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The objective of this study is to describe the technique and evaluate the clinical value of normal saline (NS) injection for expanding the anterior perirectal space during prostate cryoablation for prostate cancer (PCa) patients.PCa patients who received cryoablation between August 2014 and December 2019 were enrolled, and the technique of NS injection was adopted. The complications were evaluated. The prostate-specific antigen (PSA) nadir and biochemical progression-free survival (bPFS) were measured in localized PCa patients who received cryoablation as the primary treatment.A total of 159 PCa patients were included. Among 147 patients with the data of anterior perirectal space, the median (interquartile range [IQR]) distance of estimated iceball edge beyond the prostatic capsule was 8.3 (7.0-10.0) mm. No cases of urethrorectal fistula were reported; 29 patients developed urinary retention and 25 patients presented scrotal edema. All complications below Clavien-Dindo grade IIIb disappeared within 7 weeks after surgery. Urinary incontinence was reported in 6 patients. Among localized PCa patients, the median (IQR) follow-up time was 56.5 (36.0-73.5) months. The estimated 5-year bPFS was 82.3% overall, 82.8% for low-to intermediate-risk PCa patients, and 82.1% for high-risk PCa patients. For 52 patients received cryoablation alone, the median (IQR) PSA nadir was 0.147 (0.027-0.381) ng/mL.The technique of NS injection for expanding the anterior perirectal space during cryoablation surgery could avoid urethrorectal fistula and might benefit localized PCa patients with lower PSA nadir and longer bPFS.

Chlorsulfuron, metsulfuron-methyl and ethametsulfuron can damage sensitive crops in rotation pattern as a result of their long persistence in soil. To explore novel sulfonylurea (SU) herbicides with favorable soil degradation rates, four series of SUs were synthesized through a structure-based drug design (SBDD) strategy.The target compounds, especially Ia, Id and Ie, exhibited prospective herbicidal activity against dicotyledon oil seed rape (Brassica campestris), amaranth (Amaranthus retroflexus), monocotyledon barnyard grass (Echinochloa crusgalli) and crab grass (Digitaria sanguinalis) at a concentration of 15 a.i. g haOverall, based on the synthetic procedure, herbicidal activity, soil degradation and crop safety, the Ia sulfonylureas series were chosen to be investigated as prospective AHAS inhibitors. The 5-dimethylamino group on SUs accelerated the degradation rate at different levels in alkaline soils which seems to be controllable in conventional cropping systems in their further application. © 2022 Society of Chemical Industry.

Supplementary Figure S1. CircPRMT5 is upregulated in UCB cells. Supplementary Figure S2. CircPRMT5 promotes migration and invasion of UCB cells. Supplementary Figure S3. CircPRMT5 contains multiple target sites of miRNAs. Supplementary Figure S4. CircPRMT5 promotes migration and invasion of UCB cells by reducing the inhibitory effect of miR-30c via sponge activity. Supplementary Figure S5. SNAIL1 is a target of miR-30c. Supplementary Figure S6. Representative images of SNAIL1 and E-cadherin expressions examined by IHC in UCB tissues with high (left) and low (right) expression of circPRMT5. Supplementary Figure S7. The correlation between expressions of SNAIL1 and miR-200 family in UCB tissues derived from TCGA database. Supplementary Figure S8. CircPRMT5 was secreted into exosomes derived from serum and urine of UCB patients. Supplementary Table S1. Correlation between expression of circPRMT5 and patients' clinicopathological variables in UCB patients Supplementary Table S2. The up-regulated and down-regulated circRNAs in UBCs Supplementary Table S3. Correlation of miR-30c expression with patients' clinicopathological variables in TCGA UCB cohorts Supplementary Table S4. Correlation of circPRMT5 expression in serum exosomes with patients' clinicopathological variables in 71 cases of UCB

Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs.Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.

Background: Depression leads to a cognitive decline and decreases in ghrelin are observed in depression. Ghrelin affects the level of Brain-derived nerve growth factor (BDNF) through the cAMP-CREB signalling pathway, and lower BDNF levels lead to cognitive decline. Therefore, it is reasonable to assume that in depression, lower ghrelin causes a decrease in BDNF levels and cognitive decline though the cAMP- CREB signalling pathway.Methods: A total of 120 C57BL/6J male mice were randomly divided into six groups of 20 mice: non-depression groups (sham group, ghrelin group, and ghrelin + (D-lys3)-GHRP-6 group) and depression groups (depression group, depression + ghrelin group and depression + ghrelin + (D-lys3)-GHRP group). A depression mouse model was established by injecting normal saline, ghrelin or ghrelin + (D-lys3) -GHRP-6 into the lateral ventricle of each group. Cognition, hippocampal long-term potentiation (LTP), ghrelin mRNA and protein level, BDNF level and CREB level in the hippocampus were detected.Results: In the depression mouse model groups, all comparison indexes (cognition and hippocampal levels of LTP, ghrelin mRNA and proteins, and BDNF and CREB) had significant negative changes. In the mice with depression, ghrelin or ghrelin + (D-lys3)-GHRP-6 was injected, and all the comparison indicators showed significant positive changes. Supplementation of ghrelin+(D-lys3))-GHRP-6 resulted in more significant positive changes in all comparison indexes than those of ghrelin alone.Conclusions: In the depression model, lower ghrelin causes hippocampal BDNF to decrease and results in cognitive decline via the cAMP-CREB signalling pathway.

In the present study, we have designed and synthesized a series of 42 novel sulfonylurea compounds with ortho-alkoxy substitutions at the phenyl ring and evaluated their herbicidal activities. Some target compounds showed excellent herbicidal activity against monocotyledon weed species. When applied at 7.5 g ha-1, 6-11 exhibited more potent herbicidal activity against barnyard grass (Echinochloa crus-galli) and crab grass (Digitaria sanguinalis) than commercial acetohydroxyacid synthase (AHAS; EC 2.2.1.6) inhibitors triasulfuron, penoxsulam, and nicosulfuron at both pre-emergence and postemergence conditions. 6-11 was safe for peanut for postemergence application at this ultralow dosage, suggesting that it could be considered a potential herbicide candidate for peanut fields. Although 6-11 and triasulfuron share similar chemical structures and have close Ki values for plant AHAS, a significant difference has been observed between their LUMO maps from DFT calculations, which might be a possible factor that leads to their different behaviors toward monocotyledon weed species.

Based on the previous finding that a substitution at 5-position of the benzene ring is favorable to enhance the degradation rates of sulfonylurea herbicides, a total of 16 novel 2,5-disubsituted sulfonylurea compounds were chemically synthesized and fully characterized by means of

In order to investigate the effects of furrow and ridge rainwater harvesting, straw mulching, and reduced and slow-release fertilizer on soil microbial community structure of rapeseed, a two-year field study was conducted in rainy (2016-2017) and drought (2017-2018) seasons, which included three cultivation patterns:1 conventional flat planting, 2 straw mulching, and 3 ridge-furrow rainfall harvesting system and four fertilization patterns:1 conventional fertilization (100% of the amount), 2 reduced slow-release fertilizer Ⅰ (80% of the amount), 3 reduced slow-release fertilizer Ⅱ (60% of the amount), and 4 no fertilizer. The results indicated that it was rainy in 2016-2017, with seasonal drought during the nutritional growth stage in 2017-2018. The two technologies (straw mulching+80% slow-release fertilizer, J80 and ridge-furrow rainfall harvesting system+80% slow-release fertilizer, M80) were beneficial to boost the soil microbial activity. J80 and M80 increased the microbial biomass carbon by 9.94% and 10.32% and microbial biomass nitrogen by 2.38% and 1.19%, respectively, compared with that of the local cultivation pattern under two different climate conditions. The total amount of microbial phospholipid fatty acid (PLFA) decreased by 30.75% in the rainy year compared with that in the drought year, and mulching technology could effectively increase the total amount of soil PLFA. The PLFA contents of soil bacteria and fungi in the rainy year were 33.67% and 53.21%, respectively, lower than those in the drought year. However, the PLFA content of actinomycetes increased by 13.04%. Microbial communities were sensitive to abnormal precipitation. The bacteria/fungi ratio increased in rainy weather. The drought climate heighted the ratio of straight chain saturated fatty acid/straight chain monounsaturated fatty acid and straight chain monounsaturated fatty acid/cyclopropane acid. In conclusion, adopting the optimal cultivation technologies can stabilize the soil microenvironment under abnormal precipitation, relieve water and nutrient stress, and provide an effective means for rapeseed sustainable development.

A single-layer film of copper and/or copper oxide was deposited on a polypropylene nonwoven fabric substrate to prepare multifunctional textiles with a metallic color appearance. The pristine uncoa...

We present a protocol for controlled cyclic remote preparation of an arbitrary single-qudit state via a seven-qudit cluster state. In the protocol, Alice can help the remote agent Bob prepare an arbitrary single-qudit state, Bob can help the agent Charlie prepare an arbitrary single-qudit state and at the same time Charlie can help Alice prepare an arbitrary single-qudit state under the controller David’s control. Alice, Bob and Charlie first perform positive operator-valued measurement (POVM) on their entangled particles according to the information of the prepared state, then perform generalized X-basis measurement. The controller performs generalized X-basis measurement on his entangled particle. The arbitrary single-qudit states can be cyclic remote prepared under the controller’s control. The protocol is more convenient in application since it only requires single-particle measurement and single-particle unitary operations for controlled cyclic remote preparation of the single-qudit states.

A series of 51 novel sulfonylurea compounds with ortho-alkoxy substituent at phenyl ring were chemically synthesized and spectroscopically characterized. The biological activities of the target compounds were evaluated using the enzyme inhibition against acetohydroxyacid synthase (AHAS; EC 2.2.1.6) from fungal or plant source, as well as cell-based antifungal assay and greenhouse pot herbicidal assay. Among the target compounds, 6e showed desirable antifungal activity against Candida albicans standard isolate sc5314 with minimum inhibition concentration (MIC) of 0.39 mg/L (0.98 μM) after 24 h, and 6a demonstrated promising pre-emergence herbicidal activity against Echinochloacrus-galli at 30 g/ha dosage. Representative compounds 6a, 6e, and 6i showed no cell cytotoxicity even at 40 mg/L concentration. Theoretical DFT calculations indicated HOMO maps should be considered to understand the structure-activity relationships. The present study has hence provided useful information for further discovery of novel antifungal agents or selective herbicides.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for green agrochemical discovery. Herein, a novel N-phenylisoxazoline-thiadiazolo[3,4-a]pyridazine herbicidal active scaffold was designed by the scaffold hybridization strategy. Systematic structural optimization enabled the discovery of a series of derivatives with excellent weed control at 9.375-150 g ai/ha by the post-emergent application. Some derivatives exhibited improved Nicotiana tabacum PPO (NtPPO)-inhibitory activity than fluthiacet-methyl. Of these, 2b, with Ki = 21.8 nM, displayed higher weed control than fluthiacet-methyl at the rate of 12-75 g ai/ha, and selective to maize at 75 g ai/ha. In planta, 2b was converted into a bioactive metabolite 5 (Ki = 4.6 nM), which exhibited 4.6-fold more potency than 2b in inhibiting the activity of NtPPO. Molecular dynamics simulation explained that 5 formed stronger π-π interaction with Phe392 than that of 2b. This work not only provides a promising lead compound for weed control in maize fields but is also helpful to understand the molecular mechanism and basis of the designed hybrids.

To get a full understanding of hot extrusion, solid solution treatment and aging process on the Al−0.56Mg− 0.63Si alloy, the microstructure and mechanical properties of a U-shaped profile were studied through optical microscopy, scanning electrical microscopy, transmission electrical microscopy, hardness, and tensile tests. The coarse equiaxed grains existed near the profile edge as a result of the dynamic recrystallization nucleation and exceeding growth during hot extrusion. The fibrous deformed and sub-structured grains located between the two coarse grain layers, due to the occurrence of work-hardening and dynamic recovery. Perpendicular needle β′′ precipitates were distributed inside the grain, and obvious precipitates-free zone appeared after aging treatment. The tensile strength, yield strength and elongation of the aged Al−Mg−Si alloy U-shaped profile were no less than 279.4 MPa, 258.6 MPa, and 21.6%, respectively. The fracture morphology showed dimple rupture characteristics. The precipitates and grain boundaries played key role in the strengthening contribution.

Fluorescent adenine (A)-rich DNA-templated gold nanoclusters were demonstrated to be a novel probe for determination of biothiols (including cysteine, glutathione, and homocysteine). Fluorescence intensity of adenine-rich DNA-templated gold nanoclusters could be greatly quenched by Hg(II) ions through the formation of a gold nanoclusters-Hg(II) system. When biothiols (cysteine as the model) were introduced into the system, the fluorescence intensity recovered due to the formation of a more stable Hg(II)-thiol coordination complex using Hg-S metal-ligand bonds, which inhibited the Hg(II)-mediated fluorescence quenching of adenine-rich DNA-templated gold nanoclusters. Based on this fluorescence phenomenon, an on-off-on fluorescence strategy was designed for the sensitive determination of biothiols. The method allowed sensitive detection of cysteine with a linear detection range from 100 nM to 5 μM and a limit of detection of 30 nM. Additionally, the assay can be applied for detection of biothiol levels in human plasma samples. Therefore, it can provide a simple and rapid fluorescent platform for biothiol detection.

To evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in treating diabetic foot ulcers (DFUs), we conducted both database searches (PubMed, MEDLINE, EMBASE, CENTRAL, and Web of Science) and reference searches for randomised controlled trials from the inception of databases to 30 January 2020. Two reviewers independently scrutinised the trials, extracted data, and assessed the quality of trials. The primary outcome was the proportion of complete healing. The secondary outcomes were mean time to complete healing and adverse events. A subgroup analysis was performed by different administration routes. Statistical analyses were performed in RevMan 5.3. The time to complete healing Kaplan‐Meier curves was pooled in the R software. Of the 156 citations, 9 trials (720 participants) met eligibility criteria and were included. The rhEGF achieved a higher complete healing rate than placebo (OR: 2.79, [95% CI: 1.99, 3.99]). The rhEGF also significantly shorten complete healing time (MD: −14.10 days, [95% CI: −18.03, −10.16]). Subgroup analysis showed that topical application was superior to intralesional injection, but that may be because of different ulcer severity they included. No significant difference was shown in adverse events. Results were coherent with sensitivity analyses. Therefore, rhEGF is an effective and safe treatment for DFUs.

To evaluate the efficacy and safety of human amniotic membrane (HAM) allograft in treating chronic diabetic foot ulcers (DFUs), a comprehensive search of randomised controlled trials in MEDLINE, EMBASE, PubMed, CENTRAL and Web of Science was conducted to December 7, 2019. Two reviewers independently screened the studies, extracted data, and evaluated the quality of studies. The primary outcome was the proportion of complete healing. The secondary outcomes were mean time to complete healing and adverse events. Statistical analyses were performed using RevMan 5.3. We identified 257 articles, of which 7 articles (465 participants) were included in the meta‐analysis. The proportion of complete wound healing in HAM plus standard of care (SOC) group was 3.88 times as high as that in SOC alone (RR: 3.88 [95% CI: 2.34, 6.44]) at 6 weeks, and 2.01 times at 12 weeks (RR: 2.01 [95%CI: 1.45, 2.77]). The intervention group had a significantly shorter time to complete healing (MD: −30.33 days, [95% CI: −37.95, −22.72]). The number needed to treat within 6 weeks was 2.3 ([95% CI: 1.8, 3.1]). No significant difference was shown in adverse events. Results were consistent in a sensitivity analysis. Hence, HAM plus SOC is effective and safe in treating chronic DFUs.

Background Indoleamine 2,3‐dioxygenase 1 (IDO1) and tryptophan (Trp) catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penile squamous cell carcinoma (PSCC) and explored their clinical significance. Methods IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn) were examined in 114 PSCC patients by immunohistonchemistry and solid‐phase extraction‐liquid chromatography‐tandem mass spectrometry. The survival was analyzed using Kaplan‐Meier method and the log‐rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were defined by principal component analysis. The correlativity was assessed by Pearson's correlation analysis. Results The expression level of IDO1 in PSCC cells was positively correlated with serum Kyn concentration and Kyn/Trp radio (KTR; both P

Sulfonylurea herbicides are widely used as acetolactate synthase (ALS) inhibitors due to their super-efficient activity. However, some sulfonylurea herbicides show toxicity under crop rotation due to their long degradation time, for example, chlorsulfuron. Our research goal is to obtain chlorsulfuron-derived herbicides with controllable degradation time, good crop safety and high herbicidal activities. Based on our previously reported results in acidic soil, we studied the degradation behaviors of 5-dialkylamino-substituted chlorsulfuron derivatives (NL101–NL108) in alkaline soil (pH 8.39). The experimental data indicate that addition of the 5-dialkylamino groups on the benzene ring of chlorsulfuron greatly accelerated degradation in alkaline soil. These chlorsulfuron derivatives degrade 10.8 to 51.8 times faster than chlorsulfuron and exhibit excellent crop safety on wheat and corn (through pre-emergence treatment). With a comprehensive consideration of structures, bioassay activities, soil degradation and crop safety, it could be concluded that 5-dialkylamino-substituted chlorsulfuron derivatives are potential green sulfonylurea herbicides for pre-emergence treatment on both wheat and corn. The study also provides valuable information for the discovery of new sulfonylurea herbicides for crop rotation.

Simple Summary Penile squamous cell carcinoma (PSCC) has been regarded as an HPV-related cancer for a long time. However, the integration pattern and carcinogenic pathways of HPV in PSCC remain unclear. The results of this study provide insights into the HPV-related carcinogenic mechanism in PSCC, which may be less prone to involvement in the traditional E6/E7 carcinogenic process, and are characterized by effects on the host genome, which result in the inactivation of tumor suppressors (CADM2, etc.) and the activation of oncogenes (KLF5, etc.), thus activating oncogenic signaling pathways (MAPK, JAK/STAT, etc.). This study could enhance our understanding of HPV integration and pave the way for subsequent HPV studies in PSCC. Abstract Human papillomavirus (HPV) is a significant etiologic driver of penile squamous cell carcinoma (PSCC). The integration pattern of HPV and its carcinogenic mechanism in PSCC remain largely unclear. We retrospectively reviewed 108 PSCC cases who received surgery between 2008 and 2017. Using high-throughput viral integration detection, we identified 35 HPV-integrated PSCCs. Unlike cervical cancer, the HPV E2 oncogene was not prone to involvement in integration. Eleven of the 35 (31.4%) HPV-integrated PSCCs harbored intact HPV E2; these tumors had lower HPV E6 and E7 expression and higher expression of p53 and pRb proteins than those with disrupted E2 did (p < 0.001 and p = 0.024). Integration breakpoints are preferentially distributed in or near host genes, including previously reported hotspots (KLF5, etc.) and newly identified hotspots (CADM2, etc.), which are mainly involved in oncogenic signaling pathways (MAPK, JAK/STAT, etc.). Regarding the phosphorylation levels of JNK, p38 was higher in HPV-positive tumors with MAPK-associated integration than those in HPV-positive tumors with other integration and those in HPV-negative tumors. In vitro, KLF5 knockdown inhibited proliferation and invasion of PSCC cells, while silencing CADM2 promoted migration and invasion. In conclusion, this study enhances our understanding of HPV-induced carcinogenesis in PSCC, which may not only rely on the E6/E7 oncogenes, but mat also affect the expression of critical genes and thus activate oncogenic pathways.

In the present study, we have designed and synthesized a series of 42 novel sulfonylurea compounds with

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is a promising target for herbicide discovery. Search for new compounds with novel chemotypes is a key objective for agrochemists. Here, we describe the...

A novel type of oxime phosphonate was synthesized and used in the intermolecular cascade radical addition reaction of alkenes to access β-aminophosphonates via visible-light-driven N-centered iminyl radical-mediated and redox-neutral selective C-P single-bond cleavage in an active phosphorus radical route. The procedure is characterized by its ability to achieve the construction of Csp3-P and Csp3-N bonds without the requirement for oxidants and bases.

Purpose There are limited therapeutic options for patients with advanced penile squamous cell carcinoma (PSCC) after chemotherapy failure. Thus, we evaluated the feasibility of salvage treatment using the epidermal growth factor receptor (EGFR) mono-antibody nimotuzumab in chemotherapy-failed PSCC patients and explored potential response or resistance biomarkers. Materials and methods Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes. Results Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease. Conclusions EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for green agrochemical discovery. Herein, a novel

Climate change has been referred to as one of the greatest threats to human health, with reports citing likely increases in extreme meteorological events. In this study, we estimated the relationships between temperature and outpatients at a major hospital in Qingdao, China, during 2015-2017, and assessed the morbidity burden. The results showed that both low and high temperatures were associated with an increased risk of outpatient visits. High temperatures were responsible for more morbidity than low temperatures, with an attributed fraction (AF) of 16.86%. Most temperature-related burdens were attributed to moderate cold and hot temperatures, with AFs of 5.99% and 14.44%, respectively, with the young (0-17) and male showing greater susceptibility. The results suggest that governments should implement intervention measures to reduce the adverse effects of non-optimal temperatures on public health-especially in vulnerable groups.

Chlorsulfuron has been applied in wheat fields as a recognized herbicide worldwide, yet it was officially banned in China since 2014 for its soil persistence problem. On the basis of our previous research that 5-dimethylamino distinctively accelerated degradation rate in soils, a modified amino moiety (Ia-c) and monosubstituted amino group (Id-e) were introduced onto the fifth position of the benzene ring in sulfonylurea structures, as well as heterocyclic amino substituents (If-g) to seek a suitable soil degradation rate during such an in situ crop rotation system. Referring to the biological data and ScAHAS inhibition and ScAHAS docking results, they turned out to be AHAS inhibitors with high potent herbicidal activities. The various influence on soil degradation rate along with crop safety indicated that different substituents on the fifth position have exerted an apparent impact. Their united study of structure-activity-safety-degradation relationship has great potential to provide valuable information for further development of eco-friendly agrochemicals.

Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs. Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA). Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis. Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.

Qiang-Hua Zhou,1,2,* Chuang-Zhong Deng,1,* Jie-Ping Chen,1 Kang-Bo Huang,1,2 Ting-Yu Liu,1,2 Kai Yao,1,2 Zhuo-Wei Liu,1,2 Zi-Ke Qin,1,2 Yong-Hong Li,1,2 Sheng-Jie Guo,1,2 Yun-Lin Ye,1,2 Fang-Jian Zhou,1,2 Wenlin Huang,1,3 Ran-Yi Liu,1 Hui Han1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; 2Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China; 3Guangdong Provincial Key Laboratory of Tumor Targeted Drugs, Guangzhou Enterprise Key Laboratory of Gene Medicine, Guangzhou Doublle Bioproducts Co. Ltd., Guangzhou, China *These authors contributed equally to this work Purpose: Molecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methods: This study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan–Meier analysis with a log-rank test was used for the survival analysis.Results: LAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.Conclusion: These findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients. Keywords: penile neoplasms, serum markers, laminin, gamma 2, neoplasm metastasis

In this work, a rapid and label-free fluorescent sensing method has been established for tetracycline (TC) detection by using poly(adenine) (poly A) DNA-templated Au nanoclusters (AuNCs) as fluorescence indicator. The obtained AuNCs exhibited excellent fluorescence intensity and good stability. In the presence of tetracycline, the fluorescence intensity of AuNCs was obviously reduced due to the interactions between the tetracycline and the poly A DNA-templated AuNCs. Under the optimum conditions, the strategy permitted sensitive detection of tetracycline in a linear range from 0.1 to 60 μM and with a limit of detection of 20 nM. In addition, the sensor was successfully applied to determinate the tetracycline content in milk samples. More importantly, it could be easily performed within 10 min at room temperature. Thus, it could provide a rapid, convenient, label-free, and high-sensitive fluorescent platform for tetracycline detection.