Non-cytotoxic nanomolar concentration of arctigenin protects neuronal cells from chemotherapy-induced ferroptosis by regulating SLC7A11-cystine-cysteine axis.

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.

Research Progress on the Antioxidant Activity of Natural Diarylheptanoids: Mechanisms and Structure-activity Relationships.

Antioxidant research has recently become a popular topic. Medicinal plants are important sources of novel active compounds. Diarylheptanoids, a typical family of secondary plant metabolites, are of great interest owing to their extensive spectrum of biological activities. They possess a unique 1,7-diphenylmethane structural skeleton. Thus, this review summarizes the natural linear or macrocyclic diarylheptanoids with antioxidant activity in the last two decades. In addition, the relationships between the structural characteristics of natural diarylheptanoids and their antioxidant capacity were also discussed. All the available data highlight the potential of natural diarylheptanoids as novel antioxidants.

Dietary tryptophan decreases the impacts of seawater temperature changes on behavior and gut health of the sea cucumber Apostichopus japonicus.

Seawater temperature change is an important concern for seed production and pond culture of sea cucumbers. The present study found that tentacle activity frequency was significantly lower in sea cucumbers exposed to continuous and rapid temperature increases than that of those at ambient temperature. Feeding behavior directly determines food intake, and further affects physiology and growth efficiency of sea cucumbers. This means that the decline in feeding caused by continuous and rapid temperature increases needs to be addressed in sea cucumber aquaculture. However, a sudden temperature change of 5 °C had no significant effect on behaviors of sea cucumbers. This indicates that continuous temperature increases, rather than a sudden increase, result in behavioral impacts on sea cucumbers. Therefore, we recommend aqua-farmers reduce the feeding amount for sea cucumbers during continuous and rapid temperature increases. In the present study, feeding behavior was significantly higher in sea cucumbers fed with 3% dietary tryptophan than that of those fed with 0% and 5% dietary tryptophan. This indicates that 3% dietary tryptophan increases the food intake of sea cucumbers, and mitigates the feeding decline caused by continuous and rapid temperature increase. This indicates that tryptophan has the potential to promote the feeding of sea cucumbers in seed production and pond culture. Adhesion capacity of sea cucumbers fed with 5% dietary tryptophan was significantly higher than that of individuals fed with 0% and 3% dietary tryptophan. This suggests that dietary tryptophan increases the feeding of sea cucumbers exposed to continuous and rapid temperature increases in pond culture and seed production. In addition, this study found that sea cucumbers fed with 3% dietary tryptophan had higher intestinal colony richness under the continuously rapid temperature change. The present study provides an effective method to improve adhesion behavior and to alleviate the impacts on feeding behavior for seed production and pond culture of sea cucumbers exposed to continuous and rapid temperature increases.

Liver protecting effects and molecular mechanisms of icariin and its metabolites.

As a detoxification and metabolism organ, the liver plays a vital role in human health. However, an excessive consumption of drugs and toxins, exposure to pathogenic viruses, and unhealthy living habits can lead to liver damage, which may even develop into liver cirrhosis and liver cancer. Epimedium brevicornum Maxim. is a traditional Chinese medicine and dietary supplement in which the flavonoid icariin is a main functional component. Although the protective mechanisms of icariin and its metabolites against liver injury are not yet comprehensively understood, an increasing number of studies have confirmed their liver-protective and anticancer effects. Indeed, icaritin, one of the metabolites of icariin, is currently utilized as an active component of an anti-cancer drug. This paper presents a review of the molecular mechanisms through which icariin and its metabolites actively protect against the occurrence and development of liver injury, and, thus, provides a comprehensive reference for further research and their application in liver protection.

Modularized batch production of 12-inch transition metal dichalcogenides by local element supply.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) are regarded as pivotal semiconductor candidates for next-generation devices due to their atomic-scale thickness, high carrier mobility and ultrafast charge transfer. In analog to the traditional semiconductor industry, batch production of wafer-scale TMDs is the prerequisite to proceeding with their integrated circuits evolution. However, the production capacity of TMD wafers is typically constrained to a single and small piece per batch (mainly ranging from 2 to 4 inches), due to the stringent conditions required for effective mass transport of multiple precursors during growth. Here we developed a modularized growth strategy for batch production of wafer-scale TMDs, enabling the fabrication of 2-inch wafers (15 pieces per batch) up to a record-large size 12-inch wafers (3 pieces per batch). Each module, comprising a self-sufficient local precursor supply unit for robust individual TMD wafer growth, is vertically stacked with others to form an integrated array and thus a batch growth. Comprehensive characterization techniques, including optical spectroscopy, electron microscopy, and transport measurements unambiguously illustrate the high-crystallinity and the large-area uniformity of as-prepared monolayer films. Furthermore, these modularized units demonstrate versatility by enabling the conversion of as-produced wafer-scale MoS2 into various structures, such as Janus structures of MoSSe, alloy compounds of MoS2(1-x)Se2x, and in-plane heterostructures of MoS2-MoSe2. This methodology showcases high-quality and high-yield wafer output and potentially enables the seamless transition from lab-scale to industrial-scale 2D semiconductor complementary to silicon technology.

Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up. FINDINGS: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths. INTERPRETATION: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.

Evaluation of stability and antitumor activity of two-dimensional black phosphorus modified with positively charged protein.

Two-dimensional black phosphorus (2D BP), a novel 2D photoelectric material with excellent near-infrared optical absorption, biocompatibility, and degradability, has shown enormous potential in biomedical field. However, under the action of light, oxygen and water, 2D BP is easily degraded to phosphate and phosphonate. In this work, trastuzumab (Tmab) as a positively charged protein was used to modify 2D BP through electrostatic interaction to form BP-Tmab. The Tmab layer on the surface of 2D BP can effectively protect BP from water, which significantly enhanced the water stability of BP. PEGylated 2D BP (BP-PEG) as a control was also prepared. After 7 days in air-exposed water, the attenuation value of BP-Tmab was only 6.62 ± 2.72% at room temperature, which was much lower than that of naked 2D BP (52.47 ± 2.26%) and BP-PEG (25.84 ± 2.80%) under the same conditions. The result was further confirmed by the temperature changes at different time points under laser irradiation, suggesting that the degradation of BP was effectively reduced by Tmab modification. In addition, BP-Tmab displayed satisfactory biocompatibility and can effectively destroy cancer cells under laser irradiation, showing an excellent photothermal therapy effect.

Gastrodia elata BI.:A Comprehensive Review of Its Traditional Use, Botany, Phytochemistry, Pharmacology, and Pharmacokinetics.

Materials and Methods: This article collects information from relevant documents, including scientific papers, books, and dissertations concerning Gastrodia elata BI. Results: To date, research on Gastrodia elata BI. has identified about 100 active compounds. Many compounds in Gastrodia elata BI. have biological activities, such as sedation and hypnosis, anticonvulsion, improvement of learning and memory, protection of neurons, antidepressive effects, lowering of blood pressure, promotion of angiogenesis, protection of cardiomyocytes, antiplatelet aggregation, anti-inflammatory activity, and amelioration of labor pains. Conclusion: Although many traditional uses of this plant have been confirmed, it is necessary to continue to study the relationship between its structure and function, clarify the mechanisms of pharmacological effects, and explore new clinical applications so as to better delineate the quality control standards for Gastrodia elata BI.

The feces of sea urchins as food improves survival, growth, and resistance of small sea cucumbers Apostichopus japonicus in summer.

Mass mortality and low growth highly decrease the production efficiency and sustainable aquaculture development of the sea cucumber Apostichopus japonicus in summer. Sea urchin feces was proposed to address the summer problems. A laboratory study was conducted for ~ 5 weeks to investigate survival, food consumption, growth and resistance ability of A. japonicus cultured with the feces of sea urchins fed kelp (KF feces, group KF), the feces of sea urchins fed prepared feed (FF feces, group FF), and the prepared sea cucumber feed (group S) at high temperature (25 °C). The sea cucumbers of group KF had better survival (100%) than those of the group FF (~ 84%), higher CTmax (35.9 °C) than those of the group S (34.5 °C), and the lowest skin ulceration proportion (0%) when  they were exposed to an infectious solution among the three groups. These results suggest that the feces of sea urchins fed kelp is a promising diet for improving the survival and enhancing the resistance in A. japonicus aquaculture in summer. Sea cucumbers fed significantly less FF feces after 24 h of ageing than the fresh FF feces, suggesting this kind of feces became unsuitable for A. japonicus in a short time (within 48 h). However, the 24 h of ageing at 25 °C for the high fiber feces of sea urchins fed kelp had no significant effects on the fecal consumption of sea cucumbers. In the present study, both fecal diets provide better individual growth to sea cucumbers than the prepared feed. Yet, the feces of sea urchins fed kelp provided the highest weight gain rate (WGR) to sea cucumbers. Therefore, the feces of sea urchins fed kelp is a promising food to reduce the mortality, to address the problems of summer, and to achieve higher efficiency in A. japonicus aquaculture in summer.

Revealing the mechanisms of Arisaema cum Bile on allergic asthma with systematic pharmacology approach-experimental validation.

Arisaema cum Bile (Dan Nanxing in Chinese, DNX) have been employed to treat allergic asthma. However, the active components and its mechanisms remain unknown. Therefore, the systematic pharmacology approach-experimental validation was performed in this study. Each 5, 6, and 10 compounds of DNX were obtained by HPLC analysis, TCMSP, and literature report, respectively. A total of 379 targets on all these compounds were acquired from Swiss Target Prediction, and 1973 targets on allergic asthma were predicated. The KEGG enrichment analysis was performed. Furthermore, a rat model of allergic asthma was established and DNX (450 mg/kg, p.o.) was given for 2 weeks. DNX treatment prevented OVA-induced pathological changes in lung cell of irregular arrange and necrotic bronchial epithelial. It also decreased inflammatory cytokines IL-4, IL-5, and IL-13 of serum and BALF, and increased IL-12 and IFN-γ. The main MAPK signaling pathway predicted by KEGG enrichment was verified, as indicated by the decreased protein expression of JNK (p < 0.05 & p < 0.01), ERK (p < 0.05), and p38 MAPK (p < 0.01) in lung tissue. These findings indicated that DNX attenuated OVA-induced allergic asthma mainly by decreasing the MAPK signaling pathway.

Xanthohumol inhibits non-small cell lung cancer via directly targeting T-lymphokine-activated killer cell-originated protein kinase.

Xanthohumol is a principal prenylated chalcone isolated from hops. Previous studies have shown that xanthohumol was effective against various types of cancer, but the mechanisms, especially the direct targets for xanthohumol to exert an anticancer effect, remain elusive. Overexpression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) promotes tumorigenesis, invasion and metastasis, implying the likely potential for targeting TOPK in cancer prevention and treatment. In the present study, we found that xanthohumol significantly inhibited the cell proliferation, migration and invasion of non-small cell lung cancer (NSCLC) in vitro and suppressed tumor growth in vivo, which is well correlated with inactivating TOPK, evidenced by reduced phosphorylation of TOPK and its downstream signaling histone H3 and Akt, and decreased its kinase activity. Moreover, molecular docking and biomolecular interaction analysis showed that xanthohumol was able to directly bind to the TOPK protein, suggesting that TOPK inactivation by xanthohumol is attributed to its ability to directly interact with TOPK. The findings of the present study identified TOPK as a direct target for xanthohumol to exert its anticancer activity, revealing novel insight into the mechanisms underlying the anticancer activity of xanthohumol.

[Hepatotoxicity and mechanism of Rhododendri Mollis Flos based on zebrafish model].

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 µg·mL~(-1) of the absolute lethal concentration and 448 µg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.

Neuroprotective Effect of Ginseng Fibrous Root Enzymatic Hydrolysate against Oxidative Stress.

Oxidative stress is one of the potential causes of nervous system disease. Ginseng extract possesses excellent antioxidant activity; however, little research on the function of the ginseng fibrous root. This study aimed to investigate the neuroprotective effects of ginseng fibrous root to alleviate the pathogenesis of Alzheimer's disease (AD) against oxidative stress. Ginseng fibrous root enzymatic hydrolysate (GFREH) was first prepared by digesting ginseng fibrous roots with alkaline protease. In vitro, the GFREH showed antioxidant activities in free radical scavenging mechanisms. With a cellular model of AD, GFREH inhibited the increase in Ca2+ levels and intracellular ROS content, maintained the balance of mitochondrial membrane potential, and relieved L-glutamic acid-induced neurotoxicity. In vivo, GFREH improved the survival rate of Caenorhabditis elegans (C. elegans) under oxidative stress, upregulated SOD-3 expression, and reduced reactive oxygen species (ROS) content. Therefore, our findings provide evidence for the alleviation effect of GFREH against oxidative stress in neuroprotection, which may accelerate the development of anti-Alzheimer's drugs and treatments in the future.

[Anti-tumor and analgesic activity evaluation and mechanism of Compound Kushen Injection].

This study aims to evaluate the anti-tumor and analgesic activities of Compound Kushen Injection(CKI) based on zebrafish model in vivo and investigate the anti-tumor mechanism. To be specific, zebrafish tumor xenotransplantation model was established by microinjection of murine LPC H12 cells into yolk sac. Then the high-dose CKI(H-CKI), medium-dose CKI(M-CKI), low-dose CKI(L-CKI) groups, and the model group were set. The anti-tumor activity of CKI was evaluated with the tumor area growth fold and integral absorbance(IA) growth fold 72 h after administration. The peripheral pain and central pain in zebrafish were respectively induced with acetic acid(AA) and phorbol myristate acetate(PMA). Zebralab ViewPoint system was employed to monitor behavioral trajectory of zebrafish, and movement times, movement time, movement distance, and movement velocity were used to evaluate the analgesic activity of CKI. Finally, real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was performed to detect the expression levels of apoptosis-related B lymphocyte tumor-2(Bcl-2) and phosphatidylinositol-3-kinase(PI3 K)/protein kinase B(Akt or PKB) pathway-related genes, for the verification of the anti-tumor mechanism. Compared with the model group, M-CKI and H-CKI significantly reduced the growth folds of tumor area and IA, relief the peripheral pain and central pain. The mechanism was that CKI can up-regulate the expression of cysteine aspartic acid specific protease-3(caspase-3, Casp3) and caspase-9(Casp9), down-regulate the expression of phosphoinositide 3-kinase(PI3 K) and Akt, and significantly reduce the expression of Bcl-2, hypoxia-inducible factor-1α(HIF-1α), and vascular endothelial growth factor(VEGF). In conclusion, CKI has significant inhibitory effect on tumor growth and pain, which is related to the PI3 K/Akt signaling pathway. The pathway mediates cell apoptosis, suppresses tumor growth, and alleviates tumor pain.

Botanical, Traditional Use, Phytochemical, and Toxicological of Arisaematis rhizoma.

MATERIALS AND METHODS: This review is a collection of all possible studies on AR, published in scientific journals, papers, and books. Using the papers related to Arisaematis, such as ScienceDirect, Wiley Online Library, Springer Link, Web of Science, CNKI, and WanFang Database. In this paper, the traditional uses, botany, phytochemistry, pharmacology, and toxicology of AR were reviewed. Finally, the existing problems and research directions of the research on AR are discussed. RESULTS: Ninety-eight chemical constituents were isolated from AR. AR has a wide range of pharmacological effects, such as the effects on the central nervous system and cardiovascular system. It also has anti-tumor, sedative, analgesic, anticonvulsant, anti-inflammatory, expectorant, antiarrhythmic, anticoagulant, and other effects. It is also considered an effective drug for in vitro and in vivo validation. CONCLUSIONS: AR is an excellent traditional medicinal plant in China. Pharmacological studies support the traditional use of AR and may verify the folk use of AR in the treatment of different diseases. The anti-tumor effect of AR has been widely concerned by scholars at home and abroad. It has become a hot spot in recent years and has made great contributions to the survival and development of human beings. Although it has a high value of comprehensive utilization, its development and utilization are far from enough. Therefore, the comprehensive development of AR is worthy of further analysis.

18ß-glycyrrhetinic acid improves high-intensity exercise performance by promoting glucose-dependent energy production and inhibiting oxidative stress in mice.

It has been shown that 18ß-glycyrrhetinic acid (18ß-GA), the main bioactive compound of licorice, can modulate oxidative stress and metabolic processes in liver and skin. Given the critical role of oxidative stress and energy metabolism in exercise-induced fatigue, we hypothesized that 18ß-GA could exert an ergogenic action by inhibiting excess reactive oxygen species (ROS) induction and promoting energy production in muscles. Mice were gavage-fed with 18ß-GA for four consecutive days. Running ability was assessed based on the exhaustive treadmill test with high- and moderate-intensity. Western blot analysis, enzyme-linked immunosorbent assay, and immunofluorescence staining were used to measure the changes of muscle fatigue-related markers, oxidative stress status, and energy metabolism in response to 18ß-GA exposure. Treatment with 18ß-GA significantly increased the exhaustive running distance (~37%) in the high-intensity exercise, but not in the moderate-intensity exercise. Mechanistically, reduction of oxidative stress and induction of antioxidants (SOD, CAT, and GSH) by 18ß-GA were observed. Moreover, 18ß-GA treatment caused an improved preservation of muscle glycogen (12%), which was associated with upregulation of glucose transporter 4 (GLUT4) (91%) and increased insulin level (17%). The findings of the present study clearly suggest that 18ß-GA holds excellent potential as a novel bioactive agent against high-intensity exercise-induced fatigue.

Food Sources of Selenium and Its Relationship with Chronic Diseases.

Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials.

Mechanisms of Physical Fatigue and its Applications in Nutritional Interventions.

Physical fatigue during exercise can be defined as an impairment of physical performance. Multiple factors have been found contributing to physical fatigue, including neurotransmitter-mediated defense action, insufficient energy supply, and induction of oxidative stress. These mechanistic findings provide a sound theoretical rationale for nutritional intervention since most of these factors can be modulated by nutrient supplementation. In this review, we summarize the current evidence regarding the functional role of nutrients supplementation in managing physical performance and propose the issues that need to be addressed for better utilization of nutritional supplementation approach to improve physical performance.

Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. METHODS: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. FINDINGS: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. INTERPRETATION: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. FUNDING: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

[Study on liver diseases with zebrafish as an important tool].

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.