The abnormal regulation and expression of microRNA (miRNA) are closely related to the aging process and the occurrence and development of aging-related diseases. Lethal-7 (let-7) was discovered in Caenorhabditis elegans (C. elegans) and plays an important role in development by regulating cell fate regulators. Accumulating evidence has shown that let-7 is elevated in aging tissues and participates in multiple pathways that regulate the aging process, including affecting tissue stem cell function, body metabolism, and various aging-related diseases (ARDs). Moreover, recent studies have found that let-7 plays an important role in the senescence of B cells, suggesting that let-7 may also participate in the aging process by regulating immune function. Therefore, these studies show the diversity and complexity of let-7 expression and regulatory functions during aging. In this review, we provide a detailed overview of let-7 expression regulation as well as its role in different tissue aging and aging-related diseases, which may provide new ideas for enriching the complex expression regulation mechanism and pathobiological function of let-7 in aging and related diseases and ultimately provide help for the development of new therapeutic strategies.

During the past decades, prostate cancer (PCa), with an annual incident rate much higher than any other cancer, is the most commonly diagnosed cancer in American men. PCa has a relatively low progression rate yet the survival percentage decreases dramatically once the cancer has metastasized. Identifying aggressive from indolent PCa to prevent metastasis and death is critical to improving outcomes for patients with PCa. Standard procedure for assessing the aggressiveness of PCa involves the removal of tumor tissues by transrectal (TR) ultrasound (US) guided needle biopsy. The microscopic architecture of the biopsied tissue is visualized by histological or immunohistochemical staining procedures. The heterogeneity of the microscopic architecture is characterized by a Gleason score, a quantitative description of the aggressiveness of PCa. Due to the inability to identify the cancer cells, most noninvasive imaging modalities can only provide diagnosis of PCa at limited accuracy. This study investigates the feasibility of identifying PCa tumors and characterizing the aggressiveness of PCa by photoacoustic imaging assisted by cancer targeting polyacrylamide (PAA) nanoparticles (NPs). PAA is a biocompatible material used in clinics for the past 20 years. PAA NPs can protect capsulated optical contrast agents from interference by enzymes and enable prolonged systematic circulation in the living biological environment. The cancer targeting mechanism is achieved by conjugating the NPs to F3 peptides, which trace nucleolin overexpressed on the surface of cancer cells. Preliminary studies have shown that the NPs are capable of staining the PCa cells in vivo.

Although immune-targeted therapies, particularly agents targeting the interleukin (IL)-23/IL-17 axis, have markedly improved short-term disease control in psoriasis, inadequate responses in a subset of patients and relapse after treatment discontinuation remain unresolved challenges. One possible reason is that immune-centred therapies may not fully address the active contribution of epidermal keratinocytes to inflammatory amplification and disease persistence. In this review, we integrate immune-driven inflammation and epidermal amplification mechanisms from a loop- and network-based perspective, and ­propose an immune–epidermal dual-targeting framework centred on proinflammatory feedback between immune cells and keratinocytes. We systematically summarize three potential implementation routes: combination therapy, single-agent dual targeting and blockade of bridging nodes within immune–epidermal feedback circuits. We further discuss the potential roles and realistic boundaries of artificial intelligence and multi-omics analysis, organoids and engineered skin models, and precision local delivery technologies in target discovery, mechanistic validation and therapeutic translation. Importantly, this framework is not intended to replace existing therapeutic paradigms, but rather to refine their mechanistic interpretation and extend future therapeutic strategies. It may provide additional translational opportunities for stratified, stage-specific and precision management of psoriasis, although several components remain at the stage of mechanistic research and clinical validation.

Background We tested the hypothesis that the circulating tumour cells (CTCs) in preoperative peripheralblood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long term survival in surgically resected NSCLC patients. Method CTCs were separated from the blood using magnetic beads coated by antibody against epithelial-cell adhesion molecule (EpCAM) through magnetic activated cell sorting (MACS). The CTCs were quantified with fluorescence labelled antibodies against pan-cytokeratin through flow cytometry. CTCs were prospectively quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with surgically resected NSCLC. Association between CTCs and prognosis of these patients was evaluated after 5-year follow-up. Results In the NSCLC patients, outcomes were assessed according to levels of CTCs at surgery, and compared with CTCs detected in benign pulmonary diseases, and healthy volunteers, wherethe mean and 95% CI of CTCs counts were all 5 CTCs/15 mL in PPB and >50 CTCs/15 mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that CTCs count in PPB or IPVB was an independent risk factor for tumour-free and overall survivals. The high risk group of patients had a shorter median tumour-free survival (22 months vs. >60.0 months, P < 0.0012) and shorter overall survival (27 months vs. >60 months, P < 0.0015). Conclusions CTCs countin PPBand IPVB was an independent risk factor for tumour-free and overall survivalin surgically resected NSCLC patients.

Endoplasmic reticulum stress (ERS) and autophagy regulate tumor-infiltrating T cell function and exhaustion, but the underlying mechanisms remain unclear. Here, we identified the ERS-related transmembrane protein TMED4 (transmembrane emp24 domain-containing 4) as a critical regulator of CD8 ⁺ T cell antitumor immunity. Tmed4 deletion in T cells enhanced antitumor responses by promoting CD8 ⁺ T proliferation, infiltration, and killing capacity, while reducing terminal exhaustion. Mechanistically, Tmed4 deficiency hyperactivated the inositol-requiring enzyme 1α (IRE1α)–X-box binding protein 1 (XBP1) axis and induced autophagy flux in an IRE1α-dependent manner. Genetic deletion of Ern1 (IRE1α) or Becn1 (Beclin1) impaired the antitumor effects of Tmed4 deficiency, underscoring the role of ERS and autophagy in CD8 ⁺ T cell function. Moreover, Tmed4 -deficient chimeric antigen receptor T cells (CAR T cells) displayed improved antitumor immunity. Pharmacological inhibition of Tmed4 using antisense oligonucleotide also enhanced CD8 ⁺ T cell–mediated tumor control. In summary, our study reveals that TMED4 governs CD8 ⁺ T cell effector function and limits terminal exhaustion through IRE1α-driven autophagy, establishing TMED4 as a promising immunotherapeutic target for improving CAR T cell efficacy.