Highly efficient iron-catalyzed conjugate reduction of α,ß-unsaturated ketones with polymethylhydrosiloxane.

An iron-catalyzed ligand free conjugate reduction of α,ß-unsaturated ketones with PMHS (polymethylhydrosiloxane) was reported to deliver the corresponding carbonyl compounds with up to 93% yield. This operationally simple protocol shows a broad substrate scope using readily available PMHS as a cost-effective and easy-to-handle reductive reagent.

Development and validation of an early diagnosis model for bone metastasis in non-small cell lung cancer based on serological characteristics of the bone metastasis mechanism.

Background: Bone metastasis significantly impact the prognosis of non-small cell lung cancer (NSCLC) patients, reducing their quality of life and shortening their survival. Currently, there are no effective tools for the diagnosis and risk assessment of early bone metastasis in NSCLC patients. This study employed machine learning to analyze serum indicators that are closely associated with bone metastasis, aiming to construct a model for the timely detection and prognostic evaluation of bone metastasis in NSCLC patients. Methods: The derivation cohort consisted of 664 individuals with stage IV NSCLC, diagnosed between 2015 and 2018. The variables considered in this study included age, sex, and 18 specific serum indicators that have been linked to the occurrence of bone metastasis in NSCLC. Variable selection used multivariate logistic regression analysis and Lasso regression analysis. Six machine learning methods were utilized to develop a bone metastasis diagnostic model, assessed with Area Under the Curve (AUC), Decision Curve Analysis (DCA), sensitivity, specificity, and validation cohorts. External validation used 113 NSCLC patients from the Medical Alliance (2019-2020). Furthermore, a prospective validation study was conducted on a cohort of 316 patients (2019-2020) who were devoid of bone metastasis, and followed-up for at least two years to assess the predictive capabilities of this model. The model's prognostic value was evaluated using Kaplan-Meier survival curves. Findings: Through variable selection, 11 serum indictors were identified as independent predictive factors for NSCLC bone metastasis. Six machine learning models were developed using age, sex, and these serum indicators. A random forest (RF) model demonstrated strong performance during the training and internal validation cohorts, achieving an AUC of 0.98 (95% CI 0.95-0.99) for internal validation. External validation further confirmed the RF model's effectiveness, yielding an AUC of 0.97 (95% CI 0.94-0.99). The calibration curves demonstrated a high level of concordance between the anticipated risk and the observed risk of the RF model. Prospective validation revealed that the RF model could predict the occurrence of bone metastasis approximately 10.27 ± 3.58 months in advance, according to the results of the SPECT. An online computing platform (https://bonemetastasis.shinyapps.io/shiny_cls_1model/) for this RF model is publicly available and free-to-use by doctors and patients. Interpretation: This study innovatively employs age, gender, and 11 serological markers closely related to the mechanism of bone metastasis to construct an RF model, providing a reliable tool for the early screening and prognostic assessment of bone metastasis in NSCLC patients. However, as an exploratory study, the findings require further validation through large-scale, multicenter prospective studies. Funding: This work is supported by the National Natural Science Foundation of China (NO.81974315); Shanghai Municipal Science and Technology Commission Medical Innovation Research Project (NO.20Y11903300); Shanghai Municipal Health Commission Health Industry Clinical Research Youth Program (NO.20204Y034).

Spike timing-based coding in neuromimetic tactile system enables dynamic object classification.

Rapid processing of tactile information is essential to human haptic exploration and dexterous object manipulation. Conventional electronic skins generate frames of tactile signals upon interaction with objects. Unfortunately, they are generally ill-suited for efficient coding of temporal information and rapid feature extraction. In this work, we report a neuromorphic tactile system that uses spike timing, especially the first-spike timing, to code dynamic tactile information about touch and grasp. This strategy enables the system to seamlessly code highly dynamic information with millisecond temporal resolution on par with the biological nervous system, yielding dynamic extraction of tactile features. Upon interaction with objects, the system rapidly classifies them in the initial phase of touch and grasp, thus paving the way to fast tactile feedback desired for neuro-robotics and neuro-prosthetics.

Disulfidptosis status influences prognosis and therapeutic response in clear cell renal cell carcinoma.

Disulfidptosis is a recently identified type of programmed cell death. It is characterized by aberrant accumulation of intracellular disulfides. The clinical implications of disulfidptosis in clear cell renal cell carcinoma (ccRCC) remain unclear. A series of bioinformatics approaches were employed to analyze ten disulfidptosis-related molecules. Firstly, the expression patterns of the disulfidptosis-related molecules were different between normal and ccRCC tissues. A comprehensive cohort of patients with ccRCC was then assembled from three public databases and subjected to cluster analysis based on disulfidptosis-related molecules. Consensus cluster analysis revealed three distinct disulfidptosis clusters. We then conducted weighted gene co-expression network analysis (WGCNA) to identify highly correlated genes. 267 hub genes were screened out through WGCNA, and three gene clusters were then determined. Finally, we identified 87 genes with prognostic value and then used them to develop a disulfidptosis scoring (DSscore) system, which was proven to independently predict survival in ccRCC. Patients in the high-DSscore group exhibited a significant survival advantage and better immunotherapeutic responses compared with those in the low-DSscore group. However, the patients in the low-DSscore group exhibited a greater degree of chemotherapeutic response. In addition, the expression of disulfidptosis-related molecules was validated by qRT-PCR, and the potential of disulfidptosis-related molecules to indicate distinct cell subtypes were validated by single-cell RNA-sequencing. In conclusion, DSscore is a promising index for predicting the prognosis and efficacy of immunotherapy in patients with ccRCC and may provide a basis for novel strategies for future studies.

Characterizing Genetic Alterations Related to Radioiodine Avidity in Metastatic Thyroid Cancer.

CONTEXT: Patients with differentiated thyroid cancer (DTC) with distant metastasis (DM) are usually not recognized as radioactive iodine (RAI)-refractory DTC in a timely manner. The elucidation of genetic features related to RAI uptake patterns may shed light on the early recognition of RAI-refractory DTC. OBJECTIVE: This work aimed to elucidate the underlying molecular features behind different RAI uptake patterns. METHODS: A total of 214 patients with DM-DTC were retrospectively included in the analysis. RAI uptake patterns were defined as initially RAI refractory (I-RAIR) and initially RAI avid (I-RAIA) according to the first post-treatment scan, then I-RAIA was further divided into continually RAIA (C-RAIA), partly RAIR (P-RAIR), and gradually RAIR (G-RAIR) according to subsequent scans. The molecular subtype groups-BRAFV600E mutated, RAS mutated, fusions, and others-were classified according to main driver genes status. RESULTS: BRAF, TERT promoter, and TP53 mutations are more frequently detected in the I-RAIR pattern while RET fusions and RAS mutations are more frequent in the I-RAIA pattern. A late-hit mutation including TERT, TP53, or PIK3CA is more common in I-RAIR than that in I-RAIA (50.0% vs 26.9%, P = .001), particularly for those with RAS mutations in the I-RAIR group, always accompanied by TERT promoter. Isolated RET fusions accounts for 10% of I-RAIR. When compared among driver gene groups, BRAFV600E-mutated tumors have a higher rate of the I-RAIR pattern (64.4%) than RAS-mutated (4.5%, P < .001) and fusion-positive (20.7%, P < .001) tumors. In I-RAIA subgroups, BRAFV600E-mutated tumors have lower prevalence of the C-RAIA pattern than those with RAS mutation or fusions. CONCLUSION: Patients with the I-RAIR pattern predominantly featured mutations of the BRAF and/or TERT promoter, of which RAS mutations were usually accompanied by late-hit mutations, while fusions mostly occurred alone.

Evolution characteristics of micromechanics provides insights into the microstructure of pharmaceutical tablets fabricated by bimodal mixtures.

This research focuses on the evolution of mechanical behavior of bimodal mixtures undergoing compaction and diametrical compression. The clusters were built and discrete element method (DEM) was used to investigate the densification process and micromechanics of bimodal mixtures. Additionally, a more comprehensive investigate of the respective breakage of the bimodal mixtures has been carried out. On this basis, qualitative and quantitative analysis of the compressive force, force chain, contact bonds and density field evolution characteristics of the clusters are investigated during the compression process. The entire loading process of the clusters is divided into three stages: rearrangement, breakage and elastic-plastic deformation. Additionally, there are differences in the evolution of micromechanics behavior of different particles in the bimodal mixture, with pregelatinized starch breakage and deformation occurring before microcrystalline cellulose. With the tablet deformation, the fragmentation process of the tablet started at the point of contact and extended toward the center, and the curvature of the force chain increased. This approach may potentially hold a valuable new information relevant to important transformation forms batch manufacturing to advanced manufacturing for the oral solid dosage form.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

Thyroid Accumulation of 99m Tc-DTPA in Graves Disease.

ABSTRACT: 99m Tc-DTPA dynamic renal scintigraphy for evaluating glomerular filtration rate was performed in a 29-year-old woman with hyperuricemia and Graves disease. Subsequently, 99m Tc-DTPA orbital scintigraphy was conducted to determine the activity of Graves ophthalmopathy. Thyroid accumulation of 99m Tc-DTPA was incidentally identified. This should be cautiously distinguished from 99m Tc-pertechnetate uptake, considering that the salivary glands, oral cavity, and stomach were not visualized. Our case demonstrates that augmentation of blood supply, enhancement of capillary permeability, and accumulation of inflammatory exudate may be involved in the pathological process of Graves disease.

Second radioiodine treatment hardly benefits TT-DTC patients with radioiodine-negative metastases on initial post-therapeutic whole-body scans.

BACKGROUND: The effect of second 131I treatment (RT) in totally thyroidectomized differentiated thyroid cancer (TT-DTC) patients with true-positive thyroid beds and false-negative metastasis (TB+/M-) on initial post-therapeutic whole-body scan (Rx-WBS) remains unknown. METHODS: TT-DTC patients with TB+/M- on initial Rx-WBS receiving and not receiving second RT were categorized into group A and group B, respectively, while patients with 131I-avid metastasis receiving second RT were referred to as group C. Biochemical remission (BR) was defined as a decrease of ≥25.0% in thyrotropin-suppressed thyroglobulin (Tgon) level, while the structural response (SR) was determined by the change in the size of the largest lesion. RESULTS: In total, 145 patients were eligible. In group A, the median Tgon measured 3.3 ng/mL before and 3.0 ng/mL at 4 months after second RT (P=0.307), yielding a decrease in the median Tgon (∆Tgon%) of 13.3%, a BR rate of 36%, and an insignificant SR, which were comparable to those in group B. In group C, however, a median ∆Tgon% of 37.8% and a BR rate of 64% were obtained, which were significantly higher than those in group A (P=0.038 and 0.022, respectively), with SR distributions similar to those in group A. In addition, 131I uptake in the neck was not statistically associated with the detection of metastasis on initial Rx-WBS. CONCLUSIONS: This controlled study demonstrated a subtle response to second RT in TT-DTC patients with TB+/M- on initial Rx-WBS, representing a meaningful advancement in avoiding ineffective repeated RT.

m6A-mediated upregulation of lncRNA RMRP boosts the progression of bladder cancer via epigenetically suppressing SCARA5.

Aim: This study aimed to elucidate the relationship between SCARA5 and RMRP in bladder cancer and their underlying mechanism. Methods: Biological functions were evaluated using cell-counting kit 8 assay, 5-ethynyl-2'-deoxyuridine incorporation, wound healing and Transwell assays. RNA immunoprecipitation, RNA pull-down and chromatin immunoprecipitation were employed. A xenograft tumor model in nude mice was also conducted. Results & conclusion: RMRP and SCARA5 exhibited an inverse correlation. Downregulation of RMRP significantly suppressed bladder cancer cell proliferation, migration and invasion, which was reversed by SCARA5 overexpression. RMRP recruited DNA methyltransferases to the promoter region of SCARA5, thereby triggering the methylation of the SCARA5 promoter to epigenetically suppress its expression. Our findings elucidate the machinery by which RMRP, stabilized by METTL3, exerts a promoter role in bladder cancer tumorigenesis by triggering SCARA5 methylation.

SCARA5 as a downstream factor of PCAT29, inhibits proliferation, migration, and invasion of bladder cancer.

Scavenger receptor class A, member 5 (SCARA5) has been identified a novel tumor suppressor in several cancers. However, the functional and underlying mechanism of SCARA5 in bladder cancer (BC) need investigation. Here, we found SCARA5 expression was downregulated in both BC tissues and cell lines. Low SCARA5 in BC tissues was associated with a shorter overall survival. Moreover, SCARA5 overexpression reduced BC cell viability, colony formation, invasion, and migration. Further investigation demonstrated that the expression of SCARA5 was negatively regulated by miR-141. Furthermore, the long non-coding RNA prostate cancer associated transcript 29 (PCAT29) inhibited the proliferation, invasion, and migration of BC cells by sponging miR-141. Luciferase activity assays revealed that PCAT29 targeted miR-141 and miR-141 targeted SCARA5. In conclusion, SCARA5, as a downstream factor of the PCAT29/miR-141 axis, inhibited the proliferation, migration, and invasion of BC cells. These findings provide novel insights into the detailed molecular mechanisms of BC development.

Epigenetic Targets and Their Inhibitors in Thyroid Cancer Treatment.

Although biologically targeted therapies based on key oncogenic mutations have made significant progress in the treatment of locally advanced or metastatic thyroid cancer, the challenges of drug resistance are urging us to explore other potentially effective targets. Herein, epigenetic modifications in thyroid cancer, including DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling and RNA alterations, are reviewed and epigenetic therapeutic agents for the treatment of thyroid cancer, such as DNMT (DNA methyltransferase) inhibitors, HDAC (histone deacetylase) inhibitors, BRD4 (bromodomain-containing protein 4) inhibitors, KDM1A (lysine demethylase 1A) inhibitors and EZH2 (enhancer of zeste homolog 2) inhibitors, are updated. We conclude that epigenetics is promising as a therapeutic target in thyroid cancer and further clinical trials are warranted.

Explore the diagnostic performance of 2020 Chinese Thyroid Imaging Reporting and Data Systems by comparing with the 2017 ACR-TIRADS guidelines: a single-center study.

OBJECTIVE: To compare the diagnostic efficacy of the Chinese Thyroid Imaging Reporting and Data Systems (C-TIRADS) with the well-accepted ACR-TIRADS guidelines in identifying benign from malignant thyroid nodules. METHODS: A total of 2064 nodules were collected from 1627 patients undergoing thyroid ultrasonography in our center between October 2019 and November 2021. Nodules were divided into two groups: "≥1 cm" and "<1 cm". Ultrasound features of each nodule were observed and recorded by two physicians with more than 15 years of experience and classified according to the ACR-TIRADS and C-TIRADS guidelines, respectively. RESULTS: The area under the curve of the ACR-TIRADS guideline was higher than that of the C-TIRADS guideline (0.922, P = 0.017), the specificity and positive predictive value of the C-TIRADS guideline were higher (81.64%, 88.72%, all P < 0.05), which was more significant in the subgroup of nodules <1 cm (P = 0.001). In addition, there was no statistical difference between the two guidelines in the diagnostic efficacy indicators for nodules ≥1 cm. The ACR-TIRADS effectively reduced unnecessary biopsies compared with the C-TIRADS (P < 0.05). CONCLUSIONS: There was high agreement between the two guidelines for the diagnosis of thyroid nodules, C-TIRADS guidelines had a higher specificity and simplicity while were inferior to the ACR-TIRADS guidelines in terms of reducing the number of biopsies.

Verification of the detachment-transport coupling relationship of rill erosion using colluvium material in steep nonerodible slopes.

The detachment-transport coupling equation by Foster and Meyer is a classical equation that describes the relationship between detachment and transport. The equation quantifies the relationship between sediment loads and soil detachment rates, deepens the understanding of soil erosion and provides a reliable basis for the establishment of an erosion model. However, the applicability of this equation to slopes with gradients greater than 47% is limited. In this work, the detachment-transport coupling relationship is investigated using the colluvium material of Benggang. A nonerodible rill flume 4 m long and 0.12 m wide was adopted. The slope gradient ranged from 27% to 70%, the unit flow discharge ranged from 0.56 × 10-3 to 3.33 × 10-3 m2 s-1, and the sediment transport capacity (Tc ) was measured under each slope and discharge combination. The sediment was inputted into the flume according to the predetermined sediment addition rate (from 0% to 100% of Tc ), and the detachment rate (Dr ) under each combination of the slope and discharge was measured. Dr linearly decreased with increasing sediment loads, which is consistent with the detachment-transport coupling equation by Foster and Meyer. The linear equations can predict the detachment capacity (Dc ) and Tc well (Nash-Sutcliffe efficiency coefficient (NSE) = 0.98 for Dc , and NSE = 0.99 for Tc ). The detachment-transport coupling equation can adequately predict the Dr (NSE = 0.89). However, its applicability to slopes of <47% (NSE: 0.92-0.96) was greater than that to slopes of ≥47% (NSE: 0.81-0.89), and the predicted Dr under Tc levels of 20% and 40% were higher than the measured values, while the predicted value under a Tc level of 80% was lower than the measured value. In summary, the detachment-transport coupling equation by Foster and Meyer can accurately reflect the negative feedback relationship between detachments and transports along steep-slope fixed beds and is suitable for colluvial deposit research. The results provide a basis for the construction of steep-slope colluvial deposit erosion models. In the future, the study of the hydrodynamic characteristics of sediment transport processes should be strengthened to clarify the detachment-transport effect of flows through hydrodynamics.

Ambient temperature variability and hospital admissions for pneumonia: A nationwide study.

Few investigations have assessed the impact of short-term ambient temperature change on pneumonia risk. We aimed to study the relation of temperature variability (TV) with daily hospitalizations for pneumonia in China. We conducted a time-series study in 184 major cities by extracting daily hospital data between 2014 and 2017 from a medical insurance claims database of 0.28 billion beneficiaries. TV was calculated as standard deviation of daily minimum and maximum temperatures over exposure days. We estimated associations of pneumonia admissions with TV for each city using over-dispersed generalized linear models controlling for weather conditions and ambient air pollution, and pooled city-specific estimates using random effects meta-analyses. We also investigated exposure-response relationship curve and potential effect modifiers. We identified 4.2 million pneumonia hospitalizations during the study period. TV was positively related to daily pneumonia admissions. At the national-average level, each 1-°C increase in TV at 0-6 days' exposure corresponded to a 0.65 % (95 % CI: 0.34 %-0.96 %) increase in pneumonia admissions. An approximately linear exposure-response curve for the relation of TV with pneumonia admission was noted. The relations were more evident in cities with larger average age (P = 0.038). As the first study in China to assess the impact of temperature change on pneumonia on a national scale, our results indicated that acute TV exposure was related to higher admissions for pneumonia. Our findings should provide new insight into the health impacts associated with climate change.

Diagnostic Performance of Contrast-Enhanced Ultrasound and High-Resolution Magnetic Resonance Imaging for Carotid Atherosclerotic Plaques: A Systematic Review and Meta-Analysis.

OBJECTIVES: The aim of this meta-analysis was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) and high-resolution magnetic resonance imaging (HR-MRI) in patients with carotid vulnerable plaques. METHODS: A systematic review was conducted in PubMed, Embase, Cochrane Library, and Web of Science using the search terms carotid artery, atherosclerotic plaque, CEUS, contrast-enhanced ultrasound, HR-MRI, and high-resolution magnetic resonance. Studies published since the establishment of the library until December 2021 were retrieved. The statistical analyses were performed with Meta-DiSc version 1.4. Beyond that, the potential sources of heterogeneity for CEUS and HR-MRI were explored. RESULTS: Nine articles were included in this study. For CEUS, the pooled sensitivity and specificity for detecting carotid vulnerable plaques 91% (95% confidence interval [CI]: 84%, 95%) and 67% (95% CI: 54%, 79%), respectively. For HR-MRI, the pooled sensitivity and specificity were 78% (95% CI: 72%, 83%) and 65% (95% CI, 56%, 73%), respectively. The area under the summary receiver operating characteristic curve for CEUS and HR-MRI were 0.9218 and 0.8129, respectively. However, the difference in diagnostic accuracy between CEUS and HR-MRI diagnostic accuracy was not statistically significant. CONCLUSIONS: The study shows that the sensitivity of CEUS was higher than that of HR-MRI, and the specificity was similar to HR-MRI. CEUS and HR-MRI provide a similar diagnostic yield in detecting a vulnerable plaque. Thus, CEUS may be a useful tool for the diagnosis of carotid vulnerable plaques.

Diagnosis and Treatment of Acute Pleural Effusion following Radioiodine Remnant Ablation Post Lobectomy for Thyroid Cancer.

Radioiodine remnant ablation (RRA) was previously demonstrated to be a safe and effective alternative to completion thyroidectomy for patients with differentiated thyroid cancer (DTC). However, its side effects have not been fully investigated, particularly in patients with lobectomy. We reported a young euthyroidal female who underwent RRA post lobectomy and lymph node dissection for papillary thyroid cancer, whose post-ablation 131I-whole-body scan accidentally showed diffuse radioiodine distribution on chest-mimicking pulmonary metastases. Immediately-added single-photon emission computed tomography/computed tomography (SPECT/CT), nevertheless, revealed a 131I-accumulating swollen left thyroid lobe and emerging pleural effusion, which relieved after short-term treatment with prednisone. In summary, acute pleural effusion ascribed to RRA-induced thoracic duct compression was reported for the first time. 131I-lobectomy-induced pleural effusion could be precisely diagnosed by SPECT/CT and efficiently manipulated via treating radiation thyroiditis with the short-term administration of corticosteroid.

ERBB2 as a prognostic biomarker correlates with immune infiltrates in papillary thyroid cancer.

Epidermal growth factor receptor 2 (ERBB2) is commonly over-expressed in advanced or metastatic tissues of papillary thyroid cancer (PTC) with poor prognosis, while it remains unknown whether ERBB2 plays a role in the progression of PTC. Thus, we analyzed the data derived from online repositories, including TCGA, KEGG, GO, GeneMANIA, and STRING, to explore the relationship between ERBB2 expression and prognosis, tumor phenotypes of interest, and immune infiltrates in PTC. Compared to normal thyroid tissue, ERBB2 was up-regulated in PTC samples (p < 0.001); In comparison with the group with low expression of ERBB2, the group with high expression of ERBB2 had poorer progression-free interval in stage III/IV patients (p = 0.008) and patients aged >45 years (p = 0.019). The up-regulated ERBB2 was associated with iodine metabolism dysfunction, proliferation, metastasis, angiogenesis, and drug resistance. The expression of ERBB2 negatively correlated with enrichment scores of B cells (r = -0.176, p < 0.001), CD8+ T cells (r = -0.160, p < 0.001), cytotoxic cells (r = -0.219, p < 0.001), NK CD56dim cells (r = -0.218, p < 0.001), plasmacytoid dendritic cells (r = -0.267, p < 0.001), T cells (r = -0.164, p < 0.001), T follicular helper cells (r = -0.111, p = 0.012), gamma delta T cells (r = -0.105, p = 0.017), and regulatory T cells (r = -0.125, p = 0.005). In conclusion, ERBB2 may serve as a prognostic biomarker and an immunotherapeutic target in PTC, deserving further exploration.

PDCD5 inhibits progression of renal cell carcinoma by promoting T cell immunity: with the involvement of the HDAC3/microRNA-195-5p/SGK1.

BACKGROUND: Epigenetics exerts a vital role in the onset and development of renal cell carcinoma (RCC). Mounting evidence has shed light on the significance of human immune system in response to tumor infiltrating T cells. Hereby, we sought to unmask the immunomodulatory role of histone deacetylase 3 (HDAC3) and its potential upstream molecule, programmed cell death 5 (PDCD5) in RCC. METHODS: RCC and adjacent non-cancerous tissues were clinically resected from 58 patients, in which the expression profile of microRNA-195-5p (miR-195-5p), PDCD5, HDAC3, and serum glucocorticoid-inducible kinase 1 (SGK1) was determined by RT-qPCR and Western blot analysis. Their relations were investigated by a series of luciferase assays in combination with ChIP and co-IP. RCC cells (A498) were intervened using gain- and loss-of-function approaches, followed by cell proliferation evaluation. After co-culture with CD3+ T cells, flow cytometry and interferon-γ (IFN-γ) determination were performed. A xenograft tumor mouse model was developed for in vivo validation. RESULTS: PDCD5 was downregulated in RCC tissues and A498 cells. Upregulation of HDAC3, as well as of SGK1, resulted in suppression of A498 cell proliferation and promotion of T cell activation as evidenced by higher IFN-γ expression. Re-expression of PDCD5 downregulated HDAC3, causing a subsequent upregulation of miR-195-5p, while miR-195-5p could inversely modulate its target gene, SGK1. The regulatory mechanism appeared to be functional in vivo. CONCLUSION: Our results highlight the possible manipulation by PDCD5 on RCC cell proliferation and T cell activation, which provides new clues to better understand the immune balance in RCC progression.

Short-term exposure to ambient nitrogen dioxide and increased hospitalization burden for depression in China: a multicity analysis.

Evidence for the increased hospitalization burden, including admissions, expenditures and length of hospital stay (LOS) for depression attributable to ambient nitrogen dioxide (NO2) is lacking. We investigated the associations between short-term exposure to ambient NO2 and attributable admissions, hospitalization expenditures and LOS for depression in 57 Chinese cities during 2013-2017 using a well-established two-stage time-series study approach. Short-term exposure to ambient NO2 was associated with significantly increased admissions, hospitalization expenditures and LOS for depression, and the attributable fractions were 6.87% (95% CI: 2.90%, 10.65%), 7.12% (3.01%, 11.04%) and 6.12% (2.59%, 9.50%) at lag02, respectively. The projected total attributable admissions, hospitalization expenditures and LOS for depression related to ambient NO2 at the national level were 23,335 (9,863, 36,181) admissions, 318.70 (134.43, 492.21) million CNY and 539.55 (227.99, 836.99) thousand days during the study period, respectively. Short-term exposure to ambient NO2 is associated with increased hospitalization burden for depression.