Investigating nonflow contribution subtraction in d-Au collisions with AMPT model

This paper presents research that focuses on nonflow contribution subtraction in heavy-ion collisions, using a multiphase transport model (AMPT). Specifically, the study aims to investigate the behavior of charged particle elliptic flow ($v_{\rm 2}$) in d-Au collisions at a collision energy of $\sqrt{s_{\rm NN}} = 200$ GeV and to determine the impact of nonflow sources, such as jet correlations and resonance decays, in small collision systems. To reduce nonflow effects, the per-trigger yield distribution in peripheral d-Au collisions or pp collisions with the same collision energy is subtracted. Our results show that the nonflow effects in central and mid-central collisions are not strongly dependent on subtracting the per-trigger yield distribution in peripheral d-Au collisions or pp collisions. Furthermore, the elliptic flow of charged particles, after removing nonflow effects through two subtracting methods from this work, exhibits consistency in various collision centrality classes. We also discuss comparisons with measurements from d-Au collisions at $\sqrt{s_{\rm NN}} = 200$ GeV. Overall, this work provides valuable insights and serves as a reference for researchers studying nonflow contribution subtraction in experiments with small collision systems

Study of neutron density fluctuation and neutron-proton correlation in Au+Au collisions using PYTHIA8/Angantyr

Utilizing the PYTHIA8 Angantyr model, which incorporates the multiple-parton interactions (MPI) based color reconnection (CR) mechanism, we study the relative neutron density fluctuation and neutron-proton correlation in Au+Au collisions at $\sqrt{s_\text{NN}}$ = 7.7, 11.5, 14.5, 19.6, 27, 39, 62.4, and 200 GeV. In this study, we have not only delved into the dependence of these two remarkable observations on rapidity, centrality, and energy, but also presented an analysis of their interplay with the MPI and CR. Our results have shown that the light nuclei yield ratio of proton, deuteron, and triton, expressed by the elegant expression $N_tN_p/N_d^2$, remains unchanged even as the rapidity coverage and collision centrality increase. Interestingly, we have also revealed that the effect of CR is entirely dependent on the presence of MPI; CR has no impact on the yield ratio if MPI is off. Our findings further demonstrate that the light nuclei yield ratio experiences a slight increase with increasing collision energy as predicted by the PYTHIA8 Angantyr model, but it cannot describe the non-monotonic trend observed by the STAR experiment. Based on the Angantyr model simulation results, it is essential not to overlook the correlation between neutron and proton fluctuations. The Angantyr model is a good baseline for studying collisions in the absence of a Quark-Gluon Plasma (QGP) system, given its lack of flow and jet quenching.Comment: arXiv admin note: text overlap with arXiv:2211.03297 by other author

New insights from GWAS for the cleft palate among han Chinese population

Genome wide association studies (GWAS) already have identified tens of susceptible loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, whether these loci associated with nonsyndromic cleft palate only (NSCPO) remains unknown. In this study, we replicated 38 SNPs (Single nucleotide polymorphisms) which has the most significant p values in published GWASs, genotyping by using SNPscan among 144 NSCPO trios from Western Han Chinese. We performed the transmission disequilibrium test (TDT) on individual SNPs and gene-gene (GxG) interaction analyses on the family data; Parent-of-Origin effects were assessed by separately considering transmissions from heterozygous fathers versus heterozygous mothers to affected offspring. Allelic TDT results showed that T allele at rs742071 (PAX7) (p=0.025, ORtransmission=3.00, 95%CI: 1.09-8.25) and G allele at rs2485893 (10kb 3? of SYT14) were associated with NSCPO (p=0.0036, ORtransmission= 0.60, 95%CI: 0.42-0.85). Genotypic TDT based on 3 pseudo controls further confirmed that rs742071 (p-value=0.03, ORtransmission=3.00, 95%CI: 1.09-8.25) and rs2485893 were associated with NSCPO under additive model (p-value= 0.02, ORtransmission= 0.66, 95%CI: 0.47-0.92). Genotypic TDT for epistatic interactions showed that rs4844913 (37kb 3? of DIEXF) interacted with rs11119388 (SYT14) (p-value=1.80E-08) and rs6072081 (53kb 3? of MAFB) interacted with rs6102085 (33kb 3? of MAFB) (p-value=3.60E-04) for NSCPO, suggesting they may act in the same pathway in the etiology of NSCPO. In this study, we found that rs742071 and rs2485893 were associated NSCPO from Han Chinese population; also, interactions of rs4844913:rs11119388 and rs6072081:rs6102085 for NSCPO were identified, gene-gene interactions have been proposed as a potential source of the remaining heritability, these findings provided new insights of the previous GWAS

Efficacy of guideline-directed medical treatment in heart failure with mildly reduced ejection fraction.

Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline-directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, β-blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple-drug therapy (TT) and non-triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all-cause mortality (HR 0.656, 95% CI 0.447-0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380-0.946, P = 0.028), any-cause rehospitalization (HR 0.687, 95% CI 0.541-0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565-0.948, P = 0.018). In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF. [Abstract copyright: © 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on “VEGF uncoupling with nitric oxide” and “competitive angiopoietin 1/angiopoietin 2” mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics

Efficacy of guideline‐directed medical treatment in heart failure with mildly reduced ejection fraction

Aims: Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline‐directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, β‐blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. Methods: This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple‐drug therapy (TT) and non‐triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Results: Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all‐cause mortality (HR 0.656, 95% CI 0.447–0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380–0.946, P = 0.028), any‐cause rehospitalization (HR 0.687, 95% CI 0.541–0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565–0.948, P = 0.018). Conclusions: In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF

Case Report: Potential Predictive Value of MMR/MSI Status and PD-1 Expression in Immunotherapy for Urothelial Carcinoma

Immune checkpoint inhibitors (ICIs) have shown encouraging outcomes against Lynch syndrome (LS)-associated colorectal cancer (CRC) and endometrial cancer with mismatch repair deficient/microsatellite instability–high (dMMR/MSI-H). However, there is as yet no clarity on the safety and efficacy of immunotherapy combined with chemotherapy in LS-associated urothelial carcinoma (UC). Here, we report a patient with recurrent and metastatic LS-associated UC who achieved sustained response to programmed death protein 1 (PD-1) inhibitor combined with chemotherapy over 31 months, during which the side effects of immunotherapy could be controlled and managed. Our findings indicate that the dMMR/MSI status and PD-1 expression in UC may have potential predictive value for the response to PD-1-targeted immunotherapy. Our case supports the inclusion of such combination and/or monotherapy for UC in clinical studies and using dMMR/MSI status and PD-1 expression as potential predictive biomarkers for assessment of the therapeutic response

Corrigendum: Case report: Potential predictive value of MMR/MSI status and PD-1 expression in immunotherapy for urothelial carcinoma

Immune checkpoint inhibitors (ICIs) have shown encouraging outcomes against Lynch syndrome (LS)-associated colorectal cancer (CRC) and endometrial cancer with mismatch repair deficient/microsatellite instability–high (dMMR/MSI-H). However, there is as yet no clarity on the safety and efficacy of immunotherapy combined with chemotherapy in LS-associated urothelial carcinoma (UC). Here, we report a patient with recurrent and metastatic LS-associated UC who achieved sustained response to programmed death protein 1 (PD-1) inhibitor combined with chemotherapy over 31 months, during which the side effects of immunotherapy could be controlled and managed. Our findings indicate that the dMMR/MSI status and PD-1 expression in UC may have potential predictive value for the response to PD-1-targeted immunotherapy. Our case supports the inclusion of such combination and/or monotherapy for UC in clinical studies and using dMMR/MSI status and PD-1 expression as potential predictive biomarkers for assessment of the therapeutic response

Coevolution in Hybrid Genomes: Nuclear-Encoded Rubisco Small Subunits and Their Plastid-Targeting Translocons Accompanying Sequential Allopolyploidy Events in Triticum

The Triticum/Aegilops complex includes hybrid species resulting from homoploid hybrid speciation and allopolyploid speciation. Sequential allotetra- and allohexaploidy events presumably result in two challenges for the hybrids, which involve 1) cytonuclear stoichiometric disruptions caused by combining two diverged nuclear genomes with the maternal inheritance of the cytoplasmic organellar donor; and 2) incompatibility of chimeric protein complexes with diverged subunits from nuclear and cytoplasmic genomes. Here, we describe coevolution of nuclear rbcS genes encoding the small subunits of Rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase) and nuclear genes encoding plastid translocons, which mediate recognition and translocation of nuclear-encoded proteins into plastids, in allopolyploid wheat species. We demonstrate that intergenomic paternal-to-maternal gene conversion specifically occurred in the genic region of the homoeologous rbcS3 gene from the D-genome progenitor of wheat (abbreviated as rbcS3D) such that it encodes a maternal-like or B-subgenome-like SSU3D transit peptide in allohexaploid wheat but not in allotetraploid wheat. Divergent and limited interaction between SSU3D and the D-subgenomic TOC90D translocon subunit is implicated to underpin SSU3D targeting into the chloroplast of hexaploid wheat. This implicates early selection favoring individuals harboring optimal maternal-like organellar SSU3D targeting in hexaploid wheat. These data represent a novel dimension of cytonuclear evolution mediated by organellar targeting and transportation of nuclear proteins

AAV-mediated human PEDF inhibits tumor growth and metastasis in murine colorectal peritoneal carcinomatosis model

<p>Abstract</p> <p>Background</p> <p>Angiogenesis plays an important role in tumor growth and metastasis, therefore antiangiogenic therapy was widely investigated as a promising approach for cancer therapy. Recently, pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis. Adeno-associated virus (AAV) vectors have been intensively studied due to their wide tropisms, nonpathogenicity, and long-term transgene expression <it>in vivo</it>. The objective of this work was to evaluate the ability of AAV-mediated human PEDF (hPEDF) as a potent tumor suppressor and a potential candidate for cancer gene therapy.</p> <p>Methods</p> <p>Recombinant AAV₂encoding hPEDF (rAAV₂-hPEDF) was constructed and produced, and then was assigned for <it>in vitro </it>and <it>in vivo </it>experiments. Conditioned medium from cells infected with rAAV₂-hPEDF was used for cell proliferation and tube formation tests of human umbilical vein endothelial cells (HUVECs). Subsequently, colorectal peritoneal carcinomatosis (CRPC) mouse model was established and treated with rAAV₂-hPEDF. Therapeutic efficacy of rAAV₂-hPEDF were investigated, including tumor growth and metastasis, survival time, microvessel density (MVD) and apoptosis index of tumor tissues, and hPEDF levels in serum and ascites.</p> <p>Results</p> <p>rAAV₂-hPEDF was successfully constructed, and transmission electron microscope (TEM) showed that rAAV₂-hPEDF particles were non-enveloped icosahedral shape with a diameter of approximately 20 nm. rAAV₂-hPEDF-infected cells expressed hPEDF protein, and the conditioned medium from infected cells inhibited proliferation and tube-formation of HUVECs <it>in vitro</it>. Furthermore, in CRPC mouse model, rAAV₂-hPEDF significantly suppressed tumor growth and metastasis, and prolonged survival time of treated mice. Immunofluorescence studies indicated that rAAV₂-hPEDF could inhibit angiogenesis and induce apoptosis in tumor tissues. Besides, hPEDF levels in serum and ascites of rAAV₂-hPEDF-treated mice were significant higher than those in rAAV₂-null or normal saline (NS) groups.</p> <p>Conclusions</p> <p>Thus, our results suggest that rAAV₂-hPEDF may be a potential candidate as an antiangiogenic therapy agent.</p