Combination of UPLC-Q-TOF/MS and network pharmacology to reveal the mechanism of Chaihu-jia-Longgu-Muli decoction for treating vertigo with anxiety disorder.

Chaihu-jia-Longgu-Muli decoction (CLMD) has been proven clinically effective in treating vertigo with anxiety disorder. However, the mechanism is not clear. This study aimed to explore the mechanism of CLMD in treating vertigo with anxiety disorder based on ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) and network pharmacology. UPLC-Q-TOF/MS was performed to identify the compounds in blood and the targets of compounds of CLMD in vertigo and anxiety were searched using databases. A protein-protein interaction network was built to screen the core targets. The core targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, the vertigo with anxiety rat model was used to verify the results. A total of 22 compounds were absorbed into the blood. Eighty-one potential targets associated with CLMD for vertigo with anxiety disorder were identified through network pharmacological analysis. Subsequently, GO and KEGG analysis showed that CLMD treatment for vertigo with anxiety disorder is associated with neurotransmitter levels and other pertinent physiological processes. The results of the animal experiments showed that CLMD decreased the levels of serotonin, norepinephrine and dopamine, alleviating the symptoms of vertigo and anxiety disorder in model rats. The study revealed CLMD could alleviate vertigo and anxiety symptoms through reducing the levels of neurotransmitters.

Chitosan-coated liposome with lysozyme-responsive properties for on-demand release of levofloxacin.

As an anti-infection antibiotic delivery route, a drug-controlled release system based on a specific condition stimulus response can enhance drug stability and bioavailability, reduce antibiotic resistance, achieve on-demand release and improve targeting and utilization efficiency. In this study, chitosan-coated liposomes containing levofloxacin (Lef@Lip@CS) were prepared with lysozyme in body fluids serving as an intelligent "switch" to enable accurate delivery of antibiotics through the catalytic degradation ability of chitosan. Good liposome encapsulation efficacy (64.89 ± 1.86 %) and loading capacity (5.28 ± 0.18 %) were achieved. The controlled-release behavior and morphological characterization before and after enzymatic hydrolysis confirmed that the levofloxacin release rate depended on the lysozyme concentration and the degrees of deacetylation of chitosan. In vitro bacteriostatic experiments showed significant differences in the effects of Lef@Lip@CS before and after enzyme addition, with 6-h inhibition rate of 72.46 % and 100 %, and biofilm removal rates of 51 % and 71 %, respectively. These findings show that chitosan-coated liposomes are a feasible drug delivery system responsive to lysozyme stimulation.

Low-intensity pulsed ultrasound promotes the osteogenesis of mechanical force-treated periodontal ligament cells via Piezo1.

Background: Low-intensity pulsed ultrasound (LIPUS) can accelerate tooth movement and preserve tooth and bone integrity during orthodontic treatment. However, the mechanisms by which LIPUS affects tissue remodeling during orthodontic tooth movement (OTM) remain unclear. Periodontal ligament cells (PDLCs) are pivotal in maintaining periodontal tissue equilibrium when subjected to mechanical stimuli. One notable mechano-sensitive ion channel, Piezo1, can modulate cellular function in response to mechanical cues. This study aimed to elucidate the involvement of Piezo1 in the osteogenic response of force-treated PDLCs when stimulated by LIPUS. Method: After establishing rat OTM models, LIPUS was used to stimulate rats locally. OTM distance and alveolar bone density were assessed using micro-computed tomography, and histological analyses included hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining and immunohistochemical staining. GsMTx4 and Yoda1 were respectively utilized for Piezo1 functional inhibition and activation experiments in rats. We isolated human PDLCs (hPDLCs) in vitro and evaluated the effects of LIPUS on the osteogenic differentiation of force-treated hPDLCs using real-time quantitative PCR, Western blot, alkaline phosphatase and alizarin red staining. Small interfering RNA and Yoda1 were employed to validate the role of Piezo1 in this process. Results: LIPUS promoted osteoclast differentiation and accelerated OTM in rats. Furthermore, LIPUS alleviated alveolar bone resorption under pressure and enhanced osteogenesis of force-treated PDLCs both in vivo and in vitro by downregulating Piezo1 expression. Subsequent administration of GsMTx4 in rats and siPIEZO1 transfection in hPDLCs attenuated the inhibitory effect on osteogenic differentiation under pressure, whereas LIPUS efficacy was partially mitigated. Yoda1 treatment inhibited osteogenic differentiation of hPDLCs, resulting in reduced expression of Collagen Ⅰα1 and osteocalcin in the periodontal ligament. However, LIPUS administration was able to counteract these effects. Conclusion: This research unveils that LIPUS promotes the osteogenesis of force-treated PDLCs via downregulating Piezo1.

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

Bridging the gap: Integrating exercise mimicry into chronic disease management through suppressing chronic inflammation.

BACKGROUND: Chronic inflammation is a common hallmark of many chronic diseases. Although exercise holds paramount importance in preventing and managing chronic diseases, adherence to exercise programs can be challenging for some patients. Consequently, there is a pressing need to explore alternative strategies to emulate the anti-inflammatory effects of exercise for chronic diseases. AIM OF REVIEW: This review explores the emerging role of green tea bioactive components as potential mitigators of chronic inflammation, offering insights into their capacity to mimic the beneficial effects of exercise. We propose that bioactive components in green tea are promising agents for suppressing chronic inflammation, suggesting their unique capability to replicate the health benefits of exercise. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review focuses on several key concepts, including chronic inflammation and its role in chronic diseases, the anti-inflammatory effects of regular exercise, and bioactive components in green tea responsible for its health benefits. It elaborates on scientific evidence supporting the anti-inflammatory properties of green tea bioactive components, such as epigallocatechin gallate (EGCG), and theorizes how these bioactive components might replicate the effects of exercise at a molecular level. Through a comprehensive analysis of current research, this review proposes a novel perspective on the application of green tea as a potential intervention strategy to suppress chronic inflammation, thereby extending the benefits akin to those achieved through exercise.

Lipidomic Comparisons of Whole Cream Buttermilk Whey and Cheese Whey Cream Buttermilk of Caprine Milk.

Buttermilk is a potential material for the production of a milk fat globule membrane (MFGM) and can be mainly classified into two types: whole cream buttermilk and cheese whey cream buttermilk (WCB). Due to the high casein micelle content of whole cream buttermilk, the removal of casein micelles to improve the purity of MFGM materials is always required. This study investigated the effects of rennet and acid coagulation on the lipid profile of buttermilk rennet-coagulated whey (BRW) and buttermilk acid-coagulated whey (BAW) and compared them with WCB. BRW has significantly higher phospholipids (PLs) and ganglioside contents than BAW and WCB. The abundance of arachidonic acid (ARA)- and eicosapentaenoic acid (EPA)-structured PLs was higher in WCB, while docosahexaenoic acid (DHA)-structured PLs were higher in BRW, indicating that BRW and WCB intake might have a greater effect on improving cardiovascular conditions and neurodevelopment. WCB and BRW had a higher abundance of plasmanyl PL and plasmalogen PL, respectively. Phosphatidylcholine (PC) (28:1), LPE (20:5), and PC (26:0) are characteristic lipids among BRW, BAW, and WCB, and they can be used to distinguish MFGM-enriched whey from different sources.

Mechanisms of Sorafenib Resistance in HCC Culture Relate to the Impaired Membrane Expression of Organic Cation Transporter 1 (OCT1).

Introduction: Sorafenib, an FDA-approved drug for advanced hepatocellular carcinoma (HCC) treatment, encounters resistance in many patients. Deciphering the mechanisms underlying sorafenib resistance is crucial for devising alternative strategies to overcome it. Aim: This study aimed to investigate sorafenib resistance mechanisms using a diverse panel of HCC cell lines. Methods: HCC cell lines were subjected to continuous sorafenib treatment, and stable cell lines (Huh 7.5 and Huh 7PX) exhibiting sustained growth in its presence were isolated. The investigation of drug resistance mechanisms involved a comparative analysis of drug-targeted signal transduction pathways (EGFR/RAF/MEK/ERK/Cyclin D), sorafenib uptake, and membrane expression of the drug uptake transporter. Results: HCC cell lines (Huh 7.5 and Huh 7PX) with a higher IC50 (10µM) displayed a more frequent development of sorafenib resistance compared to those with a lower IC50 (2-4.8µM), indicating a potential impact of IC50 variation on initial treatment response. Our findings reveal that activated overexpression of Raf1 kinases and impaired sorafenib uptake, mediated by reduced membrane expression of organic cation transporter-1 (OCT1), contribute to sorafenib resistance in HCC cultures. Stable expression of the drug transporter OCT1 through cDNA transfection or adenoviral delivery of OCT1 mRNA increased sorafenib uptake and successfully overcame sorafenib resistance. Additionally, consistent with sorafenib resistance in HCC cultures, cirrhotic liver-associated human HCC tumors often exhibited impaired membrane expression of OCT1 and OCT3. Conclusion: Intrinsic differences among HCC cell clones, affecting sorafenib sensitivity at the expression level of Raf kinases, drug uptake, and OCT1 transporters, were identified. This study underscores the potential of HCC tumor targeted OCT1 expression to enhance sorafenib treatment response.

Enantioselective biomarkers of maize toxicity induced by hexabromocyclododecane based on submicroscopic structure, gene expression and molecular docking.

Hexabromocyclododecane (HBCD), as a monitored chemical of the Chemical Weapons Convention, the Stockholm Convention and the Action Plan for New Pollutants Treatment in China, raises significant concerns on its impact of human health and food security. This study investigated enantiomer-specific biomarkers of HBCD in maize (Zea mays L.). Upon exposure to HBCD enantiomers, the maize root tip cell wall exhibited thinning, uneven cell gaps, and increased deposition on the cell outer wall. Elevated malondialdehyde (MDA) indicated lipid peroxidation, with higher mitochondrial membrane potential (MMP) inhibition in (+)-enantiomer treatments (47.2%-57.9%) than (-)-enantiomers (14.4%-37.4%). The cell death rate significantly increased by 37.7%-108.8% in roots and 16.4%-62.4% in shoots, accompanied by the upregulation of superoxide dismutase isoforms genes. Molecular docking presenting interactions between HBCD and target proteins, suggested that HBCD has an affinity for antioxidant enzyme receptors with higher binding energy for (+)-enantiomers, further confirming their stronger toxic effects. All indicators revealed that oxidative damage to maize seedlings was more severe after treatment with (+)-enantiomers compared to (-)-enantiomers. This study elucidates the biomarkers of phytotoxicity evolution induced by HBCD enantiomers, providing valuable insights for the formulation of more effective policies to safeguard environmental safety and human health in the future.

Reducing air pollution does not necessarily reduce related adults' mortality burden: Variations in 177 countries with different economic levels.

Prolonged exposure to PM2.5 is associated with increased mortality. However, reducing air pollution concentrations does not necessarily reduce the related burden of deaths. Here, we aim to estimate the variations in PM2.5-related mortality due to contributions from key factors - PM2.5 concentration, population exposure, and healthcare levels - for 177 countries from 2000 to 2018 at the 1-km grid scale according to the Global Mortality Exposure Model (GEMM) model. We find that global reductions in PM2.5-related deaths mainly come from high and upper-middle income countries, where lowered air pollutant concentration and better healthcare can offset mortality burdens caused by increasing exposed populations. Changes in population exposure to PM2.5 contribute the most (54 %) to change in global related deaths over the examined period, followed by changes in healthcare (-42 %) and pollution concentrations (4 %). The impacts vary across countries and regions within them due to other drivers, which are significantly influenced by development status. Policies aiming at reducing PM2.5 associated health risks need to account for country-specific balances of these key socioeconomic drivers.

Tuning the Thermochemistry and Reactivity of a Series of Cu-Based 4H+/4e- Electron-Coupled-Proton Buffers.

Electron-coupled-proton buffers (ECPBs) store and deliver protons and electrons in a reversible fashion. We have recently reported an ECPB based on Cu and a redox-active ligand that promoted 4H+/4e- reversible transformations (J. Am. Chem. Soc. 2022, 144, 16905). Herein, we report a series of Cu-based ECPBs in which the ability of these to accept and/or donate H• equivalents can be tuned via ligand modification. The thermochemistry of the 4H+/4e- ECPB equilibrium was determined using open-circuit potential measurements. The reactivity of the ECPBs against proton-coupled electron transfer (PCET) reagents was also analyzed, and the results obtained were rationalized based on the thermochemical parameters. Experimental and computational analysis of the thermochemistry of the H+/e- transfers involved in the 4H+/4e- ECPB transformations found substantial differences between the stepwise (namely, BDFE1, BDFE2, BDFE3, and BDFE4) and average bond dissociation free energy values (BDFEavg.). Our analysis suggests that this "redox unleveling" is critical to promoting the disproportionation and ligand-exchange reactions involved in the 4H+/4e- ECPB equilibria. The difference in BDFEavg. within the series of Cu-based ECPBs was found to arise from a substantial change in the redox potential (E1/2) upon modification of the ligand scaffold, which is not fully compensated for by a change in the acidity/basicity (pKa), suggesting "thermochemical decompensation".

A chitosan-coated PCL/nano-hydroxyapatite aerogel integrated with a nanofiber membrane for providing antibacterial activity and guiding bone regeneration.

A guided bone regeneration (GBR) membrane can act as a barrier to prevent the invasion and interference from foreign soft tissues, promoting infiltration and proliferation of osteoblasts in the bone defect area. Herein, a composite scaffold with dual functions of osteogenesis and antibacterial effects was prepared for GBR. A polycaprolactone (PCL)/nano-hydroxyapatite (n-HA) aerogel produced by electrospinning and freeze-drying techniques was fabricated as the loose layer of the scaffold, while a PCL nanofiber membrane was used as the dense layer. Chitosan (CS) solution served as a middle layer to provide mechanical support and antibacterial effects between the two layers. Morphological results showed that the loose layer had a porous structure with n-HA successfully dispersed in the aerogels, while the dense layer possessed a sufficiently dense structure. In vitro antibacterial experiments illustrated that the CS solution in the middle layer stabilized the scaffold structure and endowed the scaffold with good antibacterial properties. The cytocompatibility results indicated that both fibroblasts and osteoblasts exhibited superior cell activity on the dense and loose layers, respectively. In particular, the dense layer made of nanofibers could work as a barrier layer to inhibit the infiltration of fibroblasts into the loose layer. In vitro osteogenesis analysis suggested that the PCL/n-HA aerogel could enhance the bone induction ability of bone mesenchymal stem cells, which was confirmed by the increased expression of the alkaline phosphatase activity. The loose structure facilitated the infiltration and migration of bone mesenchymal stem cells for better osteogenesis. In summary, such a composite scaffold exhibited excellent osteogenic and antibacterial properties as well as the barrier effect, thus holding promising potential for use as GBR materials.

Insight into effect of polyethylene microplastic on nitrogen removal in moving bed biofilm reactor: Focusing on microbial community and species interactions.

Microplastics (MPs) pollution has emerged as a global concern, and wastewater treatment plants (WWTPs) are one of the potential sources of MPs in the environment. However, the effect of polyethylene MPs (PE) on nitrogen (N) removal in moving bed biofilm reactor (MBBR) remains unclear. We hypothesized that PE would affect N removal in MBBR by influencing its microbial community. In this study, we investigated the impacts of different PE concentrations (100, 500, and 1000 µg/L) on N removal, enzyme activities, and microbial community in MBBR. Folin-phenol and anthrone colorimetric methods, oxidative stress and enzyme activity tests, and high-throughput sequencing combined with bioinformation analysis were used to decipher the potential mechanisms. The results demonstrated that 1000 µg/L PE had the greatest effect on NH4+-N and TN removal, with a decrease of 33.5 % and 35.2 %, and nitrifying and denitrifying enzyme activities were restrained by 29.5-39.6 % and 24.6-47.4 %. Polysaccharide and protein contents were enhanced by PE, except for 1000 µg/L PE, which decreased protein content by 65.4 mg/g VSS. The positive links of species interactions under 1000 µg/L PE exposure was 52.07 %, higher than under 500 µg/L (51.05 %) and 100 µg/L PE (50.35 %). Relative abundance of some metabolism pathways like carbohydrate metabolism and energy metabolism were restrained by 0.07-0.11 % and 0.27-0.4 %. Moreover, the total abundance of nitrification and denitrification genes both decreased under PE exposure. Overall, PE reduced N removal by affecting microbial community structure and species interactions, inhibiting some key metabolic pathways, and suppressing key enzyme activity and functional gene abundance. This paper provides new insights into assessing the risk of MPs to WWTPs, contributing to ensuring the health of aquatic ecosystems.

Flowering genes identification, network analysis, and database construction for 837 plants.

Flowering is one of the most important biological phenomena in the plant kingdom, which not only has important ecological significance, but also has substantial horticultural ornamental value. In this study, we undertook an exhaustive review of the advancements in our understanding of plant flowering genes. We delved into the identification and conducted comparative analyses of flowering genes across virtually all sequenced angiosperm plant genomes. Furthermore, we established an extensive angiosperm flowering atlas, encompassing a staggering 183 720 genes across eight pathways, along with 10 155 ABCDE mode genes, which play a pivotal role in plant flowering regulation. Through the examination of expression patterns, we unveiled the specificities of these flowering genes. An interaction network between flowering genes of the ABCDE model and their corresponding upstream genes offered a blueprint for comprehending their regulatory mechanisms. Moreover, we predicted the miRNA and target genes linked to the flowering processes of each species. To culminate our efforts, we have built a user-friendly web interface, named the Plant Flowering-time Gene Database (PFGD), accessible at http://pfgd.bio2db.com/. We firmly believe that this database will serve as a cornerstone in the global research community, facilitating the in-depth exploration of flowering genes in the plant kingdom. In summation, this pioneering endeavor represents the first comprehensive collection and comparative analysis of flowering genes in plants, offering valuable resources for the study of plant flowering genetics.

Inadequate pregnancy-specific knowledge among patients with inflammatory bowel disease: A multicenter survey in China.

OBJECTIVES: The perceptions and attitudes of inflammatory bowel disease (IBD) patients towards pregnancy may affect their fertility plan and disease progression. We performed a nationwide multicenter survey of pregnancy-related knowledge among gastroenterologists and IBD patients in China to investigate whether specific educational interventions could improve their understanding and broadly influence fertility plan. METHODS: A cross-sectional questionnaire regarding pregnancy-specific knowledge was carried out among 63 IBD centers in China. Questionnaires were collected from 185 physicians and 609 patients. The patients then received education regarding pregnancy during IBD and filled in the same questionnaire again. Their knowledge regarding pregnancy during IBD was compared before and after education. RESULTS: Compared to physicians, patients' knowledge regarding fertility (39.1% vs 70.8%), imaging examinations (22.8% vs 72.4%), endoscopy performed during pregnancy (19.9% vs 71.4%), and vaccination for infants (16.6% vs 46.5%) was significantly more limited (all P < 0.001). There was a lack of knowledge among gastroenterologists regarding the delivery mode (36.8%), medications (36.8%), and emergency surgery (26.5%) during pregnancy in patients with IBD. After education, the patients showed significant improvement in knowledge regarding medications (26.7% vs 51.7%), fertility (45.0% vs 63.3%), heritability (40.0% vs 58.3%), indications for emergency surgery (15.0% vs 53.3%), imaging examinations during pregnancy (20.0% vs 40.0%), and vaccinations for infants (26.7% vs 45.0%) (all P < 0.05). CONCLUSIONS: Pregnancy-specific IBD knowledge needs to be improved among certain gastroenterologists and patients in China. Educational interventions can partially improve the knowledge levels of the patients.

Liver receptor homolog-1: structures, related diseases, and drug discovery.

Liver receptor homolog-1 (LRH-1), a member of the nuclear receptor superfamily, is a ligand-regulated transcription factor that plays crucial roles in metabolism, development, and immunity. Despite being classified as an 'orphan' receptor due to the ongoing debate surrounding its endogenous ligands, recent researches have demonstrated that LRH-1 can be modulated by various synthetic ligands. This highlights the potential of LRH-1 as an attractive drug target for the treatment of inflammation, metabolic disorders, and cancer. In this review, we provide an overview of the structural basis, functional activities, associated diseases, and advancements in therapeutic ligand research targeting LRH-1.

Brain Immune Cell Infiltration and Serum Metabolomic Characteristics Reveal that Lauric Acid Promotes Immune Cell Infiltration in Brain and Streptococcus suis Meningitis in Mice.

Although naturally Streptococcus suis serotype 2 (SS2) causes meningitis resulting in death or sequela of neurological symptoms in pigs and humans, severely threatening public health in the world, it has been difficult to build up and confirm experimental meningitis mouse models with obvious neurological syndrome for about two decades, which strongly hampers the in-depth study on the control measures and mechanisms of SS2-induced meningitis. In this study, a typical meningitis mouse model of SS2 was successfully established, as confirmed by the behavioral indicators of balance beam test, suspension test, and gait analysis. With bacteria gathering in the brain, distinguishable unique features including meningeal thickening, vacuolization of the Nissl body, brain barrier damage, glial cell activation, and more infiltration of T cells, macrophages, and DCs are observed in SS2 meningitis mice with typical neurological signs. Some meningitis mice were also accompanied by identical nephritis, ophthalmia, and cochlearitis. Investigation of the metabolic features demonstrated the downregulated cholic acid and upregulated 2-hydroxyvaleric acid, tetrahydrocortisone, nicotinic acid, and lauric acid in blood serum of mice and piglets with meningitis. And feeding trials show that lauric acid can promote meningitis by promoting the infiltration of immune cells into brain. These findings demonstrated that infection of ICR (improved castle road) mice with SS2 was able to induce typical meningitis accompanied by immune cell infiltration and lauric acid upregulation. These data provide a basis for the deep study of SS2 meningitis.

Concentration Recognition-Based Auto-Dynamic Regulation System (CRUISE) Enabling Efficient Production of Higher Alcohols.

Microbial factories lacking the ability of dynamically regulating the pathway enzymes overexpression, according to in situ metabolite concentrations, are suboptimal, especially when the metabolic intermediates are competed by growth and chemical production. The production of higher alcohols (HAs), which hijacks the amino acids (AAs) from protein biosynthesis, minimizes the intracellular concentration of AAs and thus inhibits the host growth. To balance the resource allocation and maintain stable AA flux, this work utilizes AA-responsive transcriptional attenuator ivbL and HA-responsive transcriptional activator BmoR to establish a concentration recognition-based auto-dynamic regulation system (CRUISE). This system ultimately maintains the intracellular homeostasis of AA and maximizes the production of HA. It is demonstrated that ivbL-driven enzymes overexpression can dynamically regulate the AA-to-HA conversion while BmoR-driven enzymes overexpression can accelerate the AA biosynthesis during the HA production in a feedback activation mode. The AA flux in biosynthesis and conversion pathways is balanced via the intracellular AA concentration, which is vice versa stabilized by the competition between AA biosynthesis and conversion. The CRUISE, further aided by scaffold-based self-assembly, enables 40.4 g L-1 of isobutanol production in a bioreactor. Taken together, CRUISE realizes robust HA production and sheds new light on the dynamic flux control during the process of chemical production.

Bibliometric analysis and global trends in uterus transplantation.

AIM: The purpose of this study was to characterize publication patterns, academic influence, research trends, and the recent developments in uterus transplantation (UTx) across the globe. METHODS: The Web of Science Core Collection database was searched for documents published from the time the database began to include relevant articles to December 15, 2023. With the use of VOSviewer, Citespace, BICOMB, and Incites, a cross-sectional bibliometric analysis was conducted to extract or calculate the evaluative indexes. Publications were categorized by country, institution, author, journal, highly cited papers, and keywords. The variables were compared in terms of publication and academic influence, which further included citation count, citation impact, Hirsh index, journal impact factor, total link strength, collaboration metrics, and impact relative to the world. RESULTS: A total of 581 papers concerning UTx were initially identified after retrieval, and 425 documents were included. Of the 41 countries participating in relevant studies, the USA and Sweden were in leading positions in terms of publications, citations, and academic influence. The most versatile institution was the University of Gothenburg, which is followed by Baylor University. The most productive scholars and journals were Brännström M. and Fertility and Sterility, respectively. Five groups of cutting-edge keywords were identified: venous drainage, donors and donation, women, fertility preservation, and fertility. Topics about surgery, first live birth, risk, and in vitro fertilization remain hot in this field. CONCLUSIONS: UTx is anticipated to enter a golden era in the coming years. This study provides some guidance concerning the authors involved in promoting UTx research, the current development of UTx, and journals to submit their innovative research. This also helps to reach a comprehensive insight and prospect in the near future. In order to establish recognized standards and benefit more patients who are disturbed by uterine infertility, large-scale and well-designed clinical trials are required.

Mechanisms and potential applications of COPS6 in pan-cancer therapy.

The COP9 signalosome subunit 6 (COPS6) is abnormally overexpressed in many malignancies, yet its precise role in carcinogenesis is unknown. To gain a better understanding of COPS6's role, the authors conducted a pan-cancer analysis using various bioinformatics techniques such as differential expression patterns, prognostic value, gene mutations, immune infiltration, correlation analysis, and functional enrichment assessment. Results showed that COPS6 was highly correlated with prognosis, immune cell infiltration level, tumor mutation burden, and microsatellite instability in patients with a range of tumor types. This suggests that COPS6 may be a potential target for cancer treatment. Overall, this research provides insight into COPS6's role in cancer development and its potential therapeutic applications.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells.

BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. CONCLUSION: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.