Targeting necrotic lipid release in tumors enhances immunosurveillance and cancer immunotherapy of glioblastoma.

Tumors evolve to avoid immune destruction and establish an immunosuppressive microenvironment. Syngeneic mouse tumor models are critical for understanding tumor immune evasion and testing cancer immunotherapy. Derived from established mouse tumor cell lines that can already evade the immune system, these models cannot simulate early phases of immunoediting during initial tumorigenesis.

Investigation of the efficacy and safety of lung biopsy plus microwave ablation for a solitary suspected malignant pulmonary nodule after radical mastectomy.

Purpose: To evaluate the safety and efficacy of CT-guided lung biopsy combined with microwave ablation (MWA) for solitary suspected malignant pulmonary nodules in post-radical surgery breast cancer patients.

Materials And Methods: This retrospective study included 37 post-radical surgery breast cancer patients with solitary suspected malignant pulmonary nodules, treated with CT-guided lung biopsy and MWA between January 2014 and December 2018. Institutional review board approval was obtained.

Necrotic Bone Fluid Suppresses Energy Metabolism of Porcine PBMC-Derived Macrophages In Vitro.

Legg-Calvé-Perthes disease is a juvenile ischemic osteonecrosis (ON) of the femoral head. A disruption of blood supply to the femoral head produces extensive cell death and necrotic debris. Macrophages are innate immune cells recruited to the necrotic bone to orchestrate the repair process.

A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis.

Functional inactivation of tumor suppressor genes drives cancer initiation, progression, and treatment responses. Most tumor suppressor genes are inactivated through 1 of 2 well-characterized mechanisms: DNA-level mutations, such as point mutations or deletions, and promoter DNA hypermethylation. Here, we report a distinct third mechanism of tumor suppressor inactivation based on alterations to the histone rather than DNA code.

Baseline-free wavelength modulation spectroscopy based on cepstral analysis.

This paper demonstrates what we believe to be a new WMS m-FID technique based on cepstral analysis, incorporating wavelength modulation spectroscopy (WMS) with a modified form of the time-domain molecular free-induction decay (m-FID) signal. Detailed theoretical framework of the WMS m-FID technique, as well as the fitting routine, has been investigated. The proposed WMS m-FID technique is first validated through a static CO gas cell experiment using the CO (9) absorption line near 2179.

Defect-mediated electron/hole trapping in BiWO for concurrent Cr(VI) decontamination and ciprofloxacin mineralization.

The remediation of multicomponent wastewater containing high-valent heavy metals and organic pollutants remains a significant environmental challenge. Visible-light-driven photocatalysis holds promise for concurrent pollutants decontamination, but is often hindered by sluggish interfacial charge transfer, rapid electron-hole recombination, and inadequate redox-active carriers. In this work, we present a dual-vacancy-incorporated BiWO (V-BWO) photocatalyst, featuring strategically introduced oxygen vacancies (OVs) and bismuth vacancies (BiVs), to overcome these constraints.

A programmed decline in ribosome levels governs human early neurodevelopment.

Many neurodevelopmental defects are linked to genes involved in housekeeping functions, such as those encoding ribosome biogenesis factors. How reductions in ribosome biogenesis can result in tissue- and developmental-specific defects remains unclear. Here we describe variants in the ribosome biogenesis factor AIRIM/C1orf109 that are primarily associated with neurodevelopmental disorders.

Chiral Artificial Antigen-Presenting Cells Enhancing Tumor Immunotherapy: Evasion of Macrophage Uptake through Inhibition of Serum Protein Corona Formation.

Biomimetic artificial antigen-presenting cells (aAPCs) have emerged as a promising platform for the immune system activation and modulation. However, abundant serum proteins in the living body prefer to adsorb on the aAPC surface to form a protein corona, leading to rapid clearance of aAPCs by mononuclear phagocytes, causing inefficient tumor immunotherapy by aAPCs. To achieve long-lasting antitumor immunity, chiral aAPCs with left-handed (aAPCs-L) or right-handed (aAPCs-D) helices are constructed via coassembly, chiral induction, chiral memory, and a click reaction.

Broadening the mutational spectrum of ASAH1, as a susceptibility gene for keloids.

Keloids are fibroproliferative scars influenced by genetic predisposition, notably involving the ASAH1 gene, which encodes acid ceramidase. A prior study identified a pathogenic ASAH1 variant (NM_004315.6:c.

Hair follicle epithelial stem cells contribute to interfollicular epidermis during homeostasis.

Mammalian skin is a vital barrier with the epidermis serving as its protective outer layer, continually undergoing renewal. Given that loss of the epidermis or its barrier function is lethal for mammals, multiple stem cell populations likely exist for the interfollicular epidermis (IFE), enhancing evolutionary survival. Here, we demonstrate that transcription factor KROX20 marks a heterogeneous stem cell population in the upper and middle mouse hair follicle (HF), partially overlapping with known HF stem cell markers in those regions.

Tumoral RCOR2 promotes tumor development through dual epigenetic regulation of tumor plasticity and immunogenicity.

Gain of plasticity and loss of MHC-II enable tumor cells to evade immune surveillance contributing to tumor development. Here, we showed that the transcriptional corepressor RCOR2 is a key factor that integrates two epigenetic programs surveilling tumor plasticity and immunogenicity. RCOR2 was upregulated predominantly in tumor cells and promoted tumor development in mice through reducing tumor cell death by CD4+/CD8+ T cells and inducing cancer stemness.

From Layered Crystals to Permselective Membranes: History, Fundamentals, and Opportunities.

Membranes are crucial in permselective processes, such as water purification, gas sequestration, ion separation, membrane distillation and pervaporation, and energy conversion and storage. The two-decade development of two-dimensional (2D) membranes has shifted the membrane transport from solution-diffusion in the polymer matrix to size-dependent migration in Ångström-to-nanoscale slit-like channels, delivering distinctive fundamentals within nanoconfinements and potential implementations. In this review, we delve into the comprehensive information that facilitates the transformation of layered crystals into continuous thin-film architectures boasting well-defined nanopores.

Biodegradation of Neonicotinoid Insecticides Thiacloprid and Thiamethoxam by Microorganisms: Metabolic Process, Metabolic Enzymes and Toxicity Assessments of their Metabolites.

The extensive agricultural use of neonicotinoid insecticides, particularly thiacloprid (THI) and thiamethoxam (THIA), has raised profound environmental and ecological concerns. Microbial bioremediation has emerged as a promising strategy to mitigate these impacts. While numerous microorganisms capable of degrading THI and THIA have been identified and characterized, the underlying degradation mechanisms remain poorly understood.

Using healthcare claims data to identify health disparities for individuals with familial hypercholesterolemia.

Background: Intensive lipid-lowering therapy is crucial for individuals with familial hypercholesterolemia (FH) to reach target low-density lipoprotein cholesterol (LDL-C) levels. However, there are limited data on disparities in therapy use among FH patients in the US.

Methods: An epidemiologic analysis of a US healthcare claims database (2016-2020) covering 324 million individuals.

Identification of α-azacyclic acetamide-based inhibitors of Na pump ( ATP4) with fast-killing asexual blood-stage antimalarial activity by phenotypic screening.

Malaria treatments are compromised by drug resistance, creating an urgent need to discover new drugs. We used a phenotypic high-throughput screening (HTS) platform to identify new antimalarials, uncovering three related pyrrole-, indole-, and indoline-based series with a shared α-azacyclic acetamide core. These compounds showed fast-killing activity on asexual blood-stage parasites, were not cytotoxic, and disrupted parasite intracellular pH and Na regulation similarly to cipargamin (KAE609), a clinically advanced inhibitor of the Na pump ( ATP4).

Microalgal glutaredoxin 1 interacts with transcription factor bZIP to resist cadmium stress via lipid metabolism alteration.

Triacylglycerol (TAG), a universal energy reserve and biodiesel feedstock, accumulates under stress in microalgae. However, the regulatory mechanisms linking stress signals to TAG synthesis remain unclear. In this study, we identified ApGRX1724, a novel glutaredoxin 1 family member found in Auxenochlorella protothecoides, that could translocate to the nucleus and interact with the transcription factor ApbZIP4896, which regulating TAG synthesis by interacting with the synthetase ApPAP6812.

Versatile and programmable dual-mode logic gold nanoflares for intracellular correlated DNA repair enzymes imaging.

In situ monitoring of correlated DNA repair enzyme activities in living cells is crucial for clinical and biomedical research. Here, we introduce a versatile, programmable dual-mode logic gold nanoflares strategy for OR/AND gate logic imaging the activity of apurinic/apyrimidinic endonuclease 1 (APE1) and flap endonuclease 1 (FEN1) within cells. The logic gold nanoflares were designed via conjugating enzyme-activatable sites modified branched double-stranded DNA structures to gold nanoparticles.

RNA polymerase II partitioning is a shared feature of diverse oncofusion condensates.

Condensates regulate transcription by selectively compartmentalizing biomolecules, yet the rules of specificity and their relationship to function remain enigmatic. To identify rules linked to function, we leverage the genetic selection bias of condensate-promoting oncofusions. Focusing on the three most frequent oncofusions driving translocation renal cell carcinoma, we find that they promote the formation of condensates that activate transcription by gain-of-function RNA polymerase II partitioning through a shared signature of elevated π and π-interacting residues and depletion of aliphatic residues.

ZMYND8 drives HER2 antibody resistance in breast cancer via lipid control of IL-27.

Anti-HER2 antibodies are effective but often lead to resistance in patients with HER2+ breast cancer. Here, we report an epigenetic crosstalk with aberrant glycerophospholipid metabolism and inflammation as a key resistance mechanism of anti-HER2 therapies in HER2+ breast cancer. Histone reader ZMYND8 specifically confers resistance to cancer cells against trastuzumab and/or pertuzumab.

A DNA concatemer-encoded CRISPR/Cas12a fluorescence sensor for sensitive detection of Pb based on DNAzymes.

Lead pollution presents a significant threat to ecological systems and human health, underscoring the urgent need for highly sensitive detection methods. Herein, we introduce a novel DNA concatemer-encoded CRISPR/Cas12a fluorescence sensor (MDD-Cas12a) for sensitive detection of Pb based on DNAzymes. To accomplish this, we designed a substrate strand containing a long DNA concatemer encoding multiple protospacer adjacent motifs (PAMs) and protospacer sequences for activation of the CRISPR/Cas12a system.

Effects of nitrogen-driven eutrophication on the horizontal transfer of extracellular antibiotic resistance genes in water-sediment environments.

Excessive nitrogen and other nutrients can trigger the eutrophication of freshwater bodies. Antibiotic resistance genes (ARGs) are now recognized as environmental pollutants, with extracellular ARGs (eARGs) being the dominant form in sediments. However, research on the propagation characteristics of eARGs remains limited.

Self-Sorted Chiral Nanofibrous Hydrogels for Enhanced Osteoarthritis Cartilage Regeneration.

Self-sorting by supramolecular assembly involving homochiral building blocks is of vital importance in life systems, which allows the coexistence of multiple species in an orthogonal complex mixture to achieve respective biological functions simultaneously. However, self-sorting of chiral molecules, typically homochiral molecules, remains a challenge in artificial systems, limiting the biological function development of chiral materials. Herein, we report a self-sorted supramolecular hydrogel network formed by two l-phenylalanine derivatives, LPPF and LPFA, which independently self-assemble into nanofibers with distinct helical orientations and diameters.

Defects in nephrogenesis result in an expansion of the + stromal progenitor population.

Reciprocal signaling interactions coordinate multiple aspects of kidney development. While signals from the stroma have been shown to regulate nephron progenitor cell (NPC) differentiation, much less is known about regulation of the stromal progenitor population. Here, we demonstrate that disruption of the NPC lineage via loss of (i.