UPK3A+ umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome.

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor-like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3-NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self-repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland.

The critical role of P2XR/PGC-1α signalling pathway in hypoxia-mediated pyroptosis and M1/M2 phenotypic differentiation of mouse microglia.

Microglia are endogenous immune cells in the brain, and their pyroptosis and phenotype dichotomy are proved to play roles in neurodegenerative diseases. We investigated whether and how hypoxia affected pyroptosis and phenotype polarization in mouse microglia. Primary mouse microglia and BV2 microglia were exposed to hypoxia. Pyroptosis and M1/M2 phenotype were assessed by measuring gasdermin D truncation and M1/M2 surface marker expression. Mechanisms including purinergic ionotropic receptor (P2XR), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) and NOD-like receptor protein 3 (NLRP3) inflammasome were investigated. We reported hypoxia (90% N2, 5% O2 and 5% CO2) induced pyroptosis and promoted M1 phenotype polarization in primary mouse microglia and BV2 microglia, and the effect appeared after 6 h exposure. Although hypoxia (90% N2, 5% O2 and 5% CO2, 6 h) had no effect on P2X1R and P2X7R expression, it increased P2X4R expression and decreased PGC-1α expression. Interestingly, blockade of P2X4R or P2X7R abolished hypoxia-modulated PGC-1α expression, pyroptosis and M1 polarization. PGC-1α overexpression or overactivation alleviated hypoxia-induced pyroptosis and M1 polarization, while PGC-1α knockdown or deactivation promoted pyroptosis and M1 polarization under normoxic situation. Further, hypoxia induced NLRP3 expression and activated caspase-1 and induced the phosphorylation of NF-κB and reduced the phosphorylation of STAT3/6. NLRP3 inhibitor and caspase-1 inhibitor abolished hypoxia-induced pyroptosis, while NF-κB inhibitor and STAT phosphorylation inducer ameliorated hypoxia-induced M1 polarization. In addition, NF-κB activator and STAT3/6 inhibitor caused microglia M1 polarization under normoxic situation. We concluded in cultured mouse microglia, hypoxia may induce pyroptosis via P2XR/PGC-1α/NLRP3/caspase-1 pathway and trigger M1 polarization through P2XR/PGC-1α/NF-κB/STAT3/6 pathway.

Mullerian adenosarcoma of the uterus with MASO: a case report of cervical adenosarcoma in a young female that never had sexual behavior.

BACKGROUND: Cervical mullerian adenosarcoma is a rare uterine sarcoma, especially in young women. Its pathological features are low-grade malignant tumors with bidirectional differentiation, and the degree of malignancy is similar to that of low-grade endometrial stromal sarcoma. This paper reports the case of a young asexual patient who has been closely followed up after tumor resection and has not had any recurrences. CASE PRESENTATION: A 20-year-old, young asexual woman was diagnosed with cervical mullerian adenosarcoma with sarcomatous overgrowth (MASO). Cervical tumor resection was performed after admission, and the resection margin was negative. After the operation, she refused to undergo secondary surgery due to fertility requirements and did not receive adjuvant treatment. The patient was closely followed up after the operation and has not yet relapsed. CONCLUSION: A young woman with cervical MASO did not receive adjuvant treatment after cervical tumor resection. For women with fertility requirements, close follow-ups should be conducted after the operation to guard against tumor recurrence and radical tumor resection should be performed as early as possible after the patient no longer requires their fertility.

Functional to structural plasticity in unilateral sudden sensorineural hearing loss: neuroimaging evidence.

A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.

Correlation between clinical characteristics and tinnitus severity in tinnitus patients of different sexes: an analytic retrospective study.

PURPOSE: This study aimed to explore whether sex is influences tinnitus severity and whether the risk factors for tinnitus severity are the same in tinnitus patients of different sexes. METHODS: This was a retrospective study of data from 1427 patients complaining of tinnitus in a local hospital otolaryngology clinic from November 2019 to January 2022. All patients were interviewed and assessed by otoscopy, pure-tone audiometry, tinnitus handicap inventory (THI), visual analogue scale (VAS), and tinnitus refinement test. RESULTS: THI values were higher in females than in males (P = 0.00). Types of tinnitus sounds (OR 0.667, P = 0.000) and degree of hearing loss (OR 1.318, P = 0.000) were risk factors for tinnitus severity in males. Types of tinnitus sounds (OR 0.789, P = 0.005), sensation level (OR 1.023, P = 0.037), tinnitus types (OR 1.163, P = 0.041), tinnitus location (OR 1.198, P = 0.026), and the degree of hearing loss (OR 1.303, P = 0.000) were risk factors for tinnitus severity in females. Sex was an influencing factor for tinnitus severity. There were different risk factors for the tinnitus severity in different sexes. CONCLUSION: The risk factors for tinnitus severity differed according to sex in tinnitus patients, and the risk factors for tinnitus severity were greater in women than in men. These findings add to the literature on sex differences in tinnitus and suggest that medical and psychological screening of affected individuals and customized tinnitus treatment for each individual with tinnitus are needed. TRIAL REGISTRATION NUMBER/DATE OF REGISTRATION: ChiCTR2200057958, 2022/3/24 (retrospectively registered trials).

Development of an audiological assessment and diagnostic model for high occupational noise exposure.

PURPOSE: To explore the diagnostic auditory indicators of high noise exposure and combine them into a diagnostic model of high noise exposure and possible development of hidden hearing loss (HHL). METHODS: We recruited 101 young adult subjects and divided them according to noise exposure history into high-risk and low-risk groups. All subjects completed demographic characteristic collection (including age, noise exposure, self-reported hearing status, and headset use) and related hearing examination. RESULTS: The 8 kHz (P = 0.039) and 10 kHz (P = 0.005) distortion product otoacoustic emission amplitudes (DPOAE) (DPs) in the high-risk group were lower than those in the low-risk group. The amplitudes of the summating potential (SP) (P = 0.017) and action potential (AP) (P = 0.012) of the electrocochleography (ECochG) in the high-risk group were smaller than those in the low-risk group. The auditory brainstem response (ABR) wave III amplitude in the high-risk group was higher than that in the low-risk group. When SNR = - 7.5 dB (P = 0.030) and - 5 dB (P = 0.000), the high-risk group had a lower speech discrimination score than that of the low-risk group. The 10 kHz DPOAE DP, ABR wave III amplitude and speech discrimination score under noise with SNR = - 5 dB were combined to construct a combination diagnostic indicator. The area under the ROC curve was 0.804 (95% CI 0.713-0.876), the sensitivity was 80.39%, and the specificity was 68.00%. CONCLUSIONS: We expect that high noise exposure can be detected early with this combined diagnostic indicator to prevent HHL or sensorineural hearing loss (SNHL). TRIAL REGISTRATION NUMBER/DATE OF REGISTRATION: ChiCTR2200057989, 2022/3/25.

Mesh size control in forming an Ag/AgO nano-network structure for transparent conducting application.

The variation behaviors of the morphology, transmission, and sheet resistance of the surface Ag/AgO nano-network (NNW) structures fabricated under different illumination conditions and with different Ag deposition thicknesses and thermal annealing temperatures in forming initial Ag nanoparticles (NPs) are studied. Generally, an NNW structure with a smaller mesh size or a denser branch distribution has a lower transmission and a lower sheet resistance level. Under the fabrication condition of a broader illumination spectrum, a lower thermal annealing temperature, or a thicker Ag deposition, we can obtain an NNW structure of a smaller mesh size. The mesh size of an NNW structure is basically controlled by the seed density of Brownian tree (BT) at the beginning of light illumination. A BT seed can be formed through a stronger local localized surface plasmon resonance for accelerating Ag oxidation in a certain region. Once an Ag/AgO BT seed is formed, the surrounding Ag NPs are reorganized to form the branches of a BT. Multiple BTs are connected to form a large-area NNW structure, which can serve as a transparent conductor. Under the fabrication conditions of a broader illumination spectrum, 3 nm Ag deposition, and 100 °C thermal annealing, we can implement an NNW structure to achieve ∼1.15µm in mesh size, ∼90 Ω sq-1in sheet resistance, and 93%-77% in transmittance within the wavelength range between 370 and 700 nm.

A Data-Driven Model with Feedback Calibration Embedded Blood Pressure Estimator Using Reflective Photoplethysmography.

Ambulatory blood pressure (BP) monitoring (ABPM) is vital for screening cardiovascular activity. The American College of Cardiology/American Heart Association guideline for the prevention, detection, evaluation, and management of BP in adults recommends measuring BP outside the office setting using daytime ABPM. The recommendation to use night-day BP measurements to confirm hypertension is consistent with the recommendation of several other guidelines. In recent studies, ABPM was used to measure BP at regular intervals, and it reduces the effect of the environment on BP. Out-of-office measurements are highly recommended by almost all hypertension organizations. However, traditional ABPM devices based on the oscillometric technique usually interrupt sleep. For all-day ABPM purposes, a photoplethysmography (PPG)-based wrist-type device has been developed as a convenient tool. This optical, noninvasive device estimates BP using morphological characteristics from PPG waveforms. As measurement can be affected by multiple variables, calibration is necessary to ensure that the calculated BP values are accurate. However, few studies focused on adaptive calibration. A novel adaptive calibration model, which is data-driven and embedded in a wearable device, was proposed. The features from a 15 s PPG waveform and personal information were input for estimation of BP values and our data-driven calibration model. The model had a feedback calibration process using the exponential Gaussian process regression method to calibrate BP values and avoid inter- and intra-subject variability, ensuring accuracy in long-term ABPM. The estimation error of BP (ΔBP = actual BP-estimated BP) of systolic BP was -0.1776 ± 4.7361 mmHg; ≤15 mmHg, 99.225%, and of diastolic BP was -0.3846 ± 6.3688 mmHg; ≤15 mmHg, 98.191%. The success rate was improved, and the results corresponded to the Association for the Advancement of Medical Instrumentation standard and British Hypertension Society Grading criteria for medical regulation. Using machine learning with a feedback calibration model could be used to assess ABPM for clinical purposes.

Transmembrane (TMEM) protein family members: Poorly characterized even if essential for the metastatic process.

The majority of cancer-associated deaths are related to secondary tumor formation. This multistep process involves the migration of cancer cells to anatomically distant organs. Metastasis formation relies on cancer cell dissemination and survival in the circulatory system, as well as adaptation to the new tissue notably through genetic and/or epigenetic alterations. A large number of proteins are clearly identified to play a role in the metastatic process but the structures and modes of action of these proteins are essentially unknown or poorly described. In this review, we detail the involvement of members of the transmembrane (TMEM) protein family in the formation of metastases or in the mechanisms leading to cancer cell dissemination such as migration and extra-cellular matrix remodelling. While the phenotype associated with TMEM over or down-expression is clear, the mechanisms by which these proteins allow cancer cell spreading remain, for most of them, unclear. In parallel, the 3D structures of these proteins are presented. Moreover, we proposed that TMEM proteins could be used as prognostic markers in different types of cancers and could represent potential targets for cancer treatment. A better understanding of this heterogeneous family of poorly characterized proteins thus opens perspectives for better cancer patient care.

Combined effects of surface plasmon coupling and Förster resonance energy transfer on the light color conversion behaviors of colloidal quantum dots on an InGaN/GaN quantum-well nanodisk structure.

By forming nanodisk (ND) structures on a blue-emitting InGaN/GaN quantum-well (QW) template, the QWs become close to the red-emitting quantum dots (QDs) and Ag nanoparticles (NPs) attached onto the sidewalls of the NDs such that Förster resonance energy transfer (FRET) and surface plasmon (SP) coupling can occur to enhance the efficiency of blue-to-red color conversion. With a larger ND height, more QWs are exposed to open air on the sidewall for more QD/Ag NP attachment through QD self-assembly and Ag NP drop casting such that the FRET and SP coupling effects, and hence the color conversion efficiency can be enhanced. A stronger FRET process leads to a longer QD photoluminescence (PL) decay time and a shorter QW PL decay time. It is shown that SP coupling can enhance the FRET efficiency.

Nalbuphine on postoperative gastrointestinal tract dysfunction after laparoscopic surgery for gynaecological malignancies: A randomized controlled trial.

The aim of this study was to compare the effects of nalbuphine and sufentanil on the gastrointestinal (GI) tract after laparoscopic surgery for gynaecological malignancies. A total of 100 patients with American Society of Anesthesiologists (ASA) physical status I-II undergoing laparoscopic radical hysterectomy under general anaesthesia were enrolled. The patients were randomized to receive sufentanil (Group S) or nalbuphine (Group N) intraoperatively and postoperatively. The time to first passage of flatus, the time to first defaecation, the time to toleration of diet, the serum gastrin level, and the duration of hospital stay of the groups were compared. The Visual Analogue Scale (VAS) score for postoperative pain, the number of dispensed patient-controlled analgaesics (PCAs), and the prevalence of postoperative nausea, vomiting, and dizziness of the groups were also compared. The time to first passage of flatus (P = .551), time to first defaecation (P = .310), time to toleration of diet (P = .182), serum gastrin level (P = .397), prevalence of postoperative nausea (P = .920) and vomiting (P = .334), number of dispensed PCAs (P = .167), and the duration of hospital stay (P = .482) of the two groups were not significantly different. The VAS scores at 6 hours (P = .008), 12 hours (P = .002), and 24 hours (P = .013) postoperatively were lower in Group N than in Group S. In conclusion, nalbuphine was not associated with improved postoperative GI dysfunction after laparoscopic surgery for gynaecological malignancies, but it was associated with reduced postoperative pain.

Epidemiological survey of adult female stress urinary incontinence.

BACKGROUND: The prevalence of stress urinary incontinence (SUI) in adult female in Taiyuan and what are the related risk factors are not clear. The aim of this study was to provide a basis for exploring the prevention and treatment of SUI in adult female in Taiyuan. METHODS: A voluntary online questionnaire was used to investigate adult female in the community and surrounding townships of Taiyuan. Most of the questionnaires refer to the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms, and adapt to the specific circumstances of the region. Data were analyzed using SPSS software (version 22.0). RESULTS: A total of 4004 eligible questionnaires were obtained. The prevalence of SUI in adult female in Taiyuan was 33.5%. Univariate analysis and multivariate logistic regression analysis showed that place of residence, smoking, body mass index, diet, number of deliveries, mode of delivery, dystocia, menopause, oral contraceptives, urinary tract infection, making the bladder empty faster by pushing down and holding urine were risk factors for adult female stress urinary incontinence in Taiyuan. CONCLUSION: The prevalence of SUI in adult female in Taiyuan was high, and based on risk factors identified in this survey, population-level intervention strategies should be developed for the prevention and treatment of adult female SUI in Taiyuan.

[A Preliminary Study of Applying Geometric Deep Learning in Brain Morphometry for Diagnosis of Alzheimer's Disease].

OBJECTIVE: A predictive model of Alzheimer's disease (AD) was established based on brain surface meshes and geometric deep learning, and its performance was evaluated. METHODS: Seventy-six clinically diagnosed AD patients and 83 healthy older adults were enrolled and randomly assigned to the training set and the test set according to a 4-to-1 ratio. Brain surface mesh was constructed from 3-D T1-weighted high-resolution structural MR volumes of each participant. After applying a series of simplification to the surface meshes, the training set was fed into the geometric deep neural network for training. The performance of the prediction model was evaluated with the test set, and the evaluation metrics included accuracy, sensitivity and specificity. RESULTS: The prediction model trained on the right brain surface meshes with 6 000 faces achieved the best performance, with accuracy reaching 93.8%, sensitivity, 91.7%, and specificity, 94.1%. The evolution of the brain surface meshes during convolution and pooling revealed that AD patients had diffuse brain tissue loss compared with healthy older adults. CONCLUSION: Morphological brain analysis based on mesh data and geometric deep learning has great potential in the differential diagnosis of AD.

Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer?

Pancreatic cancer is a very aggressive cancer type associated with one of the poorest prognostics. Despite several clinical trials to combine different types of therapies, none of them resulted in significant improvements for patient survival. Pancreatic cancers demonstrate a very broad panel of resistance mechanisms due to their biological properties but also their ability to remodel the tumour microenvironment. Radiotherapy is one of the most widely used treatments against cancer but, up to now, its impact remains limited in the context of pancreatic cancer. The modern era of radiotherapy proposes new approaches with increasing conformation but also more efficient effects on tumours in the case of charged particles. In this review, we highlight the interest in using charged particles in the context of pancreatic cancer therapy and the impact of this alternative to counteract resistance mechanisms.

Propofol attenuates TNF-α-induced MMP-9 expression in human cerebral microvascular endothelial cells by inhibiting Ca2+/CAMK II/ERK/NF-κB signaling pathway.

Metalloproteinase 9 (MMP-9) is able to degrade collagen IV, an important component of blood-brain barrier (BBB). Expression of MMPs, especially MMP-9, correlates with BBB disruption during central nervous system inflammation. Propofol has been reported to have anti-inflammation effects. In this study, we investigated the effects of propofol on TNF-α-induced MMP-9 expression in human cerebral microvascular endothelial cells (hCMEC/D3 cells) and explored the underlying mechanisms. The hCMEC/D3 cells were treated with propofol (25 µM), followed by TNF-α (25 ng/mL). We showed that TNF-α treatment markedly increased MMP-9 expression and decreased collagen IV expression in hCMEC/D3 cells, which was blocked by pretreatment with propofol. TNF-α-induced downregulation of collagen IV was also reversed by MMP-9 knockdown with siRNA. We revealed that TNF-α upregulated MMP-9 expression in hCMEC/D3 cells through activation of Ca2+/CAMK II/ERK/NF-κB signaling pathway; co-treatment with inhibitors of CaMK II (KN93), ERK (LY3214996), NF-κB (PDTC) or Ca2+chelator (BAPTA-AM) abrogated the effect of TNF-α on MMP-9 expression. We further established an in vitro BBB model by co-culturing of hCMEC/D3 cells and human astrocytes for 6 days and measuring trans-endothelial electrical resistance (TEER) to reflect the BBB permeability. TNF-α treatment markedly decreased TEER value, which was attenuated by pretreatment with propofol (25 µM) or MMP-9 knockdown with siRNA. In conclusion, propofol inhibits TNF-α-induced MMP-9 expression in hCMEC/D3 cells via repressing the Ca2+/CAMKII/ERK/NF-κB signaling pathway. TNF-α-impaired BBB integrity could be reversed by propofol, and propofol attenuates the inhibitory effect of TNF-α on collagen IV.

C1q/TNF-related protein 1 promotes endothelial barrier dysfunction under disturbed flow.

Endothelial hyper-permeability is a major determinant factor that contributes to the accelerated development of atherosclerotic lesions at hemodynamically disturbed sites. Previously, we showed that C1q/TNF related protein (CTRP) 1 promotes endothelium-leukocyte interactions and inflammatory responses in vascular cells. Here, we sought to investigate the role of CTRP1 in modulation of endothelial permeability under disturbed flow condition. By using en face staining of mouse aorta, we found CTRP1 expression was significantly increased in vascular endothelial cells under disturbed flow as compared to steady laminar flow. Vascular permeability to Evans blue dye was notably enhanced in CTRP1 knockin mice as compared to wild type animals, whereas aortic hyper-permeability at disturbed sites was remarkably restored after deletion of CTRP1. In cultured endothelial cells, treatment of CTRP1 led to increased permeability to fluorescent-labelled dextran and apparent formation of paracellular holes as observed after disturbed flow exposure, which was evidently reduced in the presence of a CTRP1-specific neutralizing antibody. Mechanistically, we found activation of VEGFR2 by CTRP1 might be involved in vascular hyper-permeability under disturbed flow condition. Taken together, this study suggests that CTRP1 is a mechano-sensitive proinflammatory factor that mediates disturbed flow-induced vascular barrier dysfunction. Inhibition of CTRP1 may inhibit the pathogenesis of atherosclerosis at early stage.

New Approach for the Synthesis of Nanozirconia Fortified Microcapsules.

Robust poly(urea-formaldehyde) (PUF) microcapsules with composite shells comprising zirconia (ZrO2) nanopowder incorporated in PUF were fabricated via a novel and facile one-pot synthesis. ZrO2 nanopowder was chosen because it owns one of the highest mechanical strengths among ceramics. The nanopowder was predispersed in the core material to combine encapsulation and fortification into a single process. In the core, the well-dispersed nanopowder migrated to the interface, where PUF polymerization took place. The mechanical strength of the microcapsule with nano-ZrO2 incorporated in the shell (42% by weight) is three times greater than that of the microcapsule without ZrO2. In a preliminary application wherein the microcapsules were embedded in a model of poly(vinyl alcohol) (PVA) membrane, the PVA specimen exhibited a higher ultimate tensile strength when fortified microcapsules were embedded than when unfortified microcapsules were used.

Wavefront measurement made by an off-the-shelf laser-scanning pico projector.

Focal plane testing methods such as the Shack-Hartmann wavefront sensor and phase-shifting deflectometry are valuable tools for optical testing. In this study, we propose a novel wavefront slope testing method that uses a scanning galvo laser, in which a single-mode Gaussian beam scans the pupils of the tested optics in the system. In addition, the ray aberration is reconstructed by the four-step phase-shifting measurement by modulating the angular domain. The measured wavefront is verified by a Fizeau interferometer in terms of Zernike polynomials.

A Lego®-like swappable fluidic module for bio-chem applications.

A Lego®-like swappable fluidic module (SFM) is proposed in this research. We designed and fabricated selected modular fluidic components, including functional and auxiliary types that can be effortlessly swapped and integrated into a variety of modular devices to rapidly assemble a fully-portable, disposable fluidic system. In practice, an integrated SFM uses finger-operated, electricity-free pumps to deliver fluids. Using a swirling mechanism, the vortex mixer can rapidly mix two liquids in a one-shot mixing event. We demonstrate the successful application of this SFM in several microfluidic applications, such as the synthesis of gold nanoparticles (AuNPs) from chloroauric acid (HAuCl4), and nucleic acid amplification from the Hepatitis B virus (HBV) with a capillary convective polymerase chain reaction (ccPCR).

The neuroprotective effect of near infrared light therapy in aged mice with postoperative neurocognitive disorder by upregulating IRF7.

BACKGROUND: Postoperative neurocognitive disorder (PND) is a common central nervous system complication after undergoing surgery and anesthesia especially in elderly patients, while the therapeutic options are very limited. This study was carried out to investigate the beneficial effects of transcranial near infrared light (NIRL) which was employed to the treatment of PND and propose the involved mechanisms. METHODS: The PND mice were established through left carotid artery exposure under isoflurane anesthesia and received transcranial NIRL treatment. Behavioral testing was performed to evaluate the cognitive function of PND mice after transcranial NIRL therapy. Changes in the transcriptomic profiles of prefrontal cortex (PFC) and hippocampus (HP) were identified by next generation sequencing (NGS), and the molecular mechanisms involved were examined by both in vivo mouse model and in vitro cell culture studies. RESULTS: We found that transcranial NIRL therapy effectively ameliorated learning and memory deficit induced by anesthesia and surgery in aged mice. Specifically, we identified down-regulation of interferon regulatory factor 7 (IRF7) in the brains of PND mice that was mechanistically associated with increased pro-inflammatory M1 phenotype of microglia and elevated neuroinflammatory. NIRL treatment produced protective effects through the upregulation of IRF7 expression and reversing microglial phenotypes from pro-inflammatory to neuroprotective, resulting in reduced brain damage and improved cognitive function in PND mice. CONCLUSION: Our results indicate that transcranial NIRL is an effective and safe therapy for PND via alleviating neuroinflammation, and IRF7 plays a key transcription factor in regulating the M1-to-M2 switch of microglia.