Unveiling potential: urinary exosomal mRNAs as non-invasive biomarkers for early prostate cancer diagnosis.

BACKGROUND: This study investigated the use of urinary exosomal mRNA as a potential biomarker for the early detection of prostate cancer (PCa). METHODS: Next-generation sequencing was utilized to analyze exosomal RNA from 10 individuals with confirmed PCa and 10 individuals without cancer. Subsequent validation through qRT-PCR in a larger sample of 43 PCa patients and 92 healthy controls revealed distinct mRNA signatures associated with PCa. RESULTS: Notably, mRNAs for RAB5B, WWP1, HIST2H2BF, ZFY, MARK2, PASK, RBM10, and NRSN2 showed promise as diagnostic markers, with AUC values between 0.799 and 0.906 and significance p values. Combining RAB5B and WWP1 in an exoRNA diagnostic model outperformed traditional PSA tests, achieving an AUC of 0.923, 81.4% sensitivity, and 89.1% specificity. CONCLUSIONS: These findings highlight the potential of urinary exosomal mRNA profiling, particularly focusing on RAB5B and WWP1, as a valuable strategy for improving the early detection of PCa.

Carboxymethyl chitosan and octadecylamine-coated liposome-containing WPTS: design, optimization, and evaluation.

Liposomes (LPs) are a delivery system for stabilizing pharmaceuticals with limited use due to their propensity to congregate and fuse. A proposed method of addressing these problems is polymer coating. In this study, the potential of octadecylamine (ODA)-coated liposomes and carboxymethyl chitosan (CMCS/ODA-LPs) for enhancing Wacao pentacyclic triterpene saponin (WPTS) transport capacity was investigated. CMCS/ODA-LPs were produced by electrostatic adsorption and thin-film hydration. Response surface methodology (RSM) was employed to enhance the process and encapsulation efficiency (EE) for optimum drug encapsulation efficiency. The synthesized WPTS-CMCS/ODA-LPs were uniformly dispersed in a circular shape, and during 14 days of storage at 4 °C, the particle size and morphology did not significantly change. Vesicle size, zeta potential, polydispersity index (PDI), and entrapment efficiency (%) were 179.1 ± 7.31 nm, -29.6 ± 1.35 mV, 0.188 ± 0.052, and 75.62 ± 0.43, respectively. The hemolysis test revealed that WPTS-CMCS/ODA-LPs were sufficiently biocompatible. Compared to WPTS-LPs, WPTS-CMCS/ODA-LPs consistently showed a much more significant cytotoxic effect on cancer cells. Early and WPTS-CMCS/ODA-LPs-induced apoptosis resulted in almost seven times more cell death than the control. Compared to physiological pH 7.3, the pH-sensitive CMCS coupled LPs increased drug release at acidic pH 6.5. These findings suggest the efficacy of pH-sensitive CMCS/ODA-LPs as a medication delivery method for WPTS.

Identification of tumor immunophenotypes associated with immunotherapy response in bladder cancer.

OBJECTIVES: This study aims to reveal immunophenotypes associated with immunotherapy response in bladder cancer, identify the signature genes of immune subtypes, and provide new molecular targets for improving immunotherapy response. METHODS: Bladder cancer immunophenotypes were characterized in the bulk RNA sequencing dataset GSE32894 and Imvigor210, and gene expression signatures were established to identify the immunophenotypes. Expression of gene signatures were validated in single-cell RNA sequencing dataset GSE145140 and human proteins expression data source. Investigation of Immunotherapy Response was performed in IMvigor210 dataset. Prognosis of tumor immunophenotypes was further analyzed. RESULTS: Inflamed and immune-excluded immunophenotypes were characterized based on the tumor immune cell scores. Risk score models that were established rely on RNA sequencing profiles and overall survival of bladder cancer cohorts. The inflamed tumors had lower risk scores, and the low-risk tumors were more likely to respond to atezolizumab, receiving complete response/partial response (CR/PR). Patients who responded to atezolizumab had higher SRRM4 and lower NPHS1 and TMEM72 expression than the non-responders. SRRM4 expression was a protective factor for bladder cancer prognosis, while the NPHS1 and TMEM72 showed the opposite pattern. CONCLUSION: This study provided a novel classification method for tumor immunophenotypes. Bladder cancer immunophenotypes can predict the response to immune checkpoint blockade. The immunophenotypes can be identified by the expression of signature genes.

A study comparing dusting to basketing for renal stones ≤ 2 cm during flexible ureteroscopy.

OBJECTIVES: To compare the dusting efficiency and safety with basketing for treating renal stones ≤ 2 cm during flexible ureteroscopy (fURS). MATERIALS AND METHODS: This study included 218 patients with renal stones ≤ 2 cm treated with fURS. Among them, 106 patients underwent dusting, and 112 patients underwent fragmentation with basket extraction. All patients were followed up for 3 months postoperatively. The operating time, lasing time, stone-free rate (SFR) and complication rate were compared. RESULTS: The mean stone size in the dusting group was 1.3 cm, whereas 1.4 cm in the basketing group. The mean operative time was significantly lower in the dusting group than in the basketing group (43.1±11.7 minutes VS 60.5±13.4 minutes, P < 0.05), but the lasing time was significantly longer for the dusting group than for the basketing group (17.7±3.9 minutes VS 14.1±3.6 minutes, P < 0.05). SFR was significantly higher in the basketing group immediately after the operation and follow-up after 1 month (76.8% vs 55.7%, P= 0.001 and 88.4% vs 78.3%, P = 0.045). However, the SFR was similar for both groups (88.8% in the dusting group vs. 90.2% in the basketing group) after 3 months postoperatively. There was no statistical difference in the complication rates between the two groups. CONCLUSIONS: Dusting has advantages in shortening the operation time and reducing the operation cost, but the lasing time was longer compared with the basketing. Although there is no difference in long-term effect, basketing is superior to dusting in terms of short-term SFR. Moreover, dusting should be avoided in some special cases and basketing a better choice. Both techniques are effective for the treatment of renal stones ≤ 2 cm and choice depends on patient demographic and stone characteristics.

Comparative study on the structure characterization and activity of RS5 made from Canna edulis native starch and high-amylose corn starch.

In this study, the high amylose corn starch and Canna edulis native starch were compounded with lauric acid and fermented by human fecal inoculation in vitro. Changes in beneficial metabolite profile and microbiota composition were evaluated. The structural properties showed that both NS-12C and HAMS-12C formed V-shaped crystals under the same preparation method, but NS-12C had a higher composite index and resistance content than HAMS-12C. At the end of fermentation, the starch-lauric acid complexes prepared from the two types of starch significantly promoted the formation of short-chain fatty acids and the contents of acetic acid, butyric acid and valeric acid produced by NS-12C were higher than those of HAMS-12C(p>0.05). HAMS-12C and NS-12C both increased the relative abundance of Blautia. Notably, NS-12C also increased the relative abundance of beneficial bacteria Bifidobacterium and Meganomas, while HAMS-12C did not. These results suggested that this effect may be related to starch type and provide a basis for designing and producing functional foods to improve intestinal health in Canna edulis native starch.

Machine Learning System for Lung Neoplasms Distinguished Based on Scleral Data.

Lung cancer remains the most commonly diagnosed cancer and the leading cause of death from cancer. Recent research shows that the human eye can provide useful information about one's health status, but few studies have revealed that the eye's features are associated with the risk of cancer. The aims of this paper are to explore the association between scleral features and lung neoplasms and develop a non-invasive artificial intelligence (AI) method for detecting lung neoplasms based on scleral images. A novel instrument was specially developed to take the reflection-free scleral images. Then, various algorithms and different strategies were applied to find the most effective deep learning algorithm. Ultimately, the detection method based on scleral images and the multi-instance learning (MIL) model was developed to predict benign or malignant lung neoplasms. From March 2017 to January 2019, 3923 subjects were recruited for the experiment. Using the pathological diagnosis of bronchoscopy as the gold standard, 95 participants were enrolled to take scleral image screens, and 950 scleral images were fed to AI analysis. Our non-invasive AI method had an AUC of 0.897 ± 0.041(95% CI), a sensitivity of 0.836 ± 0.048 (95% CI), and a specificity of 0.828 ± 0.095 (95% CI) for distinguishing between benign and malignant lung nodules. This study suggested that scleral features such as blood vessels may be associated with lung cancer, and the non-invasive AI method based on scleral images can assist in lung neoplasm detection. This technique may hold promise for evaluating the risk of lung cancer in an asymptomatic population in areas with a shortage of medical resources and as a cost-effective adjunctive tool for LDCT screening at hospitals.

Rhodium-Catalyzed Asymmetric 1,4-Addition of α/ß-(N-Indolyl) Acrylates.

A rhodium-catalyzed asymmetric 1,4-addition of α/ß-(N-indolyl) acrylates to access highly enantioenriched chiral N-alkylindoles promoted by chiral diene or sulfur-olefin ligands under mild reaction conditions has been developed, which provides an efficient and practical approach for constructing carbon stereocenters adjacent to the indole nitrogen. The reaction can be applied to various N-indolyl-substituted α,ß-unstaturated esters and arylboron reagents, providing access to a wide range of α- and ß-(N-indolyl) propionate derivatives in high yields with excellent enantioselectivities (≤99% ee).

Fate and emission behavior of heavy metals during hazardous chemical waste incineration.

The fate and emission behavior of heavy metals (As, Cd, Co, Cr, Cu, Ni, Pb, Se, and Zn) from a hazardous chemical waste incinerator were systematically explored. The results show that the main components of incineration fly ashes and slags contain minerals such as salt, plagioclase, pyroxene, gypsum, calcite, and slaked lime. The elements As, Cd, Pb, and Se are enriched in the fly ash particles during flue gas condensation. Co and Ni are more likely to be deposited in the rotary kiln slag and cooling tower slag owing to their lower volatility. Zn, Cr, and Cu are usually volatilized into the flue gas as oxides or chlorides are condensed and enriched in the slag of the cooling tower during the flue gas cooling process. The content of As, Cd, Pb, Ni, Cr, and Se increase with decreasing fly ash particle size. After the flue gas purification equipment was employed, the concentration of particulate metals significantly reduced. In the exhaust flue gas, the concentrations of Cu and Zn are 29.85 and 28.47 µg/m3, those of As, Cr, Ni, Pb, and Se range from 2.54 to 9.25 µg/m3, and those of Co and Cd are 0.42 and 0.13 µg/m3, respectively.

SmDXS5, acting as a molecular valve, plays a key regulatory role in the primary and secondary metabolism of tanshinones in Salvia miltiorrhiza.

Red sage, the dry root and rhizome of the herbaceous plant Salvia miltiorrhiza Bunge, is widely used for treating various diseases. The low content of tanshinones (terpenoids) has always restricted development of the S. miltiorrhiza industry. Here, we found that SmDXS5, a rate-limiting enzyme-coding gene located at the intersection of primary and secondary metabolism, can effectively change the transcription level and secondary metabolome profile of hairy roots of S. miltiorrhiza, and significantly increase the content of tanshinones. Agrobacterium rhizogenes was used to infuse S. miltiorrhiza explants, and hairy roots of S. miltiorrhiza expressing the SmDXS5 gene were obtained successfully. We identified 39 differentially accumulated metabolites (DAMs) by metabolomics based on ultra-high performance liquid chromatography quadrupole exactive mass spectrometry and multivariate statistics. These DAMs might be key metabolites of SmDXS5 gene regulation. RNA sequencing was used to compare gene expression between the hairy roots of the SmDXS5 overexpressing group and the blank control (BC) group. Compared with the BC group, 18,646 differentially expressed genes were obtained: 8994 were upregulated and 9,652 downregulated. The combined transcriptome and metabolome analyses revealed that the mevalonate and methylerythritol phosphate pathways and synthase gene expression levels in the SmDXS5 overexpressing group were upregulated significantly, and the accumulation of tanshinone components was increased significantly, which promoted the process of glycolysis and promoted the transformation of carbohydrates to secondary metabolism. Moreover, the expression of SmPAL, the first rate-limiting enzyme gene of the phenylpropane pathway, decreased, reducing the accumulation of phenolic acid, another secondary metabolite. Therefore, SmDXS5 can be defined as a 'valve' gene, mainly responsible for regulating the distribution of primary and secondary metabolic flow of tanshinones in S. miltiorrhiza, and for other secondary metabolic pathways. The discovery of SmDXS5 and its molecular valve function in regulating primary and secondary metabolism will provide a basis for the industrial production of tanshinone components, and cultivation of high quality S. miltiorrhiza.

Primary and secondary metabolites produced in Salvia miltiorrhiza hairy roots by an endophytic fungal elicitor from Mucor fragilis.

Salvia miltiorrhiza is one of the most commonly used medicinal materials in China. In recent years, the quality of S. miltiorrhiza has attracted much attention. Biotic and abiotic elicitors are widely used in cultivation to improve the quality of medicinal plants. We isolated an endophytic fungus, Mucor fragilis, from S. miltiorrhiza. We compared the effects of endophytic fungal elicitors with those of yeast extract together with silver ion, widely used together as effective elicitors, on S. miltiorrhiza hairy roots. Seventeen primary metabolites (amino acids and fatty acids) and five secondary metabolites (diterpenoids and phenolic acids) were analyzed after elicitor treatment. The mycelium extract promoted the accumulation of salvianolic acid B, rosmarinic acid, stearic acid, and oleic acid in S. miltiorrhiza hairy roots. Additionally, qPCR revealed that elicitors affect the accumulation of primary and secondary metabolites by regulating the expression of key genes (SmAACT, SmGGPPS, and SmPAL). This is the first detection of both the primary and secondary metabolites of S. miltiorrhiza hairy roots, and the results of this work should help guide the quality control of S. miltiorrhiza. In addition, the findings confirm that Mucor fragilis functions as an effective endophytic fungal elicitor with excellent application prospect for cultivation of medicinal plants.

A study comparing dusting to basketing for renal stones ≤ 2 cm during flexible ureteroscopy

ABSTRACT Objectives To compare the dusting efficiency and safety with basketing for treating renal stones ≤ 2 cm during flexible ureteroscopy (fURS). Materials and methods This study included 218 patients with renal stones ≤ 2 cm treated with fURS. Among them, 106 patients underwent dusting, and 112 patients underwent fragmentation with basket extraction. All patients were followed up for 3 months postoperatively. The operating time, lasing time, stone-free rate (SFR) and complication rate were compared. Results The mean stone size in the dusting group was 1.3 cm, whereas 1.4 cm in the basketing group. The mean operative time was significantly lower in the dusting group than in the basketing group (43.1±11.7 minutes VS 60.5±13.4 minutes, P <0.05), but the lasing time was significantly longer for the dusting group than for the basketing group (17.7±3.9 minutes VS 14.1±3.6 minutes, P <0.05). SFR was significantly higher in the basketing group immediately after the operation and follow-up after 1 month (76.8% vs 55.7%, P= 0.001 and 88.4% vs 78.3%, P = 0.045). However, the SFR was similar for both groups (88.8% in the dusting group vs. 90.2% in the basketing group) after 3 months postoperatively. There was no statistical difference in the complication rates between the two groups. Conclusions Dusting has advantages in shortening the operation time and reducing the operation cost, but the lasing time was longer compared with the basketing. Although there is no difference in long-term effect, basketing is superior to dusting in terms of short-term SFR. Moreover, dusting should be avoided in some special cases and basketing a better choice. Both techniques are effective for the treatment of renal stones ≤ 2 cm and choice depends on patient demographic and stone characteristics.