Platycodin D facilitates antiviral immunity through inhibiting cytokine storm via targeting K63-linked TRAF6 ubiquitination.

Influenza virus infection is a worldwide challenge that causes heavy burdens on public health. The mortality rate of severe influenza patients is often associated with hyperactive immunological abnormalities characterized by hypercytokinemia. Due to the continuous mutations and the occurrence of drug-resistant influenza virus strains, the development of host-directed immunoregulatory drugs is urgently required. Platycodon grandiflorum is among the top 10 herbs of traditional Chinese medicine used to treat pulmonary diseases. As one of the major terpenoid saponins extracted from Platycodon grandiflorum, Platycodin D (PD) has been reported to play several roles, including anti-inflammation, analgesia, anti-cancer, hepatoprotection, and immunoregulation. However, the therapeutic roles of PD to treat influenza virus infection remains unknown. Here, we show that PD can protect the body weight loss in severely infected influenza mice, alleviate lung damage, and thus improve the survival rate. More specifically, PD protects flu mice via decreasing the immune cell infiltration into lungs and downregulating the overactivated inflammatory response. Western blot and immunofluorescence assays exhibited that PD could inhibit the activation of TAK1/IKK/NF-κB and MAPK pathways. Besides that, CETSA, SPR and immunoprecipitation assays indicated that PD binds with TRAF6 to decrease its K63 ubiquitination after R837 stimulation. Additionally, siRNA interference experiments exhibited that PD could inhibit the secretion of IL-1ß and TNF-α in TRAF6-dependent manner. Altogether, our results suggested that PD is a promising drug candidate for treating influenza. Our study also offered a scientific explanation for the commonly used Platycodon grandiflorum in many anti-epidemic classic formulas. Due to its host-directed regulatory role, PD may serve as an adjuvant therapeutic drug in conjunction with other antiviral drugs to treat the flu.

Fei-Yan-Qing-Hua decoction decreases hyperinflammation by inhibiting HMGB1/RAGE signaling and promotes bacterial phagocytosis in the treatment of sepsis.

ETHNOPHARMACOLOGICAL RELEVANCE: Fei-Yan-Qing-Hua decoction (FYQHD), derived from the renowned formula Ma Xing Shi Gan tang documented in Zhang Zhong Jing's "Treatise on Exogenous Febrile Disease" during the Han Dynasty, has demonstrated notable efficacy in the clinical treatment of pneumonia resulting from bacterial infection. However, its molecular mechanisms underlying the therapeutic effects remains elusive. AIM OF THE STUDY: This study aimed to investigate the protective effects of FYQHD against lipopolysaccharide (LPS) and carbapenem-resistant Klebsiella pneumoniae (CRKP)-induced sepsis in mice and to elucidate its specific mechanism of action. MATERIALS AND METHODS: Sepsis models were established in mice through intraperitoneal injection of LPS or CRKP. FYQHD was administered via gavage at low and high doses. Serum cytokines, bacterial load, and pathological damage were assessed using enzyme-linked immunosorbent assay (ELISA), minimal inhibitory concentration (MIC) detection, and hematoxylin and eosin staining (H&E), respectively. In vitro, the immunoregulatory effects of FYQHD on macrophages were investigated through ELISA, MIC, quantitative real-time PCR (Q-PCR), immunofluorescence, Western blot, and a network pharmacological approach. RESULTS: The application of FYQHD in the treatment of LPS or CRKP-induced septic mouse models revealed significant outcomes. FYQHD increased the survival rate of mice exposed to a lethal dose of LPS to 33.3%, prevented hypothermia (with a rise of 3.58 °C), reduced pro-inflammatory variables (including TNF-α, IL-6, and MCP-1), and mitigated tissue damage in LPS or CRKP-induced septic mice. Additionally, FYQHD decreased bacterial load in CRKP-infected mice. In vitro, FYQHD suppressed the expression of inflammatory cytokines in macrophages activated by LPS or HK-CRKP. Mechanistically, FYQHD inhibited the PI3K/AKT/mTOR/4E-BP1 signaling pathway, thereby suppressing the translational level of inflammatory cytokines. Furthermore, it reduced the expression of HMGB1/RAGE, a positive feedback loop in the inflammatory response. Moreover, FYQHD was found to enhance the phagocytic activity of macrophages by upregulating the expression of phagocytic receptors such as CD169 and SR-A1. CONCLUSION: FYQHD provides protection against bacterial sepsis by concurrently inhibiting the inflammatory response and augmenting the phagocytic ability of immune cells.

Effect of Lacticaseibacillus paracasei strain Shirota supplementation on clinical responses and gut microbiome in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor issues and a range of non-motor symptoms. Microbial therapy may be a useful approach for the treatment of PD. However, comprehensive analyses of the impact of probiotic supplementation on motor and non-motor symptoms are still lacking and the mechanisms whereby the treatment works remain unclear. This study investigated Lacticaseibacillus paracasei strain Shirota (LcS) supplementation on clinical responses, gut microbiota and faecal metabolites in PD patients. Patients (n = 128) were randomised to receive either probiotics (LcS-fermented milk, containing 1 × 1010 living LcS cells) or placebo for 12 weeks. All participants were examined and the basic clinical features were recorded using questionnaires. Fecal and blood samples were collected at the baseline and after 12 weeks for further omics analysis. We found that LcS intervention significantly alleviated patients' constipation-related symptoms and non-motor symptoms. We found no significant shifts in the composition of gut microbiota or faecal metabolites. Several taxa were differentially abundant between the groups, especially with regard to LcS intake, which increased the abundance of the genus Lacticaseibacillus in the probiotic group compared with those at the baseline and in the placebo group. The faecal concentration of L-tyrosine was significantly decreased and the plasma concentration of L-tyrosine was increased in the probiotic group compared with the placebo group. Our study demonstrated that although supplementation with LcS did not induce major changes in the global gut microbiome, the probiotic had favorable effects in managing constipation and other non-motor symptoms in PD patients. This study was registered at the Chinese Clinical Trial Registry: ChiCTR1800016795.

Body size determines multitrophic soil microbiota community assembly associated with soil and plant attributes in a tropical seasonal rainforest.

To understand soil biodiversity we need to know how soil communities are assembled. However, the relationship between soil community assembly and environmental factors, and the linkages between soil microbiota taxonomic groups and their body sizes, remain unexplored in tropical seasonal rainforests. Systematic and stratified random sampling was used to collect 243 soil and organism samples across a 20-ha plot in a tropical seasonal rainforest in southwestern China. High-throughput sequencing, variation analysis and principal coordinates of neighbourhood matrices were performed. Soil community composition, spatial distribution and assembly processes based on propagule size (including archaea, bacteria, fungi and nematodes) were investigated. The results showed that: (i) the community assembly of small soil microorganisms (bacteria, fungi) was mostly influenced by stochastic processes while that of larger soil organisms (nematodes) was more deterministic; (ii) the independent effects of habitat (including soil and topographic variables) and its interaction with plant attributes for community structure significantly decreased with increasing body size; and (iii) plant leaf phosphorus directly influenced the spatial distribution of soil-available phosphorus, which indicates their indirect impact on the assembly of the soil communities. Our data suggest that the assembly of multitrophic soil communities can be explained to some extent by changes in above-ground plant attributes. This highlights the importance of above- and below-ground linkages in influencing multitrophic soil microbiota community assembly.

Negative emotion-conditioned prepulse induces the attentional enhancement of prepulse inhibition in humans.

Prepulse inhibition (PPI) is a reduction of the acoustic startle reflex (ASR) when the startling stimulus is preceded by a weaker and non-startling stimulus (i.e., prepulse). Previous studies have revealed that PPI can be top-down modulated by selective attention to the fear-conditioned prepulse in animals. However, few researchers have tested this assumption in humans. Thus, in this study, the negative emotional-conditioned prepulse (CS+) was used to explore whether it could improve participants' attention, and further improve the PPI. The results showed that the CS+ prepulse increased the PPI only in females, PPI produced by CS+ prepulse was larger in females than in males, and the perceptual spatial attention further improved the PPI in both females and males. The results suggested that the PPI was affected by emotional, perceptual spatial attention, and sex. These findings highlight an additional method to measure top-down attentional regulation of PPI in humans. Which may offer a useful route to enhance the diagnosis of affective disorders, such as anxiety, depression, and post-traumatic stress disorder.

Downregulation of Circ-PITHD1 Suppressed Colorectal Cancer via Glycolysis Inhibition through miR-590-5p/HK2 Axis.

Colorectal cancer (CRC) is a frequent malignancy around the globe. Circular RNAs (circRNAs) are implicated in CRC development. Nevertheless, the regulatory mechanisms and biological functions regarding circRNAs in CRC progression are largely unclear. The present investigation employed next-generation sequencing (NGS) to study the abnormal circRNA expression in CRC tissues. The regulatory mechanism and targets were then analyzed by bioinformatics, luciferase reporter analysis, CCK8, colony formation, and Transwell migration. In vivo metastasis and tumorigenesis assays were conducted to elucidate circ-PITHD1 roles regarding CRC. The data showed that circ-PITHD1 expression increased in a CRC cell line and tissues, which indicated that circ-PITHD1 functioned in CRC progression. circ-PITHD1 downregulation inhibited CRC invasion and proliferation in the experiments. Luciferase reporter results confirmed that both miR-590-5p and hexokinase 2 (HK2) were circ-PITHD1 downstream targets. HK2 overexpression or miR-590-5p suppression reversed CRC cell proliferation and invasion after silencing of circ-PITHD1 by regulation of glycolysis. Taken together, this investigation discovered that circ-PITHD1 downregulation suppressed CRC progression by inhibiting glycolysis via the miR-590-5p/HK2 axis.

Spatial pattern of functional genes abundance reveals the importance of PhoD gene harboring bacterial community for maintaining plant growth in the tropical forest of Southwestern China.

The concept of microbial functional genes has added a new dimension to microbial ecology research by improving the model of microbial community-ecosystem functions relationship. However, our knowledge vis-à-vis fine-scale spatial distribution pattern of functional genes and their probable impact on plant community in the hyper-diverse tropical forest ecosystem is very limited. Here, we investigated the spatial pattern of functional genes abundance (NirK, AOA, AOB, and PhoD), identified key influencing factors, and distinguished the key functional group supporting the plant community in a tropical rainforest located in Xishuangbanna. In total, 200 soil samples and vegetation data of ~4800 individuals of plants across a 1 ha study area were collected. Our results detected higher spatial variability with a maximum magnitude of abundance for PhoD gene (4.53 × 107 copies) followed by NirK (2.71 × 106 copies), AOA (1.97 × 106 copies), and AOB (7.38 × 104 copies). A strong spatial dependence was observed for PhoD and NirK over the distance of 17 and 18 m, respectively. Interestingly, the N:P stoichiometry played a critical role in structuring the spatial pattern of the most abundant PhoD gene. The significant positive and negative relationship of PhoD with N:P ratio and available phosphorus, respectively, indicated that the P-limiting environment was a driving factor for recruitment of PhoD gene community. The structural equation modeling ascertained the direct positive impact of PhoD on plant biomass and high demand of available P by plants suggesting that the organic phosphorus mineralization process is essential to maintain plant productivity by re-establishing the availability of the most limiting P nutrient. Our preliminary study improves our understanding of how microbial functional genes-environment associations could be used for monitoring soil health and its overall impact on ecosystem multifunctionality. Finally, we intend to conduct the study at a large spatial scale for achieving a holistic view.

Perceptual spatial position induces the attentional enhancement of prepulse inhibition and its neural mechanism.

Prepulse inhibition (PPI) is a sensorimotor gating process that reduces the startling response when a weaker sensory stimulus precedes a sudden startling stimulus. Perceptual spatial separation (PSS) between the prepulse and the background noise was found to enhance PPI compared to perceptual spatial co-location (PSC). However, little is known about the perceptual characteristics of prepulses in the PSS that induce more inhibition of the startling response and the associated neural mechanism. The dorsocentral striatum (DCS) was the convergence of spatial information from the cortical and thalamic circuits. Our study investigated whether the perceptual spatial position of prepulses induced spatial attentional modulation of PPI. In addition, whether the DCS was involved in spatial attentional modulation's neural circuits of PPI. In our study, the relative perceptual image positions of the prepulse and masker were controlled by the playback time difference between the two loudspeakers, i.e., PSS and PSC. The specific spatial attention of the prepulse was conditioned by foot shock. The results revealed that PPI was generally enhanced after fear conditioning/conditioning-control manipulation across all rats. Further enhancement of PPI in the PSS condition occurred only in the fear conditioning position, not in the conditioning-control position. We first found that PPI did not show specific spatial enhancement in the drug-blocking bilateral DCS rats with 2 mM kynurenic acid. These results demonstrated that the perceptual spatial position modulated the spatial attention of prepulse and improved PPI. DCS was involved in the attentional modulation neural circuits of PPI and processed spatial information of prepulse.

Investigation of selenium nutritional status and dietary pattern among children in Kashin-Beck disease endemic areas in Shaanxi Province, China using duplicate portion sampling method.

BACKGROUND AND OBJECTIVES: Selenium deficiency is a primary risk factor of Kashin-Beck disease (KBD). This study aimed to investigate whether children in endemic areas could maintain sufficient selenium intake after termination of selenium supplement administration, and evaluate their comprehensive nutritional status and dietary structure. METHODS: Duplicate portion sampling combined with a questionnaire was adopted to collect data on categories and quantity of all food ingested in three consecutive days. Occipital hair was also collected to detect selenium content by hydride generation atomic fluorescence spectrometry (HGAFS). CDGSS3.0 software and factor analysis were integrated to assess the children's comprehensive nutritional status and dietary structure. RESULTS: This study included 240 sex-matched (1:1) children aged 7-12 years from KBD endemic (n = 120) and non-endemic (n = 120) areas. Overall, 720 solid food, 720 liquid, and 240 hair samples were collected for selenium determination. The mean selenium level in hair of children in endemic areas (0.38 ± 0.16 mg/kg) was significantly lower than that in children in non-endemic areas (0.56 ± 0.28 mg/kg, Z = -5.249, p < 0.001). The dietary selenium intake of children in endemic areas was 40.0% lower than that in children in non-endemic areas (Z = -9.374, p < 0.001). Children in endemic areas consumed significantly less diverse dietary items leading to significantly less intake of multiple nutrients compared to children in non-endemic areas. CONCLUSIONS: The dietary selenium intake of most children in endemic areas was less than the recommended amount. The dietary structure of children was undiversified, which limited the intake of multiple nutrients. Therefore, comprehensive nutrition rather than sole selenium intake should be the primary concern in the future.

Mucosal-associated invariant T cells: A cryptic coordinator in HIV-infected immune reconstitution.

Human immunodeficiency virus type 1 (HIV-1) infection causes considerable morbidity and mortality worldwide. Although antiretroviral therapy (ART) has largely transformed HIV infection from a fatal disease to a chronic condition, approximately 10%-40% of HIV-infected individuals who receive effective ART and sustain long-term viral suppression still cannot achieve optimal immune reconstitution. These patients are called immunological nonresponders, a state associated with poor clinical prognosis. Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved unconventional T-cell subset defined by expression of semi-invariant αß T-cell receptor (TCR), which recognizes metabolites derived from the riboflavin biosynthetic pathway presented on major histocompatibility complex-related protein-1. MAIT cells, which are considered to act as a bridge between innate and adaptive immunity, produce a wide range of cytokines and cytotoxic molecules upon activation through TCR-dependent and TCR-independent mechanisms, which is of major importance in defense against a variety of pathogens. In addition, MAIT cells are involved in autoimmune and immune-mediated diseases. The number of MAIT cells is dramatically and irreversibly decreased in the early stage of HIV infection and is not fully restored even after long-term suppressive ART. In light of the important role of MAIT cells in mucosal immunity and because microbial translocation is inversely associated with CD4+ T-cell counts, we propose that MAIT cells participate in the maintenance of intestinal barrier integrity and microbial homeostasis, thus further affecting immune reconstitution in HIV-infected individuals.

Bacterial community profile of the crude oil-contaminated saline soil in the Yellow River Delta Natural Reserve, China.

Crude oil contamination greatly influence soil bacterial community. Proliferative microbes in the crude oil-contaminated soil are closely related to the living conditions. Oil wells in the Yellow River Delta Natural Reserve (YRDNR) region is an ideal site for investigating the bacterial community of crude oil-contaminated saline soil. In the present study, 18 soil samples were collected from the depths of 0-20 cm and 20-40 cm around the oil wells in the YRDNR. The bacterial community profile was analyzed through high-throughput sequencing to trace the oil-degrading aerobic and anaerobic bacteria. The results indicated that C15-C28 and C29-C38 were the main fractions of total petroleum hydrocarbon (TPH) in the sampled soil. These TPH fractions had a significant negative effect on bacterial biodiversity (Shannon, Simpson, and Chao1 indices), which led to the proliferation of hydrocarbon-degrading bacteria. A comprehensive analysis between the environmental factors and soil microbial community structure showed that Streptococcus, Bacillus, Sphingomonas, and Arthrobacter were the aerobic hydrocarbon-degrading bacteria; unidentified Rhodobacteraceae and Porticoccus were considered to be the possible facultative anaerobic bacteria with hydrocarbon biodegradation ability; Acidithiobacillus, SAR324 clade, and Nitrosarchaeum were predicted to be the anaerobic hydrocarbon-degrading bacteria in the sub-surface soil. Furthermore, large amount of carbon sources derived from TPH was found to cause depletion of bioavailable nitrogen in the soil. The bacteria associated with nitrogen transformation, such as Solirubrobacter, Candidatus Udaeobacter, Lysinibacillus, Bradyrhizobium, Sphingomonas, Mycobacterium, and Acidithiobacillus, were highly abundant; these bacteria may possess the ability to increase nitrogen availability in the crude oil-contaminated soil. The bacterial community functions were significantly different between the surface and the sub-surface soil, and the dissolved oxygen concentration in soil was considered to be potential influencing factor. Our results could provide useful information for the bioremediation of crude oil-contaminated saline soil.

A rapid quality grade discrimination method for Gastrodia elata powderusing ATR-FTIR and chemometrics.

Gastrodia elata is an obligate fungal symbiont used in traditional Chinese medicine. There are currently 4 grades of the plant based on the "Commodity Specification Standard of 76 Kinds of Medicinal Materials". The traditional discrimination methods for determining the medicinal grade of G. elata powders are complex and time-consuming which are not suitable for rapid analysis. We developed a rapid analysis method for this plant using attenuated total reflection and Fourier-transform infrared spectroscopy (ATR-FTIR) together with machine learning algorithms. The original spectroscopic data was first pre-treated using the multiplicative scatter correction (MSC) method and 4 principal components were extracted using extremely randomized trees (Extra-trees) and principal component analysis (PCA) algorithms, and different kinds of classification models were established. We found that multilayer perceptron classifier (MLPC) modeling was superior to support vector machine (SVM) and resulted in validation and prediction accuracies of 99.17% and 100%, respectively and a modeling time of 2.48 s. The methods established from the current study can rapidly and effectively distinguish the 4 different types of G. elata powders and thus provides a platform for rapid quality inspection.

[Research on quality difference of standard decoction of raw and fried Paeoniae Radix Alba based on fingerprint and multicomponent determination].

The extract rates, multicomponent content and fingerprint were determined in this study to investigate the quality diffe-rence between standard decoction of raw Paeoniae Radix Alba and fried Paeoniae Radix Alba. UPLC fingerprint was established for 17 batches of standard decoction of raw and fried Paeoniae Radix Alba, and the contents of gallic acid, catechin, albiflorin, paeoniflorin and benzoyl paeoniflorin were determined. The peak areas of standard decoction were analyzed by the independent t-test and orthogonal partial least squares discriminant analysis. There was no significant difference in extract rates between the standard decoction of raw and fried Paeoniae Radix Alba. After fried processing, the content of albiflorin increased by 0.26%, while the contents of gallic acid, catechin, paeoniflorin and benzoyl paeoniflorin decreased by 13.04%, 27.97%, 10.30% and 18.79% respectively. There were 14 common peaks in the fingerprint of standard decoction of raw Paeoniae Radix Alba, and 16 common peaks in the fried Paeoniae Radix Alba. Peak 1 and peak 3 were new ones after processing, among which the peak 3 was 5-hydroxymethylfurfural. The results showed that peak 1, peak 3, peak 11 and peak 15 were the key compounds to distinguish standard decoction of raw and fried Paeoniae Radix Alba. In conclusion, this method is stable and can be used for the study of quantity transfer and quality control in the preparation process of standard decoction, granules and other dosage forms for raw and fried Paeoniae Radix Alba, providing reference for the identification of raw and fried Paeoniae Radix Alba and related preparations.

Metagenomics analysis identifies nitrogen metabolic pathway in bioremediation of diesel contaminated soil.

Nitrogen amendment is known to effectively enhance the bioremediation of hydrocarbon-contaminated soil, but the nitrogen metabolism in this process is not well understood. To unravel the nitrogen metabolic pathway(s) of diesel contaminated soil, six types of nitrogen sources were added to the diesel contaminated soil. Changes in microbial community and soil enzyme genes were investigated by metagenomics analysis and chemical analysis through a 30-day incubation study. The results showed that ammonium based nitrogen sources significantly accelerated the degradation of total petroleum hydrocarbon (TPH) (79-81%) compared to the control treatment (38%) and other non-ammonium based nitrogen amendments (43-57%). Different types of nitrogen sources could dramatically change the microbial community structure and soil enzyme gene abundance. Proteobacteria and Actinobacteria were identified as the two dominant phyla in the remediation of diesel contaminated soil. Metagenomics analysis revealed that the preferred metabolic pathway of nitrogen was from ammonium to glutamate via glutamine, and the enzymes governing this transformation were glutamine synthetase and glutamate synthetase; while in nitrate based amendment, the conversion from nitrite to ammonium was restrained by the low abundance of nitrite reductase enzyme and therefore retarded the TPH degradation rate. It is concluded that during the process of nitrogen enhanced bioremediation, the most efficient nitrogen cycling direction was from ammonium to glutamine, then to glutamate, and finally joined with carbon metabolism after transforming to 2-oxoglutarate.

Yidu-toxicity blocking lung decoction ameliorates inflammation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome by eliminating IL-6 and TNF-a.

The present study investigates the differences in inflammatory agents alterations, immune function, and leukocyte differential count evaluation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome after the recommended Chinese medicine prescription of Yidu-toxicity blocking lung decoction. A total of 40 patients with yidu-toxicity blocking lung syndrome, diagnosed as severe pneumonia of SARS-COV-2 following the latest Chinese national recommendations for the diagnosis and treatment of pneumonia caused by SARS-COV-2 (the 5th edition), were recruited. They were randomly divided into the pure western medicine therapy group (PWM) and integrated into Chinese and Western medicine therapy group (ICW). The general strategies were given to both groups according to the national recommendations, and the ICW group was given Yidu-toxicity blocking lung decoction extraorally. A radioimmunoassay method was adopted to detect the content of IL-6, IL-8,IL-2R,TNF-α, procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in sera. Flow cytometry was used to determine the peripheral blood lymphocyte subsets (the levels of CD3+, CD4+, CD8+, and the ratios of CD4+/CD8+). The white blood cell counts (WBC#), neutrophils count(N#), and lymphocyte counts (L#) were measured using a fully automatic blood rheological instrument. The t-test or Rank Sum Test and Spearman analysis were conducted to evaluate the differences. The results showed that IL-6 (P = 0.013) and TNF-α (P = 0.035) levels in the PWM group were significantly higher than those in the ICW group after treatment. Infection related indicators such as WBC#, N#, L#, hs-CRP showed no differences. The analysis showed that there was no statistical difference in the values of CD4 and CD8 between the two groups. By the end of Day 29, all patients were discharged and the final cure rate for both group were 100 %. Taken together, we conclude that Yidu-toxicity blocking lung decoction could relieve inflammation of SARS-COV-2 patients with yidu-toxicity blocking lung syndrome by eliminating inflammatory agents. CM can serve as a complementary medication to western medicine, which should be highlighted in clinical settings.

A Comparison of Gastric and Jejunal Feeding in Hypercatabolism Associated With Hypothalamic AMPK-Autophagy-POMC in Endotoxemic Rats.

BACKGROUND: Hypercatabolism is associated with increased infectious rates and mortality in critically ill patients. Enteral nutrition (EN) is usually used to counteract hypercatabolism. However, the impact of different routes of EN on hypercatabolism remains unknown. Here, we compared the impact of gastric feeding (GF) and jejunal feeding (JF) on gastrointestinal hormones and hypercatabolism, which is associated with hypothalamic adenosine 5'-monophosphate-activated protein kinase (AMPK)-autophagy-proopiomelanocortin (POMC). METHODS: Sixty adult male Sprague-Dawley rats were divided into 5 groups: Sham and lipopolysaccharide (LPS) groups fed a standard chow diet, a pair-fed group that was a subset of saline-treated rats pair-fed with the LPS group, and LPS + JF and LPS + GF groups (received EN via jejunal and gastric tube, respectively, for 3 days [100 kcal/kg/d]). Hypercatabolism was measured by insulin resistance, muscle protein synthesis, and atrophy. Serum gastrointestinal hormones, hypothalamic ghrelin, growth hormone secretagogue receptor-1α (GHS-R1α), and AMPK-autophagy-POMC markers were also detected. RESULTS: GF increased serum total, acylated, desacylated, and hypothalamic ghrelin and decreased glucagon-like peptide-1 (GLP-1). But no effect on pancreatic polypeptide (PYY) and hypothalamic GHS-R1α was observed. JF showed no effect on hypothalamic ghrelin, GHS-R1α, and serum total, acylated, and desacylated ghrelin and even further aggravated GLP-1 and PYY. GF could effectively augment hypothalamic AMPK-autophagy-POMC and hypercatabolism. However, JF showed no effect on hypothalamic AMPK-autophagy-POMC and hypercatabolism. CONCLUSIONS: GF could activate hypothalamic AMPK-autophagy and suppress POMC expression via gastrointestinal hormones to ameliorate hypercatabolism compared with JF, which suggested that GF may be the preferred route of EN in endotoxemic rats.

Design and optimization of crocetin loaded PLGA nanoparticles against diabetic nephropathy via suppression of inflammatory biomarkers: a formulation approach to preclinical study.

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus whose expand process is linked with the fibrosis, renal hypertrophy and inflammation. The current study was to formulate and optimize the nano-formulation of crocetin (CT-PLGA-NPs) against Streptozotocin-induced renal nephropathy in rats. Double emulsion evaporation technique was used for the preparation of CT-PLGA-NPs. CT-PLGA-NPs were scrutinized for polydispersity index, size, gastric stability, entrapment, drug-loading capacity and in-vitro drug release and in vivo preclinical study. Single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg) and rats were divided into different group. Renal function and metabolic parameters of urine and serum were estimated. Fibrotic protein, renal pro-inflammatory cytokines and degree of renal damage expression were also determined. We also estimated the fibronectin, type IV collagen and transforming growth factor-ß1 for a possible mechanism of action. Crocetin supplement (10 mg/kg) and CT-PLGA-NPs exhibited the accumulation of the drug in kidney and liver of diabetic rats. Crocetin reduced the BGL and enhanced plasma insulin and body weight. Dose dependent treatment of crocetin significantly (p < .001) down-regulated the expression of renal tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin (IL)-1ß (IL-1ß) and Monocyte Chemoattractant Protein-1 (MCP-1). Crocetin significantly (p < .001) altered the expression of fibronectin, type IV collagen, and transforming growth factor-ß1 (TGF-1ß). Crocetin significantly (p < .001) down-regulated the protein kinase C activity and the expression of nuclear factor κB (NF-κB) p65 activity and protein production in renal tissue. On the basis of the available result, we can conclude that nano-formulation of crocetin could attenuate the diabetic nephropathy via antifibrotic and anti-inflammatory effect.

Identification of unhealthy Panax notoginseng from different geographical origins by means of multi-label classification.

Root-knot nematode is a common plant-parasitic pest with a highly destructive that infects more than 2000 plant species. Panax notoginseng (P. notoginseng) is one of the most susceptible traditional medicine. More importantly, it is difficult to distinguish the powders of P. notoginseng infected with root-knot nematode from those of healthy P. notoginseng due to the color and shape are same after being ground into powder. In this paper, Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) was used to identify P. notoginseng samples. Multiplicative scatter correction (MSC) was applied to preprocess the spectral data. Competitive adaptive reweighted sampling (CARS) and successive projection algorithm (SPA) were employed to select feature variables. Density-based spatial clustering of application with noise (DBSCAN) was adopted to discover groups within the data. Also, we found that the geographical origin is a pivotal factor to consider when identifying unhealthy P. notoginseng. Therefore, we introduced a novel multi-label classification (MLC) method to identify healthy and unhealthy P. notoginseng powders from three different geographical origins. In addition, binary relevance method (BR), classifier chain (CC), ensembles of classifier chains (ECC), and multilayer perceptron classifier (MLPC) were applied to create classification models, ECC exhibits superior performance in particular.

Effects of Selenium on Mercury Bioaccumulation in a Terrestrial food Chain from an Abandoned Mercury Mining Region.

Few reports of the relationship exist between mercury (Hg) and selenium (Se) from locations of severe Hg contamination in terrestrial environments. Here, we report the concentrations of Hg and Se as well as Se:Hg molar ratios in biotic samples collected from a region with a long history of Hg mining. Nitrogen isotopes (δ15N) were analyzed to confirm the trophic levels. Results showed that bird feathers at the top trophic level exhibited the highest Hg concentrations, while the lowest concentrations were found in herbivorous insects, demonstrating a significant biomagnification across the food chain. In contrast, herbivorous insects of different types (generalists vs. specialized rice pests) exhibited both the highest and the lowest concentrations of Se, indicating a lack of biomagnification. Indeed, Se was correlated positively with Hg when Se:Hg ratios were greater than one, suggesting Se:Hg molar ratios can be a controlling influence on Hg in terrestrial organisms.