Effect of acupotomy combined with electroacupuncture on knee function of patients with knee osteoarthritis. / åˆƒé’ˆç»“åˆç”µé’ˆæ²»ç–—å¯¹è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žæ‚£è€ è†å ³èŠ‚åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To compare the clinical effect of combined therapy of acupotomy and electroacupuncture (EA) with the simple application of EA on knee osteoarthritis (KOA), and their influence on knee function. METHODS: Sixty-eight KOA patients were randomly divided into 2 groups, an acupotomy group and an EA group. In the acupotomy group, the combined therapy of acupotomy and EA was adopted. In the EA group, EA was simply used, delivered once every two days, 3 treatments a week；and the duration of treatment was 4 weeks. In the acupotomy group, besides the treatment as the EA group, acupotomy was combined once weekly, and the duration of treatment was 4 weeks. Separately, before and after treatment, and in 4 and 12 weeks after treatment completion (1-month and 3-month follow-up), the results of the timed up and go test (TUG), the 9-step stair climb test (9-SCT) and the knee function (Western Ontario and McMaster University osteoarthritis index visualization scale ［WOMAC］) were measured in the two groups. RESULTS: By the intention-to-treat analysis, the results of TUG, 9-SCT and WOMAC scores were reduced after treatment and in 1-month and 3-month follow-up when compared with those before treatment in the patients of the two groups (P<0.05). Compared with the EA group at the same time point, TUG results were decreased after treatment and in 1-month follow-up, and WOMAC score was reduced after treatment in the acupotomy group. WOMAC score in 1-month follow-up was reduced when compared with that before treatment within the acupotomy group (P<0.05). CONCLUSIONS: Either the simple application of EA or the combined therapy of acupotomy and EA can improve knee function, but the combined therapy obviously increases the walking speed and relieves the symptoms such as joint pain and morning stiffness. The treatment with acupotomy and EA is safe and effective on KOA and the long-term effect is satisfactory.

The causal association between artificial sweeteners and the risk of cancer: a Mendelian randomization study.

Artificial sweeteners (ASs) have been widely added to food and beverages because of their properties of low calories and sweet taste. However, whether the consumption of ASs is causally associated with cancer risk is not clear. Here, we utilized the two-sample Mendelian randomization (MR) method to study the potential causal association. Genetic variants like single-nucleotide polymorphisms (SNPs) associated with exposure (AS consumption) were extracted from a genome-wide association study (GWAS) database including 64 949 Europeans and the influence of confounding was removed. The outcome was from 98 GWAS data and included several types of cancers like lung cancer, colorectal cancer, stomach cancer, breast cancer, and so on. The exposure-outcome SNPs were harmonized and then MR analysis was performed. The inverse-variance weighted (IVW) with random effects was used as the main analytical method accompanied by four complementary methods: MR Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses consisted of heterogeneity, pleiotropy, and leave-one-out analysis. Our results demonstrated that ASs added to coffee had a positive association with high-grade and low-grade serous ovarian cancer; ASs added to tea had a positive association with oral cavity and pharyngeal cancers, but a negative association with malignant neoplasm of the bronchus and lungs. No other cancers had a genetic causal association with AS consumption. Our MR study revealed that AS consumption had no genetic causal association with major cancers. Larger MR studies or RCTs are needed to investigate small effects and support this conclusion.

Subhealth Status of Nursing Staff and Its Influencing Factors in Shaanxi Province.

Background: The concept of subhealth, defined as a state between health and illness characterized by diminished vitality and adaptability, is emerging as a significant concern, particularly among nursing staff. In Shaanxi Province, there is a notable prevalence of subhealth conditions among nurses, influenced by various factors, including lifestyle, work environment, and psychological stress. Purpose: This study aims to investigate the level of subhealth status among nursing staff in Shaanxi hospitals, identify the primary causes and risk factors affecting their subhealth, and propose relevant countermeasures. The goal is to provide a scientific basis for developing strategies to enhance nursing staff's physical and mental well-being. Methods: A comprehensive questionnaire survey was conducted among 1068 nursing staff members from different hospitals in Shaanxi Province. The survey assessed various dimensions of subhealth, including physical, psychological, and social aspects. Data were analyzed to determine the relationships between subhealth status and factors like exercise frequency, dietary habits, smoking and alcohol consumption, occupational injuries, work situation, and stress levels. Results: Most respondents were female, aged between 21 and 40 years. The study found no significant gender-related differences in subhealth scores. Key factors affecting subhealth included physical exercise, dietary habits, occupational stress, and work conditions. The data revealed higher physical subhealth but lower psychological subhealth among nursing staff compared to regional norms. Notable relationships were observed between lifestyle choices, work-related factors, and the subhealth status of nursing staff. Conclusion: The subhealth status of nursing staff in Shaanxi hospitals is influenced by a combination of lifestyle, occupational, and psychological factors. The study underscores the need for targeted interventions focusing on lifestyle modifications, stress management, and improved work conditions to enhance the overall health status of nursing staff. This research provides valuable insights for healthcare policymakers and administrators to develop effective strategies for managing subhealth conditions among nursing professionals.

Application of Natural Medicinal Plants Active Ingredients in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant cancer of the head and neck, with high morbidity and mortality, ranking as the sixth most common cancer in the world. The treatment of OSCC is mainly radiotherapy, chemotherapy and surgery, however, the prognosis of patients is still poor and the recurrence rate is high. This paper reviews the range of effects of natural medicinal plant active ingredients (NMPAIs) on OSCC cancer, including the types of NMPAIs, anti-cancer mechanisms, involved signaling pathways, and clinical trials. The NMPAIs include terpenoids, phenols, flavonoids, glycosides, alkaloids, coumarins, and volatile oils. These active ingredients inhibit proliferation, induce apoptosis and autophagy, inhibit migration and invasion of OSCC cells, and regulate cancer immunity to exert anti-cancer effects. The mechanism involves signaling pathways such as mitogen-activated protein kinase, phosphatidylinositol 3 kinase/protein kinase B, nuclear factor kappa B, miR-22/WNT1/ß-catenin and Nrf2/Keap1. Clinically, NMPAIs can inhibit the growth of OSCC, and the combined drug is more effective. Natural medicinal plants are promising candidates for the treatment of OSCC.

Desulfovibrio desulfuricans and its derived metabolites confer resistance to FOLFOX through METTL3.

BACKGROUND: Chemoresistance is a critical factor contributing to poor prognosis in clinical patients with cancer undergoing postoperative adjuvant chemotherapy. The role of gut microbiota in mediating resistance to tumour chemotherapy remains to be investigated. METHODS: Patients with CRC were categorised into clinical benefit responders (CBR) and no clinical benefit responders (NCB) based on chemotherapy efficacy. Differential bacterial analysis using 16S rRNA sequencing revealed Desulfovibrio as a distinct microbe between the two groups. Employing a syngeneic transplantation model, we assessed the effect of Desulfovibrio on chemotherapy by measuring tumour burden, weight, and Ki-67 expression. We further explored the mechanisms underlying the compromised chemotherapeutic efficacy of Desulfovibrio using metabolomics, western blotting, colony formation, and cell apoptosis assays. FINDINGS: In comparison, Desulfovibrio was more abundant in the NCB group. In vivo experiments revealed that Desulfovibrio colonisation in the gut weakened the efficacy of FOLFOX. Treatment with Desulfovibrio desulfuricans elevates serum S-adenosylmethionine (SAM) levels. Interestingly, SAM reduced the sensitivity of CRC cells to FOLFOX, thereby promoting the growth of CRC tumours. These experiments suggest that SAM promotes the growth and metastasis of CRC by driving the expression of methyltransferase-like 3 (METTL3). INTERPRETATION: A high abundance of Desulfovibrio in the intestines indicates poor therapeutic outcomes for postoperative neoadjuvant FOLFOX chemotherapy in CRC. Desulfovibrio drives the manifestation of METTL3 in CRC, promoting resistance to FOLFOX chemotherapy by increasing the concentration of SAM. FUNDING: This study is supported by Wuxi City Social Development Science and Technology Demonstration Project (N20201005).

[Qualitative and semiquantitative analyses of the chemical components of the seed coat and kernel of Ziziphi Spinosae Semen].

Ziziphi Spinosae Semen refers to the dried seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou. The seed is composed of a reddish brown coat and a yellow kernel. A comparative study was conducted to investigate differences in the chemical composition and their relative contents between the seed coat and kernel of Ziziphi Spinosae Semen. First, the chemical compounds found in the seed coat and kernel were characterized and identified using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The analytical results tentatively identified 57 chemical compounds based on reference-compound comparison, literature retrieval, and chemical-database (e. g., MassBank) searches; these compounds included 14 triterpenes, 23 flavonoids, 7 alkaloids, 6 carboxylic acids, and 7 other types of compounds. The mass error of the identified compounds was within the mass deviation range of 5×10-6 (5 ppm). Next, two methods of multivariate statistical analysis, namely, principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), were used to compare the differential compounds between the two seed parts. A total of 17 differential compounds were screened out via OPLS-DA based on a variable importance in projection (VIP) value of >5. The results revealed that betulinic acid, betulonic acid, alphitolic acid, and jujuboside Ⅰ mainly existed in the seed coat whereas the 13 other compounds, such as spinosin, jujuboside A, and 6‴-feruloylspinosin, mainly existed in the seed kernel. Therefore, these 17 differential compounds can be used to distinguish between the two seed parts. Finally, a semiquantitative method was established using UPLC and a charged aerosol detector (CAD) with inverse gradient compensation in the mobile phase. Six representative compounds with different types were selected to examine the CAD response consistency: magnoflorine (alkaloid), spinosin (flavone), 6‴-feruloylspinosin (flavone), jujuboside A (triterpenoid saponin), jujuboside B (triterpenoid saponin), and betulinic acid (triterpenoid acid). The results showed that the relative standard deviation (RSD) of the average response factors at different levels of these six compounds was 7.04% and that their response intensities were similar. Moreover, each compound in the fingerprint demonstrated good response consistency, and the peak areas obtained directly reflected the contents of each compound. Based on the semiquantitative fingerprints obtained, betulinic acid and oleic acid were considered the main components of the seed coat. The betulinic acid content in the seed coat was approximately 7 times higher than that in the seed kernel. Spinosin, jujuboside A, linoleic acid, betulinic acid, and oleic acid were the main components of the seed kernel. The spinosin content in the seed kernel was 18 times higher than that in the seed coat. In addition, the jujuboside A content in the seed kernel was 24 times higher than that in the seed coat. The proposed method can accurately determine the main components and compare the relative contents of these components in different seed parts. In summary, this study identified the differences in chemical components between the seed coat and kernel of Ziziphi Spinosae Semen and clarified the main components and their relative contents in these parts. The findings can not only provide a basis for the identification of chemical compounds and quality research on different parts of Ziziphi Spinosae Semen but also promote the development and utilization of this traditional Chinese medicine.

Demystifying wine expertise through the lens of imagination: Descriptions and imagery vividness across sensory modalities.

For most untrained novices, talking about wine or imagining the smells and flavours of wine is difficult. Wine experts, on the other hand, have been found to have better imagery for wine, and are also more proficient in describing wine. Some scholars have suggested that imagery and language are based on similar underlying processes, but no conclusive evidence has been found regarding mental imagery and language production. In this study, we examined the relationship between imagery and language use in both novices and experts. In an online experiment, wine experts and novices were asked to imagine the colour, smell, taste and mouthfeel of wines in different situations, and were asked to rate the vividness of the imagined experience as well as describe it with words. The results show that experts differ from novices on a number of linguistic measures when describing wine, including the number of words used, the type of words used, the concreteness of those words, and the adjective to noun ratio. Similarly, imagery for wine was more vivid in wine experts compared to novices in the modalities of smell, taste, and mouthfeel, in alignment with previous work. Surprisingly, we found that no single linguistic variable significantly predicted the reported vividness of wine imagery, neither in experts nor in novices. However, the linguistic model predicted imagery vividness better using data from experts compared to novices. Taken together, these findings underscore that imagery and language are different facets of wine cognition.

Preparation of phosphorus containing products by co-incineration of sludge ash and calcium-based additives: Focusing one-step and multi-step method.

Due to the irreplaceable nature of phosphorus (P) in biological growth and the shortage of P rock, it is necessary to recover P from waste, such as sludge ash. P-containing products were prepared using sludge ash and calcium-based additives (CaCO3 and eggshell). In addition, the effects of different incineration methods (one-step method (OSM) and multi-step method (MSM)), additive doses, and incineration temperature on the P content and species in the products were investigated. The results indicated that as the dose of calcium-based additives increased, total P (TP) content in P-containing products reduced, apatite P (AP) content increased, non-apatite P (NAIP) content declined, and P solubility in citric acid content decreased. The amount of AP increased, NAIP reduced, and P solubility in citric acid decreased as the incineration temperature climbed. Although P in P-containing products prepared by OSM and MSM changed in a similar way at different additive doses and temperatures, P-containing products prepared by MSM had at least a 6.1% increase in P solubility in citric acid. Compared with OSM, MSM could save 10% of calcium-based additives when reaching the maximum AP value. Additionally, pure materials were employed to investigate how P species changed during the incineration procedure. The advantage of the MSM-prepared product over the OSM-prepared product may be explained by the high concentration of Ca3(PO4)2 and low concentration of amorphous calcium bound P (Ca-P). Overall, MSM is an effective method to reduce the dose of calcium-based additives and increase the bioavailability of P in P-containing products.

Effects of trigonelline, diosgenin, and Cistanche deserticola polysaccharide on the culture of female germline stem cells in vitro.

Female germline stem cells (FGSCs) are renewable sources of oocytes that play an indispensable role in re-establishing mammal fertility. Here, we have established FGSCs from neonatal mice, which exhibit characteristics of germline stem cells. We show that compared with monomeric trigonelline and diosgenin, macromolecular compounds Cistanche deserticola polysaccharides (CDPs) in Chinese herbal medicine can enhance the ability of FGSCs to differentiate into oocytes at appropriate concentrations while maintaining self-renewal in vitro. In contrast, trigonelline and diosgenin inhibited the expression of germ cell-specific genes while reducing cell proliferation activity. In summary, CDPs could induce the differentiation and self-renewal of FGSCs in vitro. The comparison of the effects of the active components of different types of Chinese medicine will provide a reference for the development of clinical drugs in the future, and help to elucidate the development process of FGSCs.

Preliminary investigation on the analysis of the whole components of Pogejiuxin decoction and its formulation pattern based on ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

RATIONAL: Pogejiuxin decoction (PGJXD) is one of the most important formulas for the treatment of heart failure. However, there is a great lack of research on the material basis of this formula, especially research on its compatibility laws, which restricts its clinical use. Studying the complete ingredients and compatibility rules of PGJXD has great significance for guiding clinical medication. METHODS: The entire formula, the major single herbs, the drug pairs and the disassembled formula were analyzed by ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS/MS), matching the chemical composition database and global natural product social molecular networking to explain the chemical composition as well as the combination pattern of PGJXD. RESULTS: A total of 1048 chemical constituents were fully analyzed from the major single herbs, the drug pairs and the disassembled formula and 188 chemical constituents, including 13 potential novel compounds, were firstly identified from the whole formula. We found that the chemical compositions were reduced after the single herbs were matched to the other herbs, especially the significant reduction of highly toxic diester alkaloids after compatibility, indicating that the medicines of PGJXD were interdependent and controlled by each other. CONCLUSION: This study innovatively researches and compares the compositional differences between the entire formula of PGJXD, the single, paired and separated formulas, greatly extending our understanding of the chemical substance basis of these compounds, and preliminarily explores the compatibility laws of PGJXD, providing some theoretical guidance for clinical medication.

Topochemical-like bandgap regulation engineering: A bismuth thiooxide nanocatalyst for breast cancer phototherapy.

The physical property tuning of nanomaterials is of great importance in energy, medicine, environment, catalysis, and other fields. Topochemical synthesis of nanomaterials can achieve precise control of material properties. Here, we synthesized a kind of element-doped bismuth-based nanomaterial (BOS) by topochemical-like synthesis and used it for the phototherapy of tumors. In this study, we employed bismuth fluoride nanoflowers as a template and fabricated element-doped bismuth oxide nanoflowers by reduction conditions. The product is consistent with the precursor in crystal structure and nanomorphology, realizing topochemical-like synthesis under mild conditions. BOS can generate reactive oxygen species, consume glutathione, and perform photothermal conversion under 730 nm light irradiation. In vitro and in vivo studies demonstrate that BOS could suppress tumor growth by inducing apoptosis and ferroptosis through phototherapy. Therefore, this study offers a general regulation method for tuning the physical properties of nanomaterials by using a topochemical-like synthesis strategy.

Withanolides from the active extract of Physalis angulate and their anti-hepatic fibrosis effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L., a traditional Chinese medicine called "Kuzhi" in China, was used traditionally to treat liver diseases (eg. icterus, hepatitis) as well as malaria, asthma, and rheumatism. AIM OF THE STUDY: Our study aimed to investigate the withanolides with anti-hepatic fibrosis effect from P. angulate. MATERIALS AND METHODS: Withanolides were obtained from the EtOH extract of P. angulate by bioassay-molecular networking analysis-guided isolation using column chromatography and normal/reversed-phase semipreparative HPLC. The structures of new withanolides were elucidated by combinations of spectroscopic techniques with NMR and ECD calculations. MTT cell viability assay, AO/EB staining method, cell wound healing assay, ELISA and Western blot experiments were employed to evaluate the anti-hepatic fibrosis activity and to uncover related mechanism. Molecular docking analysis and cellular thermal shift assay were used to evaluate and verify the interaction between the active withanolides and their potential targets. RESULTS: Eight unreported withanolides, withagulides A-H (1-8), along with twenty-eight known ones were obtained from P. angulate. Withanolides 6, 9, 10, 24, 27, and 29-32 showed marked anti-hepatic fibrosis effect with COL1A1 expression inhibition above 50 %. Physalin F (9), the main component in the active fraction, significantly decreased the TGF ß1-stimulated expressions of collagen I and α-SMA in LX-2 cells. Mechanism study revealed that physalin F exerted its anti-hepatic fibrosis effect via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: This study suggested that withanolides were an important class of natural products with marked anti-hepatic fibrosis effect. The main withanolide physalin F might be a promising candidate for hepatic fibrosis treatment. The work provided experimental foundation for the use of P. angulate to treat hepatic fibrosis.

E. globulus leaf EO exhibits anti-inflammatory effects by regulating GSDMD-mediated pyroptosis, thereby alleviating neurological impairment and neuroinflammation in experimental stroke mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aromatic and medicinal plants continue to be a major component of alternative and traditional medicine in the developing countries. Eucalyptus globulus (Labill.) is being employed to cultivation and production in China. However, few studies have reported the chemical composition and anti-inflammatory activity of Eucalyptus globulus (Labill.) leaf essential oil (E. globulus leaf EO) extracted from Eucalyptus globulus. AIM OF THE STUDY: This study aimed to assess the composition of E. globulus leaf EO and identify its bacteriostatic action as well as anti-inflammatory activity. Importantly, we evaluated the effect of E. globulus leaf EO on neurological impairment and neuroinflammation in experimental stroke mice. MATERIALS AND METHODS: Gas Chromatography-Mass Spectrometer (GC-MS) analyses was employed to evaluate the chemical components of E. globulus leaf EO, and the relative content of each component was determined by area normalization method. The antimicrobial activity of E. globulus leaf EO was determined by Oxford cup method and microbroth dilution assay. Cytotoxic activity of E. globulus leaf EO on THP-1 cells or BV2 cells in vitro was determined by CCK8 assay. In addition, the lipopolysaccharide (LPS)/ATP-induced inflammation model in THP-1 cells or BV2 cells were established, and the relative expression of TNF-α, IL-1ß, MCP-1and IL-6 were confirmed by RT-PCR. Furthermore, the expression of protein GSDMD, IL-lß, NLRP3 and NFκB signaling pathway were assessed by immunoblotting. In vivo,the experimental stroke model constructed by middle cerebral artery occlusion/reperfusion (MCAO/R) in mice was employed and subsequently treated with E. globulus leaf EO (50,100 mg/kg, subcutaneous injection) for 3 days to assess neurological impairment and neuroinflammation. Behavioral and neuronal damage were assessed using grip strength test, rod trarod test, and Nissl staining. Pro-inflammatory factors in serum or ischemic brain tissue was detected by ELISA kits. RESULTS: GC-MS analyses revealed that the major compound in E. globulus leaf EO was eudesmol (71.967%). E. globulus leaf EO has antimicrobial activity against Staphylococcus aureus (gram positive bacteria, MIC = 0.0625 mg/mL), Escherichia coli (gram negative bacteria, MIC = 1 mg/mL), and Candida albicans (MIC = 4 mg/mL). E. globulus leaf EO (0.5312, 1.0625, and 2.15 mg/mL) significantly decreased the expression of inflammation-related genes, including IL-1ß, TNF-α, MCP-1, and IL-6. Furthermore, reduced levels of TLR4, Myd88, phosphorylated NF-κB P65, and IκBα were found in the E. globulus leaf EO group for BV2 cells (1.025, and 2.125 mg/mL). In addition, the expression levels of GSDMD, NLRP3, IL-1ß and AIM2 were significantly decreased in the E. globulus leaf EO group when compared with the LPS -stimulated group, regulating GSDMD-mediated pyroptosis. In vivo, E. globulus leaf EO improved neurological functional deficits, inhibited excessive activation of microglia, and reduced the secretion of pro-inflammatory factors IL-1ß, TNF-α in the ischemic tissue and serum after MCAO/R. CONCLUSION: E. globulus leaf EO has strong antibacterial and anti-inflammatory activity, which has been implicated in blocking GSDMD-mediated pyroptosis. Moreover, E. globulus leaf EO could exert neuroprotective effect on cerebral ischemia-reperfusion injury.

Genome-wide characterization of the CPA gene family in potato and a preliminary functional analysis of its role in NaCl tolerance.

BACKGROUND: The cation/proton antiporter (CPA) superfamily plays a crucial role in regulating ion homeostasis and pH in plant cells, contributing to stress resistance. However, in potato (Solanum tuberosum L.), systematic identification and analysis of CPA genes are lacking. RESULTS: A total of 33 StCPA members were identified and classified into StNHX (n = 7), StKEA (n = 6), and StCHX (n = 20) subfamilies. StCHX owned the highest number of conserved motifs, followed by StKEA and StNHX. The StNHX and StKEA subfamilies owned more exons than StCHX. NaCl stress induced the differentially expression of 19 genes in roots or leaves, among which StCHX14 and StCHX16 were specifically induced in leaves, while StCHX2 and StCHX19 were specifically expressed in the roots. A total of 11 strongly responded genes were further verified by qPCR. Six CPA family members, StNHX1, StNHX2, StNHX3, StNHX5, StNHX6 and StCHX19, were proved to transport Na+ through yeast complementation experiments. CONCLUSIONS: This study provides comprehensive insights into StCPAs and their response to NaCl stress, facilitating further functional characterization.

A multistep approach for exploring quality markers of Shengjiang Xiexin decoction by integrating plasma pharmacochemistry-pharmacokinetics-pharmacology.

Shengjiang Xiexin decoction (SXD), a well-known traditional Chinese medicine (TCM), was used to alleviate delayed-onset diarrhea induced by the chemotherapeutic agent irinotecan (CPT-11). Our previous study showed that SXD regulated multidrug resistance-associated protein 2 (Mrp-2) to alter the pharmacokinetics of CPT-11 and its metabolites. However, the pharmacodynamic constituents and the related quality markers of SXD are unclear. In this study, ultra-high performance liquid chromatography coupled with quadrupole orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was utilized to identify the prototypes and metabolites in rat plasma after oral administration of SXD. The pharmacokinetic markers (PK markers) were screened through quantification and semiquantification of SXD-related xenobiotics in plasma using liquid chromatography-mass spectrometry (LC-MS) combined with statistical analysis. Computational molecular docking was performed to assess the potential binding ability of the PK markers with the target Mrp-2. The results were verified by evaluating the impact on Mrp-2 function using Caco-2 cells. The quality markers were chosen from these PK markers based on the binding affinities with Mrp-2, the specificity and the traceability. As a result, a total of 142 SXD-related exogenous components, including 77 prototypes and 65 metabolites, were detected in rat plasma. Among these, 83 xenobiotics were selected as PK markers due to their satisfactory pharmacokinetic behaviors. Based on the characteristics of quality markers, the prototype-based PK markers were considered the indices of quality control for SXD, including baicalin, baicalein, wogonoside, wogonin, liquiritigenin, isoliquiritigenin, norwogonin, oroxylin A, dihydrobaicalin, chrysin, glycyrrhizic acid, glycyrrhetinic acid, oroxylin A 7-O-glucuronide, liquiritin and isoliquiritin. This study provided an interesting strategy for screening the quality markers involved in the pharmacokinetics of SXD and its action target, which offered important information for the modernization of SXD and other TCM formulae.

Neural response properties predict perceived contents and locations elicited by intracranial electrical stimulation of human auditory cortex.

Intracranial electrical stimulation (iES) of auditory cortex can elicit sound experiences with a variety of perceived contents (hallucination or illusion) and locations (contralateral or bilateral side), independent of actual acoustic inputs. However, the neural mechanisms underlying this elicitation heterogeneity remain undiscovered. Here, we collected subjective reports following iES at 3062 intracranial sites in 28 patients (both sexes) and identified 113 auditory cortical sites with iES-elicited sound experiences. We then decomposed the sound-induced intracranial electroencephalogram (iEEG) signals recorded from all 113 sites into time-frequency features. We found that the iES-elicited perceived contents can be predicted by the early high-γ features extracted from sound-induced iEEG. In contrast, the perceived locations elicited by stimulating hallucination sites and illusion sites are determined by the late high-γ and long-lasting α features, respectively. Our study unveils the crucial neural signatures of iES-elicited sound experiences in human and presents a new strategy to hearing restoration for individuals suffering from deafness.

PTOV1-AS1 desensitizes colorectal cancer cells to 5-FU through depressing miR-149-5p to activate the positive feedback loop with Wnt/ß-catenin pathway.

5-Fluorouracil is a commonly used chemotherapy drug for colorectal cancer. Resistance to 5-Fluorouracil remains a challenge. This research aimed to explore the mechanism of 5-Fluorouracil resistance in colorectal cancer. RT-qPCR and Western blot were used to determine the RNA and protein expression in both cells and exosome. Assays in vitro and in vivo were performed to measure the role of miR-149-5p in colorectal cancer cells. RIP, luciferase activity report, and RNA pulldown assay were applied to detect the association of PTOV1-AS1, SUV39H1, miR-149-5p, and FOXM1. MiR-149-5p was down-expressed in 5-Fluorouracil-resistant cells. MiR-149-5p enhanced the effectiveness of 5-Fluorouracil both in vitro and in vivo. Sensitive colorectal cancer cells released exosomal miR-149-5p to sensitize resistant cells to chemotherapy. Mechanistically, miR-149-5p targeted the FOXM1 to inactivate Wnt/ß-catenin pathway, and PTOV1-AS1 recruited SUV39H1 to suppress miR-149-5p transcription, in turn activating Wnt/ß-catenin pathway, and forming a positive feedback loop with FOXM1. PTOV1-AS1 inhibits miR-149-5p by a positive feedback loop with FOXM1-mediated Wnt/ß-catenin pathway, which provides insights into a potential novel target for enhancing the effectiveness of chemotherapy in colorectal cancer patients.

Integrated microbiome and metabolomics revealed the protective effect of baicalin on alveolar bone inflammatory resorption in aging.

BACKGROUND: With the growing aging population and longer life expectancy, periodontitis and tooth loss have become major health concerns. The gut microbiota, as a key regulator in bone homeostasis, has gathered immense interest. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis Georgi, has shown antioxidant and anti-inflammatory activities. PURPOSE: This study investigated, for the first time, the protective mechanism of baicalin against alveolar bone inflammatory resorption in aging mice by regulating intestinal flora and metabolites, as well as intestinal barrier function. METHODS: A ligature-induced periodontitis model was established in d-galactose (D-gal)-induced aging mice, and baicalin was administered at different dosages for 13 weeks. Body weight was measured weekly. The antioxidant and anti-inflammatory activity of baicalin were evaluated using serum superoxide dismutase (SOD), malonaldehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. The immune capability was assessed by thymus and spleen indices. Histopathological changes were observed in the heart, liver, ileum, and periodontal tissues. Alveolar bone absorption of maxillary second molars was examined, and osteoclasts were counted by tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, fecal samples were analyzed using 16S rRNA sequencing and non-targeted metabolomics to identify differences in intestinal bacterial composition and metabolites. RESULTS: Baicalin exhibited anti-aging properties, as evidenced by increased SOD activity and decreased levels of MDA, IL-6, and TNF-α in serum compared to the control group. Baicalin also ameliorated alveolar bone loss in the d-gal-induced aging-periodontitis group (p < 0.05). Furthermore, baicalin restored ileal permeability by up-regulating the expression of ZO-1 and occludin in aging-periodontitis groups (p < 0.05). Alpha diversity analysis indicated that baicalin-treated mice harbored a higher diversity of gut microbe. PCoA and ANOSIM results revealed significant dissimilarity between groups. The Firmicutes/Bacteroidetes (F/B) ratio, which decreased in periodontitis mice, was restored by baicalin treatment. Additionally, medium-dosage baicalin promoted the production of beneficial flavonoids, and enriched short-chain fatty acids (SCFAs)-producing bacteria. CONCLUSION: Intestinal homeostasis is a potential avenue for treating age-related alveolar bone loss. Baicalin exerts anti-inflammatory, antioxidant, and osteo-protective properties by regulating the gut microbiota and metabolites.

Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial.

BACKGROUND: Depressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in adult depression. The primary objective of this study was to investigate the efficacy of adjuvant ω3 treatment on depressive symptoms in adolescent depression. Secondarily, we explored the effects of ω3 on cognitive function and memory and niacin skin flushing response (NSFR), as their robust associations with adolescent depression. METHODS: A total of 71 adolescents with depression (aged 13-24; 59.2 % female) were randomly assigned to receive ω3 plus Paxil (n = 34) or Paxil alone (n = 37) for 12 weeks. Primary outcome was depression severity according to scores on Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes were cognitive function and memory, and NSFR. RESULTS: Significant improvements in depressive symptoms over time (p = 0.00027 at week 12) were observed in the ω3 + Paxil group compared with Paxil group. Additionally, in the ω3 + Paxil group, significant improvements in memory over time, and greater cognitive function and NSFR were also observed compared with the Paxil group; the NSFR was negatively correlated with MADRS scores at baseline. LIMITATIONS: The trial was open label; thus, the outcome measures should be viewed as preliminary since inherent bias in outcomes due to the potential of a placebo effect. CONCLUSIONS: Our results demonstrate that adjuvant ω3 treatment is effective for reducing depressive symptoms as well as improving cognitive function, memory and the NSFR; these results suggest ω3 is a promising adjuvant treatment for adolescent depression.

Extraction and characterization of polysaccharides from Schisandra sphenanthera fruit by Lactobacillus plantarum CICC 23121-assisted fermentation.

Improving the yield of polysaccharides extracted from Schisandra sphenanthera is a major challenge in traditional Chinese medicinal plants. In this study, we investigated the potential of Lactobacillus plantarum CICC 23121-assisted fermentation as an extraction tool for S. sphenanthera polysaccharides (SSP). We observed that 11.12 ± 0.28 % of polysaccharides were extracted from S. sphenanthera using strain CICC 23121 -assisted fermentation (F-SSP), which was 53.38 % higher than that using hot water extraction (NF-SSP). The optimized parameters were a fermentation time of 15.5 h, substrate concentration of 4 %, and inoculum size of 3 %. Lactic acid produced by strain CICC 23121 increased the release of intracellular polysaccharides by breaking down cell walls. Compared to NF-SSP, F-SSP contained higher and lower total carbohydrate and protein contents, respectively, and its monosaccharide composition was the same as that of NF-SSP; however, their distributions were different. F-SSP had a higher molecular weight, better aqueous stability, and looser surface morphology, and strain CICC 23121-assisted fermentation did not change the molecular structure of SSP. Both NF-SSP and F-SSP showed the potential to regulate human intestinal microflora. Our findings revealed that strain CICC 23121-assisted fermentation is an efficient method for extracting S. sphenanthera polysaccharides without affecting their physicochemical and bioactive properties.