METTL3-Mediated N6-methyladenosine mRNA Modification and cGAS-STING Pathway Activity in Kidney Fibrosis.

BACKGROUND: Chemical modifications on RNA profoundly impact RNA function and regulation. m6A, the most abundant RNA modification in eukaryotes, plays a pivotal role in diverse cellular processes and disease mechanisms. However, its importance is understudied in human chronic kidney disease (CKD) samples regarding its influence on pathological mechanisms. METHODS: LC-MS/MS and Methylated RNA Immunoprecipitation (MeRIP) sequencing were utilized to examine alterations in m6A levels and patterns in CKD samples. Overexpression of the m6A writer METTL3 in cultured kidney tubular cells was performed to confirm the impact of m6A in tubular cells and explore the biological functions of m6A modification on target genes. Additionally, tubule-specific deletion of Mettl3 (Ksp-Cre Mettl3f/f) mice and the use of anti-sense oligonucleotides inhibiting Mettl3 expression were utilized to reduce m6A modification in an animal kidney disease model. RESULTS: By examining 127 human CKD samples, we observed a significant increase in m6A modification and METTL3 expression in diseased kidneys. Epitranscriptomic analysis unveiled an enrichment of m6A modifications in transcripts associated with the activation of inflammatory signaling pathways, particularly the cGAS-STING pathway. m6A hypermethylation increased mRNA stability in cGAS and STING1, as well as elevated the expression of key proteins within the cGAS-STING pathway. Both the tubule-specific deletion of Mettl3 and the use of anti-sense oligonucleotides to inhibit Mettl3 expression protected mice from inflammation, reduced cytokine expression, decreased immune cell recruitment, and attenuated kidney fibrosis. CONCLUSIONS: Our research revealed heightened METTL3-mediated m6A modification in fibrotic kidneys, particularly enriching the cGAS-STING pathway. This hypermethylation increased mRNA stability for cGAS and STING1, leading to sterile inflammation and fibrosis.

Controversies in terminology associated with management of BCG-unresponsive NMIBC in Asia-Pacific.

OBJECTIVES: Examine the understanding of terminologies and management patterns of bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) in six territories in Asia-Pacific. METHODS: This study involved two phases: (1) a survey with 32 urologists and 7 medical oncologists (MOs) and (2) a factorial experiment and in-depth interviews with 23 urologists and 2 MOs. All clinicians had ≥8 years' experience managing NMIBC patients in Australia, Hong Kong, Japan, South Korea, Singapore, and Taiwan. Data from Phase 1 were summarized using descriptive statistics; content and thematic analyses applied in Phase 2. RESULTS: In phase 1, 35% of clinicians defined BCG-unresponsive as BCG-refractory, -relapse and -resistant, 6% defined it as BCG-refractory and -relapse; 22% classified BCG-failure as BCG-refractory, -relapse, -resistant, and when muscle-invasive bladder cancer is detected. If eligible and willing, 50% (interquartile range [IQR], 50%-80%) of BCG-unresponsive patients would undergo radical cystectomy (RC), and 50% (IQR 20%-50%) of RC-eligible patients would receive bladder-sparing treatment or surveillance. In phase 2, we found that 32%, 88%, and 48% of clinicians, respectively, used "BCG-unresponsive," "BCG-refractory," and "BCG-relapse" in clinical practice but with no consistent interpretation of the terms. Compared with EAU definitions, 8%-60% of clinicians appropriately classified 9 tumor types that are persistent or recurrent after adequate BCG. Fifty percent of clinicians mentioned a lack of bladder-preserving treatment that outperforms RC in quality of life as a reason to retreat BCG-unresponsive patients with BCG. CONCLUSIONS: Our study revealed varied understanding and application of BCG-unresponsive terminologies in practice. There is a need for a uniform and simple definition of BCG-unresponsive disease in Asia-Pacific.

Risk stratification and management of non-muscle-invasive bladder cancer: A physician survey in six Asia-Pacific territories.

OBJECTIVES: Multiple clinical practice guidelines, conflicting evidence, and physician perceptions result in variations in risk stratification among patients with non-muscle-invasive bladder cancer (NMIBC). This study aims to describe the extent of this variation and its impact on management approaches in the Asia-Pacific region. METHODS: We conducted a cross-sectional survey involving 32 urologists and seven medical oncologists with ≥8 years of experience managing early-stage bladder cancer patients across Australia, Hong Kong, Japan, South Korea, Singapore, and Taiwan. The physicians completed an anonymous questionnaire that assessed their risk stratification and respective management approaches, based on 19 NMIBC characteristics. For each NMIBC characteristic, they were required to select one risk group, and their most preferred management approach. RESULTS: Our results demonstrated a higher consensus on risk classification versus management approaches. More than 50% of the respondents agreed on the risk classification of all NMIBC characteristics, but 42% or fewer chose the same treatment option as their preferred choice for all but two characteristics-existence of variant histology (55%) and persistent high-grade T1 disease on repeat resection (52%). Across territories, there was the greatest variation in preferred treatment options (i.e., no treatment, intravesical chemotherapy, or Bacillus Calmette-Guérin [BCG] treatment) for intermediate-risk patients and the highest consensus on the treatment of very high-risk patients, namely radical cystectomy. CONCLUSIONS: Our study revealed considerable variation in risk stratification and management of NMIBC in the region. It is critical to develop practical algorithms to facilitate the recognition of NMIBC and standardize the treatment of NMIBC patients.

Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study.

PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter Evaluation.

PURPOSE: We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. MATERIALS AND METHODS: This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). RESULTS: A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. CONCLUSIONS: Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.

Influence of preoperative body mass index on prognosis for patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. METHODS: This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70 years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. RESULTS: The median follow-up duration was 36 months. Patients with higher versus lower BMI (cutoff: 25 kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). CONCLUSION: Younger UTUC patients with higher BMI were independently associated with a favorable DFS.

Influence of microclimate control on the growth of asparagus under greenhouse in tropical climates.

High temperatures have become common in cities in Taiwan, and this phenomenon has spread to surrounding agricultural areas. Tainan, a city located in a tropical climate zone with agriculture as its primary development industry, is one of the cities considerably affected by the high temperature. High temperatures can reduce crop yields and even cause plant death, especially for vulnerable high-value crops, which are severely to microclimate conditions. Asparagus is a high-value crop that has long been cultivated in the Jiangjun District of Tainan. Recently, asparagus has been planted in greenhouses to protect against pests and natural disasters. However, the greenhouses can overheat. To identify the optimal growth environment for asparagus, this study applies vertical monitoring to record the temperature in the greenhouse and the soil moisture content of a control (canal irrigation) and an experimental (drip irrigation) group. When the surface layer of the soil exceeds 33°C, the tender stems of asparagus bloom readily, reducing its commercial value. Therefore, drip irrigation was conducted with cool water (26°C) to reduce soil temperature in summer and warm water (28°C) to increase soil temperature in winter. The study also recorded the growth of asparagus using daily yields measured by farmers during weighing and packing to understand the benefits of controlling the greenhouse microclimate. This study reports a correlation of 0.85 between asparagus yield and temperature and a correlation of 0.86 between asparagus yield and soil moisture content. The use of a drip irrigation system with a water temperature adjustment function not only saves up to 50% of water but also resulted in an average yield increase of 10% through maintaining stable soil moisture content and temperature. Therefore, the findings of this study can be applied to asparagus yields affected by high temperature and can solve the problems of poor quality in summer and low yield in winter.

Applying expanded metal mesh for outdoor shades in outdoor thermal environments.

This study investigated the applicability of expanded metal meshes (EMMs) in horizontal shading devices. We performed simulations and experiments with EMMs with different opening ratios and directions. We established various experimental and control groups to measure air temperature, surface temperature, and black globe temperature. After the comparison of simulation and experimental data, we used Grasshopper to simulate long-term climate situations. The research results can serve as reference for users in Tainan and provide customized suggestions. The findings can serve as a paradigm for parametric design to analyze EMMs. In design projects involving outdoor horizontal shading devices, these results can be used in the design phase for evaluation. Full-day measurements revealed that EMMs with small openings exhibited favorable shading effects. In the Tainan area, we suggest using north-facing EMMs; in our simulations result, 70% of sunshine did not pass through the mesh in a day. For shading equipment in the morning, west-facing EMMs should be used because they blocked 50-90% of sunshine. For recreational areas in the afternoon and evening, east-facing EMMs can block 50-90% of sunshine after noon. In Taiwan, south-facing EMMs are not advised because their shading performance is suboptimal in the morning and afternoon.

Whole-genome-sequence-based characterization of an NDM-5-producing uropathogenic Escherichia coli EC1390.

BACKGROUND: Urinary tract infection (UTI) is one of the most common outpatient bacterial infections. In this study, we isolated and characterized an extensively-drug resistant (XDR) NDM-5-producing Escherichia coli EC1390 from a UTI patient by using whole-genome sequencing (WGS) in combination with phenotypic assays. METHODS: Antimicrobial susceptibility to 23 drugs was determined by disk diffusion method. The genome sequence of EC1390 was determined by Nanopore MinION MK1C platform. Conjugation assays were performed to test the transferability of EC1390 plasmids to E. coli recipient C600. Phenotypic assays, including growth curve, biofilm formation, iron acquisition ability, and cell adhesion, were performed to characterize the function of EC1390 plasmids. RESULTS: Our results showed that EC1390 was only susceptible to tigecycline and colistin, and thus was classified as XDR E. coli. A de novo genome assembly was generated using Nanopore 73,050 reads with an N50 value of 20,936 bp and an N90 value of 7,624 bp. WGS analysis showed that EC1390 belonged to the O101-H10 serotype and phylogenetic group A E. coli. Moreover, EC1390 contained 2 conjugative plasmids with a replicon IncFIA (pEC1390-1 with 156,286 bp) and IncFII (pEC1390-2 with 71,840 bp), respectively. No significant difference was observed in the bacterial growth rate in LB broth and iron acquisition ability between C600, C600 containing pEC1390-1, C600 containing pEC1390-2, and C600 containing pEC1390-1 and pEC1390-2. However, the bacterial growth rate in nutrition-limited M9 broth was increased in C600 containing pEC1390-2, and the cell adhesion ability was increased in C600 containing both pEC1390-1 and pEC1390-2. Moreover, these plasmids modulated the biofilm formation under different conditions. CONCLUSIONS: In summary, we characterized the genome of XDR-E. coli EC1390 and identified two plasmids contributing to the antimicrobial resistance, growth of bacteria in a nutrition-limited medium, biofilm formation, and cell adhesion.

Whole ureter replacement with Yang-Monti principle: successful treatment of challenging conditions.

BACKGROUND: No clear consensus has been reached on the reconstruction of long-segment or total ureter discontinuation. Here we present our experience using the Yang-Monti technique in total ureter reconstruction. METHODS: This study was a single-center retrospective study of patients who underwent Yang-Monti ileal whole ureter reconstruction (from the ureteropelvic junction[UPJ] to the ureterovesical junction). Data were collected on patients' baseline characteristics, stricture etiology, the time interval between insult and surgical repair, pre/postoperative serum creatinine, estimated glomerular filtration rate (eGFR), split renal function, complications during admission and follow-ups, and the indwelling durations of JJ tubes and nephrostomy tubes, if presented. RESULTS: Seven patients underwent Yang-Monti ileal ureter reconstruction in 2010-2020 at our hospital. One of the patients underwent single-session bilateral ureter repair. Radiation therapy-related fibrosis and degloving injury were the most common etiologies for ureter injury. The median interval between ureter insult and operation was 8 months. The median follow-up was 36.7 months. The average operation time was 11.4 h, and the average blood loss was 273 ml. Postoperatively, no significant differences were found in serum creatinine, eGFR, or split renal function. As for postoperative complications, two patients experienced ileus and were treated conservatively. One patient had UPJ stenosis, which resolved after re-anastomosis surgery 11 months later. Metabolic acidosis or electrolyte imbalance was not reported. CONCLUSION: We found that ileal replacement of total ureteral loss using the Yang-Monti principle is effective and durable. This is the largest cohort study conducted with more than 2 years of follow-up.

Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue.

AIMS: Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. It has been estimated to constitute 4% of previously diagnosed papillary renal cell carcinoma (PRCC). Renal papillary adenoma (PA) is suggested to be the precursor of PRCC. This study aimed to investigate the association between PRNRP and PA, particularly the morphologically similar type D PA. METHODS AND RESULTS: Nephrectomy specimens of PRCC and PA from our 10-year pathology archives were retrieved and reviewed. GATA3 immunohistochemistry and RAS/BRAF testing were performed in all cases reclassified as PRNRP and all PAs with sufficient materials. Overall, PRNRP accounted for 9.1% (10 of 110) of PRCC and there was no recurrence/metastasis with a mean follow-up period of 39 months. Three novel morphological features were described, including clear cell change, mast cell infiltration and metaplastic ossification. Nine of the 10 PRNRPs showed diffuse and strong GATA3 expression and KRAS missense mutations at codon 12. One case exhibited moderate GATA3 staining on 80% of the tumour cells and RAS/BRAF wild-type. In a total of 73 PAs, 11 were classified as type D. GATA3 expression was significantly more frequent in type D versus non-type D PAs (100 versus 35%, P < 0.01). KRAS missense mutations were identified in six of eight (75%) of the type D PAs but none of the 18 non-type D PAs. CONCLUSIONS: Type D PA was different from other types of PA and represented an analogue or a small-sized PRNRP for their identical morphology, immunophenotype and molecular signature.

Patients with preoperative asymptomatic pyuria are not prone to develop febrile urinary tract infection after ureteroscopic lithotripsy.

BACKGROUND: This study aimed to evaluate the association of asymptomatic pyuria before ureterorenoscopic lithotripsy (URSL) with postoperative febrile urinary tract infection (UTI). METHODS: This observational case-control study identified the patients undergoing URSL for ureteral stones between May 2011 and October 2015. The included patients were classified into two groups: the asymptomatic pyuria group (6-50 white blood cells [WBCs]/high-power field [HPF]) and the non-pyuria group (≤ 5 WBCs/HPF). All data were collected by reviewing medical records. Postoperative outcomes were collected in terms of febrile UTI, emergency visits, and stone-free rate. RESULTS: A total of 232 patients were included, 101 in the pyuria group, 131 in the non-pyuria group. Two (0.9%) patients developed febrile UTI after URSL and 12 (5.2%) patients visited emergency department for URSL-related symptoms. The overall stone-free rate was 90.9%. There was no significant difference between the pyuria and non-pyuria groups regarding febrile UTI, emergency visits, and stone-free rate. Multivariate analysis revealed that pyuria was neither significantly associated with postoperative febrile UTI (OR = 1.03, 95% CI = 0.06-18.10, P = 0.98), nor with emergency visits (OR = 0.48, 95% CI = 0.13-1.85, P = 0.29). CONCLUSIONS: Compared to the patients with sterile urine prior to URSL, those with asymptomatic pyuria were not prone to develop febrile UTI after URSL.

Autosegmentation of Prostate Zones and Cancer Regions from Biparametric Magnetic Resonance Images by Using Deep-Learning-Based Neural Networks.

The accuracy in diagnosing prostate cancer (PCa) has increased with the development of multiparametric magnetic resonance imaging (mpMRI). Biparametric magnetic resonance imaging (bpMRI) was found to have a diagnostic accuracy comparable to mpMRI in detecting PCa. However, prostate MRI assessment relies on human experts and specialized training with considerable inter-reader variability. Deep learning may be a more robust approach for prostate MRI assessment. Here we present a method for autosegmenting the prostate zone and cancer region by using SegNet, a deep convolution neural network (DCNN) model. We used PROSTATEx dataset to train the model and combined different sequences into three channels of a single image. For each subject, all slices that contained the transition zone (TZ), peripheral zone (PZ), and PCa region were selected. The datasets were produced using different combinations of images, including T2-weighted (T2W) images, diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) images. Among these groups, the T2W + DWI + ADC images exhibited the best performance with a dice similarity coefficient of 90.45% for the TZ, 70.04% for the PZ, and 52.73% for the PCa region. Image sequence analysis with a DCNN model has the potential to assist PCa diagnosis.

Effectiveness of a couple-based psychosocial intervention on patients with prostate cancer and their partners: A quasi-experimental study.

AIMS: To understand the effectiveness of a couple-based psychosocial information package (PIP) and multimedia psychosocial intervention (MPI) on patients with prostate cancer and their partners. DESIGN: A random assignment and quasi-experimental design were used. METHODS: From August 2015-March 2018, 103 newly diagnosed patients with prostate cancer and their partners were divided into a control group (CG) (N = 50), PIP group (N = 25) and MPI group (N = 28). The CG received usual care, the PIP group received information manuals and telephone counselling for 6-week and the MPI group received multimedia films and manuals and professional support for 6 weeks. The three groups were posttested 6, 10, 18 and 24 weeks after the pre-test. The outcome measurements included disease appraisals, emotion status, relationship satisfaction, health-related quality of life (HRQOL) and satisfaction with MPI. RESULTS/FINDINGS: Partners in the MPI and PIP groups experienced significant improvements in positive and negative affect or mental HRQOL as compared with the CG. The effectiveness of MPI and PIP on negative affect, mental HRQOL, however, were not statistically significant in patients with prostate cancer. Nevertheless, patients were satisfied with the MPI. CONCLUSION: Nurses can provide different types of interventions for partners, depending on personal preferences and available resources. IMPACT: There is a lack of studies that focus on the effectiveness of couple-based psychosocial intervention on both the patients with prostate cancer and their partners in Asia. Partners in the multimedia psychosocial intervention group and psychosocial information package group experienced improvements in positive affect, negative affect or health-related quality of life as compared with the control group. Patients in both intervention groups experienced similar negative affect and health-related quality of life as compared with the control group. The couple-based psychosocial interventions can be provided by nurses based on partners' preferences and available resources.

Safety and effectiveness of high-power thulium laser enucleation of the prostate in patients with glands larger than 80 mL.

BACKGROUND: The efficacy of thulium laser prostate enucleation (ThuLEP) for large prostates is unclear. This study aimed to explore the expanded utility of 150-200-W ThuLEP by studying patients with a large prostate (> 80 mL). METHODS: We retrospectively reviewed records of 125 patients with large prostate glands (> 80 mL) who underwent ThuLEP performed by a single surgeon from June 2012 to June 2016. The ThuLEP data from our previous pilot study were used as the control. Operative variables, patient profiles, preoperative and postoperative urine flow rates, prostate volume, and the international prostate symptom score (IPSS) were recorded and analyzed using Student's t-test, the z-test, and logistic regression analysis. RESULTS: Of 366 patients who underwent ThuLEP, 125 (34.15%) were enrolled. The ages and estimated prostate volumes were compared with those of the control. Overall, 39.2% underwent Foley placement and 4% received an anticoagulant agent preoperatively. Maximum urinary flow rates before and 3 and 12 months postoperatively were 9.93, 23.20, and 19.00 mL/s, respectively, which were generally equal to those of the control groups (P = 0.68, 0.18, 0.98, respectively). Preoperative and postoperative IPSSs were 27.09 and 7.35, respectively. The postoperative prostate-specific antigen was reduced by 85.59% in comparison to the preoperative level. The estimated prostate size was reduced by 74.17% postoperatively. The modified Clavien-Dindo classification system was used to identify the overall rate of complications, which was approximately 22.4%. The mortality rate was 0.8%. CONCLUSIONS: High-power ThuLEP is safe and effective for patients with large prostate glands (> 80 mL). Prostate enucleation using a high-power thulium laser is feasible for patients who exhibit contraindications for surgery.

A simple approach for the development of urban climatic maps based on the urban characteristics in Tainan, Taiwan.

Motivated by the increasing thermal load in urban environment, this work established Urban Climatic map (UCmap) focusing on thermal environment issues based on urban development factors, e.g., land cover and building characteristics, representing thermal load of human body and ventilation path in the urban structures. In the established process of UCmap in this work, Tainan city, which is a highly developed city in southern Taiwan, is selected as the research area. A 50-m resolution grid is used to capture urban development factors and the climate data based on 1 year of mobile and fix-point measurements, from which the thermal load and the wind environment map are constructed. The results herein reveal that a higher urban development level is associated with a higher thermal load, and similar areas are more likely than others to suffer from an extreme thermal load and low wind pass conditions. Open and sparse low-rise buildings constitute the most appropriate urban characteristics for urban built environment in Tainan. By the simple approach of establishing UCmap, the microclimate condition and development intensity of regions can be easily detected and linked, for example the compact high-rise areas should be limited by floor area ratio in order to prevent the formation of hot spots. The government, urban planners, and architects without a meteorological background can efficiently obtain climate information by way of mapping the certain area, and making regulations to mitigate the growing problem of thermal stress and urban heat island.

Long-term perceptions of outdoor thermal environments in an elementary school in a hot-humid climate.

Previous studies on thermal comfort in school environments have focused more on indoor thermal environments than outdoor ones, thus providing a limited understanding of occupants' long-term thermal perceptions. Taiwan is located in a subtropical region, where it can be stiflingly hot outside in summer. This highlights the need to ensure proper thermal comfort on campus. In the present study, thermal environment parameters were measured and collected in several outdoor spaces of an elementary school in southern Taiwan. In addition, a questionnaire was used to explore occupants' long-term thermal perceptions of these spaces. During summer months, the physiological equivalent temperature (PET) of these outdoor spaces in over 60% of the daytime in summer between 10 a.m. and 4 p.m. was higher than 38 °C PET, indicating high heat stress. The results of occupants' long-term perceptions of the thermal comfort of these spaces suggested that dissatisfaction with thermal comfort was associated more with solar radiation than with wind speed. Finally, this study simulated a campus environment where more trees are planted and compared the thermal comfort indices before and after the simulation. The results indicated that this solution contributed to a decrease in the PET of these environments, thereby alleviating high heat stress. This study can inform the improvement of microclimates and thermal comfort during campus layout planning. Planting trees judiciously across a campus increases outdoor shades and creates outdoor spaces that are more comfortable and adaptable to hot weather conditions, thereby ensuring frequent use of these spaces.

Four-and-a-Half LIM Domains Protein 2 Is a Coactivator of Wnt Signaling in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a microvascular complication that leads to kidney dysfunction and ESRD, but the underlying mechanisms remain unclear. Podocyte Wnt-pathway activation has been demonstrated to be a trigger mechanism for various proteinuric diseases. Notably, four-and-a-half LIM domains protein 2 (FHL2) is highly expressed in urogenital systems and has been implicated in Wnt/ß-catenin signaling. Here, we used in vitro podocyte culture experiments and a streptozotocin-induced DKD model in FHL2 gene-knockout mice to determine the possible role of FHL2 in DKD and to clarify its association with the Wnt pathway. In human and mouse kidney tissues, FHL2 protein was abundantly expressed in podocytes but not in renal tubular cells. Treatment with high glucose or diabetes-related cytokines, including angiotensin II and TGF-ß1, activated FHL2 protein and Wnt/ß-catenin signaling in cultured podocytes. This activation also upregulated FHL2 expression and promoted FHL2 translocation from cytosol to nucleus. Genetic deletion of the FHL2 gene mitigated the podocyte dedifferentiation caused by activated Wnt/ß-catenin signaling under Wnt-On, but not under Wnt-Off, conditions. Diabetic FHL2(+/+) mice developed markedly increased albuminuria and thickening of the glomerular basement membrane compared with nondiabetic FHL2(+/+) mice. However, FHL2 knockout significantly attenuated these DKD-induced changes. Furthermore, kidney samples from patients with diabetes had a higher degree of FHL2 podocyte nuclear translocation, which was positively associated with albuminuria and progressive renal function deterioration. Therefore, we conclude that FHL2 has both structural and functional protein-protein interactions with ß-catenin in the podocyte nucleus and that FHL2 protein inhibition can mitigate Wnt/ß-catenin-induced podocytopathy.

Monoamine oxidase A inhibitor-near-infrared dye conjugate reduces prostate tumor growth.

Development of anti-cancer agents with high tumor-targeting specificity and efficacy is critical for modern multidisciplinary cancer research. Monoamine oxidase A (MAOA), a mitochondria-bound enzyme, degrades monoamine neurotransmitters and dietary monoamines. Recent evidence suggests a correlation between increased MAOA expression and prostate cancer (PCa) progression with poor outcomes for patients. MAOA induces epithelial-mesenchymal transition (EMT) and augments hypoxic effects by producing excess reactive oxygen species. Thus, development of MAOA inhibitors which selectively target tumors becomes an important goal in cancer pharmacology. Here we describe the design, synthesis, and in vitro and in vivo evaluation of NMI, a conjugate that combines a near-infrared dye for tumor targeting with the moiety derived from the MAOA inhibitor clorgyline. NMI inhibits MAOA with low micromolar IC50, suppresses PCa cell proliferation and colony formation, and reduces migration and invasion. In mouse PCa xenografts, NMI targets tumors with no detectable accumulation in normal tissues, providing effective reduction of the tumor burden. Analysis of tumor specimens shows reduction in Ki-67(+) and CD31(+) cells, suggesting a decrease of cell proliferation and angiogenesis and an increase in M30(+) cells, indicating increased apoptosis. Gene expression profiles of tumors treated with NMI demonstrate reduced expression of oncogenes FOS, JUN, NFKB, and MYC and cell cycle regulators CCND1, CCNE1, and CDK4/6, along with increases in the levels of tumor suppressor gene TP53, cell cycle inhibitors CDKN1A and CDKN2A, and MAOA-downstream genes that promote EMT, tumor hypoxia, cancer cell migration, and invasion. These data suggest that NMI exerts its effect through tumor-targeted delivery of a MAOA-inactivating group, making NMI a valuable anti-tumor agent.