New 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors.

In this study, new 2-indolinone-indole hybrid compounds (4a-s) carrying a benzoyl moiety were synthesized and their cytotoxic effects were examined against pancreatic (MIA-PaCa-2) and colon (HT-29 and HCT-116) cancer cells by MTT assays. Most of the tested compounds exhibited a better inhibitory activity and safety profile than the reference standard sunitinib malate against MIA-PaCa-2 and HCT-116 cancer cells. Compound 4e displayed the greatest cytotoxic effect on HCT-116 cell with an IC value of 0.

The effects of autophagy-modifying drugs chloroquine and lithium on the skin melanoma microenvironment.

Background: Skin melanoma is a highly metastatic cancer with an increasing global incidence. Despite advancements in immunotherapy, new treatment strategies based on tumor biology are essential for improving outcomes and developing novel therapies. Autophagy plays a critical role in melanoma cell metabolism and affects the tumor microenvironment (TME).

Anaerobic probiotics-in situ Se nanoradiosensitizers selectively anchor to tumor with immuno-regulations for robust cancer radio-immunotherapy.

Developing translational nanoradiosensitizers with multiple activities in sensitizing tumor cells and re-shaping tumor immunosuppressive microenvironments are urgently desired for addressing the poor therapeutic efficacy of radiotherapy in clinic. Inspired by the anaerobic and immunoagonist properties of the probiotic (bifidobacterium longum, BL), herein, a biomimetic Selenium nanoradiosensitizer in situ-formed on the surface of the probiotic (BL@SeNPs) is developed in a facile method to potentiate radiotherapy. BL@SeNPs selectively target to hypoxia regions of tumors and then anchor on the surface of tumor cells to inhibit its proliferation.

Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.

Hematopoietic stem cells (HSCs) generate blood and immune cells. Here, we present a protocol to differentiate human pluripotent stem cells (hPSCs) into hematopoietic progenitors that express the signature HSC transcription factors HLF, HOXA5, HOXA7, HOXA9, and HOXA10. hPSCs are dissociated, seeded, and then sequentially differentiated into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and hematopoietic progenitors through the sequential addition of defined, serum-free media.

Mina53 catalyzes arginine demethylation of p53 to promote tumor growth.

Arginine methylation is a common post-translational modification that plays critical roles in many biological processes. However, the existence of arginine demethylases that remove the modification has not been fully established. Here, we report that Myc-induced nuclear antigen 53 (Mina53), a member of the jumonji C (JmjC) protein family, is an arginine demethylase.

Progenitor effect in the spleen drives early recovery via universal hematopoietic cell inflation.

Hematopoietic stem cells (HSCs) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remain an enigma. Clinically, the initial hematopoiesis in the post-transplantation period is critical, necessitating strategies to accelerate hematopoietic recovery.

The first reported case of candidemia caused by the novel Candida tropicalis diploid sequence type 1515.

Introduction: Since the dawn of the new millennium, Candida species have been increasingly implicated as a cause of both healthcare-associated as well as opportunistic yeast infections, due to the widespread use of indwelling medical devices, total parenteral nutrition, systemic corticosteroids, cytotoxic chemotherapy, and broad-spectrum antibiotics. Candida tropicalis is a pathogenic Candida species associated with considerable morbidity, mortality, and drug resistance issues on a global scale.

Methodology: We report a case of a 43-year-old man who was admitted to our hospital for further management of severe coronavirus disease 2019 (COVID-19) pneumonia.

Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

A Comprehensive Atlas of AAV Tropism in the Mouse.

Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.

A typical NLR recognizes a family of structurally conserved effectors to confer plant resistance against adapted and non-adapted Phytophthora pathogens.

Plants possess remarkably durable resistance against non-adapted pathogens in nature. However, the molecular mechanisms underlying this resistance remain poorly understood, and it is unclear how the resistance is maintained without coevolution between hosts and the non-adapted pathogens. In this study, we used Phytophthora sojae (Ps), a non-adapted pathogen of N.

The developmental lipidome of Nippostrongylus brasiliensis.

Background: Nippostrongylus brasiliensis-a nematode of rodents-is commonly used as a model to study the immunobiology of parasitic nematodes. It is a member of the Strongylida-a large order of socioeconomically important parasitic nematodes of animals. Lipids are known to play essential roles in nematode biology, influencing cellular membranes, energy storage and/or signalling.

Foliar application of nano biochar solution elevates tomato productivity by counteracting the effect of salt stress insights into morphological physiological and biochemical indices.

Nano-biochar considers a versatile and valuable sorbent to enhance plant productivity by improving soil environment and emerged as a novel solution for environmental remediation and sustainable agriculture in modern era. In this study, roles of foliar applied nanobiochar colloidal solution (NBS) on salt stressed tomato plants were investigated. For this purpose, NBS was applied (0%, 1% 3% and 5%) on two groups of plants (control 0 mM and salt stress 60 mM).

The myometrial transcriptome changes in mares with endometrosis.

Mares with endometrosis exhibit histological changes not only in the endometrium but also in the myometrium that suggest possible functional impairment. The molecular background of these changes is not well understood. We hypothesize that the transcriptomic profile of the mare myometrium varies depending on the degree of endometrosis in mares.

De novo transcriptome assembly of the Perna viridis: A novel invertebrate model for ecotoxicological studies.

Mussels, particularly Perna viridis, are vital sentinel species for toxicology and biomonitoring in environmental health. This species plays a crucial role in aquaculture and significantly impacts the fisheries sector. Despite the ecological and economic importance of this species, its omics resources are still scarce.

Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.

Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase.

Ferroptosis triggers mitochondrial fragmentation via Drp1 activation.

Constitutive mitochondrial dynamics ensure quality control and metabolic fitness of cells, and their dysregulation has been implicated in various human diseases. The large GTPase Dynamin-related protein 1 (Drp1) is intimately involved in mediating constitutive mitochondrial fission and has been implicated in mitochondrial cell death pathways. During ferroptosis, a recently identified type of regulated necrosis driven by excessive lipid peroxidation, mitochondrial fragmentation has been observed.

ZBP1-mediated PANoptosis is a crucial lethal form in diverse keratinocyte death modalities in UVB-induced skin injury.

UVB irradiation induces diverse modalities of regulatory cell death in keratinocytes. Recently, the pattern of coexistence of pyroptosis, apoptosis, and necroptosis has been termed PANoptosis; however, whether PANoptosis occurs in keratinocytes in UVB-induced skin injury remains unclear. We observed that the key molecules of GSDMD-mediated pyroptosis, apoptosis, and necroptosis, which are N-terminal GSDMD, cleaved caspase-3/PARP, and phosphorylated MLKL, respectively, were elevated in keratinocytes of UVB-challenged mice and human skin tissue.

CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair.

To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.

Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.

Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.

Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria.

Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria.

Aberrant promoter methylation of CTHRC1 gene and its clinicopathological characteristics in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is genetically complex and difficult to treat. Detection in the early stage is challenging, leading to diagnosis at advanced stages with limited treatment options. This study examined the collagen triple helix repeat containing 1 gene (CTHRC1) as a potential biomarker and therapeutic target in HNSCC.

Genetically attenuated parasites show promise as a next-generation malaria vaccine.

Metabolically active, genetically attenuated Plasmodium falciparum parasite lines are promising second-generation malaria vaccine candidates. Lamers et al. and Roozen et al.

Protocol for a systematic review and individual participant data meta-analysis for risk factors for lung cancer in individuals with lung nodules identified by low-dose CT screening.

Background: Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20-24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign.

Characterizing tumor-infiltrating group 1 innate lymphoid cells in PyMT breast tumors.

Breast cancer is the most common cancer in women and continues to have a significant impact in cancer-associated deaths worldwide. Investigating the complex roles of infiltrating immune subsets within the tumor microenvironment (TME) will enable a better understanding of disease progression and reveal novel therapeutic strategies for patients with breast cancer. The mammary-specific expression of polyomavirus middle T oncoprotein (MMTV-PyMT) was first established in 1992 by William Muller and is the most commonly used genetically engineered mouse model (GEMM) for breast cancer research.

Blood-brain barrier integrity disruption is associated with both chronic vascular risk factors and white matter hyperintensities.

Background: Cardiovascular risk factors (CRFs) like hypertension, high cholesterol, and diabetes mellitus are increasingly linked to cognitive decline and dementia, especially in cerebral small vessel disease (cSVD). White matter hyperintensities (WMH) are closely associated with cognitive impairment, but the mechanisms behind their development remain unclear. Blood-brain barrier (BBB) dysfunction may be a key factor, particularly in cSVD.