Efficacy and Safety Evaluation of 177Lu-FAP-2286 in the Treatment of Advanced Lung Cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of peptide-targeted radionuclide therapy (PTRT) with 177Lu-FAP-2286 in advanced lung cancer. PATIENTS AND METHODS: This single-center prospective study included 9 patients diagnosed with advanced lung cancer. These patients met the inclusion criteria and received PTRT with 177Lu-FAP-2286. Short-term efficacy was assessed using RECIST 1.1 and PERCIST 1.0 criteria. Long-term efficacy was evaluated through overall survival, progression-free survival (PFS), overall response rate, EORTC QLQ-C30 v3.0, Eastern Cooperative Oncology Group, and Karnofsky Performance Status. Toxicity response was assessed using CTCAE v5.0. RESULTS: The results based on RECIST 1.1 and PERCIST 1.0 criteria were comparable, with 44% of patients showing a partial metabolic response, 33.3% with stable metabolic disease, and 22.22% with progressive metabolic disease. The highest metabolic response after treatment reached 66.89%, and the overall response rate could reach 77.78%. In the long-term efficacy assessment, the median overall survival and PFS were 10 months and 6 months, respectively. The 2 patients with the lowest PFS (3 months) started PTRT relatively late. EORTC QLQ-C30 v3.0, Eastern Cooperative Oncology Group, and Karnofsky Performance Status scores showed that the overall health status, symptom response, and quality of life of patients improved after 177Lu-FAP-2286 treatment. The most noticeable improvements in clinical symptoms were dyspnea and cancer-related pain. No grade III/IV toxicity events were observed during follow-up period, and fibrinogen decreased significantly after treatment. CONCLUSIONS: 177Lu-FAP-2286 has the potential to be a viable PTRT option for patients with advanced lung cancer.

Single nucleotide polymorphisms in SEPALLATA 2 underlie fruit length variation in cucurbits.

Complete disruption of critical genes is generally accompanied by severe growth and developmental defects, which dramatically hinder its utilization in crop breeding. Identifying subtle changes, such as single nucleotide polymorphisms (SNPs), in critical genes that specifically modulate a favorable trait is a prerequisite to fulfill breeding potential. Here, we found two SNPs in the E-class floral organ identity gene cucumber (Cucumis sativus) SEPALLATA2 (CsSEP2) that specifically regulate fruit length. Haplotype (HAP) 1 (8G2667A) and HAP2 (8G2667T) exist in natural populations, whereas HAP3 (8A2667T) is induced by ethyl methanesulfonate mutagenesis. Phenotypic characterization of four near-isogenic lines and a mutant line showed that HAP2 fruits are significantly longer than those of HAP1, and those of HAP3 are 37.8% longer than HAP2 fruit. The increasing fruit length in HAP1-3 was caused by a decreasing inhibitory effect on CRABS CLAW (CsCRC) transcription (a reported positive regulator of fruit length), resultinged in enhanced cell expansion. Moreover, a 7638G/A-SNP in melon (Cucumis melo) CmSEP2 modulates fruit length in a natural melon population via the conserved SEP2-CRC module. Our findings provide a strategy for utilizing essential regulators with pleiotropic effects during crop breeding.

Optimizing air quality and health Co-benefits of mitigation technologies in China: An integrated assessment.

Carbon mitigation technologies lead to air quality improvement and health co-benefits, while the practical effects of the technologies are dependent on the energy composition, technological advancements, and economic development. In China, mitigation technologies such as end-of-pipe treatment, renewable energy adoption, carbon capture and storage (CCS), and sector electrification demonstrate significant promise in meeting carbon reduction targets. However, the optimization of these technologies for maximum co-benefits remains unclear. Here, we employ an integrated assessment model (AIM/enduse, CAM-chem, IMED|HEL) to analyze air quality shifts and their corresponding health and economic impacts at the provincial level in China within the two-degree target. Our findings reveal that a combination of end-of-pipe technology, renewable energy utilization, and electrification yields the most promising results in air quality improvement, with a reduction of fine particulate matter (PM2.5) by -34.6 µg m-3 and ozone by -18.3 ppb in 2050 compared to the reference scenario. In contrast, CCS technology demonstrates comparatively modest improvements in air quality (-9.4 µg m-3 for PM2.5 and -2.4 ppb for ozone) and cumulative premature deaths reduction (-3.4 million from 2010 to 2050) compared to the end-of-pipe scenario. Notably, densely populated regions such as Henan, Hebei, Shandong, and Sichuan experience the most health and economic benefits. This study aims to project effective future mitigation technologies and climate policies on air quality improvement and carbon mitigation. Furthermore, it seeks to delineate detailed provincial-level air pollution control strategies, offering valuable guidance for policymakers and stakeholders in pursuing sustainable and health-conscious environmental management.

Ubiquitin-modifying enzymes in thyroid cancer：Mechanisms and functions.

Thyroid cancer is the most common malignant tumor of the endocrine system, and evidence suggests that post-translational modifications (PTMs) and epigenetic alterations play an important role in its development. Recently, there has been increasing evidence linking dysregulation of ubiquitinating enzymes and deubiquitinases with thyroid cancer. This review aims to summarize our current understanding of the role of ubiquitination-modifying enzymes in thyroid cancer, including their regulation of oncogenic pathways and oncogenic proteins. The role of ubiquitination-modifying enzymes in thyroid cancer development and progression requires further study, which will provide new insights into thyroid cancer prevention, treatment and the development of novel agents.

Effectiveness of telerehabilitation in patients with post-COVID-19: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the effects of telerehabilitation on clinical symptoms, physical function, psychological function and quality of life (QoL) in patients with post-COVID-19. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: PubMed, Web of Science, Embase and Cochrane Library were searched for publications from 1 January 2020 to 17 April 2024. ELIGIBILITY CRITERIA: RCTs investigating the effects of telerehabilitation in patients with post-COVID-19 were included. The outcomes of interest encompassed clinical symptoms, physical function, psychological function and QoL. Only studies reported in English were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and evaluated the risk of bias. Statistical analysis was conducted using Review Manager V.5.3, employing mean difference (MD) with a 95% CI, and the corresponding P value was used to ascertain the treatment effect between groups. Heterogeneity was quantified using the I2 statistic. The quality of evidence was assessed by GRADE. RESULTS: 16 RCTs (n=1129) were included in this systematic review, 15 of which (n=1095, 16 comparisons) were included in the meta-analysis. The primary pooled analysis demonstrated that, compared with no rehabilitation or usual care, telerehabilitation can improve physical function (measured by 30 s sit-to-stand test [6 RCTs, n=310, MD=1.58 stands, 95% CI 0.50 to 2.66; p=0.004]; 6 min walking distance [6 RCTs, n=324, MD=76.90 m, 95% CI 49.47 to 104.33; p<0.00001]; and physical function from the 36-item short-form health survey [5 RCTs, n=380, MD=6.12 units, 95% CI 2.85 to 9.38; p=0.0002]). However, the pooled results did not indicate significant improvements in clinical symptoms, pulmonary function, psychological function or QoL. The quality of the evidence was graded as low for physical function and Hospital Anxiety and Depression Scale-anxiety and very low for other assessed outcomes. The overall treatment completion rate was 78.26%, with no reports of severe adverse events in any included trials. CONCLUSIONS: Despite the lack of significant improvements in certain variables, telerehabilitation could be an effective and safe option for enhancing physical function in patients with post-COVID-19. It is advisable to conduct further well-designed trials to continue in-depth exploration of this topic. STUDY REGISTRATION: PROSPERO, CRD42023404647.

Biplane Reduction: A Novel Technique for Restoring Fibula Length in Maisonneuve Fracture.

OBJECTIVE: Fibular length is important for ankle stability. Failure to adequately restore and stabilize fibula length may result in malunion, hindering postoperative functional exercises and recovery of ankle function. However, there is no unified and effective reduction method for fibular shortening in Maisonneuve fractures. In this study, we introduce the biplane reduction as an effective surgical technique for restoring the length of the fibula in Maisonneuve fractures. METHODS: This retrospective study enrolled 12 patients preoperatively diagnosed with Maisonneuve fractures between June 2019 and June 2022. All patients underwent our biplane reduction technique to restore the length of their fibula. Operation time, hospital stay, complications, FTA (the angle between the fibular tip and the superior articular surface of the talus), visual analog pain score, and the American Orthopaedic Foot and Ankle Society ankle-hindfoot score were recorded. An independent sample t-test was used for component comparisons, and a paired sample t-test or one-way analysis of variance was used for intra-group comparisons. RESULTS: No patient was lost to follow-up and no obvious postoperative complications were observed. After operation, FTA recovered from 37.52 ± 0.37 ° to 40.42 ± 0.43 °, which was significantly improved compared with that before operation (p < 0.01). At the last follow-up, both the VAS and AOFAS scores showed significant improvement compared to pre-surgery scores. CONCLUSIONS: The reduction technique proposed in this study to restore the length of the fibula in Maisonneuve fractures is simple and effective, does not require special equipment, and has the advantage of directly examining the reduction condition.

The CEBPB+ glioblastoma subcluster specifically drives the formation of M2 tumor-associated macrophages to promote malignancy growth.

Rationale: The heterogeneity of tumor cells within the glioblastoma (GBM) microenvironment presents a complex challenge in curbing GBM progression. Understanding the specific mechanisms of interaction between different GBM cell subclusters and non-tumor cells is crucial. Methods: In this study, we utilized a comprehensive approach integrating glioma single-cell and spatial transcriptomics. This allowed us to examine the molecular interactions and spatial localization within GBM, focusing on a specific tumor cell subcluster, GBM subcluster 6, and M2-type tumor-associated macrophages (M2 TAMs). Results: Our analysis revealed a significant correlation between a specific tumor cell subcluster, GBM cluster 6, and M2-type TAMs. Further in vitro and in vivo experiments demonstrated the specific regulatory role of the CEBPB transcriptional network in GBM subcluster 6, which governs its tumorigenicity, recruitment of M2 TAMs, and polarization. This regulation involves molecules such as MCP1 for macrophage recruitment and the SPP1-Integrin αvß1-Akt signaling pathway for M2 polarization. Conclusion: Our findings not only deepen our understanding of the formation of M2 TAMs, particularly highlighting the differential roles played by heterogeneous cells within GBM in this process, but also provided new insights for effectively controlling the malignant progression of GBM.

Enhancing Medical Imaging Segmentation with GB-SAM: A Novel Approach to Tissue Segmentation Using Granular Box Prompts.

Recent advances in foundation models have revolutionized model development in digital pathology, reducing dependence on extensive manual annotations required by traditional methods. The ability of foundation models to generalize well with few-shot learning addresses critical barriers in adapting models to diverse medical imaging tasks. This work presents the Granular Box Prompt Segment Anything Model (GB-SAM), an improved version of the Segment Anything Model (SAM) fine-tuned using granular box prompts with limited training data. The GB-SAM aims to reduce the dependency on expert pathologist annotators by enhancing the efficiency of the automated annotation process. Granular box prompts are small box regions derived from ground truth masks, conceived to replace the conventional approach of using a single large box covering the entire H&E-stained image patch. This method allows a localized and detailed analysis of gland morphology, enhancing the segmentation accuracy of individual glands and reducing the ambiguity that larger boxes might introduce in morphologically complex regions. We compared the performance of our GB-SAM model against U-Net trained on different sizes of the CRAG dataset. We evaluated the models across histopathological datasets, including CRAG, GlaS, and Camelyon16. GB-SAM consistently outperformed U-Net, with reduced training data, showing less segmentation performance degradation. Specifically, on the CRAG dataset, GB-SAM achieved a Dice coefficient of 0.885 compared to U-Net's 0.857 when trained on 25% of the data. Additionally, GB-SAM demonstrated segmentation stability on the CRAG testing dataset and superior generalization across unseen datasets, including challenging lymph node segmentation in Camelyon16, which achieved a Dice coefficient of 0.740 versus U-Net's 0.491. Furthermore, compared to SAM-Path and Med-SAM, GB-SAM showed competitive performance. GB-SAM achieved a Dice score of 0.900 on the CRAG dataset, while SAM-Path achieved 0.884. On the GlaS dataset, Med-SAM reported a Dice score of 0.956, whereas GB-SAM achieved 0.885 with significantly less training data. These results highlight GB-SAM's advanced segmentation capabilities and reduced dependency on large datasets, indicating its potential for practical deployment in digital pathology, particularly in settings with limited annotated datasets.

Cleaner heating policies contribute significantly to health benefits and cost-savings: A case study in Beijing, China.

Cleaner heating policies aim to reduce air pollution and may bring about health benefits to individuals. Based on a fixed-effect model focusing on Beijing, this study found that after the onset of air pollution, daily clinic visits, hospitalization days, and hospitalization expenses increased several days after the occurrence of air pollution. These hospitalization changes were observed in males and females and three different age groups. A difference-in-differences (DID) model was constructed to identify the influences of cleaner heating policies on health consequences. The study revealed that the policy positively affects health outcomes, with an average decrease of 3.28 thousand clinic visits for all diseases. The total hospitalization days and expenses tend to decrease by 0.22 thousand days and 0.34 million CNY (Chinese Yuan), respectively. Furthermore, implementing the policy significantly reduced the number of daily clinic visits for respiratory diseases, asthma, stroke, diabetes, and chronic obstructive pulmonary diseases (COPDs).

Rapid Detection of Uropathogens Using an Integrated Multiplex Digital Nucleic Acid Detection Assay Powered by a Digital-to-Droplet Microfluidic Device.

The digital nucleic acid detection assay features the capability of absolute quantitation without the need for calibration, thereby facilitating the rapid identification of pathogens. Although several integrated digital nucleic acid detection techniques have been developed, there are still constraints in terms of automation and analysis throughput. To tackle these challenges, this study presents a digital-to-droplet microfluidic device comprising a digital microfluidics (DMF) module at the bottom and a droplet microfluidics module at the top. Following sample introduction, the extraction of nucleic acid and the dispensation of nucleic acid elution for mixing with the multiple amplification reagents are carried out in the DMF module. Subsequently, the reaction droplets are transported to the sample inlet of the droplet microfluidic module via a liquid outlet, and then droplet generation in four parallel units within the droplet microfluidics module is actuated by negative pressure generated by a syringe vacuum. The digital-to-droplet microfluidic device was employed to execute an integrated multiplex digital droplet nucleic acid detection assay (imDDNA) incorporating loop-mediated isothermal amplification (LAMP). This assay was specifically designed to enable simultaneous detection of four uropathogens, namely, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecalis. The entire process of the imDDNA is completed within 75 min, with a detection range spanning 5 orders of magnitude (9.43 × 10-2.86 × 104 copies µL-1). The imDDNA was employed for the detection of batched clinical specimens, showing a consistency of 91.1% when compared with that of the conventional method. The imDDNA exhibits simplicity in operation and accuracy in quantification, thus offering potential advantages in achieving rapid pathogen detection.

Elevated 68Ga-FAPI Activity in Benign Carotid Body Tumors.

ABSTRACT: We present 68Ga-FAPI PET/CT findings of benign carotid body tumor in a 33-year-old woman. Benign carotid body tumor demonstrated intense tracer uptakes on 68Ga-FAPI PET/CT. Our case suggests that benign carotid body tumors should be considered in the differential diagnosis of neck mass with elevated 68Ga-FAPI activity.

An interpretable Bayesian clustering approach with feature selection for analyzing spatially resolved transcriptomics data.

Recent breakthroughs in spatially resolved transcriptomics (SRT) technologies have enabled comprehensive molecular characterization at the spot or cellular level while preserving spatial information. Cells are the fundamental building blocks of tissues, organized into distinct yet connected components. Although many non-spatial and spatial clustering approaches have been used to partition the entire region into mutually exclusive spatial domains based on the SRT high-dimensional molecular profile, most require an ad hoc selection of less interpretable dimensional-reduction techniques. To overcome this challenge, we propose a zero-inflated negative binomial mixture model to cluster spots or cells based on their molecular profiles. To increase interpretability, we employ a feature selection mechanism to provide a low-dimensional summary of the SRT molecular profile in terms of discriminating genes that shed light on the clustering result. We further incorporate the SRT geospatial profile via a Markov random field prior. We demonstrate how this joint modeling strategy improves clustering accuracy, compared with alternative state-of-the-art approaches, through simulation studies and 3 real data applications.

Cmai: Predicting Antigen-Antibody Interactions from Massive Sequencing Data.

The interaction between antigens and antibodies (B cell receptors, BCRs) is the key step underlying the function of the humoral immune system in various biological contexts. The capability to profile the landscape of antigen-binding affinity of a vast number of BCRs will provide a powerful tool to reveal novel insights at unprecedented levels and will yield powerful tools for translational development. However, current experimental approaches for profiling antibody-antigen interactions are costly and time-consuming, and can only achieve low-to-mid throughput. On the other hand, bioinformatics tools in the field of antibody informatics mostly focus on optimization of antibodies given known binding antigens, which is a very different research question and of limited scope. In this work, we developed an innovative Artificial Intelligence tool, Cmai, to address the prediction of the binding between antibodies and antigens that can be scaled to high-throughput sequencing data. Cmai achieved an AUROC of 0.91 in our validation cohort. We devised a biomarker metric based on the output from Cmai applied to high-throughput BCR sequencing data. We found that, during immune-related adverse events (irAEs) caused by immune-checkpoint inhibitor (ICI) treatment, the humoral immunity is preferentially responsive to intracellular antigens from the organs affected by the irAEs. In contrast, extracellular antigens on malignant tumor cells are inducing B cell infiltrations, and the infiltrating B cells have a greater tendency to co-localize with tumor cells expressing these antigens. We further found that the abundance of tumor antigen-targeting antibodies is predictive of ICI treatment response. Overall, Cmai and our biomarker approach filled in a gap that is not addressed by current antibody optimization works nor works such as AlphaFold3 that predict the structures of complexes of proteins that are known to bind.

Rapid and sensitive detection of heart-type fatty acid binding protein using aggregation-induced emission nanoparticles on digital microfluidics workstation.

Early and rapid diagnostic of acute myocardial infarction (AMI) during its developing stage is crucial due to its high fatality rate. Heart-type fatty acid binding protein (h-FABP) is an ideal biomarker for the quantitative diagnosis of AMI, surpassing traditional markers such as myoglobin, creatine phosphokinase-MB, and troponin in terms of sensitivity, specificity, and prognostic value. To obtain diagnostic and prognostic information, a precise and fully quantitative measurement of h-FABP is essential, typically achieved through an immunosorbent assay like the enzyme-linked immunosorbent assay. Nevertheless, this method has several limitations, including extended detection time, complex assay procedures, the necessity for skilled technicians, and challenges in implementing automated detection. This research introduces a novel biosensor, utilizing aggregation-induced emission nanoparticles (AIENPs) and integrated with a digital microfluidic (DMF) workstation, designed for the sensitive, rapid, and automated detection of h-FABP in low-volume serum samples. AIENPs and magnetic beads in nanoscale were served as the capture particles and the fluorescent probe, which were linked covalently to anti-h-FABP antibodies respectively. The approach was based on a sandwich immunoassay and performed on a fully automated DMF workstation with assay time by 15 min. We demonstrated the determination of h-FABP in serum samples with detection limit of 0.14 ng/mL using this biosensor under optimal condition. Furthermore, excellent correlations (R2 = 0.9536, n = 50) were obtained between utilizing this biosensor and commercialized ELISA kits in clinical serum detecting. These results demonstrate that our flexible and reliable biosensor is suitable for direct integration into clinical diagnostics, and it is expected to be promising diagnostic tool for early detection and screening tests as well as prognosis evaluation for AMI patients.

ZBTB7A regulates LncRNA HOTAIR-mediated ELAVL1/SOX17 axis to inhibit malignancy and angiogenesis in endometrial carcinoma.

BACKGROUND: Endometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified. METHODS: The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression. RESULTS: The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/ß-catenin pathway, promoting malignant behaviors in EC cells. CONCLUSION: HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/ß-catenin pathway underlines its potential as a therapeutic target.

Rheumatoid arthritis patients harbour aberrant enteric bacteriophages with autoimmunity-provoking potential: a paired sibling study.

OBJECTIVES: Viruses have been considered as important participants in the development of rheumatoid arthritis (RA). However, the profile of enteric virome and its role in RA remains elusive. This study aimed to investigate the atlas and involvement of virome in RA pathogenesis. METHODS: Faecal samples from 30 pairs of RA and healthy siblings that minimise genetic interferences were collected for metagenomic sequencing. The α and ß diversity of the virome and the virome-bacteriome interaction were analysed. The differential bacteriophages were identified, and their correlations with clinical and immunological features of RA were analysed. The potential involvement of these differential bacteriophages in RA pathogenesis was further investigated by auxiliary metabolic gene annotation and molecular mimicry study. The responses of CD4+ T cells and B cells to the mimotopes derived from the differential bacteriophages were systemically studied. RESULTS: The composition of the enteric bacteriophageome was distorted in RA. The differentially presented bacteriophages correlated with the immunological features of RA, including anti-CCP autoantibody and HLA-DR shared epitope. Intriguingly, the glycerolipid and purine metabolic genes were highly active in the bacteriophages from RA. Moreover, peptides of RA-enriched phages, in particular Prevotella phage and Oscillibacter phage could provoke the autoimmune responses in CD4+ T cells and plasma cells via molecular mimicry of the disease-associated autoantigen epitopes, especially those of Bip. CONCLUSIONS: This study provides new insights into enteric bacteriophageome in RA development. In particular, the aberrant bacteriophages demonstrated autoimmunity-provoking potential that would promote the occurrence of the disease.

A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis.

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a range of associated genomic and transcriptomic data, clinical metadata, pathologic assessments of cell composition, and, in several cases, detailed pathologic annotations of neoplastic, stromal, and necrotic regions. The amenability of these images to deep learning was highlighted through three applications: (i) development of a classifier for neoplastic, stromal, and necrotic regions; (ii) development of a predictor of xenograft-transplant lymphoproliferative disorder; and (iii) application of a published predictor of microsatellite instability. Together, this PDX Development and Trial Centers Research Network image repository provides a valuable resource for controlled digital pathology analysis, both for the evaluation of technical issues and for the development of computational image-based methods that make clinical predictions based on PDX treatment studies. Significance: A pan-cancer repository of >1,000 patient-derived xenograft hematoxylin and eosin-stained images will facilitate cancer biology investigations through histopathologic analysis and contributes important model system data that expand existing human histology repositories.

MDSCs are important osteoclast precursors primed by B cells in rheumatoid arthritis.

Osteoclast-mediated bone erosion and deformation represent significant pathological features in rheumatoid arthritis (RA). Myeloid-derived suppressor cells (MDSCs) and B cells have emerged as key contributors to the progression of RA. Nevertheless, their involvement, especially the interaction in RA osteoclastogenesis remains elusive. In this study, our results revealed a marked expansion of MDSCs in RA patients, and importantly, their abundance was positively correlated with radiographic damage evaluated by the Sharp/van der Heijde score. Notably, MDSCs derived from both RA patients and arthritic mice exhibited a heightened propensity to differentiate into osteoclasts compared with those from healthy individuals. Intriguingly, we observed that B cells from RA patients could augment the osteoclastogenic potential of MDSCs, which was also observed in arthritic mice. The impact of B cells on MDSC-mediated osteoclastogenesis was found to be most pronounced in switched memory B cells, followed by CD21low B cells and naïve B cells. MDSCs from B-cell-deficient mice exhibited diminished capacity to differentiate into osteoclasts, accompanied by distinct gene expression profiles associated with osteoclastogenesis. Taken together, our findings suggested that MDSCs were important osteoclast precursors primed by B cells in RA, serving as novel therapeutic targets for the persistent disease.

Moderating effects of PER3 gene DNA methylation on the association between problematic mobile phone use and chronotype among Chinese young adults: Focus on gender differences.

Objective: To investigate the rates of problematic mobile phone use (PMPU) and chronotypes in young adults, and examine the associations of PMPU with chronotypes, as well as its gender differences. Furthermore, we explored the moderating role of PER3 gene DNA methylation on the associations. Methods: From April to May 2019, a total of 1,179 young adults were selected from 2 universities in Anhui and Jiangxi provinces. The Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) and reduced Morningness-Eveningness Questionnaire (rMEQ) were adopted to investigate PMPU and chronotypes in young adults, respectively. Moreover, 744 blood samples were collected to measure PER3 gene DNA methylation. Multivariate logistic regression models were established to analyze the associations between PMPU and chronotypes. Moderating analysis was used to determine whether PER3 gene DNA methylation moderated the relationships between PMPU and chronotypes. Results: The prevalence of PMPU, morning chronotypes (M-types), neutral chronotypes (N-types), and evening chronotypes (E-types) of young adults were 24.6%, 18.4%, 71.1%, and 10.5%, respectively. Multivariate logistic regression results indicated that PMPU was positively correlated with E-types (OR = 3.53, 95%CI: 2.08-6.00), and the association was observed only in females after stratified by gender (OR = 5.36, 95%CI: 2.70-10.67). Furthermore, PER3 gene DNA methylation has a negative moderating role between PMPU and chronotypes and has a sex-based difference. Conclusions: This study can provide valuable information for the prevention and control of circadian rhythm disturbance among young adults from the perspective of epidemiology and biological etiology.