An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression.

Somatic cells can be reprogrammed into pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. Specifically, overexpression of OCT4 alone has been demonstrated to reprogram mouse fibroblasts into iPSCs. However, it remains unclear whether any other single factor can induce iPSCs formation.

Haplotype-Resolved Genotyping and Association Analysis of 1,020 β-Thalassemia Patients by Targeted Long-Read Sequencing.

Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.

Enhancing human ACE2 expression in mouse models to improve COVID-19 research.

Mice are one of the most common biological models for laboratory use. However, wild-type mice are not susceptible to COVID-19 infection due to the low affinity of mouse ACE2, the entry protein for SARS-CoV-2. Although mice with human ACE2 (hACE2) driven by Ace2 promoter reflect its tissue specificity, these animals exhibit low ACE2 expression, potentially limiting their fidelity in mimicking COVID-19 manifestations and their utility in viral studies.

Deep Learning-Based Ion Channel Kinetics Analysis for Automated Patch Clamp Recording.

The patch clamp technique is a fundamental tool for investigating ion channel dynamics and electrophysiological properties. This study proposes the first artificial intelligence framework for characterizing multiple ion channel kinetics of whole-cell recordings. The framework integrates machine learning for anomaly detection and deep learning for multi-class classification.

HIV risk and influence factors among MSM who had sought sexual partners in core venues: a continuous sentinel surveillance in 2010-2022.

Background: Seeking sexual partners in men who have sex with men (MSM) venues has been regarded as a high-risk behavior for HIV among MSM. Nevertheless, with the implementation of venue-based interventions and the change in the way MSM seek sexual partners, the continued status of MSM venues as the HIV risk factor remains inconclusive. This study endeavors to delve into this ambiguity by examining the MSM sexual contact network (SCN) as a foundation.

Lipidomic analysis of plant-derived extracellular vesicles for guidance of potential anti-cancer therapy.

Plant-derived extracellular vesicles (PEVs) have been regarded as a superior source for nanomedicine and drug delivery systems. Nevertheless, their clinical translation is hindered by the lack of clarity and even contradiction in their biomedical applications. Herein, we conducted a comprehensive compositional analysis of four commonly used PEVs to fully understand their functional lipid contents and assess their potential therapeutic applications.

Targeting the Ajuba/Notch axis increases the sensitivity of colon cancer cells to 5-fluorouracil.

Objective: Colorectal cancer is severely challenging because of the insufficient understanding of the mechanism underlying its resistance to clinical chemotherapy. The purpose of our study is to investigate the role of the LIM protein Ajuba (JUB) in the chemoresistance of colon cancer and its potential effect on clinical treatment.

Material And Methods: The protein levels of JUB in colon cancer tissues were evaluated using Western blot analysis and immunohistochemistry assays.

Nuclear receptor subfamily 4 group a member 1 eases angiotensin II-arose oxidative stress in vascular smooth muscle cell by boosting nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 3 transcription.

Objective: Hypertension significantly contributes to morbidity and mortality. Nuclear receptor subfamily 4 group a member 1 (Nur77) participates in regulating oxidative stress, but the mechanism in hypertension remains unclear. This study aimed to explore the function of Nur77 in oxidative stress induced by Angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs) in hypertension.

Intrinsic anti-inflammatory nanomedicines for enhanced pain management.

Introduction: Effective postoperative pain management remains a significant challenge due to the severe side effects of opioids and the limitations of existing analgesic delivery systems. Inflammation plays a critical role in pain exacerbation, highlighting the need for therapies that combine analgesic effects with intrinsic anti-inflammatory properties.

Methods: Herein, we develop an intrinsic anti-inflammatory nanomedicine designed to enhance pain management by integrating controlled anesthetic release with inherent anti-inflammatory activity.

Intensified conditioning containing decitabine versus standard myeloablative conditioning for adult patients with KMT2A-rearranged leukemia: a multicenter retrospective study.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended for patients with KMT2A-rearranged (KMT2A-r) leukemia whereas relapse remains high. We aimed to determine whether intensified conditioning containing decitabine (Dec) could reduce relapse compared with standard myeloablative conditioning in adult patients with KMT2A-r leukemia.

Methods: We performed a multicenter retrospective study at seven institutions in China.

Suture techniques in the surgical management of flexor tendon, Achilles tendon and cruciate ligament injuries: a systematic review.

Objective: To provide clinicians with reliable recommendations for the selection of appropriate suturing techniques for surgical management of common musculoskeletal soft tissue injuries.

Methods: A systematic search of PubMed, Springer, Web Science, Vip Database, China National Knowledge, and Wanfang Data for in vitro biomechanical studies on suture techniques in the surgical treatment of musculoskeletal soft tissue injuries covering relevant studies from April 2009 to April 2024 was performed. A generalized classification was made based on the characteristics of the techniques, and recommendations for the selection of suture techniques were made according to the GRADE concept.

Development of an individualized dementia risk prediction model using deep learning survival analysis incorporating genetic and environmental factors.

Background: Dementia is a major public health challenge in modern society. Early detection of high-risk dementia patients and timely intervention or treatment are of significant clinical importance. Neural network survival analysis represents the most advanced technology for survival analysis to date.

N6-methyladenosine regulates metabolic remodeling in kidney aging through transcriptional regulator GLIS1.

Background: Age-related kidney impairment, characterized by tubular epithelial cell senescence and renal fibrosis, poses a significant global public health threat. Although N6-methyladenosine (m6A) methylation is implicated in various pathological processes, its regulatory mechanism in kidney aging remains unclear.

Methods: An m6A-mRNA epitranscriptomic microarray was performed to identify genes with abnormal m6A modifications in aged human kidney tissues.

Transcriptional landscape and predictive potential of long noncoding RNAs in peritoneal recurrence of gastric cancer.

Background: Long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) progression and metastasis. However, research comprehensively exploring tissue-derived lncRNAs for predicting peritoneal recurrence in patients with GC remains limited. This study aims to investigate the transcriptional landscape of lncRNAs in GC with peritoneal metastasis (PM) and to develop an integrated lncRNA-based score to predict peritoneal recurrence in patients with GC after radical gastrectomy.

Global, regional and national burden due to retinoblastoma in children aged younger than 10 years from 1990 to 2021.

Background: Retinoblastoma (RB), an aggressive intraocular malignancy, significantly adds to the global disease burden in early childhood. This study offers insights into the global burden of retinoblastoma (RB) in children aged 0-9 years, examining incidence, mortality, and DALYs from 1990 to 2021, across age, sex, location, and SDI levels. It aims to inform health policy, resource allocation, and RB combat strategies.

Comparison of the results of medical approach and surgical approach of septic arthritis in native joints: a single-center retrospective study.

Background: The consequences of septic arthritis of natural joints may be devastating. The purpose of this study was to evaluate the functional results of medical approach and surgical approach for septic arthritis of native joints, and to explore whether the number of drainage tubes after arthroscopic surgery will affect the knee function of patients.

Methods: A single-center retrospective study was conducted on patients diagnosed with septic arthritis from January 2018 to January 2023.

Screening and identification of vascular endothelial cell targeting peptide in gastric cancer through novel integrated in vitro and in vivo strategy.

Purpose: Antiangiogenesis therapy has become a hot field in cancer research. Given that tumor blood vessels often express specific markers related to angiogenesis, the study of these heterogeneous molecules in different tumor vessels holds promise for advancing anti-angiogenic therapy. Previously using phage display technology, we identified a targeting peptide named GX1 homing to gastric cancer vessels for the first time.

Depressive symptoms among the oldest-old in China: a study on rural-urban differences.

Background: In China, In China, depression among the oldest-old (aged 80 + years) is a major public health issue. As the gap in development between urban and rural China widens, the aim of this study was to demonstrated whether there are disparities in the incidence of depressive symptoms between the urban and rural oldest-old (aged 80+) in China and to quantify the contribution of relevant influencing factors.

Methods: The study evaluated data on 5,116 oldest adults (female, 55.

A new distal radius fracture classification depending on the specific fragments through machine learning clustering method.

Purposes: The objective of this study was to investigate intra-articular distal radius fractures, aiming to provide a comprehensive analysis of fracture patterns and discuss the corresponding treatment strategies for each pattern.

Methods: 294 cases of intra-articular distal radius fractures lines were collected and clustered thorough K-means and hierarchical clustering algorithm. The demographic data of patients and the clinical treatment outcomes were recorded.

Higher interfragmentary compression force improves lateral tibial plateau fracture stability using locking plate fixation: experimental and simulation verification.

Background: This study investigated the impact of higher interfragmentary compression force (IFCF) on the stability of locking plate fixation in lateral tibial plateau fractures.

Methods: Biomechanical experiments and finite element analysis (FEA) were employed to compare the performance of the AO cancellous lag screw (AOCLS) and a newly developed combined cancellous lag screw (CCLS).

Results: The results demonstrated that the CCLS provided a higher IFCF without the risk of over-screwing, significantly improving fixation stability.

The potential mechanisms and material basis of Fuzheng Jiedu decoction broad-spectrum inhibiting coronaviruses.

Traditional Chinese medicine has unique advantages in preventing and treating COVID-19, and Fuzheng Jiedu decoction (FZJDD) was reported to be effective against COVID-19 in clinical trials. To investigate the potential mechanisms and material basis of FZJDD against SARS-CoV-2, we performed SARS-CoV-2 target protein inhibition analyses and a metabolite full spectrum analysis of FZJDD. Interestingly, FZJDD was found to block the binding of SARS-CoV-2 Spike protein with the receptor ACE2 and inhibit the activity of SARS-CoV-2 3CLpro.

Bioinformatics identification based on causal association inference using multi-omics reveals the underlying mechanism of Gui-Zhi-Shao-Yao-Zhi-Mu decoction in modulating rheumatoid arthritis.

Object: Rheumatoid arthritis (RA) is a prevalent and currently incurable autoimmune disease. Existing conventional medical treatments are limited in their efficacy, prolonged disease may lead to bone destruction, joint deformity, and loss of related functions, which places a huge burden on RA patients and their families. For millennia, the use of traditional Chinese medicine (TCM), exemplified by the Gui-Zhi-Shao-Yao-Zhi-Mu decoction (GZSYZM), has been demonstrated to offer distinct therapeutic advantages in the management of RA.

Surface-functionalized bacteria: Frontier explorations in next-generation live biotherapeutics.

Screening robust living bacteria to produce living biotherapeutic products (LBPs) represents a burgeoning research field in biomedical applications. Despite their natural abilities to colonize bio-interfaces and proliferate, harnessing bacteria for such applications is hindered by considerable challenges in unsatisfied functionalities and safety concerns. Leveraging the high degree of customization and adaptability on the surface of bacteria demonstrates significant potential to improve therapeutic outcomes and achieve tailored functionalities of LBPs.