Deep learning models in classifying primary bone tumors and bone infections based on radiographs.

Primary bone tumors (PBTs) present significant diagnostic challenges due to their heterogeneous nature and similarities with bone infections. This study aimed to develop an ensemble deep learning framework that integrates multicenter radiographs and extensive clinical features to accurately differentiate between PBTs and bone infections. We compared the performance of the ensemble model with four imaging models based solely on radiographs utilizing EfficientNet B3, EfficientNet B4, Vision Transformer, and Swin Transformers.

Single-Cell Transcriptomic Analysis of Myeloid Lineage Evolution from CD19 CAR-T Cell Therapy.

Introduction: We report a case of relapse and refractory acute B-lymphoblastic leukemia (r/r B-ALL) apparently turned into acute myeloid leukemia, which is occasional and fatal during CAR-T treatment. There are still limited data to clarify the molecular mechanism of myeloid blast populations proliferation during CAR-T treatment.

Case Presentation: A 21-year-old man with an established history of r/r B-ALL with a complex chromosome karyotype and renal extramedullary infiltration presented to our institution.

Heterogeneous seafloor deposition of heavy microplastics in the North Pacific estimated over 65 years.

Marine plastic pollution has been a public concern for many decades; however, transport processes of heavy microplastics to the seafloor have long been overlooked given the difficulties in sampling and modeling. The distribution of heavy microplastic deposition on the seafloor in the North Pacific for 65 years since 1951, was estimated using a particle tracking model with 577,143,840 particles. The model revealed that 22 % of heavy microplastics were deposited over 100 km offshore from their release locations.

Photochemical bomb: Precision nuclear targeting to activate cGAS-STING pathway for enhanced bladder cancer immunotherapy.

Activating the cGAS-STING pathway presents a promising strategy to enhance the innate immunity and combat the immunosuppressive tumor microenvironment. One key mechanism for triggering this pathway involves the release of damaged DNA fragments caused by nuclear DNA damage. However, conventional cGAS-STING agonists often suffer from limited nucleus-targeting efficiency and potential biotoxicity.

Carbonyl index of miniaturized microplastics at the sea surface.

We investigated the carbonyl index (CI) of small microplastics (SMPs; 50-350 μm) and large microplastics (LMPs; >350 μm) in the surface waters of the Tokai region and Tokyo Bay in Japan. The degradation was evaluated by determining the CI from the infrared spectrum of microplastics (MPs) adopting the specified area under the band technique. Average CIs of SMPs and LMPs in polyethylene were 2.

Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication.

In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression.

Cooperative blockade of FLT3 and ALK synergistically suppresses growth of osteosarcoma.

Osteosarcoma is a common primary malignant bone tumor in children and young adults, with limited progress in improving survival rates for metastatic or recurrent cases. Kinase inhibitors have emerged as potential treatments for osteosarcoma due to the critical role kinases play in regulating cellular networks. However, single-agent kinase inhibitors often face challenges due to the activation of compensatory oncogenic signaling pathways, which can undermine treatment efficacy.

Developing and applying a virus-induced gene silencing system for functional genomics in walnut (Juglans regia L.) mediated by tobacco rattle virus.

Walnut (Juglans regia L.) is a high-value tree species planted worldwide, but the incomplete less developed genetic transformation system limits its gene function analysis. In this study, virus-induced gene silencing (VIGS) mediated by tobacco rattle virus (TRV) technology was applied to walnut seedlings to degrade the transcript of target gene.

MetaDegron: multimodal feature-integrated protein language model for predicting E3 ligase targeted degrons.

Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequences they recognize in the target proteins, are key parts of the ubiquitin-mediated proteolysis, and their interactions determine the degradation specificity and maintain cellular homeostasis. To date, only a limited number of targeted degron instances have been identified, and their properties are not yet fully characterized.

ImmuneApp for HLA-I epitope prediction and immunopeptidome analysis.

Advances in mass spectrometry accelerates the characterization of HLA ligandome, necessitating the development of efficient methods for immunopeptidomics analysis and (neo)antigen prediction. We develop ImmuneApp, an interpretable deep learning framework trained on extensive HLA ligand datasets, which improves the prediction of HLA-I epitopes, prioritizes neoepitopes, and enhances immunopeptidomics deconvolution. ImmuneApp extracts informative embeddings and identifies key residues for pHLA binding.

Cytoplasmic mtDNA clearance suppresses inflammatory immune responses.

Upon various stresses, mtDNA leaks from mitochondria into the cytoplasm, leading to cellular dysfunction and inflammation, thereby exacerbating disease progression. The autophagy-lysosome pathway has emerged as a pivotal quality control mechanism for eliminating abnormal cytoplasmic mtDNA. This article summarizes the mechanisms underlying mtDNA-triggered inflammation and how cytoplasmic mtDNA is eliminated.

Identification and functional analysis of C-type lectin from mosquito Aedes albopictus in response to dengue virus infection.

Background: C-type lectins (CTLs) are a large family of proteins with sugar-binding activity. CTLs contain an evolutionarily conserved C-type lectin domain (CTLD) that binds microbial carbohydrates in a calcium-dependent manner, thereby playing a key role in both microbial pathogenesis and innate immune responses. Aedes albopictus is an important vector for transmitting dengue virus (DENV) worldwide.

Traditional Chinese medicine for sjögren's syndrome: a national survey of attitudes and perceptions among Chinese patients and rheumatologists.

Background: This study explored similarities and differences among Chinese patients and rheumatologists in their attitudes towards and perceptions of traditional Chinese medicine (TCM) for Sjögren's syndrome (SS), including analyzing factors that influenced their decision making.

Methods: An anonymous questionnaire was used to conduct a multicenter survey among patients with SS at three tertiary care medical centers in Beijing and among rheumatology clinicians at several hospitals across China. Results were analyzed using descriptive statistics.

Histopathologic evaluation of Asian-American patients with chronic rhinosinusitis with nasal polyps.

Asian-American (AA) patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have comparable rates of tissue eosinophilia compared to Caucasians when defined as >10 eosinophils/high-powered field (HPF). AA patients with CRSwNP have significantly higher incidence of mixed inflammation defined as >10 eosinophils/HPF and >10 neutrophils/HPF.

PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT.

Chemoresistance is one of the major causes of poor prognosis in osteosarcoma. Alternative therapeutic strategies for osteosarcoma are limited, indicating that increasing sensitivity to currently used chemotherapies could be an effective approach to improve patient outcomes. Using a kinome-wide CRISPR screen, we identified PRKDC as a critical determinant of doxorubicin (DOX) sensitivity in osteosarcoma.

Discovery and Mechanistic Understanding of a Lipase from Rhizorhabdus dicambivorans for Efficient Ester Aminolysis in Aromatic Amines.

The formation of amide bonds via aminolysis of esters by lipases generates a diverse range of amide frameworks in biosynthetic chemistry. Few lipases have satisfactory activity towards bulky aromatic amines despite numerous attempts to improve the efficiency of this transformation. Here, we report the discovery of a new intracellular lipase (Ndbn) with a broad substrate scope.

Natural compounds modulating mitophagy: Implications for cancer therapy.

Cancer is considered as the second leading cause of mortality, and cancer incidence is still growing rapidly worldwide, which poses an increasing global health burden. Although chemotherapy is the most widely used treatment for cancer, its effectiveness is limited by drug resistance and severe side effects. Mitophagy is the principal mechanism that degrades damaged mitochondria via the autophagy/lysosome pathway to maintain mitochondrial homeostasis.

DegronMD: Leveraging Evolutionary and Structural Features for Deciphering Protein-Targeted Degradation, Mutations, and Drug Response to Degrons.

Protein-targeted degradation is an emerging and promising therapeutic approach. The specificity of degradation and the maintenance of cellular homeostasis are determined by the interactions between E3 ubiquitin ligase and degradation signals, known as degrons. The human genome encodes over 600 E3 ligases; however, only a small number of targeted degron instances have been identified so far.

Endotype evaluation of Hispanic/Latinx-American patients with chronic rhinosinusitis with nasal polyps.

Hispanic-American patients with chronic rhinosinusitis with nasal polyps have a comparable level of tissue eosinophilia compared to their Caucasian counterparts in the United States. Mixed inflammation involving both neutrophils and eosinophils is more common in this population compared to Caucasians. Findings from this study may indicate that Hispanic-American patients have a unique endotype or endotypes that deserves further investigation.

Identification of a Potential Antimycobacterial Drug Sensitizer Targeting a Flavin-Independent Methylenetetrahydrofolate Reductase.

The increasing antibiotic resistance of and pathogenic nontuberculosis mycobacteria highlights the urgent need for new prevention and treatment strategies. Recently, the cocrystal structure of a flavin-independent 5,10-methylenetetrahydrofolate reductase (MTHFR) that binds with a reduced nicotinamide adenine dinucleotide (NADH) has been well-determined, providing a structural basis for the screening of antimycobacterial leads targeting MTHFR, a new enzyme involved in tetrahydrofolic acid (THF) biosynthesis. In this study, we identified compound AB131 as a promising candidate that fits well into the NADH binding pocket of MTHFR through virtual screening.

Effect of acupuncture on regulating IL-17, TNF-ɑ and AQPs in Sjögren's syndrome.

Aim: The aim of the study was to observe the effect of acupuncture on regulating interleukin (IL)-17, tumor necrosis factor (TNF)-ɑ, and aquaporins (AQPs) in Sjögren's syndrome (SS) on patients and on non-obese diabetic (NOD) models.

Methods: Levels of anti-AQP 1, 5, 8, and 9 antibodies, IL-17, and TNF-ɑ in the serum of SS patients were compared prior and following 20 acupuncture treatment visits during 8 weeks. While in murine model, five groups were divided to receive interventions for 4 weeks, including control, model, acupuncture, isoflurane, and hydroxychloroquine.

Alkali-Amide-Catalyzed One-Pot Aminoallylation of Aldehydes with Allylbenzenes.

The deprotonation of allylbenzene was successfully demonstrated with a catalytic alkali amide base (NaN(SiMe)). The deprotonated allyl anion could be trapped by in situ generated -(trimethylsilyl) aldimines to provide value-added homoallylic amines (39 examples, 68-98% yields) in a one-pot manner with excellent liner selectivity. Compared with the previously reported method for the synthesis of homoallylic amines, this method does not need to use the preinstalled protection groups on the imines, which need to be removed after the reaction to obtain the N-H free homoallylic amine derivatives.

An interpretable ML model to characterize patient-specific HLA-I antigen presentation.

Personalized immunotherapy holds the promise of revolutionizing cancer prevention and treatment. However, selecting HLA-bound peptide targets that are specific to patient tumors has been challenging due to a lack of patient-specific antigen presentation models. Here, we present epiNB, a white-box, positive-example-only, semi-supervised method based on Naïve Bayes formulation, with information content-based feature selection, to achieve accurate modeling using Mass Spectrometry data eluted from mono-allelic cell lines and patient-derived cell lines.

Deep learning for detecting and elucidating human T-cell leukemia virus type 1 integration in the human genome.

Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus, is the causative agent for adult T cell leukemia/lymphoma and many other human diseases. Accurate and high throughput detection of HTLV-1 virus integration sites (VISs) across the host genomes plays a crucial role in the prevention and treatment of HTLV-1-associated diseases. Here, we developed DeepHTLV, the first deep learning framework for VIS prediction from genome sequence, motif discovery, and -regulatory factor identification.

Properties of flame-retardant leaf fiber cement-based composites at high temperatures.

Flame retardant modification of leaf fibers was carried out to solve the technical problem of poor fire resistance of plant fibers and improve the utilization rate of urban fallen leaves in building materials. The modification scheme adopts three flame retardants, i.e.