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ObjectivesTo evaluate the changes in distal vascular morphology and hemodynamics in patients with extremely severe aortic coarctation (CoA) after covered palliative (CP) stent dilation with different surgical strategies.Materials and methodsPerioperative computed tomography angiography and digital subtraction angiography were utilized to construct three aortic models with varying stenosis rates and one follow-up model in a patient with extremely severe CoA. The models included: an idealized non-stenosed model (A: 0%), a model post initial stent deployment (B: 28%), a model post balloon expansion (C: 39%), and a model 18 months after post-balloon expansion (D: 39%). Consistent boundary conditions were applied to all models, and hemodynamic simulation was conducted using the pure fluid method.ResultsThe narrowest and distal diameter of the stent increased by 34.71% and 59.29%, respectively, from model B to C. Additionally, the distal diameter of the stent increased by −13.80% and +43.68% compared to the descending aorta diameter, respectively. Furthermore, the ellipticity of the maximum cross-section of the aneurysm region in model A to D continued to increase. The oscillatory shear index at the stenosis to the region of the aneurysm were found to be higher in Models A and B, and lower in Models C and D. At the moment of maximum flow velocity, the blood flow distribution in models A and B was more uniform in the widest section of the blood vessels at the distal end of the stenosis, whereas models C and D exhibited disturbed blood flow with more than 2 eddy currents. The time-averaged wall shear stress (TAWSS) decreased in the distal and basal aneurysms, while it significantly increased at the step position. The aneurysmal region exhibited an endothelial cell activation potential value lower than 0.4 Pa−1.ConclusionIn patients with extremely severe CoA, it is crucial to ensure that the expanded diameter at both ends of the CP stent does not exceed the native vascular diameter during deployment. Our simulation results demonstrate that overdilation leads to a decrease in the TAWSS above the injured vessel, creating an abnormal hemodynamic environment that may contribute to the development and enlargement of false aneurysms in the early postoperative period. Clinical Trial RegistrationClinicalTrials.gov, (NCT02917980).

ObjectiveThe progression of carotid intima-media thickness (cIMT) can partially predict the occurrence of future cardiovascular events. This network meta-analysis compared the effects of 14 antidiabetic drugs (acarbose, alogliptin, exenatide, glibenclamide, glimepiride, ipragliflozin, metformin, nateglinide, pioglitazone, rosiglitazone, sitagliptin, tofoglifozin, troglitazone, voglibose) on the progression of cIMT.MethodPubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of treatment of cIMT with hypoglycemic agents before March 1, 2024. The differences in the changes in cIMT between the treatment group and control group were evaluated.ResultAfter screening 8395 citations, 25 studies (6675 patients) were included. The results indicated that exenatide had the best efficacy in slowing down cIMT progress, and exenatide [MD=-0.13,95%CI (-0.25, -0.01)], alogliptin [MD=-0.08,95%CI (-0.13, -0.02)] and metformin [MD=-0.05, 95%CI (-0.09, -0.02)] are more effective than placebo.ConclusionLong-term treatment of exenatide, alogliptin, and metformin may be more effective than other hypoglycemic drugs in slowing the progression of cIMT.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024519474.

ObjectiveIt is advised that patients engage in physical activity to enhance their quality of life and achieve better results. The purpose of the current study was to measure the efficacy of exercise on the physical ability, cardiac function and cardiopulmonary fitness of patients with AF.MethodA comprehensive systematic literature search was performed in PubMed, Embase, and Web of Science from 1991 to 2023 for RCTs comparing physical exercise combined with AF routine treatments to routine treatments alone. The meta-analysis was conducted following PRISMA guidelines. Our main outcomes were physical ability (measured by the 6-min walk test, 6MWT), cardiac function (measured by left ventricular ejection fraction, LVEF) and cardiopulmonary fitness (measured by peak oxygen uptake and resting heart rate). Quality assessments were conducted using the Cochrane Collaboration tool.ResultsThirteen trials involving 672 patients met the criteria for analysis. The results showed that physical exercise increased physical ability by improving the 6MWT (m) performance (MD = 96.99, 95% CI: 25.55–168.43; Z = 2.66; p = 0.008); and enhanced peak VO2 (ml/kg per min) (MD = 4.85, 95% CI: 1.55–8.14; Z = 2.89; p = 0.004) while reducing resting heart rate (beats per minute, bpm) (MD = −6.14, 95% CI: −11.30 to −0.98; Z = 2.33; p = 0.02). However, the results showed that regular exercise could improve LVEF (%) inpatients clinically, which had no statistic difference between experimental and control group (MD = 1.49, 95% CI: −0.25–3.24; Z = 1.68; p = 0.09).ConclusionOur meta-analysis shows that physical exercise is an effective intervention to improve the exercise ability and cardiopulmonary fitness for AF patients. Meanwhile, we also do not exclude the positive effect of exercise on the improvement of cardiac function (LVEF) in patients with AF. To this end, doctors should consider the positive impact of exercise on patients and give advice on exercise limits in practical clinical practice.

BackgroundLead-induced tricuspid regurgitation is one of the complications after permanent pacemaker implantation (PPI) and refers to tricuspid regurgitation (TR) caused by the lead in the right ventricle (RV).ObjectivesTo study the clinical characteristics of severe TR after PPI and the effect of transcatheter tricuspid valve replacement (TTVR) with the guidance of 3-dimensional (3D) printing.MethodsThis study was a single-center, descriptive study. Six patients with severe TR after PPI were enrolled in Xijing Hospital from January 2020 to May 2020. Before TTVR, the 3D printed tricuspid valve (TV) model was used for evaluation in the bench test. LuX-Valve was implanted under the guidance of TEE and x-ray fluoroscopy, and all patients underwent transatrial access. Six patients’ data were collected at baseline, before discharge, and 6 months, 1 year and 2 years after TTVR.ResultsThe LuX-Valve was successfully implanted in 6 patients, TR was significantly reduced to ≤2+, and no deaths or cardiopulmonary bypass occurred during procedures. Three cases were caused by TV expansion: Patient #4 had TR caused by lead adhesion to TV, Patient #2 had TR caused by lead winding, and Patient #6 had TR caused by lead impingement on TV. During the 2-year follow-up, TTE revealed that 5 patients had no/trace regurgitation, and one patient (Patient #5) had mild regurgitation. All 6 patients (100.0%) reached primary endpoints.ConclusionTTVR guided by 3D printing is safe and effective in the treatment of severe TR associated with permanent pacemaker lead, providing prospects and possibilities for the precise treatment of TV-related diseases.Clinical Trial Registration: ClinicalTrials.gov Protocol Registration System (NCT02917980).

Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases (CVDs), including coronary artery disease, hypertension, myocardial infarction, and heart failure. Hence, the mechanisms of AS are still being explored. A growing compendium of evidence supports that the activity of the mechanistic/mammalian target of rapamycin (mTOR) is highly correlated with the risk of AS. The mTOR signaling pathway contributes to AS progression by regulating autophagy, cell senescence, immune response, and lipid metabolism. Various botanical drugs and their functional compounds have been found to exert anti- AS effects by modulating the activity of the mTOR signaling pathway. In this review, we summarize the pathogenesis of AS based on the mTOR signaling pathway from the aspects of immune response, autophagy, cell senescence, and lipid metabolism, and comb the recent advances in natural compounds from botanical drugs to inhibit the mTOR signaling pathway and delay AS development. This review will provide a new perspective on the mechanisms and precision treatments of AS.

ObjectiveThe aim was to evaluate the safety and efficacy of TTVR in patients with severe TR at the 1-year follow-up.Materials and methodsThis project was a single-center, observational study. From September 2020 to May 2021, 15 patients with severe or extremely severe TR at high risk of traditional surgery were enrolled. All patients had preoperative imaging assessments to evaluate the tricuspid valve and the anatomy of the right heart. All patients were planned to treated with the LuX-Valve (Ningbo Jenscare Biotechnology, Ningbo, China). The LuX-Valve was implanted under the intraoperative guidance of TEE and X-ray fluoroscopy. Data were collected at baseline, before discharge, and at 30 days, 6 months, and 1 year postoperatively.ResultsThe LuX-Valves were successfully implanted in all 15 patients. TR was significantly reduced to ≤ 2 +. One patient died on postoperative day 12 of a pulmonary infection that was considered unrelated to the procedures or the devices. The remaining 14 patients (100.0%) reached the primary end point. One patient (7.1%) was rehospitalized during 1-year follow-up because of device thrombosis. The number of patients who survived at 1 year with New York Heart Association (NYHA) functional class II was higher than that before TTVR (11/14 vs. 0/15, P = 9.11 × 10–4). Patients with peripheral edema and ascites decreased from 100.0 to 46.7% at baseline to 28.6% and 14.3% at 1 year (P = 1.57 × 10–3 and 2.53 × 10–2).ConclusionTTVR is associated with RV remodeling, increased cardiac output, and improvement in NYHA functional class. Using the LuX-Valve for TTVR to treat patients with severe TR is a feasible and relatively safe method with reliable clinical results. Further studies are needed to determine long-term outcomes.

A total of 480 one-day-old AA broiler chicks were randomly allocated to one of four treatments in a 2 × 2 factorial to investigate the effects of tannic acid (TA) on growth performance, relative organ weight, antioxidant capacity, and intestinal health in broilers dietary exposed to aflatoxin B1 (AFB1). Treatments were as follows: (1) CON, control diet; (2) TA, CON + 250 mg/kg TA; (3) AFB1, CON + 500 μg/kg AFB1; and (4) TA+AFB1, CON + 250 mg/kg TA + 500 μg/kg AFB1. There were 10 replicate pens with 12 broilers per replicate. Dietary AFB1 challenge increased the feed conversion ratio during days 1 to 21 (P < 0.05). The TA in the diet did not show significant effects on the growth performance of broilers during the whole experiment period (P > 0.05). The liver and kidney relative weight was increased in the AF challenge groups compared with the CON (P < 0.05). The addition of TA could alleviate the relative weight increase of liver and kidney caused by AFB1 (P < 0.05). Broilers fed the AFB1 diets had lower activity of glutathione peroxidase, catalase, total superoxide dismutase, S-transferase, and total antioxidant capacity in plasma, liver and jejunum, and greater malondialdehyde content (P < 0.05). Dietary supplemented with 250 mg/kg TA increased the activities of antioxidative enzymes, and decreased malondialdehyde content (P < 0.05). In addition, AFB1 significantly reduced the villus height and crypt depth ratio in the ileum on day 42 (P < 0.05). In conclusion, supplementation with 250 mg/kg TA could partially protect the antioxidant capacity and prevent the enlargement of liver in broilers dietary challenged with 500 μg/kg AFB1.

BackgroundQuadricuspid aortic valve (QAV) is a rare congenital malformation that can present with aortic regurgitation or aortic stenosis (AS)), requiring surgical treatment. Transcatheter aortic valve replacement (TAVR) is an alternative treatment for older patients and its prognosis for QAV therapy remains challenging. We sought to examine our early experience with TAVR in patients with QAV.Materials and methodsProspectively collected data were retrospectively reviewed in patients with QAV undergoing TAVR in our institution.ResultsFive patients with QAV and AR or AS were treated with TAVR between January 2016 and January 2022. The mean age was 73.8 years (range 69–82 years), and the median Society of Thoracic Surgeons score was 7.51% (range 2.668–18.138%). Two patients had type B and three had either type A, D, or F according to the Hurwitz and Roberts classification for QAV. Four patients with pure aortic regurgitation underwent transapical TAVR using the J-Valve system, and the patient with severe AS underwent transfemoral TAVR using the Venus-A system. Procedural success was achieved in all five patients. Trivial paravalvular leak was only detected in one case after the procedure, and one patient received a permanent pacemaker due to high-degree atrioventricular block three days later. The median follow-up period was 18 (12–56) months. After discharge, no deaths occurred during the 1 year follow-up. All patients improved by ≥1 New York Heart Association functional class at 30 days; four patients were in functional class ≤II later in the follow-up period. All patients’ heart failure symptoms improved considerably.ConclusionOur early experience with TAVR in QAV demonstrates these procedures to be feasible with acceptable early results. Further follow-up is necessary to determine the long-term outcomes of this modality.Clinical trial registration[ClinicalTrials.gov], identifier [NCT02917980].

BackgroundOur goal was to explore the role of 3-dimensional (3D) printing in facilitating the outcome of a mitral valve-in-valve (V-in-V) implant of a balloon-expandable valve.MethodsFrom November 2020 to April 2021, 6 patients with degenerated mitral valves were treated by a transcatheter mitral V-in-V implant of a balloon-expandable valve. 3D printed mitral valve pre- and post-procedure models were prepared to facilitate the process by making individualized plans and evaluating the outcomes.ResultsEach of the 6 patients was successfully implanted with a balloon-expandable valve. From post-procedural images and the 3D printed models, we could clearly observe the valve at the ideal position, with the proper shape and no regurgitation. 3D printed mitral valve models contributed to precise decisions, the avoidance of complications, and the valuation of outcomes.Conclusions3D printing plays an important role in guiding the transcatheter mitral V-in-V implant of a balloon-expandable valve.Clinical Trial RegistrationClinicalTrials.gov Protocol Registration System (NCT02917980).

BackgroundClosure of a percutaneous paravalvular leak (PVL) is a technically challenging procedure because of the specific anatomy postoperatively and the complex catheter techniques required. Transesophageal echocardiography (TEE) and three-dimensional (3D) printing might be helpful in identifying complex anatomical structures and the procedural design.ObjectivesThe purpose of this study was to review our experiences with transcatheter closure of PVL guided by TEE and 3D (TEE&3D) printing.MethodsA total of 166 patients with PVL after surgical valve replacement underwent transcatheter closure, from January 2015 through December 2020. Among these patients, 68 had preoperative guidance from TEE&3D printing. We reviewed the catheter techniques, perioperative characteristics, and prognosis. The median follow-up period was 36 (3–70) months.ResultsAcute procedural success was achieved in 154/166 (92.8%) patients; of these, 64/68 (94.1%) had TEE&3D guidance and 90/98 (91.8%) had transthoracic echocardiography (TTE) guidance. No hospital deaths occurred. All patients having percutaneous procedures were given local anesthesia, while 13 patients having transapical procedures were given general anesthesia. Multiple approaches were used, including transfemoral, transapical, and transseptal via the arteriovenous loop. We also deployed multiple devices, including the Amplatzer Vascular Plug II (AVP II), the Amplatzer duct occluder II, the patent ductus arteriosus (PDA) occluder, and the Amplatzer muscular ventricular septal defect occluder. Those cases guided by TEE&3D printing had shorter procedural times compared with those guided by TTE [(61.2 ± 23.4) vs. (105.7 ± 53.9) min, p < 0.05]. The fluoroscopic time was also shorter for operations guided by TEE&3D printing compared with those guided by TTE alone [(18.5 ± 11.4) vs. (27.3 ± 5.6) min, p < 0.05]. The complications included recurrent hemolysis, residual regurgitation, acute renal insufficiency, and anemia. There was no significant difference in the incidence of complications between the 2 groups.ConclusionTransesophageal echocardiography and 3D printing show advantages compared with standalone TTE in guiding the transcatheter closure of PVL with shorter procedural and fluoroscopic times. This minimally invasive treatment could provide reliable outcomes in selected patients.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT02917980].

ObjectivesWe proposed a novel deep learning radiomics (DLR) method to distinguish cognitively normal adults at risk of Alzheimer’s disease (AD) from normal control based on T1-weighted structural MRI images.MethodsIn this study, we selected MRI data from the Alzheimer’s Disease Neuroimaging Initiative Database (ADNI), which included 417 cognitively normal adults. These subjects were divided into 181 individuals at risk of Alzheimer’s disease (preAD group) and 236 normal control individuals (NC group) according to standard uptake ratio >1.18 calculated by amyloid Positron Emission Tomography (PET). We further divided the preaAD group into APOE+ and APOE− subgroups according to whether APOE ε4 was positive or not. All data sets were divided into one training/validation group and one independent test group. The proposed DLR method included three steps: (1) the pre-training of basic deep learning (DL) models, (2) the extraction, selection and fusion of DLR features, and (3) classification. The support vector machine (SVM) was used as the classifier. In the comparative experiments, we compared our proposed DLR method with three existing models: hippocampal model, clinical model, and traditional radiomics model. Ten-fold cross-validation was performed with 100 time repetitions.ResultsThe DLR method achieved the best classification performance between preAD and NC than other models with an accuracy of 89.85% ± 1.12%. In comparison, the accuracies of the other three models were 72.44% ± 1.37%, 82.00% ± 4.09% and 79.65% ± 2.21%. In addition, the DLR model also showed the best classification performance (85.45% ± 9.04% and 92.80% ± 2.61%) in the subgroup experiment.ConclusionThe results showed that the DLR method provided a potentially clinical value to distinguish preAD from NC.

ObjectOur goal was to assess the implant depth of a Venus-A prosthesis during transcatheter aortic valve replacement (TAVR) when the areas of eccentric calcification were distributed in different sections of the aortic valve.MethodsA total of 53 patients with eccentric calcification of the aortic valve who underwent TAVR with a Venus-A prosthesis from January 2018 to November 2019 were retrospectively analyzed. The patients were divided into three groups (A, B, and C) according to the location of the eccentric calcification, which was determined by preprocedural computerized tomography angiography (CTA) images. The prosthesis release process and position were evaluated by contrast aortography during TAVR, and the differences in valve implant depths were compared among the three groups. The effects of different aortic root structures and procedural strategies on prosthesis implant depth were analyzed.ResultsEleven patients had eccentric calcification in region A; 19 patients, in region B; and 23 patients, in region C. The patients with eccentric calcification in region B had a higher risk of prosthesis migration (10.5% upward and 21.1% downward), and the position of the prosthesis after TAVR in group B was the deepest among the three groups. When eccentric calcification was located in region A or C, the prosthesis was released at the standard position with more stability, and the location of the prosthesis was less deep after TAVR (region A: 4.12 ± 3.4 mm; region B: 10.2 ± 5.3 mm; region C: 8.4 ± 4.0 mm; region A vs. region B, P = 0.0004; region C vs. region B; and P = 0.0360). In addition, the left ventricular outflow tract (LVOT) (P = 0.0213) and aortic root angulation (P = 0.0263) also had a significant effect on implant depth in the aortic root structure of the patients. The prosthesis size was 28.3 ± 2.4 in the deep implant group and 26.4 ± 2.0 in the appropriate implant group (P = 0.0068).ConclusionThe implant depth of the Venus-A prosthesis is closely related to the distribution of eccentric calcification in the aortic valve during TAVR. Surgeons should adjust the surgical strategy according to aortic root morphology to prevent prosthesis migration.

Background: Detection of SHOX2 methylation has been used to assist in the early diagnosis of lung cancer in many hospitals as SHOX2 may be important in the tumorigenesis of lung cancer. However, there are few studies on the mRNA expression, methylation, and molecular mechanism of SHOX2 in lung cancer. We aimed to explore the role of SHOX2 in lung adenocarcinoma (LUAD).Methods: First, we examined the differential expression of SHOX2 mRNA and methylation in cancerous and normal tissues using databases. Second, we analyzed the relationship between SHOX2 expression and common clinical parameters in LUAD patients. Third, we further explored the methylated level and its specific location of SHOX2 and the mainly factors of SHOX2 gene expression. Finally, we screened the correlatively expressed genes to analyze the pathways from the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes using DAVID.Results: We found that the mRNA expression of SHOX2 was higher in multiple cancers, including LUAD and lung squamous cell carcinoma (LUSC), than in normal tissues. Among LUAD patients, SHOX2 expression was higher in patients of middle–young age, with smoking history, in advanced stages, and with nodal distant metastasis. In addition, our results showed that patients with high expression of SHOX2 are prone to recurrence, poor differentiation, and poor prognosis. Thus, we identified that SHOX2 might be an oncogene for LUAD progression. The main factor influencing the high expression of SHOX2 mRNA may be DNA methylation, followed by copy number variation (CNV), but not by gene mutations in LUAD. Unexpectedly, we found that SHOX2 undergoes hypomethylation in the gene body instead of hypermethylation in the promoter. Additionally, SHOX2 has cross talk in the PI3K–Akt signaling pathway and ECM–receptor interaction.Conclusion:SHOX2 is highly expressed in most cancers. SHOX2 gene expression might be mainly regulated by methylation of its gene body in LUAD, and its high expression or hypomethylation indicates poor differentiation and poor prognosis. SHOX2 could be involved in PI3K–Akt and other important cancer-related signaling pathways to promote tumorigenesis.

Long non-coding RNAs (lncRNA) and microRNAs (miRNA) are new found classes of non-coding RNAs (ncRNAs) that are not translated into proteins but regulate various cellular and biological processes. In this study, we conducted a transcriptomic analysis of ncRNA and mRNA expression in Aohan fine wool sheep (AFWS) at different growth stages (embryonic day 90, embryonic day 120, and the day of birth), and explored their relationship with wool follicle growth. In total, 461 lncRNAs, 106 miRNAs, and 1,009 mRNAs were found to be differentially expressed during the three stages of wool follicle development. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to clarify the roles of the differentially expressed lncRNA, miRNA, and mRNA in the different stages of wool follicle development. Quantitative real-time PCR (qRT-PCR) was used to validate the results of RNA-seq analysis. lncRNA (MSTRG.223165) was found to act as a competing endogenous RNA (ceRNA) and may participate in wool follicle development by acting as an miR-21 sponge. Network prediction implicated the MSTRG.223165-miR-21-SOX6 axis in the wool follicle development. The targeting relationships of miR-21 with SOX6 and MSTRG.223165 were validated in dual-luciferase assays. This is the first report indicating the association of the lncRNA–miRNA–mRNA network with wool follicle development in AFWS. This study provides new insights into the regulation of the wool follicle growth and represents a solid foundation for wool sheep breeding programs.

Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Most lncRNAs have been proven to have biological and clinical significance in acute myeloid leukemia (AML), but further investigation remains necessary. In this study, we investigated lncRNA NR-104098 in AML and its specific mechanism. The microarray analysis was performed on NB4 cells. Based on the related analysis results, we identified that lncRNA NR-104098 is a suppressor gene that is significantly upregulated in AML cells. LncRNA NR-104098 could inhibit proliferation and induce differentiation in AML cells in vitro and also play main role in the mouse xenografts. Mechanically, it was confirmed that lncRNA NR-104098 may effectively inhibit EZH2 transcription by directly binding to E2F1 and recruiting E2F1 to the EZH2 promoter. In addition, ATPR can significantly increase the expression of lncRNA NR-104098, whereas knocking down NR104098 can inhibit the inhibitory effect of ATPR on the proliferation and induction differentiation of AML cells. Taken together, these results lead to deeper insight into the mechanism of ATPR-induced AML differentiation and prevent proliferation by inhibiting EZH2 on the transcriptional level.

The development of efficient, stable, and low-cost catalytic material for the oxygen reduction reaction (ORR) is currently highly desirable but challenging. In this work, based on first-principles calculation, the stabilities, catalytic activities and catalytic mechanisms of isolated Au atom supported on defective porous BN (p-BN) have been studied in detail. The results reveal that the defective p-BN anchor Au atom strongly to ensure the stability of Au/p-BN. Based on frontier molecular orbital and charge-density analysis, isolated Au atom supported on porous BN with VN defect (Au/p-BN-VN) is an effective ORR catalyst. Especially, the low barriers of the formation (0.38 eV) and dissociation (0.31 eV) of *OOH and the instability of H2O2 on Au/p-BN-VN catalyst suggest that ORR proceeds via 4-electron pathway. Along the favorable pathway, the reduction of O2 to *OOH is the rate-limiting step with the largest activation barrier of 0.38 eV and the maximum free energy change is 1.88 eV. Our results provide a useful guidance for the design and fabrication of new Au-base catalyst with high-efficiency and are beneficial for the developing of novel isolated metal atom catalysts for ORR.

Developing efficient and earth-abundant electrocatalysts for the oxygen evolution reaction (OER) is still a big challenge. Here, perovskite La0.4Sr0.6Ni0.5Fe0.5O3 nanoparticles were rationally designed and synthesized by the sol-gel method with an average size around 25 nm, and it has a remarkable intrinsically activity and stability in 1 M KOH solution. Compared with other perovskite (LaNiO3, LaFeO3, and LaNi0.5Fe0.5O3) catalysts, La0.4Sr0.6Ni0.5Fe0.5O3 exhibits superior OER performance, smaller tafel slope and lower overpotential. The high electrochemical performance of La0.4Sr0.6Ni0.5Fe0.5O3 is attributed to its optimized eg filling (~1.2), as well as the excellent conductivity. This study demonstrates co-doping process is an effective way for increasing the intrinsic catalytic activity of the perovskite.

BackgroundCodonopsis pilosula (Campanulaceae) is a traditional herbal plant that is widely used in China, and the drought stress during the seedling stage directly affects the quality, ultimately impacting its yield. However, the molecular mechanisms underlying the drought resistance of C. pilosula seedlings remain unclear.MethodHerein, we conducted extensive comparative transcriptome and physiological studies on two distinct C. pilosula cultivar (G1 and W1) seedlings subjected to a 4-day drought treatment.ResultsOur findings revealed that cultivar G1 exhibited enhanced retention of proline and chlorophyll, alongside a marked elevation in peroxidase activity, coupled with diminished levels of malondialdehyde and reduced leaf relative electrolyte leakage compared with cultivar W1. This suggested that cultivar G1 had relatively higher protective enzyme activity and ROS quenching capacity. We discerned a total of 21,535 expressed genes and identified 4,192 differentially expressed genes (DEGs) by RNA sequencing (RNA-seq). Our analysis revealed that 1,764 DEGs unique to G1 underwent thorough annotation and functional categorization utilizing diverse databases. Under drought conditions, the DEGs in G1 were predominantly linked to starch and sucrose metabolic pathways, plant hormone signaling, and glutathione metabolism. Notably, the drought-responsive genes in G1 were heavily implicated in hormonal modulation, such as ABA receptor3-like gene (PYL9), regulation by transcription factors (KAN4, BHLH80, ERF1B), and orchestration of drought-responsive gene expression. These results suggest that cultivar G1 possesses stronger stress tolerance and can better adapt to drought growing conditions. The congruence between qRT-PCR validation and RNA-seq data for 15 DEGs further substantiated our findings.ConclusionOur research provides novel insights into the physiological adaptations of C. pilosula to arid conditions and lays the groundwork for the development of new, drought-tolerant C. pilosula cultivars.

ObjectiveTo investigate whether using Zishen Yutai Pills (ZYP) following embryo transfer would affect the live birth rate in frozen-thawed embryo transfer (FET) cycles.MethodsA retrospective analysis was performed on 15044 FET cycles in the Reproductive Medicine Center of The Affiliated Chenggong Hospital of Xiamen University from January 2013 to December 2020. Patients who used Zishen Yutai Pills were defined as Zishen Yutai Pills Group (ZYP, n=2735), while patients who did not use them were defined as Non- Zishen Yutai Pills Group (Non-ZYP, n=12309). The propensity score matching method was used to control for potential confounders between the two groups, and logistic regression analysis was also used to assess whether using ZYP would affect the live birth rate.ResultsAfter propensity score matching, basic characteristics were similar between the two groups. Using ZYP did not increase the pregnancy rate (51.5% vs. 52.7%, P=0.372), and live birth rate (43.0% vs. 44.7%, P=0.354). This was also confirmed by the logistic regression analysis results (OR=0.95, 95%CI=0.85-1.06). In the subgroup analysis of the endometrial preparation protocols, however, it was found that the use of ZYP in patients with natural cycles increased the live birth rate (47.4% vs. 41.5%, P=0.004). A significant interaction between endometrial preparation and ZYP was found (OR=1.38, 95%CI=1.07-1.79) in the multivariate model.ConclusionThe use of ZYP may not improve the live birth rate of unselected patients in FET cycles. However, a future study is needed on the effect of ZYP in natural cycles for endometrial preparation.

IntroductionThe proportion of retroperitoneal malignant peripheral nerve sheath tumours (RMPNST) in retroperitoneal tumors is less than 5%, but the mortality rate is very high. However, there is no relevant research focused on RMPNST only.MethodsWe retrospectively analyzed data from the SEER database of patients with primary RMPNST from 2000 to 2019, by leveraging the advantages of the Seer database, we can explore the prognosis of such rare diseases. Kaplan-Meier method was used to construct the survival curve, and cox regression model was used to analyze the factors affecting the prognosis of patients. In addition, a model was developed to distinguish high-risk and low-risk patients.ResultsThis study included a total of 52 patients, with a median survival time of 39 months (95% CI 12.740–65.260) and a 5-year survival rate of 44.2% (95% CI 0.299–0.565). Radiotherapy (p = 0.004, OR: 1.475, 95% CI 0.718–3.033), metastasis disease (p = 0.002, OR: 5.596, 95% CI 2.449–47.079) and surgery (p = 0.003, OR: 5.003, 95% CI 0.011–0.409) were associated with overall survival (OS). The 5-year distant metastasis rate was 36% (95% CI 0.221–0.499). We used the above risk factors to separate patients into high and low groups and evaluate the results through the receiver operating characteristic (ROC) curve. This model is beneficial for guiding the selection of treatment strategies.ConclusionThe majority of RMPNST patients have a good prognosis after surgery, and the establishment of high-low group is helpful for clinical decision-making.

ObjectiveTo investigate the interaction between atosiban and growth hormone (GH) as adjuvants in frozen-thawed embryo transfer (FET) cyclesMethodA total of 11627 patients who underwent FET at Xiamen University Affiliated Chenggong Hospital between January 2018 to December 2022 were retrospectively analyzed. Among them, 482 patients received atosiban and 275 patients received GH. The interactions were estimated by comparing the odds ratio (OR) for pregnancy comparing patients with or without atosiban adjuvant in cohorts stratified according to the presence of GH use in either the overall cohort or a propensity score (PS) matched cohort. An interaction term (atosiban × GH) was introduced to a multivariate model to calculate the ratio of OR (ORR) adjusted for confounders.ResultsFor all patients receiving atosiban administration, no obvious effect on pregnancy was observed in comparison with either matched or unmatched controls. However, when the patients were stratified according to GH administration, atosiban showed a significant association with clinical pregnancy in comparison with either matched or unmatched controls among patients with GH treatment with rate ratios (RR) of 1.32 (95%CI: 1.05,1.67) and 1.35 (95%CI: 1,1.82), respectively. On the other hand, however, the association was absent among patients without GH treatment. The adjusted ORRs in both matched and unmatched cohorts were 2.44 (95%CI: 1.07,5.84) and 1.95 (95%CI: 1.05, 3.49) respectively.ConclusionThe combination use of atosiban and GH in FET cycles is potentially beneficial to the pregnancy. However, indications for the use of atosiban and GH may need further assessment.

BackgroundLow-dose aspirin is one of the widely used adjuvants in assisted reproductive technologies with the hope of improving the live birth rate. However, the studies regarding its effects are conflicting. The study aimed to investigate the association between aspirin administration and live birth following frozen-thawed embryo transfer (FET) in patients with different body mass index (BMI).MethodsA retrospective cohort study was performed on 11,993 patients receiving FET treatments. 644 of which received a low-dose aspirin (100 mg/day) during endometrial preparation until 10 weeks after transfer. Propensity score matching was performed to avoid selection biases and potential confounders.ResultsThe clinical pregnancy rate and live birth rate were similar before matching (54.4% versus 55.4%, RR: 1.02, 95%CI: 0.95-1.09, and 46.3 versus 47.8, RR: 1.03, 95%CI: 0.95-1.12 respectively). A weak association in favor of aspirin administration was found in the matched cohort (49.5% versus 55.4%, RR: 1.12, 95%CI: 1.01-1.24, and 41.9% versus 47.8%, RR: 1.14, 95%CI: 1.01-1.29 respectively). However, when stratified the patients with WHO BMI criteria, a significant increase in live birth rate associated with aspirin treatment was found only in patients with low BMI (

The central nervous system (CNS) harbors its own special immune system composed of microglia in the parenchyma, CNS-associated macrophages (CAMs), dendritic cells, monocytes, and the barrier systems within the brain. Recently, advances in the immune cells in the CNS provided new insights to understand the development of tuberculous meningitis (TBM), which is the predominant form of Mycobacterium tuberculosis (M.tb) infection in the CNS and accompanied with high mortality and disability. The development of the CNS requires the protection of immune cells, including macrophages and microglia, during embryogenesis to ensure the accurate development of the CNS and immune response following pathogenic invasion. In this review, we summarize the current understanding on the CNS immune cells during the initiation and development of the TBM. We also explore the interactions of immune cells with the CNS in TBM. In the future, the combination of modern techniques should be applied to explore the role of immune cells of CNS in TBM.

Hypoxia induced by high altitude can lead to severe neurological dysfunction. Mitophagy is known to play a crucial role in hypoxic nerve injury. However, the regulatory mechanism of mitophagy during this injury remains unclear. Recent studies have highlighted the role of Sestrin2 (SESN2), an evolutionarily conserved stress-inducible protein against acute hypoxia. Our study demonstrated that hypoxia treatment increased SESN2 expression and activated mitophagy in PC12 cells. Furthermore, the knock-out of Sesn2 gene led to a significant increase in mitochondrial membrane potential and ATP concentrations, which protected the PC12 cells from hypoxic injury. Although the AMPK/mTOR pathway was significantly altered under hypoxia, it does not seem to participate in mitophagy regulation. Instead, our data suggest that the mitophagy receptor FUNDC1 plays a vital role in hypoxia-induced mitophagy. Moreover, SESN2 may function through synergistic regulation with other pathways, such as SESN2/AMPK, to mediate cellular adaptation to hypoxia, including the regulation of mitophagy in neuron cells. Therefore, SESN2 plays a critical role in regulating neural cell response to hypoxia. These findings offer valuable insights into the underlying molecular mechanisms governing the regulation of mitophagy under hypoxia and further highlight the potential of SESN2 as a promising therapeutic target for hypoxic nerve injury.

BackgroundOocyte degeneration was mostly described in intracytoplasmic sperm injection (ICSI) cycles; there is no report showing the relationship between oocyte degeneration and clinical outcomes in conventional in vitro fertilization (IVF) cycles. This retrospective study using the propensity score (PS) matching method aimed to explore whether the presence of oocyte degeneration in conventional IVF cycles would affect the sibling embryo development potential and clinical outcomes.MethodsPatients with at least one oocyte degenerated after short-term insemination and stripping were defined as the degeneration (DEG) group, while patients with no oocyte degenerated were defined as the non-degeneration (NONDEG) group. The PS matching method was used to control for potential confounding factors, and a multivariate logistic regression analysis was made to evaluate whether the presence of oocyte degeneration would affect the cumulative live birth rate (CLBR).ResultsAfter PS matching, basic characteristics were similar between the two groups, oocyte yield was significantly higher in the DEG group than the NON-DEG group (P < 0.05), mature oocyte number, 2 pronuclear (2PN) embryo number, 2PN embryo clearage rate, “slow” embryo number, “accelerated” embryo number, rate of cycles with total day 3 embryo extended culture, number of frozen embryo transfer (FET) cycles, transferred embryo stage, transferred embryo number, and live birth rate in fresh embryo transfer cycles were all similar between the two groups (P > 0.05), but the 2PN fertilization rate, available embryo number, high-quality embryo number, “normal” embryo number, frozen embryo number, blastocyst formation rate, and no available embryo cycle rate were all significantly lower in the DEG group than the NON-DEG group (P < 0.05). The cumulative live birth rate was also significantly lower in the DEG group than in the NON-DEG group (70.2% vs. 74.0%, P = 0.0019). Multivariate logistic regression analysis further demonstrated that the presence of oocyte degeneration in conventional IVF cycles adversely affects the CLBR both before (OR = 0.83, 95% CI: 0.75–0.92) and after (OR = 0.82, 95% CI: 0.72–0.93) PS matching.ConclusionOur findings together revealed that the presence of oocyte degeneration in a cohort of oocytes may adversely affect subsequent embryo development potential and clinical outcomes in conventional IVF cycles.

ObjectiveTo evaluate the utility of apparent diffusion coefficient (ADC) values for differentiating breast tumors.MethodsThe medical records of 17 patients with phyllodes tumor [PT; circular regions of interest (ROI-cs) n = 171], 74 patients with fibroadenomas (FAs; ROI-cs, n = 94), and 57 patients with breast cancers (BCs; ROI-cs, n = 104) confirmed by surgical pathology were retrospectively reviewed.ResultsThere were significant differences between PTs, FAs, and BCs in ADCmean, ADCmax, and ADCmin values. The cutoff ADCmean for differentiating PTs from FAs was 1.435 × 10−3 mm2/s, PTs from BCs was 1.100 × 10−3 mm2/s, and FAs from BCs was 0.925 × 10−3 mm2/s. There were significant differences between benign PTs, borderline PTs, and malignant PTs in ADCmean, ADCmax, and ADCmin values. The cutoff ADCmean for differentiating benign PTs from borderline PTs was 1.215 × 10−3 mm2/s, and borderline PTs from malignant PTs was 1.665 × 10−3 mm2/s.ConclusionDWI provides quantitative information that can help distinguish breast tumors.

Background: Male and female gametes factors might contribute to the total fertilization failure (TFF). In first in vitro fertilization (IVF) cycles, decision-making of insemination protocol was mainly based on semen quality for the contribution of female clinical characteristics to TFF remained obscure. The purpose of the study was to evaluate the role of semen quality in predicting unexpected TFF.Methods: A single-center retrospective cohort analysis was performed on 19539 cycles between 2013 and 2021. Two algorithms, a Least Absolute Shrinkage and Selection Operator (LASSO) and an Extreme Gradient Boosting (Xgboost) were used to create models with cycle characteristics parameters. By including semen parameters or not, the contribution of semen parameters to the performance of the models was evaluated. The area under the curve (AUC), the calibration, and the net reclassification index (NRI) were used to evaluate the performance of the models.Results: The prevalence of TFF were .07 (95%CI:0.07-0.08), and .08 (95%CI:0.07-0.09) respectively in the development and validation group. Including all characteristics, with the models of LASSO and Xgboost, TFF was predicted with the AUCs of .74 (95%CI:0.72-0.77) and .75 (95%CI:0.72-0.77) in the validation group. The AUCs with models of LASSO and Xgboost without semen parameters were .72 (95%CI:0.69-0.74) and .73 (95%CI:0.7-0.75). The models of LASSO and Xgboost with semen parameters only gave the AUCs of .58 (95%CI:0.55-0.61) and .57 (95%CI:0.55-0.6). For the overall validation cohort, the event NRI values were −5.20 for the LASSO model and −.71 for the Xgboost while the non-event NRI values were 10.40 for LASSO model and 0.64 for Xgboost. In the subgroup of poor responders, the prevalence was .21 (95%CI:0.18-0.24). With refitted models of LASSO and Xgboost, the AUCs were .72 (95%CI:0.67-0.77) and .69 (95%CI:0.65-0.74) respectively.Conclusion: In unselected patients, semen parameters contribute to limited value in predicting TFF. However, oocyte yield is an important predictor for TFF and the prevalence of TFF in poor responders was high. Because reasonable predicting power for TFF could be achieved in poor responders, it may warrant further study to prevent TFF in these patients.

ObjectivesTo investigate the prevalence of adverse pregnancy outcomes (APOs) in women and the impact of pre-pregnancy couples' genital Chlamydia Trachomatis (GCT) infection and other infections on APOs.Study designData on genital infections were collected from the Free Pre-pregnancy Health Check (FPHC) in Shenzhen, China. Data on APOs were collected from a 1-year telephone follow-up of pregnancy status and subsequent pregnancy outcomes.MethodsAPO data were used to count adverse outcomes, and logistic regression was conducted to determine the association between APOs and GCT infection.ResultsFrom December 2018 to December 2019, among 4,429 couples who underwent FPHC; 1,925 were pregnant, and 1,816 couples were tracked for pregnancy outcomes, including 1,471 normal pregnancies and 345 (19.00%) APOs. The rest of 109 pregnant couples did not answer the phone or refused to answer the pregnancy outcome during the follow-up. Among APOs, the number of spontaneous abortions was 122 (35.36%), the number of macrosomia was 85 (24.64%), the number of low birth weight (LBW) & preterm births (PTB) was 39 (11.30%), the number of LBW was 34 (9.86%), and the number of PTB was 31 (8.99%). The prevalence of GCT infection in females and males was 4.24% [95% Confidence Interval, (CI): 3.41–5.27%] and 3.58% (95% CI: 2.79–4.57%), respectively. More than half (52.69%, 49/93) of the couples were GCT-concordant. The prevalence of APOs in couples without GCT infection was 18.74% (332/1,772). The prevalence of APOs in female GCT-discordant was 32.14% (9/28), and the prevalence of APOs in male GCT-discordant was 25% (4/16). The prevalence of APOs in GCT-concordant was 12.24% (6/49). Multivariable analysis indicated that females 30–35 years old [adjusted Odds Ratio (aOR) = 1.08, 95% CI: 1.01–1.17] and over 35 years old (aOR = 1.16, 95% CI: 1.03–1.32) were more likely to experiencing APOs.ConclusionAlthough only women's age was found to be associated with APOs, the prevalence of APOs with GCT-discordant in couples, especially female GCT-discordant, was higher than in those without infection or who were GCT-concordant, suggesting that these groups, especially in older women, should be paid more attention to in follow-ups to improve reproductive health.

BackgroundDERL3 has been implicated as an essential element in the degradation of misfolded lumenal glycoproteins induced by endoplasmic reticulum (ER) stress. However, the correlation of DERL3 expression with the malignant phenotype of lung adenocarcinoma (LUAD) cells is unclear and remains to be elucidated. Herein, we investigated the interaction between the DERL3 and LUAD pathological process.MethodsThe Cancer Genome Atlas (TCGA) database was utilized to determine the genetic alteration of DERL3 in stage I LUAD. Clinical LUAD samples including carcinoma and adjacent tissues were obtained and were further extracted to detect DERL3 mRNA expression via RT-qPCR. Immunohistochemistry was performed to evaluate the protein expression of DERL3 in LUAD tissues. The GEPIA and TIMER website were used to evaluate the correlation between DERL3 and immune cell infiltration. We further used the t-SNE map to visualize the distribution of DERL3 in various clusters at the single-cell level via TISCH database. The potential mechanisms of the biological process mediated by DERL3 in LUAD were conducted via KEGG and GSEA.ResultsIt was indicated that DERL3 was predominantly elevated in carcinoma compared with adjacent tissues in multiple kinds of tumors from the TCGA database, especially in LUAD. Immunohistochemistry validated that DERL3 was also upregulated in LUAD tissues compared with adjacent tissues from individuals. DERL3 was preliminarily found to be associated with immune infiltration via the TIMER database. Further, the t-SNE map revealed that DERL3 was predominantly enriched in plasma cells of the B cell population. It was demonstrated that DERL3 high-expressed patients presented significantly worse response to chemotherapy and immunotherapy. GSEA and KEGG results indicated that DERL3 was positively correlated with B cell activation and unfolded protein response (UPR).ConclusionOur findings indicated that DERL3 might play an essential role in the endoplasmic reticulum-associated degradation (ERAD) process in LUAD. Moreover, DERL3 may act as a promising immune biomarker, which could predict the efficacy of immunotherapy in LUAD.

Phoebe bournei (Hemsl.) Yang is used as a commercial wood in China and is enlisted as a near-threatened species. Prolonged droughts pose a serious threat to young seedlings (1-2 years old). A transcriptome sequencing approach, together with the measurement of growth parameters and biochemical analyses were used to understand P. bournei’s drought responses on 15d, 30d, and 45d of drought stress treatment. The stem and root dry weights decreased significantly with drought stress duration. Activities of antioxidative enzymes i.e., peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) increased significantly with the increase in drought stress duration. A total of 13,274, 15,648, and 9,949 genes were differentially expressed in CKvs15d, CKvs30d, and CKvs45d, respectively. The differential expression analyses showed that photosystem I and II underwent structural changes, chlorophyll biosynthesis, and photosynthesis were reduced. The genes annotated as POD, SOD, and CAT were upregulated in drought-treated leaves as compared to control. Additionally, plant-hormone signal transduction, MAPK signaling-plant, phenylpropanoid biosynthesis, flavonoid biosynthesis, and starch and sucrose metabolism pathways showed large-scale expression changes in major genes. We also found that members of 25 transcription factor families were differentially expressed. Our study presents and discusses these transcriptome signatures. Overall, our findings represent key data for breeding towards drought stress tolerance in P. bournei.

BackgroundPrevious studies have arguably associated poor embryo morphology with low birth weight in singletons following single embryo transfer. However, the association between birth weight and specific morphological features in the cleavage stage remains less known. The purpose of the study was to investigate whether morphological features of embryos at the cleavage stage affect birth weight following blastocyst transfer.MethodsThe single-center retrospective cohort study included 4,226 singletons derived from fresh single cleavage-stage embryo transfer (ET; n = 1,185), fresh single blastocyst transfer (BT; n = 787), or frozen-thawed single blastocyst transfer (FBT; n = 2,254) between 2016 and 2019. Morphological parameters including early cleavage, day-3 fragmentation, symmetry, blastomere number, and blastocyst morphology were associated with neonatal birth weight and birth weight z-score in multivariate regression models. The models were adjusted for maternal age, body mass index (BMI), parity, peak estradiol level, endometrial thickness, insemination protocol, female etiologies, order of transfer, mode of delivery, and year of treatment.ResultsAdjusted for confounders, day-3 fragmentation was the only morphological feature associated with birth weight and birth weight z-score, while early cleavage, symmetry, blastomere number, and blastocyst morphology were not. Day-3 fragmentation increased the birth weight in both the ET (115.4 g, 95% CI: 26.6–204.2) and BT groups (168.8 g, 95% CI: 48.8–288.8) but not in the FBT group (7.47 g, 95% CI: -46.4 to 61.3). The associations between birth weight and these morphological parameters were confirmed through birth weight z-score analyses. The adjusted odds of large for gestational age (LGA) and high birth weight were also significantly greater in singletons following the transfer of fragmented embryos in the BT group [odds ratio (OR) 3, 95% CI: 1.2–7.51 and OR 3.65, 95% CI: 1.33–10, respectively]. The presence of fragmentation at the cleavage stage also affected the association between the blastocyst morphology and birth weight. Inner cell mass grades were negatively associated with birth weight in blastocysts with day-3 fragmentation but not in blastocysts without.ConclusionsThe birth weight following blastocyst transfer was found to be positively associated with fragmentation at the cleavage stage. The data did not support the argument that transferring a poor-looking embryo may increase the risks of low birth weight. However, concerns for LGA infants remain.

In recent years, the emerging highly pathogenic avian influenza (HPAI) A(H5N8) virus has been reported with features of widely spread, an expanding host range, and cross-species transmission, attracting wide attention. The domestic duck plays a major role in the epidemiological cycle of the HPAI H5N8 virus, but little is known concerning innate immune responses during influenza infection in duck species. In this study, we used two wild-bird-origin viruses, H5N8 and H4N6, to conduct duck infection experiments, and detect the load of the two viruses, and retinoic acid-inducible gene I (RIG-I) and interferon β (IFN-β) in the host’s natural immune response. Through comparison, it is found that the expression levels of RIG-I and IFN-β are both fluctuating. The innate immunity starts rapidly within 6 h after infection and is inhibited by the virus to varying degrees. The expression of RIG-I and IFN-β decreased on 1–2 days post-infection (dpi). The HPAI H5N8 virus has a stronger inhibitory effect on RIG-I than the low pathogenic avian influenza (LPAI) H4N6 virus and is the strongest in the lungs. After infection with HPAI H5N8 virus, 2 dpi, viral RNA replicates in large amounts in the lungs. It has been proven that RIG-I and IFN-β play an important role in the innate immune response of ducks to HPAI H5N8 virus infection, especially in the lungs. The main battlefield of RIG-I and IFN-β after infection with the LPAI H4N6 virus is in the rectum. Both viruses have been effectively controlled after 7 dpi. These results will help to understand the transmission mechanisms of avian influenza virus in wild ducks and help effectively prevent and control avian influenza.

BackgroundRenal cell carcinoma is the most common malignant tumor of the kidney. The 5-year survival of renal cell carcinoma with distant metastasis is very low. Sohlh2 is a newly discovered tumor suppressor gene playing inhibitory roles in a variety of tumors, but its role in renal cell carcinoma has not been reported.MethodsTo clarify the role of Sohlh2 in the occurrence and development of renal cell carcinoma, we constructed stably transfected human renal cell carcinoma cell lines with Sohlh2 overexpression and Sohlh2 knockdown, separately. First, we studied the effects of Sohlh2 on proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of renal cell carcinoma cells in vitro and in vivo. Then, we detected whether Sohlh2 functions through DNMT3a/Klotho using Western blotting, qPCR, and Cell Counting Kit-8 (CCK-8) assay. Finally, we collected 40 resected renal cell carcinoma samples to study the relevance between Sohlh2, DNMT3a, and Klotho by immunohistochemistry.ResultsOur results showed that Sohlh2 was downregulated in renal cell carcinoma, and its expression level was negatively correlated with tumor staging. Both in vitro and in vivo experiments confirmed that Sohlh2 overexpression inhibited the proliferation, migration, invasion, metastasis, and EMT of renal cell carcinoma. Sohlh2 functions through demethylation of Klotho by downregulating the expression of DNA methyltransferase of DNMT3a. In renal cell carcinoma, Sohlh2 was positively correlated with Klotho and negatively correlated with DNMT3a.ConclusionSohlh2 functions as a tumor suppressor gene in renal cell carcinoma by demethylation of Klotho via DNMT3a. Sohlh2 correlated with Klotho positively and with DNMT3a negatively in renal cell carcinoma. Our study suggests that Sohlh2 and DNMT3a/Klotho can be used as potential targets for the clinical treatment of renal cell carcinoma.

Background: Lung adenocarcinoma (LUAD) is the most predomintnt lung cancer subtype with increasing morbidity and mortality. Previous studies have shown that aquaporin (AQP) family genes were correlated with tumor progression and metastasis in several kinds of malignancies. However, their biological behaviors and prognostic values in LUAD have not been comprehensively elucidated.Methods: RNA sequencing and real-time reverse transcription PCR (RT-PCR) were used to assess AQP1/3/4/5 gene expressions in LUAD patients using GEPIA and UALCAN databases. And then Kaplan–Meier analysis, cBioPortal, Metascape, GeneMANIA, TISIDB, and TIMER were utilized to determine the prognostic value, mutation frequency, and immune cell infiltration of AQP family members in LUAD.Results: We found that AQP3 expression was significantly elevated and AQP1 expression was markedly reduced in LUAD patients, whereas the expression levels of AQP4 and AQP5 exhibited no significant changes. The Kaplan–Meier survival analysis indicated that the higher expressions of AQP1/4/5 were related to longer overall survival (OS). Of interest, AQP3 was significantly correlated with the clinical tumor stage and lower AQP3 expression showed favorable prognosis in stage I LUAD patients, which indicated that AQP3 may be a potential prognostic biomarker for patients. Through functional enrichment analysis, the functions of these four AQPs genes were mainly involved in the passive transport by aquaporins, water homeostasis, and protein tetramerization. Moreover, AQP1/3/4/5 expression was strongly associated with tumor-infiltrating lymphocytes (TILs) in LUAD.Conclusion: AQP3 can be used as a prognosis and survival biomarker for stage I LUAD. These findings may provide novel insights into developing molecular targeted therapies in LUAD.

Erythromycins produced by Saccharopolyspora erythraea have broad-spectrum antibacterial activities. Recently, several TetR-family transcriptional regulators (TFRs) were identified to control erythromycin production by multiplex control modes; however, their regulatory network remains poorly understood. In this study, we report a novel TFR, SACE_0303, positively correlated with erythromycin production in Sac. erythraea. It directly represses its adjacent gene SACE_0304 encoding a MarR-family regulator and indirectly stimulates the erythromycin biosynthetic gene eryAI and resistance gene ermE. SACE_0304 negatively regulates erythromycin biosynthesis by directly inhibiting SACE_0303 as well as eryAI and indirectly repressing ermE. Then, the SACE_0303 binding site within the SACE_0303-SACE_0304 intergenic region was defined. Through genome scanning combined with in vivo and in vitro experiments, three additional SACE_0303 target genes (SACE_2467 encoding cation-transporting ATPase, SACE_3156 encoding a large transcriptional regulator, SACE_5222 encoding α-ketoglutarate permease) were identified and proved to negatively affect erythromycin production. Finally, by coupling CRISPRi-based repression of those three targets with SACE_0304 deletion and SACE_0303 overexpression, we performed stepwise engineering of the SACE_0303-mediated mini-regulatory network in a high-yield strain, resulting in enhanced erythromycin production by 67%. In conclusion, the present study uncovered the regulatory network of a novel TFR for control of erythromycin production and provides a multiplex tactic to facilitate the engineering of industrial actinomycetes for yield improvement of antibiotics.

Diabetes mellitus (DM) is a chronic inflammatory disease, and the rapidly increasing DM is becoming a major problem of global public health. Traditional Chinese medicine (TCM) has a long history of treating diabetes. It has been developed and utilized because of its good efficacy and no toxic side effects. Lobelia chinensis is a traditional whole grass herbal. With the continuous deepening of pharmacological research on TCM, the active ingredients of L. chinensis are continuously revealed, which contained the alkaloids, flavonoids, flavonoid glycosides and amino acids that have the good effects of anti-inflammatory, anti-viral and anti-diabetic. In order to further explore the targets of active ingredients and its anti-diabetic mechanism, a feasible network pharmacology analysis model based on chemical, pharmacokinetic and pharmacological data was developed by network construction method to clarify the anti-diabetic mechanism of L. chinensis. The present study conducted by gas chromatography–mass spectrometer (GC/MS), which identified 208 metabolites of L. chinensis, of which 23 ingredients may have effective pharmacological effects after absorption, distribution, metabolism, and excretion (ADME) screening. Network pharmacological analysis on the active ingredients revealed that 5-hydroxymethylfurfural in L. chinensis affects the insulin resistance signaling pathway by acting on GSK3B, TNF, and MAPK1, acacetin affects the diabetic pathway by acting on INSR, DPP4, and GSK3B, that regulate type 2 diabetes, non-insulin-dependent DM, and inflammatory diseases. These results successfully indicated the potential anti-diabetic mechanism of the active ingredients of L. chinensis.

The pathogenesis of diabetes mellitus is a complicated process involving much gene regulation. The molecular mechanism of mulberry (Morus alba L.) leaf in the treatment of diabetes is not fully understood. In this study, we used the Illumina HiSeq™ 2,500 platform to explore the liver transcriptome of normal mice, STZ-induced diabetic mice, and mulberry leaf-treated diabetic mice, and we obtained 52,542,956, 52,626,414, and 52,780,196 clean reads, respectively. We identified differentially expressed genes (DEGs) during the pathogenesis of diabetes in mice. The functional properties of DEGs were characterized by comparison with the GO and KEGG databases, and the results show that DEGs are mainly involved in the metabolic pathway. qRT-PCR was used to analyse 27 differential genes involved in liver expression in different groups of diabetic mice. Among the DEGs, the expression of Scube1, Spns3, Ly6a, Igf2, and other genes between the control (C) and diabetic control (DC) groups was significantly upregulated; the expression of Grb10, Mup2, and Fasn was significantly downregulated; the expression of the Sqle, Lss, and Irs2 genes between the C group and diabetic group treated with mulberry (DD) was significantly upregulated; the expression of Fabp2, Ly6a, and Grb10 was significantly downregulated; and the expression of Sqle and Lss was significantly upregulated in the DC and DD groups, but Tap1, Igf2, and Spns3 were significantly downregulated. The results of Western blot validation showed that dynamic changes in proteins, such as IGF2, Ly6a, Grb10, and UBD, occurred to regulate the incidence of diabetes by influencing the insulin receptor substrate (IRS) signaling pathway.