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Abstract The reconstruction method was proposed more than a decade ago to boost the signal of baryonic acoustic oscillations measured in galaxy redshift surveys, which is one of key probes for dark energy. After moving the observed overdensities in galaxy surveys back to their initial position, the reconstructed density field is closer to a linear Gaussian field, with higher-order information moved back into the power spectrum. We find that by jointly analysing power spectra measured from the pre- and post-reconstructed galaxy samples, higher-order information beyond the 2-point power spectrum can be efficiently extracted, which generally yields an information gain upon the analysis using the pre- or post-reconstructed galaxy sample alone. This opens a window to easily use higher-order information when constraining cosmological models.

BackgroundTemporomandibular joint disorders (TMD) are highly prevalent among people. Numerous investigations have revealed the impact of gut microbiota in many diseases. However, the causal relationship between Temporomandibular joint disorders and gut microbiota remains unclear.MethodsGenome-Wide Association Studies (GWAS) refer to the identification of sequence variations, namely single nucleotide polymorphisms (SNPs), existing across the entire human genome. GWAS data were collected on gut microbiota and TMD. Then, instrumental variables were screened through F-values and removal of linkage disequilibrium. These SNPs underwent mendelian analysis using five mathematical models. Sensitivity analysis was conducted to further verify the stability of the results. Pathogenic factors of TMD mediate the causal relationship between gut microbiota and TMD were explored through a two-step Mendelian randomization analysis. Finally, reverse mendelian analysis was conducted to account for potential reverse effects.ResultsThe analysis of the data in this article suggests that some gut microbiota, including Coprobacter, Ruminococcus torques group, Catenibacterium, Lachnospiraceae, Turicibacter, Victivallis, MollicutesRF9, Methanobacteriales, Methanobacteriaceae, FamilyXI, Methanobacteria were identified as risk factors, while Peptococcaceae provides protection for TMD.ConclusionThe research reveals the relation of gut microbiota in TMD. These findings provide insights into the underlying mechanisms and suggest potential therapeutic strategy.

In this work, a new type of FE-1 COF material is prepared by a reversible imine condensation reaction with diaminoferrocene and diaminodiformaldehyde as materials. The material is connected by imine bonds to form a COF skeleton, and the presence of plenty of nitrogen-containing groups gives the material good hydrophilicity; the presence of metal Fe ions provides the material application potential in the enrichment of phosphopeptides. According to the different binding abilities of N-glycopeptide and phosphopeptide on FE-1 COF, it can simultaneously enrich N-glycopeptide and phosphopeptide through different elution conditions to realize its controllable and selective enrichment. Using the above characteristics, 18 phosphopeptides were detected from α-casein hydrolysate, 8 phosphopeptides were detected from β-casein hydrolysate and 21 glycopeptides were detected from IgG hydrolysate. Finally, the gradual elution strategy was used; 16 phosphopeptides and 19 glycopeptides were detected from the α-casein hydrolysate and IgG hydrolysate. The corresponding glycopeptides and phosphopeptides were identified from the human serum. It proves that the FE-1 COF material has a good enrichment effect on phosphopeptides and glycopeptides.

Abstract Prostate cancer poses a great threat to men’s health worldwide, yet its treatment is still limited by the unclear understanding of its molecular mechanisms. CDKL3 is a molecule with a recently discovered regulatory role in human tumors, and its relationship with prostate cancer is unknown. The outcomes of this work showed that CDKL3 was significantly upregulated in prostate cancer tissues compared with adjacent normal tissues, and was significantly positively correlated with tumor malignancy. Knockdown of CDKL3 levels in prostate cancer cells significantly inhibited cell growth and migration and enhanced apoptosis and G2 arrest of the cell cycle. Cells with lower CDKL3 expression also had relatively weaker in vivo tumorigenic capacity as well as growth capacity. Exploration of downstream mechanisms of CDKL3 may regulate STAT1, which has co-expression characteristics with CDKL3, by inhibiting CBL-mediated ubiquitination of STAT1. Functionally, STAT1 is aberrantly overexpressed in prostate cancer and has a tumor-promoting effect similar to that of CDKL3. More importantly, the phenotypic changes of prostate cancer cells induced by CDKL3 were dependent on ERK pathway and STAT1. In summary, this work identifies CDKL3 as a new prostate cancer-promoting factor, which also has the potential to be a therapeutic target for prostate cancer.

Browning and other undesirable effects on Agaricus bisporus (A. bisporus) during storage seriously affect its commercial value. In this study, a strain, Lactiplantibacillus plantarum NML21, that resists browning and delays the deterioration of A. bisporus was screened among 72 strains of lactic acid bacteria (LAB), and its preservative effect was analyzed. The results demonstrated that gallic acid, catechin, and protocatechuic acid promoted the growth of NML21, and the strain conversion rates of gallic acid and protocatechuic acid reached 97.16% and 95.85%, respectively. During a 15 d storage of the samples, the NML21 treatment displayed a reduction in the browning index (58.4), weight loss (2.64%), respiration rate (325.45 mg kg−1 h−1), and firmness (0.65 N). The treatment further inhibited Pseudomonas spp. growth and polyphenol oxidase activity, improved the antioxidant capacity, reduced the accumulation of reactive oxygen species, and reduced the malonaldehyde content and cell membrane conductivity. Taken together, the optimized concentrations of NML21 may extend the shelf life of A. bisporus for 3–6 d and could be a useful technique for preserving fresh produce.

Abstract Exposure to heavy metals (HMs) is a threat to human health. Although probiotics can detoxify HMs in animals, their effectiveness and mechanism of action in humans have not been studied well. Therefore, we conducted this randomized, double-blind, controlled trial on 152 occupational workers from the metal industry, an at-risk human population, to explore the effectiveness of probiotic yogurt in reducing HM levels. Participants were randomly assigned to two groups: one consumed probiotic yogurt containing the HM-resistant strain Pediococcus acidilactici GR-1 and the other consumed conventional yogurt for 12 weeks. Analysis of metal contents in the blood revealed that the consumption of probiotic yogurt resulted in a higher and faster decrease in copper (34.45%) and nickel (38.34%) levels in the blood than the consumption of conventional yogurt (16.41% and 27.57%, respectively). Metagenomic and metabolomic studies identified a close correlation between gut microbiota (GM) and host metabolism. Significantly enriched members of Blautia and Bifidobacterium correlated positively with the antioxidant capacities of GM and host. Further murine experiments confirmed the essential role of GM and protective effect of GR-1 on the antioxidative role of the intestine against copper. Thus, the use of probiotic yogurt may be an effective and affordable approach for combating toxic metal exposure through the protection of indigenous GM in humans. ClinicalTrials.gov identifier: ChiCTR2100053222

A novel PANI@CS solid-phase dispersive extractant combined with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the first time, which was used for high-throughput, multi-component, real-time online rapid pretreatment and quantitative classification of 16 mycotoxins from five different medicinal parts of 13 genuine traditional Chinese medicines (TCMs). Ultra performance liquid chromatography combined with triple quadrupole mass spectrometry was used for separation and ESI detection. An internal standard isotope matching calibration was used for quantification purposes to compensate for matrix effects. The limits of detection (LOD) of 16 mycotoxins ranged from 0.1 to 6.0 μg/kg. The linear coefficients (R2) were ≥0.996 in the linear range from 10.0 to 200 μg/L. The recoveries of the 16 mycotoxins ranged from 90.1% to 105.8%, and the relative standard deviations (RSDs) ranged from 1.3% to 4.1%. Thirteen TCMs from five representative medicinal parts were selected and tested under the best sample preparation procedure and chromatographic analysis conditions. The results showed that the method could improve the sensitivity and accuracy of the sample analysis, improve the selectivity and reproducibility of the decolorization and purification of TCMs, which is suitable for the practical application of mycotoxin in trace analysis. This method can also provide a new idea for accurate, efficient, rapid and multi-component online detection of mycotoxins for quality and safety control of TCMs.

By optimizing the chromatographic conditions and sample pretreatment conditions, a method for determination of NMN content in NMN capsules and NMN tablets matrix was established based on high performance liquid chromatography, and the methodology was verified. The results showed that, the method with range of 5~500 μg/mL had a good linear relationship. The limit of detection (LOD, S/N=3) of NMN was 1.0 mg/kg, while the limit of quantitative (LOQ, S/N=10) was 3.0 mg/kg. The precision of the instrument was 0.3%. For NMN tablet samples, the stability of the method was 1.7% and the repeatability was 1.8%, while for NMN capsule samples, the stability of the method was 0.6%, and the repeatability RSD value was 0.6%. The recovery of NMN in NMN tablets and NMN capsules was between 90.9% and 108.9% with the RSD all no more than 1.9%. In conclusion, this method had good reproducibility, precision, stability and repeatability, could give accurate and reliable results, and could be used for the accurate determination of NMN in actual samples. Through the detection of 6 kinds of commercially available NMN products, NMN was detected in all samples, but the actual contents of some products were less than their nominal content. It was found that some products had the problem of false reporting of NMN content. This study would lay a methodological foundation for formulating the detection method standard of NMN content in NMN related dietary supplement products, and was of far-reaching significance for improving the quality of NMN related products and promote the convenient supervision of related industries.

Background The Tibetan Plateau has an abundance of yak milk resources. The complex microbiota found in traditional fermented yak milk produced and sold by local Tibetans endows the yak milk with unique quality characteristics such as tissue morphology, flavor, and function. However, the diversity of bacterial flora in traditional fermented yak milk have not been elucidated. Methods In this study, 15 samples of fermented yak milk were collected for 16S rRNA high-throughput sequencing to analyze the bacterial community composition and function. Results After filtering for quality, 792,642 high-quality sequences were obtained, and 13 kinds of different phyla and 82 kinds of different genera were identified, of which the phylum Firmicutes (98.94%) was the dominant phylum, Lactobacillus (64.73%) and Streptococcus (28.48%) were identified as the dominant genus, in addition, the bacterial community richness and diversity were higher in Manang Village, followed by Bola Village. Bacterial community richness and diversity in Huage Village were relatively low. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional classification, the microorganisms in traditional fermented yak milk have rich metabolic functions (77.60%). These findings suggest that a large number of bacteria in traditional fermented yak milk contain abundant metabolic genes and can carry out a variety of growth and metabolic activities. This study established a theoretical foundation for further exploring the microbial flora of traditional fermented yak milk in Gannan.

The 3′-untranslated region (3′-UTR) of PD-L1 is significantly longer than the coding sequences (CDSs). However, its role and regulators have been little studied. We deleted whole 3′-UTR region by CRISPR-Cas9. Prognostic analysis was performed using online tools. Immune infiltration analysis was performed using the Timer and Xcell packages. Immunotherapy response prediction and Cox regression was performed using the R software. MicroRNA network analysis was conducted by the Cytoscape software. The level of PD-L1 was significantly and dramatically up-regulated in cells after deleting the 3′-UTR. Additionally, we discovered a panel of 43 RNA-binding proteins (RBPs) whose expression correlates with PD-L1 in the majority of cancer cell lines and tumor tissues. Among these RBPs, PARP14 is widely associated with immune checkpoints, the tumor microenvironment, and immune-infiltrating cells in various cancer types. We also identified 38 microRNAs whose individual expressions are associated with PD-L1 across different cancers. Notably, miR-3139, miR-4761, and miR-15a-5p showed significant associations with PD-L1 in most cancer types. Furthermore, we revealed 21 m6A regulators that strongly correlate with PD-L1. Importantly, by combining the identified RBP and m6A regulators, we established an immune signature consisting of RBMS1, QKI, ZC3HAV1, and RBM38. This signature can be used to predict the responsiveness of cancer patients to immune checkpoint blockade treatment. We demonstrated the critical role of the 3′-UTR in the regulation of PD-L1 and identified a significant number of potential PD-L1 regulators across various types of cancer. The biomarker signature generated from our findings shows promise in predicting patient prognosis. However, further biological investigation is necessary to explore the potential of these PD-L1 regulators.

Abstract Background Infection with Salmonella enterica usually results in diarrhea, fever, and abdominal cramps, but some people become asymptomatic or chronic carrier as a source of infection for others. This study aimed to analyze the difference in serotype, antimicrobial resistance, and genetic profiles between Salmonella strains isolated from patients and those from asymptomatic people in Nantong city, China. Methods A total of 88 Salmonella strains were collected from patients and asymptomatic people from 2017 to 2018. Serotyping, antimicrobial susceptibility testing, and PFGE analysis were performed to analyze the characteristics of these strains. Results Twenty serotypes belonging to 8 serogroups were identified in the 88 Salmonella strains. S. Typhimurium remained to be the predominant serotype in strains from both patients and asymptomatic people. Among the 27 strains from patients, S. Enteritidis and S. Rissen were shown as the other two major serotypes, while S. London, S. Derby, and S. Meleagridis were demonstrated as the other significant serotypes among the 61 strains from asymptomatic people. Antimicrobial resistance testing revealed that 84.1% of strains from both resources were multi-drug resistant. PFGE displayed a highly discriminative ability to differentiate strains belonging to S. Derby, S. Typhimurium, etc., but could not efficiently differentiate serotypes like S. Enteritidis. Conclusions This study’s results demonstrated that S. Typhimurium could cause human infection in both symptomatic and asymptomatic state; S. London, S. Derby, and S. Meleagridis usually cause asymptomatic infection, while S. Enteritidis infection mainly results in human diseases. The high multi-drug resistance rate detected in the antimicrobial resistance and diverse PFGE profiles of these strains implied that the strains were isolated from different sources, and the increased surveillance of Salmonella from both patients and asymptomatic people should be taken to control the disease.

Between 2018 and 2022, a total of 231 PM2.5 samples were collected in Nantong, China, and analyzed online for 16 US EPA PAHs utilizing a variety of analytical methodologies, including high-performance liquid chromatography data analysis, principal component analysis, and characteristic ratio analysis. The seasonal variation and pollution characteristics of 16 PAHs in PM2.5 over a long period in Nantong, China, were analyzed, and correlations and traceability changes with a variety of emission sources were established. Additionally, health assessment models for BaP equivalent concentration, daily exposure dose, lifetime excess risk of cancer, and life expectancy loss were constructed for various ages and genders. The results indicated that the total number of days with BaP concentrations less than the national limit standard of 1.0 ng/m3 was 60.17% (139/231), with rates of 25.40%, 35.71%, and 94.05% from 2019 to 2021, respectively; the total concentration range of 16 PAHs demonstrated a downward trend, but pollution was relatively severe in winter. The seasonal variation showed winter > autumn > spring > summer. The detection rates of 4 and 5 rings were generally high and fluctuated between dropping and increasing. Principal factor analysis and characteristic ratio traceability analysis indicated that PAH pollution is primarily caused by local coal-fired sources and traffic emissions, with a new trend of biomass combustion. Furthermore, BaP remains the primary contributor to carcinogenic factors, and the health risk is higher in females than in males, and in adults than in children. A low level of PAHs in the air may have health benefits. Traffic control and flow restrictions, as well as production restrictions, are all part of Nantong’s COVID-19 pandemic prevention and control policies. These policies contributed to PAH risk prevention and control, as well as pollution reduction.

From the perspective of social and economic regulation, the development trend of regional water security in different periods and under different regulation strengths is evaluated by using the fuzzy set pair analysis method. The results show: the degree of regional water resources security changes from insecurity in the pilot period of water-saving society construction to basic security, and then to security in the planning period, with the enhancement of economic and social regulation. The order of importance of each index is C19 > C1 = C5 > C18 > C14 > C10 > C13 > C3 = C4 > C8 > C7 > C15 > C16 > C12 > C2 > C11 > C17 > C6 > C9, the long-term shortage of water resources is the most important factor, the contribution rate is 60%, but the index weight of economic and social coordination ability is large, and its rapid change causes the improvement of water resources security; the contradiction between the regulation intensity of social and economic indicators in the planning year and the demand for water resources is not matched, and the degree of water security is mainly restricted by the shortage of regional water resources. HIGHLIGHTS The important role of social and economic regulation and control measures in water shortage was discussed.; The influencing factors on water resource shortage were discussed.; The evaluation of water resource safety can be judged by comprehensive connection degree.; The contribution of factors in different years to regional water resources security was analyzed.; Strengthening economic and social control measures is conducive to solving the problems of regional water resource shortage.;

In this study, the microbial diversity in Tibetan flavor Daqu was analyzed based on single molecule real-time sequencing (SMRT). The volatile flavor compounds in Daqu were detected using the headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). In addition, the correlation between various microbes and volatile flavor compounds was explored. Our studies indicated that the dominant bacterial genera in Tibetan flavor Daqu were Oceanobacillus, Kroppenstedtia, Virgibacillus, Enterococcus, Pediococcus, Streptomyces, Saccharopolyspora, Leuconostoc, uncultured_bacterium_f_Lachnospiraceae and Lactobacillus. The dominant fungal genera were Wickerhamomyces, Monascus, Aspergillus and Rhizomucor. 101 volatile compounds were detected in the Daqu samples, including alcohols, acids, esters, aldehydes, hydrocarbons, ketones, ethers, aromatics and pyrazines, and 10 key flavor compounds were identified using the relative odor activity value (ROAV). The results of our correlation analysis showed that Enterococcus was mainly associated with the synthesis of aldehydes such as trans-2-octenal, and uncultured_bacterium_f_lachnospiraceae was associated with the synthesis of most aldehydes. This paper has systematically investigated the physicochemical indices, microbial community structure and flavor compounds of Tibetan flavor Daqu, which is helpful in gaining a deeper understanding of the characteristics of Tibetan flavor Daqu.

Tenebrio molitor larvae is an edible insect with high protein content; researchers have extracted several proteases from gut of T. molitor larvae. However, information on the milk-clotting protease of T. molitor larvae remains unknown. We found that while most of the milk-clotting activity (MCA) was concentrated in the midgut (H) of T. molitor larvae, some activity was also seen in the hindgut (T). To evaluate the possible functional activity of the protease, we used TMT labelling-coupled with LC-MS/MS for proteomics analysis of T and H. The results showed that a total of 223 differentially expressed proteins (DEPs) between T and H. The upregulated proteins were enrich the cysteine-type endopeptidase and serine-type peptidase. A serine endopeptidase with a molecular mass of 29.681 kDa and a C/P value of 104.7 with milk-clotting activity was obtained from midgut of T. molitor larvae by ultrafiltration and multistage chromatography, and characterized by Edman degradation. The main cleavage site in κ-casein (κ-CN) was Lys116-Thr117 bond for the protease, as determined by mass spectrometry analysis. The protease had a Michaelis constant (Km) of 1.39 g/L, an optimal pH of 5.5, and an optimal temperature of 65 °C, indicating it could serve as a new milk coagulant and provide a theoretical basis for the development of insect chymosin.

Porcine circovirus type 3 (PCV3), a novel circovirus, imposes great burdens on the global pig industry. The penside tests for detecting PCV3 are critical for assessing the epidemiological status and working out disease prevention and control programs due to the unavailability of a commercial vaccine. A one-step molecular assay based on visual loop-mediated isothermal amplification (vLAMP) was developed for simple and rapid detection of PCV3. We compared its sensitivity and specificity with TaqMan quantitative real-time polymerase chain reaction (qPCR) and applied the developed assay in the epidemiological study of (n = 407) pooled swine sera collected from almost the entire mainland China during the years 2017–2018. We also explored the feasibility of the vLAMP assay for detecting raw samples without a prior DNA isolation step to expand its application capability. Results showed that the vLAMP assay could reliably detect the PCV3 cap gene with a detection limit of 10 DNA copies equal to that of the Taqman qPCR assay. In the epidemiological study, the PCV3 positive detection rate for 407 swine pooled sera detected by the vLAMP assay was 37.35% (152/407), whereas it was 39.01% (159/407) for Taqman qPCR. For the detection method without genome extraction, the results kept satisfactory specificity (100%) but displayed lower sensitivity (100% for CT < 32), indicating the direct detection is not sensitive enough to discriminate the samples with low viral loads. The one-step vLAMP is a convenient, rapid, and cost-effective diagnostic for penside detection and will enable the epidemiological surveillance of PCV3, which has widely spread in mainland China.

Yak is a rare breed of resources in Tibetan Plateau, with high protein and low-fat content, and has other important application value. Yaks are managed by herders and slaughtered in various ages, changing from three years to twelve years of age, and there has a significant difference on meat tenderness in different ages. This study was conducted to investigate the effects of age at harvest, ageing time and the correlation analysis to meat tenderness calpains activity. The work may be used to establish a classification system and grading standards for yak meat. Four groups were established as fewer than 3 years-old, 3-5 years-old, 5-7 years-old and more than 7-years old. The results demonstrated that the content of tenderness has significantly different (P

In current study, bacterial diversity and community in different tissues of pork bacon were determined using high-throughput sequencing. In total, six phyla and 111 bacterial genera were identified. Among them, three dominant genera (Staphylococcus, Acinetobacter, and Macrococcus) were shared by all bacon samples. The linear discriminant analysis showed that 24 bacterial taxa significantly differentiated between the tissues. Results of non-metric Multidimensional Scaling and redundancy analysis showed that physicochemical characteristics of the tissue prominently structured the bacterial communities. Network analysis also illustrated that tissue type was an important factor impacting the bacterial interactions in different types of tissue. The results of current study can add valuable insights to the traditional homemade pork bacon.

Visual loop-mediated isothermal amplification (LAMP) is qualified to be applied in the field to detect pathogens due to its simplicity, rapidity and cost saving. However, the color changes in currently reported visual reverse transcription LAMP (RT-LAMP) for foot-and-mouth disease virus (FMDV) detection are not so obvious to the naked eye, so interpretation of results is troublesome. In this study, a new naked-eye visual RT-LAMP to detect all seven distinct serotypes of FMDV was established based on the 3D genes by using pH-sensitive neutral red as the indicator, rendering a sharp contrast of color changes between the negative (light orange) and the positive (pink). Analytical sensitivity tests showed that the detection limit of the visual RT-LAMP was 104 copies/µL while those were 103 and 104 copies/µL for the RT-qPCR and conventional RT-PCR methods, respectively. Specificity tests proved that the established visual RT-LAMP assay had no cross-reactivity with other common livestock viruses. Furthermore, the analysis of 59 clinical samples showed 98.31% and 100% concordance with the RT-qPCR and the RT-PCR, respectively. The pan-serotypic FMD visual RT-LAMP assay could be suitable for a pen-side test of all seven serotypes of FMDV because the results could be easily distinguished by the naked eye without the requirement of complicated instruments and professional technicians. Hence, the novel method may have a promising prospect in field tests which exert an important role in monitoring, preventing, and controlling FMD, especially in regions with no PCR or qPCR instrument available.

This study investigated the pollution characteristics, exposure levels and health risk assessments of seven kinds of biogenic amines (BAs) in eight varieties of canned sea fish products (n = 131) on the Chinese market. Carbon spheres QuEChERS mixed dispersion solid phase extraction combined with HPLC was used for the classification and analysis of batch samples. The average recovery of single BAs obtained by this method is 92.3~97.7%, and the relative standard deviation is 1.9~4.8%. Different varieties of samples have different degrees of pollution, the mass concentration of single BAs range 0.45~27.74 mg/kg, and the total concentration of ΣBAs range 18.77~368.50 mg/kg, of which the concentration of Σ4BAs range 11.53~368.50 mg/kg. The composition of four BAs is mainly putrescine, cadaverine, histamine and tyramine, which always play an important role in the exposure level and risk assessment of samples. The exposure level of BAs in the human body ranges 67.03~209.52 μg∙kg−1∙d−1. The health risk assessment shows that the gender trend of exposure risk level of BAs is male > female (young age), female > male (middle and old age), the age trend is young age > old age > middle age, and the regional trend is city > countryside. The food safety index of BAs in samples is 0.0062~0.0195, which is far less than 1, so the risk is within the controllable range.

This study aimed to the variations of fungal diversity and community structure in different parts of traditional homemade Sichuan pork bacon. A total of seven phyla and 91 fungal genera were identified. Among them, Ascomycota and Basidiomycota were the first and second most abundant phyla in the bacon tissues. In addition, five dominant genera (Aspergillus, Candida, Debaryomyces, Malassezia, and Penicillium) were shared by all bacon tissues. The numbers of OTUs unique to individual groups were 14, 67, and 65 for the muscle tissue, the adipose tissue, and pork skin, respectively. Linear discriminant analysis showed that a total of 31 taxa significantly differed among the groups. Results of redundancy analysis indicated that fat content, protein content, aw, and pH of bacon tissue shaped the bacon fungal communities. Results of network analysis also indicated that tissue type was a crucial factor influencing the fungal interactions in different tissues. This study can lay a foundation for further isolation and identification of fungi in the product and provides a basis for further research of food health in homemade traditional pork bacon.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases showed that the immune-related gene (IRG) hematopoietic cell signal transducer (HCST) could provide guidance for the diagnosis, prognosis, and treatment of ccRCC. The RNA-seq data of ccRCC tissues were extracted from two databases: TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/). Corresponding clinical information was downloaded from TCGA. Immune-related gene data were extracted from the IMMPORT website (https://www.immport.org/). Differential analysis with R software (https://www.r-project.org/) was used to obtain a prognosis model of ccRCC IRGs. The differences were combined with the clinical data to assess the usefulness of the HCST as a prognostic biomarker. Based on data obtained from the Oncomine (https://www.oncomine.org/), Human Protein Atlas (https://www.proteinatlas.org/), and PubMed (https://pubmed.ncbi.nlm.nih.gov/) databases, the expression levels of the HCST in ccRCC, clinical-pathological indicators of relevance, and influence on prognosis were analyzed. Regulation of the HCST gene in ccRCC was assessed by gene set enrichment analysis (GSEA). In TCGA/GEO databases, the high HCST expression in tumor tissues was significantly correlated to the TMN stage, tumor grade, invasion depth, and lymphatic metastasis (p < 0.05). The overall survival (OS) of patients with high HCST gene expression was significantly lower than that of patients with low HCST gene expression (p < 0.001). Multivariate Cox regression analysis suggested that the HCST expression level [hazard ratio (HR) = 1.630, 95% confidence interval (CI) = 1.042–2.552], tumor cell grade (HR = 1.829, 95% CI = 1.115–3.001), and distant metastasis (HR = 2.634, 95%, CI = 1.562–4.442) were independent risk factors affecting the OS of ccRCC patients (all, p < 0.05). The GSEA study showed that there was significant enrichment in cell adhesion, tumorigenesis, and immune and inflammatory responses in HCST high expression samples. Hematopoietic cell signal transducer expression was closely associated with the levels of infiltrating immune cells around ccRCC tissues, especially dendritic cells (DCs). In conclusion, the present study suggested that the HCST was interrelated to the clinicopathology and poor prognosis of ccRCC. High HCST expression was also closely correlated with the levels of tumor-infiltrating immune cells, especially DCs.

Although genetic variants in autophagy pathway genes were associated with the risk of oral cancers and early development in embryos, their associations with non-syndromic cleft lip with or without cleft palate (NSCL/P) risk remained unclear. A two-stage case-control study (2,027 NSCL/P cases and 1,843 controls) was performed to investigate the associations between single nucleotide polymorphisms (SNPs) in 23 autophagy pathway genes and NSCL/P susceptibility. The logistic regression model was used to calculate effects of SNPs on NSCL/P susceptibility. Gene-based analysis was performed via the sequence kernel association test (SKAT) and multi-marker analysis of genomic annotation (MAGMA) methods. Expression quantitative trait loci (eQTL) analysis was conducted using NSCL/P lip tissue samples. Gene expression during embryonic development was evaluated using RNA-Seq. Functional roles were explored by luciferase activity assay, cell apoptosis, proliferation, and cycle in vitro. Rs2301104 in HIF1A was significantly associated with NSCL/P susceptibility in the combined analysis (OR: 1.29, 95% CI: 1.09–1.29, P = 3.39 × 10–03), and showed strong evidence of association heterogeneity (P = 9.06 × 10–03) with obvious association in the female (OR: 1.80; 95% CI: 1.32–2.45; P = 1.79 × 10–04). The G allele of rs2301104 was associated with enhanced transcription activity and high expression of HIF1A compared with that of C allele. Moreover, rs2301104 exhibited an eQTL effect for HIF1A with its GC/CC genotypes associated with decreased HIF1A expression compared with those with GG genotypes (P = 3.1 × 10–2). Knockdown of HIF1A induced cell apoptosis and inhibited cell proliferation in human embryonic palate mesenchyme (HEPM) and human oral epithelium cells (HOEC). This study demonstrated that rs2301104 in autophagy pathway gene HIF1A was associated with susceptibility of NSCL/P.

Doushen, a traditional Chinese fermented soybean product, may be spiced or spicy depending on whether pepper powder is added. While numerous studies have investigated the microbial communities of other fermented foods, little is known on the fungal diversity of Doushen. Therefore, in this study, we investigated the fungal community and diversity in both spiced and spicy Doushen. Our results revealed that fungal species richness significantly differed between the samples with different flavors. A total of nine phyla and 188 fungal genera were identified, and Ascomycota and Aspergillus were predominant in all samples. Based on linear discriminant analysis, a total of 57 OTUs were significantly different between the two samples. Results of non-metric multidimensional scaling and unweighted pair-group analysis suggested that the presence of pepper powder affects the microbial community in Doushen. Network analysis showed that microbial interactions between fungal communities in Doushen with different flavors were significantly different. The results on the enumeration and identification of fungi were consistent with the composition of the dominant genera in the samples with different flavors. This study provides a theoretical basis for future research on food ecology in Doushen.

Abstract Background Adipose-derived stem cells (ADSCs) are an attractive cell source for bone tissue engineering and have great potential for bone regeneration and defect repair. The transcriptional coactivator with PDZ-binding motif (TAZ) has been demonstrated to modulate osteogenic and adipogenic differentiation of mesenchymal stem cells. However, its roles during ADSC differentiation and therapeutic potentials for bone regeneration have as yet not been well established. Methods TAZ expression was measured during osteogenic differentiation of ADSCs in vitro. Both loss-of-function and gain-of-function approaches by TAZ knockdown or enforced overexpression were utilized to determine its functions during osteogenic differentiation of ADSCs. TM-25659, a chemical activator of TAZ, was used to determine whether pharmacological activation of TAZ in ADSCs enhanced osteogenic differentiation in vitro and bone formation in animal models. The molecular mechanisms underlying TAZ in promoting osteogenesis of ADSCs were also explored. Results Increased TAZ expression was observed during osteogenic differentiation of human ADSCs. TAZ knockdown resulted in compromised osteogenic differentiation and enhanced adipogenic differentiation of ADSCs. In contrast, enforced TAZ overexpression yielded increased osteogenic differentiation and bone regeneration in vivo, and impaired adipogenic differentiation of ADSCs. Pharmacological activation of TAZ by its chemical activator TM-25659 facilitated osteogenic differentiation of ADSCs. Noticeably, transient treatment of ADSCs with TM-25659 or intraperitoneal injection of TM-25659 significantly enhanced bone regeneration of ADSCs loaded with porous β-TCP in vivo. Mechanistically, TM-25659 exposure significantly promoted TAZ phosphorylation and nuclear translocation, and potentiated the assembly of the TAZ-Runx2 complex. Subsequently, the TAZ-Runx2 complex was further recruited to the promoter of osteocalcin and in turn enhanced its transcription. Conclusions Our findings indicate that TAZ is a key mediator that promotes ADSC commitment to the osteoblast lineage. Pharmacological activation of TAZ in ADSCs might become a feasible and promising approach to enhance bone regeneration and repair.

Src is a prototypical signaling non-receptor protein tyrosine kinase that interconverts between distinct conformations. Here the authors use variants of the kinase-inhibitor dasatinib to define three specific conformational states of the Src kinase and shed insight on the effect of conformation-specific inhibitors on Src dynamics.

Qula is a cheese-like product usually prepared with unpasteurized yak milk under open conditions, with both endogenous and exogenous microorganisms involved in the fermentation process. In the present study, 15 Qula samples were collected from five different regions in China to investigate the diversity of microbial communities using high-throughput sequencing targeting the V3–V4 region of 16S rRNA gene. The bacterial diversity significantly differed among samples of different origins, indicating a possible effect of geography. The result also showed that microbial communities significantly differed in samples of different origin and these differences were greater at the genus than the phylum level. A total of six phyla were identified in the samples, and Firmicutes and Proteobacteria had a relative abundance >20%. A total of 73 bacterial genera were identified in the samples. Two dominant genera (Lactobacillus and Acetobacter) were common to all samples, and a total of 47 operational taxonomic units at different levels significantly differed between samples of different origin. The predicted functional genes of the bacteria present in samples also indicated differences in bacterial communities between the samples of different origin. The network analysis showed that microbial interactions between bacterial communities in Qula were very complex. This study lays a foundation for further investigations into its food ecology.

Douchi has been consumed as a flavoring ingredient for centuries. During production of douchi, numerous microorganisms play important roles in the hydrolysis and conversion of proteins and starch, which are related to the quality and flavor of the end product. Therefore, in the present study, the microbial diversity in two types of home-made traditional bacterial douchi from Gansu province in northwest China was studied by high-throughput sequencing, and a corresponding analysis of the bacterial and fungal communities were conducted. The results showed that geography may have impacted the fungal diversity and the bacterial and fungal species richness in the samples. The results also showed that the microbial community was significantly different in samples of different origin and the difference in the microbial community at the genus level was greater than at phylum level. Two dominant bacterial genera (Bacillus and Ignatzschineria) were common to the two samples, both of which had a relative abundance of more than 1%. Four bacterial genera (Staphylococcus, Aerococcus, Geobacillus, and Jeotgalicoccus) were dominant only in the sample from Qingyang, while another four (Carnobacterium, Proteus, Aneurinibacillus, and Enterococcus) were dominant only in the sample from Longnan. Two dominant fungal genera (Pichia and Candida) were shared by the two samples. Additionally, two genera (Rhodosporidium and Yarrowia) were dominant only in samples from Longnan. The functional genes of the bacteria present in samples indicated that a significant difference was observed in the bacterial community between samples of different origin. We also found that microbial interactions between bacterial and fungal communities in the samples were very complex. This study provides previously unknown information regarding the impact of the environment on microbial communities in douchi and lays a foundation for further investigations into food ecology in bacterial douchi.

[This corrects the article DOI: 10.1371/journal.pone.0194876.].

Non-syndromic tooth agenesis (or non-syndromic congenitally missing tooth) is one of the most common congenital defects in humans affecting the craniofacial function and appearance. Single nucleotide polymorphisms (SNPs) have been associated with an individual's susceptibility to these anomalies. The aim of the present study was therefore to investigate the roles of the potentially functional SNPs of BMP2 in the occurrence of tooth agenesis. Overall, four potentially functional SNPs of BMP2 (rs15705, rs235768, rs235769 and rs3178250) were selected, and their associations with the susceptibility of tooth agenesis were evaluated in a case-control study of 335 non-syndromic tooth agenesis cases and 444 healthy controls. The SNPs rs15705 and rs3178250 were found to be associated with an individual's risk of tooth agenesis (P = 0.046 and P = 0.039, respectively). Both SNPs showed an increased risk of mandibular incisor agenesis (rs15705, AA/AC vs. CC = 1.58, 95% CI = [1.06-2.34], P = 0.024; rs3178250, TT/TC vs. CC = 1.60, 95% CI = [1.08-2.37], P = 0.020). Bioinformatics analysis indicated that these two SNPs located at the 3'-untranslated region (3'-UTR) of BMP2 might alter the binding ability of miR-1273d and miR-4639-5p, respectively, which was confirmed by luciferase activity assays in the 293A and COS7 cell lines (P < 0.001 in 293A and P < 0.01 in COS7 for miR-1273d; and P < 0.001 in both cells for miR-4639-5p). Furthermore, BMP2 mRNA expression decreased after transfecting either miR-1273d or miR-4639-5p into these two cell lines (P < 0.01 in 293A and P < 0.001 in COS7 for miR-1273d, and P < 0.01 in both cell lines for miR-4639-5p). Taken together, our findings indicate that rs15705 and rs317250 are associated with the susceptibility of non-syndromic tooth agenesis by possibly affecting miRNAs and mRNA interaction.

A common virulence mechanism among bacterial pathogens is the use of specialized secretion systems that deliver virulence proteins through a translocation channel inserted in the host cell membrane. During Yersinia infection, the host recognizes the type III secretion system mounting a pro-inflammatory response. However, soon after they are translocated, the effectors efficiently counteract that response. In this study we sought to identify YopD residues responsible for type III secretion system function. Through random mutagenesis, we identified eight Y. pseudotuberculosis yopD mutants with single amino acid changes affecting various type III secretion functions. Three severely defective mutants had substitutions in residues encompassing a 35 amino acid region (residues 168-203) located between the transmembrane domain and the C-terminal putative coiled-coil region of YopD. These mutations did not affect regulation of the low calcium response or YopB-YopD interaction but markedly inhibited MAPK and NFκB. [corrected] activation. When some of these mutations were introduced into the native yopD gene, defects in effector translocation and pore formation were also observed. We conclude that this newly identified region is important for YopD translocon function. The role of this domain in vivo remains elusive, as amino acid substitutions in that region did not significantly affect virulence of Y. pseudotuberculosis in orogastrically-infected mice.

HfAlO2 based resistive random access memory (RRAM) devices were fabricated using atomic layer deposition by modulating deposition cycles for HfO2 and Al2O3. Effect of ozone treatment on the resistive switching uniformity of HfAlO2 based RRAM devices was investigated. Compared to the as-fabricated devices, the resistive switching uniformity of HfAlO2 based RRAM devices with the ozone treatment is significantly improved. The uniformity improvement of HfAlO2 based RRAM devices is related to changes in compositional and structural properties of the HfAlO2 resistive switching film with the ozone treatment.

Mechanical regulation of bone formation involves a complex biophysical process, yet the underlying mechanisms remain poorly understood. Polycystin-1 (PC1) is postulated to function as a mechanosensory molecule mediating mechanical signal transduction in renal epithelial cells. To investigate the involvement of PC1 in mechanical strain-induced signaling cascades controlling osteogenesis, PKD1 gene was stably silenced in osteoblastic cell line MC3T3-E1 by using lentivirus-mediated shRNA technology. Here, our findings showed that mechanical tensile strain sufficiently enhanced osteogenic gene expressions and osteoblastic proliferation. However, PC1 deficiency resulted in the loss of the ability to sense external mechanical stimuli thereby promoting osteoblastic osteogenesis and proliferation. The signal pathways implicated in this process were intracellular calcium and Akt/β-catenin pathway. The basal levels of intracellular calcium, phospho-Akt, phospho-GSK-3β and nuclear accumulation of active β-catenin were significantly attenuated in PC1 deficient osteoblasts. In addition, PC1 deficiency impaired mechanical strain-induced potentiation of intracellular calcium, and activation of Akt-dependent and Wnt/β-catenin pathways, which was able to be partially reversed by calcium ionophore A23187 treatment. Furthermore, applications of LiCl or A23187 in PC1 deficient osteoblasts could promote osteoblastic differentiation and proliferation under mechanical strain conditions. Therefore, our results demonstrated that osteoblasts require mechanosensory molecule PC1 to adapt to external mechanical tensile strain thereby inducing osteoblastic mechanoresponse, partially through the potentiation of intracellular calcium and downstream Akt/β-catenin signaling pathway.

BACKGROUND: Matrix metalloproteinase-1 (MMP-1) plays an important role during the destruction of periodontal tissue. Although multiple studies had focused on the association between MMP-1 g.-1607dupG and periodontitis susceptibility, the results remained inconclusive. The purpose of this meta-analysis was to explore its role in the development of periodontitis. METHODS: Retrieved studies from Pubmed, Web of Science, Medline and Google Scholar Search regarding MMP-1 g.-1607dupG and periodontitis susceptibility were included into the final analysis with definite selection and exclusion criteria. Overall and stratified analyses based on disease type, severity, ethnicity and smoking status were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between MMP-1 g.-1607dupG and periodontitis susceptibility, while Q test and Egger's test were adopted respectively to assess heterogeneity among studies and publication bias. RESULTS: A total of 1580 periodontitis cases and 1386 controls in 11 case-control studies were included in the meta-analysis. The pooled results showed significant association between periodontitis susceptibility and MMP-1 g.-1607dupG polymorphism in homozygote (2G/2G versus 1G/1G, OR = 1.50, 95% CI = 1.02-2.20) and dominant model analysis (2G/2G+2G/1G versus 1G/1G, OR = 1.28, 95% CI = 1.04-1.57). For subgroups by type of periodontitis, increased risk of chronic periodontitis was observed on heterozygote (2G/1G versus 1G/1G, OR = 2.01, 95% CI = 1.58-2.56) and dominant model (OR = 1.27, 95% CI = 1.03-1.57). Furthermore, similar association was also detected in severe chronic periodontitis (2G/2G versus 1G/1G, OR = 2.15, 95% CI = 1.35-3.43; 2G/2G+2G/1G versus 1G/1G, OR = 1.64, 95% CI = 1.12-2.39; 2G/2G versus 2G/1G+1G/1G, OR = 1.86, 95% CI = 1.31-2.64). CONCLUSIONS: Our meta-analysis demonstrated that MMP-1 g.-1607dupG polymorphism was associated with chronic periodontitis, especially the severity of the disease condition.