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Background: Poststroke depression (PSD) is a common neuropsychiatric disorder that affects the disability, mortality, functional recovery, and quality of daily life of patients. Xiaoyao Recipe (XYR) is often used to treat PSD and has achieved good clinical effects, but it lacks reliable evidence., Objective: This study aims to evaluate the effectiveness and safety of XYR on PSD through meta-analysis., Methods: A comprehensive literature search was carried out in multiple databases, including PubMed, the Cochrane Library, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and ClinicalTrials, from inception to July 1, 2021, to collect randomized controlled trials that applied XYR for patients with PSD. For a controlled trial, the search time limit was set from the time of the database's establishment to July 2021. Two experienced researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data, evaluated the quality of the literature, and used RevMan 5.3 software for meta-analysis., Results: A total of 12 studies were included in this study, involving 882 patients with PSD who were hospitalized or outpatients. The meta-analysis results showed that the total effective rate ( p < 0.00001) of the test group (XYR or XYR combined with antidepressants) after treatment was high; Hamilton's Depression Scale score ( p < 0.000001), Scandinavian Stroke Scale score ( p =0.004 < 0.05), and Barthel index ( p < 0.00001) were improved; the incidence of adverse reactions ( p < 0.00001) was low; and the serum serotonin content ( p < 0.00001) was high., Conclusion: Compared with antidepressant drugs, XYR is more effective and safer in the treatment of PSD patients. However, more high-quality studies are needed to further support the above conclusions., Competing Interests: All authors declare that there are no conflicts of interest., (Copyright © 2022 Dou Wang et al.)

Phosphatidylinositol 4-phosphate (PI4P) is a low abundant phospholipid with important roles in lipid transport and membrane trafficking. However, little is known of its metabolism and function in neurons. Here, we investigate its subcellular distribution and functional roles in dendrites of rodent hippocampal neurons during resting state and long-term synaptic potentiation (LTP). We show that neural activity causes dynamic reversible changes in PI4P metabolism in dendrites. Upon LTP induction, PI4KIIIα, a type III phosphatidylinositol 4-kinase, localizes to the dendritic plasma membrane (PM) in a calcium-dependent manner and causes substantial increase in the levels of PI4P. Acute inhibition of PI4KIIIα activity abolishes trafficking of the AMPA-type glutamate receptor to the PM during LTP induction, and silencing of PI4KIIIα expression in the hippocampal CA1 region causes severe impairment of LTP and long-term memory. Collectively, our results identify an essential role for PI4KIIIα-dependent PI4P synthesis in synaptic plasticity of central nervous system neurons., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Shenlian (SL) decoction is a herbal formula composed of Coptis and ginseng, of which berberine and ginsenoside are the main constituents. Even though SL decoction is widely used in treating diabetes in China, the mechanism of its antidiabetes function still needs further study. Gut microbiota disorder is one of the important factors that cause diabetes. To explore the effect of SL decoction on intestinal microbiota, gut microbiota of mice was analyzed by sequencing the gut bacterial 16S rRNA V3+V4 region and metagenomics. In this study, results demonstrated that SL decoction had a better hypoglycemic effect and β cell protection effect than either ginseng or Coptis chinensis. Alpha diversity analysis showed that all interventions with ginseng, Coptis, and SL decoction could reverse the increased diversity and richness of gut microbiota in db/db mice. PCoA analysis showed oral SL decoction significantly alters gut microbiota composition in db/db mice. 395 OTUs showed significant differences after SL treatment, of which 37 OTUs enriched by SL decoction showed a significant negative correlation with FBG, and 204 OTUs decreased by SL decoction showed a significant positive correlation with FBG. Results of KEGG analysis and metagenomic sequencing showed that SL decoction could reduce the Prevotellaceae , Rikenellaceae , and Helicobacteraceae , which were related to lipopolysaccharide biosynthesis, riboflavin metabolism, and peroxisome, respectively. It could also upregulate the abundance of Bacteroidaceae , which contributed to the metabolism of starch and sucrose as well as pentose-glucuronate interconversions. In the species level, SL decoction significantly upregulates the relative abundance of Bacteroides&#95;acidifaciens which showed a significant negative correlation with FBG and was reported to be a potential agent for modulating metabolic disorders such as diabetes and obesity. In conclusion, SL decoction was effective in hypoglycemia and its mechanism may be related to regulating gut microbiota via upregulating Bacteroides&#95;acidifaciens., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Rui-xi Sun et al.)

Background: It is of critical importance to understand how anammox consortia respond to disturbance events and fluctuations in the wastewater treatment reactors. Although the responses of anammox consortia to operational parameters (e.g., temperature, dissolved oxygen, nutrient concentrations) have frequently been reported in previous studies, less is known about their responses and resilience when they suffer from nutrient interruption., Results: Here, we investigated the anammox community states and transcriptional patterns before and after a short-term nutrient starvation (3 days) to determine how anammox consortia respond to and recover from such stress. The results demonstrated that the remarkable changes in transcriptional patterns, rather than the community compositions were associated with the nutritional stress. The divergent expression of genes involved in anammox reactions, especially the hydrazine synthase complex (HZS), and nutrient transportation might function as part of a starvation response mechanism in anammox bacteria. In addition, effective energy conservation and substrate supply strategies (ATP accumulation, upregulated amino acid biosynthesis, and enhanced protein degradation) and synergistic interactions between anammox bacteria and heterotrophs might benefit their survival during starvation and the ensuing recovery of the anammox process. Compared with abundant heterotrophs in the anammox system, the overall transcription pattern of the core autotrophic producers (i.e., anammox bacteria) was highly resilient and quickly returned to its pre-starvation state, further contributing to the prompt recovery when the feeding was resumed., Conclusions: These findings provide important insights into nutritional stress-induced changes in transcriptional activities in the anammox consortia and would be beneficial for the understanding of the capacity of anammox consortia in response to stress and process stability in the engineered ecosystems. Video Abstract., (© 2022. The Author(s).)

Optoelectronic science and 2D nanomaterial technologies are currently at the forefront of multidisciplinary research and have numerous applications in electronics and photonics. The unique energy and optically induced interfacial electron transfer in these nanomaterials, enabled by their relative band alignment characteristics, can provide important therapeutic modalities for healthcare. Given that nano-heterostructures can facilitate photoinduced electron-hole separation and enhance generation of reactive oxygen species (ROS), 2D nano-heterostructure-based photosensitizers can provide a major advancement in photodynamic therapy (PDT), to overcome the current limitations in hypoxic tumor microenvironments. Herein, a bismuthene/bismuth oxide (Bi/BiOx)-based lateral nano-heterostructure synthesized using a regioselective oxidation process is introduced, which, upon irradiation at 660 nm, effectively generates 1 O 2 under normoxia but produces cytotoxic •OH and H 2 under hypoxia, which synergistically enhances PDT. Furthermore, this Bi/BiOx nano-heterostructure is biocompatible and biodegradable, and, with the surface molecular engineering used here, it improves tumor tissue penetration and increases cellular uptake during in vitro and in vivo experiments, yielding excellent oxygen-independent tumor ablation with 660 nm irradiation, when compared with traditional PDT agents., (© 2021 Wiley-VCH GmbH.)

The neuroinflammatory pathway regulated by nuclear factor kappa-B (NF- κ B) plays an important role in the occurrence, development, and prognosis of poststroke depression (PSD). The regulatory effect of the traditional Chinese medicine compound Xingnao Jieyu decoction (XNJY) on the NF- κ B pathway of PSD is still unclear. This study aimed to observe the effect of XNJY on PSD and explore the molecular mechanism of its intervention in the NF- κ B pathway. Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress were used to establish a PSD rat model. Body mass measurement, behavioral testing, Nissl staining, ELISA, and Western blot were also performed. XNJY and fluoxetine hydrochloride (Flu) treatment of PSD model rats showed significant antidepressant effects. XNJY and Flu treatment could reduce cortical and hippocampal neuronal damage. XNJY reduced inflammation and restored the levels of IL-4, IL-10, and BDNF. In addition, XNJY showed a significant regulatory effect on the NF- κ B pathway and the expression of synapse-related proteins PSD-95 and SYN. These results showed that XNJY could significantly reduce the depressive symptoms of PSD rats, and this reduction may be related to the regulation of the NF- κ B signaling pathway to improve neuroinflammation and synaptic function., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this study., (Copyright © 2021 Dou Wang et al.)

An experiment was conducted to investigate the effects of glutamine (Gln) on the lymphocyte proliferation and intestinal immune relevant gene expression in broilers infected with Salmonella Enteritidis. 240 1-day-old broilers were divided randomly into four groups in a completely randomized design, each of which had 6 replicates. Birds were reared in battery cages for 21 days. The experimental groups were as follows: control group (unchallenged group, CON), basal diet; Salmonella Enteritidis challenged group (challenged with 2.0 × 10 4  CFU/mL of Salmonella Enteritidis, SCC), basal diet; Gln 1, basal diet plus Salmonella Enteritidis challenged plus Gln at 0.5% diet; Gln 2, basal diet plus Salmonella Enteritidis challenged plus Gln at 1.0% diet. The results showed that Salmonella Enteritidis infection led to some decrease in the relative weight of spleen and bursa (except at 21 d), lymphocyte percentage, number of proliferation peripheral blood T and B lymphocytes, and increased the heterophil percentage, H/L ratio, mRNA expression levels of TNF-α, NF-κB p65, IL-1β, IL-6, and IL-8 in the jejunal and ileal mucosa compared with the measurements of these parameters in the CON group at d 4, 7, 14, and 21 (p < 0.05). On the other hand, chickens fed the Gln showed improved the relative weight of spleen and bursa, increased the lymphocyte percentage, number of proliferation peripheral blood T and B lymphocytes, and decreased the heterophil percentage, H/L ratio, and immune relevant gene expression in the jejunal and ileal mucosa compared with the measurements of these parameters in the SCC group (p < 0.05). These results suggest that Gln as a feed additive could be effective for reducing the detrimental effects of Salmonella Enteritidis infection, and increase the intestinal immune barrier function of broilers., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The natural co-occurrence of multiple mycotoxins has been reported in cereals and cereal products worldwide. Even though the dietary exposure to mycotoxins constitutes a serious human health, most reports are limited to the toxic effect of individual mycotoxins. The purpose of the present study was to assess the combined toxic effects of zearalenone (ZEN) and fumonisin B1 (FB1) and the potential interaction of their mixture on zebrafish (Danio rerio) embryos. Our results showed that ZEN possessed the higher toxicity to embryonic zebrafish (7-day LC 50 value of 0.78 mg a.i. L -1 ) compared with FB1 (7-day LC 50 value of 227.7 mg a.i. L -1 ). The combination of ZEN and FB1 exerted an additive effect on zebrafish embryos. Meanwhile, the activities of antioxidant CAT, caspase-3, and detoxification enzyme CYP450, as well as the expressions of six genes (Mn-sod, cas9, bax, cc-chem, ERα, and crh) associated with oxidative stress, cellular apoptosis, immune system, and endocrine system were prominently altered in the mixture exposure compared with the corresponding single treatment group of ZEN or FB1. Taken together, the regulatory standards of mycotoxins in food and feed should be updated based on the mixture effects of mycotoxins, and there is an increased need on effective detoxification methods for controlling and reducing the toxicity of multiple mycotoxins in animal feed and throughout the food supply chain., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Novel flame retardants (FRs) are of increasing concern, given growing evidence of health effects and use to replace polybrominated diphenyl ethers (PBDEs). This study modeled combined effects of use policies and decoration on indoor FRs and human exposure for 18 widely used PBDEs, organophosphate esters (OPEs), and novel brominated flame retardants in typical urban indoor environments in China. The current estimated indoor emission rates and average concentrations in air and dust of the 18 FRs were 10 2 -10 3 ng/h, 561 ng/m 3 , and 1.5 × 10 4 ng/g, respectively, with seven OPEs dominant (>69%). Different use patterns exist between China and the US and Europe. Scenarios modeled over 2010-2030 suggested that decoration would affect indoor concentrations of FRs more than use policies, and use policies were mainly responsible for shifts of FR composition. Additional use of hexabromobenzene and 2,3,4,5,6-pentabromotoluene and removal of BDE-209 would make the total human exposure to the modeled FR mixture increase after the restriction of penta- and octa-BDE but decrease after deca-BDE was banned. Better knowledge of the toxicity of substitutes is needed for a complete understanding of the health implications of such changes. Toddlers may be more affected by use changes than adults. Such studies are supportive to the management of FR use.

Induction of long-term potentiation (LTP) in excitatory neurons triggers a large transient increase in the volume of dendritic spines followed by decays to sustained size expansion, a process termed structural LTP (sLTP) that contributes to the cellular basis of learning and memory. Although mechanisms regulating the early and sustained phases of sLTP have been studied intensively, how the acute spine enlargement immediately after LTP stimulation is achieved remains elusive. Here, we report that endophilin A1 orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in NMDAR-mediated LTP. Upon LTP induction, Ca2+/calmodulin enhances binding of endophilin A1 to both membrane and p140Cap, a cytoskeletal regulator. Consequently, endophilin A1 rapidly localizes to the plasma membrane and recruits p140Cap to promote local actin polymerization, leading to spine head expansion. Moreover, its molecular functions in activity-induced rapid spine growth are required for LTP and long-term memory. Thus, endophilin A1 serves as a calmodulin effector to drive acute structural plasticity necessary for learning and memory., (© 2021 Yang et al.)

A novel sensing platform for sensitive detection of copper(ii) ions (Cu 2+ ) in living cells and body fluids was developed by taking advantage of the excellent fluorescence quenching ability of graphdiyne (GDY) and the high specificity of click chemistry for the first time., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Organophosphate esters (OPEs) in atmospheric fine particles (PM 2.5 ) were comprehensively investigated in the Beijing-Tianjin-Hebei (BTH) region from April 2016 to March 2017. The concentrations of Σ 8 OPEs in all the five sampling sites ranged from 90 to 8291 pg/m 3 (mean 1148 ± 1239 pg/m 3 ; median 756 pg/m 3 ). The highest level (median 1067 pg/m 3 ) was found at one of the urban sites in Beijing, followed by Tianjin (746 pg/m 3 ) and Shijiazhuang (724 pg/m 3 ). Tris(2-chloroethyl) phosphate (TCEP) and tri[(2R)-1-chloro-2-propyl] phosphate (TCPP) were the dominant compounds across the five sampling locations. Generally, the concentrations of chlorinated OPEs were relatively higher in summer than in winter (p < 0.05), but no significant seasonal difference was discovered for non-chlorinated individual OPEs. The concentrations of tri-n-butyl phosphate (TBP), TCEP, TCPP and triphenyl phosphate (TPP) were positively correlated with the meteorological parameters (i.e. temperature and relative humidity) (p < 0.05), indicating an evident influence of meteorological condition on OPE distribution. We observed a negative correlation (p < 0.05) between octanol-air partition coefficients (logK oa ) and the ratio of PM 2.5 -bound OPE concentrations to total suspended particulates-bound OPE concentrations, suggesting that physicochemical properties affect the particle-size distribution of OPEs. Furthermore, the median value of cancer hazard quotients (HQs) of TCEP was higher than TBP and tris(2-ethylhexyl) phosphate (TEHP). The health risk assessment showed that HQ values for children were ~1.6 times higher than those for adults. Relatively higher health risk induced by PM 2.5 -bound OPEs via inhalation was found during severe hazy days than in clear days., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Although chemicals have been traditionally regulated on an individual basis in aquatic ecosystems, they often co-exist as different types of complex mixtures. Laboratory assays were conducted for assessing the responses of rare minnow (Gobiocypris rarus) to individual and mixture chemicals [trace element cadmium (Cd), thiamethoxam, deltamethrin, malathion and prochloraz]. Data obtained from 96 h semi-static toxicity assays implied that deltamethrin elicited the highest toxic effect on the various developmental phases (larval, juvenile and adult phases) of G. rarus with LC 50 values ranging from 0.00061 to 0.25 mg a.i. L -1 , followed by prochloraz, malathion and Cd with 96-h LC 50 values ranging from 0.49 to 1.1, from 7.1 to 26, and from 7.6 to 15 mg a.i. L -1 , respectively. Thiamethoxam elicited the lowest toxic effect on the organisms with 96-h LC 50 values ranging from 38 to 202 mg a.i. L -1 . Larval phase was not always the most sensitive period in the three detected phases to most of chemicals. Chemical combinations containing deltamethrin and malathion displayed synergetic responses to the larvae of G. rarus. Besides, the binary mixtures of Cd-deltamethrin and Cd-prochloraz also exhibited synergetic response to rare minnows. Our results indicate that extra information is necessary to develop practical criteria for selecting chemical combinations that require legislative attention according to their likelihood to exert synergetic responses. Thence, more investigations on mixture toxicities of various chemicals should be taken as a priority for producing synergetic interaction to improve the environmental risk assessment of chemicals.

The toxicity of neonicotinoid insecticide imidacloprid (IMI) to mammals has recently received increasing attention. However, the effects of IMI on the gut barrier and liver function of male C57BL/6J mice are still unknown. The study showed that exposure to IMI could reduce relative liver weights, change hepatic tissue morphology and induce hepatic oxidative stress. The gut barrier function was greatly impaired by IMI exposure, which might increase the body's susceptibility to harmful substances in the gut. Meanwhile, the synthesis and metabolism of hepatic bile acids (BAs) was also affected by IMI exposure. The levels of serum and hepatic total bile acids (TBAs) decreased; in contrast, the fecal TBA levels increased after exposure to 30 mg/L IMI for 10 weeks. Sequencing of colonic contents revealed that the operational taxonomic units (OTUs) and α-diversity index increased and that the gram-negative bacteria overgrew, indicating that the balance of the gut microbiota was disrupted. The present study indicated that subchronic exposure to IMI interfered with the gut barrier function, interfering with BAs metabolism and causing gut microbiota imbalance in male C57BL/6J mice. Taken together, IMI residues appear to be potentially toxic to mammals and even humans., 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 Ltd. All rights reserved.)

Aquatic organisms are usually exposed to various co-existing pollutants. However, toxic effects of pesticide mixtures on aquatic organisms and its potential underlying mechanism still remain unclear. The joint effects of fenpropathrin (FEN) and paclobutrazol (PAC) on zebrafish (Danio rerio) using diverse toxicological endpoints were investigated in the current work. Our data exhibited that the 96-h LC 50 values of FEN to zebrafish at multiple life phases ranged from 0.0029 (0.0013-0.0042) to 0.16 (0.082-0.23) mg a.i. L -1 , which were lower by comparison to PAC ranging from 13.16 (8.564-21.03) to 23.43 (17.94-29.91) mg a.i. L -1 . Combination of FEN and PAC displayed synergistic effect on embryonic zebrafish. Activities of T-SOD, Cu/Zn-SOD and CYP450 were remarkably changed in the majority of single and mixture treatments by comparison to the untreated group. The mRNA levels of 17 genes related to oxidative stress, cellular apoptosis, immune system and endocrine system were assessed, and the data suggested that embryonic zebrafish were affected by both single pesticides and their mixtures. Five genes (P53, tsh, ERα, crh and cxcl-clc) showed greater alterations when exposed to pesticide mixtures by comparison to their individual chemicals. Therefore, it is urgently necessary to conduct more studies on mixture toxicities of different pesticides to explore the chemical mixtures with synergistic interactions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Tumor vaccines are a promising form of cancer immunotherapy, but difficulties such as neo-antigen identification, activation of immune cells, and tumor infiltration prevent their clinical breakthrough. Interestingly, nanotechnology-based photothermal therapy (PTT) has great potential to overcome these barriers. Previous studies have shown that serum exosomes (hEX) from hyperthermia-treated tumor-bearing mice displayed an array of patient-specific tumor-associated antigens (TAAs), and strong immunoregulatory abilities in promoting dendritic cell (DC) differentiation and maturation. Here, we developed a tumor vaccine (hEX@BP) by encapsulating black phosphorus quantum dots (BPQDs) with exosomes (hEX) against a murine subcutaneous lung cancer model. In comparison with BPQDs alone (BP), hEX@BP demonstrated better long-term PTT performance, greater elevation of tumor temperature and tumor targeting efficacy in vivo. Vaccination with hEX@BP in combination with PTT further demonstrated an outstanding therapeutic efficacy against established lung cancer, and promoted the infiltration of T lymphocytes into the tumor tissue. Our findings demonstrated that hEX@BP might be an innovative cancer photo-nanovaccine that offers effective immuno-PTT against cancers.

The circulating tumor cell (CTC) count is closely related to cancer recurrence and metastasis. The technology that can in vivo destroy CTCs may bring great benefits to patients, which is an urgent clinical demand. Here, a minimally invasive therapeutic intravenous catheter for in vivo enriching and photothermal killing of CTCs is developed. The surface of catheter is modified with anti-EpCAM antibody and the interior is filled with black phosphorus nanosheets (BPNSs). CTCs in the peripheral blood are captured by the catheter continually with the aid of circulation. The captured CTCs are used for downstream analyses or in vivo eliminated by the near-infrared (NIR) photothermal effect of BPNSs. A capture efficiency of 2.1% is obtained during the 5 min of treatment, and 100% of the captured CTCs are killed by following NIR light irradiation in both an in vitro closed-loop circulation system and an in vivo rabbit model. This cost-effective modality for lowering the CTCs burden can be a good supplement to traditional therapies, which holds great promise as an effective clinical intervention for cancer patients., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Pesticides scarcely exist as individual compounds in the water ecosystem, but rather as mixtures of multiple chemicals at relatively low concentrations. In this study, we aimed to explore the mixture toxic effects of fludioxonil (FLU) and triadimefon (TRI) on zebrafish (Danio rerio) by employing different toxicological endpoints. Results revealed that the 96-h LC 50 values of FLU to D. rerio at multiple developmental stages ranged from 0.055 (0.039-0.086) to 0.61 (0.33-0.83) mg L -1 , which were less than those of TRI ranging from 3.08 (1.84-5.96) to 9.75 (5.99-14.78) mg L -1 . Mixtures of FLU and TRI exerted synergistic effects on embryonic zebrafish. Activities of total superoxide dismutase (T-SOD) and catalase (CAT) were markedly altered in most of the individual and pesticide mixture treatments compared with the control. The expressions of 16 genes involved in oxidative stress, cellular apoptosis, immune system and endocrine system displayed that embryonic zebrafish were affected by the individual pesticides and their mixtures, and greater variations of four genes (ERɑ, Tnf, IL and bax) were found when exposed to pesticide mixtures compared with their individual compounds. Therefore, more studies on mixture toxicities among different pesticides should be taken as a priority when evaluating their ecological risk., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Two-dimensional nanomaterial-based photothermal therapy (PTT) is currently under intensive investigation as a promising approach toward curative cancer treatment. However, high toxicity, moderate efficacy, and low uniformity in shape remain critical unresolved issues that hamper their clinical application. Thus, there is an urgent need for developing versatile nanomaterials to meet clinical expectations. To achieve this goal, we developed a stable, highly uniform in size, and nontoxic nanomaterials made of tellurium-selenium (TeSe)-based lateral heterojunction. Systemic delivery of TeSe nanoparticles in mice showed highly specific accumulation in tumors relative to other healthy tissues. Upon exposure to light, TeSe nanoparticles nearly completely eradicated lung cancer and hepatocellular carcinoma in preclinical models. Consistent with tumor suppression, PTT altered the tumor microenvironment and induced immense cancer cell apoptosis. Together, our findings demonstrate an exciting and promising PTT-based approach for cancer eradication., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Objective: To identify the antidepressant effect of Xingnao Jieyu (XNJY) decoction on a post-stroke depression (PSD) rat model and the underlying molecular mechanism., Methods: We established a rat PSD model by middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress (CUMS). Healthy SD rats were randomly divided into six groups: sham, PSD, fluoxetine (Flu), and XNJY groups at low, middle, and high doses. The sham group underwent sham operation, while the other groups underwent MCAO+CUMS. The Flu and XNJY decoction groups were intragastrically administered with Flu or different doses of XNJY for 21 consecutive days. Histopathological changes in the cortex and hippocampus were observed by staining with hematoxylin and eosin and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling. Iba1 positive cells were evaluated by immunofluorescence assay. The expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in the cortex and hippocampus were measured by enzyme linked immunosorbent assay., Results: The PSD group rats had a significant decrease in body weight, consumption of sucrose water, and locomotor activity but an increase in immobility time during a forced swimming test (P < 0.01) compared with sham group. Flu and different doses of XNJY significantly recovered these indices (P < 0.01). XNJY also inhibited neuronal damage and apoptosis in the cortex induced by PSD (P < 0.01). Furthermore, XNJY reduced the number of Iba1 positive cells and the expressions of TNF-α, IL-6, and IL-1β, in addition to recovered the levels of 5-HT and NE in the cortex and hippocampus (P < 0.01)., Conclusion: The alleviation of neuroinflammation might be an important mechanism of the XNJY decoction against PSD. Thus, XNJY might be a promising candidate for the treatment of PSD.

Migratory Birds have been considered biovectors of persistent organic pollutants (POPs) from sources to remote areas. In the present study, Kentish Plovers (Charadrius alexandrines) were collected in different periods, including immigration, breeding and emigration, to investigate the effects of migration and reproduction on POP variations in this bird species. Significant differences were found for dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene (HCB) concentrations in muscles between the immigration and emigration periods (p < 0.01 and p < 0.001, respectively), which could be attributed to the higher pesticide residues in the wintering grounds of plovers. Female plovers could excrete about 20.8-42.7% of POP load into eggs. Nevertheless, the POP levels didn't exhibit great reduction during the breeding period compared with other seasons, which suggested that the breeding status had little impact on POP levels in female plovers. The estimated mean transport masses of POPs driven by plover migration were at the milligram level (range: 0.02-7.05 mg), suggesting that the migration of plovers had limited impacts on the redistributions of POPs along their migratory routes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The intraoperative visualization of tumor cells is a powerful modality for surgical treatment of solid tumors. Since the completeness of tumor excision is closely correlated with the survival of patients, probes that can assist in distinguishing tumor cells are highly demanded. Purpose: In the present study, a fluorescent probe JF1 was synthesized for imaging of tumor cells by conjugating a substrate of cathepsin B (quenching moiety) to Oregon Green derivative JF2 using a self-immolative linker. Methods: JF1 was then loaded into the folate-PEG modified CaCO 3 nanoparticles. The folate receptor-targeted, pH-dependent, and cathepsin B activable CaCO 3 nanoprobe was test in vitro and in vivo for tumor imaging. Results: CaCO 3 nanoprobe demonstrated good stability and fast lighting ability in tumors under low pH conditions. It also showed lower fluorescence background than the single cathepsin B dependent fluorescent probe. The pH-dependent and cathepsin B controlled "turn-on" property enables precise and fast indication of tumor in vitro and in vivo. Conclusion:  This strategy of controlled drug delivery enables in vivo imaging of tumor nodules with a high signal-to-noise ratio, which has great potential in surgical tumor treatment., Competing Interests: The authors report no conflicts of ineterest in this work.

Indoor exposure to legacy and novel brominated flame retardants (NBFRs) may cause potential risks to human health. Studies on seasonal variations of indoor PM 2.5 -bound BFRs are scant. This study comprehensively investigated the seasonal variations of PM 2.5 -bound polybrominated diphenyl ethers (PBDEs) and NBFRs in various indoor environments (i.e. activity room, dormitory, home and office) and outdoor PM 2.5 in Beijing, China over one year. The levels of PBDE (226 ± 108 pg m -3 ) were higher than that of NBFRs (27.0 ± 16.0 pg m -3 ) in all indoor environments. Decabromodiphenyl ether (BDE-209) and decabromodiphenyl ethane (DBDPE) were the most abundant BFRs. Office showed the highest mean concentrations of Σ 15 PBDEs (251 ± 125 pg m -3 ) and Σ 9 NBFRs (33.0 ± 18.0 pg m -3 ), which may be related to the higher number density of indoor materials. The concentrations of Σ 9 NBFRs and Σ 15 PBDE in indoor PM 2.5 were found to be significantly higher than those in the corresponding outdoor PM 2.5 (p < 0.05). Two to twenty-fold seasonal variations were observed for levels of PM 2.5 -bound BFRs during one year, and indoor concentrations increased slightly during the central-heating period (November 2016-March 2017). Seasonal variations of BFRs could be affected by temperature, relative humidity and concentrations of particle matters. The PM 2.5 -bound BFRs concentrations in PM 2.5 were negatively correlated with temperature and relative humidity, while positively correlated with PM 2.5 concentrations (p < 0.05). Atmospheric haze pollution could possibly contribute to higher levels of indoor PM 2.5 -bound BFRs. Human daily intake of BFRs via PM 2.5 inhalation showed seasonal differences, and the highest exposure risk occurred in winter. Toddlers were assessed to be more vulnerable to indoor PM 2.5 -bound BFRs in all seasons. This study provided the first-hand measurements of seasonal concentrations and human exposure to PM 2.5 -bound BFRs in different indoor scenarios in Beijing., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In the present study, the temporal distribution of PM 2.5 -bound organophosphate flame retardants (OPFRs) was comprehensively investigated in various indoor environments as well as outdoor air in Beijing, China over a one-year period. The mean concentrations of Σ 9 OPFRs were 22.7 ng m -3 and 1.40 ng m -3 in paired indoor and outdoor PM 2.5 , respectively. The concentrations of tri-n-butyl phosphate (TNBP), tris (2-chloroethyl) phosphate (TCEP) and tris (2-chloroisopropyl) phosphate (TCIPP) in indoor PM 2.5 were significantly correlated with those in outdoor PM 2.5 . For different indoor microenvironments, mean concentrations of Σ 9 OPFRs were in the order of office (29.0 ± 11.7 ng m -3 ) > home (24.0 ± 9.4 ng m -3 ) > dormitory (19.4 ± 4.9 ng m -3 ) > activity room (14.4 ± 3.1 ng m -3 ). TCIPP was the most abundant compound in the indoor PM 2.5 , followed by TCEP. Significantly higher concentrations of OPFRs were observed in indoor environments with more furnishing, electronics or other materials (p < 0.05). Moreover, lower levels of OPFRs in indoor air were observed at well-ventilated (with higher air exchange rate) indoor sampling sites. Concentrations of Σ 9 OPFRs in the activity room, dormitory, homes and outdoor sites generally increased in summer and heating seasons (November 2016 to February 2017). Significant correlations (p < 0.05) were observed between temperatures and mass concentrations of OPFRs with higher vapor pressures, i.e. TNBP, TCEP and TCIPP in all indoor and outdoor samples. Seasonal differences in human exposure were observed and the highest daily exposure dose occurred in summer. Toddlers may suffer the highest exposure risk of PM 2.5 -bound OPFRs via inhalation among all age groups. This is one of the very few studies that have revealed the seasonal variation and human exposure of PM 2.5 -bound OPFRs in different microenvironments, which shed light on emission sources and fate of OPFRs and potential human exposure pathway., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Atmospheric fine particle (PM 2.5 ) samples were collected over a whole year (April 2016 - March 2017) across five sampling locations in the Beijing-Tianjin-Hebei (BTH) region, to investigate the occurrence of novel brominated flame retardants (NBFRs) and polybrominated diphenyl ethers (PBDEs). The concentrations of ∑ 9 NBFRs were in the range of 0.63-104 pg/m 3 (15.6 ± 16.8 pg/m 3 ) in atmospheric PM 2.5 , while the levels of ∑ 9 PBDEs (excluding BDE-209) ranged from 0.05 to 19.1 pg/m 3 (2.9 ± 3.8 pg/m 3 ) and BDE-209 concentrations ranged from 0.88 to 138 pg/m 3 (22 ± 28 pg/m 3 ). Relatively higher levels of NBFRs and PBDEs were found at urban sampling sites in Beijing City and Shijiazhuang City. Decabromodiphenylethane (DBDPE) and BDE-209 were the dominant compounds with the relative abundances of 72% in ∑ 9 NBFRs and 90% in ∑ 10 PBDEs, respectively. Generally, the levels of most target BFRs in summer were lower than those in other seasons. However, there were no notable seasonal differences in levels of DBDPE and BDE-209 in atmospheric PM 2.5 samples across the BTH region. Significant and positive correlations were found between the concentrations of BFRs and PM 2.5 . Daily human exposure via inhalation revealed that children have a higher probability of suffering from the adverse effects of BFRs than that of adults. In addition, residents living near sampling locations across the BTH region may suffer high exposure risks to BDE-209 and NBFRs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The exocyst complex plays multiple roles via tethering secretory or recycling vesicles to the plasma membrane. Previous studies have demonstrated that the exocyst contains eight components, which possibly have some redundant but distinct functions. It is therefore interesting to investigate the biological function of each component. Here, we found that Sec3, one component of exocyst complex, is involved in Drosophila egg chamber development. Loss of sec3 results in egg chamber fusion through the abolishment of cell differentiation. In addition, loss of sec3 increases cell numbers but decreases cell size. These defects phenocopy Notch pathway inactivation. In line with this, loss of sec3 indeed leads to Notch protein accumulation, suggesting that the loss of Sec3 inhibits the delivery of Notch onto the plasma membrane and accumulates inactive Notch in the cytoplasm. Loss of sec3 also leads to the ectopic expression of two Notch pathway target genes, Cut and FasciclinIII, which should normally be downregulated by Notch. Altogether, our study revealed that Sec3 governs egg chamber development through the regulation of Notch, and provides fresh insights into the regulation of oogenesis.

High volume air samples were collected from April 2016 to March 2017 at five locations across the Beijing-Tianjin-Hebei (BTH) region, to investigate the atmospheric occurrence of organophosphate esters (OPEs). The mean atmospheric concentrations of ∑ 8 OPEs (gas and particle phases) varied from 531 ± 393 pg/m 3 to 2180 ± 1490 pg/m 3 with the highest level observed at the urban sampling site in Tianjin City. ∑ 8 OPEs were predominated by the chlorinated OPEs (TCEP, TCPP, and TDCIPP), which accounted for 60% ± 16% of the OPE concentrations across the BTH region. Generally, higher levels of gaseous OPEs were found in summer, while higher levels of particle-bound OPEs were observed in winter. The concentrations of gaseous OPEs were positively and significantly correlated with local temperatures (p < 0.05) and relative humidity (p < 0.01), while significantly positive correlations were found between concentrations of particle-bound OPEs and total suspended particulates (TSP) (p < 0.01). These findings confirmed that temperatures, relative humidity and levels of TSP are the main drivers for OPE distributions in different seasons and areas. Gas/particle partitioning of OPEs was also investigated based on the absorption-partitioning model (octanol-air partitioning coefficient (K oa ) -based model) and Junge-Pankow adsorption-partitioning model (J-P model). K oa -based model generally showed a better performance in comparison with the measured results. The assessment of inhalation exposure risks indicated that relatively higher exposure risks were found in the urban areas, in particular, in Tianjin City (a median value of the estimated daily intake (EDI) of 106 pg/kg body weight/day), suggesting that more attention should be drawn to OPE distributions in the heavily industrialized megacities., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A novel lateral flow biosensor for rapid detection of Pb2+ was established for the first time based on Pb2+-induced G-quadruplex structure-switching. Semi-quantitative results could be read by reference to a colorimetric card. The whole process only took 15 minutes with a visual detection limit of 25 nM.

Transarterial embolization (TAE) is a palliative option commonly used for the treatment of advanced, unresectable hepatocellular carcinoma (HCC). However, patient prognosis in regards to overall survival has not improved with this method, mainly due to hypoxia‑inducible factor‑1α (HIF‑1α)‑induced angiogenesis and invasiveness. Thus, it is hypothesized that HIF‑1α may be an ideal knockout target for the treatment of HCC in combination with TAE. Thus, in the present study, HIF‑1α knockout was conducted in human liver cancer SMMC‑7721 cells and a xenograft HCC model was established using a lentivirus‑mediated CRISPR/Cas system (LV‑Cas) with small guide RNA‑721 (LV‑H721). Furthermore, hepatic artery ligation (HAL) was used to mimic human transarterial chemoembolization in mice. The results revealed that HIF‑1α was highly expressed in both HCC patient tissues and SMMC‑7721‑induced tumor tissues. The HIF‑1α knockout in SMMC‑7721 cells significantly suppressed cell invasiveness and migration, and induced cell apoptosis under CoCl2‑mimicking hypoxic conditions. Compared with the control groups, HAL + LV‑H721 inhibited SMMC‑7721 tumor growth in orthotopic HCC and markedly prolonged the survival of HCC‑bearing mice, which was accompanied by a lower CD31 expression (tumor angiogenesis) and increased apoptosis in the tumor cells. These findings demonstrated a valuable antitumor synergism in combining CRISPR/Cas9‑mediated HIF‑1α knockout with TAE in mice and highlighted the possibility that HIF‑1α may be an effective therapeutic knockout target in combination with TAE for HCC treatment.

Background. The neurotrophic pathway regulated by the brain-derived neurotrophic factor (BDNF) plays a crucial role in the pathogenesis of poststroke depression (PSD). How the traditional Chinese medicine compound preparation Xingnao Jieyu (XNJY) decoction regulates the neurotrophic pathway to treat PSD is unclear. Objective. This study aimed to investigate the antidepressant effect of XNJY decoction on a rat model of PSD and the molecular mechanism intervening in the neurotrophic pathway. Methods. After a middle cerebral artery occlusion model was established, chronic unpredictable mild stress was applied for 21 days to prepare a PSD model. XNJY groups and a fluoxetine (Flu) group of rats were intragastrically administered with XNJY and Flu, respectively, for 21 consecutive days. Depressive-like behaviors, including sucrose preference, open field test, and forced swimming test, were assessed. The survival and apoptosis of cortical and hippocampal neurons were evaluated by immunofluorescence assay and TUNEL staining. The contents of serotonin (5-HT), norepinephrine (NE), and BDNF in the cortex and hippocampus were determined by ELISA. The protein levels of BDNF, p-ERK/ERK, and p-CREB/CREB in the cortical and hippocampal regions were tested by Western blot. Results. The depressive-like behaviors markedly improved after XNJY and Flu treatment. XNJY and Flu promoted neuronal survival and protected cortical and hippocampal neurons from apoptosis. XNJY also increased the contents of 5-HT, NE, and BDNF and recovered the protein levels of p-ERK/ERK, p-CREB/CREB, and BDNF in the cortical and hippocampal regions. Conclusion. These results indicated that the XNJY decoction exerts an obvious antidepressant effect, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway.

Two-dimensional (2D) inorganic nanomaterials for biomedical applications still face the challenge of simultaneously offering a high photothermal conversion efficiency (PTCE), efficient drug delivery, biocompatibility and biodegradability. Herein, cancer treatment using tin sulfide nanosheet (SnS NS)-based dual therapy nano-platforms (SDTNPs), including photothermal- and chemo-therapy, is demonstrated. SnS, a black phosphorus (BP) analogue binary IV-VI compound, was synthesized using liquid phase exfoliation. SnS NSs comprising 2-4 layers exhibited good biocompatibility and a high PTCE of 39.3%, which is higher than other popular 2D materials. The SnS NSs showed a stable photothermal performance over 2 h of laser irradiation and exhibited ∼14% degradation after 10 h of irradiation. It was also found that SnS NSs show high loading of small molecules such as doxorubicin (DOX) (up to ∼200% in weight). Consequently, the SDTNPs achieved notable tumor therapy through the combination of photothermal- and chemo-therapy both in vitro and in vivo. Our study may pave the way for the biomedical application of SnS and other IV-VI compound-based 2D nanomaterials. Compared with traditional therapies, SnS NS-based laser therapy is green and efficient, due to its biocompatibility, photo-degradability, high efficiency photothermal properties and high drug loading.

Black phosphorus (BP) has recently emerged as an intriguing photothermal agent in photothermal therapy (PTT) against cancer by virtue of its high photothermal efficiency, biocompatibility, and biodegradability. However, naked BP is intrinsically characterized by easy oxidation (or natural degradation) and sedimentation inside the tumor microenvironment, leading to a short-term therapeutic and inhomogeneous photothermal effect. Development of BP-based nanocomposites for PTT against cancer therefore remains challenging. The present work demonstrates that green and injectable composite hydrogels based on cellulose and BP nanosheets (BPNSs) are of great efficiency for PTT against cancer. The resultant cellulose/BPNS-based hydrogel possesses 3D networks with irregular micrometer-sized pores and thin, strong cellulose-formed walls and exhibits an excellent photothermal response, enhanced stability, and good flexibility. Importantly, this hydrogel nanoplatform is totally harmless and biocompatible both in vivo and in vitro. This work may facilitate the development of BP-polymer-based photothermal agents in the form of hydrogels for biomedical-related clinic applications., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Main Conclusion: Autophagy is involved in cytoplasmic degradation through directly engulfing cytosol and organelles by autophagosomes and then fusing with lysosome-like vesicles during the development of nonarticulated laticifers in Euphorbia kansui Liou. Autophagy has been reported to play an important role in a wide range of eukaryotic organisms during responses to various abiotic and biotic stresses. However, until recently, the functions of autophagy in normal plant differentiation and development were still in their infancy. Nonarticulated laticifers, a type of secretory tissue in plants, undergo the degradation of cytosol and organelles during their development. However, little evidence of autophagy in laticifer differentiation has been provided. In the present study, using anti-ATG8 antibody-Alexa Fluor 488, Lyso-Tracker Red (LTR) and monodansylcadaverine (MDC) as markers for detecting autophagosomes, as well as autophagy-related structures, we observed that the green fluorescence of ATG8a largely colocalized with the red fluorescence of LTR and purple fluorescence of MDC and the quantity of autophagosomes experienced a trend from less to more to less during laticifer development. Additionally, we described the autophagy process during the development of nonarticulated laticifers in Euphorbia kansui Liou at the ultrastructural level in detail. In addition, further immunogold TEM studies also verified the presence of autophagosomes, autolysosomes and lysosome-like structures in laticifers. Taken together, these results suggest that autophagy contributes to the development of the nonarticulated laticifers in E. kansui Liou and that autophagosomes fuse with lysosome-like structures for degradation. These results will lay an important foundation for further studies on laticifer regulation.

Cell growth and cell differentiation are two distinct yet coupled developmental processes, but how they are coordinated is not well understood. During Drosophila oogenesis, we found that the growth-promoting InR/Akt/TOR pathway was involved in suppressing the fate determination of the migratory border cells. The InR/Akt/TOR pathway signals through TOR and Raptor, components of TORC1, to downregulate the JAK/STAT pathway, which is necessary and sufficient for border cell fate determination. TORC1 promotes the protein stability of SOCS36E, the conserved negative regulator of JAK/STAT signaling, through physical interaction, suggesting that TORC1 acts as a key regulator coordinating both cell growth and cell differentiation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Hydrothermally-pretreated rice straw (HPRS) from various pretreatment temperatures was anaerobically-digested in whole slurry. Results indicated promoting pretreatment temperature significantly deconstructed rice straw, and facilitated the conversion of insoluble fractions to soluble fractions. Although 306.6 mL/g TS biogas was maximally yielded in HPRS-90 and HPRS-180, respectively, via digestion in whole slurry, it was only 3% promotion compared to the unpretreated rice straw. HPRS-210 yielded 208.5 mL/g TS biogas, which was 30% reduction with longer lag period of 19.8 d, suggesting serious inhibitions happened. Through slightly increasing organic loading, more serious acidification and reduction on biogas yield, especially at higher pretreatment temperatures, indicated the soluble fractions controlled digestion performances. Pearson correlation analysis suggested negative relationship existed between methane yield and the soluble fractions including soluble carbohydrates, formic acid and furfural. Hydrothermal pretreatment, especially at higher temperature, did not improve anaerobic digestion, thereby, was not recommended, however, lower temperature can be considered potentially., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work., Competing Interests: The authors declare no conflict of interest.

Background: Terpenoids, the largest class of natural products in the plant kingdom, have been widely used in medicine. The precursors of terpenoids, isoprene phosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), were synthesized from a mevalonate (MVA) pathway and a 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway respectively. The acetyl-CoA acetyltransferase (AACT) is the initial enzyme in MVA pathway and is considered presently to be essential for terpenoid backbone biosynthesis. The basic research on cytochemistry of terpenoid metabolic enzymes is important for understanding the mechanisms underlying major metabolic processes. However, compartmentalization of AACT in plants is in controversy. Euphorbia helioscopia L. containing laticifers in the whole plant is a famous ancient folk medicine for tumor treatment, and the terpenoid is an active ingredient. Furthermore, the laticifer cell is the main synthesizing and storing site for terpenoids., Results: The gene of AACT was cloned successfully from E. helioscopia, and named as EhAACT. The EhAACT expression has no significant difference among roots, stems and leaves. However, compared with the roots and stems, the EhAACT expression level is slightly higher in leaves. In addition, EhAACT recombinant protein was expressed by procaryotic expression system and anti-EhAACT antibody was prepared, the molecular weight is about 43 kDa. Western blotting results illustrated that the EhAACT antibodies specifically recognized the endogenous proteins in E. helioscopia laticifers. At last, the subcellular localization of EhAACT in E. helioscopia laticifers was observed by using colloidal gold immune-electron microscopy. EhAACT was found to mainly distribute in the endoplasmic reticulum (ER), vacuoles originated from ER and cytosol aound vacuoles originated from ER., Conclusions: As a result, we speculated that in E. helioscopia laticifers, EhAACT located in cytosol would be transferred to small vacuoles dilated from ER, and the precursors of terpenoids were synthesized in these small vacuoles, then terpenoids were further synthesized into latex particles. This result would provide theoretical basis for regulating and controlling of terpenoid biosynthesis in laticifers.

Objective: To investigate the effects of dandelion polysaccharide on IL-6/STAT3 signaling pathway in rats with ulcerative colitis., Methods: Forty SD rats were randomly divided into four groups ( n =10):control group, model group, positive control group and dandelion polysaccharide group. The ulcerative colitis model was established by treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS). The positive control group was treated with mesalazine 10 mg/kg·d and dandelion polysaccharide group was treated with dandelion polysaccharide 10 mg/kg·d. The levels of interleukin -6(IL-6), colonic myeloperoxidase (MPO) and interleukin-6 receptor (sIL-6Rα) were measured after 4 weeks of treatment. The pathological changes of colonic mucosa were observed in rats. The gene expressions of glycoprotein 130 (gp130), transcriptional activator3(STAT3) and IL-6 were detected., Results: Compared with the normal control group, the level of serum IL-6 in the model group was significantly higher than that in the control group ( P <0.01). Compared with the model group, the serum levels of IL-6 in the dandelion polysaccharide group and the methacetin group were significantly decreased ( P <0.01). Compared with the model group, the MPO positive density of the rats in the dandelion polysaccharide group and the methacetin group was significantly lower than that in the normal group ( P <0.01). Compared with the model group, the levels of sIL-6Rα and gp130 in the rats were significantly lower than those in the model group ( P <0.01). Compared with the model group, the expressions of STAT3 and IL-6 mRNA in the intestinal tissue of the rats in the dandelion polysaccharide group and the methacetin group were decreased significantly., Conclusions: Dandelion polysaccharide can decrease the level of IL-6 in rats with ulcerative colitis, regulate the expression of sIL-6Rα and gp130 protein in IL-6/STAT3 pathway, and then down-regulate the expressions of STAT3 and IL-6 mRNA in intestinal tissue of rats, alleviate the colon inflammation state, protect and repair the mucosal tissue. Dandelion polysaccharide plays a role in the treatment of ulcerative colitis.

During collective migration, guidance receptors signal downstream to result in a polarized distribution of molecules, including cytoskeletal regulators and guidance receptors themselves, in response to an extracellular gradient of chemotactic factors. However, the underlying mechanism of asymmetry generation in the context of the migration of a group of cells is not well understood. Using border cells in the Drosophila ovary as a model system for collective migration, we found that the receptor tyrosine kinase (RTK) PDGF/VEGF receptor (PVR) is required for a polarized distribution of recycling endosome and exocyst in the leading cells of the border cell cluster. Interestingly, PVR signaled through the small GTPase Rac to positively affect the levels of Rab11-labeled recycling endosomes, probably in an F-actin-dependent manner. Conversely, the exocyst complex component Sec3 was required for the asymmetric localization of RTK activity and F-actin, similar to that previously reported for the function of Rab11. Together, these results suggested a positive-feedback loop in border cells, in which RTKs such as PVR act to induce a higher level of vesicle recycling and tethering activity in the leading cells, which in turn enables RTK activity to be distributed in a more polarized fashion at the front. We also provided evidence that E-cadherin, the major adhesion molecule for border cell migration, is a specific cargo in the Rab11-labeled recycling endosomes and that Sec3 is required for the delivery of the E-cadherin-containing vesicles to the membrane.

Objective: To determine the methods for establishing an in vivo model of long-term hepatitis B virus (HBV) infection in the Chinese tree shrew (Tupaia belangeri chinensis)., Methods: Seventy-seven neonate (1-3 days old) and 49 young adult (2 weeks to 1 year old) tree shrews were inoculated with different HBV sources (chronic hepatitis B (CHB) human patient serum, single or pooled; HBV-infected tree shrew serum, single only; HBV-infected HepG2.2.15 cells' culture medium supernatant; HBV genome-transfected HepG2.2.15 cells' culture medium supernatant) through various routes of injection (subcutaneous, intraperitoneal, and direct liver via abdominal skin; adults also received intravenous and indirect liver via spleen). Serum and liver biopsies were collected from the animals at various time points post-inoculation for detection of HBV markers by fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, time-resolved immunofluorescence, Southern blotting, dot blotting, immunohistochemistry, and microscopy., Results: Among the neonatal group of tree shrews, six (7.8%) were confirmed as HBV-infected for more than 72 (up to 228) weeks after inoculation and another seven (9.1%) were suspected of persistent infections. None of the young adult tree shrews developed persistent infection. Inoculation with single-source serum from either CHB humans or tree shrews were responsible for the most cases of infections, and the subcutaneous injection produced more infections than the other inoculation routes. The most reliable methods of determining HBV infection status were detection of serum HBV immunoreactive markers and intrahepatic HBV DNA., Conclusion: In order to establish an in vivo model of CHB in the tree shrew, the animals should be inoculated in the neonatal period using subcutaneous injection.

Background: Little is known about predictors for the onset of different types of homeboundness among community-living older adults., Purpose: This 2-year prospective study examined predictors for the onset of "type 1" and "type2" homeboundness (see definitions below) among community-living older adults., Methods: Study subjects comprised all residents aged 65 years and over living in Yoita town, Niigata, Japan, who answered the baseline (2000) and follow-up (2002) surveys. Persons were defined as being homebound if he/she went outdoors once a week or less often. Homeboundness was further classified into "type 1" or "type 2", based on the hierarchical mobility level classification (levels 1 or 2 vs. levels 3 or over). "Type 1" homebound persons included those who could not get out into the neighborhood without assistance (i.e., level 3 or over). "Type 2" included those who were homebound, though they could get out at least into the neighborhood unassisted (i.e., level 1 or 2). A stepwise, multiple logistic regression model was used to identify the most parsimonious combination of risk factors for each type of homeboundness., Results: Out of 1,322 persons who were level 1,2 non-homebound at the baseline, 77.6% remained as level 1,2 non-homebound (n = 1,026), but 1.7% were "type 1" homebound (n = 22), and 4.8% were "type 2" homebound (n = 66) at follow-up. The final model for prediction of "type 1" homeboundness at follow-up included: advanced age (OR for 5 year-increment: 2.10; 95%CI: 1.36-3.24), not having a job (OR: 4.42; 95%CI: 1.21-16.2), unable to walk 1 km (OR: 4.24; 95%CI: 1.37-13.1), and a low cognitive function identified as MMSE <24 (OR: 5.22; 95%CI: 1.98-13.8). The final model for prediction of "type 2" homeboundness at follow-up included: advanced age (OR for 5 year-increment: 1.65; 95%CI: 1.32-2.06), a depressive mode indicated by a GDS short version score >5 (OR: 2.18; 95%CI: 1.23-3.88), a low cognitive function (OR: 2.72; 95% CI: 1.47-5.05), not having close friends (OR: 2.30; 95%CI: 1.08-4.87), and not having a walking or calisthetics habit (OR: 2.21; 95%CI: 1.26-3.86)., Conclusions: Reduced physical and mental functioning contribute to the subsequent occurrence of "type 1" homeboundness. Additionally, psychosocial factors are independent predictors of "type 2" homeboundness. These results suggest that different public health strategies might be required for prevention of the different types of homeboundness in Japanese older adults.

Purpose: This 2-year prospective study was conducted to determine prognosis of two different types of homeboundness among community-living older adults and explore whether those types of homeboundness exert independent effects even after controlling for potential confounders., Methods: Out of all residents aged 65 years and over who lived in Yoita, Niigata, Japan (n = 1,673), 1,544 persons participated in the baseline survey which was conducted in November, 2000 (response rate, 92.2%). They were followed for the subsequent 2 years in terms of mortality, institutionalization and functional status (mobility, IADL, BADL, and cognition). Persons were defined as being homebound if he/she went outdoors only once a week or less often. Homeboundness was further classified into types 1 or 2, based on the hierarchical mobility level classification (levels 1 or 2 vs. levels 3 or over). Type 1 homebound persons included those who could not get out into the neighborhood without assistance (i.e., levels 3 or over). Type 2 included those who were homebound though they could get out at least into the neighborhood unassisted (i.e., levels 1 or 2). We compared two-year prognosis between the type 2 homebound cases and controls (the non-homebound individuals in levels 1 or 2), or the type 1 homebound and controls (the non-homebound in levels 3 or over). Multiple regression analysis or multiple logistic regression models were used to analyze independent effects of the homebound status on the prognosis, controlling for potential confounders such as age, gender, chronic conditions, functional status, and psychosocial variables at baseline., Results: At baseline there were 1,322 non-homebound in levels 1 or 2 (87.0%), 81 type 2 homebound (5.3%), 39 non-homebound in levels 3 or over (2.6%), and 78 type 1 homebound older persons (5.1%) . As compared to controls, type 2 homebound elderly showed increased risks of functional decline even after controlling for potential confounders. Relative risks of type 2 homeboundness for developing mobility loss, IADL and ADL disability, and cognitive impairment (MMSE < 20) were 3.20(95% CI, 1.60-6.38), 2.85(1.20-6.82), 1.52(0.61-3.75), and 3.05(1.06-8.78) in the partially adjusted model, and 2.49(1.20-5.17), 2.25(0.90-5.63), 1.46(0.54-3.94) and 2.41(0.71-8.17) in the fully adjusted model. Type 1 homebound elderly showed an increased risk for mortality (33.3% vs. 5.1%), but a lower risk for institutionalization (9.0% vs. 25.6%). The independent effect of type 1 was not significant when mortality and institutionalization were combined (relative risk, 2.05[0.54-7.75] in the fully adjusted model)., Conclusions: Type 2 homeboundness is an independent risk factor for functional decline among competent older persons, while the prognosis of older persons with a low functional state is poor, regardless of type 1 homeboundness or not.

Background: Little is known about the epidemiologic features of different types of homeboundness among the elderly., Purpose: This cross-sectional study examined prevalence and characteristics of "type 1" and "type 2" homeboundness (see definitions below) among community-living older adults., Methods: The subjects comprised all residents aged 65 years and over living in Yoita, Niigata Prefecture, and Hatoyama, Saitama Prefecture. Subject data on sociodemographics, and physical, mental and social functioning were collected through in-person interview. Persons were defined as being homebound if he/she went outdoors only once a week or less often. Homeboundness was further classified into "type 1" or "type 2", based on the hierarchical mobility level classification (levels 1 or 2 vs. levels 3, 4, or 5). "Type 1" homebound persons included those who could not get out into the neighborhood without assistance (i.e, levels 3, 4, or 5). "Type 2" included those who were homebound, though they could get out at least into the neighborhood unassisted (i.e., levels 1 or 2). We focused on characteristics of "type 1" and "type 2" homeboundness as compared with those of respective controls, ie., non-homebound persons within the same mobility categories., Results: Out of the eligible subjects (1588 in Yoita, and 1135 in Hatoyama), 1544 and 1002 persons participated in the survey (response rates of 97.2% and 88.3%, respectively). Among the participants, "type 1" and "type 2" homeboundness was found for 4.1% and 5.4%, respectively, in Yoita, and 3.3% and 6.8% in Hatoyama. After adjustment for potential confounders such as age, gender and mobility level, we found a significant regional difference in the prevalence of "type 2" but not of "type 1" (OR of "type 2" for Hatoyama/Yoita 1.44; 95% CI 1.02-2.03). Both types of homeboundness increased with advancing age; "type 1" and "type 2" featured in over 10% of persons aged at least 85 years and 80 years, respectively. Even after controlling for potential confounders, "type 2" showed a higher prevalence with walking disability and incontinence, and reported lower self-rated health, more depressed mood, lower functional capacity and lower social functioning. "Type 1" showed a higher prevalence with fear of falls, but a lower prevalence with basic ADL disability and a high score for Intellectual Activity, indicating reduced self-efficacy., Conclusions: Prevalence of "type 1" and "type 2" homeboundness among community-living older adults differs depending on the residential area and age of the subjects. A substantial proportion of "type 2" homebound persons are at high risk of functional decline, indicating that "type 2" as well as "type 1" homebound persons need care-preventive programs.

This paper describes how to estimate the uncertainty when Fe in metallic silicon is determined by ICP-AES (Inductively Coupled Plasma Atomic Emission Spectrometry). The technique of the averaged moving range (MR) pooled in-statistical-dynamic-monitor is proposed. The study suggests that the uncertainty contribution of ICP-AES measurement system is, by using this technique, a combination of quality control (QC) and linear fit. This conclusion maximized the combination of the effects on various variances, refrained from the complicated relativity, and favored the uncertainty evaluation for ICP-AES measurement system.