(Z)-2-Hydr­oxy-3-(4-methoxy­phen­yl)acrylic acid

In the structure of the title compound, C10H10O4, inversion dimers linked by pairs of O—H⋯O hydrogen bonds link the carboxylic acid groups. Further O—H⋯O links cross-link the dimers into sheets running along the b-axis direction

(Z)-2-Acetamido-3-(4-chloro­phen­yl)acrylic acid

In the title compound, C11H10ClNO3, the mol­ecule consists of a benzene ring and an acetamido­acrylic acid unit on opposite sides of the C=C double bond. In the crystal, inter­molecular O—H⋯O and N—H⋯O hydrogen bonds assemble the mol­ecules into infinite two-dimensional ribbons. These ribbons are linked into a network by inter­molecular C—H⋯π contacts

Dietary fatty acids and risk of non-alcoholic steatohepatitis: A national study in the United States

BackgroundNon-alcoholic steatohepatitis (NASH), the early invertible stage of non-alcoholic fatty liver disease, has become a public health challenge due to the great burden and lack of effective treatment. Dietary nutrients are one of the modifiable factors to prevent and slow down disease progression. However, evidence linking dietary fatty acids intake and risk of NASH is lacking.ObjectivesThis study aimed to examine the association between dietary total saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), their subtypes, the ratio of unsaturated (UFAs) to SFAs, and the risk of NASH among a nationwide population in the United States.MethodsThis cross-sectional study was conducted among 4,161 adults in the national health and nutrition examination survey in 2017–2018 cycle. Moreover, NASH was defined by transient elastography. Dietary fatty acids were assessed using a validated 24-h food recall method. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsA total of 2,089 (50.2%) participants with NASH were identified. Compared with participants in the bottom tercile of dietary intakes of total PUFAs, those in the highest tercile had lower risk of NASH, with an adjusted OR of 0.67 (95% CI: 0.46–0.97). Similar associations were found between the subtype of PUFA 18:3 and NASH, while the fully adjusted OR in the highest tercile was 0.67 (95% CI: 0.47–0.96). Interactions of dietary PUFAs and body mass index (BMI) could be found influencing NASH risk. Stronger associations of dietary total PUFAs intakes with NASH risk were found in obese participants (OR, 95% CI: 0.41, 0.22–0.75) than in the non-obese participants (OR, 95% CI: 1.00, 0.70–1.43; p-interaction = 0.006). Similar effects on risk of NASH were also observed between BMI and dietary intakes of PUFA 18:3. However, no significant associations were observed between NASH risk and dietary total SFAs, MUFAs, their subtypes as well as the ratio of UFAs to SFAs.ConclusionDietary intakes of total PUFAs, as well as its subtype of PUFA 18:3, were inversely associated with risk of NASH. The further large prospective studies need to be conducted to confirm the findings of this study

Human papillomavirus viral load as a useful triage tool for non-16/18 high-risk human papillomavirus positive women: A prospective screening cohort study

ASCCP cervical cancer screening guidelines recommend triaging high-risk human papillomavirus (hrHPV) positive women with cytology and genotyping, but cytology is often unavailable in resource-limited areas. We compared the long-term risk of cervical cancer and precancers among type-specific hrHPV-positive women triaged by viral load to cytology and visual inspection with acetic acid (VIA).A cohort of 1742 Chinese women was screened with cytology, VIA, and Hybrid Capture 2 (HC2) test and followed for ten years. All HC2-positive samples were genotyped. Viral load was measured by HC2 relative light units/cutoff (RLU/CO). Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) for type-specific hrHPV viral load was estimated using Kaplan-Meier methods.Baseline hrHPV viral load stratified by specific genotypes was positively correlated with prevalent cytological lesions. Ten-year CIR of CIN2 + was associated with cytological lesions and viral load. Among HPV 16/18-positive women, ten-year CIR of CIN2 + was high, even with normal cytology (15.3%), normal VIA (32.4%), viral load with RLU/CO < 10 (23.6%) or RLU/CO < 100 (33.8%). Among non-16/18 hrHPV positive women, ten-year CIR of CIN2 + was significantly stratified by cytology grade of atypical squamous cell of undetermined significance or higher (2.0% VS. 34.6%), viral load cutoffs at 10 RLU/CO (5.1% VS. 27.2%), at 100 RLU/CO (11.0% VS. 35.5%), but not by VIA (19.1% VS. 19.0%).Our findings support the guidelines in referring all HPV16/18 positive women to colposcopy and suggest triaging non-16/18 hrHPV positive women using viral loads in resource-limited areas where cytology screening was inaccessible

Identification and analysis of differential miRNA–mRNA interactions in coronary heart disease: an experimental screening approach

ObjectiveThis aim of this study is to screen the differential molecules of kidney deficiency and blood stasis (KDBS) syndrome in coronary heart disease by high-throughput sequencing. In addition, the study aims to verify the alterations in the expression levels of miR-4685-3p and its regulated downstream, namely, C1QC, C4, and C5, using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), and to determine whether the complement and coagulation cascade pathway is the specific pathogenic pathway.MethodsPatients diagnosed with unstable angina pectoris with KDBS syndrome, patients with non-kidney deficiency blood stasis (NKDBS) syndrome, and a Normal group were recruited. The clinical symptoms of each group were further analyzed. Illumina's NextSeq 2000 sequencing platform and FastQC software were used for RNA sequencing and quality control. DESeq software was used for differential gene expression (DGE) analysis. qPCR and ELISA verification were performed on DGE analysis.ResultsThe DGE profiles of 77 miRNA and 331 mRNA were selected. The GO enrichment analysis comprised 43 biological processes, 49 cell components, and 42 molecular functions. The KEGG enrichment results included 40 KEGG pathways. The PCR results showed that, compared with the Normal group, the miR-4685-3p levels decreased in the CHD_KDBS group (P = 0.001), and were found to be lower than those observed in the CHD_NKDBS group. The downstream mRNA C1 regulated by miR-4685-3p showed an increasing trend in the CHD_KDBS group, which was higher than that in the Normal group (P = 0.0019). The mRNA C4 and C5 in the CHD_KDBS group showed an upward trend, but the difference was not statistically significant. ELISA was utilized for the detection of proteins associated with the complement and coagulation cascade pathway. It was found that the expression level of C1 was significantly upregulated in the CHD_KDBS group compared with the Normal group (P &lt; 0.0001), which was seen to be higher than that in the CHD_NKDBS group (P &lt; 0.0001). The expression levels of C4 and C5 in the CHD_KDBS group were significantly lower than the Normal group, and were lower than that in the CHD_NKDBS group (P &lt; 0.0001).ConclusionThe occurrence of CHD_KDBS might be related to the activation of the complement and coagulation cascade pathway, which is demonstrated by the observed decrease in miR-4685-3p and the subsequent upregulation of its downstream C1QC. In addition, the expression levels of complement C4 and C5 were found to be decreased, which provided a research basis for the prevention and treatment of this disease

The rational dose for MaXingShiGan decoction is crucial for its clinical effectiveness in treating bronchial pneumonia: three randomized, double-blind, dose-parallel controlled clinical studies

Objective: Evaluate the impact of adjusting the overall dose, Gypsum Fibrosum [Mineral; Gypsum] (ShiGao, SG) dose, and Prunus armeniaca L. [Rosaceae; Semen Armeniacae Amarum] (KuXingRen, KXR) dose on the efficacy of MaXingShiGan Decoction (MXSG) in treating children with bronchial pneumonia (Wind-heat Blocking the Lung), in order to provide strategy supported by high-quality evidence for the selection of rational clinical doses of MXSG.Methods: Based on the basic dose of MXSG, we conducted three randomized, double-blind, dose parallel controlled, multicenter clinical trials, involving adjustments to the overall dose, SG dose, and KXR dose, and included 120 children with bronchial pneumonia (Wind-heat Blocking the Lung) respectively. And the patients were divided into low, medium, and high dose groups in a 1:1:1 ratio, with 40 cases in each group. The intervention period lasted for 10 days. The primary outcome was the clinical cured rate, while the secondary outcomes included the effectiveness in alleviating major symptoms of bronchial pneumonia (including fever, cough, dyspnea, and phlegm congestion). And the occurrence of adverse events was recorded.Results: We first recorded and analyzed the baseline characteristics of the three studies, including age, gender, height, and so on. The results indicated that there were no significant differences among the dose groups within each study. For the study adjusting the overall dose of MXSG, the results showed that both the medium-dose group and high-dose group had significantly higher clinical cured rates compared to the low-dose group (Chi-square value 9.01, p = 0.0111). However, there was no significant benefit between the high-dose group and the medium-dose group (81.58% vs. 81.08%). Regarding phlegm congestion, excluding fever, cough, and dyspnea, both the medium-dose group and high-dose group had significantly higher clinical cured rates than the low-dose group (Chi-square value 6.31, p = 0.0426), and there was no significant benefit between the high-dose group and the medium-dose group (69.23% vs. 75.00%). A total of 5 adverse events were observed, of which only 1 case in the medium-dose group was possibly related to the experimental medication. For the study adjusted the SG dose in MXSG, the results showed that the high-dose group had the highest clinical cured rate, but the inter-group difference was not statistically significant (Chi-square value 3.36, p = 0.1864). The area under the curve (AUC) for cough in the medium-dose group was significantly lower than in the low-dose group and high-dose group (F-test value 3.14, p = 0.0471). Although no significant differences were observed in fever and dyspnea among the groups, the AUC in the high-dose group was lower than in the medium-dose and low-dose groups. In comparing the complete defervescence time, both the high-dose group (p &lt; 0.0001) and the medium-dose group (p = 0.0015) achieved faster than the low-dose group. The high-dose group slightly outperformed the medium-dose group (0.50 (0.50, 0.80) vs. 0.80 (0.40, 1.40)), although the difference was not significant. In the medium-dose group, 1 adverse event was observed, but it was not related to the experimental medication. For the study adjusted the KXR dose in MXSG, the results showed that both the medium-dose group and high-dose group had significantly higher cured rates compared to the low-dose group (Chi-square value 47.05, p &lt; 0.0001). However, there was no significant benefit comparing the high-dose group to the medium-dose group (90.00% vs. 92.50%). Regarding clinical symptoms, the results indicated that for cough (F-test value 3.16, p = 0.0460) and phlegm congestion (F-test value 3.84, p = 0.0243), the AUC for both the medium-dose group and high-dose group were significantly lower than in the low-dose group. Although there was benefit in the high-dose group compared to the medium-dose group, it was not statistically significant. No adverse events were observed during the study period.Conclusion: The synthesis of the three conducted clinical studies collectively indicates that for children with bronchial pneumonia (Wind-heat Blocking the Lung), the basic clinical dose of MXSG may represents an optimal intervention dose based on the accumulated clinical experience of doctors. If the dose is insufficient, the clinical effects might be compromised, but using a higher dose does not significantly enhance benefits. Concerning different symptoms, increasing the overall formula’s dose has a favorable impact on improving phlegm congestion, increasing the SG is effective in improving symptoms such as fever, cough, and dyspnea, while higher dose of KXR is effective in alleviating cough and phlegm congestion. These findings suggest that for MXSG, achieving the optimal intervention dose is crucial to achieve better clinical efficacy. For the SG and KXR, if certain symptoms are more severe, increasing the dose can be considered within safe limits, can lead to significant clinical benefits in symptom improvement. This also explains why the dose of MXSG might vary among clinical doctors, while maintaining a balance between safety and effectiveness. Of course, our study is still exploratory clinical trials, and further studies are needed to confirm our findings.Clinical Trial Registration:https://www.chictr.org.cn/index.html; Identifier: ChiCTR-TRC-13003093, ChiCTR-TRC-13003099

The DSF family of quorum sensing signals: diversity, biosynthesis, and turnover

The diffusible signaling factor (DSF)-based quorum sensing (QS) system has emerged as a widely conserved cell–cell communication mechanism in Gram-negative bacteria. Typically, signals from the DSF family are cis-2-unsaturated fatty acids which regulate diverse biological functions. Recently, substantial progress has been made on the characterization of new members of this family of signals. There have also been new developments in the understanding of the biosynthesis of these molecules where dual enzymatic activities of the DSF synthase and the use of various substrates have been described. The recent discovery of a naturally occurring DSF turnover mechanism and its regulation provides a new dimension in our understanding of how DSF-dependent microorganisms modulate virulence gene expression in response to changes in the surrounding environment