Improving polyketide biosynthesis by rescuing the translation of truncated mRNAs into functional polyketide synthase subunits.

Modular polyketide synthases (mPKSs) are multidomain enzymes in bacteria that synthesize a variety of pharmaceutically important compounds. mPKS genes are usually longer than 10 kb and organized in operons. To understand the transcriptional and translational characteristics of these large genes, here we split the 13-kb busA gene, encoding a 456-kDa three-module PKS for butenyl-spinosyn biosynthesis, into three smaller separately translated genes encoding one PKS module in an operon.

Time in Target Range for Blood Pressure and Adverse Health Outcomes: A Systematic Review.

Background: Blood pressure (BP) time in target range (TTR) reflects the proportion of time that BP measurement is within a specified target range. We aim to summarize the evidence for relationships between TTR and adverse health outcomes.

Methods: Seven databases were searched.

Evaluating Neoadjuvant Immunochemotherapeutic Response for Bladder Carcinoma Using Amide Proton Transfer-Weighted MRI.

Rationale And Objectives: To investigate the feasibility of amide proton transfer-weighted (APTw) and diffusion-weighted MRI in evaluating the response of bladder cancer (BCa) to neoadjuvant immunochemotherapy.

Materials And Methods: From June 2021 to July 2023, participants with pathologically confirmed BCa were prospectively recruited to undergo MRI examinations, including APTw and diffusion-weighted MRI before and after neoadjuvant immunochemotherapy. Histogram analysis features (mean, median, and entropy) were extracted from pre- and post-treatment APTw and apparent diffusion coefficient (ADC) maps, respectively.

Arthroscopic Repair of Subscapularis Tendon Using a Percutaneous Continuous Sewing Machine-Like Suture Technique Through a Single Working Portal.

Tearing of the subscapularis tendon is a common shoulder injury that typically requires arthroscopic repair. The suture-passing device is a standard tool for repairing the subscapularis tendon. However, it poses the risk of device breakage and may cause additional damage to the tendon.

Enhancing Neuron Activity Promotes Functional Recovery by Inhibiting Microglia-Mediated Synapse Elimination After Stroke.

Background: Activating glutamatergic neurons in the ipsilesional motor cortex can promote functional recovery after stroke. However, the underlying molecular mechanisms remain unclear. Clarifying key molecular mechanisms involved in recovery could help understand the development of neuromodulation strategies after stroke.

Rapidly Manufactured CAR-T with Conserved Cell Stemness and Distinctive Cytokine-Secreting Profile Shows Improved Anti-Tumor Efficacy.

The emergence of chimeric antigen receptor T-cell (CAR-T) immunotherapy holds great promise in treating hematologic malignancies. While advancements in CAR design have enhanced therapeutic efficacy, the time-consuming manufacturing process has not been improved in the commercial production of CAR-T cells. In this study, we developed a "DASH CAR-T" process to manufacture CAR-T cells in 72 h and found the excelling anti-tumor efficacy of DASH CAR-T cells over conventionally manufactured CAR-T cells.

How to monitor and discriminate the causes of lower limb swelling during home-based rehabilitation after total knee arthroplasty? A delphi study.

Purpose: Swelling in the lower limbs after total knee arthroplasty (TKA) affects surgical outcomes. Prolonged swelling requires monitoring and remote management during home-based rehabilitation. Causes of swelling vary but, so far, no indicators are available to monitor and identify causes of lower limb swelling, making it difficult to implement targeted interventions.

BRISC-Mediated PPM1B-K63 Deubiquitination and Subsequent TGF-β Pathway Activation Promote High-Fat/High-Sucrose Diet-Induced Arterial Stiffness.

Background: Metabolic syndrome heightens cardiovascular disease risk primarily through increased arterial stiffness. We previously demonstrated the involvement of YAP (Yes-associated protein) in high-fat/high-sucrose diet (HFHSD)-induced arterial stiffness via modulation of PPM1B (protein phosphatase Mg/Mn-dependent 1B)-lysine63 (K63) deubiquitination. In this study, we aimed to elucidate the role and mechanisms underlying PPM1B deubiquitination in HFHSD-induced arterial stiffness.

Effectiveness, pharmacokinetics, and safety of triptorelin acetate microspheres in patients with locally advanced and metastatic prostate cancer.

Background: A newly generic microspheres, sustained-release formulation of triptorelin acetate 3.75 mg has been developed.

Objectives: To evaluate the efficacy, pharmacokinetics, and safety of triptorelin 1-month formulation in Chinese patients with prostate cancer.

ROS scavenging and corneal epithelial wound healing by a self-crosslinked tissue-adhesive hydrogel based-on dual-functionalized hyaluronic acid.

Reactive oxygen species (ROS) scavenging is a viable approach to promote corneal epithelium wound healing. This study created a single-component hydrogel (HA Gel) with a novel dual-functionalized hyaluronic acid derivative (HA-GA-PBA) containing gallol and phenylboronic acid (PBA) moieties. Both of these moieties were dual-functional.

A Systematic Method to Detect Next-Generation Sequencing-Based Microsatellite Instability in Plasma Cell-Free DNA: plasmaMSI.

Microsatellite instability (MSI) detection using tumor tissue is a well-established prognostic and predictive biomarker for certain types of cancers. However, tumor tissue samples are less convenient to obtain than blood plasma samples. The main challenge facing next-generation sequencing-based MSI detection in blood plasma samples is the ultralow signal/noise ratio in plasma cell-free DNA (cfDNA).

Papillary Renal Neoplasm With Reverse Polarity: CT and MR Imaging Characteristics in 26 Patients.

Rationale And Objectives: To improve the diagnostic recognition of papillary renal neoplasm with reverse polarity (PRNRP) through comprehensive analysis of computed tomography (CT) and magnetic resonance imaging (MRI) findings.

Materials And Methods: A retrospective multi-center study was conducted on patients with pathologically confirmed PRNRPs from 2019 to 2024, encompassing six institutions. Clinical and pathological data were meticulously documented.

Tendon Groove Technique: A Double-Bundle Footprint Technique for Anterior Cruciate Ligament Reconstruction.

Double-bundle (DB) anterior cruciate ligament (ACL) reconstruction has biomechanical advantages over single-bundle reconstruction. However, most studies perform the DB reconstruction with 2 femoral tunnels, which fails to provide an entire femoral footprint for ACL reconstruction. In this study, we describe a femoral double-bundle footprint technique for ACL reconstruction, named the tendon groove technique.

Minipatellar Tunnels for Transosseous Fixation of Medial Patellofemoral Ligament Graft Using High-strength Suture.

Patellar dislocation is a common knee injury, with concomitant pathoanatomical risk factors that synergistically interact and predispose to patellofemoral instability. Medial patellofemoral ligament (MPFL) reconstruction has demonstrated significant potential in the re-establishment of MPFL anatomic and biological function, with low patellar redislocation rates. Although many techniques for MPFL reconstruction have been developed, challenges such as patella fractures and high costs persist.

Engineering bacteria for cancer immunotherapy by inhibiting IDO activity and reprogramming CD8+ T cell response.

Inhibiting indoleamine 2,3 dioxygenase (IDO) for anticancer therapy has garnered significant attention in recent years. However, current IDO inhibitors face significant challenges which limit their clinical application. Here, we genetically engineered a high tryptophan-expressing (L-Trp CB) strain that can colonize tumors strictly following systemic administration.

Genome-wide single-cell and single-molecule footprinting of transcription factors with deaminase.

Decades of research have established that mammalian transcription factors (TFs) bind to each gene's regulatory regions and cooperatively control tissue specificity, timing, and intensity of gene transcription. Mapping the combination of TF binding sites genome wide is critically important for understanding functional genomics. Here, we report a technique to measure TFs' binding sites on the human genome with a near single-base resolution by footprinting with deaminase (FOODIE) on a single-molecule and single-cell basis.

METTL4-Mediated Mitochondrial DNA N6-Methyldeoxyadenosine Promoting Macrophage Inflammation and Atherosclerosis.

Background: Mitochondrial dysfunction is a key factor in the development of atherogenesis. METTL4 (methyltransferase-like protein 4) mediates N6- methyldeoxyadenosine (6mA) of mammalian mitochondrial DNA (mtDNA). However, the role of METTL4-mediated mitoepigenetic regulation in atherosclerosis is still unknown.

Retraction Note: MiR-5692a promotes the invasion and metastasis of hepatocellular carcinoma via MMP9.

The article "MiR-5692a promotes the invasion and metastasis of hepatocellular carcinoma via MMP9" by S.-J. Sun, N.

Considerations for building and using integrated single-cell atlases.

The rapid adoption of single-cell technologies has created an opportunity to build single-cell 'atlases' integrating diverse datasets across many laboratories. Such atlases can serve as a reference for analyzing and interpreting current and future data. However, it has become apparent that atlasing approaches differ, and the impact of these differences are often unclear.

DCBLD1 Modulates Angiogenesis by Regulation of the VEGFR-2 Endocytosis in Endothelial Cells.

Background: Unwanted angiogenesis is involved in the progression of various malignant tumors and cardiovascular diseases, and the factors that regulate angiogenesis are potential therapeutic targets. We tested the hypothesis that DCBLD1 (discoidin, CUB, and LCCL domain-containing protein 1) is a coreceptor of VEGFR-2 (vascular endothelial growth factor receptor-2) and modulates angiogenesis in endothelial cells.

Methods: A carotid artery ligation model and retinal angiogenesis assay were used to study angiogenesis using globe knockout or endothelial cell-specific conditional knockout mice in vivo.

Efficient non-viral immune cell engineering using circular single-stranded DNA-mediated genomic integration.

The use of adeno-associated viruses (AAVs) as donors for homology-directed repair (HDR)-mediated genome engineering is limited by safety issues, manufacturing constraints and restricted packaging limits. Non-viral targeted genetic knock-ins rely primarily on double-stranded DNA (dsDNA) and linear single-stranded DNA (lssDNA) donors. dsDNA is known to have low efficiency and high cytotoxicity, while lssDNA is challenging for scaled manufacture.

Association Between Time to Treatment and Outcomes of Endovascular Therapy vs Medical Management in Patients With Large Ischemic Stroke.

Background And Objectives: Randomized trials have proven the benefit of endovascular therapy (EVT) for acute large ischemic stroke. This study was to characterize the effect of time to treatment on benefit of EVT vs medical management (MM) among patients with large ischemic stroke.

Methods: This was a post hoc analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core randomized trial.

Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children.

Background: B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.