Ginseng fermentation solution affects the gut microbiota in zebrafish with alcoholic liver disease via PI3K/Akt pathway.

BACKGROUND: Ginsenosides have received increased amounts of attention due to their ability to modulate the intestinal flora, which may subsequently alleviate alcoholic liver disease (ALD). The effects of ginseng fermentation solution (GFS) on the gut microbiota and metabolism in ALD patients have not been explored. PURPOSE: This research aimed to explore the regulatory effect of GFS on ALD both in vitro and in vivo. METHOD: This study assessed the anti-ALD efficacy of GFS using an LO2 cell model and a zebrafish model. Untargeted metabolomics was used for differentially abundant metabolite analysis, and high-throughput 16S rRNA sequencing was used to examine the effect of GFS on ALD. RESULTS: The LO2 cell line experiments demonstrated that GFS effectively mitigated alcohol-induced oxidative stress and reduced apoptosis by upregulating PI3K and Bcl-2 expression and decreasing the levels of malondialdehyde, total cholesterol, and triglycerides. In zebrafish, GFS improved morphological and physiological parameters and diminished oxidative stress-induced ALD. Meanwhile, the results from Western blotting indicated that GFS enhanced the expression of PI3K, Akt, and Bcl-2 proteins while reducing Bax protein expression, thereby ameliorating the ALD model in zebrafish. Metabolomics data revealed significant changes in a total of 46 potential biomarkers. Among them, metabolites such as prostaglandin F2 alpha belong to arachidonic acid metabolism. In addition, GFS also partly reversed the imbalance of gut microbiota composition caused by alcohol. At the genus level, alcohol consumption elevated the presence of Flectobacillus, Curvibacter, among others, and diminished Elizabethkingia within the intestinal microbes of zebrafish. Conversely, GFS reversed these effects, notably enhancing the abundance of Proteobacteria and Archaea. Correlation analyses further indicated a significant negative correlation between prostaglandin F2 alpha, 11,14,15-THETA, Taurocholic acid and Curvibacter. CONCLUSION: This study highlights a novel mechanism by which GFS modulates anti-ALD activity through the PI3K/Akt signalling pathway by influencing the intestinal flora-metabolite axis. These results indicate the potential of GFS as a functional food for ALD treatment via modulation of the gut flora.

Influence of hyperbaric oxygen therapy-specialized care on limb motor function and mental state of cerebral infarction patients with hemiplegia.

BACKGROUND: Currently, cerebral infarction (CI) is mainly treated by emergency craniotomy or conservative treatment. However, some studies have questioned the functional recovery of patients after hyperbaric oxygen therapy (HBOT)-specialized care. OBJECTIVE: This paper mainly explores the influence of HBOT-specialized care on limb motor function (LMF) and mental state of CI patients with hemiplegia. METHODS: The medical records of 113 CI patients with hemiplegia treated in our hospital from March 2020 to March 2022 were collected. Of these, 53 received routine care nursing (conventional group) and 60 cases were given HBOT-specialized care (research group). Patient general data, scores of Fugl-Meyer Assessment (FMA), National Institutes of Health Stroke Scale (NIHSS), Self-rating Anxiety/Depression Scale (SAS/SDS) and Barthel Index (BI), and nursing efficiency were comparatively analyzed. RESULTS: The two groups showed comparability in general data. FMA and BI scores were increased in the research group after rehabilitation treatment, higher than the baseline and those of the conventional group, while NIHSS, SAS, and SDS scores were reduced, lower compared with baseline and those of the conventional group. In addition, significantly higher nursing efficiency was determined in the research group. CONCLUSION: HBOT-specialized care has beneficial effects on LMF, mental state, negative emotions and self-care ability of CI patients with hemiplegia and can enhance nursing efficacy, which deserves clinical popularization.

Optimizing phosphate fertilizer input to reduce phosphorus loss in rice-oilseed rape rotation.

Identifying the major sources and critical periods of P loss from agricultural fields provides important guidance for reducing P loss. A rice-oilseed rape rotation with no P fertilization (NP, control), medium P fertilization (MP, 90 kg P2O5 ha-1 season-1), and high P fertilization (HP, 180 kg P2O5 ha-1 season-1) was conducted from 2019 to 2021 in the middle Yangtze River Basin. Runoff and leaching P losses were measured simultaneously using runoff event monitoring and a percolation device. Applying P fertilizer increased the P concentration in the field ponding water and percolation water of the rice-oilseed rape rotation. During the rice growing season, total P (TP), dissolved P (DP), and particulate P (PP) concentrations in the field ponding water and percolation water peaked 1 day after P was applied, and then decreased rapidly. After 10 days of fertilization, P concentration in the field ponding water of the MP treatment decreased to a minimum and stabilized, while the HP treatment extended this period to 20 days. The highest P concentration in percolation water was observed at the first sampling during the oilseed rape season, and then it continued to decrease. Inputting P fertilizer increased P loss by 55.0-109.9% compared to the NP treatment, with annual P losses of 0.89-1.10 kg P ha-1, of which runoff loss accounted for 61.7-62.9%. Fertilization and precipitation resulted in varied P loss within and between seasons. Runoff from heavy precipitation during the rice season was the main source of P loss, while PP accounted for 54.7-77.6% of runoff P loss. The strong utilization of soil P by rice resulted in a lower demand for exogenous P fertilizer than oilseed rape. Excessive P input increased the soil P surplus and vertical migration. Therefore, reducing rice season P fertilizer inputs to achieve annual P balance in rice-oilseed rape rotation can effectively reduce soil P surplus and loss while ensuring crop P demand, and the initial 10 d after fertilization in the rice season was a critical period for reducing P runoff loss.

Sufficient potassium improves inorganic phosphate-limited photosynthesis in Brassica napus by enhancing metabolic phosphorus fractions and Rubisco activity.

Crop photosynthesis (A) and productivity are often limited by a combination of nutrient stresses, such that changes in the availability of one nutrient may affect the availability of another nutrient, in turn influencing A. In this study, we examined the synergistic effects of phosphorus (P) and potassium (K) on leaf A in a nutrient amendment experiment, in which P and K were added individually or in combination to Brassica napus grown under P and K co-limitation. The data revealed that the addition of P gradually removed the dominant limiting factor (i.e. the limited availability of P) and improved leaf A. Strikingly, the addition of K synergistically improved the overall uptake of P, mainly by boosting plant growth, and compensated for the physiological demand for P by prioritizing investment in metabolic pools of P (P-containing metabolites and inorganic phosphate, Pi). The enlarged pool of metabolically active P was partially associated with the upregulation of Pi regeneration through release from triose phosphates rather than replacement of P-containing lipids. This process mitigated P restrictions on A by maintaining the ATP/NADPH and NADPH/NADP+ ratios and increasing the content and activity of Rubisco. Our findings demonstrate that sufficient K increased Pi-limited A by enhancing metabolic P fractions and Rubisco activity. Thus, ionic synergism may be exploited to mitigate nutrient-limiting factors to improve crop productivity.

Gambogic acid suppresses nasopharyngeal carcinoma via rewiring molecular network of cancer malignancy and immunosurveillance.

Nasopharyngeal carcinoma (NPC) is a malignant tumor highly prevalent in Southeast Asia. The distant metastasis and disease recurrence are still unsolved clinical problems. In recent years, traditional Chinese medicine (TCM) monomers have become significantly attractive due to their advantages. Using high throughput drug sensitivity screening, we identified gambogic acid (GA) as a common TCM monomer displaying multiple anti-NPC effects. GA could effectively inhibit the proliferation of low differentiated cells and highly metastatic cells in NPC via inducing apoptosis and G2/M cell cycle arrest. In addition, GA obviously repressed the abilities of cell clone, migration, invasion, angiogenesis and represented satisfied synergistic effects combined with chemotherapy. Importantly, we found the elevated immune checkpoint CD47 stimulated after chemotherapy was dramatically impaired by GA treatment. Mechanically, the network pharmacology analyses unraveled that the oncogenic signaling pathways including STATs were rewired by GA treatment. Taken together, our study reveals a molecular basis and provides a rationale for GA application as the treatment regime in NPC therapy in future.

Keratinase improves the growth performance, meat quality and redox status of broiler chickens fed a diet containing feather meal.

The objective of this study was to assess the effects of dietary supplementation of keratinase on the production of broilers fed a diet containing feather meal. A total of 162 1-d-old Cobb 500 male broiler (n = 9 cages/diet with 6 chicks/cage) were randomly allocated to 3 dietary treatments. The broilers were fed a corn-soybean-feather meal based diet (BD), or BD supplemented with keratinase at 100,000 or 200,000 U/kg for 6 weeks. Compared to the control, dietary supplementation with 200,000 U/kg keratinase increased (P < 0.05) body weight gain (3.6-4.3%) and reduced feed conversion ratio (2.4-5.6%) during the various experimental periods, and also improved (P < 0.05) apparent total tract digestibility of ash and calcium by 45.0% and 8.8%, respectively. Meanwhile, dietary supplementation of keratinase at 100,000 U/kg reduced (P < 0.05) the drip loss (29.2%), while 200,000 U/kg keratinase supplementation increased (P < 0.05) the pH value (1.6%) at 45 min and decreased (P < 0.05) the lightness (L* value; 13.6%) and drip loss (22.1%) of pectoral muscle. Moreover, dietary supplementation of keratinase at both levels of 100,000 and 200,000 U/kg increased (P < 0.05) Glutathione peroxidase activity (82.5-87.5%) and decreased the Malondialdehyde concentration (14.5-18.3%) in the pectoral muscle. In conclusion, dietary supplementation of keratinase at 200,000 U/kg can improve the performance, meat quality, apparent total tract digestibility of nutrients, and redox status of broiler chickens fed a diet containing feather meal.

The Combination of Aquilaria sinensis (Lour.) Gilg and Aucklandia costus Falc. Volatile Oils Exerts Antidepressant Effects in a CUMS-Induced Rat Model by Regulating the HPA Axis and Levels of Neurotransmitters.

The Aquilaria sinensis (Lour.) Gilg (CX)-Aucklandia costus Falc. (MX) herbal pair is frequently used in traditional Chinese medicine prescriptions for treating depression. The volatile oil from CX and MX has been shown to have good pharmacological activities on the central nervous system, but its curative effect and mechanism in the treatment of depression are unclear. Therefore, the antidepressant effect of the volatile oil from CX-MX (CMVO) was studied in chronic unpredictable mild stress (CUMS) rats. The suppressive effects of CMVO (25, 50, 100 µL/kg) against CUMS-induced depression-like behavior were evaluated using the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT). The results showed that CMVO exhibited an antidepressant effect, reversed the decreased sugar preference in the SPT and prolongation of immobility time in the FST induced by CUMS, increased the average speed, time to enter the central area, total moving distance, and enhanced the willingness of rats to explore the environment in the OFT. Inhalational administration of CMVO decreased levels of adrenocorticotropic hormone and corticosterone in serum and the expression of corticotropin-releasing hormone mRNA in the hypothalamus, which indicated regulation of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, CMVO restored levels of 5-hydroxytryptamine (5-HT), dopamine, norepinephrine and acetylcholine in the hippocampus. The RT-PCR and immunohistochemistry results showed that CMVO up-regulated the expression of 5-HT1A mRNA. This study demonstrated the antidepressant effect of CMVO in CUMS rats, which was possibly mediated via modulation of monoamine and cholinergic neurotransmitters and regulation of the HPA axis.

Research on Quality Markers of Guizhi Fuling Prescription for Endometriosis Treatment Based on Gray Correlation Analysis Strategy.

Guizhi Fuling prescription (GFP), a prestigious prescription of traditional Chinese medicine (TCM) recorded in "Jingui Yaolue," was composed of five Chinese medicines, including Moutan Cortex, Paeoniae Radix Alba, Persicae Semen, Poria Cocos, and Cinnamomi Ramulus. It was used for the treatment of endometriosis, primary dysmenorrhea, and blood stasis for centuries. However, its Quality Markers of treating endometriosis have not been clearly elucidated. In this study, a rapid ultraperformance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS/MS) method was established for Quality Markers investigation on GFP, and a total of 50 potentially bioactive constituents including triterpenoids, paeoniflorin and its derivatives, phenolic acids, and other species were identified based on their retention time, fragmentation pattern, and accurately measured mass value. Furthermore, regularity of recipe composition and gray correlation analysis revealed that all of the characteristic peaks contributed to the treatment of endometriosis. The relative correlation degrees were greater than 0.6. Among them, peaks 1 and 10, which were most closely correlated to the endometriosis, were identified as amygdalin and cinnamic acid. Finally, all of the active ingredients were molecularly docked with proteins associated with endometriosis by Schrodinger method. Among them, amygdalin, cinnamic acid, paeonol, gallic acid, and paeoniflorin had the lower binding energies. It was proposed that these constituents could be directed at Quality Markers for GFP. Thus, the integrated approach describing for revealing Quality Markers of GFP could be expected to provide a method for quality evaluation.

Leaf photosynthetic capacity is regulated by the interaction of nitrogen and potassium through coordination of CO2 diffusion and carboxylation.

Combined application of nitrogen (N) and potassium (K) fertilizer could significantly enhance crop yield. Crop yield and photosynthesis are inseparable. However, the influence of N and K interaction on photosynthesis is still not fully understood. Field and hydroponic experiments were conducted to examine the effects of N and K interaction on leaf photosynthesis characteristics and to explore the mechanisms in the hydroponic experiment. CO2 conductance and carboxylation characteristic parameters of oilseed leaves were measured under different N and K supplies. Results indicated that detectable increases in leaf area, biomass and net photosynthetic rate (An ) were observed under optimal N and K supply in field and hydroponic experiments. The ratio of total CO2 diffusion conductance to the maximum carboxylation rate (gtot /Vcmax ) and An presented a linear-plateau relationship. Under insufficient N, increased K contributed to the CO2 transmission capacity and improved the proportion of N used for carboxylation, promoting gtot /Vcmax . However, the low Vcmax associated with N insufficiency limited the An . High N supply obviously accelerated Vcmax , yet K deficiency led to a reduction of gtot , which restricted Vcmax . Synchronous increases in N and K supplementation ensured the appropriate ratio of N to K content in leaves, which simultaneously facilitated gtot and Vcmax and preserved a gtot /Vcmax suitable for guaranteeing CO2 transmission and carboxylation coordination; the overall effect was increased An and leaf area. These results highlight the suitable N and K nutrients to coordinate CO2 diffusion and carboxylation, thereby enhancing photosynthetic capacity and area to obtain high crop yield.

Discovery of N-(4-(6-Acetamidopyrimidin-4-yloxy)phenyl)-2-(2-(trifluoromethyl)phenyl)acetamide (CHMFL-FLT3-335) as a Potent FMS-like Tyrosine Kinase 3 Internal Tandem Duplication (FLT3-ITD) Mutant Selective Inhibitor for Acute Myeloid Leukemia.

Most of the current FMS-like tyrosine kinase 3 (FLT3) inhibitors lack selectivity between FLT3 kinase and cKIT kinase as well as the FLT3 wt and internal tandem duplication (ITD) mutants. We report a new compound 27, which displays GI50 values of 30-80 nM against different ITD mutants and achieves selectivity over both FLT3 wt (8-fold) and cKIT kinase in the transformed BaF3 cells (>300-fold). 27 potently inhibits the proliferation of the FLT3-ITD-positive acute myeloid leukemia cancer lines through suppression of the phosphorylation of FLT3 kinase and downstream signaling pathways, induction of apoptosis, and arresting the cell cycle into the G0/G1 phase. 27 also displays potent antiproliferative effect against FLT3-ITD-positive patient primary cells, whereas it does not apparently affect FLT3 wt primary cells. In addition, it also exhibits a good therapeutic window to PBMC compared to PKC412. In the in vivo studies, 27 demonstrates favorable PK profiles and suppresses the tumor growth in the MV4-11 cell inoculated mouse xenograft model.

Therapeutic Effect of Duck Interferon-Alpha Against H5N1 Highly Pathogenic Avian Influenza Virus Infection in Peking Ducks.

The antiviral cytokine interferon-alpha (IFN-α) plays a critical role in the innate immune system. Previous studies have shown that recombinant chicken IFN-α inhibits avian influenza virus (AIV) replication in vivo; however, the antiviral effect of recombinant duck IFN-α (rDuIFN-α) on highly pathogenic AIV remains unknown. In this study, the duck IFN-α gene was cloned, expressed, and purified. The antiviral effects of the resulting rDuIFN-α were further evaluated in vitro and in vivo. Our results showed that rDuIFN-α inhibited the replication of vesicular stomatitis virus (VSV) and AIV in duck embryo fibroblasts in vitro, with antiviral activities against VSV and AIV of 2.1 × 105 and 4.1 × 105 U/mg, respectively. We next investigated the anti-H5N1 AIV effect of intramuscular injection of rDuIFN-α in vivo. rDuIFN-α reduced viral titers in the brains, lungs, and spleens of 2-day-old (2D) ducks compared with that in the virus-challenged control group, and pretreatment with rDuIFN-α reduced mortality from 60% to 10% in 2D ducks. Moreover, rDuIFN-α increased the expression of IFN-stimulated genes in the brains and spleens of 2D ducks. Our results demonstrate that rDuIFN-α blocks VSV and H5N1 influenza virus infection in vitro and exhibits antiviral effects against H5N1 influenza virus infection in 2D ducks.

Cytotoxic and Anti-inflammatory Sesquiterpenes from Ainsliaea henryi.

Three new sesquiterpenoids, 4α-hydroxyeudesm-11(13)-en-12-yl 3-methylbutanoate (1), diaspanolide E (2), and (13α)-germacra-1(10),4-dien-12,8α-olid-15-oic acid (3), along with eight known sesquiterpenoids (4 - 11), were isolated from the aerial parts of Ainsliaea henryi. The chemical structures of compounds 1 - 3 were elucidated by spectroscopic analysis (1D-, 2D-NMR, MS and HR/MS). All isolates were evaluated for their inhibitory activities against nitric oxide (NO) production in lipopolysaccharide-induced RAW264.7 macrophage cells. Compound 10 exhibited significantly inhibition against NO release with an IC50 value of 6.54 ± 0.16 µm. Also, all isolated compounds were tested for cytotoxicity against three human tumor cell lines A549, MGC803, and HCT116, among which compound 5 significantly inhibited the proliferation of MGC803 cell lines with an IC50 value of 2.2 ± 0.2 µm.

Genotypic variation in photosynthetic limitation responses to K deficiency of Brassica napus is associated with potassium utilisation efficiency.

Cultivars with higher potassium utilisation efficiency (KUtE) are likely to have superior photosynthesis (A) under K deficiency. However, the inner link between KUtE and photosynthesis remains unclear. A quantitative analysis of stomatal (SL), mesophyll conductance (MCL) and biochemical (BL) limitations on A in response to K supplementation was performed on upper and lower leaves of Brassica napus L. Huayouza No. 9 (H9, high KUtE) and Zhongshuang No. 11 (Z11, low KUtE). Both cultivars showed remarkable improvement in leaf area and lower leaf photosynthesis with elevated K supply. The total photosynthetic limitation of Z11 in lower leaf was 51.9% higher than that of H9 under K deficiency. Most of limitation under K deficiency was dominated by MCL for Z11, yet it was equally controlled by MCL and SL for H9. Nevertheless, with increasing K supply, SL became the primary limitation for both cultivars. Z11 needed a 12.0% higher leaf K concentration to avoid A decline, and higher K-based thresholds for each limitation. Overall, cultivars higher in KUtE have improved inherent leaf photosynthesis and area, and present lower K-based thresholds for SL, MCL and BL.

Terpenoids from Ainsliaea latifolia and their cytotoxic activities.

Two new compounds including one new sesquiterpenoid and one new monoterpenoid, together with 10 known compounds were isolated from the whole plants of Ainsliaea latifolia. The structures of these compounds were elucidated by analysis of spectroscopic data. All compounds were evaluated for their cytotoxic activities.

Dysfunctional cortico-basal ganglia-thalamic circuit and altered hippocampal-amygdala activity on cognitive set-shifting in non-neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To explore sequential brain activities throughout cognitive set-shifting, which is critical to understanding the basic pathophysiology of cognitive dysfunction, in patients with new-onset systemic lupus erythematosus (SLE) without neuropsychiatric symptoms. METHODS: Fourteen patients with new-onset SLE but without neuropsychiatric symptoms and 14 healthy controls matched for age, sex, education level, and intelligence quotient with the patients performed a cognitive set-shifting task derived from the Wisconsin Card Sorting Test while they were undergoing event-related functional magnetic resonance imaging of the brain. Blood oxygen level-dependent signals were compared between different stages of cognitive set-shifting in the lupus patients and in the healthy subjects. RESULTS: Lupus patients and healthy subjects demonstrated comparable cognitive function performance, but the cortico-basal ganglia-thalamic-cortical circuit and amygdala-hippocampus coupling, which were involved in response inhibition and active forgetting-learning dynamics, respectively, were demonstrated to be compromised in patients with SLE. Moreover, an increase in contralateral cerebellar-frontal activity was found to compensate for the compromised cortico-basal ganglia-thalamic-cortical circuit in lupus patients in order to maintain their cognitive test performance as comparable to that of the healthy subjects. CONCLUSION: Our study revealed significant differences in the sequential brain signals during cognitive set-shifting between patients with SLE without neuropsychiatric symptoms and healthy subjects. The results prompt further in-depth investigation for the functional neural basis of cognitive dysfunction involving the aforementioned neural circuits and compensatory pathways in patients with SLE.

[Inhibition of glucoraphenin enzymolysis in Raphani Semen by processing].

OBJECTIVE: To explore material basis of the pharmacological differences between the roasting and pro-roasting Raphani Semen. METHOD: The two new sulfur-containing compounds (A209 and B221) were found changed after processing in the water decoction. The common precursor-C3 of A209 and B211 and the precursor of C3 were seperated and purified. Their transforming relationship was proved. RESULT: The result showed that glucosinolates could decompose into sulforaphane and transform into A209 and B221 further in the boiling process. CONCLUSION: This study provides some experimental evidences for revealing the mechanism of Raphani Semen processing.

Anti-fatigue activity of extracts of stem bark from Acanthopanax senticosus.

In the present study, we investigated the anti-fatigue activity in male Kunming mice of extracts of stem bark from Acanthopanax senticosus (ASSE) using a forced swimming test. Mice were divided into four groups (three ASSE administered groups and the control group). The control group were gavaged with distilled water and ASSE administered groups were gavaged with ASSE (100, 200 and 400 mg/kg). After four weeks, a forced swimming test was performed and the biochemical parameters related to fatigue were examined. The results suggested that ASSE could extend the swimming time to exhaustion of the mice, as well as increase the tissue glycogen contents, while decreasing the blood lactate and serum urea nitrogen contents. This indicated that ASSE had anti-fatigue activity and could elevate the exercise tolerance.