Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma.

Background: Pancreatic adenocarcinoma, a malignancy that arises in the cells of the pancreas, is a devastating disease with unclear etiology and often poor prognosis. Locally advanced pancreatic cancer, a stage where the tumor has grown significantly but has not yet spread to distant organs, presents unique challenges in treatment. This article aims to discuss the current strategies, challenges, and future directions in the management of locally advanced pancreatic adenocarcinoma (LAPC).

Triterpenoid and trichothecenes from a rhizospheric soil-derived sp. KMU22107.

A new phthalide derivative named paramlyktone () and a new arborinane-type triterpenoid named paramyrpenoid (), together with ten previously described trichothecenes derivatives () were isolated and identified from a rhizospheric soil-derived sp. KMU22107 associated with . Their structural elucidation was achieved by the comprehensive analysis of spectroscopic data and comparison with literature values.

Genomes of Meniocus linifolius and Tetracme quadricornis reveal the ancestral karyotype and genomic features of core Brassicaceae.

Brassicaceae represents an important plant family from both a scientific and economic perspective. However, genomic features related to the early diversification of this family have not been fully characterized, especially upon the uplift of the Tibetan Plateau, which was followed by increasing aridity in the Asian interior, intensifying monsoons in Eastern Asia, and significantly fluctuating daily temperatures. Here, we reveal the genomic architecture that accompanied early Brassicaceae diversification by analyzing two high-quality chromosome-level genomes for Meniocus linifolius (Arabodae; clade D) and Tetracme quadricornis (Hesperodae; clade E), together with genomes representing all major Brassicaceae clades and the basal Aethionemeae.

Positive selection and relaxed purifying selection contribute to rapid evolution of male-biased genes in a dioecious flowering plant.

Sex-biased genes offer insights into the evolution of sexual dimorphism. Sex-biased genes, especially those with male bias, show elevated evolutionary rates of protein sequences driven by positive selection and relaxed purifying selection in animals. Although rapid sequence evolution of sex-biased genes and evolutionary forces have been investigated in animals and brown algae, less is known about evolutionary forces in dioecious angiosperms.

Nivolumab Plus 5-Azacitidine in Pediatric Relapsed/Refractory Acute Myeloid Leukemia (AML): Phase I/II Trial Results from the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium.

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium.

Fungal polyketides produced by an endophytic fungus Phoma sp. associated with Gastrodia elata.

Two novel fungal polyketides, phometides A (1) and B (2), together with four known compounds (3-6), were isolated from the endophytic fungus Phoma sp. YUD17001 obtained from Gastrodia elata Blume. The structures were elucidated based on spectroscopic analyses, X-ray crystal diffraction, and time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations.

SETD2 Deficiency Confers Sensitivity to Dual Inhibition of DNA Methylation and PARP in Kidney Cancer.

Unlabelled: SETD2 deficiency alters the epigenetic landscape by causing depletion of H3K36me3 and plays an important role in diverse forms of cancer, most notably in aggressive and metastatic clear-cell renal cell carcinomas (ccRCC). Development of an effective treatment scheme targeting SETD2-compromised cancer is urgently needed. Considering that SETD2 is involved in DNA methylation and DNA repair, a combination treatment approach using DNA hypomethylating agents (HMA) and PARP inhibitors (PARPi) could have strong antitumor activity in SETD2-deficient kidney cancer.

IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ.

Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ.

Zn-interference and HS-mediated gas therapy based on ZnS-tannic acid nanoparticles synergistic enhancement of cell apoptosis for specific treatment of prostate cancer.

Zn and HS are essential to maintain normal prostate function, and sometimes can evolve into weapons to attack and destroy prostate cancer (PCa) cells. Nevertheless, how to achieve the targeted and effective release of Zn and HS, and reverse the concentration distribution within PCa tumor cells still highly challenging. Herein, combined with these pathological characteristics of prostate, we proposed a tumor microenvironment (TME) responsive Zn-interference and HS-mediated gas synergistic therapy strategy based on a nanoplatform of tannic acid (TA) modified zinc sulfide nanoparticles (ZnS@TA) for the specific treatment of PCa.

Asymmetric Synthesis of Triphenylmethanes via Organocatalytic Regio- and Enantioselective Friedel-Crafts Alkylation of Aniline Derivatives.

Herein, we described a highly regio- and enantioselective Friedel-Crafts alkylation of aniline derivatives with generated -quinone methides enabled by chiral phosphoric acid, furnishing a wide range of enantioenriched triarylmethanes bearing three similar benzene rings in high yields (up to 98%) with excellent stereoselectivities (up to 98% ee). Furthermore, the large-scale reactions and diversified transformations of product demonstrate the practicality of the protocol. Density functional theory calculations elucidate the origin of the enantioselectivity.

Regulation of secondary metabolites in the endophytic fungus sp. KMU18029 by the chemical epigenetic modifier 5-azacitidine.

The chemical epigenetic modifier 5-azacitidine (5-Aza C), a DNA methyltransferase inhibitor, was used to manipulate the endophytic fungus sp. KMU18029. From its rice fermentation extract, a new polyketone compound (3,4)-3,4,8-trihydroxy-6-methyl-3,4-dihydronaphthalen-1(2)-one (), along with 13 known compounds, 3,4,8-trihydroxy-6-(hydroxymethyl)-3,4-dihydronaphthalen-1(2)-one (), decaturin B (), 15-hydroxydecaturin A (), oxalicine A (), pileotin A (), pyrandecarurin A (), decaturenol A (), decaturenoid (), penisarins A (), oxaline (), (4,8)-N-D-2'-hydroxyocta-decanoyl-1-O--D-glycopy-ranosyl-9-methyl-4,8-sphingadienine (), ergosterol () and stigma-5-en-3-O--glucoside (), were separated.

Bioactive sorbicillinoids from a rhizospheric soil-derived Paecilomyces sp. KMU21009.

A new hybrid sorbicillinoid named paeciureallin (1) and a new monomeric sorbicillinoid named paecillyketide (2), along with six known analogues (3-8), were isolated from the rhizospheric soil-derived fungus Paecilomyces sp. KMU21009 associated with Delphinium yunnanense. Their structures were elucidated by extensive spectroscopic analysis and comparison with literature values.

Comprehensive Evaluation of The Infinium Human MethylationEPIC v2 BeadChip.

Infinium Methylation BeadChips are widely used to profile DNA cytosine modifications in large cohort studies for reasons of cost-effectiveness, accurate quantification, and user-friendly data analysis in characterizing these canonical epigenetic marks. In this work, we conducted a comprehensive evaluation of the updated Infinium MethylationEPIC v2 BeadChip (EPICv2). Our evaluation revealed that EPICv2 offers significant improvements over its predecessors, including expanded enhancer coverage, applicability to diverse ancestry groups, support for low-input DNA down to one nanogram, coverage of existing epigenetic clocks, cell type deconvolution panels, and human trait associations, while maintaining accuracy and reproducibility.

Phylogenomics and the flowering plant tree of life.

The advances accelerated by next-generation sequencing and long-read sequencing technologies continue to provide an impetus for plant phylogenetic study. In the past decade, a large number of phylogenetic studies adopting hundreds to thousands of genes across a wealth of clades have emerged and ushered plant phylogenetics and evolution into a new era. In the meantime, a roadmap for researchers when making decisions across different approaches for their phylogenomic research design is imminent.

Fungal polyketides from a rhizospheric soil-derived Penicillium sp. YUD17004 associated with Gastrodia elata.

Five unprecedented polyketide metabolites were isolated and characterized from a rhizospheric soil-derived Penicillium sp. YUD17004. Their diverse structures included two indanone-type polyketides penicillyketides A and B, a phthalide-like polyketides penicillyketide C, a symmetrical chromone dimer penicillyketide D, along with a pyrone derivative pyranlyketide, which were elucidated by spectroscopic data interpretation and quantum chemical electronic circular dichroism calculation.

DNA barcoding of Cymbidium by genome skimming: Call for next-generation nuclear barcodes.

Cymbidium is an orchid genus that has undergone rapid radiation and has high ornamental, economic, ecological and cultural importance, but its classification based on morphology is controversial. The plastid genome (plastome), as an extension of plant standard DNA barcodes, has been widely used as a potential molecular marker for identifying recently diverged species or complicated plant groups. In this study, we newly generated 237 plastomes of 50 species (at least two individuals per species) by genome skimming, covering 71.

IL-24 Contributes to Neutrophilic Asthma in an IL-17A-Dependent Manner and Is Suppressed by IL-37.

Purpose: Neutrophilic asthma is associated with asthma exacerbation, steroid insensitivity, and severe asthma. Interleukin (IL)-24 is overexpressed in asthma and is involved in the pathogenesis of several allergic inflammatory diseases. However, the role and specific mechanism of IL-24 in neutrophilic asthma are unclear.

Application of 3 dimension-printed injection-molded polyether ether ketone lunate prosthesis in the treatment of stage III Kienböck's disease: A case report.

Background: Polyether ether ketone (PEEK) is a high-performance medical polymer, and there are some clinical cases of PEEK prosthesis implantation. However, application of 3D-printed injection-molded PEEK lunate prosthesis for treatment of stage III Kienböck's disease has not been reported. This study's purpose was to analyze the clinical efficacy of 3D-printed injection-molded PEEK lunate prosthesis in the treatment of stage III Kienböck's disease and thus provide a good therapeutic choice for Kienböck's disease.

IL-37 protects against airway remodeling by reversing bronchial epithelial-mesenchymal transition via IL-24 signaling pathway in chronic asthma.

Background: Epithelial-mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown.

DNMT and EZH2 inhibitors synergize to activate therapeutic targets in hepatocellular carcinoma.

The development of more effective targeted therapies for hepatocellular carcinoma (HCC) patients due to its aggressiveness is urgently needed. DNA methyltransferase inhibitors (DNMTis) represented the first clinical breakthrough to target aberrant cancer epigenomes. However, their clinical efficacies are still limited, in part due to an "epigenetic switch" in which a large group of genes that are demethylated by DNMTi treatment remain silenced by polycomb repressive complex 2 (PRC2) occupancy.