[Preparation and effectiveness evaluation of placebo of Jiawei Ermiao Granules].

This study explored the preparation process of the placebo of Jiawei Ermiao Granules and evaluated the placebo effect, aiming to provide qualified placebo samples for clinical trials of Jiawei Ermiao Granules and a reference for the preparation and quality evaluation of placebos of traditional Chinese medicine granules. On the basis of the comprehensive analysis results of Jiawei Ermiao Granules, the orthogonal experiment was conducted to optimize the flavoring agents and colorants. After manual evaluation, the placebo formula was determined as dextrin 10 g, Codonopsis Radix extract 5.0 g, bitter melon extract 1.6 g, Mume Fructus extract 0.3 g, stevioside 0.1 g, sucrose octaacetate 0.004 g, indigo 0.004 g, lemon yellow 0.003 1 g, sunset yellow 0.001 8 g, bitter tea powder 0.001 8 g, caramel 0.001 3 g. Pilot trials were conducted on the placebo formula. The simulation effect of placebo was evaluated independently and comparatively, and the objectively evaluated by electronic nose and electronic tongue. The results showed that the independent manual evaluation of the placebo formula had higher error rate, and the placebo and Jiawei Ermiao Granules showed the similarity of 99.61% in the comparative manual evaluation. The smell similarity between the placebo and Jiawei Ermiao Granules was 99.19%, and the electronic tongue test showed little difference in the taste. In conclusion, the placebo prepared in this study shows a high similarity to Jiawei Ermiao Granules, which is not easy to break the blindness when being applied to clinical trials. This study provides a reference for the preparation and quality evaluation and promotes the large-scale production of placebos of traditional Chinese medicine granules, playing a role in improving the persuasiveness and acceptance of the efficacy of traditional Chinese medicines.

Rieske Iron-Sulfur Protein Mediates Pulmonary Hypertension Following Nicotine/Hypoxia Coexposure.

The high mortality rate in patients with chronic obstructive pulmonary disease (COPD) may be due to pulmonary hypertension (PH). These diseases are highly associated with cigarette smoke and its key component nicotine. Here, we created a novel animal model of PH using coexposure to nicotine (or cigarette smoke) and hypoxia. This heretofore unreported model showed significant early-onset pulmonary vasoremodeling and PH. Using newly generated mice with complementary smooth muscle-specific Rieske iron-sulfur protein (RISP) gene knockout and overexpression, we demonstrate that RISP is critically involved in promoting pulmonary vasoremodeling and PH, which are implemented by oxidative ataxia telangiectasia-mutated-mediated DNA damage and NF-κB-dependent inflammation in a reciprocal positive mechanism. Together, our findings establish for the first time an animal model of hypoxia-induced early-onset PH in which mitochondrial RISP-dependent DNA damage and NF-κB inflammation play critical roles in vasoremodeling. Specific therapeutic targets for RISP and related oxidative stress-associated signaling pathways may create unique and effective treatments for PH, chronic obstructive pulmonary disease, and their complications.

Ginsenoside F2-Mediated Intestinal Microbiota and Its Metabolite Propionic Acid Positively Impact the Gut-Skin Axis in Atopic Dermatitis Mice.

Atopic dermatitis (AD) is a complex inflammatory skin disease induced by multiple factors. AD can also cause intestinal inflammation and disorders of the gut microbiota. Ginseng is a kind of edible and medicinal plant; its main active components are ginsenosides. Ginsenosides have a variety of anti-inflammatory effects and regulate the gut microbiota; however, their role in AD and the underlying mechanisms are unclear. In this study, we found that intragastric administration of ginsenoside F2 improved AD-like skin symptoms and reduced inflammatory cell infiltration, serum immunoglobulin E levels, and mRNA expression of inflammatory cytokines in AD mice. 16s rRNA sequencing analysis showed that ginsenoside F2 altered the intestinal microbiota structure and enriched the short-chain fatty acid-producing microbiota in AD mice. Metabolomic analysis revealed that ginsenoside F2 significantly increased the propionic acid (Pa) content of feces and serum in AD mice, which was positively correlated with significant enrichment of Parabacteroides goldsteinii and Lactobacillus plantarum in the intestines. Pa inhibits inflammatory responses in the gut and skin of AD mice through the G-protein-coupled receptor43/NF-κB pathway, thereby improving skin AD symptoms. These results revealed, for the first time, the mechanism by which ginsenoside F2 improves AD through the Pa (a metabolite of intestinal microbiota)-gut-skin axis.

[Effect of acupuncture on HIF-1α/NLRP3 inflammatory signaling pathway in the rats with cerebral ischemia-reperfusion injury].

OBJECTIVE: To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury. METHODS: Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side. RESULTS: Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group. CONCLUSION: Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.

Methylprednisolone sodium succinate retroauricular injection combined with acupuncture in the treatment of Bell's Palsy.

Background: Retroauricular injection is a local steroid hormone administration method commonly used to treat deafness or tinnitus. The acute stage of Bell's Palsy is an acute disease that requires steroid therapy. Retroauricular injection may replace oral administration of steroid hormones in the treatment of this disease as well as reduce the occurrence of adverse reactions. Methods: This study included patients with Bell's Palsy within seven days of onset. A total of 120 patients were enrolled as the study subjects and randomly divided into two groups: the experimental group and the control group. Both groups received routine acupuncture treatment and took a traditional Chinese medicine decoction corresponding with the syndrome type. Methylprednisolone sodium succinate was injected into the bone surface of retroauricula in the experimental group, and prednisone acetate was orally administered in the control group. The main outcome indicators were the House-Brackmann (HB) grade, the facial disability index (FDI), and time of postauricular pain after one month of treatment. Results: There were no significant differences in the HB grade (2.00 ± 1.06 vs. 1.88 ± 1.06, P=), FDIP (97.25 ± 6.00 vs. 97.17 ± 7.39, P=), and FDIS (0.60 ± 3.02 vs. 1.33 ± 4.27, P=) at 30 days after treatment between the two groups (P > 0.05). Postauricular pain disappeared earlier in the experimental group (3.66 ± 1.67 days) than in the control group (6.31 ± 2.34); the difference was statistically significant (P ≤ 0.001). The adverse reaction rate was lower in the experimental group (15.00%) than in the control group (21.66%). Interpretation: Although the dose of steroid hormone injected into the bone surface of retroauricula in the treatment of Bell's Palsy is lower than the administered dose of oral hormones, it has the same curative effect; however, it has a better effect regarding to the duration of postauricular pain and adverse reactions.

Multichip multidimensional quantum networks with entanglement retrievability.

Quantum networks provide the framework for quantum communication, clock synchronization, distributed quantum computing, and sensing. Implementing large-scale and practical quantum networks relies on the development of scalable architecture and integrated hardware that can coherently interconnect many remote quantum nodes by sharing multidimensional entanglement through complex-medium quantum channels. We demonstrate a multichip multidimensional quantum entanglement network based on mass-manufacturable integrated-nanophotonic quantum node chips fabricated on a silicon wafer by means of complementary metal-oxide-semiconductor processes. Using hybrid multiplexing, we show that multiple multidimensional entangled states can be distributed across multiple chips connected by few-mode fibers. We developed a technique that can efficiently retrieve multidimensional entanglement in complex-medium quantum channels, which is important for practical uses. Our work demonstrates the enabling capabilities of realizing large-scale practical chip-based quantum entanglement networks.

Transcutaneous electronic acupoint stimulation improves bone marrow suppression in lung cancer patients following chemotherapy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficacy of transcutaneous electronic acupoint stimulation (TEAS) on bone marrow suppression in patients with lung cancer after chemotherapy. METHODS: We conducted a comprehensive search of 6 databases until November 2022 and included 6 randomized controlled trials comprising 534 patients in our analysis. Eligible randomized controlled trials were included based on predefined inclusion criteria. The weighted mean difference (WMD) was calculated with all of the continuous outcomes. Heterogeneity among the included studies was evaluated using Cochran I2 and Q statistics. When the value of I2 was over 50%, a random-effects model was used. Egger test was used to assess publication bias, and trim and fill analysis was conducted if bias was detected. RESULTS: Our analysis found that TEAS significantly increased white blood cell counts (WMD: 0.79, 95% confidence interval (CI): 0.40-1.18, P < .001), platelet counts (WMD: 45.45, 95% CI: 30.47-60.43, P < .001), and comfort score (WMD: 6.89, 95% CI: 5.12-8.66, P < .001) compared to the conventional group. However, no significant difference was observed in red blood cell counts (WMD: 0.00, 95% CI: -0.10 to 0.10, P = .97) and hemoglobin level (WMD: -0.01, 95% CI: -2.49 to 2.46, P = .99) between the 2 groups. CONCLUSIONS: We tentatively conclude that TEAS can reduce bone marrow suppression risk and improve comfort in lung cancer patients undergoing chemotherapy. However, larger randomized controlled trials with more diverse patient populations and blood routine indexes are urgently needed to confirm these findings.

Hair Follicles as a Critical Model for Monitoring the Circadian Clock.

Clock (circadian) genes are heterogeneously expressed in hair follicles (HFs). The genes can be modulated by both the central circadian system and some extrinsic factors, such as light and thyroid hormones. These circadian genes participate in the regulation of several physiological processes of HFs, including hair growth and pigmentation. On the other hand, because peripheral circadian genes are synchronized with the central clock, HFs could provide a noninvasive and practical method for monitoring and evaluating multiple circadian-rhythm-related conditions and disorders among humans, including day and night shifts, sleep-wake disorders, physical activities, energy metabolism, and aging. However, due to the complexity of circadian biology, understanding how intrinsic oscillation operates using peripheral tissues only may be insufficient. Combining HF sampling with multidimensional assays such as detection of body temperature, blood samples, or certain validated questionnaires may be helpful in improving HF applications. Thus, HFs can serve as a critical model for monitoring the circadian clock and can help provide an understanding of the potential mechanisms of circadian-rhythm-related conditions; furthermore, chronotherapy could support personalized treatment scheduling based on the gene expression profile expressed in HFs.

Salvia miltiorrhiza extract may exert an anti-obesity effect in rats with high-fat diet-induced obesity by modulating gut microbiome and lipid metabolism.

BACKGROUND: Studies have shown that a high-fat diet (HFD) can alter gut microbiota (GM) homeostasis and participate in lipid metabolism disorders associated with obesity. Therefore, regulating the construction of GM with the balance of lipid metabolism has become essential for treating obesity. Salvia miltiorrhiza extract (Sal), a common traditional Chinese medicine, has been proven effective against atherosclerosis, hyperlipidemia, obesity, and other dyslipidemia-related diseases. AIM: To investigate the anti-obesity effects of Sal in rats with HFD-induced obesity, and explore the underlying mechanism by focusing on GM and lipid metabolism. METHODS: Obesity was induced in rats with an HFD for 7 wk, and Sal (0.675 g/1.35 g/2.70 g/kg/d) was administered to treat obese rats for 8 wk. The therapeutic effect was evaluated by body weight, body fat index, waistline, and serum lipid level. Lipid factors (cAMP, PKA, and HSL) in liver and fat homogenates were analyzed by ELISA. The effect of Sal on GM and lipid metabolism was assessed by 16S rRNA-based microbiota analysis and untargeted lipidomic analysis (LC-MS/MS), respectively. RESULTS: Sal treatment markedly reduced weight, body fat index, serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein, glucose, free fatty acid, hepatic lipid accumulation, and adipocyte vacuolation, and increased serum high-density lipoprotein (HDL-C) in rats with HFD-induced obesity. These effects were associated with increased concentrations of lipid factors such as cAMP, PKA, and HSL in the liver and adipose tissues, enhanced gut integrity, and improved lipid metabolism. GM analysis revealed that Sal could reverse HFD-induced dysbacteriosis by promoting the abundance of Actinobacteriota and Proteobacteria, and decreasing the growth of Firmicutes and Desulfobacterita. Furthermore, LC-MS/MS analysis indicated that Sal decreased TGs (TG18:2/18:2/20:4, TG16:0/18:2/22:6), DGs (DG14:0/22:6, DG22:6/22:6), CL (18:2/ 18:1/18:1/20:0), and increased ceramides (Cers; Cer d16:0/21:0, Cer d16:1/24:1), (O-acyl)-ω-hydroxy fatty acids (OAHFAs; OAHFA18:0/14:0) in the feces of rats. Spearman's correlation analysis further indicated that TGs, DGs, and CL were negatively related to the abundance of Facklamia and Dubosiella, and positively correlated with Blautia and Quinella, while OAHFAs and Cers were the opposite. CONCLUSION: Sal has an anti-obesity effect by regulating the GM and lipid metabolism.

[Acupuncture regulates autophagic flux to antagonize cerebral ischemic injury in rats].

OBJECTIVE: To observe the effect of acupuncture on the cerebral infarct volume and expressions of Beclin1, microtubule-associated protein 1 light chain 3 (LC3) and p62 proteins related to cell autophagy in rats with cerebral ischemia (CI), so as to explore its mechanisms underlying improvement of CI injury. METHODS: Male SD rats were randomized into 3 groups: sham operation, model and acupuncture which were further divided into 4 subgroups according to different ischemia time-points: 3, 6, 12 and 24 h (n=7 in each subgroup). The CI model was established by occlusion of the middle cerebral artery (MCAO) with surgical suture-embolus. For rats of the acupuncture group, acupuncture was applied to "Shuigou" (GV26) and bilateral "Neiguan" (PC6), and twirled for 1-3 min every time, 10 times altogether, and kept for 30 min. The neurological deficit score accoding to Longa's method was used for assessing the neurological function. The CI volume was measured after 2, 3, 5-triphenyltetrazolium chloride staining. The expression levels of autophagy-related proteins Beclin1，LC3 and p62 in the brain tissue were detected using Western blot. RESULTS: Compared with those of the sham operation group，the neurological deficit scores at 2, 3, 6， 12 and 24 h after CI, and the infarct volumes, the expression levels of Beclin1 and the ratios of LC3-Ⅱ/LC3-Ⅰ at 3, 6, 12 and 24 h were considerably increased (P<0.01, P<0.05), and the expression levels of p62 at 3, 6, 12 and 24 h were significantly decreased (P<0.01) in the model group. Relevant to the model group, acupuncture stimulation of GV26 and PC6 induced an obvious decrease in the neurological deficit scores at 6, 12 and 24 h, CI volumes at 3, 6, 12 and 24 h, and the expression levels of Beclin1 and the ratios of LC3-Ⅱ/LC3-Ⅰ both at 6 and 12 h (P<0.01, P<0.05), and an evident increase in the expression levels of p62 at 6, 12 and 24 h after CI (P<0.05, P<0.01). CONCLUSION: Acupuncture stimulation of GV26 and PC6 can reduce the CI volume and improve neurological function in CI rats， which may be related to its efficacy in down-regulating the expression of Beclin1 and the ratio of LC3-Ⅱ/LC3-Ⅰ, and up-regulating the expression of p62 in the ischemic brain tissue， thereby improving autophagy flux.

[Nitric Oxide Emissions from Chinese Upland Cropping Systems and Mitigation Strategies: A Meta-analysis].

Agroecosystems are a significant source of nitric oxide (NO), a potent atmospheric pollutant. It has been well documented that the NO emissions from upland cropping systems and their emission factors are large relative to those from paddy fields. However, a clear understanding of their uncertainty and regulating factors is still lacking. To date, various field experiments have been conducted to investigate NO emissions and mitigation, providing an opportunity for a Meta-analysis. The aims of this study were to 1 investigate the uncertainty and regulating factors of NO emissions and emission factors from maize-winter wheat rotations, non-waterlogging period in rice-winter wheat rotations, vegetable fields, tea plantations, and fruit orchards across China by extracting data from peer-reviewed publications, and 2 quantify the mitigation potential of management practices, such as reducing nitrogen fertilizer input, organic substitution with chemical fertilizers, and application of enhanced-efficiency nitrogen fertilizers or biochar by performing a pairwise Meta-analysis. A total of 49 references (published from 2006 to 2021) were collected. The results showed that annual NO emissions from the maize-winter wheat rotations, tea plantations, and fruit orchards averaged 1.44, 7.45, and 0.92 kg·hm-2, respectively, with significant differences among the three cropping systems (P<0.05). The seasonal NO emissions from the non-waterlogging period in rice-winter wheat rotations and vegetable fields within a single growth period averaged 2.13 kg·hm-2 and 2.09 kg·hm-2, respectively. The NO emissions positively related to nitrogen inputs in the maize-winter wheat rotations, non-waterlogging period in rice-winter wheat rotations, and tea plantations (P<0.01) but not in the vegetable fields and fruit orchards. The emission factors averaged 0.31%, 0.71%, 0.96%, 1.74%, and 0.13% in the maize-winter wheat rotations, non-waterlogging period in rice-winter wheat rotations, vegetable fields, tea plantations, and fruit orchards, respectively, with significant differences among the cropping systems (P<0.01), except between the maize-winter wheat rotations and non-waterlogging period in rice-winter wheat rotations or vegetable fields (P>0.05). Considering the substantial differences in emission factors among the cropping systems, a specific emission factor for each system should be applied when estimating an agricultural NO budget at a regional or national scale. Reducing nitrogen input only mitigated NO emissions (by 36%) at a reducing nitrogen ratio above 25% but did not impact emission factors. An optimal reducing nitrogen ratio has to be further evaluated without crop productivity penalties. Organic substitution in soils with organic carbon content<15 g·kg-1 or pH<7 and application of enhanced-efficiency fertilizers in the maize-winter wheat rotation simultaneously mitigated NO emissions (by -46%- -38%) and emission factors (by -62%- -45%). By contrast, biochar amendment had no significant effects on either NO emissions or emission factors. These findings highlight a possibility of choosing an effective NO mitigation strategy under specific field conditions.

Sishen Pill Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis with Spleen-Kidney Yang Deficiency Syndromes: Role of Gut Microbiota, Fecal Metabolites, Inflammatory Dendritic Cells, and TLR4/NF-κB Pathway.

Sishen pill (SSP) is an old Chinese medicine used to treat colitis with spleen-kidney-yang deficiency (SKYD) syndromes. However, its exact mechanism of action has not yet been fully elucidated. The aim of this study was to evaluate the effects and potential mechanisms of SSP on colitis with SKYD syndromes in mice. Colitis with SKYD syndromes was induced by rhubarb, hydrocortisone, and dextran sulfate sodium (DSS), and treatment was provided with SSP. Flow cytometry was performed to examine the inflammatory dendritic cell (infDC) regulations of SSP. The changes in the gut microbiota (GM) and fecal metabolites post-SSP treatment were investigated using the combination of 16S rRNA sequencing and untargeted metabolomics. Additionally, we also examined whether SSPs could regulate the infDCs by modifying TLR4/NF-κB signaling pathways. Compared with the DSS group, the disease activity index, colonic weight, index of colonic weight, and colonic injury scores, as well as the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-12p70 decreased significantly in the DSS + SSP group, while free triiodothyronine (FT3), free tetraiodothyronine (FT4), testosterone (TESTO), body weight change, colonic length, and the levels of IL-10 increased. Also, SSP decreased the amounts of CD103+CD11c+iNOS+, CD103+CD11c+TNF-α +, CD11c+CD103+CD324+, CD103+CD11c+MHC-II+, and CD103+CD11c+CD115+. Interestingly, 16S rRNA sequencing and untargeted metabolomics showed that SSP treatment restored the dysbiosis of GM and improved the dysfunction in fecal metabolism in colitis mice with SKYD syndromes. Correlation analysis indicated that the modulatory effects of SSP on FT3, FT4, IL-10, colonic weight index, CD103+CD11c+TNF-α +, CD103+CD11c+MHC-II+, and 13 common differential metabolites were related to alterations in the abundance of Parvibacter, Aerococcus, norank_f_Lachnospiraceae, Lachnospiraceae_UCG-006, Akkermansia, and Rhodococcus in the GM. In addition, SSP markedly inhibited the activation of the TLR4, MyD88, TRAF6, TAB2, and NF-κBp65 proteins and activated IκB. These results indicate that SSP can effectively alleviate colitis mice with SKYD syndrome by regulating infDCs, GM, fecal metabolites, and TLR4/NF-κB signaling pathways.

Application of Acupoint Catgut Embedding Therapy Combined with Liuzijue Breathing Exercise in the Treatment of Patients with Stable Chronic Obstructive Pulmonary Disease.

Objective: To evaluate the application value of acupoint catgut embedding therapy combined with Liuzijue breathing exercise in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) and its impact on immune function and quality of life. Methods: A total of 100 patients with stable COPD admitted to our hospital from February 2020 to February 2021 were included and assigned to the experimental group (n = 50) and the control group (n = 50) according to the order of admission. Both groups of patients received conventional treatment. The control group was given daily inhalation of budesonide and formoterol fumarate powder for inhalation (320 ug/bottle), and the experimental group received additional acupoint catgut embedding therapy combined with Liuzijue breathing exercise. The clinical efficacy, pulmonary function indexes, activities of daily living (ADL) scores, quality of life (QOL) scores, traditional Chinese medicine (TCM) syndrome scores, the number of acute exacerbations, medical expenses, the incidence of adverse reactions, and immune indicators were compared between the two groups of patients. Results: The experimental group yielded a significantly higher effective rate of treatment than the control group (P < 0.05). After the treatment, the experimental group obtained a superior outcome in terms of lung function indexes, immune function indexes, ADL and QOL scores, and the TCM syndrome scores when compared with the control group (P < 0.05). The number of acute exacerbations in the experimental group was remarkably lower than that in the control group (P < 0.05). No serious adverse reactions were observed in the two groups of patients, and no significant difference in the incidence of adverse reactions was found (P > 0.05). Conclusion: Acupoint catgut embedding therapy combined with Liuzijue breathing exercise, with high safety, can improve the treatment effect and the quality of life of patients with stable COPD, which merits clinical promotion.

Supplementing cholamine to diet lowers laying rate by promoting liver fat deposition and altering intestinal microflora in laying hens.

The effects of cholamine, a raw material for synthesis of some active lipids, are unknown in poultry. To address this, 180 52-wk-old Hyline laying hens were randomly divided into 3 groups (20 replicates per group with three hens per replicate). The control group and the treatment groups (treatment 1 and 2) were fed basal diet and the diet supplemented with 500 or 1,000 mg of cholamine per kilogram of the diet for 35 d, respectively. The data showed that supplementary cholamine significantly lowered egg production, daily feed intake, serum high-density lipoprotein cholesterol level, liver index, and the percentages of C15:0 and C20:0 in fatty acid composition of liver, significantly elevated hepatic triglyceride content, the ratio of villus height to crypt depth (P < 0.05), and the percentage of C18:2n-6 and the ratio of n-6 to n-3 polyunsaturated fatty acids in liver fat (P < 0.10). Moreover, supplementary cholamine altered the relative abundance of some intestinal bacteria with a decrease in the alpha biodiversity (P < 0.10). Additionally, transcriptome analysis on the livers of the treatment vs. the control groups identified 1,151 up- and 914 down-regulated differentially expressed genes (DEGs), and pathway analysis revealed that the suppressed Notch signaling pathway and the enhanced Oxidative phosphorylation pathway were enriched with DEGs. Particularly, fat absorption, transport and oxidative phosphorylation-related DEGs (e.g., FABP1, APOA4, and PCK1) were significantly induced, but fatty acid synthesis, and lipid package and secretion-related DEGs (e.g., FASN, SCD, and MTTP) were not. In conclusion, supplementary cholamine may lower egg production by promoting hepatic lipid deposition and reducing abundances of beneficial intestinal bacteria and microfloral biodiversity in laying hens.

[Determination of absolute configuration of a new triterpenic acid in leaves of Ilex hainanensis].

This study aimed to explore the triterpenic acid components in leaves of Ilex hainanensis. Alkaline water extraction, macroporous resin adsorption, and high performance liquid chromatography were used to separate and purify the triterpenic acid components in leaves of I. hainanensis. The physical and chemical property analysis, MS, NMR spectroscopy, and literature comparison were performed to identify the structures, and a new triterpene acid compound was discovered:(3S, 4R, 5R, 8R, 9R, 10R, 14S, 17S, 18S, 19R)-3,19-dihydroxyursa-12,20(30)-diene-24,28-dioic-acid, and named ilexhainanin F. In addition, according to its structural characteristics, the ~(19)F-NMR Mosher method was further employed to study its absolute configuration. By comparison of the ~(19)F-NMR chemical shifts of Mosher esters, it was determined that the absolute configuration of the 3-position chiral center of the compound was the S configuration.

[Rapid quality evaluation of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle based on color digitization and multi-component determination].

To explore the color value changes after processing and further explore the correlations between color values and internal components, we established a rapid evaluation method for the quality of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle. In this study, the color values of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle were digitized by a spectrophotometer, and the standard ranges of color values of the two herbal medicines were established. Further, a discriminant analysis model was established to quickly and accurately distinguish the two herbal medicines. The content of 9 flavonoids and 1 triterpene in Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle were determined by HPLC, and Pearson correlation analysis was adopted to analyze the correlations between the color values and the content of 10 components. The standard ranges of L~*, a~*, and b~* values were 65.539 6-68.305 8, 7.296 3-8.467 3, and 29.998 8-32.212 8 for Glycyrrhizae Radix et Rhizoma, and 43.654 3-47.166 4, 14.050 0-15.133 8, and 16.424 6-20.984 8 for Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, respectively. Glycyrrhizae Radix et Rhizoma had higher L~* and b~* values and lower a~* value than Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, which indicated that processing with honey decreased the white and yellow values and increased the red value. The original and cross validation of the established discriminant analysis model met the requirements, and the external validation of the model showed the prediction accuracy of 100%. Pearson correlation analysis showed that the a~* value was positively correlated with the content of liquiritin apioside and isoliquiritin apioside(P<0.05), while the L~* and b~* values were negatively correlated with the content of the above two components(P<0.05). After processing with honey, L~* and b~* decreased while a~* increased, and the content of liquiritin apioside and isoliquiritin apioside increased, which was consistent with the content determination results. This study reveals the regularity of the color values of Glycyrrhizae Radix et Rhizoma after processing with honey roasting, as well as the correlations between color values and component content, which provides a basis for the rapid quality evaluation of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle.

Jug-PLGA-NPs, a New Form of Juglone with Enhanced Efficiency and Reduced Toxicity on Melanoma.

OBJECTIVE: To verrify the anti-tumor efficacy and toxicity between juglone (Jug) and Jug-loaded PLGA nanoparticles (Jug-PLGA-NPs). METHODS: Jug-PLGA-NPs were prepared by ultrasonic emulsification. The anti-tumor activity of Jug (2, 3, 4 µg/mL) and Jug-PLGA-NPs (Jug: 2, 3, 4 µg/mL) in vitro was measured by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety in vivo was evaluated on A375 nude mice. RESULTS: With the advantage of good penetration and targeting properties, Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both in vitro and in vivo (P<0.05 or P<0.01) with acceptable biocompatibility. CONCLUSIONS: Jug can inhibit the growth of melanoma but is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug.

Curcumin Inhibits T Follicular Helper Cell Differentiation in Mice with Dextran Sulfate Sodium (DSS)-Induced Colitis.

Follicular helper T cells (Tfh) regulate the differentiation of germinal center B cells and maintain humoral immunity. Notably, imbalances in Tfh differentiation often lead to the development of autoimmune diseases, including inflammatory bowel disease (IBD). Curcumin, a natural product derived from Curcuma longa, is effective in relieving IBD in humans and animals, and its mechanisms of immune regulation need further elaboration. In this study, dextran sodium sulfate induced ulcerative colitis in BALB/c mice, and curcumin was administered simultaneously for 7 days. Curcumin effectively upregulated the change rate of mouse weight, colonic length, down-regulated colonic weight, index of colonic weight, colonic damage score and the levels of pro-inflammatory cytokines IL-6, IL-12, IL-23 and TGF-[Formula: see text]1 in colonic tissues of colitis mice. Importantly, curcumin regulated the differentiation balance of Tfh and their subpopulation in colitis mice; the percentages of Tfh (CD4[Formula: see text]CXCR5[Formula: see text]BCL-6[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-L1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]ICOS[Formula: see text], Tfh17 and Tem-Tfh were downregulated significantly, while CD4[Formula: see text]CXCR5[Formula: see text]Blimp-1[Formula: see text], Tfh1, Tfh10, Tfh21, Tfr, Tcm-Tfh and Tem-GC Tfh were upregulated. In addition, curcumin inhibited the expression of Tfh-related transcription factors BCL-6, p-STAT3, Foxp1, Roquin-1, Roquin-2 and SAP, and significantly upregulated the protein levels of Blimp-1 and STAT3 in colon tissue. In conclusion, curcumin may be effective in alleviating dextran sulfate sodium-induced colitis by regulating Tfh differentiation.

[Acupuncture intervention prolongates thrombolysis time window by regulating cerebral cortex angiogenesis-related genes and proteins in cerebral infarction rats].

OBJECTIVE: To observe the effect of acupuncture on the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (Endostatin, ES) mRNAs and proteins (angiogenesis related factors) in the ischemic penumbra region in rats with cerebral infarction (CI), so as to explore its underlying mechanisms in prolonging the time window of thrombolysis therapy for CI. METHODS: A total of 48 male SD rats were randomly divided into sham operation, model, medication (6 h thrombolysis) and acupuncture (Acupunct)+medication groups (n=12 in each group). The CI model was established using modified auto-thrombus method. Six hours after thrombolysis, recombinant human tissue plasminogen activator (rt-PA,10 mg/kg) was given to rats of the thrombolysis group through tail vein. Acupuncture was applied at "Shuigou"(CV26) and bilateral "Neiguan" (PC6) 2 h after successful modeling, and the needles were retained for 30 minutes. Cerebral blood flow (CBF) was monitored during modeling in each group, and the neurological deficit score (0-7 points) was given 2 h and 24 h after successful modeling according to Bederson's methods. The cerebral infarction volume was observed after triphenyltetrazole chloride (TTC) staining. The protein and mRNA expression levels of VEGF, bFGF and ES in the ischemic penumbra region of the right cerebral cortex were detected by Western blot and real-time PCR, separately. RESULTS: The neurological deficit score at both 2 h and 24 h after modeling, percentage of cerebral infarction volume, and the expression levels of VEGF, bFGF and ES proteins and mRNAs in the model group were significantly higher than those of the sham operation group (P<0.01, P < 0.05). Compared with the model group, the neurological deficit score 24 h (not at 2 h) after modeling and percentage of cerebral infarction volume, and the expression levels of ES protein and mRNA in the Acupunct+medication group (not in the medication group) were notably lower (P<0.05, P<0.01), while the expression levels of VEGF and bFGF proteins and mRNAs in the Acupunct +medication group (not in the medication group) were considerably higher (P<0.01, P<0.05). No significant differences were found between medication and model groups in the CI percentage, VEGF, bFGF and ES proteins and mRNAs (P>0.05). The therapeutic effect of Acupunct +medication group was significantly superior to that of medication in lowering neurological deficit score, percentage of CI volume and expression of ES protein and mRNA and in up-regulating the expression of VEGF and bFGF proteins and mRNAs (P<0.05, P<0.01). CONCLUSION: Acupuncture and timely intervention can prolong the time window of thrombolysis in CI rats, which may be related to its function in up-regulating the expression of VEGF and bFGF mRNAs and proteins and in down-regulating the expression of ES mRNA and protein in ischemic cerebral cortex.