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Transparent exopolymer particles (TEPs) are a class of transparent gel-like polysaccharides, which have been widely detected in almost every kind of feed water to membrane systems, including freshwater, seawater and wastewater. Although TEP have been thought to be related to the membrane fouling, little information is currently available for their influential mechanisms and the pertinence to biofouling development. The present study, thus, aims to explore the impact of TEPs on biofouling development during ultrafiltration. TEP samples were inoculated with bacteria for several hours before filtration and the formation of “protobiofilm” (pre-colonized TEP by bacteria) was examined and its influence on biofouling was determined. It was observed that the bacteria can easily and quickly attach onto TEPs and form protobiofilms. Ultrafiltration experiments further revealed that TEP-protobiofilms served as carriers which facilitated and accelerated transport of bacteria to membrane surface, leading to rapid development of biofouling on the ultrafiltration membrane surfaces. Moreover, compared to the feed water containing independent bacteria and TEPs, more flux decline was observed with TEP-protobiofilms. Consequently, it appeared from this study that TEP-protobiofilms play a vital role in the development of membrane biofouling, but unfortunately, this phenomenon has been often overlooked in the literature. Obviously, these findings in turn may also challenge the current understanding of organic fouling and biofouling as membrane fouling caused by TEP-protobiofilm is a combination of both. It is expected that this study might promote further research in general membrane fouling mechanisms and the development of an effective mitigation strategy.

Eight new sesquiterpene derivatives (2, 4–6 and 10–13), along with five known analogues were isolated from the mangrove endophytic fungus Phomopsis sp. SYSU-QYP-23. Their structures of new compounds were established by spectroscopic methods, and the absolute configurations were confirmed by single-crystal X-ray diffraction analysis and comparison of the experimental ECD spectra. The absolute configuration of the side chain in 1 was first defined by modified Mosher’s method. Compounds 1–7 showed potent inhibitory activities against nitric oxide (NO) production in lipopolysaccharides (LPS) induced RAW 264.7 cells with IC50 values ranging from 8.6 to 14.5 μM. The molecular docking results implied that the bioactive sesquiterpenes may directly bind with targeting residues in the active cavity of iNOS protein.

BACKGROUND AND OBJECTIVES The safety of laparoscopic resection of very large pheochromocytomas is unclear, and preoperative preparation may benefit from refinement. This retrospective study was designed to determine the correlation between tumor size and perioperative characteristics by evaluating data from patients who underwent laparoscopic resection of pheochromocytomas. METHODS A total of 253 patients were grouped according to their tumor diameter: diameter ≥8 cm, Glarge (Glg ) (n = 30); diameter 6 to 8 cm, Gmedium (Gmd ) (n = 57); and diameter

Objective Although classical hemifacial spasm (HFS) has been attributed to an atraumatic pulsatile vascular compression around the root exit zone (REZ) of the facial nerve, rare tumor-related HFS associated with meningiomas, epidermoid tumors, lipomas, and schwannomas in the cerebellopontine angle have been reported. The exact mechanism and the necessity of microvascular decompression for tumor-induced HFS is not clear, especially for vestibular schwannomas. Methods We retrospectively analyzed 10 patients with vestibular schwannomas out of 5218 cases of hemifacial spasm between 2004 and 2014. Results Hemifacial spasm occurred ipsilateral to the vestibular schwannoma in 9 patients and contralateral to the lesion in 1 patient. The mean follow-up period was 86 months (range, 22–140 months). All patients underwent surgery for resection of the vestibular schwannoma. Following the principle of neurovascular compression, offending vessels were found in 7 patients, no offending vessels in 2 patients, and a tumor with the displacement of brain stem contributing to contralateral facial nerve compression in 1 patient. HFS was relieved immediately postoperatively in 9 patients, whereas it improved gradually and then resolved after one month in one patient with a contralateral vestibular schwannoma. Conclusions For HFS induced by vestibular schwannomas in our study, the majority of cases are caused by a combination of tumor and vascular co-compression at the REZ. Surgical intervention resulted in resolution of symptoms. For HFS with ipsilateral vestibular schwannoma, exploration of the facial nerve root for vascular compression should be performed routinely after tumor resection. It is critical to check that no vessel is contact with the entire nerve root.

A new β-tetralonyl glucoside, methylberchemiaside (1), along with five known compounds (2–6) were isolated from a fungus Colletotrichum sp. GDMU-1 derived from the leaves of Santalum album. Their structures were determined by detailed analysis of spectroscopic data. All compounds were tested for the inhibitory effects on the nitric oxide (NO) production in lipopolysaccharide (LPS)-treated RAW264.7 cells. Among them, compounds 4 and 5 showed moderate anti-inflammatory activity with IC50 value of 30.4 and 8.9 μM, respectively.

Two new spiromeroterpenoids, namely fusariumin A (1) and B (2), along with four known terpenoids, asperterpenoid A (3), agathic acid (4), guignardone N (5), and trametenolic acid (6), were obtained from the endophytic fungus Fusarium sp. YD-2, derived from the twigs of Santalum album. Their structures were elucidated by a combination of spectroscopic analyses. The absolute configuration of 1 was determined by single-crystal X-ray diffraction using Cu Kα radiation, and that of 2 was elucidated on the basis of experimental and calculated electronic circular dichroism spectra. Compound 2 exhibited moderate anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide activated RAW264.7 cells with an IC50 value of 50 μM, and compound 3 showed strong anti-inflammatory activity with an IC50 value of 1.6 μM. In the antibacterial assay, compound 1 displayed significant activities against Staphylococcus aureus and Pseudomonas aeruginosa with an MIC value of 6.3 μg mL−1, and compound 3 showed moderate activities against Salmonella enteritidis and Micrococcus luteus with MIC values of 6.3 and 25.2 μg mL−1, respectively.

We conducted the first real-world study of treatment with omalizumab, a humanized monoclonal anti-immunoglobulin E antibody, in Chinese patients with severe allergic asthma.The primary objective was the steroid-sparing effect of omalizumab after 12 and 16 weeks of treatment. Characteristics of the patient population, treatment patterns, response rate, and other measures of therapeutic effectiveness were also reported.This nationwide, retrospective, real-world study was conducted in patients with severe allergic asthma who were treated with omalizumab in China. Data, including demographics, Asthma Control Test (ACT) and laboratory and lung function test results, and omalizumab use information, were extracted from patient records collected as part of a previously conducted real-world survey (Asthma Group of the Respiratory Disease Society of the Chinese Medical Association).In total, 139 patient records were included; 131 and 118 patients remained on treatment at the ≥12- and ≥16-week time points, respectively. The mean ± standard deviation age and median asthma duration (interquartile range) were 47.4 ± 14.3 and 7 (4, 15) years, respectively; 75.6% of patients had a history of allergic disease. Reductions (versus baseline) in inhaled corticosteroid/long-acting β2 agonists or oral corticosteroids were reported in 61.1% and 63.6% of patients at ≥12 and ≥ 16 weeks, respectively. There were significant improvements in ACT scores (6.08, P .001) and nitric oxide fraction in exhaled air (-13.0, P = .01) from baseline. Multivariate analysis revealed that age and allergic medical history were predictors of omalizumab treatment response. No serious adverse events were reported.Real-world omalizumab treatment was efficacious and well-tolerated in Chinese patients with severe allergic asthma.

Adjunctive lacosamide treatment might be promising to treat seizures. However, the results remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy and safety of adjunctive lacosamide versus placebo in patients with seizures.PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of adjunctive lacosamide versus placebo on seizures were included. Two investigators independently searched articles, extracted data and assessed the quality of included studies. The primary outcomes were 50% responder rate and seizure freedom.Four RCTs involving 1199 patients were included in the meta-analysis. Overall, compared with placebo treatment, adjunctive lacosamide treatment was associated with a significantly increased 50% responder rate (RR = 1.89; 95% CI = 1.51-2.36; P0.00001) and seizure freedom (RR = 4.97; 95% CI = 1.78-13.91; P = 0.002), but improved dizziness (RR = 3.97; 95% CI = 2.91-5.42; P0.00001), nausea (RR = 2.85; 95% CI = 1.75-4.66; P0.0001), vomiting (RR = 4.11; 95% CI = 2.23-7.57; P0.00001), diplopia (RR = 6.85; 95% CI = 3.36-13.94; P0.00001), treatment-emergent adverse events (RR = 2.29; 95% CI = 1.93-2.71; P0.00001) and serious adverse events (RR = 2.52; 95% CI = 1.33-4.78; P = 0.005).Compared to placebo, adjunctive lacosamide resulted in a significantly improved 50% responder rate and seizure freedom, but with increased dizziness, nausea, vomiting, diplopia, treatment-emergent adverse events and serious adverse events.

Background This retrospective analysis of patients who underwent adrenalectomy for pheochromocytoma aimed to determine preoperative risk factors for intraoperative massive blood loss. Preoperative identification of patients at high-risk of massive blood loss may be helpful in anesthesia management and preoperative preparation. Materials and Methods The study involved data of 268 patients who had undergone pheochromocytoma surgery at the Peking Union Medical College Hospital between January 1, 2013 and October 31, 2016. For analysis, the patients were grouped according to intraoperative blood loss: ≥ 20% of estimated blood volume (group A, n = 38) and < 20% of estimated blood volume (group B, n = 230). Perioperative characteristics were compared between the two groups. Significant variables were selected for a forward stepwise binary logistic regression analysis to determine the independent risk factors for massive blood loss. Results The two groups showed significant differences in tumor location, tumor size, operative approach, preoperative 24-hour urine level of total noradrenaline, preoperative hemoglobin concentration, phenoxybenzamine maximum daily dose, preoperative preparation time, intraoperative urine volume, crystalloid and colloidal fluid volumes, allogeneic red blood cell transfusion, plasma and autologous blood transfusion volumes, incidence of prolonged hypotension, postoperative drainage volume, lowest and discharge hemoglobin concentrations, length of stay in intensive care unit and length of postoperative hospitalization. Binary logistic regression analysis indicated increased risk of intraoperative massive blood loss in subjects with tumors proximal to vessels or other organs (odds ratio (OR): 4.227), with tumors ≥ 5 cm (OR: 7.321), or with preoperative preparation time of ≤ 14 days (OR: 17.747). Conclusions Tumors proximal to vessels and other organs or with maximum diameter of ≥ 5 cm (as shown by preoperative radiographic evidence), and preoperative preparation time of ≤ 14 days were independent risk factors of intraoperative massive blood loss in patients treated with adrenalectomy for pheochromocytoma.

Advancements in mobile technologies mean that consumers can engage the digital world wherever they are and whenever they want. This intersection between the digital and the physical has important implications for consumer decision-making. We propose that mobile ecosystems vary in their capabilities and pervasivity (i.e., the degree to which a mobile ecosystem is accessible everywhere and at all times). Further, we propose that accounting for distinguishing aspects of mobile ecosystems, the context in which mobile ecosystems are used, and interactions between mobile ecosystems and mobile contexts are critical in advancing theoretical and substantive understanding of the role of mobile technologies in the marketplace. Based on this perspective, we identify important research topics as well as opportunities and challenges for modeling mobile consumer decision-making.

Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HU-like epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.

The myogenesis of skeletal muscle has several stages, including satellite cell proliferation, differentiation, fusion and specific muscle formation. Recent studies have shown that myomaker, a muscle-specific transmembrane protein, was critical for myoblasts fusion. However, the regulatory mechanism of myomaker and its effects on myogenesis remain elusive. In this study, miR-491 was identified as a post-transcriptional regulator of myomaker, which binds specifically to its 3' untranslated region leading to its down-regulation. At the end of myotube differentiation, the expression levels of miR-491 increased drastically, while myomaker was significantly down-regulated, which indicated that miR-491 shut down the expression of myomaker. Functional studies showed that miR-491 overexpression suppressed muscle cell differentiation and adult muscle regeneration, while the inhibition of miR-491 promoted myotube differentiation. Taken together, our findings identified miR-491 as a novel negative regulator of myogenic differentiation through targeting myomaker.

Disuse leads to severe muscle atrophy and a slow-to-fast myofiber-type transition. PGC-1α (Peroxisome proliferator-activated receptor γ coactivator 1α) is documented to play an important role in muscle atrophy and slow-twitch myofiber determination. Transcription of atrophy-related Atrogin-1 by FoxO3 can be reduced by PGC-1α. While Smad3 augments FoxO3-induced Atrogin-1 and MuRF1 promoter activity. So PGC-1α, as a transcription co-activator, may regulate hindlimb unloading (HU)-induced myofiber-type transition and muscle atrophy through Smad3. Our results showed that transgenic PGC-1α mice resisted HU-induced muscle loss, atrophy-related genes expression, and slow-to-fast myofiber-type transition. Furthermore, over-expression of PGC-1α resisted the increase in pSmad3 during muscle atrophy in vivo and in vitro. And, PGC-1α over-expression inhibited the expression of atrogenes via suppressing the phosphorylation of Smad3 in vitro. Thus, PGC-1α is effective in regulating myofiber-type transition during HU, and it alleviates skeletal muscle atrophy partially through suppressing the activation of Smad3.

Membrane technology has been one of the most promising techniques to solve the water problem in future. Unfortunately, it suffers from the fouling problem which is ubiquitous in membrane systems. The origin of the bewilderments of the fouling problem lies in the lack of deep understanding. Recent studies have pointed out that the molecular structure of foulant affects its fouling propensity which has been ignored in the past. In this study, the filtration behaviors of alginate blocks derived from the same source were comprehensively explored. Alginate blocks share the same chemical composition but differ from each other in molecular structure. The alginate was first extracted from natural seaweed using calcium precipitation and ion-exchange methods. Extracted alginate was further fractionized into MG-, MM- and GG-blocks and the characteristics of the three blocks were examined by Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM) observations, and transparent exopolymer particles&rsquo, (TEPs) measurements. Results showed that MG-, MM- and GG-blocks had the same functional groups, but they showed different intermolecular interactions. TEP formation from MG-, MM- and GG-blocks revealed that the molecule crosslinking of them decreased in the order of MM-blocks &gt, GG-blocks &gt, MG-blocks. It was further found from microfiltration tests that these alginate blocks had completely different fouling propensities which can be explained by the TEP formation. TEPs would accumulate on membrane surfaces and worked as a pre-filter to avoid serious pore blocking of membrane. That all suggested that the membrane fouling was closely related to the molecular structure of foulant. It is expected that this study can provide useful insights into the fouling propensities of different types of polysaccharides during filtration processes.

It is known that many diseases are caused by mutations or abnormalities in microRNA (miRNA). The usual method to predict miRNA disease relationships is to build a high-quality similarity network of diseases and miRNAs. All unobserved associations are ranked by their similarity scores, such that a higher score indicates a greater probability of a potential connection. However, this approach does not utilize information within the network. Therefore, in this study, we propose a machine learning method, called STIM, which uses network topology information to predict disease&ndash, miRNA associations. In contrast to the conventional approach, STIM constructs features according to information on similarity and topology in networks and then uses a machine learning model to predict potential associations. To verify the reliability and accuracy of our method, we compared STIM to other classical algorithms. The results of fivefold cross validation demonstrated that STIM outperforms many existing methods, particularly in terms of the area under the curve. In addition, the top 30 candidate miRNAs recommended by STIM in a case study of lung neoplasm have been confirmed in previous experiments, which proved the validity of the method.

China established a self-organized and market-driven recycling system, which was dominated by the informal sectors. In recent years, the amount of domestically-recycled waste paper grew slower than expectation in China, which may be resulted from a decline in economic sustainability of current recycling system. For understanding the waste paper recycling system in most cities in China, the economic mechanism remains unclear and the city-level data is extremely insufficient. In this work, an index of recycling sustainability (IRS, benefit divided by cost) is analyzed with a resolution of 1 km2 grid in Beijing City, by adopting value chain and GIS methodology. Five degrees of IRS are defined, from high-degree (IRS > 1.10) to low-degree (IRS

Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management., Interactions among spinal dorsal horn neurons and microglia contribute to the induction and maintenance of neuropathic pain after peripheral nerve injury. The authors show that depletion of macrophages in the dorsal root ganglia prevents and reverses ongoing nerve injury-induced hypersensitivity.

Background To investigate the effects of core stability training (CST) on an unstable support surface (USS) on the balance and ambulation function of individuals with chronic spinal cord injury (SCI). Methods Twenty-nine chronic patients with SCI were randomly divided into experiment group (N.=14) and control group (N.=15). The two groups received residual extremity muscle strengthening exercises (REMSE), body weight supported treadmill (BWSTT) training and CST five times per week for 12 weeks. Patients in control group were implemented CST on a stable support surface (SSS), but patients in experiment group on an unstable support surface (USS) created by sling in lying and physio-ball in sitting position. Gait and balance, static and dynamic, data were collected and analyzed by 3D Motion Analysis Software Version 1.0 (America) and Active Balancer EAB-100 (Sakai Iryo, Japan) respectively. Results After the 12-week intervention, stride length, cadence, comfortable walking speed (P=0.025, 0.028, 0.009), and Romberg ratio of WPL, UPL, circumference area (CA), effective value area (EVA) (P=0.009, 0.009, 0.043, 0.049) and DCDX with eyes closed (P=0.036) of static balance showed significant differences between the two groups with the unstable group showing a better outcome. Conclusions Our pilot study was feasible to deliver. When combined with REMSE and BWSTT, CST on an USS surpasses SSS in terms of improving chronic SCI patients' ambulation and static balance function after a 12-week intervention.

Eight new dimeric sorbicillinoids (1–3, 5–9) and 12 new monomeric sorbicillinoids (10–20, 25), along with five known analogues (4 and 21–24), were isolated from the marine-derived fungus Trichoderma reesei 4670. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-ESIMS, and ECD) and X-ray crystallography. Compound 1, containing a pyrrolidin-2-one moiety, is reported for the first time in the sorbicillinoid family. Compounds 8 and 9 are the first examples of bisorbicillinoids possessing a benzofuro[2,3-h]chromene scaffold from a natural source. Compounds 3–11, 13–16, 18, 21, 22, 24, and 25 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide with IC50 values in the range from 0.94 to 38 μM. Structure–activity relationships of the sorbicillinoids were discussed.

Four new polyketides, including an unusual naphthoquinone derivative (1), two azaphilone analogous (2, 7) and an α-pyrone (12), were isolated from the gorgonian-derived fungus Penicillium sclerotiorum CHNSCLM-0013 together with nine known compounds. Their structures were identified based on the 1D, 2D NMR, HRESIMS, single crystal X-ray diffraction and the absolute configurations were determined by comparing the 1H NMR chemical shift and optical rotations with those reported in literature. In the bioassay, compounds 2, 6, 7, 10 and 12 exhibited significant inhibitory activities against the nitric oxide (NO) production in the LPS-induced macrophage RAW 264.7 with the IC50 values in the range of 2.5–18.0 μM. Compounds 2, 6 and 7 exhibited the possible mechanism of downregulating the expression of iNOS and COX-2 in mRNA level. The primary structure-activity relationship was also discussed based on the molecular-modeling. This study will make a contribution to the chemical diversities of polyketides especially the azaphilone derivatives and the discovery of potential anti-inflammatory agent from marine fungi.

Experiments were conducted using a bubbling reactor to investigate nitrogen oxide absorption in the calcium sulfite slurry. The effects of CaSO3 concentration, NO2/NO mole ratio and O2 concentrations on NO2 and SO2 absorption efficiencies were investigated. Five types of additives, including MgSO4, Na2SO4, FeSO4, MgSO4/Na2SO4 and FeSO4/Na2SO4, had been evaluated for enhancing NO2 absorption in CaSO3 slurry. Results showed that CaSO3 concentration had significant impact on NO2 and SO2 absorption efficiencies, and the highest absorption efficiencies of SO2 and NO2 could reach about 99.5 and 75.0 %, respectively. Furthermore, the NO2 absorption was closely related to the NO2/NO mole ratio, and the existence of NO2 in flue gas may promote NO absorption. The presence of O2 in simulated flue gas was disadvantage for NO x removal because it can oxidize sulfite to sulfate. It was worth pointing out that FeSO4/Na2SO4 was the best additive among those investigated additives, as the NO2 removal efficiency was significantly increased from 74.8 to 95.0 %. IC and in situ FTIR results suggest that the main products were NO3 − and NO2 − in liquid phase and N2O, N2O5 and HNO3 in gas phase during the CaSO3 absorption process.

An unusual austinoid, 1,2-dehydro-terredehydroaustin (1), together with two known meroterpenoids (2 and 3), were isolated from the mangrove endophytic fungus Aspergillus terreus. The structures were elucidated on the basis of spectroscopic data, X-ray diffraction and ECD calculations. The anti-inflammatory activity was assayed and compound 1 exhibited weak inhibition effect against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 246.7 mouse macrophages with an IC50 value of 42.3 μM.

Five new maleimide derivatives, (+)- and (−)- farinomalein F (1), (+)- and (−)- farinomalein G (2), farinomalein H (3) and one new linearly fused prenylated indole alkaloid phomoamide (8), along with five known compounds 4–7 and 9 were isolated from the mangrove endophytic fungus Phomopsis sp. SYSUQYP-23. Their structures and absolute configurations were determined by HRESIMS, spectroscopic and electronic circular dichroism (ECD) calculations. Bioassay results showed that compounds 3–9 exhibited significant inhibitory activities against nitric oxide (NO) production in lipopolysaccharides (LPS) induced RAW 264.7 cells, with IC50 values ranging from 4.5 to 25 μM. Moreover, the molecular docking study implied the probable binding interaction of compounds 4 and 5 with nitric oxide synthase.

Polyvinyl chloride (PVC) is a widely consumed plastic material and may lead various environmental pollutions. China produces and consumes the largest amount of PVC material in the world, owing to its rapid urbanization and economic growth. Herein, we establish a dynamic material flow analysis methodology for quantifying PVC stocks and flows in China, including material input, manufacturing and consumption distribution, and waste management stage. We examine the material flow of PVC in China from 1980 to 2015. The PVC trajectory analysis from 2016 to 2050 is based on the historical PVC material consumption data and scenario analysis. Total amount of PVC consumption in all types of products dramatically increased from 0.4 Mt (0.4 kg/capita) in 1980 to 14.5 Mt (10.7 kg/capita) in 2015, with a cumulative amount of 173.7 Mt. The rapid increase of PVC consumption in China significantly accelerated the PVC waste accumulation, reaching 66.3 Mt, accounting for 38.2% of total PVC use from 1980 to 2015. Building & construction sector has the largest PVC in-use stock, while consumer goods sector generated the largest PVC waste. In recent fifteen years, mechanical recycling, chemical recycling, incineration, and landfill of PVC waste ratios are 25.5%, 0.8%, 9.3%, and 36.0%, respectively. The PVC trajectory analysis shows that by the end of 2050, the accumulative PVC waste in China will be 508.6 Mt in the limited growth scenario and 562.0 Mt in the business as usual scenario. Based on the MFA results, policies for improving PVC recycling system were analyzed in this work.

Diaporindenes A-D (1-4), four unusual 2,3-dihydro-1 H-indene isomers, a novel isoprenylisobenzofuran A (5), two new isoprenylisoindole alkaloids diaporisoindoles D and E (6 and 7), and a new benzophenone derivative tenellone D (11), together with four known biogenetic agents (8-10 and 12), were all separated from the endophytic fungus Diaporthe sp. SYSU-HQ3 guided by ultraperformance liquid chromatography high-resolution mass spectrometry. The absolute configurations of 1-7 and 11 were defined by X-ray diffraction, quantum chemical calculations, and spectroscopic analysis. Diaporindenes A-D (1-4) possessed an unprecedented chemical skeleton featuring a 2,3-dihydro-1 H-indene ring and a 1,4-benzodioxan moiety. All of the isolates (1-12) were tested for their inhibitory effects on the production of nitric oxide in lipopolysaccharide-induced microglial cells (RAW 264.7 cells). Compounds 1-5, 8, and 9 were found to exhibit significant inhibitory effects against nitric oxide production with IC50 values from 4.2 to 9.0 μM and SI values from 3.5 to 6.9. In addition, the structure-activity relationships of all compounds were summarized.

Two new spiromeroterpenoids, namely fusariumin A (1) and B (2), along with four known terpenoids, asperterpenoid A (3), agathic acid (4), guignardone N (5), and trametenolic acid (6), were obtained from the endophytic fungus

OBJECT Typical hemifacial spasm (HFS) commonly initiates from the orbicularis oculi muscle to the orbicularis oris muscle. Atypical HFS (AHFS) is different from typical HFS, in which the spasm of muscular orbicularis oris is the primary presenting symptom. The objective of this study was to analyze the sites of compression and the effectiveness of microvascular decompression (MVD) for AHFS. METHODS The authors retrospectively analyzed the clinical data for 12 consecutive patients who underwent MVD for AHFS between July 2008 and July 2013. RESULTS Postoperatively, complete remission of facial spasm was found in 10 of the 12 patients, which gradually disappeared after 2 months in 2 patients. No recurrence of spasm was observed during follow-up. Immediate postoperative facial paralysis accompanied by hearing loss occurred in 1 patient and temporary hearing loss with tinnitus in 2. All 3 patients with complications had gradual improvement during the follow-up period. CONCLUSIONS The authors conclude that most cases of AHFS were caused by neurovascular compression on the posterior/rostral side of the facial nerve distal to the root entry zones. MVD is a safe treatment for AHFS, but the incidence of postoperative complications, such as facial paralysis and decrease in hearing, remains high.

Sustainable human space exploration could progress further with the development of strategies and preparatory activities. However, this progression is largely dependent on ground-based experimental programmes that reflect the limitations of space. The head-down bed rest (HDBR) model simulates the effects of weightlessness on humans. While many physiological indices and their associations with HDBR-induced weightlessness have been well documented in the last several years, the underlying molecular mechanisms remain unknown. Therefore, we used a 6° HDBR model, combined with a metabolomics approach, to reveal novel molecular mechanisms underlying the human responses to weightlessness. A total of 7 volunteers (male, 26.13 ± 4.05 years) were recruited for a standard 45-day HDBR experiment, and their physiological indices associated with bone, muscle, and the gut microbiota were measured. Furthermore, urine samples were collected in nine different phases and analysed using one-dimensional proton nuclear magnetic resonance spectroscopy (1H-NMR) to investigate human metabolic responses to HDBR. The results showed that the urinary excretion of metabolites associated with the deconditioning of bone, muscle and the gut microbiota in response to HDBR changed dramatically over the 45-day experimental period. Meanwhile, the bone, muscle and gut microbiota of the subjects declined after HDBR. Thus, bioinformatics approaches, such as metabolomics analysis, could achieve a more accurate and comprehensive analysis and subsequently provide new insight.

Introduction: Disuse muscle atrophy, induced by prolonged space flight, bed rest, or denervation, is a common process with obvious changes in slow-twitch soleus muscles. Methods: Proteomic analysis was performed on mouse soleus subjected to hindlimb unloading (HU) and hindlimb reloading (HR) to identify new dysregulated proteins. Results: Following HU, the mass and cross-sectional area of muscle fibers decreased, but they recovered after HR. Proteomic analyses revealed 9 down-regulated and 7 up-regulated proteins in HU, and 2 down-regulated and 5 up-regulated proteins in HR. The dysregulated proteins were mainly involved in energy metabolism, protein degradation, and cytoskeleton stability. Among the dysregulated proteins were fatty acid binding protein 3, α-B crystalline, and transthyretin. Conclusions: These results indicate that muscle atrophy induced by unloading is related to activation of proteolysis, metabolic alterations toward glycolysis, destruction of myofibrillar integrity, and dysregulation of heat shock proteins (HSPs). The dysregulated proteins may play a role in muscle atrophy and the recovery process. Muscle Nerve 52: 803–811, 2015

Chemical investigation of the endophytic fungus Aspergillus sp. 16-5B cultured on Czapek’s medium led to the isolation of four new metabolites, aspergifuranone (1), isocoumarin derivatives (±) 2 and (±) 3, and (R)-3-demethylpurpurester A (4), together with the known purpurester B (5) and pestaphthalides A (6). Their structures were determined by analysis of 1D and 2D NMR spectroscopic data. The absolute configuration of Compound 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra, and that of Compound 4 was revealed by comparing its optical rotation data and CD with those of the literature. The structure of Compound 6 was further confirmed by single-crystal X-ray diffraction experiment using CuKα radiation. All isolated compounds were evaluated for their α-glucosidase inhibitory activities, and Compound 1 showed significant inhibitory activity with IC50 value of 9.05 ± 0.60 μM. Kinetic analysis showed that Compound 1 was a noncompetitive inhibitor of α-glucosidase. Compounds 2 and 6 exhibited moderate inhibitory activities.

Iron is involved in various physiological processes of the human body to maintain normal functions. Abnormal iron accumulation in brain has been reported as a pathogenesis of several neurodegenerative disorders and cognitive impairments. Hemojuvelin (HVJ) is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis. Although iron accumulation in brain has been related to neurodegenerative diseases, it remains unknown the effect of mutation of HVJ gene on cognitive performance. In our studies, HJV(−/−) mice showed deficits in novel object recognition and Morris water maze tests. Furthermore, the expression ration of apoptotic marker Bax and anti-apoptotic marker Bcl-2 in the hippocampus and prefrontal cortex showed higher levels in HJV(−/−) mice. Our results suggested that deletion of HJV gene could increase apoptosis in brain which might contribute to learning and memory deficits in mutant mice. These results indicated that HJV(−/−) mice would be a useful model to study cognitive impairment induced by iron overload in brain.

Objective Although repeat microvascular decompression (MVD) for hemifacial spasm (HFS) in patients with failed prior MVD is potentially curative, little is known about the long-term results of repeat MVD. We aimed to evaluate the long-term outcomes and complications after repeat MVD for HFS. Methods We performed repeat MVD on 78 consecutive patients who had undergone a prior MVD >1 year previously. Follow-up data were available for 58 patients, with a median follow-up period of 8.6 years (range, 6.9–10.2 years). The patients were assessed for intraoperative findings, relief results, and complications at discharge and at follow-up, as well as the associations between the preoperative characteristics and outcomes. Results At discharge, of 78 patients with repeat MVD, 72 (92.3%) achieved complete spasm resolution and 1 (2.6%) had significantly improved spasm resolution. Of all patients, 9% (7 of 78) presented short-term complications, including partial hearing loss, hemifacial paresis, and cerebrospinal fluid leak. At follow-up, 45 of 58 (77.6%) patients had complete relief and 10 of 58 (17.2%) had improved relief. Permanent complications occurred in 14 patients (24.1%), with partial hearing loss and mild hemifacial paresis being the most common. Despite the complications, 51 of 58 patients (91.4%) reported an excellent life quality. No significant correlation was found between preoperative characteristics, such as age, interval to prior MVD, or interval to recurrence, and outcomes including short-term or long-term relief results and complications. Conclusions Repeat MVD provides lasting relief for most patients with persistent or recurrent HFS, albeit with a relatively high complication rate.

Four previously undescribed meroterpenoids, amestolkolides A−D, along with three known compounds were isolated from the mangrove endophytic fungus Talaromyces amestolkiae YX1 cultured on wheat solid-substrate medium culture. Their structures were elucidated by a combination of spectroscopic analyses. The absolute configurations of amestolkolides B and C, and purpurogenolide E were determined by single-crystal X-ray diffraction using Cu Kα radiation, and those of amestolkolides A and D were elucidated on the basis of experimental and calculated electronic circular dichroism spectra. The absolute configuration of amestolkolides A-D, and purpurogenolide E (9R) at C-9 was different from that of analogues (9S) in references, so that their plausible and distinct biosynthetic pathways were proposed. Amestolkolide B showed strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide activated in RAW264.7 cells with IC50 value of 1.6 ± 0.1 μM.

Five isocoumarin derivatives including three new compounds, aspergisocoumrins A–C (1–3), together with two known analogues, 8-dihydroxyisocoumarin-3-carboxylic acid (4) and dichlorodiaportin (5) were obtained from the culture of the endophytic fungus Aspergillus sp. HN15-5D derived from the fresh leaves of the mangrove plant Acanthus ilicifolius. Their structures were elucidated using comprehensive spectroscopic methods. The double bond geometry of compounds 1 and 2 were assigned as E and Z on the basis of the distinct coupling constants, respectively. Compounds 1 and 2 showed cytotoxicity against MDA-MB-435 with IC50 values of 5.08 ± 0.88 and 4.98 ± 0.74 μM, respectively.

Background Simvastatin might be beneficial to the patients with aneurysmal subarachnoid hemorrhage. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the efficacy of simvastatin for aneurysmal subarachnoid hemorrhage. Methods PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of simvastatin versus placebo on aneurysmal subarachnoid hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were delayed ischaemic deficit and delayed cerebral infarction. Meta-analysis was performed using the random-effect model. Results Six RCTs involving 1053 patients were included in the meta-analysis. Overall, compared with control intervention, simvastatin intervention had no influence on delayed ischaemic deficit (RR = 0.99; 95% CI = 0.78 to 1.27; P = 0.96), delayed cerebral infarction (RR = 1.17; 95% CI = 0.60 to 2.29; P = 0.65), mRS ≤ 2 (RR = 0.97; 95% CI = 0.87 to 1.09; P = 0.61), vasospasm (RR = 0.79; 95% CI = 0.49 to 1.29; P = 0.35), ICU stay (Std. mean difference = 0.04; 95% CI = − 0.54 to 0.63; P = 0.88), hospital stay (Std. mean difference = 0.01; 95% CI = − 0.13 to 0.14; P = 0.90) and mortality (RR = 0.71; 95% CI = 0.25 to 2.05; P = 0.53) after aneurysmal subarachnoid hemorrhage. Conclusions Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS ≤ 2, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage.

Membrane technology has been widely applied for water treatment, while membrane fouling still remains a big challenge. The polysaccharides in extracellular polymeric substances (EPS) have been known as a significant type of foulant due to their high fouling propensity. However, polysaccharides have many varieties which definitely behave differently in membrane filtration. Therefore, in this study, different polysaccharides alginate sodium and xanthan gum were chosen to study their effects on membrane fouling in a wide concentration range. The results demonstrated that the filtration behaviors of alginate sodium and xanthan gum were completely different, which was due to their different molecular structures. Alginate had a small molecular weight and it was easy for alginate to penetrate membrane pores resulting in pore blocking. A series of concentrations of alginate including 5 mg/L, 10 mg/L, 20 mg/L, 30 mg/L, 40 mg/L, and 50 mg/L were examined and it was found that the permeate flux decline highly depended on the level of alginate in the feed water. While for the filtration of xanthan gum, the same concentration of xanthan gum led to more serious fouling than that observed in alginate, which might be due to its large molecule. In addition, calcium chloride was added in the solutions of both alginate and xanthan gum to examine the influence of a divalent cation on polysaccharide fouling. A &ldquo, unimodal&rdquo, peak can be observed in the fouling propensity caused by Ca2+ and alginate with increasing the concentration of alginate. Such a phenomenon was not found in the fouling of xanthan gum and Ca2+ led to more serious fouling for all concentrations of xanthan gum. In light of this, this study gave new insights into the fouling propensities of different polysaccharides.

Aims and objectives To investigate the developing course of postoperative pain in a Chinese sample of patients following thoracic surgery. Background Chronic postoperative pain following thoracic surgery including both thoracotomy and video-assisted thoracic surgery is often reported. However, research on pain trends concerning this topic is scarce with a notable lack of culturally focused studies by nurses. Design A prospective observational study. Methods The sample included patients undergoing thoracotomy (n = 137) and video-assisted thoracic surgery (n = 143). Pain intensity and interference of pain with function were assessed during hospitalisation (day 1 to day 7 postoperatively) and followed up by telephone at 2 weeks and then at 1, 2, 3 and 6 months after surgery. Results Moderate-to-severe pain when coughing and moving was reported in over 85% during hospitalisation, and a significant difference in pain was found between those undergoing a thoracotomy (61%) and those having video-assisted surgery (34%). Many patients whose immediate postoperative pain was poorly managed tended to report high pain levels after discharge and continued to have clinically important chronic pain 6 months after surgery. The pain intensity mean score during movement in the first five postoperative days was an important predictor of clinically important chronic pain, and those experiencing severe acute pain during hospitalisation had a higher probability of developing chronic pain. Conclusions Postoperative pain after thoracic surgery warrants greater attention because those experiencing severe acute pain during hospitalisation have a higher probability of developing chronic pain. Aggressive pain management and multimodal analgesia are recommended to prevent long-term suffering in patients. Relevance to clinical practice Chronic pain after thoracic surgery remains a challenge in clinical nursing. To improve pain management quality and to prevent the transition of acute postoperative pain to chronic pain, standardised practice protocols and comprehensive physician and nurse education are highly recommended.

Muscle biopsy has long been expected to be replaced by noninvasive biomarkers with diagnostic value and prognostic applications for muscle atrophy. Growing evidence suggests that circulating microRNAs (miRNAs) could act as biomarkers for numerous pathophysiological statuses. In the present study, our results showed that the serum levels of six muscle-specific miRNAs (miR-1/23a/133/206/208b/499) were all elevated in unloading induced mice. The medium levels of these six muscle-specific miRNAs were all elevated in starvation induced atrophic C2C12 myotubes. Moreover, the serum levels of miR-23a/206/499 were induced in participants after 45 days of head-down bed rest (HDBR). The levels of miR-23a/206/499 were positively correlated with the ratio of soleus volume loss in HDBR participants, indicating that they might represent the process of muscle loss. In conclusion, our results demonstrated that circulating miRNAs could serve as useful biochemical and molecular indicators for muscle atrophy diagnosis and disease progression.

A simple, sensitive and specific liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantitate nevadensin in rat plasma using genistein as the internal standard (IS). The assay was based on protein precipitation treatment with acetonitrile and liquid chromatography performed on a reverse-phase Zorbax SB-C(18) column (50 mm × 2.1 mm, 1.8 μm). Elution was achieved with a mobile phase consisted of aqueous solution containing 0.1% formic acid (solvent A) and methanol solution containing 0.1% formic acid (solvent B) at a flow rate of 300 μL/min (30:70, v/v). Quantification was through tandem-mass spectrometry with positive electrospray ionization (ESI) and multiple reaction monitoring (MRM) at m/z 345.1→315.1 and 271.1→215.1 for nevadensin and IS, respectively. Calibration curves were linear over the nevadensin rat plasma concentration range of 0.1-300 ng/mL. The lower limit of quantification (LLOQ) was 0.100 ng/mL and the inter- and intra-day accuracy and precision ranged between -1.67% and 7.60%. The average recovery of nevadensin was 95.6-99.1%. The validated method was successfully applied to the pharmacokinetic evaluation of nevadensin using the rat as an animal model following an oral administration of 50mg/kg nevadensin.

Our objective was to identify suitable reference genes in serum miRNA for normalization and screen potential new biomarkers for osteoporosis diagnosis by a systematic study. Two types of osteoporosis models were used like as mechanical unloading and estrogen deficiency. Through a large-scale screening using microarray, qPCR validation and statistical algorithms, we first identified miR-25-3p as a suitable reference gene for both type of osteoporosis, which also showed stability during the differentiation processes of osteoblast and osteoclast. Then 15 serum miRNAs with differential expression in OVX rats were identified by microarray and qPCR validation. We further detected these 15 miRNAs in postmenopausal women and bedrest rhesus monkeys and evaluated their diagnostic value by ROC analysis. Among these miRNAs, miR-30b-5p was significantly down-regulated in postmenopausal women with osteopenia or osteoporosis; miR-103-3p, miR-142-3p, miR-328-3p were only significantly decreased in osteoporosis. They all showed positive correlations with BMD. Except miR328-3p, the other three miRNAs were also declined in the rhesus monkeys after long-duration bedrest. Their AUC values (all >0.75) proved the diagnostic potential. Our results provided a reliable normalization reference gene and verified a group of circulating miRNAs as non-invasive biomarkers in the detection of postmenopausal- and mechanical unloading- osteoporosis.

This paper proposes a remote intelligent medical monitoring network solution. It can make real time acquisition and storage of physiological parameters of patients and send corresponding data to monitoring center. The location of patient can be also tracked by locating technology. The scheme can provide the doctors better methods to diagnose the patient remotely and prompt medical service, which is conducive to the realization of the patient's physiological monitoring. By the analysis of test results in monitoring network, it is found that the monitoring end can provide better medical service and it completes the expected design objects.

Background— Sustained cardiac pressure overload–induced hypertrophy and pathological remodeling frequently leads to heart failure. Casein kinase-2 interacting protein-1 (CKIP-1) has been identified to be an important regulator of cell proliferation, differentiation, and apoptosis. However, the physiological role of CKIP-1 in the heart is unknown. Methods and Results— The results of echocardiography and histology demonstrate that CKIP-1–deficient mice exhibit spontaneous cardiac hypertrophy with aging and hypersensitivity to pressure overload–induced pathological cardiac hypertrophy, as well. Transgenic mice with cardiac-specific overexpression of CKIP-1 showed resistance to cardiac hypertrophy in response to pressure overload. The results of GST pull-down and coimmunoprecipitation assays showed the interaction between CKIP-1 and histone deacetylase 4 (HDAC4), through which they synergistically inhibited transcriptional activity of myocyte-specific enhancer factor 2C. By directly interacting with the catalytic subunit of phosphatase 2A, CKIP-1 overexpression enhanced the binding of catalytic subunit of phosphatase-2A to HDAC4 and promoted HDAC4 dephosphorylation. Conclusions— CKIP-1 was found to be an inhibitor of cardiac hypertrophy by upregulating the dephosphorylation of HDAC4 through the recruitment of protein phosphatase 2A. These results demonstrated a unique function of CKIP-1, by which it suppresses cardiac hypertrophy through its capacity to regulate HDAC4 dephosphorylation and fetal cardiac genes expression.

A sensitive, selective and robust liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the rapid determination of linarin in rat plasma. Separation of the analyte and warfarin as internal standard (IS) from 100 μL rat plasma was carried out by simple protein precipitation treatment. Chromatographic separation of the analyte was performed on a Diamonsil® C18 column (150 × 4.6 mm, 5 µm) using isocratic mobile phase consisting of methanol–0.5% formic acid (80:20, v/v). The flow rate was 0.6 mL/min and the total run time was not more than 4.0 min. The method was validated over a wide dynamic concentration range of 1.00–1000 ng/mL for linarin. The precision and accuracy values for linarin met the acceptance criteria according to US Food and Drug Administration guidelines. Linarin was stable in the stability studies including a long-term test (−80°C for 43 days), a short-term test (ambient for 2 h and autosampler for 8 h) and three freeze–thaw cycles (−80–25°C). The developed assay method was applied to the pharmacokinetic study in rats after a single intramuscular administration of 713 µg/kg linarin. Copyright © 2012 John Wiley & Sons, Ltd.

Nintendo lost its dominant position in the video game industry during the console war between its Nintendo 64 and Sony's PlayStation. However, Nintendo could have made several different strategic decisions to change the outcome. This article develops a structural model and investigates these alternative strategies through policy simulations. In particular, the author provides a framework to study firms' optimal pricing strategies under network effects, consumer heterogeneity, and oligopolistic competition. Consumer heterogeneity provides an incentive for a durable goods manufacturer to price skim, while network effects lead to an opposite motive for penetration pricing. The proposed framework incorporates these two competing motives under oligopolistic competition. The author estimates a demand system that allows for indirect network effects and consumer heterogeneity and then numerically solves for the Markov perfect equilibrium in firms' dynamic pricing game. Policy simulations indicate that Nintendo could have won the console war either with 10% more games or with a “head start” of one million units in installed base at the time of the PlayStation introduction.

Activation of cytotoxic T lymphocytes (CTLs) is a primary goal of many cancer vaccination therapies. We have evaluated two vaccination platforms, dendritic cells (DCs) and recombinant adenoviruses (rAds), for their ability to elicit CTL response and antitumor protection. Although rAd was more potent in CTL priming, DC vaccination provided greater protective and therapeutic antitumor activity. Subsequent analyses ruled out the possibility that the two vaccines elicit qualitatively distinct CTL, and demonstrated instead that DCs could better engage natural killer (NK) cells as an additional effector mechanism. We demonstrated that, although both DCs and rAd can stimulate rapid NK expansion, only DC-activated NK cells are able to produce interferon-gamma (IFN gamma) and mediate antitumor protection. Moreover, our data showed that exogenously delivered DCs preferentially engaged the Mac-1(high)CD27(high) NK subset, thereby suggesting that this NK population plays a predominant role in NK:DC interaction. Interestingly, at least 3 days were required for DC-triggered NK cells to acquire effector functions, indicating that a similar priming process operates between T cells and NK cells. Our results suggest that the nature of the vaccine platform can determine the relative involvement of NK and T cells in antitumor immunity, and that methods to augment NK function should be included in vaccination strategies in order to complement CTL-mediated control of tumor growth.

Advancements in mobile technologies mean that consumers can engage the digital world wherever they are and whenever they want. This intersection between the digital and the physical has important implications for consumer decision-making. We propose that mobile ecosystems vary in their capabilities and pervasivity (i.e., the degree to which a mobile ecosystem is accessible everywhere and at all times). Further, we propose that accounting for distinguishing aspects of mobile ecosystems, the context in which mobile ecosystems are used, and interactions between mobile ecosystems and mobile contexts are critical in advancing theoretical and substantive understanding of the role of mobile technologies in the marketplace. This perspective helps identify: 1) the types of data that empirical researchers may seek to gather and 2) the ways in which this data may be analyzed. Based on this perspective, we identify important research questions as well as opportunities and challenges for modeling mobile consumer decision-making.

Rhodiola rosea (R. rosea), a type of adaptogen, has been previously reported to exhibit immunostimulating activity in rodents and in human peripheral blood mononuclear cells (PBMCs) in vitro. To examine the effect of R. rosea on T cells under simulated microgravity, spaceflight analogs of human head‑down bed rest (HDBR) at ‑6˚ and murine hind limb unloading (HU) were used. A decrease in the levels of interferon‑γ (IFN‑γ) and interleukin‑17 (IL‑17) and an increase in regulatory T (Treg) cells were observed in the placebo group following HDBR. The R. rosea treated HBDR group demonstrated further decreased IFN‑γ production, however, R. rosea exhibited no effect on the ratio of circulating Tregs or Treg cell differentiation. By contrast, the treatment of R. rosea on human T cells in vitro did not alter IFN‑γ secretion, however, Treg differentiation was significantly reduced. An R. rosea‑induced upregulation of hypoxia‑inducible factor 1α (HIF‑1α) contributed to the suppression of Treg differentiation in vitro. Differences in the effect of R. rosea in vitro and in vivo were also observed using a mouse model of microgravity. The results of the current study suggest that R. rosea has differential modulatory effects on T cells in vivo and in vitro and care should be taken when evaluating the effects of R. rosea on the immune system.

The immune systems can be altered by spaceflight in many aspects, but microgravity-related mucosal immune changes and its clinical significance have not been well studied. The purpose of this study was to investigate whether simulated microgravity influences the intestinal homeostasis and increases the susceptibility to colon inflammation. The hindlimb unloading (HU) mouse model was used to simulate the microgravity condition. Three percent dextran sulfate sodium (DSS) was given to mice to induce colitis. Compared to ground control (Ctrl) mice, the HU ones revealed an impaired intestinal homeostasis and increased susceptibility to DSS-induced colitis. This includes an early-onset, 4-fold expansion of segmented filamentous bacteria (SFB), more than 2-fold decrease in regulatory T (Treg) cell numbers and IL-10 production, ∼2-fold increase in colonic IL-1β expression, 2-fold increase in circulating neutrophils, and colonic neutrophil infiltration. The application of antibiotics ameliorated the Treg and IL-10 reductions but did not significantly dampen neutrophilia and elevated expression of colonic IL-1β. These results indicate that the intestinal microflora and innate immune system both respond to simulated microgravity and together, contribute to the proinflammatory shift in the gut microenvironment. The data also emphasize the necessity for evaluating the susceptibility to inflammatory bowel diseases (IBDs) in distant space travels.