Beneficial effects of Dendrobium officinale National Herbal Drink on metabolic immune crosstalk via regulate SCFAs-Th17/Treg.

BACKGROUND: The development of gut-liver axis metabolic immune crosstalk is intimately associated with intestinal barrier disorder, intestinal SCFAs-Th17/Treg immunological imbalance, and disorders of the gut microbiota. Prior research has discovered that Dendrobium officinale National Herbal Drink (NHD), a traditional Chinese medicine drink with enhanced immunity, may enhance the immunological response in animals with impaired immune systems brought on by cyclophosphamide by repairing intestinal barrier function and controlling turbulence in the gut microbiota. However, whether NHD can further improve the gut-liver axis metabolic immune crosstalk and its related mechanisms need to be systematically studied. OBJECTIVES: The purpose of this study is to clarify the function and mechanism of NHD in enhancing the gut-liver axis metabolic immunological crosstalk brought on by excessive alcohol intake. METHODS: In this work, we set up a mouse model to analyze the metabolic and immunological crosstalk involving the gut-liver axis across 7 weeks of continuous, excessive drinking. At the same time, high and low doses (20,10 ml/kg) of NHD were given by gavage. The effect of NHD on improving the metabolism of gut-liver axis was evaluated by blood lipid, liver lipid deposition, liver function and intestinal pathophysiology. By measuring serum immunological indices, intestinal barrier, and intestinal immune barrier, the impact of NHD on enhancing immune and intestinal barrier function was assessed. Furthermore, immunohistochemistry, immunofluorescence, 16S rRNA, Western blot, q-PCR and other methods were used to detect gut microbiota, SCFAs-GPR41/43 pathway, intestinal Th17/Treg immune cells and PPAR-α-NPC1L1/SREBP1 pathway to elucidate the mechanism by which NHD enhances the gut-liver axis' metabolic immune crosstalk. RESULTS: Our study demonstrated that NHD has the potential to improve the pathophysiological damage caused by gut-liver axis in model mice. NHD also ameliorated the disorder of lipid metabolism. In addition, it regulated the levels of peripheral blood T cell immunity and serum immune factors. And NHD can restore intestinal mechanical and immune barrier damage. NHD has a favorable impact on the quantity of beneficial bacteria, including uncultured_bacterium_g__norank_f__muribaculacea and uncultured_bacterium_g__Turicibacter. Additionally, it raised the model mice's levels of SCFAs (n-butyric acid, isovaleric acid, etc.). This resulted in the promotion of intestinal GPR41/43-ERK1/2 expression and the reshaping of intestinal CD4+T cell Th17/Treg homeostasis. As a consequence, colon IL-22 and IL-10 levels increased, while colon IL-17A levels decreased. Lastly, NHD raised the amount of intestinal IAP/LPS, regulated the development of PPAR-α-NPC1L1/SREBP1 pathway in gut-liver axis, and improve lipid metabolism disorder. CONCLUSIONS: Our study found that NHD can improve the gut-liver axis metabolic immune crosstalk in model mice caused by excessive drinking. The mechanism might be connected to how NHD controls gut microbiota disorders in model mice, the activation of intestinal SCFAs-GPR41/43 pathway, the remodeling of Th17/Treg immune homeostasis of intestinal CD4+T cells, the improvement of IAP/LPS abnormality, and further mediating the PPAR-α-NPC1L1/SREBP1 pathway of lipid metabolism in gut-liver axis.

The effect of modified Qiyuan paste on mice with low immunity and sleep deprivation by regulating GABA nerve and immune system.

BACKGROUND: Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. METHODS: Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin-eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. RESULTS: The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. CONCLUSIONS: LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions.

Dendrobium officinale flowers' topical extracts improve skin oxidative stress and aging.

BACKGROUND: Dendrobium officinale flowers (DOF) have the effects of antiaging and nourishing yin, but it lacks pharmacological research on skin aging. OBJECTIVE: Confirming the role of DOF in delaying skin aging based on the "in vitro animal-human" model. METHODS: In this experiment, three kinds of free radical scavenging experiments in vitro, D-galactose-induced aging mouse model, and human antiaging efficacy test were used to test whether DOF can improve skin aging through anti-oxidation. RESULTS: In vitro experiment shows that DOF has certain scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, hydroxyl free radical, and superoxide free radical, and its IC50 is 0.2090 µg/mL, 15.020, and 1.217 mg/mL respectively. DOF can enhance the activities of T-AOC, SOD, CAT, and GSH Px in the serum of aging mice, increase the content of GSH, and reduce the content of MDA when administered with DOF of 1.0, 2.0, and 4.0 g/kg for 6 weeks. In addition, it can enhance the activity of SOD in the skin of aging mice, increase the content of Hyp, and decrease the content of MDA, activated Keap1/Nrf2 pathway in the skin of aging mice. Applying DOF with a concentration of 0.2 g/mL on the face for 8 weeks can significantly improve the skin water score and elasticity value, reduce facial wrinkles, pores, acne, and UV spots, and improve the facial brown spots and roughness. CONCLUSION: DOF can significantly improve skin aging caused by oxidative stress, and its mechanism may be related to scavenging free radicals in the body and improving skin quality.

Osteopontin modulates microglial activation states and attenuates inflammatory responses after subarachnoid hemorrhage in rats.

AIMS: Osteopontin (OPN) has demonstrated neuroprotective effects in various stroke models. Its role in neuroinflammation after brain injury remains to be elucidated. This study aims to clarify the effect of OPN on neuroinflammation, particularly on the functional states of microglia after subarachnoid hemorrhage (SAH). METHODS: 77 rats were randomly divided into the following groups: Sham, SAH 24 h, SAH + rOPN, SAH + Vehicle (PBS), SAH + OPN siRNA, and SAH + Scr siRNA, SAH + rOPN+Fib-14 and SAH + rOPN+DMSO. Modified Garcia and beam balance tests were used to evaluate neurobehavioral outcomes. Semi-quantitative immunofluorescence staining was performed to measure expression of myeloperoxidase (MPO) and microglia activation state markers CD16, CD206 after SAH and recombinant OPN treatment. The quantification of microglia activation and functional markers CD16, CD206, TNF-α and IL-10 were further evaluated using Western-blotting. RESULTS: Nasal administration of rOPN improved neurological dysfunction, attenuated neutrophil infiltration, and decreased expression of phenotypic and functional markers of pro-inflammatory microglia CD16 and TNF-α. It also promoted an anti-inflammatory microglial state, as evidenced by increased expression of CD206 and IL-10. Furthermore, after blocking the phosphorylation of FAK signaling, the effects of rOPN on microglial activation states were partially reversed. The downstream pathways of STAT3 and NF-κB also exhibited consistent changes, suggesting the involvement of the STAT3 and NF-κB pathways in OPN's modulation of microglial activation via integrin-FAK signaling. CONCLUSION: OPN attenuates inflammatory responses after SAH by promoting an anti-inflammatory microglial state, potentially mediated through the integrin-FAK-STAT3 and NF-κB signaling pathways.

The Mechanisms of Polysaccharides from Tonic Chinese Herbal Medicine on the Enhancement Immune Function: A Review.

Tonic Chinese herbal medicine is a type of traditional Chinese medicine, and its primary function is to restore the body's lost nutrients, improve activity levels, increase disease resistance, and alleviate physical exhaustion. The body's immunity can be strengthened by its polysaccharide components, which also have a potent immune-system-protecting effect. Several studies have demonstrated that tonic Chinese herbal medicine polysaccharides can improve the body's immune response to tumor cells, viruses, bacteria, and other harmful substances. However, the regulatory mechanisms by which various polysaccharides used in tonic Chinese herbal medicine enhance immune function vary. This study examines the regulatory effects of different tonic Chinese herbal medicine polysaccharides on immune organs, immune cells, and immune-related cytokines. It explores the immune response mechanism to understand the similarities and differences in the effects of tonic Chinese herbal medicine polysaccharides on immune function and to lay the foundation for the future development of tonic Chinese herbal medicine polysaccharide products.

Advanced low-strength wastewater treatment, side-stream phosphorus recovery, and in situ sludge reduction with aerobic granular sludge.

Modern paradigm has upgraded wastewater treatment plants (WWTPs) to water resources recovery facilities (WRRFs), where aerobic granular sludge (AGS) is a sewage treatment technology with promising phosphorus recovery (PR) potential. Herein, the AGS-based simultaneous nitrification, denitrification, and phosphorus removal coupling side-stream PR process (AGS-SNDPRr) was developed with municipal wastewater. Results revealed that AGS always maintained good structural stability, and pollutant removal was unaffected and effective after 40 days of anaerobic phosphorus-rich liquid extraction (fixed rate of 30%). The AGS-SNDPRr achieved a stable phosphorus recovery efficiency of 63.40%, and the side-stream PR further exaggerated in situ sludge reduction by 7.7-10%. Apart from responses of extracellular polymeric substances (EPS), the Matthew effect of typical denitrifying glycogen accumulating organisms (DGAOs) Candidatus_Competibacter up to 67.40% mainly contributed to enhanced performance of this new process. This study demonstrated a new approach for simultaneous advanced wastewater treatment, phosphorus recovery, and excess sludge minimization.

[Correlation between four limbs perfusion index and lactic acid in patients with severe neurological diseases].

OBJECTIVE: To observe the correlation between the four limbs perfusion index (PI) and blood lactic acid in patients with neurosis, and evaluate the predictive value of PI on microcirculation perfusion metabolic disorder in patients with neurosis. METHODS: A prospective observational study was conducted. Adult patients admitted to the department of neurological intensive care unit (NICU) of the First Affiliated Hospital of Xinjiang Medical University from July 1 to August 20 in 2020 were enrolled. Under the condition of indoor temperature controlled at 25 centigrade, all patients were placed in the supine position, and the blood pressure, heart rate, PI of both fingers and thumb toes and arterial blood lactic acid were measured within 24 hours and 24-48 hours after NICU. The difference of four limbs PI at different time periods and its correlation with lactic acid were compared. Receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of four limbs PI on patients with microcirculatory perfusion metabolic disorder. RESULTS: A total of 44 patients with neurosis were enrolled, including 28 males and 16 females; average age (61.2±16.5) years old. There were no significant differences in PI of the left index finger and the right index finger [2.57 (1.44, 4.79) vs. 2.70 (1.25, 5.33)], PI of the left toe and the right toe [2.09 (0.85, 4.76) vs. 1.88 (0.74, 4.32)] within 24 hours after entering the NICU, and the PI of the left index finger and the right index finger [3.17 (1.49, 5.07) vs. 3.14 (1.33, 5.36)], PI of the left toe and the right toe [2.07 (0.75, 5.20) vs. 2.07 (0.68, 4.67)] at 24-48 hours after NICU admission (all P > 0.05). However, compared to the PI of the upper and lower limbs on the same side, except for the 24-48 hours after ICU of the PI difference between the left index finger and the left toe (P > 0.05), the PI of the toe was lower than that of the index finger at the other time periods (all P < 0.05). The correlation analysis showed that the PI value of four limbs of patients in both time periods were significantly negatively correlated with arterial blood lactic acid (the r values of the left index finger, the right index finger, the left toe and the right toe were -0.549, -0.482, -0.392 and -0.343 respectively within 24 hours after entering the NICU; the r values of the left index finger, the right index finger, the left toe and the right toe were -0.331, -0.292, -0.402 and -0.442 respectively after entering the NICU 24-48 hours, all P < 0.05). Taking lactic acid ≥ 2 mmol/L as the diagnostic standard for metabolic disorder of microcirculation perfusion (total 27 times, accounting for 30.7%). The efficacy of four limbs PI in predicting microcirculation perfusion metabolic disorder were compared. ROC curve analysis showed that the area under the curve (AUC) and 95% confidence interval (95%CI) of left index finger, right index finger, left toe and right toe predicting microcirculation perfusion metabolic disorder were 0.729 (0.609-0.850), 0.767 (0.662-0.871), 0.722 (0.609-0.835), 0.718 (0.593-0.842), respectively. There was no significant difference in AUC compare with each other (all P > 0.05). The cut-off value of PI of right index finger for predicting microcirculation perfusion metabolic disorder was 2.46, the sensitivity was 70.4%, the specificity was 75.4%, the positive likelihood ratio was 2.86, and the negative likelihood ratio was 0.30. CONCLUSIONS: There are no significant differences in PI of bilateral index fingers, bilateral toes in patients with neurosis. However, unilateral upper and lower limbs showed lower PI in the toe than in the index finger. There is a significantly negatively correlation between PI and arterial blood lactic acid in all four limbs. PI can predict the metabolic disorder of microcirculation perfusion, and its cut-off value is 2.46.

Chemical Constitution, Pharmacological Effects and the Underlying Mechanism of Atractylenolides: A Review.

Atractylenolides, comprising atractylenolide I, II, and III, represent the principal bioactive constituents of Atractylodes macrocephala, a traditional Chinese medicine. These compounds exhibit a diverse array of pharmacological properties, including anti-inflammatory, anti-cancer, and organ-protective effects, underscoring their potential for future research and development. Recent investigations have demonstrated that the anti-cancer activity of the three atractylenolides can be attributed to their influence on the JAK2/STAT3 signaling pathway. Additionally, the TLR4/NF-κB, PI3K/Akt, and MAPK signaling pathways primarily mediate the anti-inflammatory effects of these compounds. Atractylenolides can protect multiple organs by modulating oxidative stress, attenuating the inflammatory response, activating anti-apoptotic signaling pathways, and inhibiting cell apoptosis. These protective effects extend to the heart, liver, lung, kidney, stomach, intestine, and nervous system. Consequently, atractylenolides may emerge as clinically relevant multi-organ protective agents in the future. Notably, the pharmacological activities of the three atractylenolides differ. Atractylenolide I and III demonstrate potent anti-inflammatory and organ-protective properties, whereas the effects of atractylenolide II are infrequently reported. This review systematically examines the literature on atractylenolides published in recent years, with a primary emphasis on their pharmacological properties, in order to inform future development and application efforts.

Local monitoring of SARS-CoV-2 variants in two large California counties in 2021.

Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to persist due to mutations resulting in newer, more infectious variants of concern. We aimed to leverage an ongoing private SARS-CoV-2 testing laboratory's infrastructure to monitor SARS-CoV-2 variants in two large California counties. Study enrollment was offered to adults aged 18 years or older in Los Angeles County and Riverside County who recently tested positive for SARS-CoV-2 with a polymerase chain reaction (PCR) assay. A cycle threshold value less than or equal to 30 cycles was considered a positive test for sequencing purposes. Within 5 days of study enrollment, clinician-monitored, self-collected oral fluid and anterior nares swab specimens were obtained from participants. Specimens were transported and stored at 8 °C or cooler. Samples underwent ribonucleic acid extraction, library preparation, and sequencing. SARS-CoV-2 lineages were identified using sequencing data. Participant and genomic data were analyzed using statistical tools and visualized with toolkits. The study was approved by Advarra Institutional Review Board (Pro00053729). From May 27, 2021 to September 9, 2021, 503 individuals were enrolled and underwent specimen collection. Of the 503 participants, 238 (47.3%) participants were women, 329 (63.6%) participants were vaccinated, and 221 (43.9%) participants were of Hispanic or Spanish origin. Of the cohort, 496 (98.6%) participants had symptoms at the time of collection. Among the 503 samples, 443 (88.1%) nasal specimens and 353 (70.2%) oral specimens yielded positive sequencing results. Over our study period, the prevalence of the Alpha variant of SARS-CoV-2 decreased (initially 23.1% [95% confidence interval (95% CI): 0-0.49%] to 0% [95% CI 0.0-0.0%]) as the prevalence of the Delta variant of SARS-CoV-2 increased (initially 33.3% [95% CI 0.0-100.0%] to 100.0% [95% CI 100.0-100.0%]). A strain that carried mutations of both Delta and Mu was identified. We found that outpatient SARS-CoV-2 variant surveillance could be conducted in a timely and accurate manner. The prevalence of different variants changed over time. A higher proportion of nasal specimens yielded results versus oral specimens. Timely and regional outpatient SARS-CoV-2 variant surveillance could be used for public health efforts to identify changes in SARS-CoV-2 strain epidemiology.

Seizure prophylaxis following aneurysmal subarachnoid haemorrhage (SPSAH): study protocol for a multicentre randomised placebo-controlled trial of short-term sodium valproate prophylaxis in patients with acute subarachnoid haemorrhage.

INTRODUCTION: Seizures are a common complication that leads to neurological deficits and affects outcomes after aneurysmal subarachnoid haemorrhage (aSAH). However, whether to use prophylactic anticonvulsants in patients with aSAH remains controversial. Our study aims to determine whether short-term (7 days) sodium valproate could prevent seizure occurrence and improve neurological function in patients with SAH caused by anterior circulation aneurysm rupture and treated with clipping. METHODS AND ANALYSIS: In this multicentre randomised evaluator-blind placebo-controlled trial, 182 eligible patients with good-grade aSAH planned for surgical clipping will be enrolled from four neurosurgical centres in China. In addition to standard care, patients will be randomly assigned to receive sodium valproate 20 mg/kg daily or matching placebo. After aneurysmal clipping, patients will be followed up at discharge, 90 days and 180 days. The primary outcomes are the incidence of early and late seizures. The secondary outcomes include aSAH-related complications, sodium valproate-related adverse effects, modified Rankin Scale (mRS) (on discharge, at 90 days, 180 days), rate of good outcome (defined as mRS 0-2), all-cause death (at 90 days, 180 days) and Montreal Cognitive Assessment score (at 180 days). All analyses are by intention-to-treat. ETHICS AND DISSEMINATION: This study will be conducted according to the principles of Declaration of Helsinki and good clinical practice guidelines. This trial involves human participants and has been approved by the ethics committee of West China Hospital. Informed consent will be achieved from each included patient and/or their legally authorised representative. Preliminary and final results from this study will be disseminated through manuscript publishing and international congresses presentations. Any protocol amendments will be approved by the ethics committee of West China Hospital and subsequently updated on ChiCTR. TRIAL REGISTRATION NUMBER: ChiCTR.org identifier: ChiCTR2100050161.

Distinct responses of aerobic granular sludge sequencing batch reactors to nitrogen and phosphorus deficient conditions.

The nutrients availability determines efficiency of biological treatment systems, along with the structure and metabolism of microbiota. Herein nutrients deficiencies on aerobic granular sludge were comparatively evaluated, treating wastewater with mass ratios of chemical oxygen demand : nitrogen : phosphorus being 200:20:4, 200:2:4, and 200:20:0.4 (deemed as nutrient-balanced, nitrogen-deficient, and phosphorus-deficient), respectively. Results revealed that both nitrogen and phosphorus deficiencies significantly raised the effluent qualities especially nitrogen removal. However, nitrogen deficiency aroused considerable growth of filamentous bacteria, while granules kept compact structure under phosphorus deficient condition. Extracellular polymeric substances (EPS) also varied in contents and structures in response to different wastewaters. Microbial community structure analysis demonstrated that nitrogen deficiency led to lower richness and higher diversity, while the reverse was observed under phosphorus deficient condition. Nitrogen deficiency mainly induced decrease of nitrifying bacteria, while similarly phosphorus deficiency led to loss of phosphorus accumulating organisms. Dramatic enrichment Candidatus_Competibacter and filamentous Thiothrix were found under nutrients deficiencies, in which the latter explained and indicated filamentous bulking potential especially under nitrogen limited condition. Bacterial metabolism patterns verified the functions of microbial community responding to nutrients via PICRUSt2 prediction mainly by up-regulating cell motility, and cellular processes and signaling. This study could aid understanding of long-term stability of aerobic granular sludge for low-strength wastewater treatment.

Soporific effect of modified Suanzaoren Decoction on mice models of insomnia by regulating Orexin-A and HPA axis homeostasis.

AIM: Modified Suanzaoren Decoction (MSZRD) is obtained by improving Suanzaoren Decoction (SZRT), a traditional Chinese herbal prescription that has been used to treat insomnia for more than thousands of years. Our previous study showed that MSZRD can improve the gastrointestinal discomfort related insomnia by regulating Orexin-A. This study is the first study to evaluate the effects and possible mechanisms of MSZRD in mice with insomnia caused by p-chlorophenylalanine (PCPA) combined with multifactor random stimulation. METHODS: After 14 days of multifactor stimulation to ICR mice, a PCPA suspension (30 mg/mL) was injected intraperitoneally for two consecutive days to establish an insomnia model. Three different doses of MSZRD (3.6, 7.2, and 14.4 g/kg/day) were given to ICR mice for 24 days. The food intake and back temperature were measured, and behavioral tests and pentobarbital sodium-induced sleep tests were conducted. The levels of Orexin-A, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and adrenocortical hormones (CORT) in the serum and 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in hypothalamus were measured using enzyme-linked immunosorbent assay (ELISA) kits. The levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) were measured by high-performance liquid chromatography (HPLC). The expression of 5HT1A receptor (5-HTRIA) and orexin receptor 2 antibody (OX2R) was measured by Western blot (WB) and immunohistochemical staining (ICH). Hematoxylin and eosin (H&E) staining and Nissl staining were used to assess the histological changes in hypothalamus tissue. RESULTS: Of note, MSZRD can shorten the sleep latency of insomnia mice (P < 0.05, 0.01), prolonged the sleep duration of mice (P < 0.05, 0.01), and improve the circadian rhythm disorder relative to placebo-treated animals. Furthermore, MSZRD effectively increased the content of 5-HT and 5-HTR1A protein in the hypothalamus of insomnia mice (P < 0.05, 0.01), while downregulated the content of DA and NE (P < 0.05, 0.01). Importantly, serum GABA concentration was increased by treatment with MSZRD (P < 0.05), as reflected by a decreased Glu/GABA ratio (P < 0.05). Moreover, MSZRD decreased the levels of CORT, ACTH, and CRH related hormones in HPA axis (P < 0.05, 0.01). At the same time, MSZRD significantly downregulated the serum Orexin-A content in insomnia mice (P < 0.05), as well as hypothalamic OX2R expression (P < 0.05). In addition, MSZRD also improved the histopathological changes in hypothalamus in insomnia mice. CONCLUSION: MSZRD has sleep-improvement effect in mice model of insomnia. The mechanism may be that regulating the expression of Orexin-A affects the homeostasis of HPA axis and the release of related neurotransmitters in mice with insomnia.

Insights into the simultaneous nitrification, denitrification and phosphorus removal process for in situ sludge reduction and potential phosphorus recovery.

A simultaneous nitrification-denitrification and phosphorus removal (SNDPR) system operated in an alternating anaerobic/aerobic/anoxic (A/O/A) mode was revisited from new perspectives of sludge reduction and potential phosphorus recovery. Reliable and robust removal performance was obtained even under winter temperatures, with average removal efficiency of COD, TP, NH4+-N and TIN being 89.68%, 93.60%, 92.15% and 79.01% at steady state, respectively. Inoculated sludge got enhanced in biomass density, settleability, and bioactivity. And relatively stable amounts of extracellular polymeric substances (EPS) with a stable protein/ polysaccharide (PN/PS) ratio were observed over operation. Meanwhile, a low observed sludge yield (Yobs) of 0.083 g MLSS/g COD (0.082 g MLVSS/g COD) was obtained. A maximum anaerobic phosphorus release up to 43.54 mg/L was found, thus providing phosphorus-rich and low-turbidity stream for further phosphorus recovery. Overall, the SNDPR system deserved attention for in situ sludge reduction and potential phosphorus recovery, beyond reliable and stable wastewater treatment.

Extravascular Lung Water and Intrathoracic Blood Volume Index Are Associated With Liver Function in Brain Dead Donors for Organ Transplant.

OBJECTIVES: Hemodynamic measurements during organ transplant procedures are essential. MATERIALS AND METHODS: In this observational study, we measured clinical and hemodynamic parameters in 11 patients with advanced pulse indicator continuous cardiac output monitoring. Normally distributed clinical data were calculated as means ± standard deviation; hemodynamic, metabolic, and respiratory parameters related to liver and renal function were compared by linear regression analysis using Pearson correlation. RESULTS: Compared with the normal range, systemic vascular resistance was high (2278.02 ± 719.6 dyne·s/cm²/m²) and intrathoracic blood volume was low (787.37 ± 224.01 mL/m²) in our patient group. C-reactive protein and interleukin 6 levels were 96.26 ± 68.10 mg/mL and 246.24 ± 355.74 mmol/L, respectively. Liver and renal function parameters were in normal ranges. Extravascular lung water was correlated with total, conjugated, and unconjugated bilirubin and albumin (r = 0.342/P = .005; r = 0.338/ P = .005; r = 0.394/P = .001, and r = 0.358/P = .003) but not with aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and serum creatinine. Intrathoracic blood volume index was correlated with total bilirubin, unconjugated bilirubin, and albumin (r = 0.324/P = .007; r = 0.394/P = .001, and r = 0.296/P = .015) but not with conjugated bilirubin, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and serum creatinine. Lactate was not correlated with total bilirubin, unconjugated bilirubin, albumin, and serum creatinine, but base excess was correlated with total bilirubin, unconjugated bilirubin, alanine aminotransferase, and albumin. PO2 and Pco2 were not correlated with liver function, although PO2 was correlated with albumin. CONCLUSIONS: No correlations were shown between intrathoracic blood volume index, extravascular lung water, and liver function, but metabolic parameters, including base excess and lactate, were correlated with liver function. Pulse indicator continuous cardiac output monitoring may be a useful method to assess organ function and tissue perfusion in organ transplant.

Exendin-4 Preserves Blood-Brain Barrier Integrity via Glucagon-Like Peptide 1 Receptor/Activated Protein Kinase-Dependent Nuclear Factor-Kappa B/Matrix Metalloproteinase-9 Inhibition After Subarachnoid Hemorrhage in Rat.

In this study, we investigated the role of Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, in blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH) in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats. Ex-4 was intraperitoneally injected 1 h after SAH induction. To elucidate the underlying molecular mechanism, small interfering ribonucleic acid (siRNA) for GLP-1R and Dorsomorphin, a specific inhibitor of adenosine monophosphate-activated protein kinase (AMPK), were intracerebroventricularly injected 48 h before induction of SAH correspondingly. Immunofluorescence results supported GLP-1R expressed on the endothelial cells of microvessels in the brain after SAH. Administration of Ex-4 significantly reduced brain water content and Evans blue extravasation in both hemispheres, which improved neurological scores at 24 h after SAH. In the mechanism study, Ex-4 treatment significantly increased the expression of GLP-1R, p-AMPK, IκB-α, Occludin, and Claudin-5, while the expression of p-nuclear factor-kappa B (NF-κB) p65, matrix metalloproteinase-9 (MMP-9), and albumin was significantly decreased. The effects of Ex-4 were reversed by the intervention of GLP-1R siRNA or Dorsomorphin, respectively. In conclusion, Ex-4 could preserve the BBB integrity through GLP-1R/AMPK-dependent NF-κB/MMP-9 inhibition after SAH, which should be further investigated as a potential therapeutic target in SAH.

Effects of phenol on extracellular polymeric substances and microbial communities from aerobic granular sludge treating low strength and salinity wastewater.

The effects of phenol on aerobic granular sludge including extracellular polymeric substances (EPS) and microbial community were investigated for low strength and salinity wastewater treatment. Elevated phenol over 20 mg/L stimulated biological phosphorus removal mainly via co-metabolism with nearly complete phenol degradation, whereas resulted in significant accumulation of nitrate around 4 mg/L. Aerobic granules kept structural stability via enhancing production of extracellular polymeric substances (EPS), especially folds of polysaccharides (PS) and varying functional groups identified through EEM, FTIR and XPS spectral characterizations at increasing phenol loads. Illumina MiSeq sequencing results indicated that elevated phenol decreased the bacterial diversity and richness, and caused remarkable variations in structural and compositions of microbial population. Multiple halophilic bacteria including Stappia, Luteococcus, and Formosa laid the biological basis for stability of aerobic granules and efficient biological nutrients and phenol removal. Redundancy analysis (RDA) suggested the key role of phenol in shaping the relative abundances and predominant genera. This study proved that aerobic granular sludge was feasible for low-saline and phenol-laden low-strength wastewater treatment.

Interaction and removal of oxytetracycline with aerobic granular sludge.

Aerobic granular sludge as a promising technology showed great resistance to adverse conditions. However, the interaction between oxytetracycline (OTC) and granular sludge was not studied sufficiently. This study therefore investigated OTC-tolerance ability of incomplete and complete granulation sludge from aspects of simultaneous nutrients removal, sludge characteristics, microbial activity, community changes, and vice versa OTC removal performance. Incomplete granulation sludge showed better denitrification performance and resistance. Whereas, denitrification and phosphorus removal of complete granulation sludge suffered a permanent collapse under 5 mg/L OTC. OTC could be removed by rapid adsorption and slow biodegradation via granular sludge. The EPS, especially TB-PS, played a significant role during the operational period subjected to OTC. The major genera of Lysobacter and Candidatus_Competibacter laid the biological basis for stability and functionality of granules, which acted as the putative contributors for resisting and removing OTC. This study showed that incomplete-granulated sludge qualified more promising application prospect.

Flexible endoscope visualization to assist in the removal of a string of 10 schwannomas at the cauda equina: technical case report.

Bead-like schwannomas at the cauda equina are rare but benign intraspinal tumors. They can involve multiple nerve roots and spread within the spinal canal, and open resection would cause significant trauma. The authors have successfully applied a novel minimally invasive technique for the total removal of such schwannomas. A 68-year-old woman presented with a 1-month history of left waist and leg pain. MRI demonstrated multiple intraspinal lesions located from L1 to S1. The diagnosis was bead-like schwannomas at the cauda equina. Two incisions were made at the T12 and L5 levels. A flexible endoscope was introduced into the spinal canal following hemisemilaminectomy under a microscope to identify the relationship between the tumors and the carrying nerves. After dissecting both cranial and caudal ends of the carrying nerve, the string of bead-like tumors was gently pulled out from the caudal end as a whole. The endoscope was reintroduced into the spinal canal to ensure complete tumor removal. The patient recovered quickly, and no tumor residual was found at postoperative MRI. Flexible endoscope-assisted visualization plus microscopic hemisemilaminectomy via 2 incisions is a feasible minimally invasive approach for selected patients with bead-like schwannomas at the cauda equina.

Recombinant OX40 attenuates neuronal apoptosis through OX40-OX40L/PI3K/AKT signaling pathway following subarachnoid hemorrhage in rats.

Subarachnoid hemorrhage (SAH) is the most devastating form of stroke. Reducing neuronal apoptosis is an important countermeasure against early brain injury (EBI) after SAH. Recent evidence indicates that OX40-OX40L coupling is critical for cell survival and proliferation. Current study was performed to detect the role of recombinant OX40 (ReOX40) against neuronal apoptosis after SAH. The endovascular perforation model of SAH was performed on Sprague-Dawley (SD) rats. ReOX40 was injected intracerebroventricularly (i.c.v) 1 h after SAH induction and the following methods were employed: neurological function evaluation, immunofluorescence staining, fluoro-Jade C staining, and western blot. To study the underlying precise molecular mechanism, small interfering ribonucleic acid (siRNA) for OX40L and a specific inhibitor of PI3K, LY294002, were injected i.c.v. into SAH + ReOX40 rats before induction of SAH. When compared with sham rats, the expression of OX40 and OX40L was seen to decrease in the brain at 24 h after SAH induction. Administration of ReOX40 (5 µg/kg) increased expression of the OX40L, reduced the neuronal apoptosis, and improved short and long-term neurological function deficits. Furthermore, ReOx40 heightened activation of OX40L/PI3K/AKT axis, increased the downstream anti-apoptotic protein (Bcl2, Bcl-XL), and depressed the apoptotic protein (cleaved caspase 3, Bax). However, the protective effects of ReOX40 were abolished by the administration of OX40L siRNA and LY294002, respectively. These results demonstrate that ReOX40 attenuates neuronal apoptosis through OX40-OX40L/PI3K/AKT pathway in EBI after SAH.