Congenital muscular dystrophies (CMDs) represent a genetically heterogeneous group of disorders characterized by muscle weakness, dystrophic changes on muscle biopsy, and onset typically in infancy or childhood. Variants in the INPP5K gene, which encodes a phosphoinositide 5-phosphatase that regulates phosphoinositide signaling, have recently been identified as a rare cause of congenital muscular dystrophy, commonly associated with early-onset cataracts and intellectual disability. This case report describes the first Chinese patient with INPP5K-related muscular dystrophy, a 28-year-old male with a notably mild phenotype that lacked intellectual disability, expanding the clinical spectrum of this disorder. The patient presented with bilateral cataracts requiring surgical correction at age 5, followed by adolescent-onset limb girdle weakness with postural hand tremors beginning at age 15 and progressive lower limb weakness at age 16. Muscle magnetic resonance imaging revealed a characteristic pattern of selective fatty infiltration, with severe involvement of gluteal and thigh muscles and striking sparing of the rectus femoris, sartorius, and gracilis muscles, a pattern that provides important diagnostic clues. Genetic analysis identified compound heterozygous novel INPP5K variants: a missense variant c.274C>T, p.(Arg92Cys), and a synonymous variant c.261G>A, p.(Lys87=).

Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as a transformative treatment strategy for stage III non-small cell lung cancer (NSCLC), significantly improving outcomes in both neoadjuvant and adjuvant settings. However, predictive biomarkers of response to immunotherapy remain limited, and identifying patients most likely to benefit from these treatments remains a critical unmet need. DNA polymerase epsilon (POLE) mutations, although rare in NSCLC, are associated with an increased tumor mutational burden (TMB) and enhanced neoantigen presentation, both of which are mechanistically linked to increased sensitivity to immune checkpoint inhibitor therapy. This case report describes a 52-year-old woman diagnosed with stage IIIA NSCLC whose tumor demonstrated negative programmed death-ligand 1 (PD-L1) expression, a factor typically associated with reduced likelihood of response to immunotherapy. Molecular profiling revealed a somatic POLE mutation (NM_006231.4: c.1270C>G, p.Leu424Val) in the absence of additional targetable tumor alterations. A perioperative chemo-immunotherapy approach was implemented, consisting of three cycles of neoadjuvant carboplatin, pemetrexed, and pembrolizumab, followed by curative-intent surgery. Restaging computed tomography after neoadjuvant therapy revealed a significant radiographic response, and histopathological examination of the surgical specimen demonstrated a pathological complete response (pCR), with no viable tumor cells identified.

Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening hematological emergency defined by severe deficiency of ADAMTS13, a metalloproteinase that cleaves ultra-large von Willebrand factor multimers. However, TTP-like syndromes without ADAMTS13 reduction can occur in the context of systemic infections such as human immunodeficiency virus (HIV), posing significant diagnostic and therapeutic challenges, particularly in high-risk and underdiagnosed populations. This case report describes a 45-year-old transgender woman who presented with abdominal and lumbar pain, severe anemia, and thrombocytopenia. Laboratory evaluation revealed schistocytes on peripheral blood smear, elevated lactate dehydrogenase, and indirect hyperbilirubinemia, prompting a high PLASMIC score and urgent initiation of plasma exchange for suspected primary TTP. However, subsequent investigations revealed preserved ADAMTS13 activity, effectively excluding immune-mediated TTP, and uncovered a previously undiagnosed advanced HIV infection with profound immunosuppression (CD4+ T-cell count of 33 cells/µL), accompanied by active Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) viremia. Further evaluation revealed disseminated AIDS-related Kaposi's sarcoma. Despite timely initiation of antiretroviral therapy and comprehensive supportive care, the patient experienced progressive clinical deterioration and died on day 69 of hospitalization.

Hereditary spherocytosis (HS) and thalassemia are among the most common inherited hemolytic anemias, yet their co-occurrence presents unique diagnostic challenges due to overlapping clinical manifestations. This case report describes a unique presentation of concurrent hematological disorders in a 2-year-old Chinese boy: hereditary spherocytosis caused by a novel gene mutation, together with α-globin gene triplication. The child presented with a history of longstanding hemolytic disease, with recurrent episodes of anemia, jaundice, and abdominal pain triggered by upper respiratory infections, accompanied by splenomegaly and cholecystolithiasis. Laboratory evaluation revealed increased osmotic fragility of red blood cells and elevated reticulocyte count, supporting a diagnosis of hemolytic anemia. Mutation analysis identified a de novo heterozygous mutation in the SPTB gene: c.149-1G>A, a novel splicing mutation not detected in either parent and not previously reported in the literature. This pathogenic variant is speculated to affect pre-mRNA splicing of β-spectrin, a critical component of the erythrocyte cytoskeleton. Concurrently, the child was found to carry α-globin gene triplication (αααanti4.2), a relatively rare numerical variation that may complicate the clinical presentation by altering hemoglobin synthesis.

Glioblastoma (GBM) remains the most aggressive and lethal primary brain tumor, with a dismal prognosis despite decades of intensive research. While immunotherapy has revolutionized treatment for many cancers, GBM has proven remarkably refractory to immune-based interventions due to the absence of effective immunotherapeutic targets and the profoundly immunosuppressive tumor microenvironment. In this groundbreaking study, researchers employed CRISPR screening to systematically identify novel drivers of GBM progression, uncovering Niemann-Pick C1-like 1 (NPC1L1) as a previously unrecognized key regulator of GBM pathogenesis. Mechanistically, NPC1L1 modulates cholesterol metabolism to concurrently enhance tumor cell stemness and suppress CD8+ T-cell activation, creating a dual mechanism that drives tumor progression while evading immune surveillance. Most notably, combined treatment with ezetimibe, an FDA-approved NPC1L1 inhibitor, and anti-PD-1 antibody elicited potent antitumor activity in GBM orthotopic mouse models, offering a promising translational strategy. These findings establish NPC1L1 as a critical regulator of GBM pathogenesis and underscore the therapeutic potential of targeting NPC1L1-mediated cholesterol metabolism for developing novel GBM immunotherapies, opening new avenues for treating this devastating disease.

The hidden world of quantum mechanics exists at scales many orders of magnitude smaller than living organisms, and yet scientists have long theorized that quantum effects play an important role in biology. Birds’ ability to sense magnetic fields during migration is one of the most well-known mysteries in this field, with leading theories suggesting that this sensing could be achieved by exploiting quantum entanglement. By proving the Pontryagin Maximum Principle for quantum systems, researchers have come up with a recipe to control quantum effects that may finally be able to put this avian hypothesis to the test, while also unlocking new biological platforms for quantum computing.

A novel mechanism based on Yinxie Granules and its core active ingredients (quercetin and kaempferol) to ameliorate psoriasis by blocking the STING-NF-κB signaling pathway to simultaneously suppress cutaneous inflammation and pathological angiogenesis is provided, and a new strategy for dual-targeting therapy of psoriasis is opened.

Nitrilases are critical industrial biocatalysts for converting nitriles into high-value carboxylic acids, yet their application is often hindered by the formation of insoluble inclusion bodies during heterologous expression. A new study introduces a robust engineering strategy utilizing superfolder green fluorescent protein (sfGFP) fusion to screen for solubility-enhancing mutations. By targeting surface hydrophobic residues, researchers successfully developed a triple mutant, PD1Mut3, which exhibits significantly improved soluble yield, thermostability, and catalytic efficiency, offering a generalizable platform for optimizing enzyme production.