Automatic diagnosis for adenomyosis in ultrasound images by deep neural networks.

OBJECTIVE: To present a new noninvasive technique for automatic diagnosis of adenomyosis, using a novel end-to-end unified network framework based on transformer networks. STUDY DESIGN: This is a prospective descriptive study conducted at a university hospital.1654 patients were recruited to the study according to adenomyosis diagnosed by transvaginal ultrasound (TVS). For adenomyosis characteristics and ultrasound images, automatic identification of adenomyosis were performed based on deep learning methods. We called this unique technique A2DNet: Adenomyosis Auto Diagnosis Network. RESULTS: The A2DNet exhibits excellent performance in diagnosis of adenomyosis, achieving an accuracy of 92.33%, a precision of 96.06%, a recall of 91.71% and an F1 score of 93.80% in the test group. The confusion matrix of experimental results show that the A2DNet can achieve a correct diagnosis rate of 92% or more for both normal and adenomyosis samples, which demonstrate the superiority of the A2DNet comparing with the state-of-the-arts. CONCLUSION: The A2DNet is a safe and effective technique to aid in automatic diagnosis of adenomyosis. The technique which is nondestructive and non-invasive, is new and unique due to the advantages of artificial intelligence.

Dysregulation of plasma circulating microRNAs in all-cause and cause-specific cancers: the Rotterdam Study.

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation of gene expression. Mounting evidence underscores the dysregulation of miRNAs to be associated with cancer development and progression by acting as tumour suppressors and oncogenes. However, their potential as biomarkers for early diagnosis of different cancers remains incompletely unraveled. We explored the relationship between plasma circulatory miRNAs and cancer risk within the population-based Rotterdam Study cohort. Plasma samples were collected at baseline (between 2002 and 2005) and miRNA levels were measured in 1,999 participants, including 169 prevalent cancer cases. The occurrence of cancer was assessed by continuous monitoring of medical records in 1,830 cancer-free participants until January 1, 2015. We assessed the association between incidence of five common cancers (blood, lung, breast, prostate, and colorectal) and 591 miRNAs well-expressed in plasma, using adjusted Cox proportional-hazards regression models. Our longitudinal analysis identified 13 miRNAs significantly associated with incident hematologic tumors surpassing the Bonferroni-corrected P < 8.46 × 10- 5, 12 of them (miR-6124, miR-6778-5p, miR-5196, miR-654-5p, miR-4478, miR-4430, miR-4534, miR-1915-3p, miR-4644, miR-4292, miR-7111-5p, and miR-6870-5p) were also associated with prevalent hematologic tumors in the cross-sectional analysis at the baseline. In-silico analyses of the putative target genes of 13 identified miRNAs highlighted relevant genes and pathways linked to hematologic tumors. While no significant miRNA association was found for other four studied cancers, two miRNAs (miR-3157-5p and miR-3912-5p) showed nominal association with incident of three different cancer types. Overall, this study indicates that plasma levels of several miRNAs are dysregulated in hematologic tumors, highlighting their potential as biomarkers for early diagnosis as well as being involved in the pathogenesis of blood cancers.

Effect of different physical activity interventions on perinatal depression: a systematic review and network meta-analysis.

BACKGROUND: Perinatal depression can have profound impacts on both families and society. Exercise therapy is gradually becoming a widely used adjunct treatment for perinatal depression. Some studies have already focused on the relationship between physical activity and perinatal depression (PND). However, there is currently a lack of systematic and comprehensive evidence to address the crucial question of making optimal choices among different forms of physical activity. This study aims to compare and rank different physical activity intervention strategies and identify the most effective one for perinatal depression. METHODS: Four databases, namely PubMed, Cochrane Library, Embase, and Web of Science, were searched for randomized controlled trials assessing the impact of physical activity interventions on perinatal depression. The search covered the period from the inception of the databases until May 2024. Two researchers independently conducted literature screening, data extraction, and quality assessment. Network meta-analysis was performed using Stata 15.1. RESULTS: A total of 48 studies were included in the analysis. The results indicate that relaxation therapy has the most effective outcome in reducing perinatal depression (SUCRA = 99.4%). Following that is mind-body exercise (SUCRA = 80.6%). Traditional aerobics and aquatic sports were also effective interventions (SUCRA = 70.9% and 67.1%, respectively). CONCLUSION: Our study suggests that integrated mental and physical (MAP) training such as relaxation therapy and mind-body exercise show better performance in reducing perinatal depression. Additionally, while exercise has proven to be effective, the challenge lies in finding ways to encourage people to maintain a consistent exercise routine. TRIAL REGISTRATION: This study has been registered on PROSPERO (CRD 42,023,469,537).

Preoperative oral hygiene treatment reduces bacterial transport and colonization during intubation for orthopedic surgery.

PURPOSE: The process of infection by bacteria and viruses involves invasion, establishment, growth, and parasitization. Poor oral hygiene and dysbiosis are significant risk factors for pneumonia. The aim of this study was to evaluate bacterial transport into the trachea during intubation for orthopedic surgery and the impact of oral hygiene treatment. METHODS: The study cohort included 53 patients with fracture who underwent surgical procedures under general anesthesia and were divided into two groups: an oral hygiene treatment (OHT) group (n = 27) and a control group (n = 26). Before intubation, the OHT group underwent preoperative oral hygiene treatment. Microbiological culture was used for detection and counting of bacteria from the oropharynx, trachea, and tip of the endotracheal tube (ETT). RESULTS: Patients in the OHT group had a lower pathogen detection rate and lower degree of bacterial colonization in the oropharynx, trachea, and ETT tip. CONCLUSION: Preoperative oral hygiene treatment is able to reduce bacterial transport and colonization during orthopedic surgery, thus providing an important adjunct to pre-anesthesia care.

Association of blood cell-based inflammatory markers with gut microbiota and cancer incidence in the Rotterdam study.

The immune response-gut microbiota interaction is implicated in various human diseases, including cancer. Identifying the link between the gut microbiota and systemic inflammatory markers and their association with cancer will be important for our understanding of cancer etiology. The current study was performed on 8090 participants from the population-based Rotterdam study. We found a significant association (false discovery rate [FDR] ≤0.05) between lymphocytes and three gut microbial taxa, namely the family Streptococcaceae, genus Streptococcus, and order Lactobacillales. In addition, we identified 95 gut microbial taxa that were associated with inflammatory markers (p < 0.05). Analyzing the cancer data, we observed a significant association between higher systemic immune-inflammation index (SII) levels at baseline (hazard ratio (HR): 1.65 [95% confidence interval (CI); 1.10-2.46, p ≤ 0.05]) and a higher count of lymphocytes (HR: 1.38 [95% CI: 1.15-1.65, p ≤ 0.05]) and granulocytes (HR: 1.69 [95% CI: 1.40-2.03, p ≤ 0.05]) with increased risk of lung cancer after adjusting for age, sex, body mass index (BMI), and study cohort. This association was lost for SII and lymphocytes after additional adjustment for smoking (SII = HR:1.46 [95% CI: 0.96-2.22, p = 0.07] and lymphocytes = HR: 1.19 [95% CI: 0.97-1.46, p = 0.08]). In the stratified analysis, higher count of lymphocyte and granulocytes at baseline were associated with an increased risk of lung cancer in smokers after adjusting for age, sex, BMI, and study cohort (HR: 1.33 [95% CI: 1.09-1.62, p ≤0.05] and HR: 1.57 [95% CI: 1.28-1.92, p ≤0.05], respectively). Our study revealed a positive association between gut microbiota, higher SII levels, and higher lymphocyte and granulocyte counts, with an increased risk of developing lung cancer.

Effect of butorphanol-soaked nasal packing after endoscopic nasal surgery: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: This study was designed to investigate the effect of butorphanol-soaked nasal packing on analgesia and sleep quality in patients undergoing bilateral endoscopic nasal surgery. METHODS: Sixty-six patients were enrolled and randomly allocated into three groups: group B1 (butorphanol 0.03mg/kg), group B2 (butorphanol 0.04mg/kg) and group N (control group). The primary outcome was postoperative pain scores evaluated by a Visual Analogue Scale (VAS) at 2h (T1), 8h (T2), 24h (T3) and 48h (T4) after surgery. Secondary outcome was postoperative sleep quality measured using Subjective Sleep Quality Value (SSQV). RESULTS: Postoperative VAS scores of butorphanol groups were significantly lower than the control group at T2, T3 and T4. VAS scores at each time point did not differ between groups B1 and B2. On the first and second nights after surgery, SSQV was higher in butorphanol groups than in the control group. There were no significant differences in SSQV1 and SSQV2 between group B1 and group B2. The incidence of respiratory depression, dizziness, agitation and rescue analgesic use did not show difference among three groups. CONCLUSIONS: Butorphanol-soaked nasal packing can reduce pain and improve sleep quality after bilateral endoscopic nasal surgery without increasing adverse effects. A concentration of 0.03mg/kg may be appropriate for clinical application. LEVEL OF EVIDENCE: Level 1B.

Effect of butorphanol-soaked nasal packing after endoscopic nasal surgery: a double-blind, randomized, placebo-controlled trial

Abstract Objective This study was designed to investigate the effect of butorphanol-soaked nasal packing on analgesia and sleep quality in patients undergoing bilateral endoscopic nasal surgery. Methods Sixty-six patients were enrolled and randomly allocated into three groups: group B1 (butorphanol 0.03 mg/kg), group B2 (butorphanol 0.04 mg/kg) and group N (control group). The primary outcome was postoperative pain scores evaluated by a Visual Analogue Scale (VAS) at 2 h (T1), 8 h (T2), 24 h (T3) and 48 h (T4) after surgery. Secondary outcome was postoperative sleep quality measured using Subjective Sleep Quality Value (SSQV). Results Postoperative VAS scores of butorphanol groups were significantly lower than the control group at T2, T3 and T4. VAS scores at each time point did not differ between groups B1 and B2. On the first and second nights after surgery, SSQV was higher in butorphanol groups than in the control group. There were no significant differences in SSQV1 and SSQV2 between group B1 and group B2. The incidence of respiratory depression, dizziness, agitation and rescue analgesic use did not show difference among three groups. Conclusions Butorphanol-soaked nasal packing can reduce pain and improve sleep quality after bilateral endoscopic nasal surgery without increasing adverse effects. A concentration of 0.03 mg/kg may be appropriate for clinical application. Level of Evidence Level 1B.

The Genetic Polymorphism and Structural Analysis of 47 Microhaplotypes in a Jiangsu Changshu Chinese Han Population / 生物化学与生物物理进展

ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (Ae) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

Research progress of thrombus permeability in acute ischemic stroke / 中华神经科杂志

In patients with acute ischemic stroke, there is a wide variation in the composition of blood clots that block the blood vessels. Some imaging features are associated with the components of the clot, such as thrombus permeability, which is related to higher red blood cell density and lower fibrinogen density. The different components and mechanical properties of the clot may have an impact on treatment effectiveness and risk. Therefore, this article aims to summarize the correlation between thrombus permeability and biological, imaging characteristics, and explore the clinical significance of thrombus permeability in the treatment of patients with acute ischemic stroke, providing reference and assistance for neurologists.

Association between napping and cognitive impairment: A systematic review and meta-analysis.

STUDY OBJECTIVES: Increasing evidence suggests that napping is associated with cognitive impairment and dementia, but the conclusions are inconsistent. Moreover, the extent of the risk is uncertain. We therefore conducted a systematic review and meta-analysis to quantify the connection between napping and cognitive impairment. METHODS: We performed a systematic search of PubMed, EMBASE, Web of Science, and Cochrane Library for studies that were published up to June 2023, and assessed associations between napping and cognitive impairment. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as the effect sizes for all studies. Heterogeneity and potential publication biases were assessed. RESULTS: A total of 4535 papers were retrieved, with 20 reports assessing the relationships between napping and cognitive impairment. Pooled analysis indicated that napping was associated with dementia (OR = 1.14; 95% CI: 1.07-1.21). Importantly, we found that those napping longer than 30, 45, and 60 min/day were 35%, 41%, and 40%, respectively, more likely to have an increased risk of cognitive impairment (30 min: OR = 1.35; 95% CI: 1.24-1.48; 45 min: OR = 1.41; 95% CI: 1.27-1.58; 60 min: OR = 1.40; 95% CI: 1.26-1.56). North America and Europe showed that associations existed between napping and cognitive impairment (North America: OR = 1.15; 95% CI: 1.04-1.27; Europe: OR = 1.13; 95% CI: 1.08-1.18). CONCLUSIONS: This meta-analysis indicated associations between long napping durations and cognitive impairment or dementia, suggesting that longer napping might be a potential risk factor of adverse cognitive outcomes.

Preparation of Ir-Cu/C nanosheets for the oxygen evolution reaction by room temperature plasma carbonization.

Ir-Cu/C nanosheets with a thickness of about 2 nm were prepared using Ar plasma carbonization and reduction at room temperature. The obtained Ir-Cu/C catalyst, composed of single atom Ir-doped Cu nanoparticles embedded in a carbon framework, exhibits efficient oxygen evolution reaction activity with a low overpotential.

Smoking-related dysregulation of plasma circulating microRNAs: the Rotterdam study.

BACKGROUND: MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Differential miRNA expression, which is widely shown to be associated with the pathogenesis of various diseases, can be influenced by lifestyle factors, including smoking. This study aimed to investigate the plasma miRNA signature of smoking habits, the potential effect of smoking cessation on miRNA levels, and relate the findings with lung cancer incidence. RESULTS: A targeted RNA-sequencing approach measured plasma miRNA levels in 2686 participants from the population-based Rotterdam study cohort. The association between cigarette smoking (current versus never) and 591 well-expressed miRNAs was assessed via adjusted linear regression models, identifying 41 smoking-associated miRNAs that passed the Bonferroni-corrected threshold (P < 0.05/591 = 8.46 × 10-5). Moreover, we found 42 miRNAs with a significant association (P < 8.46 × 10-5) between current (reference group) and former smokers. Then, we used adjusted linear regression models to explore the effect of smoking cessation time on miRNA expression levels. The expression levels of two miRNAs were significantly different within 5 years of cessation (P < 0.05/41 = 1.22 × 10-3) from current smokers, while for cessation time between 5 and 15 years we found 19 miRNAs to be significantly different from current smokers, and finally, 38 miRNAs were significantly different after more than 15 years of cessation time (P < 1.22 × 10-3). These results imply the reversibility of the smoking effect on plasma levels of at least 38 out of the 41 smoking-miRNAs following smoking cessation. Next, we found 8 out of the 41 smoking-related miRNAs to be nominally associated (P < 0.05) with the incidence of lung cancer. CONCLUSIONS: This study demonstrates smoking-related dysregulation of plasma miRNAs, which might have a potential for reversibility when comparing different smoking cessation groups. The identified miRNAs are involved in several cancer-related pathways and include 8 miRNAs associated with lung cancer incidence. Our results may lay the groundwork for further investigation of miRNAs as potential mechanism linking smoking, gene expression and cancer.

Ultrasound assessment of gastric residual volume in patients over 60 years of age undergoing gastroscopy under sedation: a prospective cohort study.

BACKGROUND: We aimed to assess the accuracy of ultrasonographic measurement of the antral cross-sectional area (CSA) in the preprocedural evaluation of gastric contents and volume in fasted patients > 60 yr of age scheduled for gastroscopy under sedation. METHODS: We included n = 81 patients > 60 yr of age and n = 79 younger controls scheduled to undergo elective gastroscopy in a prospective cohort study. A gastric ultrasound examination was performed to measure the antral CSA in both semisitting and right lateral decubitus (RLD) positions. Afterward, patients were graded using the Perlas qualitative grading scale. The actual gastric volume was endoscopically suctioned. Full stomach was defined as gastric volume > 1.5 mL·kg-1 and/or the presence of solid particles. We constructed receiver operating characteristic curves to determine the accuracy of ultrasonographic measurement of RLD CSA to detect a gastric volume > 1.5 mL·kg-1 and calculated the diagnostic test attributes of RLD CSA for the identification of a gastric volume > 1.5 mL·kg-1 RESULTS: The incidence of full stomach was 8/81 (9.8%) in patients > 60 yr of age and 1/79 (1.2%) in young patients (risk difference, 8.6%; 95% CI, 1.3 to 15.8; P = 0.03). The cut-off value of RLD CSA was 10.4 cm2 for the detection of gastric volume > 1.5 mL·kg-1 in patients > 60 yr of age, with a sensitivity of 75%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 98.6%. CONCLUSION: Patients > 60 yr of age scheduled for gastroscopy under sedation had a higher incidence of a full stomach detected with ultrasound compared with a younger cohort, which is potentially associated with a higher aspiration risk. We calculated a cut-off value of RLD CSA for detecting gastric volume in patients > 60 yr of age of approximately 10 cm2, which may help to quickly assess patients at risk of aspiration. TRIAL REGISTRATION: www.chictr.org.cn (ChiCTR2100048994); registered 19 July 2021.

RéSUMé: CONTEXTE: Notre objectif était d'évaluer la précision de la mesure échographique de la section transversale antrale (CSA) dans l'évaluation préprocédurale du contenu et du volume gastriques chez les patient·es à jeun > 60 ans devant bénéficier d'une gastroscopie sous sédation. MéTHODE: Nous avons inclus n = 81 patient·es > 60 ans et n = 79 patient·es témoins plus jeunes devant bénéficier d'une gastroscopie non urgente dans une étude de cohorte prospective. Une échographie gastrique a été réalisée pour mesurer la CSA antrale en position semi-assise et en décubitus latéral droit (DLD). Par la suite, la patientèle a été classée à l'aide de l'échelle de classement qualitatif de Perlas. Le volume gastrique réel était aspiré par endoscopie. Un estomac plein a été défini comme un volume gastrique > 1,5 mL·kg­1 et/ou la présence de particules solides. Nous avons construit des courbes de la fonction d'efficacité du récepteur (courbes ROC) afin de déterminer la précision de la mesure échographique de la CSA en DLD pour détecter un volume gastrique > 1,5 mL·kg­1 et calculé les attributs du test diagnostique de la CSA en DLD pour identifier un volume gastrique > 1,5 mL·kg­1. RéSULTATS: L'incidence d'estomac plein était de 8/81 (9,8 %) chez les patient·es > 60 ans et 1/79 (1,2 %) chez les patient·es jeunes (différence de risque, 8,6 %; IC 95 %, 1,3 à 15,8; P = 0,03). La valeur seuil de la CSA en DLD était de 10,4 cm2 pour la détection d'un volume gastrique > 1,5 mL·kg­1 chez la patientèle > 60 ans, avec une sensibilité de 75 %, une spécificité de 100 %, une valeur prédictive positive de 100 % et une valeur prédictive négative de 98,6 %. CONCLUSION: La patientèle > 60 ans devant bénéficier d'une gastroscopie sous sédation avait une incidence plus élevée d'estomac plein détecté par échographie par rapport à une cohorte plus jeune, ce qui est potentiellement associé à un risque d'aspiration plus élevé. Nous avons calculé une valeur seuil de la CSA en DLD pour détecter le volume gastrique chez les patient·es > 60 ans d'environ 10 cm2, ce qui peut aider à évaluer rapidement les personnes à risque d'aspiration. ENREGISTREMENT DE L'éTUDE: www.chictr.org.cn (ChiCTR2100048994); enregistrée le 19 juillet 2021.

ARID1A Inactivation Increases Expression of circ0008399 and Promotes Cisplatin Resistance in Bladder Cancer.

OBJECTIVE: Cisplatin (CDDP)-based chemotherapy is a first-line, drug regimen for muscle-invasive bladder cancer (BC) and metastatic bladder cancer. Clinically, resistance to CDDP restricts the clinical benefit of some bladder cancer patients. AT-rich interaction domain 1A (ARID1A) gene mutation occurs frequently in bladder cancer; however, the role of CDDP sensitivity in BC has not been studied. METHODS: We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology. IC50 determination, flow cytometry analysis of apoptosis, and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A. qRT-PCR, Western blotting, RNA interference, bioinformatic analysis, and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC. RESULTS: It was found that ARID1A inactivation was associated with CDDP resistance in BC cells. Mechanically, loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3 (EIF4A3) through epigenetic regulation. Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399 (circ0008399), a novel circular RNA (circRNA) identified in our previous study, which, to some extent, showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells. Importantly, EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP. CONCLUSION: Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.

The TREM2 H157Y Variant Influences Microglial Phagocytosis, Polarization, and Inflammatory Cytokine Release.

Previously, we reported that H157Y, a rare coding variant on exon 3 of the triggering receptor expressed on myeloid cells 2 gene (TREM2), was associated with Alzheimer's disease (AD) risk in a Han Chinese population. To date, how this variant increases AD risk has remained unclear. In this study, using CRISPR-Cas9-engineered BV2 microglia, we tried to investigate the influence of the Trem2 H157Y variant on AD-related microglial functions. For the first time, we revealed that the Trem2 H157Y variant inhibits microglial phagocytosis of amyloid-ß, promotes M1-type polarization of microglia, and facilitates microglial release of inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. These findings provide new insights into the cellular mechanisms by which the TREM2 H157Y variant elevates the risk of AD.

WITHDRAWN: Identification and Validation of Autophagy-related Genes in Sepsis-related Acute Kidney Injury (S-AKI) via Bioinformatics Analysis

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the journal "Combinatorial Chemistry & High Throughput Screening".Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

AVE 0991 Suppresses Astrocyte-Mediated Neuroinflammation of Alzheimer's Disease by Enhancing Autophagy.

Purpose: Our previous study has shown that AVE 0991, a nonpeptide analogue of Ang-(1-7), ameliorates cognitive decline and inhibits NLRP3 inflammasome of astrocytes in Alzheimer's disease model mice. Additionally, several studies have suggested that activation of autophagy appears to effectively inhibit the progression of neuroinflammation. However, it is unclear whether AVE 0991 can modulate astrocyte autophagy to suppress neuroinflammation in Alzheimer's disease. Materials and Methods: APP/PS1 mice and Aß-treated primary astrocytes were used as the research objects in vivo and in vitro, respectively. Water maze test was used to evaluate cognitive function of mice, Nissl staining and immunofluorescence staining was used to assess neuronal damage. ELISA kits were used to detect the levels of Ang-(1-7) and Aß in the cortex, and qRT-PCR was used to detect the expression of cortical inflammation-related mediators. The expression of autophagy-related proteins in cortex were detected by Western blot. The upstream molecular responses involved in inflammation inhibition by AVE 0991 were validated by means of using the Mas1 antagonist and autophagy inhibitor. Results: We found that 30 days of intraperitoneal administration of AVE 0991 improved. Aß deposition, neuronal death, and cognitive deficits in APP/PS1 Alzheimer's disease model mice. Moreover, AVE 0991 treatment greatly suppressed astrocyte-mediated inflammation and up-regulated the expression of autophagy. Furthermore, the inhibitory effect of AVE 0991 on the expression of inflammatory factors was reversed by 3-MA, an autophagy inhibitor. Conclusion: These findings suggest that regulation of autophagy is critical for inhibiting astrocyte neuroinflammatory responses and demonstrate a potential neuroprotective mechanism by which AVE 0991 could suppress neuroinflammatory responses by enhancing autophagy.

A high-throughput KASP assay provides insights into the evolution of multiple resistant mutations in populations of the two-spotted spider mite Tetranychus urticae across China.

BACKGROUND: The two-spotted spider mite (TSSM), Tetranychus urticae (Acari: Tetranychidae), is a cosmopolitan phytophagous pest in agriculture and horticulture. It has developed resistance to many acaricides by target-site mutations. Understanding the status and evolution of resistant mutations in the field is essential for resistance management. Here, we applied a high-throughput Kompetitive allele-specific polymerase chain reaction (KASP) method for detecting six mutations conferring resistance to four acaricides of the TSSM. We genotyped 3274 female adults of TSSM from 43 populations collected across China in 2017, 2020, and 2021. RESULTS: The KASP genotyping of 24 testing individuals showed 99% agreement with Sanger sequencing results. KASP assays showed that most populations had a high frequency of mutations conferring avermectin (G314D and G326E) and pyridaben (H92R) resistance. The frequency of mutation conferring bifenazate (A269V and G126S) and etoxazole (I1017F) resistance was relatively low. Multiple mutations were common in the TSSM, with 70.2% and 24.6% of individuals having 2-6 and 7-10 of 10 possible resistant alleles, respectively. No loci were linked in most populations among the six mutations, indicating the development of multiple resistance is mainly by independent selection. However, G314D and I1017F on the nuclear genome deviated from Hardy-Weinberg equilibrium in most populations, indicating significant selective pressure on TSSM populations by acaricides or fitness cost of the mutations in the absence of acaricide selection. CONCLUSION: Our study revealed that the high frequency of TSSMs evolved multiple resistant mutations in population and individual levels by independent selection across China, alarming for managing multiple-acaricides resistance. © 2023 Society of Chemical Industry.

The Alzheimer's disease-associated gene TREML2 modulates inflammation by regulating microglia polarization and NLRP3 inflammasome activation.

Triggering receptor expressed on myeloid cells-like 2 (TREML2) is a newly identified susceptibility gene for Alzheimer's disease (AD). It encodes a microglial inflammation-associated receptor. To date, the potential role of microglial TREML2 in neuroinflammation in the context of AD remains unclear. In this study, APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression. In addition, lipopolysaccharide (LPS) stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD. Our results show that TREML2 levels gradually increased in the brains of APP/PS1 mice during disease progression. LPS stimulation of primary microglia led to the release of inflammatory cytokines including interleukin-1ß, interleukin-6, and tumor necrosis factor-α in the culture medium. The LPS-induced microglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knockdown. LPS increased the levels of microglial M1-type polarization marker inducible nitric oxide synthase. This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown. Furthermore, the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown. LPS stimulation increased the levels of NLRP3 in primary microglia. The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown. In summary, this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation. These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.