Cascade [3 + 2] Annulation of 1,3-Dicarbonyl Compounds and Ethyl Secondary Amines for Pyrrole Synthesis via Poly C(sp3)-H Bond Functionalization.

The synthesis of polyfunctionalized pyrroles via the cascade reactions of 1,3-dicarbonyl compounds and two molecules of ethyl secondary amines has been realized via simple iodine catalysis in the presence of Dess-Martin periodinane (DMP). The formation of the target pyrrole products involves the formation of one new C-C and two new C-N bonds via the major functionalization of six C(sp3)-H bonds, presenting a highly novel and efficient synthetic protocol toward pyrrole scaffolds.

Iridium-catalyzed reduction of o-hydroxyl phenyl enaminones for the synthesis of propiophenones and their application in 3-methyl chromone synthesis.

A method of reducing o-hydroxyphenyl enaminones with silane as the reductant to provide o-hydroxyl propiophenones has been achieved with iridium catalysis. The reduction reactions were found to proceed via the assistance of the hydroxyl group in the phenyl ring. In addition, the o-hydroxyl propiophenone products were used for the easy synthesis of 3-methyl chromones by directly incorporating N,N-dimethyl formamide dimethyl acetal (DMF-DMA) without using any catalyst.

The interaction between neutrophils and atrial myocytes in the occurrence and development of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias, strongly associated with neutrophils. However, the underlying mechanism remain unclear. This study aims to explore the interaction between neutrophils and atrial myocytes in the pathogenesis of AF. METHODS: Patch-clamp was employed to record the action potential duration (APD) and ion channels in HL-1 cells. Flow cytometry was used to assess the differentiation of neutrophils. The mRNA and protein levels of CACNA1C, CACNA2D, and CACNB2 in HL-1 cells were detected. RESULTS: High-frequency electrical stimulation resulted in a shortening of the APD in HL-1 cells. Flow cytometry demonstrated that neutrophils were polarized into N1 phenotype when cultured with stimulated HL-1 cells medium. Compared to control neutrophils conditioned medium (CM), cocultured with TNF-α knockout neutrophils CM prolonged APD and the L-type Ca (2+) channel (LTCC) of HL-1 cells. Additionally, the expression of CACNA2D, CACNB2 and CACNA1C in HL-1 cells were upregulated. Compared with CACNA1C siRNA-transfected HL-1 cells treated with TNF-α siRNA-transfected neutrophils CM, the APD and LTCC of CACNA1C siRNA-transfected HL-1 cells were shortened in control N1 neutrophil CM. The APD and LTCC of control HL-1 cells were also shortened in control N1 neutrophil CM, but prolonged in TNF-α siRNA-transfected neutrophils CM. CONCLUSION: These findings suggest that neutrophils were polarized into N1 phenotype in AF, TNF-α released from N1 neutrophils contributes to the pathogenesis of AF, via decreasing the APD and LTCC in atrial myocytes through down-regulation of CACNA1C expression.

Recent advances in the multicomponent synthesis of pyrazoles.

Pyrazole moiety is considered as an important N-heterocycle in pharmaceuticals and many other functional molecules. The utilization of multicomponent reaction is a major tool in the current approaches of pyrazole synthesis. Considering the power and significance of multicomponent pyrazole synthesis, we review herein the latest developments in this field. According to the typical features, the contents are divided into reactions with different NN fragment sources, such as hydrazine, hydrazone, amidine, nitrile, and diazo compounds, in the pyrazole ring construction, covering the works published since 2019 to date.

GLT-1 downregulation in hippocampal astrocytes induced by type 2 diabetes contributes to postoperative cognitive dysfunction in adult mice.

AIMS: Type 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT-1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT-1 expression. METHODS: T2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT-1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long-term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT-1 in GFAP-Cre mice. Besides, AAV-Camkllα-hM4Di-mCherry was injected to inhibit neuronal hyperexcitability in CA1 region. RESULTS: Our study found T2DM but not A/S reduced GLT-1 expression in hippocampal astrocytes. Interestingly, GLT-1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT-1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT-1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction. CONCLUSIONS: These findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT-1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis.

Evaluation of the thickness of acetabular cartilage by ultrasound in developmental dysplasia of the hip.

Introduction: It has been reported that the cartilaginous roof of the acetabulum is thicker in infants with developmental dysplasia of the hip (DDH) than in those with healthy hips. However, there is limited research on the changes in the thickness of acetabular cartilage after follow-up or treatment of DDH. This study aims to report the thickness of acetabular cartilage before and after treatment of DDH. Materials and methods: In this prospective study, infants with clinical suspicion of DDH were enrolled in the pediatric outpatient service in our hospital from January 2022 to August 2023. The thickness of acetabular cartilage was measured in the standard coronal plane. Borderline hips (Graf IIa type) were monitored with monthly ultrasound examination until they were classified as normal hips (Graf I type), while dysplastic hips (Graf IIb type or worse) were treated with the Pavlik harness until they were also classified as normal hips in the final ultrasound examination. Results: A total of 592 children [median age, 96 days (interquartile range, 70-142 days); 197 boys] were enrolled in the study. The thickness of acetabular cartilage in dysplastic hips (4.3 ± 1.6 mm) was greater than that in normal hips (3.0 ± .39 mm, P < 0.001) and borderline hips (3.1 ± .57 mm, P < 0.001). In borderline hips, the thickness of acetabular cartilage decreased from 3.1 ± .57 mm in the initial evaluation to 2.9 ± .53 mm in the final follow-up scan (P = 0.01). In dysplastic hips, the thickness of acetabular cartilage decreased from 4.3 ± 1.6 mm in the initial evaluation to 3.5 ± .51 mm after treatment (P = 0.003). The thickness of acetabular cartilage in dysplastic hips after treatment remained greater than that in normal hips (P < 0.0001). Conclusion: The thickness of acetabular cartilage decreased after follow-up or treatment of DDH. Further research is required to determine whether cartilage that remain thicker in dysplastic hips than that in normal hips after treatment should be considered an early indicator of residual acetabular dysplasia.

Comparative efficacy of the five most common traditional Chinese medicine monomers in reducing intimal hyperproliferation in arterial balloon injury models: A network meta-analysis.

Objective: This study utilized network meta-analysis (NMA) to compare the efficacy of five commonly used traditional Chinese medicine monomers in reducing intimal hyperproliferation in arterial balloon injury models. Methods: Relevant literature up to January 2024 was systematically retrieved from seven major databases. The intima-to-media (I/M) ratio was chosen as the primary outcome measure. The risk of bias in animal studies was assessed using the SYstematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Statistical analysis was conducted using Stata 17 software. Results: A total of 43 studies were included in this meta-analysis. NMA results showed that in the rat model, compared to the control group, GS (SMD: 0.99, 95%CI: 1.25 to -0.73), ASIV (SMD: 1.16, 95%CI: 1.65 to -0.67), TMP (SMD: 0.68, 95%CI: 1.31 to -0.05), and TPNS (SMD: 1.36, 95%CI: 1.91 to -0.80) exhibited inhibitory effects on postoperative intimal hyperproliferation, reducing the I/M ratio. In the rabbit model, compared to the control group, TPNS (SMD: 1.23, 95%CI: 1.97 to -0.49) inhibited postoperative intimal hyperproliferation and reduced the I/M ratio. Superiority ranking analysis suggested that total Panax notoginseng saponin (TPNS) might be the most effective traditional Chinese medicine monomer in reducing intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio. Conclusion: NMA indicates that traditional Chinese medicine monomers can effectively reduce postoperative intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio, with TPNS showing optimal efficacy. However, the research on TIIA is insufficient, and the limited sample size may affect the robustness of the results. Furthermore, the majority of research on traditional Chinese medicine monomers is currently limited to the experimental stage, lacking further clinical validation. Conducting standardized animal experiments and reporting their findings can enhance the quality of evidence from animal studies, laying the foundation for future clinical trials.

Identification of histopathological classification and establishment of prognostic indicators of gastric adenocarcinoma based on deep learning algorithm.

The aim of this study is to establish a deep learning (DL) model to predict the pathological type of gastric adenocarcinoma cancer based on whole-slide images(WSIs). We downloaded 356 histopathological images of gastric adenocarcinoma (STAD) patients from The Cancer Genome Atlas database and randomly divided them into the training set, validation set and test set (8:1:1). Additionally, 80 H&E-stained WSIs of STAD were collected for external validation. The CLAM tool was used to cut the WSIs and further construct the model by DL algorithm, achieving an accuracy of over 90% in identifying and predicting histopathological subtypes. External validation results demonstrated the model had a certain generalization ability. Moreover, DL features were extracted from the model to further investigate the differences in immune infiltration and patient prognosis between the two subtypes. The DL model can accurately predict the pathological classification of STAD patients, and provide certain reference value for clinical diagnosis. The nomogram combining DL-signature, gene-signature and clinical features can be used as a prognostic classifier for clinical decision-making and treatment.

Causal relationships between GLP1 receptor agonists, blood lipids, and heart failure: a drug-target mendelian randomization and mediation analysis.

BACKGROUND: Glucagon-like peptide-1 receptor (GLP1R) agonists have been shown to reduce major cardiovascular events in diabetic patients, but their role in heart failure (HF) remains controversial. Recent evidence implies their potential benefits on cardiometabolism such as lipid metabolism, which may contribute to lowering the risk of HF. Consequently, we designed a Mendelian randomization (MR) study to investigate the causal relationships of circulating lipids mediating GLP1R agonists in HF. METHODS: The available cis-eQTLs for GLP1R target gene were selected as instrumental variables (IVs) of GLP1R agonism. Positive control analyses of type 2 diabetes mellitus (T2DM) and body mass index (BMI) were conducted to validate the enrolled IVs. Two-sample MR was performed to evaluate the associations between GLP1R agonism and HF as well as left ventricular ejection fraction (LVEF). Summary data for HF and LVEF were obtained from two genome-wide association studies (GWASs), which included 977,323 and 40,000 individuals of European ancestry, respectively. The primary method employed was the random-effects inverse variance weighted, with several other methods used for sensitivity analyses, including MR-Egger, MR PRESSO, and weighted median. Additionally, multivariable MR and mediation MR were applied to identify potentially causal lipid as mediator. RESULTS: A total of 18 independent IVs were included. The positive control analyses showed that GLP1R agonism significantly reduced the risk of T2DM (OR = 0.79, 95% CI = 0.75-0.85, p < 0.0001) and decreased BMI (OR = 0.95, 95% CI = 0.93-0.96, p < 0.0001), ensuring the effectiveness of selected IVs. We found favorable evidence to support the protective effect of GLP1R agonism on HF (OR = 0.75, 95% CI = 0.71-0.79, p < 0.0001), but there was no obvious correlation with increased LVEF (OR = 1.01, 95% CI = 0.95-1.06, p = 0.8332). Among the six blood lipids, only low-density lipoprotein cholesterol (LDL-C) was both associated with GLP1R agonism and HF. The causal effect of GLP1R agonism on HF was partially mediated through LDL-C by 4.23% of the total effect (95% CI = 1.04-7.42%, p = 0.0093). CONCLUSIONS: This study supported the causal relationships of GLP1R agonists with a reduced risk of HF. LDL-C might be the mediator in this association, highlighting the cardiometabolic benefit of GLP1R agonists on HF.

Deep learning based method for predicting DNA N6-methyladenosine sites.

DNA N6 methyladenine (6mA) plays an important role in many biological processes, and accurately identifying its sites helps one to understand its biological effects more comprehensively. Previous traditional experimental methods are very labor-intensive and traditional machine learning methods also seem to be somewhat insufficient as the database of 6mA methylation groups becomes progressively larger, so we propose a deep learning-based method called multi-scale convolutional model based on global response normalization (CG6mA) to solve the prediction problem of 6mA site. This method is tested with other methods on three different kinds of benchmark datasets, and the results show that our model can get more excellent prediction results.

68Ga-PSMA PET/CT and 18F-FDG PET/CT in the diagnosis of prostatic ductal cancer.

PURPOSES: To explore the characteristics of PSMA PET/CT and FDG PET/CT images in prostatic ductal adenocarcinoma (DA) patients. METHODS: We retrospectively enrolled prostatic DA patients with PET/CT scans at Tongji Hospital from 2018 to 2022. Patients with prostatic acinar adenocarcinoma (AA) and benign pathology (BP) were enrolled by 1:1 matching. Differences in the uptake of primary and metastatic foci on PET among the groups were analyzed. RESULTS: A total of 42 patients were enrolled: 14 in each group. In primary foci, the mean PSMA uptake in the DA group was lower than that in the AA group (14.2 ± 9.6 vs. 27.1 ± 14.3, P = 0.009) and greater than that in the BP group (14.2 ± 9.6 vs. 4.7 ± 1.3, P = 0.003). The AUCs of the DA-AA ROC curve and DA-BP ROC curve were 0.781 and 0.872, respectively. The median PSMA uptake of metastatic lymph nodes in the DA group was lower than that in the AA group (5.6 vs. 14.2, P = 0.033), with no significant difference in metastatic bone lesions (9.5 vs 19.1, P = 0.485). No significant difference was found in the FDG uptake of primary and metastatic foci between the DA and AA groups (P > 0.05). CONCLUSION: Prostatic DA has greater PSMA uptake than BP diseases, but lower uptake in both primary foci and metastatic lymph nodes than AA on PSMA PET/CT, aiding in the differential diagnosis of DA, AA and BP diseases. Clinicians should combine traditional imaging with PSMA PET/CT to avoid underestimating the clinical stage of DA patients.

Role of the circRNA_34414/miR-6960a-5p/SIRT3 axis in postoperative delirium via CA1 Vglut1+ neurons in older mice.

AIMS: Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD. METHODS: The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression. RESULTS: Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3. CONCLUSIONS: CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p.

Suicidal ideation and suicide attempts among students aged 12 to 24 after the lifting of COVID-19 restrictions in China: prevalence and associated factors.

Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

Photocatalytic Pyridine Synthesis with Enaminones and TMEDA under Metal-Free Conditions.

Reported herein is a new photocatalytic annulation for the synthesis of 2,3,4,6-tetrasubstituted pyridines with enaminones and N,N,N',N'-tetramethyl ethylenediamine (TMEDA). The photocatalytic reactions take place without requiring a transition metal reagent and provide products with broad scope. The methyl in TMEDA acts as the carbon source in pyridine ring construction, and BrCF2CO2Et plays the role of the terminal oxidant for free radical quenching.

Compartment syndrome associations with drugs: a pharmacovigilance study of the FDA adverse event reporting system (FAERS).

BACKGROUND: Compartment syndrome is an uncommon but life-threatening condition. No study has comprehensively compared compartment syndrome (CS) association with available drugs. The objective of this study was to estimate the association between CS and drugs using the FDA Adverse Event Report System (FAERS). RESEARCH DESIGN AND METHODS: FAERS reports from the first quarter of 2004 to the third quarter of 2023 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CS cases. Reporting odds ratio (ROR), corresponding to 95% confidence intervals (95% CI) were calculated to detect a positive signal. RESULTS: A total of 2197 reports were considered in the study after the inclusion criteria were applied. Totally 100 drugs were found to be associated with CS. The median time for drug-associated CS was 45 days. CONCLUSIONS: By analyzing the FAERS database, the study revealed that certain drugs are significantly associated with compartment syndrome. Further studies are needed to verify whether these drugs are associated with such a risk.

Women and opioid use disorder treatment: A scoping review of experiences, use of patient-reported experience measures, and integration of person-centred care principles.

BACKGROUND: Patient-reported experience measures (PREMs) are an important aspect of assessing and improving women's experiences of person-centred care during treatment for Opioid Use Disorder (OUD). This scoping review aimed to 1) examine the extent, type, and characteristics of evidence regarding women's OUD treatment experiences, and 2) describe the extent to which PREMs and person-centred care principles are incorporated within research methods. METHODS: Following Joanna Briggs Institute guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), we conducted a scoping review to identify peer-reviewed articles on women's OUD treatment experiences. Data were extracted from 39 included studies and synthesised based on study design, method of assessment/analysis (including use of PREMs), key findings, and the integration of person-centred care principles. RESULTS: Analysis of included studies revealed a predominance of qualitative research focused on women's experiences of pharmacological OUD treatment (methadone and/or buprenorphine) in Western countries. Women in these studies reported predominantly negative or mixed experiences of treatment. Few studies used validated PREMs and there was a lack of direct assessment or focus on recognised person-centred care principles. However, common categories of outcomes/findings identified in results across studies broadly aligned with person-centred care principles (e.g., fast access to reliable healthcare, effective treatment by trusted professionals), emphasising their applicability to women's experiences of treatment. CONCLUSIONS: Although there has been an increased focus on women's experiences of treatment for OUD in recent years, results highlighted room for improvement regarding the systematic and comprehensive assessment of women's experiences across different contexts. Given the often negative or mixed experiences reported by women, an increased focus on assessing service provision through a person-centred care lens (including utilising PREMs) may allow for service improvements or adaptations targeted towards the needs and experiences of women.

Visible-light-induced Ritter-type amidation of α-hydroxy ketones in the selective synthesis of α,α-diamido and monoamido ketones.

Visible light-induced, transition metal-free oxidative dehydroxylation and C-H amidation of α-hydroxy ketones involving Ritter-type amidation has been developed, leading to the selective synthesis of α,α-diamido- and α-monoamido ketones with tunable selectivity as well as broad substrate tolerance.

Advances in novel biomaterials combined with traditional Chinese medicine rehabilitation technology in treatment of peripheral nerve injury.

Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two most crucial factors influencing functional rehabilitation post peripheral nerve injury. Over time, traditional Chinese medicine (TCM) rehabilitation approaches such as acupuncture, Tuina, and microneedles serve as pivot means to activate the regeneration of injured nerve Schwann cells. By promoting axon regeneration, these approaches can accomplish nerve repair, reconstruction, and functional rehabilitation. Although TCM rehabilitation approaches have clinically demonstrated effectiveness in promoting the repair and regeneration of PNI, the related molecular mechanisms remain unclear. This significantly hampers the application and promotion of TCM rehabilitation in PNI recovery. Therefore, deeply delving into the cellular and molecular mechanisms of TCM rehabilitation technologies to foster nerve regeneration stands as the most pressing issue. On the other hand, in recent years, novel biomaterials represented by hydrogels, microfluidic platforms, and new chitosan scaffolds have showed their unique roles in treating various degrees of nerve injury. These methods exhibit immense potential in conducting high-throughput cell and organoid culture in vitro and synthesizing diverse tissue engineering scaffolds and drug carriers. We believe that the combination of TCM rehabilitation technology and novel biomaterials can more effectively address precise treatment issues such as identification of treatment target and dosage control. Therefore, this paper not only summarizes the molecular mechanisms of TCM rehabilitation technology and novel biomaterials in treating peripheral nerve injury individually, but also explores the research direction of precise treatment by integrating the two at both macro and micro levels. Such integration may facilitate the exploration of cellular and molecular mechanisms related to neurodegeneration and regeneration, providing a scientific and theoretical foundation for the precise functional rehabilitation of PNI in the future.

MicroRNAs in opisthorchiids and their definitive hosts: Current Status and Perspectives.

Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis (family Opisthorchiidae) are parasitic flatworms that pose serious threats to humans in certain countries and cause opisthorchiasis/clonorchiasis. Opisthorchiid flukes parasitize the biliary tract of the host, causing cholangitis, cholecystitis, cholelithiasis and cholangiocarcinoma. In this review, we primarily focus on recent microRNAs (miRNAs) studies of opisthorchiid flukes and their definitive hosts. Many miRNAs are conserved and expressed in a developmentally stage specific manner in the three opisthorchiid flukes, which play important roles in the growth and development of Opisthorchiidae spp., as well as host-pathogen interactions. Some miRNAs might be potential biomarkers related to carcinogenesis of cholangiocarcinoma. Therefore, this review provides the basis for further investigating the roles of miRNAs in opisthorchiid flukes and their definitive hosts, as well as promoting the development of novel approaches to prevent and treat opisthorchiasis/clonorchiasis.

Spatial metabolomics reveals key features of hippocampal lipid changes in rats with postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a common complication after cardiac surgery. Numerous evidence suggest that dysregulation of lipid metabolism is associated with cognitive impairment; however, its precise role in the development of POCD is still obscure. In this study, we established a cardiopulmonary bypass (CPB) model in rats and employed the Barnes maze to assess cognitive function, selecting POCD rats for subsequent experimentation. Utilizing mass spectrometry imaging, we detected plenty of lipids accumulates within the hippocampal CA1in the POCD group. Immunofluorescence staining revealed a significant reduction in the fluorescence intensity of calcium-independent phospholipases A2 (iPLA2) in the POCD group compared to the control, while serine palmitoyl transferase (SPT) was markedly increased in the POCD group. Transmission electron microscopy revealed that the number of synapses in hippocampal CA1decreased significantly and postsynaptic density became thinner in POCD group. Furthermore, after reversing the metabolic disorders of iPLA2 and SPT in the rat brain with docosahexaenoic acid and myriocin, the incidence of POCD after CPB was significantly reduced and the disrupted lipid metabolism in the hippocampus was also normalized. These findings may offer a novel perspective for exploring the etiology and prevention strategies of POCD after CPB.