Urban vs. rural: colorectal cancer survival and prognostic disparities from 2000 to 2019.

This study aimed to analyze the differences in colorectal cancer (CRC) survival between urban and rural areas over the past 20 years, as well as investigate potential prognostic factors for CRC survival in both populations. Using registry data from Surveillance, Epidemiology, and End Results (SEER) from 2000 to 2019, 463,827 CRC cases were identified, with 85.8% in urban and 14.2% in rural areas. The mortality of CRC surpassed its survival rate by the sixth year after diagnosis in urban areas and the fifth year in rural areas. Furthermore, the 5-year overall survival (OS) of CRC increased by 2.9-4.3 percentage points in urban and 0.6-1.5 percentage points in rural areas over the past two decades. Multivariable Cox regression models identified independent prognostic factors for OS and disease-specific survival (DSS) of CRC in urban and rural areas, including age over 40, Black ethnicity, and tumor size greater than 5 cm. In addition, household income below $75,000 was found to be an independent prognostic factor for OS and DSS of CRC in urban areas, while income below $55,000 was a significant factor for rural areas. In conclusion, this study found a notable difference in CRC survival between rural and urban areas. Independent prognostic factors shared among both rural and urban areas include age, tumor size, and race, while household income seem to be area-specific predictive variables. Collaboration between healthcare providers, patients, and communities to improve awareness and early detection of CRC may help to further advance survival rates.

Downregulation of Wtap causes dilated cardiomyopathy and heart failure.

RNA binding proteins have been shown to regulate heart development and cardiac diseases. However, the detailed molecular mechanisms is not known. In this study, we identified Wilms' tumor 1-associating protein (WTAP, a key regulatory protein of the m6A RNA methyltransferase complex) as a key regulator of heart function and cardiac diseases. WTAP is associated with heart development, and its expression is downregulated in both human and mice with heart failure. Cardiomyocyte-specific knockout of Wtap (Wtap-CKO) induces dilated cardiomyopathy, heart failure and neonatal death. Although WTAP deficiency in the heart decreases METTL3 (methyltransferase-like 3) protein levels, cardiomyocyte-specific overexpression of Mettl3 in Wtap-CKO mice does not rescue the phenotypes of Wtap-CKO mice. Instead, WTAP deficiency in the heart decreases chromatin accessibility in the promoter regions of Mef2a (myocyte enhancer factor-2α) and Mef2c, leading to reduced mRNA and protein levels of these genes and lower expression of their target genes. Conversely, WTAP directly binds to the promoter of the Mef2c gene and increases its promoter luciferase activity and expression. These data demonstrate that WTAP plays a key role in heart development and cardiac function by maintaining the chromatin accessibility of cardiomyocyte specific genes.

Next-generation self-adhesive dressings: Highly stretchable, antibacterial, and UV-shielding properties enabled by tannic acid-coated cellulose nanocrystals.

Hydrogels with excellent high-water uptake and flexibility have great potential for wound dressing. However, pure hydrogels without fiber skeleton faced poor water retention, weak fatigue resistance, and mechanical strength to hinder the development of the dressing as next-generation functional dressings. We prepared an ultrafast gelation (6 s) Fe3+/TA-CNC hydrogel (CTFG hydrogel) based on a self-catalytic system and bilayer self-assembled composites. The CTFG hydrogel has excellent flexibility (800% of strain), fatigue resistance (support 60% compression cycles), antibacterial, and self-adhesive properties (no residue or allergy after peeling off the skin). CTFG@S bilayer composites were formed after electrospun silk fibroin (SF) membranes were prepared and adhesive with CTFG hydrogels. The CTFG@S bilayer composites had significant UV-shielding (99.95%), tensile strain (210.9 KPa), and sensitive humidity-sensing properties. Moreover, the integrated structure improved the mechanical properties of electrospun SF membranes. This study would provide a promising strategy for rapidly preparing multifunctional hydrogels for wound dressing.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

Recent Progress in Spinel Ferrite (MFe2O4) Chemiresistive Based Gas Sensors.

Gas-sensing technology has gained significant attention in recent years due to the increasing concern for environmental safety and human health caused by reactive gases. In particular, spinel ferrite (MFe2O4), a metal oxide semiconductor with a spinel structure, has emerged as a promising material for gas-sensing applications. This review article aims to provide an overview of the latest developments in spinel-ferrite-based gas sensors. It begins by discussing the gas-sensing mechanism of spinel ferrite sensors, which involves the interaction between the target gas molecules and the surface of the sensor material. The unique properties of spinel ferrite, such as its high surface area, tunable bandgap, and excellent stability, contribute to its gas-sensing capabilities. The article then delves into recent advancements in gas sensors based on spinel ferrite, focusing on various aspects such as microstructures, element doping, and heterostructure materials. The microstructure of spinel ferrite can be tailored to enhance the gas-sensing performance by controlling factors such as the grain size, porosity, and surface area. Element doping, such as incorporating transition metal ions, can further enhance the gas-sensing properties by modifying the electronic structure and surface chemistry of the sensor material. Additionally, the integration of spinel ferrite with other semiconductors in heterostructure configurations has shown potential for improving the selectivity and overall sensing performance. Furthermore, the article suggests that the combination of spinel ferrite and semiconductors can enhance the selectivity, stability, and sensing performance of gas sensors at room or low temperatures. This is particularly important for practical applications where real-time and accurate gas detection is crucial. In conclusion, this review highlights the potential of spinel-ferrite-based gas sensors and provides insights into the latest advancements in this field. The combination of spinel ferrite with other materials and the optimization of sensor parameters offer opportunities for the development of highly efficient and reliable gas-sensing devices for early detection and warning systems.

Deficiency of mindin reduces renal injury after ischemia reperfusion.

BACKGROUND: Acute renal injury (AKI) secondary to ischemia reperfusion (IR) injury continues to be a significant perioperative problem and there is no effective treatment. Mindin belongs to the mindin/F-spondin family and involves in inflammation, proliferation, and cell apoptosis. Previous studies have explored the biological functions of mindin in liver and brain ischemic injury, but its role in AKI is unknown. METHOD: To investigate whether mindin has a pathogenic role, mindin knockout (KO) and wild-type (WT) mice were used to establish renal IR model. After 30 min of ischemia and 24 h of reperfusion, renal histology, serum creatinine, and inflammatory response were examined to assess kidney injury. In vitro, proinflammatory factors and inflammatory signaling pathways were measured in mindin overexpression or knockdown and vector cells after hypoxia/reoxygenation (HR). RESULTS: Following IR, the kidney mindin level was increased in WT mice and deletion of mindin provided significant protection for mice against IR-induced renal injury as manifested by attenuated the elevation of serum creatinine and blood urea nitrogen along with less severity for histological alterations. Mindin deficiency significantly suppressed inflammatory cell infiltration, TNF-α and MCP-1 production following renal IR injury. Mechanistic studies revealed that mindin deficiency inhibits TLR4/JNK/NF-κB signaling activation. In vitro, the expression levels of TNF-α and MCP-1 were increased in mindin overexpression cells compared with vector cells following HR. Moreover, TLR4/JNK/NF-κB signaling activation was elevated in the mindin overexpression cells in response to HR stimulation while mindin knockdown inhibited the activation of TLR4/JNK/ NF-κB signaling after HR in vitro. Further study showed that mindin protein interacted directly with TLR4 protein. And more, mindin protein was confirmed to be expressed massively in renal tubule tissues of human hydronephrosis patients. CONCLUSION: These data demonstrate that mindin is a critical modulator of renal IR injury through regulating inflammatory responses. TLR4/JNK/NF-κB signaling most likely mediates the biological function of mindin in this model of renal ischemia.

Analysis of ARHGAP4 Expression With Colorectal Cancer Clinical Characteristics and Prognosis.

Background: This study aims to analyze the correlation between ARHGAP4 in the expression and clinical characteristics of colorectal cancer (CRC), and the influence of ARHGAP4 expression on the prognosis of CRC, and to evaluate whether ARHGAP4 is a potential prognostic oncotarget for CRC. Methods: ARHGAP4 was identified using the Gene Expression Omnibus database through weighted gene coexpression network analysis. Using the Gene Expression Profiling Interactive Analysis to perform and analyze the expression and prognosis of ARHGAP4 in CRC. The expression of AGRGAP4 and immune cells was analyzed by the Tumor IMmune Estimation Resource online database. Finally, immunohistochemistry was used to analyze the expression difference and prognosis of ARHGAP4 in CRC and adjacent normal tissues, as well as the relationship between AGRGAP4 expression and clinical features of CRC. Results: We identified ARHGAP4 that is related to the recurrence of CRC from GSE97781 data. ARHGAP4 has not been reported in CRC. The high expression of ARHGAP4 in select colon adenocarcinoma indicates a poor prognosis by database analysis. In our clinical data results, ARHGAP4 is highly expressed in CRC and lowly expressed in normal tissues adjacent to cancer. Compared with the low-expression group, the high-expression group has a significantly poorer prognosis. In colon cancer, the B-cell, macrophage, neutrophil, and dendritic-cell levels are downregulated after ARHGAP4 gene knockout; the levels of CD8+ and CD4+ T cells, neutrophils, and dendritic cells are upregulated after the amplification of the ARHGAP4 gene. In addition, ARHGAP4 expression is related to N,M staging and clinical staging. Conclusion: ARHGAP4 is highly expressed in CRC, and the high expression of ARHGAP4 has a poor prognosis. The expression of ARHGAP4 in CRC is related to the immune cells such as B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells. ARHGAP4 is correlated with N,M staging and clinical staging in CRC. ARHGAP4 may be a potential biomarker for the prognosis of CRC.

Preoperative Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and CEA as the Potential Prognostic Biomarkers for Colorectal Cancer.

Background: This study was to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) in colorectal cancer (CRC) patients and to identify the potential and easily accessible prognostic biomarkers for CRC. Methods: We retrospectively reviewed altogether the records of 330 CRC patients according to inclusion criteria. The clinical characteristics include age at diagnosis, body mass index (BMI), preoperative CEA level, neutrophil , lymphocyte, and platelet count, tumor primary site and size, clinical pathological TNM stage, and survival status were recorded through the review of medical records. The overall survival (OS) was calculated using the Kaplan-Meier method. The Cox proportional hazards model was used for the univariate and multivariate analysis to evaluate the prognostic factors of CRC. Results: A total of 330 patients were finally included in the current study. The mean follow-up duration was 32.8 ± 19.1 months (range, 0.1-67.7). Compared with the median OS, preoperative high NLR, PLR, and CEA, and low BMI had lower median OS. The NLR and PLR value rise indicates lower median OS in stage I-II CRC; however, the NLR value and CEA level rise indicates lower median OS in stage III-IV CRC. Preoperative high NLR, PLR, and CEA level and low BMI have poorer OS by univariate analysis. By multivariate analysis, the age, sex, N, M stage, and BMI demonstrated independently influence the OS of CRC. NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC. Conclusions: Our results show that preoperative high NLR, PLR, CEA, and low BMI had poorer OS, NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC.

Implications of cell division cycle associated 4 on the Wilm's tumor cells viability via AKT/mTOR signaling pathway.

OBJECTIVE: The aim of present report was to elucidate the effect of cell division cycle associated 4 (CDCA4) on the proliferation and apoptosis of Wilm's tumor cells, and to further evaluate its underlying mechanism. METHODS: The expression profiles of CDCA4 and clinical information of Wilm's tumor patients were obtained from public Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database portal. Real-time qPCR and western blot analyses were utilized to determine the expression levels of CDCA4. Gain- and loss-of-function of CDCA4 assays were conducted with transfection technology to investigate the biological role of CDCA4 in Wilm's tumor cells. Cell counting kit 8 and flow cytometer assays were employed to examine the effect of CDCA4 on the cells proliferation and apoptosis. Protein expression levels of indicated markers in each group of Wilm's tumor cells were measured by western blot. RESULTS: The transcriptional expression of CDCA4 was drastically upregulated in Wilm's tumor tissues according to the public TARGET database and in Wilm's tumor cells. The cells viability was remarkably reduced whereas the cells apoptosis was increased in CDCA4-knockdown group compared with negative control group. However, CDCA4-overexpression group promoted the cells proliferation and suppressed the cells apoptosis. Furthermore, the protein expression levels of p-AKT, p-mTOR, and Cyclin D1 were significantly reduced after depletion of CDCA4, whereas overexpression of CDCA4 dramatically elevated these markers' expression levels. CONCLUSIONS: CDCA4 is highly expressed in Wilm's tumor and promoted the proliferation whereas inhibited the apoptosis of Wilm's tumor cells through activating the AKT/mTOR signaling pathway.

Adipose-Derived Stem Cells Inhibited the Proliferation of Bladder Tumor Cells by S Phase Arrest and Wnt/ß-Catenin Pathway.

Adipose-derived stem cells (ADSCs), which are present in most organs and tissues, were evaluated as a novel medium for stem cell therapy. In this study, we investigated the effects and underlying mechanisms of ADSCs in bladder tumor (BT) cells. SV-HUC, T24, and EJ cells were cultured with ADSCs and conditioned medium from ADSCs (ADSC-CM). We observed that in routine culture, ADSCs significantly inhibited the proliferation of T24 and EJ cells in a dose-dependent manner. In addition, ADSC-CM attenuated the viability of T24 and EJ cells in a dose-dependent manner. Cell cycle analysis indicated that ADSC-CM was capable of inducing T24 and EJ cells S phase arrest and downregulating the expression of CDK 1, whereas the expression of cyclin A was increased. ADSC-CM could induce apoptosis in T24 cells. The mechanism of this effect likely involved the caspase3/7 pathway and Wnt/ß-catenin pathway. These findings demonstrated that ADSCs could inhibit the proliferation of BT cells via secretory factors.

Identification of Factors Associated with Postoperative Urosepsis after Ureteroscopy with Holmium: Yttrium-Aluminum-Garnet Laser Lithotripsy.

OBJECTIVE: To report the incidence and risk factors of urosepsis after ureteroscopic lithotripsy (URSL). PATIENTS AND METHODS: We retrospectively reviewed 1,421 patients who underwent URSL for ureteral calculi between July 2015 and June 2018 at our department to identify factors predicting postoperative urosepsis. Demographic characteristics, clinical data, operative information, and complications were compared, and risk factors of postoperative urosepsis were identified and analyzed. RESULTS: Of the 1,421 patients treated with URSL using holmium: yttrium-aluminum-garnet laser, 12 (0.8%) developed a urosepsis after operation. The positive preoperative multidrug resistance (MDR) urine culture and operative duration were statistically different between those who did and did not develop a urosepsis (4.61 vs. 25%, p = 0.017; 70 vs. 62 min, p < 0.001). However, patient age, sex, body mass index, diabetes mellitus, history of urolithiasis, positive preoperative urine cultures, stone size and location, degree of hydronephrosis, and prior stent placement were similar in 2 groups. Multivariate analysis revealed that positive preoperative MDR urine culture and long operation duration significantly increased the risk of postoperative urosepsis (OR 5.090, 95% CI 1.312-19.751, p = 0.019; OR 1.034, 95% CI 1.004-1.063; p = 0.024). Matched-pair analysis demonstrated that positive preoperative MDR urine culture and operation duration were significantly associated with postoperative urosepsis (OR 15.77, 95% CI 1.033-240.7, p = 0.047; OR 1.087, 95% CI 1.011-1.169, p = 0.025). CONCLUSIONS: Patients with positive preoperative MDR urine culture or long operation duration had a higher risk of developing urosepsis after URSL. When treating patients who present with positive preoperative MDR urine culture or long operation duration, urologists should be vigilant and aware of the potential risk of urosepsis.

Cryptotanshinone ameliorates renal ischaemia-reperfusion injury by inhibiting apoptosis and inflammatory response.

Cryptotanshinone (CTS) is a natural compound from the Chinese herb Salvia miltiorrhiza. Previous studies demonstrated that CTS possesses anti-apoptotic and anti-inflammatory properties. However, its effects and underlying mechanism on renal ischaemia reperfusion (IR) injury remain unknown. In the present study, we investigated the effects of CTS on renal IR injury and its potential underlying mechanisms. Mice were randomized into four groups as follows: (a) sham operation + vehicle, (b) sham operation + CTS, (c) IR + vehicle, (d) IR + CTS. The CTS-treated group were injected intraperitoneally with CTS (10 mg/kg/d) for 7 days prior to IR operation. Renal IR injury was induced by clamping the bilateral renal artery for 30 minutes followed by 24 hours of reperfusion. The mice were then killed to collect the serum and the kidneys for analysis. The results of the present study showed that CTS pretreatment significantly attenuates IR-induced renal functional and morphological injuries, which was accompanied with inhibition of cell apoptosis and inflammatory response. Moreover, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the activation of nuclear factor-κB (NF-κB) signalling were inhibited by CTS. Therefore, CTS could be a useful therapeutic agent in the fight against renal IR injury.

Long non-coding RNA HOTTIP affects renal cell carcinoma progression by regulating autophagy via the PI3K/Akt/Atg13 signaling pathway.

OBJECTIVE: Renal cell carcinoma (RCC) is the most common malignancy of the urinary system, and it is a serious threat to human health. HOXA transcript at the distal tip (HOTTIP), located at the 5' end of the HOXA locus, is a long non-coding RNA that has been newly discovered in recent years. It has been reported to promote the development of several types of tumors. Moreover, accumulating evidence has indicated that autophagy plays an important role in tumor cell survival or death. However, whether HOTTIP affects RCC development by regulating autophagy remains unknown. METHODS: In this study, we first measured HOTTIP expression in 42 paired RCC and adjacent non-tumor tissues, as well as in 4 RCC cell lines and 1 normal renal tubular epithelial cell line. Then, we selected 2 RCC cell lines to silence HOTTIP expression and 1 RCC cell line to overexpress HOTTIP, and we measured their proliferation, migration and invasion, as well as autophagy, after pretreatment with an autophagy inhibitor or inducer. In addition, we assessed the growth, metastasis and autophagy of tumors in nude mice and explored the mechanism involved. RESULTS: The results showed that HOTTIP expression was significantly upregulated in the RCC tissues and cell lines, and it was closely associated with TNM stage, histological grade, lymph node metastasis and patient prognosis. The in vitro and in vivo assays indicated that HOTTIP silencing inhibited RCC cell proliferation, migration and invasion and induced autophagy, and 3-MA (an autophagy inhibitor) reversed these effects. In contrast, HOTTIP overexpression and rapamycin (an autophagy inducer) yielded the opposite results. Further research revealed that HOTTIP modification could affect RCC cell autophagy via the PI3K/Akt/Atg13 signaling pathway. CONCLUSIONS: Our study will help in finding a potential marker for RCC diagnosis and supply a target molecule for RCC treatment.

Tisp40 deficiency limits renal inflammation and promotes tubular cell proliferation in renal ischemia reperfusion injury.

Renal ischemia reperfusion (IR) is a common cause of acute kidney injury (AKI), and no effective treatment is available to date. In our previous studies, we demonstrated that Tisp40 exacerbates tubular cell apoptosis and tubulointerstitial fibrosis after renal IR injury. However, the role of Tisp40 in renal inflammatory responses and tubular cell proliferation during renal IR injury remains unknown. In this study, Tisp40 knockout (KO) and wild-type (WT) mice were induced with or without renal IR injury. For renal IR, bilateral renal pedicels were exposed and clamped to induce 30 min of ischemia. After 48 h of reperfusion, the kidneys were collected for analyses. Results showed that Tisp40 deficiency attenuates neutrophil and macrophage infiltration after renal IR. Consistently, the protein levels of TNF-α and MCP-1 were markedly decreased, and the phosphorylation levels of IκBα and P65 were inhibited in Tisp40-deficient mice than in WT mice in renal IR injury. In addition, compared with WT mice, Tisp40 deficiency significantly increased the expression levels of proliferative cellular nuclear antigen and phosphorylated Erk1/2 after renal IR injury. In conclusion, Tisp40 deficiency limits renal inflammatory responses and promotes tubular cell proliferation in ischemic AKI.

Rapamycin Alleviates Hormone Imbalance-Induced Chronic Nonbacterial Inflammation in Rat Prostate Through Activating Autophagy via the mTOR/ULK1/ATG13 Signaling Pathway.

Chronic prostatitis (CP) is a clinically common disease with high morbidity. It affects the patients' quality of life (QoL) as well as physical and mental health seriously due to the recurring symptoms of lower urinary tract and genitalia. As the opinions about the etiology of CP are still not uniform, it is very difficult to be treated or even cured. Autophagy is a highly conserved physiological function which is widely found in eukaryotic cells. In general, cells maintain a certain level of autophagy under physiological conditions, and the basal level of autophagy can be regulated by a variety of autophagy-related genes under stress such as hunger, infection, trauma, and other circumstances. Therefore, the main purpose of this study is to investigate the role of autophagy in chronic nonbacterial prostatitis (CNP, also called CP). In this paper, we established the CNP model via hypodermic injection of 17ß-estradiol and subsequently abdominal rapamycin (a common autophagy inducer) treatment based on castrated rats. Then, the expression of nuclear factor-κB (NF-κB), interleukin-1ß (IL-1ß), and autophagy-related markers as well as autophagosome formation in prostate tissues, peripheral blood mononuclear cells (PBMCs), and serum of rats were evaluated respectively. In addition to some histological changes in the prostate tissues, we found the levels of NF-κB and IL-1ß were significantly increased in the model group, along with significantly suppressed autophagy, whereas rapamycin could reverse these effects which involved in the mTOR/ULK1/ATG13 signaling pathway. In conclusion, our results suggested that rapamycin could ameliorate hormone imbalance-induced CNP by activating autophagy.

Ubiquitin-Specific Peptidase 10 (USP10) Inhibits Hepatic Steatosis, Insulin Resistance, and Inflammation Through Sirt6.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and inflammation, and the pathogenic mechanism of NAFLD is poorly understood. Ubiquitin-specific peptidase 10 (USP10), a member of the ubiquitin-specific protease family, is involved in environmental stress responses, tumor growth, inflammation, and cellular metabolism. However, the role of USP10 in hepatic steatosis, insulin resistance, and inflammation remains largely unexplored. USP10 expression was detected in livers of patients with NAFLD, mice with high-fat diet (HFD)-induced obesity, and genetically obese (ob/ob) mice, as well as in palmitate-induced hepatocytes. The function of USP10 in hepatic steatosis, insulin resistance, and inflammation was investigated using hepatocyte-specific USP10 deficiency or overexpression in mice induced by HFD treatment or genetic defect. The molecular mechanisms underlying USP10-regulated hepatic steatosis were further investigated in HFD-treated mice. USP10 expression was significantly decreased in the fatty livers of NAFLD patients and obese mice and in palmitate-treated hepatocytes. USP10 deficiency exacerbated the metabolic dysfunction induced by HFD treatment for 12 weeks. Conversely, USP10 overexpression significantly suppressed metabolic dysfunction in mice after HFD treatment and inhibited the development of NAFLD in ob/ob mice. Further investigation indicated that USP10 regulates hepatic steatosis by interacting with Sirt6 and inhibiting its ubiquitination and degradation. Sirt6 overexpression markedly ameliorated the effects of USP10 deficiency in hepatic steatosis, insulin resistance, and inflammation. Conversely, Sirt6 deficiency decreased the ameliorative effects of USP10 overexpression in response to HFD treatment. Conclusion: USP10 inhibits hepatic steatosis, insulin resistance, and inflammation through Sirt6.

Anti-inflammatory effects of Lefty-1 in renal tubulointerstitial inflammation via regulation of the NF-κB pathway.

Renal tubulointerstitial inflammation has an important role in fibrosis, which is the main pathogenetic alteration associated with chronic kidney disease (CKD). The left­right determination factor 1 (Lefty­1) gene pleiotropically and biologically regulates transforming growth factor, mitogen­activated protein kinase and other signaling pathways, and is considered to have a potential anti­inflammatory function. However, its role in renal tubulointerstitial inflammation, which is often a long­term consequence of renal fibrosis, is currently unknown. In the present study, the effects of adenovirus­mediated overexpression of Lefty­1 (Ad­Lefty­1­flag) on renal tubulointerstitial inflammation were determined using a mouse model of unilateral ureteral obstruction (UUO) and a rat renal tubular duct epithelial cell line (NRK­52E), which was treated with lipopolysaccharide (LPS). In vivo results indicated that the inflammatory response was increased in UUO mice, as evidenced by the increase in inflammatory cytokines and chemokines. Conversely, Lefty­1 significantly reversed the effects of UUO. Furthermore, the results of the in vitro study demonstrated that Lefty­1 significantly inhibited LPS­induced inflammatory marker expression in cultured NRK­52E cells via the nuclear factor (NF)­κB signaling pathway. These results suggested that Lefty­1 may ameliorate renal tubulointerstitial inflammation by suppressing NF­κB signaling. In conclusion, the findings of the present study indicated that Lefty­1 may be considered a potential novel therapeutic agent for inhibiting renal tubulointerstitial inflammation or even reversing the CKD process.

Synthesis and Enhanced Ethanol Gas Sensing Properties of the g-C3N4 Nanosheets-Decorated Tin Oxide Flower-Like Nanorods Composite.

Flower-like SnO2/g-C3N4 nanocomposites were synthesized via a facile hydrothermal method by using SnCl4·5H2O and urea as the precursor. The structure and morphology of the as-synthesized samples were characterized by using the X-ray powder diffraction (XRD), electron microscopy (FESEM and TEM), and Fourier transform infrared spectrometer (FT-IR) techniques. SnO2 displays the unique 3D flower-like microstructure assembled with many uniform nanorods with the lengths and diameters of about 400-600 nm and 50-100 nm, respectively. For the SnO2/g-C3N4 composites, SnO2 flower-like nanorods were coupled by a lamellar structure 2D g-C3N4. Gas sensing performance test results indicated that the response of the sensor based on 7 wt. % 2D g-C3N4-decorated SnO2 composite to 500 ppm ethanol vapor was 150 at 340 °C, which was 3.5 times higher than that of the pure flower-like SnO2 nanorods-based sensor. The gas sensing mechanism of the g-C3N4nanosheets-decorated SnO2 flower-like nanorods was discussed in relation to the heterojunction structure between g-C3N4 and SnO2.

Tisp40 deficiency attenuates renal ischemia reperfusion injury induced apoptosis of tubular epithelial cells.

Renal ischemia reperfusion (IR) is a major cause of acute kidney injury (AKI) and no effective treatments have been established. Tisp40 is a transcription factor of the CREB/ATF family and involves in cell apoptosis, proliferation and differentiation, but its role in renal IR remains unknown. Here, we investigated the role of Tisp40 in renal IR injury. In vivo, Tisp40 knockout (KO) and wild-type (WT) mice were subjected to thirty minutes of bilateral renal ischemia and 48h reperfusion, the blood and kidneys were harvested for analysis. In vitro, Tisp40 overexpression and vector cells were subjected to hypoxia/reoxygenation (HR), the apoptosis rate and the expressions of related proteins were measured. Following IR, the expressions of Tisp40 protein, serum creatinine (sCr), blood urea nitrogen (BUN) and apoptosis of tubular cells were significantly increased in WT mice. However, Tisp40 deficiency significantly attenuated the increase of sCr, BUN and apoptosis of tubular cells. Following HR, apoptosis of tubular cells was increased in Tisp40 overexpression cells compared with vector cells. Mechanistically, Tisp40 promoted the expressions of C/EBP homologous protein (CHOP), Bax and Cleaved caspase3 and suppressed the expression of Bcl-2 in renal IR injury. In conclusion, Tisp40 aggravates tubular cells apoptosis in renal IR injury.

Solid-State Method Synthesis of SnO2-Decorated g-C3N4 Nanocomposites with Enhanced Gas-Sensing Property to Ethanol.

SnO2/graphitic carbon nitride (g-C3N4) composites were synthesized via a facile solid-state method by using SnCl4·5H2O and urea as the precursor. The structure and morphology of the as-synthesized composites were characterized by the techniques of X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), energy dispersive spectrometer (EDS), thermogravimetry-differential thermal analysis (TG-DTA), X-ray photoelectron spectroscopy (XPS), and N2 sorption. The results indicated that the composites possessed a two-dimensional (2-D) structure, and the SnO2 nanoparticles were highly dispersed on the surface of the g-C3N4 nanosheets. The gas-sensing performance of the samples to ethanol was tested, and the SnO2/g-C3N4 nanocomposite-based sensor exhibited admirable properties. The response value (Ra/Rg) of the SnO2/g-C3N4 nanocomposite with 10 wt % 2-D g-C3N4 content-based sensor to 500 ppm of ethanol was 550 at 300 °C. However, the response value of pure SnO2 was only 320. The high surface area of SnO2/g-C3N4-10 (140 m²·g-1) and the interaction between 2-D g-C3N4 and SnO2 could strongly affect the gas-sensing property.