The impact of tertiary lymphoid structures on tumor prognosis and the immune microenvironment in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a common malignancy whose prognosis and treatment outcome are influenced by many factors. Some studies have found that tertiary lymphoid structures (TLSs) in cancer may contribute to prognosis and the prediction of immunotherapy efficacy However, the combined role of TLSs in NSCLC remains unclear. We accessed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to obtain mRNA sequencing data and clinical information as the TCGA cohort, and used our own sample of 53 advanced NSCLC as a study cohort. The samples were divided into TLS+ and TLS- groups by pathological tissue sections. Patients of the TLS+ group had a better OS (p = 0.022), PFS (p = 0.042), and DSS (p = 0.004) in the TCGA cohort, and the results were confirmed by the study cohort (PFS, p = 0.012). Furthermore, our result showed that the count and size of TLSs are closely associated with the efficacy of immunotherapy. In addition, the TLS+ group was associated with better immune status and lower tumor mutation load. In the tumor microenvironment (TME), the expression levels of CD4+ T cells and CD8+ T cells of different phenotypes were associated with TLSs. Overall, TLSs are a strong predictor of survival and immunotherapeutic efficacy in advanced NSCLC, and T cell-rich TLSs suggest a more ordered and active immune response site, which aids in the decision-making and application of immunotherapy in the clinic.

Gas-Phase-Induced Engineering for Fabrication of 3D Hierarchical Porous Nickel and Its Application toward High-Performance Supercapacitors.

Commercial nickel foam (NF), which is composed of numerous interconnected ligaments and hundred-micron pores, is widely acknowledged as a current collector/electrode material for catalysis, sensing, and energy storage applications. However, the commonly used NF often does not work satisfactorily due to its smooth surface and hollow structure of the ligaments. Herein, a gas-phase-induced engineering, two-step gaseous oxidation-reduction (GOR) is presented to directly transform the thin-walled hollow ligament of NF into a three-dimensional (3D) nanoporous prism structure, resulting in the fabrication of a unique hierarchical porous nickel foam (HPNF). This 3D nanoporous architecture is achieved by utilizing the spontaneous reconstruction of nickel atoms during volume expansion and contraction in the GOR process. The process avoids the involution of acid-base corrosion and sacrificial components, which are facile, environmentally friendly, and suitable for large-scale fabrication. Furthermore, MnO2 is electrochemically deposited on the HPNF to form a supercapacitor electrode (HPNF/MnO2). Because of the fully open structure for ion transport, superhydrophilic properties, and the increased contact area between MnO2 and the current collector, the HPNF/MnO2 electrode exhibits a high specific capacitance of 997.5 F g-1 at 3 A g-1 and remarkable cycling stability with 99.6% capacitance retention after 20000 cycles in 0.1 M Na2SO4 electrolyte, outperforming most MnO2-based supercapacitor electrodes.

Association Between Multisensory Impairment and Depression Among Older Adults: A Population-Based Analysis.

OBJECTIVE: In this study, we examine how impairments in vision, hearing, touch, and olfaction relate to depression in older adults, considering both individual and multisensory impairments (MSIs). STUDY DESIGN: Analysis of cross-sectional data from a longitudinal investigation involving black and white older adults aged 70 to 79 at enrollment. SETTING: We studied 1640 black and white participants in the Health ABC study using complete sensory evaluation data from years 3 to 5. METHODS: Our MSI assessment utilized data obtained for visual acuity, hearing perception, olfactory performance, and tactile function. We performed multivariable logistic regression analyses to examine the associations between the presence of individual and MSIs and depression which was defined as the presence of antidepressants prescribed for depression, or a Center for Epidemiological Studies Depression Scale score of greater than 10. RESULTS: We observed a possible dose-response relationship between the number of sensory impairments and depression. In adjusted models, when compared to no impairments, vision (odds ratio [OR] = 1.45, 95% confidence interval [CI]: 1.09-1.93) and hearing impairments (OR = 1.49, 95% CI: 1.11-1.99) were significantly associated with depression, whereas olfaction (OR = 1.11, 95% CI: 0.83-1.47) and tactile impairments (OR = 1.28, 95% CI: 0.96-1.70) were not. Participants with 3 sensory impairments had a higher rate of depression (OR = 2.05, 95% CI: 1.22-3.54) compared to those without impairments, and this risk increased further for those with 4 sensory impairments (OR = 2.95, 95% CI: 1.48-5.88). CONCLUSION: The findings suggest that individuals with MSI represent a high-risk population for depression, warranting close monitoring to screen for depression. The study emphasizes the importance of considering multiple sensory impairments in the context of mental health and supports the early identification and monitoring of depression in this population.

Validation of artificial intelligence-based bowel preparation assessment in screening colonoscopy (with video).

BACKGROUND AND AIMS: Accurate bowel preparation assessment is essential for determining colonoscopy screening intervals. Patients with suboptimal bowel preparation are at a high risk of missing >5 mm adenomas and should undergo an early repeat colonoscopy. In this study, we used artificial intelligence (AI) to evaluate bowel preparation and validated the ability of the system to accurately identify patients who are at high risk of having >5 mm adenomas missed due to inadequate bowel preparation. METHODS: This prospective, single-center, observational study was conducted at the Eighth Affiliated Hospital, Sun Yat-sen University, from October 8, 2021, to November 9, 2022. Eligible patients who underwent screening colonoscopy were consecutively enrolled. The AI assessed bowel preparation using the e-Boston Bowel Preparation Scale (e-BBPS) while endoscopists made evaluations using BBPS. If both BBPS and e-BBPS deemed preparation adequate, the patient immediately underwent a second colonoscopy; otherwise, the patient underwent bowel re-cleansing before the second colonoscopy. RESULTS: Among the 393 patients, 72 adenomas >5 mm in size were detected; 27 adenomas >5 mm in size were missed. In unqualified-AI patients, the >5 mm adenoma miss rate (AMR) was significantly higher than in qualified-AI patients (35.71% vs 13.19% [P = .0056]; odds ratio [OR], .2734 [95% CI, .1139-.6565]), as were the AMR (50.89% vs 20.79% [P < .001]; OR, .2532 [95% CI, .1583-.4052]) and >5 mm polyp miss rate (35.82% vs 19.48% [P = .0152]; OR, .4335 [95% CI, .2288-.8213]). CONCLUSIONS: This study confirmed that patients classified as inadequate by AI exhibited an unacceptable >5 mm AMR, providing key evidence for implementing AI in guiding bowel re-cleansing and potentially standardizing future colonoscopy screening. (Clinical trial registration number: NCT05145712.).

Exosome, a Rising Biomarkers in Liquid Biopsy: Advances of Label-Free and Label Strategy for Diagnosis of Cancer.

Cancer is commonly considered as one of the most severe diseases, posing a significant threat to human health and society due to various serious challenges. These challenges include difficulties in accurate diagnosis and a high propensity to form metastasis. Tissue biopsy remains the gold standard for diagnosing and subtyping cancer. However, concerns arise from its invasive nature and the potential risk of metastasis during these complex diagnostic procedures. Meanwhile, liquid biopsy has recently witnessed the rapid advancements with the emergence of three prominent detection biomarkers: circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Whereas, the very low abundance of CTCs combined with the instability of ctDNA intensify the challenges and decrease the accuracy of these two biomarkers for cancer diagnosis. While exosomes have gained widespread recognition as a promising biomarker in liquid biopsy due to their relatively low-invasive detection method, excellent biostability, rich resources, high abundance, and ability to provide valuable information about cancer. Therefore, it is crucial to systematically summarize recent advancements mainly in exosome-based detection methods for early cancer diagnosis. Specifically, this review will primarily focus on label-based and label-free strategies for detecting cancer using exosomes. We anticipate that this comprehensive analysis will enhance readers' understanding of the significance and value of exosomes in the fields of cancer diagnosis and therapy.

Identification of a DNA-methylome-based signature for prognosis prediction in driver gene-negative lung adenocarcinoma.

"Driver gene-negative" lung adenocarcinoma (LUAD) was of rare treatment options and a poor prognosis. Presently, for them, few biomarkers are available for stratification analysis to make appropriate treatment strategy. This study aimed to develop a DNA-methylome-based signature to realize the precise risk-stratifying. Here, an Illumina MethylationEPIC Beadchip was applied to obtain differentially methylated CpG sites (DMCs). A four-CpG-based signature, named as TLA, was successfully established, whose prognosis-predicting power was well verified in one internal (n = 78) and other external (n = 110) validation cohorts. Patients with high-risk scores had shorter overall survival (OS) in all cohorts [hazard ratio (HR): 11.79, 5.16 and 2.99, respectively]. Additionally, it can effectively divide patients into low-risk and high-risk groups, with significantly different OS in the diverse subgroups stratified by the standard clinical parameters. As an independent prognostic factor, TLA may assist in improving the nomogram's 5-year OS-predicting ability (AUC 0.756, 95% CI:0.695-0.816), superior to TNM alone (AUC 0.644, 95% CI: 0.590-0.698). Additionally, the relationship of TLA-related genes, TAC1, LHX9, and ALX1, with prognosis and tumour invasion made them serve as potential therapy targets for driver gene-negative LUAD.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

Multi-omic profiling reveals associations between the gut microbiome, host genome and transcriptome in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the leading cancer worldwide. Microbial agents have been considered to contribute to the pathogenesis of different disease. But the underlying relevance between CRC and microbiota remain unclear. METHODS: We dissected the fecal microbiome structure and genomic and transcriptomic profiles of matched tumor and normal mucosa tissues from 41 CRC patients. Of which, the relationship between CRC-associated bacterial taxa and their significantly correlated somatic mutated gene was investigated by exome sequencing technology. Differentially expressed functional genes in CRC were clustered according to their correlation with differentially abundant species, following by annotation with DAVID. The composition of immune and stromal cell types was identified by XCELL. RESULTS: We identified a set of 22 microbial gut species associated with CRC and estimate the relative abundance of KEGG ontology categories. Next, the interactions between CRC-related gut microbes and clinical phenotypes were evaluated. 4 significantly mutated gene: TP53, APC, KRAS, SMAD4 were pointed out and the associations with cancer related microbes were identified. Among them, Fusobacterium nucleatum positively corelated with different host metabolic pathways. Finally, we revealed that Fusobacterium nucleatum modified the tumor immune environment by TNFSF9 gene expression. CONCLUSION: Collectively, our multi-omics data could help identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC.

Air Pollutants and Risk of Parkinson's Disease among Women in the Sister Study.

BACKGROUND: Air pollutants may contribute to the development of Parkinson's disease (PD), but empirical evidence is limited and inconsistent. OBJECTIVES: This study aimed to prospectively investigate the associations of PD with ambient exposures to fine particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) and nitrogen dioxide (NO2). METHODS: We analyzed data from 47,108 US women from the Sister Study, enrolled from 2003-2009 (35-80 years of age) and followed through 2018. Exposures of interest included address-level ambient PM2.5 and NO2 in 2009 and their cumulative averages from 2009 to PD diagnosis with varying lag-years. The primary outcome was PD diagnosis between 2009 and 2018 (n=163). We used multivariable Cox proportional hazards and time-varying Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: NO2 exposure in 2009 was associated with PD risk in a dose-response manner. The HR and 95% CI were 1.22 (95% CI: 1.03, 1.46) for one interquartile [4.8 parts per billion (ppb)] increment in NO2, adjusting for age, race and ethnicity, education, smoking status, alcohol drinking, caffeine intake, body mass index, physical activity, census region, residential area type, area deprivation index (ADI), and self-reported health status. The association was confirmed in secondary analyses with time-varying averaged cumulative exposures. For example, the multivariable adjusted HR for PD per 4.8 ppb increment in NO2 was 1.25 (95% CI: 1.05, 1.50) in the 2-year lag analysis using cumulative average exposure. Post hoc subgroup analyses overall confirmed the association. However, statistical interaction analyses found that the positive association of NO2 with PD risk was limited to women in urban, rural, and small town areas and women with ≥50th percentile ADI but not among women from suburban areas or areas with <50th percentile ADI. In contrast, PM2.5 exposure was not associated with PD risk with the possible exception for women from the Midwest region of the US (HRinterquartile-range=2.49, 95% CI: 1.20, 5.14) but not in other census regions. DISCUSSION: In this nationwide cohort of US women, higher level exposure to ambient NO2 is associated with a greater risk of PD. This finding needs to be independently confirmed and the underlying mechanisms warrant further investigation. https://doi.org/10.1289/EHP13009.

Olfaction and Mobility in Older Adults.

Importance: Decreased mobility is a hallmark of aging. Olfactory dysfunction is common in older adults and may be associated with declines in mobility. Objective: To determine whether poor olfaction was associated with faster declines in mobility in older adults. Design, Setting, and Participants: This cohort study included 2500 participants from the Health, Aging, and Body Composition Study. Participants completed the Brief Smell Identification Test during the year 3 clinical visit (1999-2000) and were followed for up to 7 years. A data analysis was conducted between January and July 2023. Exposures: Olfaction was defined as good (test score, 11-12), moderate (9-10), hyposmia (7-8), or anosmia (0-6). Main Outcomes and Measures: Mobility was measured using the 20-m usual and fast walking tests in clinical visit years 3 to 6, 8, and 10 and the 400-m fast walking test in years 4, 6, 8, and 10. Results: The primary analyses included 2500 participants (1292 women [51.7%]; 1208 men [48.3%]; 960 Black [38.4%] and 1540 White [61.6%] individuals; mean [SD] age, 75.6 [2.8] years). Multivariate-adjusted analyses showed that poor olfaction was associated with slower walking speed at baseline and a faster decline over time. Taking the 20-m usual walking test as an example, compared with participants with good olfaction, the speed at baseline was 0.027 (95% CI, 0-0.053) m/s slower for those with hyposmia and 0.034 (95% CI, 0.005-0.062) m/s slower for those with anosmia. Longitudinally, the annual decline was 0.004 (95% CI, 0.002-0.007) m/s/year faster for those with hyposmia and 0.01 (95% CI, 0.007-0.013) m/s/year faster for those with anosmia. Similar results were obtained for the 20-m and 400-m fast walking tests. Further, compared with participants with good olfaction, the odds of being unable to do the 400-m test were 2.02 (95% CI, 1.17-3.48) times higher for those with anosmia at the year 8 visit and 2.73 (95% CI, 1.40-5.35) times higher at year 10. Multiple sensitivity and subgroup analyses supported the robustness and generalizability of the findings. Conclusion and Relevance: The results of this cohort study suggest that poor olfaction is associated with a faster decline in mobility in older adults. Future studies should investigate underlying mechanisms and potential health implications.

Polygenic risk score for Parkinson's disease and olfaction among middle-aged to older women.

INTRODUCTION: Olfactory impairment and Parkinson's disease (PD) may share common genetic and environmental risk factors. This study investigates the association of a PD polygenic risk score (PRS) with olfaction, and whether the associations are modified by environmental exposures of PM2.5, NO2, or smoking. METHODS: This analysis included 3358 women (aged 50-80) from the Sister Study with genetic data and results from the Brief Smell Identification Test (B-SIT) administered in 2018-2019. PD PRS was calculated using 90 single nucleotide polymorphisms. Olfactory impairment was defined with different B-SIT cutoffs, and PD diagnosis was adjudicated via expert review. We report odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression. RESULTS: As expected, PD PRS was strongly associated with the odds of having PD (OR highest vs. lowest quartile = 3.79 (1.64, 8.73)). The highest PRS quartile was also associated with olfactory impairment, with OR ranging from 1.24 (0.98, 1.56) for a B-SIT cutoff of 9 to 1.42 (1.04, 1.92) for a cutoff of 6. For individual B-SIT items, the highest PRS quartile was generally associated with lower odds of correctly identifying the odorant, albeit only statistically significant for pineapple (0.72 (0.56, 0.94), soap (0.76 (0.58, 0.99)) and rose (0.70 (0.54, 0.92)). The association of PD PRS with olfactory impairment was not modified by airborne environmental exposures or smoking. CONCLUSION: These preliminary data suggest that high PD genetic susceptibility is associated with olfactory impairment in middle-aged and older women.

Comparative analysis of the vaginal microbiome of healthy and polycystic ovary syndrome women: a large cross-sectional study.

RESEARCH QUESTION: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women? DESIGN: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n = 733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated. RESULTS: The PCOS group had a higher alpha diversity than the control group (Shannon P = 0.03, Simpson P = 0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR] = 0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR = 0.006; 1.2% versus 0.6%, FDR = 0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-Müllerian hormone (AMH), and triglyceride (P = 2.01E-05, P = 0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P = 0.002, P = 0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P = 0.004, P = 0.005, P = 0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25). CONCLUSIONS: The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.

Targeting inhibition of prognosis-related lipid metabolism genes including CYP19A1 enhances immunotherapeutic response in colon cancer.

BACKGROUND: Lipid metabolic reprogramming in colon cancer shows a potential impact on tumor immune microenvironment and is associated with response to immunotherapy. Therefore, this study aimed to develop a lipid metabolism-related prognostic risk score (LMrisk) to provide new biomarkers and combination therapy strategies for colon cancer immunotherapy. METHODS: Differentially expressed lipid metabolism-related genes (LMGs) including cytochrome P450 (CYP) 19A1 were screened to construct LMrisk in TCGA colon cancer cohort. The LMrisk was then validated in three GEO datasets. The differences of immune cell infiltration and immunotherapy response between LMrisk subgroups were investigated via bioinformatic analysis. These results were comfirmed by in vitro coculture of colon cancer cells with peripheral blood mononuclear cells, human colon cancer tissue microarray analysis, multiplex immunofluorescence staining and mouse xenograft models of colon cancer. RESULTS: Six LMGs including CYP19A1, ALOXE3, FABP4, LRP2, SLCO1A2 and PPARGC1A were selected to establish the LMrisk. The LMrisk was positively correlated with the abundance of macrophages, carcinoma-associated fibroblasts (CAFs), endothelial cells and the levels of biomarkers for immunotherapeutic response including programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden and microsatellite instability, but negatively correlated with CD8+ T cell infiltration levels. CYP19A1 protein expression was an independent prognostic factor, and positively correlated with PD-L1 expression in human colon cancer tissues. Multiplex immunofluorescence analyses revealed that CYP19A1 protein expression was negatively correlated with CD8+ T cell infiltration, but positively correlated with the levels of tumor-associated macrophages, CAFs and endothelial cells. Importantly, CYP19A1 inhibition downregulated PD-L1, IL-6 and TGF-ß levels through GPR30-AKT signaling, thereby enhancing CD8+ T cell-mediated antitumor immune response in vitro co-culture studies. CYP19A1 inhibition by letrozole or siRNA strengthened the anti-tumor immune response of CD8+ T cells, induced normalization of tumor blood vessels, and enhanced the efficacy of anti-PD-1 therapy in orthotopic and subcutaneous mouse colon cancer models. CONCLUSION: A risk model based on lipid metabolism-related genes may predict prognosis and immunotherapeutic response in colon cancer. CYP19A1-catalyzed estrogen biosynthesis promotes vascular abnormality and inhibits CD8+ T cell function through the upregulation of PD-L1, IL-6 and TGF-ß via GPR30-AKT signaling. CYP19A1 inhibition combined with PD-1 blockade represents a promising therapeutic strategy for colon cancer immunotherapy.

Coupling CO2-to-Ethylene Reduction with the Chlor-Alkaline Process in Seawater through In Situ-Formed Cu Catalysts.

The overall commercial value of a CO2 electroreduction system is hindered by the valueless product and high energy consumption of the oxygen evolution reaction (OER) at the anode. Herein, with an in situ-formed copper catalyst, we employed the alternative chlorine evolution reaction for OER, and high-speed formation of both C2 products and hypochlorite in seawater can be realized. The EDTA in the sea salt electrolyte can trigger an intense dissolution and deposition of Cu on the surface of the electrode, resulting in the in situ formation of dendrites of Cu with high chemical activity. In this system, a faradaic efficiency of 47% can be realized for C2H4 production at the cathode and a faradaic efficiency of 85% can be realized for hypochlorite production at the anode with an operation current of 100 mA/cm2. This work presents a system for designing a highly efficient coupling system for the CO2 reduction reaction and alternative anodic reactions toward value-added products in a seawater environment.

Tumor immune microenvironment components and the other markers can predict the efficacy of neoadjuvant chemotherapy for breast cancer.

Breast cancer is an epithelial malignant tumor that occurs in the terminal ducts of the breast. Neoadjuvant chemotherapy (NACT) is an important part of breast cancer treatment. Its purpose is to use systemic treatment for some locally advanced breast cancer patients, to decrease the tumor size and clinical stage so that non-operable breast cancer patients can have a chance to access surgical treatment, or patients who are not suitable for breast-conserving surgery can get the opportunity of breast-conserving. However, some patients who do not respond to NACT will lead deterioration in their condition. Therefore, prediction of NACT efficacy in breast cancer is vital for precision therapy. The tumor microenvironment (TME) has a crucial role in the carcinogenesis and therapeutic response of breast cancer. In this review, we summarized the immune cells, immune checkpoints, and other biomarkers in the TME that can evaluate the efficacy of NACT in treating breast cancer. We believe that the detection and evaluation of the TME components in breast cancer are helpful to predict the efficacy of NACT, and the prediction methods are in the prospect. In addition, we also summarized other predictive factors of NACT, such as imaging examination, biochemical markers, and multigene/multiprotein profiling.

Case report: Cholesterol granuloma of femur.

Background: Cholesterol granuloma (CG) is a particular type of granulation tissue reaction. It is a very rare benign lesion characterized by swelling growth due to a large number of cholesterol crystals and foreign body giant cells. There has been no report of a CG of the femur. Case presentation: A 74-year-old woman suffered from pain and discomfort in the upper right knee for 10 years, which became aggravated for 10 days. She was diagnosed with CG of the right femur at our hospital and was treated with surgery. During the operation, a large amount of yellow-brown, oily, crystal structures was found. Postoperative pathology investigations confirmed the lesion as a CG. Postoperative follow-up was carried out for 15 months that confirmed the effect of treatment was satisfactory. Conclusions: CG of the femur is an extremely rare benign lesion. Surgical treatment can provide effective treatment results.

GOLM1 and FAM49B: Potential Biomarkers in HNSCC Based on Bioinformatics and Immunohistochemical Analysis.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. We aimed to identify potential genetic markers that could predict the prognosis of HNSCC. A total of 44 samples of GSE83519 from Gene Expression Omnibus (GEO) datasets and 546 samples of HNSCC from The Cancer Genome Atlas (TCGA) were adopted. The differently expressed genes (DEGs) of the samples were screened by GEO2R. We integrated the expression information of DEGs with clinical data from GES42743 using the weighted gene co-expression network analysis (WGCNA). A total of 17 hub genes were selected by the module membership (|MM| > 0.8), and the gene significance (|GS| > 0.3) was selected from the turquoise module. GOLM1 and FAM49B genes were chosen based on single-gene analysis results. Survival analysis showed that the higher expression of GOLM1 and FAM49B genes was correlated with a worse prognosis of HNSCC patients. Immunohistochemistry and multiplex immunofluorescence techniques verified that GOLM1 and FAM49B genes were highly expressed in HNSCC cells, and high expressions of GOLM1 were associated with the pathological grades of HNSCC. In conclusion, our study illustrated a new insight that GOLM1 and FAM49B genes might be used as potential biomarkers to determine the development of HNSCC, while GOLM1 and FAM49B have the possibility to be prognostic indicators for HNSCC.

BAF53A drives colorectal cancer development by regulating DUSP5-mediated ERK phosphorylation.

BAF53A, an important subunit of the SWI/SNF epigenetic chromatin regulatory complex, has been implicated as the driver of diverse cancers. However, the role of BAF53A in colorectal cancer (CRC) remains poorly understood. Here, we examined the expression of BAF53A in CRC samples and observed that BAF53A was significantly upregulated in CRC tissues compared with paired adjacent normal tissues. In vitro and in vivo studies suggested that ectopic expression of BAF53A promoted colorectal cancer cell proliferation, colony formation, and tumorigenesis, whereas knockdown of BAF53A hindered these cellular functions. DUSP5 (dual-specificity phosphatase 5), an ERK1/2-specific endogenous phosphatase, was expressed at low levels in CRC. We found a negative correlation between BAF53A and DUSP5 expression in a set of CRC samples. Mechanistic studies revealed that P63 was a potential transcription repressor of DUSP5. BAF53A could interact with P63, decreasing the DUSP5 expression level and subsequently promoting ERK1/2 phosphorylation. Thus, our study provides insights into the applicability of the BAF53A-DUSP5-ERK1/2 axis as a potential therapeutic target in CRC.

Associations among Visual, Auditory, and Olfactory Functions in Community-Based Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.

Purpose: Objective examination of relationships among visual, hearing, and olfactory function may yield mechanistic insights and inform our understanding of the burden of multiple-sensory impairments. Methods: This cross-sectional study capitalized on continuous measures of visual acuity (VA), contrast sensitivity, pure tone audiometry, Quick Speech-in-Noise (QuickSIN), and Sniffin' Sticks from a subset of ARIC participants at two community sites (EyeDOC Study, 2017-2019). Scales of all measures were aligned such that higher values indicated greater impairment. Intersensory bivariate associations were assessed graphically, and correlations assessed using Kendall's tau. Intersensory associations, independent of age, education, smoking, diabetes, and hypertension, were examined using linear regression. Analyses were stratified by community/race (Washington County/White vs Jackson/Black) and sex (men vs women) to explore community-sex heterogeneity. Results: We included 834 participants (mean age, 79 years); 39% were from Jackson and 63% females. We found weak intersensory correlations (tau generally ≤0.15). In the demographics-adjusted regression models, results were heterogeneous across communities and sex. Worse near VA, contrast sensitivity, and olfaction were associated with worse QuickSIN and worse near VA was associated with worse olfaction in some but not all community/race-sex groups (e.g., Jackson/Black women, 0.1 logMAR worse near VA was associated with 0.27 units increase in QuickSIN [95% confidence interval, 0.10-0.45]). Associations were modestly attenuated by adjustment for the shared risk factors of smoking, diabetes, and hypertension. Conclusions: Visual dysfunction showed little or no association with hearing or olfaction impairments, suggesting a modest role for shared risk factors. Translational Relevance: Visually impaired individuals have only a modestly higher risk of other sensory impairment.

A novel hypoxia-driven gene signature that can predict the prognosis and drug resistance of gliomas.

Hypoxia spontaneously forms in the interior of glioma tissues and regulates the expression of various genes. However, the status of hypoxia-driven genes in glioma tissues is not completely known. In the current study, RNA-seq data of 695 glioma tissues in The Cancer Genome Atlas (TCGA) were set as a discovery cohort and were used to identify hypoxia-driven genes and construct a novel gene signature. The prognostic values of that signature were verified in data from the TCGA and the Chinese Glioma Genome Atlas (CGGA). The expression and diagnostic values of hypoxia-driven genes were analyzed using immunohistochemistry and receiver operator characteristic curves. Finally, the effects of hypoxia-driven genes on temozolomide (TMZ) resistance were analyzed by western blot, CCK-8 and colony formation assay. A total of 169 hypoxia-driven genes were identified, which were associated with a poor outcome in glioma patients. Among them, 22 genes had a degree score ≥10 and 6 genes (WT1, HOXA2, HOXC6, MMP9, SHOX2 and MYOD1) were selected to construct a signature to classify glioma patients into low- or high-risk groups. That signature had a remarkable prognostic value for glioma patients in TCGA and CGGA. The expression of HOXC6, MMP9, SHOX2 and MYOD1 was associated with hypoxia degree in glioma tissues and in recurrent cases, had a remarkable diagnostic value and a significant relationship with disease free survival in glioma patients. Moreover, SHOX2 was highly expressed in glioma tissues with O-6-methylguanine-DNA methyltransferase (MGMT)-unmethylation and temozolomide (TMZ) resistant glioma cell lines, and associated with MGMT expression. Knockdown the expression of SHOX2 significantly reduced the TMZ-resistance induced by hypoxia in glioma cells. Ultimately, we identified six novel hypoxia-driven genes for reliable prognostic prediction in gliomas and found that SHOX2 might be a potential target to overcome the TMZ resistance induced by hypoxia.