AI and biotech
Depression is one of the leading causes of disability worldwide. Cognitive behavioral therapy (CBT) is an effective treatment, but it is difficult to access due to clinician shortages, waitlists, and logistical barriers. Smartphone-based CBT interventions offer a scalable alternative to traditional …
Precise prediction of bioactive conformations represents a central challenge in drug discovery. Traditional computational methods often rely on the assumption that the global minimum energy state corresponds to the bioactive conformation─a hypothesis with inherent limitations. Data-driven art…
Messenger RNA (mRNA) technology holds great promise in biomedicine; however, its therapeutic efficacy relies heavily on translation efficiency and the in vivo stability of mRNA sequences, both of which are governed by dynamic interactions between the coding and noncoding regions. Existing optimizati…
Nanoparticle-based mechanistic and multifunctional strategies for targeted osteosarcoma therapy.
2026-04-16
Osteosarcoma is the most common malignant bone tumor in children and adolescents, usually affecting the long bones of the limbs. Despite progress in surgery, chemotherapy, and radiotherapy, patient outcomes remain poor, highlighting the need for better treatments. Nanoparticles have emerged as promi…
Metastatic castration‑resistant prostate cancer (mCRPC) remains a lethal disease due to universal resistance to androgen‑receptor pathway inhibitors (ARPI). Tumor progression is orchestrated by a spectrum of androgen‑receptor‑independent drivers, including genomic alterat…
Despite unprecedented technological progress, most drug candidates continue to fail in clinical trials, reflecting a persistent gap between preclinical models and human biology. New approach methodologies (NAMs), by spanning human-derived cellular systems, microphysiological platforms, and artificia…
Gene editing
Myotonic dystrophy type 1 is the most prevalent adult-onset muscular dystrophy and is characterized by progressive muscle weakness, myotonia, cardiac conduction defects, endocrine dysfunction, and central nervous system involvement. Myotonic dystrophy type 1 is caused by an unstable CTG repeat …
Islet transplantation offers a physiological approach for restoring endogenous insulin secretion in type 1 diabetes, yet its broad clinical application remains constrained by donor scarcity, immune-mediated rejection, and limited graft durability. Stem cell-derived islets have emerged as a scalable …
Staphylococcus aureus Cas9 (SaCas9) is smaller than the widely used Streptococcus pyogenes Cas9 (SpCas9) and has been harnessed for gene therapy using an adeno-associated virus vector. However, SaCas9 requires a longer NNGRRT (where N is any nucleotide and R is A or G) protospacer adjacent motif (PA…
Long-term in vivo production of therapeutic proteins and development of vaccines that elicit protective levels of broadly neutralizing antibodies (bNAbs) against major pathogens face challenges. In this study, we report on an alternative gene editing approach using small numbers of hematopoietic ste…
Genomics
Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by dysregulated keratinocyte proliferation, immune cell infiltration, and systemic comorbidities. Despite the identification of numerous genetic susceptibility loci for psoriasis through genome-wide association studies (G…
Immunotherapy
In response to treatment with immune checkpoint inhibitors (ICIs), patients with cancer can develop immune-related adverse events (irAEs), which are off-target toxicities affecting non-tumour tissues. Development of an irAE can require cessation of ICI treatment and cause additional morbidities, unr…
Hereditary breast cancers (hBCs) exhibit genomic heterogeneity, but their underlying genomic instability and clinical implications remain unclear. We conducted whole-genome sequencing on 129 BRCA1/2-negative hBCs, with subsets analyzed by methylome and transcriptome sequencing, and integrated COSMIC…
This international consensus statement synthesizes key findings on the complex roles of microglia and macrophages (tumor-associated microglia/macrophages or TAMs) in glioma progression and therapeutic resistance. Recent advances have highlighted the cellular, spatial, and temporal heterogeneity…
This study aimed to systematically analyze the research status, hotspots, and trends of oncolytic virotherapy (OV) for hepatocellular carcinoma (HCC) from 2000 to mid-2025, scientifically predict future directions, facilitate clinical translation, and provide a reference for subsequent studies in th…
Immune checkpoint blockade (ICB) induces frequent and durable responses in metastatic dMMR CRC, yet substantial molecular heterogeneity and resistance remain. We sought to identify candidate tumor- and immune-related biomarkers associated with clinical outcomes following anti-PD-1 therapy….
Immune-checkpoint blockade (ICB) has demonstrated efficacy across tumor types. However, “cold” tumors characterized by low intraepithelial T-cell infiltration exhibit poor responsiveness. We investigated whether low-dose radiotherapy (LDRT) could enhance ICB efficacy in patients with multimetastatic…
Overcoming drug resistance in pancreatic ductal adenocarcinoma (PDAC) remains a major challenge due to dense fibrotic stroma, DNA repair-mediated resistance, drug efflux mechanisms, and an immunosuppressive tumor microenvironment (TME). Here, we use photoactivatable multi-inhibitor liposomes (PMILs)…
The spatial distribution of immune cells in the tumor microenvironment (TME) is a key determinant of immunotherapy response, while current methods are limited by sequencing dependence and restricted spatial resolution. We developed SpaHE-Infil, a multimodal computational framework integrating spatia…
Melanoma, the most lethal form of skin cancer, remains a significant therapeutic challenge despite advances in immunotherapy. Although PD-1/PD-L1 blockade improves clinical outcomes, its effectiveness is frequently limited by suboptimal response rates and treatment resistance. Here, we developed a n…
Multiple myeloma (MM) is an incurable malignancy exhibiting immune evasion and resistance to proteasome inhibitors like bortezomib. We engineered an oncolytic vaccinia virus encoding an anti-mouse CD47 nanobody (OVV-αCD47nb) that combines direct oncolysis with localized CD47-SIRPα axis b…
Due to late diagnosis, high molecular diversity, and limited response to therapeutic intervention, gastrointestinal (GI) cancers result in a considerable number of cancer-related deaths. Classic clinicopathological classification and single omics analysis fail to adequately convey the extensive biol…
Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) typically polarize toward an M2 phenotype that promotes tumor progression and immune suppression. Reprogramming TAMs to the proinflammatory M1 phenotype has emerged as a promising strategy to boost antitumor immunity. This study…
This study investigates changes in NK cell subsets in the blood of NPC patients and explores JAB1’s role in shaping the tumor immune environment….
ICOS-Targeted Peptide Imaging Informs Therapeutic Response of STING Agonist in Lung Adenocarcinoma.
2026-04-16
The innovation of cancer immunotherapy is improving clinical theranostics for lung cancer. Given the variation of therapeutic effects among patients, there is an urgent need to develop novel tools for precisely evaluating immune responses. Methods: Herein, we first described the potential of the ind…
Mucosal melanoma (MM) carries a high risk of postoperative relapse and poorer survival than cutaneous disease. Prospective data from China support adjuvant temozolomide-cisplatin (TMZ/DDP) in resected MM, while radiotherapy (RT) may augment antitumour immunity and synergise with programmed death 1 (…
Anti-N-methyl-D-aspartate (NMDA) encephalitis is marked by rapidly evolving and severe neuropsychiatric symptoms that can affect any age. This case illustrates a woman in her early 40s who was admitted with refractory headache, hallucinations and progressive encephalopathy. After imaging failed to d…
Chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment of B-cell malignancies, yet challenges including manufacturing delays, T-cell exhaustion, and limited persistence impede broader clinical success. Here, we report the single day production of non-activated CAR T-cells en…
Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy of the oral cavity, frequently preceded by oral potentially malignant disorder (OPMD). Despite therapeutic advances, survival rates remain unsatisfactory, primarily due to late diagnosis, recurrence, and molecular al…
Tumor-targeted CD40 agonists have emerged as one of the novel strategies to activate intratumoral antigen-presenting cells (APCs), subsequently inducing T-cell-specific antitumor responses. However, their clinical efficacy as monotherapy has been limited, highlighting the need for effective combinat…
While thyroid dysfunction during PD-L1 inhibitor therapy correlates with efficacy in recurrent/metastatic nasopharyngeal carcinoma, the prognostic value of basal thyroid function remains unclear. This study investigated the relationship between baseline serum thyroid-stimulating hormone (TSH) and cl…
Longevity
Context: Sirtuin-2 (SIRT2) is a longevity-related protein implicated in apoptosis, metabolic regulation and oxidative stress; however, its role in ageing pancreas remains unclear. Objective: This study investigated the effects of the selective SIRT2 inhibitor, Arabidopsis guanylate kinases-2 (AGK-2)…
Foreign-born residents in high-income countries often outlive the native-born population, but it remains unclear how this advantage varies across countries and socioeconomic groups. We aimed to assess socioeconomic inequalities in the life expectancy advantage of foreign-born populations across 10 E…
Background: The increasing longevity of people with intellectual disabilities has intensified the need to promote participation, autonomy and quality of life in later adulthood. However, ageing often occurs in contexts with limited opportunities for decision-making and personal agency. Virtual reali…
Biological aging is a complex process associated with declining physiological function and increased risk of aging-related diseases. However, its risk factors and molecular mechanisms remain poorly understood. Here, we performed a comprehensive integrative analysis to identify putative risk factors …
The past decade has defined molecular hallmarks of aging, yet interventions that extend lifespan in short-lived organisms show limited and context-dependent translation to humans. Comparative studies of exceptional longevity remain largely genome-centric, although genomic instability alone cannot co…
Mitochondria
Lipid droplets (LDs) are ubiquitous intracellular organelles that store neutral lipids such as triacylglycerols and sterol esters within a phospholipid monolayer decorated by a specialized proteome. Far from being inert depots, LDs are highly dynamic hubs that integrate lipid storage with cellular a…
Targeting erythroid cell-derived asparagine inhibits alloimmunization in sickle cell disease.
2026-04-17
Red blood cell (RBC) transfusions remain a lifesaving therapy for patients with sickle cell disease (SCD), yet their safety and efficacy are limited by a high incidence of alloimmunization. Emerging evidence suggests that metabolites, including amino acids, can influence humoral immune responses. He…
Metabolic memory-the persistent risk of diabetic complications after early hyperglycemia-drives progressive renal injury in diabetic kidney disease (DKD) via sustained oxidative stress, inflammation, and epigenetic reprogramming. We synthesize clinical and experimental evidence showing the nicotinam…