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A Zn(II) coordination polymer (CP), namely, {[Zn(DTPB)]·DMF}n (H2DTPB = 1-(3,5-di(2H-tetrazol-5-yl)phenyl)-1H-benzeimidazole, Zn-DTPB), was assembled from a new tetrazolyl–benzimidazolyl heterotopic triangular ligand. In Zn-DTPB, the tetrazolyl groups connect the Zn(II) ions into a 2D network with a (4·82) topology, and the 2D network is further interconnected by Zn–N bonds between Zn(II) and benzimidazolyl groups to a 3D framework featuring a 4-connected sra topology. The DMF molecules were tightly encapsulated in the framework and could not be released until the framework decomposed. The framework is stable up to 300 °C and can be retained in water for 72 h. The luminescence in the solid-state and in various solvents was investigated, implying that Zn-DTPB can be used to detect acetone and triethylamine (TEA) in water by fluorescence quenching with good sensitivity and selectivity. Moreover, Zn-DTPB exhibited excellent reproducibility in sensing acetone. Mechanistic studies have shown that the fluorescence quenching of acetone and triethylamine is caused by competitive absorption and structural amorphization, respectively. Interestingly, the amorphous product can be transformed into Zn-DTPB crystals through a solvent-media structural transformation process. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is a significant clinical issue, particularly for high Gleason score (GS) malignancy patients. Our study aimed to engineer and validate a risk model based on the profiles of high-GS PCa patients for early identification and the prediction of prognosis. Methods: We conducted differential gene expression analysis on patient samples from The Cancer Genome Atlas (TCGA) and enriched our understanding of gene functions. Using the least absolute selection and shrinkage operator (LASSO) regression, we established a risk model and validated it using an independent dataset from the International Cancer Genome Consortium (ICGC). Clinical variables were incorporated into a nomogram to predict overall survival (OS), and machine learning was used to explore the risk factor characteristics' impact on PCa prognosis. Our prognostic model was confirmed using various databases, including single-cell RNA-sequencing datasets (scRNA-seq), the Cancer Cell Line Encyclopedia (CCLE), PCa cell lines, and tumor tissues. Results: We identified 83 differentially expressed genes (DEGs). Furthermore, WASIR1, KRTAP5-1, TLX1, KIF4A, and IQGAP3 were determined to be significant risk factors for OS and progression-free survival (PFS). Based on these five risk factors, we developed a risk model and nomogram for predicting OS and PFS, with a C-index of 0.823 (95% CI, 0.766–0.881) and a 10-year area under the curve (AUC) value of 0.788 (95% CI, 0.633–0.943). Additionally, the 3-year AUC was 0.759 when validating using ICGC. KRTAP5-1 and WASIR1 were found to be the most influential prognosis factors when using the optimized machine learning model. Finally, the established model was interrelated with immune cell infiltration, and the signals were found to be differentially expressed in PCa cells when using scRNA-seq datasets and tissues. Conclusions: We engineered an original and novel prognostic model based on five gene signatures through TCGA and machine learning, providing new insights into the risk of scarification and survival prediction for PCa patients in clinical practice. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa's pathogenesis. Our review aims to investigate the multifaceted mechanisms underlying radiation therapy resistance in PCa. Specifically, we will examine how various factors, such as cell cycle regulation, DNA damage repair, hypoxic conditions, oxidative stress, testosterone levels, epithelial–mesenchymal transition, and tumor stem cells, contribute to radiation therapy resistance. By exploring these mechanisms, we hope to offer new insights and directions towards overcoming the challenges of radiation therapy resistance in PCa. This can also provide a theoretical basis for the clinical application of novel ultra-high-dose-rate (FLASH) radiotherapy in the era of PCa. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the potential clinical benefits of using stereotactic body radiation therapy (SBRT) with simultaneous integrated boost (SIB) technique for locally advanced pancreatic cancer (LAPC) among different treatment modalities and planning strategies, including photon and proton. Method: A total of 19 patients were retrospectively selected in this study: 13 cases with the tumor located in the head of the pancreas and 6 cases with the tumor in the body of the pancreas. SBRT-SIB plans were generated using volumetric modulated arc therapy (VMAT), two-field Intensity Modulated Proton Therapy (IMPT), and three-field IMPT. The IMPT used the robust optimization parameters of ± 3.5% range and 5-mm setup uncertainties. Root-mean-square deviation dose (RMSD) volume histograms were used to evaluate the target coverage robustness quantitatively. Dosimetric metrics based on the dose-volume histogram (DVH), homogeneity index (HI), and normal tissue complication probability (NTCP) were analyzed to evaluate the potential clinical benefits among different planning groups. Results: With a similar CTV and SIB coverage, two-field IMPT provided a lower maximum dose for the stomach (median: 18.6GyE, p<0.05) and duodenum (median: 32.62GyE, p<0.05) when the target was located in the head of the pancreas compared to VMAT and three-field IMPT. The risks of gastric bleed (3.42%) and grade ≥ 3 GI toxicity (4.55%) were also decreased. However, for the target in the body of the pancreas, VMAT showed a lower maximum dose for the stomach (median 30.93GyE, p<0.05) and toxicity of gastric bleed (median: 8.67%, p<0.05) compared to two-field IMPT and three-field IMPT, while other maximum doses and NTCPs were similar. The RMSD volume histogram (RVH) analysis shows that three-field IMPT provided better robustness for targets but not for OARs. Instead, three-field IMPT increased the Dmean of organs such as the stomach, duodenum, and intestine. Conclusion: The results indicated that the tumor locations could play a critical role in determining clinical benefits among different treatment modalities. Two-field IMPT could be a better option for LAPC patients whose tumors are located in the head of the pancreas. It provides lower severe toxicity for the stomach and duodenum. Nevertheless, VMAT is preferred for the body with better protection for the possibility of gastric bleed. [ABSTRACT FROM AUTHOR]

Background: It is not known which risk stratification system has the best discrimination ability for predicting prostate cancer death. Methods: We identified patients with non-metastatic primary prostate adenocarcinoma diagnosis between 2004 and 2015 using the Surveillance, Epidemiology, and End Results database. Patients were categorized in different risk groups using the three frequently used risk stratification systems of the National Comprehensive Cancer Network guideline (NCCN-g), American Urological Association guideline (AUA-g), and European Association of Urology guideline (EAU-g), respectively. Associations between risk classification and prostate cancer-specific mortality (PCSM) were determined using Kaplan–Meier analyses and multivariable regression with Cox proportional hazards model. Area under the receiver operating characteristics curve (AUC) analyses were used to test the discrimination ability of the three risk grouping systems. Results: We analyzed 310,062 patients with a median follow-up of 61 months. A total of 36,368 deaths occurred, including 6,033 prostate cancer deaths. For all the three risk stratification systems, the risk groups were significantly associated with PCSM. The AUC of the model relying on NCCN-g, AUA-g, and EAU-g risk stratification systems for PCSM at specifically 8 years were 0.818, 0.793, and 0.689 in the entire population; 0.819, 0.795, and 0.691 in Whites; 0.802, 0.777, and 0.681 in Blacks; 0.862, 0.818, and 0.714 in Asians; 0.845, 0.806, and 0.728 in Chinese patients. Regardless of the age, marital status, socioeconomic status, and treatment modality, AUC of the model relying on NCCN-g and AUA-g for PCSM was greater than that relying on EAU-g; AUC of the model relying on NCCN-g system was greater than that of the AUA-g system. Conclusions: The NCCN-g and AUA-g risk stratification systems perform better in discriminating PCSM compared to the EAU-g system. The discrimination ability of the NCCN-g system was better than that of the AUA-g system. It is recommended to use NCCN-g to evaluate risk groups for prostate cancer patients and then provide more appropriate corresponding treatment recommendations. [ABSTRACT FROM AUTHOR]

Highlights • Combined toxic effects of UV-B radiation and DEHP on S. acuminatus were investigated. • UV-B radiation decreases photosynthesis and destroys antioxidant system of S. acuminatus. • The addition of low DEHP concentration alleviates the cell damage of S. acuminatus induced by UV-B radiation. • UV-B radiation can photodegrade DEHP via ROS generation in S. acuminatus. Abstract The co-contamination discharge of Phthalate esters (PAEs) by human activities and the increased UV radiation is increasing in aquatic ecosystems. However, little information is available about the combined detrimental effects of UV and PAEs on phytoplankton. In this study, the combined effects of UV-B irradiation and di-(2-ethylhexyl) phthalate (DEHP) on photosynthesis and antioxidant system of Scenedesmus acuminatus , and the DEHP degradation were investigated. Results showed that UV-B radiation decreased the chlorophyll a fluorescence yield, photosynthetic activity (Fv/Fm), pigment content and superoxide dismutase activity. This radiation also increased the reactive oxygen species (ROS) production and soluble protein and malondialdehyde contents. UV-B radiation with 10 mg L−1 DEHP improved the Fv/Fm and alleviated the cell damage of S. acuminatus, and the addition of high DEHP concentration (≥50 mg L−1) aggravated cell damage. The ROS generation also decreased with the increased DEHP concentration. UV-B radiation can effectively promote the DEHP degradation, with the highest degradation rate of 89.9% at an initial DEHP concentration of 10 mg L−1 within 6 h. This result may be attributed to that UV-B irradiance induced DEHP degradation under the regulation of ROS generated by S. acuminatus. Our findings will contribute to the understanding of the combined toxic mechanisms of UV-B and DEHP and in the evaluation of ecological environment risks for primary producers in aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Purpose: In our previous study, we found that AKR1C3 was a radioresistance gene in KY170R cells. Downregulating the expression of AKR1C3 could enhance the radiosensitivity of esophageal carcinoma cells. In this study, we investigated whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1 member C3 (AKR1C3), could overcome radiation resistance in AKR1C3 highly expressed cells.Patients and methods: We used clone formation assays to detect radiosensitivity effects. Flow cytometry assays were used to detect reactive oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2) and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression.Results: We found that AKR1C3 was highly expressed in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells expressing high levels of AKR1C3 (P [ABSTRACT FROM AUTHOR]

Purpose: Bulky non-small cell lung cancer (NSCLC) is difficult to achieve effective local control by conventionally fractionated radiotherapy (CRT). The present work aims to evaluate the safety and efficacy of partial stereotactic ablative boost radiotherapy (P-SABR) in bulky NSCLC. Patients and methods: From December 2012 through August 2017, 30 patients with bulky NSCLC treated with P-SABR technique were analyzed. The P-SABR plan consisted of one partial SABR plan (5–9 Gy/f, 3–6 fractions) to gross tumor boost (GTVb), followed by one CRT plan to the planning target volume (PTV). GTVb was the max volume receiving SABR to guarantee the dose of organs-at-risks (OARs) falloff to about 3 Gy/f. The total dose of PTV margin was planned to above 60 Gy. The simply CRT plans were created using the same planning parameters as the original plan, with the goal to achieve comparable OARs doses and PTV margin dose to the P-SABR plan. Dosimetric variables were acquired in both P-SABR and compared CRT plans. Toxicity, local control, and survival were also evaluated. Results: Median follow-up in survivors was 10.3 months (range=2.3–39.4 months). Eleven patients (36.7%) had partial response (PR) and ten patients (33.3%) had stable disease (SD). Two-year overall survival was 55.6%. Two-year local control rate was 85.7%. No severe acute side effects.CTCAE Grade III were observed. Compared to the simply CRT plan, P-SABR plans achieved similar doses to the OARs and Dmin, but increased dose at the isocenter, Dmean, Dmax, and biological equivalent dose (BED) significantly (P<0.05). BED in the tumor center could reach 107.3 Gy (93.2–132 Gy). Patients with B90≥65% achieved a higher local control rate than those with B90<65% (P=0.010). Conclusion: This retrospective study suggests that P-SABR is feasible and well tolerated in bulky NSCLC. Local control rate is encouraging, especially for the B90≥65% group, which may due to the ability of P-SABR to optimize BED with equivalent toxicity. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we investigated the combined effects of UV-B irradiation and herbicides (glyphosate, GPS; 2-Methyl-4-chlorophenoxyacetic acid, MCPA-Na; 3-(3,4-dichlorophenyl)-1,1-dimethylurea, DCMU) and the antioxidant (ascorbic acid, ASC) on photosynthesis, antioxidant enzymes and DNA damage in two bloom-forming cyanobacteria, Anabaena sp. and Microcystis viridis. UV-B irradiance increased reactive oxygen species (ROS) production, which decreased chlorophyll a fluorescence yield, pigment content and superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA) content and caused serious DNA damage. The degree of these damages was aggravated by the addition of DCMU, GPS and MCPA, and was partially mitigated by the addition of ASC. During the recovery process, the degree and mechanism in restoring DNA damage and photosynthesis inhibition were different by the removal of UV-B and herbicides (DCMU, GPS and MCPA) in both cyanobacteria. These results suggest that the combination of UV-B and exogenous herbicides have detrimental effects on cyanobacterial metabolism through either a ROS-mediated process or by affecting the electron transport chain, and may cause the shifts in the phytoplankton community. [Copyright &y& Elsevier]

Abstract, Results section, "Two-year overall survival was 55.6%. Two-year local control rate was  85.7%" should read "One-year overall survival was  64.9%. One-year local control rate was 100%".On page 2574, Response and survival outcomes section, 3rd and 4th sentences, "One-year over-all survival was 88.2%. Two-year overall survival was 55.6% (Figure 2A)." should read "One-year over-all survival was 64.9%. Two-year overall survival was 44.5% (Figure 2A)."On page 2574, Response and survival outcomes section, 10th sentence, "Two-year local control rate was 85.7%. (Figure  2B)." should read "Two-year local control rate was 57.1%. (Figure 2B)."On page 2575, Figure 2 legend, "(A) Kaplan–Meier plots of overall survival for all patients. One-year overall survival was  88.2%. Two-year overall survival was 55.6%. (B) Kaplan–Meier plots of local control for all patients. One-year local control rate was 100%. Two-year local control rate was 85.7%. (C) Patients with B90≥ 65% (n=19) achieved a higher local control rate than those with B90< 65% (n=11) (median survival=15.2 months vs 3.5 months, CI=6.8– 23.6 and 2.2– 4.9 months, respectively; P=0.010). (D) Patients with B80≥ 90% (n=20) achieved a higher local control rate than those with B80< 90% (n=10) (median survival=14.9 months vs 3.5 months, CI=3.4– 26.3 and 1.8– 5.2 months, respectively; P=0.045)." should read "(A) Kaplan–Meier plots of overallsurvival for all patients. One-year overall survival was 64.9%. Two-year overall survival was 44.5%. (B) Kaplan–Meier plots of local control for all patients. One-year local control rate was  100%. Two-year local control rate was 57.1%. (C) Patients with B90≥ 65% (n=19) achieved a higher local control rate than those with B90< 65% (n=11) (median survival=15.2 months vs 3.5 months, CI=6.8– 23.6 and 2.2– 4.9 months, respectively; P=0.010). (D) Patients with B80≥ 90% (n=20) achieved a higher local control rate than those with B80< 90% (n=10) (median survival=14.9 months vs 3.5 months, CI=3.4– 26.3 and 1.8– 5.2 months, respectively; P=0.045)."On page 2576, Discussion section, last sentence "Therefore, daily SABR was applied in our article and the 2-year local control rate was as high as 85.7%, even stage IV NSCLC were 40%." should read "Therefore, daily SABR was applied in our article and the 1-year local control rate was as high as 100%, even stage IV NSCLC were 40%."Despite the correction in the text list as above, the Figures of Kaplan–Meier plots of overall survival and local control are correct, and the error doesn't the change the overall findings reported in the paper. We can still conclude that "This retrospective study suggests that P-SABR is feasible and well tolerated in bulky NSCLC. Local control rate is encouraging, especially for the B90≥ 65% group, which may due to the ability of P-SABR to optimize BED with equivalent toxicity". The authors apologize for this error. Read the original article [ABSTRACT FROM AUTHOR]

The title AgII complex, [Ag2(C5H10NS2)4], has been obtained by the reaction of AgNO3 and Na(detc) with a 1:2 molar ratio in a methanol solution at 353 K (detc = N, N-diethyl­dithio­carbamate). In the crystal structure of the complex, two detc anions chelate to an AgII ion in an S, S′-bidentate manner, and an S atom of the detc anion bridges to the neighboring AgII ion to form the centrosymmetric dinuclear mol­ecule. [ABSTRACT FROM AUTHOR]

Purpose: It is difficult to contour nerve structures with the naked eye due to poor differentiation between the nerve structures with other soft tissues on CT images. Magnetic resonance neurography (MRN) has the advantage in nerve visualization. The purpose of this study is to identify one MRN sequence to better assist the delineation of the lumbosacral plexus (LSP) nerves to assess the radiation dose to the LSP using the magnetic resonance (MR)/CT deformable coregistration technique., Methods: A total of 18 cases of patients with prostate cancer and one volunteer with radiation-induced lumbosacral plexopathy (RILSP) were enrolled. The data of simulation CT images and original treatment plans were collected. Two MRN sequences (Lr&#95;NerveVIEW sequence and Cs&#95;NerveVIEW sequence) were optimized from a published MRN sequence (3D NerveVIEW sequence). The nerve visualization ability of the Lr&#95;NerveVIEW sequence and the Cs&#95;NerveVIEW sequence was evaluated via a four-point nerve visualization score (NVS) scale in the first 10 patients enrolled to determine the better MRN sequence for assisting nerve contouring. Deformable registration was applied to the selected MRN sequence and simulation CT images to get fused MR/CT images, on which the LSP was delineated. The contouring of the LSP did not alter treatment planning. The dosimetric data of the LSP nerve were collected from the dose-volume histogram in the original treatment plans. The data of the maximal dose (D max ) and the location of the maximal radiation point received by the LSP structures were collected., Results: The Cs&#95;NerveVIEW sequence gained lower NVS scores than the Lr&#95;NerveVIEW sequence (Z=-2.887, p=0.004). The LSP structures were successfully created in 18 patients and one volunteer with MRN (Lr&#95;NerveVIEW)/CT deformable registration techniques, and the LSP structures conformed with the anatomic distribution. In the patient cohort, the percentage of the LSP receiving doses exceeding 50, 55, and 60 Gy was 68% (12/18), 33% (6/18), and 17% (3/18), respectively. For the volunteer with RILSP, the maximum irradiation dose to his LSP nerves was 69 Gy., Conclusion: The Lr&#95;NerveVIEW MRN sequence performed better than the Cs&#95;NerveVIEW sequence in nerve visualization. The dose in the LSP needs to be measured to understand the potential impact on treatment-induced neuropathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cao, Gao, Li, Liu, Qin, Dou, Li, Shang, Gu, Ma, Qi, Xie and Wang.)

Background: The standard management for upper urinary tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU). However, some patients cannot undergo this procedure for several reasons, such as unresectable disease, old age, and multiple comorbidities. Our study explored the potential safety and effectiveness of radiotherapy as a curative treatment for UTUC patients unfit for surgery., Methods: The data of patients treated with radiotherapy between December 2017 and November 2019 were retrospectively reviewed. For the literature review, computerized PubMed Medline, Index Medicus, and Web of Science databases and reference lists from the identified publications of interest were used. And "upper-tract urothelial carcinoma" and "radiotherapy" were used as key words in the search., Results: We describe 8 patients with UTUC who were treated with radiotherapy. The median follow-up time was 13.5 months (range, 8.6-30.9 months). Local tumor control was achieved in all patients. However, distant metastases were observed in 2 patients with T3-4/N+ status. One patient had T4 status and the other had N2+ status. The patients died of tumor progression at 15.0 and 17.7 months. In addition, the other 6 patients who were still alive had relatively early-stage tumors without nodal involvement. Regarding acute toxicity, according to the CTCAE v5.0, mild side effects were noted, including grade 1 nausea and diarrhea. Four patients developed mild anemia, generally of grade 1-2. One patient experienced grade 3 anemia, but it was manageable and improved with symptomatic support. In addition, no grade 4 acute or late toxicities were observed. No significant long-term impairment of renal function occurred., Conclusions: For patients with nonmetastatic UTUC who are not suitable for surgery, radiotherapy is a safe treatment and can achieve good local tumor control., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tau-21-291). The authors have no conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Purpose: In our previous study, we found that AKR1C3 was a radioresistance gene in KY170R cells. Downregulating the expression of AKR1C3 could enhance the radiosensitivity of esophageal carcinoma cells. In this study, we investigated whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1 member C3 ( AKR1C3 ), could overcome radiation resistance in AKR1C3 highly expressed cells., Patients and Methods: We used clone formation assays to detect radiosensitivity effects. Flow cytometry assays were used to detect reactive oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2) and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression., Results: We found that AKR1C3 was highly expressed in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells expressing high levels of AKR1C3 ( P <0.05). MeJ could inhibit the 11-ketoprostaglandin reductase activity of AKR1C3 in a dose-dependent manner in KY170R cells. Incubation of KY170R cells with 200 µmol/L of MeJ for 24 h reduced the expression of PGF2 by roughly 30% ( P <0.05). The PPAR pathway inhibitor GW9662 prevented the radiation sensitivity enhancement imparted by MeJ. After adding GW9662, there were no significant differences between the radiation sensitivities of MeJ-treated and -untreated KY170R cells ( P >0.05). The radiation sensitivity effect of MeJ also depended upon the generation of ROS in KY170R cells; 48 h after irradiation, ROS levels in the MeJ group was twofold higher than in the untreated KY170R cells ( P <0.05). The ROS scavenger, N-acetyl cysteine, could reverse the radiosensitivity effects of MeJ ( P >0.05)., Conclusion: Our results indicate that MeJ can increase the radiation sensitivity of AKR1C3 -overexpressing KY170R cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3 and increasing cellular ROS levels., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The aim of this study was to focus on clinicopathological characteristics and prognosis in men with prostate cancer (PCa) harboring a breast cancer 2 (BRCA2) gene mutation and to offer convincing evidence to consider BRCA2 mutation as a marker of poor prognosis in the molecular classification of PCa. We searched relevant articles from PubMed, Embase, Web of Science, and the Cochrane Library databases to evaluate the differences in the overall survival (OS) and cancer-specific survival (CSS) between BRCA2 mutation carriers and non-carriers in patients with PCa. We included 525 BRCA2 mutation-carriers and 8,463 non-carriers in total from 10 studies in our meta-analysis. The results showed that carrying a BRCA2 mutation was correlated with a reduced CSS and OS when compared with that of non-carriers, with pooled Hazard Ratios (HRs) of 2.53 (95% confidence interval (CI): 2.10-3.06, P < 0.001) and 2.21 (95% CI: 1.64-2.99, P < 0.001), respectively. The results also demonstrated that BRCA2 mutation-carriers harbored a higher Gleason Score (GS) (> 7), TNM stage (> T3, N1, M1), and risk level than non-carriers. Our meta-analysis showed that a BRCA2 mutation predicted poor survival outcomes in patients with prostate cancer, especially in those undergoing treatments with radiotherapy. Therefore, the use of BRCA2 mutation as a clinical prognostic factor could help stratify the high-risk patients and provide clinical strategies for more effective targeted treatments for patients with prostate cancer.

The present study was aim to investigate the prognostic role of platelet to lymphocyte ratio (PLR) for patients with gastric cancer (GC) using meta-analysis. A total of 13 studies (14 cohorts) with 6,280 subjects were included. By pooling hazard ratios (HRs) and 95% confidence intervals (CIs) and odds ratios (ORs) and 95% CIs from each study, we found that elevated PLR was significantly associated with poorer overall survival (OS) (HR: 1.3, 95% CI: 1.1-1.52, p = 0.001; Ι² = 68.5%, Ph < 0.001) but not with poor disease-free survival (DFS) (HR: 1.6, 95% CI: 0.88-2.9, p = 0.122; I2 = 87.8%, Ph < 0.001). Subgroup analysis showed that a high PLR significantly predicted poor OS in Caucasian populations, patients receiving chemotherapy and patients at advanced stage. In addition, the cut-off value of PLR > 160 showed adequately prognostic value. Furthermore, elevated PLR was associated with lymph node metastasis and CEA levels in GC. Our meta-analysis showed that elevated PLR could be a significant prognostic biomarker for poor OS in patients with GC., Competing Interests: The authors declare no conflicts of interest.

Purpose: Accumulating studies have investigated the prognostic and clinical significance of programmed death ligand-1 (PD-L1) expression in patients with hepatocellular carcinoma (HCC); however, the results were conflicting and inconclusive. We conducted a meta-analysis to combine controversial data to precisely evaluate this issue., Methods: Relevant studies were thoroughly searched on PubMed, Web of Science, and Embase until April 2016. Eligible studies were evaluated by selection criteria. Hazard ratio (HR) with 95% confidence interval (CI) was used to estimate the prognostic role of PD-L1 for overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Odds ratio (OR) with 95% CI were selected to assess the relationship between PD-L1 and clinicopathological features of HCC patients. Publication bias was tested using Begg's funnel plot., Results: A total of seven studies published from 2009 to 2016 were included for meta-analysis. The data showed that high PD-L1 expression was correlated to shorter OS (HR =2.09, 95% CI: 1.66-2.64, P<0.001) as well as poor DFS/RFS (HR =2.3, 95% CI: 1.46-3.62, P<0.001). In addition, increased PD-L1 expression was also associated with tumor differentiation (HR =1.51, 95% CI: 1-2.29, P=0.05), vascular invasion (HR =2.16, 95% CI: 1.43-3.27, P<0.001), and α-fetoprotein (AFP; HR =1.46, 95% CI: 1-2.14, P=0.05), but had no association with tumor stage, tumor size, hepatitis history, sex, age, or tumor multiplicity. No publication bias was found for all analyses., Conclusion: This meta-analysis revealed that overexpression of PD-L1 was predictive for shortened OS and DFS/RFS in HCC. Furthermore, increased PD-L1 expression was associated with less differentiation, vascular invasion, and AFP elevation.

The objective of this study was to develop an amiodarone hydrochloride (ADHC)-loaded liposome (ADHC-L) formulation and investigate its potential for cardiomyocyte targeting after cardiac radiofrequency ablation (CA) in vivo. The ADHC-L was prepared by thin-film method combined with ultrasonication and extrusion. The preparation process was optimized by Box-Behnken design with encapsulation efficiency as the main evaluation index. The optimum formulation was quantitatively obtained with a diameter of 99.9±0.4 nm, a zeta potential of 35.1±10.9 mV, and an encapsulation efficiency of 99.5%±13.3%. Transmission electron microscopy showed that the liposomes were spherical particles with integrated bilayers and well dispersed with high colloidal stability. Pharmacokinetic studies were investigated in rats after intravenous administration, which revealed that compared with free ADHC treatment, ADHC-L treatment showed a 5.1-fold increase in the area under the plasma drug concentration-time curve over a period of 24 hours (AUC0-24 h) and an 8.5-fold increase in mean residence time, suggesting that ADHC-L could facilitate drug release in a more stable and sustained manner while increasing the circulation time of ADHC, especially in the blood. Biodistribution studies of ADHC-L demonstrated that ADHC concentration in the heart was 4.1 times higher after ADHC-L treatment in CA rat model compared with ADHC-L sham-operated treatment at 20 minutes postinjection. Fluorescence imaging studies further proved that the heart-targeting ability of ADHC-L was mainly due to the CA in rats. These results strongly support that ADHC-L could be exploited as a potential heart-targeting drug delivery system with enhanced bioavailability and reduced side effects for arrhythmia treatment after CA.

TDP-43 (TAR DNA-binding protein of 43 kDa) is a major deposited protein in amyotrophic lateral sclerosis and frontotemporal dementia with ubiquitin. A great number of genetic mutations identified in the flexible C-terminal region are associated with disease pathologies. We investigated the molecular determinants of TDP-43 aggregation and its underlying mechanisms. We identified a hydrophobic patch (residues 318-343) as the amyloidogenic core essential for TDP-43 aggregation. Biophysical studies demonstrated that the homologous peptide formed a helix-turn-helix structure in solution, whereas it underwent structural transformation from an α-helix to a β-sheet during aggregation. Mutation or deletion of this core region significantly reduced the aggregation and cytoplasmic inclusions of full-length TDP-43 (or TDP-35 fragment) in cells. Thus, structural transformation of the amyloidogenic core initiates the aggregation and cytoplasmic inclusion formation of TDP-43. This particular core region provides a potential therapeutic target to design small-molecule compounds for mitigating TDP-43 proteinopathies.

Objective: To study the major risk factors and characteristics of Schistosoma japonicum in the newly identified areas around the Dong Ting Lake., Methods: Data was collected regarding the distribution of snails, prevalence of infection as well as the source of transmission in the newly identified areas in Hunan province from 1979 to 2003., Results: In all the newly identified sites, Schistosomiasis japonica patients appeared to be the first-seen evidence, some even under acute phase. The highest infection rate among residents had reached 87.1% in the newly identified villages. Most of the new endemic areas concentrated in the ditch and beach areas that close to cities and towns., Conclusions: Evidence showed that snails had been transferred through boats and fishing nets to be disseminated. Data also revealed that the sources of transmission would include those local infected residents who had been infected in the old endemic areas and the newly imported domestic animals with infection.