A multi-omic single-cell landscape of cellular diversification in the developing human cerebral cortex.

The vast neuronal diversity in the human neocortex is vital for high-order brain functions, necessitating elucidation of the regulatory mechanisms underlying such unparalleled diversity. However, recent studies have yet to comprehensively reveal the diversity of neurons and the molecular logic of neocortical origin in humans at single-cell resolution through profiling transcriptomic or epigenomic landscapes, owing to the application of unimodal data alone to depict exceedingly heterogeneous populations of neurons. In this study, we generated a comprehensive compendium of the developing human neocortex by simultaneously profiling gene expression and open chromatin from the same cell. We computationally reconstructed the differentiation trajectories of excitatory projection neurons of cortical origin and inferred the regulatory logic governing lineage bifurcation decisions for neuronal diversification. We demonstrated that neuronal diversity arises from progenitor cell lineage specificity and postmitotic differentiation at distinct stages. Our data paves the way for understanding the primarily coordinated regulatory logic for neuronal diversification in the neocortex.

USP54 is a potential therapeutic target in castration-resistant prostate cancer.

BACKGROUND: USP54, a ubiquitin-specific protease in the deubiquitinase (DUB) family, facilitates the malignant progression of several types of cancer. However, the role of USP54 in prostate cancer (PCa), especially castration-resistant prostate cancer (CRPC), remains unknown. METHODS: We established the CRPC LNCaP-AI cell line from the hormone-sensitive prostate cancer (HSPC) LNCaP cell line. RNA-Seq was utilized to explore DUB expression levels in LNCaP and LNCaP-AI. USP54 was knocked down, and its effects on cell growth were evaluated in vitro and in vivo. Bioinformatics analyses were conducted to explore signaling pathways affected by USP54 in PCa. Quantitative polymerase chain reaction was used to confirm key signaling pathways involved. RESULTS: USP54 was the most strongly upregulated DUB in LNCaP-AI cells compared with LNCaP cells. USP54 levels were higher in PCa than in normal tissues. USP54 silencing suppressed the proliferation of PCa cell lines, both in vitro and in vivo. USP54 expression was positively correlated with the androgen receptor (AR) signaling level in PCa samples, and USP54 knockdown inhibited AR signaling in PCa cells. CONCLUSIONS: USP54 was upregulated during HSPC progression to CRPC. USP54 depletion suppressed CRPC cell proliferation both in vitro and in vivo. USP54 may facilitate PCa progression by regulating AR signaling.

PROST: quantitative identification of spatially variable genes and domain detection in spatial transcriptomics.

Computational methods have been proposed to leverage spatially resolved transcriptomic data, pinpointing genes with spatial expression patterns and delineating tissue domains. However, existing approaches fall short in uniformly quantifying spatially variable genes (SVGs). Moreover, from a methodological viewpoint, while SVGs are naturally associated with depicting spatial domains, they are technically dissociated in most methods. Here, we present a framework (PROST) for the quantitative recognition of spatial transcriptomic patterns, consisting of (i) quantitatively characterizing spatial variations in gene expression patterns through the PROST Index; and (ii) unsupervised clustering of spatial domains via a self-attention mechanism. We demonstrate that PROST performs superior SVG identification and domain segmentation with various spatial resolutions, from multicellular to cellular levels. Importantly, PROST Index can be applied to prioritize spatial expression variations, facilitating the exploration of biological insights. Together, our study provides a flexible and robust framework for analyzing diverse spatial transcriptomic data.

ANP32B inhibition suppresses the growth of prostate cancer cells by regulating c-Myc signaling.

ANP32B is a histone chaperone that interacts with various transcription factors that regulate cancer cell proliferation, immigration, and apoptosis. c-Myc, a well-known oncogenic protein, is a principal player in the initiation and progression of prostate cancer (PC). The means by which ANP32B and c-Myc act remain unknown. We downloaded clinical data from the GEO, TCGA, and other databases to explore ANP32B expression and its effects on the survival of PC and normal tissues. ANP32B-knockdown cell lines were used to evaluate how ANP32B affected cell proliferation in vitro and in vivo. Gene set enrichment analysis and RNAseq were employed to define how ANP32B regulated PC pathways. Immunohistochemical measures were used to detect the expression levels of relevant proteins in xenografts and PC tissues. ANP32B expression increased in PC tissues; ANP32B knockdown inhibited cell growth but this was rescued by c-Myc signaling. ANP32B is thus a PC oncogene and may serve as a valuable therapeutic target when seeking to treat PC.

Visible-light Excited and Highly Photostable Organic Fluorophore with dual-state Emission.

Organic fluorophores with dual-state emission (DSE) are rare or difficult to observe because most of them display either aggregation-induced emission (AIE) or aggregation-caused quenching (ACQ). Amazing works have been accomplished, yet most of the DSE compounds were excited by UV light which limits their wide application in bioimaging. In this work, we achieved a visible-light excited DSE fluorophore and realized its imaging in SKOV-3 cells and zebrafish. The naphtho[2',3':4,5]imidazo[1,2-a]pyridine (NIP) core ensures its emission in dilute solution. Meanwhile, the twisted phenyl ring blocks fluorescence quenching induced by the π-π stacking and leads to the emission of the solid. The fluorescence intensity is steady even after 6 h of continuous intense sunlight. More importantly, photostability of NIP in cells is much better than commercial dye (mitochondrial green).

Predicting the speciation of ionizable antibiotic ciprofloxacin by biochars with varying carbonization degrees.

Sorption mechanisms of ionizable organic pollutants by biochars and approaches for the prediction of sorption are still unclear. In this study, batch experiments were conducted to explore the sorption mechanisms of woodchip-derived biochars prepared at 200-700 °C (referred as WC200-WC700) for cationic, zwitterionic and anionic species of ciprofloxacin (referred as CIP+, CIP± and CIP-, respectively). The results revealed that the sorption affinity of WC200 for different CIP species was in the order of CIP± > CIP+ > CIP-, while that of WC300-WC700 remained the order of CIP+ > CIP± > CIP-. WC200 exhibited a strong sorption ability, which could be attributed to hydrogen bonding and electrostatic attraction with CIP+, electrostatic attraction with CIP±, and charge-assisted hydrogen bonding with CIP-. Pore filling and π-π interactions contributed to the sorption of WC300-WC700 for CIP+, CIP± and CIP-. Rising temperature facilitated CIP sorption to WC400 as verified by site energy distribution analysis. Proposed models including the proportion of the three CIP species and sorbent aromaticity index (H/C) can quantitatively predict CIP sorption to biochars with varying carbonization degrees. These findings are vital to elucidating the sorption behaviors of ionizable antibiotics to biochars and exploring potential sorbents for environmental remediation.

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

Fibrinogen/poly(l-lactide-co-caprolactone) copolymer scaffold: A potent adhesive material for urethral tissue regeneration in urethral injury treatment.

Since a scarcity of sufficient grafting materials, several complications can arise after urothelial defect reconstruction surgery, including severe hypospadias. Accordingly, developing alternative therapies, such as urethral restoration via tissue engineering are needed. In the present study, we developed a potent adhesive and repairing material using fibrinogen-poly(l-lactide-co-caprolactone) copolymer (Fib-PLCL) nanofiber scaffold to achieve effective urethral tissue regeneration after seeding with epithelial cells on the surface. The in vitro result found the Fib-PLCL scaffold promoted the attachment and viability of epithelial cells on their surface. The increased expression levels of cytokeratin and actin filaments were observed in Fib-PLCL scaffold than PLCL scaffold. The in vivo urethral injury repairing potential of Fib-PLCL scaffold was evaluated using a rabbit urethral replacement model. In this study, a urethral defect was surgically excised and replaced with the Fib-PLCL and PLCL scaffolds or autograft. As expected, the animals healed well after surgery in the Fib-PLCL scaffold group, and no significant strictures were identified. As expected, the cellularized Fib/PLCL grafts have induced the luminal epithelialization, urethral smooth muscle cell remodelling, and capillary development all at the same time. Histological analysis revealed that the urothelial integrity in the Fib-PLCL group had progressed to that of a normal urothelium, with enhanced urethral tissue development. Based on the results, the present study suggests that the prepared fibrinogen-PLCL scaffold is more appropriate for urethral defect reconstruction.

Endoscopic balloon cryoablation plus transurethral resection for bladder cancer: A phase 2, multicenter, randomized, controlled trial.

BACKGROUND: Cryotherapy is a prevalent percutaneous ablative therapy for solid tumors. Here, we report a novel device using liquid nitrogen for endoscopic cryotherapy of bladder cancer. METHODS: In this multicenter, randomized, parallel controlled, Phase 2 trial, we compared endoscopic balloon cryoablation (EBCA) with a single instillation (SI) of pirarubicin after transurethral resection (TUR). Eligible participants were randomly assigned (1:1) to the TUR-EBCA or TUR-SI group. Repeat TUR or tissue biopsies were performed to evaluate residual tumor at 4 to 6 weeks after primary treatment. The primary end point was the local control rate. The secondary end points included the tumor upgrading/upstaging, catheter indwelling duration, and adverse events. RESULTS: In total, 205 patients received EBCA or SI after TUR between November 2017 and September 2020, of whom 163 completed all the required interventions. In the per-protocol set, the local control rate was 91.5% (75/82) in TUR-EBCA group compared with 76.5% (61/81) in TUR-SI group (risk difference, 15%; 95% CI, 0.03-0.27, p < .001), meeting the criteria for noninferiority. Similar results were found in the modified intention-to-treat analysis. Tumor upgrading/upstaging was found in five patients from the TUR-SI group. There was no significant difference in the catheter indwelling duration (5.1 vs. 5.2 days, p = .76) or serious adverse event rate (3.0% vs. 3.9%, p = .52). The median follow-up time of post hoc analysis was 31 (range, 15-50) months. Patients in the TUR-EBCA group had a better recurrence-free survival and progression-free survival. CONCLUSION: EBCA is a safe and effective adjuvant therapy with TUR for non-muscle-invasive bladder cancer. PLAIN LANGUAGE SUMMARY: This is the first randomized trial that evaluated endoscopic cryotherapy after transurethral resection (TUR) of bladder tumors. The efficacy and safety analysis shows endoscopic balloon cryoablation (EBCA) is a promising alternative. Results report that EBCA is not inferior to a single instillation of intravesical chemotherapy in eliminating residual bladder tumor. Further analysis with ∼3 years' median follow-up suggested a better prognosis in patients who received EBCA after TUR.

Simple and Commercially Available 6-chloroimidazo[1,2-a]pyridine-2-carboxylic Acid-based Fluorescent Probe for Monitoring pH Changes.

Commercially available compounds that can be directly used as fluorescent probes will greatly promote the development of fluorescent imaging. Based on our previously work related to nitrogen bridgehead heterocycles, herein, a commercially available compound, 6-chloroimidazo[1,2-a]pyridine-2-carboxylic acid, has been detected for monitoring pH value (3.0-7.0). The probe proves to have high selectivity and sensitivity, brilliant reversibility, and extremely short response time. The real-time imaging of pH changes in yeast was also conducted.

Pharmaceuticals in multi-media environment from the Jin River to adjacent marine embayment in Southeast China.

Multi-media environmental distribution of 21 pharmaceuticals in river water, coastal water, groundwater and sediments from the Jin River to adjacent marine embayment, Southeast China, was reported for the first time. All the detected 10 pharmaceuticals were antibiotics. Oxytetracycline (OTC), ciprofloxacin (CFC) and enrofloxacin (EFC) were the most ubiquitous antibiotics and could be detected in all water samples. EFC also showed the highest detection frequency (100%) in both riverine and coastal sediments. The detected antibiotics were more widely distributed in coastal environment of Asia, especially China, rather than Europe, USA and Australia. Sulfamethoxazole (SMX) showed stronger sorption onto sediments compared with other antibiotics due to its higher pseudo-partitioning coefficients (846-10,786 L kg-1). The discharged wastewater and aquaculture were the main sources of antibiotics in the multi-media environment. Risk assessment indicated that CFC and SMX posed high risks to Microcystis aeruginosa and Synechococcus leopolensis in river water, coastal water and groundwater.

[Effect of functional acupoint electrical stimulation combined with tadalafil on erectile dysfunction in middle-aged and elderly patients].

OBJECTIVE: To investigate the application effect of functional acupoint electrical stimulation combined with tadara irregular administration in middle-aged and elderly patients with erectile dysfunction (ED), and to provide reference for clinical treatment. METHODS: A total of 40 middle-aged and elderly patients with ED admitted to the pelvic floor Center of our hospital from March 2021 to March 2023 were randomly divided into two groups with 20 cases in each group.The control group was treated with tadalafil regularly, and the observation group was treated with functional acupoint electrical stimulation on the basis of this treatment. The total course of treatment was 6 weeks.The clinical efficacy of the two groups was compared. The therapeutic efficacy was evaluated by the International Erectile Function Index (IIEF-5), penile hardness score (EHS), serum total testosterone (TT) level, sexual satisfaction scale (SS) and pelvic floor electromyography, and the occurrence of adverse events was recorded. RESULTS: The total effective rate of the observation group was significantly higher than that of the control group (90% vs 70%, P < 0.05). After 6 weeks of treatment, both groups showed improvements in IIEF-5, EHS, SS, and TT compared to before treatment (P < 0.01). However, the improvement in the observation group was significantly better than that in the control groupï¼»IIEF-5: (22.13±2.11) vs (19.69±2.04), EHS: (3.68±0.47) vs (2.89±0.60), SS: (77.41±7.59) vs (70.32±7.28), TT: (13.43±3.89) nmol/L vs (8.85±3.02) nmol/L, all P < 0.01ï¼½; There were no significant changes in pelvic floor muscle electromyography values in the control group before and after treatment (P > 0.05), while in the observation group, pelvic floor muscle electromyography values (PFMV) in the pre-resting phase, fast muscle (Type II muscle) phase, slow muscle (Type I muscle) phase, endurance testing phase, and post-resting phase all improved compared to before treatment and were superior to the control group (P < 0.05). CONCLUSION: Functional acupoint electrical stimulation combined with tadara irregular administration can improve the therapeutic effect of middle-aged and elderly patients with ED, improve pelvic floor function, safe and reliable.

Efficacy of Yun-type pelvic floor optimal training therapy and PFMT on middle aged women with mild to moderate overactive bladder: a randomized controlled trial.

Background: The symptoms of overactive bladder (OAB) are highly bothersome to patients. In behavioral therapy, traditional pelvic floor muscle training (PFMT) can be boring and monotonous, which can cause poor compliance. It's important to establish a new safe and effective crotch-pelvic floor functional reconstruction training method [Yun-type pelvic floor optimal training (Yun-type training)] for OAB patients. Methods: This randomized, double-blind, crossover trial recruited a total of 150 women with mild to moderate OAB. Patients were randomly assigned to receive Yun-type training (n=83) or PFMT (n=67). The intervention group was first given Yun-type training for 6 weeks, then switched to PFMT for 6 weeks after 2 weeks of elution. Patients in the control group were first treated with PFMT for 6 weeks, and changed to the use of Yun-type training for 6 weeks after 2 weeks of elution. The primary endpoint was overactive bladder symptom scores (OABSS) after 6 and 14 weeks of Yun-type training and PFMT. Results: Yun-type training could significantly improve OABSS compared with PFMT after 6 and 14 weeks (P<0.001). Yun-type training was associated with an improvement in urine, urgency, urge urinary incontinence (UUI), urogenital distress inventory-6 (UDI-6), patient's perception of bladder condition (PPBC), voiding volume (VV), incontinence impact questionnaire-7 (IIQ-7), female sexual function index (FSFI), sexual desire, arousal, pain, satisfaction, pelvic floor muscle tone, type I muscle strength, type II muscle strength, and sex partner satisfaction as compared with PFMT after 6 and 14 weeks. Moreover, nocturia, maximum flow rate (Qmax), and climax in the Yun-type training group were significantly improved after 6 weeks, and the average flow rate (Qave) was improved after 14 weeks in the Yun-type training group. Conclusions: Yun-type training could yield additional benefits on OAB symptoms, sexual function, and sex partner satisfaction as compared with PFMT. The superior sexual function resulting from Yun-type training can be explained by the fact that it can contract deep and superficial muscle layers, resulting in increased vaginal wall pressure and blood flow, which further improves FSFI and sex partner satisfaction. It could lead to a new non-invasive treatment for OAB patients. Trial Registration: Chinese Clinical Trial Registry ChiCTR-INR-17012192.

Study of female pelvic floor muscle in overactive bladder based on MRI 3D reconstruction.

BACKGROUND: This study examined the three-dimensional (3D) morphological changes of the urination and urinary continence anatomical structures in overactive bladder (OAB) patients, to offer a morphological data for OAB diagnosis and treatment. METHODS: Eleven OAB patients, 9 healthy females and 22 pelvic organ prolapse (POP) patients were enrolled and underwent MRI scans. The anatomical components of urination (bladder detrusor) and the urinary continence (main part of the urethral sphincter, compressor urethrae, and levator ani muscle (LAM) were 3D reconstructed and measured with Amira software. We also analyze the relativity between pelvic floor muscle's morphological parameters among the volunteers, OAB and POP group. RESULTS: Through 3D reconstruction, increased thickness and volume of the bladder detrusor were found in the OAB patients compared with volunteers (3.1 ± 0.7 mm vs. 1.9 ± 0.3 mm; P = 0.000 and 50,632.0 ± 19,724.7 mm3 vs. 23,386.6 ± 7826.3 mm3; P = 0.001). The volume of LAM showed no significant difference between the OAB patients and volunteers (27,089.4 ± 5015.0 mm3 vs. 27,294.4 ± 4461.4 mm3; P = 0.924); whereas, LAM's volume of the POP patients was significantly larger than that of the volunteers (34,130.6 ± 7968.3 mm3 vs. 27,294.4 ± 4461.4 mm3; P = 0.023). The thickness and volume of the main part of urethral sphincter were significantly lower in the OAB patients compared with volunteers (2.2 ± 0.5 mm vs. 2.7 ± 0.3 mm; P = 0.018 and 2558.6 ± 703.2 mm3 vs. 23,267.3 ± 681.9 mm3; P = 0.035). The volume of the compressor urethrae was significantly lower in the OAB patients than that in the volunteers (630.3 ± 301.2 mm3 vs. 866.1 ± 514.2 mm3; P = 0.247). CONCLUSIONS: In OAB patients, the bladder detrusor has long-term tension and contraction, which thickened muscle and increased volume, and aggravate urination. The compressor urethral and main part of urethral sphincter are weaker and the anterior part of LAM hiatus is relaxed, easily resulting in leakage of urine and ultimately incontinence. The MRI 3D reconstruction and measurement can help to evaluate pelvic floor urination and continence function, and accurately diagnose.

Efficacy of optimized pelvic floor training of YUN combined with pelvic floor magnetic stimulation on female moderate stress urinary incontinence and sexual function: a retrospective cohort study.

Background: Owing to its tediousness and monotony, traditional pelvic floor muscle training (PFMT) is difficult to ensure the correctness of exercise, and it is difficult for patients to adhere to treatment. We designed this study to evaluate and analyze the efficacy of optimized pelvic floor training of YUN combined with pelvic floor magnetic stimulation on female moderate stress urinary incontinence (SUI) and sexual function. Methods: This is a retrospective cohort study. This study was carried out in 95 female patients with moderate SUI. The inclusion criteria were as follows: premenopausal women aged 25-45; moderate SUI; over 3 months of disease duration; informed consent and cooperation with treatment and follow-up. The participants in group 1 (control group, n=46) were treated with pelvic floor magnetic stimulation, while those in group 2 (trial group, n=49) were treated with pelvic floor magnetic stimulation combined with optimized pelvic floor training of YUN. Evaluations were scheduled before the treatment (0 week), after 6 weeks of treatment (6 weeks), and after 12 weeks of treatment (12 weeks). And compare the differences between the two groups. Results: There was no significant difference in age, body mass index (BMI), duration of disease, and abdominal leak point pressure (ALPP) between the two groups (P>0.05). The total effective rate of the trial group was higher than that of the control group (89.80%, 44/49 vs. 78.26%, 36/46) (P<0.05). The electromyographic values, the International Consultation on Incontinence Questionnaire Short Form (ICI-Q-SF) score, Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) score, physiological factors, and emotional factors were all improved significantly in both groups after active treatment, and the improvement of the trial group was more obvious (P<0.05). Conclusions: Optimized pelvic floor training of YUN combined with pelvic floor magnetic are more effective for the treatment of female moderate SUI and sexual function. It has become a safe, effective, and well tolerated new type of pelvic floor functional reconstruction training method with good patient compliance.

Hengli® Chinese Botulinum Toxin Type A for Treatment of Patients With Overactive Bladder: A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: To evaluate the efficacy and safety of Hengli® Chinese botulinum toxin type A (BTX-A; 100 U) in Chinese patients with overactive bladder. Methods: This study was a multicenter, randomized, double-blind, placebo-controlled trial in Chinese patients who were inadequately managed with anticholinergic medications. Eligible patients were randomized 2:1 to receive intradetrusor injections of Hengli® BTX-A (n = 144) or placebo (n = 72). The primary endpoint was the change in the number of daily micturition episodes at week 6 from baseline. The secondary efficacy endpoints included the average frequency of urgency and urinary incontinence (UI) episodes per day, urgency score, average micturition volume per day, OABSS, and QoL score. Results: In the Hengli® BTX-A group, there was a significantly greater reduction in the average number of micturition episodes per 24 h compared with the placebo group (3.28 vs. 1.43; p = 0.003). Moreover, there was a significantly greater improvement in the daily number of urgency episodes, micturition volume and OABSS score. An increased post-void residual urine volume, dysuria, and urinary tract infection represented adverse events (AEs) in the Hengli® BTX-A group. Most AEs were mild or moderate in severity. One patient in the BTX-A group initiated clean intermittent catheterization (CIC) during treatment. Conclusion: Hengli® BTX-A treatment was well-tolerated and resulted in significant improvements in OAB symptoms among Chinese patients inadequately managed by anticholinergics. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/clinicaltrials.prosearch.dhtml, Identifier: CTR20131190.

Potential biomarkers and the molecular mechanism associated with DLL4 during renal cell carcinoma progression.

BACKGROUND: Delta-like canonical notch ligand 4 (DLL4) is considered a potential prognostic gene for renal cell carcinoma (RCC). We assessed the molecular mechanisms and novel biomarkers associated with DLL4 during RCC development. METHODS: Four gene expression profiles were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified between RCC and normal renal samples, including common DEGs (co-DEGs). Thereafter, RCC-associated gene exploration was performed and a PPI network was constructed to identify the core genes. Survival analysis of core genes in the high expression group (H group) and low expression group (L group) was also performed. The key genes related to the core genes were investigated, and the miRNA-target genes and TFs-target genes were analyzed. Finally, the expression levels of VEGFA, FLT1, EGLN3, and DLL4 in RCC and paracancerous tissues were determined. RESULTS: A total of 11,867 DEGs and 622 co-DEGs were identified in this study, and 67 RCC-associated genes that were mainly enriched in signal transduction and angiogenesis function were further explored. VEGFA was identified as the core gene. Further, 30 DEGs and 9 DE-miRNAs were identified between the H and L groups. VEGFA was positively correlated with 19 genes, including EGLN3, FLT1, and DLL4. A total of 18 miRNA-target interactions, including miR-134-5p-DLL4, were obtained. VEGFA, FLT1, EGLN3, and DLL4 were significantly expressed in RCC tissues compared with paracancerous tissues. CONCLUSIONS: DLL4 may contribute to the development of RCC by participating in signal transduction and angiogenesis. VEGFA, FLT1, EGLN3, DLL4, and miR-134-5p may be novel biomarkers for RCC.

Occurrence and Risk Assessment of Perfluorooctanoate (PFOA) and Perfluorooctane Sulfonate (PFOS) in Surface Water, Groundwater and Sediments of the Jin River Basin, Southeastern China.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) levels were determined in surface water, groundwater and sediments of the Jin River Basin, southeastern China. PFOA was detected in most of the samples, and its concentrations ranged from 0.53 to 8.77 ng/L, 0.26 to 15.1 ng/L and not detected (ND) to 23.9 ng/g in surface water, groundwater and sediments, respectively. Unlike PFOA, the detection frequency of PFOS was lower than 32%, and its concentrations ranged from ND to 2.56 ng/L, ND to 7.01 ng/L, ND to 11.1 ng/g in surface water, groundwater and sediments, respectively. The environmental risk assessment showed that PFOA could pose a high risk to surface water and groundwater, and both PFOA and PFOS posed a high risk to sediments. Moreover, the adults living in the Jin River Basin were at insignificant health risk to exposure to PFOA and PFOS through water consumption.