Urine-derived exosomes and their role in modulating uroepithelial cells to prevent hypospadias.

PURPOSE: Urethral hypospadias, a common congenital malformation in males, is closely linked with disruptions in uroepithelial cell (UEC) processes. Evidence exists reporting that urine-derived exosomes (Urine-Exos) enhance UEC proliferation and regeneration, suggesting a potential role in preventing hypospadias. However, the specific influence of Urine-Exos on urethral hypospadias and the molecular mechanisms involved are not fully understood. This study focuses on investigating the capability of Urine-Exos to mitigate urethral hypospadias and aims to uncover the underlying molecular mechanisms. METHODS: Bioinformatics analysis was performed to identify key gene targets in Urine-Exos potentially involved in hypospadias. Subsequent in vitro and in vivo experiments were conducted to validate the regulatory effects of Urine-Exos on hypospadias. RESULTS: Bioinformatics screening revealed syndecan-1 (SDC1) as a potential pivotal gene for the prevention of hypospadias. In vitro experiments demonstrated that Urine-Exos enhanced the proliferation and migration of UECs by transferring SDC1 and inhibiting cell apoptosis. Notably, Urine-Exos upregulated ß-catenin expression through SDC1 transfer, further promoting UEC proliferation and migration. These findings were confirmed in a congenital hypospadias rat model induced by di(2-ethylhexyl) phthalate (DEHP). CONCLUSION: This study reveals the therapeutic potential of Urine-Exos in hypospadias, mediated by the SDC1/ß-catenin axis. Urine-Exos promote UEC proliferation and migration, thereby inhibiting the progression of hypospadias. These findings offer new insights and potential therapeutic targets for the management of congenital malformations.

Enhancing surface sensing performance of cascaded high contrast gratings using bound states in the continuum.

We proposed the cascaded high contrast grating (CHCG) structure to enhance surface sensing capabilities through bound states in the continuum (BICs). Utilizing the finite element method (FEM) and rigorous coupled-wave analysis (RCWA), we studied the dispersion relations, far-field contribution CHCGs, and near-field distributions of BICs corresponding to resonance peaks at different wavelengths. Results demonstrate the ability to precisely control symmetry-protected BIC (SP-BIC) and Friedrich-Wintgen BIC (FW-BIC) resonance peaks by altering incident angles and structural parameters, enhancing structure robustness and tunability. Significantly, modes 1 and 2 have demonstrated substantial enhancement in surface refractive index sensing, achieving highest sensitivities at 51 nm/RIU and the figure of merit reaching 490.8 RIU-1, indicating notable advancement in detecting subtle surface changes. In contrast, mode 3 has shown robust performance in bulk refractive index sensing, achieving a sensitivity of 602 nm/RIU and a figure of merit of 5189.65 RIU-1. These findings underscore the significant potential of the structure as a high-performance integrated sensor, particularly for precise environmental and biological monitoring in surface refractive index sensing.

Urban park green space use analysis based on trajectory big data: Experience from a medium-sized city in China.

Regular visits to park green space offer remarkable benefits for the physical and mental health of urban residents. Achieving a comprehensive understanding of the utilization across the entire city is a prerequisite for improving the overall utilization rate of park green spaces. Traditional social survey methods are limited by their sample size and time-consuming nature, while methods based on geographic location big data are gaining momentum. This study focuses on Xuchang, a medium-sized city in China, and systematically analyzes the current state and influencing factors of park green space utilization by mining GPS trajectory big data from April 3 to 12, 2022. Results indicate that residents' choices of park green spaces are highly diverse. Approximately 20% of visitors on holidays and weekends, and about 25% of visitors on weekdays, prefer the park green space closest to their homes. Notably, the distance threshold for park green space visits on weekdays, weekends, and holidays is 3633, 3824, and 4127 m, respectively. These distances are significantly higher than the several hundred meters specified in planning documents or commonly used in accessibility analyses. For individuals who frequently visit park green spaces, distance is the most critical influencing factor. Conversely, for those who occasionally visit, distance is not the primary consideration. For individuals who rarely or never visit park green spaces, personal attitudes play an essential role. In comparison to weekdays, the number of visitors on holidays and weekends is larger, the travel distance is longer, and they are more inclined to choose larger parks. Visits are concentrated in the afternoon and evening, and weather changes remarkably affect park green space utilization. Importantly, no compensatory effect is observed between the frequency and duration of park green space visits. These findings hold important implications for urban planning, management, and the promotion of park green space utilization.

Self-healing FBG sensor network fault-detection based on a multi-class SVM algorithm.

We propose a three-layer ring architecture with enhanced reconfigurable capabilities for fiber Bragg grating (FBG) sensor networks. The proposed network is capable of self-healing when three fiber links fail. In addition to self-healing, soft faults in the FBG sensors can be detected using a multi-classification support vector machine (multi-class SVM) algorithm. The detection accuracy reached 99%. Additionally, we used an artificial neural network (ANN) reliability estimation model to estimate the reliability of the FBG self-healing network. The results show that the ANN reliability analysis model can accurately estimate the reliability of the architecture at a reasonable cost.

Thermal Stability Improvement of Core Material via High Internal Phase Emulsion Gels.

Biocompatible particle-stabilized emulsions have gained significant attention in the biomedical industry. In this study, we employed dynamic high-pressure microfluidization (HPM) to prepare a biocompatible particle emulsion, which effectively enhances the thermal stability of core materials without the addition of any chemical additives. The results demonstrate that the HPM-treated particle-stabilized emulsion forms an interface membrane with high expansion and viscoelastic properties, thus preventing core material agglomeration at elevated temperatures. Furthermore, the particle concentration used for constructing the emulsion gel network significantly impacts the overall strength and stability of the material while possessing the ability to inhibit oxidation of the thermosensitive core material. This investigation explores the influence of particle concentration on the stability of particle-stabilized emulsion gels, thereby providing valuable insights for the design, improvement, and practical applications of innovative clean label emulsions, particularly in the embedding and delivery of thermosensitive core materials.

Urinary extracellular vesicles prevent di-(2-ethylhexyl) phthalate-induced hypospadias by facilitating epithelial-mesenchymal transition via PFN2 delivery.

BACKGROUND: Urinary extracellular vesicles (EVs) have gained increasing interest in recent years as a potential source of noninvasive biomarkers of diseases related to urinary organs, but knowledge of the mechanism is still limited. The current study sought to clarify the mechanism of urinary EVs behind di-(2-ethylhexyl) phthalate (DEHP)-induced hypospadias via PFN2 delivery. METHOD: PFN2 expression in hypospadias was predicted by bioinformatics analysis. Following the induction of a hypospadias rat model using DEHP, rats were injected with EVs and/or underwent alteration of PFN2 and TGF-ß1 to assess their effects in vivo. The extracted rat urothelial cells (UECs) were co-cultured with EVs extracted from urine for in vitro experiments. RESULT: Microarray analysis predicted poor PFN2 expression in hypospadias. Upregulated PFN2 was found in urinary EVs, and restrained epithelial-mesenchymal transition (EMT) was observed in DEHP-exposed rats. Urinary EVs or PFN2 overexpression increased SMAD2, SMAD3, and TGF-ß1 protein expression and SMAD2 and SMAD3 phosphorylation in UECs and DEHP-exposed rats. UEC migration, invasion, and EMT were augmented by EV co-culture or upregulation of PFN2. Of note, the silencing of TGF-ß1 counterweighed the effect of PFN2. Besides, EV co-culture or overexpression of PFN2 or TGF-ß1 elevated the body weight, anal-genital distance (AGD), anal-genital index (AGI), and EMT of DEHP-exposed rats. CONCLUSION: In summary, urinary EVs activated the SMAD/TGF-ß1 pathway to induce EMT via PFN2 delivery, thus protecting against DEHP-induced hypospadias. (1) EMT in epithelial cells inhibits DEHP-induced hypospadias. (2) Urine-derived EVs deliver PFN2 to promote EMT in epithelial cells. (3) PFN2 can activate the SMAD/TGF-ß1 signaling axis. (4) Urine-derived EVs can transmit PFN2 to activate the SMAD/TGF-ß1 signaling axis, thus promoting EMT and inhibiting the occurrence of hypospadias.

High-performance gas sensor with symmetry-protected quasi-bound states in the continuum.

A high-performance optical sensor with a vertical cavity structure comprising high-contrast gratings (HCGs) and a distributed Bragg reflector was designed. The structure has two peaks with different mechanisms, among which the first peak is formed by breaking the symmetry of the structure and coupling between the incident wave and the symmetric protection mode. The joint action of the HCG resonance and Fabry-Perot resonance formed a second peak. Moreover, changing the structural parameters, such as the grating width, period, and cavity length, can tune the spectral reflection dips. The sensitivity of the designed structure was as high as 674 nm/RIU, and the corresponding figure of merit was approximately 34741. The presented gas sensor provides a method for applying a vertical cavity structure to the sensing domain.

Monocyte to high-density lipoprotein ratio as a novel-potential biomarker for predicting prognosis of Bell's palsy.

OBJECTIVES: In several disorders, the monocyte to high-density lipoprotein ratio (MHR) has been considered a biomarker of systemic inflammation and oxidative stress. However, its role in Bell's palsy (BP) remains unclear. This study investigates the relationship between elevated MHR and poor recovery in BP patients. METHODS: The clinical data of 729 BP patients were analyzed retrospectively. The House-Brackmann Facial Nerve Grading System (H-B) was utilized to assess the severity of facial motor dysfunction during admission and the follow-up period after discharge. According to the 6 months follow-up data, H-B grades 1-2 were classified as recovered (n = 557), and H-B grades 3-6 as unrecovered (n = 172). The patients were split into MHR ≤ 0.26 (n = 361) and MHR > 0.26 (n = 368) groups based on the median MHR to further analyze the connection between different MHRs and prognosis. RESULTS: The level of MHR was substantially greater in the unrecovered group of BP patients than in the restored group (medians[interquartile range], 0.32[0.20, 0.49] vs 0.24[0.11, 0.39], P < 0.001). MHR was an independent risk factor for BP prognosis as indicated by the multivariate logistic regression analysis (OR = 4.467, 95% CI = 1.875-10.646, P = 0.001). The area under the curve (AUC) was 0.615 (95% CI = 0.566-0.664, P < 0.001). The initial H-B score did not differ significantly between MHR ≤ 0.26 (n = 361) and MHR > 0.26 (n = 368) groups. However, after 6 months of follow-up, the high-MHR group's H-B score was considerably greater than the low-MHR group's. CONCLUSIONS: MHR is expected to be an accessible and effective biomarker of BP. In BP patients, elevated MHR is related to an increased chance of poor recovery.

The impact of Chinese COVID-19 pandemic on the incidence of peripheral facial nerve paralysis after optimizing policies.

Objective: To evaluate the impact of the COVID-19 pandemic on the occurrence of Peripheral Facial Nerve Paralysis (PFNP) in Chinese patients, identify contributing factors, and explore the relationship between COVID-19 and PFNP. Methods: We conducted a retrospective study covering the years 2020 to 2023, categorizing patients into three groups based on their visit dates: Group 1 (December 8, 2020 to February 28, 2021), Group 2 (December 8, 2021 to February 28, 2022), and Group 3 (December 8, 2022 to February 28, 2023). We collected and compared data on disease onset and patient characteristics among these groups. Results: In Group 3, following the widespread COVID-19 outbreak, there was a significant increase of 22.4 and 12.1% in PFNP cases compared to the same periods in the preceding 2 years (p < 0.001). Group 3 patients were more likely to be aged between 30 and 60 years, experience onset within 7 days, present with Hunter syndrome, and have a higher H-B score of VI compared to the previous 2 years (p < 0.017). Logistic regression analysis revealed a strong association between the COVID-19 pandemic and the incidence of Hunter syndrome in PFNP (OR = 3.30, 95% CI 1.81-6.03, p < 0.001). Conclusion: The incidence of PFNP increased in China after the COVID-19 pandemic, particularly in patients with Hunter syndrome, indicating that COVID-19 infection can trigger and worsen PFNP.

Effect of temperature and air pressure on the incidence of Bell's palsy in Hangzhou: a distributed lag non-linear analysis.

The etiology of Bell's palsy (BP) is currently unknown, and the findings from previous studies examining the association between seasonal or meteorological factors and BP have been inconsistent. This research aims to clarify this relationship by analyzing a larger dataset and employing appropriate statistical methods. Data from 5387 patients with BP treated at Zhejiang Provincial Hospital of Traditional Chinese Medicine in Hangzhou, Zhejiang Province, from May 1, 2018, to June 30, 2023, was gathered. We assessed the temporal distribution of meteorological factors and the incidence of BP across seasons and months. A distributed lag non-linear model was used to further investigate the lagged and overall effects of temperature and air pressure on the onset of BP. The temporal distribution of BP incidence revealed the highest average number of cases occurring in December and the lowest in June. A correlation existed between BP episodes and temperature or air pressure. The model revealed a higher relative risk during periods of low temperature and high air pressure, characterized by a time lag effect. This correlation was notably more pronounced in female patients and individuals in the young and middle-aged groups. Our findings suggest that exposure to low temperatures and high air pressure constitute risk factors for BP development.

Prognostic Signature Constructed of Seven Ferroptosis-Related lncRNAs Predicts the Prognosis of HBV-Related HCC.

BACKGROUND: Ferroptosis and lncRNAs both play crucial roles in cancers. But the roles of ferroptosis-related lncRNAs (FRLncs) in HBV-related HCC (HBV-HCC) remain ambiguous. METHODS: The gene expression profile and clinical data were originated from the Cancer Genome Atlas (TCGA) database. The risk signature was constructed by FRLncs based on the Cox regression analysis. The survival curve, Cox regression analysis, and time-dependent receiver operating characteristic (ROC) curve were adopted to verify the independence and reliability of the signature. A nomogram was established. Immune-infiltrating cells, immune functions, and checkpoints were analyzed. RESULTS: A risk signature composed of 7 FRLncs (LINC00942, AC131009.1, POLH-AS1, AC090772.3, MKLN1-AS, AC009403.1, AL031985.3) was constructed and divided HBV-HCC patients into high- and low-risk groups. Patients in the high-risk group showed a poor prognosis. The area under curves (AUC) of the signature for 1-, 3-, and 5-year was satisfactory. A nomogram composed of gender, stage, age, grade, and risk signature was established. The risk signature and nomogram displayed appreciable independence and reliability in HBV-HCC patients. The T-cell CD8 + , monocyte, and macrophage M1 were expressed differently significantly in HCC patients, while macrophage M2 showed an obvious difference in the HBV-HCC patients between the different risk groups. PDCD1 and CTL4 were expressed higher in the high-risk group of HCC patients. CONCLUSION: A 7-lncRNA signature was identified as a potential prognostic predictor for HBV-HCC patients. Immune therapy may be a promising strategy for HCC patients, especially HBV-HCC patients.

Granulocyte colony stimulating factor in decompensated cirrhosis, acute alcoholic hepatitis, and acute-on-chronic liver failure: A comprehensive meta-analysis of randomized controlled trials.

BACKGROUND: GCSF may improve the prognosis of severe liver disease by promoting liver regeneration and immune restoration. Our Aim was to investigate its controversial efficacy in decompensated cirrhosis, acute alcoholic hepatitis (AAH), or acute-on-chronic liver failure (ACLF) through meta-analysis. METHODS: Meta-analysis of proportions (random effect model) including 19 RCTs (1287 patients from 16 Asian and 3 European studies including 487 ACLF, 231 AAH and 569 cirrhotic patients) evaluating survival at day-28, day-90, 6 months, one year, and/or occurrence of sepsis as major outcomes. RESULTS: In patients with decompensated cirrhosis, G-CSF administration was associated with a reduction in the weight-adjusted risk of mortality of 9% at day-90 (OR=0.33; 95%CI: 0.18-0.58; p = 0.0002), 16% at 6 months (OR=0.31; 95%CI: 0.15-0.62; p = 0.0009), 26% at one year (OR=0.21; 95%CI:0.12-0.38, p<0.0001) and a weight-adjusted 28% risk reduction for sepsis (OR=0.28; 95%CI: 0.16-0.49; p<0.0001). Only Asian studies were positive. In AAH, G-CSF was associated with an 18% reduction in weight-adjusted mortality risk at day-28 (OR=0.31; 95%CI:0.11-0.83, p = 0.021), 32% at day-90 (OR=0.20; 95%CI:0.09-0.46, p<0.0001) and a weight-adjusted 42% risk reduction for sepsis (OR=0.17; 95%CI: 0.08-0.38; p<0.0001). Only Asian studies, in which corticosteroids were not given systematically in case of severe AAH, were positive. In patients with ACLF, the results on mortality at day-28 were heterogeneous, and GCSF had no beneficial effect on sepsis or survival at day-90. CONCLUSION: G-CSF may be effective in patients with decompensated cirrhosis or AAH by reducing the occurrence of sepsis and mortality. Further meta-analyses of individual data, or new, powerful and methodologically flawless therapeutic trials, are warranted to confirm these results, which harbor wide divergences between Asian and European RCTs.

Clinical manifestations and early effectiveness of methimazole in patients with graves' hyperthyroidism-related severe hepatic dysfunction.

BACKGROUND: Graves' hyperthyroidism (GH) is often accompanied by mild to moderate liver injury, but severe hepatic dysfunction (SHD) is relatively rare. Whether patients with GH-related SHD can be treated with methimazole (MMI) remains controversial. This study aimed to determine the clinical characteristics and to evaluate the role of low-dose MMI for such patients. METHODS: 33 patients with GH-related SHD were selected for this retrospective study in the Fifth Medical Center of Chinese PLA General Hospital from January 2017 to July 2022. The clinical manifestations, therapeutic responses, and effectiveness of MMI were evaluated. RESULTS: Systemic jaundice (100.0%), yellow urine (100.0%), fatigue (87.9%), and goiter (66.7%) were the main symptoms. Total bilirubin (TBIL) had no linear correlation with free triiodothyronine (FT3) (r = -0.023, p = .899), free thyroxine (FT4) (r = 0.111, p = .540), T3 (r = -0.144, p = .425), and T4 (r = 0.037, p = .837). On the 14th day after admission, FT3, FT4, T3, T4, TBIL, direct bilirubin (DBIL), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), and international normalized ratio (INR) decreased compared with the baseline (p < .05). The decrease rates of FT3, FT4, T3, T4, TBIL, and DBIL in the MMI group were higher than those in the non-MMI group (p < .05). The improvement rate of the MMI group (77.8%) was higher than that of the non-MMI group (9.5%, p = .001). MMI treatment is an independent predictor affecting the early improvement of patients (OR = 0.022, p = .010). CONCLUSIONS: The main clinical manifestations of patients with GH-related SHD were symptoms related to liver disease. Low-dose MMI was safe and effective for them.

Advances on the anti-tumor mechanisms of the carotenoid Crocin.

Saffron is located in the upper part of the crocus stigma of iridaceae, which has a long history of medicinal use. Crocin (molecular formula C44H64O24) is a natural floral glycoside ester compound extracted from saffron, which is a type carotenoid. Modern pharmacological studies have shown that crocin has multiple therapeutic effects including anti-inflammatory, anti-oxidant, anti-hyperlipidemic and anti-stone effects. In recent years, crocin has been widely noticed due to its considerable anti-tumor effects manifested by the induction of tumor cell apoptosis, inhibition of tumor cell proliferation, inhibition of tumor cell invasion and metastasis, enhancement of chemotherapy sensitivity and improvement of immune status. The anti-tumor effects have been shown in various malignant tumors such as gastric cancer, liver cancer, cervical cancer, breast cancer and colorectal cancer. In this review, we compiled recent studies on the anti-tumor effects of crocin and summarized its anti-tumor mechanism for developing ideas of treating malignancies and exploring anti-tumor drugs.

Effects of metformin on bone mineral density and bone turnover markers: a systematic review and meta-analysis.

OBJECTIVES: Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and bone turnover markers. DESIGN: Systematic review and meta-analysis of randomised controlled trials. METHODS: Searches were carried out in PubMed, EMBASE, Web of science, Cochrane library, ClinicalTrials.gov from database inception to 26 September 2022. Two review authors assessed trial eligibility in accordance with established inclusion criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB V.2.0). Data analysis was conducted with Stata Statistical Software V.16.0 and Review Manager Software V.5.3. RESULTS: A total of 15 studies with 3394 participants were identified for the present meta-analysis. Our pooled results indicated that metformin had no statistically significant effects on BMD at lumbar spine (SMD=-0.05, 95% CI=-0.19 to 0.09, p=0.47, participants=810; studies=7), at femoral (MD=-0.01 g/cm2, 95% CI=-0.04 to 0.01 g/cm2, p=0.25, participants=601; studies=3) and at hip (MD=0.01 g/cm2, 95% CI=-0.02 to 0.03 g/cm2, p=0.56, participants=634; studies=4). Metformin did not lead to significant change in osteocalcin, osteoprotegerin and bone alkaline phosphatase. Metformin induced decreases in N-terminal propeptide of type I procollagen (MD=-6.09 µg/L, 95% CI=-9.38 to -2.81 µg/L, p=0.0003, participants=2316; studies=7) and C-terminal telopeptide of type I collagen (MD=-55.80 ng/L, 95% CI=-97.33 to -14.26 ng/L, p=0.008, participants=2325; studies=7). CONCLUSION: This meta-analysis indicated that metformin had no significant effect on BMD. Metformin decreased some bone turnover markers as N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen. But the outcomes should be interpreted with caution due to several limitations.

Two cases reports: Severe liver injury caused by 1,2,3-trichloropropane poisoning.

Background: 1,2,3-trichloropropane (TCP) poisoning can induce liver damage in humans and animals, but reports of severe liver injury and its histology are rare. We presented two cases of 1,2,3-TCP inhalation poisoning resulting in severe liver injury confirmed by exposure history, toxicology, biochemical index and pathology. Case description: Two young male presented acute poisoning process with mild to moderate early symptoms, and developed severe jaundice and coagulation dysfunction after exposure to 1,2,3-TCP. The total bilirubin (TBIL) in case 1 and case 2 reached the peak value of 635.8 µmol/L and 437.1 µmol/L on the 25th and 22nd days, respectively. Their liver enzymes and international normalized ratio increased rapidly to peak and fell back, and TBIL remained at a high level. 1,2,3-TCP was detected in their blood, and their liver histology indicated severe necrosis of hepatocytes, infiltration of massive inflammatory cells, and cholestasis. They all finally recovered after a long time of treatment. Conclusion: The two cases in this study demonstrate that 1,2,3-TCP inhalation poisoning without any protective measures can induce severe liver injury in humans.

Dual-band refractive index sensor with cascaded asymmetric resonant compound grating based on bound states in the continuum.

We propose a cascaded asymmetric resonant compound grating (ARCG) for high-performance dual-band refractive index sensing. The physical mechanism of the sensor is investigated using a combination of temporal coupled-mode theory (TCMT) and ARCG eigenfrequency information, which is verified by rigorous coupled-wave analysis (RCWA). The reflection spectra can be tailored by changing the key structural parameters. And by altering the grating strip spacing, a dual-band quasi-bound state in the continuum can be achieved. The simulation results show that the highest sensitivity of the dual-band sensor is 480.1 nm/RIU, and its figure of merit is 4.01 × 105. The proposed ARCG has potential application prospects for high-performance integrated sensors.

Recognition and localization of asymmetric spectra in FBG sensing networks.

We propose a deep learning demodulation method based on a long short-term memory (LSTM) neural network for fiber Bragg grating (FBG) sensing networks. Interestingly, we find that both low demodulation error and distorted spectrum recognition are realized using the proposed LSTM-based method. Compared with conventional demodulation methods, including Gaussian-fitting, convolutional neural network, and the gated recurrent unit, the proposed method improves the demodulation accuracy being close to 1 pm and achieves a demodulation time of 0.1s for 128-FBG sensors. Furthermore, our approach can realize 100% accuracy of distorted spectra recognition and complete the location of spectra with spectrally encoded FBG sensors.