Identification of a negative-strand RNA virus with natural plant and fungal hosts.

The presence of viruses that spread to both plant and fungal populations in nature has posed intriguingly scientific question. We found a negative-strand RNA virus related to members of the family Phenuiviridae, named Valsa mali negative-strand RNA virus 1 (VmNSRV1), which induced strong hypovirulence and was prevalent in a population of the phytopathogenic fungus of apple Valsa canker (Valsa mali) infecting apple orchards in the Shaanxi Province of China. Intriguingly, VmNSRV1 encodes a protein with a viral cell-to-cell movement function in plant tissue. Mechanical leaf inoculation showed that VmNSRV1 could systemically infect plants. Moreover, VmNSRV1 was detected in 24 out of 139 apple trees tested in orchards in Shaanxi Province. Fungal inoculation experiments showed that VmNSRV1 could be bidirectionally transmitted between apple plants and V. mali, and VmNSRV1 infection in plants reduced the development of fungal lesions on leaves. Additionally, the nucleocapsid protein encoded by VmNSRV1 is associated with and rearranged lipid droplets in both fungal and plant cells. VmNSRV1 represents a virus that has adapted and spread to both plant and fungal hosts and shuttles between these two organisms in nature (phyto-mycovirus) and is potential to be utilized for the biocontrol method against plant fungal diseases. This finding presents further insights into the virus evolution and adaptation encompassing both plant and fungal hosts.

The P1 protein of wheat yellow mosaic virus exerts RNA silencing suppression activity to facilitate virus infection in wheat plants.

Wheat yellow mosaic virus (WYMV) causes severe wheat viral disease in Asia. However, the viral suppressor of RNA silencing (VSR) encoded by WYMV has not been identified. Here, the P1 protein encoded by WYMV RNA2 was shown to suppress RNA silencing in Nicotiana benthamiana. Mutagenesis assays revealed that the alanine substitution mutant G175A of P1 abolished VSR activity and mutant Y10A VSR activity remained only in younger leaves. P1, but not G175A, interacted with gene silencing-related protein, N. benthamiana calmodulin-like protein (NbCaM), and calmodulin-binding transcription activator 3 (NbCAMTA3), and Y10A interacted with NbCAMTA3 only. Competitive Bimolecular fluorescence complementation and co-immunoprecipitation assays showed that the ability of P1 disturbing the interaction between NbCaM and NbCAMTA3 was stronger than Y10A, Y10A was stronger than G175A. In vitro transcript inoculation of infectious WYMV clones further demonstrated that VSR-defective mutants G175A and Y10A reduced WYMV infection in wheat (Triticum aestivum L.), G175A had a more significant effect on virus accumulation in upper leaves of wheat than Y10A. Moreover, RNA silencing, temperature, and autophagy have significant effects on the accumulation of P1 in N. benthamiana. Taken together, WYMV P1 acts as VSR by interfering with calmodulin-associated antiviral RNAi defense to facilitate virus infection in wheat, which has provided clear insights into the function of P1 in the process of WYMV infection.

Therapeutic effects and mechanisms of isoxanthohumol on DSS-induced colitis: regulating T cell development, restoring gut microbiota, and improving metabolic disorders.

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.

[Mechanism of Zhenwu Decoction in improving renal inflammatory injury in mice with DN of spleen-kidney Yang deficiency syndrome by regulating ROCK/IKK/NF-κB pathway].

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1ß, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1ß, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.

Natural Compound 2,2',4'-Trihydroxychalcone Suppresses T Helper 17 Cell Differentiation and Disease Progression by Inhibiting Retinoid-Related Orphan Receptor Gamma T.

Retinoid-related orphan receptor γt (RORγt), a vital transcription factor for the differentiation of the pro-inflammatory Th17 cells, is essential to the inflammatory response and pathological process mediated by Th17 cells. Pharmacological inhibition of the nuclear receptor RORγt provides novel immunomodulators for treating Th17-driven autoimmune diseases and organ transplant rejection. Here, we identified 2,2',4'-trihydroxychalcone (TDC), a natural chalcone derivant, binds directly to the ligand binding domain (LBD) of RORγt and inhibited its transcriptional activation activity. Using three mice models of Th17-related diseases, it was found that the administration of TDC effectively alleviated the disease development of experimental autoimmune encephalomyelitis (EAE), experimental colitis, and skin allograft rejection. Collectively, these results demonstrated TDC targeting RORγt to suppress Th17 cell polarization, as well as its activity, thus, indicating the potential of this compound in treating of Th17-related autoimmune disorders and organ transplant rejection disorders.

Additive interaction between potentially modifiable risk factors and ethnicity among individuals in the Han, Tujia and Miao populations with first-ever ischaemic stroke.

BACKGROUND: As a country with one-fifth of the global population, China has experienced explosive growth in ischaemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to examine the differences in potentially modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao). METHODS: A case-control study was conducted with 324 cases of first-ever ischaemic stroke from the hospitals of the Xiangxi Tujia and Miao Autonomous Prefecture and 394 controls from communities covering the same area between May 1, 2018, and April 30, 2019. Structured questionnaires were administered, and physical examinations were performed in the same manner for cases and controls. Univariate and multivariate logistic regression analyses with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were used to examine the association between risk factors and ischaemic stroke. An additive model was used to study the interaction between the modifiable risk factors and ethnicity with R software. RESULTS: Higher high-sensitivity C-reactive protein levels (OR 50.54, 95%CI 29.76-85.85), higher monthly family income (4.18, 2.40-7.28), increased frequency of hot pot consumption (2.90, 1.21-6.93), diabetes mellitus (2.62, 1.48-4.62), a higher apolipoprotein (Apo)B/ApoA1 ratio (2.60, 1.39-4.85), hypertension (2.52, 1.45-4.40) and moderate-intensity physical activity (0.50, 0.28-0.89) were associated with ischaemic stroke. There was an additive interaction between the ApoB/ApoA1 ratio and ethnicity in the Tujia and Miao populations with first-ever ischaemic stroke (the relative excess risk due to the interaction was 5.75, 95% CI 0.58 ~ 10.92; the attributable proportion due to the interaction was 0.65, 95% CI 0.38 ~ 0.91; the synergy index was 3.66, 95% CI 1.35 ~ 9.93). CONCLUSIONS: This is the first case-control study examining modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao) in China. Some differences were observed in the impact of risk factors among these ethnic groups. Our results may help interpret health-related data, including surveillance and research, when developing strategies for stroke prevention.

Efficiency of hybrid systems enhanced with different sludge ratios in improving resistance to short-term low temperatures.

Complete autotrophic nitrogen removal over nitrite (CANON) is used in wastewater treatment. However, the performance of the CANON system significantly decreases at low temperatures; thus, a new strategy to improve the resistance of the CANON system is required. To investigate the impact of sludge ratio control (high-granule, equivalent, and high-floc systems) on the resistance of CANON to low temperatures, and their recovery after restoring to normal temperature, the nitrogen removal performance of hybrid systems with different ratios was evaluated. The equivalent system had the lowest nitrite accumulation rate and highest nitrogen removal rate. Anaerobic ammonia oxidation was the rate-limiting step of each system, and hzs was the rate-limiting gene. The higher anaerobic ammonium oxidizing bacteria (AAOB) abundance and hzs expression levels resulted in an equivalent system with better resistance and recovery to short-term low temperatures at the gene level.

Hypertension Among Hemorrhagic Stroke Patients in Northeast China: A Population-Based Study 2017-2019.

BACKGROUND We aimed to profile the current epidemiology of hypertension among the survivors of hemorrhagic stroke in northeast China. MATERIAL AND METHODS Our cross-sectional study included 18 796 adults aged 40 years or older and residing in northeast China. Hemorrhagic stroke was identified according to the CT and/or MRI results. Hypertension was defined based on the Chinese hypertension guidelines. RESULTS We identified 208 patients with previous hemorrhagic stroke in this population-based study. The overall prevalence of hypertension in the studied population was 88%. Out of all the survivors of hemorrhagic stroke, 80.9% were aware of their hypertensive condition, 70.5% of the patients were in antihypertensive medications treatment, and only 12% of the patients had their blood pressure under control. Furthermore, only 17.10% of the patients who took hypertensive medications achieved appropriate blood pressure. Calcium channel blockers were more commonly used than other medications. Patients with controlled hypertension had significantly higher percentages of comorbidities when compared to those with uncontrolled hypertension. In our patient sample, the rates of stage 2 and stage 3 hypertension in the hemorrhagic stroke population were 28.8% and 15.9%, respectively, and women had a significantly higher prevalence of stage 3 hypertension when compared with men (21.3% vs. 10.0%, P=0.026). CONCLUSIONS The high prevalence of uncontrolled hypertension and high rates of blood pressure at stages 2 and 3 in patients with prior hemorrhagic stroke indicated a considerable stroke burden in northeast China. Therefore, effective and long-time management of hypertension in stroke survivors should be a priority.

[Survey on Toxoplasma gondii Infection in Depressed Patients and Genotype Identification in Guizhou Province].

Objective: To survey on Toxoplasma gondii infection in depressed patients in Guizhou Province and identify the genotype of T. gondii. Methods: Enzyme-linked immunosorbent assay (ELISA) was applied to detect the T. gondii-specific antibodies IgG, IgM and circulating antigens (CAg) of T. gondii in 141 patients and 150 healthy subjects. The specific repeated DNA fragment (529 bp) of T. gondii was amplified by PCR. The genotype of T. gondii was determined by multiplex multilocus nested polymerase chain reaction-restriction fragment length polymorphism (Mn-PCR-RFLP). Results: ELISA showed that the positive rate of anti-T. gondii antibody in depressed patients and healthy subjects was 21.3%（30/141） and 7.3%（11/150）, respectively. The positive rate of IgG in depressed patients was 18.4% （26/141）, significantly higher than that in healthy subjects （7.3%, 11/150）（P<0.05）. The positive rate of IgM and CAg in depressed patients was both 1.4% （2/141）, while these were not found in healthy subjects. PCR revealed one patient positive for T. gondii, whose genotype was further identified to be Toxo DB #9（Chinese 1 type） by Mn-PCR-RFLP. Conclusion: The positive rate of T. gondii is higher in depressed patients than in the healthy subjects in Guizhou Province. The genotype of T. gondii detected in one depressed patient is the Chinese 1 type.

[Toxoplasma gondi Antibody Profile in Patients with Leukemia or Lymphoma].

Blood samples were collected from patients with leukemia (n = 150) or lymphoma (n = 150) in the Cancer Hospital from March to September 2014. The specific antibodies (IgG, IgM) to, and circulating antigens (CAg) of Toxoplasma gondii were determined by ELISA. A 529 bp specific sequence was amplified by PCR from the genomic DNA of T. gondii. T. gondii-specific IgG positive rate in patients with leukemia and lymphoma were 16.0% (24/150) and 20.0% (30/150), respectively, which were significantly higher than that of healthy persons (6.4%, 7/110) (P < 0.05). IgM positive rate of the leukemia patients, lymphoma patients, and healthy persons was 2.7% (4/150), 1.3% (2/150), and 0.9% (1/110) (P > 0.05), respectively. No significant difference was found in IgM and CAg positive rate among leukemia patients, lymphoma patients, and healthy persons (P > 0.05). No specific band (529 bp) was detected in all samples.

Denitrification effect and strengthening mechanism of SAD/A system at low temperature by gel-immobilization technology.

Sulfur autotrophic denitrification coupled anaerobic ammonia oxidation (SAD/A) has several advantages over other denitrification processes; for example, it does not consume the organic carbon source, has low operation costs, and produces less excess sludge; however, it has certain disadvantages as well, such as a long start-up time, easy loss of bacteria, and low microbial activity at low temperature. The use of microbial immobilization technology to embed functional bacteria provides a feasible method of resolving the above problems. In this study polyvinyl alcohol­sodium alginate was used to prepare a composite carrier for fixing anaerobic ammonia oxidizing bacteria (AAOB) and sulfur oxidizing bacteria (SOB), and the structure and morphology of the encapsulated bodies were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Subsequently, the nitrogen removal performance of the immobilized microbial carriers in the gradient cooling process (30 °C to 10 °C) was determined, and the corresponding mechanism was discussed. The results showed that the nitrate-removal efficiencies observed with granular sludge and gel embedding were at 10 °C 21.44 % and 14.31 % lower, than those at 30 °C, respectively, whereas the ammonia-removal efficiency decreased by up to approximately three-fold. The main mechanism was the 'insulation' provided by the external gel composed of PVA and SA for the internal sludge and subsequent improvement of its low temperature resistance, while protecting AAOB and SOB from oxygen inhibition, which is conducive to enriching denitrifying bacteria. In addition, the gel does not change the internal sludge species, it can shift the dominance of specific microorganisms and improve the removal efficiency of nitrogen. In summary, the immobilization of AAOB and SOB by the gel can achieve effectively mitigate nitrogen pollution in low temperature environments, thus indicating that the SAD/A process has broad engineering application prospects.

Cross-Kingdom Interactions Between Plant and Fungal Viruses.

The large genetic and structural divergences between plants and fungi may hinder the transmission of viruses between these two kingdoms to some extent. However, recent accumulating evidence from virus phylogenetic analyses and the discovery of naturally occurring virus cross-infection suggest the occurrence of past and current transmissions of viruses between plants and plant-associated fungi. Moreover, artificial virus inoculation experiments showed that diverse plant viruses can multiply in fungi and vice versa. Thus, virus cross-infection between plants and fungi may play an important role in the spread, emergence, and evolution of both plant and fungal viruses and facilitate the interaction between them. In this review, we summarize current knowledge related to cross-kingdom virus infection in plants and fungi and further discuss the relevance of this new virological topic in the context of understanding virus spread and transmission in nature as well as developing control strategies for crop plant diseases.

Milk exosomes: an oral drug delivery system with great application potential.

Exosomes are extracellular vesicles with the smallest diameter, usually divided into cellular sources and body fluid sources. Due to their special properties different from cell-derived exosomes, the application of milk exosomes as an oral drug delivery system has increased greatly. This article introduces the physical and chemical properties of exosomes, separation technology, dyeing and labeling technology, targeted modification technology, and the application of milk exosomes in drug loading and disease therapies.

An immortal porcine preadipocyte cell strain for efficient production of cell-cultured fat.

Adding adipose cells to cell-cultured meat can provide a distinctive aroma and juicy texture similar to real meat. However, a significant challenge still exists in obtaining seed cells that can be propagated for long periods, maintain their adipogenic potential, and reduce production costs. In this study, we present a cell strain derived from immortalized porcine preadipocytes that can be subculture for over 40 passages without losing differentiation capacity. This cell strain can be differentiated within 3D bioscaffolds to generate cell-cultured fat using fewer chemicals and less serum. Additionally, it can be expanded and differentiated on microcarriers with upscaled culture to reduce costs and labor. Moreover, it can co-differentiate with muscle precursor cells, producing a pattern similar to real meat. Therefore, our cell strain provides an exceptional model for studying and producing cell-cultured fat.

Betel quid chewing and oral potential malignant disorders and the impact of smoking and drinking: A meta-analysis.

BACKGROUND: Oral potential malignant disorders (OPMDs) are a precancerous condition of oral disease. Several studies have found that betel quid chewing, smoking and alcohol drinking might be the risk factors of OPMDs. But the relationships of them, especially their interaction are still inconclusive. AIM: To evaluate the relationship between betel quid chewing and OPMDs and to explore the interaction of smoking and alcohol drinking on the relationship. METHODS: We searched PubMed, Web of Science, Embase and the Cochrane Library databases with items complete until January 2021 for relevant studies. The research data were extracted according to the inclusion criteria. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the effect size. Subgroup analysis was performed to assess interactions between exposures and OPMDs. Relative excess risk of interaction (RERI) was used to estimate the size of interaction. RESULTS: Nine articles were selected in the final meta-analysis. The results showed that betel quid chewing (pooled OR: 8.70, 95%CI: 5.18-14.61), alcohol consumption (pooled OR: 1.95, 95%CI: 1.5-2.55), and smoking (pooled OR:4.35, 95%CI: 3.06-6.2) could significantly increase the risk of OPMDs compared to individuals without these behaviors. Smoking and alcohol drinking synergistically increased the association between betel quid chewing and OPMDs (pooled OR(BQ+SM):14.38, 95%CI: 7.14-28.95; pooled OR(BQ+DK): 11.12, 95%CI: 8.00-15.45, respectively). The RERI(BQ+SM) and RERI(BQ+DK) were 2.33 and 1.47, respectively. CONCLUSION: The synergistic effects between smoking/drinking and betel quid highlights the importance of focusing on individuals with multiple exposures. Further study should be conducted to confirm these interactions.

Lipid Metabolic Process Involved in Oocyte Maturation During Folliculogenesis.

Oocyte maturation is a complex and dynamic process regulated by the coordination of ovarian cells and numerous extraovarian signals. From mammal studies, it is learnt that lipid metabolism provides sufficient energy for morphological and cellular events during folliculogenesis, and numerous lipid metabolites, including cholesterol, lipoproteins, and 14-demethyl-14-dehydrolanosterol, act as steroid hormone precursors and meiotic resumption regulators. Endogenous and exogenous signals, such as gonadotropins, insulin, and cortisol, are the upstream regulators in follicular lipid metabolic homeostasis, forming a complex and dynamic network in which the key factor or pathway that plays the central role is still a mystery. Though lipid metabolites are indispensable, long-term exposure to a high-fat environment will induce irreversible damage to follicular cells and oocyte meiosis. This review specifically describes the transcriptional expression patterns of several lipid metabolism-related genes in human oocytes and granulosa cells during folliculogenesis, illustrating the spatiotemporal lipid metabolic changes in follicles and the role of lipid metabolism in female reproductive capacity. This study aims to elaborate the impact of lipid metabolism on folliculogenesis, thus providing guidance for improving the fertility of obese women and the clinical outcome of assisted reproduction.

Activity enhancement and the anammox mechanism under low temperature via PVA-SA and nano Fe2O3-PVA-SA entrapped beads.

Anaerobic ammonia-oxidizing bacteria (AAOB) have a long growth time and low activity at low temperatures. In suspended systems, sludge is easily lost, which limits the mainstream application of anaerobic ammonia oxidation (anammox).Entrapment provides effective ideas for solving these problems. In this study, polyvinyl­sodium alginate (PVA-SA) and nano Fe2O3-PVA-SA entrapment beads were prepared to discuss the effectiveness of entrapment enhanced anammox sludge at low temperatures. The differences in the entrapped beads and granules were compared to analyze the strengthening mechanism. The results show that the nitrogen removal performance of granules, PVA-SA and nano Fe2O3-PVA-SA entrapped beads, first decreased and then increased during the cooling and low-temperature operation. Nano Fe2O3-PVA-SA entrapped beads showed the smallest decline and the highest degree of recovery. Reaction metering ratio (△NO2--N/△NH4+-N and △NO3--N/△NH4+-N) showed that entrapment could realize Nitrite oxidizing bacteria (NOB) inhibition and improve the activity of denitrifying bacteria (DNB) to promote the removal of total nitrogen by providing a strict anaerobic environment. The results demonstrate that entrapment is beneficial for maintaining the content of heme c, specifically, nano Fe2O3 can stimulate its production, and is beneficial for alleviating the reduction of hydrazine dehydrogenase (HDH) enzyme activity. The extracellular polymeric substances (EPS) content and analysis showed that entrapment does not change the composition of EPS, and can maintain the EPS content. Nano Fe2O3 can stimulate AAOB to secrete more EPS to maintain sludge stability. From a molecular perspective, entrapment can maintain the expression of functional genes, promote the enrichment of AAOB, thus improving the nitrogen removal performance from the dual perspectives of "quality" and "quantity".

Combination effect between gut microbiota and traditional potentially modifiable risk factors for first-ever ischemic stroke in Tujia, Miao and Han populations in China.

China has had explosive growth in ischemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to explore the possible combination effect between gut microbiota and traditional potentially modifiable risk factors for IS among two ethnic minorities (Tujia and Miao) and the Han population. Herein, we first used the 16 S rRNA sequencing to compare the gut microbial compositions of 82 patients with first-ever IS vs. 82 normal controls (NCs) among Han, Tujia, and Miao people between 1 May 2018 and 30 April 2019, from Xiangxi Tujia and Miao Autonomous Prefecture in China. An additive model was used to study the interaction between traditional risk factors and gut microbiota with R software. Linear discriminant analysis (LDA) and LDA effect size (LEfSe) results showed that the identified key gut microbiota's taxonomic composition varied in different ethnicity between the IS patients and NCs. Furthermore, families Lactobacillaceae, Enterococcaceae, Streptococcaceae, and Enterobacteriaceae were found to be positively correlated with high-risk factors and negatively correlated with preventive factors in the IS patients, but families Ruminococcaceae and Lachnospiraceae were just the opposite in the NCs. There were additive interactions between traditional risk factors (systolic blood pressure, diastolic blood pressure, and high-sensitive C-reactive protein) and family Enterococcaceae for first-ever IS with the attributable proportion due to the interaction was 0.74, 0.71, and 0.85, respectively; and the synergy index was 4.45, 3.78, and 7.01, respectively. This preliminary but promising study showed that the gut microbiota disturbances may potentially interact to IS with different ethnic host's traditional risk factors.

Natural Cross-Kingdom Spread of Apple Scar Skin Viroid from Apple Trees to Fungi.

Viroids are the smallest known infectious agents that are thought to only infect plants. Here, we reveal that several species of plant pathogenic fungi that were isolated from apple trees infected with apple scar skin viroid (ASSVd) carried ASSVd naturally. This finding indicates the spread of viroids to fungi under natural conditions and further suggests the possible existence of mycoviroids in nature. A total of 117 fungal isolates were isolated from ASSVd-infected apple trees, with the majority (85.5%) being an ascomycete Alternaria alternata and the remaining isolates being other plant-pathogenic or -endophytic fungi. Out of the examined samples, viroids were detected in 81 isolates (69.2%) including A. alternata as well as other fungal species. The phenotypic comparison of ASSVd-free specimens developed by single-spore isolation and ASSVd-infected fungal isogenic lines showed that ASSVd affected the growth and pathogenicity of certain fungal species. ASSVd confers hypovirulence on ascomycete Epicoccum nigrum. The mycobiome analysis of apple tree-associated fungi showed that ASSVd infection did not generally affect the diversity and structure of fungal communities but specifically increased the abundance of Alternaria species. Taken together, these data reveal the occurrence of the natural spread of viroids to plants; additionally, as an integral component of the ecosystem, viroids may affect the abundance of certain fungal species in plants. Moreover, this study provides further evidence that viroid infection could induce symptoms in certain filamentous fungi.

2', 4'-Dihydroxy-2,3-dimethoxychalcone: A pharmacological inverse agonist of RORγt ameliorating Th17-driven inflammatory diseases by regulating Th17/Treg.

Multiple sclerosis, inflammatory bowel disease and organ transplant rejection are related to Th17 cell development and inflammatory respond. RORγt, a specific transcription factor regulating Th17 cell differentiation, is a pivotal target for the treatment of diseases. However, the clinical application of RORγt inverse agonists reported so far has been hindered due to limited efficacy and toxic side effects. Plant-derived natural products with drug-like properties and safety are wide and valuable resources for candidate drug discovery. Herein, structure-based virtual screening was used to find out 2',4'-Dihydroxy-2,3-dimethoxychalcone (DDC), a chalcone derivative rich in plants and food, located in the binding pocket of RORγt and targeted to inhibit RORγt activity. DDC repressed murine Th17 differentiation and promoted Treg differentiation remarkably in a dose-dependent manner. In addition, DDC treatment improved experimental autoimmune encephalomyelitis recovery, ameliorated experimental colitis severity, and prevented graft rejection significantly. Mechanically, DDC indirectly stabilized Foxp3 expression by inhibiting RORγt activity and the expression of its target gene profile in vitro and in vivo, which realized its regulation of Th17/Treg balance. In conclusion, our study provides a scientific basis that DDC, as an inverse agonist of RORγt with simple structure, rich sources, low cost, high efficiency, and low toxicity, has great potential for the development of a novel effective immunomodulator for the treatment of Th17-mediated inflammatory diseases.