Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer.

Prostate cancer (PCa) is a common malignancy in elderly men. We have applied Traditional Chinese Medicine CFF-1 in clinical treatments for PCa for several years. Here, we aimed to identify the underlying mechanism of CFF-1 on PCa using network pharmacology and experimental validation. Active ingredients, potential targets of CFF-1 were acquired from the public databases. Subsequently, protein-protein interaction (PPI) and the herbs-active ingredients-target network was constructed. A prognostic model for PCa was also constructed based on key targets. In vitro experiments using PCa cell lines CWR22Rv1 and PC-3 were carried out to validate the potential mechanism of CFF-1 on PCa. A total of 112 bioactive compounds and 359 key targets were screened from public databases. PPI and herbs-active ingredients-target network analysis determined 12 genes as the main targets of CFF-1 on PCa. Molecular docking studies indicated that the primary active ingredients of CFF-1 possess strong binding affinity to the top five hub targets. DNMT3B, RXRB and HPRT1 were found to be involved in immune regulation of PCa. In vitro, CFF-1 was found to inhibit PCa cell proliferation, migration, invasion and induce apoptosis via PI3K-Akt, HIF-1, TNF, EGFR-TKI resistance and PD-1 checkpoint signaling pathways. This study comprehensively elucidates the underlying molecular mechanism of CFF-1 against PCa, offering a strong rationale for clinical application of CFF-1 in PCa treatment.

Amplification-Free Analysis of Bladder Cancer MicroRNAs on Wrinkled Silica Nanoparticles with DNA-Functionalized Quantum Dots.

Bladder cancer (BC) occurrence and progression are accompanied by alterations in microRNAs (miRNAs) expression levels. Simultaneous detection of multiple miRNAs contributes to the accuracy and reliability of the BC diagnosis. In this work, wrinkled silica nanoparticles (WSNs) were applied as the microreactor for multiplex miRNAs analysis without enzymes or nucleic acid amplification. Conjugated on the surface of WSNs, the S9.6 antibody was adopted as the universal module for binding DNA/miRNA duplexes, regardless of their sequence. Furthermore, single-stranded DNA (ssDNA) was labeled with quantum dots (QDs) for identifying a given miRNA to form QDs-ssDNA/miRNA, which enabled the specific capture of the corresponding QDs on the wrinkled surface of WSNs. Based on the detection of fluorescence signals that were ultimately focused on WSNs, target miRNAs could be sensitively identified to a femtomolar level (5 fM) with a wide dynamic range of up to 6 orders of magnitude. The proposed strategy achieved high specificity to obviously distinguish single-base mutation sequences and possessed multiplex assay capability. Moreover, the assay exhibited excellent practicability in the multiplex detection of miRNAs in clinical serum specimens.

Soil Organic Matter Estimation Model Integrating Spectral and Profile Features.

The accurate measurement of soil organic matter (SOM) is vital for maintaining soil quality. We present an innovative model for SOM prediction by integrating spectral and profile features. We use PCA, Lasso, and SCARS methods to extract important spectral features and combine them with profile data. This hybrid approach significantly improves SOM prediction across various models, including Random Forest, ExtraTrees, and XGBoost, boosting the coefficient of determination (R2) by up to 26%. Notably, the ExtraTrees model, enriched with PCA-extracted features, achieves the highest accuracy with an R2 of 0.931 and an RMSE of 0.068. Compared with single-feature models, this approach improves the R2 by 17% and 26% for PCA features of full-band spectra and profile features, respectively. Our findings highlight the potential of feature integration, especially the ExtraTrees model with PCA-extracted features and profile features, as a stable and accurate tool for SOM prediction in extensive study areas.

Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma.

Background: Immunogenic cell death (ICD) is considered a particular cell death modality of regulated cell death (RCD) and plays a significant role in various cancers. The connection between kidney renal clear cell carcinoma (KIRC) and ICD remains to be thoroughly explored. Methods: We conducted a variety of bioinformatics analyses using R software, including cluster analysis, prognostic analysis, enrichment analysis and immune infiltration analysis. In addition, we performed Quantitative Real-time PCR to evaluate RNA levels of specific ICD genes. The proliferation was measured through Cell Counting Kit-8 (CCK-8) assay and colony-formation assay in RCC cell lines. Results: We determined two ICD subtypes through consensus clustering analysis. The two subtypes showed significantly different clinical outcomes, genomic alterations and tumor immune microenvironment. Moreover, we constructed the ICD prognostic signature based on TF, FOXP3, LY96, SLC7A11, HSP90AA1, UCN, IFNB1 and TLR3 and calculated the risk score for each patient. Kaplan-Meier survival analysis and ROC curve demonstrated that patients in the high-risk group had significantly poorer prognosis compared with the low-risk group. We then validated the signature through external cohort and further evaluated the relation between the signature and clinical features, tumor immune microenvironment and immunotherapy response. Given its critical role in ICD, we conducted further analysis on LY96. Our results indicated that downregulation of LY96 inhibited the proliferation ability of RCC cells. Conclusions: Our research revealed the underlying function of ICD in KIRC and screened out a potential biomarker, which provided a novel insight into individualized immunotherapy in KIRC.

Ballistic Behavior of Bioinspired Nacre-like Composites.

In this paper, the ballistic performance of a multilayered composite inspired by the structural characteristics of nacre is numerically investigated using finite element (FE) simulations. Nacre is a natural composite material found in the shells of some marine mollusks, which has remarkable toughness due to its hierarchical layered structure. The bioinspired nacre-like composites investigated here were made of five wavy aluminum alloy 7075-T651 (AA7075) layers composed of ~1.1-mm thick square tablets bonded together with toughened epoxy resin. Two composite configurations with continuous layers (either wavy or flat) were also studied. The ballistic performance of the composite plates was compared to that of a bulk monolithic AA7075 plate. The ballistic impact was simulated in the 300-600 m/s range using two types of spherical projectiles, i.e., rigid and elastoplastic. The results showed that the nacre plate exhibited improved ballistic performance compared to the bulk plate and the plates with continuous layers. The structural design of the nacre plate improved the ballistic performance by producing a more ductile failure and enabling localized energy absorption via the plastic deformation of the tablets and the globalized energy dissipation due to interface debonding and friction. All the plate configurations exhibited a better ballistic performance when impacted by an elastoplastic projectile compared to a rigid one, which is explained by the projectile plastic deformation absorbing some of the impact energy and the enlarged contact area between the projectile and the plates producing more energy absorption by the plates.

R-LESS-RP versus C-LESS-RP: a single-institution retrospective comparative study.

This study aimed to compare the peri- and postoperative outcomes of patients treated with conventional versus robot-assisted laparoendoscopic single-site radical prostatectomy (C-LESS-RP vs. R-LESS-RP). Data of patients with prostate cancer (106 who underwent C-LESS-RP, 124 underwent R-LESS-RP) were retrospectively collected and analyzed. All operations were performed by the same surgeon from January 8, 2018, to January 6, 2021, in the same institution. Information on clinical characteristics and perioperative outcomes was obtained from records at the medical institution. Postoperative outcomes were acquired from follow-up. Intergroup differences were retrospectively analyzed and compared. All patients had similar clinical characteristics in meaningful aspects. The perioperative outcomes were better with R-LESS-RP than with C-LESS-RP in terms of operation time (120 min vs. 150 min, p < 0.05), estimated blood loss (17.68 ml vs. 33.68 ml, p < 0.05), and analgesic duration (0 days vs. 1 days, p < 0.05). The drainage tube duration and postoperative stay did not differ significantly between groups. However, R-LESS-RP was more expensive than C-LESS-RP (56559.510 CNY vs. 44818.27 CNY, p < 0.05). The patients who underwent R-LESS-RP had better urinary incontinence recovery and higher European quality of life visual analog scale scores than those who underwent C-LESS-RP. However, no significant intergroup difference was noted in biochemical recurrence. In conclusion, R-LESS-RP could achieve better perioperative outcomes, especially for those skilled surgeons who have mastered C-LESS-RP. Additionally, R-LESS-RP accelerated the recovery from urinary incontinence effectively and presented some benefits in health-related quality of life with additional costs.

Heteroscedastic sparse Gaussian process regression-based stochastic material model for plastic structural analysis.

Describing the material flow stress and the associated uncertainty is essential for the plastic stochastic structural analysis. In this context, a data-driven approach-heteroscedastic sparse Gaussian process regression (HSGPR) with enhanced efficiency is introduced to model the material flow stress. Different from other machine learning approaches, e.g. artificial neural network (ANN), which only estimate the deterministic flow stress, the HSGPR model can capture the flow stress and its uncertainty simultaneously from the dataset. For validating the proposed model, the experimental data of the Al 6061 alloy is used here. Without setting a priori assumption on the mathematical expression, the proposed HSGPR-based flow stress model can produce a better prediction of the experimental stress data than the ANN model, the conventional GPR model, and Johnson Cook model at elevated temperatures. After the HSGPR-based flow stress model is implemented into finite element analysis, two numerical examples with synthetic material properties are performed to demonstrate the model's capability in stochastic plastic structural analysis. The results have shown that with sufficient data, the distribution of the structural load carrying capacity at elevated temperatures and the variation of load-displacement curves during the loading and unloading processes can be accurately predicted by the HSGPR-based flow stress model.

Using Artificial Neural Networks to Predict Influences of Heterogeneity on Rock Strength at Different Strain Rates.

Pre-existing cracks and associated filling materials cause the significant heterogeneity of natural rocks and rock masses. The induced heterogeneity changes the rock properties. This paper targets the gap in the existing literature regarding the adopting of artificial neural network approaches to efficiently and accurately predict the influences of heterogeneity on the strength of 3D-printed rocks at different strain rates. Herein, rock heterogeneity is reflected by different pre-existing crack and filling material configurations, quantitatively defined by the crack number, initial crack orientation with loading axis, crack tip distance, and crack offset distance. The artificial neural network model can be trained, validated, and tested by finite 42 quasi-static and 42 dynamic Brazilian disc experimental tests to establish the relationship between the rock strength and heterogeneous parameters at different strain rates. The artificial neural network architecture, including the hidden layer number and transfer functions, is optimized by the corresponding parametric study. Once trained, the proposed artificial neural network model generates an excellent prediction accuracy for influences of high dimensional heterogeneous parameters and strain rate on rock strength. The sensitivity analysis indicates that strain rate is the most important physical quantity affecting the strength of heterogeneous rock.

Unusual Force Constants Guided Distortion-Triggered Loss of Long-Range Order in Phase Change Materials.

Unusual force constants originating from the local charge distribution in crystalline GeTe and Sb2Te3 are observed by using the first-principles calculations. The calculated stretching force constants of the second nearest-neighbor Sb-Te and Ge-Te bonds are 0.372 and -0.085 eV/Å2, respectively, which are much lower than 1.933 eV/Å2 of the first nearest-neighbor bonds although their lengths are only 0.17 Å and 0.33 Å longer as compared to the corresponding first nearest-neighbor bonds. Moreover, the bending force constants of the first and second nearest-neighbor Ge-Ge and Sb-Sb bonds exhibit large negative values. Our first-principles molecular dynamic simulations also reveal the possible amorphization of Sb2Te3 through local distortions of the bonds with weak and strong force constants, while the crystalline structure remains by the X-ray diffraction simulation. By identifying the low or negative force constants, these weak atomic interactions are found to be responsible for triggering the collapse of the long-range order. This finding can be utilized to guide the design of functional components and devices based on phase change materials with lower energy consumption.

Laparoendoscopic radical prostatectomy (LRP): stepwise transition from multi-site to single-site with the aid of the transurethral port.

PURPOSE: To describe our initial experience with laparoendoscopic radical prostatectomy (LRP) and a stepwise transition towards transurethral assisted laparoendoscopic single-site RP (TU-LESS RP). PATIENTS AND METHODS: From Jan. 2007 to Dec. 2016, 195 patients underwent RP, of which 89 patients were performed by LRP (Group A), 106 by TU-LESS RP (Group B). The peri-operative data were collected and analyzed. All data referring to patient demographics, surgery, pathology, and peri-operative outcomes were recorded. The cosmetic result was investigated by the Patient Scar Assessment Questionnaire (PSAQ). Analysis of variance or Chi squared test were adopted to analyze the data. RESULTS: 195 procedures were completed successfully. The operation time (109.6 ± 31.9 vs. 151.5 ± 87.3, P = 0.025) and anastomosis time (10.1 ± 4.8 vs. 21.8 ± 9.9, P < 0.001) of Group B was significantly reduced compared with Group A. Estimated blood loss in Group B was significantly lower than that in Group A (95.9 ± 11.1 vs. 180.2 ± 99.7, P = 0.006). About perioperative complications, Group B was also less compared with Group A (1.9% vs. 7.9%, P = 0.047). As to the usage of postoperative analgesics, Group B apparently used less than that in Group A (6.6% vs. 62.9%, P < 0.001), which is consistent with the visual analogue scale (VAS) of the two groups (1.7 ± 1.3 vs. 7.8 ± 1.1, P < 0.001). Patients in Group B were significantly more satisfied with incision healing than in group A (74.9 ± 9.3 vs. 49.7 ± 5.8, P < 0.001). There was no significant difference both in BCR rate and time between Group B and Group A. In urination control, more patients in Group B did not have urinary incontinence 3 month after RP compared with Group A (81.1% vs. 67.4%, P = 0.028). CONCLUSIONS: LESS RP is proved to be feasible for the proper patients, but it is difficult to popularized due to inconvenient operation. While by means of TU-LESS, operating difficulty can be significantly decreased. TU-LESS RP will be wildly accepted by surgeons and patients because of cosmetic satisfaction and quicker recovery.

Comparison of Laparoendoscopic Single-Site and Laparoscopic Radical Cystectomy for Male Patients with Bladder Cancer: Perioperative and Oncologic Outcomes.

Objective: To compare the surgical and early oncological outcomes in patients with bladder cancer who had laparoendoscopic single-site radical cystectomy (RC) or laparoscopic RC. Materials and Methods: From July 2012 to May 2019, 28 consecutive men suffering from bladder cancer underwent laparoendoscopic single-site RC or laparoscopic RC with extracorporeally ileal conduit diversion. Data regarding the patient characteristics, surgical outcomes, and short-term oncological outcomes were analyzed retrospectively. Results: Compared with laparoscopic RC, laparoendoscopic single-site RC was associated with less postoperative pain (mean, 4.67 versus 6.08 scores; P = .004), and shorter convalescence (time to ambulation, mean, 1.13 days versus 2.15 days; P = .000; hospital stay after surgery, mean, 13 days versus 19 days; P = .001). In addition, differences in patient characteristics, mean total operation time, and mean estimated blood loss were not statistically significant between laparoendoscopic single-site RC and laparoscopic RC groups. There was no difference in the early or late complication rate between the two groups as well. It is also revealed that there was no significant difference in the overall survival rate at 24 months between laparoendoscopic single-site RC and laparoscopic RC groups. Conclusions: Based on our initial experience with laparoendoscopic single-site RC, it is a safe procedure with acceptable complications and oncological outcomes. Notably, laparoendoscopic single-site RC is associated with less postoperative pain and rapider convalescence compared with the historical series of laparoscopic RC. However, further comparative studies with longer follow-up period are warranted to validate this procedure.

Influence of Parent Concrete Properties on Compressive Strength and Chloride Diffusion Coefficient of Concrete with Strengthened Recycled Aggregates.

Parent concrete coming from a wide range of sources can result in considerable differences in the properties of recycled coarse aggregate (RCA). In this study, the RCAs were obtained by crushing the parent concrete with water-to-cement ratios (W/Cparent) of 0.4, 0.5 and 0.6, respectively, and were strengthened by carbonation and nano-silica slurry wrapping methods. It was found that when W/Cparen was 0.3, 0.4 and 0.5, respectively, compared with the mortar in the untreated RCA, the capillary porosity of the mortar in the carbonated RCA decreased by 19%, 16% and 30%, respectively; the compressive strength of concrete containing the carbonated RCA increased by 13%, 11% and 13%, respectively; the chloride diffusion coefficient of RAC (DRAC) containing the nano-SiO2 slurry-treated RCA decreased by 17%, 16% and 11%; and that of RAC containing the carbonated RCA decreased by 21%, 25% and 26%, respectively. Regardless of being strengthened or not, both DRAC and porosity of old mortar in RCAs increased with increasing W/Cparent. For different types of RCAs, DRAC increased obviously with increasing water absorption of RCA. Finally, a theoretical model of DRAC considering the water absorption of RCA was established and verified by experiments, which can be used to predict the DRAC under the influence of different factors, especially the water absorption of RCA.

Particle-shape-, temperature-, and concentration-dependent thermal conductivity and viscosity of nanofluids.

In this study, using the Green-Kubo-method-based molecular dynamics simulations, correlations for predicting the thermophysical properties of nanofluids are developed based on particle shape, fluid temperature, and volume concentration. Silver nanofluids with various nanoparticle shapes including spheres, cubes, cylinders, and rectangular prisms are investigated. The numerical study is conducted within the concentration range 0.14-1.4 vol % and temperature range 280-335 K. The relative thermal conductivity and relative viscosity predicated by the proposed correlations are within a mean deviation of 2% and 5%, respectively, as compared with the experimental results from this study and the available literature. The proposed correlation will be a useful tool for engineers in designing the nanofluids for different applications in industry.

Atomistic Study of Dynamic Contact Angles in CO2-Water-Silica System.

The dynamic wetting for the CO2-water-silica system occurring in deep reservoirs is complex because of the interactions among multiple phases. This work aims to quantify the contact angle of CO2-water flow in the silica channel at six different flow velocities using molecular dynamics. The dynamic contact angle values at different contact line velocities are obtained for the CO2-water-silica system. By calculating the rates of the adsorption-desorption process of CO2 and water molecules on the silica surface using molecular dynamics simulations, it has been found that the results of the dynamic contact angle can be explained by the molecular kinetic theory and predicted from the equilibrium molecular simulations. Moreover, the capillary pressure at different contact line velocities is predicted according to the Young-Laplace equation. The change in contact angles at different velocities is compared with empirical equations in terms of capillary number. The results of this study can help us better understand the dynamic process of the multiphase flow at the nanoscale under realistic reservoir conditions.

Laparoendoscopic single-site nephrectomy with the aid of intraabdominal retractors.

OBJECTIVES: To evaluate the feasibility and clinical efficacy of a novel intraabdominal retractor device in laparoendoscopic single-site nephrectomy(LESS-N). METHODS: Between February 2012 and February 2017, 98 patients underwent LESS-N in our institution, including 38 patients with benign renal disease and 60 patients with malignant renal disease. 39 were performed conventional LESS-N(C-LESS-N) and 59 were performed intraabdominal retractor-assisted LESS-N(IAR-LESS-N). Demographic data, and perioperative and postoperative data were collected and analyzed retrospectively. RESULTS: All the procedures were completed successfully. In C-LESS-N group, four patients were added one 5-mm additional trocar and two patients were converted to open surgery. In IAR-LESS-N group, no patients required additional trocars or conversion to open surgery. The mean operative time was lower in IAR-LESS-N group than that in C-LESS-N group (94.2 min vs 127.4 min, P < 0.05). The mean renal vascular management time declined from 25.4 min in C-LESS-N group to 18.4 min in IAR-LESS-N group (P < 0.05). The mean estimated blood loss was 128.6 ml in C-LESS-N group and 102.3 ml in IAR-LESS-N group (P < 0.05). Two patients in C-LESS-N group required blood transfusion, while none of the patients in IAR-LESS-N group did. No severe postoperative complications occurred in both groups. Study limitations included retrospective study, short follow-up, and accumulated surgical experience and skills. CONCLUSIONS: Intraabdominal retractors allow performance of LESS-N with improved working space, quicker renal hilar management, and shortened total operative time. It is expected that the application of intraabdominal retractors, along with the new robotic platform might revive LESS and translate into a renewed future interest of LESS.

Coarse-grained modeling of multiphase interactions at microscale.

The objective of this study is to develop and test a coarse-grained molecular dynamics framework to model microscale multiphase systems with different inter-particle interactions and recover emerging thermodynamic and mechanical properties at the microscale. A water-vapor model and a fused silica model are developed to demonstrate the capability of our framework. The former can reproduce the water density and surface tension over a wide range of temperatures; the latter can reproduce experimental density, tensile strength, and Young's modulus of fused silica. Therefore, the deformable solid model is implemented in the proposed framework. Validations of spatial scaling methods for solid, liquid, and multiphase systems suggest that the proposed framework can be calibrated at an arbitrary microscale and used at a different length scale without recalibration. Different values of wettability for a solid-liquid-vapor system that is characterized by the contact angle can be achieved by changing the solid-liquid inter-particle potential. Thanks to these features, the proposed coarse-grained molecular dynamics framework can potentially find applications in modeling systems in which multiple phases coexist and have substantial interactions.

Current opinions on nephrolithiasis associated with primary hyperparathyroidism.

Nephrolithiasis is a common urological disease and could be secondary to primary hyperparathyroidism (PHPT). PHPT is traditionally characterised with hypercalcaemia. Recently, a normocalcemic PHPT has been officially recognised at the International Workshops. Regarding this new phenotype, nephrolithiasis is frequently found in studies that evaluate low bone mass. However, until now, no study on aetiology of nephrolithiasis considered normocalcemic PHPT. Hypercalciuria related to PHPT is considered as an important risk factor of stone formation in hypercalcemic PHPT, but the precise relationships between hypercalcemic PHPT and nephrolithiasis and between normocalcemic PHPT and nephrolithiasis remain unclear. In patients with hypercalcemic PHPT, after a surgical cure of PHPT, the renal calcium excretion and stone recurrence rate reduce but remain higher above health controls. This finding implies that abnormalities not caused by PHPT also probably affect stone formation. According to the new guideline, the presence of stones indicates the need for parathyroidectomy in patients with either hypercalcemic or normocalcemic PHPT unless contraindications exist. Patients with contraindications for parathyroidectomy or those who do not want to receive parathyroidectomy should be monitored for signs of disease progression and given of medical management. Moreover, due to decreased but significantly higher frequency of nephrolithiasis above those of healthy controls, patients with nephrolithiasis associated with PHPT after parathyroidectomy still should be motivated to explore strategies to prevent stone occurrence.