Unveiling Low Temperature Assembly of Dense Fe-N4 Active Sites via Hydrogenation in Advanced Oxygen Reduction Catalysts.

The single-atom Fe-N-C is a prominent material with exceptional reactivity in areas of sustainable energy and catalysis research. It is challenging to obtain the dense Fe-N4 site without the Fe nanoparticle (NPs) sintering during the Fe-N-C synthesis via high-temperature pyrolysis. Thus, a novel approach is devised for the Fe-N-C synthesis at low temperatures. Taking FeCl2 as Fe source, a hydrogen environment can facilitate oxygen removal and dechlorination processes in the synthesis, efficiently favouring Fe-N4 site formation without Fe nanoparticle clustering at as low as 360 °C. We shed light on the reaction mechanism about hydrogen promoting Fe-N4 formation in the synthesis. By adjusting the temperature and duration, the Fe-N4 structural evolution and site density can be precisely tuned to directly influence the catalytic behavior of the Fe-N-C material. The FeNC-H2-360 catalyst demonstrates a remarkable Fe dispersion (8.3 wt%) and superior acid ORR activity with a half-wave potential of 0.85 V and a peak power density of 1.21 W cm-2 in fuel cell. This method also generally facilitates the synthesis of various high-performance M-N-C materials (M = Fe, Co, Mn, Ni, Zn, Ru) with elevated single-atom loadings.

Regulation Strategies on Fe-N-C and Co-N-C Catalysts for Oxygen Reduction Reaction: A Review.

Proton exchange membrane fuel cells (PEMFCs) and alkaline membrane fuel cells (AEMFCs) have received great attention as the energy device of next generation. Accelerating oxygen reduction reaction (ORR) kinetics is the key to improve PEMFCs and AEMFCs performance. Platinum-based catalysts are the most widely used catalysts for ORR, but their high price and low abundance limit the commercialization of fuel cell. Non-noble metal-nitrogen-carbon (M-N-C) is considered to be the most likely material to replace Pt-based catalysts, among which Fe-N-C and Co-N-C have been widely studied due to their excellent intrinsic ORR performance and have made great progress in the past decades. With the improvement of synthesis technology and deepening understanding of the ORR mechanism, some reported Fe-N-C and Co-N-C catalysts have shown excellent ORR activity close to that of commercial Pt/C catalysts. Inspired by the progress, regulation strategies on Fe-N-C or Co-N-C catalysts are summarized in this review from 5 aspects: (1) coordinated atoms, (2) environmental heteroatoms and defects, (3) dual-metal active sites, (4) metal-based particle promoter and (5) curved carbon layer. Next, we make our own suggestions on some challenges facing Fe-N-C and Co-N-C research.

Syk-dependent homologous recombination activation promotes cancer resistance to DNA targeted therapy.

Enhanced DNA repair is an important mechanism of inherent and acquired resistance to DNA targeted therapies, including poly ADP ribose polymerase (PARP) inhibition. Spleen associated tyrosine kinase (Syk) is a non-receptor tyrosine kinase acknowledged for its regulatory roles in immune cell function, cell adhesion, and vascular development. This study presents evidence indicating that Syk expression in high-grade serous ovarian cancer and triple-negative breast cancers promotes DNA double-strand break resection, homologous recombination (HR), and subsequent therapeutic resistance. Our investigations reveal that Syk is activated by ATM following DNA damage and is recruited to DNA double-strand breaks by NBS1. Once localized to the break site, Syk phosphorylates CtIP, a pivotal mediator of resection and HR, at Thr-847 to promote repair activity, particularly in Syk-expressing cancer cells. Inhibition of Syk or its genetic deletion impedes CtIP Thr-847 phosphorylation and overcomes the resistant phenotype. Collectively, our findings suggest a model wherein Syk fosters therapeutic resistance by promoting DNA resection and HR through a hitherto uncharacterized ATM-Syk-CtIP pathway. Moreover, Syk emerges as a promising tumor-specific target to sensitize Syk-expressing tumors to PARP inhibitors, radiation and other DNA-targeted therapies.

RGS20 promotes non-small cell lung carcinoma proliferation via autophagy activation and inhibition of the PKA-Hippo signaling pathway.

BACKGROUND: Novel therapeutic targets are urgently needed for treating drug-resistant non-small cell lung cancer (NSCLC) and overcoming drug resistance to molecular-targeted therapies. Regulator of G protein signaling 20 (RGS20) is identified as an upregulated factor in many cancers, yet its specific role and the mechanism through which RGS20 functions in NSCLC remain unclear. Our study aimed to identify the role of RGS20 in NSCLC prognosis and delineate associated cellular and molecular pathways. METHODS: Immunohistochemistry and lung cancer tissue microarray were used to verify the expression of RGS20 between NSCLC patients. CCK8 and cell cloning were conducted to determine the proliferation ability of H1299 and Anip973 cells in vitro. Furthermore, Transcriptome sequencing was performed to show enrichment genes and pathways. Immunofluorescence was used to detect the translocation changes of YAP to nucleus. Western blotting demonstrated different expressions of autophagy and the Hippo-PKA signal pathway. In vitro and in vivo experiments verified whether overexpression of RGS20 affect the proliferation and autophagy of NSCLC through regulating the Hippo pathway. RESULTS: The higher RGS20 expression was found to be significantly correlated with a poorer five-year survival rate. Further, RGS20 accelerated cell proliferation by increasing autophagy. Transcriptomic sequencing suggested the involvement of the Hippo signaling pathway in the action of RGS20 in NSCLC. RGS20 activation reduced YAP phosphorylation and facilitated its nuclear translocation. Remarkably, inhibiting Hippo signaling with GA-017 promoted cell proliferation and activated autophagy in RGS20 knock-down cells. However, forskolin, a GPCR activator, increased YAP phosphorylation and reversed the promoting effect of RGS20 in RGS20-overexpressing cells. Lastly, in vivo experiments further confirmed role of RGS20 in aggravating tumorigenicity, as its overexpression increased NSCLC cell proliferation. CONCLUSION: Our findings indicate that RGS20 drives NSCLC cell proliferation by triggering autophagy via the inhibition of PKA-Hippo signaling. These insights support the role of RGS20 as a promising novel molecular marker and a target for future targeted therapies in lung cancer treatment.

Deep Learning Radiomics Nomogram Based on Enhanced CT to Predict the Response of Metastatic Lymph Nodes to Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

BACKGROUND: We aimed to construct and validate a deep learning (DL) radiomics nomogram using baseline and restage enhanced computed tomography (CT) images and clinical characteristics to predict the response of metastatic lymph nodes to neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer (LAGC). METHODS: We prospectively enrolled 112 patients with LAGC who received NACT from January 2021 to August 2022. After applying the inclusion and exclusion criteria, 98 patients were randomized 7:3 to the training cohort (n = 68) and validation cohort (n = 30). We established and compared three radiomics signatures based on three phases of CT images before and after NACT, namely radiomics-baseline, radiomics-delta, and radiomics-restage. Then, we developed a clinical model, DL model, and a nomogram to predict the response of LAGC after NACT. We evaluated the predictive accuracy and clinical validity of each model using the receiver operating characteristic curve and decision curve analysis, respectively. RESULTS: The radiomics-delta signature was the best predictor among the three radiomics signatures. So, we developed and validated a DL delta radiomics nomogram (DLDRN). In the validation cohort, the DLDRN produced an area under the receiver operating curve of 0.94 (95% confidence interval, 0.82-0.96) and demonstrated adequate differentiation of good response to NACT. Furthermore, the DLDRN significantly outperformed the clinical model and DL model (p < 0.001). The clinical utility of the DLDRN was confirmed through decision curve analysis. CONCLUSIONS: In patients with LAGC, the DLDRN effectively predicted a therapeutic response in metastatic lymph nodes, which could provide valuable information for individualized treatment.

FeN4 Active Sites Electronically Coupled with PtFe Alloys for Ultralow Pt Loading Hybrid Electrocatalysts in Proton Exchange Membrane Fuel Cells.

The exorbitant cost of Pt-based electrocatalysts and the poor durability of non-noble metal electrocatalysts for proton exchange membrane fuel cells limited their practical application. Here, FeN4 active sites electronically coupled with PtFe alloys (PtFe-FeNC) were successfully prepared by a vapor deposition strategy as an ultralow Pt loading (0.64 wt %) hybrid electrocatalyst. The FeN4 sites on the FeNC matrix are able to effectively anchor the PtFe alloys, thus inhibiting their aggregation during long-life cycling. These PtFe alloys, in turn, can efficiently restrain the leaching of the FeN4 sites from the FeNC matrix. Thus, the PtFe-FeNC demonstrated an improved Pt mass activity of 2.33 A mgPt-1 at 0.9 V toward oxygen reduction reaction, which is 12.9 times higher than that of commercial Pt/C (0.18 A mgPt-1). It demonstrated great stability, with the Pt mass activity decreasing by only 9.4% after 70,000 cycles. Importantly, the fuel cell with an ultralow Pt loading in the cathode (0.012 mgPt cm-2) displays a high Pt mass activity of 1.75 A mgPt-1 at 0.9 ViR-free, which is significantly better than commercial MEA (0.25 A mgPt-1). Interestingly, PtFe-FeNC catalysts possess enhanced durability, exhibiting a 12.5% decrease in peak power density compared to the 51.7% decrease of FeNC.

Ga-Modification Near-Surface Composition of Pt-Ga/C Catalyst Facilitates High-Efficiency Electrochemical Ethanol Oxidation through a C2 Intermediate.

In electrochemical ethanol oxidation reactions (EOR) catalyzed by Pt metal nanoparticles through a C2 route, the dissociation of the C-C bond in the ethanol molecule can be a limiting factor. Complete EOR processes producing CO2 were always exemplified by the oxidative dehydrogenation of C1 intermediates, a reaction route with less energy utilization efficiency. Here, we report a Pt3Ga/C electrocatalyst with a uniform distribution of Ga over the nanoparticle surface for EOR that produces CO2 at medium potentials (>0.3 V vs SCE) efficiently through direct and sustainable oxidation of C2 intermediate species, i.e., acetaldehyde. We demonstrate the excellent performance of the Pt3Ga-200/C catalyst by using electrochemical in situ Fourier transform infrared reflection spectroscopy (FTIR) and an isotopic labeling method. The atomic interval structure between Pt and Ga makes the surface of nanoparticles nonensembled, avoiding the formation of poisonous *CHx and *CO species via bridge-type adsorption of ethanol molecules. Meanwhile, the electron redistribution from Ga to Pt diminishes the *O/*OH adsorption and CO poisoning on Pt atoms, exposing more available sites for interaction with the C2 intermediates. Furthermore, the dissociation of H2O into *OH is facilitated by the high hydrophilicity of Ga, which is supported by DFT calculations, promoting the deep oxidation of C2 intermediates. Our work represents an extremely rare EOR process that produces CO2 without observing kinetic limitations under medium potential conditions.

Instantaneous Free Radical Scavenging by CeO2 Nanoparticles Adjacent to the Fe-N4 Active Sites for Durable Fuel Cells.

To achieve the Fe-N-C materials with both high activity and durability in proton exchange membrane fuel cells, the attack of free radicals on Fe-N4 sites must be overcome. Herein, we report a strategy to effectively eliminate radicals at the source to mitigate the degradation by anchoring CeO2 nanoparticles as radicals scavengers adjacent (Scaad-CeO2 ) to the Fe-N4 sites. Radicals such as ⋅OH and HO2 ⋅ that form at Fe-N4 sites can be instantaneously eliminated by adjacent CeO2 , which shortens the survival time of radicals and the regional space of their damage. As a result, the CeO2 scavengers in Fe-NC/Scaad-CeO2 achieved ∼80 % elimination of the radicals generated at the Fe-N4 sites. A fuel cell prepared with the Fe-NC/Scaad-CeO2 showed a smaller peak power density decay after 30,000 cycles determined with US DOE PGM-relevant AST, increasing the decay of Fe-NCPhen from 69 % to 28 % decay.

A plasma-assisted approach to enhance density of accessible FeN4 sites for proton exchange membrane fuel cells.

Enhancing the density and utilization of FeN4 sites can serve as a viable approach to enhance the catalytic efficacy of iron nitrogen carbon (FeNC) catalysts for oxygen reduction reaction (ORR). Herein, we present a plasma-assisted method for enhancing the porosity of nitrogen-doped carbon. Our findings indicate that the ideal ratio of mesopore to micropore area is 0.463. This ratio not only promotes the diffusion of Fe3+ but also creates additional active sites for Fe3+ loading, leading to an increase in the number of available FeN4 sites in FeNC electrocatalysts during pyrolysis. The density (76.5 µmol g-1) and utilization (21.08 %) of d-FeNC-30 are significantly higher than those of FeNC without plasma treatment, with a 2.8-fold and 2-fold increase, respectively. Remarkably, it displays outstanding performance, evidenced by a half-wave potential of 0.835 V (vs. RHE) in a 0.1 M HClO4 solution and a power density of 0.860 W cm-2 in proton exchange membrane fuel cells (PEMFCs). The developed plasma-assisted approach for improving the site density (SD) and utilization of FeN4 provides a new perspective for high-performance ORR FeNC catalysts.

Identification of hub genes associated with osteoporosis development by comprehensive bioinformatics analysis.

Osteoporosis (OP) is a systemic bone disease caused by various factors, including, the decrease of bone density and quality, the destruction of bone microstructure, and the increase of bone fragility. It is a disease with a high incidence in a large proportion of the world's elderly population. However, osteoporosis lacks obvious symptoms and sensitive biomarkers. Therefore, it is extremely urgent to discover and identify disease-related biomarkers for early clinical diagnosis and effective intervention for osteoporosis. In our study, the Linear Models for Microarray Data (LIMMA) tool was used to screen differential expressed genes from transcriptome sequencing data of OP blood samples downloaded from the GEO database, and cluster Profiler was used for enriching analysis of differently expressed genes. In order to analyzed the relevance of gene modules, clinical symptoms, and the most related module setting genes associated with disease progression, we adapted Weighted Gene Co-expression Network Analysis (WGCNA) to screen and analyze the related pathways and relevant molecules. We used the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to construct protein interaction network of key modules, and Cytoscape software was used to complete network visualization and screen of core genes in the network. Various plug-in algorithms of cytoHubba were used to identify key genes of OP. Finally, correlation analysis and single-gene gene probe concentration analysis (GSEA) analysis were performed for each core gene. Results of a total of 8 key genes that were closely related to the occurrence and development of OP were screened out, which provided a brand-new idea for the clinical diagnosis and early prevention of OP. Quantitative real-time PCR (qRT-PCR) was performed for validation, the expression levels of CUL1, PTEN and STAT1 genes in the OS group were significantly higher than in the non-OS groups. Receiver operating characteristic analysis demonstrated that CUL1, PTEN and STAT1 displayed considerable diagnostic accuracy for OS.

Observation of the delineation of the target volume of radiotherapy in adult-type diffuse gliomas after temozolomide-based chemoradiotherapy: analysis of recurrence patterns and predictive factors.

BACKGROUND: Radiation therapy is the cornerstone of treatment for adult-type diffuse gliomas, but recurrences are inevitable. Our study assessed the prognosis and recurrence pattern of different radiotherapy volumes after temozolomide-based chemoradiation in our institution. METHODS: The treatment plans were classified into two groups, the plan 1 intentionally involved the entire edema area while plan 2 did not. Retrospectively investigate the differences in outcomes of 118 adult-type diffuse gliomas patients between these two treatment plans. Then, patients who underwent relapse were selected to analyze their recurrence patterns. Continuous dynamic magnetic resonance images (MRI) were collected to categorized the recurrence patterns into central, in-field, marginal, distant, and cerebrospinal fluid dissemination (CSF-d) recurrence. Finally, the clinical and molecular characteristics which influenced progression were analyzed. RESULTS: Plan 1 (n = 63) showed a median progression-free survival (PFS) and overall survival (OS) of 9.5 and 26.4 months while plan 2 (n = 55) showed a median PFS and OS of 9.4 and 36.5 months (p = 0.418; p = 0.388). Treatment target volume had no effect on the outcome in patients with adult-type diffuse gliomas. And there was no difference in radiation toxicity (p = 0.388). Among the 90 relapsed patients, a total of 58 (64.4%) patients had central recurrence, 10 (11.1%) patients had in-field recurrence, 3 (3.3%) patients had marginal recurrence, 11 (12.2.%) patients had distant recurrence, and 8 (8.9%) patients had CSF-d recurrence. By treatment plans, the recurrence patterns were similar and there was no significant difference in survival. Reclassifying the progression pattern into local and non-local groups, we observed that oligodendroglioma (n = 10) all relapsed in local and no difference in PFS and OS between the two groups (p > 0.05). Multivariable analysis showed that subventricular zone (SVZ) involvement was the independent risk factor for non-local recurrence in patients with GBM (p < 0.05). CONCLUSION: In our study, deliberately including or not the entire edema had no impact on prognosis and recurrence. Patients with varied recurrence patterns had diverse clinical and genetic features.

A nomogram for predicting prognosis of multiple myeloma patients based on a ubiquitin-proteasome gene signature.

BACKGROUND: Multiple myeloma (MM) is a malignant hematopoietic disease that is usually incurable. However, the ubiquitin-proteasome system (UPS) genes have not yet been established as a prognostic predictor for MM, despite their potential applications in other cancers. METHODS: RNA sequencing data and corresponding clinical information were acquired from Multiple Myeloma Research Foundation (MMRF)-COMMPASS and served as a training set (n=787). Validation of the prediction signature were conducted by the Gene Expression Omnibus (GEO) databases (n=1040). To develop a prognostic signature for overall survival (OS), least absolute shrinkage and selection operator regressions, along with Cox regressions, were used. RESULTS: A six-gene signature, including KCTD12, SIAH1, TRIM58, TRIM47, UBE2S, and UBE2T, was established. Kaplan-Meier survival analysis of the training and validation cohorts revealed that patients with high-risk conditions had a significantly worse prognosis than those with low-risk conditions. Furthermore, UPS-related signature is associated with a positive immune response. For predicting survival, a simple to use nomogram and the corresponding web-based calculator (https://jiangyanxiamm.shinyapps.io/MMprognosis/) were built based on the UPS signature and its clinical features. Analyses of calibration plots and decision curves showed clinical utility for both training and validation datasets. CONCLUSIONS: As a result of these results, we established a genetic signature for MM based on UPS. This genetic signature could contribute to improving individualized survival prediction, thereby facilitating clinical decisions in patients with MM.

The intrarenal landscape of T cell receptor repertoire in clear cell renal cell cancer.

BACKGROUND: Clear cell renal cell cancer (ccRCC) is accompanied by T-cell infiltration. In this study, we sought to determine the difference in T-cell infiltration and the T-cell receptor (TCR) immune repertoire between ccRCC and peritumour tissue. METHODS: T-cell infiltration was examined using immunohistochemistry (IHC) and haematoxylin and eosin (HE) staining. The chi-squared test and Pearson correlation analysis were applied to evaluate the relationship between clinical traits and CD3, CD4, and CD8 expression. Immune repertoire sequencing (IR-Seq) was used to describe the profile of the TCR repertoire. RESULTS: The adjacent tissue showed increased expression of CD3, CD4 and CD8 compared with ccRCC tissue (PCD3 = 0.033; PCD4 = 0.014; PCD8 = 0.004). Indicated CD3+ T-cell density in ccRCC tissue was positively correlated with that in peritumour tissue (P = 0.010, r = 0.514), which implied the T cells in peritumour tissue directly infect the number of cells infiltrating in ccRCC tissue. Moreover, there was a positive correlation between Vimentin expression and indicated positive T-cell marker in ccRCC tissue (PCD3 = 0.035; PCD4 = 0.020; PCD8 = 0.027). Advanced stage revealed less CD4+ T-cell infiltration in ccRCC tissue (PCD4 = 0.023). The results from IR-Seq revealed an obvious increase in VJ and VDJ segment usage, as well as higher complementarity-determining region 3 (CDR3) amino acid (aa) clonotypes in ccRCC. The matched antigen recognized by the TCR of ccRCC may be potential targets. CONCLUSIONS: The current study collectively demonstrates diminished T-cell infiltration and increased CDR3 aa diversity in ccRCC, which may be associated with immunotherapeutic targets for ccRCC patients.

Biphasic squamoid alveolar papillary renal cell carcinoma: A unique papillary renal cell carcinoma with distinctive morphology, immunophenotype and molecular genetic features.

Biphasic squamoid alveolar papillary renal cell carcinoma (BSARCC) is a recently described renal tumor, considered as a unique rare morphological pattern of PRCC in the 2022 WHO classification. We aimed to further explore the clinicopathological, immunophenotypic, and molecular genetic characteristics of BSARCC in a Chinese cohort. The clinicopathological data of 8 patients with BSARCC were collected for morphology observation and immunohistochemical staining. QRT-PCR was performed to detect BRAF gene mutation. The abnormalities of chromosomes 7, 17 and Y, and CCND1 gene were investigated by fluorescence in situ hybridization (FISH). Among the 8 cases, 5 were males and 3 were females. 6 cases were revealed by physical examination incidentally, and 2 cases were presented with low back pain and hematuria. Microscopically, the tumors were mainly composed of small cells with different proportions of large cells. The small cells were arranged in acinar, compact and long narrow tubular, solid sheet or papillary structures. Single or clustered large cells were arranged in glomerular structures in the acinar cavity formed by small cells. Among the 8 cases, 2 cases had a small amount of typical type I papillary renal cell carcinoma without large cells at the edge of the tumor. And 5 cases presented the swallowing phenomenon of lymphocytes or neutrophils in the cytoplasm of a few large cells. Immunohistochemical staining showed both large and small cells were diffusely and strongly positive for CK7, P504s, EMA, and vimentin. MET was expressed in most tumors (6/8), and large cells (70-90%) exhibited a prominent higher positive rate than small cells (20-90%). CD57 was positive in both large and small cells in 5 cases. Notably, CyclinD1 was exclusively expressed in large cells, while RCC marker was mainly expressed in small cells. Large cells showed a higher ki67 index than small cells. BRAF V600E mutation was negative in all cases. FISH showed 4 cases had chromosome 7 trisomy, 2 cases had chromosome 17 trisomy, and 4 of 5 male patients had Y chromosome deletion. CCND1 gene amplification or rearrangement was not revealed in any case. Follow-up data were available in 8 cases ranging from 3 to 66 months, and there was no recurrence or metastasis of the tumor. BSARCC is a rare unique morphological pattern of papillary renal cell carcinoma, featured by the presence of two cell populations of different morphology and immunophenotype. Distinctive CyclinD1 and RCC immunostainings are essential in diagnosing this type of renal tumor. Large and small cells may be tumor cells in different stages of proliferation and differentiation, and large cells immunoreactive to CyclinD1 and presenting higher ki67 index might be more aggressive than small cells. The anomalous expression of CyclinD1 in large cells is not due to the aberrance of CCND1 gene itself. Most BSARCC is low-stage and inert with a favorable prognosis. Our study not only validates previously described clinicopathological features, but also supplements the clinicopathological features and expands the potential genetic alterations and available clinical outcome data of BSARCC.

Identification of a novel ceRNA network related to prognosis and immunity in HNSCC based on integrated bioinformatic investigation.

Head and neck squamous cell carcinoma (HNSCC) is characterized by an immunosuppression environment and necessitates the development of new immunotherapy response predictors. The study aimed to build a prognosis-related competing endogenous RNA (ceRNA) network based on immune-related genes (IRGs) and analyze its immunological signatures. Differentially expressed IRGs were identified by bioinformatics analysis with Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and ImmPort databases. Finally, via upstream prognosis-related microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) prediction and co-expression analysis, we built an immune-related ceRNA network (LINC00052/hsa-miR-148a-3p/PLAU) related to HNSCC patient prognosis. CIBERSORT analysis demonstrated that there were substantial differences in 11 infiltrating immune cells in HNSCC, and PLAU was closely correlated with 10 type cells, including T cells CD8+ (R = - 0.329), T cells follicular helper (R = - 0.342) and macrophage M0 (R = 0.278). Methylation and Tumor Immune Dysfunction and Exclusion (TIDE) analyses revealed that PLAU upregulation was most likely caused by hypomethylation and that high PLAU expression may be associated with tumor immune evasion in HNSCC, respectively.

Papillary renal neoplasm with reverse polarity may be a novel renal cell tumor entity with low malignant potential.

AIMS: This study retrospectively investigated the morphological, immunohistochemical and molecular genetic features of papillary renal neoplasm with reverse polarity (PRNRP), a recently described renal tumor. METHODS AND RESULTS: Eleven cases of PRNRP were collected, and 16 cases of type I and 9 cases of type II papillary renal cell carcinoma were included as a control series. Pathological features were evaluated based on HE staining and immunohistochemistry. KRAS exon 2 and BRAF V600E mutations were detected by Real-time PCR and Sanger sequencing. Fluorescence in situ hybridization was conducted for identification of chromosomal abnormalities. Hemosiderin deposition was found in a small amount of tumor cells in 6 cases. Multifocal or patchy necrosis (5/11), small focal invasion of the pseudocapsules or renal parenchyma (6/11), and breakthrough of renal capsule with nerve invasion (1/11) were revealed, inconsistent with the previous view that the tumor lacks necrosis and intercellular hemosiderin. Immunohistochemical staining (diffusely positive for CK7 and GATA3, negative for CD117 and vimentin, and negative to weakly positive for P504S) and high frequency of KRAS mutations in exon 2 (9/10) supported the identification and inclusion of our cases. Chromosome 7 trisomy (1/7), chromosome 17 trisomy (0/7) and chromosome Y deletion (0/5 male patients) were seldom detected in this tumor. All patients were alive without metastasis or recurrence at the end of the follow-up. CONCLUSION: Our findings may highlight the possibility of a low malignant potential of this emerging entity. We suggest that the tumor be classified as a novel renal cell tumor subtype independent of papillary renal cell carcinoma.

Analysis of clinicopathological and molecular features of ELOC(TCEB1)-mutant renal cell carcinoma.

OBJECTIVE: This study aimed to investigate the clinicopathological and molecular characteristics of ELOC(TCEB1)-mutant renal cell carcinoma. METHODS: Sanger sequencing was used to assess 32 cases originally diagnosed as clear cell renal cell carcinoma with CK7 positive and/or fibromyomatous stroma. Of these, 4 patients with ELOC(TCEB1) gene mutation were screened, and their clinicopathological data were collected for histomorphological observation, immunohistochemical staining, and follow-up, and relevant pieces of literature were reviewed. RESULTS: The 4 patients with ELOC(TCEB1) mutations were all males and aged between 57 and 64 years (median age: 59 years old). The tumor was located in the renal cortex, with a diameter of 2-3.5 cm. The cross-section was grayish-yellow and grayish brown, solid and nodular, and clearly demarcated from the surrounding tissues. Of the 4 patients, 3 harbored a thick fibrous pseudocapsule rich in smooth muscle and were separated from the surrounding normal renal tissue, and 2 of them showed focal invasion into the pseudocapsule, whereas 1 patient had no capsule but had focal invasion into the surrounding renal parenchyma. The tumor tissues mainly exhibited elongated or branched aciniform or tubular structures, commonly accompanied by interspersed small cystic and focal clustered short papillary structures. The cytoplasm of the tumor cells was rich and lightly stained, and the nuclear grading ranged from 1 to 2. All patients showed loose edema in the stroma, and 2 patients showed a small number of interspersed smooth muscle bundles. All 4 patients showed EMA, CA9, AMACR, and TCEB1 expression, and TCEB1 was mainly located in the nucleus. Vimentin, CK7, and CD10 expressions were observed in most cases; CD117, TFE3, HMB45, and melanA were not expressed in all tumors; the expression rate of Ki67 was 3%- 8%. All 4 patients had a point mutation in ELOC(TCEB1) Y79C. The patients were followed up for 24-93 months (mean 49 months), and all of them survived to date without recurrence or metastasis. CONCLUSION: ELOC(TCEB1)-mutant renal cell carcinoma is a rare type of renal cell carcinoma, which tends to occur in middle-aged and elderly men. The main characteristics of this tumor are the branching alveolar or tubular structure with clustered short papillae, presence of fibromyomatous stroma, and the expression of CK7, CA9, CD10, and AMACR. Positive TCEB1 nuclear staining may be an important marker and the Sanger sequencing method is helpful for the diagnosis of this type of RCC. Most patients harbor tumors exhibiting low nuclear grade and inert clinical behavior, and a few tumors exhibit high nuclear grade and aggressive characteristics.

Silencing LINC00491 Inhibits Pancreatic Cancer Progression through MiR-188-5p-induced Inhibition of ZFP91.

Background: Pancreatic cancer is recognized as one of the most malignant tumors with poor prognosis. Recently, long noncoding RNAs (lncRNAs) are considered as a potential prognostic biomarker of PC. However, the concrete biological effect of lncRNAs in PC remains unmasked. Herein, we explored the mechanism of LINC00491 in PC. Methods: Quantitative real-time PCR (qRT-PCR) was administrated to detected the expression of LINC00491 in PC tissues and cell lines. Loss-of-function experiment in vitro and in vivo was carried out to figure out the biological effects of LINC00491 on PC carcinogenesis. Luciferase reporter assay, subcellular fractionation, western blotting, pull-down assay and RNA immunoprecipitation assay were further used to explore the mechanism of PC tumorigenesis of LINC00491. Results: An increase of LINC00491 was detected in PC cell lines and tissues. Silencing LINC00491 in vitro and in vivo subsequently hindered cell migration, invasion, proliferation and tumor growth, respectively. Further research confirmed a negative and a positive connection of LINC00491 with microRNA 188-5p (miR-188-5p) level and Zinc finger protein 91 (ZFP91), a target of miR-188-5p, respectively. qRT-PCR and western blotting found that miR-188-5p was upregulated while LINC00491 was downregulated, concomitant with ZFP91 decreasing in PC cells or node mouse tumors, which could be significantly restored by inhibiting miR-188-5p. Besides, overexpression of miR-188-5p partially restored the inhibitory effect of LINC00491 diminution on proliferation, migration, and invasion of PC cells. Conclusion: LINC00491 promotes PC proliferation, migration, invasion via the miR-188-5p/ZFP91 axis, suggesting LINC00491 could be a new therapeutic target for PC.

Cefoperazone sodium/sulbactam sodium vs piperacillin sodium/tazobactam sodium for treatment of respiratory tract infection in elderly patients.

BACKGROUND: Respiratory tract infections in the elderly are difficult to cure and can easily recur, thereby posing a great threat to patient prognosis and quality of life. AIM: To investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection. METHODS: Seventy-four elderly patients with respiratory tract infection were randomly allocated to a study (n = 37; treated with cefoperazone sodium/sulbactam sodium) or control (n = 37; treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support) group. Both groups were treated for 7 d. Time to symptom relief (leukocyte recovery; body temperature recovery; cough and sputum disappearance; and rale disappearance time), treatment effect, and laboratory indexes [procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (NE)] before and 7 d after treatment and the incidence of adverse reactions were assessed. RESULTS: In the study group, the time to WBC normalization (6.79 ± 2.09 d), time to body temperature normalization (4.15 ± 1.08 d), time to disappearance of cough and sputum (6.19 ± 1.56 d), and time to disappearance of rales (6.68 ± 1.43 d) were shorter than those of the control group (8.89 ± 2.32 d, 5.81 ± 1.33 d, 8.77 ± 2.11 d, and 8.69 ± 2.12 d, respectively; P = 0.000). Total effective rate was higher in the study group (94.59% vs 75.68%, P = 0.022). Serum PCT (12.89 ± 3.96 µg/L), CRP (19.62 ± 6.44 mg/L), WBC (20.61 ± 6.38 × 109/L), and NE (86.14 ± 7.21%) levels of the study group before treatment were similar to those of the control group (14.05 ± 4.11 µg/L, 18.79 ± 5.96 mg/L, 21.21 ± 5.59 × 109/L, and 84.39 ± 6.95%, respectively) with no significant differences (P = 0.220, 0.567, 0.668, and 0.291, respectively). After 7 d of treatment, serum PCT, CRP, WBC, and NE levels in the two groups were lower than those before treatment. Serum PCT (2.01 ± 0.56 µg/L), CRP (3.11 ± 1.02 mg/L), WBC (5.10 ± 1.83 × 109/L), and NE (56.35 ± 7.17%) levels were lower in the study group than in the control group (3.29 ± 0.64 µg/L, 5.67 ± 1.23 mg/L, 8.13 ± 3.01 × 109/L, and 64.22 ± 8.08%, respectively; P = 0.000). There was no significant difference in the incidence of adverse reactions between the groups (7.50% vs 12.50%, P = 0.708). CONCLUSION: Piperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/ sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.