Uncovering the Power of HSCCC: Separation of Diastereomeric and Regioisomeric Styrylpyrones from the Stem Bark of Goniothalamus leiocarpus.

The plant Goniothalamus leiocarpus of the Annonaceae family is used as an alternative medicine in tropical regions. Applying high-speed counter current chromatography (HSCCC), eight new bioactive styrylpyrone isomers, including 6R,7S,8R,2'S-goniolactone B (1), 6S,7S,8S,2'S-goniolactone B (2), 6R,7R,8R,2'S-goniolactone B (3), 6R,7S,8S,2'S-goniolactone C (4), 6R,7S,8R,2'S-goniolactone C (5), 6S,7R,8S,2'S-goniolactone C (6), and two positional isomers, 6R,7R,8R,2'S-goniolactone G (7) and 6S,7R,8R,2'S-goniolactone G (8), were isolated from a chloroform fraction (2.1 g) of G. leiocarpus, which had a prominent spot by TLC analysis. The structures of the new compounds were elucidated by MS, NMR, IR, and UV spectra, and their absolute configurations were determined by Mosher's method, ECD, and X-ray diffraction analysis. The isolates are characteristic components found in plants of the genus Goniothalamus and consist of two structural moieties: a styrylpyrone and a dihydroflavone unit. The isolation of the eight new compounds demonstrates the effectiveness of HSCCC in separating the isomers of natural styrylpyrone. In a bioactivity assessment, compounds 1 and 6 exhibited cytotoxic effects against the human colon carcinoma cell lines LS513 and SW620 with IC50 values ranging from 1.6 to 3.9 µM. Compounds 1, 2, 7, and 8 showed significant synergistic activity against antibiotic-resistant Staphylococcus aureus strains.

Activities of BiFeO3/carbon-dots catalysts in piezo-photocatalytic degradation of ciprofloxacin upon light/ultrasonic excitation.

Designing catalysts that can effectively make use of renewable energy benefits to solve the current challenges of environmental pollution and increasing energy demands. Piezo-photocatalysis that can utilize solar energy and natural vibration-energy has emerged as a "green" technique. In this work, we fabricated BiFeO3/C nano composites that can harvest solar and vibration energies and degrade organic pollutants. The incorporated carbon quantum dots bring about more efficient visible light absorbance and separation of photoinduced electron-hole pairs. The piezoelectric polarization further suppresses the recombination of photoinduced electron-hole pairs. The catalysts own higher reaction rates in piezo-photocatalysis and the BiFeO3/C-0.12 shows the highest degradation efficiency (k-value of 0.0835 min-1).

RNA-Seq Analysis of ceRNA-Related Networks in the Regulatory Metabolic Pathway of Mice with Diabetic Nephropathy Subjected to Empagliflozin Intervention.

OBJECTIVE: We conducted bioinformatics analysis of the gene chip data of empagliflozin for diabetic nephropathy (DN). The differentially expressed genes (DEGs) between DN and control mice and between DN and DN treated with empagliflozin (DNE) mice were screened to explore the related metabolic pathogenesis and predict the potential competing endogenous RNA (ceRNA)-related networks' metabolic mechanism of the empagliflozin effect on DN. METHODS: The intersection of DEGs in mice between the control and DN groups and between the DN and DNE groups was selected. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were performed, and the metabolic items involving the most genes in the coregulation were considered. A protein-interaction network was constructed with the STRING website. Cytoscape software and its plug-ins were utilised to analyse the hotspot differential genes. The noncoding RNAs in which the differential genes may play a role were obtained from the miRanda, miRDB, and TargetScan databases to establish network diagrams. RESULTS: Analysis of the diabetes and control groups showed that 424 genes were upregulated and 354 were downregulated. In the analysis of DEGs between the DN and diabetic groups, the comparison between the diabetic and empagliflozin groups showed that 430 genes were upregulated and 84 were downregulated. The co-downregulated enrichment results were primarily reflected in various metabolic disorders, including glucose metabolism, lipid metabolism, amino acid metabolism, and others. The co-upregulated genes were associated with the inflammatory response, apoptosis, and cell senescence. This finding indicated that empagliflozin may inhibit the progression of diabetic nephropathy by inhibiting inflammation, apoptosis, and senescence. The key genes and related mechanisms of noncoding RNA were determined through Cytoscape analysis and the prediction of common DEGs in metabolic items. CONCLUSIONS: The analysis of DEGs and key core genes in this study enhanced our understanding of the effect of empagliflozin on the pathogenesis of DN and provided more potential gene targets and application ideas for DN treatment.

Reduced PATL2 Impairs the Proliferation of Ovarian Granulosa Cells by Decreasing ADM2 Expression in Patients with PCOS.

It is recognized that PCOS patients are often accompanied with aberrant follicular development, which is an important factor leading to infertility in patients. However, the relevant regulatory mechanisms of abnormal follicular development are not well understood. In the present study, by collecting human ovarian granulosa cells (GCs) from PCOS patients who underwent in vitro fertilization (IVF), we found that the proliferation ability of GCs in PCOS patients was significantly reduced. Surprisingly, PATL2 and adrenomedullin 2 (ADM2) were obviously decreased in the GCs of PCOS patients. To further explore the potential roles of PATL2 and ADM2 on GC, we transfected PATL2 siRNA into KGN cells to knock down the expression of PATL2. The results showed that the growth of GCs remarkably repressed after knocking down the PATL2, and ADM2 expression was also weakened. Subsequently, to study the relationship between PATL2 and ADM2, we constructed PATL2 mutant plasmid lacking the PAT construct and transfected it into KGN cells. The cells showed the normal PATL2 expression, but attenuated ADM2 expression and impaired proliferative ability of GCs. Finally, the rat PCOS model experiments further confirmed our findings in KGN cells. In conclusion, our study suggests that PATL2 promoted the proliferation of ovarian GCs by stabilizing the expression of ADM2 through "PAT" structure, which is beneficial to follicular development, whereas, in the ovary with polycystic lesions, reduction of PATL2 could result in the decreased expression of ADM2, subsequently weakened the proliferation ability of GCs and finally led to the occurrence of aberrant follicles.

Effects of perchlorate and exogenous T4 exposures on body condition and endochondral ossification of Rana chensinensis tadpoles.

Perchlorate, as an endocrine-disrupting chemical (EDC), is largely produced and used in the military, fireworks, fertilizers, and other industries and widely exists in water. Although perchlorate is known to destroy the normal function of thyroid hormones (THs) in amphibians and interfere with their growth and development, the impact of TH levels caused by sodium perchlorate (NaClO4) on endochondral ossification and skeletal development is poorly investigated, and the underlying molecular mechanism has not been clarified. The present study aimed to explore the potential effects of NaClO4 and exogenous thyroxine (T4) on the skeletal development of Rana chensinensis tadpoles and elucidate the related molecular mechanisms. Our results showed that histological changes occurred to the femur and tibia-fibula of tadpoles raised in 250 µg/L NaClO4 and 5 µg/L exogenous T4, and the length of their hindlimbs was significantly reduced. In addition, exogenous T4 exposure significantly interfered with the expression of Dio3, TRß, MMP9, MMP13, and Runx2, inhibiting the endochondral ossification process. Therefore, we provide robust evidence that the changes in TH levels caused by NaClO4 and exogenous T4 will adversely affect the endochondral ossification and skeletal development of R. chensinensis tadpoles.

Forces driving transposable element load variation during Arabidopsis range expansion.

Genetic load refers to the accumulated and potentially life-threatening deleterious mutations in populations. Understanding the mechanisms underlying genetic load variation of transposable element (TE) insertion, a major large-effect mutation, during range expansion is an intriguing question in biology. Here, we used 1,115 global natural accessions of Arabidopsis (Arabidopsis thaliana) to study the driving forces of TE load variation during its range expansion. TE load increased with range expansion, especially in the recently established Yangtze River basin population. Effective population size, which explains 62.0% of the variance in TE load, high transposition rate, and selective sweeps contributed to TE accumulation in the expanded populations. We genetically mapped and identified multiple candidate causal genes and TEs, and revealed the genetic architecture of TE load variation. Overall, this study reveals the variation in TE genetic load during Arabidopsis expansion and highlights the causes of TE load variation from the perspectives of both population genetics and quantitative genetics.

Wolfberry, Yam, and Chrysanthemum polysaccharides increased intestinal Akkermansia muciniphila abundance and hepatic YAP1 expression to alleviate DILI.

Drug-induced liver injury (DILI) is frequently induced by high dose of acetaminophen (APAP) and is concomitant with disturbances of gut flora. Akkermansia muciniphila is beneficial for the repair of liver injury. Lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide all have anti-inflammatory and antioxidation effects. The objective of this study is to investigate the potential of lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide (LYC) in improving DILI by increasing the abundance of A. muciniphila. Initially, screening for the optimal concentrations of wolfberry, yam, and chrysanthemum (WYC) or LYC to promote A. muciniphila proliferation in vitro and validated in antibiotic (ATB)-treated KM mice. Subsequently, APAP-induced DILI model in BALB/c mice were constructed to examine the treatment effects of LYC. Our findings indicate that the optimal concentration ratio of WYC was 2:3:2, and LYC was 1:1:1. WYC increased A. muciniphila proliferation in vitro and in ATB-treated mice under this ratio. Meanwhile, LYC increased A. muciniphila abundance in vitro and the combination LYC with A. muciniphila promoted the proliferation of A. muciniphila in ATB-treated mice. The overdose of APAP resulted in the impairment of the intestinal barrier function and subsequent leakage of lipopolysaccharide (LPS). Moreover, LYC increased A. muciniphila abundance, reduced intestinal inflammation and permeability, and upregulated the expression of the tight junction protein zonula occludens protein 1 (ZO-1) and occludin contents in the gut. Lastly, LYC inhibited LPS leakage and upregulated hepatic YAP1 expression, ultimately leading to the repair of DILI.

RNA-Seq Analysis of ceRNA-Related Networks in the Regulatory Metabolic Pathway of Mice with Diabetic Nephropathy Subjected to Empagliflozin Intervention

Objective: We conducted bioinformatics analysis of the gene chip data of empagliflozin for diabetic nephropathy (DN). The differentially expressed genes (DEGs) between DN and control mice and between DN and DN treated with empagliflozin (DNE) mice were screened to explore the related metabolic pathogenesis and predict the potential competing endogenous RNA (ceRNA)-related networks’ metabolic mechanism of the empagliflozin effect on DN. Methods: The intersection of DEGs in mice between the control and DN groups and between the DN and DNE groups was selected. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were performed, and the metabolic items involving the most genes in the coregulation were considered. A protein-interaction network was constructed with the STRING website. Cytoscape software and its plug-ins were utilised to analyse the hotspot differential genes. The noncoding RNAs in which the differential genes may play a role were obtained from the miRanda, miRDB, and TargetScan databases to establish network diagrams. Results: Analysis of the diabetes and control groups showed that 424 genes were upregulated and 354 were downregulated. In the analysis of DEGs between the DN and diabetic groups, the comparison between the diabetic and empagliflozin groups showed that 430 genes were upregulated and 84 were downregulated. The co-downregulated enrichment results were primarily reflected in various metabolic disorders, including glucose metabolism, lipid metabolism, amino acid metabolism, and others. The co-upregulated genes were associated with the inflammatory response, apoptosis, and cell senescence. This finding indicated that empagliflozin may inhibit the progression of diabetic nephropathy by inhibiting inflammation, apoptosis, and senescence. The key genes and related mechanisms of noncoding RNA were determined through Cytoscape analysis and the prediction of common DEGs in metabolic items (AU)

Osimertinib inhibits brain metastases and improves long-term survival in a patient with advanced squamous cell lung cancer: a case report and literatures review.

Background: Squamous cell carcinoma (SCC) is one of the most common subtypes of non-small cell lung cancer, but its treatment options remain limited. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have limited efficacy in the treatment of lung SCC. Here, we report an SCC patient who developed EGFR-T790M mutation and showed gefitinib resistance achieved an extremely long survival by taking Osimertinib alternatively. Case summary: A patient, 66-year-old non-smoking and drinking male with advanced SCC who was deemed inoperable at the time of diagnosis. The first genetic testing showed deletion mutation of exon 19 of EGFR. The patient was then treated with gefitinib with no significant efficacy. EGFR-T790M mutation was found in the second genetic test. The treatment regimen was changed to radiotherapy with Osimertinib, and the patient's primary lesion and the brain metastases were well controlled. Conclusion: This typical case highlights the important role of Osimertinib in patients with SCC carrying EGFR mutations.

Erratum to "Phillyrin Mitigates Apoptosis and Oxidative Stress in Hydrogen Peroxide-Treated RPE Cells through Activation of the Nrf2 Signaling Pathway".

[This corrects the article DOI: 10.1155/2020/2684672.].

Performance Characteristics of Silicone Rubber for Use in Acidic Environments.

Silicone rubber insulators are widely used in power grids because of their excellent performance, but aging has been an inevitable problem of silicone rubber, especially in extreme conditions, such as acidic conditions. In order to clarify the performance changes in silicone rubber in an acidic environment, this paper uses the developed acid-resistant silicone rubber sheet and common silicone rubber samples as the research objects, and conducts an aging comparison test on them in a natural acidic environment. The electrical properties, physical properties, and chemical properties of the two types of silicone rubber specimens with different aging times are analyzed to obtain the performance characteristics of silicone rubber under a natural acidic environment. The research results show that the dry flash voltage and pollution flashover voltage of the acid-resistant silicone rubber after one year of aging are greater than those of the common type; the water repellency of both types of silicone rubber remains in good condition. The silicone rubber produced by our team according to the self-developed acid-resistant silicone rubber formula has indeed played a role in delaying aging in an acidic environment compared with the common-type silicone rubber.

Effects of perchlorate and exogenous T4 on growth, development and tail resorption of Rana chensinensis.

Endocrine disruptors have been demonstrated to exert adverse effects on growth and development of amphibians by disrupting hormone levels. Tail resorption, which is one of the most remarkable events during amphibian metamorphosis, is closely associated with thyroid hormones levels. However, limited research has been conducted on the effects of endocrine disruptors on tail resorption in amphibians. This study explored the effects of NaClO4 and T4 on the growth, development and tail resorption during the metamorphosis of Rana Chensinensis. The results demonstrated that exposure to NaClO4 led to an increase in body size and a delay in metamorphosis of R. Chensinensis tadpoles. Histological analysis revealed that both NaClO4 and exogenous T4 exposure resulted in thyroid gland injury, and NaClO4 treatment delayed the degradation of notochord and muscles, thereby delaying tail resorption. Moreover, transcriptome sequencing results showed that apoptosis-related genes (APAF1, BAX and CASP6) and cell component degradation-related genes (MMP9 and MMP13) were highly expressed in the T4 exposure group, and the expression of oxidative stress-related genes (SOD and CAT) was higher in the NaClO4 exposure group. Taken together, both NaClO4 and exogenous T4 affect tail resorption in R. Chensinensis, thereby affecting their adaptation to terrestrial life. The present study will not only provide a reference for future experimental research on the effects of other endocrine disruptors on the growth, development and tail resorption of amphibians but will also provide insights into environmental protection and ecological risk assessment.

Local injection of micro-dose anti-interleukin-17A antibody for palmoplantar pustulosis: A real-world study.

Palmoplantar pustulosis (PPP), a chronic and stubborn skin disease, is mainly confined to the palms or/and soles, making it possible for localized use of therapeutic antibodies. In this real-world prospective cohort study, 8 patients with PPP received palms/soles injections of ixekizumab (0.8 mg in 0.1 ml) every 2 to 8 weeks due to the COVID-19 pandemic. The treatment endpoint was a 75% improvement from baseline in Palmoplantar Pustulosis/Psoriasis Area and Severity Index (PPPASI 75). At week 8, 75%, 50% and 12.5% of 8 patients reached PPPASI 50, PPPASI 75 and PPPASI 90. At week 12, 100%, 75% and 25% of 8 patients reached PPPASI 50, PPPASI 75 and PPPASI 90. This is the first study to evaluate the efficacy and safety of local injection of micro-dose ixekizumab for PPP in real clinical practice. A high proportion of patients rapidly achieved PPPASI 75, and maintained long-term efficacy with satisfactory safety.

Biomarkers based on multiplatform comprehensive analysis: A systematic analysis of Geng-Nian-Shu in perimenopausal syndrome.

Although Geng-Nian-Shu has been shown to be clinically effective in perimenopausal syndrome, its active components and mechanism have not yet been elucidated. To demonstrate the mechanism-based biomarkers of Geng-Nian-Shu in treating perimenopausal syndrome, a total of 135 chemical constituents including 52 prototype blood constituents were identified via high-performance liquid chromatography-quadrupole-time of flight/mass spectrometry. Then, network pharmacology showed significant enrichment for the PhosphoInositide-3 Kinase/Akt pathway, suggesting that it may be the main regulatory pathway for the Geng-Nian-Shu treatment of the perimenopausal syndrome. Subsequently, multivariate analysis was performed between the Geng-Nian-Shu sham-treated and Geng-Nian-Shu ovariectomy-treated groups and further screened out 18 prototype blood constituents by correlation analysis with plasma estrogen levels to identify potential biomarkers associated with Geng-Nian-Shu treat the ovariectomy-induced perimenopausal syndrome. Finally, the results of pharmacological experimental verification and Pearson correlation analysis indicated that catalpol, ligustilide, paeoniflorin, and gallic acid were selected as biomarkers of Geng-Nian-Shu which were strongly and positively correlated with PhosphoInositide-3 Kinase/Akt signaling pathway. In this study, based on high-performance liquid chromatography-quadrupole-time of flight/mass spectrometry combined with pharmacodynamics, network pharmacology, pharmacology, and other disciplines, we explored the effects and mechanisms of Geng-Nian-Shu in the treatment of perimenopausal syndrome at multiple levels. Using multiplatform technology to investigate the role of Geng-Nian-Shu represents a new strategy for the selection and verification of biomarkers of Geng-Nian-Shu and provides a basis for further development and utilization of Geng-Nian-Shu.

Risk factors for medical device-related pressure injury in ICU patients: A systematic review and meta-analysis.

BACKGROUND: Medical device-related pressure injury (MDRPI) in intensive care unit (ICU) patients is a serious issue. We aimed to evaluate the risk factors for MDRPI associated with ICU patients through systematic review and meta-analysis, and provide insights into the clinical prevention of MDRPI. METHODS: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Database, and China BioMedical Literature Database (CBM) (from inception to January 2023) for studies that identified risk factors of MDRPI in ICU patients. In order to avoid the omission of relevant literature, we performed a secondary search of the above database on February 15, 2023. Meta-analysis was performed using Revman 5.3. RESULTS: Fifteen studies involving 4850 participants were selected to analyze risk factors for MDRPI in ICU patients. While conducting a meta-analysis, we used sensitivity analysis to ensure the reliability of the results for cases with significant heterogeneity among studies. When the source of heterogeneity cannot be determined, we only described the risk factor. The risk factors for MDRPI in ICU patients were elder age (OR = 1.06, 95% CI: 1.03-1.10), diabetes mellitus (OR = 3.20, 95% CI: 1.96-5.21), edema (OR = 3.62, 95% CI: 2.31-5.67), lower Braden scale score (OR = 1.22, 95%CI: 1.11-1.33), higher SOFA score (OR = 4.21, 95%CI: 2.38-7.47), higher APACHE II score (OR = 1.38, 95%CI: 1.15-1.64), longer usage time of medical devices (OR = 1.11, 95%CI: 1.05-1.19), use of vasoconstrictors (OR = 6.07, 95%CI: 3.15-11.69), surgery (OR = 4.36, 95% CI: 2.07-9.15), prone position (OR = 24.71, 95% CI: 7.34-83.15), and prone position ventilation (OR = 17.51, 95% CI: 5.86-52.36). Furthermore, we found that ICU patients who used subglottic suction catheters had a higher risk of MDRPI, whereas ICU patients with higher hemoglobin and serum albumin levels had a lower risk of MDRPI. CONCLUSION: This study reported the risk factors for MDRPI in ICU patients. A comprehensive analysis of these risk factors will help to prevent and optimize interventions, thereby minimizing the occurrence of MDRPI.

Dihydroartemisinin increased the abundance of Akkermansia muciniphila by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD-1 immunotherapy.

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

Si-Ni-San reduces lipid droplet deposition associated with decreased YAP1 in metabolic dysfunction-associated fatty liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. However, its complex pathogenesis and lack of effective drugs for treating it present significant challenges. Si-Ni-San (SNS) is one of the representative formulas for treating patients with MAFLD in traditional Chinese medicine (TCM) clinics. According to our previous work, SNS reduces lipid droplet (LD) deposition in livers of mice with MAFLD. AIM OF THE STUDY: To elucidate the mechanism of SNS in reducing LD deposition in MAFLD. MATERIALS AND METHODS: First, LD areas were detected with Oil red O staining in HepG2 cells induced by oleic acid (OA). Cell Counting Kit-8 (CCK-8) assay was used to test cell viability after treatment with different concentrations of SNS serum. The expression of Yes-associated protein 1 (YAP1) was monitored by Western blot. Second, C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and gavaged with SNS decoction during the 11th and 12th weeks. Then, the weight of the body and the liver was examined. LD numbers and their locations in the liver were detected by triglyceride (TG) assay and hematoxylin and eosin staining (H&E). The expression levels of YAP1 and perilipin2 (PLIN2) were detected using Western blot and immunohistochemistry (IHC) in liver tissues. Finally, active ingredients of SNS decoction and SNS serum were identified by liquid chromatography-mass spectrometry (LC-MS). Finally, molecular docking was performed between the compounds in SNS and YAP1 to analyze their active interaction. RESULTS: Cellular experiments showed that SNS serum reduced LD vacuoles and YAP1 expression in OA-induced HepG2 cells. Animal experiments confirmed that LD vacuoles, PLIN2 expression (3.16-fold), and YAP1 expression (2.50-fold) were increased in the HFD group compared with the normal diet (ND) group. SNS reduced LD vacuoles, TG content (0.84-fold), PLIN2 expression (0.33-fold), and YAP1 expression (0.27-fold) compared with the normal saline (NS) group in Yap1Flox mice with MAFLD. In SNS, baicalein-6-glucuronide, desoxylimonin, galangin-7-glucoside, glycyrrhizic-acid, licoricesaponin-K2, and nobiletin showed a high binding effect with YAP1. Knockout of hepatocyte YAP1 reduced LD vacuoles, TG content (0.40-fold), and PLIN2 expression (0.62-fold) in mice. Meanwhile, SNS reduced LD vacuoles, TG content (0.70-fold), and PLIN2 expression (0.19-fold) in Yap1LKO mice with MAFLD. The effect of SNS in reducing TG and PLIN2 was diminished in Yap1LKO mice compared with Yap1Flox mice. CONCLUSION: SNS reduced LD deposition and YAP1 expression in MAFLD liver cells both in vivo and in vitro. YAP1 was highly expressed in livers with MAFLD, and knockout of hepatocellular YAP1 reduced LD deposition in mice. SNS reduced LD deposition associated with decreased YAP1 in MAFLD liver cells.

Effect of female coronavirus disease 2019 vaccination on assisted reproductive outcomes: a systematic review and meta-analysis.

IMPORTANCE: The effect of coronavirus disease 2019 (COVID-19) vaccination on fertility warrants clarification in women undergoing assisted reproductive treatment. OBJECTIVE: To study the association between female COVID-19 vaccination and outcomes of assisted reproductive treatment. DATA SOURCES: PubMed, Embase, the Web of Science, Cochrane Library, and medRxiv and bioRxiv were searched for eligible studies from December 1, 2019, to November 30, 2022, with no language restrictions. STUDY SELECTION AND SYNTHESIS: Observational studies comparing assisted reproductive outcomes between women with and without COVID-19 vaccination were included. The pooled estimates were calculated using the random-effects models as mean differences (MDs), standardized MDs, or odds ratios with 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic. MAIN OUTCOMES: The number of oocytes retrieved and clinical pregnancy rate. RESULTS: Twenty-one cohort studies involving a total of 19,687 treatment cycles were included. In a comparison of the vaccinated vs. unvaccinated groups, the pooled MD for oocyte number was -0.06 (95% CI, -0.51 to 0.39; I2 = 0), and the pooled odds ratio for clinical pregnancy was 0.95 (95% CI, 0.85-1.05; I2 = 0). Similarly, there were no statistically significant adverse effects identified in other outcomes determined a priori, including 4 cycle characteristics, 6 laboratory parameters, and 3 pregnancy indicators. Most results were consistently unchanged in subgroup and sensitivity analyses, with no evidence of publication bias according to Egger's test. CONCLUSION AND RELEVANCE: Our work did not find significant differences in assisted reproductive outcomes between vaccinated and unvaccinated women. However, more data are warranted to confirm the safety of COVID-19 vaccination for assisted reproductive treatment and in female fertility in general.

Dihydroartemisinin inhibited the Warburg effect through YAP1/SLC2A1 pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) was the third most common cause of cancer death. But it has only limited therapeutic options, aggressive nature, and very low overall survival. Dihydroartemisinin (DHA), an anti-malarial drug approved by the Food and Drug Administration (FDA), inhibited cell growth in HCC. The Warburg effect was one of the ten new hallmarks of cancer. Solute carrier family 2 member 1 (SLC2A1) was a crucial carrier for glucose to enter target cells in the Warburg effect. Yes-associated transcriptional regulator 1 (YAP1), an effector molecule of the hippo pathway, played a crucial role in promoting the development of HCC. This study sought to determine the role of DHA in the SLC2A1 mediated Warburg effect in HCC. In this study, DHA inhibited the Warburg effect and SLC2A1 in HepG2215 cells and mice with liver tumors in situ. Meanwhile, DHA inhibited YAP1 expression by inhibiting YAP1 promoter binding protein GA binding protein transcription factor subunit beta 1 (GABPB1) and cAMP responsive element binding protein 1 (CREB1). Further, YAP1 knockdown/knockout reduced the Warburg effect and SLC2A1 expression by shYAP1-HepG2215 cells and Yap1LKO mice with liver tumors. Taken together, our data indicated that YAP1 knockdown/knockout reduced the SLC2A1 mediated Warburg effect by shYAP1-HepG2215 cells and Yap1LKO mice with liver tumors induced by DEN/TCPOBOP. DHA, as a potential YAP1 inhibitor, suppressed the SLC2A1 mediated Warburg effect in HCC.

Dihydroartemisinin broke the tumor immunosuppressive microenvironment by inhibiting YAP1 expression to enhance anti-PD-1 efficacy.

The efficacy of anti-PD-1 therapy is not as expected in hepatocellular carcinoma (HCC). YAP1 was overexpressed and activated in HCC. The mechanism of YAP1 in HCC immune escape is unclear. Anti-PD-1 treatment increased YAP1 expression in liver tumor cells, and exhausted CD4+ and CD8+ T cells in the blood and spleen of liver tumor mice. YAP1 knockdown suppressed PD-L1 expression, which was involved in JAK1/STAT1, 3 pathways. Moreover, Yap1 knockout elevated CD4+ and CD8+ T cells in liver tumor niche. Consistently, verteporfin, YAP1 inhibitor, decreased TGF-ß and IFN-γ in liver tumor niche and exhausted CD8+ T cell in the spleen. DHA suppressed YAP1 expression and break immune evasion in liver tumor niche, characterized by decreased PD-L1 in liver tumor cells and increased CD8+ T cell infiltration. Furthermore, DHA combined with anti-PD-1 treatment promoted CD4+ T cell infiltration in the spleen and CD8+ T cell in tumor tissues of mice. In summary, YAP1 knockdown in liver tumor cells suppressed PD-L1 expression and recruited cytotoxic T lymphocytes (CTLs), leading to break immune evasion in tumor niche. Mechanistically, YAP1 knockdown suppressed PD-L1 expression, which was involved in JAK1/STAT1, 3 pathways. Finally, DHA inhibited YAP1 expression, which not only inhibited liver tumor proliferation but also break the immunosuppressive niche in liver tumor tissues and improve the effect of anti-PD-1 therapy.