New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Therapeutic effects and molecular mechanisms of natural products in thrombosis.

Thrombotic disorders, such as myocardial infarction and stroke, are the leading cause of death in the global population and have become a health problem worldwide. Drug therapy is one of the main antithrombotic strategies, but antithrombotic drugs are not completely safe, especially the risk of bleeding at therapeutic doses. Recently, natural products have received widespread interest due to their significant efficacy and high safety, and an increasing number of studies have demonstrated their antithrombotic activity. In this review, articles from databases, such as Web of Science, PubMed, and China National Knowledge Infrastructure, were filtered and the relevant information was extracted according to predefined criteria. As a result, more than 100 natural products with significant antithrombotic activity were identified, including flavonoids, phenylpropanoids, quinones, terpenoids, steroids, and alkaloids. These compounds exert antithrombotic effects by inhibiting platelet activation, suppressing the coagulation cascade, and promoting fibrinolysis. In addition, several natural products also inhibit thrombosis by regulating miRNA expression, anti-inflammatory, and other pathways. This review systematically summarizes the natural products with antithrombotic activity, including their therapeutic effects, mechanisms, and clinical applications, aiming to provide a reference for the development of new antithrombotic drugs.

Unregulated GmAGL82 due to Phosphorus Deficiency Positively Regulates Root Nodule Growth in Soybean.

Nitrogen fixation, occurring through the symbiotic relationship between legumes and rhizobia in root nodules, is crucial in sustainable agriculture. Nodulation and soybean production are influenced by low levels of phosphorus stress. In this study, we discovered a MADS transcription factor, GmAGL82, which is preferentially expressed in nodules and displays significantly increased expression under conditions of phosphate (Pi) deficiency. The overexpression of GmAGL82 in composite transgenic plants resulted in an increased number of nodules, higher fresh weight, and enhanced soluble Pi concentration, which subsequently increased the nitrogen content, phosphorus content, and overall growth of soybean plants. Additionally, transcriptome analysis revealed that the overexpression of GmAGL82 significantly upregulated the expression of genes associated with nodule growth, such as GmENOD100, GmHSP17.1, GmHSP17.9, GmSPX5, and GmPIN9d. Based on these findings, we concluded that GmAGL82 likely participates in the phosphorus signaling pathway and positively regulates nodulation in soybeans. The findings of this research may lay the theoretical groundwork for further studies and candidate gene resources for the genetic improvement of nutrient-efficient soybean varieties in acidic soils.

Clerodane diterpenoids with in-vitro anti-neuroinflammatory activity from the tuberous root of Tinospora sagittata (Menispermaceae).

Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as "Jin Guo Lan". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1-8), and 18 known diterpenoids (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 µM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 µM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 that were increased by LPS stimulation.

Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. METHODS: High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. RESULTS: Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. CONCLUSIONS: These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.

The Long-Term Effect of Maternal Iron Levels in the Second Trimester on Mild Thinness among Preschoolers: The Modifying Effect of Small for Gestational Age.

The supplementation of multiple micronutrients throughout pregnancy can reduce the risk of adverse birth outcomes and various diseases in children. However, the long-term effect of maternal multiple micronutrient levels in the second trimester on the overall development of preschoolers remains unknown. Therefore, 1017 singleton mother-infant pairs and 6-year-old preschoolers were recruited based on the China-Wuxi Birth Cohort Study. Meanwhile, information on the demographic characteristics of pregnant women and preschoolers, maternal copper, calcium, iron, magnesium, and zinc levels in whole blood during the second trimester, and neonatal outcomes, were collected. We aimed to investigate the long-term impact of maternal copper, calcium, iron, magnesium, and zinc levels in the second trimester on mild thinness among 6-year-old preschoolers, and the modifying effect of small for gestational age (SGA), within the Chinese population. Multiple logistic regression models revealed that high-level maternal iron in the second trimester reduced the risk of mild thinness [adjusted OR: 0.46 (95% CI: 0.26, 0.80)] among 6-year-old preschoolers. However, no significant association was found for the remaining four maternal essential metal elements. Additionally, the restricted cubic spline function showed that the risk of mild thinness decreased when maternal iron concentration exceeded 7.47 mmol/L in whole blood during the second trimester. Furthermore, subgroup analysis indicated that the long-term protective effect of high-level maternal iron on mild thinness was only observed in SGA infants. Summarily, high-level maternal iron in the second trimester distinctly lowers the risk of mild thinness among 6-year-old preschoolers, especially in preschoolers with birth outcomes of SGA. Our findings offer evidence for the implementation of iron supplementation in the second trimester as a preventive measure against mild thinness in children.

Dual Drug-Loaded Nanoliposomes Encapsulating Curcumin and 5-Fluorouracil with Advanced Medicinal Applications: Self-Monitoring and Antitumor Therapy.

Due to the presence of physiological barriers, it is difficult to achieve the desired therapeutic efficacy of drugs; thus, it is necessary to develop an efficient drug delivery system that enables advanced functions such as self-monitoring. Curcumin (CUR) is a naturally functional polyphenol whose effectiveness is limited by poor solubility and low bioavailability, and its natural fluorescent properties are often overlooked. Therefore, we aimed to improve the antitumor activity and drug uptake monitoring by simultaneously delivering CUR and 5-Fluorouracil (5-FU) in the form of liposomes. In this study, dual drug-loaded liposomes (FC-DP-Lip) encapsulating CUR and 5-FU were prepared by the thin-film hydration method; their physicochemical properties were characterized; and their biosafety, drug uptake distribution in vivo, and tumor cell toxicity were evaluated. The results showed that the nanoliposome FC-DP-Lip showed good morphology, stability, and drug encapsulation efficiency. It showed good biocompatibility, with no side effects on zebrafish embryonic development. In vivo uptake in zebrafish showed that FC-DP-Lip has a long circulation time and presents gastrointestinal accumulation. In addition, FC-DP-Lip was cytotoxic against a variety of cancer cells. This work showed that FC-DP-Lip nanoliposomes can enhance the toxicity of 5-FU to cancer cells, demonstrating safety and efficiency, and enabling real-time self-monitoring functions.

Exogenous and Endophytic Fungal Communities of Dendrobium nobile Lindl. across Different Habitats and Their Enhancement of Host Plants' Dendrobine Content and Biomass Accumulation.

Both the biosynthesis and array of bioactive and medicinal compounds in plants can be influenced by interactions with endophytic and exogenous fungi. However, the composition of endophytic and exogenous fungal communities associated with many medicinal plants is unknown, and the mechanism by which these fungi stimulate the secondary metabolism of host plants is unclear. In this study, we conducted a correlative analysis between endophytic and exogenous fungi and dendrobine and biomass accumulation in Dendrobium nobile across five Chinese habitats: wild Danxia rock, greenhouse-associated large Danxia stone, broken Danxia stone, broken coarse sandstone, and wood spile. Across habitats, fungal communities exhibited significant differences. The abundances of Phyllosticta, Trichoderma, and Hydropus were higher in wild habitats than in greenhouse habitats. Wild habitats were host to a higher diversity and richness of exogenous fungi than were greenhouse habitats. However, there was no significant difference in endophytic fungal diversity between habitats. The differences between the fungal communities' effects on the dendrobine content and biomass of D. nobile were attributable to the composition of endophytic and exogenous fungi. Exogenous fungi had a greater impact than endophytic fungi on the accumulation of fresh weight (FW) and dendrobine in D. nobile. Furthermore, D. nobile samples with higher exogenous fungal richness and diversity exhibited higher dendrobine content and FW. Phyllosticta was the only genus to be significantly positively correlated with both FW and dendrobine content. A total of 86 strains of endophytic fungi were isolated from the roots, stems, and leaves of D. nobile, of which 8 strains were found to be symbiotic with D. nobile tissue-cultured seedlings. The strain DN14 (Phyllosticta fallopiae) was found to promote not only biomass accumulation (11.44%) but also dendrobine content (33.80%) in D. nobile tissue-cultured seedlings. The results of this study will aid in the development of strategies to increase the production of dendrobine in D. nobile. This work could also facilitate the screening of beneficial endophytic and exogenous fungal probiotics for use as biofertilizers in D. nobile.

Electroacupuncture alleviated depression-like behaviors in ventromedial prefrontal cortex of chronic unpredictable mild stress-induced rats: Increasing synaptic transmission and phosphorylating dopamine transporter.

AIMS: Electroacupuncture (EA) shows advantages in both clinical practice and depression animal models. Dopaminergic-related dysfunction in the prefrontal cortex (PFC) may be a hidden antidepressant mechanism of EA, where dopamine transporter (DAT) plays an essential role. This study aimed to investigate the synaptic transmission and DAT-related changes of EA in depression. METHODS: Male Sprague-Dawley rats were subjected to 3-week chronic unpredictable mild stress (CUMS). The successfully modeled rats were then randomly and equally assigned to CUMS, selective serotonin reuptake inhibitor (SSRI), and EA or SSRI + EA groups, followed by a 2-week treatment respectively. After monitoring body weight and behavioral tests of all rats, the ventromedial PFC (vmPFC) tissue was collected for electrophysiology and the expression detection of DAT, phosphorylated DAT (p-DAT), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and trace amine-associated receptor 1 (TAAR1). RESULTS: Depressive-like behaviors induced by CUMS were alleviated by EA, SSRI, and SSRI + EA treatments through behavioral tests. Compared with CUMS group, EA improved synaptic transmission in vmPFC by upregulating spontaneous excitatory postsynaptic currents amplitude. Molecularly, EA reversed the increased total DAT and p-DAT expression as well as the decreased ratio of p-DAT/total DAT along with the activation of TAAR1, cAMP, and PKA in vmPFC. CONCLUSION: We speculated that the antidepressant effect of EA was associated with enhanced synaptic transmission in vmPFC, and the upregulated phosphorylation of DAT relevant to TAAR1, cAMP, and PKA may be the potential mechanism.

Perturbated glucose metabolism augments epithelial cell proinflammatory function in chronic rhinosinusitis.

BACKGROUND: Glucose concentrations are increased in nasal secretions in chronic rhinosinusitis (CRS). However, the glucose metabolism and its contribution to disease pathogenesis in CRS remain unexplored. OBJECTIVES: We sought to explore the glucose metabolism and its effect on the function of nasal epithelial cells in CRS with and without nasal polyps (CRSwNP and CRSsNP). METHODS: Glucose metabolites were detected with mass spectrometry. The mRNA levels of glucose transporters (GLUTs), metabolic enzymes, and inflammatory mediators were detected by quantitative RT-PCR. The protein expression of GLUTs was studied by immunofluorescence staining, Western blotting, and flow cytometry. Glucose uptake was measured by using fluorescent glucose analog. Human nasal epithelial cells (HNECs) were cultured. Bioenergetic analysis was performed with Seahorse XF analyzer. Gene expression in HNECs was profiled by RNA sequencing. RESULTS: Increased glucose concentrations in nasal secretions was confirmed in both CRSsNP and CRSwNP. GLUT4, GLUT10, and GLUT11 were abundantly expressed in HNECs, whose expression was upregulated by inflammatory cytokines and D-glucose and was increased in CRS. Glucose uptake, glycolysis and tricarboxylic acid cycle metabolites, metabolic enzymes, and extracellular acidification rate and oxygen consumption rates were increased in HNECs in CRSsNP and CRSwNP, with a predominant shift to glycolysis. HNECs treated with high-level apical D-glucose showed enhanced glucose uptake, predominant glycolysis, and upregulated production of IL-1α, IL-1ß, TNF-α, CCL20, and CXCL8, which was suppressed by 2-deoxy-D-glucose, an inhibitor of glycolysis. CONCLUSIONS: Increased glucose in nasal secretions promotes glucose uptake and predominant glycolysis in epithelial cells, augmenting the proinflammatory function of epithelial cells in CRS.

Dietary tea seed saponin combined with aerobic exercise attenuated lipid metabolism and oxidative stress in mice fed a high-fat diet (HFD).

Tea seed saponins (TSS) are oleanolane-type pentacyclic triterpenoid saponin mixtures with various pharmacological effects. We aimed to explore the effects of a total of 4 weeks intragastric administration of TSS (140 mg/kg·day) combined with aerobic exercise (AE) on lipid metabolism and its associated oxidative stress in HFD-induced obese mice and to investigate the possible molecular mechanisms. TSS + AE intervention significantly reduced body weight and the adiposity index (including subcutaneous, epididymal, perirenal, and abdominal adipose) in obese mice; improved dyslipidemia by lowering serum TC, TG, and LDL-c levels; and increased HDL-c levels. TSS + AE intervention significantly improved hepatic steatosis by inhibiting lipogenetic Acc, Srebp1c, and Scd1 and upregulating lipolysis genes (Pgc1α, Pgc1ß, Pparα, and Cpt1). TSS + AE intervention increased the hepatic protein expression of p-AMPK, SIRT1, and PGC-1α, as well as PPAR-γ and GLUT-4 in skeletal muscle compared with expression in the HFD group. In addition, TSS + AE also modulated oxidative stress in obese mice, which was indicated by the increased serum and liver levels of SOD, GSH, and T-AOC and decreased ROS and MDA levels. These results suggest that TSS + AE intervention can reduce fat accumulation and improve HFD-induced lipid metabolism disorders and oxidative stress. PRACTICAL APPLICATIONS: Obesity is a metabolic disease induced by excess nutritional intake and insufficient energy expenditure. Dietary modifications combined with aerobic exercise are currently an effective method for weight loss. Tea seed saponins (TSS) are a variety of biologically active oleanolane-type pentacyclic triterpenoid saponins that naturally exist in tea seeds. Few articles have focused on the effects and mechanisms of TSS combined with aerobic exercise (AE) in regulating lipid metabolism and improving oxidative damage in vivo. Using an HFD-induced obese mice model to explore the mechanism of TSS + AE in regulating lipid metabolism and its associated oxidative stress damage will help provide reliable data for the application of dietary nutrition combined with AE in anti-obesity.

[Effects of Straw Returning and Fertilizer Application on Soil Nutrients and Winter Wheat Yield].

In order to explore the effects of straw returning combined with fertilizer on soil nutrients and winter wheat yield in the Guanzhong area, an experimental split plot design was utilized. The main plot consisted of no straw returning (S0) and straw returning (S). The sub-regions consisted of no fertilizer (WF), nitrogen fertilizer (NF), and nitrogen and phosphate fertilizer (NPF). Ecological stoichiometry was used to study the relationship between soil carbon, nitrogen, phosphorus content, and yield under straw returning combined with nitrogen and phosphorus fertilizer conditions. The results showed that straw and fertilization interactions had significant effects on soil organic carbon, total nitrogen, and total phosphorus contents in the surface layer (0-20 cm) (P<0.05). Compared with that in the S0WF treatment, the SNPF treatment significantly increased soil organic carbon and total nitrogen contents in the surface layer (0-20 cm) (P<0.05). The interaction between straw and year had significant effects on soil total nitrogen content in the surface layer (0-20 cm) (P<0.05). With the increase in straw returning time, the total nitrogen content of soil 0-20 cm under the SWF treatment was significantly higher than that under the S0WF treatment (P<0.05). Straw and fertilization and their interaction had no significant effects on organic carbon and total nitrogen contents in the 20-40 cm soil layer (P>0.05). Straw and straw interaction with fertilization significantly affected total P content in 20-40 cm soil (P<0.05). Compared with that in the SWF treatment, the SNPF treatment significantly increased the total phosphorus content in the 20-40 cm soil layer (P<0.05). Straw returning combined with chemical fertilizer also had a significant effect on soil stoichiometry. Compared with that in the S0WF treatment, the S0NPF treatment decreased soil C:N in the surface layer (0-20 cm) and increased soil C:P and N:P in the surface layer (0-20 cm). Compared with that in the SWF treatment, the SNF treatment reduced soil C:N in the surface layer (0-20 cm). Straw returning combined with chemical fertilizer also had a significant effect on winter wheat yield. In 2020 and 2021, the SNPF treatment increased production by 24.23% and 28.9%, respectively, compared with that of the S0WF treatment. Correlation analysis showed that yield was significantly positively correlated with C:N (P<0.05) and C:P (P<0.01). At the same time, total nitrogen and N:P were positively correlated with treatment years (P<0.001). In conclusion, straw returning and that combined with nitrogen and phosphate fertilizer (SNPF) can improve soil nutrient characteristics, change soil stoichiometric characteristics, and increase yield in the Guanzhong area. Therefore, the results of this study indicate that straw returning combined with nitrogen and phosphate fertilizer (SNPF) is an effective way to optimize regional farmland nutrient management and improve grain production capacity.

Gut microbiota: Linking nutrition and perinatal depression.

Perinatal depression is a mood disorder that is reported in women during pregnancy (prenatal) and after childbirth (postnatal). The onset of perinatal depression is associated with changes in reproductive hormones, stress hormones and neurosteroids. These chemical compounds can be modulated by the gut microbiota, which may affect maternal mental health during the perinatal period via the gut-brain-axis. Recent studies suggest that nutritional and dietary interventions (vitamin D, ω-3 fatty acids, iron, and fiber) effectively prevent or mitigate maternal depression and anxiety, but their efficacy is confounded by various factors, including the gut microbiota. Probiotics are efficacious in maintaining microbiota homeostasis, and thus, have the potential to modulate the development of perinatal mood disorders, despite no evidence in human. Therefore, clinical trials are warranted to investigate the role of probiotic supplementation in perinatal depression and behavioral changes. This article reviews the interplay between nutrition, gut microbiota and mood and cognition, and the evidence suggesting that probiotics affect the onset and development of perinatal depression.

Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.

Aberrant amino acid metabolism is a common event in obesity. Particularly, subjects with obesity are characterized by the excessive plasma kynurenine (Kyn). However, the primary source of Kyn and its impact on metabolic syndrome are yet to be fully addressed. Herein, we show that the overexpressed indoleamine 2,3-dioxygenase 1 (IDO1) in adipocytes predominantly contributes to the excessive Kyn, indicating a central role of adipocytes in Kyn metabolism. Depletion of Ido1 in adipocytes abrogates Kyn accumulation, protecting mice against obesity. Mechanistically, Kyn impairs lipid homeostasis in adipocytes via activating the aryl hydrocarbon receptor (AhR)/Signal transducer and activator of transcription 3 /interleukin-6 signaling. Genetic ablation of AhR in adipocytes abolishes the effect of Kyn. Moreover, supplementation of vitamin B6 ameliorated Kyn accumulation, protecting mice from obesity. Collectively, our data support that adipocytes are the primary source of increased circulating Kyn, while elimination of accumulated Kyn could be a viable strategy against obesity.

Oil plant genomes: current state of the science.

Vegetable oils are an indispensable nutritional component of the human diet as well as important raw materials for a variety of industrial applications such as pharmaceuticals, cosmetics, oleochemicals, and biofuels. Oil plant genomes are highly diverse, and their genetic variation leads to a diversity in oil biosynthesis and accumulation along with agronomic traits. This review discusses plant oil biosynthetic pathways, current state of genome assembly, polyploidy and asymmetric evolution of genomes of oil plants and their wild relatives, and research progress of pan-genomics in oil plants. The availability of complete high-resolution genomes and pan-genomes has enabled the identification of structural variations in the genomes that are associated with the diversity of agronomic and environment fitness traits. These and future genomes also provide powerful tools to understand crop evolution and to harvest the rich natural variations to improve oil crops for enhanced productivity, oil quality, and adaptability to changing environments.

Ameliorative Effects of Malonyl Ginsenoside from Panax ginseng on Glucose-Lipid Metabolism and Insulin Resistance via IRS1/PI3K/Akt and AMPK Signaling Pathways in Type 2 Diabetic Mice.

Our previous study has revealed that malonyl-ginsenosides from Panax ginseng (PG-MGR) play a crucial role in the treatment of T2DM. However, its potential mechanism was still unclear. In this study, we investigated the anti-diabetic mechanisms of action of PG-MGR in high fat diet-fed (HFD) and streptozotocin-induced diabetic mice and determined the main constituents of PG-MGR responsible for its anti-diabetic effects. Our results showed that 16 malonyl ginsenosides were identified in PG-MGR by HPLC-ESI-MS/MS. PG-MGR treatment significantly reduced fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels and improved insulin resistance and glucose tolerance. Simultaneously, PG-MGR treatment improved liver injury by decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) expression. Furthermore, Western blot analysis demonstrated that the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, p-AMPK/AMPK, p-ACC/ACC and GLUT4 in liver and skeletal muscle were significantly up-regulated after PG-MGR treatment, and the protein expression levels of p-IRS-1/IRS-1, Fas and SREBP-1c were significantly reduced. These findings revealed that PG-MGR has the potential to improve glucose and lipid metabolism and insulin resistance by activating the IRS-1/PI3K/AKT and AMPK signal pathways.

Near-infrared spectroscopy and machine learning-based technique to predict quality-related parameters in instant tea.

The traditional method for analyzing the content of instant tea has disadvantages such as complicated operation and being time-consuming. In this study, a method for the rapid determination of instant tea components by near-infrared (NIR) spectroscopy was established and optimized. The NIR spectra of 118 instant tea samples were used to evaluate the modeling and prediction performance of a combination of binary particle swarm optimization (BPSO) with support vector regression (SVR), BPSO with partial least squares (PLS), and SVR and PLS without BPSO. Under optimal conditions, Rp for moisture, caffeine, tea polyphenols, and tea polysaccharides were 0.9678, 0.9757, 0.7569, and 0.8185, respectively. The values of SEP were less than 0.9302, and absolute values of Bias were less than 0.3667. These findings indicate that machine learning can be used to optimize the detection model of instant tea components based on NIR methods to improve prediction accuracy.

Cirsium japonicum var. Maackii Improves Cognitive Impairment under Amyloid Beta25-35-Induced Alzheimer's Disease Model.

Abnormal production and degradation of amyloid beta (Aß) in the brain lead to oxidative stress and cognitive impairment in Alzheimer's disease (AD). Cirsium japonicum var. maackii (CJM) is widely used as an herbal medicine and has antibacterial and anti-inflammatory properties. This study focused on the protective effect of the ethyl acetate fraction from CJM (ECJM) on Aß 25-35-induced control mice. In the T-maze and novel object recognition test, ECJM provided higher spatial memory and object recognition compared to Aß 25-35 treatment alone. In the Morris water maze test, ECJM-administered mice showed greater learning and memory abilities than Aß 25-35-induced control mice. Additionally, ECJM-administered mice experienced inhibited lipid peroxidation and nitric oxide production in a dose-dependent manner. The present study indicates that ECJM improves cognitive impairment by inhibiting oxidative stress in Aß 25-35-induced mice. Therefore, CJM may be useful for the treatment of AD and may be a potential material for functional foods.

Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Hypoglycemic and Hypolipidemic Effects of Malonyl Ginsenosides from American Ginseng (Panax quinquefolius L.) on Type 2 Diabetic Mice.

American ginseng (Panax quinquefolius L.) is popularly consumed as traditional herbal medicine and health food for the treatment of type 2 diabetes mellitus (T2DM). Malonyl ginsenosides (MGR) are the main natural ginsenosides in American ginseng. However, whether the malonyl ginsenosides in P. quinquefolius (PQ-MGR) possess antidiabetic effects has not been explored yet. In this study, the antidiabetic effects and the underlying mechanism of PQ-MGR in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM mice were investigated. The chemical composition was analyzed by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Our results showed that 14 malonyl ginsenosides were identified in the PQ-MGR. Among them, the content of m-Rb1 represented about 77.4% of the total malonyl ginsenosides. After a 5-week experiment, the PQ-MGR significantly reduced the fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), nonesterified fatty acid (NEFA), alanine transaminase (ALT), and aspartate transaminase (AST) levels and improved glucose tolerance and insulin resistance. Furthermore, Western blot analysis demonstrated that the protein expressions of p-PI3K, p-AKT, p-AMPK, p-ACC, PPARγ, and GLUT4 in the liver and skeletal muscle were significantly upregulated after PQ-MGR treatment. In contrast, the protein expressions of p-IRS1 and p-JNK were significantly downregulated. Our results revealed that PQ-MGR could ameliorate glucose and lipid metabolism and insulin resistance in T2DM via regulation of the insulin receptor substrate-1/phosphoinositide3-kinase/protein-kinase B (IRS1/PI3K/Akt) and AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) pathways. These findings suggest that PQ-MGR may be used as an antidiabetic candidate drug for T2DM treatment.