Pulmonary cavernous hemangioma: a case report

We report a rare case of pulmonary cavernous hemangioma in a 51-year-old female. A computed tomographic scan of the chest showed an ill-defined mass measuring 2.3 cm × 2.2 cm in the right lower lobe. Surgical resection was performed and postoperative histological examination revealed cavernous hemangioma. We reviewed the clinical features and therapeutic methcds of hemangioma.

TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and homeostasis.However,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood.Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l infusion.Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload.Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre mice.Echocardiographic and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac remodeling.Mechanistically,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 target.TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression.Furthermore,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 promoter.In conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.

Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1^(high)CD11b^(+)cells elimination in hepatocellular carcinoma

Cryoablation(CRA)and microwave ablation(MWA)are two main local treatments for hepatocellular carcinoma(HCC).However,which one is more curative and suitable for combining with immunotherapy is still controversial.Herein,CRA induced higher tumoral PD-L1 expression and more T cells infiltration,but less PD-L1^(high)CD11b^(+)myeloid cells infiltration than MWA in HCC.Furthermore,CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models.Mechanistically,anti-PD-L1 antibody facilitated infiltration of CD8^(+)T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy.On the other hand,anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^(high)CD11b^(+)myeloid cells by antibody-dependent cell-mediated cytotoxicity(ADCC)effect after CRA therapy.Both aspects relieved the immunosuppressive microenvironment after CRA therapy.Notably,the wild-type PD-L1 Avelumab(Bavencio),compared to the mutant PD-L1 atezolizumab(Tecentriq),was better at inducing the ADCC effect to target PD-L1^(high)CD11b^(+)myeloid cells.Collectively,our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses,which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

HIV-1 Vif suppresses antiviral immunity by targeting STING

HIV-1 infection-induced cGAS–STING–TBK1–IRF3 signaling activates innate immunity to produce type I interferon(IFN).The HIV-1 nonstructural protein viral infectivity factor(Vif)is essential in HIV-1 replication,as it degrades the host restriction factor APOBEC3G.However,whether and how it regulates the host immune response remains to be determined.In this study,we found that Vif inhibited the production of type I IFN to promote immune evasion.HIV-1 infection induced the activation of the host tyrosine kinase FRK,which subsequently phosphorylated the immunoreceptor tyrosine-based inhibitory motif(ITIM)of Vif and enhanced the interaction between Vif and the cellular tyrosine phosphatase SHP-1 to inhibit type I IFN.Mechanistically,the association of Vif with SHP-1 facilitated SHP-1 recruitment to STING and inhibited the K63-linked ubiquitination of STING at Lys337 by dephosphorylating STING at Tyr162.However,the FRK inhibitor D-65495 counteracted the phosphorylation of Vif to block the immune evasion of HIV-1 and antagonize infection.These findings reveal a previously unknown mechanism through which HIV-1 evades antiviral immunity via the ITIM-containing protein to inhibit the posttranslational modification of STING.These results provide a molecular basis for the development of new therapeutic strategies to treat HIV-1 infection.

The effects of nicotinamide adenine dinucleotide in cardiovascular diseases: Molecular mechanisms, roles and therapeutic potential

Recently, cardiovascular diseases (CVDs) were identified as the leading cause of mortality, imposing a heavy burden on health care systems and the social economy. Nicotinamide adenine dinucleotide (NAD+), as a pivotal co-substrate for a range of different enzymes, is involved in many signal transduction pathways activated in CVDs. Emerging evidence has shown that NAD+ can exert remediating effects on CVDs by regulating metabolism, maintaining redox homeostasis and modulating the immune response. In fact, NAD+ might delay ageing through sirtuin and non-sirtuin pathways and thus contribute to interventions for age-related diseases such as CVDs. Considering that robust clinical studies of NAD+ are ongoing, we discuss current challenges and the future translational potential of NAD+ based on existing studies and our understanding. Despite some remaining gaps in its clinical application, NAD+ has been shown to have broad prospects and pan-effects, making it a suitable prophylactic drug for CVDs.

Origin and Spread of the ALDH2 Glu504Lys Allele

Gene polymorphism of acetaldehyde dehydrogenase 2(ALDH2),a key enzyme for alcohol metabolism in humans,can affect catalytic activity.The ALDH2 Glu504Lys mutant allele has a high-frequency distribution in East Asian populations and has been demonstrated to be associated with an increased risk of cardiovascular disease,stroke,and tumors.Available evidence suggests that the evolution of the ALDH2 gene has been influenced by multiple factors.Random mutations pro-duce Glu504Lys,and genetic drift alters the frequency of this allele;additionally,environmental factors such as hepatitis B virus infection and high-elevation hypoxia affect its frequency through selective effects,ultimately resulting in a high frequency of this allele in East Asian populations.Here,the origin,selection,and spread of the ALDH2 Glu504Lys allele are discussed,and an outlook for further research is proposed to realize a precision medical strategy based on the genetic and environmental variations in ALDH2.

Nanobiochar for the remediation of contaminated soil and water:challenges and opportunities

Although research on biochar has received increasing attention for environmental and agricultural applications,the significance of nanobiochar for environmental pollutant remediation is poorly understood.In contrast to bulk biochar,nanobiochar has superior physicochemical properties such as high catalytic activity,unique nanostructure,large specific surface area and high mobility in the soil environment.These unique characteristics make nanobiochar an ideal candidate for pollution remediation.Thus far,the research on nanobiochar is still in its infancy and most of the previous studies have only been conducted for exploring its properties and environmental functions.The lack of in-depth summary of nanobiochar’s research direction makes it a challenge for scientists and researchers globally.Hence in this review,we established some key fabrication methods for nanobiochar with a focus on its performance for the removal of pollutants from the environment.We also provided up-to-date information on nanobiochar’s role in environmental remediation and insights into different mechanisms involved in the pollutant removal.Although,nanobiochar application is increasing,the associated drawbacks to the soil ecosystem have not received enough research attention.Therefore,further research is warranted to evaluate the potential environmental risks of nanobiochar before large scale application.