Transcript isoform diversity defines molecular subtypes and prognosis in acute myeloid leukemia through long-read sequencing.

Acute myeloid leukemia (AML) is a genetically complex and clinically heterogeneous hematopoietic malignancy. This study employs long-read transcriptome analysis using oxford nanopore technologies sequencing on 60 primary AML bone marrow samples. This approach delivers comprehensive isoform-level resolution of splicing abnormalities and overcomes limitations of short-read sequencing.

Proteomic subtypes enrich current acute myeloid leukemia nomenclature and reflect intrinsic pathogenesis alongside aging.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy that increasingly affects the elderly population, with its post-transcriptional landscape remaining largely elusive. Establishing a stable proteomics-based classification system and systematically screening age-related proteins and regulatory networks are crucial for understanding the pathogenesis and outcomes of AML. In this study, we leveraged a multi-omics cohort of 374 newly diagnosed AML patients, integrating proteome, phosphoproteome, genome, transcriptome, and drug screening data.

Mouse trophectoderm stem cells generated with morula signalling inducers capture an early trophectoderm state.

The first embryonic cell differentiation in mice segregates the trophectoderm and the inner cell mass. Successful derivation of mouse trophoblast stem cells (TSCs) and trophectoderm stem cells (TESCs) has greatly facilitated the understanding of trophoblast differentiation. However, our understanding of early trophectoderm differentiation remains incomplete.

Thylakoids for enhanced photodynamic therapy in hypoxic tumours.

Current tumor therapies face significant limitations such as hypoxic microenvironments, systemic toxicity, and immunosuppression. Thylakoid-based nanomaterials strategically integrate the structural-functional properties of natural biological components with the versatility of nanotechnology. These biomaterials have garnered substantial scientific interest due to their promising therapeutic potential in oncology.

A molecular-based risk score for predicting leukemia-free survival in adult AML patients undergoing Allo-HSCT.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the cornerstone of curative therapy for acute myeloid leukemia (AML), yet precise molecular prognostic tools are currently insufficient. This study developed a prognostic model, AML-PRSS, integrating genomic and clinical factors from 389 adult AML patients undergoing their first allo-HSCT between 2013 and 2021. Seven genetic mutations significantly associated with leukemia-free survival (LFS) were categorized as favorable (, bZIP domain, without or with plus tyrosine kinase inhibitors), unfavorable ( and ), and high-risk ( and ).

Fucoidan: A marine-derived polysaccharide with therapeutic potential in atherosclerotic cardiovascular diseases: A review.

Fucoidan, a marine polysaccharide composed mainly of L-fucose and sulfate groups, has been widely studied for its applications in cancer therapy, wound healing, and the food industry. Atherosclerotic cardiovascular disease (ASCVD) encompasses a range of cardiovascular conditions, including acute myocardial infarction, coronary artery disease, ischemic stroke, and peripheral arterial atherosclerosis (AS), with AS being the fundamental pathological basis. However, the application of fucoidan in ASCVD remains understudied.

IPSS-M outperforms IPSS-R in prognostic stratification and guides effective interventions for very High-Risk myelodysplastic syndrome patients undergoing allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation represents a curative modality for patients with myelodysplastic syndrome (MDS), yet relapse risk persists. The prognostic performances of the Revised International Prognostic Scoring System (IPSS-R) and the Molecular International Prognostic Scoring System (IPSS-M) for 129 MDS patients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) were evaluated. Using IPSS-M, 29.

Identification of spastic ataxia-related proteins via comparative proteomic analysis of the cerebellum of conditional Ankfy1 knockout mice.

Ankyrin repeat and FYVE domain containing 1 (ANKFY1) is an indispensable protein in the development of cerebellar Purkinje cells. Our preliminary study revealed that its absence caused progressive spastic ataxia, accompanied by the loss of Purkinje cells in mice. Here, we generated Ankfy1-floxed (Ankfy1) mice, in which conditional inactivation of the Ankfy1 gene was achieved specifically in cerebellar Purkinje cells via crossing with a transgenic mouse strain expressing Cre recombinase under the regulatory control of the Purkinje cell protein 2 (PCP2) promoter.

Parous female donor is not inferior to the young male donor under the low-dose ATG/PTCy combination-based regimen for GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation.

Background: An optimal donor is critical for patient survival undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The impacts of different donors on outcomes under the combination regimens of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis had limited data.

Methods: Therefore, a single-center retrospective study was performed for patients undergoing haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with ATG/PTCy combination-based regimen.

Association between hemoglobin glycation index and the risk of cardiovascular disease in early-stage cardiovascular-kidney-metabolic syndrome: evidence from the China health and retirement longitudinal study.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interplay among metabolic risk factors, chronic kidney disease, and cardiovascular disease (CVD). While the hemoglobin glycation index (HGI) has demonstrated prognostic value for cardiovascular events, its clinical utility remains unexplored in early-stage CKM syndrome.

Methods: Participants with early-stage CKM syndrome (stage 0-3) were recruited from the China Health and Retirement Longitudinal Study (CHARLS) database.

SELP can affect the immune microenvironment of gastric cancer and is associated with poor prognosis.

The tumor microenvironment (TME) plays a crucial role in the occurrence and progression of gastric cancer. Yet, we still don't understand how immune and stromal components of TMEs are modulated. In this study, we applied the ESTIMATE algorithm to calculate the number of immune and stromal components in 410 STAD cases in the Cancer Genome Atlas (TCGA) database.

Heat stress induces specific methylation, transcriptomic and metabolic pattern in dairy cows and their female progeny.

A heat stress (HS) cattle research design was implemented to study HS effects on the three different "omics features" methylations, gene expressions and metabolic pattern from a direct perspective in pregnant cows and from an indirect time-lagged intergenerational perspective in offspring (the respective F1 and as F1 offspring before calving). In this regard, a total number of 88 German Holstein dairy cows and their 93 female calves were blood sampled for DNA and RNA extraction and for metabolic phenotyping, and allocated to HS and respective control groups (the cows (dams) as well as their calves) according to a temperature-humidity threshold of 60. Separate principal component analyses for all "omics-tiers" revealed clear separations of HS from respective control groups, as well as dam-offspring separations according to gene expressions and metabolic pattern.

Exploring WNT pathway dysregulation in serrated colorectal cancer for improved diagnostic and therapeutic strategies.

Background: Serrated colorectal cancer (SCC) is a rare and aggressive subtype of colorectal cancer. Identifying SCC is crucial due to its high mortality rate and limited therapeutic options. Traditional methods to identify BRAF hotspot mutations and MLH1 methylation are insufficient in clinical practice.

Epstein-Barr virus reactivation after haplo-peripheral blood stem cell transplantation in patients with hematological malignancies: immune reconstitution and influence on survival.

Background: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a common alternative for patients with hematological malignancies. Epstein-Barr virus (EBV) reactivation is a common complication post-transplantation, but its impact on immune reconstitution and survival remains unclear.

Objective: To compare immune reconstitution and survival between patients with and without EBV reactivation after haplo-HSCT.

Copy Number Gains of VPS72 Drive De Novo Lipogenesis and Hepatocarcinogenesis via ATF3/mTORC1/SREBP1 Axis.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and a major contributor to cancer-related mortality globally. Central to its pathogenesis is the dysregulation of lipid metabolism in hepatocytes, leading to abnormal lipid accumulation. Our bioinformatics analysis has identified the histone acetyltransferase complex subunit VPS72 as being associated with HCC, yet the precise molecular mechanisms through which VPS72 contributes to hepatocarcinogenesis remain poorly understood.

Dynamic change in Epstein-Barr virus DNA predicts prognosis in early stage natural killer/T-cell lymphoma with pegaspargase-based treatment: long-term follow-up and biomarker analysis from the NHL-004 multicenter randomized study.

The multi-center randomized phase 3 NHL-004 study compared etoposide, dexamethasone and pegaspargase (ESA) versus methotrexate, etoposide, dexamethasone and pegaspargase (MESA) regimen, combined with sandwiched radiotherapy, in newly diagnosed early-stage nasal natural killer/T-cell lymphoma (NKTCL). Here we report the long-term outcomes (median follow-up, 64 months) and biomarker analysis. 256 eligible patients aged 14-70 years were randomly assigned (1:1) to ESA or MESA arm.

Improved survival in older patients with myeloid malignancies undergoing haploidentical peripheral blood stem cell transplantation with low-dose anti-thymocyte globin (ATG)/post-cyclophosphamide (PTCy)-based regimen for graft-versus-host disease prophylaxis.

Our study delved into the clinical outcomes of haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) for older patients, utilizing a novel low-dose antithymocyte globin (ATG)/post-cyclophosphamide (PTCy)-based regimen to prevent graft-versus-host disease (GVHD). We juxtaposed these outcomes with transplants from matched unrelated/sibling donors (MUD/MSD) for elderly patients with myeloid malignancies from 2016 to 2023. The study encompassed 127 patients, with 40 undergoing MUD/MSD-PBSCT and 87 receiving haplo-PBSCT.

Nicotinamide adenine dinucleotide rejuvenates septic bone marrow mesenchymal stem cells.

Background: Sepsis is a severe illness characterized by systemic and multiorgan reactive responses and damage. However, the impact of sepsis on the bone marrow, particularly on bone marrow mesenchymal stem cells (BMSCs), is less reported. BMSCs are critical stromal cells in the bone marrow microenvironment that maintain bone stability and hematopoietic homeostasis; however, the impairment caused by sepsis remains unknown.

Intrahepatic ductoplasty effectively corrects the ductal dilatation in Todani type IV-A choledochal cyst in children.

Primary ductal stricture and intrahepatic duct dilatation are characteristic features in Todani type IV-A choledochal cysts (CDC) and necessitate thorough evaluation and management during surgical treatment. This study aimed to present our experience with ductoplasties for type IV-A CDCs with primary ductal strictures. Between June 2015 and June 2022, 54 patients were reviewed.

ATF3-SLC7A7 Axis Regulates mTORC1 Signaling to Suppress Lipogenesis and Tumorigenesis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) poses a substantial global health burden, with poor prognosis and high mortality rates. Dysregulated lipid metabolism has emerged as a critical driver of HCC progression. While mTORC1 signaling is known to promote lipid synthesis in HCC, the regulatory mechanisms governing mTORC1 remain largely unclear.

Confronting the anxiety of Generation Z: electroacupuncture therapy regulates oxidative stress and microglia activity in amygdala-basolateral of socially isolated mice.

Introduction: Anxiety disorders are prevalent mental health conditions characterized by significant impairments in daily functioning and social interactions. Despite the effectiveness of pharmacological treatments, challenges such as medication resistance, adverse side effects, and the high rate of relapse necessitate the exploration of alternative therapies. Recently, electroacupuncture (EA) has garnered attention as a promising non-pharmacological intervention for anxiety disorders; however, the mechanisms by which EA exerts its anxiolytic effects remain poorly understood.

Evaluation of crossbreeding strategies for improved adaptation and productivity in African smallholder cattle farms.

Background: Crossbreeding is successfully implemented worldwide to improve animal productivity and adaptability. However, recurrent failures of crossbreeding programmes in African countries imply the need to design effective strategies for the predominant smallholder production systems.

Methods: A comprehensive simulation procedure mimicked body weight (BW) and tick count (TC) incidence in a local taurine cattle breed and in an exotic indicine beef cattle breed (BW and TC, respectively).

Metabolomic insights into pathogenesis and therapeutic potential in adult acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) poses challenges in adult patients, considering its heterogeneous nature and often suboptimal treatment outcomes. Here, we performed a study on 201 newly diagnosed adult ALL cases (age ≥ 15 y) to generate intracellular and dynamic serum metabolomic profiles. Our findings revealed a predominant increase in bile acid (BA) metabolites in serum, alongside metabolic rewiring that supported highly proliferative states and actively metabolic signaling, such as enriched nucleotide metabolism in leukemic blasts.

Effects of alcalase hydrolysis combined with TGase-type glycosylation of self-assembled zein for curcumin delivery: Stability, bioavailability, and antioxidant properties.

In this study, zein was hydrolyzed by alcalase and conjugated to oligochitosan under transglutaminase (TGase) catalysis to construct novel self-assembly complex for the delivery of curcumin. The effects of enzyme hydrolysis and TGase-type glycosylation of zein/curcumin on the stability, bioavailability, and antioxidant properties were evaluated. The obtained glycosylated zein hydrolysate had a uniform distribution and small particle sizes.