[Research progress on effect evaluation and application status of acupoint drug delivery].

Acupoint drug delivery is a traditional external therapy of traditional Chinese medicine(TCM). Guided by the meridian and collateral theory in TCM, it applies medications to the skin at acupoints, exerting a dual therapeutic effect by stimulating the acupoints and the conduction of meridians. Acupoint drug delivery is widely used in clinical practice. Different from traditional oral admi-nistration and injection, it absorbs medications through the skin, effectively avoiding the first-pass effect of drugs and the toxic side effects caused by injection. Acupoint selection and transdermal drug absorption are pivotal factors affecting the efficacy of acupoint drug delivery. Recent research on acupoint drug delivery mainly focuses on the evaluation of clinical efficacy, yet the systematic investigations on acupoint selection and pharmacodynamic factors are scarce. This study reviews the mechanism, efficacy evaluation and application status of acupoint drug delivery. It integrates the theory of TCM with modern medicine to explore the mechanism of acupoint drug delivery, evaluate its clinical efficacy, and assess the transdermal penetration in vivo and in vitro. The application status of acupoint drug delivery is also summarized, including the selection of acupoints, application dosage form, application time and the absorption of acupoints. This review aims to offer insights and references for the research, development and clinical application of acupoint drug delivery products.

Potential role for microRNA in facilitating physiological adaptation to hypoxia in the Pacific whiteleg shrimp Litopenaeus vannamei.

Hypoxia is one of the most common physiological stressors in shrimp farming. Post-transcriptional regulation by microRNAs has been recognized as a ubiquitous strategy to enable transient phenotypic plasticity and adaptation to stressful environment, but involvement of microRNAs in hypoxia stress response of penaeid shrimp remains elusive. In this study, small RNA sequencing and comparative transcriptomic analysis was conducted to construct a comprehensive microRNA dataset for the whiteleg shrimp Litopenaeus vannamei exposed to hypoxia challenge. A total of 3324 known miRNAs and 8 putative novel miRNAs were identified, providing a valuable resource for future investigation on the functional mechanism of miRNAs in shrimp. Upon hypoxia, 1213 miRNAs showed significant differential expression, and many well-known miRNAs involved in hypoxia tolerance such as miR-210, let-7, miR-143 and miR-101 were identified. Remarkably, the vast majority of these miRNAs were up-regulated, suggesting that up-regulation of miRNAs may represent an effective strategy to inhibit protein translation under stressful hypoxic condition. The differentially expressed miRNAs were potentially targeting a wide variety of genes, including those with essential roles in hypoxia tolerance such as HIF1a and p53. GO and KEGG enrichment analysis further revealed that a broad range of biological processes and metabolic pathways were over-represented. Several GO terms associated with gene transcription and translation and KEGG pathways related to cytoskeleton remodeling, immune defense and signaling transduction were enriched, highlighting the crucial roles of these cellular events in the adaptation to hypoxia. Taken together, our study revealed that the differentially expressed miRNAs may regulate host response to hypoxia by modulating the expression of stress response genes such as HIF1a and p53 and affecting key cellular events involved in hypoxia adaptation. The findings would expand our knowledge of the biochemical and molecular underpinnings of hypoxia response strategies used by penaeid shrimp, and contribute to a better understanding of the molecular mechanisms of hypoxia tolerance in decapod crustaceans.

Multi-Epitope Fusion Protein Eg mefAg-1 as a Serodiagnostic Candidate for Cystic Echinococcosis in Sheep.

Cystic echinococcosis (CE) in sheep is a hazardous zoonotic parasitic disease that is caused by Echinococcus granulosus (Eg). At present, serological test is an important diagnostic method for Eg infection in domestic animals. Here, a fusion protein Eg mefAg-1 harboring 8 dominant B-cell epitopes of Eg such as antigen B, tetraspanin 1, tetraspanin 6, reticulon and Eg95 was produced in E. coli and evaluated for CE in sheep by indirect ELISA. Eg mefAg-1 showed in ELISA a high sensitivity (93.41%) and specificity (99.31%), with a coincidence rate of 97.02%. Overall, it is suggested that the Eg mefAg-1 could be a potential antigen candidate for CE serodiagnosis in sheep.

Efficacy and tolerance of GELOXD/P-GEMOXD in newly diagnosed nasal-type extranodal NK/T-cell lymphoma: A multicenter retrospective study.

OBJECTIVES: Nasal-type extranodal natural killer NK/T-cell lymphoma (ENKTCL) is a distinct type of non-Hodgkin lymphoma with poor prognosis. This research aimed to evaluate the efficacy and safety of the GELOXD or P-GEMOXD regimens in patients with ENKTCL. METHODS: Newly diagnosed ENKTCL patients treated with either the GELOXD or the P-GEMOXD regimen were identified from three cancer centers between January 2010 and December 2016. Kaplan-Meier and Cox regression analyses were used to calculate overall survival (OS) and progression-free survival (PFS) and to investigate prognostic factors. RESULTS: One hundred and eighty-four cases were identified from three cancer centers. After 1-5 treatment cycles of GELOXD or P-GEMOXD chemotherapy, 155 (84%) patients showed a complete response (CR). The 3-year OS (73.0% vs 38.2%, P = .001) and PFS (72.8% vs 32.4%, P = .000) rates were significantly higher in early-stage patients compared with advanced-stage patients. A multivariate analysis revealed that patient CR status was a significant independent factor in disease prognosis. Grade 3/4 leukopenia occurred in 43 (23.4%) patients. Major non-hematological toxicities included nausea (n = 117, 63.6%) and vomiting (n = 66, 35.9%). CONCLUSIONS: The GELOXD and P-GEMOXD chemotherapy regimens are well tolerated and provide favorable survival outcomes in patients with ENKTCL.

Characterization of bacterial composition and diversity in a long-term petroleum contaminated soil and isolation of high-efficiency alkane-degrading strains using an improved medium.

Bacterial community and diversity in a long-term petroleum-contaminated soil of an oilfield were characterized using 16S rRNA gene-based Illumina MiSeq high-throughput sequencing. Results indicated that Proteobacteria (49.11%) and Actinobacteria (24.24%) were the most dominant phyla, and the most abundant genera were Pseudoxanthomonas (8.47%), Luteimonas (3.64%), Alkanindiges (9.76%), Acinetobacter (5.26%) and Agromyces (8.56%) in the soil. Meanwhile a series of cultivations were carried out for isolation of alkane degraders from petroleum-contaminated soil with gellan gum and agar as gelling agents. And the isolates were classified by their 16S rRNA genes. Nine of the isolates including Enterobacter, Pseudomonas,Acinetobacter, Rhizobium, Bacillus, Sphingomonas, Paenibacillus, Variovorax and Rhodococcus showed strong biodegradability of alkane mixture (C9-C30) in a wide range of chain-length, which could be potentially applied in enhancement of bioremediation.

Serological and molecular investigation of porcine sapovirus infection in piglets in Xinjiang, China.

Porcine sapovirus (PoSaV) is one of the important pathogens that cause acute gastroenteritis in piglets. A survey on the infection and epidemic status of PoSaV in Xinjiang Province, Northwest China, was conducted in this study. We applied indirect viral protein 1 (VP1)-ELISA method to detect specific antibodies in 1218 serum samples of 3-month-old piglets collected from eight regions in Xinjiang during 2013-2014 and also detected PoSaV in 146 diarrhea stools of piglets in these eight regions using RT-PCR technology. The results showed that the PoSaV-serological positive rates in piglets in eight different regions in Xinjiang were between 32.82 and 47.06% with a mean rate of 37.68%. The average positive rate of PCR in stools of piglets was 3.42%. Sequencing and comparative analysis of five PCR-amplified DNA fragments revealed that four epidemic strains of PoSaV (swine/XJ-KO1, swine/XJ-AK2, swine/XJ-KS1, and swine/XJ-SHZ1) shared high nucleotide and amino acid identities with Cowden strain, while strain swine/XJ-AK1 shared higher high identities with Po/OH-JJ681/2000/US isolate. Phylogenetic clustering further verified that the epidemic strains of PoSaVs, i.e., swine/XJ-KO1, swine/XJ-AK2, swine/XJ-KS1, and swine/XJ-SHZ1, belong to genogroup (GIII) while swine/XJ-AK1 belongs to GVI. This survey confirmed for the first time that PoSaV infection was common in piglets in Xinjiang, China, and that the epidemic strains exist at least in both GIII and GVI clusters. This study provided the useful epidemiological data for scientific control and prevention of this disease.

GSK-3ß suppresses the proliferation of rat hepatic oval cells through modulating Wnt/ß-catenin signaling pathway.

AIM: Glycogen synthase kinase 3ß (GSK-3ß) plays a crucial role in hepatic biology, including liver development, regeneration, proliferation and carcinogenesis. In this study we investigated the role of GSK-3ß in regulation of growth of hepatic oval cells in vitro and in liver regeneration in partially hepatectomized rats. METHODS: WB-F344 cells, the rat hepatic stem-like epithelial cells, were used as representative of oval cells. Cell viability was examined using a WST-8 assay. The cells were transfected with a recombinant lentivirus expressing siRNA against GSK-3ß (GSK-3ßRNAiLV) or a lentivirus that overexpressed GSK-3ß (GC-GSK-3ßLV). Adult rats underwent partial (70%) hepatectomy, and liver weight and femur length were measured at d 7 after the surgery. The expression of GSK-3ß, phospho-Ser9-GSK-3ß, ß-catenin and cyclin D1 was examined with immunoblotting assays or immunohistochemistry. RESULTS: Treatment of WB-F344 cells with the GSK-3ß inhibitor SB216763 (5 and 10 µmol/L) dose-dependently increased the levels of phospho-Ser9-GSK-3ß, but not the levels of total GSK-3ß, and promoted the cell proliferation. Knockout of GSK-3ß with GSK-3ßRNAiLV increased the cell proliferation, whereas overexpression of GSK-3ß with GC-GSK-3ßLV decreased the proliferation. Both SB216763 and GSK-3ßRNAiLV significantly increased the levels of ß-catenin and cyclin D1 in the cells, whereas GSK-3ß overexpression decreased their levels. In rats with a partial hepatectomy, administration of SB216763 (2 mg/kg, ip) significantly increased the number of oval cells, the levels of phospho-Ser9-GSK-3ß, ß-catenin and cyclin D1 in liver, as well as the ratio of liver weight to femur length at d 7 after the surgery. CONCLUSION: GSK-3ß suppresses the proliferation of hepatic oval cells by modulating the Wnt/ß-catenin signaling pathway.

Serological and molecular survey of sheep infected with Mycoplasma ovipneumoniae in Xinjiang, China.

Mycoplasma pneumonia is one of the most important infectious diseases that threaten sheep production. In order to investigate the epidemic status of Mycoplasma ovipneumoniae infection in sheep, indirect hemagglutination assay was used to analyze 1679 serum samples collected from four different breeds of sheep (Kazak sheep, Hu sheep, Merino sheep, and Duolang sheep) in six regions in Xinjiang between 2012 and 2014. One thousand one hundred sixty-nine sheep nasal swabs and 180 lungs were PCR analyzed. The results showed that the average positive rates of the serum samples were 17.75 %. The positive rates were between 9.76 and 30.61 % in the four breeds. Among them, the Hu sheep had a significantly higher rate than other breeds (P < 0.05). The average positive rates of nasal swabs and lungs were 10.18 and 28.89 %, respectively. Based on the phylogenetic trees of 16S RNA gene, the isolates were closest to those strains isolated from inland areas of China, indicating that these epidemic isolates came from the trans-province introductions. Our survey suggests that quarantine is necessary for sheep imported from inland, and effective immunization should be implemented in sheep susceptible to M. ovipneumoniae in Xinjiang, China.

Prevalence of hydatid cysts in livestock animals in Xinjiang, China.

Hydatid worms, hosted by humans and animals, impose serious human health risk and cause significant livestock production loss. To better understand the disease infection status in Xinjiang, China, we investigated the disease epidemics in 4 livestock animals, i.e., cattle, sheep (both sheep and goat), camels, and horses, slaughtered at the abattoirs in Urumqi, Yining, Tacheng, and Altay areas. The results showed that the animals were infected at different rates, in the order of sheep (9.8%), cattle (8.4%), camels (6.8%), and horses (4.3%). The infection rates were found to be different between the abattoirs in various regions even for the same animals. For sheep, the rates increased significantly as the animals grew older. It was 1.9% before 1 year of age and increased to 8.2% in the age of 1-2 years, and further increased to 12.3% when the animals were 3-4 years old, and reached 17.2% when they were 5-6 year old. Sheep older than 6 years had an infection rate of 19.5%. This study demonstrates that the 4 livestock animals in the pastoral areas in Xinjiang were infected by the parasites to various extend. This study is the first systematic investigation of the hydatid worms in various livestock animals in Xinjiang, China, which provides epidemiological information about the infection of hydatid worms in livestock, and is valuable in developing strategies for prevention and control of the hydatid disease.

Radioactive impact of the Fukushima nuclear accident on Shenyang in the northeast of China.

Environmental monitoring was carried out in Shenyang in the northeast of China after the Fukushima Daiichi nuclear accident which was caused by the earthquake and tsunami on 11 March 2011. The fission product radionuclide (131)I was detected as present in the atmosphere on the 20th day after the nuclear accident, while the radionuclides (134)Cs and (137)Cs were found in the atmosphere on the 27th day after the accident. The radionuclides (131)I, (134)Cs and (137)Cs continued to be present in the atmosphere for 25, 4 and 6 days, respectively, with maximum concentrations of 4.60 ± 0.2, 0.29 ± 0.06 and 0.42 ± 0.08 mBq m(-3). The contents of fission radionuclides in vegetables, drinking water and milk from Shenyang were below the detection limits. The atmosphere was slightly contaminated in Shenyang due to the Fukushima nuclear accident, but no contamination was detected in vegetables, milk and drinking water.

Conservation genomic study of Hopea hainanensis (Dipterocarpaceae), an endangered tree with extremely small populations on Hainan Island, China.

Introduction: Hopea hainanensis Merrill & Chun is considered a keystone and indicator species in the tropical lowland rainforests of Hainan Island. Owing to its high-quality timber, H. hainanensis has been heavily exploited, leading to its classification as a first-class national protected plant in China and a plant species with extremely small populations (PSESPs). Methods: This study analyzed genome-wide single nucleotide polymorphisms obtained through restriction site-associated DNA sequencing from 78 adult trees across 10 H. hainanensis populations on Hainan Island. Results and discussion: The nucleotide diversity of the sampled populations ranged from 0.00096 to 0.00138, which is lower than that observed in several other PSESPs and endangered tree species. Bayesian unsupervised clustering, principal component analysis, and neighbor-joining tree reconstruction identified three to five genetic clusters in H. hainanensis, most of which were geographically widespread and shared by multiple populations. Demographic history analysis based on pooled samples indicated that the decline in the H. hainanensis population began approximately 20,000 years ago, starting from an ancestral population size of approximately 10,000 individuals. The reduction in population size accelerated approximately 4,000 years ago and has continued to the present, resulting in a severely reduced population on Hainan Island. Intensified genetic drift in small and isolated H. hainanensis populations may contribute to moderate differentiation between some of them, as revealed by pairwise F st. In conclusion, our conservation genomic study confirms a severe population decline and an extremely low level of nucleotide variation in H. hainanensis on Hainan Island. These findings provide critical insights for the sustainable management and genetic restoration of H. hainanensis on Hainan Island.

The efficacy and safety of anti-vascular endothelial growth factor combined with Ahmed glaucoma valve implantation in the treatment of neovascular glaucoma: a systematic review and meta-analysis.

Background: The intraocular injections of anti-vascular endothelial growth factor (anti-VEGF) demonstrates significant efficacy in inhibiting the formation of ocular neovascularization in neovascular glaucoma (NVG). Ahmed glaucoma valve implantation (AGVI) is extensively employed for the management of diverse glaucoma types. Objective: To further evaluate the efficacy and safety of anti-VEGF combined with AGVI in the treatment of neovascular glaucoma. Methods: A thorough search for randomized controlled trials (RCTs) was conducted across eight databases: PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP. The search period was set from the inception of each database until March 2, 2024, to identify RCTs investigating the effectiveness and safety of combining AGVI with anti-VEGF therapy for NVG. We used the Cochrane Risk of Bias Assessment Tool to evaluate the quality of the literature and performed statistical analysis using Stata 15.0 software. Results: Fourteen RCTs were included in this study. Compared with AGVI alone, the combination of anti-VEGF drugs and AGVI can reduce postoperative intraocular pressure (IOP) at 1 week [WMD = -4.03, 95% CI (-5.73, -2.34), p < 0.001], 1 month [WMD = -5.39, 95% CI (-7.05, -3.74), p < 0.001], 3 months [WMD = -6.59, 95% CI (-7.85, -5.32), p < 0.001], 6 months [WMD = -4.99, 95% CI (-9.56, -0.43), p = 0.032], and more than 12 months [WMD = -3.86, 95% CI (-6.82, -0.90), p = 0.011], with a higher Effective rate [RR = 1.27, 95% CI (1.18, 1.37), p < 0.001], decreased incidence of postoperative hyphema [RR = 0.24, 95% CI (0.15, 0.39), p < 0.001], reduced use of postoperative antiglaucoma medications [WMD = -0.48, 95% CI (-0.61, -0.35), p < 0.001], and decreased aqueous humor VEGF levels [SMD = -2.84, 95% CI (-4.37, -1.31), p < 0.001]. Conclusion: In comparison to AGVI alone, the combination of AGVI with anti-VEGF therapy has better effects in reducing IOP at various time intervals, diminishing postoperative antiglaucoma medication requirements and reducing aqueous humor VEGF levels. Furthermore, it effectively minimizes the incidence of postoperative hyphema. Nevertheless, due to the variability in the quality of the trials included, further high-quality experiments will be required in the future to substantiate this conclusion. Systematic review registration: PROSPERO, identifier CRD42024519862, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024519862.

[Regulation effect of adipose-derived mesenchymal stem cells on pancreatic cancer cells].

OBJECTIVE: To analyze the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer (PaCa) cells and the the possible mechanism involved. METHODS: ADSCs were isolated and co-cultured with PaCa cells. CCK-8 assay was used to detect the proliferation of PaCa cells. An ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. The proliferation of PaCa cells by SDF-1 was measured. AMD3100 regulated the co-culture of ADSCs and PaCa. The tumor growth of PaCa cells was assessed after treatment by ADSCs in vivo. RESULTS: ADSCs can promote the proliferation and invasion of PaCa cells (proliferation: SW1990: 1.535 ± 0.153; PANC-1: 1.370 ± 0.100; the value of control was 1; invasion: SW1990: 47.0 ± 2.6 vs. 28.3 ± 1.3; PANC-1: 40.3 ± 1.8 vs. 24.3 ± 1.3; t = 4.332-9.558, P < 0.05). The expression of SDF-1 was high in ADSCs, but not in PaCa cells (69 ± 5 vs. 0 and 0, F = 389.134, P < 0.01). The promotion of SDF-1 on PaCa cells depends on the concentration. AMD3100 significantly downregulates these growth-promoting effects of ADSCs on PaCa cells. ADSCs significantly promoted the growth of SW1990 in nude mice at the 5(th) week (volume: (1295 ± 102) mm(3) vs. (967 ± 81) mm(3), t = 5.614, P < 0.05) , but not in PANC-1 cell. CONCLUSION: ADSCs can promote the proliferation and invasion of PaCa cells, which may involve the SDF-1/CXCR4 axis.

The regulatory roles of Fasciola hepatica GSTO1 protein in inflammatory cytokine expression and apoptosis in murine macrophages.

Fascioliasis, a global zoonotic parasitic disease, is mainly caused by Fasciola hepatica (F. hepatica) parasitizing in the livers of hosts, mainly humans and herbivores. Glutathione S-transferase (GST) is one of the important excretory- secretory products (ESPs) from F. hepatica, however, the regulatory roles of its Omega subtype in the immunomodulatory effects remain unknown. Here, we expressed F. hepatica recombinant GSTO1 protein (rGSTO1) in Pichia pastoris and analyzed its antioxidant properties. Then, the interaction between F. hepatica rGSTO1 and RAW264.7 macrophages and its effects on inflammatory responses and cell apoptosis were further explored. The results revealed that GSTO1 of F. hepatica owned the potent ability to resist oxidative stress. F. hepatica rGSTO1 could interact with RAW264.7 macrophages and inhibit its cell viability, furthermore, it may suppress the production of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α, but promote the expression of anti-inflammatory cytokine IL-10. In addition, F. hepatica rGSTO1 may down-regulate the ratio of Bcl-2/Bax, and increase the expression of pro-apoptotic protein caspase-3, thereby eliciting the apoptosis of macrophages. Notably, F. hepatica rGSTO1 inhibited the activation of nuclear factor-κB (NF-κB) and mitogen­activated protein kinases (MAPKs p38, ERK and JNK) pathways in LPS-activated RAW264.7 cells, exerting potent modulatory effects on macrophages. These findings suggested that F. hepatica GSTO1 can modulate the host immune response, which provided new insights into the immune evasion mechanism of F. hepatica infection in host.

A study on the sustainability assessment of China's basic medical insurance fund under the background of population aging-evidence from Shanghai.

Objective: As China's population aging process accelerates, the expenditure of China's basic medical insurance fund for employees may increase significantly, which may threaten the sustainability of China's basic medical insurance fund for employees. This paper aims to forecast the future development of China's basic medical insurance fund for employees in the context of the increasingly severe aging of the population. Methods: This paper taking an empirical study from Shanghai as an example, constructs an actuarial model to analyze the impact of changes in the growth rate of per capita medical expenses due to non-demographic factors and in the population structure on the sustainability of the basic medical insurance fund for employees. Results: Shanghai basic medical insurance fund for employees can achieve the goal of sustainable operation in 2021-2035, with a cumulative balance of 402.150-817.751 billion yuan in 2035. The lower the growth rate of per capita medical expenses brought about by non-demographic factors, the better the sustainable operation of the fund. Conclusion: Shanghai basic medical insurance fund for employees can operate sustainably in the next 15 years, which can further reduce the contribution burden of enterprises, which lays the foundation for improving the basic medical insurance treatment for employees.

Children's internal migration and subjective wellbeing of older parents left behind: Spiritual or financial support?

Introduction: Against the background of population aging and large-scale internal migration, this study uses an ordered logit with two-way fixed effects to examine the effect of children's internal migration on the subjective wellbeing of parents left behind. The study is based on the China Family Panel Studies database. Methods: Data were obtained from CFPS (China Family Panel Studies), and ordered logit with two-way fixed effects was used to test the total effect of children's internal migration on subjective wellbeing of parents left behind, and KHB test was used to separate intergenerational spiritual support and intergenerational financial support to examine the intergenerational support preferences of parents left behind. Results: The results show that children's internal migration has a significant negative effect on the subjective wellbeing of parents left behind, mainly through the reduction of intergenerational spiritual support. Furthermore, intergenerational financial support significantly mitigates this negative effect. There is heterogeneity in the direction of the total wellbeing effect across parents' preferences, as well as in the masking effect of financial support. However, the effect of financial support never fully offsets the effect of spiritual support. Discussion: To cope with the negative effects of children's internal migration on parents, positive measures should be taken to change parental preferences.

Neuroprotective α-pyrones from Nigrospora oryzae, an endophytic fungus residing in Taxus chinensis var. mairei.

Endophytes coevolve with plant hosts and thus are more probable to acquire the character (in favor) of producing undescribed bioactive metabolites. Consequently, the topic has been intensely investigated for over two decades, but endophytic metabolites with neuroprotective effect remain scarce. The study presents the discovery of eight undescribed (named solanapyrones U-Z and prosolanapyrones A and B) and six known pyrones (solanapyrones A-C and E-G) from the culture of Nigrospora oryzae, an endophytic fungus associated with Taxus chinensis var. mairei. The structures and absolute configurations of undescribed pyrones were elucidated by extensive spectroscopic analysis, modified Mosher's method, and induced circular dichroism (ICD) spectrum. Solanapyrones A and B and an undescribed pyrone (solanapyrone U) were demonstrated to be more neuroprotective than clenbuterol in inducing bone marrow mesenchymal stem cells (bMSCs) to secret nerve growth factor (NGF). The work updates the pyrone chemodiversity in nature and extends the biofunction repertoire of solanapyrone-related polyketides.

Structure-Based Design of 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor as a Potential Herbicide for Cotton Fields.

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is one of the most promising herbicide targets for the development of agricultural chemicals owing to its unique mechanism of action in plants. We previously reported on the co-crystal structure of Arabidopsis thaliana (At) HPPD complexed with methylbenquitrione (MBQ), an inhibitor of HPPD that we previously discovered. Based on this crystal structure, and in an attempt to discover even more effective HPPD-inhibiting herbicides, we designed a family of triketone-quinazoline-2,4-dione derivatives featuring a phenylalkyl group through increasing the interaction between the substituent at the R1 position and the amino acid residues at the active site entrance of AtHPPD. Among the derivatives, 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-(1-phenylethyl)quinazoline-2,4(1H,3H)-dione (23) was identified as a promising compound. The co-crystal structure of compound 23 with AtHPPD revealed that hydrophobic interactions with Phe392 and Met335, and effective blocking of the conformational deflection of Gln293, as compared with that of the lead compound MBQ, afforded a molecular basis for structural modification. 3-(1-(3-Fluorophenyl)ethyl)-6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethylquinazoline-2,4(1H,3H)-dione (31) was confirmed to be the best subnanomolar-range AtHPPD inhibitor (IC50 = 39 nM), making it approximately seven times more potent than MBQ. In addition, the greenhouse experiment showed favorable herbicidal potency for compound 23 with a broad spectrum and acceptable crop selectivity against cotton at the dosage of 30-120 g ai/ha. Thus, compound 23 possessed a promising prospect as a novel HPPD-inhibiting herbicide candidate for cotton fields.

A serological survey of Akabane virus infection in cattle and sheep in northwest China.

PURPOSE: Akabane disease characterized mainly by fetal damage is a ruminant disease caused by insect-transmitted Akabane virus infection. METHODS: We investigated Akabane disease using serum neutralization tests in 446 blood samples collected from 187 cattle and 259 sheep of Xinjiang province, northwest China. RESULTS: (1) The overall prevalence rate of neutralizing antibody was 19.06 % (85/446), (2) the prevalence rates of Akabane disease in cattle and sheep were 20.32 % (38/187) and 18.15 % (47/259), respectively, (3) the disease prevalence rates were not significantly different between cattle and sheep, but significantly different among samples collected from different sampling months, (4) the disease was most prevalent in July when mosquitoes and culicoides were most active, and (5) the disease prevalence rates were significantly different between individuals with abortion experience and without abortion experience (P < 0.05), suggesting that Akabane virus infection may significantly increase abortion risk in cattle and sheep. CONCLUSIONS: To our knowledge, this is the first report confirming that Akabane virus infection is common in cattle and sheep of Xinjiang province, northwest China and providing useful epidemiological information for cattle and sheep abortion prevention and control.

[Effects of glycogen synthase kinase 3ß overexpression in rat and glycogen synthase kinase 3ß inhibitor SB-216763 on proliferation of hepatic oval cells].

OBJECTIVE: To research the effects of glycogen synthase kinase (GSK3ß) overexpression and GSK3ß inhibitor SB-216763 on the proliferation of hepatic oval cells in rats and its regulatory mechanisms by Wnt signaling pathway. METHODS: The hepatic oval cells WBF-344 were divided into the blank control group, GSK3ß over-expression group, DMSO control group and GSK3ß inhibitor groups, while the inhibitor groups set up three concentration gradients, that was 1, 5, 10 µmol/L. Using the GSK3ß over-expression lentivirus, which had been identified correctly, and SB-216763 dealt with the cells WBF-344. The cells morphology of each group was observed under the phase contrast inverted microscope, and the expression of fluorescence in the lentivirus-transfected group was observed under the fluorescent microscope. The proliferation of each group cells was tested by CCK8 kits. The cells' apoptosis was detected by AnnexinV-FITC/PI kits. The expression of GSK3ß, ß-catenin and cyclin D1 were detected by Western blot. RESULTS: The cells of GSK3ß over-expression group were fewer and obvious aging. However, in each inhibitor added group, the cells' division and proliferation was vigorous, and the condition was good. Moreover, the cells' proliferation was getting stronger with the concentration of SB-216763 increasing. A large number of green fluorescence was expressed in the lentivirus-transfected cells. The cells' proliferation in GSK3ß over-expression group restrained (t = 7.178, P < 0.01, as compared with control), while the cells' proliferation was vigorous in inhibitor groups (F = 45.030, P < 0.01, as compared with control). Flow Cytometry showed that the cells apoptosis was significant in GSK3ß over-expression group. Western blot showed that the expression of GSK3ß was increased, while the expression of ß-catenin and cyclin D1 was decreased in the over-expression group. The expression of GSK3ß had no significant difference among the control group and inhibitor groups. However, the expression of ß-catenin and cyclin D1 was significantly increased with the concentration of SB-216763 increasing. CONCLUSIONS: The overexpression of GSK3ß can inhibit the Wnt signaling pathway, thus restrain the cells' proliferation and promotes apoptosis. SB-216763 can activate the Wnt pathway, thus promotes cells' proliferation.