Spatiotemporal insight into early pregnancy governed by immune-featured stromal cells.

Endometrial decidualization connecting embryo implantation and placentation is transient but essential for successful pregnancy, which, however, is not systematically investigated. Here, we use a scStereo-seq technology to spatially visualize and define the dynamic functional decidual hubs assembled by distinct immune, endothelial, trophoblast, and decidual stromal cells (DSCs) in early pregnant mice. We unravel the DSC transdifferentiation trajectory and surprisingly discover a dual-featured type of immune-featured DSCs (iDSCs). We find that immature DSCs attract immune cells and induce decidual angiogenesis at the mesenchymal-epithelial transition hub during decidualization initiation. iDSCs enable immune cell recruitment and suppression, govern vascularization, and promote cytolysis at immune cell assembling and vascular hubs, respectively, to establish decidual homeostasis at a later stage. Interestingly, dysfunctional and spatially disordered iDSCs cause abnormal accumulation of immune cells in the vascular hub, which disrupts decidual hub specification and eventually leads to pregnancy complications in DBA/2-mated CBA/J mice.

Chemically Modified Platforms for Better RNA Therapeutics.

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors. This comprehensive review delves into these platforms, underscoring their significance in augmenting the performance and translational prospects of RNA-based therapeutics. It encompasses an in-depth analysis of various chemically modified delivery platforms that have been instrumental in propelling RNA therapeutics toward clinical utility. Moreover, the review scrutinizes the rationale behind diverse chemical modification techniques aiming at optimizing the therapeutic efficacy of RNA molecules, thereby facilitating robust disease management. Recent empirical studies corroborating the efficacy enhancement of RNA therapeutics through chemical modifications are highlighted. Conclusively, we offer profound insights into the transformative impact of chemical modifications on RNA drugs and delineates prospective trajectories for their future development and clinical integration.

Inhaled mRNA nanoparticles dual-targeting cancer cells and macrophages in the lung for effective transfection.

Messenger RNA (mRNA)-based therapeutics are transforming the landscapes of medicine, yet targeted delivery of mRNA to specific cell types while minimizing off-target accumulation remains challenging for mRNA-mediated therapy. In this study, we report an innovative design of a cationic lipid- and hyaluronic acid-based, dual-targeted mRNA nanoformulation that can display the desirable stability and efficiently transfect the targeted proteins into lung tissues. More importantly, the optimized dual-targeted mRNA nanoparticles (NPs) can not only accumulate primarily in lung tumor cells and inflammatory macrophages after inhalation delivery but also efficiently express any desirable proteins (e.g., p53 tumor suppressor for therapy, as well as luciferase and green fluorescence protein for imaging as examples in this study) and achieve efficacious lung tissue transfection in vivo. Overall, our findings provide proof-of-principle evidence for the design and use of dual-targeted mRNA NPs in homing to specific cell types to up-regulate target proteins in lung tissues, which may hold great potential for the future development of mRNA-based inhaled medicines or vaccines in treating various lung-related diseases.

Approximate estimation of cell-type resolution transcriptome in bulk tissue through matrix completion.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for uncovering cellular heterogeneity. However, the high costs associated with this technique have rendered it impractical for studying large patient cohorts. We introduce ENIGMA (Deconvolution based on Regularized Matrix Completion), a method that addresses this limitation through accurately deconvoluting bulk tissue RNA-seq data into a readout with cell-type resolution by leveraging information from scRNA-seq data. By employing a matrix completion strategy, ENIGMA minimizes the distance between the mixture transcriptome obtained with bulk sequencing and a weighted combination of cell-type-specific expression. This allows the quantification of cell-type proportions and reconstruction of cell-type-specific transcriptomes. To validate its performance, ENIGMA was tested on both simulated and real datasets, including disease-related tissues, demonstrating its ability in uncovering novel biological insights.

Intravesical delivery of KDM6A-mRNA via mucoadhesive nanoparticles inhibits the metastasis of bladder cancer.

Lysine-specific demethylase 6A (KDM6A), also named UTX, is frequently mutated in bladder cancer (BCa). Although known as a tumor suppressor, KDM6A's therapeutic potential in the metastasis of BCa remains elusive. It also remains difficult to fulfill the effective up-regulation of KDM6A levels in bladder tumor tissues in situ to verify its potential in treating BCa metastasis. Here, we report a mucoadhesive messenger RNA (mRNA) nanoparticle (NP) strategy for the intravesical delivery of KDM6A-mRNA in mice bearing orthotopic Kdm6a-null BCa and show evidence of KDM6A's therapeutic potential in inhibiting the metastasis of BCa. Through this mucoadhesive mRNA NP strategy, the exposure of KDM6A-mRNA to the in situ BCa tumors can be greatly prolonged for effective expression, and the penetration can be also enhanced by adhering to the bladder for sustained delivery. This mRNA NP strategy is also demonstrated to be effective for combination cancer therapy with other clinically approved drugs (e.g., elemene), which could further enhance therapeutic outcomes. Our findings not only report intravesical delivery of mRNA via a mucoadhesive mRNA NP strategy but also provide the proof-of-concept for the usefulness of these mRNA NPs as tools in both mechanistic understanding and translational study of bladder-related diseases.

Generation of mega brown adipose tissue in adults by controlling brown adipocyte differentiation in vivo.

Brown adipose tissue (BAT) is a highly specialized adipose tissue in its immobile location and size during the entire adulthood. In response to cold exposure and other ß3-adrenoreceptor stimuli, BAT commits energy consumption by nonshivering thermogenesis (NST). However, the molecular machinery in controlling the BAT mass in adults is unknown. Here, we show our surprising findings that the BAT mass and functions can be manipulated in adult animals by controlling BAT adipocyte differentiation in vivo. Platelet-derived growth factor receptor α (PDGFα) expressed in BAT progenitor cells served a signaling function to avert adipose progenitor differentiation. Genetic and pharmacological loss-of-function of PDGFRα eliminated the differentiation barrier and permitted progenitor cell differentiation to mature and functional BAT adipocytes. Consequently, an enlarged BAT mass (megaBAT) was created by PDGFRα inhibition owing to increases of brown adipocyte numbers. Under cold exposure, a microRNA-485 (miR-485) was identified as a master suppressor of the PDGFRα signaling, and delivery of miR-485 also produced megaBAT in adult animals. Noticeably, megaBAT markedly improved global metabolism, insulin sensitivity, high-fat-diet (HFD)-induced obesity, and diabetes by enhancing NST. Together, our findings demonstrate that the adult BAT mass can be increased by blocking the previously unprecedented inhibitory signaling for BAT progenitor cell differentiation. Thus, blocking the PDGFRα for the generation of megaBAT provides an attractive strategy for treating obesity and type 2 diabetes mellitus (T2DM).

Engineered nanoparticles enable deep proteomics studies at scale by leveraging tunable nano-bio interactions.

SignificanceDeep profiling of the plasma proteome at scale has been a challenge for traditional approaches. We achieve superior performance across the dimensions of precision, depth, and throughput using a panel of surface-functionalized superparamagnetic nanoparticles in comparison to conventional workflows for deep proteomics interrogation. Our automated workflow leverages competitive nanoparticle-protein binding equilibria that quantitatively compress the large dynamic range of proteomes to an accessible scale. Using machine learning, we dissect the contribution of individual physicochemical properties of nanoparticles to the composition of protein coronas. Our results suggest that nanoparticle functionalization can be tailored to protein sets. This work demonstrates the feasibility of deep, precise, unbiased plasma proteomics at a scale compatible with large-scale genomics enabling multiomic studies.

Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy.

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.

Protein Corona Sensor Array Nanosystem for Detection of Coronary Artery Disease.

Coronary artery disease (CAD) is the most common type of heart disease and represents the leading cause of death in both men and women worldwide. Early detection of CAD is crucial for decreasing mortality, prolonging survival, and improving patient quality of life. Herein, a non-invasive is described, nanoparticle-based diagnostic technology which takes advantages of proteomic changes in the nano-bio interface for CAD detection. Nanoparticles (NPs) exposed to biological fluids adsorb on their surface a layer of proteins, the "protein corona" (PC). Pathological changes that alter the plasma proteome can directly result in changes in the PC. By forming disease-specific PCs on six NPs with varying physicochemical properties, a PC-based sensor array is developed for detection of CAD using specific PC pattern recognition. While the PC of a single NP may not provide the required specificity, it is reasoned that multivariate PCs across NPs with different surface chemistries, can provide the desirable information to selectively discriminate the condition under investigation. The results suggest that such an approach can detect CAD with an accuracy of 92.84%, a sensitivity of 87.5%, and a specificity of 82.5%. These new findings demonstrate the potential of PC-based sensor array detection systems for clinical use.

Enhancing Fano resonances through coupling of dark modes in a dual-ring nanostructure.

In this paper we investigate the Fano resonances of a ring-disc nanostructure that consists of two nanodiscs and two concentric nanorings. The dark modes of both nanorings can couple to the bright mode of the nanodiscs, leading to separate Fano resonances from the outer and the inner nanoring. The concentric arrangement of the two nanorings allows for a coupling between the dark modes of the outer and the inner nanoring, thus creating an additional interaction that influences the Fano resonances of the dual-ring nanostructure. This interaction is investigated by comparing the Fano resonances of the complete dual-ring structure with the isolated Fano resonances of the individual single-ring structures. The effect of the coupling between dark modes on the Fano resonances is verified using a model of coupled harmonic oscillators that describe the Fano resonances of this system in a classical analogy. Lastly we compare the sensitivity of a single-ring nanostructure with that of a dual-ring nanostructure to investigate the effects of a coupling between dark modes on the sensing performance.

Optimization of parameters for a fringe projection measurement system by use of an improved differential evolution method.

Fringe projection 3D measurement is widely used for object surface reconstruction. While improving measurement accuracy is a crucial task. Measurement accuracy is profoundly affected by various optical structural parameters. However, the current practice of system construction lacks theoretical guidelines and often relies on the experience of the operator, inevitably leading to unpredictable error. This paper investigates a theoretical optimization model and proposes an automatic optimization method for qualitatively determining the multiple optimal optical structural parameters in fringe projection measurement system. The aim is to enhance measurement accuracy conducting a rational comprehensive optimal structural parameters design prior to the system construction. Firstly, the mathematical model of the measurement system is established based on the principle of optical triangulation, and the phase sensitivity criterion is defined as the optimization norm. Within the full measurement range, the optimization merit function is formulated by combing three positions: the center position, the left and right boundary of the CCD. The imaging effectiveness criteria and sensor geometric dimensions are taken into account as the constraint boundaries. Subsequently, a combined improved differential evolution and Levy flight optimization algorithm is applied to search for the optimal parameters. The optimal structural parameters of the system were designed based on the optimization process. Experimental results validated the improvement in measurement accuracy achieved by the optimized structural parameters.

Electronic Modulation in Homonuclear Dual-Atomic Catalysts for Enhanced CO2 Electroreduction.

Homonuclear dual-atomic catalysts showcase unique electronic modulation due to their dual metal centres, providing new direction in development of efficient catalysts for CO2 electroreduction. This article highlights a few cutting-edge homonuclear dual-atomic catalysts, focusing on their inherent advantages in efficient and selective CO2 electroreduction, to spotlight the potential application of dual-atomic catalysts in CO2 electroreduction.

Clinical application of serum tumor abnormal protein in prostate cancer patients.

PURPOSE: To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. METHODS: This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. RESULTS: A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. CONCLUSION: The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients.

Collective effects of rising average temperatures and heat events on oviparous embryos.

Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.

Efectos colectivos del aumento de las temperaturas promedio y los eventos de calor en embriones ovíparos Resumen La supervivencia de los embriones inmóviles en respuesta al incremento de temperatura es importante para determinar la vulnerabilidad de las especies al cambio climático. Sin embargo, los efectos colectivos de dos características térmicas claves asociadas con el cambio climático (i. e., aumento de temperatura promedio y eventos de calor agudo) sobre la supervivencia embrionaria permanecen en gran parte inexplorados. Utilizamos mediciones empíricas y modelos de nicho para investigar cómo el estrés térmico crónico y agudo influye de forma independiente y colectiva en la supervivencia embrionaria de los lagartos en todas las latitudes. Recolectamos y criamos lagartos de cinco latitudes e incubamos sus huevos en un rango de temperaturas para cuantificar las respuestas específicas de la población al estrés por calor crónico y agudo. Posteriormente, mediante un modelo de desarrollo embrionario parametrizado con mediciones de tolerancia embrionaria al calor, identificamos un impacto colectivo de las tolerancias embrionarias al calor agudo y crónico en la supervivencia embrionaria. También incorporamos la tolerancia embrionaria crónica y aguda al calor en modelos de distribución de especies híbridas para determinar los cambios de distribución de las especies bajo el cambio climático. La tolerancia embrionaria al calor crónico (T­crónico) permaneció constante, mientras que la tolerancia al calor agudo (T­agudo) fue mayor en latitudes altas que en latitudes bajas. La tolerancia al calor agudo ejerció una influencia más pronunciada que la tolerancia al calor crónico. En los modelos de distribución de especies, el cambio climático provocó la pérdida de hábitat más significativa para cada población y especie en su distribución de latitudes bajas. En consecuencia, el hábitat para poblaciones en todas las latitudes se desplazará a latitudes altas. Nuestro estudio también resalta la importancia de considerar la supervivencia embrionaria bajo estrés térmico crónico y agudo para predecir la vulnerabilidad de las especies al cambio climático.

Temperature-Dependent Evaporative Anthropogenic VOC Emissions Significantly Exacerbate Regional Ozone Pollution.

The evaporative emissions of anthropogenic volatile organic compounds (AVOCs) are sensitive to ambient temperature. This sensitivity forms an air pollution-meteorology connection that has not been assessed on a regional scale. We parametrized the temperature dependence of evaporative AVOC fluxes in a regional air quality model and evaluated the impacts on surface ozone in the Beijing-Tianjin-Hebei (BTH) area of China during the summer of 2017. The temperature dependency of AVOC emissions drove an enhanced simulated ozone-temperature sensitivity of 1.0 to 1.8 µg m-3 K-1, comparable to the simulated ozone-temperature sensitivity driven by the temperature dependency of biogenic VOC emissions (1.7 to 2.4 µg m-3 K-1). Ozone enhancements driven by temperature-induced AVOC increases were localized to their point of emission and were relatively more important in urban areas than in rural regions. The inclusion of the temperature-dependent AVOC emissions in our model improved the simulated ozone-temperature sensitivities on days of ozone exceedance. Our results demonstrated the importance of temperature-dependent AVOC emissions on surface ozone pollution and its heretofore unrepresented role in air pollution-meteorology interactions.

Interleukin-37 ameliorates periodontitis development by inhibiting NLRP3 inflammasome activation and modulating M1/M2 macrophage polarization.

OBJECTIVE: Our study was designed to explore the role of IL-37 in M1/M2 macrophage polarization imbalance in the pathogenesis of periodontitis. BACKGROUND: Periodontitis is a chronic progressive inflammatory disease featured by gingival inflammation and alveolar bone resorption. Recent research has revealed that regulating macrophage polarization is a viable method to ameliorate periodontal inflammation. IL-37 is an anti-inflammatory cytokine, which has been reported to inhibit innate and adaptive immunity. METHODS: For in vitro experiment, mouse macrophage RAW264.7 cells were pretreated with 0.1 ng/mL recombinant human IL-37. M1 and M2 polarizations of RAW264.7 cells were induced by 100 ng/mL LPS and 20 ng/mL IL-4, respectively. The expression of M1 (iNOS, TNF-α, and IL-6) and M2 (CD206, Arg1, and IL-10) phenotype markers in RAW264.7 cells was detected by RT-qPCR, western blotting, and immunofluorescence staining. For in vivo experiment, experimental periodontitis mouse models were established by sterile silk ligation (5-0) around the bilateral maxillary second molar of mice for 1 week. H&E staining of the maxillary alveolar bone was used to show the resorption of root cementum and dentin. Alveolar bone loss in mouse models was evaluated through micro-CT analysis. The expression of iNOS and CD206 in gingival tissues was assessed by immunohistochemistry staining. NLRP3 inflammasome activation was confirmed by western blotting. RESULTS: IL-37 pretreatment reduced iNOS, TNF-α, and IL-6 expression in LPS-treated RAW264.7 cells but increased CD206, Arg1, and IL-10 in IL-4-treated RAW264.7 cells. LPS-induced upregulation in NLRP3, GSDMD, cleaved-IL-1ß, and cleaved-caspase-1 expression was antagonized by IL-37 treatment. In addition, IL-37 administration ameliorated the resorption of root cementum and dentin in periodontitis mouse models. IL-37 prominently decreased iNOS+ cell population but increased CD206+ cell population in gingival tissues of periodontitis mice. The enhancement in NLRP3, GSDMD, cleaved-IL-1ß, and cleaved-caspase-1 expression in the gingival tissues of periodontitis mice was offset by IL-37 administration. CONCLUSION: IL-37 prevents the progression of periodontitis by suppressing NLRP3 inflammasome activation and mediating M1/M2 macrophage polarization.

Artificial intelligence-powered pharmacovigilance: A review of machine and deep learning in clinical text-based adverse drug event detection for benchmark datasets.

OBJECTIVE: The primary objective of this review is to investigate the effectiveness of machine learning and deep learning methodologies in the context of extracting adverse drug events (ADEs) from clinical benchmark datasets. We conduct an in-depth analysis, aiming to compare the merits and drawbacks of both machine learning and deep learning techniques, particularly within the framework of named-entity recognition (NER) and relation classification (RC) tasks related to ADE extraction. Additionally, our focus extends to the examination of specific features and their impact on the overall performance of these methodologies. In a broader perspective, our research extends to ADE extraction from various sources, including biomedical literature, social media data, and drug labels, removing the limitation to exclusively machine learning or deep learning methods. METHODS: We conducted an extensive literature review on PubMed using the query "(((machine learning [Medical Subject Headings (MeSH) Terms]) OR (deep learning [MeSH Terms])) AND (adverse drug event [MeSH Terms])) AND (extraction)", and supplemented this with a snowballing approach to review 275 references sourced from retrieved articles. RESULTS: In our analysis, we included twelve articles for review. For the NER task, deep learning models outperformed machine learning models. In the RC task, gradient Boosting, multilayer perceptron and random forest models excelled. The Bidirectional Encoder Representations from Transformers (BERT) model consistently achieved the best performance in the end-to-end task. Future efforts in the end-to-end task should prioritize improving NER accuracy, especially for 'ADE' and 'Reason'. CONCLUSION: These findings hold significant implications for advancing the field of ADE extraction and pharmacovigilance, ultimately contributing to improved drug safety monitoring and healthcare outcomes.

Robotic versus laparoscopic pelvic lateral lymph node dissection in locally advanced rectal cancer: a systemic review and meta-analysis.

BACKGROUND: There are few available studies that compare the feasibility, efficacy, and safety of robotic pelvic lateral lymph node dissection compared to laparoscopic pelvic lateral lymph node dissection (LPLND) in advanced rectal cancer. This meta-analysis aims to compare perioperative outcomes between robotic and LPLND. METHODS: We performed a systemic literature review of PubMed, Embase, and Web of Science databases. Perioperative parameters were extracted and pooled for analysis. This meta-analysis provided an analysis of heterogeneity and prediction intervals. RESULTS: Five studies were included: 567 patients divided between 266 robotic and 301 LPLND. Overall operation time was longer in the robotic group than laparoscopic group (difference in means = 67.11, 95% CI [30.80, 103.42], p < 0.001) but the difference in the pelvic lateral lymph dissection time was not statistically significant (difference in means = - 1.212, 95% CI [ - 11.594, 9.171], p = 0.819). There were fewer overall complications in the robotic than in the laparoscopic group (OR = 1.589, 95% CI [1.009, 2.503], p = 0.046), especially with respect to urinary retention (OR = 2.23, 95% CI [1.277, 3.894], p = 0.005). More pelvic lateral lymph nodes were harvested by robotic surgery than by laparoscopy (differences in means = - 1.992, 95% CI [ - 2.421, 1.563], p < 0.001). CONCLUSIONS: In this meta-analysis, robotic pelvic lateral lymph node dissection was associated with more pelvic lateral lymph nodes harvested and lower overall complications, especially urinary retention when compared to LPLND. Further studies are needed to reinforce these findings.

Analysis of Postoperative Urinary Incontinence and Influencing Factors of Transurethral Holmium Laser Enucleation of the Prostate.

INTRODUCTION: Aims of the study were to investigate the related factors of urinary incontinence after transurethral holmium laser enucleation of the prostate (HoLEP) and to provide guidance for clinical urinary control of HoLEP. METHODS: The clinical data of 548 patients who underwent HoLEP were retrospectively analyzed. The patients were followed up for the occurrence of urinary incontinence in the short term (2 weeks), medium term (3 months), and long term (6 months) after HoLEP. RESULTS: Among the 548 benign prostatic hyperplasia patients, 79 cases (14.42%) had urinary incontinence at 2 weeks, 19 cases (3.47%) at 3 months, and 2 cases (0.36%) at 6 months after surgery. Logistic regression analysis showed that age, prostate volume, diabetes mellitus, operation time, prostate tissue weight, and histological prostatitis were risk factors for recent urinary incontinence (p < 0.05). Age, diabetes, and operation time were risk factors for mid-term urinary incontinence (p < 0.05). The incidence of long-term urinary incontinence was low and no risk factor analysis was performed. CONCLUSIONS: For good urinary control after HoLEP, in addition to surgery-related factors such as surgical skills, proficiency, and precise anatomy, patients' risk factors should also be paid attention to in order to improve postoperative urinary control more effectively and reduce the incidence of urinary incontinence.

Measurement of Zinc Ions in Seawater Samples Using a Microfluidic System Based on the GR/CeO2/Nafion Material.

Considering that heavy-metal contamination of seawater is getting worse, building a quick, accurate and portable device for detecting trace zinc in seawater in real time would be very beneficial. In this work, a microfluidic system was developed that includes a planar disc electrode, a micro-cavity for detection, an electrochemical workstation, a computer, a container for waste liquid reprocessing, an external pipeline and other components as well as a graphene/cerium oxide/nano-cerium oxide/Nafion composite membrane was used to modify the planar disc electrode (GR/CeO2/Nafion/Au) to investigate the electrochemical behaviour of Zn(II) using cyclic voltammetry, square-wave voltammetry and orthogonal test methods. Under optimal experimental conditions, the peak reaction current of Zn(II) showed a good linear relationship with the concentration of Zn(II) in the range of 1-900 µg/L with a correlation coefficient of 0.998, and the detection limit of the method was 0.87 µg/L. In addition, the microfluidic system had good stability, reproducibility and anti-interference. The system was used for determining zinc ions in real seawater samples, and the results were very similar to those of inductively coupled plasma-emission spectrometry, demonstrating the practicality of the system for the detection of trace zinc.