Biomimetic Electrochemical Sensor Based on Single-Atom Nickel Laccase Nanoenzyme for Quercetin Detection.

Laccase, a member of the copper oxidase family, has been used as a green catalyst in the environmental and biochemical industries. However, laccase nanoenzymes are limited to materials with copper as the active site, and noncopper laccase nanoenzymes have been scarcely reported. In this study, inspired by the multiple copper active sites of natural laccase and the redox Cu2+/Cu+ electron transfer pathway, a novel nitrogen/nickel single-atom nanoenzyme (N/Ni SAE) with high laccase-like activity was prepared by inducing Ni and dopamine precipitation through a controllable water/ethanol interface reaction. Compared with that of laccase, the laccase activity simulated by N/Ni SAE exhibited excellent stability and reusability. The N/Ni SAE exhibited a higher efficiency toward the degradation of 2,4-dichlorophenol, hydroquinone, bisphenol A, and p-aminobenzene. In addition, a sensitive electrochemical biosensor was constructed by leveraging the laccase-like activity of N/Ni SAE; this sensor offered unique advantages in terms of catalytic activity, selectivity, stability, and repeatability. Its detection ranges for quercetin were 0.01-0.1 and 1.0-100 µM, and the detection limit was 3.4 nM. It was also successfully used for the quantitative detection of quercetin in fruit juices. Therefore, the single-atom biomimetic nanoenzymes prepared in this study promote the development of a new electrochemical strategy for the detection of various bioactive molecules and show great potential for practical applications.

[Clinical value of fluorescence laparoscopy in pelvic lymph node dissection for intermediate- and high-risk prostate cancer patients].

OBJECTIVE: We explore the clinical value of fluorescence laparoscopy in the management of intermediate- and high-risk prostate cancer (PCa) patients by radical prostatectomy plus pelvic lymph node dissection (RP+PLND). METHODS: We retrospectively analyzed the clinical data on 45 PCa patients (32 intermediate- and 13 high-risk cases) treated by RP+PLND in our hospital from 2018 to 2020. The patients received injection of 1 ml Indocyanine Green bilaterally into the prostate under the cystoscope 30 minutes before surgical dissection of the lymph nodes, including those by the external iliac, distal internal iliac and obturator, common and presacral ones, and those visualized in the fluorescence image. We recorded the total numbers of lymph nodes, the fluorescence-manifested ones, and the positive ones. RESULTS: The mean postoperative Gleason score of the patients was 7.5 ± 0.7. Totally 967 lymph nodes were removed, and 134 were observed under the fluorescence laparoscope in 42 cases. Fourteen positive lymph nodes were found in 5 cases. Positive lymph nodes were also detected by the external iliac, distal internal iliac and obturator in 4 cases, with a sensitivity of 80% and a specificity of 100%. Fluorescence imaging exhibited positive lymph nodes in the lymphangion in 3 cases, with a sensitivity of 60% and a specificity of 100%. The lymph nodes by the external iliac, distal internal iliac and obturator and the fluorescence-manifested ones were also dissected, which were found positive in 5 cases, with a sensitivity of 100% and a specificity of 100%. CONCLUSION: Pelvic lymph nodes can be observed by fluorescence laparoscopy in most PCa patients. Dissection of the lymph nodes by the external iliac, distal internal iliac and obturator and the fluorescence-manifested ones contributes to a higher detection rate of positive pelvic lymph nodes in intermediate- and high-risk PCa patients.

Gradual unlocking of plate boundary controlled initiation of the 2014 Iquique earthquake.

On 1 April 2014, Northern Chile was struck by a magnitude 8.1 earthquake following a protracted series of foreshocks. The Integrated Plate Boundary Observatory Chile monitored the entire sequence of events, providing unprecedented resolution of the build-up to the main event and its rupture evolution. Here we show that the Iquique earthquake broke a central fraction of the so-called northern Chile seismic gap, the last major segment of the South American plate boundary that had not ruptured in the past century. Since July 2013 three seismic clusters, each lasting a few weeks, hit this part of the plate boundary with earthquakes of increasing peak magnitudes. Starting with the second cluster, geodetic observations show surface displacements that can be associated with slip on the plate interface. These seismic clusters and their slip transients occupied a part of the plate interface that was transitional between a fully locked and a creeping portion. Leading up to this earthquake, the b value of the foreshocks gradually decreased during the years before the earthquake, reversing its trend a few days before the Iquique earthquake. The mainshock finally nucleated at the northern end of the foreshock area, which skirted a locked patch, and ruptured mainly downdip towards higher locking. Peak slip was attained immediately downdip of the foreshock region and at the margin of the locked patch. We conclude that gradual weakening of the central part of the seismic gap accentuated by the foreshock activity in a zone of intermediate seismic coupling was instrumental in causing final failure, distinguishing the Iquique earthquake from most great earthquakes. Finally, only one-third of the gap was broken and the remaining locked segments now pose a significant, increased seismic hazard with the potential to host an earthquake with a magnitude of >8.5.

[Entecavir improves the reproductive function of male patients with chronic hepatitis B].

OBJECTIVE: To study the effect of entecavir on the reproductive function of male patients with chronic hepatitis B (CHB). METHODS: This study included 56 CHB male patients (aged 18－45 ï¼»33.14 ± 5.38ï¼½ years) initially treated with entecavir at 0.5 mg/d for 24 weeks from 2015 to 2018 and another 24 healthy fertile male volunteers (aged 21－45 ï¼»32.62 ± 5.94ï¼½ years) as normal controls. We obtained the body mass index (BMI), reproductive hormone levels, semen parameters and IIEF-5 scores from the subjects and compared them between the two groups before and after treatment. RESULTS: There were no statistically significant differences between the CHB and normal control groups in age, BMI, lifestyle and baseline reproductive hormone levels except in the levels of FSH (ï¼»3.92 ± 1.29ï¼½ vs ï¼»3.08 ± 0.85ï¼½ mIU/ml, P = 0.003) and E2 (ï¼»35.79 ± 7.49ï¼½ vs ï¼»28.25 ± 7.09ï¼½ pg/ml, P < 0.01). The semen parameters were significantly lower in the CHB patients than in the normal controls, including total sperm motility (ï¼»37.75 ± 13.33ï¼½% vs ï¼»49.58 ± 9.27ï¼½%, P = 0.004), the percentage of progressively motile sperm (PMS) (ï¼»30.70 ± 10.03ï¼½% vs ï¼»42.46 ± 8.90ï¼½%, P < 0.01), sperm concentration (ï¼»51.51 ± 19.50ï¼½ vs 70.33 ± 30.62) ×106/ml, P = 0.007), and total sperm count (ï¼»160.2 ± 51.8ï¼½ vs ï¼»225.91 ± 97.97ï¼½ ×106, P = 0.002), and so were the IIEF-5 scores (19.32 ± 2.34 vs 21.25 ± 2.35, P = 0.0006). After 24 weeks of entecavir treatment, the CHB patients showed no significant difference from the baseline in the semen volume, semen pH and days of abstinence, but remarkable improvement in total motility (ï¼»37.75 ± 13.33ï¼½ vs ï¼»44.1 ± 11.89ï¼½%, P = 0.004), PMS (ï¼»30.70 ± 10.03ï¼½ vs ï¼»38.30 ± 7.42ï¼½%, P < 0.01), sperm concentration (ï¼»51.51 ± 19.50ï¼½ vs ï¼»62.00 ± 24.64ï¼½ ×106/ml, P = 0.007), total sperm count (ï¼»160.21 ± 51.8ï¼½ vs ï¼»207.65 ± 81.69ï¼½ ×106, P = 0.0002), and IIEF-5 score (20.13 ± 1.82 vs 19.32 ± 2.34, P = 0.02). CONCLUSIONS: CHB patients have lower sexual function and semen quality than normal males. Entecavir can significantly improve the liver function, sexual function and semen quality of the CHB patients, but whether it directly improves the sexual function and semen quality of the patients or indirectly through liver function improvement needs to be further studied.

[Application of artificial intelligence combined with multi-parametric MRI in the early diagnosis of prostate cancer].

OBJECTIVE: To explore the value of artificial intelligence combined with multi-parametric MRI (AI-mpMRI) in the early diagnosis of prostate cancer. METHODS: This retrospective study included 64 cases of prostate cancer confirmed by biopsy and treated by radical prostatectomy from May 2017 to February 2018. The mpMRI images of T2 weighted imaging (T2WI), diffusion weighted imaging (DWI) and dynamic-contrast enhanced (DCE) MRI and the pathological sections corresponding to the three sequential MRI images were collected. The benign and malignant regions were labeled on the pathological slice level, the three sequential MRI axial images at the same level were virtually covered with the pathological slice using computer-aided transparent mapping technology, and selected the fixed-sized benign and malignant regions of interest (ROI). The MATLAB software was used to display the features of the images and screen out the characteristic parameters with P < 0.05, so as to derive high-accuracy analytical methods for the diagnosis of prostate cancer. RESULTS: A total of 31 image characteristics were extracted with the MATLAB software, and 3 high-accuracy analytical methods screened out for the diagnosis of prostate cancer, including the linear discrimination, logistic regression analysis, and support vector machine classification, with the accuracy rates of 75.9%, 75.4% and 74.9% and the areas under the curve (AUC) of 0.83, 0.82 and 0.82, respectively. CONCLUSIONS: AI-mpMRI can achieve a high detection rate in the early diagnosis of prostate cancer and therefore has a high clinical application value.

How to accelerate the upper urinary stone discharge after extracorporeal shockwave lithotripsy (ESWL) for < 15 mm upper urinary stones: a prospective multi-center randomized controlled trial about external physical vibration lithecbole (EPVL).

OBJECTIVE: To asset the efficacy and safety of EPVL plus ESWL compared with ESWL alone for the treatment of simple upper urinary stones (< 15 mm). MATERIALS AND METHODS: All patients with upper urinary stones (< 15 mm) were prospectively randomized into two groups. In treatment group, patients were assigned to immediate EPVL after ESWL, while in control group, ESWL alone was offered. All patients were reexamined at 1, 2, and 4 weeks after ESWL. Stone size, stone location, stone-free rate (SFR), and complication rate were compared. RESULTS: 56 males and 20 females in treatment group were compared to 52 male and 25 females in control group (p = 0.404). Median ages were 42.9 ± 1.5 years in treatment group and 42.7 ± 1.3 years in control group (p = 0.943). Median stone size was 10.0 ± 0.4 mm (3-15 mm) in treatment group and 10.4 ± 0.4 mm (4-15 mm) in control group (p = 0.622). The stone clearance rate in treatment and control group at 1 week after ESWL was 51.3% (39/76) and 45.4% (35/77) (p > 0.05), at 2 weeks was 81.6% (62/76) and 64.9% (50/77) (p < 0.05), and at 4 weeks was 90.8% (69/76) and 75.3% (58/77) (p < 0.05), respectively. CONCLUSIONS: EPVL is a noninvasive, effective, and safe adjunctive treatment which increases and accelerates upper urinary stones discharge after ESWL treatment.

External Physical Vibration Lithecbole Promotes the Clearance of Upper Urinary Stones after Retrograde Intrarenal Surgery: A Prospective, Multicenter, Randomized Controlled Trial.

PURPOSE: We assessed the efficacy and safety of external physical vibration lithecbole for the treatment of residual stones after retrograde intrarenal surgery. MATERIALS AND METHODS: A total of 173 patients (128 males and 45 females) were selected for study. All patients had residual fragments after retrograde intrarenal surgery for renal or upper ureteral stones. They were prospectively randomized into 2 groups. One group underwent external physical vibration lithecbole 1 week after retrograde intrarenal surgery and the other underwent only retrograde intrarenal surgery as the control group. Stone size and location, stone-free rate and complications were compared. RESULTS: Of 173 patients 87 (66 males and 21 females) were in the treatment group and 86 (62 males and 24 females) were in the control group. The stone-free rate in the treated and control groups 2 weeks after retrograde intrarenal surgery was 52.9% and 31.4%, at 3 weeks it was 71.3% and 51.2%, and at 5 weeks it was 89.7% and 59.3%, respectively (all p <0.05). The hematuria incidence 5 weeks after retrograde intrarenal surgery was 3.4% in the treated group compared to 20.9% in the control group (p <0.05). The incidence of positive urine leukocytes in the treated vs control groups was 4.6% vs 19.8% 3 weeks after retrograde intrarenal surgery and 3.4% vs 11.6% at 5 weeks (p <0.05). CONCLUSIONS: External physical vibration lithecbole as a supplement to retrograde intrarenal surgery was more effective than retrograde intrarenal surgery alone in terms of stone clearance speed, stone-free rate and patient compliance.

RNA sequencing reveals differential thermal regulation mechanisms between sexes of Glanville fritillary butterfly in the Tianshan Mountains, China.

The Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae) has been extensively studied as a model species in metapopulation ecology. We investigated in the earlier studies that female butterflies exhibit higher thermal tolerance than males in the Tianshan Mountains of China. We aim to understand the molecular mechanism of differences of thermal responses between sexes. We used RNA-seq approach and performed de novo assembly of transcriptome to compare the gene expression patterns between two sexes after heat stress. All the reads were assembled into 84,376 transcripts and 72,701 unigenes. The number of differential expressed genes (DEGs) between control and heat shock samples was 175 and 268 for males and females, respectively. Heat shock proteins genes (hsps) were up-regulated in response to heat stress in both males and females. Most of the up-regulated hsps showed higher fold changes in males than in females. Females expressed more ribosomal subunit protein genes, transcriptional elongation factor genes, and methionine-rich storage protein genes, participating in protein synthesis. It indicated that protein synthesis is needed for females to replace the damaged proteins due to heat shock. In addition, aspartate decarboxylase might contribute to thermal tolerance in females. These differences in gene expression may at least partly explain the response to high temperature stress, and the fact that females exhibit higher thermal tolerance.

[Transurethral resection of the prostate versus transurethral holmium laser enucleation of the prostate for benign prostatic hyperplasia with bladder detrusor overactivity].

OBJECTIVE: To compare and analyze the effects of transurethral resection of the prostate (TURP) and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with bladder detrusor overactivity. METHODS: his study included 51 cases of BPH with bladder detrusor overactivity treated by TURP and another 58 treated by HoLEP. We evaluated the urination of the two groups of patients during the recovery period and at 3 and 6 months postoperatively. RESULTS: There were no statistically significant differences in such baseline data as the blood PSA level, prostate volume, International Prostate Symptom Score (IPSS), and quality of life (QOL) between the two groups of patients, except in effective bladder capacity, which was higher in the TURP than in the HoLEP group (ï¼»315±59ï¼½ vs ï¼»287±76ï¼½ ml, P<0.05). Urine storage symptoms were obviously improved in both of the groups postoperatively, with the storage symptoms score significantly decreased from 12.6±4.9 preoperatively to 7.5±3.9 at 3 months and 6.1±4.2 at 6 months after surgery in the TURP group (P<0.01) and from 13.7±5.7 to 7.9±4.2 and 7.0±5.1 in the HoLEP group (P<0.01). HoLEP manifested significant advantages over TURP in the postoperative urethral catheterization time (ï¼»2.7±0.8ï¼½ vs ï¼»5.1±1.2ï¼½ d, P<0.05), postoperative bladder contracture time (ï¼»4.1±1.9ï¼½ vs ï¼»5.8±2.4ï¼½ d, P<0.05), postoperative hospital stay (ï¼»4.4±1.8ï¼½ vs ï¼»5.9±2.5ï¼½ d, P<0.05), and improvement of the maximum urinary flow rate, which was increased from (7.9±3.7) ml/s preoperatively to (16.8±4.3) ml/s at 3 months after surgery in the HoLEP group and from (8.6±3.2) ml/s to (14.6±4.3) ml/s in the TURP group (P<0.05). CONCLUSIONS: Both TURP and HoLEP can improve bladder function and detrusor overactivity in BPH patients, with similar effects in improving urination at 3 to 6 months after surgery. However, HoLEP has more advantages over TURP during the period of postoperative recovery.

Vitamin A and risk of bladder cancer: a meta-analysis of epidemiological studies.

BACKGROUND: Epidemiological studies have reported the preventive effect of vitamin A intake on bladder cancer. However, the findings are inconsistent. To address this issue we conducted a meta-analysis to investigate the quantitative effects of vitamin A on bladder cancer. METHODS: We searched MEDLINE and Embase databases and the references of the relevant articles in English to include studies on dietary or blood vitamin A for the risk of bladder cancer. We performed a meta-analysis using both fixed-effects and random-effects models. RESULTS: Twenty-five articles on dietary vitamin A or blood vitamin A were included according to the eligibility criteria. The pooled risk estimates of bladder cancer were 0.82 (95% CI 0.65, 0.95) for total vitamin A intake, 0.88 (95% CI 0.73, 1.02) for retinol intake, and 0.64 (95% CI 0.38, 0.90) for blood retinol levels. We also found inverse associations between subtypes of carotenoids and bladder cancer risk. CONCLUSION: The findings of this meta-analysis indicate that high vitamin A intake was associated with a lower risk of bladder cancer. Larger studies with prospective design and rigorous methodology should be considered to validate the current findings.

Phenotypic plasticity in thermal tolerance in the Glanville fritillary butterfly.

Ambient temperature is an ubiquitous environmental factor affecting all organisms. Global climate change increases temperature variation and the frequency of extreme temperatures, which may pose challenges to ectotherms. Here, we examine phenotypic plasticity to temperature and genotypic effects on thermal tolerance in the Glanville fritillary butterfly (Melitaea cinxia). We found no significant difference in heat or cold tolerance in populations originating from a continental climate in China and from Finland with moderate temperature variation. Acclimation to large-amplitude temperature variation increased heat tolerance in both populations, but decreased cold tolerance and increased hsp70-2 expression in the Chinese population only. The latter result indicates a genotypic effect in the response to temperature variation. In the Finnish population, a non-synonymous SNP in the phosphoglucose isomerase (Pgi) gene was associated with heat knock-down time.

Computer-aided detection of prostate cancer in early stages using multi-parameter MRI: A promising approach for early diagnosis.

BACKGROUND: Transrectal ultrasound-guided prostate biopsy is the gold standard diagnostic test for prostate cancer, but it is an invasive examination of non-targeted puncture and has a high false-negative rate. OBJECTIVE: In this study, we aimed to develop a computer-assisted prostate cancer diagnosis method based on multiparametric MRI (mpMRI) images. METHODS: We retrospectively collected 106 patients who underwent radical prostatectomy after diagnosis with prostate biopsy. mpMRI images, including T2 weighted imaging (T2WI), diffusion weighted imaging (DWI), and dynamic-contrast enhanced (DCE), and were accordingly analyzed. We extracted the region of interest (ROI) about the tumor and benign area on the three sequential MRI axial images at the same level. The ROI data of 433 mpMRI images were obtained, of which 202 were benign and 231 were malignant. Of those, 50 benign and 50 malignant images were used for training, and the 333 images were used for verification. Five main feature groups, including histogram, GLCM, GLGCM, wavelet-based multi-fractional Brownian motion features and Minkowski function features, were extracted from the mpMRI images. The selected characteristic parameters were analyzed by MATLAB software, and three analysis methods with higher accuracy were selected. RESULTS: Through prostate cancer identification based on mpMRI images, we found that the system uses 58 texture features and 3 classification algorithms, including Support Vector Machine (SVM), K-nearest Neighbor (KNN), and Ensemble Learning (EL), performed well. In the T2WI-based classification results, the SVM achieved the optimal accuracy and AUC values of 64.3% and 0.67. In the DCE-based classification results, the SVM achieved the optimal accuracy and AUC values of 72.2% and 0.77. In the DWI-based classification results, the ensemble learning achieved optimal accuracy as well as AUC values of 75.1% and 0.82. In the classification results based on all data combinations, the SVM achieved the optimal accuracy and AUC values of 66.4% and 0.73. CONCLUSION: The proposed computer-aided diagnosis system provides a good assessment of the diagnosis of the prostate cancer, which may reduce the burden of radiologists and improve the early diagnosis of prostate cancer.

Three amino acid substitutions contributing to thermostability of phosphoglucose isomerase in the Glanville fritillary butterfly.

Temperature is one of the most important environmental factors that affect organisms, especially ectotherms, due to its effects on protein stability. Understanding the general rules that govern thermostability changes in proteins to adapt high-temperature environments is crucial. Here, we report the amino acid substitutions of phosphoglucose isomerase (PGI) related to thermostability in the Glanville fritillary butterfly (Melitaea cinxia, Lepidoptera: Nymphalidae). The PGI encoded by the most common allele in M. cinxia in the Chinese population (G3-PGI), which is more thermal tolerant, is more stable under heat stress than that in the Finnish population (D1-PGI). There are 5 amino acid substitutions between G3-PGI and D1-PGI. Site-directed mutagenesis revealed that the combination of amino acid substitutions of H35Q, M49T, and I64V may increase PGI thermostability. These substitutions alter the 3D structure to increase the interaction between 2 monomers of PGI. Through molecular dynamics simulations, it was found that the amino acid at site 421 is more stable in G3-PGI, confining the motion of the α-helix 420-441 and stabilizing the interaction between 2 PGI monomers. The strategy for high-temperature adaptation through these 3 amino acid substitutions is also adopted by other butterfly species (Boloria eunomia, Aglais urticae, Colias erate, and Polycaena lua) concurrent with M. cinxia in the Tianshan Mountains of China, i.e., convergent evolution in butterflies.

Prognostic significance and mechanisms of CXCL genes in clear cell renal cell carcinoma.

This study aimed to investigate the clinical significance, biological functions, and underlying mechanisms of CXCL genes in clear cell renal cell carcinoma (ccRcc) based on patient datasets and pan-cancer analysis. The interaction between CXCL genes in ccRcc and immune components, particularly in relation to neutrophil recruitment and polarization mechanisms, was also evaluated. Furthermore, a risk score was developed using a signature for neutrophil polarization. The role of CXCL2 was assessed through in vitro experiments. Results showed that five CXCL genes (CXCL 2, 5, 9, 10, and 11) were upregulated in renal cancer tissue, while seven genes (CXCL 1, 2, 3, 5, 8, 13, and 14) significantly impacted patient survival. Moreover, CXCL 1, 5, and 13 affected progression-free survival. Besides, differences in mRNA expression and immune components affected renal cancer outcomes. Furthermore, three pairs of CXCL gene-immune cell interactions (CXCL13-CD8+ T cells, CXCL9/10-M1 cells, CXCL1/2/3/8-neutrophils) were identified through single-cell and pan-cancer analysis. A TAN risk score with prognostic value for KIRC patients was constructed using 11 genes and a TAN signature. Neutrophil polarization significantly impacted survival. Notably, CXCL2 was involved in neutrophil recruitment and polarization, thus promoting ccRcc progression. In conclusion, seven prognostic CXCL genes (CXCL 1/2/3/5/8/13/14) for ccRcc patients and three pairs of CXCL gene-immune cell interactions were identified. Furthermore, results showed that CXCL 2 promotes ccRcc progression through neutrophil recruitment and polarization.

Complex multi-fault rupture and triggering during the 2023 earthquake doublet in southeastern Türkiye.

Two major earthquakes (MW 7.8 and MW 7.7) ruptured left-lateral strike-slip faults of the East Anatolian Fault Zone (EAFZ) on February 6, 2023, causing >59,000 fatalities and ~$119B in damage in southeastern Türkiye and northwestern Syria. Here we derived kinematic rupture models for the two events by inverting extensive seismic and geodetic observations using complex 5-6 segment fault models constrained by satellite observations and relocated aftershocks. The larger event nucleated on a splay fault, and then propagated bilaterally ~350 km along the main EAFZ strand. The rupture speed varied from 2.5-4.5 km/s, and peak slip was ~8.1 m. 9-h later, the second event ruptured ~160 km along the curved northern EAFZ strand, with early bilateral supershear rupture velocity (>4 km/s) followed by a slower rupture speed (~3 km/s). Coulomb Failure stress increase imparted by the first event indicates plausible triggering of the doublet aftershock, along with loading of neighboring faults.

Fatty acid metabolism-related signature predicts survival in patients with clear cell renal carcinoma.

OBJECTIVE: To explore fatty acid metabolism-related genes and signature, which could predict survival outcomes of clear cell renal carcinoma (ccRCC) patients. MATERIALS AND METHODS: Transcriptional and survival data of fatty acid genes in ccRCC patients were retrieved from UCSC Xena and Geo DataSets. We first performed Lasso Cox regression analysis to identify survival-related genes. These genes were then used to construct metabolic-related gene signature and risk score. Enrichment analysis and immune component and chemotherapy response prediction were also performed. RESULTS: In total, five survival-related genes were identified: AGR2, HAO2, IGF2BP1, MCCD1 and OLFM4 (p < 0.05). A series of survival value analyses revealed survival-related signature and risk score, including KM analysis (training set: p < 0.001; test set: p = 0.008). Four clinical indexes (T stage, N stage, M stage, and pathology) were positively correlated with risk score. Time-dependent ROC analysis yielded AUC value of 0.813. Immune landscape analysis revealed that risk score was strongly correlated with TAM score and cytotoxic score. Patients with high risk score and TAM score or cytotoxic score had the shortest survival time. Finally, inhibition of fatty acid metabolism in human ccRCC cell line produced corresponding changes in five genes, consistent with our preliminary results. CONCLUSION: We identified five survival-related genes (AGR2, HAO2, IGF2BP1, MCCD1 and OLFM4) in ccRCC patients. Our results also indicated that survival-related signature based on these genes is a potential robust prognostic biomarker for ccRCC in patients.

mRNA-Modified FUS/NRF2 Signalling Inhibits Ferroptosis and Promotes Prostate Cancer Growth.

Objective: Regarding the imperfect mechanism of occurrence and development of prostate adenocarcinoma (PRAD), this study investigated mRNA-modified FUS/NRF2 signalling to inhibit ferroptosis and promote prostate adenocarcinoma growth. Methods: Bioinformatics analysis was used to obtain the expression of FUS and its mRNA modification in PRAD. The expression of FUS in prostate cells (CRPC) and the level of m6A methylation modification, ferroptosis (P53 and GPX4), apoptosis (Caspase3), ferroptosis (P53 and GPX4), and apoptosis (Caspase3) in CRPC after ferroptosis inducer Erastin, ferroptosis inhibitor, and FUS knockdown were detected. Autophagy (LC3B), oxidative stress (GSH and ROS), and expression of NRF2/HO-1 pathway are indicators. Results: FUS was highly expressed in PRAD and phenomenally reduced the survival rate of patients. After knocking down FUS, the level of m6A methylation was significantly reduced, and the expressions of ferroptosis markers P53 and GPX4 were phenomenally reduced, while the levels of apoptosis and autophagy markers Caspase3 and LC3B remained unchanged. Upregulated and NRF2/HO-1 pathway indicators were upregulated. It shows that m6A methylation modification is reduced when FUS is the low expression, inhibits the expression of P53 and GPX4, downregulates GSH, upregulates ROS, activates the NRF2/HO-1 pathway, and promotes ferroptosis to inhibit the occurrence of RPAD. Conclusions: The increase of m6A methylation modification can increase the expression of FUS, thereby promoting the expression of P53 and GPX4, upregulating GSH, downregulating ROS, inhibiting the NRF2/HO-1 pathway, inhibiting ferroptosis, and promoting the growth of PRAD.

Comprehensive analysis of expression profiles and prognosis of TRIM genes in human kidney clear cell carcinoma.

OBJECTIVE: To determine survival rates and the underlying mechanism of genes in the TRIM family in Kidney Clear Cell Carcinoma (KIRC). METHODS: Transcriptional and survival data of TRIM genes in KIRC patients were retrieved from the UCSC Xena, and GEPIA databases. The function of TRIM genes in KIRC was investigated, focusing on potential ubiquitination, miRNAs regulation, and enrichment analysis. Next, TRIM gene survival values were determined, followed by the development of a survival-related signature. RESULTS: Only TRIM26 was down expressed in the carcinoma tissue and had a survival value in KIRC relative to control tissues, which was supplied by vitro experiment. The patients with lower expression of TRIM26 would have the chance to live a shorter time. SNRPB, which also plays a role in ubiquitination, directly interacted with TRIM26. Moreover, two miRNAs (hsa-let-7i-5p, and hsa-miR-1228-5p) that regulated levels of TRIM26 expression were also identified. Next, we constructed a signature (TRIM4/7/27/58/65/72) and found that high-risk scores of the signature were associated with poor survival rates in KIRC patients. while its resultant risk scores were correlated with immune cell components and markers. CONCLUSIONS: TRIM26 was differentially expressed between KIRC and normal tissues and had a survival value in the KIRC. hsa-let-7i-5p/hsa-miR-1228-5p-TRIM26-SNRPB was a potential mechanism axis that may play a role on the KIRC cells. A survival signature (TRIM4/7/27/58/65/72) was successfully established to predict the survival of KIRC patients.

Calbindin S100A16 Promotes Renal Cell Carcinoma Progression and Angiogenesis via the VEGF/VEGFR2 Signaling Pathway.

Purpose: Recent research has indicated that the calcium-binding protein S100A16 promotes carcinogenesis and tumor growth in several forms of cancer. The objective of this study was to examine the relationship between S100A16 and renal cell cancer. Methods: By using The Cancer Genome Atlas (TCGA) database, the differentially expressed gene S100A16 was identified, and its appearance and link to the prognosis of persons with renal cancer were confirmed. Cox regression was used in multivariate analysis, and a nomogram was developed for internal validation. The correlation between S100A16 and immune cells was analyzed in the TIMER database. Moreover, the potential mechanism of action was investigated utilizing GO and KEGG enrichment analyses. Proliferation, migration, and angiogenesis were investigated in vitro, and the involvement of S100A16 in the undesirable biological events of renal cell carcinoma (RCC) was further explored. Results: S100A16 was the differentially expressed molecule identified through database screening. Malignant tissues showed higher S100A16 expression than noncancerous tissues, and S100A16 expression was mostly localized in the cytoplasm. According to the TCGA and KM-plotter datasets, patients with RCC and low S100A16 expression had superior OS, PFI, and DSS. The C-index of the nomogram was 0.754 (0.726-0.782), and the accuracy of the prediction model was high. The TIMER database shows that the expression of S100A16 is associated with immune infiltration and may play an important role in promoting tumor cell immune escape in the RCC tumor microenvironment. S100A16 may influence the biological processes of RCC via the VEGF/VEGFR2 signaling route and PI3K-Akt signaling pathway and through P53 alteration and cell cycle according to the gene enrichment technique. In vitro cytological experiments demonstrated that S100A16 knockdown can inhibit the proliferation and migration of renal cancer cells and the expression levels of VEGF, VEGFR2, and phosphorylated AKT within renal cancer cells, thereby inhibiting angiogenesis in renal cancer cells and resulting in a poor prognosis of RCC. Conclusion: A decrease in S100A16 expression may dramatically increase the OS, PFI, and DSS of patients with RCC and may thus be used as a biomarker for predicting RCC. It may be associated with the immune infiltration of RCC and play a crucial role in the immune evasion of tumor cells within the RCC microenvironment. Intervention of s100a16 can promote the progression and angiogenesis of renal cell carcinoma through the VEGF/VEGFR2 signal transduction pathway and lead to poor prognosis of renal cell carcinoma. These findings suggest a potential target for the development of anticancer strategies for renal cancer.

The clinical value of indocyanine green fluorescence navigation system for laparoscopic partial nephrectomy in the case of complex renal clear cell carcinoma (R.E.N.A.L score ≥7).

Objective: We demonstrated the potential clinical utility of the indocyanine green (ICG) fluorescence navigation system for laparoscopic partial nephrectomy in the case of complex renal clear cell carcinoma (R.E.N.A.L score ≥7). Methods: Compared with the general laparoscopic partial nephrectomy and ICG fluorescence laparoscopic partial nephrectomy, a series of indicators were analyzed: the basic information like age, sex, and the tumor location; the operative information like the time of renal ischemia, the blood loss, and the complications; and other important indexes like the renal function, the volume of the tumor, and the weight of the specimens. Results: 60 patients were included in this study. 21 patients in the group of fluorescence laparoscopy, and 39 patients in the group of general laparoscopy. There was no statistical difference for most indexes except the renal function. Preoperative serum creatinine was close (82.4±11.7 vs. 77.5±12.7, mmol/l, p=0.15). However, the patients in the group of fluorescence laparoscopy got a smaller serum creatinine growth degree (12.9±5.3 vs. 17.9±7.3, mmol/l, p=0.008), and a less decreasing level of GFR (16.5±6.4 vs. 24.4±9.8, mL/(min*1.73m2), p=0.001) after the operation. In addition, the average volume of the tumor (28.8±9.8 vs. 26.9±8.2, cm3, p=0.43) and the weight of the specimens (32.3±10.4 vs. 33.9±8.9, g, p=0.52) were no statistical difference. But the group of fluorescence laparoscopy had a smaller ratio of the weight/ the volume (1.13±0.06 vs. 1.28±0.10, g/cm3, p<0.001). And the two groups had a similar test-positivity rate of surgical margins (p=0.19). Conclusion: Without increasing the rate of positive surgical margins, ICG fluorescence navigation system for laparoscopic partial nephrectomy for complex renal clear cell carcinoma could conserve more normal renal tissue.