Performance and mechanism of co-culture of Monascus purpureus, Lacticaseibacillus casei, and Saccharomyces cerevisiae to enhance lovastatin production and lipid-lowering effects.

To facilitate lipid-lowering effects, a lovastatin-producing microbial co-culture system (LPMCS) was constituted with a novel strain Monascus purpureus R5 in combination with Lacticaseibacillus casei S5 and Saccharomyces cerevisiae J7, which increased lovastatin production by 54.21% compared with the single strain R5. Response Surface Methodology (RSM) optimization indicated lovastatin yield peaked at 7.43 mg/g with a fermentation time of 13.88 d, water content of 50.5%, and inoculum ratio of 10.27%. Meanwhile, lovastatin in LPMCS co-fermentation extracts (LFE) was qualitatively and quantitatively analyzed by Thin-Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC). Cellular experiments demonstrated that LFE exhibited no obvious cytotoxicity to L-02 cells and exhibited excellent biosafety. Most notably, high-dose LFE (100 mg/L) exhibited the highest reduction of lipid accumulation, total cholesterol, and triglycerides simultaneously in oleic acid-induced L-02 cells, which decreased by 71.59%, 38.64%, and 58.85% than untreated cells, respectively. Overall, LPMCS provides a potential approach to upgrade the lipid-lowering activity of Monascus-fermented products with higher health-beneficial effects.

The TNF-α rs361525 and IFN-γ rs2430561 polymorphisms are associated with liver cirrhosis risk: a comprehensive meta-analysis.

Background: Inflammation serves as an essential driver of liver cirrhosis (LC) incidence. Accordingly, a meta-analysis was carried out to explore the association between specific polymorphisms in the interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) genes and the incidence of LC based on comparisons of genotype and allele frequencies. Objectives: To study the relationship between TNF-α rs361525 and IFN-γ rs2430561 polymorphisms and the risk of LC. Methods: A database search was performed for all studies published as of September 10, 2022. The strength of risk relationships was assessed based on odds ratios (ORs) with 95% confidence intervals (CIs). Results: Pooled analyses were conducted for one common TNF-α polymorphism (rs361525) as well as one common IFN-γ polymorphism (rs2430561). Both of these SNPs were identified as LC-related risk factors. Specifically, rs361525 was related to LC incidence in both alcoholic liver cirrhosis (OR: 1.86, 95%CI: 1.03-3.34) and hepatitis B virus (HBV)-related cirrhosis cases (OR: 1.44, 95%CI: 1.00-2.06) when using an allelic contrast model. Moreover, rs2430561 was significantly related to LC in an Asian population (OR: 1.45, 95%CI: 1.13-1.86) and in the context of HBV-related cirrhosis (OR: 1.48, 95%CI: 1.13-1.93) when using an allelic contrast model. Conclusion: These findings indicate that rs361525 and rs2430561 represent LC-related risk factors, although additional large-scale clinical and case-control studies will be vital to confirm these results.

Effect of bioaugmentation on tetracyclines influenced chicken manure composting and antibiotics resistance.

Antibiotic residue in husbandry waste has become a serious concern. In this study, contaminated chicken manure composting was conducted to reveal the bioaugmentation effect on tetracyclines residue and antibiotics resistance genes (ARGs). The bioaugmented composting removed most of the antibiotics in 7 days. Under bioaugmentation, 96.88 % of tetracycline and 92.31 % of oxytetracycline were removed, 6.32 % and 20.93 % higher than the control (P < 0.05). The high-temperature period was the most effective phase for eliminating antibiotics. The treatment showed a long high-temperature period (7 days), while no high-temperature period was in control. After composting, the treatment showed 13.87 % higher TN (26.51 g/kg) and 13.42 % higher NO3--N (2.45 g/kg) than control (23.28 and 2.16 g/kg, respectively) but 12.72 % lower C/N, indicating fast decomposition and less nutrient loss. Exogenous microorganisms from bioaugmentation significantly reshaped the microbial community structure and facilitated the enrichment of genera such as Truepera and Fermentimonas, whose abundance increased by 71.10 % and 75.37 % than the control, respectively. Remarkably, ARGs, including tetC, tetG, and tetW, were enhanced by 198.77 %, 846.77 %, and 62.63 % compared with the control, while the integron gene (intl1) was elevated by 700.26 %, indicating horizontal gene transfer of ARGs. Eventually, bioaugmentation was efficient in regulating microbial metabolism, relieving antibiotic stress, and eliminating antibiotics in composting. However, the ability to remove ARGs should be further investigated. Such an approach should be further considered for treating pollutants-influenced organic waste to eliminate environmental concerns.

Interleukin 13 participates in terminal differentiation of esophageal squamous cell carcinoma cells.

Background: In China, esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of all esophageal cancer cases. Interleukin 13 (IL-13) was widely reported to play a key role in tumor progression. Our previous study reported that IL-13 was a favorable predictive marker for the overall survival of esophageal squamous cell carcinoma (ESCC) patients, but how IL-13 contributes to ESCC progression remains unknown. This study aims to explore the role of IL-13 and its underlying downstream molecular mechanisms in ESCC progression. Methods: Tissue microarrays including 262 primary ESCC tumor tissues were collected and analyzed. The expression of IL-13 in ESCC tumor tissue was detected with immunohistochemistry staining (IHC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to qualify the expressions of KRT13, KRT4 and 15-lipoxygenase-1 (15-LOX-1) in cultured ESCC cell lines with recombinant IL-13 treatment. Results: IL-13 was expressed in the esophageal epithelium cells and ESCC tumor cells. High IL-13 expression in ESCC tumor cells predicted a good prognosis for patients. Recombinant human IL-13 raised KRT13 and 15-LOX-1 mRNA levels, but lowered KRT4 mRNA level 15-LOX-1 in ESCC cells in vitro. Conclusions: In summary, our study suggests that IL-13 might improve the prognosis of ESCC by promoting the terminal differentiation of ESCC cells. This may offer potential new therapeutic target for early treatment of ESCC.

Responsive change of crop-specific soil bacterial community to cadmium in farmlands surrounding mine area of Southeast China.

In arable soils co-influenced by mining and farming, soil bacteria significantly affect metal (Cadmium, Cd) bioavailability and accumulation. To reveal the soil microecology response under this co-influence, three intersection areas (cornfield, vegetable field, and paddy field) were investigated. With a similar nutrient condition, the soils showed varied Cd levels (0.31-7.70 mg/kg), which was negatively related to the distance from mining water flow. Different soils showed varied microbial community structures, which were dominated by Chloroflexi (19.64-24.82%), Actinobacteria (15.49-31.96%), Acidobacteriota (9.46-20.31%), and Proteobacteria (11.88-14.57%) phyla. A strong correlation was observed between functional microbial taxon (e. g. Acidobacteriota), soil physicochemical properties, and Cd contents. The relative abundance of tolerant bacteria including Vicinamibacteraceae, Knoellia, Ardenticatenales, Lysobacter, etc. elevated with the increase of Cd, which contributed to the enrichment of heavy metal resistance genes (HRGs) and integration genes (intlI), thus enhancing the resistance to heavy metal pollution. Cd content rather than crop species was identified as the dominant factor that influenced the bacterial community. Nevertheless, the peculiar agrotype of the paddy field contributed to its higher HRGs and intlI abundance. These results provided fundamental information about the crop-specific physiochemical-bacterial interaction, which was helpful to evaluate agricultural environmental risk around the intersection of farmland and pollution sources.

Lipid degrading microbe consortium driving micro-ecological evolvement of activated sludge for cooking wastewater treatment.

In this study, a lipid degrading microbe consortium (LDMC) was assembled to improve the performance of activated sludge (AS) on cooking wastewater purification. LDMC can rapidly degrade high-level oil (efficiency beyond 93.0% at 5.0 g/L) as sole carbon source under various environmental conditions (10.0-45.0 °C, pH 2.0-12.0). With LDMC inoculation, AS' water treatment performance was significantly enhanced, which removed 36.10 and 48.93% more chemical oxygen demand (COD) and ammonia nitrogen from wastewater than control. A better settling property and smaller bulking risk were found with LDMC inoculation, indicated by a lower SV30 and SVI index but a higher MLSS. By GC/MS analysis, a gradual degradation on the end of the fatty acid chain was suggested. LDMC inoculation significantly changed AS's microbial community structure, improved its stability, decreased the microbial community diversity, facilitated the enrichment of lipid degraders and functional genes related to lipid bio-degradation. Lipid degraders including Nakamurella sp. and Stenotrophomona sp., etc. played a crucial role during oil degradation. Sludge structure maintainers such as Kineosphaera sp. contributed largely to the stability of AS under exogenous stress. This study provided an efficient approach for cooking wastewater treatment along with the underlying mechanism exploration, which should give insights into oil-containing environmental remediation.

IL-6 and IL-10 gene polymorphisms and cirrhosis of liver risk from a comprehensive analysis.

BACKGROUND: Different inflammatory and immune cytokines play a key role in the development of cirrhosis of liver (CL). To investigate the association between interleukin-6,10 (IL-6,10) genes polymorphisms and CL risk through comparison of the allele and genotype distribution frequencies by meta-analysis. METHODS: A literature search covered with the PubMed, Embase, Cochrane Library, Web of Science, Google Scholar, SinoMed (CNKI and Wanfang) through 20th April, 2021. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of associations. RESULTS: After a comprehensive search, three common polymorphisms (rs1800872, rs1800871, rs1800896) in IL-10 gene were selected, and three common polymorphisms (rs1800795, rs1800796, rs1800797) in IL-6 gene were also identified. The important finding was that IL-10 rs1800872 was a risk factor for CL development. For example, there has a significantly increased relationship between rs1800872 polymorphism and CL both in the whole group (OR: 1.30, 95%CI: 1.01-1.67 in heterozygote model), Asian population (OR: 1.40, 95%CI: 1.03-1.88 in heterozygote model) and hospital-based source of control (OR: 1.40, 95%CI: 1.01-1.96 in dominant model). In addition, significant association was found between rs1800896 and primary biliary cirrhosis subtype disease (OR: 1.30, 95%CI: 1.01-1.68 in allelic contrast model). No association was observed in all three polymorphisms in IL-6 gene. CONCLUSION: Our present study suggests that the IL-10 rs1800872 and rs1800896 polymorphisms is potentially associated with the risk of CL susceptibility.

Establishment and validation of a mathematical diagnosis model to distinguish benign pulmonary nodules from early non-small cell lung cancer in Chinese people.

BACKGROUND: In this study, we aimed to establish and validate a mathematical diagnosis model to distinguish benign pulmonary nodules (BPNs) from early non-small cell lung cancer (eNSCLC) based on clinical characteristics, radiomics features, and hematological biomarkers. METHODS: Medical records from 81 patients (27 BPNs, 54 eNSCLC) were used to establish a novel mathematical diagnosis model and an additional 61 patients (21 BPNs, 40 eNSCLC) were used to validate this new model. To establish a clinical diagnosis model, a least absolute shrinkage and selection operator (LASSO) regression was applied to select predictors for eNSCLC, then multivariate logistic regression analysis was performed to determine independent predictors of the probability of eNSCLC, and to establish a clinical diagnosis model. The diagnostic accuracy and discriminative ability of our model were compared with the PKUPH and Mayo models using the following 4 indices: area under the receiver-operating characteristics curve (ROC), net reclassification improvement index (NRI), integrated discrimination improvement index (IDI), and decision curve analysis (DCA). RESULTS: Multivariate logistic regression analysis identified age, border, and albumin (ALB) as independent diagnostic markers of eNSCLC. In the training cohort, the AUC of our model was 0.740, which was larger than the AUCs for the PKUPH model (0.717, P=0.755) and the Mayo model (0.652, P=0.275). Compared with the PKUPH and Mayo models, the NRI of our model increased by 3.7% (P=0.731) and 27.78% (P=0.008), respectively, while the IDI changed -4.77% (P=0.437) and 11.67% (P=0.015), respectively. Moreover, the DCA demonstrated that our model had a higher overall net benefit compared to previously published models. Importantly, similar findings were confirmed in the validation cohort. CONCLUSIONS: Age, border, and serum ALB levels were independent diagnostic markers of eNSCLC. Thus, our model could more accurately distinguish BPNs from eNSCLC and outperformed previously published models.

Prognostic significance of combined pretreatment body mass index (BMI) and BMI loss in patients with esophageal cancer.

Background: Body mass index (BMI) has been associated with a risk of esophageal cancer. However, the influence of BMI and BMI loss on people with esophageal cancer that were treated with different therapies has not been described in China. Methods: In total, 615 consecutive patients that underwent esophagectomy and/or chemotherapy/radiotherapy were classified according to the Asian-specific BMI (kg/m2) cutoff values. The impact of BMI and BMI loss on long-term overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. Results: Multivariate analysis showed that overweight and obese patients had a more favorable survival than normal weight and underweight patients (p=0.017). Patients with a low BMI and high BMI loss before therapy had worse OS than others (p=0.001). Subgroup analysis showed that patients with a high BMI were more likely to suffer hypertension (p<0.001) and receive only surgery (p<0.001), and they were less likely to be smokers (p=0.007) and anemic (p<0.001). Conversely, patients with high BMI loss were more likely to be anemic (p=0.001), to have advanced pathological stage (p=0.012), and to receive chemotherapy and radiotherapy (p=0.001). Moreover, the mortality rate was higher when patients had a high BMI loss. There is no survival benefit of higher BMI in the non-esophageal squamous cell carcinoma (ESCC) group. Conclusion: Pretreatment BMI was an independent prognostic factor for long-term survival in esophageal cancer patients treated with different treatments. The overall survival was increased in esophageal cancer patients with a high pretreatment BMI and no BMI loss. There is no survival benefit of higher BMI in the non-ESCC group.

Lipase-catalyzed synthesis of ethyl (R)-2-benzyloxy-2-isopropylhydrogenmalonate: a useful combination of chemical synthesis with enzymatic methods.

Ethyl (R)-2-benzyloxy-2-isopropylhydrogenmalonate is a key intermediate for the synthesis of the side chain in ergopeptines. In this work, we adopted a method to prepare enantiomerically pure title monoester via immobilized Candida antarctica lipase B (Novozym 435)-catalyzed hydrolysis of the corresponding diester.

Acid-catalysed intramolecular addition of ß-ketoesters to 1,3-dienes.

1,3-Dienyl ß-keto esters are cyclised into bicyclolactones using the Bi(OTf)3/TfOH catalytic system. This reaction represents a rare case of simultaneous C-C and C-O bond formation at positions 1 and 3 of a 1,3-diene. Application to the synthesis of ramulosin is presented.

Association of the CTLA4 gene CT60/rs3087243 single-nucleotide polymorphisms with Graves' disease.

It has been widely reported that the CT60 single-nucleotide polymorphism (SNP), which is in the 3'-untranslated region of the cytotoxic T lymphocyte associated 4 (CTLA4) gene, is strongly correlated with certain immune-mediated diseases. The present case-control study aimed to investigate the genetic association between the CT60 SNP within the CTLA4 gene and Graves' disease (GD). A total of 288 patients with GD and 290 control subjects were recruited for the study. The CT60 SNP of the CTLA4 gene was detected by direct DNA sequencing. The results indicated that the frequencies of the GG genotype and G allele in the case group were evidently higher than that in the control group (P=4×10-6 and P=2.9×10-5, respectively). Furthermore, the G/G genotype of the CT60 SNP was associated with an increased risk for GD (odds ratio=2.223). In conclusion, these results suggested that the CT60 SNP is associated with susceptibility to GD. The frequency of the disease-susceptible G allele of CT60 was significantly associated with an increased risk of GD development.

Association between IL-21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population.

Interleukin-21 (IL-21) is a pleiotropic cytokine linking innate and adaptive immune responses, which has been reported to play a key role in multiple autoimmune diseases. The aim of the present case-control study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of rs907715 within the IL-21 gene and Graves' disease (GD) in a Southern Chinese population. A total of 211 patients with GD and 212 control subjects were recruited for the study. IL-21 gene rs907715 polymorphisms were detected by direct DNA sequencing. The results indicated that the frequencies of the GG genotype and the G allele in GD patients were significantly increased when compared with the frequencies in the controls (P=6.7×10-3 and P=2.0×10-5, respectively). In addition, the frequency of the AA genotype was much lower in the patient group when compared with the control group (16.6 vs. 34.0%; P=4.0×10-5). Furthermore, the G allele of rs907715 was associated with relapse in GD patients. These observations indicated that polymorphisms of IL-21/rs907715 may affect the susceptibility to GD in a Southern Chinese population. The G allele was significantly associated with an increased risk of GD development, whereas the A allele may lower the susceptibility to GD.

Silver-free two-component approach in gold catalysis: activation of [LAuCl] complexes with derivatives of copper, zinc, indium, bismuth, and other Lewis acids.

Complexes of type [LAuCl] (L = phosphine, phosphite, NHC and others) are widely employed in homogeneous catalysis, however, they are usually inactive as such and must be used jointly with a halide scavenger. To date, this role has mostly been entrusted to silver salts (AgSbF6 , AgPF6, AgBF4, AgOTf, etc.). However, silver salts can be the source of deactivation processes or side reactions, so it is sometimes advisable to use silver-free cationic gold complexes, which can be difficult to synthesize and to handle compared with the more robust chloride. We show in this study that various Lewis acids of the transition and main group metal families are expedient substitutes to silver salts. We have tested Cu(I), Cu(II), Zn(II), In(III), Si(IV), Bi(III), and other salts in a variety of typical Au(I)-catalyzed transformations, and the results have revealed that [LAuCl] can form active species in their presence.