Exploration of the Dynamic Variations of the Characteristic Constituents and the Degradation Products of Catalpol during the Process of Radix Rehmanniae.

Radix Rehmanniae (RR), a famous traditional Chinese medicine (TCM) widely employed in nourishing Yin and invigorating the kidney, has three common processing forms in clinical practice, including fresh Radix Rehmanniae (FRR), raw Radix Rehmanniae (RRR), and processed Radix Rehmanniae (PRR). However, until now, there has been less exploration of the dynamic variations in the characteristic constituents and degradation products of catalpol as a representative iridoid glycoside with the highest content in RR during the process from FRR to PRR. In this study, an ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was successfully established for the simultaneous determination of ten characteristic components to explore their dynamic variations in different processed products of RR. Among them, iridoid glycosides, especially catalpol, exhibited a sharp decrease from RRR to PRR. Then, three degradation products of catalpol were detected under simulated processing conditions (100 °C, pH 4.8 acetate buffer solution), which were isolated and identified as jiofuraldehyde, cataldehyde, and norviburtinal, respectively. Cataldehyde was first reported as a new compound. Moreover, the specificity of norviburtinal in self-made PRR samples was discovered and validated, which was further confirmed by testing in commercially available PRR samples. In conclusion, our study revealed the decrease in iridoid glycosides and the production of new degradation substances during the process from FRR to PRR, which is critical for unveiling the processing mechanism of RR.

Steroidal Saponins from Solanum lyratum Thunb.

Four undescribed steroidal compounds along with twenty known compounds were isolated from n-butanol extracted fraction of the whole plants of Solanum lyratum Thunb (SLNF). Their structures were assigned based on analyses of the extensive spectroscopic data (including MS, 1D/2D NMR, and ECD) or comparisons of the NMR data with those reported. Among the knowns, three compounds were isolated from Solanum plants for the first time, while one compound was isolated from S. lyratum for the first time. In addition, the cytotoxicities of these isolates against human colon SW480 and hepatoma Hep3B cells were evaluated by a MTT assay. And, nine of them and SLNF exhibited significant activities against both SW480 and Hep3B cells, while twelve of them significantly inhibited the activities of SW480 cells. This study allows for the exploitation of chemical markers with potential significance in discrimination of Solanum plants, and uncovers the diverse steroidal constituents from S. lyratum dedicated for its future application in cancer treatment.

Unraveling the Potential Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Mechanisms of Ginger by Computational Target Fishing.

Ginger (Zingiber officinale) is one of the most commonly consumed botanical foods. Owing to its anti-inflammatory and antiviral properties, ginger has been widely used as a homemade remedy during the corona virus disease 2019 (COVID-19) pandemic; however, the mechanisms of its therapeutic activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain obscure. In this study, we used a drug-likeness approach to screen the active compounds of ginger. Next, we identified candidate targets of active compounds responsible for the anti-SARS-CoV-2 effects of ginger using chemical similarity searching and SARS-CoV-2-human protein-protein interaction (PPI) data. Finally, we analyzed PPIs, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment of the candidate proteins using different bioinformatics tools. A network comprising ginger compounds, human proteins, and SARS-CoV-2 proteins was built through Cytoscape 3.3. The results indicate that the anti-SARS-CoV-2 activity of ginger involves 20 active compounds, 18 potential human targets, and 12 SARS-CoV-2 proteins. These form a pharmacological network in which sigma nonopioid intracellular receptor 1 (SIGMAR1) and histone deacetylase 2 may be druggable hub proteins. In addition, molecular docking showed that 8-gingerdione and dihydrocapsaicin may preferentially interact with SIGMAR1, which was confirmed by further molecular dynamics simulation (150 ns) experiments. In conclusion, ginger targets multiple human proteins and affects multiple SARS-CoV-2 proteins to exert anti-COVID-19 effects. Although further experimental verification is needed, this study provides a quick visual overview of the anti-SARS-CoV-2 action of ginger.

Effects of Multi-Dimensional Nursing Based on HAPA Theory on Self-Care Ability and Cardiac Function in Patients with Coronary Heart Failure and Heart Failure.

Objective: This study aimed to investigate the effects of multi-dimensional nursing based on the Health Action Process Approach (HAPA) theory on self-care ability and cardiac function in patients with coronary heart disease (CHD) and heart failure. To explore the effects of multi-dimensional nursing based on the health action process approach (HAPA) theory on self-care ability and cardiac function in patients with coronary heart disease (CHD) and heart failure. Methods: A total of 94 patients with CHD and heart failure admitted to the hospital were enrolled between January 2021 and October 2022. The random number table method divided them into a control group (47 cases, routine nursing in cardiology department) and observation group (47 cases, multi-dimensional nursing based on HAPA theory, which is a mental model used to explain and predict the health behavior of individuals). Before and after the intervention, self-care ability, negative emotions, cardiac function and quality of life in both groups were evaluated by the exercise of self-care agency scale (ESCA), self-rating anxiety scale (SAS), self-rating depression scale (SDS), 6-minute walking test, left ventricular ejection fraction (LVEF) and Minnesota living with heart failure questionnaire (MLWHFQ). Results: During the study period, at discharge, self-care ability in both groups was improved, which was better in the observation group than the control group (P < .05). At discharge, SAS and SDS scores in both groups were decreased, which were lower in the observation group than control group (P < .05). At 6 weeks after discharge, cardiac function (LVEF, 6 min walking distance) in both groups was improved, and the improvement effect was better in the observation group than control group (P < .05). There was no significant difference in the quality of life at discharge and 6 weeks after discharge in the observation group (P > .05), but it was worse in the control group at 6 weeks after discharge (P < .05). Conclusions: Multi-dimensional nursing based on HAPA theory can significantly improve self-care ability, improve cardiac function, and quality of life in patients with CHD and heart failure.

Interleukin 6 (IL-6) Regulates GABAA Receptors in the Dorsomedial Hypothalamus Nucleus (DMH) through Activation of the JAK/STAT Pathway to Affect Heart Rate Variability in Stressed Rats.

The dorsomedial hypothalamus nucleus (DMH) is an important component of the autonomic nervous system and plays a critical role in regulating the sympathetic outputs of the heart. Stress alters the neuronal activity of the DMH, affecting sympathetic outputs and triggering heart rate variability. However, the specific molecular mechanisms behind stress leading to abnormal DMH neuronal activity have still not been fully elucidated. Therefore, in the present study, we successfully constructed a stressed rat model and used it to investigate the potential molecular mechanisms by which IL-6 regulates GABAA receptors in the DMH through activation of the JAK/STAT pathway and thus affects heart rate variability in rats. By detecting the c-Fos expression of neurons in the DMH and electrocardiogram (ECG) changes in rats, we clarified the relationship between abnormal DMH neuronal activity and heart rate variability in stressed rats. Then, using ELISA, immunohistochemical staining, Western blotting, RT-qPCR, and RNAscope, we further explored the correlation between the IL-6/JAK/STAT signaling pathway and GABAA receptors. The data showed that an increase in IL-6 induced by stress inhibited GABAA receptors in DMH neurons by activating the JAK/STAT signaling pathway, while specific inhibition of the JAK/STAT signaling pathway using AG490 obviously reduced DMH neuronal activity and improved heart rate variability in rats. These findings suggest that IL-6 regulates the expression of GABAA receptors via the activation of the JAK/STAT pathway in the DMH, which may be an important cause of heart rate variability in stressed rats.

Psychological Status and Influencing Factors Among Pregnant Women Undergoing In Vitro Fertilization.

Objective: This retrospective study aimed to observe the psychological status and analyze the influencing factors among pregnant women undergoing in vitro fertilization (IVF). Methods: A total of 456 pregnant women who underwent IVF and were admitted to the Second Hospital of Hebei Medical University from June 2021 to January 2022 were included as research subjects. General data of all subjects, including previous miscarriage history, infertility duration, number of IVF treatments, factors contributing to infertility, endometrial thickness, and embryo quality, were collected. Univariate/multivariate logistic regression analysis was performed to identify the risk factors associated with the psychological status of pregnant women undergoing IVF. Results: In this study, 191 (41.89%) patients were diagnosed with anxiety disorder, and 131 (28.73%) patients were diagnosed with depression. Significant differences were observed between the anxiety group and the non-anxiety group in terms of previous miscarriage history, infertility duration, number of IVF treatments, ovarian factors of infertility, oviduct factors of infertility, uterus factors of infertility, endometrial thickness, and embryo quality (all P < .05). Similarly, significant differences were found between the depression group and the non-depression group in terms of previous miscarriage history, infertility duration, number of IVF treatments, ovarian factors of infertility, oviduct factors of infertility, uterus factors of infertility, endometrial thickness, and embryo quality (all P < .05). Multivariate logistic regression analysis indicated that the number of IVF treatments was an independent risk factor for both anxiety and depression status (all P < .05). Conclusions: Among pregnant women undergoing IVF, psychological states such as anxiety and depression may be associated with the number of IVF treatments, endometrial thickness, and embryo quality.

Steroidal constituents from Solanum nigrum.

Three previously undescribed steroidal constituents including two sterols (1-2) and one pregnane-type steroidal glycoside (6), along with nineteen known ones (3-5, 7-22), were isolated from the 80% alcohol extraction of Solanum nigrum L. Their structures and the absolute configurations were established by analysis of the extensive spectroscopic data (1H/13 NMR, 1H1H COSY, HSQC, HMBC, and NOESY), and/or by comparisons of the experimental electronic circular dichroism (ECD) spectra with those calculated ones by TDDFT method. Further, a MTT assay was applied to demonstrate that compounds 1-4, 6-12, 18, and 22 exhibited significant cytotoxic activities against SW480 cells, and compounds 1-4, 6-14, and 16-22 showed significant cytotoxic activities against Hep3B cells.

Phytochemistry, data mining, pharmacology, toxicology and the analytical methods of Cyperus rotundus L. (Cyperaceae): a comprehensive review.

Cyperus rotundus L. has been widely used in the treatment and prevention of numerous diseases in traditional systems of medicine around the world, such as nervous, gastrointestinal systems diseases and inflammation. In traditional Chinese medicine (TCM), its rhizomes are frequently used to treat liver disease, stomach pain, breast tenderness, dysmenorrheal and menstrual irregularities. The review is conducted to summarize comprehensively the plant's vernacular names, distribution, phytochemistry, pharmacology, toxicology and analytical methods, along with the data mining for TCM prescriptions containing C. rotundus. Herein, 552 compounds isolated or identified from C. rotundus were systematically collated and classified, concerning monoterpenoids, sesquiterpenoids, flavonoids, phenylpropanoids, phenolics and phenolic glycosides, triterpenoids and steroids, diterpenoids, quinonoids, alkaloids, saccharides and others. Their pharmacological effects on the digestive system, nervous system, gynecological diseases, and other bioactivities like antioxidant, anti-inflammatory, anti-cancer, insect repellent, anti-microbial activity, etc. were summarized accordingly. Moreover, except for the data mining on the compatibility of C. rotundus in TCM, the separation, identification and analytical methods of C. rotundus compositions were also systematically summarized, and constituents of the essential oils from different regions were re-analyzed using multivariate statistical analysis. In addition, the toxicological study progresses on C. rotundus revealed the safety property of this herb. This review is designed to serve as a scientific basis and theoretical reference for further exploration into the clinical use and scientific research of C. rotundus. Supplementary Information: The online version contains supplementary materials available at 10.1007/s11101-023-09870-3.

Clinicopathological features and long-term prognosis of glomerular diseases associated with mercury-containing cosmetics.

OBJECTIVE: The pathological types and long-term prognosis of glomerular diseases related to mercury exposure are unclear. This study retrospectively examined 41 cases of glomerulonephropathy caused by mercury-containing cosmetics. METHODOLOGY: Forty-one subjects with glomerular diseases presumably caused by mercury-containing cosmetics were selected. Clinical features, kidney biopsy, treatment, and follow-up data were collected. RESULTS: All patients were female with an average age of 39.4 ± 6.6 years at diagnosis. Median time of exposure to mercury-containing cosmetics was six months, and average urine mercury level was 66.80 ± 38.55ug/(g·Cr). Most patients presented with nephrotic syndrome. Renal histopathology showed membranous nephropathy in 22 patients (53.65%), minimal change disease in 13 patients (31.71%), IgA nephropathy with minimal change disease in 5 patients (12.20%), and focal segmental glomerulosclerosis in 1 patient. Median time of exposure to mercury was longer and the proportion of patients with autoantibodies (mainly antinuclear antibodies) was higher in patients with membranous nephropathy. Both blood phospholipase A2 receptor -Ab and kidney tissue phospholipase A2 receptor were negative. Thirty-six patients received glucocorticosteroids and/or immunosuppressants. Five patients were treated with an angiotensin receptor blocker, and nine patients were treated with chelation therapy. The median follow-up time was 40 months (range 27-94). All patients achieved complete remission, and the median time to complete remission was one month. They all successfully discontinued the drugs without relapsing; withdrawal time was 26 months. CONCLUSION: Membranous nephropathy was the most common pathological type in mercury-induced glomerular disease. Patients were sensitive to glucocorticosteroids and immunosuppressants and achieved complete remission quickly. Contrary to primary glomerulonephritides, patients with mercury-induced glomerular diseases had no relapses after withdrawal of the mercury containing cosmetics.

YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6.

BACKGROUND: Tumor-associated macrophages are mainly polarized into the M2 phenotype, remodeling the tumor microenvironment and promoting tumor progression by secreting various cytokines. METHODS: Tissue microarray consisting of prostate cancer (PCa), normal prostate, and lymph node metastatic samples from patients with PCa were stained with Yin Yang 1 (YY1) and CD163. Transgenic mice overexpressing YY1 were constructed to observe PCa tumorigenesis. Furthermore, in vivo and in vitro experiments, including CRISPR-Cas9 knock-out, RNA sequencing, chromatin immunoprecipitation (ChIP) sequencing, and liquid-liquid phase separation (LLPS) assays, were performed to investigate the role and mechanism of YY1 in M2 macrophages and PCa tumor microenvironment. RESULTS: YY1 was highly expressed in M2 macrophages in PCa and was associated with poorer clinical outcomes. The proportion of tumor-infiltrated M2 macrophages increased in transgenic mice overexpressing YY1. In contrast, the proliferation and activity of anti-tumoral T lymphocytes were suppressed. Treatment targeting YY1 on M2 macrophages using an M2-targeting peptide-modified liposome carrier suppressed PCa cell lung metastasis and generated synergistic anti-tumoral effects with PD-1 blockade. IL-4/STAT6 pathway regulated YY1, and YY1 increased the macrophage-induced PCa progression by upregulating IL-6. Furthermore, by conducting H3K27ac-ChIP-seq in M2 macrophages and THP-1, we found that thousands of enhancers were gained during M2 macrophage polarization, and these M2-specific enhancers were enriched in YY1 ChIP-seq signals. In addition, an M2-specific IL-6 enhancer upregulated IL-6 expression through long-range chromatin interaction with IL-6 promoter in M2 macrophages. During M2 macrophage polarization, YY1 formed an LLPS, in which p300, p65, and CEBPB acted as transcriptional cofactors. CONCLUSIONS: Phase separation of the YY1 complex in M2 macrophages upregulated IL-6 by promoting IL-6 enhancer-promoter interactions, thereby increasing PCa progression.

[Exploration on acupuncture treatment ideas for knee osteoarthritis from the perspective of Dongyuan needling technology].

The treatment ideas with acupuncture for knee osteoarthritis (KOA) are explored on the base of Dongyuan needling technology. Regarding the rules of acupoint selection, Zusanli (ST 36) is predominant, the back-shu points are used for the disorders related to the invasion of exogenous factors, and the front-mu points are for the cases caused by internal injury. Besides, the xing-spring points and shu-stream points are preferred. In treatment of KOA, besides the local points, the front-mu points, i.e. Zhongwan (CV 12), Tianshu (ST 25) and Guanyuan (CV 4), are selected specially to tonifying the spleen and stomach. The earth points and acupoints on the earth meridians (i.e. Yinlingquan [SP 9], Xuehai [SP 10], Liangqiu [ST 34], Dubi [ST 35], Zusanli [ST 36] and Yanglingquan [GB 34]) are optional to coordinate yin and yang, essence and qi , and regulate the qi movement of spleen and stomach. The shu-stream points of liver, spleen and kidney meridians (Taichong [LR 3], Taibai [SP 3] and Taixi [KI 3]) are chosen to promote meridian circulation and regulate zangfu functions.

Deciphering in vivo metabolic profile and pharmacological mechanisms of Jitongning Tablet for the treatment of Ankylosing spondylitis.

Jitongning tablet (JTNT) is a Traditional Chinese Medicine (TCM) prescription used for the treatment of Ankylosing spondylitis (AS). Currently, it is in phase II clinical trial (NCT03932019) for patients with active axial Spondyloarthritis (axSpA), showing great promise for the treatment of AS. However, the potential material basis and the underlying mechanisms for JTNT to treat AS remain elusive. Here, we performed UPLC-Q-TOF-MS to determine the in vivo metabolic profile of JTNT in rats and conducted in vivo studies including acetic acid-induced writhing, hot plate models, and collagen-induced arthritis (CIA) in rats to evaluate and validate the analgesic and anti-inflammatory effects of JTNT, two main symptoms for AS. Additionally, network pharmacology combined with molecular docking was performed to investigate the potential underlying mechanisms. As a result, a total of 116 xenobiotics were identified from the plasma, urine, and brain tissues of rats after oral administration of JTN extracts. Pharmacological evaluation revealed that fractions JTN-3 and JTN-4 exerted significant analgesic activities by reducing the number of writhes in an acetic acid-induced writhing mice model. JTN extract also exerted excellent therapeutic effects in the CIA model by ameliorating paw edema and decreasing systemic manifestation of inflammation and the level of circulating immune complex (CIC) and interferon γ (IFN-γ). Fractions of JTN extract, especially JTN-2 and JTN-4, on the other hand, ameliorated the secondary lesions caused by chicken type II collagen (CII) to a certain extent. Further, network pharmacology combined with molecular docking suggested crucial roles of inflammation and immune-related genes such as MAPK1, MAPK14, NOS3, and RELA in the treatment of AS by JTNT. In conclusion, our studies suggest that the isoquinoline and diterpenoid alkaloids from Corydalis Rhizoma and Aconiti Radix Cocta, along with coumarins from Angelicae Pubescentis Radix, may be the main bioactive components, and the AS treatment mechanism may mainly involve immune regulation of JTNT. These results help clarify the potential material basis and underlying mechanisms of JTNT for the treatment of AS, facilitating the broad application of this TCM in clinical practice.

Sesquiterpenoids and monoterpenoids from the water decoction of Valeriana officinalis L.

Nine previously undescribed compounds including three sesquiterpenoids, three iridoids, two monoterpenoids and a furan fatty acid, along with seventeen known ones, were isolated from the water decoction of roots and rhizomes of Valeriana officinalis L. Structure elucidation of the twenty-six compounds were accomplished by analysis of the extensive spectroscopic data, and the absolute configurations of the nine previously undescribed ones were established by NOESY experiment and the electronic circular dichroism (ECD) simulations. Among them, ß-patchoulene-8-O-ß-D-glucopyranoside, 11-methoxyl-viburtinal, and protocatechuic acid showed anti-neuroinflammatory potentials by significantly inhibiting the secretion of nitric oxide (NO) on BV-2 cells upon LPS stimulation (p < 0.001) without affecting the cell viability.

Anti-apoptotic effect of HeidihuangWan in renal tubular epithelial cells via PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Heidihuang Wan (HDHW) is a classic Chinese herbal formula, which was first recorded in the "Suwen Bingji Qiyi Baoming Collection" written by Liu Wansu during the Jin Dynasty (1115-1234 AD). It is commonly used clinically for the treatment of kidney diseases and its curative effect is stable. Previous animal experiments have confirmed that HDHW can effectively improve renal fibrosis. However, the underlying pharmacological mechanism remains unclear. AIMS OF THIS STUDY: Renal tubular epithelial cell (RTEC) apoptosis is one of the main pathological features of renal fibrosis. This study aimed to observe the effect and underlying mechanism of HDHW on the apoptosis of RTECs to further explore the pathological mechanism of HDHW against renal fibrosis. MATERIALS AND METHODS: We examined the HDHW composition in rat serum. In vitro, we first screened out the optimal intervention concentration of HDHW on RTECs using the MTT assay. Hypoxia/reoxygenation was then used to induce apoptosis of RTECs (H/R-RTECs), which were divided into H/R-RTEC, astragaloside IV (positive control), HDHW, and RTECs groups. After 48 h of drug intervention, apoptosis of RTECs was detected using flow cytometry and protein expression was detected by western blotting. The 5/6 nephrectomy rat model was constructed and divided into the normal control, 5/6 nephrectomy, HDHW, and astragaloside IV groups. After 8 weeks of treatment, TUNEL staining was used to detect cell apoptosis, and western blotting was used to detect protein expression. RESULTS: HDHW downregulated the expression of pro-apoptotic proteins Bax and Caspase3, up-regulated the expression of anti-apoptotic protein Bcl-2, activated the PI3K/Akt/mTOR signaling pathway, and reversed the early apoptosis of RTECs, thereby resisting the apoptosis of RTECs. CONCLUSION: HDHW inhibits apoptosis of RTECs by modulating the PI3K/Akt/mTOR signaling pathway. This study provides experimental evidence for the anti-fibrotic effect of HDHW on the kidneys and partially elucidates its pharmacological mechanism of action.

Noninvasive neuroimaging and spatial filter transform enable ultra low delay motor imagery EEG decoding.

Objective.The brain-computer interface (BCI) system based on sensorimotor rhythm can convert the human spirit into instructions for machine control, and it is a new human-computer interaction system with broad applications. However, the spatial resolution of scalp electroencephalogram (EEG) is limited due to the presence of volume conduction effects. Therefore, it is very meaningful to explore intracranial activities in a noninvasive way and improve the spatial resolution of EEG. Meanwhile, low-delay decoding is an essential factor for the development of a real-time BCI system.Approach.In this paper, EEG conduction is modeled by using public head anatomical templates, and cortical EEG is obtained using dynamic parameter statistical mapping. To solve the problem of a large amount of computation caused by the increase in the number of channels, the filter bank common spatial pattern method is used to obtain a spatial filter kernel, which reduces the computational cost of feature extraction to a linear level. And the feature classification and selection of important features are completed using a neural network containing band-spatial-time domain self-attention mechanisms.Main results.The results show that the method proposed in this paper achieves high accuracy for the four types of motor imagery EEG classification tasks, with fairly low latency and high physiological interpretability.Significance.The proposed decoding framework facilitates the realization of low-latency human-computer interaction systems.

AKR1C3-dependent lipid droplet formation confers hepatocellular carcinoma cell adaptability to targeted therapy.

Rationale: Increased lipid droplet (LD) formation has been linked to tumor metastasis, stemness, and chemoresistance in various types of cancer. Here, we revealed that LD formation is critical for the adaptation to sorafenib in hepatocellular carcinoma (HCC) cells. We aim to investigate the LD function and its regulatory mechanisms in HCC. Methods: The key proteins responsible for LD formation were screened by both metabolomics and proteomics in sorafenib-resistant HCC cells and further validated by immunoblotting and immunofluorescence staining. Biological function of AKR1C3 was evaluated by CRISPR/Cas9-based gene editing. Isotopic tracing analysis with deuterium3-labeled palmitate or carbon13-labeled glucose was conducted to investigate fatty acid (FA) and glucose carbon flux. Seahorse analysis was performed to assess the glycolytic flux and mitochondrial function. Selective AKR1C3 inhibitors were used to evaluate the effect of AKR1C3 inhibition on HCC tumor growth and induction of autophagy. Results: We found that long-term sorafenib treatment impairs fatty acid oxidation (FAO), leading to LD accumulation in HCC cells. Using multi-omics analysis in cultured HCC cells, we identified that aldo-keto reductase AKR1C3 is responsible for LD accumulation in HCC. Genetic loss of AKR1C3 fully depletes LD contents, navigating FA flux to phospholipids, sphingolipids, and mitochondria. Furthermore, we found that AKR1C3-dependent LD accumulation is required for mitigating sorafenib-induced mitochondrial lipotoxicity and dysfunction. Pharmacologic inhibition of AKR1C3 activity instantly induces autophagy-dependent LD catabolism, resulting in mitochondrial fission and apoptosis in sorafenib-resistant HCC clones. Notably, manipulation of AKR1C3 expression is sufficient to drive the metabolic switch between FAO and glycolysis. Conclusions: Our findings revealed that AKR1C3-dependent LD formation is critical for the adaptation to sorafenib in HCC through regulating lipid and energy homeostasis. AKR1C3-dependent LD accumulation protects HCC cells from sorafenib-induced mitochondrial lipotoxicity by regulating lipophagy. Targeting AKR1C3 might be a promising therapeutic strategy for HCC tumors.

Characteristics of carbon, nitrogen, phosphorus and sulfur cycling genes, microbial community metabolism and key influencing factors during composting process supplemented with biochar and biogas residue.

Carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) cycling functional genes and bacterial and fungal communities during composting with biochar and biogas residue amendments were studied. Correlations between microbial community structure, functional genes and physicochemical properties were investigated by network analysis and redundancy analysis. It was shown that the gene of acsA abundance accounted for about 50% of the C-related genes. Biogas residue significantly decreased the abundance of denitrification gene nirK. Biogas residues can better promote the diversity of bacteria and fungi during composting. Biochar significantly increased the abundance of Humicola. Redundancy analysis indicated that pile temperature, pH, EC were the main physicochemical factors affecting the microbial community. WSC and NO3--N have significant correlation with C, N, P, S functional genes. The research provides a theoretical basis for clarifying the metabolic characteristics of microbial communities during composting and for the application of biochar and biogas residues in composting.

Discovery of a cysteine-rich peptide with glycation modification from Achyranthes bidentata Blume.

Cysteine-rich peptides (CRPs) are stable molecules that contain multiple disulphide bonds. Various CRPs are found in plants and animals, representing potential compounds for drug development with diverse activities. Modification of CRPs, such as glycation, has attracted increased attention due to its special structural and functional properties. Hence, this study explored a CRP isolated from the Chinese herb Achyranthes bidentata Blume, which contains a glycation modification. Herein, a reverse phase high-performance liquid chromatography system with mobile phases was used to extract and purify the peptide. The eluted peptide was detected using high resolution mass spectrometry and structurally identified using high resolution mass spectrometry and nuclear magnetic resonance. The effect of the peptide on the viability of N-methyl-D-aspartic acid (NMDA)-induced HT22 cells was determined using a cell assay. Here, a new cysteine-rich glycation peptide, termed glycation-bidentatide (Gly-BTP), with three pairs of disulphide bonds and a glycation modification at the N-terminus linked to cysteine, was discovered. Cell bioactivity assay results suggested that Gly-BTP might be a potential therapeutic and provide a neuroprotective effect in NMDA-induced HT22 murine hippocampal neuronal cells. The discovery of Gly-BTP will promote the understanding of the role of CRPs in neuroprotection.

Comparison of MI-EEG Decoding in Source to Sensor Domain.

Brain-computer interface (BCI) system based on sensorimotor rhythm (SMR) is a more natural brain-computer interaction system. In this paper, we propose a new multi-task motor imagery EEG (MI-EEG) classification framework. Unlike traditional EEG decoding algorithms, we perform the decoding task in the source domain rather than the sensor domain. In the proposed algorithm, we first build a conduction model of the signal using the public ICBM152 head model and the boundary element method (BEM). The sensor domain EEG was then mapped to the selected cortex region using standardized low-resolution electromagnetic tomography (sLORETA) technology, which benefit to address volume conduction effects problem. Finally, the source domain features are extracted and classified by combining FBCSP and simple LDA. The results show that the classification-decoding algorithm performed in the source domain can well solve the classification task of MI-EEG. In addition, we found that the source imaging method can significantly increase the number of available EEG channels, which can be expanded at least double. The preliminary results of this study encourage the implementation of EEG decoding algorithms in the source domain. Clinical Relevance- This confirms that better results can be obtained by performing MI-EEG decoding in the source domain than in the sensor domain.

Screening and identification of anti-acetylcholinesterase ingredients from Tianzhi granule based on ultrafiltration combined with ultra-performance liquid chromatography-mass spectrometry and in silico analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Tianzhi granule (TZG) is a traditional Chinese formula that is widely used for the treatment of vascular dementia (VaD). AIM OF THE STUDY: To discover the herbs in TZG possessing acetylcholinesterase (AChE) inhibitory activity and to screen the anti-acetylcholinesterase ingredients from active herbs. MATERIALS AND METHODS: In vitro AChE inhibitory activity assay of eleven herbal extracts was conducted. An ultrafiltration combined with ultra-performance liquid chromatography-mass spectrometry method was established to screen and identify the anti-acetylcholinesterase ingredients from active extracts. In addition, in vitro AChE inhibitory activity assay and molecular docking were adopted for further investigation. Moreover, ultra-performance liquid chromatography-mass spectrometry was performed for the content determination of active compounds in TZG. RESULTS: Three herbs in TZG showed significant AChE inhibitory activity. A total of thirteen active ingredients were screened out and identified, and all of these compounds were present in TZG. Five available commercial standards presented moderate AChE inhibitory activity, and all of which have a relatively high content in TZG. CONCLUSION: A number of herbs and compounds with acetylcholinesterase inhibitory activity were found in TZG, which provided a scientific basis for the material basis and quality control research of TZG.