Table of Contents Alert: The FASEB Journal, Vol. 40, No. 4, 28 February 2026
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The FASEB Journal Volume 40, Issue 4 28 February 2026
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COVER
Free AccessCover Image
e71617 | First Published: 18 February 2026
The cover image is based on the article Cholesterol Lowering Alone Fails to Reverse Atherosclerotic Plaque Necrosis, Granulopoiesis, and Neurovascular Neutrophils in Middle-Aged Mice by Olivia Gannon et al., https://doi.org/10.1096/fj.202503638RR.
PERSPECTIVE
Free AccessUntold: Marshall Nirenberg and Hexose Transport
e71529 | First Published: 13 February 2026
HYPOTHESIS
Open AccessTau Phosphorylation as an Adaptive Physiological Response: Implications for the Therapy of Tauopathies
e71538 | First Published: 09 February 2026
Drawing on recent studies suggesting that tau phosphorylation is reversible, therapies for tauopathies could enhance reversibility, for example, by dismantling aggregated tau species.
REVIEW ARTICLE
Open AccessCirculating Myokine Responses to Acute Endurance Exercise and Their Role in Immunoregulation: A Systematic Review and Meta‐Analysis
e71536 | First Published: 09 February 2026
This systematic review and meta-analysis, which examined the effects of acute endurance training on immunoregulatory myokines, showed significant small-moderate to very large positive effect sizes for IL-6, IL-10, IL-1ra, IL-8, IL-15, and TNF-α. These effects were significantly moderated by risk of bias, sex, age, V̇O2peak, experience, type of exercise, intensity, duration, dose, sample, fasting status, and time of day. This suggests that endurance training is a key component in the treatment of a variety of diseases.
Free AccessExosomes: From Non‐Invasive Detection to Engineered Targeted Therapy
e71564 | First Published: 10 February 2026
Exosomes isolated from liquid biopsy samples, including blood, urine, and cerebrospinal fluid, serve as nano-vesicles carrying diagnostic biomarkers such as proteins and miRNAs. Beyond non-invasive disease detection, exosomes can be engineered through surface ligand modification and cargo loading to enhance targeting specificity. This strategy bridges liquid biopsy–based diagnosis with precision targeted therapy.
Free AccessMapping the Regulatory Landscape of Sheep Pituitary Gland Associated With Puberty at Single‐Cell Resolution
e71574 | First Published: 12 February 2026
We constructed a high-resolution single-cell transcriptional atlas of the sheep pituitary across the pre-pubertal (3 month) and post-pubertal (6 month) stages using scRNA-seq. This analysis revealed dynamic molecular and cellular remodeling associated with puberty onset, including changes in key genes and signaling pathways. Among pituitary cell populations, gonadotrophs displayed prominent transcriptional shifts, with Secretogranin II (SCG2) identified as a key gene. Functional validation indicated that SCG2 influences follicle-stimulating hormone (FSH) secretion, suggesting that SCG2 may play a regulatory role during pubertal activation.
Free AccessUnexplored Domain: The Unconventional T Cells in the Male Genitourinary Tract and Related Diseases
e71566 | First Published: 13 February 2026
The immune microenvironment of the male genitourinary tract is orchestrated by immune cells including unconventional T cells, which mainly consist of γδ T cells, natural killer T (NKT) cells, and mucosal-associated invariant T (MAIT) cells. In this review, we summarized the knowledge including subset, distribution, and function of unconventional T cell populations across the male genitourinary tract. Moreover, we compared unconventional T cells in the blood, urine, and semen and discussed their clinical significance served as biomarkers and therapeutic targets.
Free AccessDEAH‐Box RNA Helicases in the Spliceosome: Advances in Structure and Function
e71588 | First Published: 14 February 2026
DEAH-box RNA helicases drive spliceosome remodeling through coordinated RNA and protein rearrangements. Recent high-resolution cryo-EM structures capture all five spliceosomal DEAH-box helicases bound to their RNA substrates at distinct functional stages, revealing how they regulate catalytic activation, exon ligation, and disassembly. Integrating structural and biochemical evidence, this review presents a unified framework for helicase recruitment, substrate engagement, and regulation in ensuring accurate pre-mRNA splicing.
Open AccessThe Application of PD‐1 Inhibitors in Immunotherapy for Glioblastoma
e71589 | First Published: 14 February 2026
The molecular mechanism of PD-1. When PD-1 binds to PD-L1, the ITIM and ITSM domains within PD-1 are phosphorylated and subsequently recruit SHP-2. This then dephosphorylates downstream molecules of the TCR, such as PI3K/AKT and ZAP70, reduces the secretion of IFN-γ, and inhibits the presentation of antigens to T cells via MHC molecules through the binding of CD80 and CD86 to CD28, thereby inhibiting the activation and recognition of tumor antigens by T cells. (A) Inhibiting the activation of T cells. (B) T cells are unable to recognize tumor cells. (C) Tumor cells will proliferate infinitely. The mechanism of action of PD-1 inhibitors and their relationship with GBM. PD-1 inhibitors block the interaction between PD-1 and PD-L1, restoring the anti-tumor function of T cells and enabling them to re-recognize tumor cells. This inhibits the proliferation of tumor cells while enhancing the body's immune response against the tumor. (A) The binding of PD-1 to PD-L1 suppresses T cell activation. (B) PD-1 inhibitors bind to the PD-1/PD-L1 complex, blocking the interaction between PD-1 and PD-L1. (C) The suppressed activated T cells are reactivated, restoring their function. (D) Glioblastoma cells are identified, and tumor cell proliferation is inhibited.
Open AccessAging‐Driven Inter‐Organ Crosstalk in Postmenopausal Osteoporosis: From Immunometabolic Drift to Multisystem Frailty
e71541 | First Published: 21 February 2026
Postmenopausal osteoporosis (PMOP) is increasingly recognized as an aging-associated, multisystem state of fragility, in which estrogen deficiency exacerbates immune and metabolic drift across the bone marrow, skeletal muscle, adipose tissue, gut, vascular system, and neural circuits. This metabolic and immune dysregulation further amplifies bone resorption, ultimately driving postmenopausal osteoporosis.
Free AccessTNXB Regulates Spermatogenesis by Maintaining Cytoskeleton and Cell Junction Stability
e71585 | First Published: 19 February 2026
This schematic diagram depicts the function of Tenascin-X (TNXB) in preserving testicular architecture and spermatogenesis. In normal testes, TNXB is predominantly expressed in germ cells and moderately in Sertoli cells. TNXB sustains the organization of the extracellular matrix and basement membrane, the structure of the cytoskeleton, and the integrity of the blood–testis barrier. Germline-specific deletion of Tnxb results in disrupted collagen arrangement, disorganization of the cytoskeleton, compromised function of the blood–testis barrier, increased apoptosis of germ cells, and consequently leads to impaired spermatogenesis.
Free AccessBiological Characteristics of Exosomes and Their Applications in Aquatic Organisms
e71601 | First Published: 20 February 2026
This schematic summary elucidates the biological characteristics of exosomes and their applications in aquatic organisms, encompassing exosome biogenesis, cargo composition, isolation techniques, identification methodologies, and their diverse applications in aquatic species. It comprehensively illustrates the promising potential of exosome-based technologies, thereby facilitating the advancement of exosome research and utilization in the field of aquatic biology.
RESEARCH ARTICLE
Attenuation of Transforming Growth Factor‐β Signaling Promotes Complete Recovery of Trabecular Bone Structure Following Immobilization With Traumatic Spinal Cord Injury
e71531 | First Published: 07 February 2026
Spinal cord injury (SCI) is associated with severe distal femoral and proximal tibial trabecular bone loss that is resistant to treatment. We determined the efficacy of 1D11, a TGF-β inhibitory antibody to restore trabecular bone architecture in SCI male mice. We demonstrate that treatment of SCI mice with 1D11 for 5 weeks completely regained distal femoral trabecular bone structure. Inhibitors of TGF-β signaling may therefore be used to restore trabecular bone structure and reduce the fracture risk after SCI.
Cholesterol Lowering Alone Fails to Reverse Atherosclerotic Plaque Necrosis, Granulopoiesis, and Neurovascular Neutrophils in Middle‐Aged Mice
e71508 | First Published: 07 February 2026
Young (8 week) and middle-aged (40 week) mice were injected with gain-of-function AAV8-PCSK9 and fed a Western diet for 20 weeks to induce atherosclerosis. After 20 weeks, mice were switched to a chow diet to induce lipid lowering and various tissues (aortic root, blood, bone marrow, brain) were collected for analysis. Middle-aged atherosclerotic mice had sustained nonresolving plaque necrosis and increased circulating neutrophils including within brain vasculature compared with young mice in the same context.