Abnormal HCK/glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis.

The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.

Microsphere lens array embedded microfluidic chip for SERS detection with simultaneous enhancement of sensitivity and stability.

Surface enhanced Raman spectroscopy (SERS) utilizes the fingerprint features of molecular vibrations to identify and detect substances. However, in traditional single focus excitation scenarios, its signal collection efficiency of the objective is restricted. Furthermore, the uneven distribution of samples on the SERS substrate would result in poor signal stability, while the excitation power is limited to avoid sample damage. SERS detection system always requires precise adjustment of focal length and spot size, making it difficult for point-of-care testing applications. Here, we proposed a SERS microfluidic chip with barium titanate microspheres array (BTMA) embedded using vacuum self-assembled hot-pressing method for SERS detection with simultaneous enhancement of sensitivity and stability. Due to photonic nano-jets and directional antenna effects, high index microspheres are perfect micro-lens for effective light focusing and signal collecting. The BTMA can not only disperse excitation beam into an array of focal points covering the target uniformly with very low signal fluctuation, but enlarge the power threshold for higher signal intensity. We conducted a proof-of-principle experiment on chip for the detection of bacteria with immuno-magnetic tags and immuno-SERS tags. Together with magnetic and ultrasonic operations, the target bacteria in the flow were evenly congregated on the focal plane of BTMA. It demonstrated a limit of detection of 5 cells/mL, excellent signal reproducibility (error∼4.84%), and excellent position tolerance of 500 µm in X-Y plane (error∼5.375%). It can be seen that BTMA-SERS microfluidic chip can effectively solve the contradiction between sensitivity and stability in SERS detection.

Effect of Time Window on Endovascular Thrombectomy with or without Intravenous Thrombolysis in Acute Ischemic Stroke: Results from DIRECT-MT.

INTRODUCTION: Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0-3 h and >3-4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT. METHODS: The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0-3 h or >3-4.5 h. RESULTS: Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3-4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0-3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0-3 h: 1.06 [95% CI: 0.73-1.52], acOR in patients within >3-4.5 h: 1.19 [95% CI: 0.78-1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0-3 treated within >3-4.5 h (62.90 vs. 48.72%) but not within 0-3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction. CONCLUSIONS: Our results did not support thrombectomy-alone administration within 3-4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT.

Robust global arrangement by coherent enhancement in Huygens-Fresnel traveling surface acoustic wave interference field.

The application of standing surface acoustic wave (SSAW) tweezers based on backpropagation superposition to achieve precise behavior manipulation of microscale cells and even nanoscale bacteria has been widely studied and industrialized. However, the structure requires multiple transducer components or full channel resonance. It is very challenging to design a simple structure for nano-control by complex acoustic field. In this study, a reflector-interdigital transducer (R-IDT) acoustofluidic device based on unilateral coherence enhancement is proposed to achieve SSAW definition features of periodic particle capture positions. The SAW device based on a unilateral transducer can not only generate leaky-SAW in water-filled microchannel, but also have a contribution of spherical waves in the vibration area of the substrate-liquid interface due to the Huygens-Fresnel diffractive principle. Both of them form a robust time-averaged spatial periodicity in the pressure potential gradient, accurately predicting the lateral spacing of these positions through acoustic patterning methods. Furthermore, a reflector based on Bragg-reflection is used to suppress backward transmitted SAW and enhance forward conducted SAW beams. By using a finite element model, R-IDT structure's amplitude enhances 60.78% compared to single IDT structure. The particle manipulation range of the diffractive acoustic field greatly improves, verified by experimental polystyrene microspheres. Besides, biocompatibility is conformed through red blood cells and Bacillus subtilis. We investigate the overall shift of periodic pressure field that can still occur when the phase changes. This work provides a simpler and low-cost solution for the application of acoustic tweezer in biological cell culture and filtering.

Percutaneous angioplasty and/or stenting versus aggressive medical therapy in patients with symptomatic intracranial atherosclerotic stenosis: a 1-year follow-up study.

Background: Symptomatic intracranial atherosclerotic stenosis (sICAS) is one of the common causes of ischemic stroke. However, the treatment of sICAS remains a challenge in the past with unfavorable findings. The purpose of this study was to explore the effect of stenting versus aggressive medical management on preventing recurrent stroke in patients with sICAS. Methods: We prospectively collected the clinical information of patients with sICAS who underwent percutaneous angioplasty and/or stenting (PTAS) or aggressive medical therapy from March 2020 to February 2022. Propensity score matching (PSM) was employed to ensure well-balanced characteristics of two groups. The primary outcome endpoint was defined as recurrent stroke or transient ischemic attack (TIA) within 1 year. Results: We enrolled 207 patients (51 in the PTAS and 156 in the aggressive medical groups) with sICAS. No significant difference was found between PTAS group and aggressive medical group for the risk of stroke or TIA in the same territory beyond 30 days through 6 months (P = 0.570) and beyond 30 days through 1 year (P = 0.739) except for within 30 days (P = 0.003). Furthermore, none showed a significant difference for disabling stroke, death and intracranial hemorrhage within 1 year. These results remain stable after adjustment. After PSM, all the outcomes have no significant difference between these two groups. Conclusion: The PTAS has similar treatment outcomes compared with aggressive medical therapy in patients with sICAS across 1-year follow-up.

The Role of High-Resolution Magnetic Resonance Imaging in Cerebrovascular Disease: A Narrative Review.

High-resolution magnetic resonance imaging (HRMRI) is the most important and popular vessel wall imaging technique for the direct assessment of vessel wall and cerebral arterial disease. It can identify the cause of stroke in high-risk plaques and differentiate the diagnosis of head and carotid artery dissection, including inflammation, Moya Moya disease, cerebral aneurysm, vasospasm after subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, blunt cerebrovascular injury, cerebral arteriovenous malformations, and other stenosis or occlusion conditions. Through noninvasive visualization of the vessel wall in vitro, quantified assessment of luminal stenosis and pathological features of the vessel wall can provide clinicians with further disease information. In this report, technical considerations of HRMRI are discussed, and current clinical applications of HRMRI are reviewed.

Blood pressure excursion on admission and intravenous thrombolysis in ischemic stroke.

BACKGROUND: Blood pressure (BP) excursion on admission was common in patients with acute ischemic stroke, but its influence on thrombolysis effect was not fully evaluated. METHODS: Patients with acute ischemic stroke who received thrombolysis without subsequent thrombectomy were included. Admission BP excursion was defined as higher than 185/110 mmHg. Multivariate logistic regression analysis was used to evaluate the relationship between admission BP excursion and poor outcome as well as hemorrhage rates and mortality. Poor outcome was defined as a 90-day modified Rankin Scale score 3-6. Subgroup analysis was performed according to stroke severity, which was assessed by the National Institutes of Health Stroke Scale (NIHSS) score, and hypertension status. RESULTS: A total of 633 patients were enrolled and 240 participants (37.9%) had admission BP excursion. Admission BP excursion was associated with poor outcome [adjusted odds ratio (OR) 0.64, 95% confidence interval 0.42-0.99, P  = 0.046]. No significant difference was found regarding hemorrhage rates or mortality between patients with and without admission BP excursion. In subgroup analysis, admission BP excursion was related to poor outcome in patients with NIHSS score at least 7 (adjusted OR 1.89, 95% confidence interval 1.03-3.45, P  = 0.038), but not in patients with NIHSS score less than 7 ( P for interaction <0.001). CONCLUSION: Admission BP excursion above the guideline thresholds did not increase postthrombolysis hemorrhage risk or mortality, but was associated with poor outcome, especially in patients with severe stroke.

Heme induced progesterone-resistant profiling and promotion of endometriosis in vitro and in vivo.

Endometriosis is an estrogen-dependent, progesterone-resistant gynecological disease with an unknown pathogenesis. Compared to women without endometriosis, women with endometriosis have a remarkably high heme level in the peritoneal fluid. To further investigate the pathomechanisms of heme in endometriosis, we aimed to identify the dysregulated expression of heme-trafficking proteins, such as PGRMC1/2 that are also receptors that mediate the non-genomic responses to progesterone, and heme-degrading enzymes between ectopic endometrial stromal cells and their normal counterparts. We found that heme could regulate progesterone receptor-related gene expression. Functional human endometrial stromal cell experiments showed that heme promotes cell proliferation and migration in a heme oxygenase-1-independent manner; moreover, blocking oxidative phosphorylation/ATP generation could abolish these effects of heme in vitro, whereas intraperitoneal hemopexin administration could alleviate heme-triggered ectopic lesions in vivo. Therefore, heme likely mediates the induction of progesterone resistance and simultaneously induces endometriosis via the mitochondrial oxidative phosphorylation pathway.

An ultra-compact acoustofluidic device based on the narrow-path travelling surface acoustic wave (np-TSAW) for label-free isolation of living circulating tumor cells.

Obtaining highly purified intact living cells from complex environments has been a challenge, such as the isolation of circulating tumor cells (CTCs) from blood. In this work, we demonstrated an acoustic-based ultra-compact device for cell sorting, with a chip size of less than 2 × 1.5 cm2. This single actuator device allows non-invasive and label-free isolation of living cells, offering greater flexibility and applicability. The device performance was optimized with different-sized polystyrene (PS) particles and blood cells spiked with cancer cells. Using the narrow-path travelling surface acoustic wave (np-TSAW), precise isolation of 10 µm particles from a complex mixture of particles (5, 10, 20 µm) and separation of 8 µm and 10 µm particles was achieved. The purified collection of 10 µm particles with high separation efficiency (98.75%) and high purity (98.1%) was achieved by optimizing the input voltage. Further, we investigated the isolation and purification of CTCs (MCF-7, human breast cancer cells) from blood cells with isolation efficiency exceeding 98% and purity reaching 93%. Viabilities of the CTCs harvested from target-outlet were all higher than 97% after culturing for 24, 48, and 72 h, showing good proliferation ability. This novel ultra-miniaturized microfluidic chip demonstrates the ability to sorting cells with high-purity and label-free, providing an attractive miniaturized system alternative to traditional sorting methods.

Peritoneal immune microenvironment of endometriosis: Role and therapeutic perspectives.

Endometriosis, an estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, affects 10% of reproductive-age women. Although the pathogenesis of endometriosis is uncertain, it is widely accepted that retrograde menstruation results in ectopic endometrial tissue implantation. Given that not all women with retrograde menstruation develop endometriosis, immune factors have been hypothesized to affect the pathogenesis of endometriosis. In this review, we demonstrate that the peritoneal immune microenvironment, including innate immunity and adaptive immunity, plays a central role in the pathogenesis of endometriosis. Current evidence supports the fact that immune cells, such as macrophages, natural killer (NK) cells, dendritic cells (DCs), neutrophils, T cells, and B cells, as well as cytokines and inflammatory mediators, contribute to the vascularization and fibrogenesis of endometriotic lesions, accelerating the implantation and development of ectopic endometrial lesions. Endocrine system dysfunction influences the immune microenvironment through overexpressed estrogen and progesterone resistance. In light of the limitations of hormonal therapy, we describe the prospects for potential diagnostic biomarkers and nonhormonal therapy based on the regulation of the immune microenvironment. Further studies are warranted to explore the available diagnostic biomarkers and immunological therapeutic strategies for endometriosis.

Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis.

Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4+ T/CD8+ T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3+ T,CD4+T and CD8+T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4+ and CD8+ T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.

Cost-Effectiveness of Low-Dose Compared to Standard-Dose Alteplase for Acute Ischemic Stroke in China: A Within-Trial Economic Evaluation of the ENCHANTED Study.

INTRODUCTION: The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) showed that a low-dose alteplase was safe but not clearly non-inferior to standard-dose alteplase in acute ischemic stroke (AIS). Given the significant cost of this medicine, we undertook a cost-effectiveness analysis to determine the probability that low-dose is cost-effective relative to standard-dose alteplase in China. METHODS: For ENCHANTED participants in China with available health cost data, cost-effectiveness and cost-utility analyses were undertaken in which death or disability (modified Rankin scale scores 2-6) at 90 days and quality-adjusted life-years (QALYs) were used as outcome measures, respectively. There was adherence to standard guidelines for health economic evaluations alongside non-inferiority trials and according to a health-care payer's perspective. The equivalence margin for cost and effectiveness was set at USD 691 and -0.025 QALYs, respectively, for the base-case analysis. Probabilistic sensitivity analyses were used to evaluate the probability of low-dose alteplase being non-inferior. RESULTS: While the mean cost of alteplase was lower in the low-dose group (USD 1,569 vs. USD 2,154 in the standard-dose group), the total cost was USD 56 (95% confidence interval [CI]: -1,000-1,113) higher compared to the standard-dose group due to higher hospitalization costs in the low-dose group. There were 462 (95% CI: 415-509) and 410 (95% CI: 363-457) patients with death or disability per 1,000 patients in the low-dose and standard-dose groups, respectively. The low-dose group had marginally lower (0.008, 95% CI: -0.016-0.001) QALYs compared to their standard-dose counterparts. The low-dose group was found to have an 88% probability of being non-inferior based on cost-effectiveness versus the standard-dose group. CONCLUSIONS: This health economic evaluation alongside the ENCHANTED indicates that the use of low-dose alteplase does not save overall healthcare costs nor lead to a gain in QALYs in the management of Chinese patients with AIS compared to the use of standard dose. There is little justification on economic grounds to shift from standard-of-care thrombolysis in AIS.

Clinical characteristics and risk factors for a prolonged length of stay of patients with asymptomatic and mild COVID-19 during the wave of Omicron from Shanghai, China.

BACKGROUND: This study aims to investigate the clinical characteristics and the length of hospital stay (LOS), as well as risk factors for prolonged LOS in a cohort of asymptomatic and mild COVID-19 patients infected with the Omicron variant. METHODS: A total of 1166 COVID-19 patients discharged from the inpatient ward of the largest makeshift hospital (May 8-10, 2022) in Shanghai, China, were included. The demographics, medical history, and the lowest and admission cycle threshold (Ct) values of the RT-PCR tests for SARS-CoV-2 genes of the open reading frame 1ab (Ct-ORF) and the nucleocapsid protein (Ct-N) during hospitalization were recorded. Patients with LOS > 7 days, or LOS ≤ 7 days were included in the Prolonged group or the Control group, separately. The clinical characteristics and LOS of the participants in the two groups were described and compared. Multivariate Logistic and linear regression analyses were applied to explore the risk factors for prolonged LOS. The diagnostic efficacy of the lowest and admission Ct values for the Prolonged group was tested via the receiver operating characteristic (ROC) curve analysis. RESULTS: The median LOS was 6 days in the total study population. The age was older (45.52 ± 14.78 vs. 42.54 ± 15.30, P = 0.001), while both the lowest and admission Ct-ORF (27.68 ± 3.88 vs. 37.00 ± 4.62, P < 0.001; 30.48 ± 5.03 vs. 37.79 ± 3.81, P < 0.001) and Ct-N (25.79 ± 3.60 vs. 36.06 ± 5.39, P < 0.001; 28.71 ± 4.95 vs. 36.95 ± 4.59, P < 0.001) values were significantly lower in the Prolonged group. There were more mild cases in the Prolonged group (23.8% vs. 11.5%, P < 0.001). The symptom spectrum differed between the two groups. In multivariate analyses, age, disease category, and the lowest Ct-N values were shown to be associated with prolonged LOS. Besides, both the lowest and admission Ct-ORF (AUC = 0.911 and 0.873) and Ct-N (AUC = 0.912 and 0.874) showed robust diagnostic efficacy for prolonged LOS. CONCLUSIONS: Our study firstly reports the clinical characteristics and risk factors for prolonged LOS during the wave of the Omicron epidemic in Shanghai, China. These findings provide evidence for the early identification of asymptomatic and mild COVID-19 patients at a high risk of prolonged hospitalization who may require early intervention, and long-term monitoring and management.

A Novel Detachable, Reusable, and Versatile Acoustic Tweezer Manipulation Platform for Biochemical Analysis and Detection Systems.

Multifunctional, integrated, and reusable operating platforms are highly sought after in biochemical analysis and detection systems. In this study, we demonstrated a novel detachable, reusable acoustic tweezer manipulation platform that is flexible and versatile. The free interchangeability of different detachable microchannel devices on the acoustic tweezer platform was achieved by adding a waveguide layer (glass) and a coupling layer (polydimethylsiloxane (PDMS) polymer film). We designed and demonstrated the detachable multifunctional acoustic tweezer platform with three cell manipulation capabilities. In Demo I, the detachable acoustic tweezer platform is demonstrated to have the capability for parallel processing and enrichment of the sample. In Demo II, the detachable acoustic tweezer platform with capability for precise cell alignment is demonstrated. In Demo III, it was demonstrated that the detachable acoustic tweezer platform has the capability for the separation and purification of cells. Through experiments, our acoustic tweezer platform has good acoustic retention ability, reusability, and stability. More capabilities can be expanded in the future. It provides a simple, economical, and multifunctional reusable operating platform solution for biochemical analysis and detection systems.

A Glycemia-Based Nomogram for Predicting Outcome in Stroke Patients after Endovascular Treatment.

Objective: Higher fasting glucose is thought to be associated with adverse outcome in patients receiving endovascular treatment (EVT), while the effect of glycosylated hemoglobin (HbA1c) on outcome is controversial. We combined fasting blood glucose (FBG) with HbA1c and evaluated their relationship with the three-month functional outcome in patients who underwent EVT. Methods: Data from 739 consecutive ischemic stroke patients who underwent EVT from April 2015 to August 2021 were retrospectively reviewed. HbA1c was used to estimate the chronic glucose level according to the following formula: chronic glucose level (mg/dL) = 28.7 × HbA1c (%) - 6.7. Patients were split into two groups in accordance with the three-month modified Rankin Scale (mRS). Univariate and multivariate analyses were utilized to investigate the association of outcome with blood glucose and to identify other predictors of prognosis. Results: Patients with poor outcome had significantly higher FBG, chronic glycemia, FBG/chronic glycemic ratio, and difference between FBG and chronic glycemia (ΔA-C). FBG, the FBG/chronic glycemic ratio, and ΔA-C remained to be associated with poor outcome after adjustment. We then established a glycemia-based nomogram with a concordance index of 0.841, and it showed favorable clinical utility according to decision curve analysis. Conclusions: Glycemia after EVT was connected with the functional outcome and a nomogram based on glycemia may be used to predict prognosis in stroke patients treated with EVT.

Human chorionic gonadotropin elevation in gliomatosis peritonei complicated with immature teratoma: A case report and review of the literature.

RATIONALE: Gliomatosis peritonei (GP) refers to the implantation of glial tissue on the visceral and parietal peritoneal surface, often associated with immature teratoma. It is a rare condition and the pathogenesis is not fully understood. In addition, the indistinguishable radiological appearance of immature and mature teratomas, and limited pathology samples make an accurate diagnosis difficult in most cases. More importantly, patients are also at risk of recurrence after surgery. This report aims to describe the process of diagnosis and treatment of GP with immature teratoma. PATIENT CONCERNS: The patient, a 38-year-old woman presented with GP complicated with immature teratoma after laparoscopic ovarian cyst excision. DIAGNOSES: On physical examination, a 15 cm-pelvic mass, with poor mobility, was palpated. And tumor marker demonstrated a moderate increase in α-fetoprotein and carbohydrate antigen 125. We suspected malignancy according to the comprehensive preoperative evaluation, the postoperative pathology revealed an immature teratoma of the left ovary and complicated with gliomatosis peritonei. Three months after the second surgery, possible recurrence of immature teratoma was considered and the patient underwent the third laparotomy. But the postoperative pathology indicated mature teratoma and mature glial components in the pelvic lesions. INTERVENTIONS AND OUTCOME: The patient underwent 2 more surgical resections after the initial resection and 3 cycles of bleomycin, etoposide, and cisplatin regimen chemotherapy. She was regularly followed up in the outpatient after surgery, and no recurrence has been reported in the pelvic cavity till date. LESSON: The case illuminated that the primary diagnosis of GP complicated with immature teratoma is critical but highly challenging for both gynecologists and pathologists and more attention should be paid to "GP complicated with immature cystic teratoma" patients to avoid inappropriate treatment.

Neurokinin 3 receptor antagonist-induced adipocyte activation improves obesity and metabolism in PCOS-like mice.

AIMS: Neurokinin-B (NKB)-Neurokinin-3-receptor (NK3R) pathway is remarkably sensitive to energy equilibrium; however, its role in metabolic regulation remains unexplored in polycystic ovary syndrome (PCOS). Therefore, this work aimed to investigate the role of NK3R antagonists (NK3Ra) on metabolic dysfunction and obesity in in vitro and in vivo PCOS models. MAIN METHODS: First, an observational study using serum samples collected from 19 PCOS patients was performed. Second, prospective case-control experimental studies where NK3Ra (SB222200) was used to treat PCOS-like mice (BALB/c mice), ovariectomized+estrogen implanted obese mice (C57BL/6J mice) and 3T3-L1 murine preadipocytes were carried out to investigate its effect on metabolism in vivo and in vitro. The fat volumes, serum biochemical indexes, adipokines and inflammatory cytokines, metabolism-related gene expression and the concentrations of ATP, NAD+, NADPH…etc. were studied. KEY FINDINGS: We found a positive correlation between serum NKB and lipid metabolism indicators in PCOS women. Using the mouse models, we demonstrated that administration of NK3Ra regulates serum adipokines, inhibits weight gain with a marked decrease in fat volume, adipocyte size, and inflammatory cytokines, and promotes oxidative metabolism and energy consumption. NK3Ra reduces lipid accumulation in mature murine adipocytes by inhibiting the expression of peroxisome proliferator- activated receptor gamma (PPAR-γ) and fatty acid binding protein 4 (FABP4) genes. NK3Ras also enhances oxidative metabolism and energy consumption by maintaining intracellular redox homeostasis. SIGNIFICANCE: This study backs the use of NK3Ras as a potential therapeutic for PCOS since it ameliorates both reproductive and metabolic aberrations.

Influence of Structural Parameters on Performance of SAW Resonators Based on 128° YX LiNbO3 Single Crystal.

The seeking of resonator with high Q and low insertion loss is attractive for critical sensing scenes based on the surface acoustic wave (SAW). In this work, 128° YX LiNbO3-based SAW resonators were utilized to optimize the output performance through IDT structure parameters. Once the pairs of IDTs, the acoustic aperture, the reflecting grid logarithm, and the gap between IDT and reflector are changed, a better resonance frequency of 224.85 MHz and a high Q of 1364.5 were obtained. All the results demonstrate the structure parameters design is helpful for the performance enhancement with regard to SAW resonators, especially for designing and fabricating high-Q devices.

Enhanced Detection in Droplet Microfluidics by Acoustic Vortex Modulation of Particle Rings and Particle Clusters via Asymmetric Propagation of Surface Acoustic Waves.

As a basis for biometric and chemical analysis, issues of how to dilute or concentrate substances such as particles or cells to specific concentrations have long been of interest to researchers. In this study, travelling surface acoustic wave (TSAW)-based devices with three frequencies (99.1, 48.8, 20.4 MHz) have been used to capture the suspended Polystyrene (PS) microspheres of various sizes (5, 20, 40 µm) in sessile droplets, which are controlled by acoustic field-induced fluid vortex (acoustic vortex) and aggregate into clusters or rings with particles. These phenomena can be explained by the interaction of three forces, which are drag force caused by ASF, ARF caused by Leaky-SAW and varying centrifugal force. Eventually, a novel approach of free transition between the particle ring and cluster was approached via modulating the acoustic amplitude of TSAW. By this method, multilayer particles agglomerate with 20 µm wrapped around 40 µm and 20 µm wrapped around 5 µm can be obtained, which provides the possibility to dilute or concentrate the particles to a specific concentration.

A Novel Perturbed Spiral Sheathless Chip for Particle Separation Based on Traveling Surface Acoustic Waves (TSAW).

The combination of the new perturbed spiral channel and a slanted gold interfingered transducer (IDT) is designed to achieve precise dynamic separation of target particles (20 µm). The offset micropillar array solves the defect that the high-width flow (avoiding the occurrence of channel blockage) channel cannot realize the focusing of small particles (5 µm, 10 µm). The relationship between the maximum design gap of the micropillar (Smax) and the particle radius (a) is given: Smax = 4a, which not only ensures that small particles will not pass through the micropillar gap, but also is compatible with the appropriate flow rates. A non-offset micropillar array was used to remove 20 µm particles in the corner area. The innovation of a spiral channel structure greatly improves the separation efficiency and purity of the separation chip. The separation chip designed by us achieves deflection separation of 20 µm particles at 24.95-41.58 MHz (κ = 1.09-1.81), at a flow rate of 1.2 mL per hour. When f = 33.7 MHz (κ = 1.47), the transverse migration distance of 20 µm particles is the smallest, and the separation purity and efficiency are as high as 92% and 100%, respectively.