Phytochemistry of genus Buxus and pharmacology of Cyclovirobuxine D.

BACKGROUND: Genus Buxus plants, commonly known as "boxwood", are widely distributed in China. The stems, branches, and leaves of the plant are traditionally used for rheumatism, toothache, chest pain, abdominal gas, and other diseases. However, an overview of the genus Buxus remains to be provided. PURPOSE: To provide a scientific basis for the appropriate use and further research the recent advancements in the traditional usage, phytochemistry, and, pharmacology of Buxus. STUDY DESIGN: Chemical composition and pharmacological correlation studies through a literature review. METHODS: Between 1970 and 2023, the available data concerning Buxus was compiled from online scientific sources, such as Sci-Finder, PubMed, CNKI, Google Scholar, and the Chinese Pharmacopoeia. Plant names were verified from "The Plant List'. Results: To date, 266 structurally diverse chemicals have been extracted and identified from the genus Buxus. Alkaloids constitute one of its primary bioactive phytochemicals. A summary of the channels of action of Cyclovirobuxine D on the cytotoxicity of a variety of cancers has been provided. CONCLUSION: Numerous findings from contemporary phytochemical and pharmacological studies support the traditional use, facilitating its application. Further research is necessary to address various shortcomings, including the identification of the active ingredients and quality control of the genus Buxus.

Moslae Herba: Botany, Traditional Uses, Phytochemistry, and Pharmacology.

Moslae Herba (MH) can be used for both medicine and food and has a long history of medicine. MH has the effects of sweating and relieving the exterior, removing dampness and harmonizing, and is mainly used for colds caused by damp heat in summer. It is called "Xiayue Zhi Mahuang" in China. So far, 123 chemical compounds have been isolated and identified from MH, including flavonoids, terpenoids, phenolic acids, phenylpropanoids, and other chemical compounds. Its chemical components have a wide range of pharmacological activities, including antibacterial, antiviral, anti-inflammatory, antioxidant, analgesic sedation, antipyretic, immune regulation, insecticidal, and other effects. In addition, because of its aromatic odor and health care function, MH also has development and utilization value in food, chemical, and other fields. This paper reviewed the research progress of MH in botany, traditional uses, phytochemistry, and pharmacology and provided a possible direction for further research.

Extraction, purification, structural characteristics, biological activities, and applications of polysaccharides from the genus Lilium: A review.

The genus Lilium (Lilium) has been widely used in East Asia for over 2000 years due to its rich nutritional and medicinal value, serving as both food and medicinal ingredient. Polysaccharides, as one of the most important bioactive components in Lilium, offer various health benefits. Recently, polysaccharides from Lilium plants have garnered significant attention from researchers due to their diverse biological properties including immunomodulatory, anti-oxidant, anti-diabetic, anti-tumor, anti-bacterial, anti-aging and anti-radiation effects. However, the limited comprehensive understanding of polysaccharides from Lilium plants has hindered their development and utilization. This review focuses on the extraction, purification, structural characteristics, biological activities, structure-activity relationships, applications, and relevant bibliometrics of polysaccharides from Lilium plants. Additionally, it delves into the potential development and future research directions. The aim of this article is to provide a comprehensive understanding of polysaccharides from Lilium plants and to serve as a basis for further research and development as therapeutic agents and multifunctional biomaterials.

[Research on mechanism of hypolipidemic effect of Massa Medicata Fermentata based on metabolomics].

This paper aims to study the therapeutic effect of Massa Medicata Fermentata on hyperlipidemia model rats and investigate its mechanism of hypolipidemic effect with the help of non-targeted metabolomics. The mixed hyperlipidemia model rats were constructed by giving high-fat chow. After successful modeling, the rats were divided into the model group, pravastatin sodium group(4.4 mg·kg~(-1)), lipotropic group(0.1 g·kg~(-1)), high-dose group(2.4 g·kg~(-1)), medium-dose group(1.2 g·kg~(-1)), and low-dose group(0.6 g·kg~(-1)) of Massa Medicata Fermentata, and they were administered for four weeks once daily. An equal volume of ultrapure water was given to the blank group and model group. Serum lipid level and liver hematoxylin-eosin(HE) staining were used as indicators to estimate the intervention effect of Massa Medicata Fermentata on mixed hyperlipidemia, and the changes in metabolites in plasma of mixed hyperlipidemia model rats were analyzed by non-targeted metabolomics. The mechanism of the hypolipidemic effect of Massa Medicata Fermentata was analyzed through metabolite pathway enrichment. The results showed that compared with the model group, the Massa Medicata Fermentata administration group, especially the high-dose group, could significantly reduce the content of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.05 or P<0.01), and liver HE staining revealed that the number of adipocytes in the high-dose group was reduced to some extent. The potential biomarkers obtained by non-targeted metabolomics screening included glycerol 3-phosphate, sphingomyelin, sphingosine 1-phosphate, and deoxyuridine, which were mainly involved in the sphingolipid metabolism process, glycerophospholipid metabolism process, glycerol ester metabolism pathway, and pyrimidine metabolism pathway, totaling four possible metabolic pathways related to lipid metabolism. This study provides a reference for an in-depth investigation of the hypolipidemic mechanism of Massa Medicata Fermentata, which is of great significance for further promoting the clinical application of Massa Medicata Fermentata and increasing the indications.

Targeting EFHD2 Inhibits Interferon-γ Signaling and Ameliorates Non-Alcoholic Steatohepatitis.

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of nonalcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. This study investigates the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in NASH pathogenesis. METHODS: Hepatic EFHD2 expression was characterized in NASH patients and two diet-induced NASH mouse models. Single-cell RNA-sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma (HCC) were assessed. Molecular mechanisms underlying EFHD2 function were investigated, along with its potential as a therapeutic target by chemical and genetic means. RESULTS: EFHD2 expression was significantly elevated in liver tissue macrophages/monocytes in both NASH patients and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related HCC. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of interferon-γ receptor-2 (IFNγR2) onto the plasma membrane. This interaction mediates IFNγ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a developed stapled α-helical peptide targeting EFHD2 demonstrated its efficacy in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Nonalcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all NAFLD patients progress to NASH. A key challenge is identifying the factors triggering inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of IFNγ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings suggest EFHD2 as a promising target for drug development aimed at NASH treatment.

Immunotherapy and the ovarian cancer microenvironment: Exploring potential strategies for enhanced treatment efficacy.

Despite progress in cancer immunotherapy, ovarian cancer (OC) prognosis continues to be disappointing. Recent studies have shed light on how not just tumour cells, but also the complex tumour microenvironment, contribute to this unfavourable outcome of OC immunotherapy. The complexities of the immune microenvironment categorize OC as a 'cold tumour'. Nonetheless, understanding the precise mechanisms through which the microenvironment influences the effectiveness of OC immunotherapy remains an ongoing scientific endeavour. This review primarily aims to dissect the inherent characteristics and behaviours of diverse cells within the immune microenvironment, along with an exploration into its reprogramming and metabolic changes. It is expected that these insights will elucidate the operational dynamics of the immune microenvironment in OC and lay a theoretical groundwork for improving the efficacy of immunotherapy in OC management.

10-Secocycloartane (=9,19-cyclo-9,10-secolanostane) triterpenoid saponins: Huangqiyenins M-X from Astragalus membranaceus (Fisch.) Bge.

Phytochemical investigations of the leaves of Astragalus membranaceus (Fisch.) Bge. have led to the isolation of 12 undescribed triterpenoid saponins named huangqiyenins M-X. The structures of the undescribed compounds were determined using NMR and HRESIMS data. The cytotoxicity of these compounds against the RKO and HT-29 colon cancer cell lines was evaluated. Among these compounds, huangqiyenin W exhibited the highest cytotoxic activity against RKO colon cancer cells, whereas huangqiyenin Q and W showed moderate cytotoxic activity against HT-29 colon cancer cells. The network pharmacology results indicated that STAT3, IL-2 and CXCR1 are the correlated targets of huangqiyenin W against colon cancer, with AGE-RAGE and Th17 cell differentiation as the key signaling pathways.

[Shenqi Dihuang Decoction inhibits high-glucose induced ferroptosis of renal tubular epithelial cells via Nrf2/HO-1/GPX4 pathway].

This study aims to explore the effects of Shenqi Dihuang Decoction on high-glucose induced ferroptosis and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) axis in human renal tubular epithelial cells(HK-2) and to clarify the underlying mechanism. The cell injury model was established by exposing HK-2 to high glucose, and the Shenqi Dihuang Decoction-medicated serum was prepared. The optimal concentration and intervention time of Shenqi Dihuang Decoction were determined. HK-2 were divided into normal, high glucose, and low-, medium-, and high-dose Shenqi Dihuang Decoction groups. After interventions, the cell proliferation rate in each group was determined and the cell morphology and mitochondrial ultrastructure were observed. Then, the levels of intracellular reactive oxygen species(ROS), ferrous ion(Fe~(2+)), glutathione(GSH), and malondialdehyde(MDA) and the protein levels of Nrf2, HO-1, GPX4, and xCT were measured. The optimal concentration and intervention time of Shenqi Dihuang Decoction-medicated serum were determined to be 10% and 24 h, respectively. Compared with the high glucose group, high-dose Shenqi Dihuang Decoction promoted the proliferation of HK-2. The cells in the low-, medium-, and high-dose Shenqi Dihuang Decoction groups presented tight arrangement, an increased cell count, improved morphology from a spindle-fiber shape to a cobblestone shape, and improved morphology and structure of mitochondrial membrane and cristae, compared with those in the high glucose group. Meanwhile, all the doses of Shenqi Dihuang Decoction inhibited ROS elevation to mitigate the peroxidation damage, lowered the Fe~(2+) and MDA levels and elevated the GSH level to inhibit lipid peroxidation, and activated the antioxidant pathway to upregulate the protein levels of Nrf2, HO-1, xCT, and GPX4. In conclusion, Shenqi Dihuang Decoction-medicated serum can inhibit high-glucose induced ferroptosis of HK-2 in vitro, which involves the antioxidant effect and the activation of the Nrf2/HO-1/GPX4 pathway.

[Study on the Correlation between Elevated Serum Free Light Chain and Inferior Clinical Features or Hematological Parameters of Lymphoma Patients in Chengdu Area].

OBJECTIVE: To analyze the correlation of the serum free light chain elevated (sFLC) and clinical characteristics and hematological parameters of lymphoma in Chengdu area. METHODS: 249 cases of non-Hodgkin lymphoma （NHL） out of 274 patients with lymphoma diagnosed in Sichuan People's Hospital from April 2019 to July 2021 were selected, the sFLC, clinical features and hematological parameters of the patients were analyzed retrospectively. The difference of clinical features between the patients with normal sFLC and elevated sFLC was examined by chi-square test. The difference of hematological parameters between patients with normal sFLC and elevated sFLC were examined by chi-square test and nonparametric Mann-Whitney U test. RESULTS: Among the 249 NHL patients, 55.42% （138/249） patients had an elevated sFLC, of which 9.24% （23/138） were being monoclonal and 46.18% （115/138） were polyclonal. The sFLC elevation was common in NHL, but varied according to the types of sFLC secretion （monoclonal or polyclonal）, and types of lymphoma. Furthermore, there were no significant statistical differences in clinical characteristics, including age, sex, stage disease, International Prognostic Index （IPI）, B symptoms, and bone marrow invasion between elevated sFLC and normal sFLC of the NHL patients （P＞0.05）. However, the patients with elevated sFLC had adverse hematological parameters more frequently, including higher WBC, ANC, AMC, hsCRP, Cr, Glb, LDH, and lower Hb, Alb. CONCLUSION: Elevated sFLC is associated with inferior hematological parameters, revealing the uniqueness of the diagnostic and prognostic value of sFLC in lymphoma in chengdu area.

Roles of TRPM7 in ovarian cancer.

Ovarian cancer stands as the prevailing gynecologic malignancy, afflicting over 313,959 individuals annually worldwide, accompanied by more than 207,252 fatalities. Perturbations in calcium signaling contribute significantly to the pathogenesis of numerous cancers, including ovarian cancer, wherein alterations in calcium transporter expression have been reported. Overexpression of TRPM7, a prominent calcium transporter, has been linked to adverse prognostic outcomes in various cancer types. The focus of this comprehensive review centers around delineating the oncogenic role of TRPM7 in cancer development and exploring its therapeutic potential as a target in combating this disease. Notably, TRPM7 fosters cancer invasion, metastasis, and uncontrolled cell proliferation, thereby perpetuating the expansion and reinforcement of these malignant entities. Furthermore, this review takes ovarian cancer as an example and summarizes the "dual-mode" regulatory role of TRPM7 in cancer. Within the domain of ovarian cancer, TRPM7 assumes the role of a harsh tyrant, firmly controlling the calcium ion signaling pathway and metabolic reprogramming pathways.

[Morin induces autophagy and apoptosis in hepatocellular carcinoma cells through Akt/mTOR/STAT3 pathway].

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 µmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 µmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.

[Inhibitory effect and molecular mechanism of sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells].

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.

Clinical characterization of EFHD2 (swiprosin-1) in Glioma-associated macrophages and its role in regulation of immunosuppression.

Glioblastoma has been extensively studied due to its high mortality and short survival. The evolution mechanism of tumor-associated macrophages (TAMs) to Glioma-associated microglia and macrophages (GAMs) in the tumor microenvironment (TME) remains to be elucidated. The tumor cell-to-cell interaction patterns have not been well defined yet. The EF-Hand Domain Family Member D2 (EFHD2) has been reported to be differentially expressed as an immunomodulatory molecule in a variety of cancers. But large-scale clinical data from multiple ethnic communities have not been used to investigate the role of EFHD2 in glioma. RNA-seq data from 313 or 657 glioma patients from the Chinese Glioma Genome Atlas (CGGA) database and 603 glioma patients from the Cancer Genome Atlas (TCGA) database were analyzed retrospectively. Cell localization was performed using single-cell sequencing data from the CGGA database and the GSE131928 dataset. Mouse glioma cell lines and primary macrophages isolated from Efhd2 knockout mice were co-cultured to validate the immunomodulatory effects of EFHD2 on macrophages and the remodeling of TME of glioblastoma. EFHD2 is enriched in high-grade gliomas, isocitrate dehydrogenase wild-type, and 1p/19q non-co-deficient gliomas. It is a potential biomarker of glioma-proneuronal subtypes and an independent prognostic factor for overall survival in patients with malignant glioblastoma. EFHD2 regulates the monocyte-macrophage system function and positively correlates with immunosuppressive checkpoints. Further experimental data demonstrates that Efhd2 influences the polarization state of GAMs and inhibits the secretion of TGF-ß1. In vitro experiments have revealed that macrophages lacking Efhd2 suppress the vitality of two glioma cell lines and decelerate the growth of glioma xenografts. In conclusion, EFHD2 promises to be a key target for TME-related immunotherapy.

Discovery of species-specific peptide markers and development of quality-evaluation strategies for deer horn gelatin using liquid chromatography-tandem mass spectrometry and a label-free methodology.

Deer horn gelatin (DHG) is a valuable nutritional dietary supplement. Due to the significant variation in the price of DHG from different sources, it is important to assess its quality and to clarify the species of its raw material. However, due to the similarity in appearance and physicochemical properties, as well as the destruction of genetic material during the manufacturing process, it is difficult to distinguish DHG from gelatin derived from other sources. Furthermore, current methods are unable to evaluate the overall quality of DHG. Using Nano LC-Orbitrap MS and data analysis software, DHG samples from five deer species were analyzed to identify peptide markers specific to alpha-2-HS-glycoprotein (AHSG) and collagen. The peptide markers were validated using HPLC-Triple Quadrupole MS, and strategies for assessing the quality of DHG were developed. Eighteen peptide markers were discovered, comprising peptides with differing specificities. Three strategies for the identification, characteristic mapping, and content determination of DHG were developed. These strategies can be used to assess the quality of deer gelatin.

Screening of Potential α-Glucosidase Inhibitors from the Roots and Rhizomes of Panax Ginseng by Affinity Ultrafiltration Screening Coupled with UPLC-ESI-Orbitrap-MS Method.

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening.

Comprehensive Identification of Ginsenosides in the Roots and Rhizomes of Panax ginseng Based on Their Molecular Features-Oriented Precursor Ions Selection and Targeted MS/MS Analysis.

Panax ginseng is widely used in Asian countries and its active constituents-ginsenosides-need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack of the fragmentation ions of many more ginsenosides. In order to comprehensively identify ginsenosides in RRPG, molecular features of ginsenosides orienting precursor ions selection and targeted tandem mass spectrometry (MS/MS) analysis strategy were proposed in our study, in which the precursor ions were selected according to the molecular features of ginsenosides irrespective of their peak abundances, and targeted MS/MS analysis was then performed to obtain their fragmentation ions for substance characterization. Using this strategy, a total of 620 ginsenosides were successfully characterized in RRPG, including 309 protopanaxadiol-type ginsenosides, 258 protopanaxatriol-type ginsenosides and 53 oleanane-type ginsenosides. It is worth noting that, except for the known aglycones mass-to-charge ratio (m/z) 459, 475 and 455, twelve other aglycones, including m/z 509, 507, 493, 491, 489, 487, 477, 473, 461, 457, 443 and 441, were first reported in our experiment and they were probably the derivatizations of the protopanaxatriol and protopanaxadiol. Our study will not only help people to improve the cognition of ginsenosides in RRPG, but will also play a guiding and reference role for the isolation and characterization of potentially new ginsenosides from RRPG.

Carrier-envelope-phase-dependent below-threshold harmonic generation in few-cycle mid-infrared laser fields.

We theoretically study the dependence of below-threshold harmonic generation (BTHG) of atoms on the carrier-envelope phase (CEP) driven by few-cycle mid-infrared laser pulses. The BTHG spectra can be accurately and efficiently calculated by solving the three-dimensional time-dependent Schrödinger equation using the time-dependent generalized pseudospectral method. We present the BTHG spectra as a function of the laser-field CEP. CEP-dependent enhancement or suppression occurred at low laser field intensities owing to the changes in the resonant effects associated with multiple quantum trajectories. However, the BTHG of atoms driven by high laser intensities is insensitive to the CEP. The synchrosqueezing time-frequency transform of the BTHG and extended semiclassical analysis are performed to elucidate the underlying physical mechanism.

Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo.

BACKGROUND: Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol (PEG) crosslinked decellularized single liver lobe scaffolds (DLSs), and establish its suitability as a graft for long-term liver tissue engineering. METHODS: Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate (SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor (VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells (HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. RESULTS: The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young's modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. CONCLUSIONS: The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.

[Correlation between Serum Free Light Chain and Blood Routine Parameters in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the correlation between serum free light chain (sFLC) and blood routine parameters in patients with multiple myeloma (MM). METHODS: 347 patients with multiple myeloma diagnosed in Sichuan people's Hospital from April 2019 to July 2021 were selected. sFLC, serum total light chain (sTLC), peripheral blood routine, coagulation and biochemical parameters were analyzed retrospectively. The correlation analysis between sFLC and blood routine parameters were calculated by Pearson or Spearman correlation coefficients. Multiple stepwise linear regression was used to screen the combined blood routine parameters related to sFLC. The efficacy of the selected blood routine parameters eflecting sFLC level was evaluated, the Kruskal Wallis test of independent samples was used for inter group comparison, and the receiver operating characteristic (ROC) curve was drawn at the same time. RESULTS: In MM patients, sFLC was positively related with sTLCκ, sTLCλ, sTLCκ/λ, Cr, Urea, Cr and Cys_C significantly, while negatively correlated with eGFR markedly (｜r｜≥0.3). Multivariate stepwise linear regression showed that the influence factors of sFLCκ were Cr and sTLCκ (P=0.000, P=0.003), the influence factors of sFLCλ were eGFR and sTLCλ(P=0.000, P=0.000), the sFLCκ/λ influence factor was sTLCκ/λ (P=0.032). Kruskal Wallis test of independent samples showed that Cr and sTLCκ, eGFR and sTLCλ, TLCκ/λ were good or better parameters to reflect the level of sFLCκ, sFLCλ and sFLCκ/λ in MM patients(P＜0.05), respectively. ROC curve analysis shows that Cr, sTLCκ, eGFR, sTLCλ and sTLCκ/λ had the ability to judge the abnormality of sFLC in MM patients (AUC=0.684-0.875, P＜0.05). CONCLUSION: In MM patients, sTLCκ and sTLCλ with renal function parameters could evaluate sFLCκ or sFLCλ level respectively, while sFLC κ/λ was estimated by sTLCκ/λ.