How RAG1/2 evolved from ancestral transposases to initiate V(D)J recombination without transposition.

The recombination activating genes 1 and 2 (RAG1/2) recombinase, which initiates V(D)J recombination in jawed vertebrates, evolved from RNaseH-like transposases such as Transib and ProtoRAG. However, its postcleavage transposase activity is strictly suppressed. Previous structural studies have focused only on the conserved core domains of RAG1/2, leaving the regulatory mechanisms of the noncore regions unclear.

Olfactory mucosal mesenchymal stem cells delivered by gelatin sponge scaffolds promote functional recovery of spinal cord injury.

Spinal cord injury (SCI) is a pathological condition that damages the central nervous system. Due to the persistence of neuroinflammation after injury, the prognosis is often poor. Recent studies have found that local transplantation of mesenchymal stem cells (MSCs) can improve SCI.

In situ cryo-electron tomography reveals the progressive biogenesis of basal bodies and cilia in mouse ependymal cells.

Cilia, essential organelles for cell motility and signaling, comprise an axoneme extended from the basal body (BB). The assembly process of BBs and axonemes during ciliogenesis, however, remains largely unknown due to the lack of structural information. Here, we leverage in-situ cryo-electron tomography to capture within mouse ependymal cells the dynamic processes of BB biogenesis and multiciliogenesis at various stages.

Innovative MRSA-infected wound repair strategy: NIR-triggered controllable NO releasing from plant extracts quercetin composite chitosan/hyaluronic acid hydrogel.

Bacterial infection reduces quality of wound healing and even cause severe complications, but most current dressings adopt single antibacterial mode showed limited effectiveness. Herein, a plant extract quercetin (Que) composite chitosan/hyaluronic acid hydrogel (named CBCQ) with near-infrared (NIR) triggered controllable NO releasing was developed for efficient photothermal therapy/nitric oxide (PTT/NO) synergistic antibacterial and wound healing. Specifically, CBCQ hydrogel with chemical/physical crosslinked network was fabricated via host-guest interaction, metal coordination and Schiff base reaction.

The safety of combining Endostar with concurrent chemoradiotherapy for the treatment of locally advanced cervical cancer and the evaluation of its anti-angiogenic effects via transrectal contrast-enhanced ultrasound.

Background: In recent years, exploring the addition of angiogenesis inhibitors to chemoradiotherapy for locally advanced cervical cancer (LACC) has gained research interest. This study assessed the safety and anti-angiogenic effects of combining Endostar with concurrent chemoradiotherapy (CCRT) via transrectal contrast-enhanced ultrasound.

Methods: A total of 120 patients with locally advanced cervical cancer (LACC) were randomly allocated to two groups: CCRT combined with Endostar (CRT+E group, n = 60) and CCRT alone (CRT group, n = 60).

A clinically applicable AI system for detection and diagnosis of bone metastases using CT scans.

Manual interpretation of CT images for bone metastasis (BM) detection in primary cancer remains challenging. We present an automated Bone Lesion Detection System (BLDS) developed using CT scans from 2518 patients (9177 BMs; 12,824 non-BM lesions) across five hospitals. The system, developed on 1271 patients and tested on 1247 multicenter cases, demonstrates 89.

Rapamycin exerts neuroprotective effects by inhibiting FKBP12 instead of mTORC1 in the mouse model of Parkinson's disease.

Parkinson's disease (PD), characterized by the selective loss of nigral dopaminergic neurons, is a common neurodegenerative disorder for which effective disease-modifying therapies remain unavailable. Rapamycin, a clinical immunosuppressant used for decades, has demonstrated neuroprotective effects in various animal models of neurological diseases, including PD. These effects are believed to be mediated through the inhibition of mammalian target of rapamycin (mTOR) complex 1 (mTORC1) signaling, with rapamycin binding to FKBP12.

Impact of Relaxation and Music Intervention on Psychological and Gastrointestinal Health in Military Recruits: A Prospective Study.

Background And Aims: Gastrointestinal symptoms are closely associated with psychological problems, such as anxiety and depression. This prospective before-after study aimed to explore whether progressive muscular relaxation training combined with music intervention, which is potentially beneficial for psychological conditions, can improve gastrointestinal symptoms.

Methods: A total of 623 recruits' effective questionnaires before and after intervention were collected.

Acoustically activated nanoplatforms achieve tumor regression by exacerbating tumor hypoxia.

Background: Rapid tumor proliferation can be mitigated by "starving the cancer cells" through nutrient and oxygen blood supply blockade to the tumor, which is a significant challenge in oncological treatment.

Methods: We developed a multipathway nano platform designed to improve hypoxia-exacerbated cancer starvation therapy. This was achieved by co-loading the acoustic sensitizer-IR780-and the vascular disruptor-vadimezan (DMXAA)-into dendritic silica nanocarriers to establish acid-responsive nanoplatforms, termed DMXAA/IR780@SiO2 (DIS NPs), using a simple one-pot synthesis method.

Research Progress on the Role and Mechanism in the Change of Cardiac Structure and Function of Cardiac Fibrosis in the Elderly.

Heart failure is closely related to aging. Elderly patients with heart failure are often able to retain normal systolic function, manifested by left ventricular hypertrophy with decreased diastolic function. Relevant studies have shown that age-related cardiac fibrosis plays an important role in the pathogenesis of cardiac diastolic heart failure.

Optimal injection sites for therapeutic angiogenesis: HGF-mediated regulation of HIF-1α via MAPK/PI3K pathways in hypoxic endothelial cells.

Therapeutic angiogenesis offers a promising strategy for patients with critical limb-threatening ischemia (CLTI) who are unsuitable candidates for revascularization. However, the optimal administration sites for gene therapy agents, such as pCK-HGF-X7, remains undefined. Clinical trials commonly employ multiple intramuscular injections at sites of arterial occlusion; yet the necessity and efficacy of such extensive and repetitive protocols remains unclear.

Dual-modality immune nano-activator harnessing Mn⁺ and quercetin to potentiate the cGAS-STING pathway for advanced cancer metalloimmunotherapy.

Manganese ions (Mn) have emerged as promising activators of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. However, their clinical application was hindered by low bioavailability and limited immune activation pathways, which impaired their ability to trigger robust immune responses and achieve significant antitumor effects. To address these challenges, we developed a dual-modality immune nano-activator by coordinating manganese ions with quercetin.

Head-to-head immunogenicity comparison of one-dose Cecolin and Gardasil in Chinese girls aged 9-14 years: A randomized and open-label clinical trial.

Background: The World Health Organization (WHO) urges global administration of at least one dose of the HPV vaccine, particularly for girls aged 9-14, to work towards the elimination of cervical cancer. However, data on the efficacy of a single dose of Cecolin®, a bivalent HPV vaccine, remain quite limited. Therefore, it is crucial to design studies investigating the protective effects of a single dose of Cecolin® in Chinese girls.

Mitochondrial phosphate carrier plays an important role in virulence of .

is a common fungal pathogen that can cause life-threatening infections. is considered to be a mitochondrial phosphate carrier of , while its role in virulence has not been fully elucidated. In this study, we found that mutant exhibited severe virulence defect in both nematode and murine models.

Divergent responses of abundant and rare bacterial communities to environmental variables in highly urbanized coastal regions: N-NO mediates the community assembly and co-occurrence networks.

Understanding how rare and abundant bacterial taxa respond to environmental shifts is essential for predicting microbial community dynamics in highly urbanized estuarine ecosystems, where anthropogenic disturbances and nutrient fluctuations significantly reshape ecological processes. Here, we investigated the responses of rare and abundant bacterial communities to the environments in densely urbanized coastal areas (i.e.

Indole-3-Propionic Acid Attenuates Neuroinflammation and Cognitive Deficits by Inhibiting the RAGE-JAK2-STAT3 Signaling Pathway.

Cognitive disorders such as Alzheimer's disease (AD) are highly prevalent and place heavy burdens on society. Neuroinflammation is a driver of cognitive impairment, with no effective drugs. Indole 3-propionic acid (IPA) is a tryptophan metabolite mainly produced by, which exhibits multiple functions, including antioxidant, anti-inflammatory, antiaging, and neuroprotective properties.

How RAG1/2 evolved from ancestral transposases to initiate V(D)J recombination without transposition.

The RAG1/2 recombinase, which initiates V(D)J recombination in jawed vertebrates, evolved from RNaseH-like transposases such as Transib and ProtoRAG . However, its post-cleavage transposase activity is strictly suppressed. Previous structural studies have focused only on the conserved core domains of RAG1/2, leaving the regulatory mechanisms of the non-core regions unclear.

Microfluidic synthesis of gold nanoparticle-doped microspherical photonic crystal as SERS substrate for methylene blue detection.

A novel microfluidic approach is presented for the one-step synthesis of gold nanoparticle-doped microspherical photonic crystal (AuNP-MPC) for ultrasensitive surface-enhanced Raman spectroscopy (SERS) detection of methylene blue (MB), a common environmental pollutant. The AuNP-MPC microspheres exhibited excellent SERS activity due to the surface plasmon resonance of Au nanoparticles. And the SERS signal was significantly enhanced by strategically manipulating the photonic band gap (PBG) of the AuNP-MPC microspheres to achieve optimal overlap with the excitation laser wavelength.

Advances in Immunotherapy and Targeted Therapy of Malignant Melanoma.

Malignant melanoma (MM) is a malignant tumor, resulting from mutations in melanocytes of the skin and mucous membranes. Its mortality rate accounts for 90% of all dermatologic tumor mortality. Traditional treatments such as surgery, chemotherapy, and radiotherapy are unable to achieve the expected results due to MM's low sensitivity, high drug resistance, and toxic side effects.

The molecular mechanism of gemcitabine in inhibiting the HIF-1α/VEGFB/FGF2/FGFR1 signaling pathway for ovarian cancer treatment.

Ovarian cancer is a common malignant tumor in women, exhibiting a certain sensitivity to chemotherapy drugs like gemcitabine (GEM). This study, through the analysis of ovarian cancer single-cell RNA sequencing (scRNA-seq) data and transcriptome data post-GEM treatment, identifies the pivotal role of hypoxia-inducible factor 1 alpha (HIF-1α) in regulating the treatment process. The results reveal that HIF-1α modulates the expression of VEGF-B, thereby inhibiting the fibroblast growth factor 2 (FGF2)/FGFR1 signaling pathway and impacting tumor formation.

Risk Factor Analysis and Prediction of Para-Aortic Lymph Node Metastases in Locally Advanced Cervical Cancer.

Background And Purpose: The indications of prophylactic extended-field radiotherapy (EFRT) remain uncertain. This study aims to identify the risk factors for para-aortic lymph node (PALN) metastases in locally advanced cervical cancer (LACC) and determine which part of patients may benefit from prophylactic EFRT.

Materials And Methods: Between January 2015 and July 2023, a single-center retrospective analysis was performed on patients with stages IB3 and IIA2-IVA cervical cancer.

Orchestrated copper-loaded nanoreactor for simultaneous induction of cuproptosis and immunotherapeutic intervention in colorectal cancer.

Ion interference, including intracellular copper (Cu) overload, disrupts cellular homeostasis, triggers mitochondrial dysfunction, and activates cell-specific death channels, highlighting its significant potential in cancer therapy. Nevertheless, the insufficient intracellular Cu ions transported by existing Cu ionophores, which are small molecules with short blood half-lives, inevitably hamper the effectiveness of cuproptosis. Herein, the ESCu@HM nanoreactor, self-assembled from the integration of H-MnO nanoparticles with the Cu ionophore elesclomol (ES) and Cu, was fabricated to facilitate cuproptosis and further induce relevant immune responses.