CAD manipulates tumor intrinsic DHO/UBE4B/NF-κB pathway and fuels macrophage cross-talk, promoting hepatocellular carcinoma metastasis.

Background And Aims: Portal vein tumor thrombosis (PVTT), an indicator of clinical metastasis, significantly shortens hepatocellular carcinoma (HCC) patients' lifespan, and no effective treatment has been established. We aimed to illustrate mechanisms underlying PVTT formation and tumor metastasis, and identified potential targets for clinical intervention.

Approach And Results: Multi-omics data of 159 HCC patients (including 37 cases with PVTT) was analyzed to identify contributors to PVTT formation and tumor metastasis.

Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2.

As one of the earliest identified susceptible animals for the SARS-CoV-2, cats are also the vulnerable hosts for feline coronaviruses, ie feline enteric coronavirus (FECV). Here, to understand the cross-presentation of coronavirus-derived peptides by cat major histocompatibility complex molecule feline leucocyte antigen (FLA) class I, unpredictable natural peptide motifs presented by FLA-K*00701 and FLA-E*00301 were identified through peptide elution and further confirmed by the structural determination of the 2 FLA class I molecules. Based on these precise motifs of FLA class I peptides, the atlas of cross-presenting peptides from different coronaviruses in cats were sketched with 3 hotspots in C-terminal half of ORF1ab protein.

Rapid clonal expansion and somatic hypermutation contribute to the fate of SARS-CoV-2 broadly neutralizing antibodies.

Several vaccines and immunization strategies, including inactivated vaccines, have proven effective in eliciting antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing an opportunity to characterize the antibody response. In this study, we investigated the monoclonal antibody responses elicited by wild-type SARS-CoV-2 inactivated vaccination compared to those elicited by natural infection and mRNA vaccination. The analysis showed that antibodies encoded by biased germline genes were shared between SARS-CoV-2 vaccinated and naturally infected individuals.

Genetically supported targets and drug repurposing for brain aging: A systematic study in the UK Biobank.

Brain age gap (BAG), the deviation between estimated brain age and chronological age, is a promising marker of brain health. However, the genetic architecture and reliable targets for brain aging remains poorly understood. In this study, we estimate magnetic resonance imaging (MRI)-based brain age using deep learning models trained on the UK Biobank and validated with three external datasets.

Active microgel particle swarms for intrabronchial targeted delivery.

Intrabronchial delivery of therapeutic agents is critical to the treatment of respiratory diseases. Targeted delivery is demanded because of the off-target accumulation of drugs in normal lung tissues caused by inhalation and the limited motion dexterity of clinical bronchoscopes in tortuous bronchial trees. Herein, we developed microrobotic swarms consisting of magnetic hydrogel microparticles to achieve intrabronchial targeted delivery.

6-methyladnosine of vRNA facilitates influenza A virus replication by promoting the interaction of vRNA with polymerase proteins.

6-methyladnosine (mA) modification is present in both positive- and negative-strand RNA of influenza A virus (IAV) and affects the replication and pathogenicity of IAV. However, little is known about the regulatory mechanism of mA in IAV RNA. In the present study, we identified the mA methylation of the viral RNA of different IAV subtypes and confirmed that mA modification promotes the polymerase activity and replication of IAV.

Single-Bacterium Diagnosis via Terahertz Near-Field Dielectric Nanoimaging.

Single-bacterium diagnostic methods with unprecedented precision and rapid turnaround times are promising tools for facilitating the transition from empirical treatment to personalized anti-infection treatment. Terahertz (THz) radiation, a cutting-edge technology for identifying pathogens, enables the label-free and non-destructive detection of intermolecular vibrational modes and bacterial dielectric properties. However, this individual dielectric property-based detection and the mismatched spatial resolution are limited for the single-bacterium identification of various species of pathogens.

Conditioned medium of engineering macrophages combined with soluble microneedles promote diabetic wound healing.

Diabetic wounds have a profound effect on both the physical and psychological health of patients, highlighting the urgent necessity for novel treatment strategies and materials. Macrophages are vital contributors to tissue repair mechanisms. Macrophage conditioned medium contains various proteins and cytokines related to wound healing, indicating its potential to improve recovery from diabetic wound.

Direct Cytosolic Delivery of siRNA Conjugates: A Paradigm in Antiangiogenic Therapy for Choroidal Neovascularization.

Small interfering RNA (siRNA) has garnered tremendous interest as a potential therapeutic tool because of its intriguing gene-silencing ability. Toward the success in the manufacture of siRNA therapeutics for the potential treatment of choroidal neovascularization (CNV), siRNA conjugated with dual functional units of membrane-penetrating heptafluoropropyl and age-related macular degeneration-targeting cyclic Arg-Gly-Asp (RGD) peptide was attempted for transcellular transportation into the cell interiors. Of note, cyclic RGD allowed selective affinities toward the angiogenic endothelial cells in the pathological CNV.

Glass-confined carbon dots: transparent afterglow materials with switchable TADF and RTP.

The confined synthesis of carbon dots (CDs) in solid matrixes is a promising avenue for developing new afterglow materials. Benefiting from the advantages of the sol-gel preparation of nanoporous glass, we report transparent glass-confined CDs with tunable afterglow luminescence. Switchable thermally-activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP) of CDs were achieved by adjusting the sintering temperature and ion doping.

Early Recurrence of Colorectal Liver Metastasis (Number ≤ 5 and Largest Diameter ≤ 3 cm) after Resection or Thermal Ablation: a Multi-center Study of Patterns, Safety, Survival and Risk Factors.

Objective: To compare early recurrence patterns, safety, survival and investigate the clinical risk factors of early recurrence (ER) after liver resection or thermal ablation (TA) for patients with colorectal liver metastases (CRLM) with number ≤ 5 and largest diameter ≤ 3 cm.

Materials And Methods: This retrospective study included patients with CRLM who underwent liver resection or TA between January 2016 and December 2021 at two hospitals in China. The Kaplan-Meier method and log-rank test were used to assess recurrence-free survival (RFS) and overall survival (OS).

Analysis of expression characteristics of ferroptosis-related lncRNAs in gastrointestinal cancer patients in Asia.

Background: Asian cancer patients have become the highest morbidity and mortality group, and gastrointestinal tumors account for the majority of them, so it is urgent to find effective targets. Therefore, ferroptosis-related lncRNAs models were established to predict the prognosis and clinical immune characteristics of GI cancer.

Methods: RNA sequencing and clinical data were collected from the TCGA database (LIHC, STAD, ESCA, PAAD, COAD, CHOL, and READ) of patients with gastrointestinal cancer in Asia.

Single-cell RNA sequencing generates an atlas of normal tibia cartilage under mechanical loading conditions.

Chondrocytes in articular cartilage can secrete extracellular matrix to maintain cartilage homeostasis. It is well known that articular cartilage chondrocytes are sensitive to mechanical loading and that mechanical stimuli can be translated to biological processes. This study provides deep insight into the impact of mechanical loading on chondrocytes via single-cell RNA sequencing (scRNA-seq).

Disulfidptosis: a novel gene-based signature predicts prognosis and immunotherapy efficacy of pancreatic adenocarcinoma.

Disulfidptosis, a novel form of disulfide stress-induced cell death involved in tumor progression, hasn't be well defined the function in tumor progression. And the clinical impacts of disulfidptosis-related genes (DRGs) in pancreatic adenocarcinoma (PAAD) remain largely unclear. In this study, we identified two distinct disulfidptosis subtypes and found that multilayer DRG alterations were associated with prognosis and TME infiltration characteristics.

Nomogram predicts risk score and likehood of orchiectomy in patients with testicular torsion: a multicenter retrospective study.

Purpose: Testicular torsion is a prevalent scrotal emergency associated with a significant risk of testicular loss, and there is no reliable scoring system available to assess the likelihood of orchiectomy following testicular torsion.

Methods: Clinical characteristics and surgical data of patients with testicular torsion from January 2015 to May 2024 were gathered from National Center for Children's Health (NCCH) and the Children's Hospital of Capital Institute of Pediatrics (CIPCH). Independent risk variables for testicular resection were evaluated by logistic regression analyses, leading to the establishment of a nomogram.

Should lymphadenectomy be recommended in radical surgery of intrahepatic cholangiocarcinoma patients? A retrospective study.

Purpose: Intrahepatic cholangiocarcinoma (ICC) is an extremely deadly cancer with high recurrence incidence, particularly in patients with lymph node metastasis (LNM). The necessity of lymphadenectomy including lymph node biology (LNB) and dissection (LND) during ICC radical surgery remains debate.

Methods: We retrospectively analyzed the patients diagnosed with ICC and underwent radical surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences from 2012 to 2023.

Tangeretin regulates oxidative stress in cutaneous melanoma cells via the Nrf2 signaling pathway.

Oxidative stress is a key factor in melanoma progression, making it an important therapeutic target. This study explored the effects of tangeretin, a citrus-derived flavonoid, on human melanoma A375 cells and its underlying mechanisms. A375 cells were treated with tangeretin at various concentrations.

Genome-wide identification of the SmPHR gene family in Salvia miltiorrhiza and SmPHR7-mediated response to phosphate starvation in Arabidopsis thaliana.

This study reveals the transcripts of S. miltiorrhiza in response to phosphate deficiency, identifies 18 SmPHRs in the genome, and tentatively establishes a role for SmPHR7 in regulating phosphate starvation. Phosphorus is essential for plant growth and development, and phosphate deficiency is a common nutritional stress.

Gut Microbiota Modulation of Dementia Related Complications.

Recent advances in microbial pathogen research have highlighted the potential of gut microbe-based microbial medicine. One of the most extensively studied biological pathways is the gut-brain axis, which has been shown to reverse neurological disorders. Evidence from animal-based studies of dysbiosis suggest complex behavioral changes, such as alterations in sociability and anxiety, can be modulated through gut microbiota.

Distance-Readout Paper-Based Microfluidic Chip with a DNA Hydrogel Valve for AFB1 Detection.

Accurate and rapid aflatoxin B1 (AFB1) detection is essential for ensuring the safety of food supplies. In this paper, we introduce a distance-readout paper-based microfluidic chip (DPMC) that offers a sensitive and reliable method for the detection of AFB1. The DPMC comprises a DNA hydrogel sensitive valve and a paper-based capillary channel.

Structure-based development of a covalent inhibitor targeting Streptococcus pyogenes over Staphylococcus aureus sortase A.

Sortase A (SrtA), a cysteine transpeptidase critical for surface protein anchoring in Gram-positive pathogens, represents an attractive antivirulence target. While covalent SrtA inhibitors show therapeutic potential, existing compounds lack species selectivity. Through structure-guided design, we developed T10, a covalent inhibitor selectively targeting Streptococcus pyogenes SrtA (SpSrtA) over Staphylococcus aureus SrtA (SaSrtA).

The LSmAD Domain of Ataxin-2 Modulates the Structure and RNA Binding of Its Preceding LSm Domain.

Ataxin-2 (Atx2), an RNA-binding protein, plays a pivotal role in the regulation of RNA, intracellular metabolism, and translation within the cellular environment. Although both the Sm-like (LSm) and LSm-associated (LSmAD) domains are considered to associated with RNA binding, there is still a lack of experimental evidence supporting their functions. To address this, we designed and constructed several recombinants containing the RNA-binding domain (RBD) of Atx2.

Finerenone Alleviates Over-Activation of Complement C5a-C5aR1 Axis of Macrophages by Regulating G Protein Subunit Alpha i2 to Improve Diabetic Nephropathy.

Diabetic nephropathy (DN), one of the most common complications of diabetes mellitus (DM), accounts for a major cause of chronic kidney disease (CKD) worldwide, with a complicated pathogenesis and limited effective strategies nowadays. The mineralocorticoid receptor (MR) is a classical ligand-activated nuclear transcription factor. It is expressed in the renal intrinsic and immune cells, especially macrophages.

Continuous R-DA-EDOCH alternated with high-dose Ara-C induces deep remission and overcomes high-risk factors in young patients with newly diagnosed mantle cell lymphoma.

Objective: Our previous studies have indicated potentially higher proliferative activity of tumor cells in Chinese patients with mantle-cell lymphoma (MCL) than those in Western. Given the success and tolerability of R-DA-EDOCH immunochemotherapy in treating aggressive B-cell lymphomas, we designed a prospective, phase 3 trial to explore the efficacy and safety of alternating R-DA-EDOCH/R-DHAP induction therapy for young patients with newly diagnosed MCL. The primary endpoint was the complete remission rate (CRR) at the end of induction (EOI).

Advances in gut microbiota-related treatment strategies for managing colorectal cancer in humans.

Colorectal cancer (CRC) is a major contributor to global cancer-related mortality with increasing incidence rates in both developed and developing regions. Therefore, CRC presents a significant challenge to global health. The development of innovative tools for enhancing early CRC screening and diagnosis, along with novel treatments and therapies for improved management, remains an urgent necessity.