Blockage of L2HGDH-mediated S-2HG catabolism orchestrates macrophage polarization to elicit antitumor immunity.

The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression. Mechanistically, based on its structural similarity to α-ketoglutarate (α-KG), S-2HG has the potential to block the enzymatic activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), consequently reshaping chromatin accessibility. Moreover, S-2HG-treated macrophages enhance CD8+ T cell-mediated antitumor activity and sensitivity to anti-PD-1 therapy. Overall, our study uncovers the role of blockage of L2HGDH-mediated S-2HG catabolism in orchestrating macrophage antitumoral polarization and, further, provides the potential of repolarizing macrophages by S-2HG to overcome resistance to anti-PD-1 therapy.

Overexpression of an Integument Esterase Gene LbEST-inte4 Infers the Malathion Detoxification in Liposcelis bostrychophila (Psocoptera: Liposcelididae).

Liposcelis bostrychophila, commonly known as booklouse, is an important stored-product pest worldwide. Studies have demonstrated that booklices have developed resistance to several insecticides. In this study, an integument esterase gene, LbEST-inte4, with upregulated expression, was characterized in L. bostrychophila. Knockdown of LbEST-inte4 resulted in a substantial increase in the booklice susceptibility to malathion. Overexpression of LbEST-inte4 in Drosophila melanogaster significantly enhanced its malathion tolerance. Molecular modeling and docking analysis suggested potential interactions between LbEST-inte4 and malathion. When overexpressed LbEST-inte4 in Sf9 cells, a notable elevation in esterase activity and malathion tolerance was observed. HPLC analysis indicated that the LbEST-inte4 enzyme could effectively degrade malathion. Taken together, the upregulated LbEST-inte4 appears to contribute to malathion tolerance in L. bostrychophila by facilitating the depletion of malathion. This study elucidates the molecular mechanism underlying malathion detoxification and provides the foundations for the development of effective prevention and control measures against psocids.

[Identification and functional analysis of jasmonic acid signaling repressor McJAZ8 gene in Mentha canadensis].

Mentha canadensis, as a plant with medicinal and culinary uses, holds significant economic value. Jasmonic acid signaling repressor JAZ protein has a crucial role in regulating plant response to adversity stresses. The M. canadensis McJAZ8 gene is cloned and analyzed for protein characterization, protein interactions, and expression patterns, so as to provide genetic resources for molecular breeding of M. canadensis for stress tolerance. This experiment will analyze the protein structural characteristics, subcellular localization, protein interactions, and gene expression of McJAZ8 using bioinformatics, yeast two-hybrid(Y2H), transient expression in tobacco leaves, qRT-PCR, and other technologies. The results show that:(1)The full length of the McJAZ8 gene is 543 bp, encoding 180 amino acids. The McJAZ8 protein contains conserved TIFY and Jas domains and exhibits high homology with Arabidopsis thaliana AtJAZ1 and AtJAZ2.(2)The McJAZ8 protein is localized in the nucleus and cytoplasm.(3)The Y2H results show that McJAZ8 interacts with itself or McJAZ1/3/4/5 proteins to form homologous or heterologous dimers.(4)McJAZ8 is expressed in different tissue, with the highest expression level in young leaves. In terms of leaf sequence, McJAZ8 shows the highest expression level in the fourth leaf and the lowest expression level in the second leaf.(5) In leaves and roots, the expression of McJAZ8 is upregulated to varying degrees under methyl jasmonate(MeJA), drought, and NaCl treatments. The expression of McJAZ8 shows an initial upregulation followed by a downregulation pattern under CdCl_2 treatment. In leaves, the expression of McJAZ8 tends to gradually decrease under CuCl_2 treatment, while in roots, it initially decreases and then increases before decreasing again. In both leaves and roots, the expression of McJAZ8 is downregulated to varying degrees under AlCl_(3 )treatment. This study has enriched the research on jasmonic acid signaling repressor JAZ genes in M. canadensis and provided genetic resources for the molecular breeding of M. canadensis.

Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway.

The current study aimed to assess the effectiveness of pharmacological intervention with Platycodin D (PD), a critically active compound isolated from the roots of Platycodon grandiflorum, in mitigating cardiotoxicity in a murine model of type 2 diabetes-induced cardiac injury and in H9c2 cells in vitro. Following oral administration for 4 weeks, PD (2.5 mg/kg) significantly suppressed the elevation of fasting blood glucose (FBG) levels, improved dyslipidemia, and effectively inhibited the rise of the cardiac injury markers creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT). PD treatment could ameliorate energy metabolism disorders induced by impaired glucose uptake by activating AMPK protein expression in the DCM mouse model, thereby promoting the GLUT4 transporter and further activating autophagy-related proteins. Furthermore, in vitro experiments demonstrated that PD exerted a concentration-dependent increase in cell viability while also inhibiting palmitic acid and glucose (HG-PA)-stimulated H9c2 cytotoxicity and activating AMPK protein expression. Notably, the AMPK activator AICAR (1 mM) was observed to upregulate the expression of AMPK in H9c2 cells after high-glucose and -fat exposure. Meanwhile, we used AMPK inhibitor Compound C (20 µM) to investigate the effect of PD activation of AMPK on cells. In addition, the molecular docking approach was employed to dock PD with AMPK, revealing a binding energy of -8.2 kcal/mol and indicating a tight interaction between the components and the target. PD could reduce the expression of autophagy-related protein p62, reduce the accumulation of autophagy products, promote the flow of autophagy, and improve myocardial cell injury. In conclusion, it has been demonstrated that PD effectively inhibits cardiac injury-induced type 2 diabetes in mice and enhances energy metabolism in HG-PA-stimulated H9c2 cells by activating the AMPK signaling pathway. These findings collectively unveil the potential cardioprotective effects of PD via modulation of the AMPK signaling pathway.

Platycodin D Ameliorates Cognitive Impairment in Type 2 Diabetes Mellitus Mice via Regulating PI3K/Akt/GSK3ß Signaling Pathway.

Objectives: The aim of this study was to investigate the ameliorative effect of platycodin D (PD) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) and its potential molecular mechanisms of action in vivo and in vitro. Materials and methods: An animal model of cognitive impairment in T2DM was established using a single intraperitoneal injection of streptozotocin (100 mg/kg) after 8 weeks of feeding a high-fat diet to C57BL/6 mice. In vitro, immunofluorescence staining and Western blot were employed to analyze the effects of PD on glucose-induced neurotoxicity in mouse hippocampal neuronal cells (HT22). Results: PD (2.5 mg/kg) treatment for 4 weeks significantly suppressed the rise in fasting blood glucose in T2DM mice, improved insulin secretion deficiency, and reversed abnormalities in serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein levels. Meanwhile, PD ameliorated choline dysfunction in T2DM mice and inhibited the production of oxidative stress and apoptosis-related proteins of the caspase family. Notably, PD dose-dependently prevents the loss of mitochondrial membrane potential, promotes phosphorylation of phosphatidylinositol 3 kinase and protein kinase B (Akt) in vitro, activates glycogen synthase kinase 3ß (GSK3ß) expression at the Ser9 site, and inhibits Tau protein hyperphosphorylation. Conclusions: These findings clearly indicated that PD could alleviate the neurological damage caused by T2DM, and the phosphorylation of Akt at Ser473 may be the key to its effect.

Artificial intelligence in the risk prediction models of cardiovascular disease and development of an independent validation screening tool: a systematic review.

BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.

Effects of environmental microplastic exposure on Chlorella sp. biofilm characteristics and its interaction with nitric oxide signaling.

Microalgal biofilm is promising in simultaneous pollutants removal, CO2 fixation, and biomass resource transformation when wastewater is used as culturing medium. Nitric oxide (NO) often accumulates in microalgal cells under wastewater treatment relevant abiotic stresses such as nitrogen deficiency, heavy metals, and antibiotics. However, the influence of emerging contaminants such as microplastics (MPs) on microalgal intracellular NO is still unknown. Moreover, the investigated MPs concentrations among existing studies were mostly several magnitudes higher than in real wastewaters, which could offer limited guidance for the effects of MPs on microalgae at environment-relevant concentrations. Therefore, this study investigated three commonly observed MPs in wastewater at environment-relevant concentrations (10-10,000 µg/L) and explored their impacts on attached Chlorella sp. growth characteristics, nutrients removal, and anti-oxidative responses (including intracellular NO content). The nitrogen source NO3--N at 49 mg/L being 20 % of the nitrogen strength in classic BG-11 medium was selected for MPs exposure experiments because of least intracellular NO accumulation, so that disturbance of intracellular NO by nitrogen availability could be avoided. Under such condition, 10 µg/L polyethylene (PE) MPs displayed most significant microalgal growth inhibition comparing with polyvinyl chloride (PVC) and polyamide (PA) MPs, showing extraordinarily low chlorophyll a/b ratios, and highest superoxide dismutase (SOD) activity and intracellular NO content after 12 days of MPs exposure. PVC MPs exposed cultures displayed highest malonaldehyde (MDA) content because of the toxic characteristics of organochlorines, and most significant correlations of intracellular NO content with conventional anti-oxidative parameters of SOD, CAT (catalase), and MDA. MPs accelerated phosphorus removal, and the type rather than concentration of MPs displayed higher influences, following the trend of PE > PA > PVC. This study expanded the knowledge of microalgal biofilm under environment-relevant concentrations of MPs, and innovatively discovered the significance of intracellular NO as a more sensitive indicator than conventional anti-oxidative parameters under MPs exposure.

Dual analysis of wild-type and attenuated Orf virus and host cell transcriptomes revealed novel virus-host cell interactions.

IMPORTANCE: Currently, the only available commercial vaccines for Orf virus (ORFV) are live attenuated vaccines, which present a potential risk of reversion to virulence. Therefore, understanding the pathogenic mechanisms of different virulent strains of ORFV and host immune responses triggered by these viruses is crucial for developing new vaccines and interventions. In this study, we found that the attenuated strain downregulates the host innate immune response and antiviral activity. In addition, we noted that the wild-type strain can induce the immune response pattern centered on interferon-stimulated genes and interferon regulatory factor gene family. We predicted that STAT1 and STAT2 are the main transcription factors upstream of target gene promoters through gene regulatory networks and exert significant regulatory effects on co-expressed genes. Our study elucidated the complex interaction between ORFV strains and host cell immune responses, providing new insights into vaccine research for ORFV.

Bacterial and Fungal Biocontrol Agents for Plant Disease Protection: Journey from Lab to Field, Current Status, Challenges, and Global Perspectives.

Plants are constantly exposed to various phytopathogens such as fungi, Oomycetes, nematodes, bacteria, and viruses. These pathogens can significantly reduce the productivity of important crops worldwide, with annual crop yield losses ranging from 20% to 40% caused by various pathogenic diseases. While the use of chemical pesticides has been effective at controlling multiple diseases in major crops, excessive use of synthetic chemicals has detrimental effects on the environment and human health, which discourages pesticide application in the agriculture sector. As a result, researchers worldwide have shifted their focus towards alternative eco-friendly strategies to prevent plant diseases. Biocontrol of phytopathogens is a less toxic and safer method that reduces the severity of various crop diseases. A variety of biological control agents (BCAs) are available for use, but further research is needed to identify potential microbes and their natural products with a broad-spectrum antagonistic activity to control crop diseases. This review aims to highlight the importance of biocontrol strategies for managing crop diseases. Furthermore, the role of beneficial microbes in controlling plant diseases and the current status of their biocontrol mechanisms will be summarized. The review will also cover the challenges and the need for the future development of biocontrol methods to ensure efficient crop disease management for sustainable agriculture.

Genetic Analysis of Orf Virus (ORFV) Strains Isolated from Goats in China: Insights into Epidemiological Characteristics and Evolutionary Patterns.

Contagious ecthyma (CE) is an acute infectious zoonosis caused by orf virus (ORFV) that mainly infects sheep and goats and causes obvious lesions and low market value of livestock, resulting in huge economic losses for farmers. In this study, two strains of ORFV were isolated from Shaanxi Province and Yunnan Province in China, named FX and LX. The two ORFVs were located in the major clades of domestic strains respectively, and exhibited distinct sequence homology. We analyzed the genetic data of core genes (B2L, F1L, VIR, ORF109) and variable genes (GIF, ORF125 and vIL-10) of ORFV to investigate its epidemiological and evolutionary characteristics. The sequences from 2007 to 2018 constituted the majority of the viral population, predominantly concentrated in India and China. Most genes were clustered into SA00-like type and IA82-like type, and the hotspots in East and South Asia were identified in the ORFV transmission trajectories. For these genes, VIR had the highest substitution rate of 4.85 × 10-4, both VIR and vIL-10 suffered the positive selection pressure during ORFV evolution. Many motifs associated with viral survival were distributed among ORFVs. In addition, some possible viral epitopes have been predicted, which still require validation in vivo and in vitro. This work gives more insight into the prevalence and phylogenetic relationships of existing orf viruses and facilitate better vaccine design.

Lobetyolin, a Q-marker isolated from Radix Platycodi, exerts protective effects on cisplatin-induced cytotoxicity in HEK293 cells.

This study investigated the protective effect of lobetyolin (LBT), a Q-marker isolated from the roots of Platycodon grandiflorum (Radix Platycodi), against cisplatin-induced cytotoxicity in human embryonic kidney (HEK293) cells. Results showed that LBT at 20 µM significantly prevented cisplatin-induced cytotoxicity by improving the viability of HEK293 cells, decreasing levels of MDA, and decreasing GSH content triggered by cisplatin. It also suppressed reactive oxygen species (ROS) levels. Molecular docking analysis revealed a strong binding affinity between LBT and the NF-κB protein, with a docking fraction of - 6.5 kcal/mol. These results provide compelling evidence suggesting a potential link between the visualization analysis of LBT and its protective mechanism, specifically implicating the NF-κB signaling pathway. LBT also reduced the expression level of tumor necrosis factor-alpha (TNF-α), phosphorylation NF-κB and IκBα in HEK293 cells which were increased by cisplatin exposure, leading to inhibition of inflammation. Furthermore, western blotting showed that LBT antagonized the up-regulation of Bax, cleaved caspase 3, 8, and 9 expression and inhibited the MAPK signaling pathway by down-regulating phosphorylation JNK, ERK, and p38, partially ameliorating cisplatin-induced cytotoxicity in HEK293 cells. Therefore, these results indicate that LBT has potentially protected renal function by inhibiting inflammation and apoptosis.

Platycodin D inhibits HFD/STZ-induced diabetic nephropathy via inflammatory and apoptotic signaling pathways in C57BL/6 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Platycodon grandiflorum (Jacq.) A.DC. (PG) is a traditional herb used in Asian countries and is widely used in formulas for the treatment of diabetes. Platycodin D (PD) is one of the most important components of PG. AIM OF THE STUDY: This study aimed to investigate the improvement effects and regulatory mechanisms of PD on kidney injury in a high-fat diet (HFD) combined with streptozotocin (STZ)-induced diabetic nephropathy (DN). MATERIALS AND METHODS: Model mice were treated with oral gavage of the PD (2.5, 5 mg/kg) for 8 weeks. Determination of serum lipid and renal function-related indexes creatinine (CRE), and blood urea nitrogen (BUN) levels in mice, and histopathological section analysis of kidney. Molecular docking and molecular dynamics were utilized to study the binding ability of PD to target NF-κB and apoptosis signaling pathway-related proteins. Moreover, Western blot was used to test the expressions of NF-κB and apoptosis-related proteins. Vitro experiments were performed to validate the related mechanisms using RAW264.7 cells and HK2 cells cultured by high glucose. RESULTS: In vivo experiments, the administration of PD (2.5 and 5.0 mg/kg) reduced fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR) levels in DN mice, while lipid levels and renal function were significantly improved. Furthermore, PD significantly inhibited the development of DN in the model mice by regulating NF-κB and apoptotic signaling pathways, reduced the abnormal elevation of serum inflammatory factors TNF-α and IL-1ß, and repaired renal cell apoptosis. In vitro experiments, NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (PDTC) was used to confirm that PD can alleviate high glucose-induced inflammation in RAW264.7 cells and inhibit the release of inflammatory factors. And in HK2 cell experiments, it was verified that PD can inhibit ROS generation, reduce the loss of JC-1 and suppress HK2 cell injury by regulating NF-κB and apoptotic pathways. CONCLUSIONS: These data suggested that PD has the potential to prevent and treat DN and is a promising natural nephroprotective agent.

A LaCl3-based lithium superionic conductor compatible with lithium metal.

Inorganic superionic conductors possess high ionic conductivity and excellent thermal stability but their poor interfacial compatibility with lithium metal electrodes precludes application in all-solid-state lithium metal batteries1,2. Here we report a LaCl3-based lithium superionic conductor possessing excellent interfacial compatibility with lithium metal electrodes. In contrast to a Li3MCl6 (M = Y, In, Sc and Ho) electrolyte lattice3-6, the UCl3-type LaCl3 lattice has large, one-dimensional channels for rapid Li+ conduction, interconnected by La vacancies via Ta doping and resulting in a three-dimensional Li+ migration network. The optimized Li0.388Ta0.238La0.475Cl3 electrolyte exhibits Li+ conductivity of 3.02 mS cm-1 at 30 °C and a low activation energy of 0.197 eV. It also generates a gradient interfacial passivation layer to stabilize the Li metal electrode for long-term cycling of a Li-Li symmetric cell (1 mAh cm-2) for more than 5,000 h. When directly coupled with an uncoated LiNi0.5Co0.2Mn0.3O2 cathode and bare Li metal anode, the Li0.388Ta0.238La0.475Cl3 electrolyte enables a solid battery to run for more than 100 cycles with a cutoff voltage of 4.35 V and areal capacity of more than 1 mAh cm-2. We also demonstrate rapid Li+ conduction in lanthanide metal chlorides (LnCl3; Ln = La, Ce, Nd, Sm and Gd), suggesting that the LnCl3 solid electrolyte system could provide further developments in conductivity and utility.

Platycodin D stimulates AMPK activity to inhibit the neurodegeneration caused by reactive oxygen species-induced inflammation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) was considered to be a neurodegenerative disease that caused cognitive impairment. Reactive Oxidative stress (ROS) was considered to be one of a major cause of the onset and progression of AD. Platycodin D (PD), a representative saponin from Platycodon grandiflorum, has conspicuous antioxidant activity. However, whether PD could protect nerve cell against oxidative injury remains unknown. AIM OF STUDY: This study investigated the regulatory effects of PD on neurodegeneration caused by ROS. To determine whether PD could play its own antioxidant role in neuronal protection. MATERIALS AND METHODS: First, PD(2.5, 5 mg/kg) ameliorated the memory impairment induced by AlCl3 (100 mg/kg) combined with D-galactose (D-Gal) (200 mg/kg) in mice, using the radial arm maze (RAM) test, and neuronal apoptosis in the hippocampus was evaluated by hematoxylin and eosin staining (HE). Next, the effects of PD (0.5, 1, and 2 µM) on okadaic-acid (OA) (40 nM) -induced apoptosis and inflammation of HT22 cells were investigated. Mitochondrial ROS production was measured by fluorescence staining. The potential signaling pathways were identified through Gene Ontology enrichment analysis. The role of PD in regulating AMP-activated protein kinase (AMPK) was assessed using siRNA silencing of genes and an ROS inhibitor. RESULTS: In vivo, PD improved memory in mice, and recovered the morphological changes of brain tissue and nissl bodies. In vitro experiment, PD increased cell viability (p < 0.01; p < 0.05;p < 0.001), decreased apoptosis (p < 0.01), reduced excessive ROS and MDA, rised SOD and CAT content(p < 0.01; p < 0.05). Morover, it can block the inflammatory response caused by ROS. Be important, PD strengthen antioxidant ability by elevating AMPK activation both in vivo and in vitro. Furthermore, molecular docking suggested a good likelihood of PD-AMPK binding. CONCLUSION: AMPK activity is vital for the neuroprotective effect of PD, suggesting that PD may be a potential pharmaceutical agent to treat ROS-induced neurodegeneration.

The Assessment of Acute Chorioretinal Changes Due to Intensive Physical Exercise in Senior Elite Athletes.

Regular physical exercise is known to lower the incidence of age-related eye diseases. We aimed to assess the acute chorioretinal alterations in older adults following intense physical strain. Seventeen senior elite athletes were recruited who underwent an aerobic exercise on a cycle ergometer and macular scanning by optical coherence tomography. A significant thinning of the entire retina was observed 1 min after exercise, followed by a thickening at 5 min, after which the thickness returned to baseline. This trend was similar in almost every single retinal layer, although a significant change was observed only in the inner retina. Choroidal thickness changes were neither significant nor did they correlate with the thickness changes of intraretinal layers. The mechanism of how these immediate retinal changes chronically impact age-related sight-threatening pathologies that, in turn, result in a substantially reduced quality of life warrants further investigation on nontrained older adults as well.

Spinal Fusion Versus Repeat Discectomy for Recurrent Lumbar Disc Herniation: A Systematic Review and Meta-Analysis.

OBJECTIVE: Recurrent lumbar disc herniation (RLDH) is one of the major causes of failure for primary surgery. Repeat discectomy (RD) and spinal fusion (SF) are 2 surgical options for RLDH. The objective of our study is to compare the effectiveness of SF compared with RD in the treatment of RLDH. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Ovid Medline for studies (published between Jan 1, 1959 and July 8, 2022; no language restriction) comparing SF and RD for the RLDH. Odds ratio and weighted mean difference were calculated for binary outcomes and continuous outcomes. The quality of each outcome was graded using the Grading of Recommendations, Assessment, Development and Evaluations criteria. RESULTS: We identified 5029 studies, of which 11 studies were included. There were 2 randomized controlled trials and the remaining were observational studies. Comparing SF and RD groups, no differences were found in visual analog scales for leg and back and Oswestry Disability Index. Furthermore, the Japanese Orthopaedic Association scores of SF were significantly higher than the RD group. In terms of complications, the incidence of neurological deficit, segmental instability, and re-recurrence is significantly lower with SF than with the RD group. Lastly, the SF group was associated with longer hospital stays and operation time, and more blood loss. CONCLUSIONS: The pooled evidence suggests that fusion achieves better results than RD for RLDH. The results of this review should be further confirmed by future high-quality randomized controlled trials.

Molecular cloning, sequence, and expression patterns of DNA damage induced transcript 3 (DDIT3) gene in female yaks (Bos grunniens).

Endoplasmic reticulum stress (ERS) plays an important role in regulating the reproductive process of female mammals, mainly involved in follicular atresia and corpus luteum regression. DNA damage induced transcript 3 (DDIT3) is a marker gene of ERS. The objectives of the present study were to clone and analyze the sequence and tissue expression characteristics of DDIT3 gene in female yaks. By reverse transcriptase-polymerase chain reaction (RT-PCR) strategy, we obtained full-length 507-bp DDIT3-cDNA, encoding for 168-aa protein. Yak DDIT3 exhibited highest and least identity with that of bison and horse, respectively. Real-time PCR analyses revealed that the expression level of DDIT3 gene in ovary was higher than that in heart, liver, kidney, spleen, lung, uterus and oviduct (p < 0.05). DDIT3 expression level in ovary and uterus during pregnancy was higher than that in follicular phase, luteal phase and fetus stage. DDIT3 was highly expressed in metaphase II oocytes and granulosa cells than that in germinal vesicle and metaphase I oocytes (p < 0.05), respectively. This is the first molecular characterization and expression patterns of DDIT3 gene in female yaks. These results indicated that the DDIT3 gene possibly plays an important role in regulating ovary function and pregnancy maintenance in yaks.

Review on potential effects of traditional Chinese medicine on glaucoma.

ETHNIC PHARMACOLOGICAL RELEVANCE: Glaucoma is the second most common blindness in the world, which seriously affects the life quality of patients. Traditional Chinese Medicines (TCM), are important plant materials, widely used for ocular disease all over the world. With the help of modern ophthalmic detection technology, TCM has gradually become an important content in the field of ophthalmology, characterized by more targets and lower toxicity. AIM OF THIS REVIEW: This review presents an overview of the pathogenesis of glaucoma in both modern and traditional medicines, and summarizes the therapeutic effect of TCM on glaucoma including their formula, crude drugs and active components, and also the application of acupuncture. METHODS: A collection and collation of relevant scientific articles from different scientific databases was performed regarding TCM and its application on glaucoma. The therapeutic effects of TCM were summarized and analyzed according to the existing experimental and clinical researches, while the GSE26299 database were employed to screen bioinformatics analysis of glaucoma based on the GEO database chip. RESULTS: There were many positive signs showing that TCM could increase the survival rate of retinal ganglion cells, which may be related to its regulation of microcirculation, oxidative stress, and the immune system. Hence, TCM plays an active role in treating glaucoma. In addition, the bioinformatics analysis predicted that the pathogenesis of glaucoma might be related to p53, MAPK, NF-κB signal, as well as other pathways by KEGG analysis, and the results from bioinformatics analysis predicted that PIK3R6, FGF1, and TYRP1 etc. CONCLUSION: TCM exerts definite effects on preventing and treating ocular disease. It could alleviate and treat glaucoma in various ways. The differentiation syndrome should thus be taken as the basis to propose appropriate treatment options of TCM making their application on glaucoma more popular.

Steroid hormone 20-hydroxyecdysone disturbs fat body lipid metabolism and negatively regulates gluconeogenesis in Hyphantria cunea larvae.

The steroid hormone 20-hydroxyecdysone (20E) has been described to regulate fat body lipid metabolism in insects, but its accurate regulatory mechanism, especially the crosstalk between 20E-induced lipid metabolism and gluconeogenesis remains largely unclear. Here, we specially investigated the effect of 20E on lipid metabolism and gluconeogenesis in the fat body of Hyphantria cunea larvae, a notorious pest in forestry. Lipidomics analysis showed that a total of 1 907 lipid species were identified in the fat body of H. cunea larvae assigned to 6 groups and 48 lipid classes. The differentially abundant lipids analysis showed a significant difference between 20E-treated and control samples, indicating that 20E caused a remarkable alteration of lipidomics profiles in the fat body of H. cunea larvae. Further studies demonstrated that 20E accelerated fatty acid ß-oxidation, inhibited lipid synthesis, and promoted lipolysis. Meanwhile, the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase were dramatically suppressed by 20E in the fat body of H. cunea larvae. As well, the transcriptions of genes encoding these 4 rate-limiting gluconeogenic enzymes were significantly downregulated in the fat body of H. cunea larvae after treatment with 20E. Taken together, our results revealed that 20E disturbed fat body lipid homeostasis, accelerated fatty acid ß-oxidation and promoted lipolysis, but negatively regulated gluconeogenesis in H. cunea larvae. The findings might provide a new insight into hormonal regulation of glucose and lipid metabolism in insect fat body.