Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses.

OBJECTIVE: Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. METHODS: We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. RESULTS: The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. CONCLUSION: P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

Puerariae lobatae Radix ameliorates chronic kidney disease by reshaping gut microbiota and downregulating Wnt/ß­catenin signaling.

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote the gut microbiota homeostasis; however, its role in renoprotection remains unknown. The present study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8­week 2% NaCl­feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, The medium and high doses of PLR significantly alleviated CKD­associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and downregulating the canonical Wnt/ß­catenin pathway. Furthermore, PLR rescued the gut microbiota dysbiosis and protected against high salt­induced gut barrier dysfunction. Enrichment of Akkermansia and Bifidobacterium was found after PLR intervention, the relative abundances of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was, at least partially, exerted through gut microbiota reestablishment and downregulation of the Wnt/ß­catenin pathway. The present study provided evidence for a new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

An artificial intelligence model for detecting pathological lymph node metastasis in prostate cancer using whole slide images: a retrospective, multicentre, diagnostic study.

Background: The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. Methods: In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. Findings: In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P = 0.023; 0.879 [0.767-0.950], P = 0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P > 0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P = 0.041) to the level of senior pathologists (both P > 0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P < 0.0001; -34%, P < 0.0001; -29%, P < 0.0001; and -27%, P = 0.00031). Interpretation: ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. Funding: National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

Sodium humate based double network hydrogel for Cu and Pb removal.

Sodium humate (SH) is one of the derivatives humic substances, which can be utilized for heavy metal removal from water due to its containing plenty of functional groups. In this study, a double network hydrogel SH/polyacrylamide (SH/PAM) was synthesized by a simple free-radical polymerization and used for Cu2+ and Pb2+ removal from water. The adsorption process can be well described by Langmuir-Freundlich model, indicating that both physical and chemical adsorption were involved. X-ray photoelectron spectroscopy (XPS) characterization demonstrated that complexation was the main mechanism for the adsorption. Two-dimensional correlation analysis of FTIR (2D-FTIR-COS) results showed that the variation order of functional groups during Cu2+ and Pb2+ adsorption in the following order: COOH ≈ -CO > -OH > C-O and -COOH ≈ C-O > -CO > -OH, respectively. According to the density functional theory (DFT) calculation results, the O atom of SH in the COO- was the main adsorption site. Meanwhile, the adsorption energy of Pb2+ was more negative than that of Cu2+ and the orbital hybridization between O atom of SH and Pb2+ was denser than that of Cu2+, which suggested that SH/PAM had a stronger combining capacity for Pb2+ than Cu2+. Therefore, the adsorption capacity for Pb2+ was larger than Cu2+. Moreover, the removal efficiencies are 30.2% for Al, 98.79% for Cu, 99.0% for Fe, 17.2% for Mn, 93.4% for Pb, and 62.4% for Zn in actual acid mine drainage using 6 g L-1 adsorbent. Collectively, this study not only provided a new adsorbent for heavy metal removal but also explicated the mechanism of heavy metal removal by SH from molecule and electron perspective, which is helpful for the application of SH in the environmental field.

Unraveling the impact of Lactobacillus spp. and other urinary microorganisms on the efficacy of mirabegron in female patients with overactive bladder.

Objective: Overactive bladder (OAB) is a disease that seriously affects patients' quality of life and mental health. To address this issue, more and more researchers are examining the relationship between OAB treatment and urinary microecology. In this study, we sought to determine whether differences in treatment efficacy were related to microbiome diversity and composition as well as the abundance of specific genera. Machine learning algorithms were used to construct predictive models for urine microbiota-based treatment of OAB. Methods: Urine samples were obtained from 64 adult female OAB patients for 16S rRNA gene sequencing. Patients' overactive bladder symptom scores (OABSS) were collected before and after mirabegron treatment and patients were divided into effective and ineffective groups. The relationship between the relative abundance of certain genera and OABSS were analyzed. Three machine learning algorithms, including random forest (RF), supporting vector machine (SVM) and eXtreme gradient boosting (XGBoost) were utilized to predict the therapeutic effect of mirabegron based on the relative abundance of certain genera in OAB patients' urine microbiome. Results: The species composition of the two groups differed. For one, the relative abundance of Lactobacillus was significantly higher in the effective group than in the ineffective group. In addition, the relative abundance of Gardnerella and Prevotella in the effective group was significantly lower than in the ineffective group. Alpha-diversity and beta-diversity differed significantly between the two groups. LEfSe analysis revealed that Lactobacillus abundance increased while Prevotella and Gardnerella abundance decreased in the effective group. The Lactobacillus abundance ROC curve had high predictive accuracy. The OABSS after treatment was negatively correlated with the abundance of Lactobacillus, whereas the relationship between OABSS and Prevotella and Gardnerella showed the opposite trend. In addition, RF, SVM and XGBoost models demonstrated high predictive ability to assess the effect of mirabegron in OAB patients in the test cohort. Conclusions: The results of this study indicate that urinary microbiota might influence the efficacy of mirabegron, and that Lactobacillus might be a potential marker for evaluating the therapeutic efficacy of mirabegron in OAB patients.

High-Precision Semiconductor Laser Current Drive and Temperature Control System Design.

To solve the problem in which the output power and wavelength of semiconductor lasers in fiber optic sensing systems are easily affected by the drive current and temperature, a high-precision current drive and temperature control system was developed in this study. The embedded system was used to provide a stable drive current for the semiconductor laser through closed-loop negative feedback control; moreover, some measures, such as linear slow-start, current-limiting protection, and electrostatic protection, were adopted to ensure the stability and safety of the laser's operation. A mathematical model of the temperature control system was constructed using mechanism analysis, and model identification was completed using the M sequence and differential evolution (DE) algorithms. Finally, the control rules of the fuzzy proportional integral differentiation (PID) algorithm were optimized through system simulation to make it more suitable for the temperature control system designed in this research, and the accurate control of the working temperature of the semiconductor laser was realized. Experimental results showed that the system could achieve a linearly adjustable drive current in the range of 0-100 mA, with an output current accuracy of 0.01 mA and a temperature control accuracy of up to 0.005 °C.

Treatment of nitrate containing wastewater by adsorption process using polypyrrole-modified plastic-carbon: Characteristic and mechanism.

Polypyrrole-modified plastic-carbon (PET-PPy) composite was prepared by using high porosity plastic-carbon materials and a special doping mechanism of polypyrrole to remove nitrate from water to achieve waste recycling. As a result, PET-PPy-500 showed remarkable nitrate adsorption in both acidic and alkaline wastewater. The pseudo-second-order kinetic and Langmuir isotherm models were fit for the nitrate adsorption by PET-PPy-500, and the maximum adsorption capacity predicted by the Langmuir model was 10.04 mg NO3-N/g (45.18 mg NO3-/g) at 30 °C. The ion exchange and electrostatic attraction were the main mechanisms of removing NO3- by PET-PPy-500, which was demonstrated by the interface characterization and theoretical calculation. The doped ions (Cl-) and/or other anions produced by charge transfer interaction were the main exchange ions in the process of NO3- adsorption. The main binding sites in the electrostatic adsorption process were nitrogen-containing functional groups, which can be confirmed by the results of XPS and density functional theory (DFT). Furthermore, DFT results also showed that the adsorption of nitrate by PET-PPy was a spontaneous exothermic process, and the adsorption energy at the nitrogen site was the lowest. The findings of this study provide a feasible strategy for the advanced treatment of nitrate containing wastewater.

KHCO3 activated biochar supporting MgO for Pb(II) and Cd(II) adsorption from water: Experimental study and DFT calculation analysis.

A new strategy that simultaneous use of KHCO3 activated biochar and nano-MgO incorporation for Pb2+ and Cd2+ removal from water was raised. After activating by KHCO3, the BC showed a higher surface area and could carry more MgO nanoparticles the BC owned. The synthesized MgO-K-BC had a large adsorption capacity for Pb2+ (1625.5 mg/g) and Cd2+ (480.8 mg/g). Multiple characterization and comparative test have been performed to demonstrate that ion-exchange, precipitation, and complexation are the main mechanisms for Pb2+ and Cd2+ removal by MgO-K-BC. In order to further explore the adsorption mechanism in-depth, the density functional theory (DFT) calculation combined with experimental results were performed. The O-top of MgO was the most stable adsorption site for Pb2+/Cd2+ adsorption compared with other adsorption sites (Mg-top, bridge, and hollow). In addition, the results of charge density maps and projected density of state (PDOS) showed that the overlap of electron cloud and orbits between MgO and Pb2+ were denser than Cd2+, indicating that MgO-K-BC had a stronger affinity for Pb2+ than Cd2+, so that, MgO-K-BC had a higher adsorption capacity for Pb2+ than Cd2+. This work provides a deep understand of the mechanism for heavy metals adsorption by metal oxide and a practical and theoretical guidance for adsorbent preparation with high adsorption ability for heavy metal.

Research on complexation ability, aromaticity, mobility and cytotoxicity of humic-like substances during degradation process by electrochemical oxidation.

The humic-like substances were the main organic components in most wastewater (e.g. domestic sewage, toilet wastewater and landfill leachate). Two types of actual humic-like substances (fulvic acid (FA) and biologically treated landfill leachate (BTLL)) were selected to describe the changes in the properties of humic-like substances (complexation ability, aromaticity and mobility) during electrochemical oxidation. Meanwhile, the acute cytotoxicity of FA and BTLL was also tested by acute toxicological test of luminescent bacteria. The results showed that the consumption of coordinating groups such as phenolic groups and hydrogen bonds reduced the complexation ability of FA and BTLL. The functional groups were degraded with the removal order of quinone group, phenolic group and aromatic group, and finally realized the molecular saturation and aromaticity decrease for humic-like substances. The mobility of FA and BTLL was decreased because of the enhancement of hydrophobicity during electrolysis process. Furthermore, the available chlorine produced during electrochemical oxidation was the main acute cytotoxicity substance, therefore, it is necessary to remove it before discharge in order to reduce ecological risks. This study provides a basis for understanding and evaluating the electrochemical degradation process of humic-like substances in detail.