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High-quality metagenome assembly from nanopore reads with nanoMDBG
Abstract Third-generation long-read sequencing technologies, significantly improve metagenome assemblies. Highly accurate PacBio HiFi reads can yield hundreds of near-complete metagenome-assembled genomes (MAGs) from a single sample. Recently, the accuracy of the more cost-effective Oxford Nanopore Technologies (ONT) platform has increased to a per-base error rate of 1-2%. However, current metagenome assemblers are optimized for HiFi and do not scale to the large data sets that ONT enables. We present nanoMDBG, an evolution of metaMDBG, which supports the latest ONT reads through an error correction pre-processing step in minimizer-space. Across a range of ONT datasets, including a large 400 Gbp soil sample, nanoMDBG reconstructs up to twice as many high-quality MAGs as the next best ONT assembler, metaFlye, while requiring a third of the CPU time and memory. Critically, the latest ONT technology can now produce comparable MAG construction results as those obtained using PacBio HiFi at the same sequencing depth.
Evaluation of the Shear Bond Strength at Resin Interface after Pretreatment with Three Dentine Biomodifiers on Primary Teeth: An In Vitro Study
Derivation and validation of a new prediction score for bacteremia in the emergency department
Abstract Early detection and treatment of bacteremia are crucial; however, blood culture takes days. We aimed to develop a prediction score using objective emergency department (ED)-available parameters. This single-center, retrospective cohort study included patients aged ≥ 16 years admitted to our ED with suspected bacteremia. The study was divided into derivation and validation periods. Data on vital signs, routine blood tests, and blood cultures were analyzed. Using multivariate logistic regression, a prediction score was developed and validated during the derivation and validation periods, respectively. A total of 3,725 and 3,471 patients were eligible for the derivation and validation periods, respectively. Continuous variables were converted to binary forms and used in logistic regression. The resulting prediction score was: Body temperature + Platelets × 2 + Neutrophil-lymphocyte ratio × 3 + Albumin + Bilirubin × 2 + Creatinine + Lactate × 2. The area under the curve in the receiver operating characteristic curve of the prediction score in the derivation and the validation period was 0.78 (95% confidence interval: 0.76–0.80) and 0.75 (95% confidence interval: 0.73–0.78), respectively. A prediction score based on routine blood tests and vital signs can effectively predict bacteremia in ED settings.
USP7 deubiquitinase stabilizes FAN1 to support DNA crosslink repair and suppress CAG repeat expansion
Abstract Human FAN1 is a structure-specific endonuclease implicated in the repair of DNA interstrand crosslinks (ICLs) and the excision of extrahelical CAG repeats–whose pathological expansion underlies Huntington’s disease (HD), a progressive and currently incurable neurodegenerative disorder. However, mechanisms of post-translational regulation of FAN1 are still largely unknown. Here, we identify the ubiquitin-specific protease 7 (USP7) as an interactor of FAN1. USP7 stabilizes FAN1 protein levels in a deubiquitination-dependent manner, preventing FAN1 from proteasomal degradation. Consequently, we demonstrate that USP7 depletion leads to reduced chromatin association of FAN1 and increased cellular hypersensitivity following ICL damage. Moreover, loss of USP7 accelerates CAG repeat expansion in an RPE-1 cell model stably expressing mutant huntingtin ( mHTT ) exon 1 containing 129 CAG repeats (RPE-1 HTT-CAG129 ). Collectively, our findings uncover a link between USP7 and FAN1 in mechanisms that preserve genome stability and influence repeat instability.
Guided Tissue Regeneration and Subepithelial Connective Tissue Graft in the Treatment of Gingival Recession: A Randomized Clinical Trial
Diagnostic value of phenotypic testing combined with molecular biology testing for tuberculosis
Abstract To evaluate the diagnostic value of combining phenotypic testing with molecular biology testing for tuberculosis, a retrospective study was conducted on 264 presumed pulmonary tuberculosis patients across four hospitals from July 2021 to September 2023. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value and negative predictive value were calculated for two phenotypic testing methods—liquid-based sandwich cup acid-fast staining and mycobacterial culture—and two molecular biology testing methods—Boao MTB TaqMan-qPCR and GeneXpert MTB/RIF—using sputum and bronchoalveolar lavage fluid specimens for the diagnosis of active pulmonary tuberculosis. Using the final clinical diagnosis as the reference standard, the combination of both two specimen types and all four testing methods yielded the highest AUROC of 0.917 and sensitivity of 83.3%, significantly outperforming either multiple specimens tested by a single method or multiple methods applied to a single specimen. Moreover, combining multiple tests on either sputum or BALF specimens provided superior diagnostic performance compared with individual tests alone. This study demonstrates that integrating phenotypic and molecular biology testing, across multiple specimen types can provide more accurate guidance for the early diagnosis and treatment of pulmonary tuberculosis.
A rubber-based sensor with over 100 million-level ultra-sensitivity (0–10% strain range) via 3D super-interface
Evaluation of the Overbite Depth Indicator and Anteroposterior Dysplasia Index in a Sample of the Arab Population
A nationwide cross-sectional survey of major allergic diseases in China during 2010–2015 involving 120,000 participants
Structural insights into insect-selective sodium channel toxins drive AI-enhanced biopesticide design
Abstract Many voltage-gated sodium channel-targeting animal peptide toxins are renowned for their potency and selectivity against insects. Understanding why these toxins selectively target insect sodium channels over their mammalian counterparts is crucial for developing safer and more effective pest control agents. Here, we present the cryoelectron microscopy (cryo-EM) structures of the insect sodium channel Na v PaS bound to two naturally occurring insect-selective toxins, Av3 from the sea anemone and LqhαIT from the scorpion. Both toxins bind to the voltage-sensing domain 4 (VSD4) of Na v PaS and disrupt fast inactivation by stabilizing the S4 segment in a deactivated conformation. While Av3 engages a membrane-embedded site between VSD4 and pore domain 1 (PD1), LqhαIT binds to the classical neurotoxin site 3, illustrating distinct binding modes that converge on a shared mechanism of action. These structures reveal the molecular determinants of insect selectivity and highlight the molecular coevolution of toxin-channel interactions, as corroborated by electrophysiology and toxicity assays. Leveraging these insights, we apply AI-driven protein design tools to increase the insecticidal potency of LqhαIT, resulting in a variant with a remarkable doubling in efficacy, as we confirm by insecticidal bioassays. This study illuminates the diverse mechanisms of sodium channel modulation and provides a framework for the structure-guided, AI-driven design of toxin-based biopesticides.
Evaluation of the Efficacy of Smear Layer Removal Using Different Irrigation Activation Methods during Root Canal Treatment: An In Vitro Study
CRISPR/Cas9-mediated mutagenesis of SMXL4 alters plant height and yield-related traits in rice (cv. Samkwang)
Necroptosis in both tumour and stromal compartments determines responsiveness to immunogenic cell death-based immunotherapy
Abstract Immunotherapy has transformed cancer treatment, including early triple-negative breast cancer (TNBC), yet most patients with advanced TNBC fail to respond to immune checkpoint blockade (ICB) plus chemotherapy. Durable control likely requires not only tumour cell killing but also immunogenic cell death (ICD) that activates antitumour immunity. Using a Brca1 ⁻/⁻ p53 ⁻/⁻ organoid-derived TNBC model that recapitulates the immune landscapes of basal-like tumours, we show that RIPK1-driven ICD synergises with anti-PD-1 therapy to induce durable tumour control and immune memory in immune-infiltrated tumours. Mechanistically, both tumour-intrinsic and stromal necroptosis are required. Deletion of Ripk1 or Mlkl in tumour cells, or Mlkl in the stromal compartment, markedly impairs therapeutic efficacy. Moreover, immunologically “cold” tumours can be rendered responsive to ICD-based therapy by STING agonists. These findings demonstrate that the benefit of IAP antagonism with checkpoint blockade critically depends on coordinated necroptosis in both tumour and stromal cells, underscoring the need to integrate tumour microenvironmental context when designing ICD-targeted immunotherapies.
Evaluation of the Efficacy of Three Remineralizing Agents on Demineralized Enamel after Orthodontic Brackets Debonding: A Comparative Study
Police UAV path planning method based on improved PSO using AFS and HJS
Tumor-induced orexigenic imbalance lowers protein appetite and drives early organ wasting symptoms
Abstract Cancer cachexia (CC) is characterized by organ wasting and ensuing involuntary weight loss. Despite advances, underlying mechanisms initiating CC remain unclear, including early symptoms like anorexia. Here, we use a fly gut-tumor model with a precise time-window before organ wasting starts. We show that tumor-induced factors involved in inflammation (unpaired 3/ Interleukin-6-like) and reduced insulin signaling (ImpL2/ Insulin Growth Factor Binding Protein) decrease NPF (Neuropeptide F/ Neuropeptide Y) in the brain prior to organ wasting. This early NPF decrease triggers low protein-specific food appetite and anorexia. We find that ImpL2 reduces NPF signaling while upd3 helps by concurrently affecting the blood brain barrier. Tumor-induced NPF decrease, and early reduction of protein appetite drive the onset of weight loss and exacerbate the risk of death during organ wasting. Altogether, we provide evidence for an early orexigenic brain imbalance causing low protein appetite that regulates the onset and outcome of organ wasting.