Causal effects of BMI, waist circumference, and body fat percentage on the risk of bladder cancer: A Mendelian randomization study.

The causal role of body mass index (BMI) in bladder cancer (BC) by Mendelian randomization (MR) has not yet been reported. We evaluated the causal associations between the measures of obesity (BMI, waist circumference, and body fat percentage) and BC. We conducted a 2-sample MR analysis to assess the genetic effect of measures of obesity on BC. The BMI dataset (GWAS ID: ukb-b-2303) comprised 454,884 Europeans, and we identified 9,851,867 single nucleotide polymorphisms (SNPs). The waist circumference data (GWAS ID: ukb-b-9405) included 462,166 Europeans and 9,851,867 SNPs. The body fat percentage dataset (GWAS ID: ukb-a-264) contained data from 331,117 Europeans and 10,894,596 SNPs. For the outcome data, the GWAS ID was finn-b-C3_BLADDER, consisting of 1115 cases and 217,677 controls, with 16,380,466 SNPs. The inverse-variance weighted (IVW) model was used as the primary MR analysis. Cochran Q-statistic was used to identify heterogeneity between the SNPs. The MR-Egger and MR-PRESSO methods were employed to assess directional pleiotropy and outlier SNPs. We detected a decisive causal link between BMI and BC by the IVW analysis (odds ratio [OR] = 1.41, 95% confidence interval [CI]: 1.08-1.85, P = .011). The IVW analyses revealed a significant correlation between BC and waist circumference (OR = 1.55, 95% CI: 1.08-2.12, P = .016). However, the IVW method (OR = 1.49, 95% CI: 0.99-2.00, P = .05) did not report any statistical significance between body fat percentage and BC. We did not observe heterogeneity and directional pleiotropy in the 3 pairs of MR studies. The 2-sample MR analysis revealed a conceivable causal association between obesity (BMI, waist circumference) and BC.

Current Status and Prospects of Pediatric Stone Disease: A Bibliometric and Visualization Study.

Pediatric stone disease, once considered rare, has emerged as a significant research area in the past two decades due to a sharp increase in its incidence. Understanding the evolving epidemiology and treatment strategies for pediatric stone disease is crucial for enhancing child health protection. This study aims to summarize the advancements in pediatric stone disease research over the last two decades through bibliometric analysis. We conducted a comprehensive search in the Web of Science Core Collection (WoSCC) for literature on pediatric stone disease from January 1, 2000 to February 20, 2024. Econometric analyses were performed using tools such as VOSviewer, CiteSpace, and the R package "bibliometrix." Our search yielded 1,208 publications, predominantly from the United States and Turkey, showing an annual increase in publications on pediatric stone disease. Leading research institutions include Dicle University, Children's Hospital of Philadelphia, and the University of Pennsylvania, with the Journal of Pediatric Urology publishing the highest number of articles. The most prolific authors were C.P. Nelson and B. Hoppe, with Caleb P. Nelson being the most co-cited author. Research themes primarily focused on risk factors and therapeutic approaches for pediatric stone disease. Emerging research hotspots are identified by keywords such as mechanism, mini-percutaneous nephrolithotomy, recurrence, and retrograde intrarenal surgery. The study forecasts a continued upward trend in global research on pediatric stone disease, with future studies likely to delve deeper into risk factors and novel therapeutic methods.

Exploring the role of coagulation-related genes in renal cell carcinoma: Implications for tumor microenvironment and prognostic biomarkers.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) frequently progresses to advanced stages due to tumor thrombus (TTs) formation. In this study, we aimed to investigate the role of coagulation-related pathway activation in the progression of ccRCC. METHODS: Consensus clustering was used to identify coagulation-related molecular clusters of ccRCC patients from The Cancer Genome Atlas Program (TCGA) database. The function of coagulation and its correlation with the immune microenvironment were investigated. Protein-protein interactions and differential expression analysis were used to identify the key gene, which was verified by external experiments. The coagulation-associated risk score was constructed by cox proportional hazards regression. RESULTS: Notable disparities were detected in immune characteristics, prognostic differentiation and drug sensitivity between two coagulation-related clusters. Through the integration of clinical stage significance and protein-protein interactions, the key gene MMP9 was screened and it was significantly correlated with CD4+T cells, CD8+T cells and Treg cells. A coagulation-related risk score prognostic model was developed in the Cancer Genome Atlas (TCGA) cohort for risk stratification and prognosis prediction. The prognostic predictive values of the coagulation-related risk score were further authenticated in both TCGA-KIRC and E-MTAB-1980 cohorts. CONCLUSION: There is an obvious correlation between the coagulation and the tumor microenvironment in ccRCC. As a key coagulation-related gene, MMP9 may promote the progression of renal cell carcinoma by influencing immune infiltration of CD8+T cells and Treg cells. Additionally, the risk score could be used as a durable prognostic biomarker, which could assist in clinical decision making for ccRCC patients.

Two chromosome-level genome assemblies of Rhodiola shed new light on genome evolution in rapid radiation and evolution of the biosynthetic pathway of salidroside.

Rhodiola L. is a genus that has undergone rapid radiation in the mid-Miocene and may represent a typic case of adaptive radiation. Many species of Rhodiola have also been widely used as an important adaptogen in traditional medicines for centuries. However, a lack of high-quality chromosome-level genomes hinders in-depth study of its evolution and biosynthetic pathway of secondary metabolites. Here, we assembled two chromosome-level genomes for two Rhodiola species with different chromosome number and sexual system. The assembled genome size of R. chrysanthemifolia (2n = 14; hermaphrodite) and R. kirilowii (2n = 22; dioecious) were of 402.67 and 653.62 Mb, respectively, with approximately 57.60% and 69.22% of transposable elements (TEs). The size difference between the two genomes was mostly due to proliferation of long terminal repeat-retrotransposons (LTR-RTs) in the R. kirilowii genome. Comparative genomic analysis revealed possible gene families responsible for high-altitude adaptation of Rhodiola, including a homolog of plant cysteine oxidase 2 gene of Arabidopsis thaliana (AtPCO2), which is part of the core molecular reaction to hypoxia and contributes to the stability of Group VII ethylene response factors (ERF-VII). We found extensive chromosome fusion/fission events and structural variations between the two genomes, which might have facilitated the initial rapid radiation of Rhodiola. We also identified candidate genes in the biosynthetic pathway of salidroside. Overall, our results provide important insights into genome evolution in plant rapid radiations, and possible roles of chromosome fusion/fission and structure variation played in rapid speciation.

[Computer-simulated osteotomy based on health-side combined with guide plate technique in treatment of cubitus varus deformity in adolescents].

Objective: To explore the feasibility and early effectiveness of computer-simulated osteotomy based on the health-side combined with guide plate technique in the treatment of cubitus varus deformity in adolescents. Methods: The clinical data of 23 patients with cubitus varus deformity who met the selection criteria between June 2019 and February 2023 were retrospectively analyzed. There were 17 males and 6 females, ranging in age from 4 to 16 years with an average of 8.5 years. The time from injury to operation was 1-4 years. The angle of distal humerus rotation was defined by humeral head posterior inclination angle using low radiation dose CT to scan the patient's upper extremity data at one time, and the preoperative rotation of the distal humerus on the affected side was (33.82±4.39)°. The CT plain scan data were imported into 9yuan3D digital orthopaedic system (V3.34 software) to reconstruct three-dimensional images of both upper extremities. The simulated operation was performed with the healthy upper extremity as the reference, the best osteotomy scheme was planned, overlapped and compared, and the osteotomy guide plate was prepared. The patients were followed up regularly after operation, and the formation of callus in the osteotomy area was observed by X-ray examination. Before and after operation, the carrying angle of both upper extremities (the angle of cubitus valgus was positive, and the angle of cubitus varus was negative) and anteversion angle were measured on X-ray and CT images. At the same time, the flexion and extension range of motion of elbow joint and the external rotation range of motion of upper extremity were measured, and Mayo score was used to evaluate the function of elbow joint. Results: The operation time ranged from 34 to 46 minutes, with an average of 39 minutes. All patients were followed up 5-26 months, with a mean of 14.9 months. All the incisions healed by first intention after the operation; 2 patients had nail path irritation symptoms after Kirschner wire fixation, which improved after dressing change; no complication such as breakage and loosening of internal fixators occurred after regular X-ray review. Continuous callus formed at the osteotomy end at 4 weeks after operation, and the osteotomy end healed at 8-12 weeks after operation. At last follow-up, the carrying angle, anteversion angle, external rotation range of motion, and extension and flexion range of motion of the elbow joint of the affected side significantly improved when compared with preoperative ones ( P<0.05). Except for the extension range of motion of the healthy elbow joint ( P<0.05), there was no significant difference in other indicators between the two sides ( P>0.05). At last follow-up, the Mayo elbow score was 85-100, with an average of 99.3; 22 cases were excellent, 1 case was good, and the excellent and good rate was 100%. Conclusion: Computer-simulated osteotomy based on health-side combined with guide plate technique for treating cubitus varus deformity in adolescents can achieve precise osteotomy, which has the advantages of short operation time and easy operation, and the short-term effectiveness is satisfactory.

Ultrasound, a new adjuvant method for treating acute Monteggia fracture in children.

PURPOSE: This study aims to evaluate the feasibility of using ultrasound-guided Kirschner wire or elastic intramedullary nail for fixation in the treatment of acute Monteggia fracture in children. METHODS: A retrospective analysis was conducted on 31 cases of acute Monteggia fracture in children treated with ultrasound-guided Kirschner wire or elastic intramedullary nail fixation between April 2020 and December 2022, including 14 cases of Kirschner wire fixation and 17 cases of elastic intramedullary nail fixation. During the operation, soft tissue compression and nerve and vascular injuries were explored, fracture reduction was performed under ultrasound guidance, and operation time was recorded. After the operation, X-ray examination was conducted to assess the quality of fracture reduction. At the last follow-up, the flexion, extension, pronation, and supination angles of both affected and unaffected elbow joints were measured, and the Mayo score was used to evaluate elbow joint function. RESULTS: The average duration of surgery was 50.16 ± 19.21 min (ranging from 20 to 100 min). Based on the evaluation criteria for assessing reduction quality, 28 cases were deemed excellent, while 3 cases were considered good. After immobilization with long-arm cast for 4-6 weeks postoperatively, elbow and forearm rotation exercises were performed. Kirschner wires were removed after an average of 6.64 ± 0.93 weeks (ranging from 6 to 9 weeks) postoperatively, and elastic intramedullary nails were removed after an average of 5.12 ± 1.54 months (ranging from 4 to 10 months) postoperatively. The average follow-up time was 19.13 ± 11.22 months (ranging from 4 to 36 months). During the final follow-up, the affected limb's range of motion in flexion, extension, pronation, and supination was (141.16 ± 4.24)°, (4.61 ± 2.81)°, (84.52 ± 3.74)°, and (84.23 ± 3.69)°, respectively. There was no notable variance when compared to the healthy limb, which had a range of motion of (141.81 ± 2.99)°, (4.81 ± 2.50)°, (85.61 ± 3.12)°, and (85.03 ± 2.73)° (P > 0.05). The Mayo Elbow Performance index classified 29 cases as excellent and 2 cases as good. CONCLUSION: Ultrasound-guided Kirschner wire or elastic intramedullary nail fixation can be used for the treatment of acute Monteggia fracture in children, which can explore the surrounding nerves, blood vessels, and soft tissue compression, reduce the difficulty of reduction, and cause minimal trauma. It can greatly reduce the risk of radiation exposure and complications such as vascular and nerve injury during the operation.

Correlation Study Between Bone Cement Distribution and Adjacent Vertebral Fractures After Percutaneous Vertebroplasty.

OBJECTIVE: We investigated the correlation between bone cement distribution and adjacent vertebral fractures (AVFs) after percutaneous vertebroplasty (PVP). METHODS: We retrospectively analyzed patients who underwent single-segment PVP for osteoporotic compression fractures in our hospital from January 2016 to January 2021 and divided the patients into 2 groups, A and B, on the basis of the criterion of whether there were AVFs of the operated vertebrae within 1 year after surgery. We compared the general data of the 2 groups, assessed the ability of 3 simple X-ray-based evaluation methods to predict the occurrence of AVF within 1 year after surgery and derived a simple and accurate evaluation method. RESULTS: A total of 570 patients were included in this study: 511 patients in group A and 59 patients in group B. There were no statistical differences in the general data such as age, gender, and fracture site between the 2 groups. The posterior-anterior (PA), lateral (LAT), and PA and LAT methods showed receiver operating characteristic curve (ROC) predicted postoperative AVF of 0.611, 0.691, and 0.714, respectively. The difference between the area under curve (AUC) of the PA method and LAT method was statistically significant (P = 0.0307), the difference between the AUC of PA method and PA and LAT method was statistically significant (P < 0.001), and the difference between the AUC of LAT method and PA and LAT method was not statistically significant (P = 0.3308).There was no statistical difference between the 2 groups of patients with PA method point of 1 and statistically different between patients with points of 2 and 3. There was statistical difference in points of 1, 2 and 3 in the LAT method between the 2 groups. There was a positive correlation between cement distribution scores and AVF by linear regression analysis of the 3 evaluation methods. CONCLUSIONS: The 3 evaluation methods reliably predict AVF after PVP, with the LAT method, PA and LAT method being more predictive than the PA method, but the LAT method is simpler, with bone cement being widely distributed after crossing the midline in the PA method and contact with the upper and lower end plates in the LAT method being a risk factor for AVF.

Clinical application of novel integrated suctioning semi-rigid ureteroscopic lithotripsy.

INTRODUCTION: Urinary calculi are frequently encountered in urology. Traditionally, the lack of a perfect water injection and drainage system means the observation field is affected during ureteroscopy. Here, we explored the effect and clinical value of a new integrated suctioning semi-rigid ureteroscopic lithotripsy (URSL) for treating ureteral calculi. MATERIAL AND METHODS: A total of 180 patients were successfully enrolled in this study (60 in each group). Group A included patients who underwent a traditional semi-rigid URSL, group B included patients who underwent a suctioning semi-rigid URSL with a sheath being connected to a vacuum device, and group C included patients who underwent a new type of suctioning integrated rigid URSL with a novel designed ureteroscope. RESULTS: In total, 164 cases of URSL were completed in one stage. Compared with group A, group C had a higher stone-clearance rate at 30 days postoperatively, shorter operation time, and fewer hospitalization days (p < .05); compared with group B, group C had a higher one-stage operation success rate, shorter operation time, and fewer hospitalization days (p < .05). CONCLUSIONS: Comparatively, the new suctioning integrated semi-rigid URSL is advantageous for treating upper urinary calculi, considering the reduced operation time, length of hospital stay, and low invasiveness.

Genomic data provide a robust phylogeny backbone for Rhodiola L. (Crassulaceae) and reveal extensive reticulate evolution during its rapid radiation.

The Tibetan Plateau and adjacent mountain regions (TP; including the Tibetan Plateau, Himalaya, Hengduan Mountains and Mountains of Central Asia) harbor great biodiversity, some lineages on which may have undergone rapid radiations. However, only a few studies have investigated the evolutionary pattern of such diversification in depth using genomic data. In this study, we reconstructed a robust phylogeny backbone of Rhodiola, a lineage that may have undergone rapid radiation in the TP, using Genotyping-by-sequencing data, and conducted a series of gene flow and diversification analyses. The concatenation and coalescent-based methods yield similar tree topologies, and five well-supported clades were revealed. Potential gene flow and introgression events were detected, both between species from different major clades and closely related species, suggesting pervasive hybridization and introgression. An initial rapid and later slowdown of the diversification rate was revealed, indicating niche filling. Molecular dating and correlation analyses showed that the uplift of TP and global cooling in the mid-Miocene might have played an important role in promoting the rapid radiation of Rhodiola. Our work demonstrates that gene flow and introgression might be an important contributor to rapid radiation possibly by quickly reassembling old genetic variation into new combinations.

Rapid genotyping of porcine reproductive and respiratory syndrome virus (PRRSV) using MinION nanopore sequencing.

The global distribution and constant evolution are challenges for the control of porcine reproductive and respiratory syndrome virus (PRRSV), one of the most important viruses affecting swine worldwide. Effective control of PRRSV benefits from genotyping, which currently relies on Sanger sequencing. Here we developed and optimized procedures for real-time genotyping and whole genome sequencing of PRRSV directly from clinical samples based on targeted amplicon- and long amplicon tiling sequencing using the MinION Oxford Nanopore platform. Procedures were developed and tested on 154 clinical samples (including lung, serum, oral fluid and processing fluid) with RT-PCR Ct values ranging from 15 to 35. The targeted amplicon sequencing (TAS) approach was developed to obtain sequences of the complete ORF5 (main target gene for PRRSV genotyping) and partial ORF4 and ORF6 sequences of both PRRSV-1 and PRRSV-2 species. After only 5 min of sequencing, PRRSV consensus sequences with identities to reference sequences above 99% were obtained, enabling rapid identification and genotyping of clinical PRRSV samples into lineages 1, 5 and 8. The long amplicon tiling sequencing (LATS) approach targets type 2 PRRSV, the most prevalent viral species in the U.S. and China. Complete PRRSV genomes were obtained within the first hour of sequencing for samples with Ct values below 24.9. Ninety-two whole genome sequences were obtained using the LATS procedure. Fifty out of 60 sera (83.3%) and 18 out of 20 lung samples (90%) had at least 80% of genome covered at a minimum of 20X sequence depth per position. The procedures developed and optimized in this study here are valuable tools with potential for field application during PRRSV elimination programs.

Allopolyploid origin and niche expansion of Rhodiola integrifolia (Crassulaceae).

Polyploidy after hybridization between species can lead to immediate post-zygotic isolation, causing saltatory origin of new species. Although the incidence of polyploidization in plants is high, it is thought that a new polyploid lineage can succeed only if it establishes a new ecological niche divergent from its progenitor lineages. We tested the hypothesis that Rhodiola integrifolia from North America is an allopolyploid produced by R. rhodantha and R. rosea and determined whether its survival can be explained by the niche divergence hypothesis. To this end, we sequenced two low-copy nuclear genes (ncpGS and rpb2) in a phylogenetic analysis of 42 Rhodiola species and tested for niche equivalency and similarity using Schoener's D as the index of niche overlap. Our phylogeny-based approach showed that R. integrifolia possesses alleles from both R. rhodantha and R. rosea. Dating analysis showed that the hybridization event that led to R. integrifolia occurred ca. 1.67 Mya and niche modeling analysis showed that at this time, both R. rosea and R. rhodantha may have been present in Beringia, providing the opportunity for the hybridization event. We also found that the niche of R. integrifolia differs from that of its progenitors in both niche breadth and optimum. Taken together, these results confirm the hybrid origin of R. integrifolia and support the niche divergence hypothesis for this tetraploid species. Our results underscore the fact that lineages with no current overlapping distribution could produce hybrid descendants in the past, when climate oscillations made their distributions overlap.

Histone methyltransferase KMT2D promotes prostate cancer progression through paracrine IL-6 signaling.

Histone methyltransferase KMT2D plays a critical role as a human oncogene in prostate cancer (PCa). Dysregulated inflammatory responses and cytokine signaling are implicated in cancer progression. Furthermore, interleukin 6 (IL-6) is a pleiotropic cytokine that contributes to PCa progression; however, the association between KMT2D and IL-6 in PCa remains unclear. PCa cell proliferative potential, migratory potential, and apoptosis in vitro were determined using cell counting kit-8 (CCK-8), EdU incorporation, wound healing, and apoptosis assays. Proliferation and migratory potential were impaired and apoptosis was induced in PCa cells cultured with the conditioned medium from KMT2D-depleted cells. Cytokine array analysis showed that IL-6 was the most affected cytokine in the conditioned media. KMT2D knockdown significantly downregulated the expression of IL-6 in PCa cells. What's more, proliferation and migration were also impaired and apoptosis was also induced by silencing IL-6R expression. Immunohistochemistry (IHC) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were performed to validate the positive correlation between KMT2D and IL-6 in PCa tissue samples. Chromatin immunoprecipitation (ChIP)-PCR demonstrated that KMT2D and H3K4me1 occupied IL-6 enhancer regions and therefore, directly regulated IL-6 expression. The present study revealed that the KMT2D knockdown suppressed prostate cancer progression through the downregulation of paracrine IL-6 signaling. These results suggest that KMT2D could be regarded as a potential new target for PCa therapy.

Closed reduction and plaster immobilization: an alternative solution for patients with developmental dysplasia of the hip who failed Pavlik harness treatment.

BACKGROUND: The current study aims to investigate the clinical efficacy of closed reduction and cast immobilization for patients with developmental dysplasia of the hip (DDH) who failed Pavlik harness treatment. METHODS: Patients with DDH who underwent cast immobilization under general anaesthesia after the failure of the Pavlik harness or Tübingen brace treatment between January 2015 and December 2020 were retrospectively recruited. General information, including Graf classification of initial diagnosis, initial treatment, age of cast immobilization, IHDI classification, AI index, avascular necrosis (AVN), and residual dysplasia, was collected. The incidence of AVN and late acetabular dysplasia (LACD) was also estimated. Moreover, factors related to AVN and LACD were investigated by multiple logistic regression analysis. RESULTS: Thirty-four patients (47 hips) were finally included in the current study. Of these patients, 31 hips (66.0%) were successfully treated with closed reduction and cast immobilization. Open reduction was successfully performed in 16 hips (34.0%). Till the latest follow-up, LACD and AVN were found in 13 (27.7%) and 10 (21.3%) hips, respectively. In the open reduction group, type III and IV of the IHDI classification and type IV of the Ultrasound Graf classification were significantly higher when compared with the closed reduction group. Multiple logistic regression showed that failure of closed reduction was related to the initial types of the Ultrasound Graf and IHDI classifications. CONCLUSIONS: Although the success rate of closed reduction after early harness failure in DDH is only 66%, we still advocate closed reduction as a first-line treatment for children who have failed sling treatment. Even if closed reduction fails, open reduction can still achieve acceptable results.

MicroRNA-181b promotes schistosomiasis-induced hepatic fibrosis by targeting Smad7.

Schistosomiasis is a common parasitic disease. Hepatosplenic schistosomiasis, caused by Schistosoma japonicum and Schistosoma mansoni, involves pathological changes, including worm egg-induced hepatic granuloma and fibrosis, which can markedly affect the liver's physiological functions. Although the drug praziquantel (PZQ) is used to treat schistosomiasis, drugs against schistosomiasis-induced liver fibrosis are rare in the clinical setting. Therefore, developing effective strategies to prevent and treat schistosomiasis-induced liver fibrosis is crucial. Previous studies have shown that miRNAs are involved in various liver diseases. In this study, we found a gradual increase in miR-181b expression in the murine liver as S. japonicum infection progressed, while the expression of Smad7 decreased. Down-regulating miR-181b significantly alleviated S. japonicum-induced hepatic granuloma and liver fibrosis. In vitro experiments showed that treatment with TGF-ß1 upregulated miR-181b levels in the hepatic stellate cell (HSC) line LX2 in a concentration- and time-dependent manner. Downregulation of miR-181b significantly decreased collagen type I alpha 1 chain (COL1A1) expression in TGF-ß1-stimulated LX2 cells. These findings indicate that miR-181b promotes HSC activation by down-regulating Smad7 expression, activating the TGF-ß1/Smad signaling pathway, and leading to excess collagen expression and deposition. Our findings suggest that miR-181b might be a potentially novel therapeutic target for schistosomiasis-induced liver fibrosis.

Integrated analysis reveals FOXA1 and Ku70/Ku80 as targets of ivermectin in prostate cancer.

Ivermectin is a widely used antiparasitic drug and shows promising anticancer activity in various cancer types. Although multiple signaling pathways modulated by ivermectin have been identified in tumor cells, few studies have focused on the exact target of ivermectin. Herein, we report the pharmacological effects and targets of ivermectin in prostate cancer. Ivermectin caused G0/G1 cell cycle arrest, induced cell apoptosis and DNA damage, and decreased androgen receptor (AR) signaling in prostate cancer cells. Further in vivo analysis showed ivermectin could suppress 22RV1 xenograft progression. Using integrated omics profiling, including RNA-seq and thermal proteome profiling, the forkhead box protein A1 (FOXA1) and non-homologous end joining (NHEJ) repair executer Ku70/Ku80 were strongly suggested as direct targets of ivermectin in prostate cancer. The interaction of ivermectin and FOXA1 reduced the chromatin accessibility of AR signaling and the G0/G1 cell cycle regulator E2F1, leading to cell proliferation inhibition. The interaction of ivermectin and Ku70/Ku80 impaired the NHEJ repair ability. Cooperating with the downregulation of homologous recombination repair ability after AR signaling inhibition, ivermectin increased intracellular DNA double-strand breaks and finally triggered cell death. Our findings demonstrate the anticancer effect of ivermectin in prostate cancer, indicating that its use may be a new therapeutic approach for prostate cancer.

Effect of applying persulfate on the accumulation of arsenic in rice plants grown in arsenic-contaminated paddy soil.

Arsenic is known to be a notorious human carcinogen and rice consumption is becoming the primary human exposure route for As, especially in many Asian countries. As one of redox-sensitive elements in soil, sulfur plays an indisputable role in controlling As behaviors. However, information on the effects of persulfe (PS) on the toxicity and accumulation of As in rice plant under flooded conditions is limited. Therefore, a pot experiment was conducted to investigate the effects of PS amendment on the growth and accumulation of As species in rice plants grown in As-contaminated paddy soil. Results revealed that PS application increased the As, Fe, and Mn in porewater at the early stage, and then declined. Application of PS increased the biomass of stem and root, while inhibited the formation of iron plaque on the root surface. The As translocation from root to rice above tissues and accumulation of As species in brown rice were declined by amendment with PS. The inorganic arsenic (iAs) and DMA were the two main species in brown rice, and decreased by 13~26% and 40~60% respectively upon PS application. The results suggested that amendment with PS might be feasible for reducing the accumulation of As in rice grains grown in As-contaminated paddy soil. However, further detailed studies on the potential soil biogeochemical and physiological mechanisms are recommended.

A review of application and development of combustion technology for oil sludge.

Oil sludge is a typical hazardous waste in the petrochemical and electric power industry. It has complex components and special properties, and has serious hazards to humans, plants, water, and soil. Therefore, how to realize the effective disposal of oil sludge has become an urgent issue to be solved worldwide. Among the existing oil sludge treatment approaches, combustion has been considered to be a promising technology to realize the large-scale industrial application. In the present work, the characteristics of oil sludge were described in detail. The application and development of oil sludge combustion technology were critically summarized and discussed, including factors affecting combustion, drying process, combustion characteristics, synergistic treatment technology, and formation and control of secondary pollution. Besides, the development of combustion equipment, and integrated thermal treatment technology for oil sludge were prospected. This work can be used for guiding the industrial disposal of oil sludge.

Design, Synthesis and Structure-Activity Relationship Studies of Meridianin Derivatives as Novel JAK/STAT3 Signaling Inhibitors.

Hyperactivation of Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling is an attractive therapeutic target for tumor therapy. Herein, forty-eight novel meridianin derivatives were designed and synthesized, and their antitumor activity was evaluated in vitro both for activity optimization and structure-activity relationship (SAR) study. The results indicated that most derivatives exhibited significantly improved antitumor activity, especially for compound 6e. The compound 6e contains an isothiouronium linked by an alkyl chain consisting of six carbon atoms with IC50 ranging from 1.11 to 2.80 µM on various cancer cell lines. Consistently, the 6e dose dependently induced the apoptosis of A549 and DU145 cells, in which STAT3 is constitutively active. Western blotting assays indicated that the phosphorylation levels of JAK1, JAK2 and STAT3 were inhibited by 6e at 5 µM without significant change in the total STAT3 level. Moreover, 6e also suppressed the expression of STAT3 downstream genes, including c-Myc, Cyclin D1 and Bcl-XL at 10 µM. An additional in vivo study revealed that 6e at the dose of 10 mg/kg could potently inhibit the DU145 xenograft tumor without obvious body weight loss. These results clearly indicate that 6e could be a potential antitumor agent by targeting the JAK/STAT3 signaling pathway.

Sodium butyrate ameliorates Schistosoma japonicum-induced liver fibrosis by inhibiting HMGB1 expression.

Schistosomiasis is a prevalent zoonotic parasitic disease caused by schistosomes. Its main threat to human health is hepatic granuloma and fibrosis due to worm eggs. Praziquantel remains the first choice for the treatment of schistosomiasis but has limited benefit in treating liver fibrosis. Therefore, the need to develop effective drugs for treating schistosomiasis-induced hepatic fibrosis is urgent. High-mobility group box 1 protein (HMGB1) is a potential immune mediator that is highly associated with the development of some fibrotic diseases and may be involved in the liver pathology of schistosomiasis. We speculated that HMGB1 inhibitors could have an anti-fibrotic effect. Sodium butyrate (SB), a potent inhibitor of HMGB1, has shown anti-inflammatory activity in some animal disease models. In this study, we evaluated the effects of SB on a murine schistosomiasis model. Mice were percutaneously infected with 20 ± 2 cercariae of Schistosoma japonicum. SB (500 mg/kg/day) was administered every 3 days for the entire experiment period. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology, HMGB1 expression, and the levels of interferon gamma (IFN-γ), transforming growth factor-ß1 (TGF-ß1), and interleukin-6 (IL-6) in serum were analyzed. SB reduced hepatic granuloma and fibrosis of schistosomiasis, reflected by the decreased levels of ALT and AST in serum and the reduced expression of pro-inflammatory and fibrogenic cytokines (IFN-γ, TGF-ß1, and IL-6). The protective effect could be attributable to the inhibition of the expression of HMGB1 and release by SB.

Combustion characteristics and kinetic analysis of oil sludge with CaO additive.

Combustion of High-sulfur oil sludge (OS) blended with CaO can significantly reduce the emission of sulfur gas pollutants, but its combustion and kinetic characteristics need to be further studied. TGA experiments showed the combustion characteristics of OS were significantly changed after adding CaO. As reflected by comprehensive combustion index (S), the combustion performance of OS decreased after adding CaO, and significantly improved with the increase of heating rate. The kinetic parameters of the main combustion process of OS with CaO were calculated by the iso-conversion methods of Friedman, FWO, and Starink, respectively. Kinetic analysis results indicated the energy required for OS combustion with CaO first increased and then decreased with deepening of reaction degree. The thermodynamic parameters of ΔH, ΔG and ΔS were determined on the basis of kinetics. The negative ΔH, positive ΔG, and negative ΔS validated the combustion of OS with CaO was an exothermic and nonspontaneous process.