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Based on a typical ozone （O 3 ） pollution process in Jinan City from June 16 to 26, 2021, the variation characteristics of O 3 and its precursor volatile organic compounds （VOCs） during different pollution periods （clean period （CP）, pollution rise period （PRP）, heavy pollution period （HPP）, and pollution decline period （PDP）） in the urban area were analyzed. Both positive matrix factorization （PMF） and an observation-based model （OBM） were used to identify the main sources of VOCs, O 3 production mechanisms, and sensitive species. The results showed that the average value of ρ （O 3 -8h） during the HPP period in the urban area was （246.67±11.24） μg·m -3 , and ρ （O 3 -1h） had a peak value of 300 μg·m -3 . The volume fractions of VOCs and NO 2 concentration were affected by the decrease in planetary boundary layer and wind speed, which were 76.99%-145.36% and 127.78%-141.18% higher than those in the other three periods, respectively, and were the main reasons for the aggravation of O 3 pollution. Alkanes, oxygenated volatile organic compounds （OVOCs）, and halogenated hydrocarbons accounted for 43.81%, 20.98%, and 17.43% of VOCs in urban areas, respectively. All of them showed significant growth during the HPP period, with acetone, propane, and ethane being the top three species by volume in each stage and isopentane showing the highest growth during the HPP period. Alkene, alkanes, and aromatic hydrocarbons accounted for 40.19%, 28.06%, and 21.92% of the ozone generation potential （OFP）. 1-butene, toluene, isopentane, and isoprene were the species with higher OFP. Isoprene had the highest OFP during the PRP phase, and 1-butene had the highest OFP during the HPP phase. The volume fraction of isopentane significantly increased OFP. The correlation coefficient between VOCs and CO preliminarily indicated that motor vehicle exhaust and oil and gas volatilization were the main sources of VOCs during the HPP period. Further use of PMF revealed that solvent use sources, combustion sources, motor vehicle exhaust+oil and gas volatilization sources, industrial emission sources, and plant sources were important sources of VOCs in urban areas. The contribution of motor vehicle exhaust+oil and gas volatilization sources in the HPP period to VOCs was 3.09-14.72 times higher than that in other periods. The contribution of solvent use sources to VOCs was approximately 2.50 times higher than that in the CP and PRP periods. The main sources of VOCs volume fraction increase were motor vehicle exhaust, oil and gas volatilization sources, and solvent use sources. Potential sources and concentration weight analysis found that VOCs were also affected by the transmission of VOCs to Binzhou and Dongying in the northeast direction. The OBM results indicated that the main pathway of O 3 formation in urban areas was the reaction of peroxide hydroxyl radicals （HO 2 ·） and methyl peroxide radicals （CH 3 O 2 ·） with NO, and the net ozone generation rate during the HPP phase [ P （O 3 ） net ] was 24×10 -9 h -1 . Based on the sensitivity experiment results, the alkene components of 1-butene, propylene, cis-2-butene, and ethylene were the dominant species for O 3 production.

Objective: Frailty is a significant public health issue facing aging societies and can be reduced by physical activity (PA), but the dose-response relationship between PA and frailty is not clear. This systematic review and dose-response meta-analysis aimed to assess the effect of PA on frailty in adults by aggregating data from observational studies., Methods: PubMed, Embase, Web of Science, Cochrane Library, Scopus, SAGE Reference Online, SinoMed, CINAHL and CNKI were retrieved for articles published before May 2024. After quality evaluation, data on PA and the risk of frailty were extracted. Stata/MP 17.0 was used for dose-response meta-analysis., Results: A total of 15 articles were included, involving 34,754 participants, including 4250 subjects with frailty or pre-frailty. The consequence of the dose-response meta-analysis revealed that compared with those who were not active at all, a 22 % (95 % CI, 16 %-28 %) reduction in the risk of frailty in individuals with 11.25 MET h/week of cumulative activity and a 55 % (95 % CI, 44 %-63 %) reduction in the risk of frailty in those with 22.5 MET h/week of cumulative activity; for higher activity levels (36.75 MET h/week), the risk of frailty was reduced by 68 % (95 % CI, 58 %-76 %) and continued to be reduced as PA volum increased., Conclusions: There is a non-linear dose-response relationship between PA and frailty risk. Even small amounts of PA could reduce the risk of frailty. Meeting the minimum recommended PA target could reduce some risks, and doubling the recommended PA volumes could reduce most risks, which continue to increase as the volum of PA accumulates., Competing Interests: 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., (© 2024 The Authors.)

Histone deacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones, leading to the silencing of genes. Targeting specific isoforms of HDACs has emerged as a promising approach for cancer therapy, as it can overcome drawbacks associated with pan-HDAC inhibitors. HDAC6 is a unique HDAC isoform that deacetylates non-histone proteins and is primarily located in the cytoplasm. It also has two catalytic domains and a zinc-finger ubiquitin binding domain (Zf-UBD) unlike other HDACs. HDAC6 plays a critical role in various cellular processes, including cell motility, protein degradation, cell proliferation, and transcription. Hence, the deregulation of HDAC6 is associated with various malignancies. In this study, we report the design and synthesis of a series of HDAC6 inhibitors. We evaluated the synthesized compounds by HDAC enzyme assay and identified that compound 8g exhibited an IC 50 value of 21 nM and 40-fold selective activity towards HDAC6. We also assessed the effect of compound 8g on various cell lines and determined its ability to increase protein acetylation levels by Western blotting. Furthermore, the increased acetylation of α-tubulin resulted in microtubule polymerization and changes in cell morphology. Our molecular docking study supported these findings by demonstrating that compound 8g binds well to the catalytic pocket via L1 loop of HDAC6 enzyme. Altogether, compound 8g represents a preferential HDAC6 inhibitor that could serve as a lead for the development of more potent and specific inhibitors., 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 Masson SAS. All rights reserved.)

This paper aims to explore the inhibitory effect of Yueju Pills on breast cancer and decipher the underlying mechanism. A total of 92 SPF-grade SD female rats were involved in this study, and 14 of them were randomly selected into control group. The remaining 78 rats were administrated with 7,12-dimethylbenzanthracene(DMBA) by gavage to establish the breast cancer model. The modeled rats were randomized into model, tamoxifen(1.9 mg·kg~(-1)·d~(-1)), and low-and high-dose(17, 34 g·kg~(-1)·d~(-1)) Yueju Pills groups. The mental state, food intake, and activities of the rats were observed daily, and the body weight was measured on alternate days. After 12 weeks of administration, the rats were sacrificed and the tumor weight was measured. The serum estrogen and progeste-rone levels were determined by enzyme-linked immunosorbent assay. The histopathological changes of the breast and tumor were observed by hematoxylin-eosin staining. Western blot was employed to measure the protein levels of glucose transporter 1(GLUT1), lactate dehydrogenase A(LDHA), phosphofructokinase muscle(PFKM), pyruvate kinase isozyme type M2(PKM2), hexokinase 2(HK2), nuclear factor-kappaB(NF-κB), and phosphorylated NF-κB. The intestinal microbiome was examined by 16S rRNA high-throughput sequencing. The results showed that compared with the model group, high and low-dose Yueju Pills showed the tumor inhibition rate of 15.8% and 64.5%, respectively, and the low dose group had stronger inhibitory effect. Compared with the control group, the model group presented elevated the levels of estrogen and progesterone in serum. The administration of Yueju Pills lowered such ele-vation, and the low-dose group showed stronger lowering effect(P<0.05). Compared with the model group, Yueju Pills reduced the glands with increased breast tissue, the degree of breast duct expansion, the number and area of acinar cavity, the secretions, and the layers of mammary epithelial cells. Furthermore, Yueju Pills down-regulated the expression of GLUT1, LDHA, PFKM, PKM2, HK2, and NF-κB(P<0.05) and altered the diversity, composition, structure, and abundance of intestinal flora. The results showed that Yueju Pills could inhibit breast cancer by regulating the secretion of estrogen and progesterone, glycolysis, inflammatory cytokines, and intestinal flora.

Androgen receptor (AR) signalling is known to be dispensable for the biology of castration-resistant prostate cancer (CRPC), whereas the AR itself and the residual androgens after castration are crucial for the growth and progression of CRPC. Therefore, there is high demand for novel therapeutic candidates targeting AR itself or aberrant AR signalling to suppress the progression to or the growth of CPRC. Here, we report that ginsenoside compound K (GCK), the primary bioactive metabolite biotransformed from protopanaxadiol (PPD) ginsenoside, acts as a novel AR signalling inhibitor by transcriptionally suppressing AR expression and tumour growth in athymic nude mice. GCK inhibited cell growth in LNCaP, PC-3 and 22Rv1 prostate cancer cell lines and suppressed the expression levels of cell cycle regulators. GCK down-regulated epithelial-mesenchymal transition markers such as vimentin and matrix metalloproteinase 9 (MMP9), whereas E-cadherin was significantly increased in GCK-stimulated LNCaP and 22Rv1 cells. Moreover, GCK treatment markedly decreased both AR and AR-V7 protein levels in LNCaP and 22Rv1 cells, possibly by decreasing AR promoter activity. Experiments with AR promoter-deleted constructs revealed that the region between -412 and -227 is critical for GCK regulation. GCK treatment in athymic nude mice implanted with 22Rv1 CRPC cell lines significantly suppressed tumour growth and AR expression levels in tumour tissues. Collectively, our results suggest that GCK, as a novel AR inhibitor, could be a potential therapeutic agent against prostate cancer and an effective chemopreventive agent to delay the progression to CRPC., (© 2022 Federation of European Biochemical Societies.)

Thermal priming of reef corals can enhance their heat tolerance; however, the legacy effects of heat stress during parental brooding on larval resilience remain understudied. This study investigated whether preconditioning adult coral Pocillopora damicornis to high temperatures (29°C and 32°C) could better prepare their larvae for heat stress. Results showed that heat-acclimated adults brooded larvae with reduced symbiont density and shifted thermal performance curves. Reciprocal transplant experiments demonstrated higher bleaching resistance and better photosynthetic and autotrophic performance in heat-exposed larvae from acclimated adults compared to unacclimated adults. RNA-seq revealed strong cellular stress responses in larvae from heat-acclimated adults that could have been effective in rescuing host cells from stress, as evidenced by the widespread upregulation of genes involved in cell cycle and mitosis. For symbionts, a molecular coordination between light harvesting, photoprotection and carbon fixation was detected in larvae from heat-acclimated adults, which may help optimize photosynthetic activity and yield under high temperature. Furthermore, heat acclimation led to opposing regulations of symbiont catabolic and anabolic pathways and favoured nutrient translocation to the host and thus a functional symbiosis. Notwithstanding, the improved heat tolerance was paralleled by reduced light-enhanced dark respiration, indicating metabolic depression for energy saving. Our findings suggest that adult heat acclimation can rapidly shift thermal tolerance of brooded coral larvae and provide integrated physiological and molecular evidence for this adaptive plasticity, which could increase climate resilience. However, the metabolic depression may be maladaptive for long-term organismal performance, highlighting the importance of curbing carbon emissions to better protect corals., (© 2022 John Wiley & Sons Ltd.)

A rapid and sensitive method was developed based on matrix solid phase dispersion (MSPD) for the determination of hexabromocyclododecane enantiomers (±α, ±β and ± γ-HBCD) in animal meat. The instrumental analysis was employed with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) at trace level (ng g -1 ). To obtain excellent efficiency, the key parameters, including the type of dispersive adsorbent and elution solvent, were investigated by single-factor experiments. The volume of elution solvent and amount of dispersive adsorbent were optimized by the Box-Behnken design through response surface methodology. Under optimized conditions, the developed method exhibited excellent methodologic characteristics and was applied to the determination of HBCD enantiomers in real chicken and pork meat. Experimental results indicated that the proposed method would be an efficient, rapid and application method for the determination of lipophilic organic pollutants in animal meat., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The successful dispersal of coral larvae is vital to the population replenishment and reef recovery and resilience. Despite that this critical early stage is susceptible to ocean warming and acidification, little is known about the responses of coral larvae to warming and acidification across different biological scales. This study explored the influences of elevated temperature (29 °C versus 33 °C) and pCO 2 (500 μatm versus 1000 μatm) on brooded larvae of Pocillopora damicornis at the organismal, cellular and gene expression levels. Heat stress caused bleaching, depressed light-enhanced dark respiration, photosynthesis and autotrophy, whereas high pCO 2 stimulated photosynthesis. Although survival was unaffected, larvae at 33 °C were ten-times more likely to settle than those at 29 °C, suggesting reduced capacity to disperse and differentiate suitable substrate. Remarkably, heat stress induced greater symbiont loss at ambient pCO 2 than at high pCO 2 , while cell-specific pigment concentrations of symbionts at 33 °C increased twofold under ambient pCO 2 relative to high pCO 2 , suggesting pCO 2 -dependent bleaching patterns. Considerable increases in activities of host antioxidants superoxide dismutase (SOD) and catalase (CAT) at 33 °C indicated oxidative stress, whereas lipid peroxidation and caspase activities were contained, thereby restraining larval mortality at 33 °C. Furthermore, the coral host mounted stronger transcriptional responses than symbionts. High pCO 2 stimulated host metabolic pathways, possibly because of the boosted algal productivity. In contrast, host metabolic processes and symbiont photosystem genes were downregulated at 33 °C. Interestingly, the upregulation of extracellular matrix genes and glycosaminoglycan degradation pathway at 33 °C was more evident under ambient pCO 2 than high pCO 2 , suggesting compromised host tissue integrity that could have facilitated symbiont expulsion and bleaching. Our results provide insights into how coral larvae respond to warming and acidification at different levels of biological organization, and demonstrate that ocean acidification can mediate thermal bleaching and gene expression in coral larvae under heat stress., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

HDAC6 and Hsp90, existing as a cytosolic complex play an important role in maintaining the protein homeostasis. The interplay of HDAC6 and Hsp90 has attracted wide attention due to their important role and promise as therapeutic targets in malignant cancers. Therefore, the discovery of dual inhibitors targeting HDAC6 and Hsp90 is of high importance. In the present study, we describe the design, synthesis, and biological evaluation of bifunctional inhibitors against HDAC6 and Hsp90 interplay. In particular, compound 6e shows a significant inhibitory activity against both HDAC6 and Hsp90 with IC 50 values of 106 nM and 61 nM, respectively. Compound 6e promotes the acetylation of HDAC6 substrate proteins such as α-tubulin and Hsp90 via HDAC6 inhibition, and also induces the degradation of Hsp90 clients such as Her2, EGFR, Met, Akt, and HDAC6 via Hsp90 inhibition. Compound 6e consequently furnishes potent antiproliferative effect on gefitinib-resistant H1975 non-small cell lung cancer (NSCLC) with a GI 50 value of 1.7 μM. In addition, compound 6e successfully achieved significant tumor growth inhibition in H1975 NSCLC xenograft model without noticeable abnormal behavior, body weight changes, and apparent ocular toxicity. We conclude that compound 6e constitutes an excellent tool as well as a valuable lead for assessment of Hsp90 and HDAC6 dual inhibition with a single molecule., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Jumonji domain-containing 3 (JMJD3/KDM6B) is a histone demethylase that plays an important role in regulating development, differentiation, immunity, and tumorigenesis. However, the mechanisms responsible for the epigenetic regulation of inflammation during mastitis remain incompletely understood. Here, we aimed to investigate the role of JMJD3 in the lipopolysaccharide (LPS)-induced mastitis model. GSK-J1, a small molecule inhibitor of JMJD3, was applied to treat LPS-induced mastitis in mice and in mouse mammary epithelial cells in vivo and in vitro. Breast tissues were then collected for histopathology and protein/gene expression examination, and mouse mammary epithelial cells were used to investigate the mechanism of regulation of the inflammatory response. We found that the JMJD3 gene and protein expression were upregulated in injured mammary glands during mastitis. Unexpectedly, we also found JMJD3 inhibition by GSK-J1 significantly alleviated the severity of inflammation in LPS-induced mastitis. These results are in agreement with the finding that GSK-J1 treatment led to the recruitment of histone 3 lysine 27 trimethylation (H3K27me3), an inhibitory chromatin mark, in vitro. Furthermore, mechanistic investigation suggested that GSK-J1 treatment directly interfered with the transcription of inflammatory-related genes by H3K27me3 modification of their promoters. Meanwhile, we also demonstrated that JMJD3 depletion or inhibition by GSK-J1 decreased the expression of toll-like receptor 4 and negated downstream NF-κB proinflammatory signaling and subsequently reduced LPS-stimulated upregulation of Tnfa, Il1b, and Il6. Together, we propose that targeting JMJD3 has therapeutic potential for the treatment of inflammatory diseases., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for inflammation and fibrosis. Moreover, using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice, our results provide a novel description of the target pathways for tetrandrine. Specifically, we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages. Taken together, our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for silicosis., (© 2021. The Author(s).)

The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is known to be highly associated with tumor progression in prostate cancer, but the molecular mechanisms underlying the regulation of HMMR expression remain unclear. Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of HMMR expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data demonstrate that such regulation occurs at the transcription level. HMMR promoter reporter assays revealed that the transcription factor SRF is responsible for the mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the suppression of HMMR expression by Torin2 was noticeably reversed by the overexpression of SRF. Moreover, our findings suggest that the SRF binding sites responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis are located in HMMR promoter sequences carrying the first intron, downstream of the translational start site. Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that mTOR activity is required for the induction of HMMR expression by androgen. Collectively, our study provides new mechanistic insights into the role of mTOR/SRF/AR signaling in HMMR regulation in prostate cancer cells.

Purpose: There has been mounting evidence that Dendrobium officinale polysaccharides (DOP), a traditional Chinese medicine, are a potential candidate treatment for N-methyl-N'-nitro-N-nitrosoguanidine- (MNNG-) induced precancerous lesions of gastric cancer (PLGC). However, the underlying mechanisms have not been adequately addressed., Method: We utilized RNA-Seq analysis to investigate possible molecular targets and then used Venn software to identify the differentially expressed genes (DEGs). Further, we analyzed these DEGs with core analysis, upstream analysis, and interaction network analysis by IPA software and validated the DEGs by real-time PCR and Western blot., Result: 78 DEGs were identified from the normal control group (CON), the PLGC model group (MOD), and the DOP-treated group (DOP) by the Venn software. Further analysis of these DEGs, including core analysis, upstream analysis, and interaction network analysis, was performed by Ingenuity Pathway Analysis (IPA). The main canonical pathways involved were SPINK1 Pancreatic Cancer Pathway (-log ( P value) = 4.45, ratio = 0.0667) and Circadian Rhythm Signaling (-log ( P value) = 2.33, ratio = 0.0606). Circadian Rhythm Signaling was strongly upregulated in the model group versus the DOP group. CLOCK was predicted to be strongly activated ( z -score = 2.236) in upstream analysis and induced the downstream PER3. In addition, the relative mRNA expression levels of seven DEGs (CD2AP, ECM1, AQP4, PER3, CMTM4, ESRRG, and KCNJ15) from RT-PCR agreed with RNA-Seq data from MOD versus CON and MOD versus DOP groups. The gene and protein expression levels of PER3 and AQP4 were significantly downregulated in the PLGC model and significantly increased by DOP treatment (9.6 g/kg)., Conclusions: These findings not only showed DOP inhibits PLGC development by upregulating the PER3 and AQP4 gene and protein expression but also suggested that its mechanism of action involved modulating the Circadian Rhythm Signaling pathway., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yi Zhao et al.)

Heat shock protein 90 (Hsp90) plays an important role in cancer cell proliferation, survival, and migration by regulating the maturation and stabilization of numerous oncoproteins. Despite significant efforts in developing Hsp90 inhibitors, none of these have been approved for clinical use, mostly due to toxicity, such as liver, cardiac, and retinal toxicity. To avoid undesirable toxicity, we herein report a hydrogen peroxide-activated Hsp90 inhibitor, Boro-BZide (3), which is capable of selectively targeting cancer cells over normal cells. Boro-BZide (3) can be activated by high levels of hydrogen peroxide, releasing its parent active Hsp90 inhibitor. The mechanism of action was determined by a series of experiments including fluorescence polarization assay, cell viability assay, western blotting, high-pressure liquid chromatography (HPLC), and fluorescence-activated cell sorting (FACS) analysis. These efforts ultimately led to the identification of a novel hydrogen peroxide-activated Hsp90 prodrug with improved therapeutic index, which was less prone to furnish unwanted adverse effects. This hydrogen peroxide-responsive prodrug strategy will be beneficial for overcoming the toxicity hurdles of Hsp90 inhibitors for clinical application., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A Gram-stain-negative, rod-shaped and facultatively aerobic bacterial strain, designated F7430 T , was isolated from coastal sediment collected at Jingzi Wharf in Weihai, PR China. Cells of strain F7430 T were 0.3-0.4 µm wide, 2.0-2.6 µm long, non-flagellated, non-motile and formed pale-beige colonies. Growth was observed at 4-40 °C (optimum, 30 °C), pH 6.0-9.0 (optimum, pH 7.5-8.0) and at NaCl concentrations of 1.0-10.0 % (w/v; optimum, 1.0 %). The sole respiratory quinone of strain F7430 T was ubiquinone 8 and the predominant cellular fatty acids were summed feature 8 (C 18 : 1  ω 7 c / C 18 : 1  ω 6 c ; 60.7 %), summed feature 3 (C 16 : 1  ω 7 c /C 16 : 1  ω 6 c ; 30.2 %) and C 15 : 0 iso (13.9 %). The polar lipids of strain F7430 T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid and three unidentified lipids. Results of 16S rRNA gene sequences analyses indicated that this strain belonged to the family Halieaceae and had high sequence similarities to Parahaliea aestuarii JCM 51547 T (95.3 %) and Halioglobus pacificus DSM 27932 T (95.2 %) followed by 92.9-95.0 % sequence similarities to other type species within the aforementioned family. The rpoB gene sequences analyses indicated that the novel strain had the highest sequence similarities to Parahaliea aestuarii JCM 51547 T (82.2 %) and Parahaliea mediterranea DSM 21924 T (82.2 %) followed by 75.2-80.5 % sequence similarities to other type species within this family. Phylogenetic analyses showed that strain F7430 T constituted a monophyletic branch clearly separated from the other genera of family Halieaceae . Whole-genome sequencing of strain F7430 T revealed a 3.3 Mbp genome size with a DNA G+C content of 52.6 mol%. The genome encoded diverse metabolic pathways including the Entner-Doudoroff pathway, assimilatory sulphate reduction and biosynthesis of dTDP-l-rhamnose. Based on results from the current polyphasic study, strain F7430 T is proposed to represent a novel species of a new genus within the family Halieaceae , for which the name Sediminihaliea albiluteola gen. nov., sp. nov. is proposed. The type strain of the type species is F7430 T (=KCTC 72873 T =MCCC 1H00420 T ).

Particulate matter of 0.3 μm in diameter (PM 0.3 ) poses a serious threat to the environment and human beings. Ultrathin and -light nanofibrous filters with excellent filtration properties can significantly prevent the detrimental effects of these particles. Here, we develop free-standing polyamide PA-66 ultrafine nanofiber papers for PM 0.3 filtration using effective and scalable blow and electro-blow spinning techniques. The smallest average fiber diameter is 61.7 nm, which is 2-3 orders of magnitude smaller than that of conventional textiles. Poly(ethylene terephthalate) nonwovens are selected to fabricate free-standing nanofiber papers of various polymers, including polyamide, poly(methyl methacrylate), poly(vinylpyrrolidone), and poly(ethylene oxide) owing to the smooth surfaces of the nonwovens. This underlying principle can be used to create similar free-standing nanofiber papers from other commodity polymers in the future. Mechanisms of capturing particulate matter with different nanofiber morphologies are discussed. Salt and oil particulates are used to characterize the filtration properties. PA-66 papers are promising reusable filters owing to their mechanical particle-capture mechanism. The blow-spun PA-66 papers show filtration performance of 98.75% efficiency and a pressure drop of 125.44 Pa owing to the "slip" effect caused by the ultrasmall diameter. In the electro-blow spinning process, a supplementary voltage supply is conducive to separating nanofiber bundles into random-oriented nanofibers. Electro-blown spun papers possess an ultrahigh efficiency of 99.99% with a reduced areal density of 0.9 g m -2 . These PA-66 papers can be used in a variety of applications, such as reusable personal protective equipment, industrial waste gas treatment, and central ventilation purification systems.

Urchin-like hierarchical IrO2 nanostructures, which are obtained by a surfactant-free, wet-chemical approach, show boosted OER performance in acid with an overpotential of 260 mV @10 mA cm-2geo under optimal pocessing conditions. The overpotential @10 mA cm-2geo can be kept below 285 mV for over 30 hours.

A Gram-stain negative, rod-shaped, facultatively aerobic, pale-beige-coloured bacterial strain, designated F7233 T , was isolated from coastal sediment sampled at Jingzi Bay, Weihai, PR China. Cells of strain F7233 T were 0.3-0.4 µm wide, 1.2-1.4 µm wide long, non-spore-forming and motile with one flagellum. Optimum growth occurred at 30 °C, with 1.0 % (w/v) NaCl and at pH 6.5-7.0. Positive for nitrate reduction, hydrolysis of Tweens and oxidase activity. The sole respiratory quinone of strain F7233 T was ubiquinone-10 and the predominant cellular fatty acid was summed feature 8 (C 18 : 1  ω 7 c /C 18 : 1  ω 6 c ). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and one unidentified aminophospholipid. The G+C content of the chromosomal DNA was 63.3 mol%. Phylogenetic analysis of the 16S rRNA gene sequence revealed that the newly isolate belonged to the genus Stappia , with 96.8 % sequence similarity to Stappia indica MCCC 1A01226 T , 96.1 % similarity to Stappia stellulata JCM 20692 T and 95.5% similarity to Stappia taiwanensis CC-SPIO-10-1 T . On the basis of phylogenetic, phenotypic and chemotaxonomic data, it is considered that strain F7233 T should represent a novel species within the genus Stappia , for which the name Stappia albiluteola sp. nov. is proposed. The type strain is F7233 T (=MCCC 1H00419 T =KCTC 72859 T ).

Cranes are widely used in the field of construction, logistics, and the manufacturing industry. Cranes that use wire ropes as the main lifting mechanism are deeply troubled by the swaying of heavy objects, which seriously restricts the working efficiency of the crane and even cause accidents. Compared with the single-pendulum crane, the double-pendulum effect crane model has stronger nonlinearity, and its controller design is challenging. In this paper, cranes with a double-pendulum effect are considered, and their nonlinear dynamical models are established. Then, a controller based on the radial basis function (RBF) neural network compensation adaptive method is designed, and a stability analysis is also presented. Finally, the hardware-in-the-loop experimental results show that the neural network compensation control can effectively improve the control performance of the controller in practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qiang, Sun, Lyu and Dong.)

Chlorambucil is a nitrogen mustard-based DNA alkylating drug, which is widely used as a front-line treatment of chronic lymphocytic leukaemia (CLL). Despite its widespread application and success for the initial treatment of leukaemia, a majority of patients eventually develop acquired resistance to chlorambucil. In this regard, we have designed and synthesised a novel hybrid molecule, chloram-HDi that simultaneously impairs DNA and HDAC enzymes. Chloram-HDi efficiently inhibits the proliferation of HL-60 and U937 leukaemia cells with GI 50 values of 1.24 µM and 1.75 µM, whereas chlorambucil exhibits GI 50 values of 21.1 µM and 37.7 µM against HL-60 and U937 leukaemia cells, respectively. The mechanism behind its remarkably enhanced cytotoxicity is that chloram-HDi not only causes a significant DNA damage of leukaemia cells but also downregulates DNA repair protein, Rad52, resulting in the escalation of its DNA-damaging effect. Furthermore, chloram-HDi inhibits HDAC enzymes to induce the acetylation of α -tubulin and histone H3.

The aim of this study was to fully understand the pollution characteristics and sources of PM 2.5 in Zhengzhou, and to investigate the differences in four seasons and between urban and suburban areas. At the Zhengzhou environmental monitoring center (urban areas) and Zhengzhou University (suburban areas), 1284 environmental PM 2.5 samples were collected in the four seasons of 2018. The concentrations of nine kinds of inorganic water-soluble ions, organic carbon, elemental carbon and 27 kinds of elements, were measured by ion chromatography, carbon analyzer, and X-ray fluorescence spectrometry, respectively. Enrichment factors (EF), index of geoaccumulation ( I geo ), potential ecological risk index (RI), chemical mass balance model (CMB), backward trajectory, and potential source contribution function were the methods used to study the chemical component characteristics and source differences of PM 2.5 in different seasons in the urban and suburban areas of Zhengzhou. The results showed that the annual average PM 2.5 concentration at the Zhengzhou environmental monitoring center and Zhengzhou University sites reached (59.7±24.0) μg·m -3 and (74.7±13.5) μg·m -3 , respectively. The PM 2.5 concentration at the suburban point was higher than at the urban point with the exception of winter, and the seasonal mean concentration decreased in the order of winter > autumn > spring > summer. Compared with the urban areas, the suburban areas were more affected by crustal substances in spring, and the concentrations of all components were higher in summer and autumn than the urban areas. Nevertheless, urban areas were more affected by coal burning sources and motor vehicle sources in winter. The component analysis results showed that the influences of soil dust and building dust were greater in the suburbs in spring than in the urban areas. In autumn, the suburbs were more affected by biomass sources than the urban areas, while the urban areas were more affected by building dust than were the suburbs. The concentrations of Cu, As, Zn, Pb, and Sb were strongly influenced by anthropogenic sources, and the enrichments of Zn, Cu, As, and Pb in urban areas were greater than in the suburbs. In addition, Zn, Cu, As, and Pb exhibited potential ecological risks. The outcomes of the CMB model showed that dust sources, secondary sulfate, secondary nitrate, and coal burning sources contributed significantly to PM 2.5 concentrations in spring, summer, autumn and winter, respectively. The contributions of secondary pollution sources (secondary organic aerosol, secondary sulfate, and secondary nitrate) and motor vehicle sources to urban areas were higher than to suburban areas, and the influences of biomass sources in autumn and winter were significantly higher than in spring and summer and urban areas. The backward trajectory results indicated that the local PM 2.5 concentration was affected by distant transmission from the northwest except in summer, was affected by neighboring provinces in the east in four seasons, and was affected by transmission from the south, with the exception of winter. Furthermore, the consequences of potential sources demonstrated that the local PM 2.5 concentration was mainly affected by the potential areas in Henan province and its boundary with neighboring provinces.

Background: Enhanced recovery after surgery (ERAS) is a multimodal, multidisciplinary, evidence-based approach to care for surgical patients and aims at optimizing the perioperative management and outcomes. The ERAS approach was first implemented in colorectal surgery patients; however, the reported applications in pancreatoduodenectomy patients are limited. In recent years, studies on ERAS for patients undergoing pancreaticoduodenectomy have been published. The accumulation of new randomized controlled trials and high-quality case-control studies stimulated us to update the analysis. Our study comprehensively collected data to provide the best evidence summary for the clinic., Aim: To evaluate the safety and feasibility of enhanced recovery after surgery in the perioperative management of pancreatoduodenectomy patients., Methods: A systematic literature search of PubMed, Embase, and the Cochrane Library was performed up to July 2019. All randomized controlled trials and case-control studies that applied ERAS for patients undergoing pancreaticoduodenectomy were considered for inclusion in this study. The patients were divided into two groups: patients who received the ERAS perioperative management approach were defined as the ERAS group and patients who received the traditional perioperative management approach were defined as the control group. All statistical analyses were conducted using the Revman5.3 software, and the outcomes were calculated as odds ratios or weighted mean differences with their corresponding 95% confidence intervals. A funnel plot was created to assess publication bias. Subgroup and sensitivity analyses were performed to explore the sources of heterogeneity., Results: A total of 20 studies involving 3613 patients (1914 patients in the ERAS group vs. 1699 patients in the control group) were included in this study. Among the 20 studies, 4 were randomized controlled trials, and 16 were case-control studies. The overall postoperative complication rate was significantly lower in the ERAS group (OR = 0.62, 95% CI: 0.53-0.74, P < 0.00001) than in the control group. In addition, the minor complication rate (Clavien-Dindo I-II) was also lower in the ERAS group (OR = 0.70, 95% CI: 0.58-0.86, P = 0.0005). The patients in the ERAS group had a lower incidence of delayed gastric emptying (OR = 0.51, 95% CI: 0.42-0.63, P < 0.00001) and shorter length of hospital stay (WMD = -4.27, 95% CI: -4.81~-3.73, P < 0.00001) than in the control group. The rates of pancreatic fistula (regardless of Grade A/B/C), wound infections, abdominal abscesses, readmission, reoperation, and morbidity were not significantly different between the two groups., Conclusion: The ERAS approach is safe and effective in the perioperative management of patients undergoing pancreaticoduodenectomy and helps to accelerate the postoperative recovery and improve prognosis., Competing Interests: There are no conflicts of interest associated with any of authors of this manuscript., (Copyright © 2020 You-Meng Sun et al.)

In this paper, the influence factors of phase noise are first analyzed in detail and verified by experiments, and its principle is theoretically derived. Besides, we propose a novel, to the best of our knowledge, frame structure for m-quadrature amplitude modulation-orthogonal frequency division multiplexing (m-QAM-OFDM) in underwater wireless optical communication. The frame structure contains OFDM signals and their phase-conjugated signals. At the receiving end, by the simple superposition of phase-conjugated symbols, the noise suppression can be achieved. The feasibility is experimentally demonstrated by transmitting m-QAM-OFDM signal in different modulation formats and scenarios. The results show that bit error rate performance can be significantly improved, and there is also a significant increase in transmission capacity compared to the traditional phase-conjugated method. Moreover, the proposed frame structure can provide a robust and simple compromise between transmission capacity and distance.

Androgen receptor (AR) plays a pivotal role as a target for amplification/mutation in pathogenesis and tumor progression in prostate, and thus, controlling AR activity or expression might be a feasible therapeutic approach for the treatment of prostate cancer. Here, we report the novel mechanisms by which 18β-glycyrrhetinic acid (GA) targets AR to stimulate cell death in both hormone-responsive and -refractory prostate cancer cells. We found that miR-488, a tumor suppressive microRNA, was markedly induced by GA treatment, resulting in the down-regulation of AR expression and inhibition of cellular responses mediated by androgens. Moreover, GA not only suppressed the expression of androgen target genes (TMPRSS2, PSA, and NKX3.1), but also enhanced the suppressive effect of anti-androgens (bicalutamide and flutamide) on LNCaP cell growth. Our data further provides evidence that down-regulation of AR expression by GA may occur through transcriptional suppression at AR promoter region between - 1014 and - 829. Ectopic expression of SFR and E2F3α reversed the inhibitory effect of GA on AR promoter activity as well as protein expression, suggesting that GA may target transcription factors SRF and E2F3α to regulate AR expression. Taken together, our study provides new insights on AR regulation and GA as a potential therapeutic candidate for human prostate cancer.

We explore the characteristics and sources of water-soluble ions in aerosol fine particulate matter (PM 2.5 ) samples collected from Anyang, China, during typical seasonal months from 2018 to 2019. Nine water-soluble ions (Na + , NH 4 + , K + , Mg 2+ , Ca 2+ , F - , Cl - , NO 3 - , and SO 4 2- ) were analyzed. The analysis of PM 2.5 , water-soluble ion concentration levels, anion-cation balance, nitrogen oxidation rate (NOR), sulfur oxidation rate (SOR), and ion correlation showed that the annual average concentrations of PM 2.5 and water-soluble ions in Anyang were (85.81±45.43) μg·m -3 and (48.21±30.04) μg·m -3 , respectively. Concentrations of ions were ranked as:NO 3 - > SO 4 2- > NH 4 + > Cl - > K + > Ca 2+ > Na + > Mg 2+ > F - . The annual average concentration of the sum of NH 4 + , NO 3 - , and SO 4 2- was (42.72±27.87) μg·m -3 , which accounted for 87.14% of total water-soluble ions. Moreover, NH 4 + was highly related to SO 4 2- and NO 3 - . The mean values of the nitrogen oxidation rate (NOR) and sulfur oxidation rate (SOR) were 0.25 and 0.37, respectively. These results suggest that these ions were the result of secondary formation. The anion-cation charge equivalent value was 0.75-0.94, which indicates that the sampled aerosols were alkaline. NH 4 + mainly existed in the form of (NH 4 ) 2 SO 4 and NH 4 NO 3 in spring, summer, and autumn, whereas in winter it mainly existed in the form of NH 4 Cl. The results of principal component analysis indicated that secondary aerosols, coal combustion, biomass burning, and dust were the main sources of the water-soluble ions in Anyang during the sampled periods.

Background: Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the "Essence of the kidney is reflected on the hair". Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction., Methods/design: Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine., Discussion: This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development., Trial Registration: Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.

To develop novel CNS penetrant HDAC inhibitors, a new series of HDAC inhibitors having benzoheterocycle were designed, synthesized, and biologically evaluated. Among the synthesized compounds, benzothiazole derivative 9b exhibited a remarkable anti-proliferative activity (GI 50  = 2.01 μM) against SH-SY5Y cancer cell line in a dose and time-dependent manner, better than the reference drug SAHA (GI 50  = 2.90 μM). Moreover, compound 9b effectively promoted the accumulation of acetylated Histone H3 and α-tubulin through inhibition of HDAC1 and HDAC6 enzymes, respectively. HDAC enzyme assay also confirmed that compound 9b efficiently inhibited HDAC1 and HDAC6 isoforms with IC 50 values of 84.9 nM and 95.9 nM. Furthermore, compound 9b inhibited colony formation capacity of SH-SY5Y cells, which is considered a hallmark of cell carcinogenesis and metastatic potential. The theoretical prediction, in vitro PAMPA-BBB assay, and in vivo brain pharmacokinetic studies confirmed that compound 9b had much higher BBB permeability than SAHA. In silico docking study demonstrated that compound 9b fitted in the substrate binding pocket of HDAC1 and HDAC6. Taken together, compound 9b provided a novel scaffold for developing CNS penetrant HDAC inhibitors and therapeutic potential for CNS-related diseases.

DiNap [( E )-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one], an analog of a natural product (the chalcone flavokawain), was synthesized and characterized in this study. Porcine reproductive and respiratory syndrome virus (PRRSV) is the most challenging threat to the swine industry worldwide. Currently, commercially available vaccines are ineffective for controlling porcine reproductive and respiratory syndrome (PRRS) in pigs. Therefore, a pharmacological intervention may represent an alternative control measure for PRRSV infection. Hence, the present study evaluated the effects of DiNap on the replication of VR2332 (a prototype strain of type 2 PRRSV). Initially, in vitro antiviral assays against VR2332 were performed in MARC-145 cells and porcine alveolar macrophages (PAMs). Following this, a pilot study was conducted in a pig model to demonstrate the effects of DiNap following VR2332 infection. DiNap inhibited VR2332 replication in both cell lines in a dose-dependent manner, and viral growth was completely suppressed at concentrations ≥0.06 mM, without significant cytotoxicity. Consistent with these findings, in the pig study, DiNap also reduced viral loads in the serum and lungs and enhanced the weight gain of pigs following VR2332 infection, as indicated by comparison of the DiNap-treated groups to the untreated control (NC) group. In addition, DiNap-treated pigs had fewer gross and microscopic lesions in their lungs than NC pigs. Notably, virus transmission was also delayed by approximately 1 week in uninfected contact pigs within the same group after treatment with DiNap. Taken together, these results suggest that DiNap has potential anti-PRRSV activity and could be useful as a prophylactic or post-exposure treatment drug to control PRRSV infection in pigs.

Background: Renal artery stenosis (RAS) is always associated with abnormalities in renal microvascular perfusion (RMP). However, few imaging methods can simultaneously evaluate the degree of luminal stenosis and RMP. Thus, this study will aim to evaluate the feasibility of using contrast-enhanced ultrasound (CEUS) for assessing both RAS and RMP to achieve a one-stop assessment of patients with suspected renovascular hypertension., Methods: This will be a single-center diagnostic study with a sample size of 440. Patients with chronic kidney disease (CKD) and suspected of having resistant hypertension will be eligible. Patients with Stages 1-3 CKD will undergo CEUS and computed tomography (CT) angiography (CTA). Values obtained by CEUS and CTA for diagnosing low-grade (lumen reduced by <60%) and high-grade (lumen reduced by ≥60%) RAS will be compared. Moreover, all patients will also undergo radionuclide imaging. The diagnostic value for RAS will be assessed by the receiver operating characteristic curve, including the accuracy, sensitivity, specificity, positive predictive values, negative predictive values, and area under the ROC. Pearson correlation analysis will be performed to assess the association between CEUS findings for RMP and glomerular filtration rate measured by a radionuclide imaging method., Conclusion: The data gathered from this study will be used to evaluate the feasibility of expanding clinical applications of CEUS for evaluation of patients with suspected renovascular hypertension., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800016252; https://www.chictr.org.cn.

The aim of this study was to investigate the inhibitory effect of salvianolic acid on inflammatory mediators of rats with collagen-induced rheumatoid arthritis (RA). Thirty rats were randomly divided into the normal control group, collagen-induced arthritis model group (CIA model group) and drug group (Salvianolic Acid-CIA group). In the model group, the CIA models were established through intradermal injection of collagen emulsion at the toes. At 3 weeks after the model establishment, grouped drug administration was conducted, of which salvianolic acid was given by gavage to Salvianolic Acid-CIA group. The degrees of joint swelling of each group of rats were recorded. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of relevant inflammatory mediators, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the messenger RNA (mRNA) expression levels of serum necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PGE2), and hematoxylin and eosin staining was utilized to detect the pathological characteristics of the synovial tissues. After the establishment of models, the ankle joint swelling degree of rats in the model group was more obvious compared with that in the normal control group (P<0.01). After 3 weeks of drug administration, the ankle joint swelling degree of rats in the Salvianolic Acid-CIA group was alleviated compared with that in the model group (P<0.05). The contents of TNF-α, IL-6 and PGE2 in Salvianolic Acid-CIA group were obviously lower than those in the model group (P<0.01). The mRNA expression levels of TNF-α, IL-6 and PGE2 in the Salvianolic Acid-CIA group were markedly lower than those in the model group. The hyperemia of rat synovial tissues in Salvianolic Acid-CIA group was obviously relieved compared with that in the CIA model group. In conclusion, the models of CIA rats are successfully established, and the results show salvianolic acid has an inhibitory effect on the RA of CIA model rats and can significantly inhibit the expression levels of relevant inflammatory mediators.

Background: Distal radius metaphyseal (DRM) fractures are very frequent childhood fractures. Whether additional percutaneous pinning improves the outcome remains controversial. In this review, we tried to systematically evaluate the effect of percutaneous pinning on re-displacement, secondary reduction, radiographs, function, and complications in children with displaced DRM fractures., Methods: PubMed, Medline, Embase, Cochrane Library, and Web of Science databases were explored systematically to identify randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing cast immobilization alone or following reduction to additional percutaneous pinning in the treatment of pediatric displaced DRM fractures. Two reviewers independently screened eligible articles and extracted relevant information from each article. The methodological quality of eligible articles was evaluated using the Cochrane Collaboration risk assessment tool (RCTs) and modified Jadad scale (CCTs)., Results: A total of 4 RCTs and 3 CCTs met the inclusion criteria, with a total patient count of 1144 children. The results showed that additional percutaneous pinning significantly reduced the rate of re-placement (Chi-square tests, P < .001) and complications (Chi-square tests, P = .030). The superior results, both radiographically and functionally seemed to be temporary. No difference was found between the 2 groups after longer-term follow-up., Conclusions: This systematic review suggested that compared with casting following reduction, percutaneous pinning had a positive effect on maintaining the initial reduction and reducing fracture complication rate of displaced DRM fractures in children, but with no significant improvement in function and radiographic outcome at the long-term follow-up. We suggest clinicians think twice before percutaneous pinning of displaced pediatric DRM fractures.

Triple-negative breast cancers (TNBCs) are the most aggressive and metastatic subtype of breast cancers and exhibit poor clinical outcome due to the lack of drug target receptors such as estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (Her2). The limited effectiveness of therapeutic options and the poor prognosis of TNBC patients emphasize the urgent need for identifying new therapeutic agents. In this regard, heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of TNBCs. Hsp90 is a molecular chaperone that regulates the folding, stability, and function of many oncogenic proteins. Hence, the inhibition of Hsp90 chaperone function leads to a simultaneous blockage of multiple signaling pathways in the proliferation and survival of cancers. In the present study, we performed the design, synthesis, and biological evaluation of Hsp90 inhibitors and found that a synthetic small molecule, DPide exerted a potent anticancer activity against TNBC cell line, MDA‑MB‑231 and non‑small cell lung cancer (NSCLC) cell line, H1975 with GI50 values of 0.478 and 1.67 µM, respectively. Soft‑agar colony formation assay also revealed that DPide suppressed the anchorage‑independent growth of MDA‑MB‑231 cells. Western blot analysis indicated that the treatment of MDA‑MB‑231 cells with DPide induced the proteasomal degradation of EGFR, Her2, Met, Akt, c‑Raf, and Cdk4 and the consequent cleavage of PARP, leading to apoptotic cell death. DPide also inhibited the migration and MMP9 activity of MDA‑MB‑231 cells, suggesting that the metastatic potential of TNBCs could be suppressed by DPide. Collectively, DPide offers an effective therapeutic option for the treatment TNBCs.

Objectives: We proposed to find out the role of miR-338-5p played in cell proliferation and invasion of rheumatoid arthritis synovial fibroblasts (RASFs) by regulating ADAMTS-9., Methods: QRT-PCR was performed to quantify the miR-338-5p and ADAMTS-9 mRNA expression in RA sample tissues and normal synovial tissues. Western blot was performed to evaluate the ADAMTS-9 protein levels in transfected RASFs. Luciferase reporter assays were used to demonstrate whether miR338-5p directly targets ADAMTS-9. MTT, Transwell and wound healing assays were respectively used to evaluate the growth and mobility of RASFs. Flow cytometry was applied to detect cell cycle distributions and apoptosis rates in transfected RASFs., Results: MiR-338-5p was significantly downregulated in rheumatoid arthritis (RA) tissues while ADAMTS-9 was obviously overexpressed (p<0.001). Luciferase reporter assays demonstrated that miR-338-5p directly targeted ADAMTS-9. Moreover, overexpression of miR-338-5p suppressed RASFs biological functions and induced G0/G1 arrest and apoptosis of RASFs (p<0.001), while all the effects could be efficiently attenuated by the upregulation of ADAMTS-9., Conclusions: By inhibiting ADAMTS-9, miR-338-5p suppressed the proliferation and metastasis of rheumatoid arthritis synovial fibroblasts. Thus, replenishing miR-338-5p may be a potential therapy for the clinic management of RA.

Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α inhibitory activity with IC 50 value of 5.3 nM and an excellent growth inhibition with GI 50 value of 0.42 μM against non-small cell lung cancer cells, H1975. Compound 30f effectively reduces the expression levels of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently, compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8, indicating that 30f induces cancer cell death via apoptotic pathway. Moreover, cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on the activities of five major P450 isoforms (IC 50  > 5 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between 30f and the substrate drugs of the five major P450 isoforms are not expected. Compound 30f also inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975 without noticeable abnormal behavior and body weight changes. The immunostaining and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of tumor further demonstrate a good agreement with the in vitro results., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: The study was aimed to investigate the impact of CX3CR1 expression on the proliferation and apoptosis of osteoarthrosis (OA) chondrocytes through Wnt/ β-catenin pathway., Methods: The expression levels of CX3CR1 and Wnt/β-catenin pathway-related genes mRNA and protein in OA chondrocytes were examined by qRT-PCR and western blot. MTT and flow cytometry (FCM) assays were employed to assess cell proliferation, cell cycle and apoptosis. XAV-939, a Wnt/β-catenin pathway inhibitor, was used to inhibit the pathway., Results: CX3CR1 was significantly overexpressed in OA cartilages than that in normal articular cartilages (P < 0.05). After siCX3CR1 transfection, the expression level of Wnt 3, nuclear β-catenin, Cyclin D1, MMP-13 and phosphorylated GSK-3β significantly increased, while cytoplasm β-catenin, GSK-3β and phosphorylated β-catenin expression was inhibited (P<0.05). XAV-939abolished the effects of siCX3CR1 on proliferation, apoptosis and cell cycle progression of OA chondrocytes (P<0.05)., Conclusions: CX3CR1 regulated chondrocyte proliferation and apoptosis through Wnt/β-catenin signaling pathway. The overexpression of CX3CR1 in chondrocytes of OA may be closely related to the pathogenesis and progression of OA., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: Investigated the correlation of nuclear factor-κB, regulatory cells and transforming growth factor-β with rheumatoid arthritis. Methods: Included 65 cases of RA patients admitted in our hospital from June 2015 to December 2016 into case group, and included 50 healthy people into control group during the same period. Collected the peripheral detection of nuclear factor-κB, regulatory cells and transforming growth factor beta levels, and compared them between two groups. Results: The percentage of CD4 + , CD25 + T cells in the case group was significantly lower than that in the control group ( P  < .05); There was no significant difference in the percentage of CD4 + , CD25 + CD127 low/- , T cells between groups ( P  > .05); The levels of TGF - beta and NF - kappa B in the case group were higher than those in the control group, and the difference between the two groups was statistically significant ( P  < .05); The levels of ESR, CRP and RF in the case group were higher than those in the control group ( P  < .05). There was a negative correlation between the expression of nuclear factor-κB, transforming growth factor-β and RF level in RA patients by pearson correlation analysis, r = -0.652, P  < .05. Conclusion: The expression levels of CD4 + , CD25 + T cells in patients with RA are significantly decrease, which has a negative correlation with RA activity index RF, and showed that the pathogenesis of RA is related to the regulation of immune system.

Rheumatoid arthritis is a chronic autoimmune disease characterized by an elevated synovial inflammatory response, with destruction or erosion of articular cartilage in major joints. The aim of the present study was to examine whether 20‑hydroxyecdysone (HES) is able to ameliorate oxidative stress and inflammatory responses in a collagen‑induced rheumatoid arthritis (CIA) rat model. A total of 40 healthy male rats were selected arbitrarily and separated into four groups. Rats treated with saline served as a control (group I), rats subjected to CIA induction by intradermal injection of bovine collagen II type served as the induced group (group II), while rats induced with CIA and administered with 10 and 20 mg/kg bodyweight HES for 28 days served as treatment groups (groups III and IV). Biochemical parameters, including paw swelling (edema), arthritis score, indexes of thymus and spleen, antioxidant levels (superoxide dismutase, catalase and glutathione), articular elastase and anti‑collagen II specific immunoglobulins (Ig)G, IgG1 and IgG2a, in addition to inflammatory markers [nitric oxide, C‑reactive protein, interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α and nuclear factor‑κB p65 subunit] were significantly decreased (P<0.01) following supplementation with HES (10/20 mg/kg). Consistently, the protein expression pattern of inducible nitric oxide synthase and cyclooxygenease‑2 were significantly downregulated (P<0.01) upon treatment with HES. In addition, histological analysis confirmed arthritis in CIA‑induced rats by revealing the presence of greater polymorphonuclear cell infiltration, with eroded articular cartilage and prominent synovitis. However, administration of HES was demonstrated to alleviate the morphological changes and maintain the normal architecture of synovial joints. In conclusion, the results of the present study indicated that treatment with HES (particularly 20 mg/kg) may effectively eradicate the inflammatory cascade and oxidative stress process in CIA‑induced rats and thereby exhibit anti‑rheumatoid arthritis properties.

In this paper, we have designed and synthesized a novel sensor L1 based on asymmetric double-azine derivatives, which showed both "naked eye" recognition and fluorescence responses for CN - in DMSO/H 2 O (v/v=4:1, pH=7.20) solution. This simple sensor L1 could distinguish CN - from coexisting anions via the way of deprotonation and sensing mechanism of intramolecular charge transfer (ICT), and the minimum detection limit on fluorescence response of the sensor L1 towards CN - was down to 9.47×10 -7 M. Moreover, we have successfully utilized the sensor L1 to detect CN - in bitter almond. Test strips containing L1 were also prepared, which could act as a practical colorimetric tool to detect CN - in aqueous media., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A simple chemosensor YS based on coumarin group was designed and synthesized. Its structure was determined by single crystal X-ray diffraction analysis. In the presence of cyanide the sensor showed an immediate visible change in color from colorless to pale yellow by naked-eyes and produced a strong blue fluorescence rapidly in DMSO/H 2 O (3:7, v/v). The detection limit on fluorescence response of the sensor to CN - is down to 1.69×10 -7 M. In addition YS could show fluorescence turn-on response rapidly for Zn 2+ over other metals ions such as Fe 3+ , Hg 2+ , Ag + , Ca 2+ , Cu 2+ , Co 2+ , Ni 2+ , Cd 2+ , Pb 2+ , Cr 3+ and Mg 2+ in aqueous solutions. Notably, this sensor served as a molecular switch, which was controlled by Zn 2+ and EDTA cyclically. Test strips based on YS were fabricated, which could act as a convenient and efficient CN - and Zn 2+ test kit. This chemosensor could achieve the detection of two ions, which need not depend on two different sensors., (Copyright © 2016 Elsevier B.V. All rights reserved.)

CO(2) retrievals with high quality facilitate resolving the sources and sinks of CO(2) are helpful in predicting the trend in climate change and understanding the global carbon cycle. Based on a nonlinear least squares spectral fitting algorithm, we investigate the optimization method for CO2 products derived from ground-based high resolution Fourier transform infrared spectra. The CO(2) vertical column densities (VCDs) are converted into column-averaged dry air mole fraction XCO(2) by using the fitted O(2) VCDs, and thus the system errors (e. g. pointing errors, ILS errors, zero-level offset) are corrected greatly. The virtual daily variation which is related to air mass factor is corrected with an empirical model. The spectra screening rule proposed in this paper can greatly improve the XCO2 quality. The CO(2) retrievals before and after the optimized method are compared using a typical CO(2) daily time series. After using the optimized method, the fitting error is reduced by 60%, and the two-hours-averaged precision is ~0.071% (equals to ~0.28 ppm), which is perfectly in line with the TCCON (the total carbon column observing network) threshold, i. e., less than 0.1%.

The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N-terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC 50  = 50.3 nM). Furthermore, it effectively inhibits the proliferation of H1975 non-small cell lung cancer (NSCLC) and Skbr3 breast cancer cell lines with GI 50 values of 0.31 μM and 0.11 μM, respectively. Compound 19 induces the degradation of the Hsp90 client proteins including EGFR, Her2, Met, c-Raf, and Akt, and consequently promotes apoptotic cancer cell death. Compound 19 also inhibits the growth of H1975 xenografts in NOD-scid IL2R gamma null mice without any apparent body-weight loss. The immunohistologic evaluation indicates that compound 19 decreases the expression of Akt in xenograft tumor tissue via an inhibition of the Hsp90 chaperon function. Additionally, the cytochrome P450 assay indicates that compound 19 has no effect on the activities of five major P450 isoforms (IC 50  > 50 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between compound 19 and the substrate drugs of the five major P450 isoforms are not expected. Overall, compound 19 represents a new class of Hsp90 inhibitor with its 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl-amide structure, and it has the therapeutic potential to overcome drug resistance in cancer chemotherapy., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

A novel highly selective chemosensor S1 for cyanide based on unsymmetrical azine derivative was successfully designed and synthesized, which showed both colorimetric and fluorescence turn-on responses for cyanide ions in aqueous. This structurally simple chemosensor could detect CN(-) anion over other anions in aqueous solution DMSO/H2O (v/v=3:2) undergo deprotonation reaction. Results showed that the chemosensor S1 exhibited 50 fold enhancement in fluorescence at 530nm and showed an obvious change in color from colorless to yellow that could be detected by naked eye under the UV-lamp after the addition of CN(-) in aqueous solution. Moreover, the detection limit on fluorescence response of the sensor to CN(-) is down to 6.17×10(-8)M by titration method. Test strips based on S1 were obtain, which could be used as a convenient and efficient CN(-) test kit to detect CN(-) in aqueous solution., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Ring effect is defined as the phenomenon that the depth of solar Fraunhofer lines in scattered light is less than those observed in direct sunlight. The aerosol could change the light path and the scattering properties in the atmospheric, and influence Raman Scattering Possibility of the photons, and finally affect the filling-up effect. Aerosol parameters (aerosol optical depth, boundary layer height, single scattering albedo, asymmetric factor) could be obtained by observation of the Ring effect in different aerosol condition. The Ring effect is measured by ground-based MAX-DOAS instrument under clear days and the measurement results is compared with McAritim results. The comparison has a good agreement. Radiation transfer model McArtim is used to study the sensitivity of the Ring effect to the aerosol parameters. The study shows that in most conditions, aerosol optical depth (AOD) and boundary layer (bh) height has a great influence to RSP, and in 90 degree elevation angle, RSP has a decrease of 24.6% when AOD varies from 0.1 to 1, and a decrease of 4.4% when bh varies from 1km to 3 km. The study shows RSP is more sensitive to AOD and boundary layer height, which may provide a new method for aerosol profile.

A rapid and simple analytical method has been developed for the determination of hexabromocyclododecane enantiomers in chicken whole blood, based on a modified quick, easy, cheap, effective, rugged, and safe approach before liquid chromatography coupled with tandem mass spectrometry. The factors influencing performance of method were investigated by single factor experiment, and further optimized by the response surface methodology based on Box-Behnken design. The matrix effects were also evaluated by the isotopic dilution method. Under the optimal conditions, the proposed method showed good linearity within the range of 1-500 μg/L and good repeatability with relative standard deviation less than 9.5% (n = 5). The limits of detection (S/N = 3) were 0.03-0.19 μg/L. The developed method was successfully applied for the analysis of hexabromocyclododecane enantiomers in real chicken blood samples. The satisfactory recoveries ranging of 83.6-115.0% were obtained (at spiked levels of 5, 20, and 100 μg/L). The results demonstrated that the proposed method would be a practical value method for the determination of hexabromocyclododecane enantiomers in animal blood. It would be further developed with confidence to analyze other lipophilic organic pollutants in blood sample., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale . However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer., Competing Interests: The authors declare that they have no conflict of interests.

The aim of the present study was to investigate the incremental value of resting three-dimensional speckle-tracking echocardiography (3D-STE) in the detection of early-stage left ventricular dysfunction in patients with coronary artery disease (CAD). A total of 110 patients suspected of having CAD were recruited. All patients underwent 3D-STE and coronary artery angiography (CAG). They were divided to a CAD group and a normal group according to the results of CAG. Using 3D-STE software, the peak values of longitudinal strain (LS), circumferential strain (CS), radial strain (RS) and area strain (AS) and the time to peak value of these strains (T-LS, T-CS, T-RS and T-AS) were measured. A receiver operator characteristic curve (ROC) was used to analyze the sensitivity of these strains for the diagnosis of CAD. ROC analysis indicated that T-LS and composite indices combining the peak strain value and time to peak of LS, CS and AS have diagnostic value for the early detection of CAD; the area under the curve (AUC) values were 0.667, 0.692, 0.621 and 0.672 respectively (P<0.005). The composite index of longitudinal strain demonstrated the highest diagnostic value for CAD with 62% sensitivity and 76% specificity. These results indicate that 3D-STE has incremental value for the diagnosis of CAD in patients at rest.

This paper proposes a novel energy-efficient oil shale pyrolysis process triggered by a topochemical reaction that can be applied in horizontal oil shale formations. The process starts by feeding preheated air to oil shale to initiate a topochemical reaction and the onset of self-pyrolysis. As the temperature in the virgin oil shale increases (to 250-300°C), the hot air can be replaced by ambient-temperature air, allowing heat to be released by internal topochemical reactions to complete the pyrolysis. The propagation of fronts formed in this process, the temperature evolution, and the reaction mechanism of oil shale pyrolysis in porous media are discussed and compared with those in a traditional oxygen-free process. The results show that the self-pyrolysis of oil shale can be achieved with the proposed method without any need for external heat. The results also verify that fractured oil shale may be more suitable for underground retorting. Moreover, the gas and liquid products from this method were characterised, and a highly instrumented experimental device designed specifically for this process is described. This study can serve as a reference for new ideas on oil shale in situ pyrolysis processes.