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Phenotypic variation among species is a product of evolutionary changes to developmental programs1,2. However, how these changes generate novel morphological traits remains largely unclear. Here we studied the genomic and developmental basis of the mammalian gliding membrane, or patagium-an adaptative trait that has repeatedly evolved in different lineages, including in closely related marsupial species. Through comparative genomic analysis of 15 marsupial genomes, both from gliding and non-gliding species, we find that the Emx2 locus experienced lineage-specific patterns of accelerated cis-regulatory evolution in gliding species. By combining epigenomics, transcriptomics and in-pouch marsupial transgenics, we show that Emx2 is a critical upstream regulator of patagium development. Moreover, we identify different cis-regulatory elements that may be responsible for driving increased Emx2 expression levels in gliding species. Lastly, using mouse functional experiments, we find evidence that Emx2 expression patterns in gliders may have been modified from a pre-existing program found in all mammals. Together, our results suggest that patagia repeatedly originated through a process of convergent genomic evolution, whereby regulation of Emx2 was altered by distinct cis-regulatory elements in independently evolved species. Thus, different regulatory elements targeting the same key developmental gene may constitute an effective strategy by which natural selection has harnessed regulatory evolution in marsupial genomes to generate phenotypic novelty.

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.

Background: Hepatocellular carcinoma (HCC) is a major health concern, necessitating a deeper understanding of its prognosis and underlying mechanisms. This study aimed to investigate the mechanism and prognostic value of CD8+ T Cell exhaustion (CD8+ TEX)-related genes in HCC and construct a survival prognosis prediction model for patients with HCC. Methods: CD8+ TEX-related genes associated with HCC prognosis were analysed and identified, and a prognostic prediction model was constructed using the 'least absolute shrinkage and selection operator' Cox regression model. Immunohistochemistry was used to verify the expression of the model genes in HCC tissues. A nomogram was constructed based on risk scores and clinical features, and its predictive efficacy was verified. The expression of STAM, ANXA5, and MAD2L2 in HCC cell lines was detected by western blotting; subsequently, these genes were knocked down in HCC cell lines by small interfering RNA, and their effects on the proliferation and migration of HCC cell lines were detected by colony formation assay, cck8, wound healing, and transwell assays. Results: Six genes related to CD8+ TEX were included in the risk-prediction model. The prognosis of patients with HCC in the low-risk group was significantly better than that of those in the high-risk group. Cox regression analysis revealed that the risk score was an independent risk factor for the prognosis of patients with HCC. The differentially expressed genes in patients with high-risk HCC were mainly enriched in the nucleotide-binding oligomerization domain-containing protein-like receptor, hypoxia-inducible factor-1, and tumour programmed cell death protein (PD)-1/PD-L1 immune checkpoint pathways. The CD8+ TEX-related genes STAM, ANXA5, and MAD2L2 were knocked down in HCC cell lines to significantly inhibit cell proliferation and migration. The prediction results of the nomogram based on the risk score showed a good fit and application value. Conclusion: The prediction model based on CD8+ TEX-related genes can predict the prognosis of HCC and provide a theoretical basis for the early identification of patients with poor HCC prognosis. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) is associated with high mortality. SAP is generally treated by conservative management at the early phase, and removal of the pancreatic and peripancreatic necrotic tissue at the late phase. However, studies have suggested that the surgical treatment of SAP should focus on pressure reduction and drainage. In this case report, 3 SAP patients of 44, 30 and 60 years of age were treated at the General Hospital of Ningxia Medical University. They underwent emergency endoscopic pancreatic stenting at the early phase and nasopancreatic drainage at the late phase when peripancreatic encapsulated effusion was observed. All patients were successfully treated and discharged from the hospital. The disease duration of the patients was 71, 58, and 88 days, respectively. Our cases suggested that the surgical strategy of endoscopic pancreatic stenting at the early phase and nasopancreatic drainage at the late phase is promising for the treatment of SAP. [ABSTRACT FROM AUTHOR]

Copper smelting slag is a useful secondary resource containing high iron and copper, which can be utilized to prepare crude Fe-Cu alloy by a direct reduction-magnetic separation process for making weathering-resistant steel. However, it is difficult to recover iron and copper from the slag by direct reduction since the iron mainly occurs in fayalite and the copper is held in copper sulfide. Therefore, enhancement reduction of copper slag is conducted to improve the recovery of copper and iron. Additives such as NaCO has been proven to be capable of reinforcing the reduction of refractory iron ore. In this research, the effect of NaCO on the carbothermic reduction of copper slag was investigated, and phase transformations during reduction and the distributing characteristics of iron and copper in the alloy and non-metallic phases of the reduced pellets were also studied. The results show that the metallization rate of iron and copper was increased with the addition of NaCO, leading to higher iron and copper recovery in Fe-Cu alloy powder. X-ray diffraction (XRD) and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) results confirm that NaCO is capable of enhancing the reduction of fayaltie, copper silicate and copper sulfide, which agrees well with thermodynamic analysis. Furthermore, the reduction mechanism of copper slag was demonstrated based on systematic experimental observations. [ABSTRACT FROM AUTHOR]

Background: This study aimed to construct an enteral nutrition evaluation system for critically ill patients using the Delphi method to direct the formulation of enteral nutrition support strategies and reduce interruption to enteral feeding., Methods: We used domestic and foreign databases to obtain and analyze the literature and form "The Whole-Proceeding Enteral Nutrition Evaluation System for Critically Ill Patients." The Delphi method was used to conduct two rounds of expert opinion consultation, combined with the suggestions from the research group to finalize the nutrition evaluation content of the system., Results: After two rounds of expert consultation, a nutrition evaluation system was formed around three dimensions: before the start, during, and after the end of nutritional support. The effective recovery rates of the two rounds of expert consultation were 90.0% (18/20) and 100.0% (18/18), respectively. Authority coefficients were 0.865 and 0.908, while Kendall coordination coefficients were 0.108 ( P < 0.05) and 0.115 ( P < 0.001), respectively. Finally, the full enteral nutrition evaluation system for critically ill patients was constructed based on the Delphi method, including three primary items and seven secondary and 28 tertiary indicators., Conclusion: The established "Whole-Proceeding Enteral Nutrition Evaluation System for Critically Ill Patients" has high consistency from expert opinions and reliability, which can provide a practical evaluation tool for the process of enteral nutrition for severe patients., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Gastroenterology.)

Background: Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease with multiple etiologies. The prevalence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has been increasing in recent years. It is reported that early triglyceride (TG) levels were associated with the severity of the disease, and TG- lowering therapies, including medical treatment and blood purification, may impact the clinical outcomes. However, there is no consensus regarding the optimal TG-lowering therapy, and clinical practice varies greatly among different centers. Our objective is to evaluate the TG-lowering effects of different therapies and their impact on clinical outcomes in HTG-AP patients with worrisome features. Methods: This is a multicenter, observational, prospective cohort study. A total of approximately 300 patients with HTG-AP with worrisome features are planned to be enrolled. The primary objective of the study is to evaluate the relationship between TG decline and the evolution of organ failure, and patients will be dichotomized depending on the rate of TG decline. The primary outcome is organ failure (OF) free days to 14 days after enrollment. Secondary outcomes include new-onset organ failure, new-onset multiple-organ failure (MOF), new-onset persistent organ failure (POF), new receipt of organ support, requirement of ICU admission, ICU free days to day 14, hospital free days to day 14, 60-day mortality, AP severity grade (Based on the Revised Atlanta Classification), and incidence of systemic and local complications. Generalized linear model (GLM), Fine and Gray competing risk regression, and propensity score matching will be used for statistical analysis. Discussion: Results of this study will reveal the current practice of TG-lowering therapy in HTG-AP and provide necessary data for future trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cao, Zhou, Chen, Chen, Liu, Mao, Lin, Hong, Yao, Sun, Qin, Guo, Zhou, Jiao, Chen, Li, Ye, Ke, Tong, Liu, Li and Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG).)

Objective: To optimize the protocols for isolation and culture of mesenchymal stem cells from rat bone marrow (BMSCs)., Methods: BMSCs were isolated by adherence to plastic with frequent medium change and reduced trypsinization time. The cell growth curves were drawn and the surface markers of BMSCs were detected by flow cytometry. The cells were induced to differentiate into osteogenic, adipogenic, hepatic and cholic lineages., Results: The cells isolated using this method were positive for CD29, CD44, and CD90 and negative for the hematopoietic surface markers CD45. The osteogenic and adipogenic differentiation of the BMSCs was verified by alkaline phosphatase staining, Alizarin red staining and Oil red staining. The cell subcultures up to passage 10 maintained capacities of differentiation into osteogenic and adipogenic lineages. The BMSCs induced with sequential addition of growth factors, cytokines and hormones differentiated into cells expressing hepatocyte- and cholangiocyte-specific markers., Conclusion: The optimized method allows efficient isolation of homogenous populations of MSCs from rat bone marrow, which can be induced into multiple cell lineages.