A review regarding the article 'Comparative efficacy and safety of mitral valve repair versus mitral valve replacement in Rheumatic heart disease: A high-value care systematic review and meta-analysis'.

Rheumatic heart disease remains a major cause of cardiovascular death worldwide. Limited real-world nationwide data are available to compare the long-term outcomes between mitral valve repair and replacement in rheumatic heart disease. For patients with RHD, MVP is the superior choice of surgical intervention owing to better long-term survival, reduced incidence of early mortality and thromboembolic events. However, it entails higher chances of re-operation at follow-up at four, eight and twelve years. Although feasible, surgeons may opt for MVR in patients with a worse prognosis. Whereas degenerative mitral repair for severe MR has been proven superior to replacement, the optimal operative strategy for mitral RHD remains unclear. In developing countries, mitral RHD commonly develops in young patients, predominantly consists of MR rather than MS, and occurs more frequently than in the United States. In addition, the predominant MR etiology (rather than MS), relatively early intervention in the RHD timeline, and variation in Carpentier MR types among developing world populations further make these rheumatic MVs more amenable to repair than replacement. Patients should be carefully selected for mitral valve repair because of its higher reoperation rate, particularly those with previous percutaneous transvenous mitral commissurotomy. Careful assessment of anterior leaflet mobility/calcification to determine mitral repair or replacement was associated with improved outcomes. This decision-making strategy may alter the threshold for rheumatic mitral replacement in the current valve-in-valve era.

The impact of regional sports industry aggregation on residents' health level in China.

Health is the basis for human survival and development and is an important symbol to evaluate a country's economic growth and social progress. This article measures the degree of sports industry agglomeration in different regions of China and uses the Moran index to verify the existence of global autocorrelation in sports agglomeration. Next, the spatial Durbin model was used to verify the spatial spillover effect of sports industry agglomeration on the health level of residents, and the following conclusions were obtained.Firstly, there is spatial autocorrelation and heterogeneity in the clustering level of China's sports industry. The spatial distribution is extremely uneven, and different regions have formed relatively stable spatial patterns. Secondly, the degree of aggregation of the sports industry can reduce the number of per capita visits and have a positive spatial spillover effect on the health of residents. Not only can it promote the health level of residents in the province, but it also has spatial spillover effects on surrounding areas.Finally, based on the research results, the following conclusions are proposed in this article. Policy recommendations include increasing investment in sports talent cultivation, accelerating the construction of sports center cities, and increasing residents' attention to sports to improve residents' health.

Identification of a lactate metabolism-related lncRNAs signature for predicting the prognosis in patients with kidney renal clear cell carcinoma.

Background: Lactate metabolism-related (LMR) long noncoding RNAs (lncRNAs) play significant roles in various cancers, but their impact on kidney renal clear cell carcinoma (KIRC) remains unclear. This study aimed to explore the value of LMR lncRNA and develop a risk model for KIRC. Methods: Data on KIRC patients were downloaded from The Cancer Genome Atlas (TCGA) database. LMR lncRNAs were identified by co-expression, univariate and multivariate analyses, and least absolute shrinkage selection operator (LASSO) regression analysis. Subsequently, a prognostic signature was constructed and its accuracy was verified. To predict the prognosis of KIRC effectively, we established a nomogram based on this information. Enrichment analysis, tumor mutational burden (TMB) analysis, immune status and the therapeutic sensitivities of KIRC patients were also investigated. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of lncRNAs. Results: We constructed and verified a predictive signature based on six LMR lncRNA (LINC00944, AC090772.3, Z83745.1, AP001267.3, AC092296.1, and AL162377.1) to assess the patient prognoses of KIRC. Survival analyses showed a more unfavorable outcome in high-risk patients (P<0.001). Enrichment analysis demonstrated that immune-related pathways were enriched in the high-risk group. Besides, patients classified by risk scores had distinguishable immune status, TMB, response to immunotherapy, and sensitivity to chemotherapy and targeted drugs. Conclusions: The LMR lncRNAs signature has significant implications for prognostic assessment and clinical treatment guidance in KIRC.

Dimensional Regulation in Metal-Free Perovskites by Compositional Engineering to Achieve Record Low X-ray Detection Limits.

Utilizing the manipulation of perovskite dimensions has been proven as an effective approach in regulating perovskite properties. Nevertheless, achieving precise control over the dimensions of perovskites within the same system poses a significant challenge. In this study, we introduce a sophisticated method to attain precise dimensional control in metal-free perovskites (MFPs), specifically through the process of octahedron tailoring by compositional engineering. Accordingly, we successfully instigated a transition from HPIP-NH4I3⋅H2O (3D), HPIP2-NH4I5 (2D) and HPIP3-NH4I7 (1D) structures. Notably, HPIP2-NH4I5 is the first 2D MFP. As anticipated, these perovskites exhibited completely distinct fluorescence and X-ray detection capabilities due to their differing dimensions. Remarkably, the 2D HPIP2-NH4I5 device effectively hindered ion migration perpendicular to the 2D layers, achieving the lowest detection limit of 12.2 nGyairs-1 among metal-free single crystals-based detectors. This study expands the dimensionality control strategies for MFPs and introduces, for the first time, the potential of 2D MFPs as high-performance X-ray detectors, thereby enriching the diversity of the MFPs family.

The top 100 most cited articles in the treatment of basal cell carcinoma over the last decade: A bibliometric analysis and review.

Basal cell carcinoma (BCC) represents the most prevalent cancer globally. The past decade has witnessed significant advancements in BCC treatment, primarily through bibliometric studies. Aiming to perform a comprehensive bibliometric analysis of BCC treatments to comprehend the research landscape and identify trends within this domain, a dataset comprising 100 scientific publications from the Web of Science Core Collection was analyzed. Country co-operation, journal co-citation, theme bursts, keyword co-occurrence, author co-operation, literature co-citation, and field-specific references were examined using VOSviewer and CiteSpace visualization tools. These articles, published between 2013 and 2020, originated predominantly from 30 countries/regions and 159 institutions, with the USA and Germany at the forefront, involving a total of 1118 authors. The keyword analysis revealed significant emphasis on the hedgehog pathway, Mohs micrographic surgery, and photodynamic therapy. The research shows developed nations are at the forefront in advancing BCC therapies, with significant focus on drugs targeting the hedgehog pathway. This treatment avenue has emerged as a crucial area, meriting considerable attention in BCC therapeutic strategies.

[Metabolomics of quality formation of different cultivars of Peucedanum praeruptorum].

This study aims to reveal the quality formation of different cultivars of Peucedanum praeruptorum based on the metabolic differences and provide a theoretical basis for the development and utilization of this medicinal herb. The non-target metabonomics analysis based on ultra-high performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS) was conducted for six cultivars(YS, H, LZ, LY, LX, and Z) of P. praeruptorum of the same origin and at the same development stage. The principal component analysis, orthogonal partial least squares discriminant analysis, and univariate statistical analysis were carried out to screen the differential metabolites of different cultivars. The potential biomarkers associated with quality formation were predicted based on the mass-to-charge ratio, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, information of relevant literature, and correlation analysis. The results showed that metabolites differed significantly among the six cultivars, and 571 and 465 differential metabolites were obtained in the positive and negative ion modes, respectively. From the differential metabolites, 22 potential biomarkers related to quality formation were predicted, which involved 9 metabolic pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, biosynthesis of phenylpropanoids, and biosynthesis of plant hormones. Compared with the YS cultivar, other cultivars showed decreased concentrations of psoralen, imperatorin, and luvangetin and increased concentrations of 7-hydroxycoumarine, esculetin, columbianetin, and jasmonic acid, which were involved in the biosynthesis of phenylpropanoids. The concentrations of 2-succinylbenzoate, heraclenol, and L-tyrosine involved in other metabolic pathways decreased, especially in the Z and H cultivars. Therefore, regulating the biosynthesis of phenylpropanoids is one of the key mechanisms for improving the cultivar quality of P. praeruptorum. The Z and H cultivars have better quality and metabolic processes than other cultivars and thus can be used for the screening and breeding of high-quality germplasm.

A chimeric adenovirus-vectored vaccine based on Beta spike and Delta RBD confers a broad-spectrum neutralization against Omicron-included SARS-CoV-2 variants.

Urgent research into innovative severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus-vectored vaccine named Ad5-Beta/Delta. This vaccine was created by incorporating the receptor-binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5-Beta/Deta vaccine induced robust broad-spectrum neutralization against Omicron BA.5-included variants. IN immunization with Ad5-Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue-resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5-Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5-Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5-Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS-CoV-2 pre-Omicron variants of concern and BA.5-included Omicron subvariants.

Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization.

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.

Genomic insights into local adaptation and vulnerability of Quercus longinux to climate change.

BACKGROUND: Climate change is expected to alter the factors that drive changes in adaptive variation. This is especially true for species with long life spans and limited dispersal capabilities. Rapid climate changes may disrupt the migration of beneficial genetic variations, making it challenging for them to keep up with changing environments. Understanding adaptive genetic variations in tree species is crucial for conservation and effective forest management. Our study used landscape genomic analyses and phenotypic traits from a thorough sampling across the entire range of Quercus longinux, an oak species native to Taiwan, to investigate the signals of adaptation within this species. RESULTS: Using ecological data, phenotypic traits, and 1,933 single-nucleotide polymorphisms (SNPs) from 205 individuals, we classified three genetic groups, which were also phenotypically and ecologically divergent. Thirty-five genes related to drought and freeze resistance displayed signatures of natural selection. The adaptive variation was driven by diverse environmental pressures such as low spring precipitation, low annual temperature, and soil grid sizes. Using linear-regression-based methods, we identified isolation by environment (IBE) as the optimal model for adaptive SNPs. Redundancy analysis (RDA) further revealed a substantial joint influence of demography, geology, and environments, suggesting a covariation between environmental gradients and colonization history. Lastly, we utilized adaptive signals to estimate the genetic offset for each individual under diverse climate change scenarios. The required genetic changes and migration distance are larger in severe climates. Our prediction also reveals potential threats to edge populations in northern and southeastern Taiwan due to escalating temperatures and precipitation reallocation. CONCLUSIONS: We demonstrate the intricate influence of ecological heterogeneity on genetic and phenotypic adaptation of an oak species. The adaptation is also driven by some rarely studied environmental factors, including wind speed and soil features. Furthermore, the genetic offset analysis predicted that the edge populations of Q. longinux in lower elevations might face higher risks of local extinctions under climate change.

[Corrigendum] Long non­coding RNA NEAT1 promotes ovarian cancer cell invasion and migration by interacting with miR­1321 and regulating tight junction protein 3 expression.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, for the cell invasion and migration assay images shown for the A2780 cell line in Figs. 1 and Fig. 3 on p. 3433 and 3435 respectively, the same data panel had apparently been selected to show the results of the si­NEAT1 experiment in Fig. 1 and the si­TJP3 experiment in Fig. 3. After having re­examined their original data, the authors have realized that the image correctly shown for Fig. 1 was inadvertently copied across to Fig. 3. The corrected version of Fig. 3, now correctly showing the data for the si­TJP3 experiment with the A2780 cell line, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper. All the authors agree to the publication of this Corrigendum, are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 3429­3439, 2020; DOI: 10.3892/mmr.2020.11428].

Impact of third-order dispersion on the dynamics of dissipative solitons in an ultrafast fiber laser.

Dissipative solitons (DSs), due to the complex interplay among dispersion, nonlinear, gain and loss, illustrate abundant nonlinear dynamics behaviors. Especially, dispersion plays an important role in the research of DS dynamics in ultrafast fiber lasers. Previous studies have mainly focused on the effect of even-order dispersion, i.e., group velocity dispersion (GVD) and fourth-order dispersion. In fact, odd-order dispersions, such as third-order dispersion (TOD), also significantly influences the dynamics of DSs. However, due to the lack of dispersion engineering tools, few experimental researches in this domain have been reported. In this work, by employing a pulse shaper in ultrafast fiber laser, an in-depth exploration of the DS dynamics influenced by TOD was conducted. With the increase of TOD value, the stable single DS undergoes a splitting into two solitons and then enters explosion state, and ultimately evolves into a chaotic state. The laser operation state is correlated to dispersion profile, which could be controlled by TOD. Here, the positive dispersion at long-wavelength side will be gradually shifted to negative dispersion by increasing the TOD, where soliton effect will drive the transitions. These findings offer valuable insights into the nonlinear dynamics of ultrafast lasers and may also foster applications involving higher-order dispersion.

Palmitoylation of KSHV pORF55 is required for Golgi localization and efficient progeny virion production.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus etiologically associated with multiple malignancies. Both latency and sporadic lytic reactivation contribute to KSHV-associated malignancies, however, the specific roles of many KSHV lytic gene products in KSHV replication remain elusive. In this study, we report that ablation of ORF55, a late gene encoding a tegument protein, does not impact KSHV lytic reactivation but significantly reduces the production of progeny virions. We found that cysteine 10 and 11 (C10 and C11) of pORF55 are palmitoylated, and the palmytoilation is essential for its Golgi localization and secondary envelope formation. Palmitoylation-defective pORF55 mutants are unstable and undergo proteasomal degradation. Notably, introduction of a putative Golgi localization sequence to these palmitoylation-defective pORF55 mutants restores Golgi localization and fully reinstates KSHV progeny virion production. Together, our study provides new insight into the critical role of pORF55 palmitoylation in KSHV progeny virion production and offers potential therapeutic targets for the treatment of related malignancies.

Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling Pathway.

Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.

Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis.

Circulating tumor cells (CTCs) are precursors of distant metastasis in a subset of cancer patients. A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis. It remains elusive how CTCs evade immune surveillance and elimination by immune cells. In this study, we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle (EVs)-derived CD45 (termed as CD45+ CTCs) that resisted T cell attack. A higher percentage of CD45+ CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients. Moreover, CD45+ tumor cells orchestrated an immunosuppressive milieu and CD45+ CTCs exhibited remarkably stronger metastatic potential than CD45- CTCs in vivo. Mechanistically, CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells, thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response. Together, these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis, providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

Macrophage polarization: an important role in inflammatory diseases.

Macrophages are crucial cells in the human body's innate immunity and are engaged in a variety of non-inflammatory reactions. Macrophages can develop into two kinds when stimulated by distinct internal environments: pro-inflammatory M1-like macrophages and anti-inflammatory M2-type macrophages. During inflammation, the two kinds of macrophages are activated alternatively, and maintaining a reasonably steady ratio is critical for maintaining homeostasis in vivo. M1 macrophages can induce inflammation, but M2 macrophages suppress it. The imbalance between the two kinds of macrophages will have a significant impact on the illness process. As a result, there are an increasing number of research being conducted on relieving or curing illnesses by altering the amount of macrophages. This review summarizes the role of macrophage polarization in various inflammatory diseases, including autoimmune diseases (RA, EAE, MS, AIH, IBD, CD), allergic diseases (allergic rhinitis, allergic dermatitis, allergic asthma), atherosclerosis, obesity and type 2 diabetes, metabolic homeostasis, and the compounds or drugs that have been discovered or applied to the treatment of these diseases by targeting macrophage polarization.

Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG).

N1-methyladenosine (m1A) modification is a crucial post-transcriptional regulatory mechanism of messenger RNA (mRNA) in living organisms. Few studies have focused on analysis of m1A regulators in lower-grade gliomas (LGG). We employed the Nonnegative Matrix Factorization (NMF) technique on The Cancer Genome Atlas (TCGA) dataset to categorize LGG patients into 2 groups. These groups exhibited substantial disparities in terms of both overall survival (OS) and levels of infiltrating immune cells. We collected the significantly differentially expressed immune-related genes between the 2 clusters, and performed LASSO regression analysis to obtain m1AScores, and established an m1A-related immune-related gene signature (m1A-RIGS). Next, we categorized all patients with LGG into high- and low-risk subgroups, predictive significance of m1AScore was confirmed by conducting univariate/multivariate Cox regression analyses. Additionally, we confirmed variations in immune-related cells and ssGSEA and among the high-/low-risk subcategories in the TCGA dataset. Finally, our study characterized the effects of MSR1 and BIRC5 on LGG cells utilizing Edu assay and flow cytometry to explore the effects of modulation of these genes on glioma. The results of this study suggested that m1A-RIGS may be an excellent prognostic indicator for patients with LGG, and could also promote development of novel immune-based treatment strategies for LGG. Additionally, BIRC5 and MSR1 may be potential therapeutic targets for LGG.

Enhanced Photocatalytic Nitrogen Reduction via Bismuth Nanoparticle-Decorating ZnCdS Solid Solution.

The construction of photocatalysts with a surface plasmon resonance effect (SPR) has been demonstrated as a highly effective strategy for enhancing photocatalytic efficiency. In this paper, we synthesized a catalyst with bismuth metal loaded on ZnCdS nanospheres for an efficient photocatalytic nitrogen reduction reaction (PNRR). The SPR effect induced by Bi nanoparticles under light excitation significantly promoted the ammonia production efficiency of the photocatalyst. Under air ambient conditions with lactic acid as the sacrificial agent, the photocatalytic NH4+ yield of 3% Bi@ZnCdS was 58.93 µmol·g-1·h-1, which exhibited an approximately 7.7 times that of the pure phase ZnCdS. The experimental characterization results demonstrate that the incorporation of metallic bismuth enhances the light absorption capacity of the catalyst and improves the separation efficiency of the photogenerated carriers. Theoretical calculations proved that Bi NPs provide more photogenerated electrons to convert N2 to NH3 for solid-solution ZnCdS. This work presents a novel concept for the development of advanced plasma nanomaterials to enhance the photocatalytic nitrogen fixation reaction.

cGMP-dependent kinase 2, Na+/H+ exchanger NHE3, and PDZ-adaptor NHERF2 co-assemble in apical membrane microdomains.

AIM: Trafficking, membrane retention, and signal-specific regulation of the Na+/H+ exchanger 3 (NHE3) are modulated by the Na+/H+ Exchanger Regulatory Factor (NHERF) family of PDZ-adapter proteins. This study explored the assembly of NHE3 and NHERF2 with the cGMP-dependent kinase II (cGKII) within detergent-resistant membrane microdomains (DRMs, "lipid rafts") during in vivo guanylate cycle C receptor (Gucy2c) activation in murine small intestine. METHODS: Small intestinal brush border membranes (siBBMs) were isolated from wild type, NHE3-deficient, cGMP-kinase II-deficient, and NHERF2-deficient mice, after oral application of the heat-stable Escherichia coli toxin (STa) analog linaclotide. Lipid raft and non-raft fractions were separated by Optiprep density gradient centrifugation of Triton X-solubilized siBBMs. Confocal microscopy was performed to study NHE3 redistribution after linaclotide application in vivo. RESULTS: In the WT siBBM, NHE3, NHERF2, and cGKII were strongly raft associated. The raft association of NHE3, but not of cGKII, was NHERF2 dependent. After linaclotide application to WT mice, lipid raft association of NHE3 decreased, that of cGKII increased, while that of NHERF2 did not change. NHE3 expression in the BBM shifted from a microvillar to a terminal web region. The linaclotide-induced decrease in NHE3 raft association and in microvillar abundance was abolished in cGKII-deficient mice, and strongly reduced in NHERF2-deficient mice. CONCLUSION: NHE3, cGKII, and NHERF2 form a lipid raft-associated signal complex in the siBBM, which mediates the inhibition of salt and water absorption by Gucy2c activation. NHERF2 enhances the raft association of NHE3, which is essential for its close interaction with the exclusively raft-associated activated cGKII.

Research on the dynamic behavior of flexible drilling tools in ultrashort-radius radial horizontal wells.

A flexible drilling tool is a special drilling tool for ultrashort-radius radial horizontal wells. This tool is composed of many parts and has the characteristics of a multibody system. In this paper, a numerical method for the dynamic analysis of flexible drilling tools is proposed. The flexible drill tool is discretized into spatial beam elements, while the multilayer contact of the flexible drilling tool is represented by the multilayer dynamic gap element, and the dynamic model of the multibody system for the flexible drilling tool's multilayer contact is established, considering the interaction force between the drill bit and the rock. The nonlinear dynamic equation is solved using the Newmark method and Newton-Raphson method. An analysis of the dynamic behavior of a flexible drilling tool is conducted. The results indicate that the flexible drilling tool experiences vortex formation due to the interaction between the flexible drilling pipe and the guide pipe, leading to increased friction and wear. This situation hinders safe drilling operations with flexible drilling tools. The collision force of the flexible drilling tool near the bottom of the hole is more severe than that of the other tool types, which may lead to failure of the connection.

The protective effects of ligustrazine on ischemic stroke: a systematic review and meta-analysis of preclinical evidence and possible mechanisms.

Introduction: The objective of this study is to systematically evaluate the effect of ligustrazine on animal models of ischemic stroke and investigate its mechanism of action. Materials and Methods: The intervention of ligustrazine in ischemic diseases research on stroke model animals was searched in the Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP Database (VIP), Chinese Biomedical Literature Database (CBM), Cochrane Library, PubMed, Web of Science, and Embase databases. The quality of the included literature was evaluated using the Cochrane risk of bias tool. The evaluation included measures such as neurological deficit score (NDS), percentage of cerebral infarction volume, brain water content, inflammation-related factors, oxidative stress-related indicators, apoptosis indicators (caspase-3), and blood-brain barrier (BBB) permeability (Claudin-5). Results: A total of 32 studies were included in the analysis. The results indicated that ligustrazine significantly improved the neurological function scores of ischemic stroke animals compared to the control group (SMD = -1.84, 95% CI -2.14 to -1.55, P < 0.00001). It also reduced the percentage of cerebral infarction (SMD = -2.97, 95% CI -3.58 to -2.36, P < 0.00001) and brain water content (SMD = -2.37, 95% CI -3.63 to -1.12, P = 0.0002). In addition, ligustrazine can significantly improve various inflammatory factors such as TNF-α (SMD = -7.53, 95% CI -11.34 to -3.72, P = 0.0001), IL-1ß (SMD = -2.65, 95% CI -3.87 to -1.44, P < 0.0001), and IL-6 (SMD = -5.55, 95% CI -9.32 to -1.78, P = 0.004). It also positively affects oxidative stress-related indicators including SOD (SMD = 4.60, 95% CI 2.10 to 7.10, P = 0.0003), NOS (SMD = -1.52, 95% CI -2.98 to -0.06, P = 0.04), MDA (SMD = -5.31, 95% CI -8.48 to -2.14, P = 0.001), and NO (SMD = -5.33, 95% CI -8.82 to -1.84, P = 0.003). Furthermore, it shows positive effects on the apoptosis indicator caspase-3 (SMD = -5.21, 95% CI -7.47 to -2.94, P < 0.00001) and the expression level of the sex-related protein Claudin-5, which influences BBB permeability (SMD = 7.38, 95% CI 3.95 to 10.82, P < 0.0001). Conclusion: Ligustrazine has been shown to have a protective effect in animal models of cerebral ischemic injury. Its mechanism of action is believed to be associated with the reduction of inflammation and oxidative stress, the inhibition of apoptosis, and the repair of BBB permeability. However, further high-quality animal experiments are required to validate these findings.