Whole-protein enteral nutrition formula supplementation reduces Escherichia and improves intestinal barrier function in HIV-infected immunological nonresponders.

People living with human immunodeficiency virus (PLWH) have persistent malnutrition, intestinal barrier dysfunction, and gut microbial imbalance. The interplay between gut microbiota and nutrients is involved in the immune reconstitution of PLWH. To evaluate the effects of whole-protein enteral nutrition formula supplementation on T-cell levels, intestinal barrier function, nutritional status, and gut microbiota composition in human immunodeficiency virus (HIV)-infected immunological nonresponders (INRs) who failed to normalize CD4+ T-cell counts, with a number <350 cells/µL, a pilot study was carried out in 13 HIV-infected INRs undergoing antiretroviral therapy who received a 3-month phase supplementation of 200 mL/200 kcal/45 g whole-protein enteral nutrition formula once daily. Our primary endpoint was increased CD4+ T-cell counts. Secondary outcome parameters were changes in intestinal barrier function, nutritional status, and gut microbiota composition. We showed that CD4+ T-cell counts of HIV-infected INRs increased significantly after the 3-month supplementation. Dietary supplementation for 3 months improved the intestinal barrier function and nutritional status of HIV-infected INRs. Furthermore, the enteral nutrition formula significantly decreased the relative abundance of Escherichia at the genus level and increased the alpha diversity of gut microbiota in HIV-infected INRs. The findings demonstrated that the whole-protein enteral nutrition formula aids in reducing Escherichia and improving intestinal barrier function in HIV-infected INRs. This study provides insight into the role of nutrients in the improvement of immune reconstitution in HIV-infected INRs. This study is registered in the Chinese Clinical Trial Registry (Document No. ChiCTR2000037839; http://www.chictr.org.cn/index.aspx).

Eco-friendly recycling of silicon-rich lye: Synthesis of hierarchically structured calcium silicate hydrate and its application for phosphorus removal.

Silicon-rich lye (SRL), a byproduct generated from pre-treatment of coal-based solid waste (CSW), was considered as a preponderant silicon source to prepare hierarchically nanostructured calcium silicate hydrate (C-S-H). Through the novel mild-causticization synthesis strategy, C-S-H was prepared under optimal caustic process conditions at time of 3 h, temperature of 80 °C, Ca/Si of 1.25:1, and active CaO to obtain a conversion rate of Si up to 97.33 % during the high-value utilization of SRL. The synthesized C-S-H possesses abundant mesoporous structure and massive exchangeable active sites, whose formation is advanced through an appropriate elevation regulation of caustic temperature and time. The silicate chain depolymerization occurs to C-S-H prepared in the highly alkaline system at higher caustic temperature, longer caustic period, especially at existence of massive sodium ions, but it presents higher polymerization degree at more aluminum co-existing. The adsorption capacity up to 119.27 mg/g for C-S-H presents a valid removal performance toward phosphorus in the wastewater than massive present reports. The removal mechanism of phosphorus can be identified as the surface chemisorption and formation of calcium phosphate co-precipitation. This study can provide considerable and potential guidance to the coordinated disposal between industrial solid wastes and wastewater purification.

Transcriptome Analysis of Stephania tetrandra and Characterization of Norcoclaurine-6-O-Methyltransferase Involved in Benzylisoquinoline Alkaloid Biosynthesis.

Stephania tetrandra (S. Moore) is a source of traditional Chinese medicine that is widely used to treat rheumatism, rheumatoid arthritis, edema, and hypertension. Benzylisoquinoline alkaloids (BIAs) are the main bioactive compounds. However, the current understanding of the biosynthesis of BIAs in S. tetrandra is poor. Metabolite and transcriptomic analyses of the stem, leaf, xylem, and epidermis of S. tetrandra were performed to identify candidate genes associated with BIAs biosynthesis. According to the metabolite analysis, the majority of the BIAs accumulated in the root, especially in the epidermis. Transcriptome sequencing revealed a total of 113,338 unigenes that were generated by de novo assembly. Among them, 79,638 unigenes were successfully annotated, and 42 candidate structural genes associated with 15 steps of BIA biosynthesis identified. Additionally, a new (S)-norcoclaurine-6-O-methyltransferase (6OMT) gene was identified in S. tetrandra, named St6OMT2. Recombinant St6OMT2 catalyzed (S)-norcoclaurine methylation to form (S)-coclaurine in vitro. Maximum activity of St6OMT2 was determined at 30°C and pH 6.0 in NaAc-HAc buffer. Its half-life at 50°C was 22 min with the Km and kcat of 28.2 µM and 1.5 s-1, respectively. Our results provide crucial transcriptome information for S. tetrandra, shedding light on the understanding of BIAs biosynthesis and further gene functional characterization.

[Effect of electroacupuncture at antagonistic muscle and agonistic muscle on motor function in patients with upper-extremity spasticity after stroke].

OBJECTIVE: To compare the improvement effect between simultaneous electroacupuncture at antagonistic muscle and agonistic muscle and simple electroacupuncture at antagonistic muscle on spasticity degree, upper-extremity motor function and activity of daily living in patients with upper-extremity spasticity after stroke. METHODS: A total of 60 patients with upper-extremity spasticity after stroke were randomized into a comprehensive group (30 cases, 1 case dropped off) and an antagonistic muscle group (30 cases, 2 cases dropped off). In the antagonistic muscle group, acupuncture was applied at Jianyu (LI 15), Binao (LI 14), Zhouliao (LI 12), Shousanli (LI 10), Waiguan (TE 5) and Houxi (SI 3), electric stimulation was attached to Jianyu (LI 15)-Binao (LI 14), Zhouliao (LI 12)-Shousanli (LI 10) and Waiguan (TE 5)-Houxi (SI 3), with discontinuous wave, 15 Hz in frequency. On the basis of the treatment in the antagonistic muscle group, acupuncture was applied at Tianquan (PC 2), Chize (LU 5), Jianshi (PC 5) and Daling (PC 7) in the comprehensive group, electric stimulation was attached to Tianquan (PC 2)-Chize (LU 5) and Jianshi (PC 5)-Daling (PC 7), with continuous wave, 5 Hz in frequency. The treatment was given once a day, 6 days a week for 4 weeks in the two groups. Before and after treatment, the scores of modified Ashworth scale (MAS), Fugl-Meyer assessment upper extremity scale (FMA-UE) and modified Barthel index (MBI) scale were observed in the two groups. RESULTS: Compared before treatment, the MAS scores of elbow flexors and wrist flexors after treatment were decreased (P<0.05), the scores of FMA-UE and MBI scale after treatment were increased in the two groups (P<0.05). The scores of FMA-UE and MBI scale after treatment in the comprehensive group were higher than those in the antagonistic muscle group (P<0.05). CONCLUSION: Simultaneous electroacupuncture at antagonistic muscle and agonistic muscle and simple electroacupuncture at antagonistic muscle can both improve the spasticity degree in patients with upper-extremity spasticity after stroke, however, the former can better restore motor function and improve activity of daily living.

Study on the correlation between Fe/Ti forms and reaction activity in high-alumina coal fly ash.

High-alumina coal fly ash (HAFA) is an important aluminum and silicon resource. In the process of preparing aluminum-silicon materials from HAFA, the influence of impurity elements on its performance must be considered. In this work, the occurrence state of impurities in HAFA, micro morphology, and the bond energy of different impurity coordination were studied. Sulfuric acid leaching method and density functional theory were used to study the leaching behavior of impurities to verify the difficulty of removing different impurity elements. The results show that iron existed in the form of magnetic particles (34.78%), amorphous phase (49.24%), and crystalline phase (15.96%) in HAFA. Titanium mainly existed in amorphous phase (29.34%) and crystalline phase (69.4%). In sulfuric acid leaching, titanium was more difficult to leach, and the content of TiO2 decreased from 2.30% to 2.25%, whereas that of Fe2O3 decreased from 1.50% to 0.86%. The actual leaching behavior of impurity elements was consistent with the simulation results, with more energy required to remove Ti than Fe. These studies of impurity elements in HAFA will provide theoretical support for the preparation of aluminum-silicon materials.

Metabolomic mechanisms of short chain chlorinated paraffins toxicity in rats.

Short chain chlorinated paraffins (SCCPs) have received increased interest worldwide since they were added to the list of controlled POPs in Annex A of the Stockholm Convention in 2017. Although many toxicological studies have already shown that SCCPs are hepatotoxic, nephrotoxic, and thyrotoxic to rodents, there have been few studies to date that have characterized changes in the metabolic pathways targeted by SCCPs. In this study, a UPLC-Q-TOF-MS based plasma metabolomics approach was used to investigate the toxicity of SCCPs in rats. Liver and kidney injury occurred rapidly after high-dose SCCP exposure, and the most relevant pathways affected were energy metabolism, amino acid metabolism, glycerophospholipid metabolism, nucleotide metabolism, and vitamin B metabolism. Exposure to SCCPs inhibited the tricarboxylic acid cycle and accelerated degradation. Fluctuating levels of phospholipids and nucleotides may have contributed to the neurotoxicity of SCCPs. In addition, the down regulation of folic acid induced by SCCPs may have led to malformations during the early development of laboratory animals. These results suggested that high exposure levels of SCCPs may have serious health risks and more research is needed to assess the health status of relevant occupational groups.

Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4+ T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders.

AIDS patients with immune non-response are prone to malnutrition, intestinal barrier damage, thus aggravating chronic immune activation and inflammation. However, nutritional interventions targeting malnutrition may be beneficial to restore immune function, improve clinical outcomes, and reduce mortality remains largely unclear. This work aimed to evaluate the efficacy of a nutritional supplement in HIV-infected immune non-responders (INRs). The subjects received oral supplementation of a pre-digested protein nutrition formula for three months. We show that the CD4+ T and CD8+ T cell counts were significantly increased after supplementation of the pre-digested enteral nutritional supplement. Among all pro-inflammatory cytokines in the serum, only IL-1ß level was significantly decreased, while TNF-ß was significantly increased (P < 0.05). The levels of intestinal mucosal damage markers, diamine oxidase (DAO), D-lactic acid (D-lactate), and lipopolysaccharide (LPS), decreased significantly (P < 0.05) after the nutritional intervention. Moreover, at month 3 after the intervention, the body weight, body mass index, albumin, and hemoglobin of all subjects were significantly increased (P < 0.05). The correlation analysis demonstrated a significantly negative correlation of CD4+ T cell count with levels of DAO (r = -0.343, P = 0.004), D-lactate (r = -0.250, P = 0.037), respectively, and a significantly positive correlation of IL-1ß level with levels of DAO (r = 0.445, P < 0.001), D-lactate (r = 0.523, P < 0.001), and LPS (r = 0.622, P < 0.001). We conclude that the pre-digested enteral nutrition supplement is effective for HIV-infected INRs.

Mechanisms of mechanochemical activation during comprehensive utilization of high-alumina coal fly ash.

High-alumina coal fly ash (HAFA) is an important aluminum and silicon resource. In terms of its comprehensive utilization, how to efficiently separate aluminum and silicon must be resolved. In this work, a mechanochemical activation method in the desilication process is adopted and investigated. Desilication ratio, efficient desilicated ratio, microscopic appearance, and coordination structure change in aluminum-silicon atoms are investigated during mechanochemical activation process. Results indicate that the Al-O-Si coordination structure in HAFA can be transformed from Q4 (3Al) and Q4 (2Al) to reactive Q2 (1Al) structure, and the radio of Q2 (1Al) with high activity increased from 6.93% to 14.47%, which can improve HAFA reaction activity obviously. During the desilication process, the aluminum-silicon mass ratio (A/S) can be elevated from 1.23 to 2.56 after the process optimization, which provides a high-quality raw material for further high-valued utilization of HAFA.

Identification of the Core Pollen-Specific Regulation in the Rice OsSUT3 Promoter.

The regulatory mechanisms of pollen development have potential value for applications in agriculture, such as better understanding plant reproductive regularity. Pollen-specific promoters are of vital importance for the ectopic expression of functional genes associated with pollen development in plants. However, there is a limited number of successful applications using pollen-specific promoters in genetic engineering for crop breeding and hybrid generation. Our previous work led to the identification and isolation of the OsSUT3 promoter from rice. In this study, to analyze the effects of different putative regulatory motifs in the OsSUT3 promoter, a series of promoter deletions were fused to a GUS reporter gene and then stably introduced into rice and Arabidopsis. Histochemical GUS analysis of transgenic plants revealed that p385 (from -385 to -1) specifically mediated maximal GUS expression in pollen tissues. The S region (from -385 to -203) was the key region for controlling the pollen-specific expression of a downstream gene. The E1 (-967 to -606), E2 (-202 to -120), and E3 (-119 to -1) regions enhanced ectopic promoter activity to different degrees. Moreover, the p385 promoter could alter the expression pattern of the 35S promoter and improve its activity when they were fused together. In summary, the p385 promoter, a short and high-activity promoter, can function to drive pollen-specific expression of transgenes in monocotyledon and dicotyledon transformation experiments.

Adefovir dipivoxil induced hypophosphatemic osteomalacia in chronic hepatitis B: a comparative study of Chinese and foreign case series.

BACKGROUND: Adefovir dipivoxil (ADV)-induced renal tubular dysfunction and hypophosphatemic osteomalacia (HO) have been given great consideration in the past few years. However, no standard guidance is available due to a lack of powerful evidence from appropriate long-term prospective case-control studies and variations in the definition of renal adverse events. The aim of this study is to clarify clinical features of ADV-related HO in Chinese chronic hepatitis B patients with long-term ADV treatment in Chinese and non-Chinese comparative case series. METHODS: Retrieval of case reports was based on Pubmed, CNKI, Wan Fang and VIP databases using the key words adefovir dipivoxil, hypophosphatemia, osteomalacia and Fanconi syndrome. We divided patients into Chinese (C group) and Foreign (F group) groups according to their nationality. Comparisons involving demographics, clinical manifestations, tests, treatment and prognosis were conducted between the two groups. RESULTS: Of the patients screened, 120 Chinese patients were identified in the C group, and 32 non-Chinese patients were identified in the F group. The average age of the C group was younger than that of the F group (51.89 years ±10.96 years versus 56.47 years ±11.36 years, t = - 2.084, P = 0.039). No significant difference was found in gender (male to female, 3.29:1 versus 3:1, χ 2 = 0.039, P = 0.844). Although there was no significant difference in the duration of ADV therapy before ostalgia onset, the C group tended to develop adverse events earlier, by 2-3 years, while the F group developed adverse events at 4-5 years (Z = - 1.517, P = 0.129). Prognosis was good after adjustment of the ADV dose and supplemental administration of phosphate and calcitriol. Time to resolution of tubular dysfunction was commenced at the first month, and Chinese patients were more prone to recover in the first 3 months than non-Chinese patients (91.3% of patients in the C group versus 56.3% in the F group, Z = - 3.013, P = 0.003). CONCLUSIONS: Sufficient attention is required for middle-aged males before and during exposure to long-term ADV therapy, regardless of nationality. The clinical picture, laboratory and radiograph alterations are important clues for those patients and are usually characterized by polyarthralgia, renal tubular dysfunction and mineralization defects. Implementation of an early renal tubular injury index is recommended for patients with higher risk, which would prevent further renal injury.

18ß-glycyrrhetinic acid inhibits migration and invasion of human gastric cancer cells via the ROS/PKC-α/ERK pathway.

18ß-glycyrrhetinic acid (18ß-GA) is a bioactive component of licorice root which exerts pharmacological activities including anti-inflammatory, antiviral, anti-oxidative and anti-cancer effects. The current study further investigated the molecular mechanisms associated with the inhibitory effects of 18ß-GA on tumor metastasis in human gastric cancer cells. The results indicated that 18ß-GA significantly reduced invasion and migration activities and suppressed MMP-2 and 9 activities on SGC-7901cells in a dose-dependent manner. Further study showed 18ß-GA upregulated E-cadherin expression but downregulated vimentin expression. The results also showed that 18ß-GA inhibited ROS formation, PKC-α expression and the phosphorylation of ERK in a dose-dependent manner. In conclusion, this study revealed that 18ß-GA inhibits migration and invasion via the ROS/PKC-α/ERK signaling pathway in gastric cancer cells. This suggests that 18ß-GA has the potential to be used as an effective chemopreventive agent for the prevention of gastric cancer metastasis.

Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an Overlooked Risk in Plants?

Agricultural use of treated wastewater, biosolids, and animal wastes introduces a multitude of contaminants of emerging concerns (CECs) into the soil-plant system. The potential for food crops to accumulate CECs depends largely on their metabolism in plants, which at present is poorly understood. Here, we evaluated the metabolism of naproxen and ibuprofen, two of the most-used human drugs from the Profen family, in Arabidopsis thaliana cells and the Arabidopsis plant. The complementary use of high-resolution mass spectrometry and 14C labeling allowed the characterization of both free and conjugated metabolites, as well as nonextractable residues. Naproxen and ibuprofen, in their parent form, were conjugated quickly and directly with glutamic acid and glutamine, and further with peptides, in A. thaliana cells. For example, after 120 h, the metabolites of naproxen accounted for >90% of the extractable chemical mass, while the intact parent itself was negligible. The structures of glutamate and glutamine conjugates were confirmed using synthesized standards and further verified in whole plants. Amino acid conjugates may easily deconjugate, releasing the parent molecule. This finding highlights the possibility that the bioactivity of such CECs may be effectively preserved through direct conjugation, a previously overlooked risk. Many other CECs are also carboxylic acids, such as the profens. Therefore, direct conjugation may be a common route for plant metabolism of these CECs, making it imperative to consider conjugates when assessing their risks.

Resveratrol-induced antinociception is involved in calcium channels and calcium/caffeine-sensitive pools.

Resveratrol has been widely investigated for its potential health properties, although little is known about its mechanism in vivo. Previous studies have indicated that resveratrol produces antinociceptive effects in mice. Calcium channels and calcium/caffeine-sensitive pools are reported to be associated with analgesic effect. The present study was to explore the involvement of Ca2+ channel and calcium/caffeine-sensitive pools in the antinociceptive response of resveratrol. Tail-flick test was used to assess antinociception in mice treated with resveratrol or the combinations of resveratrol with MK 801, nimodipine, CaCl2, ryanodine and ethylene glycol tetraacetic acid (EGTA), respectively. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) levels in the spinal cord were also investigated when treated with the above drugs. The results showed that resveratrol increased the tail flick latency in the tail-flick test, in dose-dependent manner. N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK 801 potentiated the antinociceptive effects of sub-threshold dose of resveratrol at 10 mg/kg. Ca2+ channel blocker, however, abolished the antinociceptive effects of resveratrol. In contrast to these results, EGTA or ryanodine treatment (i.c.v.) potentiated resveratrol-induced antinociception. There was a significant decrease in p-CaMKII and an increase in BDNF expression in the spinal cord when combined with MK 801, nimodipine, ryanodine and EGTA. While an increase in p-CaMKII level and a decrease in BDNF expression were observed when high dose of resveratrol combined with CaCl2. These findings suggest that resveratrol exhibits the antinociceptive effects by inhibition of calcium channels and calcium/caffeine-sensitive pools.

[Magnetic resonance spectroscopic study of memory impairment after cerebral infarction treated with electroacupuncture].

OBJECTIVE: To study the impacts of electroacupuncture (EA) on memory impairment after cerebral infarction through the observation of hydrogen proton magnetic resonance spectroscopy (1H-MRS) of brain tissue metabolites in the patients of cerebral infarction. METHODS: Sixty cases of memory impairment after cerebral infarction were randomized into an observation group and a control group, 30 cases in each one. The conventional rehabilitation training and medication were applied to all the patients. In the observation group, beside the basic treatment, EA was applied to bilateral Ezhongxian (MS 1), Dingzhongxian (MS 5), Dingniehouxiexian (MS 7), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36), Taixi (KI 3), Xuanzhong (GB 39) and Fengchi (GB 20). The treatment was given once a day, 5 times a week, for 8 weeks. The clinical memory scale was used for the score evaluation before and after treatment in all the patients. The magnetic resonance image (MRI) and 1H-MRS scanning were applied to the head. The ratio of N-acetyl aspartate (NAA) and creatine (Cr) and the ratio of choline (Cho) and Cr were determined in the foci of cerebral infarction. RESULTS: Eight weeks later, the scores of clinical memory scale were all increased after treatment as compared with those before treatment in the two group (all P<0. 01). The ratio of NAA and Cr was increased as compared with that before treatment (P<0. 05); the ratio of Cho and Cr was reduced as compared with that before treatment (P<0. 05). The changes in the observation group were more obvious than those in the control group (all P<0. 05). CONCLUSION: On the basis of the conventional medication and rehabilitation training, EA improves the metabolism of brain tissue and memory function of the patients. The efficacy of this therapy is better than that of medication combined with rehabilitation training.

Chronic hydrocephalus and perihematomal tissue injury developed in a rat model of intracerebral hemorrhage with ventricular extension.

Primary spontaneous intracerebral hemorrhage (ICH) with secondary intraventricular hemorrhage (IVH) is an important clinical problem of which little is known. IVH and hydrocephalus are independent predictors of poor outcome in ICH. The aims of this study were, therefore, to establish a rat model of ICH with ventricular extension and investigate the occurrence of post-hemorrhagic chronic hydrocephalus and perihematomal tissue injury. Based on our previous rat model of IVH, we adjusted the injection coordinates and 200 µl autologous blood was stereotaxically infused into the right striatum (coordinates: 0.2 mm posterior, 2.2 mm lateral, and 5.0 mm depth to the bregma). At 24 h post-infusion, the rats produced reproducible hematoma and ventricle expansion, which closely mimics the ICH with ventricular extension in humans. Hematoma consequences and perihematomal tissue injury were evaluated on the acute phase. At 4 weeks, ventricular dilatation, brain tissue loss, hippocampus volume, and cortical thickness were measured with magnetic resonance imaging and neurocognitive function was assessed using the Morris water maze test. With blood infusion, the animals demonstrated brain edema, blood-brain barrier breakdown, and marked perihematomal tissue injury on the acute phase. At 4 weeks, the T2 images showed remarkable hydrocephalus and tissue loss, and the Morris water maze test revealed neurocognitive deficits. The present ICH with the ventricular extension rat model features characteristics of both ICH and IVH rat models, which could be used for extending our pathophysiological understanding of post-hemorrhagic chronic hydrocephalus and perihematomal tissue damage.

[Meta-analysis on acupuncture for treatment of depression in patients of poststroke].

OBJECTIVE: To assess therapeutic effect and the safety of acupuncture for treatment of the depression in patients of poststroke. METHODS: The clinical research documents in recent 10 years of acupuncture for treatment of depression in patients of poststroke were retrieved, the homogeneity test was used and the effect amount was complicated in the clinical randomized controlled trials (RCT) documents which had been adopted in the Meta-analysis, and furthermore the Meta-analysis was used in the Hamilton Depression Scale (HAMD) score of both acupuncture group and medication group after treatment. RESULTS: Seventeen RCT heterogeneity test results which were adopted in the study indicated that chi2 = 21.98, P = 0.14, proved that they had homogeneity, and fixed effect model was adopted to analyse, after combination, OR = 2.54, 95% confidence interval was (1.91, 3.38), according to Z test, Z = 6.41, P < 0.00001, the diamond was in the right side of the vertical line, indicated that there was a significant difference in the therapeutic effect between the acupuncture group and the medication group. The evaluation of the influence of acupuncture on HAMD indicated that there was a significant difference between the acupuncture group and the medication group. CONCLUSION: The therapeutic effect of acupuncture for treatment of the depression in patients of poststroke is superior to other common medicine with safety, but it still needs more large sample RCTs to verify.