Sex-specific scaling of leaf phosphorus vs. nitrogen under unequal reproductive requirements in Eurya japonica, a dioecious plant.

PREMISE: Previous work searching for sexual dimorphism has largely relied on the comparison of trait mean vectors between sexes in dioecious plants. Whether trait scaling (i.e., the ratio of proportional changes in covarying traits) differs between sexes, along with its functional significance, remains unclear. METHODS: We measured 10 vegetative traits pertaining to carbon, water, and nutrient economics across 337 individuals (157 males and 180 females) of the diocious species Eurya japonica during the fruiting season in eastern China. Piecewise structural equation modeling was employed to reveal the scaling relationships of multiple interacting traits, and multivariate analysis of (co)variance was conducted to test for intersexual differences. RESULTS: There was no sexual dimorphism in terms of trait mean vectors across the 10 vegetative traits in E. japonica. Moreover, most relationships for covarying trait pairs (17 out of 19) exhibited common scaling slopes between sexes. However, the scaling slopes for leaf phosphorus (P) vs. nitrogen (N) differed between sexes, with 5.6- and 3.0-fold increases of P coinciding with a 10-fold increase of N in male and female plants, respectively. CONCLUSIONS: The lower ratio of proportional changes in P vs. N for females likely reflects stronger P limitation for their vegetative growth, as they require greater P investments in fruiting. Therefore, P vs. N scaling can be a key avenue allowing for sex-specific strategic optimization under unequal reproductive requirements. This study uncovers a hidden aspect of secondary sex character in dioecious plants, and highlights the use of trait scaling to understand sex-defined economic strategies.

Different seasonal dynamics, ecological drivers, and assembly mechanisms of algae in southern and northern drinking water reservoirs.

The role of environmental factors on the community structure of algae has been intensively studied, but there are few analyses on the assembly mechanism of the algal community structure. Here, changes in the community structure of algae in different seasons, the effects of environmental variables on the algal community structure, and the assembly mechanism of the algal community structure in northern and southern reservoirs were investigated in this study. The study revealed that Bacillariophyta, Cyanophyta, and Chlorophyta were the predominant algal species in the reservoirs, with Bacillariophyta and Cyanophyta exhibiting seasonal outbreaks. Compared to the northern reservoirs, the algal diversity in the southern reservoirs was greater. The diversity and algal community structure could be significantly impacted by variations in water temperature and nitrogen level. According to the ecological model, the interaction among algal communities in reservoirs was primarily cooperation. The key taxa in the northern reservoirs was Aphanizomenon sp., while the outbreak in the southern reservoirs was Coelosphaerium sp. The community formation pattern of reservoirs was stochastic, with a higher degree of explanation observed in the southern reservoirs compared to the northern reservoirs. This study preliminarily explored the assembly mechanism of the algal community, providing a theoretical basis for the control of eutrophication in drinking water reservoirs.

Observation of plaid-like spin splitting in a noncoplanar antiferromagnet.

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.

Delayed low-dose methotrexate excretion in a rheumatoid arthritis patient: A case report and literature review.

RATIONALE: Low-dose methotrexate has a relatively good safety profile. However, in cases where patients with multiple risk factors, a delayed excretion has been observed, resulting in the occurrence of severe adverse reactions. It is necessary to supervise and intervene throughout the entire process of treating patients with multiple risk factors for methotrexate, and to strengthen the rational application of methotrexate. PATIENT CONCERNS AND DIAGNOSES: A 66-year-old male patient was admitted to our hospital with rheumatoid arthritis and underlying conditions such as chronic obstructive pulmonary disease (COPD). This patient received treatment with low-dose MTX (10 mg/week) and experienced adverse reactions including anemia. He was diagnosed with methotrexate-induced bone marrow suppression. INTERVENTIONS AND OUTCOMES: The therapeutic drug monitoring revealed that the serum drug concentration of methotrexate was at a critical level and the patient was rescue with calcium folinate and other adjuvant therapy such as transfusions of red blood cells, plasma, platelets, oral Yixuesheng tablets and Leucogen tablets. We conducted a 1-month follow-up, and there was no recurrence of bone marrow suppression and anemia. LESSONS: To ensure rational administration of methotrexate, it is important to fully evaluate the clinical manifestations and physical condition of patients and regularly detecting the serum drug concentration of methotrexate when patients with multiple risk factors, Otherwise, even low-dose methotrexate administration may cause delayed excretion, resulting in severe adverse reactions.

Ecological evolution of algae in connected reservoirs under the influence of water transfer: Algal density, community structure, and assembly processes.

Reservoir connectivity provides a solution for regional water shortages. Understanding the water quality of reservoirs and the response of algal communities to water transfer could provide the basis for a long-term evolutionary model of reservoirs. In this study, a water-algal community model was established to study the effects of water transfer on water quality and algal communities in reservoirs. The results showed that water transfer significantly decreased total nitrogen and nitrate concentrations. However, the water transfer resulted in an increase in the CODMn concentration and conductivity in the receiving reservoir. Additionally, the algal density and chlorophyll-a (chl-a) concentration showed an increase with water transfer. Bacillariophyta, Cyanophyta, and Chlorophyta were the dominant algal phyllum in all three reservoirs. Water transfer induced the evolution of the algal community by driving changes in the chemical parameters of the receiving reservoir and led to more complex relationships within the algal community. The effects of stochastic processes on algal communities were also enhanced in the receiving reservoirs. These results provide specific information for water quality safety management and eutrophication prevention in connected reservoirs.

Isorhamnetin Downregulates MMP2 and MMP9 to Inhibit Development of Rheumatoid Arthritis through SRC/ERK/CREB Pathway.

OBJECTIVE: To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). METHODS: Tumor necrosis factor (TNF)- α -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 µ mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table (n=5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg·day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-α, interleukin-6 (IL-6), and IL-1 ß, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. RESULTS: In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion (P<0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 ß in RA-FLS (P<0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-α, IL-6, and IL-1 ß (P<0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB (P<0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 (P<0.05). In in vivo studies, isorhamnetin decreased arthritis index scores (P<0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 ß, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue (P<0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations (P<0.05). CONCLUSION: Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA.

A Real-World Study on Safety and Efficacy of TAF Treatment in HBV Patients with High Risk of Osteoporosis or Osteopenia in China.

Objective: Long-term antiviral treatment is necessary for chronic hepatitis B (CHB) patients, and treatment safety is imperative for these patients. Previous studies showed tenofovir alafenamide (TAF) has shown efficacy non-inferior to that of tenofovir disoproxil fumarate (TDF) with improved renal and bone safety. However, there is still a lack of a rapid and convenient method to identify CHB patients at high risk of osteoporosis before initiating antiviral treatment. The International Osteoporosis Foundation (IOF) recommended a one-minute osteoporosis risk test to identify early high-risk patients. Our aim was to evaluate the feasibility of the one-minute osteoporosis risk test, along with evaluating the effectiveness and safety for virologically suppressed CHB patients switching to TAF. Methods: In this multicenter, prospective study, patients with chronic HBV infection who had been receiving TDF or Entecavir (ETV) for 48 weeks or more with HBV DNA less than 20 IU/mL for longer than 6 months were screened by one-minute osteoporosis risk test. Patients with a high risk of osteoporosis and then diagnosed with osteopenia or osteoporosis by dual-energy X-ray absorptiometry (DEXA) were enrolled. Safety in bone and bone turnover markers and antiviral efficacy of TAF were assessed respectively at 24 and 48 weeks. Results: 84.95% (175/206) CHB patients screened by one-minute osteoporosis risk test were at risk of osteoporosis.85.71% (150/175) were diagnosed with osteopenia by DEXA. The analysis included a total of 138 patients, of whom 92(62.3%) were male and 46 (37.7%) were female, with a mean age of 45 years old. HBV DNA was suppressed at 48 weeks at 88% (35/40) in the prior ETV group and 90% (88/98) at 48 weeks group in the prior TDF group. Bone mineral density (BMD) of the lumbar spine (L1-L4) from TDF switching to TAF was improved at 24 weeks (1.03±0.11 vs. 0.97±0.12, P = .001) than baseline. Propeptides of type I procollagen (PINP) and beta-C-terminal telopeptides of type 1 collagen (CTX) in serum at 24 weeks after switching from TDF to TAF declined compared with baseline (50.35±18.90 vs. 63.65±19.17, P = .016 and 0.21±0.13 vs. 0.32±0.10, P = .017). BMD, PINP, and CTX in ETV to TAF group remained stable during treatment. Conclusion: Attention should be paid to osteoporosis risk during lone-term nucleot(s)ide analogue treatment. One minute test of osteoporosis risk could rapidly identify most CHB patients at risk of osteoporosis. Given its convenience, we recommend using this test for early screening in CHB patients prior to initiating antiviral treatment. Our results further demonstrated that an improvement in bone safety after switching to TAF in virologically suppressed CHB patients with osteoporosis.

Association between lung function and bone mineral density in children and adolescents: Insights from the NHANES.

Bone development and lung function are integral to child and adolescent health. Both influence an individual's overall well-being and potentially affect long-term health. Utilizing a comprehensive dataset from the National Health and Nutrition Examination Survey, this study aims to elucidate the relationship between lung function and bone mineral density (BMD) in a representative sample of children and adolescents. The analysis covered 3410 participants aged 8 to 19 years. We employed weighted multivariate linear regression and restricted cubic spline curve visualizations to explore the intricate association between lung function metrics, particularly first-second expiratory volume 1 second/forced vital capacity ratio, and lumbar BMD. Our data indicated a positive association between lung function and lumbar BMD in children and adolescents. Specifically, higher lung function metrics were linked with increased lumbar BMD. This association was more pronounced in younger participants or those with a lower body mass index. A significant positive relationship exists between lung function and BMD in the pediatric population. Recognizing this association is crucial for holistic health strategies for children and adolescents. This study underscores the need for integrated health monitoring during formative years, which can influence health trajectories as these individuals transition to adulthood.

[Research progress on Rhododendron molle in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.

Elucidating the Mechanism of Buyanghuanwu Decoction Acting on Pulmonary Fibrosis based on Network Pharmacology and Animal Studies.

BACKGROUND AND OBJECTIVE: Buyanghuanwu Decoction (BYHWD) is a clinically proven prescription effective in treating pulmonary fibrosis (PF), but the molecular mechanism underlying its action remains unclear. The network pharmacology analysis was performed to elucidate the acting substances and related pathways of BYHWD in treating bleomycin (BLM) induced PF mouse. METHODS: First, the pharmacologically active components and corresponding targets in BYHWD were identified through the TCMSP database and literature review. Second, PF¬-related targets were identified through the DisGeNet database. Then, the components-targets network of BYHWD in PF treatment was constructed using Cytoscape. The DAVID database was used for the enrichment analysis of GO terms and KEGG pathways. At last, the therapeutic effect of BYHWD on BLM-induced PF mice were verified, and the mRNA and protein expression of related targets was determined through RT-PCR and western blotting, respectively. RESULTS: The core component-target network contained 58 active components and 147 targets. Thirty-nine core targets were mainly involved in the regulation of biological functions and KEGG pathways, such as the positive regulation of nitric oxide biosynthesis and the TNF signaling pathway. These core targets were obtained through enrichment analysis. Moreover, animal studies revealed that BYHWD down-regulated the mRNA expression levels of TNF, IL-6, IL-1ß, and NOS2 and inhibited NF-κB and p38 phosphorylation. CONCLUSION: The effects of BYHWD on PF mice are therapeutic, and its anti-PF mechanism mainly involves the effects on inflammatory factors and the NF-κB/p38 pathway.

Maize Genotypes Sensitive and Tolerant to Low Phosphorus Levels Exhibit Different Transcriptome Profiles under Talaromyces purpurogenus Symbiosis and Low-Phosphorous Stress.

Talaromyces purpurogenus, an endophytic fungus, exhibits beneficial effects on plants during plant-fungus interactions. However, the molecular mechanisms underlying plants' responses to T. purpurogenus under low-phosphorous (P) stress are not fully understood. In this study, we investigated the transcriptomic changes in maize with low-P-sensitive (31778) and -tolerant (CCM454) genotypes under low-P stress and its symbiotic interaction with T. purpurogenus. Its colonization enhanced plant growth and facilitated P uptake, particularly in 31778. Transcriptome sequencing revealed that 135 DEGs from CCM454 and 389 from 31778 were identified, and that only 6 DEGs were common. This suggested that CCM454 and 31778 exhibited distinct molecular responses to T. purpurogenus inoculation. GO and KEGG analysis revealed that DEGs in 31778 were associated with nicotianamine biosynthesis, organic acid metabolic process, inorganic anion transport, biosynthesis of various secondary metabolites and nitrogen metabolism. In CCM454, DEGs were associated with anthocyanin biosynthesis, diterpenoid biosynthesis and metabolic process. After T. purpurogenus inoculation, the genes associated with phosphate transporter, phosphatase, peroxidase and high-affinity nitrate transporter were upregulated in 31778, whereas AP2-EREBP-transcription factors were detected at significantly higher levels in CCM454. This study provided insights on the molecular mechanisms underlying plant-endophytic fungus symbiosis and low-P stress in maize with low-P-sensitive and -tolerant genotypes.

[Spatial Distribution of Nitrogen and Phosphorus Nutrients in the Main Stream and Typical Tributaries of Tuojiang River and Fujiang River].

The Tuojiang River and Fujiang River, two important tributaries of the upper reaches of the Yangtze River, have serious water pollution problems, among which nitrogen (N) and phosphorus (P) are the most important pollutants. Therefore, the aim of this study was to identify the influencing factors of water quality in different spaces and provide a scientific basis for the prevention and control of surface water pollution in the upper reaches of the Yangtze River and its tributaries. Water samples of trunk and tributaries in the Tuojiang River and Fujiang River were collected, and the spatial distribution characteristics of water N and P were analyzed. The results showed that the Tuojiang River and Fujiang River showed serious pollution of total nitrogen (TN), with a water quality worse Ⅴ-section proportion as high as 94% and 50%, respectively. Both rivers showed that TN and TP concentrations in the tributaries were higher than those in the main stream. For both rivers, total phosphorus (TP), with moderate pollution, was mainly concentrated in Ⅱ, Ⅲ, and Ⅳ class water quality, whereas the P pollution was more serious for the Fujiang River compared to that of the Fujiang River. For the Tuojiang River, nitrate nitrogen (NN) concentration from upstream to downstream showed a trend of decreasing after the first increase, with the maximum concentration of ammonium nitrogen (AN) exhibiting at the upstream site. In particular, TP concentration increased significantly after rivers flowed through a city. For the Fujiang River trunk stream, TN and NN concentration exhibited a gradually increasing trend from the middle to lower reaches. Generally, our study revealed that TN, TP, and NN in the rivers were affected by water pH and water temperature (T). Therefore, the control of N and P pollution in rivers should pay attention to the influence of water environmental factors.

Temporal patterns of algae in different urban lakes and their correlations with environmental variables in Xi'an, China.

Urban lakes were critical in aquatic ecology environments, but how environmental factors affected the distribution and change characteristics of algal communities in urban lakes of Xi'an city was not clearly. Here, we investigated the algal community structure of six urban lakes in Xi'an and evaluated the effects of water quality parameters on algae. The results indicated that the significant differences on physicochemical parameters existed in different urban lakes. The maximum concentration of total phosphorus in urban lakes was (0.18 ± 0.01) mg/L and there was a phenomenon of phosphorus limitation. In addition, 51 genera of algae were identified and Chlorella sp. was the dominant algal species, which was affiliated with Chlorophyta. Network analysis elucidated that each lake had a unique algal community network and the positive correlation was dominant in the interaction between algae species, illustrating that mature microbial communities existed or occupied similar niches. Redundancy analysis illustrated that environmental factors explained 47.35% variance of algal species-water quality correlation collectively, indicating that water quality conditions had a significant influence on the temporal variations of algae. Structural equation model further verified that algal community structure was directly or indirectly regulated by different water quality conditions. Our study shows that temporal patterns of algal communities can reveal the dynamics and interactions of different urban ecosystem types, providing a theoretical basis for assessing eutrophication levels and for water quality management.

The signaling pathways of traditional Chinese medicine in treating diabetic retinopathy.

Diabetic retinopathy (DR) is one of the common diabetic microvascular complications that occurs in the eyes and is closely associated with vision loss in working adults. However, the clinical treatment of DR is limited or accompanied by a large number of complications. Therefore, the development of new drugs for the treatment of DR is urgently needed. Traditional Chinese medicine (TCM) is widely used to treat DR in China, and its multi-pathway and multi-level characteristics can effectively address the complex pathogenesis of DR. Growing evidence suggests that inflammation, angiogenesis, and oxidative stress are the core pathological mechanisms in the development of DR. This study innovatively considers the aforementioned processes as the fundamental unit and sheds light on the molecular mechanisms and potential of TCM against DR in terms of signaling pathways. The results showed that NF-κB, MAPK/NF-κB, TLR4/NF-κB, VEGF/VEGFR2, HIF-1α/VEGF, STAT3, and Nrf2/HO-1 are the key signaling pathways for the treatment of DR by TCMs, which involved curcumolide, erianin, quercetin, blueberry anthocyanins, puerarin, arjunolic acid, ethanol extract of Scutellaria barbata D. Don, Celosia argentea L. extract, ethanol extract of Dendrobium chrysotoxum Lindl., Shengpuhuang-tang, and LuoTong formula. The purpose of this review is to update and summarize the signaling pathways of TCM in the treatment of DR and provide ideas for the development of new drugs against DR in the future.

Explore the mechanism of ursolic acid acting on atherosclerosis through network pharmacological and bioinformatics methods.

To explore the deep mechanisms of ursolic acid (UA) for treating atherosclerosis based on network pharmacology and bioinformatics. UA target genes were derived from traditional Chinese medicine system pharmacology, BATMAN-TCM, and SwissTargetPrediction databases. Atherosclerosis-related genes were derived from genecards, NCBI genes, and OMIM databases. The protein interaction network was constructed through the STRING database, and the hub network was extracted by using the Cytoscape software MCODE app. The enrichment analysis of gene ontology and Kyoto encyclopedia of genes and genomes was performed by the R software clusterProfiler package, and the expression and prognostic value of the hub genes were verified on the data set. Screen the genes for expression and prognosis conclusions, conduct methylation analysis, and ceRNA construction. UA had 145 targets in the treatment of atherosclerosis. The top 7 gene ontology (biological process, molecular function, and cellular component) and pathways related to atherosclerosis were screened out. It is principally involved in biological processes, including response to lipopolysaccharide and regulation of inflammatory response. The main signaling pathways incorporated the TNF signaling pathway and the AGE-RAGE signaling pathway. Androgen receptor (AR) and interleukin-1 beta gene (IL1B) were further screened as core target genes. Methylation analysis demonstrated that the AR methylation level was elevated in the atherosclerotic group. On the contrary, the IL1B methylation level was lower in the atherosclerotic group. The results of the ceRNA analysis indicated that there were 43 targeted miRNAs in AR and 3 miRNAs in IL1B. We speculate that the target genes of UA regulating atherosclerosis are AR and IL1B. The mechanism may be that UA regulates the expression of target genes by regulating the methylation of target genes.

[Mining and identification of members of MYB transcription factor family in Lonicera macranthoides].

As a large family of transcription factors, the MYB family plays a vital role in regulating flower development. We studied the MYB family members in Lonicera macranthoides for the first time and identified three sequences of 1R-MYB, 47 sequences of R2R3-MYB, two sequences of 3R-MYB, and one sequence of 4R-MYB from the transcriptome data. Further, their physicochemical properties, conserved domains, phylogenetic relationship, protein structure, functional information, and expression were analyzed. The results show that the 53 MYB transcription factors had different conserved motifs, physicochemical properties, structures, and functions in wild type and 'Xianglei' cultivar of L. macranthoides, indicating their conservation and diversity in evolution. The transcript level of LmMYB was significantly different between the wild type and 'Xianglei' cultivar as well as between flowers and leaves, and some genes were specifically expressed. Forty-three out of 53 LmMYB sequences were expressed in both flowers and leaves, and 9 of the LmMYB members showed significantly different transcript levels between the wild type and 'Xianglei' cultivar, which were up-regulated in the wild type. The results provide a theoretical basis for further studying the specific functional mechanism of the MYB family.

[Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease].

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

Dingkun Pill modulate ovarian function in chemotherapy-induced premature ovarian insufficiency mice by regulating PTEN/PI3K/AKT/FOXO3a signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingkun Pill (DKP) is a traditional Chinese medicine that has been shown to have beneficial effects on reproductive function. However, the specific mechanism underlying its effect on POI is not well understood. AIM OF THE STUDY: To investigate the effect of different doses of Dingkun Pill on ovarian function in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) mice and to explore its molecular mechanism through PTEN/PI3K/AKT/FOXO3a signaling pathway. This study will provide valuable insights into the potential clinical application of Dingkun Pill for the treatment of POI. MATERIALS AND METHODS: Fifty female ICR mice were randomly divided into normal control (NC) group, model control (MC) group, and Dingkun Pill low, medium, high dose (DKP-L, M, H) groups. Mice were injected with CTX to construct the POI model. Mice in the DKP-L, M, and H groups were given 0.9 g/kg, 1.8 g/kg, and 3.6 g/kg of Dingkun Pill suspension for 21 days, respectively. Mice in the NC and MC groups were given the same amount of normal saline by gavage. Changes in body weight, estrous cycle and gonadal index were observed in each group of mice. Serum levels of FSH, LH, E2 and AMH were detected by ELISA. Hematoxylin-eosin (HE) staining observed the changes of ovarian pathological morphology and follicle counts at all levels. qRT-PCR was used to measure the levels of the PTEN and FOXO3a genes in ovarian tissue. The expression of PTEN/PI3K/AKT/FOXO3a signaling pathway related proteins were detected by Western-blot and immunohistochemistry (IHC). RESULTS: In POI mice, Dingkun Pill increased body weight, promoted the recovery of estrous cycle, increased ovarian index, and improved pathological morphology of the ovaries. The FSH level decreased in the medium dose group (P < 0.05), the LH level reduced significantly in the medium and high dose groups (P < 0.01), and the E2 level in the high dose group increased (P < 0.05). There was no significant difference in AMH levels across all dose groups. The number of growing follicles improved at all levels in the low and medium dose groups, but declined significantly in the high dose group. However, the number of corpus luteum increased significantly in the high dose group (P < 0.001), and the atretic follicles in the three dose groups decreased. Results from qRT-PCR, Western-blot and IHC showed that the moderate dose of Dingkun Pill suppressed the levels of the p-PI3K and p-AKT proteins by upregulating the expression of PTEN in the ovarian tissues of POI mice, thereby inhibiting the expression of the key protein p-FOXO3a. However, the inhibitory effect of the higher dose may be less than that of the lower and intermediate dose groups. CONCLUSIONS: The Dingkun Pill modulated hormonal levels, promoted follicle growth and induced ovulation in mice with CTX-induced POI, with better results in the low and moderate dose groups. Its mechanism may be related to the regulation of the PTEN/PI3K/AKT/FOXO3a signaling pathway.

Effect of Jiawei Tongqiao Huoxue decoction in basilar artery dolichoectasia mice through yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides 'Chuanxiong', Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's "Yilin Gaicuo" in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. AIM OF THE STUDY: This study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. MATERIALS AND METHODS: Sixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. RESULTS: Many effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). CONCLUSIONS: The mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.

Single-site laparoscopic ligation of the hernia sac in infants with congenital Morgagni hernia.

Background: Congenital Morgagni hernia (CMH) is a rare midline defect involving herniation of abdominal viscera into the thoracic cavity through triangular parasternal gaps in the diaphragm. Methods: The medical records of three patients with CMH admitted to the Department of Pediatric Surgery at the Affiliated Hospital of Zunyi Medical University between 2018 and 2022 were retrospectively reviewed. Pre-operative diagnosis was based on chest x-ray, chest computerized tomography, and barium enema. All patients were treated with single-site laparoscopic ligation of the hernia sac. Results: Hernia repair was successful in all patients (males; age: 14 months, 30 months, 48 months). The average operative time for repair of a unilateral hernia was 20 ± 5 min. Volume of surgical blood loss was 2-3 ml. There was no damage to organs such as the liver or intestines, or to tissues such as the pericardium or the phrenic nerve. Patients were allowed a fluid diet 6-8 h after surgery, and remained on bed rest until 16 h after surgery. No postoperative complications occurred, and patients were discharged on postoperative Day 2 or 3. No symptoms or complications were noted during the 1-48 months of follow-up. Aesthetic outcomes were satisfactory. Conclusions: Single-site laparoscopic ligation of the hernia sac provides pediatric surgeons a safe and effective technique for repair of CMH in infants and children. The procedure is straightforward, operative time and surgical blood loss are minimal, recurrence is unlikely, and aesthetic outcomes are satisfactory.