Inflammation, nutrition, and biological aging: The prognostic role of Naples prognostic score in nonalcoholic fatty liver disease outcomes.

AIM: This study aimed to evaluate the prognostic value of the Naples Prognostic Score (NPS) for predicting mortality in patients with nonalcoholic fatty liver disease (NAFLD) and compare its performance with established non-invasive fibrosis scores, including the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). METHODS: Data from 10,035 NAFLD patients identified within the 1999-2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. Cox regression models assessed the association between NPS and all-cause mortality, while time-dependent ROC analysis compared its predictive accuracy with FIB-4 and NFS. Mediation analysis explored the role of phenotypic age acceleration (PhenoAgeAccel). RESULTS: NPS was significantly associated with all-cause mortality, with each point increase corresponding to a 26 % increased risk (HR = 1.26, 95 % CI: 1.19-1.34). NPS demonstrated comparable predictive performance to FIB-4 and NFS, with further improvement when combined with either score (HRs of 2.03 and 2.11 for NPS + FIB-4 and NPS + NFS, respectively). PhenoAgeAccel mediated 31.5 % of the effect of NPS on mortality. CONCLUSIONS: This study found that NPS has the potential to be an independent, cost-effective, and reliable novel prognostic indicator for NAFLD that may complement existing tools and help improve risk stratification and management strategies for NAFLD, thereby preventing adverse outcomes.

Causal role of immune cells in prostate cancer: a bidirectional Mendelian-randomization analyses.

BACKGROUND: Immune cell signatures have been implicated in cancer progression and response to treatment. However, the causal relationship between immune cell signatures and prostate cancer (PCa) is still unclear. This study aimed to investigate the potential causal associations between immune cell signatures and PCa using Mendelian randomization (MR). METHOD: This study utilized genome-wide association studies (GWAS) summary statistics for PCa and immune cell signatures from publicly available datasets. MR analyses, including IVW, MR-Egger, and weighted median methods, were performed to evaluate the causal associations between immune cell signatures and PCa. Multiple sensitivity analysis methods have been adopted to test the robustness of our results. RESULTS: After FDR correction, our findings suggested that specific immune cell signatures, such as HLA DR on CD33+ HLA DR+ CD14dim (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.12-1.92, p = 0.006), HLA DR on CD33+ HLA DR+ CD14- (OR = 1.32, 95% CI = 1.05-1.67, p = 0.018), and HLA DR on monocyte (OR = 1.23, 95% CI = 1.03-1.47, p = 0.021), were significantly associated with PCa. PCa had no statistically significant effect on immunophenotypes. These results remained robust in sensitivity analyses, supporting the validity of the causal associations. CONCLUSIONS: This study provides evidence of a potential causal relationship between certain immune cell signatures and PCa. We observed that immune cell signatures involving HLA DR expression on specific cell types are associated with an increased risk of PCa.

Determination of mine fault activation degree and the division of tectonic stress hazard zones.

This article conducts a comprehensive study on the activation characteristics of faults in the mine and analyzes the distribution patterns of the original rock stress field. Through quantitative research and analysis, we determine the partitioning characteristics of tectonic stress in the mine field under the dual effects of fault activation and original rock stress. The study also reveals the significant impact of different fault activation characteristics and different tectonic stress partitions on the stability of roadway surrounding rock. Using the Mohr-Coulomb strength criterion as a foundation, we investigate the mechanisms of fault activation and establish a mathematical model for fuzzy comprehensive evaluation. This model enables us to determine the strength level of fault activation in coal seam 9 of the Limin coal mine and construct a geological structure model. It has realized the transformation of fault activation degree from qualitative evaluation to quantitative evaluation. The stress state analysis software is used to draw the division of tectonic stress dangerous areas under the synergistic effect of fault activation and original rock stress. We then analyze the impact on the stability of roadway surrounding rock in these different hazardous areas. Utilizing the fuzzy comprehensive evaluation method, we take into account the impact of faults on the distribution characteristics of stress fields and the stability of roadway surrounding rock. This approach enables us to more accurately and comprehensively determine the hazardous areas of tectonic stress in the mine field under the dual effects of faults and original rock stress.

Ternary Phase-Field Simulation of Poly(vinylidene fluoride) Microporous Membrane Structures Prepared by Nonsolvent-Induced Phase Separation with Different Additives and Solvent Treatments.

In this study, an existing ternary membrane system based on nonsolvent-induced phase separation (NIPS) with a phase-field model was optimized. To study and analyze the effects of different additives on the formation of the skin layer and the effects of the three solvents on membrane characterization under the same conditions, two-dimensional simulations of the relevant parameters of a poly(vinylidene fluoride) (PVDF) membrane system were performed. The specific application of quaternary substances in ternary membrane systems was elaborated by determining the cohesive energy density between the additives and solvents, followed by the interaction parameters χ under the joint effect of the two. The results showed that the PVDF microporous membrane formed a dense surface layer at the mass transfer exchange interface, and with an increase in the poly(ethylene glycol) (PEG) concentration, the phase separation of the skin layer was predominantly transformed from liquid-solid partitioning to liquid-liquid partitioning; the number of membrane pores increased with increasing poly(vinylpyrrolidone) (PVP) concentration. The N,N-dimethylacetamide (DMAc) solvent system had the most stable thermodynamic properties; the dimethyl sulfoxide (DMSO) solvent system had mostly large pores running through the membrane and exhibited a porous structure. Related experiments also validated the model. Therefore, this model can be applied to other PVDF ternary membrane systems to better understand the structural development of microporous PVDF membranes under different conditions.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Protective Effect of CXCR7 Against Hypoxia/Reoxygenation Injury in Renal Tubular Epithelial Cells.

Acute kidney injury (AKI) is a multifactorial syndrome with complex pathophysiology and prognosis. Ischaemia‒reperfusion injury (IRI) is a major cause of induced AKI. The aim of this study was to investigate the effect of upregulated CXCR7 expression on renal tubular epithelial cell apoptosis induced by hypoxia/reoxygenation (H/R). HK-2 cells were divided into three groups: control group (pcDNA3.1), hypoxia/reoxygenation + pcDNA3.1 group (H/R+pcDNA3.1) and CXCR7 overexpression + hypoxia/reoxygenation group (H/R+ Flag-CXCR7). Protein levels of renal tubular epithelial cell injury-, apoptosis- and autophagy-related markers were assessed by qRT‒PCR, Western blotting, flow cytometry (FCM), immunofluorescence and transmission electron microscopy (TEM). In addition, HK-2 cells were treated with the autophagy inhibitor 3-MA and divided into 3 groups: control group, 3-MA + pcDNA3.1 group, and 3-MA + Flag-CXCR7 group. Changes in autophagy and apoptosis in renal tubule epithelial cells were assessed by Western blotting and FCM. Compared with those in the control group, the protein and mRNA expression levels of CXCR7 in HK-2 cells were significantly lower under H/R conditions. Under H/R conditions, CXCR7 overexpression in HK-2 cells significantly downregulated the expression of NGAL. Moreover, CXCR7 overexpression significantly decreased H/R-induced cleaved PARP-1 and cleaved Caspase 3 levels, increased the level of the antiapoptotic protein BCL-2 and the autophagy-related molecules ATG5 and LC3B II, and significantly inhibited the expression of P62. Autophagy flow and TEM also showed that CXCR7 significantly promoted autophagy. CXCR7 significantly alleviated the 3-MA-induced inhibition of autophagy and increase in apoptosis. Upregulated CXCR7 expression can inhibit renal tubular epithelial cell apoptosis and damage by regulating autophagy. In conclusion, CXCR7 is a promising target for the prevention and/or treatment of AKI.

Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density, Fracture Risk, and Bone Metabolism in Adults With Osteoporosis/Fractures.

OBJECTIVE: To evaluate the association of serum 25-hydroxyvitamin D (25(OH) D) levels with bone mineral density (BMD), fracture risk, and bone metabolism. METHODS: This multicenter cross-sectional study recruited menopausal females and males greater than or equal to 50 year old with osteoporosis/fractures between September 2016 and September 2021. Assessment included clinical data, 25(OH)D, intact parathyroid hormone (iPTH), procollagen type 1 amino-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks (CTX), lateral thoracolumbar spine x-rays, and BMD. RESULTS: A total of 3003 individuals were stratified by 25(OH) D levels: 720 individuals (24%) <20 ng/mL, 1338 individuals (44.5%) 20 to 29 ng/mL, and 945 individuals (31.5%) ≥30 ng/mL. In unadjusted and multivariable models, BMD T-score, except spine, was significantly and positively associated with 25(OH)D levels. 25(OH) D levels were inversely associated with Fracture Risk Assessment Tool scores. Patients with 25(OH)D <20 ng/mL had significantly higher iPTH and bone turnover markers (P1NP and CTX) than patients with 25(OH)D â‰§20 ng/mL in all models. When analyzing bone-related markers and BMD, total hip and femoral neck BMD T-scores were positively correlated with 25(OH)D concentrations and BMI but negatively correlated with iPTH, P1NP, CTX, and age. In multivariate models with all bone-related markers, only 25(OH)D levels were significantly associated with total hip and femoral neck BMD. CONCLUSION: Vitamin D deficiency is significantly associated with decreased total hip and femoral neck BMD and increased fracture risk as assessed by Fracture Risk Assessment Tool. In those with osteoporosis/fractures, vitamin D is implicated in the causal relationship between bone remodeling and BMD. Assessing vitamin D status is imperative for those at risk for osteoporosis/fractures.

Sex-dependent interactions between prodromal intestinal inflammation and LRRK2 G2019S in mice promote endophenotypes of Parkinson's disease.

Gastrointestinal (GI) disruptions and inflammatory bowel disease (IBD) are commonly associated with Parkinson's disease (PD), but how they may impact risk for PD remains poorly understood. Herein, we provide evidence that prodromal intestinal inflammation expedites and exacerbates PD endophenotypes in rodent carriers of the human PD risk allele LRRK2 G2019S in a sex-dependent manner. Chronic intestinal damage in genetically predisposed male mice promotes α-synuclein aggregation in the substantia nigra, loss of dopaminergic neurons and motor impairment. This male bias is preserved in gonadectomized males, and similarly conferred by sex chromosomal complement in gonadal females expressing human LRRK2 G2019S. The early onset and heightened severity of neuropathological and behavioral outcomes in male LRRK2 G2019S mice is preceded by increases in α-synuclein in the colon, α-synuclein-positive macrophages in the colonic lamina propria, and loads of phosphorylated α-synuclein within microglia in the substantia nigra. Taken together, these data reveal that prodromal intestinal inflammation promotes the pathogenesis of PD endophenotypes in male carriers of LRRK2 G2019S, through mechanisms that depend on genotypic sex and involve early accumulation of α-synuclein in myeloid cells within the gut.

A novel method for precise implantation of tracheal Y-shaped stent.

The tracheal Y-shaped stent is mainly used for the treatment of critical patients with airway stenosis or esophagotracheal fistula near carina. A novel method for precise implantation of Y-shaped tracheal stents was developed using double-lumen endotracheal intubation and flexible bronchoscopy. This approach aims to address the limitations associated with X-ray or rigid bronchoscopy guidance, such as operational difficulties and the risk of inaccurate stent placement leading to implantation failure or suffocation. With this new technique, 13 tracheal Y-shaped stents were successfully implanted. This method shows promise in reducing the complexity of stent implantation and facilitating timely treatment for patients in need. Additionally, it has the potential to update current operating standards and guidelines for this procedure.

Clinical efficacy of tumor organoid-guided cancer therapy for locally advanced unresectable or metastatic breast cancer.

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

Photogenerated chlorine radicals activate C(sp3)-H bonds of alkylbenzenes to access quinazolinones.

An Fe-catalyzed visible-light induced condensation of alkylbenzenes with anthranilamides has been developed. Upon irradiation, the trivalent iron complex could generate chlorine radicals, which successfully abstracted the hydrogen of benzylic C-H bonds to form benzyl radicals. And these benzyl radicals were converted into oxygenated products under air conditions, which subsequently reacted with anthranilamides for the synthesis of quinazolinones.

Visible-Light-Induced Chemodivergent Synthesis of Tetracyclic Quinazolinones and 3-Iminoisoindoliones via the Substrate Control Strategy.

A visible-light-induced chemodivergent synthesis of tetracyclic quinazolinones and 3-iminoisoindoliones has been developed. This chemodivergent reaction afforded two kinds of different products by substrate control. A detailed investigation of the reaction mechanism revealed that this consecutive photoinduced electron transfer (ConPET) cascade cyclization involved a radical process, and the aryl radical was the crucial intermediate. This method employed 4-DPAIPN as a photocatalyst and i-Pr2NEt as a sacrificial electron donor leading to metal-free conditions.

Emission and spatial variation characteristics of odorous pollutants in the aerobic tank of an underground wastewater treatment plant (UWWTP) in southern China.

In this study, the spatial concentration of odorous pollutants in the aerobic tank of an underground wastewater treatment plant (UWWTP) in southern China is monitored. The odour activity value, odour contribution rate, and chemical concentration contribution rate are used to evaluate the degree of contribution of odorous substances. Computational fluid dynamics (CFD) simulations of odorous pollutant diffusion are also established. The study shows that the odorous substances detected in the aerobic tank mainly included ammonia (NH3), hydrogen sulfide (H2S), trimethylamine (C3H9N), and methanethiol (CH3SH), and their concentrations are 1.160, 0.778, 0.022, and 0.0006 mg/m3, respectively. The total odour activity value of the aerobic tank is 450.72 (dimensionless), of which the odour activity value of H2S is 432.22, and the contribution rate reaches 95.9%. H2S is the main contributor to odour and a key controlled substance. The air inlets and exhaust outlets in the aerobic tank are cross-arranged at the top of the space, and the CFD model of odorous pollutant diffusion shows that the gas flow organization determines the odorous pollutant diffusion. The spatial distribution of gas flow and odorous substances in the aerobic tank is relatively uniform, and the odour collection efficiency is higher. The production flux and production coefficient of H2S in the aerobic tank are calculated as 25.831 mg/(m2·h) and 14.149 mg/t, respectively. This study determines the reasonable air supply and exhaust design of the aerobic tank, the number of odour pollutants, and the key controlled substances. These findings offer guidance and serve as useful references for the prevention and control of odour pollution in aerobic tanks of the same type of UWWTPs.

Prevalence and relevant factors of depression among adolescents in Xinjiang, China: A cross-sectional survey.

The aim of this study is to elucidate the prevalence of depression and examine the contributing factors to depression among adolescents in Xinjiang, China. A stratified cluster sampling methodology was employed in this study, with the sample size determined through consideration of prior studies on adolescent depression. Employing this approach, 6 schools were chosen from each prefecture-level city, designated as urban areas, and 3 schools were selected from each county. Subsequently, individual classes were treated as units, and a minimum of 80 students from each grade were surveyed within the entire class. The investigation of adolescents involved the administration of a questionnaire assessing the factors influencing depression, along with the Center for Epidemiologic Studies Depression Scale (CES-D). Multivariate linear regression was used to analyze the influencing factors of depression. The occurrence rates of depression were 12.17%, 13.05%, 12.32%, and 9.29% in junior middle school, senior middle school, vocational high school, and college, respectively. The corresponding CES-D scores were 10.54 ±â€…8.26, 11.20 ±â€…8.37, 12.17 ±â€…6.94, and 11.33 ±â€…6.28. Significant associations with the CES-D score were observed for gender, smoking, alcohol consumption, and spending more than 4 hours online daily across the educational levels mentioned. The risk of experiencing depressive symptoms was elevated among female junior and senior high school students who spent more than 4 hours daily on the internet, engaged in cigarette smoking, and consumed alcohol. The findings underscore the significance of targeting high-risk groups, particularly through home-school collaborations, to mitigate excessive internet use and consequently reduce the likelihood of depressive symptoms in students.

Effect of extracorporeal shock wave combined with Kinesio taping on upper limb function during individuals with biceps brachii tendinopathy：protocol for a double-blind, randomised controlled trial.

INTRODUCTION: Long head of biceps brachii tendinopathy (LHBT) is characterised by persistent pain and disability of shoulder joint, impairing patients' quality of life. Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment, which promotes tissue regeneration and repair. However, ESWT has a side effect that often causes short-term pain and swelling in the treatment area. It is known that the effects of Kinesio taping (KT) on relieving swelling and pain. Due to insufficient clinical evidence from current limited studies, this randomised controlled study aims to explore the effects of ESWT combined with KT on upper limb function during individuals with LHBT. METHODS AND ANALYSIS: A 2×2 factorial design, double-blind, randomised controlled trial will be conducted. A total of 144 participants will be randomly allocated into one of four groups (KT+ESWT, KT+sham ESWT, sham KT+ESWT or sham KT+sham ESWT) to participate in a 4-week treatment programme. Measurements will be taken at pretreatment (baseline), immediately after treatment and 6 weeks after treatment. The primary endpoint will be the Constant-Murley score (CMS), the secondary endpoints will include the pain Numerical Rating Scale, range of motion, pressure pain threshold and soft tissue hardness of biceps, speed test and global rating of change. Repeated measures analysis of variance will be used to compare differences among the effects of different interventions. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. In addition to international conference reports, findings will be disseminated through international publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2100051324.

CXC chemokine receptor 7 ameliorates renal fibrosis by inhibiting ß-catenin signaling and epithelial-to-mesenchymal transition in tubular epithelial cells.

Renal fibrosis is a common feature of various chronic kidney diseases. However, the underlying mechanism remains poorly understood. The CXC chemokine receptor (CXCR) family plays a role in renal fibrosis; however, the detailed mechanisms have not been elucidated. In this study, we investigated the potential role of CXCR7 in mediating renal fibrosis. CXCR7 expression is decreased in unilateral ischemia-reperfusion injury (UIRI) and unilateral ureteral obstruction mouse models. Furthermore, CXCR7 was specifically expressed primarily in the Lotus Tetragonolobus Lectin-expressing segment of tubules, was slightly expressed in the peanut agglutinin-expressing segment, and was barely expressed in the Dolichos biflorus agglutinin-expressing segment. Administration of pFlag-CXCR7, an overexpression plasmid for CXCR7, significantly inhibited the activation of ß-catenin signaling and protected against the progression of epithelial-to-mesenchymal transition (EMT) and renal fibrosis in a UIRI mouse model. Using cultured HKC-8 cells, we found that CXCR7 significantly downregulated the expression of active ß-catenin and fibrosis-related markers, including fibronectin, Collagen I, and α-SMA. Furthermore, CXCR7 significantly attenuated TGF-ß1-induced changes in ß-catenin signaling, EMT and fibrosis. These results suggest that CXCR7 plays a crucial role in inhibiting the activation of ß-catenin signaling and the progression of EMT and renal fibrosis. Thus, CXCR7 could be a novel therapeutic target for renal fibrosis.

Causal effect of age first had sexual intercourse and lifetime number of sexual partners on cervical cancer.

Objective: In this study, we aimed to investigate whether age first had sexual intercourse (AFSI) and lifetime number of sexual partners (LNSP) have a direct causal effect on cervical cancer by Mendelian randomization (MR) analysis. Methods: Four approaches were used for MR Analysis, including MR-Egger, weighted method, weighted median, and inverse variance weighted (IVW). MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) as well as MR-Egger regression analysis were conducted to detect whether there was pleiotropy between IVs and outcome, and the outlier SNPs can be detected by MR-PRESSO. The presence or absence of heterogeneity among IVs was suggested according to Cochran's Q statistic. Leave-one-out sensitivity analysis was performed to identify and remove SNPs which could independently change the results. We corrected the results using Bonferroni correction. Results: From the results of IVW, AFSI had a negative effect on cervical cancer (OR = 0.996, 95 % CI: 0.995, 0.998 P = 1.70E-07), which still persisted after Bonferroni correction. However, no causal effect of LNSP on cervical cancer was found according to the IVW results (OR = 1.003, 95 % CI: 1.000, 1.007, P = 0.071). From the results of MR-PRESSO and MR-Egger, no SNP with horizontal pleiotropy between cervical cancer was detected and no SNP was identified as an outlier SNP. Cochran's Q statistic suggested that no heterogeneity existed among IVs of AFSI and LNSP. According to Leave-one-out analysis, the results of MR did not change after excluding any single IV. Conclusion: This MR study reveals that early AFSI has a causal effect on cervical cancer.

Alteration of Thyroid Hormones in Mouse Models of Alzheimer's Disease and Aging.

INTRODUCTION: Aging is characterized by the deterioration of a wide range of functions in tissues and organs, and Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Hypothyroidism occurs when there is insufficient production of thyroid hormones (THs) by the thyroid. The relationship between hypothyroidism and aging as well as AD is controversial at present. METHODS: We established an animal model of AD (FAD4T) with mutations in the APP and PSEN1 genes, and we performed a thyroid function test and RNA sequencing (RNA-Seq) of the thyroid from FAD4T and naturally aging mice. We also studied gene perturbation correlation in the FAD4T mouse thyroid, bone marrow, and brain by further single-cell RNA sequencing (scRNA-seq) data of the bone marrow and brain. RESULTS: In this study, we found alterations in THs in both AD and aging mice. RNA-seq data showed significant upregulation of T-cell infiltration- and cell proliferation-related genes in FAD4T mouse thyroid. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that upregulated genes were enriched in the functional gene modules of activation of immune cells. Downregulated energy metabolism-related genes were prominent in aging thyroids, which reflected the reduction in THs. GSEA showed a similar enrichment tendency in both mouse thyroids, suggesting their analogous inflammation state. In addition, the regulation of leukocyte activation and migration was a common signature between the thyroid, brain, and bone marrow of FAD4T mice. CONCLUSIONS: Our findings identified immune cell infiltration of the thyroid as the potential underlying mechanism of the alteration of THs in AD and aging.

Machine learning-based radiomics strategy for prediction of acquired EGFR T790M mutation following treatment with EGFR-TKI in NSCLC.

The epidermal growth factor receptor (EGFR) Thr790 Met (T790M) mutation is responsible for approximately half of the acquired resistance to EGFR-tyrosine kinase inhibitor (TKI) in non-small-cell lung cancer (NSCLC) patients. Identifying patients at diagnosis who are likely to develop this mutation after first- or second-generation EGFR-TKI treatment is crucial for better treatment outcomes. This study aims to develop and validate a radiomics-based machine learning (ML) approach to predict the T790M mutation in NSCLC patients at diagnosis. We collected retrospective data from 210 positive EGFR mutation NSCLC patients, extracting 1316 radiomics features from CT images. Using the LASSO algorithm, we selected 10 radiomics features and 2 clinical features most relevant to the mutations. We built models with 7 ML approaches and assessed their performance through the receiver operating characteristic (ROC) curve. The radiomics model and combined model, which integrated radiomics features and relevant clinical factors, achieved an area under the curve (AUC) of 0.80 (95% confidence interval [CI] 0.79-0.81) and 0.86 (0.87-0.88), respectively, in predicting the T790M mutation. Our study presents a convenient and noninvasive radiomics-based ML model for predicting this mutation at the time of diagnosis, aiding in targeted treatment planning for NSCLC patients with EGFR mutations.

RNA sequencing reveals the transcriptomic landscape and alternative splicing events induced by LGALS1 silencing in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common clinical cancer with high mortality. The lectin galactoside-binding soluble 1 (LGALS1) is an RNA-binding protein (RBP) involved in NSCLC progression. Alternative splicing (AS) is a vital function of RBPs that contributes to tumor progression. It is unknown whether LGALS1 regulates NSCLC progression through AS events. OBJECTIVES: To profile the transcriptomic landscape and LGALS1-regulated AS events in NSCLC. MATERIAL AND METHODS: The A549 cells either with silenced LGALS1 (siLGALS1 group) or without them (siCtrl group) were subjected to RNA sequencing; differentially expressed genes (DEGs) and AS events were discovered and then the AS ratio was validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: High LGALS1 expression indicates poor overall survival (OS), first progression (FP) and post-progression survival (PPS). A total of 225 DEGs were identified, including 81 downregulated and 144 upregulated in the siLGALS1 group compared to the siCtrl group. Differentially expressed genes were mainly enriched in interaction-related Gene Ontology (GO) terms and involved in cGMP-protein kinase G (PKG) and calcium signaling pathways. The RT-qPCR validation showed that the expressions of ELMO1 and KCNJ2 were upregulated, while HSPA6 was downregulated after LGALS1 silencing. The expressions of KCNJ2 and ELMO1 were upregulated to a peak at 48 h after LGALS1 knockdown, while HSPA6 expression decreased, after which their expressions returned to baseline. The overexpression of LGALS1 rescued the elevation in KCNJ2 and ELMO1 expression, and decrease in HSPA6 expression induced by siLGALS1. A total of 69,385 LGALS1-related AS events were detected, which produced 433 upregulated and 481 downregulated AS events after LGALS1 silencing. The LGALS1-related AS genes were mainly enriched in the apoptosis and ErbB signaling pathways. The LGALS1 silencing led to a decrease in the AS ratio of BCAP29 and an increase in CSNKIE and MDFIC. CONCLUSIONS: We characterized the transcriptomic landscape and profiled AS events in A549 cells following LGALS1 silencing. Our study provides abundant candidate markers and new insights into NSCLC.