.

In our recent studies, we reported that mineralocorticoid receptor (MR) had the opposite effects of glucocorticoid receptor (GR) on neural cell survival after traumatic brain injury (TBI). However, whether short-term use of high-dose natural glucocorticoids, which are mixed agonists of both MR and GR, leads to neurotoxic effects by inducing excessive GR activation is unclear, as is the threshold GR activation level and the possible signaling pathways remain unclear. In this study, we examined the dual dose-dependent effects of corticosterone (CORT) on spatial memory, hippocampal cell survival and receptor-mediated downstream signaling pathways after TBI. We found that different doses of CORT exhibited dual effects on hippocampal cell survival and rat spatial memory. Low doses of CORT (0.3 and 3 mg/kg) significantly increased MR activation, upregulated Akt/CREB/Bad phosphorylation and Bcl-2 concentration, reduced the number of apoptotic neural cells, and subsequently improved rat spatial memory. In contrast, a high dose of CORT (30 mg/kg) exerted the opposite effects by overactivating GR, upregulating P53/Bax levels, and inhibiting Erk/CREB activity. The results suggest that the neuroprotective and neurotoxic effects of endogenous GC depend on a threshold level and that a higher dose of GC, even for short-term use, should be avoided after TBI.

M-CSF and prostratin induced Mregs promote immune tolerance in transplanted mice through Arg-1 pathway.

OBJECTIVE: Regulatory macrophages (Mregs) are a group of heterogeneous macrophages. These cells could induce immunosuppressive effects through the expression of immune regulatory molecules and cytokines. METHODS: The differentiation of Mregs was induced by treating bone marrow cells with M-CSF and prostratin in vitro. The cell-phenotypes and immunosuppressive function were determined by flow cytometry. Rt-PCR was employed to assess the mechanisms of Mregs. Skin grafted mouse model was used for in vivo validation. RESULTS: Mregs induced by M-CSF + prostratin had a strong inhibitory effect on T cell proliferation and cytokines production. The phenotype of induced bone marrow cells changed towards Mregs. These Mregs could induce the differentiation of Tregs in vivo. Arg-1 expression in these cells were significantly upregulated. Inhibition of arginase (Arg) or arginine supplement significantly reversed the immunosuppressive function. In mice skin-grafted models, adoptive transfer of these Mregs significantly prolonged allograft survival. In mice models, Arg-1 expression significantly elevated on skin grafts cells and Tregs increased in graft tissues. CONCLUSIONS: We successfully developed a Mregs-inducing protocol with the combination of M-CSF and prostratin in vitro. M-CSF + prostratin induced Mregs prevented mice skin graft rejection through upregulating the expression Arg-1.

Mitochondrion-targeted selenium nanoparticles enhance reactive oxygen species-mediated cell death.

Selenium nanoparticles (SeNPs) can induce reactive oxygen species (ROS)-mediated cell death when accumulated in cancer cells, while rendering anti-oxidation and cancer prevention in healthy tissues at low doses. Although they are promising anticancer agents with fewer side effects, their application is limited by their relative low toxicity to cancer cells. Therefore, we propose a mitochondrion-targeting strategy to improve their cancer cell killing efficiency. Such mitochondrion-targeted SeNPs could efficiently increase ROS production and mitochondrion damage in cancer cells; however, only a slightly increased toxicity to normal cells was observed, indicating a potentially better therapeutic window for anticancer treatments.

Fatigue of systemic lupus erythematosus in China: contributors and effects on the quality of life.

OBJECTIVE: Fatigue is a very common symptom of systemic lupus erythematosus (SLE), which significantly impairs patients' quality of life. The purpose of this study is to evaluate contributors of fatigue and effects of fatigue on the quality of life in Chinese SLE patients. METHODS: A survey of 119 SLE patients using the Fatigue Severity Scale (FSS) to assess the severity of fatigue was carried out. SLE patients completed the Systemic Lupus Erythematosus Disease Activity Index, the Hospital Anxiety and Depression Scale, the Short Form 36 health survey and the Pittsburgh Sleep Quality Index. Meanwhile, 105 healthy individuals completed FSS, the Hospital Anxiety and Depression Scale and Short Form 36 health survey. We used chi-squared analysis, independent samples t-tests and logistic regression models to analyze data. RESULTS: Our results found that the FSS score of patients with SLE was higher than that of healthy controls. The disease duration, anxiety, depression, subjective sleep quality and sleep disorders significantly correlated with fatigue in SLE patients. Moreover, logistic regression models showed depression and sleep disorders as predictors of fatigue. In SLE patients, fatigued patients had lower quality of life than those who were non-fatigued. CONCLUSION: This is the first time to explore contributors of fatigue and the influence of fatigue on SLE patients' quality of life in China. Our study showed that depression and sleep disorders were predictors of fatigue, and fatigue seriously damaged SLE patients' quality of life. The results indicate that it is necessary to conduct holistic assessment and effective intervention, such as systemic psychiatric screening, psychological care and practical sleep guidance, to relieve symptoms of fatigue and finally improve their quality of life in SLE patients.

Disruption of Gpr45 causes reduced hypothalamic POMC expression and obesity.

A rise in the occurrence of obesity has driven exploration of its underlying genetic basis and potential targets for intervention. GWAS studies have identified obesity susceptibility pathways involving several neuropeptides that control energy homeostasis, suggesting that variations in the genes that regulate food intake and energy expenditure may contribute to obesity. In this study, we identified 5 additional obesity loci, including a neuronal orphan GPCR called Gpr45, in a forward genetic screen of mutant mice generated by piggyBac insertional mutagenesis. Disruption of Gpr45 led to increased adiposity at the time of weaning and increases in body mass, fat content, glucose intolerance, and hepatic steatosis with advancing age. Mice with disruptions in Gpr45 also displayed a reduction in expression of the metabolic regulator POMC and less energy expenditure prior to the onset of obesity. Mechanistically, we determined that GPR45 regulates POMC expression via the JAK/STAT pathway in a cell-autonomous manner. Consistent with this finding, intraventricular administration of melanotan-2, an analog of the POMC derivative α-MSH, suppressed adult obesity in Gpr45 mutants. These results reveal that GPR45 is a regulator of POMC signaling and energy expenditure, which suggests that it may be a potential intervention target to combat obesity.

Immunisation With Immunodominant Linear B Cell Epitopes Vaccine of Manganese Transport Protein C Confers Protection against Staphylococcus aureus Infection.

Vaccination strategies for Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA) infections have attracted much research attention. Recent efforts have been made to select manganese transport protein C, or manganese binding surface lipoprotein C (MntC), which is a metal ion associated with pathogen nutrition uptake, as potential candidates for an S. aureus vaccine. Although protective humoral immune responses to MntC are well-characterised, much less is known about detailed MntC-specific B cell epitope mapping and particularly epitope vaccines, which are less-time consuming and more convenient. In this study, we generated a recombinant protein rMntC which induced strong antibody response when used for immunisation with CFA/IFA adjuvant. On the basis of the results, linear B cell epitopes within MntC were finely mapped using a series of overlapping synthetic peptides. Further studies indicate that MntC113-136, MntC209-232, and MntC263-286 might be the original linear B-cell immune dominant epitope of MntC, furthermore, three-dimensional (3-d) crystal structure results indicate that the three immunodominant epitopes were displayed on the surface of the MntC antigen. On the basis of immunodominant MntC113-136, MntC209-232, and MntC263-286 peptides, the epitope vaccine for S. aureus induces a high antibody level which is biased to TH2 and provides effective immune protection and strong opsonophagocytic killing activity in vitro against MRSA infection. In summary, the study provides strong proof of the optimisation of MRSA B cell epitope vaccine designs and their use, which was based on the MntC antigen in the development of an MRSA vaccine.

Protective efficacy of the chimeric Staphylococcus aureus vaccine candidate IC in sepsis and pneumonia models.

Staphylococcus aureus causes serious sepsis and necrotic pneumonia worldwide. Due to the spread of multidrug-resistant strains, developing an effective vaccine is the most promising method for combating S. aureus infection. In this study, based on the immune-dominant areas of the iron surface determinant B (IsdB) and clumping factor A (ClfA), we designed the novel chimeric vaccine IsdB151-277ClfA33-213 (IC). IC formulated with the AlPO4 adjuvant induced higher protection in an S. aureus sepsis model compared with the single components alone and showed broad immune protection against several clinical S. aureus isolates. Immunisation with IC induced strong antibody responses. The protective effect of antibodies was demonstrated through the opsonophagocytic assay (OPA) and passive immunisation experiment. Moreover, this new chimeric vaccine induced Th1/Th17-skewed cellular immune responses based on cytokine profiles and CD4(+) T cell stimulation tests. Neutralisation of IL-17A alone (but not IFN-γ) resulted in a significant decrease in vaccine immune protection. Finally, we found that IC showed protective efficacy in a pneumonia model. Taken together, these data provide evidence that IC is a potentially promising vaccine candidate for combating S. aureus sepsis and pneumonia.

[Experimental study on inhibitory effect of wogonin on proliferation and invasion of breast cancer cells].

OBJECTIVE: To study the inhibitory effect of wogonin on the growth and proliferation of breast cancer cells MDA-MB-23, and observe its effect on the adhesion, migration and invasion of MDA-MB-23 cells, in order to further study its molecular mechanism. METHOD: MTT assay was used to detect the effect of wogonin on MDA-MB-23 cell growth. Ki-67 assay was adopted to test the effect of wogonin on cell proliferation. Scratch test, adherence test and invasion chamber assay were taken to detect the effect on the migration and invasion abilities of MDA-MB-231 cells. Proliferation and metastasis-related proteins and relevant signaling pathways were detected by Western blotting. RESULT: Wogonin could remarkably inhibit the growth and proliferation of MDA-MB-231 cells, significantly inhibit migration, adhesion and invasion abilities of breast cancer cells at a low concentration, and effectively inhibit the expression of Survivin, Bcl-2, ICAM-1, MMP-2, MMP-9 proteins of MDA-MB-231 cells. CONCLUSION: Wogonin could notably inhibit growth and proliferation of breast cancer cells, and inhibit migration, adhesion and invasion of MDA-MB-231 cells. Its invasive and adhesive effects on MDA-MB-231 cells may be related to the decrease in ICAM-1, MMP-2, MMP-9 expressions.

[Clinical application of non-collinear spinous process in the diagnosis of cervical vertebra "Gu Cuo Feng and Jin Chu Cao"].

OBJECTIVE: To analyze value of X-ray in diagnosis of cervical vertebral rotation. METHODS: From May 2010 to June 2011,129 patients with cervical spondylosis were collected and examined by X-ray. Among them, 119 cases were collinear spinous, other 10 cases were excluded with collinear. Of involved patients, 28 cases were male,91 cases were females with an average age of (48.53 +/- 14.32) (ranged, 24 to 65) years. The segments and numbers of vertebral body spinous process which were not centered were recorded, and then CT scan was performed to examine segments of vertebral body and spinous process which were not centered to observe rotation of cervical vertebra and spinous process deviation. The relationship between numbers of spinous not centered and vertebral rotation was statistical analyzed. RESULTS: When the number of spinous not centered ranged from 1 to 6, vertebral rotation rate were 45.45%, 46.67%, 56.86%, 62.07%, 77.14%, 85.19% respectively. CONCLUSION: The more numbers of vertebral spinous process not centered, the more chance of corresponding vertebral rotation.

Study of the effects of total flavonoids of Astragalus on atherosclerosis formation and potential mechanisms.

Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol (P < 0.05 to 0.01), increased HDL cholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile.