Conserved Upstream Open Reading Frame Nascent Peptides That Control Translation.

Cells utilize transcriptional and posttranscriptional mechanisms to alter gene expression in response to environmental cues. Gene-specific controls, including changing the translation of specific messenger RNAs (mRNAs), provide a rapid means to respond precisely to different conditions. Upstream open reading frames (uORFs) are known to control the translation of mRNAs. Recent studies in bacteria and eukaryotes have revealed the functions of evolutionarily conserved uORF-encoded peptides. Some of these uORF-encoded nascent peptides enable responses to specific metabolites to modulate the translation of their mRNAs by stalling ribosomes and through ribosome stalling may also modulate the level of their mRNAs. In this review, we highlight several examples of conserved uORF nascent peptides that stall ribosomes to regulate gene expression in response to specific metabolites in bacteria, fungi, mammals, and plants.

Size-consistency and orbital-invariance issues revealed by VQE-UCCSD calculations with the FMO scheme.

The fragment molecular orbital (FMO) scheme is one of the popular fragmentation-based methods and has the potential advantage of making the circuit shallow for quantum chemical calculations on quantum computers. In this study, we used a GPU-accelerated quantum simulator (cuQuantum) to perform the electron correlation part of the FMO calculation as unitary coupled-cluster singles and doubles (UCCSD) with the variational quantum eigensolver (VQE) for hydrogen-bonded (FH) 3 and (FH) 2 -H 2 O systems with the STO-3G basis set. VQE-UCCSD calculations were performed using both canonical and localized MO sets, and the results were examined from the point of view of size-consistency and orbital-invariance affected by the Trotter error. It was found that the use of localized MO leads to better results, especially for (FH) 2 -H 2 O. The GPU acceleration was substantial for the simulations with larger numbers of qubits, and was about a factor of 6.7-7.7 for 18 qubit systems.

Early predictors of brain injury in patients with acute carbon monoxide poisoning and the neuroprotection of mild hypothermia.

INTRODUCTION: Carbon monoxide (CO) poisoning can cause serious neurological sequelae. However, there is neither effective treatment strategy nor reliable indicators to determine the prognosis of patients with CO poisoning. The present study aimed to observe the changes of neurological function score, disease severity score, cerebral oxygen utilization (O2UCc), bispectral (BIS) index and neuron-specific enolase (NSE) concentration, and to elucidate the clinical significance of these potential indicators and the neuroprotective effect of mild hypothermia on brain injury in patients with severe acute CO poisoning. MATERIALS AND METHODS: A total of 277 patients with acute severe CO poisoning from 2013 to 2018 were enrolled in our hospital. Patients were divided into three groups according to their body temperature on the day of admission and their willingness to treat: a fever group (n = 78), a normal temperature group (NT group, n = 113), and a mild hypothermia group (MH group, n = 86). All patients were given hyperbaric oxygen therapy, while those in the MH group received additional mild hypothermia treatment. The severity of the disease, the neurobehavioral status, the incidence of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), and other indicators including BIS, O2UCc, NSE were further evaluated in all patients at given time-points. RESULTS: Mild hypothermia therapy improved the prognosis of patients with CO poisoning, significantly decreased the value of O2UCc and NSE, and up-regulated BIS. The incidence of DEACMP at 6 months was 27% in the fever group, 23% in the NT group, and 8% in the MH group. The values of Glasgow-Pittsburgh coma scale (G-P score), BIS index and NSE were closely related to the occurrence of DEACMP, the cutoff values were 12.41, 52.17 and 35.20 ng/mL, and the sensitivity and specificity were 79.3%, 77.6%, 79.3% and 67.6%, 89.5%, 88.6% in the receiver operating characteristic curve (ROC), respectively. CONCLUSIONS: Early mild hypothermia treatment could significantly reduce the severity of brain injury after CO poisoning, and might be further popularized in clinic. G-P scores, NSE and BIS index can be regarded as the prediction indicators in the occurrence and development of DEACMP. CLINICAL TRIAL REGISTRATION: The study protocol was granted from Qingdao University Research Ethics Committee (Clinical trial registry and ethical approval number: QD81571283).

Urothelial cell carcinoma presenting with rapid visual deterioration, a case of rare brain metastases with unique clinical presentation.

BACKGROUND: Urothelial cell carcinoma (UCC), the most common cancer of the urinary system, rarely metastasizes to the brain. 1-3 More rare still is the subset of patients with urothelial carcinoma brain metastases whose UCC primary is first diagnosed at the same time as their CNS metastatic disease, with oncologic workup prompted by CNS clinical manifestations.4 Paraneoplastic optic neuropathy (PON) is likewise a rare clinical entity, which has not yet been described in association with UCC brain metastases. CASE DESCRIPTION: Herein, we present the sentinel case of UCC believed to be of endometrial origin in an 81 year old woman initially presenting with symptoms of fatigue, nausea, vertigo, and rapidly deteriorating vision over the course of 1 month. Visual deterioration prompted neuro imaging remarkable for multiple supratentorial and infratentorial metastases as well as likely neoplastic inflammatory involvement of the bilateral optic nerves. The patient underwent a right temporal open brain biopsy, with pathology findings consistent with UCC. Subsequent PET scanning demonstrated a heavy burden of disease including an FDG-avid uterine mass with local and distal extension of disease including bilateral hydroureteronephrosis with obstruction of the distal ureters. The patient and her family elected to pursue home hospice without further workup or intervention. CONCLUSIONS: While this is the first such case presented, it is possible that UCC of the uterine wall represents a particularly aggressive form of the disease more prone to presenting with CNS metastases and PON.

An alternative method for analyzing dimensional interactions of urban carrying capacity: Case study of Guangdong-Hong Kong-Macao Greater Bay Area.

Most previous studies on comprehensive urban carrying capacity (UCC) have estimated UCC levels and comparatively analyzed the heterogeneity of the sample cities. Very few researchers have focused on the interaction effects between different categories of UCC based on synergetic theory. To fill this gap, we constructed a panel vector autoregressive (PVAR) model to study 11 cities in the Guangdong-Hong Kong-Macao Greater Bay Area from 2000 to 2016. The ultimate goal of this study is to improve comprehensive UCC levels by forming a virtuous circle of mutual reinforcement between the four types of carrying capacity. To do so, the interaction mechanisms of the four subsystems are examined. Results show that (a) only transportation and social carrying capacity had causality between them as per the Granger causality test; (b) all four carrying capacities can support themselves (i.e., the development of economic conditions helps to improve social carrying capacity and the improvement of social carrying capacity helps to improve environmental carrying capacity); and (c) both the four carrying capacities are mostly affected by their own fluctuations. Overall transportation carrying capacity is the most important driving force among the four subsystems that interact with each other; followed by economic carrying capacity, which has promotion effect on the social and environmental aspects; social carrying capacity poses impact on the environmental dimension but not vice versa. Policy suggestions and future research directions are highlighted in the final section.

Stabilized red soil-an efficient liner system for landfills containing hazardous materials.

In recent decades, disposal of hazardous material has become a challenging task especially in case of landfills where leaching out of waste is possible. In such cases, an efficient and economical liner system using locally available material is very essential. In this paper, an attempt has been made to study the suitability of red soil stabilized using lime and Prosopis juliflora fibers as liner material for landfills. Prosopis is a woody weed available abundantly in tropical and subtropical regions of the world. The fibers were used at 0.0%, 0.25%, 0.50%, 0.75%, and 1.0% by weight of the soil and the amount of lime used was kept constant as 4%. Tests results revealed decrease in plasticity index, increase in UCC strength, ductile behavior, decrease in consolidation settlement, reduction in permeability and shrinkage, and increase in CBR resistance in soils treated with both lime and Prosopis fibers. SEM images of stabilized soil revealed adherence of hydrated products of lime on the fiber surface, which facilitate efficient stress transfer between the soil and fibers. A single composite liner system was modeled using Visual MODFLOW by replacing the compacted clay layer with the stabilized red soil below the HDPE liner and the model was simulated. The simulation result showed that the performance of liner system with stabilized red soil is good and could prevent the aquifer from contamination. From the study, it can be concluded that stabilized red soil possesses the geotechnical properties required for an efficient liner system.

Diabetes mellitus medication use and catastrophic healthcare expenditure among adults aged 50+ years in China and India: results from the WHO study on global AGEing and adult health (SAGE).

BACKGROUND: Expenditure on medications for highly prevalent chronic conditions such as diabetes mellitus (DM) can result in financial impoverishment. People in developing countries and in low socioeconomic status groups are particularly vulnerable. China and India currently hold the world's two largest DM populations. Both countries are ageing and undergoing rapid economic development, urbanisation and social change. This paper assesses the determinants of DM medication use and catastrophic expenditure on medications in older adults with DM in China and India. METHODS: Using national standardised data collected from adults aged 50 years and above with DM (self-reported) in China (N = 773) and India (N = 463), multivariable logistic regression describes: 1) association between respondents' socio-demographic and health behavioural characteristics and the dependent variable, DM medication use, and 2) association between DM medication use (independent variable) and household catastrophic expenditure on medications (dependent variable) (China: N = 630; India: N = 439). The data source is the World Health Organization (WHO) Study on global AGEing and adult health (SAGE) Wave 1 (2007-2010). RESULTS: Prevalence of DM medication use was 87% in China and 71% in India. Multivariable analysis indicates that people reporting lifestyle modification were more likely to use DM medications in China (OR = 6.22) and India (OR = 8.45). Women were more likely to use DM medications in China (OR = 1.56). Respondents in poorer wealth quintiles in China were more likely to use DM medications whereas the reverse was true in India. Almost 17% of people with DM in China experienced catastrophic healthcare expenditure on medications compared with 7% in India. Diabetes medication use was not a statistically significant predictor of catastrophic healthcare expenditure on medications in either country, although the odds were 33% higher among DM medications users in China (OR = 1.33). CONCLUSIONS: The country comparison reflects major public policy differences underpinned by divergent political and ideological frameworks. The DM epidemic poses huge public health challenges for China and India. Ensuring equitable and affordable access to medications for DM is fundamental for healthy ageing cohorts, and is consistent with the global agenda for universal healthcare coverage.

Validation study of a noninvasive urine test for diagnosis and prognosis assessment of bladder cancer: evidence for improved models.

PURPOSE: We validated the performance of our previously reported test for bladder cancer based on urine gene expression patterns using an independent cohort. We also ascertained whether alternative models could achieve better accuracy. MATERIALS AND METHODS: Gene expression patterns of the previously reported 48 genes, including the 12 + 2 genes of the signature, were analyzed by TaqMan® arrays in an independent set of 207 urine samples. We pooled all samples analyzed to date to obtain a larger training set of 404 and used it to search for putative improved new models. RESULTS: Our 12 + 2 gene expression signature had overall 80% sensitivity with 86% specificity (AUC 0.914) to discriminate between bladder cancer and control samples. It had 75% sensitivity and 75% specificity (AUC 0.83) to predict tumor aggressiveness in the validation set of urine samples. After grouping all samples 3 new signatures for diagnosis containing 2, 5 and 10 genes, respectively, and 1 containing 6 genes for prognosis were designed. Diagnostic performance of the 2, 5, 10 and 12-gene signatures was maintained or improved in the enlarged sample set (AUC 0.913, 0.941, 0.949 and 0.944, respectively). Performance to predict aggressiveness was also improved in the 14 and 6-gene signatures (AUC 0.855 and 0.906, respectively). CONCLUSIONS: This validation study confirms the accuracy of the 12 + 2 gene signature as a noninvasive tool for assessing bladder cancer. We present improved models with fewer genes that must be validated in future studies.

Bladder malignancy as a cause of spontaneous bladder rupture: A systematic review.

Objectives: To characterise cases of spontaneous rupture of the urinary bladder in the context of bladder cancer. Methods: A systematic review was performed to characterise cases of spontaneous bladder rupture in patients with bladder cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) system was utilised, with databases being searched for relevant cases. Patient characteristics were extracted, including age, sex, presenting signs and symptoms, management modalities, tumour histology and mortality. Results: Thirty cases were included. Seventeen (57%) were male, and the median age of presentation was 59. Abdominal pain and peritonism were the most common presenting symptoms, in 80% and 60% of patients, respectively. Most patients (n = 16, 53%) had urothelial cell carcinoma. Nine patients (30%) died during their initial hospitalisation. Conclusion: Spontaneous bladder perforation in the context of bladder cancer is a rare cause of acute abdomen. The diagnosis is associated with high mortality, highlighting the aggressive nature of the malignancies that cause spontaneous bladder rupture. This raises important questions about the role of emergency cystectomy, the timing of systemic therapy and the appropriate involvement of palliative care.

The impact of running versus interrupted anastomosis on ureterointestinal stricture rate after radical cystectomy.

PURPOSE: Benign ureterointestinal anastomotic stricture is not uncommon after radical cystectomy and urinary diversion. We studied the impact of the running vs the interrupted technique on the ureterointestinal anastomotic stricture rate. MATERIALS AND METHODS: From July 2007 to December 2008 interrupted end-to-side anastomoses were created and from January 2009 to July 2010 running anastomoses were created. The primary study end point was time to ureterointestinal anastomotic stricture. RESULTS: Of 266 consecutive patients 258 were alive 30 days after radical cystectomy, including 149 and 109 with an interrupted and a running anastomosis, respectively. The groups did not differ in age, gender, body mass index, age adjusted Charlson comorbidity index, receipt of chemotherapy or radiation, blood loss, operative time, diversion type or postoperative pathological findings. The stricture rate per ureter was 8.5% (25 of 293) and 12.7% (27 of 213) in the interrupted and running groups, respectively (p = 0.14). Univariate analysis suggested that postoperative urinary tract infection (HR 2.1, 95% CI 1.1-4.1, p = 0.04) and Clavien grade 3 or greater complications (HR 2.6, 95% CI 1.4-4.9, p <0.01) were associated with ureterointestinal anastomotic stricture. On multivariate analysis postoperative urinary tract infection (HR 2.4, 95% CI 1.2-5.1, p = 0.02) and running technique (HR 1.9, 95% CI 1.0-3.7, p = 0.05) were associated with ureterointestinal anastomotic stricture. Median time to stricture and followup was 289 (IQR 120-352) and 351 days (IQR 132-719) in the running cohort vs 213 (IQR 123-417) and 497 days (IQR 174-1,289) in the interrupted cohort, respectively. Of the 52 strictures 33 (63%) developed within 1 year. Kaplan-Meier analysis controlling for differential followup showed a trend toward higher freedom from stricture for the interrupted ureterointestinal anastomosis (p = 0.06). CONCLUSIONS: A running anastomosis and postoperative urinary tract infection may be associated with ureterointestinal anastomotic stricture. Larger series with multiple surgeons are needed to confirm these findings.

Trends in Atrial Fibrillation Management-Results from a National Multi-Center Urgent Care Network Registry.

BACKGROUND: Atrial fibrillation (AF) is a common diagnosis in patients presenting to urgent care centers (UCCs), yet there is scant research regarding treatment in these centers. While some of these patients are managed within UCCs, some are referred for further care in an emergency department (ED). OBJECTIVES: We aimed to identify the rate of patients referred to an ED and define predictors for this outcome. We analyzed the rates of AF diagnosis and hospital referral over the years. Finally, we described trends in patient anticoagulation (AC) medication use. METHODS: This retrospective study included 5873 visits of patients over age 18 visiting the TEREM UCC network with a diagnosis of AF over 11 years. Multivariate analysis was used to identify predictors for ED referral. RESULTS: In a multivariate model, predictors of referral to an ED included vascular disease (OR 1.88 (95% CI 1.43-2.45), p < 0.001), evening or night shifts (OR 1.31 (95% CI 1.11-1.55), p < 0.001; OR 1.68 (95% CI 1.32-2.15), p < 0.001; respectively), previously diagnosed AF (OR 0.31 (95% CI 0.26-0.37), p < 0.001), prior treatment with AC (OR 0.56 (95% CI 0.46-0.67), p < 0.001), beta blockers (OR 0.63 (95% CI 0.52-0.76), p < 0.001), and antiarrhythmic medication (OR 0.58 (95% CI 0.48-0.69), p < 0.001). Visits diagnosed with AF increased over the years (p = 0.030), while referrals to an ED decreased over the years (p = 0.050). The rate of novel oral anticoagulant prescriptions increased over the years. CONCLUSIONS: The rate of referral to an ED from a UCC over the years is declining but remains high. Referrals may be predicted using simple clinical variables. This knowledge may help to reduce the burden of hospitalizations.

Implications of viral infections and oncogenesis in uterine cervical carcinoma etiology and pathogenesis.

Background: Uterine Cervical Carcinoma (UCC) is the most prevalent gynecological malignancy globally, with a rising incidence in recent years. Accumulating evidence indicates that specific viral infections, including human papillomavirus (HPV), Epstein-Barr virus (EBV), Hepatitis B and C viruses (HBV and HCV), and human herpesvirus (HHV), may contribute to UCC development and progression. Understanding the complex interplay between viral infections and UCC risk is crucial for developing novel preventative and therapeutic interventions. Methods: This comprehensive review investigates the association between viral infections and UCC risk by examining the roles of various viral pathogens in UCC etiology and pathogenesis, and possible molecular mechanisms. Additionally, we evaluate current diagnostic methods and potential therapeutic strategies targeting viral infections for UCC prevention or treatment. Results: The prevention of UCC has been significantly advanced by the emergence of self-sampling for HPV testing as a crucial tool, allowing for early detection and intervention. However, an essential challenge in UCC prevention lies in understanding how HPV and other viral coinfections, including EBV, HBV, HCV, HHV, HIV, or their concurrent presence, may potentially contribute to UCC development. The molecular mechanisms implicated in the association between viral infections and cervical cancer development include: (1) interference of viral oncogenes with cellular regulatory proteins, resulting in uncontrolled cell proliferation and malignant transformation; (2) inactivation of tumor suppressor genes by viral proteins; (3) evasion of host immune responses by viruses; (4) induction of a persistent inflammatory response, contributing to a tumor-promoting microenvironment; (5) epigenetic modifications that lead to aberrant gene expression; (6) stimulation of angiogenesis by viruses; and (7) activation of telomerase by viral proteins, leading to cellular immortalization. Additionally, viral coinfections can also enhance oncogenic potential through synergistic interactions between viral oncoproteins, employ immune evasion strategies, contribute to chronic inflammation, modulate host cellular signaling pathways, and induce epigenetic alterations, ultimately leading to cervical carcinogenesis. Conclusion: Recognizing the implications of viral oncogenes in UCC etiology and pathogenesis is vital for addressing the escalating burden of UCC. Developing innovative preventative and therapeutic interventions requires a thorough understanding of the intricate relationship between viral infections and UCC risk.

Myoepithelial carcinoma of the bladder: Case report and review of the literature.

Myoepithelial carcinoma is a neoplasm that classically arises in the parotid glands, nasopharynx, paranasal sinus, and nasal cavity of the head and neck. It rarely arises in other organs or soft tissues and involvement of genitourinary organs is distinctly rare. We describe a case of a 21-year-old male, presenting with nausea, weight loss, and worsening suprapubic pain over 3 months, found to have a large mass at the dome of the bladder. Partial cystectomy was ultimately performed revealing myoepithelial carcinoma of the bladder. The patient is free of disease at four years without the need for systemic therapy.

Pretreatment C-Reactive Protein/Albumin Ratio is Associated With Poor Survival in Patients With 2018 FIGO Stage IB-IIA HPV-Positive Cervical Cancer.

Objectives: The present study aimed to identify the predictive value of inflammatory indexes stratified according to human papillomavirus (HPV) infection status in women with FIGO 2018 stage IB∼IIA cervical cancer. We also explored the influences of HPV infection status on the survival of cervical cancer patients. Methods: We collected data for 583 women with stage IB∼IIA cervical cancer in Sun Yat-sen University Cancer Center between 2009 and 2017. The t-test, chi-squared (χ2) test and Fisher's exact test were applied to compare the differences of inflammatory indexes and clinicopathological features between HPV-positive and HPV-negative groups. Univariate and multivariate analyses were used to identify clinicopathological factors that were associated with the prognosis of cervical cancer patients. Results: There were no differences in overall survival (OS) and progression-free survival (PFS) between HPV-positive and HPV-negative groups. In HPV-positive group, the maximum tumor size, neoadjuvant chemotherapy and the body mass index (BMI) correlated significantly with C-reactive protein/albumin ratio (CAR). The maximum tumor size and the prognostic nutritional index (PNI) correlated significantly with the platelet-lymphocyte ratio (PLR). The maximum tumor size, neoadjuvant chemotherapy and PLR correlated significantly with PNI. Univariate and multivariate analyses showed that the depth of tumor invasion (HR: 3.651, 95% CI: 1.464-9.103, p = 0.005; HR: 2.478, 95% CI: 1.218-5.043, p = 0.012) and CAR (HR: 5.201, 95% CI: 2.080-13.004, p < 0.0001; HR: 2.769, 95% CI: 1.406-5.455, p = 0.003) were independent predictors of poor OS and PFS. PNI was an independent protective factor of OS (HR: 0.341, 95% CI: 0.156-0.745, p = 0.007). PLR was an independent factor of PFS (HR: 1.991, 95% CI: 1.018-3.894, p = 0.044). In HPV-negative group, BMI correlated significantly with CAR. Only depth of invasion (HR: 9.192, 95% CI: 1.016-83.173, p = 0.048) was the independent predictor of poor OS, and no inflammation indexes were independent predictors of prognosis. Conclusion: In patients with HPV-positive cervical cancer, depth of invasion, PNI and CAR are independent factors of OS, and depth of invasion, PLR and CAR are independent factors for PFS. For patients with HPV-negative disease, no inflammation indexes had predictive value for prognosis. The predictive value of inflammation indexes on prognosis is more significant in patients with HPV-positive cervical cancer. Stratification of HPV infection status promotes a more precise clinical application of inflammation indexes, thus improving their accuracy and feasibility.

Optimization of culture conditions for improved green biodecolorization of methylene blue by Rhodococcus pyridinivorans strain UCC 0003.

Methylene blue is a toxic dye present in the textile industry, and if left untreated, it causes harm to the environment. Therefore, to decolorize methylene blue from industrial effluents, a green approach using Rhodococcus pyridinivorans strain UCC 0003 was attempted. Methylene blue decolorization was measured spectro-photometrically, and the static condition yielded 86% decolorization after 24 h as compared to the shaking mode (20%). Optimization of static conditions using the one-factor-at-a-time approach resulted in 100% decolorization at 30°C, pH 6, inoculum size of 16% (v/v), and 5% (v/v) banana peel addition as a carbon source. The R. pyridinivorans strain UCC 0003 could successfully and completely decolorize 0.75 g/l methylene blue for 4 consecutive cycles, which is advantageous from an economic point of view. The rate of methylene blue disappearance was investigated using 10% (v/v) R. pyridinivorans strain UCC 0003 at 30°C over a certain incubation time with 0.4 g/l to 10.0 g/l methylene blue as the substrate. This study revealed Vmax and Km values of 37.04 g/l/h and 55.69 g/l, respectively, as the kinetic behavior of methylene blue-decolorizing enzymes from the bacterial strain. The properties of the treated solution of methylene blue resembled the control system (distilled water) for the phytotoxicity study, thereby indicating the complete removal of dye toxicity as evidenced by the growth of Vigna radiata and Triticum aestivum, respectively, in the treated methylene blue solution. This local bacterial strain has therefore a huge potential to be used as a green biocatalyst for the bioremediation of methylene blue-containing industrial effluents.

Application of Label-Free Proteomics for Quantitative Analysis of Urothelial Carcinoma and Cystitis Tissue.

A label-free approach based on a highly reproducible and stable workflow allows for quantitative proteome analysis . Due to advantages compared to labeling methods, the label-free approach has the potential to measure unlimited samples from clinical specimen monitoring and comparing thousands of proteins. The presented label-free workflow includes a new sample preparation technique depending on automatic annotation and tissue isolation via FTIR-guided laser microdissection, in-solution digestion, LC-MS/MS analyses, data evaluation by means of Proteome Discoverer and Progenesis software, and verification of differential proteins. We successfully applied this workflow in a proteomics study analyzing human cystitis and high-grade urothelial carcinoma tissue regarding the identification of a diagnostic tissue biomarker. The differential analysis of only 1 mm2 of isolated tissue cells led to 74 significantly differentially abundant proteins.

Pulmonary and hepatic metastases of low-grade urothelial cell carcinoma; A case report.

Bladder cancer is a commonly encountered malignancy of the genitourinary tract. Bladder cancer is categorized as high or low grade depending on histological analysis. Low grade urothelial cell carcinoma has an indolent clinical course as compared to high grade, with low rates of progression of disease. We present a case where a patient was identified to have low grade bladder cancer and subsequently found to have low grade bladder cancer metastases to the lung and liver. Although uncommon, low grade urothelial cell carcinoma has the potential for progression and metastasis, highlighting the importance of regular follow-up and surveillance.

Decolourization and biodegradation of azo dye methyl red by Rhodococcus strain UCC 0016.

In the present study, locally isolated Rhodococcus strains were attempted as biological tools for methyl red removal, a mutagenic azo dye posing threat to the environment if left untreated. Rhodococcus strain UCC 0016 demonstrated superior methyl red-decolourizing activity of 100% after 24 h at static condition in comparison to Rhodococcus strain UCC 0008 which recorded 65% decolourization after 72 h. Optimization of physicochemical parameters at 30°C, pH 7 and supplementing glucose as the carbon source resulted in improved methyl red-decolourizing activity at static condition and reduced the time taken to achieve complete decolourization by 80%. Higher concentration of methyl red (5 g/L) was able to be decolourized completely within 10 h by adopting the technology of immobilization. The encapsulated cells of Rhodococcus strain UCC 0016 demonstrated higher substrate affinity (Km = 0.6995 g/L) and an accelerated rate of disappearance of methyl red (Vmax = 0.3203 g/L/h) compared to the free cells. Furthermore, the gellan gum beads could be reused up to nine batches without substantial loss in the catalytic activity indicating the economic importance of this protocol. Analysis of methyl red degradation products revealed no germination inhibition on Triticum aestivum and Vigna radiata demonstrating complete toxicity removal of the parent dye after biological treatment. The occurrence of new and altered peaks (UV-Vis and FTIR) further supported the notion that the removal of methyl red by Rhodococcus strain UCC 0016 was indeed through biodegradation. Therefore, this strain has a huge potential as a candidate for efficient bioremediation of wastewater containing methyl red.

The therapeutic and prognostic implications of molecular biomarkers in urothelial carcinoma.

Urothelial cell carcinoma (UCC) of the bladder and upper urinary tract is a heterogeneous disease with distinct biologic features resulting in different clinical behaviors. Bladder cancer (BC) is classified into non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). NMIBC is associated with high recurrence rates and risk of progression to invasive disease, whereas MIBC is complicated by systemic recurrence after radical cystectomy because of the limited efficacy of available therapies. UCC of the upper urinary tract (UUT-UCC) is a rare but aggressive urologic cancer characterized by multifocality, local recurrence, and metastasis. Conventional histopathologic evaluation of UCC, including tumor stage and grade, cannot accurately predict the behavior of BC and UUT-UCC. Recent clinical and preclinical studies aimed at understanding the molecular landscape of UCC have provided insight into molecular subtyping, inter- or intratumoral heterogeneity, and potential therapeutic targets. Combined analysis of molecular markers and standard pathological features may improve risk stratification and help monitor tumor progression and treatment response, ultimately improving patient outcomes. This review discusses prognostic and therapeutic biomarkers for BC and UUT-UCC, and describes recent advances in molecular stratification that may guide prognosis, patient stratification, and treatment selection.

Evaluation of urban comprehensive carrying capacity in the Guangdong-Hong Kong-Macao Greater Bay Area based on regional collaboration.

The Guangdong-Hong Kong-Macao Greater Bay Area (GBA) is the most prominent urban agglomeration in China, with plans for further development. Using the regional collaboration theoretical framework for assessing urban comprehensive carrying capacity (UCC), the improved entropy method is applied to establish an index system based on a social, economic, environment, and transportation perspective to compare UCCs of the GBA's 11 cities for 2000-2016. Results show that the social subsystem is central to the evaluation system. Cities' performances vary significantly, with six becoming overloaded in 2016 and the other five remaining loadable. Guangzhou performed best, with a rising UCC; Shenzhen rebounded after a long period of decline; Hong Kong's capacity rose slightly, with some fluctuation; and Macao performed worse and continues to slide, with no signs of improvement. Overall, the UCC of the urban agglomeration showed a downward trend, with only a few cities continuing to improve. The spatial distribution for UCC was high in the north and low in the south, showing scope for improvement. The study enriches regional collaboration theory and proposes policy implications for GBA development.