[Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice].

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species.

The aerial parts of Mosla chinensis Maxim. and Mosla chinensis cv. 'Jiangxiangru' (MCJ) are widely utilized in traditional Chinese medicine (TCM), known collectively as Xiang-ru. However, due to clinical effectiveness concerns and frequent misidentification, the original plants have increasingly been substituted by various species within the genera Elsholtzia and Mosla. The challenge in distinguishing between these genera arises from their similar morphological and metabolic profiles. To address this issue, our study introduced a rapid method for metabolic characterization, employing high-resolution mass spectrometry-based metabolomics. Through detailed biosynthetic and chemometric analyses, we pinpointed five phenolic compounds-salviaflaside, cynaroside, scutellarein-7-O-D-glucoside, rutin, and vicenin-2-among 203 identified compounds, as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia species. This methodology holds promise for broad application in the analysis of plant aerial parts, especially in verifying the authenticity of aromatic traditional medicinal plants. Our findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

Biodiversity and distribution patterns of blooming jellyfish in the Bohai Sea revealed by eDNA metabarcoding.

BACKGROUND: The mass occurrence of scyphozoan jellyfish severely affects marine ecosystems and coastal economies, and the study of blooming jellyfish population dynamics has emerged in response. However, traditional ecological survey methods required for such research have difficulties in detecting cryptic life stages and surveying population dynamics owing to high spatiotemporal variations in their occurrence. The environmental DNA (eDNA) technique is an effective tool for overcoming these limitations. RESULTS: In this study, we investigated the biodiversity and spatial distribution characteristics of blooming jellyfish in the Bohai Sea of China using an eDNA metabarcoding approach, which covered the surface, middle, and bottom seawater layers, and sediments. Six jellyfish taxa were identified, of which Aurelia coerulea, Nemopilema nomurai, and Cyanea nozakii were the most dominant. These three blooming jellyfish presented a marked vertical distribution pattern in the offshore regions. A. coerulea was mainly distributed in the surface layer, whereas C. nozakii and N. nomurai showed a upper-middle and middle-bottom aggregation, respectively. Horizontally, A. coerulea and C. nozakii were more abundant in the inshore regions, whereas N. nomurai was mainly distributed offshore. Spearman's correlation analysis revealed a strong correlation between the eDNA of the three dominant blooming jellyfish species and temperature, salinity, and nutrients. CONCLUSIONS: Our study confirms the applicability of the eDNA approach to both biodiverstiy evaluation of blooming jellyfish and investigating their spatial distribution, and it can be used as a supplementary tool to traditional survey methods.

Clinical effects and mechanisms of a Chinese patent medicine, Tongxinluo capsule, as an adjuvant treatment in coronary heart disease.

Coronary heart disease (CHD) is the leading cause of death globally, posing a serious threat to human health. However, the current treatment approaches available for CHD fall short of the ideal results. Tongxinluo (TXL) is a traditional Chinese medicine (TCM) that has been employed in the clinical treatment of cardiovascular and cerebrovascular diseases (such as angina pectoris, stroke, etc.) in China for many years and holds great potential as a prospective treatment. TXL either as a standalone treatment or in combination with interventions recommended in CHD guidelines has been shown to be effective and well tolerated in clinical trials for CHD. Drawing on the evidence from clinical trials and experimental studies, this review will focus on the cardiovascular protective properties and related mechanisms of TXL. By searching 8 Chinese and English databases, more than 4000 articles were retrieved. These articles were categorized, then read, and finally written into this review. In this review, the pharmacological properties of TXL include regulation of blood lipids, improvement of endothelial function, anti-inflammatory, antioxidant, inhibition of apoptosis and regulation of autophagy, anti-fibrosis, promotion of angiogenesis, and modulation of exosome communication. The information provided in this review will help the reader to comprehend better the insights that TCM has developed over time in practice and provide new perspectives for the treatment of CHD.

Synergistic impact of Gui Zhi Shao Yao Zhi Mu Decoction and leflunomide on gut microbiota in rheumatoid arthritis: insights from 16S rDNA sequencing.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex pathogenesis, including alterations in the gut microbiota. Gui Zhi Shao Yao Zhi Mu Decoction (GSZD), a traditional Chinese herbal formula, has shown efficacy in RA treatment, but its impact on intestinal microflora remains unclear. This study aimed to investigate the effects of GSZD combined with leflunomide on the gut microbiota of RA patients. METHODS: The study enrolled 48 RA patients who were randomly assigned to either a control group receiving leflunomide or a treatment group receiving GSZD combined with leflunomide for 12 weeks. Gut microbiota composition was analyzed pre- and post-intervention using 16S rDNA sequencing. Changes in microbial diversity, abundance, and metabolic functions were assessed. RESULTS: Post-treatment, both groups exhibited significant alterations in gut microbiota composition. GSZD combined with leflunomide led to an increased Bacteroidetes/Firmicutes ratio and a reduction in Actinobacteria compared to leflunomide alone. This was associated with beneficial shifts in microbial genera and metabolic pathways, suggesting improved gut health and systemic immune modulation. CONCLUSION: GSZD combined with leflunomide significantly modulates the gut microbiota in RA patients. This study provides insights into the mechanisms underlying the therapeutic effects of GSZD and highlights the potential of integrating traditional Chinese medicine with conventional treatments in managing RA.

Pallidum volume as a predictor for the effectiveness of mindfulness-based cognitive therapy and psycho-education in unmedicated patients with obsessive-compulsive disorder.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) has been documented to be effective in treating obsessive-compulsive disorder (OCD). However, the neurobiological basis of MBCT remains largely elusive, which makes it clinically challenging to predict which patients are more likely to respond poorly. Hence, identifying biomarkers for predicting treatment outcomes holds both scientific and clinical values. This prognostic study aims to investigate whether pre-treatment brain morphological metrics can predict the effectiveness of MBCT, compared with psycho-education (PE) as an active placebo, among patients with OCD. METHODS: A total of 32 patients with OCD were included in this prognostic study. They received magnetic resonance imaging (MRI) brain scans before treatment. Subsequently, 16 patients received 10 weeks of MBCT, while the other 16 patients underwent a 10-week PE program. The effectiveness of the treatments was primarily assessed by the reduction rate of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score before and after the treatment. We investigated whether several predefined OCD-associated brain morphological metrics, selected based on prior published studies by the ENIGMA Consortium, could predict the treatment effectiveness. RESULTS: Both the MBCT and PE groups exhibited substantial reductions in Y-BOCS scores over 10 weeks of treatment, with the MBCT group showing a larger reduction. Notably, the pallidum total volume was associated with treatment effectiveness, irrespective of the intervention group. Specifically, a linear regression model utilizing the pre-treatment pallidum volume to predict the treatment effectiveness suggested that a one-cubic-centimeter increase in pallidum volume corresponded to a 22.3% decrease in the Y-BOCS total score reduction rate. CONCLUSIONS: Pallidum volume may serve as a promising predictor for the effectiveness of MBCT and PE, and perhaps, other treatments with the shared mechanisms by MBCT and PE, among patients with OCD.

Cowberry extract loaded chitosan hydrogel with photothermal and antioxidant properties promotes infected wound healing.

Bacterial infection and oxidative stress impede clinical wound healing. Herein, the plant-derived cowberry extract (CE) was first explored as a natural photothermal agent and antioxidant to deal with bacterial infection and oxidative stress. After loading in the carboxymethyl chitosan (CMCs)/oxidized dextran (Odex) hydrogel, the photothermal effect of CE was highly enhanced by CMCs. The controlled temperature induced by CE-containing hydrogel under NIR laser irradiation could rapidly (10 min) and effectively kill Staphylococcus aureus (S. aureus, 99.3 %) and Escherichia coli (E. coli, 94.6 %). Besides, this hydrogel exhibited a fast gelation and hemostasis abilities, high stability, adhesion and ROS scavenging capabilities, as well as good injectability and biocompatibility. Above superior properties make this hydrogel to accelerate the wound healing in S. aureus-infected mice, and it is expected to be a potential clinical wound dressing.

Berberine Metabolites Stimulate GLP-1 Secretion by Alleviating Oxidative Stress and Mitochondrial Dysfunction.

Berberine (BBR) is a principal component of Rhizoma coptidis known for its therapeutic potential in treating diseases such as type 2 diabetes mellitus (T2DM) and obesity. Despite the trace levels of BBR in plasma, it's believed that its metabolites play a pivotal role in its biological activities. While BBR is recognized to promote GLP-1 production in intestinal L cells, the cytoprotective effects of its metabolites on these cells are yet to be explored. The present study investigates the effects of BBR metabolites on GLP-1 secretion and the underlying mechanisms. Our results revealed that, out of six BBR metabolites, berberrubine (BBB) and palmatine (PMT) significantly increased the production and glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in standard mice. Moreover, a single dose of PMT could markedly increase plasma GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. Furthermore, they could effectively reverse inflammation-induced inhibition of the Akt signaling pathway. In general, these insights suggest that the beneficial effects of orally administered BBR on GLP-1 secretion are largely attributed to the pharmacological activity of BBB and PMT by their above cytoprotective effects on L cells, which provide important ideas for stimulating GLP-1 secretion and the treatment of T2DM.

Selenium yeast improve growth, serum biochemical indices, metabolic ability, antioxidant capacity and immunity in black carp Mylopharyngodnpiceus.

This experiment was conducted to investigate the impacts of dietary selenium yeast (SeY) on the growth performance, fish body composition, metabolic ability, antioxidant capability, immunity and inflammatory responses in juvenile black carp (Mylopharyngodn piceus). The base diet was supplemented with 0.00, 0.30 and 0.60 g/kg SeY (0.04, 0.59 and 1.15 mg/kg of selenium) to form three isonitrogenous and isoenergetic diets for juvenile black carp with a 60-day. Adequate dietary SeY (0.30 and 0.60 g/kg) could significantly increase the weight gain (WG), special growth rate (SGR) compared to the SeY deficient groups (0.00 g/kg) (P < 0.05). Meanwhile, 0.30 and 0.60 g/kg SeY elevated the mRNA levels of selenoprotein T2 (SEPT2), selenoprotein H (SEPH), selenoprotein S (SEPS) and selenoprotein M (SEPM) in the liver and intestine compared with the SeY deficient groups (P < 0.05). Adequate dietary SeY could promote glucose catabolism and utilization through activating glucose transport (GLUT2), glycolysis (GCK, HK, PFK, PK, PDH), tricarboxylic acid cycle (ICDH and MDH), glycogen synthesis (LG, GCS and GBE) and IRS/PI3K/AKT signal pathway molecules (IRS2b, PI3Kc and AKT1) compared with the SeY deficient groups (P < 0.05). Similarly, adequate dietary SeY could improve lipid transport and triglycerides (TG) synthesis through increasing transcription amounts of CD36, GK, DGAT, ACC and FAS in the fish liver compared with the SeY deficient groups (P < 0.05). In addition, adequate SeY could markedly elevate activities of antioxidant enzymes (T-SOD, CAT, GR, GPX) and contents of T-AOC and GSH, while increased transcription amounts of Nrf2, Cu/Zn-SOD, CAT, and GPX in fish liver and intestine (P < 0.05). However, adequate SeY notably decreased contents of MDA, and the mRNA transcription levels of Keap1 in the intestine compared with the SeY deficient groups (P < 0.05). Adequate SeY markedly increased amounts or levels of the immune factors (ALP, ACP, LZM, C3, C4 and IgM) and the transcription levels of innate immune-related functional genes in the liver and intestine (LZM, C3 and C9) compared to the SeY deficient groups (P < 0.05). Moreover, adequate SeY could notably reduce levels of IL-8, IL-1ß, and IFN-γ and elevate TGF-1ß levels in fish intestine (P < 0.05). The transcription levels of MAPK13, MAPK14 and NF-κB p65 were notably reduced in fish intestine treated with 0.30 and 0.60 g/kg SeY (P < 0.05). In conclusion, these results suggested that 0.30 and 0.60 g/kg SeY could not only improve growth performance, increase Se, glucose and lipid metabolic abilities, enhance antioxidant capabilities and immune responses, but also alleviate inflammation, thereby supplying useful reference for producing artificial feeds in black carp.

Mild hyperthermia-assisted chitosan hydrogel with photothermal antibacterial property and CAT-like activity for infected wound healing.

Infected wounds pose a serious threat to public health and pose a significant challenge and financial burden worldwide. The treatment of infected wounds is now an urgent problem to be solved. Herein, mild hyperthermia-assisted hydrogels composed of carboxymethyl chitosan (CMCs), oxidized dextran (Odex), epigallocatechin gallate (EGCG) and PtNPs@PVP (CAT-like nanoenzymes) were proposed for the repair of infected wounds. The incorporation of PtNPs@PVP nanoenzymes give the hydrogels excellent photothermal property and CAT-like activity. When the temperature is maintained at 42-45 °C under 808 nm near infrared (NIR) exposure, the CMCs/Odex/EGCG/Nanoenzymes (COEN2) hydrogel demonstrated highly enhanced antibacterial ability (95.9 % in vivo), hydrogen peroxide (H2O2) scavenging ratio (85.1 % in vitro) and oxygen supply (20.7 mg/L in vitro). Furthermore, this mild-heat stimulation also promoted angiogenesis in the damaged skin area. Overall, this multifunctional hydrogel with antibacterial, antioxidant, oxygen supply, hemostasis, and angiogenesis capabilities has shown great promise in the repair of infected wounds. This study establishes the paradigm of enhanced infected wound healing by mild hyperthermia-assisted H2O2 scavenging, oxygen supplemental, and photothermal antibacterial hydrogels.

Fruit development and ripening orchestrating the biosynthesis and regulation of Lycium barbarum polysaccharides in goji berry.

Lycium barbarum polysaccharides (LBPs) are the primary bioactive components in fruits of L. barbarum, commonly known as goji berry. Despite significant progress in understanding the chemical structures and health benefits of LBPs, the biosynthesis and regulation of LBPs in goji berry remains largely unknown. In this study, physiological indicators, including LBPs, were monitored in goji berry during fruit development and ripening (FDR), suggesting that pectin might be the major component of LBPs with increased content reaching 235.8 mg/g DW. Proteomic and transcriptomic analysis show that 6410 differentially expressed genes (DEGs) and 2052 differentially expressed proteins (DEPs) were identified with overrepresentation of flavonoids and polysaccharides-related gene ontology (GO) terms and KEGG pathways. Weighted gene co-expression network analysis (WGCNA) showed that LBPs coexpress with genes involved in pectin biosynthesis (LbGALS3, LbGATL5, LbQUA1, LbGAUT1/4/7, LbRGGAT1, LbRRT1/7, and LbRHM2), modification (LbSBT1.7), and regulation (LbAP2, LbGL2 LbTLP2, LbERF4, and LbTTG2), as well as with novel transcription factors (LbSPL9 and LbRIN homologs) and glycosyltransferases. Transgenic hairy roots overexpressing LbRIN validated that LbRIN modulate the expression of WGCNA-predicted regulators, including LbERF4, LbTTG2, and LbSPL9. These findings suggest that the biosynthesis and regulation of LBPs is conserved partially to those in Arabidopsis pectin. Taken together, this study provides valuable insights into the biosynthesis and regulation of LBPs, which can facilitate future studies on synthetic biology applications and genetic improvement of LBPs.

The Effects of Photobiomodulation on Knee Function, Pain, and Exercise Tolerance in Older Adults: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To assess whether photobiomodulation therapy (PBMT) enhances the benefits of exercise in older adults. DATA SOURCES: PubMed, Scopus, Medline, and Web of Science, dated to February 2023. STUDY SELECTION: All included studies were randomized controlled trials of PBMT combined with exercise co-intervention in persons 60 years and older. OUTCOME MEASURES: Western Ontario and McMaster University Osteoarthritis Index (WOMAC-total, pain, stiffness and function), perceived pain intensity, timed Up and Go (TUG) Test, 6-min walk test (6MWT), muscle strength, and knee range of motion were included. DATA EXTRACTION: Two researchers independently performed data extraction. Article data were extracted in Excel and summarized by a third researcher. DATA SYNTHESIS: The meta-analysis included 14 of the 1864 studies searched in the database. No statistical differences were found between the treatment and control groups in terms of WOMAC-stiffness (mean difference [MD]=-0.31, 95% confidence interval [CI] -0.64 to 0.03), TUG (MD=-0.17, 95% CI -0.71 to 0.38), 6MWT (MD=32.2, 95% CI -44.62 to 109.01), or muscle strength (standardized mean difference=0.24, 95% CI -0.02 to 0.50). However, statistically significant differences were found for WOMAC-total (MD=-6.83, 95% CI -12.3 to -1.37), WOMAC-pain (MD=-2.03, 95% CI -4.06 to -0.01), WOMAC-function (MD=-5.03, 95% CI -9.11 to -0.96), visual analog scale/numeric pain rating scale (MD=-1.24, 95% CI -2.43 to -0.06), and knee range of motion (MD=1.47, 95% CI 0.07 to 2.88). CONCLUSIONS: In older adults who exercise regularly, PBMT can potentially provide additional pain relief, improve knee joint function, and increase knee joint range of motion.

Saying no to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia.

Nitric oxide (NO), a gaseous free radical produced from L-arginine catalyzed by NO synthase, functions as an important signaling molecule in the human body. Its antiviral activity was confirmed in the 1990s, and has been studied more extensively since the outbreak of the SARS pandemic in 2003. In the fight against the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, some recent studies have revealed the potential of NO in the treatment of coronavirus disease 2019 (COVID-19). The progress in this field, including several noteworthy clinical trials of inhaled NO for the treatment of COVID-19 and the emergency approval of NO nasal spray by the regulatory agencies of Israel, Bahrain, Thailand and Indonesia for the treatment of COVID-19 pneumonia, offers a new perspective for addressing the raging coronavirus infection and greatly broadens the clinical application of NO therapy. This review aims to explore the underlying molecular mechanisms of NO-based therapy against SARS-CoV-2, including direct viral inhibition, immune regulation, and protection against pulmonary and cardiovascular symptoms. Furthermore, the potential therapeutic applications of inhaled NO, NO donors and drugs involved in the NO pathway are discussed. In the context of a global vaccination campaign and newly proposed strategy of "coexistence with COVID-19," the advantages of NO therapies as symptomatic and adjuvant treatments are expected to deliver breakthroughs in the treatment of COVID-19.

Effect of transvaginal Lactobacillus supplementation on reversing lower genital tract dysbiosis and improving perinatal outcomes in PCOS patients after IVF-FET: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization-frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. METHODS/DESIGN: This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography-mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. DISCUSSION: This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. ETHICS AND DISSEMINATION: Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. TRIAL REGISTRATION: ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

Composite Nanomaterials of Conjugated Polymers and Upconversion Nanoparticles for NIR-Triggered Photodynamic/Photothermal Synergistic Cancer Therapy.

Phototherapies such as photodynamic therapy (PDT) and photothermal therapy (PTT) have attracted great attention in the field of cancer treatment. However, the individual PDT or PTT makes it difficult to achieve optimal antitumor effects compared to the PDT/PTT combined therapy. Also, the effect of PDT is usually limited by the penetration depth of the UV-vis light source. Herein, we designed and synthesized novel composite nanoparticles UCNPs-CPs, which are constructed from two conjugated polymers and upconversion nanoparticles ß-NaYF4:Yb,Tm (UCNPs) via a coordination reaction. By virtue of the excellent spectral overlap between absorption of conjugated polymers and emission of UCNPs, the UCNPs can absorb NIR light and effectively excite conjugated polymers by energy transfer to produce massive reactive oxygen species under 980 nm excitation and heat energy under 808 nm laser irradiation, achieving photodynamic/photothermal synergistic therapy. The in vitro cellular investigation proves that the dual modal phototherapy exhibits enhanced antitumor ability compared to single PDT or PTT. Furthermore, UCNPs-CPs inhibit tumor growth 100% in a 4T1 breast tumor mice model with both NIR laser irradiation, indicating that UCNPs-CPs is an excellent platform for synergistic PDT/PTT treatment. Thus, this study provides a promising strategy for NIR-triggered dual modal phototherapy.

Liensinine and neferine exert neuroprotective effects via the autophagy pathway in transgenic Caenorhabditis elegans.

BACKGROUND: Liensinine and neferine are the main bisbenzylisoquinoline alkaloids obtained from the seeds of Nelumbo nucifera, which commonly used as edible food and traditional medicine in Asia. It was reported that liensinine and neferine could inhibit the activities of acetylcholinesterase and cross the blood-brain barriers, suggesting their therapeutic potential for the management of Alzheimer's disease. METHODS: Here, we employed SH-SY5Y human neuroblastoma cells stably transfected with the human Swedish amyloid precursor protein (APP) mutation APP695 (APP695swe SH-SY5Y) as an in vitro model and transgenic Caenorhabditis elegans as an in vivo model to investigate the neuroprotective effects and underlying mechanism of liensinine and neferine. RESULTS: We found that liensinine and neferine could significantly improve the viability and reduce ROS levels in APP695swe SH-SY5Y cells, inhibit ß-amyloid and tau-induced toxicity, and enhance stress resistance in nematodes. Moreover, liensinine and neferine had obviously neuroprotective effects by assaying chemotaxis, 5-hydroxytryptamine sensitivity and the integrity of injured neurons in nematodes. Preliminary mechanism studies revealed that liensinine and neferine could upregulate the expression of autophagy related genes (lgg-1, unc-51, pha-4, atg-9 and ced-9) and reduce the accumulation of ß-amyloid induced autophagosomes, which suggested autophagy pathway played a key role in neuroprotective effects of these two alkaloids. CONCLUSIONS: Altogether, our findings provided a certain working foundation for the use of liensinine and neferine to treat Alzheimer's disease based on neuroprotective effects.

Two zinc finger proteins, VdZFP1 and VdZFP2, interact with VdCmr1 to promote melanized microsclerotia development and stress tolerance in Verticillium dahliae.

BACKGROUND: Melanin plays important roles in morphological development, survival, host-pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. RESULTS: We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. CONCLUSIONS: Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.

Icariin inhibits hypertrophy by regulation of GPER1 and CaMKII/HDAC4/MEF2C signaling crosstalk in ovariectomized mice.

Icariin (ICA), a flavonoid phytoestrogen, was isolated from traditional Chinese medicine Yin Yang Huo (Epimedium brevicornu Maxim.). Previous studies reporting the cardioprotective effects of ICA are available; however, little is known about the impact of ICA on cardioprotection under conditions of reduced estrogen levels. This study aimed to provide detailed information regarding the antihypertrophic effects of ICA in ovariectomized female mice. Female mice were subjected to ovariectomy (OVX) and transverse aortic constriction and then orally treated with ICA at doses of 30, 60 or 120 mg/kg/day for 4 weeks. Morphological assessments, echocardiographic parameters, histological analyses, and immunofluorescence were performed to evaluate cardiac hypertrophy. Cardiomyocytes from mice or rats were stimulated using phenylephrine, and cell surface and hypertrophy markers were tested using immunofluorescence and qPCR. Western blotting, qPCR, and luciferase reporter gene assays were used to assess the expression of proteins and mRNA and further investigate the proteins related to the G-protein coupled estrogen receptor (GPER1) and CaMKII/HDAC4/MEF2C signaling pathways in vivo and in vitro. ICA blocks cardiac hypertrophy induced by pressure overload in OVX mice. Additionally, we demonstrated that ICA activated GPER1 and inhibited the nuclear export or promoted the nuclear import of histone deacetylase 4 (HDAC4) through regulation of phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and further improved the repression of myocyte enhancer factor-2C (MEF2C). ICA ameliorated cardiac hypertrophy in OVX mice by activating GPER1 and inhibiting the CaMKII/HDAC4/MEF2 signaling pathway.

SbWRKY75- and SbWRKY41-mediated jasmonic acid signaling regulates baicalin biosynthesis.

Introduction: Scutellaria baicalensis Georgi is a traditional Chinese medicinal plant with broad pharmacological activities whose main active ingredient is the flavonoid baicalin. Given its medicinal value and increasing market demand, it is essential to improve the plant's baicalin content. Flavonoid biosynthesis is regulated by several phytohormones, primarily jasmonic acid (JA). Methods: In this study, we conducted transcriptome deep sequencing analysis of S. baicalensis roots treated with methyl jasmonate for different durations (1, 3, or 7 hours). Leveraging weighted gene co-expression network analysis and transcriptome data, we identified candidate transcription factor genes involved in the regulation of baicalin biosynthesis. To validate the regulatory interactions, we performed functional assays such as yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase assays. Results: Our findings demonstrated that SbWRKY75 directly regulates the expression of the flavonoid biosynthetic gene SbCLL-7, whereas SbWRKY41 directly regulates the expression of two other flavonoid biosynthetic genes, SbF6H and SbUGT, thus regulating baicalin biosynthesis. We also obtained transgenic S.baicalensis plants by somatic embryo induction and determined that overexpressing SbWRKY75 increased baicalin content by 14%, while RNAi reduced it by 22%. Notably, SbWRKY41 indirectly regulated baicalin biosynthesis by modulating the expression of SbMYC2.1, SbJAZ3 and SbWRKY75. Discussion: This study provides valuable insights into the molecular mechanisms underlying JA-mediated baicalin biosynthesis in S. baicalensis. Our results highlight the specific roles of transcription factors, namely SbWRKY75 and SbWRKY41, in the regulation of key biosynthetic genes. Understanding these regulatory mechanisms holds significant potential for developing targeted strategies to enhance baicalin content in S. baicalensis through genetic interventions.