Highly pathogenic PRRSV upregulates IL-13 production through nonstructural protein 9-mediated inhibition of N6-methyladenosine demethylase FTO.

Porcine reproductive and respiratory syndrome virus (PRRSV), a highly infectious virus, causes severe losses in the swine industry by regulating the inflammatory response, inducing tissue damage, suppressing the innate immune response, and promoting persistent infection in hosts. Interleukin-13 (IL-13) is a cytokine that plays a critical role in regulating immune responses and inflammation, particularly in immune-related disorders, certain types of cancer, and numerous bacterial and viral infections; however, the underlying mechanisms of IL-13 regulation during PRRSV infection are not well understood. In this study, we demonstrated that PRRSV infection elevates IL-13 levels in porcine alveolar macrophages. PRRSV enhances m6A-methylated RNA levels while reducing the expression of fat mass and obesity associated protein (FTO, an m6A demethylase), thereby augmenting IL-13 production. PRRSV nonstructural protein 9 (nsp9) was a key factor for this modulation. Furthermore, we found that the residues Asp567, Tyr586, Leu593, and Asp595 were essential for nsp9 to induce IL-13 production via attenuation of FTO expression. These insights delineate PRRSV nsp9's role in FTO-mediated IL-13 release, advancing our understanding of PRRSV's impact on host immune and inflammatory responses.

The accumulation of modular serine protease mediated by a novel circRNA sponging miRNA increases Aedes aegypti immunity to fungus.

BACKGROUND: Mosquitoes transmit many infectious diseases that affect human health. The fungus Beauveria bassiana is a biological pesticide that is pathogenic to mosquitoes but harmless to the environment. RESULTS: We found a microRNA (miRNA) that can modulate the antifungal immunity of Aedes aegypti by inhibiting its cognate serine protease. Fungal infection can induce the expression of modular serine protease (ModSP), and ModSP knockdown mosquitoes were more sensitive to B. bassiana infection. The novel miRNA-novel-53 is linked to antifungal immune response and was greatly diminished in infected mosquitoes. The miRNA-novel-53 could bind to the coding sequences of ModSP and impede its expression. Double fluorescence in situ hybridization (FISH) showed that this inhibition occurred in the cytoplasm. The amount of miRNA-novel-53 increased after miRNA agomir injection. This resulted in a significant decrease in ModSP transcript and a significant increase in mortality after fungal infection. An opposite effect was produced after antagomir injection. The miRNA-novel-53 was also knocked out using CRISPR-Cas9, which increased mosquito resistance to the fungus B. bassiana. Moreover, mosquito novel-circ-930 can affect ModSP mRNA by interacting with miRNA-novel-53 during transfection with siRNA or overexpression plasmid. CONCLUSIONS: Novel-circ-930 affects the expression level of ModSP by a novel-circ-930/miRNA-novel-53/ModSP mechanism to modulate antifungal immunity, revealing new information on innate immunity in insects.

Mitochondrial genome provides species-specific targets for the rapid detection of early invasive populations of Hylurgus ligniperda in China.

BACKGROUND: Hylurgus ligniperda, a major international forestry quarantine pest, was recently found to have invaded and posed a serious threat to the Pinus forests of the Jiaodong Peninsula in China. Continuous monitoring and vigilance of the early population is imperative, and rapid molecular detection technology is urgently needed. We focused on developing a single-gene-based species-specific PCR (SS-PCR) method. RESULTS: We sequenced and assembled the mitochondrial genome of H. ligniperda to identify suitable target genes. We identified three closely related species for detecting the specificity of SS-PCR through phylogenetic analysis based on 13 protein-coding genes (PCGs). Subsequently, we analyzed the evolution of 13 PCGs and selected four mitochondrial genes to represent slow-evolving gene (COI) and faster-evolving genes (e.g. ND2, ND4, and ND5), respectively. We developed four species-specific primers targeting COI, ND2, ND4, and ND5 to rapidly identify H. ligniperda. The results showed that the four species-specific primers exhibited excellent specificity and sensitivity in the PCR assays, with consistent performance across a broader range of species. This method demonstrates the ability to identify beetles promptly, even during their larval stage. The entire detection process can be completed within 2-3 h. CONCLUSIONS: This method is suitable for large-scale species detection in laboratory settings. Moreover, the selection of target genes in the SS-PCR method is not affected by the evolutionary rate. SS-PCR can be widely implemented at port and forestry workstations, significantly enhancing early management strategies and quarantine measures against H. ligniperda. This approach will help prevent the spread of the pest and effectively preserve the resources of Chinese pine forests.

Construction of Ideal One-Dimensional Spin Chains by Topochemical Dehydration/Rehydration Route.

One-dimensional (1D) Heisenberg antiferromagnets are of great interest due to their intriguing quantum phenomena. However, the experimental realization of such systems with large spin S remains challenging because even weak interchain interactions induce long-range ordering. In this study, we present an ideal 1D S = 5/2 spin chain antiferromagnet achieved through a multistep topochemical route involving dehydration and rehydration. By desorbing three water molecules from (2,2'-bpy)FeF3(H2O)·2H2O (2,2'-bpy = 2,2'-bipyridyl) at 150 °C and then intercalating two water molecules at room temperature (giving (2,2'-bpy)FeF3·2H2O 1), the initially isolated FeF3ON2 octahedra combine to form corner-sharing FeF4N2 octahedral chains, which are effectively separated by organic and added water molecules. Mössbauer spectroscopy reveals significant dynamical fluctuations down to 2.7 K, despite the presence of strong intrachain interactions. Moreover, results from electron spin resonance (ESR) and heat capacity measurements indicate the absence of long-range order down to 0.5 K. This controlled topochemical dehydration/rehydration approach is further extended to (2,2'-bpy)CrF3·2H2O with S = 3/2 1D chains, thus opening the possibility of obtaining other low-dimensional spin lattices.

The Z-Scheme MIL-88B(Fe)/BiOBr Heterojunction Promotes Fe(III)/Fe(II) Cycling and Photocatalytic-Fenton-Like Synergistically Enhances the Degradation of Ciprofloxacin.

The Z-scheme MIL-88B/BiOBr (referred to as MxBy, whereas x and y are the mass of MIL-88B(Fe) and BiOBr) heterojunction photocatalysts are successfully prepared by a facile ball milling method. By adding low concentration H2O2 under visible light irradiation, the Z-scheme heterojunction and photocatalytic-Fenton-like reaction synergistically enhance the degradation and mineralization of ciprofloxacin (CIP). Among them, M50B150 showed efficient photodegradation efficiency and excellent cycling stability, with 94.6% removal of CIP (10 mg L-1) by M50B150 (0.2 g L-1) under 90 min of visible light. In the MxBy heterojunctions, the rapid transfer of photo-generated electrons not only directly decomposed H2O2 to generate ·OH, but also improved the cycle of Fe3+/Fe2+ pairs, which facilitated the reaction with H2O2 to generate ·OH and ·O2 - radicals. In addition, the effects of photocatalyst dosages, pH of CIP solution, and coexisting substances on CIP removal are systematically investigated. It is found that the photocatalytic- Fenton-like reaction can be carried out at a pH close to neutral conditions. Finally, the charge transfer mechanism of the Z-scheme is verified by electron spin resonance (ESR) signals. The ecotoxicity of CIP degradation products is estimated by the T.E.S.T tool, indicating that the constructed photocatalysis-Fenton-like system is a green wastewater treatment technology.

Composition and diversity of soil microbial communities change by introducing Phallus impudicus into a Gastrodia elata Bl.-based soil.

BACKGROUND: The Gastrodia elata Bl. is an orchid, and its growth demands the presence of Armillaria species. The strong competitiveness of Armillaria species has always been a concern of major threat to other soil organisms, thus disrupting the equilibrium of soil biodiversity. Introducing other species to where G. elata was cultivated, could possibly alleviate the problems associated with the disequilibrium of soil microenvironment; however, their impacts on the soil microbial communities and the underlying mechanisms remain unclear. To reveal the changes of microbial groups associated with soil chemical properties responding to different cultivation species, the chemical property measurements coupled with the next-generation pyrosequencing analyses were applied with soil samples collected from fallow land, cultivation of G. elata and Phallus impudicus, respectively. RESULTS: The cultivation of G. elata induced significant increases (p < 0.05) in soil pH and NO3-N content compared with fallow land, whereas subsequent cultivation of P. impudicus reversed these G. elata-induced increases and was also found to significantly increase (p < 0.05) the content of soil NH4+-N and AP. The alpha diversities of soil microbial communities were significantly increased (p < 0.01) by cultivation of G. elata and P. impudicus as indicated with Chao1 estimator and Shannon index. The structure and composition of soil microbial communities differed responding to different cultivation species. In particular, the relative abundances of Bacillus, norank_o_Gaiellales, Mortierella and unclassified_k_Fungi were significantly increased (p < 0.05), while the abundances of potentially beneficial genera such as Acidibacter, Acidothermus, Cryptococcus, and Penicillium etc., were significantly decreased (p < 0.05) by cultivation of G. elata. It's interesting to find that cultivation of P. impudicus increased the abundances of these genera that G. elata decreased before, which contributed to the difference of composition and structure. The results of CCA and heatmap indicated that the changes of soil microbial communities had strong correlations with soil nutrients. Specifically, among 28 genera presented, 50% and 42.9% demonstrated significant correlations with soil pH and NO3-N in response to cultivation of G. elata and P. impudicus. CONCLUSIONS: Our findings suggested that the cultivation of P. impudicus might have potential benefits as result of affecting soil microorganisms coupled with changes in soil nutrient profile.

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.

Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3ß, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1ß, IL-6, JAG2, KCNJ2, MALT1, ß-MHC, NF-κB, PCK1, PLCß1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.

Investigating Xiaochaihu Decoction's fever-relieving mechanism via network pharmacology, molecular docking, dynamics simulation, and experiments.

Xiaochaihu Decoction（XCHD）is a classic prescription for the treatment of fever, but the mechanism is not clear. In this study, We elucidated the mechanism of action through network pharmacology and molecular docking. A rat fever model was established to verify the prediction results of network pharmacology. The analysis revealed that 120 intersection targets existed between XCHD and fever. The TP53, STAT3, RELA, MAPK1, AKT1, TNF and MAPK14 as potential core targets of XCHD in fever treatment. GO and KEGG pathway enrichment analyses indicated that XCHD may act through pathways such as the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway. Molecular docking results demonstrated that quercetin, kaempferol, ß-sitosterol, stigmasterol and baicalein exhibited strong binding activity to key targets. Animal experiments showed that XCHD significantly reduced body temperature and levels of IL-1ß, IL-6, TNF-α, NO, PGE2, and cAMP in rats with fever. Importantly, no significant difference was observed between the XCHD self-emulsifying nano phase plus suspension phase and XCHD group. XCHD exerts its therapeutic effects on fever through a multi-ingredient, multi-target, and multi-pathway approach.

Comparison of clinical characteristics between patients with axial spondyloarthritis with and without acute anterior uveitis: a multicentre study of the Chinese Spondyloarthritis Registry.

OBJECTIVES: This study explores the clinical characteristics associated with the occurrence of acute anterior uveitis (AAU) in patients with axial spondyloarthritis (axSpA) within a large, multicentre database. METHODS: This observational, cross-sectional study of patients with axSpA used data from the Chinese Spondyloarthritis Registry between August 1, 2018, and March 31, 2020. The demographic and clinical features of patients with and without AAU were compared. Univariate and multivariate analyses were performed to determine the association between variables and uveitis. RESULTS: A total of 4304 patients were included in this study. The prevalence of AAU in patients with axSpA was 10.59%. Multivariate logistic regression analysis revealed a positive correlation between AAU and age at diagnosis (odds ratio [OR], 1.026; p<0.001), disease duration (OR, 2.117; p<0.001), current or past Achilles tendinitis (OR, 1.692; p<0.001), current or past dactylitis (OR, 1.687; p=0.002), current or past psoriasis (OR, 3.932; p<0.001), presence of human leukocyte antigen-B27 (HLA-B27) (OR, 2.787; p<0.001), and a good response to non-steroidal anti-inflammatory drugs (NSAIDs) (OR, 1.343; p=0.027). CONCLUSIONS: AAU was the most common extra-articular manifestation in the Chinese Spondyloarthritis Registry. In Chinese patients with axSpA, older age at diagnosis, longer disease duration, presence of HLA-B27, current or past Achilles tendinitis, current or past dactylitis, current or past psoriasis, and a good response to NSAIDs were positively associated with AAU.

Ba6RE2Ti4O17 (RE = Nd, Sm, Gd, Dy-Yb): A Family of Rare-Earth-Based Layered Triangular Lattice Magnets.

The exploration of new rare-earth (RE)-based triangular-lattice materials plays a significant role in motivating the discovery of exotic magnetic states. Herein, we report a family of hexagonal perovskite compounds Ba6RE2Ti4O17 (RE = Nd, Sm, Gd, Dy-Yb) with a space group of P63/mmc, where magnetic RE3+ ions are distributed on the parallel triangular-lattice layers within the ab-plane and stacked in an 'AA'-type fashion along the c-axis. The low-temperature magnetic characterizations indicate that all synthesized Ba6RE2Ti4O17 compounds exhibit dominant antiferromagnetic (AFM) interactions and the absence of magnetic order down to 1.8 K. The isothermal magnetization and electron spin resonance results reveal the distinct magnetic anisotropy for the compounds with different RE ions. Moreover, the as-grown Ba6Nd2Ti4O17 single crystals exhibit Ising-like magnetic anisotropy with a magnetic easy-axis perpendicular to the triangle-lattice plane and no long-range magnetic order down to 80 mK, as the quantum spin liquid candidate with dominant Ising-type interactions.

Analogous Chain Selenite Chlorides Ba2M(SeO3)2Cl2 (M = Cu2+, Ni2+, Co2+, Mn2+) and Pb2Cu(SeO3)2Cl2 with Tunable Spin S: Syntheses and Characterizations.

A series of analogous chain selenite chlorides Ba2M(SeO3)2Cl2 (M = Cu 1, Ni 2, Co 3, Mn 4) and Pb2Cu(SeO3)2Cl2 5 with tunable spin S from S = 1/2 to S = 5/2 have been hydrothermally synthesized and characterized. These analogues crystallized in the orthorhombic Pnnm space group (monoclinic P21/n space group for 5) all containing M2+-SeO3-M2+ spin chains, which are further separated by the Ba2+ ions (Pb2+ for 5). The magnetic susceptibility results of 1, 2, and 5 show broad maxima around 80.0, 18.9, and 78.0 K, respectively, indicating good one-dimensional (1D) magnetism. Meanwhile, no long-range order (LRO) is observed down to 2 K for both 1 and 5, while the isostructural compounds 2, 3, and 4 exhibit LRO at 3.4 K, 10.8 K, and 5.7 K, respectively, which are further confirmed by the heat capacity and electron spin resonance results, as well as the observed spin-flop transitions in the M-H curves measured at 2 K below TN. The magnetizations of 1-5 at 7 T are still far from saturation. In addition, thermal stability and FT-IR and UV-vis-NIR spectroscopy of 1-5 are reported.

Discovery of a potent and selective PARP1 degrader promoting cell cycle arrest via intercepting CDC25C-CDK1 axis for treating triple-negative breast cancer.

PARP1 is a multifaceted component of DNA repair and chromatin remodeling, making it an effective therapeutic target for cancer therapy. The recently reported proteolytic targeting chimera (PROTAC) could effectively degrade PARP1 through the ubiquitin-proteasome pathway, expanding the therapeutic application of PARP1 blocking. In this study, a series of nitrogen heterocyclic PROTACs were designed and synthesized through ternary complex simulation analysis based on our previous work. Our efforts have resulted in a potent PARP1 degrader D6 (DC50 = 25.23 nM) with high selectivity due to nitrogen heterocyclic linker generating multiple interactions with the PARP1-CRBN PPI surface, specifically. Moreover, D6 exhibited strong cytotoxicity to triple negative breast cancer cell line MDA-MB-231 (IC50 = 1.04 µM). And the proteomic results showed that the antitumor mechanism of D6 was found that intensifies DNA damage by intercepting the CDC25C-CDK1 axis to halt cell cycle transition in triple-negative breast cancer cells. Furthermore, in vivo study, D6 showed a promising PK property with moderate oral absorption activity. And D6 could effectively inhibit tumor growth (TGI rate = 71.4 % at 40 mg/kg) without other signs of toxicity in MDA-MB-321 tumor-bearing mice. In summary, we have identified an original scaffold and potent PARP1 PROTAC that provided a novel intervention strategy for the treatment of triple-negative breast cancer.

Outcome of nonsurgical management of large cyst-like periapical lesions using a modified apical negative pressure irrigation system: a case series study.

OBJECTIVE: To assess the effectiveness of a self-constructed modified apical negative pressure irrigation (ANPI) system employing commonly used clinical instruments in nonsurgical root canal therapy (NSRCT) for large cyst-like periapical lesions (LCPLs). METHODS: From 2017 to 2022, 35 patients diagnosed with LCPLs (5-15 mm) via preoperative clinical and radiographic evaluations of endodontic origin underwent NSRCT combined with ANPI. These patients were subjected to postoperative clinical and radiographic follow-up at 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years, with a CBCT scan specifically conducted at 6-month follow-up. Through the reconstruction of three-dimensional cone beam computed tomography (CBCT) data, an early prognosis was facilitated by monitoring changes in lesion volume. Various treatment predictors-including sex, type of treatment, lesion size, preoperative pain, jaw, type of teeth involved, sealer extrusion, and the number of root canals-were meticulously analyzed. The evaluation of post-treatment outcomes leveraged both clinical observations and radiographic data collected during the follow-up periods. The Kruskal‒Wallis test and one-way ANOVA were also conducted to determine the independent factors influencing treatment outcomes. A significance level of 5% was established. RESULTS: Thirty-five teeth from 35 patients with a median age of 28 years (range 24-34) were treated; the median follow-up duration was 19 months (range 12-26). The overall success rate was 91.4%, with a median lesion reduction of 77.0% (range 54.2-96.4%) at 6 months. Patients under 30 years of age exhibited a significantly greater success rate than older patients did (100.0% vs. 80.0%, p = 0.037). Other factors, such as sex, jaw, treatment type, preoperative pain, cyst size, tooth location, sealer extrusion, and the number of roots, did not significantly impact treatment outcomes. CONCLUSIONS: Despite limitations related to the observational case-series study design and relatively small sample size, our findings suggest that utilizing the ANPI in the NSRCT for LCPLs may hold promise. The notably higher success rate in patients younger than 30 years is worth noting.

Comparison of fixed braces and clear braces for malocclusion treatment.

BACKGROUND: To study and compare the effects of clear aligners without brackets and traditional fixed aligners in orthodontic treatment. METHODS: The samples were collected from January 2022 to April 2023. The control group (n = 26) received orthodontic treatment using traditional fixed appliances. The research group (n = 20) received orthodontic treatment using the clear aligners without brackets. Compare the therapeutic effects and related evaluation indicators between two groups. RESULTS: The total effective ratio was compared between the 2 groups, and the study group was greater(P < 0.05). After treatment, the detected values of the periodontal condition indicators (plaque index, debris index, and gingival bleeding index), serum inflammatory factors (CRP, IL-6 and TNF-α) of the two groups, were less than before, also were all less than the control group. (P < 0.05). After therapy, in comparison of the control group, the value of mastication efficiency, comfort and psychological evaluation, sleep indicators and the points of the four dimensions of life quality in the study group was greater, and the detection results were obviously greater than before(P < 0.05). CONCLUSION: In the orthodontic therapy of sufferers with malocclusion, compared with the traditional fixed appliance, the clear aligners without brackets can enhance the treatment effects, improve the periodontal condition and masticatory function, and reduce the inflammatory responses, so that patients can feel more comfortable, thereby improving their psychology, sleep and quality of life. In the future, with the continual advancement of technology and people's pursuit of beauty, the application of clear aligners without brackets in orthodontic treatment will become more and more extensive. The continuous introduction of new materials and new technologies will further improve the effects and comfort of the clear aligners without brackets, reduce treatment time and discomfort, and also reduce patients' resistance to aligners, bringing patients a better treatment experience.

[Simultaneous determination of maltol and seventeen saponins in red and black ginseng by UPLC-PDA wavelength switching method].

This study developed a UPLC-PDA wavelength switching method to simultaneously determine the content of maltol and seventeen saponins in red and black ginseng and compared the quality differences of two different processed products of red and black ginseng. A Waters HSS T3 column(2. 1 mm×100 mm, 1. 8 µm) at 30 ℃ was adopted, with the mobile phase of acetonitrile(A) and water containing 0. 1% phosphoric acid(B) under gradient elution, the flow rate of 0. 3 m L·min~(-1), and the injection volume of 2 µL.The wavelength switching was set at 273 nm within 0-11 min and 203 nm within 11-60 min. The content results of multiple batches of red and black ginseng samples were analyzed by the hierarchical cluster analysis(HCA) and principal component analysis(PCA) to evaluate the quality difference. The results showed that the 18 constituents exhibited good linear relationships within certain concentration ranges, with the correlation coefficients(r) greater than 0. 999 1. The relative standard deviations(RSDs) of precision,repeatability, and stability were all less than 5. 0%. The average recoveries ranged from 95. 93% to 104. 2%, with an RSD of 1. 8%-4. 2%. The content determination results showed that the quality of red and black ginseng samples was different, and the two types of processed products were intuitively distinguished by HCA and PCA. The method is accurate, reliable, and reproducible. It can be used to determine the content of maltol and seventeen saponins in red and black ginseng and provide basic information for the quality evaluation and comprehensive utilization of red and black ginseng.

Assessment of sustainable development capacity of resource-based cities based on ecological carrying capacity -taking Zigong City, Sichuan Province, China as an example.

In this paper, the ecological footprint model is used to analyze the ecological carrying capacity of resource-based cities, and the ecological profit and loss state is calculated to evaluate their sustainable development ability. Taking Zigong City of Sichuan Province as an example, Research has shown that the ecological carrying capacity of Zigong City has been increasing year by year from 2006 to 2012 and from 2015 to 2021. There was a sharp decline from 2013 to 2014. The ecological and economic diversity index and the development capacity of the ecological and economic system showed an upward trend from 2006 to 2021. However, from 2006 to 2020, the ecological sustainable development index of Zigong City was below 0.2, indicating a serious unsustainable state. In 2021, it was in a moderately unsustainable state. According to the protection of cultivated land resources, forest resources, grassland resources, water resources, energy utilization and building land involved in Zigong City's sustainable development ability, the corresponding suggestions are put forward.Considering the economic, environmental and social aspects, this paper propose a path for sustainable development ability of resource-based cities.

The effects of Urban Identity on Entrepreneurial Choice.

This study investigate how the Urban identity(UI) influence the entrepreneurial choice of the migrants. Drawing on the identity economics theory in combination with microscopic perspective on entrepreneurship, we conclude that the UI increases the odds of self-employment of the migrants by 19.91% after solving endogenous problem in our sample of 126385 individuals from the China Migrants Dynamic Survey. We test the moderating effect of medical insurance and find that the interaction coefficient is positive. This study further reveals that the expanding social networks, improving urban integration, and increasing income are the three main mechanisms through which the UI influences the entrepreneurial choice of the migrants. So, we derive results consistent with our hypotheses. The findings have implications for both the entrepreneurship and national policy literature.

[Study on the Role and Mechanism of METTL3 Mediating the Up-regulation of 
m6A Modified Long Non-coding RNA THAP7-AS1 in Promoting the Occurrence of 
Lung Cancer].

BACKGROUND: Lung cancer is a major threat to human health. The molecular mechanisms related to the occurrence and development of lung cancer are complex and poorly known. Exploring molecular markers related to the development of lung cancer is helpful to improve the effect of early diagnosis and treatment. Long non-coding RNA (lncRNA) THAP7-AS1 is known to be highly expressed in gastric cancer, but has been less studied in other cancers. The aim of the study is to explore the role and mechanism of methyltransferase-like 3 (METTL3) mediated up-regulation of N6-methyladenosine (m6A) modified lncRNA THAP7-AS1 expression in promoting the development of lung cancer. METHODS: Samples of 120 lung cancer and corresponding paracancerous tissues were collected. LncRNA microarrays were used to analyze differentially expressed lncRNAs. THAP7-AS1 levels were detected in lung cancer, adjacent normal tissues and lung cancer cell lines by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The diagnostic value of THAP7-AS1 in lung cancer and the relationship between THAP7-AS1 expression and survival rate and clinicopathological parameters were analyzed. Bioinformatics analysis, methylated RNA immunoprecipitation (meRIP), RNA pull-down and RNA-immunoprecipitation (RIP) assay were used to investigate the molecular regulation mechanism of THAP7-AS1. Cell proliferation, migration, invasion and tumorigenesis of SPC-A-1 and NCI-H1299 cells were determined by MTS, colony-formation, scratch, Transwell and xenotransplantation in vivo, respectively. Expression levels of phosphoinositide 3-kinase/protein kenase B (PI3K/AKT) signal pathway related protein were detected by Western blot. RESULTS: Expression levels of THAP7-AS1 were higher in lung cancer tissues and cell lines (P<0.05). THAP7-AS1 has certain diagnostic value in lung cancer [area under the curve (AUC)=0.737], and its expression associated with overall survival rate, tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.05). METTL3-mediated m6A modification enhanced THAP7-AS1 expression. The cell proliferation, migration, invasion and the volume and mass of transplanted tumor were all higher in the THAP7-AS1 group compared with the NC group and sh-NC group of SPC-A-1 and NCI-H1299 cells, while the cell proliferation, migration and invasion were lower in the sh-THAP7-AS1 group (P<0.05). THAP7-AS1 binds specifically to Cullin 4B (CUL4B). The cell proliferation, migration, invasion, and expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphoinositide-3 kinase, catalytic subunit delta (PIK3CD), phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT) and phospho-mammalian target of rapamycin (p-mTOR) were higher in the THAP7-AS1 group compared with the Vector group of SPC-A-1 and NCI-H1299 cells (P<0.05). CONCLUSIONS: LncRNA THAP7-AS1 is stably expressed through m6A modification mediated by METTL3, and combines with CUL4B to activate PI3K/AKT signal pathway, which promotes the occurrence and development of lung cancer.

Tizanidine: Advances in Pharmacology & Therapeutics and Drug Formulations.

Background: Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023 American Geriatrics Society Beers Criteria® for potentially inappropriate medication use in older adults. In our geriatric practice, off-label use of tizanidine as preemptive analgesia drove us to find recent advances in its pharmacology and therapeutics. An update review of tizanidine was thus presented, aiming to bring the latest knowledge to clinicians and promote further research and practical exploration. Methods: Relevant literature up to December 2023 was identified through searches of PubMed, Web of Science, and Embase. Results: Tizanidine, a centrally acting alpha-2 adrenoceptor agonist with both antispastic and antispasmodic activity, shows efficacy in the common indications for all SMRs. From the perspective of drug safety, tizanidine has lower incidences of adverse events (injury, delirium, encephalopathy, falls, and opioid overdose) compared to baclofen, no association with risk of Alzheimer's disease as with orphenadrine, no risk of serotonin syndrome like metaxalone when comedicated with serotonergic drugs, no significant pharmacokinetic changes in CYP2C19 poor metabolizers unlike diazepam and carisoprodol, and no physically addictive or abuse properties like carisoprodol and diazepam. From the perspective of new and potential therapeutic uses, tizanidine has additional benefits (eg, gastroprotection that can improve patient tolerance to nonsteroidal anti-inflammatory agents, anti-neuropathic pain, a key component of multimodal analgesia strategy to reduce early postoperative pain, and anti-tumor effects). New delivery systems of tizanidine are developing to improve the pharmacokinetics of oral products, including buccal patches, transdermal delivery systems, nasal spray, and in situ rectal gel. Conclusion: Tizanidine is an SMR with unique features and may be an optimal initial choice for older adults. There would be more scientific studies, wider therapeutic applications, and new drug formulations in the future.