Occurrence and risk assessment of glycidyl and 3-monochloropropanediol esters in infant formulas marketed in Taiwan.

Glycidyl esters (GEs) and 3-monochloropropanediol esters (3-MCPDEs) are process contaminants commonly found in refined edible oils which are often added to infant formulas. The Taiwan Food and Drug Administration (TFDA) launched regulations for GEs in infant formulas that went into effect on 1 July 2021. To investigate levels of GEs and 3-MCPDEs in infant formula powder, 45 products were sampled and analysed during 2020-2021. The contents of GEs and 3-MCPDEs in formulas of different brands significantly varied, but their concentrations in all of the formulas complied with European Union (EU) regulations. Infant formulas containing palm oil had significantly higher 3-MCPDE levels in both extracted oils and milk powder than those without palm oil. Concentrations of GEs and 3-MCPDEs in infant formula powder and extracted oils were significantly lower in products from Europe than those from Australia and New Zealand. Infants aged 0-1 years in Taiwan who consumed only infant formula showed a margin of exposure (MoE) exceeding 25,000. Mean consumer exposures to 3-MCPDEs stayed below the tolerable daily intake (TDI), while high exposures at the 95th percentile (P95) exceeded the TDI by 1.7-fold. Herein, we present the changing trends in the risk assessment results of infant formula across various countries in the decade. Implementation of regulations and mitigation strategy effectively reduced the risk of infants being exposed to GEs and 3-MCPDEs through infant formula.

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10, MC38 and Hep1-6 Tumor Models.

OBJECTIVE: To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model. METHODS: Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment. RESULTS: PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4+ T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8+ T cells (P<0.01 or P<0.05). CONCLUSION: This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Probabilistic risk assessment for determining nonessential metals in commercial infant formula products in Taiwan.

During the early months of life, infant formula plays a crucial role as a primary source of both food and essential nutrients for infants, serving as a replacement for or supplement to breast milk. However, nonessential metals in infant formulas are a concern because infants are highly vulnerable to chemical exposure. The aim of this study was to investigate infant exposure to nonessential metals in infant formula products in Taiwan and assess the associated health risks. In this study, concentrations of arsenic (As), barium (Ba), cadmium (Cd), manganese (Mn), lead (Pb), and vanadium (V) in 45 formula products for 0-1-year-old infants were determined by inductively coupled plasma mass spectrometry. The mean As, Ba, Cd, Mn, Pb, and V concentrations were 6.42, 280, 3.72, 1425, 20.4, and 21.9 µg/kg, respectively. According to our probabilistic simulation of the estimated daily intake of metals, the proportion of hazard quotients exceeding one was 7.69% for As and 3.29% for Mn, and that of hazard index (HI) values exceeding 1 was >17% for metals. Arsenic had the largest HI contribution (46.9%), followed by Mn (22.3%) and Pb (12.7%). The nonessential metals content in infant formula raises potential noncarcinogenic health concerns for infants in Taiwan. Therefore, regulations for nonessential metals must be imposed on related food products in Taiwan, with a particular focus on As and Mn.

Investigation of the material basis and mechanism of Lizhong decoction in ameliorating ulcerative colitis based on spectrum-effect relationship and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Lizhong decoction (LZD), a classical herbal prescription recorded by Zhang Zhongjing in Treatise on Febrile and Miscellaneous Diseases, has been extensively used to treat ulcerative colitis (UC) in clinical practice for thousands of years. However, its material basis and underlying mechanism are not yet clear. AIM OF THE STUDY: This study aims to explore the material basis and potential mechanism of LZD against UC based on the spectrum-effect relationship and network pharmacology. MATERIALS AND METHODS: First, LZD was extracted by a systematic solvent extraction method into four parts. Ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) technique was used to identify the compounds from different polar parts, and dextran sulfate sodium (DSS)-induced colitis model was used to evaluate the efficacy of each fraction. Then, the spectrum-effect analyses of compounds and efficacy indicators were established via grey relational analysis (GRA), bivariate correlation analysis (BCA) and partial least squares regression (PLSR). Finally, the potential mechanism of LZD for UC therapy was explored by network pharmacology, and the results were further verified by molecular docking and reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: 66 chemical components of LZD were identified by UPLC-Q-TOF-MS/MS technology. The pharmacodynamic results showed that extraction parts of LZD had different therapeutic effects on UC, among which ethyl acetate and n-butanol extracts had significant anti-colitis effects, which might be the main effective fractions of LZD. Furthermore, the spectrum-effect analyses indicated that 21 active ingredients such as liquiritin apioside, neolicuroside, formononetin, ginsenoside Rg1, 6-gingesulfonic acid, licoricesaponin A3, liquiritin, glycyrrhizic acid were the main material basis for LZD improving UC. Based on the above results, network pharmacology suggested that the amelioration of LZD on UC might be closely related to the PI3K-Akt signaling pathway. Additionally, molecular docking technology and RT-qPCR further verified that LZD could markedly inhibit the PI3K-Akt signaling pathway. CONCLUSION: Overall, our study first identified the chemical compositions of LZD by using UPLC-Q-TOF-MS/MS. Furthermore, the material basis and potential mechanism of LZD in improving UC were comprehensively elucidated via spectrum-effect relationships, network pharmacology, molecular docking and experimental verification. The proposed strategy provided a systematic approach for exploring how herbal medicines worked. More importantly, it laid the solid foundation for further clinical application and rational development of LZD.

The long-term effect of modulated acoustic stimulation on alteration in EEG brain network of chronic tinnitus patients: An exploratory study.

Acoustic stimulation is one of the most influential techniques for distressing tinnitus, while how it functions to reverse neural changes associated with tinnitus remains undisclosed. In this study, our objective is to investigate alterations in brain networks to shed light on the enigma of acoustic intervention for tinnitus. We designed a 75-day long-term acoustic intervention experiment, during which chronic tinnitus patients received daily modulated acoustic stimulation with each session lasting 15 days. Every 15 days, professional tinnitus assessments were conducted, collecting both electroencephalogram (EEG) and tinnitus handicap inventory (THI) data from the patients. Thereafter, we investigated the changes in EEG network organizations during continuous acoustic stimulation and their progressive evolution throughout long-term therapy, alongside exploring the associations between the evolving changes of the network alterations and THI. Our current study findings reveal reorganization in alpha/beta long-range frontal-parietal-occipital connections as well as local frontal and parietal-occipital regions induced by acoustic stimulation. Furthermore, we observed a decrease in modulation effects as therapy sessions progressed. These alterations in brain networks reflect the reversal of tinnitus-related neural activities, particularly distress and perception; thus contributing to tinnitus rehabilitation through long-term modulation effects. This study provides unique insights into how long-term acoustic intervention affects the network organizations of tinnitus patients and deepens our understanding of the pathophysiological mechanisms underlying tinnitus rehabilitation.

Effect of acupuncture on arthritic pathological injury in rats with type â ¡ collagen-induced rheumatoid arthritis. / é’ˆåˆºæ”¹å–„â ¡åž‹èƒ¶åŽŸè›‹ç™½è¯±å¯¼æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ååº”çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of acupuncture stimulation of "Yanglingquan"(GB34), "Zusanli"(ST36) and "Xuanzhong" (GB39) on arthritis index (AI), joint synovial membrane pathology, serum-related immunoinflammatory factors, and expressions of tumor suppressor gene mt-p53, nuclear factor kappa B (NF-κB) and peroxisome proliferator activated receptor gamma (PPARγ) in knee joint synovial tissue of rats with type Ⅱ collagen-induced arthritis (CIA), so as to explore its possible mechanisms underlying improvement of rheumatoid arthritis (RA). METHODS: Male SD rats were used in the present study. The CIA model was established by subcutaneous injection of collagen emulsion (200 µL/rat) in the tail root region on the first day and repeat (100 µL/rat) once on the 9th day. Eighteen successful CIA rats were randomized into model, medication and acupuncture groups, with 6 rats in each group. Other 6 normal rats were used as the normal control group. For rats of the medication group, leflunomide (1.9 mg/kg) was administrated by gavage, once a day, and for rats of the acupuncture group, manual acupuncture stimulation was applied to bilateral GB34, ST36, GB39 for 30 min, once a day, for 12 weeks. The arthritis index (AI) score (0-4 points) was evaluated once every week. The contents of IL-6, IL-17 and TNF-α in the serum were determined by ELISA. Histopathological changes of the ankle joint were observed by H.E. staining. The protein and mRNA expression levels of mt-p53, NF-κB p65, and PPARγ in the knee joint synovial tissue were determined by Western blot and quantitative real time PCR, separately. RESULTS: Compared with the normal control group, the AI scores at different time-points after modeling, contents of serum TNF-α, IL-6 and IL-17, expression levels of mt-p53, NF-κB p65, PPARγ proteins and mRNAs were significantly increased in the model group (P<0.01, P<0.05). In comparison with the model group, the AI scores at the 10th week in the medication group and at the 3rd, 9th and 10th week in the acupuncture group, contents of serum TNF-α, IL-6 and IL-17, and the expression levels of mt-p53 and NF-κB p65 proteins in both medication and acupuncture groups, as well as mt-p53 and NF-κB p65 mRNAs in the medication group were apparently decreased (P<0.01, P<0.05), while the expression levels of PPARγ protein in both medication and acupuncture group and PPARγ mRNA in the medication group were significantly up-regulated (P<0.05, P<0.01). No significant differences were found between the acupuncture and medication groups in down-regulating the AI score and serum TNF-α, IL-6 and IL-17 contents. The effect of acupuncture was weaker than that of medication in down-regulating the expression of mt-p53 and NF-κB p65 proteins and mRNAs and in up-regulating PPARγ mRNA (P<0.01). H.E. results showed ankle cartilage hyperplasia, reduced joint cavity, mild fibroproliferation and inflammatory cell infiltration in the surrounding soft tissue of the ankle joint in rats of the model group, which was milder in both medication and acupuncture groups. CONCLUSIONS: Acupuncture stimulation can improve the degree of joint inflammation and swelling in CIA rats, which may be related to its effects in inhibiting the overexpression of immunoinflammatory factors in serum and regulating expression of mt-p53, NF-κB p65, PPARγ mRNAs and proteins in the synovial tissue.

Identification of Meloidogyne species on traditional Chinese medicine plants in the Qinling mountain area of China and their aggressiveness to different medicinal herbs.

Root-knot nematodes (Meloidogyne spp.) are plant-parasitic nematodes that cause serious damage on a worldwide basis. There are many species of traditional Chinese medicine (TCM) plants, but only a few have been reported to be infected by Meloidogyne species. From 2020 to 2022, a survey was conducted in the Qinling mountain area, which is the main producing region of TCM plants in China. Obvious galling symptoms were observed on the root systems of fifteen species of TCM plants. Females were collected from diverse diseased TCM plants and subsequently identified at morphological and molecular level. Among the twenty diseased root samples collected, Meloidogyne hapla populations were identified in twelve samples (60%) and Meloidogyne incognita populations were identified in eight samples (40%). Among the fifteen species of diseased TCM plants, eight of them, namely Scutellaria baicalensis, Leonurus japonicus, Dioscorea zingiberensis, Cornus officinalis, Viola philippica, Achyranthes bidentata, Senecio scandens, and Plantago depressa were reported to be infected by Meloidogyne species for the first time. The host status of five species of TCM plants for two M. hapla isolates and one M. incognita isolate from TCM plants in this study was then evaluated. Differences in TCM plants' response to nematode infection were apparent when susceptibility was evaluated by the egg counts per gram fresh weight of root and the reproduction factor of the nematodes. Among the five species of TCM plants tested, Salvia miltiorrhiza and Gynostemma pentaphyllum were the most susceptible, while S. baicalensis and V. philippica were not considered suitable hosts for M. hapla or M. incognita.

Effect of brief mindfulness and relaxation inductions on anxiety, affect and brain activation in athletes.

The mindfulness-based intervention and psychological skills training are often used for maintaining the mental health or reducing undesirable mental states in athletes. However, their differences in acute effects on mental health and underlying neural mechanism are not well understood. Therefore, the purpose of the current study was to examine the differential effects of brief mindfulness induction (MI) and relaxation induction (RI) on state anxiety, affect and brain activation. Thirty-five track and field athletes were recruited for this study. Using a within-subjects crossover design, participants underwent three conditions that incorporated two 30-min experimental conditions (i.e., MI or RI) and a control condition. State anxiety and affect were assessed before and after intervention, and brain activation (i.e., theta, alpha bands) were recorded by electroencephalography (EEG) during each 30-min condition. Repeated measures analysis of variance revealed that MI and RI similarly reduced state anxiety and negative affect from pre-test to post-test compared to the control condition. In terms of positive affect, there were no significant differences among the three conditions across times. Furthermore, participants exhibited higher frontal theta power during the MI and RI than control condition, whereas no differences in alpha power were observed among conditions. The current study provides initial evidence from an electrophysiological perspective that brief MI and RI both improve the negative psychological states in individual sport athletes through similar neural mechanisms. Nevertheless, the moderating effects of training experiences and long-term interventions on mental state and EEG activity in athletes need further investigation in future studies.

Comparative efficacy of five most common traditional Chinese medicine monomers for promoting recovery of motor function in rats with blunt spinal cord injury: a network meta-analysis.

Objective: This research employed a network meta-analysis (NMA) to examine the effectiveness of five traditional Chinese medicine (TCM) monomers for promoting motor function recovery in rats with blunt spinal cord injury (SCI). Methods: Wangfang, China National Knowledge Infrastructure, Web of Science, Embase, Chinese Scientific Journal Database, PubMed, and the Chinese Biomedical Literature Databases were searched for retrieving relevant articles published from their inception to December 2022. Two reviewers performed screening of search results, data extraction, and literature quality assessment independently. Results: For this meta-analysis, 59 publications were included. Based on the recovery of motor function at weeks 1, 2, 3, and 4 in NMA, almost all TCM groups had significantly increased positive effects than the negative control animals. In terms of cumulative probability, the tanshinone IIA (TIIA) group ranked first in restoring motor function in the first week after blunt SCI, and the resveratrol (RSV) group ranked first during the last 3 weeks. Conclusion: The NMA revealed that TCM monomers could effectively restore motor function in the rat model of blunt SCI. In rats with blunt SCI, TIIA may be the most effective TCM monomer during the first week, whereas RSV may be the most effective TCM monomer during the last 3 weeks in promoting motor function recovery. For better evidence reliability in preclinical investigations and safer extrapolation of those findings into clinical settings, further research standardizing the implementation and reporting of animal experiments is required. Systematic Review Registration: https://inplasy.com/, identifier INPLASY202310070.

Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF ß1/Smad3 and NF-κB signaling pathways.

BACKGROUND: Hepatic fibrosis is a serious condition, and the development of hepatic fibrosis can lead to a series of complications. However, the pathogenesis of hepatic fibrosis remains unclear, and effective therapy options are still lacking. Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1 (NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis, but its role in diseases including hepatic fibrosis remains undefined. Therefore, additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment. AIM: To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1. METHODS: Twenty-four male C57BL/6 mice were randomized and separated into three groups, comprising the normal, fibrosis, and calcitriol treatment groups, and liver fibrosis was modeled by carbon tetrachloride (CCl4). To evaluate the level of hepatic fibrosis in every group, serological and pathological examinations of the liver were conducted. TGF-ß1 was administered to boost the in vitro cultivation of LX-2 cells. NS3TP1, α-smooth muscle actin (α-SMA), collagen I, and collagen III in every group were examined using a Western blot and real-time quantitative polymerase chain reaction. The activity of the transforming growth factor beta 1 (TGFß1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected. The statistical analysis of the data was performed using the Student's t test. RESULTS: NS3TP1 promoted the activation, proliferation, and differentiation of hepatic stellate cells (HSCs) and enhanced hepatic fibrosis via the TGFß1/Smad3 and NF-κB signaling pathways, as evidenced by the presence of α-SMA, collagen I, collagen III, p-smad3, and p-p65 in LX-2 cells, which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference. The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression, as shown by the luciferase assay. NS3TP1 inhibited the apoptosis of HSCs. Moreover, both Smad3 and p65 could bind to NS3TP1, and p65 increased the promoter activity of NS3TP1, while NS3TP1 increased the promoter activity of TGFß1 receptor I, as indicated by coimmunoprecipitation and luciferase assay results. Both in vivo and in vitro, treatment with calcitriol dramatically reduced the expression of NS3TP1. Calcitriol therapy-controlled HSCs activation, proliferation, and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice. Furthermore, calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1. CONCLUSION: Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique, prospective therapeutic target in hepatic fibrosis.

The effect of semen cuscutae flavonoid on Sertoli cells and blood-testis barrier in male infertility: integrating network pharmacology and experimental verification.

CONTEXT: Semen cuscutae is commonly used to treat male infertility (MI), and semen cuscutae flavonoid (SCF) is the main active component of semen cuscutae. The therapeutic mechanism of SCF on MI is still unclear. OBJECTIVE: To clarify the mechanisms of SCF against MI. MATERIALS AND METHODS: Network pharmacology and molecular docking were used to predict the potential pathways of SCF against MI. Primary Sertoli cells (SCs) were extracted from testis of 60-day-old rats and divided into Control, Model, and 3 treatment groups. The Control and Model groups were given normal medium, the treatment groups were treated with various concentrations of SCF-containing medium (200, 400, and 800 µg/mL). After 24 h, the Model and treatment groups were exposed to heat stress at 43 °C for 15 min. Western blotting and immunohistochemistry were used to detect the expression of targets. RESULT: Network pharmacology indicated that the treatment of SCF on MI was closely related to PI3K-AKT signaling pathway. The in vitro experiments showed that SCF could up-regulated the expression of AKT, AR, occludin, and Ki67, and down-regulated the expression of CK-18 in SCs after heat stress. The AKT inhibitor could block this process. CONCLUSIONS: SCF can treat MI by regulating the proliferation and differentiation of SCs and the integrity of the blood-testis barrier. The study could provide experimental basis for clinical research.

[Phenolic derivatives from root bark of Schisandra sphenanthera].

This paper aimed to study the chemical constituents from the root bark of Schisandra sphenanthera. Silica, Sephadex LH-20 and RP-HPLC were used to separate and purify the 80% ethanol extract of S. sphenanthera. Eleven compounds were identified by ~1H-NMR, ~(13)C-NMR, ESI-MS, etc., which were 2-[2-hydroxy-5-(3-hydroxypropyl)-3-methoxyphenyl]-propane-1,3-diol(1), threo-7-methoxyguaiacylglycerol(2),4-O-(2-hydroxy-1-hydroxymethylethyl)-dihydroconiferylalcohol(3), morusin(4), sanggenol A(5), sanggenon I(6), sanggenon N(7), leachianone G(8),(+)-catechin(9), epicatechin(10), and 7,4'-dimethoxyisoflavone(11). Among them, compound 1 was a new compound, and compounds 2-9 were isolated from S. sphenanthera for the first time. Compounds 2-11 were subjected to cell viability assay, and the results revealed that compounds 4 and 5 had potential cytotoxicity, and compound 4 also had potential antiviral activity.

Dietary iron modulates gut microbiota and induces SLPI secretion to promote colorectal tumorigenesis.

Dietary iron intake is closely related to the incidence of colorectal cancer. However, the interactions among dietary iron, gut microbiota, and epithelial cells in promoting tumorigenesis have rarely been discussed. Here, we report that gut microbiota plays a crucial role in promoting colorectal tumorigenesis in multiple mice models under excessive dietary iron intake. Gut microbiota modulated by excessive dietary iron are pathogenic, irritating the permeability of the gut barrier and causing leakage of lumen bacteria. Mechanistically, epithelial cells released more secretory leukocyte protease inhibitor (SLPI) to combat the leaked bacteria and limit inflammation. The upregulated SLPI acted as a pro-tumorigenic factor and promoted colorectal tumorigenesis by activating the MAPK signaling pathway. Moreover, excessive dietary iron significantly depleted Akkermansiaceae in the gut microbiota; while supplementation with Akkermansia muciniphila could successfully attenuate the tumorigenic effect from excessive dietary iron. Overall, excessive dietary iron perturbs diet - microbiome-epithelium interactions, which contributes to intestinal tumor initiation.

A Targeted and pH-Responsive Nano-Graphene Oxide Nanoparticle Loaded with Doxorubicin for Synergetic Chemo-Photothermal Therapy of Oral Squamous Cell Carcinoma.

Purpose: Oral squamous cell carcinoma (OSCC) is a malignant disease with serious impacts on human health and quality of life worldwide. This disease is traditionally treated through a combination of surgery, radiotherapy, and chemotherapy. However, the efficacy of traditional treatments is hindered by systemic toxicity, limited therapeutic effects, and drug resistance. Fibroblast activation protein (FAP) is a membrane-bound protease. Although FAP has limited expression in normal adult tissues, it is highly expressed in the tumor microenvironment of many solid cancers - a characteristic that makes it an ideal target for anticancer therapy. In this study, we constructed a nano-drug delivery system (NPF@DOX) targeting FAP to increase the therapeutic efficiency of synergistic chemo-photothermal therapy against OSCC. Methods: We utilized PEGylated nano-graphene oxide (NGO) to link doxorubicin (DOX) and fluorescently-labeled, FAP-targeted peptide chains via hydrogen bonding and π-π bonding to enhance the targeting capability of NPF@DOX. The synthesis of NPF@DOX was analyzed using UV-Vis and FT-IR spectroscopy and its morphology using transmission electron microscopy (TEM). Additionally, the drug uptake efficiency in vitro, photo-thermal properties, release performance, and anti-tumor effects of NPF@DOX were evaluated and further demonstrated in vivo. Results: Data derived from FT-IR, UV-Vis, and TEM implied successful construction of the NPF@DOX nano-drug delivery system. Confocal laser scanning microscopy images and in vivo experiments demonstrated the targeting effects of FAP on OSCC. Furthermore, NPF@DOX exhibited a high photothermal conversion efficiency (52.48%) under near-infrared radiation. The thermogenic effect of NPF@DOX simultaneously promoted local release of DOX and apoptosis based on a pH-stimulated effect. Importantly, FAP-targeted NPF@DOX in combination with PTT showed better tumor suppression performance in vivo and in vitro than did either therapy individually. Conclusion: NPF@DOX can precisely target OSCC, and combined treatment with chemical and photothermal therapy can improve the therapeutic outcomes of OSCC. This method serves as an efficient therapeutic strategy for the development of synergistic anti-tumor research.

Effects of extract solution from magnesium alloys supplemented with different compositions of rare earth elements on in vitro epithelial and osteoblast progenitor cells.

Background: Magnesium alloys (Mg-alloys) have gained significant attention in recent years as a potential bioactive material for clinical applications. The incorporation of rare earth elements (REEs) into Mg-alloys has been of particular interest due to their potential to improve both mechanical and biological properties. Although there are diverse results in terms of cytotoxicity and biological effects of REEs, investigating the physiological benefits of Mg-alloys supplemented with REEs will help in the transition from theoretical to practical applications. Methods: In this study, two culture systems were used to evaluate the effects of Mg-alloys containing gadolinium (Gd), dysprosium (Dy), and yttrium (Y): human umbilical vein endothelial cells (HUVEC) and mouse osteoblastic progenitor cells (MC3T3-E1). Different compositions of Mg-alloys were assessed, and the effects of the extract solution on cell proliferation, viability, and specific cell functions were analyzed. Results: Within the range of weight percentages tested, the Mg-REE alloys did not exhibit any significant negative impacts on either cell line. Interestingly, moderate compositions (Mg-1.5Gd-1.5Dy-0.825Y-0.5Zr and Mg-2Gd-2Dy-1.1Y-0.5Zr) demonstrated a tendency to enhance osteoblastic activity and promote the vascularization process in both HUVEC and MC3T3-E1 cell lines. Discussion: The results of this study provide valuable insights into the potential benefits of REE-supplemented Mg-alloys for clinical applications. The observed enhancement in osteoblastic activity and promotion of vascularization processes suggest that optimizing the compositions of REEs in Mg-alloys could lead to the development of novel, more effective bioactive materials. Further investigations are required to understand the underlying mechanisms and to refine the alloy compositions for improved biocompatibility and performance in clinical settings.

Traditional Chinese Manual Therapy (Tuina) reshape the function of default mode network in patients with lumbar disc herniation.

Purpose: Investigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes. Methods: Patients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs. Results: In comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs. Conclusion: The present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients.

Investigation of the material basis of Xiexin Tang to alleviate type 2 diabetes mellitus based on spectrum-effect analysis by UPLC-Q-TOF/MS.

Xiexin Tang (XXT) is a classic prescription for treating diabetes in clinical practices for thousands of years in China, which has been also proved by a large number of modern pharmacological studies. However, due to its complex composition, the bioactive ingredients of XXT is still unclear. In present researches, spectrum-effect relationship analysis is widely used to explore the material basis of traditional medical herbs, so this method was adopted in this study. Firstly, the extract of XXT was separated and enriched into 5 fractions by macroporous adsorption resin. Then, UPLC-Q-TOF/MS method was used for qualitative identification of components in each eluting part, and efficacy of each fraction was assessed by the T2DM rat model. Based on grey relational analysis and pearson bivariate correlation analysis, it was found that the components such as berberine, gallic acid, catechin, epicatechin, acteoside, berberastine and 1-O-galloyl-ß-D-glucose might be the main effective basis of XXT to improve T2DM.

Strip intercropping with local crops increased Aconitum carmichaeli yield and soil quality.

Aconitum carmichaeli Debx. is a traditional Chinese medicine that is cultivated in China and Japan. However, the monoculturing of this herb substantially decreases soil quality. Therefore, scientific planting management is crucial for resolving the current problems in the cultivation of A. carmichaeli. In this study, we conducted a comparative study on the soil environmental characteristics, herb growth and quality of A. carmichaeli intercropping with five local crops in two different areas. Herb growth and quality, including biomass and secondary metabolites, and rhizosphere soil environmental characteristics were measured. The results showed that the intercropping with the five local crops substantially improved the A. carmichaeli biomass and polysaccharide content, decreased the disease index, and altered three monoester diterpenoid alkaloids and three diester diterpenoid alkaloids accumulations. The intercrops also increased the soil pH, nitrogen-cycling-gene abundances, and potentially beneficial microorganism abundances, and it also changed the soil nutrient levels. Moreover, these intercropping patterns could alleviate the continuous cropping obstacles of A. carmichaeli. According to a comprehensive evaluation of the A. carmichaeli growth and quality, as well as the soil quality, the best intercropping systems were the A. carmichaeli intercropping with rice, maize, and peanut. In summary, the strip-intercropping systems could improve the A. carmichaeli growth and soil quality, and be beneficial to the sustainable ecological planting of A. carmichaeli.

Nuclear receptor 5A2 regulation of Agrp underlies olanzapine-induced hyperphagia.

Antipsychotic (AP) drugs are efficacious treatments for various psychiatric disorders, but excessive weight gain and subsequent development of metabolic disease remain serious side effects of their use. Increased food intake leads to AP-induced weight gain, but the underlying molecular mechanisms remain unknown. In previous studies, we identified the neuropeptide Agrp and the transcription factor nuclear receptor subfamily 5 group A member 2 (Nr5a2) as significantly upregulated genes in the hypothalamus following AP-induced hyperphagia. While Agrp is expressed specifically in the arcuate nucleus of the hypothalamus and plays a critical role in appetite stimulation, Nr5a2 is expressed in both the CNS and periphery, but its role in food intake behaviors remains unknown. In this study, we investigated the role of hypothalamic Nr5a2 in AP-induced hyperphagia and weight gain. In hypothalamic cell lines, olanzapine treatment resulted in a dose-dependent increase in gene expression of Nr5a2 and Agrp. In mice, the pharmacological inhibition of NR5A2 decreased olanzapine-induced hyperphagia and weight gain, while the knockdown of Nr5a2 in the arcuate nucleus partially reversed olanzapine-induced hyperphagia. Chromatin-immunoprecipitation studies showed for the first time that NR5A2 directly binds to the Agrp promoter region. Lastly, the analysis of single-cell RNA seq data confirms that Nr5a2 and Agrp are co-expressed in a subset of neurons in the arcuate nucleus. In summary, we identify Nr5a2 as a key mechanistic driver of AP-induced food intake. These findings can inform future clinical development of APs that do not activate hyperphagia and weight gain.

Five Post-Translational Modification Residues of CmPT2 Play Key Roles in Yeast and Rice.

Chrysanthemum (Chrysanthemum morifolium Ramat.) is one of the largest cut flowers in the world. Phosphate transporter Pht1 family member CmPht1;2 protein (CmPT2) plays an important role in response to low-phosphate (LP) stress in chrysanthemum. Post-translational modification (PTM) can modulate the function of proteins in multiple ways. Here, we used yeast and rice systems to study the role of putative PTM in CmPT2 by determining the effect of mutation of key amino acid residues of putative glycosylation, phosphorylation, and myristoylation sites. We chose nine amino acid residues in the putative PTM sites and mutated them to alanine (A) (Cmphts). CmPT2 recovered the growth of yeast strain MB192 under LP conditions. However, G84A, G222A, T239A, Y242A, and N422A mutants could not grow normally under LP conditions. Analysis of phosphorus absorption kinetics showed that the Km of CmPT2 was 65.7 µM. Among the nine Cmphts, the expression of five with larger Km (124.4-397.5 µM) than CmPT2 was further evaluated in rice. Overexpression of CmPT2-OE increased plant height, effective panicle numbers, branch numbers, and yield compared with that of wild type 'Wuyunjing No. 7' (W7). Overexpression of Cmphts-OE led to decreased plant height and effective panicle numbers compared with that of the CmPT2-OE strain. The Pi content in roots of CmPT2-OE was higher than that of the W7 under both high (normal) phosphate (HP) and LP conditions. However, the Pi content in the leaves and roots was significantly lower in the N422A-OE strain than in the CmPT2-OE strain under both HP and LP conditions. Under LP conditions, the phosphorus starvation response (PSR) genes in CmPT2-OE were inhibited at the transcription level. The expression patterns of phosphorus-related genes in T239A, Y242A, and N422A-OE under LP conditions were different from those of CmPT2-OE. In conclusion, these five post-translational modification residues of CmPT2 play key roles in modulating the function of CmPT2. This work boosters our understanding of the function of phosphate transporters and provides genetic resources for improving the efficiency of phosphorus utilization in crop plants.