The safety and efficacy of myomectomy in the treatment of recurrent uterine fibroids after HIFU.

OBJECTIVE: To evaluate the safety and efficacy of myomectomy for recurrent uterine fibroids (UFs) after high-intensity focused ultrasound (HIFU) ablation. METHODS: This was a retrospective study. Patients who underwent abdominal myomectomy (AM) and laparoscopic myomectomy (LM) from January 2018 to December 2021 at the Three Gorges Hospital of Chongqing University were included. Among them, 73 had undergone prior HIFU ablation (Group 1), while 120 had not undergone HIFU (Group 2). Outcome measures included operating time, estimated blood loss (EBL), blood transfusion, postoperative activity times (PAT), duration of hospital stay (DOHS), and complications. RESULTS: The operating time was 90.0 min (70.5, 115.0) for Group 1 and 110.0 min (81.5, 130.0) for Group 2 (P < 0.05). During all AM pathways, there were no significant differences observed between the two groups in EBL, blood transfusion, PAT, DOHS, and complications; however, operating time was shorter in Group 1. The operating time, EBL, blood transfusion, PAT, DOHS, and complications were similar in both groups during LM pathway. During the follow-up 40 (range: 24-53) months, the rate of relief, recurrence, and reintervention in Groups 1 and 2 was 78.1% versus 74.1%, 14.6% versus 16.4%, and 3.7% versus 2.6%, respectively (P > 0.05). CONCLUSION: Myomectomy is a safe and effective surgical method for treating recurrent UFs after HIFU. Myomectomy for treating recurrent UFs resulted in a shorter operative and hospital stay, reduced blood loss, faster postoperative recovery, and fewer complications, better symptom relief rates, and lower risk of recurrence or reintervention. These findings indicate that previous HIFU ablation does not worsen the outcomes of the subsequent myomectomy.

Phosphoric Acid-Catalyzed Alkene Difunctionalization of 2-Vinylpyridines via HOMO/LUMO Biactivated Diels-Alder Reaction.

The difunctionalization of vinylpyridines based on the cyclization strategy remains rare and underdeveloped, in contrast to the well-developed hydrogen functionalization. Current exploration on [4 + 2] cyclization of vinylpyridines mainly relies on extremely high temperatures and the LUMO activation of vinylpyridines using boron trifluoride as a strong Lewis acid. Herein, we established a phosphoric acid-catalyzed [4 + 2] cyclization reaction of 3-vinyl-1H-indoles and 2-vinylpyridines by means of the LUMO/HOMO bifunctional activation model. This protocol features mild reaction conditions, high functional group tolerance, broad substrate compatibility, and high diastereoselectivity, enabling the efficient construction of various functionalized pyridine-substituted tetrahydrocarbazoles with prominent potential in drug discovery.

Evaluating Fluorinated-Aniline Units with Functionalized Spiro[Fluorene-9,9'-Xanthene] as Hole-Transporting Materials in Perovskite Solar Cells and Light-Emitting Diodes.

In the field of perovskite optoelectronics, developing hole-transporting materials (HTMs) on the spiro[fluorene-9,9'-xanthene] (SFX) platform is one of the current research focuses. The SFX inherits the merits of spirobifluorene in terms of the configuration and property, but it is more easily derivatized and regulated by virtue of its binary structure. In this work, we design and synthesize four isomeric SFX-based HTMs, namely m-SFX-mF, p-SFX-mF, m-SFX-oF, and p-SFX-oF, through varying the positions of fluorination on the peripheral aniline units and their substitutions on the SFX core, and the optoelectronic performance of the resulting HTMs is evaluated in both perovskite solar cells (PSCs) and light-emitting diodes (PeLEDs) by the vacuum thermal evaporating hole-transporting layers (HTLs). The HTM p-SFX-oF exhibits an improved power conversion efficiency of 15.21% in an inverted PSC using CH3NH3PbI3 as an absorber, benefiting from the deep HOMO level and good HTL/perovskite interface contact. Meanwhile, the HTM m-SFX-mF provides a maximum external quantum efficiency of 3.15% in CsPb(Br/Cl)3-based PeLEDs, which is attributed to its perched HOMO level and shrunken band-gap for facilitating charge carrier injection and then exciton combination. Through elucidating the synergistic position effect of fluorination on aniline units and their substitutions on the SFX core, this work lays the foundation for developing low-cost and efficient HTMs in the future.

GutUDB: A comprehensive multiomics database for intestinal diseases.

Gut Universe Database (GutUDB) provides a comprehensive, systematic, and practical platform for researchers, and is dedicated to the management, analysis, and visualization of knowledge related to intestinal diseases. Based on this database, eight major categories of omics data analyses are carried out to explore the genotype-phenotype characteristics of a certain intestinal disease. The first tool for comprehensive omics data research on intestinal diseases will help each researcher better understand intestinal diseases.

Knowledge, attitude, and practice toward postoperative self-management among kidney transplant recipients.

BACKGROUND: Patient involvement is crucial to the success of kidney transplants. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward postoperative self-management among kidney transplant recipients. METHODS: A web-based cross-sectional study was conducted in Ruijin Hospital (Shanghai, China) between March 24, 2023, and April 15, 2023 in kidney transplant recipients. A questionnaire was designed to collect data about the characteristics of the participants and their KAP toward postoperative self-management. KAP scores were calculated based on participants' responses, using predefined scoring criteria tailored to evaluate each dimension of KAP effectively. RESULTS: A total of 483 valid questionnaires were collected, including 189 (39.13%) participants aged between 46 and 60 years. The mean score of knowledge, attitude and practice were 23.44 ± 4.87 (possible range: 0-28), 43.59 ± 2.65 (possible range: 10-50), 52.52 ± 4.64 (possible range: 0-58), respectively. The multivariate analysis showed knowledge scores (OR = 1.15, 95% CI = 1.10-1.20, p < 0.001), attitude scores (OR = 1.22, 95% CI = 1.12-1.32, p < 0.001) and undergone transplantation within 1 year (OR = 3.92, 95% CI = 1.60-9.63, p = 0.003) were independently associated with good practice. Knowledge scores (OR = 1.06, 95% CI = 1.02-1.10, p = 0.003), attitude scores (OR = 1.16, 95% CI = 1.08-1.25, p < 0.001), aged 16-35 years (OR = 0.38, 95% CI = 0.18-0.78, p = 0.009), underwent a single kidney transplant surgery (OR = 3.97, 95% CI = 1.28-12.38, p = 0.017) were independently associated with medication adherence. CONCLUSIONS: Kidney transplant recipients had good knowledge, positive attitude and good practice toward postoperative self-management. Implementing personalized education, psychological support, and close monitoring strategies is recommended to optimize postoperative self-management in kidney transplant recipients.

[Mechanism of Ganke Granules intervening acute lung injury based on network pharmacology and experimental verification].

This study aims to explore the potential mechanism of action in the intervention of acute lung injury(ALI) based on the blood entry components of Ganke Granules in rats and in conjunction with network pharmacology, molecular docking, and animal experimental validation. The blood entry components of Ganke Granules in rats were imported into the SwissTargetPrediction platform to predict drug targets, and ALI-related targets were collected from the disease database. Intersections were taken, and protein-protein interaction(PPI) networks were constructed to screen the core targets, followed by Gene Ontology(GO) functional and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analyses. A "blood entry components-target-pathway-disease" network was constructed, and the core components for disease intervention based on their topological parameters were screened. Molecular docking was used to predict the binding ability of the core components to key targets. The key targets of Ganke Granules in the intervention of ALI were verified by the lipopolysaccharide(LPS)-induced ALI mouse model. Through PPI topological parameter analysis, the top six key targets of STAT3, SRC, HSP90AA1, MAPK3, HRAS, and MAPK1 related to ALI were obtained. GO functional analysis showed that it was mainly related to ERK1 and ERK2 cascade, inflammatory response, and response to LPS. KEGG analysis showed that the main enrichment pathways were MAPK, neutrophil extracellular trap(NET) formation, and so on. Six core components(schizantherin B, schisandrin, besigomsin, harpagoside, isotectorigenin, and trachelanthamine) were filtered out by the "blood entry components-target-pathway-disease" network based on the analysis of topological parameters. Molecular docking results showed that the six core components and Tectoridin with the highest content in the granules had a high affinity with the key targets of MAPK3, SRC, MAPK1, and STAT3. In vivo experiment results showed that compared with the model group, Ganke Granules could effectively alleviate LPS-induced histopathological injury in the lungs of mice and reduce the percentage of inflammatory infiltration. The total protein content, nitric oxide(NO) level, myeloperoxidase(MPO) content, tumor necrosis factor-α(TNF-α), gamma interferon(IFN-γ), interleukin-1ß(IL-1ß), interleukin-6(IL-6), vascular endothelial growth factor(VEGF), and chemokine(C-X-C motif) ligand 1(CXCL1) chemokines in bronchoalveolar lavage fluid(BALF) were decreased, and the expression levels of lymphocyte antigen 6G(Ly6G), citrullinated histones 3(Cit-H3), and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue were significantly down-regulated. In conclusion, Ganke Granules could effectively inhibit the inflammatory response of ALI induced by LPS, protect lung tissue, regulate the release of inflammatory factors, and inhibit neutrophil infiltration and NET formation, and the mechanism of action may be related to inhibiting the activation of SRC/ERK1/2/STAT3 signaling pathway.

Can pre-exercise photobiomodulation improve muscle endurance and promote recovery from muscle strength and injuries in people with different activity levels? A meta-analysis of randomized controlled trials.

Photobiomodulation therapy (PBMT) was introduced as an ergogenic aid for sport performance in healthy individuals is still controversial. The main aim of this study is to assess the potential enhancements in muscle endurance and recovery from muscle strength and injuries mediated by PBMT among individuals exhibiting diverse activity levels. Randomized controlled trials (RCT) of PBMT interventions for healthy people (both trained and untrained individuals) exercising were searched (up to January 16, 2024) in four electronic databases: Web of Science, PubMed, Scopus and Embase. Primary outcome measures included muscle endurance, muscle strength and creatine kinase (CK) levels; secondary outcome measure included Lactate dehydrogenase (LDH) levels. Subgroup analyses based on physical activity levels were conducted for each outcome measure. Thirty-four RCTs were included based on the article inclusion and exclusion criteria. Statistical results showed that PBMT significantly improved muscle endurance (standardized mean difference [SMD] = 0.31, 95%CI 0.11, 0.51, p < 0.01), indicating a moderate effect size. It also facilitated the recovery of muscle strength (SMD = 0.24, 95%CI 0.10, 0.39, p < 0.01) and CK (mean difference [MD] = -77.56, 95%CI -112.67, -42.44, p < 0.01), indicating moderate and large effect sizes, respectively. Furthermore, pre-application of PBMT significantly improved muscle endurance, recovery of muscle strength and injuries in physically inactive individuals and athletes (p < 0.05), while there was no significant benefit for physically active individuals. Pre-application of PBMT improves muscle endurance and promotes recovery from muscle strength and injury (includes CK and LDH) in athletes and sedentary populations, indicating moderate to large effect sizes, but is ineffective in physically active populations. This may be due to the fact that physically active people engage in more resistance training, which leads to a decrease in the proportion of red muscle fibres, thus affecting photobiomodulation.

LDHA-mediated M2-type macrophage polarization via tumor-derived exosomal EPHA2 promotes renal cell carcinoma progression.

Lactate dehydrogenase A (LDHA) is known to promote the growth and invasion of various types of tumors, affects tumor resistance, and is associated with tumor immune escape. But how LDHA reshapes the tumor microenvironment and promotes the progression of renal cell carcinoma (RCC) remains unclear. In this study, we found that LDHA was highly expressed in clear cell RCC (ccRCC), and this high expression was associated with macrophage infiltration, while macrophages were highly infiltrated in ccRCC, affecting patient prognosis via M2-type polarization. Our in vivo and in vitro experiments demonstrated that LDHA and M2-type macrophages could enhance the proliferation, invasion, and migration abilities of ccRCC cells. Mechanistically, high expression of LDHA in ccRCC cells upregulated the expression of EPHA2 in exosomes derived from renal cancer. Exosomal EPHA2 promoted M2-type polarization of macrophages by promoting activation of the PI3K/AKT/mTOR pathway in macrophages, thereby promoting the progression of ccRCC. All these findings suggest that EPHA2 may prove to be a potential therapeutic target for advanced RCC.

Targeting tumor suppressor p53 for organ fibrosis therapy.

Fibrosis is a reparative and progressive process characterized by abnormal extracellular matrix deposition, contributing to organ dysfunction in chronic diseases. The tumor suppressor p53 (p53), known for its regulatory roles in cell proliferation, apoptosis, aging, and metabolism across diverse tissues, appears to play a pivotal role in aggravating biological processes such as epithelial-mesenchymal transition (EMT), cell apoptosis, and cell senescence. These processes are closely intertwined with the pathogenesis of fibrotic disease. In this review, we briefly introduce the background and specific mechanism of p53, investigate the pathogenesis of fibrosis, and further discuss p53's relationship and role in fibrosis affecting the kidney, liver, lung, and heart. In summary, targeting p53 represents a promising and innovative therapeutic approach for the prevention and treatment of organ fibrosis.

Expression of regional brain amyloid-ß deposition with [18F]Flutemetamol in Centiloid scale -a multi-site study.

PURPOSE: The Centiloid project helps calibrate the quantitative amyloid-ß (Aß) load into a unified Centiloid (CL) scale that allows data comparison across multi-site. How the smaller regional amyloid converted into CL has not been attempted. We first aimed to express regional Aß deposition in CL using [18F]Flutemetamol and evaluate regional Aß deposition in CL with that in standardized uptake value ratio (SUVr). Second, we aimed to determine the presence or absence of focal Aß deposition by measuring regional CL in equivocal cases showing negative global CL. METHODS: Following the Centiloid project pipeline, Level-1 replication, Level-2 calibration, and quality control were completed to generate corresponding Centiloid conversion equations to convert SUVr into Centiloid at regional levels. In equivocal cases, the regional CL was compared with visual inspection to evaluate regional Aß positivity. RESULTS: 14 out of 16 regional conversions from [18F]Flutemetamol SUVr to Centiloid successfully passed the quality control, showing good reliability and relative variance, especially precuneus/posterior cingulate and prefrontal regions with good stability for Centiloid scaling. The absence of focal Aß deposition could be detected by measuring regional CL, showing a high agreement rate with visual inspection. The regional Aß positivity in the bilateral anterior cingulate cortex was most prevalent in equivocal cases. CONCLUSION: The expression of regional brain Aß deposition in CL with [18F]Flutemetamol has been attempted in this study. Equivocal cases had focal Aß deposition that can be detected by measuring regional CL.

Artificial intelligence-empowered collection and characterization of microplastics: A review.

Microplastics have been detected from water and soil systems extensively, with increasing evidence indicating their detrimental impacts on human and animal health. Concerns surrounding microplastic pollution have spurred the development of advanced collection and characterization methods for studying the size, abundance, distribution, chemical composition, and environmental impacts. This paper offers a comprehensive review of artificial intelligence (AI)-empowered technologies for the collection and characterization of microplastics. A framework is presented to streamline efforts in utilizing emerging robotics and machine learning technologies for collecting, processing, and characterizing microplastics. The review encompasses a range of AI technologies, delineating their principles, strengths, limitations, representative applications, and technology readiness levels, facilitating the selection of suitable AI technologies for mitigating microplastic pollution. New opportunities for future research and development on integrating robots and machine learning technologies are discussed to facilitate future efforts for mitigating microplastic pollution and advancing AI technologies.

Phenotypic high-throughput screening identifies aryl hydrocarbon receptor agonism as common inhibitor of toxin-induced retinal pigment epithelium cell death.

The retinal pigment epithelium (RPE) is essential to maintain retinal function, and RPE cell death represents a key pathogenic stage in the progression of several blinding ocular diseases, including age-related macular degeneration (AMD). To identify pathways and compounds able to prevent RPE cell death, we developed a phenotypic screening pipeline utilizing a compound library and high-throughput screening compatible assays on the human RPE cell line, ARPE-19, in response to different disease relevant cytotoxic stimuli. We show that the metabolic by-product of the visual cycle all-trans-retinal (atRAL) induces RPE apoptosis, while the lipid peroxidation by-product 4-hydroxynonenal (4-HNE) promotes necrotic cell death. Using these distinct stimuli for screening, we identified agonists of the aryl hydrocarbon receptor (AhR) as a consensus target able to prevent both atRAL mediated apoptosis and 4-HNE-induced necrotic cell death. This works serves as a framework for future studies dedicated to screening for inhibitors of cell death, as well as support for the discussion of AhR agonism in RPE pathology.

Targeting PIKfyve-driven lipid homeostasis as a metabolic vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) subsists in a nutrient-deregulated microenvironment, making it particularly susceptible to treatments that interfere with cancer metabolism12. For example, PDAC utilizes and is dependent on high levels of autophagy and other lysosomal processes3-5. Although targeting these pathways has shown potential in preclinical studies, progress has been hampered by the challenge of identifying and characterizing favorable targets for drug development6. Here, we characterize PIKfyve, a lipid kinase integral to lysosomal functioning7, as a novel and targetable vulnerability in PDAC. In human patient and murine PDAC samples, we discovered that PIKFYVE is overexpressed in PDAC cells compared to adjacent normal cells. Employing a genetically engineered mouse model, we established the essential role of PIKfyve in PDAC progression. Further, through comprehensive metabolic analyses, we found that PIKfyve inhibition obligated PDAC to upregulate de novo lipid synthesis, a relationship previously undescribed. PIKfyve inhibition triggered a distinct lipogenic gene expression and metabolic program, creating a dependency on de novo lipid metabolism pathways, by upregulating genes such as FASN and ACACA. In PDAC, the KRAS-MAPK signaling pathway is a primary driver of de novo lipid synthesis, specifically enhancing FASN and ACACA levels. Accordingly, the simultaneous targeting of PIKfyve and KRAS-MAPK resulted in the elimination of tumor burden in a syngeneic orthotopic model and tumor regression in a xenograft model of PDAC. Taken together, these studies suggest that disrupting lipid metabolism through PIKfyve inhibition induces synthetic lethality in conjunction with KRAS-MAPK-directed therapies for PDAC.

CDK12 Loss Promotes Prostate Cancer Development While Exposing Vulnerabilities to Paralog-Based Synthetic Lethality.

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a unique molecular subtype of metastatic castration-resistant prostate cancer (mCRPC). It remains unclear, however, whether CDK12 loss per se is sufficient to drive prostate cancer development-either alone, or in the context of other genetic alterations-and whether CDK12-mutant tumors exhibit sensitivity to specific pharmacotherapies. Here, we demonstrate that tissue-specific Cdk12 ablation is sufficient to induce preneoplastic lesions and robust T cell infiltration in the mouse prostate. Allograft-based CRISPR screening demonstrated that Cdk12 loss is positively associated with Trp53 inactivation but negatively associated with Pten inactivation-akin to what is observed in human mCRPC. Consistent with this, ablation of Cdk12 in prostate organoids with concurrent Trp53 loss promotes their proliferation and ability to form tumors in mice, while Cdk12 knockout in the Pten-null prostate cancer mouse model abrogates tumor growth. Bigenic Cdk12 and Trp53 loss allografts represent a new syngeneic model for the study of androgen receptor (AR)-positive, luminal prostate cancer. Notably, Cdk12/Trp53 loss prostate tumors are sensitive to immune checkpoint blockade. Cdk12-null organoids (either with or without Trp53 co-ablation) and patient-derived xenografts from tumors with CDK12 inactivation are highly sensitive to inhibition or degradation of its paralog kinase, CDK13. Together, these data identify CDK12 as a bona fide tumor suppressor gene with impact on tumor progression and lends support to paralog-based synthetic lethality as a promising strategy for treating CDK12-mutant mCRPC.

Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a.

BACKGROUND: Knee osteoarthritis (KOA) is a common orthopedic condition with an uncertain etiology, possibly involving genetics and biomechanics. Factors like changes in chondrocyte microenvironment, oxidative stress, inflammation, and immune responses affect KOA development. Early-stage treatment options primarily target symptom relief. Mesenchymal stem cells (MSCs) show promise for treatment, despite challenges. Recent research highlights microRNAs (miRNAs) within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression. This suggests exosomes (Exos) as a promising avenue for future treatment. While these findings emphasize the need for effective KOA progression management, further safety and efficacy validation for Exos is essential. AIM: To explore miR-29a's role in KOA, we'll create miR-29a-loaded vesicles, testing for early treatment in rat models. METHODS: Extraction of bone marrow MSC-derived extracellular vesicles, preparation of engineered vesicles loaded with miR-29a using ultrasonication, and identification using quantitative reverse transcription polymerase chain reaction; after establishing a rat model of KOA, rats were randomly divided into three groups: Blank control group injected with saline, normal extracellular vesicle group injected with normal extracellular vesicle suspension, and engineered extracellular vesicle group injected with engineered extracellular vesicle suspension. The three groups were subjected to general behavioral observation analysis, imaging evaluation, gross histological observation evaluation, histological detection, and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis. RESULTS: General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain, gait, joint mobility, and swelling compared to the blank control group. Additionally, the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group. Imaging examination results showed that the blank control group had the fastest progression of arthritis, the normal extracellular vesicle group had a relatively slower progression, and the engineered extracellular vesicle group had the slowest progression. Gross histological observation results showed that the blank control group had the most obvious signs of arthritis, the normal extracellular vesicle group showed signs of arthritis, and the engineered extracellular vesicle group showed no significant signs of arthritis. Using the Pelletier gross score evaluation, the engineered extracellular vesicle group had the slowest progression of arthritis. Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group, and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition. Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group. Compared to the normal extracellular vesicle group, the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells. CONCLUSION: Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability, thereby protecting articular cartilage, and slowing the progression of KOA.

Meta-analysis of the relationship between the number and location of perivascular spaces in the brain and cognitive function.

BACKGROUND: Cerebral perivascular spaces are part of the cerebral microvascular structure and play a role in lymphatic drainage and the removal of waste products from the brain. Relationships of the number and location of such spaces with cognition are unclear. OBJECTIVE: To meta-analyze available data on potential associations of severity and location of perivascular spaces with cognitive performance. METHODS: We searched PubMed, EMBASE, Web of Science and the Cochrane Central Registry of Controlled Trials for relevant studies published between January 2000 and July 2023. Performance on different cognitive domains was compared to the severity of perivascular spaces in different brain regions using comprehensive meta-analysis. When studies report unadjusted and adjusted means, we use adjusted means for meta-analysis. The study protocol is registered in the PROSPERO database (CRD42023443460). RESULTS: We meta-analyzed data from 26 cross-sectional studies and two longitudinal studies involving 7908 participants. In most studies perivascular spaces was using a visual rating scale. A higher number of basal ganglia perivascular spaces was linked to lower general intelligence and attention. Moreover, increased centrum semiovale perivascular spaces were associated with worse general intelligence, executive function, language, and memory. Conversely, higher hippocampus perivascular spaces were associated with enhanced memory and executive function. Subgroup analyses revealed variations in associations among different disease conditions. CONCLUSIONS: A higher quantity of perivascular spaces in the brain is correlated with impaired cognitive function. The location of these perivascular spaces and the underlying disease conditions may influence the specific cognitive domains that are affected. SYSTEMATIC REVIEW REGISTRATION: The study protocol has been registered in the PROSPERO database (CRD42023443460).

Lipid metabolism: the potential targets for toxoplasmosis treatment.

Toxoplasmosis is a zoonosis caused by Toxoplasma gondii (T. gondii). The current treatment for toxoplasmosis remains constrained due to the absence of pharmaceutical interventions. Thus, the pursuit of more efficient targets is of great importance. Lipid metabolism in T. gondii, including fatty acid metabolism, phospholipid metabolism, and neutral lipid metabolism, assumes a crucial function in T. gondii because those pathways are largely involved in the formation of the membranous structure and cellular processes such as division, invasion, egress, replication, and apoptosis. The inhibitors of T. gondii's lipid metabolism can directly lead to the disturbance of various lipid component levels and serious destruction of membrane structure, ultimately leading to the death of the parasites. In this review, the specific lipid metabolism pathways, correlative enzymes, and inhibitors of lipid metabolism of T. gondii are elaborated in detail to generate novel ideas for the development of anti-T. gondii drugs that target the parasites' lipid metabolism.

Multifaceted role of microRNAs in gastric cancer stem cells: Mechanisms and potential biomarkers.

MicroRNAs (miRNAs) have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells (CSCs). The abnormal expression of miRNAs is responsible for different phenotypes of gastric cancer stem cells (GCSCs). Some specific miRNAs could be used as promising biomarkers and therapeutic targets for the identification of GCSCs. This review summarizes the coding process and biological functions of miRNAs and demonstrates their role and efficacy in gastric cancer (GC) metastasis, drug resistance, and apoptosis, especially in the regulatory mechanism of GCSCs. It shows that the overexpression of onco-miRNAs and silencing of tumor-suppressor miRNAs can play a role in promoting or inhibiting tumor metastasis, apart from the initial formation of GC. It also discusses the epigenetic regulation and potential clinical applications of miRNAs as well as the role of CSCs in the pathogenesis of GC. We believe that this review may help in designing novel therapeutic approaches for GC.