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Antibiotic resistance is currently an unfolding global crisis threatening human health worldwide. While antibiotic resistance genes (ARGs) are known to be pervasive in environmental media, the occurrence of antibiotic resistance at interfaces between two or more adjacent media is largely unknown. Here, we designed a microcosm study to simulate plastic pollution in paddy soil and used a novel method, stimulated Raman scattering coupled with deuterium oxide (D 2 O) labelling, to compare the antibiotic resistance in a single medium with that at the interface of multiple environmental media (plastic, soil, water). Results revealed that the involvement of more types of environmental media at interfaces led to a higher proportion of active resistant bacteria. Genotypic analysis showed that ARGs (especially high-risk ARGs) and mobile genetic elements (MGEs) were all highly enriched at the interfaces. This enrichment was further enhanced by the co-stress of heavy metal (arsenic) and antibiotic (ciprofloxacin). Our study is the first to apply stimulated Raman scattering to elucidate antibiotic resistance at environmental interfaces and reveals novel pathway of antibiotic resistance dissemination in the environment and overlooked risks to human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The immune landscape of distant unablated tumors following insufficient microwave ablation (iMWA) in hepatocellular carcinoma (HCC) remains to be clarified. The objective of this study is to define the abscopal immune landscape in distant unablated tumor before and after iMWA for HCC. Two treatment-naive patients were recruited for tumor tissue sampling, of each with two HCC lesions. Tumor samples were obtained at before and after microwave ablation in distant unablated sites for single-cell RNA sequencing (scRNA-seq). Mouse model with bilateral hepatoma tumors were developed, and distant unablated tumors were analyzed using multicolor immunofluorescence, RNA sequencing and flow cytometry. The scRNA-seq revealed that a reduced proportion of CD8 + T cells and an increased proportion of myeloid-derived suppressor cells (MDSCs) were observed in the distant unablated tumor microenvironment (TME). A notable disruption was observed in the lipid metabolism of tumor-associated immune cells, accompanied by an upregulated expression of CD36 in tumor-infiltrating immune cells in distant unablated tumor. The administration of a CD36 inhibitor has been demonstrated to ameliorate the adverse effects induced by iMWA, primarily by reinstating the anti-tumor responses of T cells in distant unablated tumor. These findings explain the recurrence and progression of tumors after iMWA and provide a new target of immunotherapy for HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate the safety and effectiveness of radiotherapy for advanced upper tract urothelial carcinoma (UTUC) patients intolerant to chemotherapy., Methods: Data for 21 patients with advanced UTUC intolerant to chemotherapy were retrospectively collected. All patients were treated with conventionally fractionated radiotherapy (50-70 Gy/20-33 f) or partial-SABR boost to the lesions (50-60 Gy/20-25 f with tumor center boosted with 6-8 Gy/f, 3-5 f) for bulky tumors., Results: The median age was 75 years (range, 58-87 years). Primary tumor resection was performed for all patients and none underwent metastatic resection. Seventeen (81%) patients had oligometastasis (1-5 metastases) at diagnosis. Eighteen (85.7%) received irradiation to all tumor lesions. Lymph node metastasis was predominant in the whole group (17/21). Other lesions were distributed as local recurrence (7/21), bone metastases (2/21) and abdominal wall/muscle (2/21). The median follow-up time was 38.5 months (interquartile range, 15.2-48.7 months). Rate of local control (LC), progression-free survival (PFS) and overall survival (OS) of the whole group at 1 year were 90%, 46.6%, and 80.4%, respectively. At 3 years, LC, PFS and OS were 65.6%, 26.6%, and 40.9%, respectively. Fourteen patients developed acute mild gastrointestinal toxicity, generally of grade 1-2; 8 patients developed acute grade 1-2 hematological toxicity, consisting mainly of anemia and leukopenia. No grade 3 or higher acute or late toxicities were observed., Conclusion: For patients with advanced UTUC who are not able to tolerate chemotherapy, radiotherapy is a safe treatment and can achieve good local tumor control., Competing Interests: Disclosure The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. β-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women., Competing Interests: Declaration of competing interest The authors assert that the research was carried out without any commercial or financial associations that could be interpreted as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction/background: Positive surgical margins (PSMs) after radical prostatectomy (RP) can increase the risk of biochemical recurrence in prostate cancer (PCa) patients. However, the prediction of the likelihood of PSMs in patients undergoing similar surgical procedures remains a challenge. We aim to develop a predictive model for PSMs in patients undergoing non-nerve-sparing RP., Patients and Methods: In this retrospective study, we analyzed data from PCa patients who underwent minimally invasive non-nerve-sparing RP at our hospital between June 2017 and June 2021. We identified independent risk factors associated with PSMs using clinical and MRI-based parameters in univariate and multivariate logistic regression analyzes. These factors were then used to develop a nomogram for predicting the probability of PSMs. The predictive performance was validated using calibration and receiver operating characteristic curve, area under the curve ,and decision curve analysis., Results: Multivariate analyzes revealed prostate-specific antigen density, tumor size, tumor location at the apex, tumor contact length, extracapsular extension (ECE) level, and apparent diffusion coefficient value as independent risk factors. A nomogram was developed and validated with high accuracy (C-index = 0.78). Furthermore, we found that 44.2% of patients diagnosed with organ-confined disease had ECE after surgery, and 29.1% of patients with Gleason scores ≤7 had higher pathological scores. Interestingly, the tumor burden calculated from PCa biopsy cores was overestimated when compared to postoperative PCa specimens., Conclusion: We developed a reliable nomogram for predicting the risk of PSMs in PCa patients undergoing non-nerve-sparing RP. The study highlights the importance of incorporating these parameters in personalized surgical management., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31 hi Emcn hi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31 hi EMCN hi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31 hi Emcn hi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationship with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any products, service and company that could be constructed as influencing as the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Canadian government aims to achieve a 40-45 % reduction of oil and gas (O&G) methane (CH 4 ) emissions by 2025, and 75 % by 2030, although recent studies consistently show that Canada's federal inventory underestimates emissions by a factor of 1.4 to 2.0. We conducted aerial mass balance measurements at sixteen upstream O&G facilities in Alberta between September 29 and November 6, 2021, and our measurements revealed that emissions were, on average, 1.7 (standard deviation (SD): 0.6) times higher than the reported emissions for the same year. On a subsequent campaign from August 12 to September 27, 2022, we focused on understudied O&G sectors covering 24 midstream and end-use facilities. These sites were found to be emitting, on average, 3.4 (SD: 1.1) times more CH 4 than reported. By extrapolating our measurements to Alberta, we found that underground gas storage contributed to 1.6 % of provincial O&G emissions, followed by natural gas power stations/refineries less than 1.0 %. The widespread underreporting of CH 4 emissions highlights the necessity for more empirical measurements of midstream and end-use facilities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hugh Li reports financial support was provided by McCall MacBain Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain., Methods: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks., Results: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05)., Conclusion: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG., Trial Registration: ChiCTR2000033890., Competing Interests: Declaration of Competing Interest The authors declare that the study was conducted in the absence of any business or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Artemisia argyi Levl. Et Vant, commonly known as "Chinese Mugwort," has been utilized in traditional Chinese medicine and cuisine for centuries. Aged Chinese Mugwort has been uncovered to possess superior quality and safety, and its ethyl acetate extract has been found to exhibit anti-hepatitis B virus (HBV) activity. In this study, twenty-five sesquiterpenoids were isolated and characterized from three-year-aged A. argyi. Among them, 14 previously undescribed sesquiterpenoids (1-14), featuring double bond oxidation or ring opening. It is hypothesized that during the aging process, sesquiterpenes undergo oxidative transformation of their double bonds to form alcohols due to external factors and inherent properties. The anti-HBV activity and cytotoxicity of all compounds were assessed in vitro using HepG 2.2.15 cells, and their structure-activity relationships were analyzed through three-dimensional quantitative structure-activity relationship (3D-QASR) techniques. The α-methylene-γ-lactone sesquiterpenoid derivatives were discovered to have potent inhibitory activity against HBV. This research may broaden the potential applications of Chinese Mugwort and offer further guidance for its development and utilization as functional food or traditional Chinese medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The peptide hormone ghrelin (an agonist) and LEAP2 (an antagonist) play important functions in energy metabolism via their receptor GHSR, an A-class G protein-coupled receptor. Ghrelin, LEAP2, and GHSR are widely present from fishes to mammals. However, our recent study suggested that fish GHSRs have different binding properties to ghrelin: a GHSR from the lobe-finned fish Latimeria chalumnae (coelacanth) is efficiently activated by ghrelin, but GHSRs from the ray-finned fish Danio rerio (zebrafish) and Larimichthys crocea (large yellow croaker) have lost binding to ghrelin. Do fish GHSRs use another peptide as their agonist? In the present study we tested to two fish motilins from D. rerio and L. chalumnae because motilin is distantly related to ghrelin. In ligand binding and activation assays, the fish GHSRs from D. rerio and L. crocea displayed no detectable or very low binding to all tested motilins; however, the fish GHSR from L. chalumnae bound to its motilin with high affinity and was efficiently activated by it. Therefore, it seemed that motilin is not a ligand for GHSR in the ray-finned fish D. rerio and L. crocea, but is an efficient agonist for GHSR in the lobe-finned fish L. chalumnae, one of the closest fish relatives of tetrapods. The results of present study suggested that GHSR might have two efficient agonists, ghrelin and motilin, in ancient fishes; however, this feature might be only preserved in some extant fishes with ancient evolutionary origins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Osteoarthritis (OA) is the most common joint disease, affecting hundreds of millions of people globally, which leads to a high cost of treatment and further medical care and an apparent decrease in patient prognosis. The recent view of OA pathogenesis is that increased vascularity, bone remodeling, and disordered turnover are influenced by multivariate risk factors, such as age, obesity, and overloading. The view also reveals the gap between the development of these processes and early stage risk factors. This review presents the latest research on OA-related signaling pathways and analyzes the potential roles of perlecan, a typical component of the well-known protective structure against osteoarthritic pericellular matrix (PCM). Based on the experimental results observed in end-stage OA models, we summarized and analyzed the role of perlecan in the development of OA. In normal cartilage, it plays a protective role by maintaining the integrin of PCM and sequesters growth factors. Second, perlecan in cartilage is required to not only activate vascular epithelium growth factor receptor (VEGFR) signaling of endothelial cells for vascular invasion and catabolic autophagy, but also for different signaling pathways for the catabolic and anabolic actions of chondrocytes. Finally, perlecan may participate in pain sensitization pathways., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

The massive food wastes pose a growing health concern for spreading of antibiotic resistance and pathogens due to food spoilage. However, little is known about these microbial hazards during collection, classification, and transportation before eventual treatment. Here, we profiled the temporal variations of antibiotic resistance genes (ARGs), pathogens, bacterial and fungal communities across four typical food wastes (vegetable, fish, meat, and rice) during storage at room temperature in summer (maximum 28-29 °C) of typical southeast city in China. A total of 171 ARGs and 32 mobile genetic elements were detected, and the absolute abundance of ARGs significantly increased by up to 126-fold with the storage time. Additionally, five bacterial pathogens containing virulence factor genes were detected, and Klebsiella pneumoniae was persistently detected throughout the storage time in all food types except rice. Moreover, fungal pathogens (e.g., Aspergillus, Penicillium, and Fusarium) were also frequently detected. Notably, animal food wastes were demonstrated to harbor higher abundance of ARGs and more types of pathogens, indicating a higher level of hazard. Mobile genetic elements and food types were demonstrated to mainly impact ARG profiles and pathogens, respectively. This work provides a comprehensive understanding of the microbial hazards associated with food waste recycling, and will contribute to optimize the food waste management to ensure biosecurity and benefit human health., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Mitogen-activated protein kinase kinase (MAPKK) was the hub component of the Mitogen-activated protein kinase (MAPK) signaling pathway and played an important role in the cellular response to environmental stress. In this study, we identified five MmMAPKK genes in hard clam Mercenaria mercenaria and found that all MmMAPKK genes contain a conserved protein kinase domain. The MmMAPKK genes derived from dispersed duplication were unevenly distributed in three chromosomes. Although the genome size was highly variable among different bivalve mollusks, the number of MAPKK genes was relatively stable. Phylogenetic analysis showed that bivalve MAPKK was divided into five clades, and amino acid sequences of MAPKK from the same clade consisted of similar conserved motifs. The syntenic analysis demonstrated that MmMAPKKs had the highest number of homologous gene pairs with Cyclina sinensis. MmMAPKKs were ubiquitously expressed in all examined tissues, and all MmMAPKK genes were highly expressed in the ovary. MmMAPKK genes showed stress-specific expression under envirionmental stress. MmMAPKK7 showed an upregulated in heat and heat plus hypoxia stress while MmMAPKK1 showed an upregulated in hypoxic stress groups. Dynamic changes of MmMAPKK7, MmMAPKK6 and MmMAPKK1 in hemocytes were observed in response to air exposure. MmMAPKK4 significantly downregulated after air exposure for five days. MmMAPKK7 and MmMAPKK6 might participate in adaptation to low salinity stress. Our results provided useful information about MAPKK and laid a foundation for further studies on MAPKK evolution in the bivalve., (Copyright © 2022. Published by Elsevier Ltd.)

A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised of four new C 21 (1-4) and one new pregnane (5) glycosides, and four known C 27 (6-9) spirostanol steroids. Their structures were identified via analysis of the spectroscopic data and the results of hydrolytic cleavage. The cytotoxic activities of the compounds were tested toward the human tumor cell line Hela (cervical cancer), and compounds 7 and 8 displayed moderate activity with IC 50 values of 35.5 and 39.6 μM, respectively., (Copyright © 2021. Published by Elsevier Inc.)

Aims: The prostate transmembrane protein, androgen induced 1 (PMEPA1) is differentially expressed in pan-cancer. However, PMEPA1 specific role in cancers has not been fully clarified. This study aims to explore the potential role of Pmepa1 in pan-cancer and specific cancer, with a view to deepening the research on the pathological mechanism of cancer., Main Methods: The Perl language and R language were used to identify the correlation between PMEPA1 expression level and clinical indicators, prognosis values, tumor microenvironment, immune cells' infiltration, immune checkpoint genes, TMB and MSI. The Therapeutic Target Database was used for identifying potential therapeutic drugs that target the pathways that are significantly affected by PMEPA1 expression., Key Findings: PMEPA1 differential expression significantly correlated with patients' age, race, tumors' stage and status. PMEPA1 high expression was closely correlated with poor prognosis in many cancer types, excluding prostate adenocarcinoma. PMEPA1 expression was closely related to tumor cells and the immune microenvironment in stromal and immune cells' level, immune cells' infiltration, immune checkpoint genes, tumor mutational burden and microsatellite instability. We also found that the activity of the olfactory transduction pathway was closely related to PMEPA1 expression. In pan-cancer, Trifluoperazine and Halofantrine have the potential to reduce PMEPA1 expression., Significance: This study integrated existing data to explore PMEPA1 potential function in cancers, provided insights for the future cancer-related studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The gastric peptide ghrelin has important functions in energy metabolism and cellular homeostasis by activating growth hormone secretagogue receptor type 1a (GHSR1a). The N-terminal residues of ghrelin orthologs from all vertebrates are quite conserved; however, in orthologs from Cavia porcellus and Phyllostomus discolor, Ser2 and Leu5 are replaced by a smaller Ala and a positively charged Arg, respectively. In the present study, we first demonstrated that the hydrophobic Leu5 is essential for the function of human ghrelin, because Ala replacement caused an approximately 100-fold decrease in activity. However, replacement of Leu5 by an Arg residue caused much less disruption; further replacement of Ser2 by Ala almost restored full activity, although the [S2A] mutation itself showed slight detriments, implying that the positively charged Arg5 in the [S2A,L5R] mutant might form alternative interactions with certain receptor residues to compensate for the loss of the essential Leu5. To identify the responsible receptor residues, we screened GHSR1a mutants in which all conserved negatively charged residues in the extracellular regions and all aromatic residues in the ligand-binding pocket were mutated separately. According to the decrease in selectivity of the mutant receptors towards [S2A,L5R]ghrelin, we deduced that the positively charged Arg5 of the ghrelin mutant primarily interacts with the essential aromatic Phe286 at the extracellular end of the sixth transmembrane domain of GHSR1a by forming cation-π and π-π interactions. The present study provided new insights into the binding mechanism of ghrelin with its receptor, and thus would facilitate the design of novel ligands for GHSR1a., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Soil-transmitted helminthiases (STHs) are caused by a group of intestinal nematode infections due to poor hygiene and environments, and clonorchiasis is a food-borne trematode (FBT) infection caused by ingestion of raw freshwater fish. Both are endemic in the People's Republic of China. To explore a suitable control strategy, integrated interventions were applied between 2007 and 2009 in ten pilot counties (eight for the STHs and two for clonorchiasis). Drug administration was used for treatment and complementary efforts to improve the situation based on health education, provision of clean water and sanitation were carried out. Significant achievements were gained as reflected by a drastic decrease in prevalence these infections were demonstrated. The overall prevalence of STHs and clonorchiasis decreased from 35.9% to 7.8% and from 41.4% to 7.0%, respectively. The reduction of prevalence and high cost-effectiveness were documented supporting large-scale application of this integrated intervention in China and elsewhere., (Copyright © 2020. Published by Elsevier B.V.)

Quantifying methane (CH 4 ) leaks of pipeline systems is critical to ensure accurate emission factors in regional and global atmospheric models. The previous emission factors in the United States Environmental Protection Agency (EPA) Greenhouse Gas Inventory (GHGI) are from 1996 and do not reflect the modern gathering pipeline system. Additional data from different basins across the United States are urgently needed to improve the emission factors. The National Energy Technology Laboratory conducted a ground-based vehicle survey at Carson National Forest in the San Juan Basin, New Mexico, in September 2019. 187 km of natural gas gathering pipeline systems were surveyed. The mobile CH 4 survey system was efficient in identifying CH 4 plumes and pinpointing the leak sources. Gaussian dispersion modeling suggested our survey system had a minimum detection limit of 1.5 LPM. No leaks were found from the pipelines while a leak of 7.1 +/- 0.2 LPM was on a pig launcher door and another leak of 0.7 +/- 0.1 LPM on a block valve. Limited access to the gathering pipeline system prevented us from quantifying all potential leaks detected by the CH 4 sensors. The low leak frequency phenomenon was also observed in the sole existing study of natural gas gathering pipelines in the Fayetteville Shale., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Volatile organic compounds (VOCs) are precursors for ozone (O 3 ) and secondary particulate matter, which contribute to asthma and cardiovascular diseases. With the technology development of hydraulic fracking, the United States experienced a shale gas boom in the last decade while the public raised concerns about the potential health impacts of co-emitted VOCs and other airborne pollutants. National Energy Technology Laboratory conducted stationary trailer-based ambient monitoring to study the sources of VOCs in Maryland, where the state enacted a moratorium on unconventional natural gas extraction. The campaign had two periods, May to August 2014 (summer) and November 2014 to February 2015 (winter). Ethane was the most abundant VOC, averaging 12.3 ppb (SD = 15.7 ppb) in summer and 21.7 ppb (SD = 21.6 ppb) in winter. The seasonal variation of VOCs indicated different source strengths. The sampling region was in the nitrogen oxides (NO x ) limited regime for O 3 production, and the O 3 concentrations were sensitive to VOC/NO x ratios in the early mornings. We derived a six-factor profile using positive matrix factorization: motor vehicles, industrial, biogenics, coal burning, fugitive and evaporative, and ozone secondary. The fugitive and evaporative factor explained 44.5% of total VOCs, and the motor vehicles factor followed second with 15.5%. Oil and gas activities had a considerable impact on the abundance of VOCs in this region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The optimization of more sustainable fertilization practice to relieve phosphorus (P) resource scarcity and increase P fertilizer utilization, a better understanding of the regulatory roles of microbes in P mobilization is urgently required to reduce P input. The genes phoD and pqqC are responsible for regulating organic and inorganic P mobilization, respectively. Using high-throughput sequencing, the corresponding bacterial communities harbored by these genes were determined. We conducted a 4-year rice-rice-crop rotation to investigate the responses of phoD- and pqqC-harboring bacterial communities to the partial replacement of inorganic P fertilizer by organic manure with reduced P input. The results showed that a combination of organic and inorganic fertilization maintained high rice yield, and also produced a more complex and stable phosphate mobilizing bacterial community, which contributed to phosphatase activities more than their gene abundances in the model analysis. Compared with the conventional mineral fertilization, organic-inorganic fertilization with the reduced P input slightly increased pqqC gene abundance while significantly enhanced the abundance of phoD-harboring bacteria, especially the genera Bradyrhizobium and Methylobacterium known as potential organic P mineralizers which can maintain high rice production. Moreover, the increased pH was the most impactful factor for the phoD- and pqqC-harboring bacterial communities, by promoting microbial P turnover and greatly increasing bioavailable P pools (H 2 O-Pi and NaHCO 3 -Pi, NaOH-Pi) in this P-deficient paddy soil. Hence, our study demonstrated that the partial replacement of mineral P with organic manure could reshape the inorganic phosphate solubilizing and alkaline-phosphomonoesterase encoding bacterial communities towards more resilient and effective to the high P utilization and productivity over intense cultivation, providing insights into the potential of soil microbes in the efficient management of agricultural P fertilization., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Previous studies showed the effectiveness of negative pressure wound therapy (NPWT) in preventing surgical site infections (SSIs), but current guidelines do not recommend its routine use for surgical wounds. The aim was to compare the effectiveness and safety of NPWT with standard surgical dressing or conventional therapy for preventing SSIs., Methods: Pubmed, Embase and the Cochrane Library were systematically searched on 10 April 2019. Also, we searched clinicaltrials.gov and references of relevant studies. Eligibility criteria were randomized controlled trials (RCTs) and adult surgical patients were included. The effectiveness of NPWT versus standard surgical dressing or conventional therapy was investigated. Relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were used to estimate the pooled effect of dichotomous outcomes and continuous outcomes respectively. The primary outcome was surgical site infections. The quality of included studies and the certainty of the evidence were assessed using the risk of bias tool and the GRADE approach., Results: A total of 45 RCTs with 6624 surgical patients were included. NPWT reduced SSIs (RR 0.58; 95% CI 0.49-0.69) and wound dehiscence(17 RCTs; RR 0.80; 95% CI 0.65-1.00). NPWT did not increase the risk of hematoma (9 RCTs; RR 0.91; 95% CI 0.40-2.07) and hospital readmission(9 RCTs; RR 0.77; 95% CI 0.52-1.12) or prolong length of hospital stay(15 RCTs; MD -0.38; 95% CI, -0.78 to 0.02). NPWT significantly increased the risk of all adverse event-related outcomes (10 RCTs; RR 3.21; 95% CI, 1.17-8.78). The level of certainty was identified as low for the primary outcome and very low for all the secondary outcomes., Conclusions: Compared with standard wound care, NPWT may reduce the risk of SSIs. We are uncertain whether NPWT reduces or increases the risk of wound dehiscence, haematoma, hospital readmission and all adverse event-related outcomes or if it shortens or prolongs length of hospital stay., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The norbisabolane-type sesquiterpenoids bearing a spiroketal functionality have been found in Phyllanthus spp. and showed anti-HBV activities. As part of an ongoing effort to search for promising anti-HBV sesquiterpenes from Phyllanthus plants, we report four new norbisabolane-type sesquiterpenoids, phyacidusin A (1), phyacidusin B (2), phllanthacidoid A1 (3) and phllanthacidoid N1 (4), from stem of P. acidus collected in Xishuangbanna, Yunnan province, China. The absolute configuration of new compounds was established by coupling constants and ROESY correlations, as well as comparation of NMR data with those of known compounds. The absolute configuration of new compounds 1 and 2 was further confirmed by X-ray diffraction. Compound 2 showed effect to HBsAg with an IC 50 value of 11.2 ± 0.01 μM, while compound 3 inhibited HBeAg secretion with an IC 50 value of 57.1 ± 0.02 μM. The results enriched the diversity of anti-HBV norbisabolane sesquiterpenes., (Copyright © 2019. Published by Elsevier B.V.)

Relaxin family peptides perform a variety of biological functions by activating four G protein-coupled receptors, namely relaxin family peptide receptor 1-4 (RXFP1-4). We recently disclosed electrostatic interactions of the homologous RXFP3 and RXFP4 with some agonists based on activation complementation. However, this activation assay-based approach cannot be applied to antagonists that do not activate receptors. Herein, we propose a general approach suitable for both agonists and antagonists based on our newly-developed NanoBiT-based binding assay. We first validated the binding assay-based approach using the agonist relaxin-3, then applied it to the chimeric antagonist R3(ΔB23-27)R/I5. Three positively charged B-chain Arg residues of the agonist and antagonist were respectively replaced by a negatively charged Glu residue; meanwhile, the negatively charged Glu and Asp residue in the essential WxxExxxD motif of both receptors were respectively replaced by a positively charged Arg residue. Based on binding complementation of mutant ligands towards mutant receptors, we deduced possible electrostatic interactions of the agonist and antagonist with both RXFP3 and RXFP4: their B-chain C-terminal Arg residue interacts with the deeply buried Glu residue in the WxxExxxD motif of both receptors, and one or two of their B-chain central Arg residues interact with the shallowly buried Asp residue in the WxxExxxD motif of both receptors. Our present work shed new light on the interaction mechanism of RXFP3 and RXFP4 with agonists and antagonists, and also provided a novel approach for interaction studies of some plasma membrane receptors with their ligands., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nanoparticular drug delivery system (NDDS) has great potential for enhancing the efficacy of traditional chemotherapeutic drugs. However, it is still a great challenge to fabricate a biocompatible NDDS with simple structure capable of optimizing therapeutic efficacy, such as high tumor accumulation, suitable drug release profile (e.g. no premature drug leakage in normal physiological conditions while having a rapid release in cancer cells), low immunogenicity, as well as good biocompatibility. In this work, a simple core/shell structured nanoparticle was fabricated for prostate cancer treatment, in which a mesoporous silica nanoparticle core was applied as a container to high-efficiently encapsulate drugs (doxorubicin, DOX), CaCO 3 interlayer was designed to act as sheddable pH-sensitive gatekeepers for controlling drug release, and cancer cell membrane wrapped outlayer could improve the colloid stability and tumor accumulation capacity. In vitro cell experiments demonstrated that the as-prepared nanovehicles (denoted as DOX/MSN@CaCO 3 @CM) could be efficiently uptaken by LNCaP-AI prostate cancer cells and even exhibited a better anti-tumor efficiency than free DOX. In addition, Live/Dead cell detection and apoptosis experiment demonstrated that MSN/DOX@CaCO 3 @CM could effectively induce apoptosis-related death in prostate cancer cells. In vivo antitumor results demonstrated that DOX/MSN@CaCO 3 @CM administration could remarkably suppress the tumor growth. Compared with other tedious approaches to optimize the therapeutic efficacy, this study provides an effective drug targeting system only using naturally biomaterials for the treatment of prostate cancer, which might have great potential in clinic usage., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A new bakuchiol compound Δ 11 -12-hydroxy-12-dimethyl bakuchiol (1), a new flavanone compound 2(S)-6-methoxy-7- hydroxymethylene-4'-hydroxyl-flavanone (8), and two new isoflavanone compounds 4',7-dihydroxy-3'-(6"β-hydroxy-3″,7″-dimethyl-,2″,7″-dibutenyl)-geranylisoflavone (9) and 4',7-dihydroxy-3'-(7″-hydroxy-7″-methyl-2″,5″-dibutenyl)-geranylisoflavone (10) together with eight known compounds (2-7, 11, 12) were isolated from the P. corylifolia. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 3, 9 and 10 were found to exhibit selective inhibitory activity on DGAT1 with IC 50 values ranging from 93.7 ± 1.3 to 96.2 ± 1.1 μM. Compound 1 showed inhibition activity on DGAT1 with IC 50 values 73.4 ± 1.3 μM and inhibition of DGAT2 with IC 50 value 121.1 ± 1.3 μM., (Copyright © 2018 Elsevier B.V. All rights reserved.)

High solid anaerobic digestion (HSAD) is a promising anaerobic digestion technology. Homogenization and mixing mechanism are essential for HSAD's performance, but relative knowledge still remains poor. In order to investigate HSAD's mixing behavior, a novel flow field measuring approach was proposed as following. Firstly, laponite suspension was selected as the model fluid of HSAD digestate, because the rheological properties and material structure they displayed were highly similar. Then, water and polyacrylamide (PAAm) solution were chosen as basic reference fluid and another non-Newtonian fluid respectively. Flow fields of the three fluids under different rotation speeds were measured via Particle Image Velocimetry (PIV). The evolution of working fluids did induce consecutively the significant flow and mixing behavior of HSAD, because their rheological properties and complexity were getting progressively closer to the real HSAD digestate. Results indicated that the flow field of simulated HSAD fluid was quite different from those of water and PAAm solution, i.e. only the fluid around the impeller could be mixed in HSAD. Besides, increasing rotation speed could not significantly enhance the mixing area of HSAD. Thus, multilayer impellers arranged abreast were recommended for HSAD's mixing. Considering that HSAD's flow field had never been measured before, this study proposed a novel flow field measuring method for such opaque non-Newtonian fluid for the first time. The visualization of HSAD's complex hydrodynamic conditions was also firstly achieved in this study, and thus could further help improve the homogenization of HSAD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We describe a β-L-arabinofuranosylation method by employing the 5-O-(2-pyridinecarbonyl)-L-arabinofuranosyl trichloroacetimidate 10 as a donor. This approach allows a wide range of acceptor substrates, especially amino acid acceptors, to be used. Stereoselective synthesis of β-(1,4)-L-arabinofuranosyl-(2S, 4R)-4-hydroxy-L-proline (β-L-Araf-L-Hyp 4 ) and its dimer is achieved readily by this method. Both the stereoselectivities and yields of the reactions are excellent. To demonstrate the utility of this methodology, the preparation of a trisaccharide in a one-pot manner was carried out., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Four new compounds, erythro-7'E-4-hydroxy-3,3'-dimethoxy-8,5'-oxyneoligna-7'-ene-7,9-diol-9'-al (1), (7S,8S)-4-hydroxy-3,1',3'-trimethoxy-4',7-epoxy-8,5'-neolign-9-ol (5), (7S,8S,7'E)-5-hydroxy-3,3'-dimethoxy-4',7-epoxy-8,5'-neolign-7'-ene-9,9'-diol (6) and (7S,8S,7'E)-5-hydroxy-3,3',9'-trimethoxy-4'-7-epoxy-8,5'-neolign-7'-ene-9-ol (7). Along with four known compounds (2-4, 8) were isolated from the EtOAc-soluble extract of Eleutherococcus senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the compounds were evaluated for in vitro inhibitory activity against PTP1B, VHR and PP1. Among them, compounds 1-4 and 6-8 were found to exhibit selective inhibitory activity on PTP1B with IC 50 values ranging from 17.2±1.6 to 32.7±1.2μM., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Twenty withanolides, including previously unknown nicanlodes A-M, were isolated from aerial parts of Nicandra physalodes. Their structural elucidations were unambiguously achieved through interpretation of extensive spectroscopic data (NMR and HRMS) and by comparison with literature data. Nicanlodes A and B have an unusual aromatic amine moiety. The isolated compounds were evaluated for their cytotoxicity against five human cancer cell lines., (Copyright © 2017. Published by Elsevier Ltd.)

A detailed chemical investigation of Chinese Dragon's Blood, which is a traditional medicine produced form the red resin of Dracaena cochinchinensis, yielded two chalcane-stilbene conjugates, named cochinchinenenes G and H, together with 25 known compounds. The structures of these compounds were determined by spectroscopic examination. HPLC analysis of the resin indicated that the major constituents were a complex mixture of oligomeric polyphenols, which were detected as a broad hump on the base line of a HPLC chromatogram. (13)C NMR analysis indicated that the oligomers were mainly composed of oxygenated chalcane units. This suggestion was supported by the results of a thiol degradation experiment with mercaptoethanol, which yielded a thioether of 4-[(4-hydroxyphenyl)propyl]-3-methoxyphenol. Furthermore, methylation followed by electrospray ionization mass spectroscopic analysis of the resulting fractions established the presence of at least one heptamer of chalcane units., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Using revised simulated body fluid (r-SBF), the electrochemical corrosion behavior of an Nb-60Ta-2Zr alloy for MRI compatible vascular stents was characterized in vitro. As indicated by XPS analysis, the surface passive oxide film of approximately 1.3nm thickness was identified as a mixture of Nb2O5, Ta2O5 and ZrO2 after immersion in the r-SBF. The Nb-60Ta-2Zr alloy manifests a low corrosion rate and high polarization resistance similar to pure Nb and Ta, as shown by the potentiodynamic polarization curves and EIS. Unlike 316L stainless steel and the L605 Co-Cr alloy, no localized corrosion has been detected. Semiconducting property of passive film on the Nb-60Ta-2Zr alloy was identified as the n-type, with growth mechanism of high-field controlled growth. The excellent corrosion resistance in simulated human blood enviroment renders the Nb-60Ta-2Zr alloy promising as stent candidate material., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A weight of evidence (WoE) framework has been applied to assess sediment quality of a typical freshwater lake, Tai Lake in China, where the sediments were contaminated by various chemicals but showed no acute lethality to the benthic invertebrate, Chironomus dilutus. A quantitative scoring method was employed to integrate three lines of evidence (LoE), including adverse effects in life cycle bioassays, biomarker responses, and bioavailability-based chemical analysis. Six biomarkers were determined in C. dilutus after the exposure to the sediments from Tai Lake and provided sensitive indication of sublethal effects at the molecular level. The biomarkers included cytochrome P450, glutathione S-transferase, carboxylesterase, acetylcholinesterase, catalase, and lipid peroxidation. The changes of the biomarkers were summarized for individual sampling sites by computing the integrated biomarker response (IBR) indices. Complementary information was also confirmed by the interrelationship of the LoEs. The IBR indices gained before pupation correlated well with the impairments of emergence of the midges, and altered acetylcholinesterase was corroborated by the detection of chlorpyrifos, an organophosphate pesticide. The relationship between bioavailable toxic units estimated by Tenax extractable concentrations of chemicals in sediment and the observed toxicity in the midges helped to identify the putative toxicity contributors to C. dilutus. Overall, the WoE method clearly distinguished the contaminated sites and ranked them by the level of contamination. Sediment-associated pesticides, particularly γ-hexachlorocyclohexane and chlorpyrifos, were the possible contributors to chronic toxicity to the midges., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Nb-60Ta-2Zr is a newly developed MRI-compatible alloy used for vascular stents. In this work, its haemocompatibility was investigated, including platelet adhesion (lactate dehydrogenase activity), platelet activation (P-selectin expression), coagulation and haemolysis. For comparison, parallel assessments for these factors were performed for the niobium, tantalum, 316L stainless steel (316L SS) and L605 Co-Cr alloy (L605). In addition, albumin and fibrinogen were selected to examine the correlation of protein adsorption with platelet adhesion and metal surface properties. The propensity for platelet adhesion and activation on the Nb-60Ta-2Zr alloy was at nearly the same level as that for Nb and Ta but was slightly less than those of 316L SS and L605. The mitigated platelet adhesion and activation of the Nb-60Ta-2Zr alloy is associated with its decreased adsorption of fibrinogen. The Nb-60Ta-2Zr alloy has a longer clotting time and exhibits significantly superior thromboresistance than 316L SS and L605. Moreover, the haemolysis rate of the Nb-60Ta-2Zr alloy satisfies the bio-safety requirement of the ISO 10993-4 standard. The favourable haemocompatiblity of the Nb-60Ta-2Zr alloy provides evidence of its good biocompatibility and of its suitability as a candidate stent material., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Six new cucurbitane-type triterpenoids, karavilagenin F (1), karavilosides XII and XIII (2, 3), momordicines VI, VII, and VIII (4, 5 and 6), along with four known ones, 5β,19-epoxy-25-methoxycucurbita-6,23-diene-3β,19-diol (7), 5β,19-epoxycucurbita-6, 23-diene-3β,19,25-triol (8), kuguacin R (9), and (19R,23E)-5β,19-epoxy-19-methoxycucurbita-6,23,25-trien-3β-ol (10), were isolated from the stems and leaves of Momordica charantia L. Their chemical structures were elucidated by extensive 1D NMR and 2D NMR (HSQC, HMBC, COSY, and ROESY), MS experiments, and CD spectrum. Compound 6 showed weak cytotoxicity against five human cancer cells lines with IC50 values of 14.3-20.5μmol/L., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Two-dimensional (2D) synchronous spectroscopy together with a new approach called "Orthogonal Sample Design Scheme" was used to study the dipole-dipole interactions in two representative ternary chemical systems (N,N-dimethyllformamide (DMF)/CH3COOC2H5/CCl4 and C60/CH3COOC2H5/CCl4). For the first system, dipole-dipole interactions among carbonyl groups from DMF and CH3COOC2H5 are characterized by using the cross peak in 2D Fourier Transform Infrared Radiation (FT-IR) spectroscopy. For the second system, intermolecular interaction among π-π transition from C60 and vibration transition from the carbonyl band of ethyl acetate is probed by using 2D spectra. The experimental results demonstrate that "Orthogonal Sample Design Scheme" can effectively remove interfering part that is not relevant to intermolecular interaction. Additional procedures are carried out to preclude the possibilities of producing interfering cross peaks by other reasons, such as experimental errors. Dipole-dipole interactions that manifest in the form of deviation from the Beer-Lambert law generate distinct cross peaks visualized in the resultant 2D synchronous spectra of the two chemical systems. This work demonstrates that 2D synchronous spectra coupled with orthogonal sample design scheme provide us an applicable experimental approach to probing and characterizing dipole-dipole interactions in complex molecular systems., (Copyright © 2014 Elsevier B.V. All rights reserved.)

With the increased usage of magnetic resonance imaging (MRI) as a diagnostic tool in clinic, the currently-used metals for vascular stents, such as 316L stainless steel (SS), Co-Cr alloys and Ni-Ti alloys, are challenged by their unsatisfactory MRI compatibility, due to their constituents containing ferromagnetic elements. To provide more MRI compatible vascular stents, the Nb-xTa-2Zr (30≤x≤70) series alloys were selected in the current work. Several key properties of these alloys were optimized in terms of stent requirements, including magnetic susceptibility, elastic modulus and tensile properties. In the as-cast state, a single-phase solid solution with bcc structure was formed in the alloys. The volume magnetic susceptibility (χv) and Young's modulus (E) of the alloys scaled linearly with the Ta content. Increasing the Ta content gave rise to the decreased χv and the increased E, together with the elevated yield strength but less-changed elongation. From multiple requirements for the stents, the Nb-60Ta-2Zr alloy exhibits an optimal properties, including the χv of about 3% of the 316L SS, the E of 142GPa superior to pure niobium, high mass density of 12.03g/cm(3) favored to the X-ray visibility, yield strength of ~330MPa comparable to the 316L SS and a elongation of ~24%. These remarkable advantages make it quite promising as a new candidate of stent metals., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the efficacy and safety of low-concentration 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of different severity of acne vulgaris and optimize the treatment regimen., Methods: A self-controlled multicenter clinical trial was carried out in 15 centers throughout China. A total of 397 acne patients of grade II-IV received 3- or 4-session PDT treatment. 5% ALA gel was applied topically to acne lesions for 1h incubation. The lesions were irradiated by a LED light of 633 nm at dose levels of 96-120 J/cm(2). Clinical assessment was conducted before and after every treatment up to 8 weeks., Results: The effective rate overall and of grade II, III and IV are 82.1%, 71.6%, 79.6% and 88.2%, respectively. The effective rate rises significantly proportionally to the severity of acne (P<0.01). No significant differences are found in the efficacy between patients received 3-session and 4-session PDT treatments (P>0.05). The count of inflammatory and non-inflammatory acne lesions gradually decrease after each treatment (P<0.01) and during the 8-week follow up (P<0.01 or P<0.05). Maximum efficacy is obtained at 8 weeks after the treatment completion., Conclusions: A low-dose topical ALA-PDT regimen using 5% ALA, 1h incubation and red light source of 3 treatment sessions is suggested as optimal scheme for the treatment of different severity of acne vulgaris in Chinese patients. Superior efficacy is found in severe cystic acne of grade IV with mild side effects., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: The objective was to assess intraoperative contrast-enhanced ultrasound (CEUS) in traumatic brain surgery., Methods: We prospectively performed intraoperative conventional ultrasound (IOUS) and CEUS in 32 patients who underwent emergency surgery for the treatment of traumatic brain injury (TBI). Sonographic appearance including echogenicity, border, and size of the traumatic lesion and adjacent brain tissue on CEUS were compared with those on IOUS using surgical results as the gold standard. The differences in the size and contrast enhancement parameters of the lesions between IOUS and CEUS were analyzed with a paired t test., Results: The accuracy of CEUS in assessing TBI was 100%, whereas IOUS was 51%. The absolute peak intensity (API) varied depending on the severity of brain injury. Lower API was observed in severely damaged brain tissue, whereas high API was seen in normal brain tissue or the brain tissue with mild injury. The border of the trauma lesion was more clearly defined on CEUS when compared to IOUS. The size of the lesions measured on CEUS was significantly larger than that on IOUS (P<.01). Importantly, small vessels supplying blood to the tissue in traumatic lesions, as an indication of possible brain vitality, were optimized on CEUS during the surgery. Based on the parameter of time intensity curve and appearances of the lesions on CEUS, the severity of lesions was reclassified and surgical intervention was redesigned in 21 (21/32, 66%) cases., Conclusion: Intraoperative CEUS improves accuracy in classification of traumatic brain injury, which helps neurosurgeons to effectively remove hematoma, preserve normal brain tissue, and prevent damaging the vessels during surgical intervention., (© 2013 Elsevier Inc. All rights reserved.)

Purpose: The expression of fibulin-5 was investigated in urothelial carcinomas of bladder and in normal bladder samples. The effects of fibulin-5 on cell proliferation, motility, and invasion were further explored in bladder cancer cell line 5637., Materials and Methods: The expression of fibulin-5 in 20 bladder carcinoma samples and 7 normal bladder samples were detected by Western blot. Fibuin-5 cDNA was cloned into p-EGFP-N1 vector and transfected into bladder cancer cell line 5637. Growth curves were estimated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay and cell number count. The migration and invasion of the transfected cells and the control cells were measured by Boyden chamber assay., Results: Compared with 1.16 ± 0.28 in the normal control, the mean ± SD expression of fibulin-5 in low grade tumors and high grade tumors were 0.57 ± 0.32 and 0.44 ± 0.42 (P = 0.002 and P = 0.018, respectively), while the expression in Ta-T1 tumors and T2+ tumors were 0.55 ± 0.31 and 0.49 ± 0.43 (P = 0.002 and P = 0.015, respectively). The differences between low grade and high grade tumors or Ta-T1 and T2+ tumors were not statistically significant (P = 0.362 and P = 0.589, respectively). The growth rate of the fibulin-5 transfected GFP-F5 cells was remarkably reduced than that of the untransfected cells or the empty vector transfected GFP-t cells. Besides, compared with control cells, the GFP-F5 cells showed significant inhibition of cell invasion with slight inhibition of cell migration., Conclusions: Fibulin-5 is down-regulated in urothelial carcinoma of bladder and acts as a tumor suppressor gene by inhibiting proliferation and invasion of bladder cancer cells., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Cardiac hypertrophy is a common pathological change accompanying cardiovascular disease. Recently, some evidence indicated that calcium-sensing receptor (CaSR) expressed in the cardiovascular tissue. However, the functional involvement of CaSR in cardiac hypertrophy remains unclear. Previous studies have shown that CaSR caused accumulation of inositol phosphate to increase the release of intracellular calcium. Moreover, Ca(2+)-dependent phosphatase calcineurin (CaN) played a vital role in the development of cardiac hypertrophy. Therefore, we investigated the expression of CaSR in cardiac hypertrophy-induced by angiotensin II (AngII) and the effects of CaSR activated by GdCl(3) on the related signaling transduction pathways. The results showed that AngII induced cardiac hypertrophy and up-regulated the expression of CaSR, meanwhile increased the intracellular calcium concentration ([Ca(2+)](i)) and activated CaN hypertrophic signaling pathway. Compared with AngII alone, the above changes were further obvious when adding GdCl(3). But the effects of GdCl(3) on the cardiac hypertrophy were attenuated by CsA, a specific inhibitor of CaN. In conclusion, these results suggest that CaSR is involved in cardiac hypertrophy-induced by AngII through CaN pathway in cultured neonatal rat cardiomyocytes.

Atropurosides A-G (1-7), seven new steroidal saponins, which possess new polyhydroxylated aglycones, were isolated from the rhizomes of Smilacina atropurpurea (Convallariaceae), together with a known saponin, dioscin (8). Their structures were elucidated on the basis of detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical methods. Antifungal testing of the eight compounds indicated that atropurosides B (2) and F (6) were fungicidal against Candida albicans, Candida glabrata, Cryptococcus neoformans, and Aspergillus fumigatus with minimum fungicidal concentrations (MFCs) < or = 20 microg/ml, while dioscin (8) was selectively active against C. albicans and C. glabrata (MFC < or = 5.0 microg/ml). Furthermore, the antifungal saponins 2, 6, and 8 were evaluated for their in vitro cytotoxicities in a panel of human cancer cell lines (SK-MEL, KB, BT-549, SK-OV-3, and HepG2) and non-cancerous Vero cells. All showed moderate cytotoxicities. It appears that the antifungal activity of these steroidal saponins correlates with their cytotoxicity against mammalian cells.

A 12(13-->14)abeospirostanol dracaenogenin A (1) and a spirostanol dracaenogenin B (2) were isolated from Chinese dragon's blood, the red resin of Dracaena cochinchinensis (Agavaceae). Their structures were established as (14S,25R)12(13-->14)abeospirosta-5,13(18)-diene-1beta,3beta,15alpha-triol (1) and (25R) spirost-5-ene-1beta,3beta,14alpha,15alpha-tetrol (2) by means of spectroscopic analysis, especially by 2D NMR spectra, and X-ray crystallographic analysis. Dracaenogenin A (1) is the first example of a 12(13-->14)abeospirostane spirostanoid found in nature. Its biogenesis from ruscogenin (3) through namogenin (4) and 2 was tentatively proposed.

Six new polyhydroxylated steroidal saponins, tupistrosides A-F (1-6), together with nine known steroids, were isolated from the fresh rhizomes of Tupistra yunnanensis. Their structures were elucidated to be (25S)-1beta,4beta,5beta-trihydroxy-spirostane-3beta-yl O-alpha-l-arabinopyranoside (1), 1beta,24beta-dihydroxy-spirost-5,25(27)-dien-3alpha-yl O-beta-d-glucopyranoside (2), (22S,25S)-1alpha,2beta,3alpha,5alpha-tetrahydroxy-furo-spirostane-26-yl O-beta-d-glucopyranoside (3), 1beta,3alpha,22 xi-trihydroxy-furost-5,25(27)-dien-26-yl O-beta-d-glucopyranoside (4), 26-O-beta-d-glucopyranosyl-1beta,22-dihydroxy-furost-5-en-3alpha-yl O-beta-d-glucopyranoside (5) and 22-methoxy-1beta,2beta,3beta,4beta,5beta,7alpha-hexahydroxy-furost-25(27)-en-6-one-26-yl O-beta-d-glucopyranoside (6), respectively, by means of spectroscopic analysis and the results of acid hydrolysis.

A further phytochemical investigation on the fresh stem of Dracaena cochinchinensis yielded 18 steroidal saponins. Fourteen of which are new compounds, designated as 25(R,S)-dracaenosides E-H, M, O-Q, dracaenosides I-L, R, and 25(S)-dracaenoside N. Their structures were determined by detailed spectroscopic analysis, including extensive 1D and 2D NMR data, and the result of hydrolytic reaction.

Recent neuroanatomical studies have revealed a direct hypothalamocerebellar histaminergic pathway. However, the functional significance of the histaminergic fibers in the cerebellum is not yet clear. In this study, the effects of histamine on the firing of cerebellar Purkinje cells (PCs) were investigated in vitro. Histamine predominantly produced excitatory (106/111, 95.5%) and in a few cases inhibitory (5/111, 4.5%) responses in PCs. The histamine-induced excitation was not blocked by perfusing the slice with low Ca2+ high/Mg2+ medium (n = 8), supporting a direct postsynaptic action of histamine. The histamine H2 receptor antagonist ranitidine effectively blocked the excitatory response of PCs to histamine (n = 20), but triprolidine, an H1 receptor antagonist, could not significantly block the histamine-induced excitation, or only very slightly decreased the excitatory effect of histamine on the cells (n = 13). On the other hand, the highly selective H2 receptor agonist dimaprit mimicked the excitatory effect of histamine on PCs and this dimaprit-induced excitation was also blocked by ranitidine (n = 20), but not triprolidine (n = 8). However, the H1 receptor agonists betahistine and 2-thiazolylethylamine did not show any effect on the PCs (n = 9 and 14). These results reveal that histamine excites cerebellar PCs via H2 receptors and suggest that the hypothalamocerebellar histaminergic fibers may play an important role in functional activities of the cerebellum.

The present study assessed the urinary protein with SDS-PAGE technique and by using gentamicin as a positive control for a comparative study to evaluate the renal toxic effect of gossypol. Results indicated that gentamicin could induce proteinuria by alteration of glomerular permeability to cause over-filtration of high molecular weight proteins, damage the brush border (BB) membrane of proximal renal tubules and impair tubular reabsorption function. Gossypol could also induce proteinuria in certain cases of guinea pigs but not at all in gossypol-treated rats. However, an increase in low molecular weight protein bands (M.W. range 20-30 kd) in urinary electrophoregram of gossypol-treated rats were detectable.