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Treatment options for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) have increased dramatically over the past decade. However, even when novel approaches have proven to be effective as monotherapy, many patients still develop progressive disease, and different strategies are needed to increase clinical response and quality of life. Strategies combining targeted therapy (TT) and immunotherapy (IO) have emerged as a way to shorten the gap between responders and nonresponders to monotherapy and have reported promising results. In this review, we discuss the current role of cabozantinib in combination with IO agents in the treatment of metastatic RCC and UC and go over future directions in the field.Lay abstract Treatment options for both advanced kidney and bladder cancers have increased significantly over the last decade. However, even when these new approaches have proven to be effective, many patients still experience disease progression. Therefore, different strategies are needed to increase the response to treatment and quality of life. Strategies combining therapies directed to reduce the tumor's blood supply (targeted therapies) and therapies that increase the ability of the body to recognize and attack tumor cells (immunotherapy) have emerged as a way to increase the effectiveness obtained when using these drugs on their own. In this review, we discuss the current role of cabozantinib, a targeted therapy, in combination with immune-based agents in the treatment of advanced kidney and bladder cancers and go over future directions in the field.

BackgroundThe need of agonists and antagonists of β2 adrenoceptor (β2AR) is warranted in various human disease conditions including cancer, cardiovascular and other metabolic disorders. However, the sources of agonists of β2AR are diverse in nature. Interestingly, there is a complete gap in the exploration of agonists of β2AR from serum that is a well-known component of culture media which supports growth and proliferation of normal and cancer cells in vitro.MethodsIn this paper, we employed a novel vertical tube gel electrophoresis (VTGE)-assisted purification of intracellular metabolites of MCF-7 cells grown in vitro in complete media with fetal bovine serum (FBS). Intracellular metabolites of MCF-7 cells were then analyzed by LC-HRMS. Identified intracellular tripeptides of FBS origin were evaluated for their molecular interactions with various extracellular and intracellular receptors including β2AR (PDB ID: 2RH1) by employing molecular docking and molecular dynamics simulations (MDS). A known agonist of β2AR, isoproterenol was used as a positive control in molecular docking and MDS analysesResultsWe report here identification of a few novel intracellular tripeptides, namely Arg-His-Trp, (PubChem CID-145453842), Pro-Ile-Glu, (PubChem CID-145457492), Cys-Gln-Gln, (PubChem CID-71471965), Glu-Glu-Lys, (PubChem CID-11441068) and Gly-Cys-Leu (PubChem CID145455600) of FBS origin in MCF-7 cells. Molecular docking and MDS analyses revealed that among these molecules, the tripeptide Arg-His-Trp shows a favorable binding affinity with β2AR (−9.8 Kcal/mol). Furthermore, agonistic effect of this tripeptide, Arg-His-Trp is significant and comparable with that of a known agonist of β2AR, isoproterenol.ConclusionIn conclusion, we identified a unique Arg-His-Trp tripeptide of FBS origin in MCF-7 cells by employing a novel approach. This unique tripeptide Arg-His-Trp is suggested to be a potential agonist of β2AR and it may have applications in the context of various human diseases like bronchial asthma and chronic obstructive pulmonary disease (COPD).NOVELTY & IMPACT STATEMENTSThis paper reports on a novel vertical tube gel electrophoresis (VTGE) system that assisted in the purification and identification of a few intracellular tripeptides in the in vitro grown breast cancer cells, MCF-7ls.Molecular docking and molecular dynamics simulation analyses strongly suggest that the tripeptide Arg-His-Trp among others forms the most stable ligand-protein complex with β2 adrenoceptor (β2AR). Its binding affinity and the nature of molecular interactions are comparable or even better than the known agonists of β2AR.This tripeptide Arg-His-Trp is predicted to show manyfold less cytotoxicity, mutagenicity, cardiotoxicity, drug-drug interactions, microsomal stability, and drug-induced liver injury over the other known agonists of β2AR.The tripeptide Arg-His-Trp is therefore suggested as an effective agonist of β2AR and this may be validated in future, in preclinical and clinical models.

Dissimilar metals joining, especially Aluminum (Al) to copper (Cu), have gained importance in batteries for electric vehicles. Although friction stir spot welding (FSSW) has recently been used for welding dissimilar materials, progress has been very slow toward understanding the effect of temperature on diffusion condition between the two materials with the same FCC crystal structure. The thermo-mechanical modeling has been used to define the trajectory of Al and Cu particles at the weld interface, but it had a limitation to quantified the diffusion coefficient. Hence, the molecular dynamics (MD) study has been used to investigate the atomic interdiffusion of Al and Cu. The transmission electron microscopy results are used to validate the MD simulation outcome to understand the formation of dislocations and intermetallic compounds. The MD results implicated the formation of γ-phase (BCC), i.e., Al4Cu9 IMC toward the Cu side. Further, the In-situ investigation of non-FCC phase formation at FSSW condition has also been studied.\ud \ud

Iron slime, the by-product of steel industry, is of environmental and ecological concern due to its disposal problem. An incubation experiment was conducted with the iron slime to study its effect on soil properties with special reference to arsenic retention in arsenic-contaminated soil. The experiment was conducted in factorial completely randomized design with three levels of arsenic spiking: 0, 5 and 10 mg kg−1 and three doses of iron slime: 0, 10 and 20 g kg−1 in three different arsenic status soils under submergence for 90 days. Application of iron slime significantly increased organic carbon and available phosphorus content in soil with increase in the dose of iron slime irrespective of level of arsenic spiking and initial soil arsenic status. Available phosphorus content in soil is increased by 10.89, 7.58 and 23.85% with 20 g iron slime kg−1 soil in low, medium and high arsenic soil over their respective control. On the other hand, available arsenic content in soil decreased with increasing dose of iron slime. Available arsenic concentration in soil is declined by 34.6, 45.9 and 46.7% from their respective initial arsenic status in low, medium and high arsenic status soil with the application of 20 g iron slime kg−1 soil. Considering the positive effect of iron slime on increasing organic carbon, available phosphorus content in soil, and retaining arsenic in plant unavailable form, it can be considered as an efficient amendment for arsenic-contaminated soils.

Aims: To optimize drying technique for the popular Dutch rose cultivar, Taj Mahal, by evaluating different drying methods and appraising the physical, biochemical and sensory quality of the product. Study Design: Completely Randomized Design. Place and Duration of Study: Department of Floriculture, Medicinal and Aromatic Plants, Faculty of Horticulture, Uttar Banga Krishi Viswavidyalaya, during 2019-2020 Methodology: Flowers of rose cultivar ‘Taj Mahal’, at their prime beauty i.e., half-opened bud stage, were subjected to embedded drying in silica gel at six different conditions viz. at room temperature (T1), in hot air oven at 45°C, (T2) and at 60°C, (T3) in micro-wave oven at 100% power level (T4), 80% power level (T5) and at 60% power level (T6). The quality of the ensuing dehydrated flowers was judged with respect to colour, weight, volume shrinkage and anthocyanin and carotenoid contents. Temperature during drying and time to reach optimum dehydrated condition under different drying techniques were recorded. Sensory evaluation for the quality of the products was done after six months of storage. Results: The time taken for optimum drying ranged from 120 hours in case of room temperature drying (25.1°C) to 3 minutes in microwave oven on high power i.e., 100% (130.4°C). Significant variation in final weight of the product was recorded between 18.34% to 28% of the fresh weight. Minimum shrinkage (42.85%) was noted in room drying (T1) and hot air oven drying at 60°C (43.53%). Maximum anthocyanin concentration (3.528 mg/g) was recorded in flowers dried at room temperature, whereas, minimum among the dried flowers, was recorded in microwave oven drying at 100% power level (1.439 mg/g). Maximum Carotenoid content (16.780 µg/g) was recorded in flowers dried in hot air oven at 45°C. Out of six treatments in the present study, maximum sensory score (30.38 out of 36) was gathered by T2, which was at par with T1 and T5. Conclusion: Dehydrating ‘Taj Mahal’ rose flowers by embedding in silica gel and drying under room temperature (25°C) for 120 hours or hot air oven at 45°C for 27.5 hours or microwave oven at 80% power level for 3.5 minutes can be recommended for commercial dry flower production.

Friction processing was used to fabricate solid sintered, open-cell, copper foam parts of different shapes and sizes. Sintering and dissolution with NaCl spacers were used to obtain the foam parts. Pressure and temperature needed for sintering were obtained by plunging a rotating tool into a top sheet in the setup. Setups and tool paths were chosen to get the desired shape and size of sintered parts. The presented method is an attractive alternative to conventional sintering methods, particularly for fabricating solid sintered metal parts with a large specific surface area and high strength to weight ratio.

Large open-cell copper (Cu) foam plates were fabricated using the sintering and dissolution process with NaCl spacers. A rotating tungsten carbide (WC) tool with a flat shoulder was used to generate the temperature and pressure needed for sintering. Sintering was done on a friction stir welding machine. Tool path and die design control the sintered part shape and size. The process allows for fabrication of large three-dimensional metal foam parts on conventional milling and friction stir welding machines. NaCl volume fraction in metal powder-NaCl filler mixture was kept at 80%. Copper foam obtained in this manner had uniform porosity. Tool traverse speed affected sintering time and temperature and influenced the mechanical properties and microstructure of sintered parts. The microstructure of copper foam was studied using a scanning electron microscope. Compression tests were used to study its mechanical properties. Macro-pores were seen to have NaCl particle morphology. Foam mechanical properties were seen to be on par with that reported in literature. The sintering and dissolution process presented in this work results in open-cell foams with large surface areas. It is an attractive alternative for the fabrication of three-dimensional porous sintered parts.

Seedlings of groundnut (Arachis hypogaea L.) ‘TG-51’ were raised in sand culture in presence of three different concentrations of cadmium (100, 300 and 500 µM) and two concentrations of zinc (50 and 150 µM) along with their combinations. In general, the root accumulated several times higher content of both the metals than leaf. It was noted that uptake of Cd by root decreased in combined treatment in comparison with the sole application of cadmium. The dry weight of root, stem, leaf as well as the whole seedling significantly decreased under cadmium stress compared to unstressed control. Zinc supplementation in the growing medium minimized the adverse effects of cadmium on seedling growth to some extent but could not completely override it. Presence of zinc in combination with cadmium could further the enhancement of proline accumulation under heavy metal stress at 100 and 300 µM Cd but not at the highest concentration. Zinc supplementation in combination with cadmium also lowered the damaging effect of cadmium on leaf membrane to some extent.Higher supplement of Zn was able to enhance dismutation of Cd-triggered superoxide radical by superoxide dismutase enzyme, facilitating its subsequent detoxification through the involvement of peroxidase and catalase enzymes, thereby highlighting its protective role against oxidative damage under heavy metal stress. The results of PCA indicated that strong positive loadings of dry weight of root, leaves as well as whole seedling at PC 1 (55.7%) while the activities of SOD, GPOX and catalase enzymes at PC 2 (16%) mostly contributed towards discrimination among different treatments.

Herein, two luminescent porous networks (CMERI-1 & CMERI-2) have been reported for the efficient detection of formaldehyde (FA) from aqueous medium. Judicious solvent screening using a high-throughput solvothermal procedure leads to two completely different metal-organic framework (MOFs) with different architectures. It is perceived that the framework CMERI-1 shows better sensitivity with a very short response time (1 min) in the realm of FA detection due to the facile imine (-N═CH-) formation, which is restricted in the case of CMERI-2. The fluorescence "turn-on" behavior is ascribed due to the inhibition of photoinduced electron transfer (PET) (from amine subunit to secondary building unit) process. The detection limits of CMERI-1 & CMERI-2 toward FA in aqueous medium were found to be 0.62 μM (0.019 ppm) and 1.39 μM (0.041 ppm), respectively, that lie far below the intracellular concentration of formaldehyde (100-400 μM). In addition, MOF-based hydrogel membrane was fabricated, which shows vapor-phase detection of FA, which is hitherto unexplored in this realm. Moreover, the response mechanisms of MOFs are supported by density functional theory (DFT) and Fukui indices analysis. The high stability of the porous frameworks along with its interesting sensing features such as fast recognition phenomenon, appreciable detection limit, etc. instigated us to explore its real-world applicability in various food sample and water analyses. In view of the modular design principle of our polymeric probe, the proposed approach could open a new horizon to construct powerful sensing materials for the ultrafast detection of other industrial pollutants in the domain of supramolecular and analytical chemistry.

Purpose: Circulating tumor cells (CTC) are under investigation as a minimally invasive liquid biopsy that may improve risk stratification and treatment selection. CTCs uniquely allow for digital pathology of individual malignant cell morphology and marker expression. We compared CTC features and T-cell counts with survival endpoints in a cohort of patients with metastatic genitourinary cancer treated with combination immunotherapy. Experimental Design: Markers evaluated included pan-CK/CD45/PD-L1/DAPI for CTCs and CD4/CD8/Ki-67/DAPI for T cells. ANOVA was used to compare CTC burden and T-cell populations across timepoints. Differences in survival and disease progression were evaluated using the maximum log-rank test. Results: From December 2016 to January 2019, 183 samples from 81 patients were tested. CTCs were found in 75% of patients at baseline. CTC burden was associated with shorter overall survival (OS) at baseline (P = 0.022), but not on-therapy. Five morphologic subtypes were detected, and the presence of two specific subtypes with unique cellular features at baseline and on-therapy was associated with worse OS (0.9–2.3 vs. 28.2 months; P < 0.0001–0.013). Increasing CTC heterogeneity on-therapy had a trend toward worse OS (P = 0.045). PD-L1+ CTCs on-therapy were associated with worse OS (P < 0.01, cycle 2). Low baseline and on-therapy CD4/CD8 counts were also associated with poor OS and response category. Conclusions: Shorter survival may be associated with high CTC counts at baseline, presence of specific CTC morphologic subtypes, PD-L1+ CTCs, and low %CD4/8 T cells in patients with metastatic genitourinary cancer. A future study is warranted to validate the prognostic utility of CTC heterogeneity and detection of specific CTC morphologies.

This study demonstrates how the self-assembly pattern of two different and isomeric peptide-appended core-substituted naphthalenediimides (NDIs) affects the modulation of their optoelectronic properties. Two isomeric peptide-attached NDIs were synthesized, purified and characterized. Interchanging the position of attachment of the peptide units and the alkyl chains in the NDI has altered the respective self-assembling patterns of these isomeric molecules in the aggregated states. The isomer having a peptide moiety in the core position and the alkyl chain in the imide position (compound N1) forms face to face stacking or 'H' aggregates in aliphatic solvents including n-hexane, and n-decane, whereas compound N2, in which the peptide moiety is at the imide position and the alkyl chain is attached at the core position of NDI exhibits edge to edge stacking or J aggregates under the same conditions as it is evident from their UV-vis studies. The H aggregated species (obtained from N1) show inter-connected nanofibers, whereas the J aggregated species (obtained from N2) exhibit the morphology of helical nanoribbons. FT-IR and X-ray diffraction studies are in favor of the same aggregation behavior. The individual packing patterns of these two peptide-based isomers have a direct impact on their respective electrical conductivity. Interestingly, the H aggregated species shows 100 times greater current conductivity than that of the J aggregate. Moreover, it is only the H aggregated species that exhibits a photocurrent, and no such photocurrent response is observed with the J aggregates. Computational studies also support that different types of aggregation patterns are formed by these two isomeric molecules in the same solvent system. This unique example of tuning of optoelectronic behavior holds future promise for the development of new peptide-conjugated π-functional materials.

Background Cabozantinib is approved for metastatic renal cell carcinoma (mRCC) based on the METEOR and CABOSUN trials. However, real‐world effectiveness and dosing patterns of cabozantinib are not well characterized. Methods Patients with mRCC treated with cabozantinib between 2011 and 2019 were identified and stratified using the International mRCC Database Consortium (IMDC) risk groups. First‐ (1L), second‐ (2L), third‐ (3L), and fourth‐line (4L) overall response rate (ORR), time to treatment failure (TTF), and overall survival (OS) were analyzed. Dose reduction rates and their association with TTF and OS were determined. Results A total of 413 patients were identified. The ORRs across 1L to 4L were 32%, 26%, 25%, and 29%, respectively, and the median TTF rates were 8.3, 7.3, 7.0, and 8.0 months, respectively. The median OS (mOS) rates in 1L to 4L were 30.7, 17.8, 12.6, and 14.9 months, respectively. For patients treated with 1L PD(L)1 combination agent (n = 31), 2L cabozantinib had ORR of 22%, median TTF of 5.4 months, and mOS of 17.4 months. About 50% (129/258) of patients required dose reductions. The TTF and mOS were significantly longer for patients who required dose reduction vs. patients who did not, with an adjusted hazard ratio of 0.37 (95% CI 0.202–0.672, p, Cabozantinib demonstrates activity for use in real‐world patients with metastatic renal cell carcinoma across the first‐ to fourth‐line treatment settings.

With the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the whole world is suffering from atypical pneumonia, which resulted in more than 559,047 deaths worldwide. In this time of crisis and urgency, the only hope comes from new candidate vaccines and potential antivirals. However, formulating new vaccines and synthesizing new antivirals are a laborious task. Therefore, considering the high infection rate and mortality due to COVID-19, utilization of previous information, and repurposing of existing drugs against valid viral targets have emerged as a novel drug discovery approach in this challenging time. The transmembrane spike (S) glycoprotein of coronaviruses (CoVs), which facilitates the virus’s entry into the host cells, exists in a homotrimeric form and is covered with N-linked glycans. S glycoprotein is known as the main target of antibodies having neutralizing potency and is also considered as an attractive target for therapeutic or vaccine development. Similarly, targeting of N-linked glycans of S glycoprotein envelope of CoV via carbohydrate-binding agents (CBAs) could serve as an attractive therapeutic approach for developing novel antivirals. CBAs from natural sources like lectins from plants, marine algae and prokaryotes and lectin mimics like Pradimicin-A (PRM-A) have shown antiviral activities against CoV and other enveloped viruses. However, the potential use of CBAs specifically lectins was limited due to unfavorable responses like immunogenicity, mitogenicity, hemagglutination, inflammatory activity, cellular toxicity, etc. Here, we reviewed the current scenario of CBAs as antivirals against CoVs, presented strategies to improve the efficacy of CBAs against CoVs; and studied the molecular interactions between CBAs (lectins and PRM-A) with Man9 by molecular docking for potential repurposing against CoVs in general, and SARSCoV- 2, in particular.

Incorporation of unconventional feed ingredients in poultry ration plays a pivotal role in successful and economic poultry production. Distillers Dried Grains with Soluble is now becoming a popular unconventional ingredient for livestock as well as poultry feed due to its high nutritive value and lower price. In West Bengal Rice based Distillers Dried Grains with Soluble (RDGS) is predominantly available. When it comes to feeding Dried Rice Distillers Grains with Solubles (RDGS) to poultry birds, there is no formal recommendation regarding dietary concentration. Hence, the present study was conducted to assess the effects of varying levels of RDGS inclusion on “Vanaraja” chicken production performance. Total 144 numbers of Vanaraja birds were included to conduct the present study. They were divided randomly into three (3) groups (n = 48) with three (3) different dietary treatments that includes Control (C) without inclusion of RDGS, Treatment – I (T1) with 6% RDGS inclusion of the total diet / day and Treatment – II (T2) with 12% RDGS inclusion of the total diet / day respectively. The experiment continued up to 32 weeks of age of the birds. The performance parameters on the basis of body weight (BW) and egg production upto that age were recorded. Result showed that inclusion of RDGS increased body weight of the birds significantly than the group without inclusion of RDGS. Among the two supplemented groups the treatment group II (T2) i.e. inclusion of RDGS @ 12% of the total diet /day was having maximum body weight (2678.37±5.20 g / bird at 32 weeks). The egg production per hen also significantly increased in the supplemented groups than the non supplemented group. So among the two doses of RDGS inclusion, the second group (T2) showed best result. Therefore, it can be concluded from the above study that in rural condition where low quality feed is available to the birds, inclusion of RDGS as a protein source is beneficial to the birds. Keywords: Dried Rice Distillers Grains with Solubles (RDGS), Vanaraja Birds, Production performance

A recent surge in finding new candidate vaccines and potential antivirals to tackle atypical pneumonia triggered by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) needs new and unexplored approaches in solving this global pandemic. The homotrimeric transmembrane spike (S) glycoprotein of coronaviruses which facilitates virus entry into the host cells is covered with N-linked glycans having oligomannose and complex sugars. These glycans provide a unique opportunity for their targeting via carbohydrate-binding agents (CBAs) which have shown their antiviral potential against coronaviruses and enveloped viruses. However, CBA–ligand interaction is not fully explored in developing novel carbohydrate-binding-based antivirals due to associated unfavorable responses with CBAs. CBAs possess unique carbohydrate-binding specificity, therefore, CBAs like mannose-specific plant lectins/lectin-like mimic Pradimicin-A (PRM-A) can be used for targeting N-linked glycans of S glycoproteins. Here, we report studies on the binding and stability of lectins (NPA, UDA, GRFT, CV-N and wild-type and mutant BanLec) and PRM-A with the S glycoprotein glycans via docking and MD simulation. MM/GBSA calculations were also performed for docked complexes. Interestingly, stable BanLec mutant (H84T) also showed similar docking affinity and interactions as compared to wild-type BanLec, thus, confirming that uncoupling the mitogenic activity did not alter the lectin binding activity of BanLec. The stability of the docked complexes, i.e. PRM-A and lectins with SARS-CoV-2 S glycoprotein showed favorable intermolecular hydrogen-bond formation during the 100 ns MD simulation. Taking these together, our predicted in silico results will be helpful in the design and development of novel CBA-based antivirals for the SARS-CoV-2 neutralization. Communicated by Ramaswamy H. Sarma

High-performance cathode materials are highly desirable for the realization of commercial Na-ion batteries. Sodium super ion conductor (NASICON)-type Na3V2(PO4)3 is one of the most promising cathod...

PURPOSE We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances. PATIENTS AND METHODS Patients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS). RESULTS Fifty-four patients were enrolled at eight dose levels with a median follow-up time of 44.6 months; data cutoff was January 20, 2020. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 75% and 87% of patients treated with CaboNivo and CaboNivoIpi, respectively, and included fatigue (17% and 10%, respectively), diarrhea (4% and 7%, respectively), and hypertension (21% and 10%, respectively); grade 3 or 4 immune-related AEs included hepatitis (0% and 13%, respectively) and colitis (0% and 7%, respectively). The RP2D was cabozantinib 40 mg/d plus nivolumab 3 mg/kg for CaboNivo and cabozantinib 40 mg/d, nivolumab 3 mg/kg, and ipilimumab 1 mg/kg for CaboNivoIpi. ORR was 30.6% (95% CI, 20.0% to 47.5%) for all patients and 38.5% (95% CI, 13.9% to 68.4%) for patients with mUC. Median DoR was 21.0 months (95% CI, 5.4 to 24.1 months) for all patients and not reached for patients with mUC. Median PFS was 5.1 months (95% CI, 3.5 to 6.9 months) for all patients and 12.8 months (95% CI, 1.8 to 24.1 months) for patients with mUC. Median OS was 12.6 months (95% CI, 6.9 to 18.8 months) for all patients and 25.4 months (95% CI, 5.7 to 41.6 months) for patients with mUC. CONCLUSION CaboNivo and CaboNivoIpi demonstrated manageable toxicities with durable responses and encouraging survival in patients with mUC and other GU tumors. Multiple phase II and III trials are ongoing for these combinations.

Precision medicine approaches for managing patients with metastatic castrate-resistant prostate cancer (mCRPC) are lacking. Non-invasive approaches for molecular monitoring of disease are urgently needed, especially for patients suffering from bone metastases for whom tissue biopsy is challenging. Here we utilized baseline blood samples to identify mCRPC patients most likely to benefit from abiraterone plus prednisone (AAP) or enzalutamide. Baseline blood samples were collected for circulating tumor cell (CTC) enumeration and qPCR-based gene expression analysis from 51 men with mCRPC beginning treatment with abiraterone or enzalutamide. Of 51 patients (median age 68 years [51–82]), 22 received AAP (abiraterone 1000 mg/day plus prednisone 10 mg/day) and 29 received enzalutamide (160 mg/day). The cohort was randomly divided into training (n = 37) and test (n = 14) sets. Baseline clinical variables (Gleason score, PSA, testosterone, and hemoglobin), CTC count, and qPCR-based gene expression data for 141 genes/isoforms in CTC-enriched blood were analyzed with respect to overall survival (OS). Genes with expression most associated with OS included MSLN, ARG2, FGF8, KLK3, ESRP2, NPR3, CCND1, and WNT5A. Using a Cox-elastic net model for our test set, the 8-gene expression signature had a c-index of 0.87 (95% CI [0.80, 0.94]) and was more strongly associated with OS than clinical variables or CTC count alone, or a combination of the three variables. For patients with a low-risk vs. high-risk gene expression signature, median OS was not reached vs. 18 months, respectively (HR 5.32 [1.91–14.80], p = 0.001). For the subset of 41 patients for whom progression-free survival (PFS) data was available, the median PFS for patients with a low-risk vs high-risk gene expression signature was 20 vs. 5 months, respectively (HR 2.95 [1.46–5.98], p = 0.003). If validated in a larger prospective study, this test may predict patients most likely to benefit from second-generation antiandrogen therapy.

High performance thermoplastic is often used in automotive and aerospace sectors. Friction stir welding (FSW) has been a suitable method for joining these thermoplastic materials. However, the process characteristics vary dynamically, even at same parametric conditions due to process disturbances. While quite a few studies have been reported in experimental investigation, the usage of sensors for the process monitoring during welding has not been explored. Therefore, the present paper focuses on various sensor-based approaches on process monitoring. The study includes an in-depth experimental investigation for joining of polycarbonate sheets using full factorial design of experiments. Three different tool pin profiles like cylindrical, square and triangular have been selected, whereas tool rotational speed and traverse speed are considered as primary process variables. Various statistical time domain features of the force and torque signals starting from average, its deviation and root mean square as well as thermal cycle based weld peak temperature and its cooling rate were found to have a strong correlation with weld bead profile. The axial force and thermal cycles were found to be the major indicators of joint strength efficiency rather than torque as per regression models developed by using response surface methodology. Finally, an attempt has been made for improving the joint strength predictability by using various sensor-based approaches. This work can be used potentially to real time welding process monitoring in industrial sectors.

An experiment was conducted to evaluate the thermal tolerance limit and oxygen consumption rates of Labeo gonius (6.23±0.19 g) fingerlings acclimated to four different temperatures (27, 30, 33 and 36 °C) for a period of 60 days. Critical thermal maxima, CTmax (40.97±0.05, 41.89±0.05, 42.69±0.04 and 43.05±0.05) and critical thermal minima, CTmin (12.72±0.04, 13.62±0.04, 13.99±0.05 and 14.39±0.021) increased significantly (p

In the era of precision oncology, liquid biopsy techniques, especially the use of plasma circulating tumour DNA (ctDNA) analysis, represent a paradigm shift in the use of genomic biomarkers with considerable implications for clinical practice. Compared with tissue-based tumour DNA analysis, plasma ctDNA is more convenient to test, more readily accessible, faster to obtain and less invasive, minimizing procedure-related risks and offering the opportunity to perform serial monitoring. Additionally, genomic profiles of ctDNA have been shown to reflect tumour heterogeneity, which has important implications for the identification of resistant clones and selection of targeted therapy well before clinical and radiographic changes occur. Moreover, plasma ctDNA testing can also be applied to cancer screening, risk stratification and quantification of minimal residual disease. These features provide an unprecedented opportunity for early treatment of patients, improving the chances of treatment success. Liquid biopsy techniques, especially the use of plasma circulating tumour DNA (ctDNA) analysis, are a convenient, fast and non-invasive approach to the diagnosis and monitoring of urological cancers, and could enable selection of targeted therapy before clinical and radiographic changes occur. In this Review, the authors discuss the uses of liquid biopsy and plasma ctDNA analysis in particular, and consider how it could be used in clinical practice now and in the future.

Graphene enticed the scientific community for its interesting properties since its discovery. Among different synthesis routes of graphene, reduction of graphene oxide (GO) is mostly preferred because of scalability and advantage of modulation of properties of the end product. Thermal reduction of GO is considered to be the simplest and economic among different reduction techniques. The current work reports an experimental analysis of the structural evolution of GO to reduced graphene oxide (rGO) during thermal treatment. GO has been thermally annealed at an optimized temperature of 350 °C in ambient. Thermal reduction is observed after 7 min of annealing and confirmed by shifting of the first major peak from 12° to 23° in X-ray diffraction pattern. Significant carbon content enrichment and exfoliation are two aspects of the thermal reduction of GO. Carbon content suddenly enriches from 38 wt% in GO to 77 wt%. Exfoliation is confirmed by morphological alterations and decrease in carbon layers from eleven to three.

Umbrella-like inversion of pyramidalized amines proceed through a planar transition state (TS). Stabilization of the TS through N(lone-pair) → σ*(C–C) “negative hyperconjugation” in diamino-o-carbo...

Here, we report a novel ammonia : ammonium salt solvent based pretreatment process that can rapidly dissolve crystalline cellulose into solution and eventually produce highly amorphous cellulose under near-ambient conditions. Pre-activating the cellulose I allomorph to its ammonia–cellulose swollen complex (or cellulose III allomorph) at ambient temperatures facilitated rapid dissolution of the pre-activated cellulose in the ammonia-salt solvent (i.e., ammonium thiocyanate salt dissolved in liquid ammonia) at ambient pressures. For the first time in reported literature, we used time-resolved in situ neutron scattering methods to characterize the cellulose polymorphs structural modification and understand the mechanism of crystalline cellulose dissolution into a ‘molecular’ solution in real-time using ammonia-salt solvents. We also used molecular dynamics simulations to provide insight into solvent interactions that non-covalently disrupted the cellulose hydrogen-bonding network and understand how such solvents are able to rapidly and fully dissolve pre-activated cellulose III. Importantly, the regenerated amorphous cellulose recovered after pretreatment was shown to require nearly ∼50-fold lesser cellulolytic enzyme usage compared to native crystalline cellulose I allomorph for achieving near-complete hydrolytic conversion into soluble sugars. Lastly, we provide proof-of-concept results to further showcase how such ammonia-salt solvents can pretreat and fractionate lignocellulosic biomass like corn stover under ambient processing conditions, while selectively co-extracting ∼80–85% of total lignin, to produce a highly digestible polysaccharide-enriched feedstock for biorefinery applications. Unlike conventional ammonia-based pretreatment processes (e.g., Ammonia Fiber Expansion or Extractive Ammonia pretreatments), the proposed ammonia-salt process can operate at near-ambient conditions to greatly reduce the pressure/temperature severity necessary for conducting effective ammonia-based pretreatments on lignocellulose.

Building up on weak orthogonal interactions in supramolecular chemistry, a six-component crystal is designed. Using five distinctly different noncovalent forces, namely, hydrogen bonding, halogen bonding, cation-π, anion-π, and ion-pair interactions, three six-component crystals were designed with crown-ether (I), thiourea (II), 2,3,5,6-tetrafluoro-1,4-dibromobenzene (III), lone-pair donating anion (IV), ammonium cation (V), and electron-rich aromatic ring (VI). The M06-2X functional which is highly suitable in describing other weak interactions fails for ion-pairs. Tuned range-separated (RS)-DFT calculations are found to be capable in describing the ionic interactions in molecular solids. Molecular dynamics simulations show that the predicted multicomponent crystals are stable at room temperature and reducing the ionic charges for the ion-pairs destabilizes them. The strong electrostatic interactions between the three ion-pairs, NH4+···ClO4-, NH4+···HSO4-, and NH4+···HCO3- is the primary driving force for the stabilization of the six-component crystal. Using a hybrid of strong and weak intermolecular interactions, one may generate exotic molecular complexity like n-component crystals.

Background: Both novel hormonal therapies and docetaxel are approved for treatment of metastatic prostate cancer (mPC, in castration sensitive or refractory settings). Present knowledge gaps include lack of real-world data on treatment patterns in patients with newly diagnosed mPC, and comparative effectiveness of novel hormonal therapies (NHT) versus docetaxel after treatment with a prior NHT. Methods: Herein we extracted patient-level data from a large real-world database of patients with mPC in United States. Utilization of NHT or docetaxel for mPC and comparative effectiveness of an alternate NHT versus docetaxel after one prior NHT was evaluated. Comparative effectiveness was examined via Cox proportional hazards model with propensity score matching weights. Each patient’s propensity for treatment was modeled via random forest based on 22 factors potentially driving treatment selection. Results: The majority of patients (54%) received only androgen deprivation therapy for mPC. In patients treated with an NHT, alternate NHT was the most common next therapy and was associated with improved median overall survival over docetaxel (abiraterone followed by docetaxel vs. enzalutamide (8.7 vs. 15.6 months, adjusted hazards ratio, aHR 1.32, p = 0.009, and enzalutamide followed by docetaxel vs. abiraterone (9.7 vs. 13.2 months aHR 1.40, p = 0.009). Limitations of the study include retrospective design.

Background In the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS) and overall survival (OS) versus everolimus in patients with advanced RCC after prior antiangiogenic therapy. Methods In this exploratory analysis, plasma biomarkers from baseline and week 4 from 621 of 658 randomized patients were analyzed for CA9, HGF, MET, GAS6, AXL, VEGF, VEGFR2, and IL-8. PFS and OS were analyzed by baseline biomarker levels as both dichotomized and continuous variables using univariate and multivariable methods. For on-treatment changes, PFS and OS were analyzed using fold change in biomarker levels at week 4. Biomarkers were considered prognostic if p interaction Results Hazard ratios for PFS and OS favored cabozantinib versus everolimus for both low and high baseline levels of all biomarkers (hazard ratios ≤0.78). In univariate analyses, low baseline HGF, AXL, and VEGF were prognostic for improvements in both PFS and OS with cabozantinib, and low HGF was prognostic for improvements in both PFS and OS with everolimus. Low AXL was predictive of relative improvement in PFS for cabozantinib versus everolimus. Results were generally consistent when baseline biomarkers were expressed as continuous variables, although none were predictive of benefit with treatment. In multivariable analysis, low baseline HGF was independently prognostic for improved PFS for both cabozantinib and everolimus; low HGF, GAS6, and VEGF were independently prognostic for improved OS with cabozantinib. No biomarkers were independently prognostic for OS with everolimus. On-treatment increases in some biomarkers appeared prognostic for PFS or OS with cabozantinib in univariate analyses; however, none were independently prognostic in multivariable analysis. Conclusions PFS and OS were improved with cabozantinib versus everolimus at high and low baseline levels of all biomarkers. Low baseline HGF was consistently identified as a prognostic biomarker for improved PFS or OS with cabozantinib or everolimus, supporting further prospective evaluation of the prognostic significance of HGF in advanced RCC. Trial registration ClinicalTrials.gov NCT01865747 (registered on 05/31/2013).

We report a series of seven cationic heteroleptic copper(I) complexes of the form [Cu(P^P)(dmphen)]BF4, where dmphen is 2,9-dimethyl-1,10-phenanthroline and P^P is a diphosphine chelate, in which the effect of the bite angle of the diphosphine ligand on the photophysical properties of the complexes was studied. Several of the complexes exhibit moderately high photoluminescence quantum yields in the solid state, with ΦPL of up to 35%, and in solution, with ΦPL of up to 98%. We were able to correlate the powder photoluminescence quantum yields with the % Vbur of the P^P ligand. The most emissive complexes were used to fabricate both organic light-emitting diodes and light-emitting electrochemical cells (LECs), both of which showed moderate performance. Compared to the benchmark copper(I)-based LECs, [Cu(dnbp)(DPEPhos)]+ (maximum external quantum efficiency, EQEmax = 16%), complex 3 (EQEmax = 1.85%) showed a much longer device lifetime (t1/2 = 1.25 h and >16.5 h for [Cu(dnbp)(DPEPhos)]+ and complex 3, respectively). The electrochemiluminescence (ECL) properties of several complexes were also studied, which, to the best of our knowledge, constitutes the first ECL study for heteroleptic copper(I) complexes. Notably, complexes exhibiting more reversible electrochemistry were associated with higher annihilation ECL as well as better performance in a LEC.

Lessons Learned Background Endoglin is an angiogenic receptor expressed on proliferating tumor vessels and renal cell carcinoma (RCC) stem cells that is implicated as a mechanism of resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors. This study evaluated an antiendoglin monoclonal antibody (carotuximab, TRC105) combined with axitinib in patients with advanced or metastatic clear cell renal cell carcinoma (mccRCC) who had progressed following one or more prior VEGF inhibitors. Methods TRAXAR was a multicenter, international randomized 1:1 (stratified by ECOG, 0 vs. 1), phase II study of carotuximab combined with axitinib versus axitinib alone in mccRCC patients who had progressed following one or more prior VEGF inhibitors. The primary endpoint was progression-free survival (PFS) assessed by independent central review (ICR) per RECIST 1.1 Results A total of 150 patients were randomized. The combination therapy resulted in shorter median PFS by RECIST 1.1 than axitinib monotherapy (6.7 vs. 11.4 months). The combination was tolerated similarly to axitinib monotherapy, and there were no treatment related deaths. Exploratory evaluation of pretreatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels. Conclusion The combination of carotuximab with axitinib did not demonstrate additional efficacy over single agent axitinib in patients with mccRCC who progressed following one or more prior VEGF inhibitor treatment.

Context No head-to-head clinical trials compare contemporary first-line therapies for metastatic renal cell carcinoma (mRCC). A network meta-analysis provides an approach for quantitative analysis. Objective To indirectly compare the efficacy and safety of first-line treatments for mRCC in the intention-to-treat (ITT) population and by clinical risk group. Evidence acquisition An updated systematic review from database inception to February 17, 2019 identified all parallel-group randomized controlled trials assessing first-line therapy for mRCC. “Clinically relevant” studies were selected for a network meta-analysis. Progression-free survival (PFS) was the primary outcome. Overall survival (OS), overall response rate (ORR), and grade 3 and 4 adverse events (AEs) were secondary outcomes. Evidence synthesis We identified 12 relevant trials: 12 reported outcomes for PFS, nine for OS, 10 for ORR, and nine for AEs. In the ITT population, cabozantinib (surface under the cumulative ranking curves [SUCRA] 84%), avelumab plus axitinib (SUCRA 68%), and pembrolizumab plus axitinib (SUCRA 82%) were superior to the other agents for PFS; pembrolizumab plus axitinib appeared superior for OS (SUCRA 95%); and atezolizumab demonstrated the lowest likelihood of AEs (SUCRA 100%). Findings were similar in the intermediate/poor-risk subgroup. Based on the limited data available, avelumab plus axitinib may be preferred in patients with favorable-risk disease. Conclusions The optimal first-line treatment for mRCC appears to differ by efficacy endpoint, toxicity, and clinical risk group. Direct comparative studies remain important in guiding treatment choice. Patient summary Head-to-head comparisons do not exist for the newest treatments of metastatic renal cell carcinoma (mRCC). In an indirect comparison, we found that pembrolizumab plus axitinib and cabozantinib are good options for most patients with mRCC.

This study attempts to join copper (Cu) and aluminium (Al) sheets in micro-thickness by using friction stir welding. These materials are being used as current collectors in lithium-ion (li-ion) battery which are employed as power sources for electric vehicles. Several experiments have been carried out, followed by the measurement of electrical conductivity by using a 4-probe setup and electrochemical analysis by using a potentiodynamic polarization test and an electro impedance spectroscopy test in lithium phosphorus hexafluoride (LiPF6), an electrolytic medium. The welded samples have been found to achieve an electrical conductivity of 9% less than the base Cu and the corrosion resistance of the welded samples has been found to be increasing because of the formation of inter-metallic compounds such as Al4Cu9, AlCu4 and AlCu at the weld interface. Among them AlCu4 has the highest hardness and the recovery elastic modulus than the rest.

Purpose We evaluated the prognostic value of 18F-sodium fluoride (NaF) PET/CT in patients with urological malignancies treated with cabozantinib and nivolumab with or without ipilimumab. Methods We prospectively recruited patients with advanced urological malignancies into a phase I trial of cabozantinib plus nivolumab with or without ipilimumab. NaF PET/CT scans were performed pre- and 8 weeks post-treatment. We measured the total volume of fluoride avid bone (FTV) using a standardized uptake value (SUV) threshold of 10. We used Kaplan-Meier analysis to predict the overall survival (OS) of patients in terms of SUVmax, FTV, total lesion fluoride (TLF) uptake at baseline and 8 weeks post-treatment, and percent change in FTV and TLF. Result Of 111 patients who underwent NaF PET/CT, 30 had bone metastases at baseline. Four of the 30 patients survived for the duration of the study period. OS ranged from 0.23 to 34 months (m) (median 6.0 m). The baseline FTV of all 30 patients ranged from 9.6 to 1570 ml (median 439 ml). The FTV 8 weeks post-treatment was 56–6296 ml (median 448 ml) from 19 available patients. Patients with higher TLF at baseline had shorter OS than patients with lower TLF (3.4 vs 14 m; p = 0.022). Patients with higher SUVmax at follow-up had shorter OS than patients with lower SUVmax (5.6 vs 24 m; p = 0.010). However, FTV and TLF 8 weeks post-treatment did not show a significant difference between groups (5.6 vs 17 m; p = 0.49), and the percent changes in FTV (12 vs 14 m; p = 0.49) and TLF (5.6 vs 17 m; p = 0.54) also were not significant. Conclusion Higher TLF at baseline and higher SUVmax at follow-up NaF PET/CT corresponded with shorter survival in patients with bone metastases from urological malignancies who underwent treatment. NaF PET/CT may be a useful predictor of OS in this population.

The current research aims at investigating role of three different types of surfactants and their binary mixtures in producing high cooling rate during jet impingement on a hot steel plate (100 mm × 100 mm × 6 mm) having initial surface temperature above 900 °C. The surfactants used are Sodium dodecyl sulphate (anionic), cetyltrimethylammonium bromide (cationic) and Polysorbate 20 (Tween 20, non-ionic). The surface tension values of the surfactants and their mixed systems have been measured and it has been observed that the binary mixtures at specific compositions show lower surface tension compared to the pure ones mainly due to synergism. The cooling results reveal that the mixture of cationic and non-ionic surfactants produces the highest cooling rate amongst all the systems. The maximum cooling rate achieved is 182 °C/s for the composition of 25 vol% CTAB and 75 vol% Tween 20 and it is 67% more than that of pure water, 23% more compared to pure CTAB and and 7.7% more than that of pure Tween 20. Thus it can be seen that ultrafast cooling of a 6 mm thick steel plate can be achieved by using optimized concentrations of mixed surfactant additives and this leads to improvement of quality of steel produced.

Summary Background Cabozantinib is approved for patients with metastatic renal cell carcinoma on the basis of studies done in clear-cell histology. The activity of cabozantinib in patients with non-clear-cell renal cell carcinoma is poorly characterised. We sought to analyse the antitumour activity and toxicity of cabozantinib in advanced non-clear-cell renal cell carcinoma. Methods We did a multicentre, international, retrospective cohort study of patients with metastatic non-clear-cell renal cell carcinoma treated with oral cabozantinib during any treatment line at 22 centres: 21 in the USA and one in Belgium. Eligibility required patients with histologically confirmed non-clear-cell renal cell carcinoma who received cabozantinib for metastatic disease during any treatment line roughly between 2015 and 2018. Mixed tumours with a clear-cell histology component were excluded. No other restrictive inclusion criteria were applied. Data were obtained from retrospective chart review by investigators at each institution. Demographic, surgical, pathological, and systemic therapy data were captured with uniform database templates to ensure consistent data collection. The main objectives were to estimate the proportion of patients who achieved an objective response, time to treatment failure, and overall survival after treatment. Findings Of 112 identified patients with non-clear-cell renal cell carcinoma treated at the participating centres, 66 (59%) had papillary histology, 17 (15%) had Xp11.2 translocation histology, 15 (13%) had unclassified histology, ten (9%) had chromophobe histology, and four (4%) had collecting duct histology. The proportion of patients who achieved an objective response across all histologies was 30 (27%, 95% CI 19–36) of 112 patients. At a median follow-up of 11 months (IQR 6–18), median time to treatment failure was 6·7 months (95% CI 5·5–8·6), median progression-free survival was 7·0 months (5·7–9·0), and median overall survival was 12·0 months (9·2–17·0). The most common adverse events of any grade were fatigue (58 [52%]), and diarrhoea (38 [34%]). The most common grade 3 events were skin toxicity (rash and palmar-plantar erythrodysesthesia; five [4%]) and hypertension (four [4%]). No treatment-related deaths were observed. Across 54 patients with available next-generation sequencing data, the most frequently altered somatic genes were CDKN2A (12 [22%]) and MET (11 [20%]) with responses seen irrespective of mutational status. Interpretation While we await results from prospective studies, this real-world study provides evidence supporting the antitumour activity and safety of cabozantinib across non-clear-cell renal cell carcinomas. Continued support of international collaborations and prospective ongoing studies targeting non-clear-cell renal cell carcinoma subtypes and specific molecular alterations are warranted to improve outcomes across these rare diseases with few evidence-based treatment options. Funding None.

Pulmonary tuberculosis (PTB) remains a major cause of morbidity and mortality all around the world. Recent studies have pointed out increased oxidative stress and also DNA damage in peripheral blood in PTB. Till date, to the best of our knowledge, no study has so far been conducted to show the mitochondrial DNA (mtDNA) deletions mapping in PTB patients. Therefore we performed the present study with the aim to investigate oxidative stress parameters along with mtDNA damage in newly diagnosed untreated PTB patients.This is a prospective study carried out in Mahatma Gandhi Institute of Medical Sciences, Sevagram,Wardha, Maharashtra during september 2017 to september 2018.Thirty newly diagnosed untreated PTB patients and thirty age matched healthy controls were enrolled in the present study. Analysis of Oxidative stress parameters such as nitric oxide (NO) and malondialdehyde (MDA) were done by calorimetric methods. Assessment of mitochondrial DNA damage was carried out by mtDNA deletions mapping using primer shift long range polymerase chain reaction technique.There was significant increase in levels of oxidative stress parameters, nitric oxide and malondialdehyde, in PTB patients compared to controls (p 0.01). Generally there are two common deletion sites of "13 bp direct repeats" (ACCTCCCTCACCA) in mtDNA. One at the junction sites from bp 8470 to 8482 bp and another from bp 13447 to 13460 bp which make mtDNA more prone for 4977bp deletion. Out of thirty cases of PTB, two cases showed mtDNA damage in the form of mtDNA deletion of 4977bp. There was no mtDNA deletion in any control which can be attributed to continuous generation of oxidative stress.This pilot study has been able to demonstrate that compared to controls, in newly diagnosed pulmonary tuberculosis patients some mtDNA damage did occur and was probably due to continuous generation of oxidative stress in tuberculous patients. However, sample size is too small to draw any conclusions but definitely a more comprehensive study, by recruiting more number of pulmonary tuberculosis patients is warranted to establish correlation between oxidative stress and mtDNA damage in PTB.

In this work we have reported two novel tetranuclear Cd(II) complexes viz. [Cd4 (LOMe)2 (μ1,1-N3)3 (μ1,3-N3)]n (1) and [Cd4 (LOEt)2 (μ1,1-N3)3(OAc)]2 (2) where (H2LOMe) and (H2LOEt) are two important less explored salen-type Schiff base ligands. Both of the complexes have been characterized by using routine spectroscopic techniques, elemental analyses (C, H and N), X-ray powder diffraction pattern (PXRD) and thermal analysis by TGA along with single x-ray crystallography. The complete structural study discloses that in both cases the fully deprotonated ligand [LOMe]2- or [LOEt]2- utilized all potential coordination sites to accommodate four Cd(II) ions. Complex 1 is a one-dimensional polymer with azide (N3) linkage having both (μ1,1 end on) and (μ1,3 end-to-end) azido bridging but complex 2 is a discrete octanuclear ensamble where two [Cd4(O)4(N)2]2+ units bridged to each other showing μ1,1 end on end on azide bridging. Exploration of photo physical properties in DMSO solvent reveals that Cd(II) complexes enhance appreciably the fluorescence behavior over free Schiff base ligands (H2LOMe) and (H2LOEt). DFT calculations performed at B3LYP/def2-TZVP level of theory reveal both the energetics and composition of FMOs in these complexes and also show electrophilic and nucleophilic areas via molecular electrostatic maps [ESP] concept. The antibacterial, membrane damage assay and anti-biofilm properties of complexes 1 and 2 were investigated very carefully against some important Gram-positive and Gram-negative bacterial strains.

Porous solids that can be switched between different forms with distinct physical properties are appealing candidates for separation, catalysis, and host-guest chemistry. In this regard, porous organic cages (POCs) are of profound interest because of their solution-state accessibility. However, the application of POCs is limited by poor chemical stability. Synthesis of an exceptionally stable imine-linked (4+6) porous organic cage (TpOMe-CDA) is reported using 2,4,6-trimethoxy-1,3,5-triformyl benzene (TpOMe) as a precursor aldehyde. Introduction of the -OMe functional group to the aldehyde creates significant steric and hydrophobic characteristics in the environment around the imine bonds that protects the cage molecules from hydrolysis in the presence of acids or bases. The electronic effect of the -OMe group also plays an important role in enhancing the stability of the reported POCs. As a consequence, TpOMe-CDA reveals exceptional chemical stability in neutral, acidic and basic conditions, even in 12 m NaOH. Interestingly, TpOMe-CDA exists in three different porous and non-porous polymorphic forms (α, β, and γ) with respect to differences in crystallographic packing and the orientation of the flexible methoxy groups. All of the polymorphs retain their crystallinity even after treatment with acids and bases. All the polymorphs of TpOMe-CDA differ significantly in their properties as well as morphology and could be reversibly switched in the presence of an external stimulus.

The focus of the present study is to investigate the effect of surfactant addition on thermo-physical properties, stability, and heat transfer performance of Cu-Zn-Al LDH nanofluid. For this purpose, both an anionic (Sodium dodecyl Sulfate (SDS), concentration: 200–800 ppm) and a non-ionic surfactant (Tween 20, concentration: 28–70 ppm) have been used at different concentrations with Cu-Zn-Al LDH nanofluid at a fixed concentration. Among both the surfactants, SDS displayed better compatibility and thermo-physical properties when combined with Cu-Zn-Al LDH nanofluid compared to LDH-Tween 20 combination. The addition of both the surfactants into the nanofluid suspension has led to reduced surface tension and viscosity value which is highly desired for better wettability and improved contact between the coolant and the hot surface. The maximum increment in thermal conductivity value was attained in the case of Cu-Zn-Al LDH at 600 ppm SDS concentration which is 20.9% higher than the water. In terms of stability analysis, the highest zeta potential value of −52.7 mV was also observed for Cu-Zn-Al LDH at 800 ppm SDS loading. The highest cooling rate of 174.8 °C/s was attained by Cu-Zn-Al LDH-SDS (600 ppm) nanofluid which is 30.7% higher than what had been achieved by water based cooling. However, the use of Tween 20 in LDH nanofluid has displayed detrimental impact on poor thermal conductivity, zeta potential, and heat transfer results for the LDH nanofluid.

Pyrvinium was identified as the first small molecule inhibitor of the androgen receptor (AR) DNA-binding domain (DBD). It was also among the first small molecules shown to directly inhibit the activity of AR splice variants (ARVs), which has important clinical implications in the treatment of castration-resistant prostate cancer. Important questions about pyrvinium's mechanism of action remain. Here, we demonstrate through mutational analysis that amino acids 609 and 612 are important for pyrvinium action. Nuclear magnetic resonance demonstrates a specific interaction between a soluble pyrvinium derivative and the AR DBD homodimer-DNA complex. Chromatin immunoprecipitation and electrophoretic mobility shift assay experiments demonstrate that, despite an interaction with this complex, pyrvinium does not alter the DNA-binding kinetics in either assay. AR immunoprecipitation followed by mass spectrometry was used to identify proteins whose interaction with AR is altered by pyrvinium. Several splicing factors, including DDX17, had reduced interactions with AR in the presence of pyrvinium. RNA sequencing of prostate cancer cells treated with pyrvinium demonstrated changes in splicing, as well as in several other pathways. However, pyrvinium did not alter the levels of ARVs in several prostate cancer cell lines. Taken together, our new data pinpoint the direct interaction between pyrvinium and AR DBD and shed light on the mechanism by which it inhibits AR transcriptional activity.

Aluminium metal matrix and hybrid composites (AMMHCs) are new materials used in recent time that have the capacity to meet the demand of advancement in processing applications. Several types of reinforcement have been used since the inception of friction stir processing (FSP). The most widely used reinforcing material is inorganic (metallic) powders such as silicon carbide, titanium alloy, graphene, iron , stainless steel, nitrides, oxides etc and fewer works have been reported on organic powders (i.e. bioprocessing using agro-wastes powders) such as fly ash, palm kernel shell ash, coconut shell ash, rice husk ash etc. Many researchers have established the roles of reinforcements in the modification of surface and texture of the reinforced metal matrix or hybrid composite material and how it enhanced the mechanical and metallurgical properties of the materials via intense, localized plastic deformation compare to the base material. FSP has advantages over other manufacturing processes in a way that it reduces defects and distortions in the material. FSP alters the physical properties of the base material without altering its physical state, this helps engineers develop attributes such as “high-state-rate superplasticity”. The grain refinement occurs on the parent material which improves the properties of the first material while mixing with the second material (reinforcement). Subsequently, allows a variety of properties to be altered and this, in turn, improves its surface modification. The survey is aimed at reviewing different combination and diversified reinforcement particulates employed in the processing of composites of aluminium metal matrix and hybrid and how it enhanced the chemical, mechanical and metallurgical efficacy of the materials. It is very much needed to have a consolidated information about the different reinforcement phases, preparation of the microchannel (groove) that accommodates the reinforcements, its dimensions and various tools geometry that have been used in the past demonstrating the optimum processing results.

The reaction of freshly prepared Na[In(SeCH2C6H5)4] with the mixture of CuCl and triphenylphosphine in methanol yielded [(PPh3)2CuIn(SeCH2C6H5)4]. The X-ray structure of the complex revealed the monomeric form of [(Ph3P)2Cu(μ-SeCH2Ph)2In(SeCH2Ph)2] consisting of tetrahedral Cu(I) and In(III) centers, bridged by two benzyl selenolate ligands. The complex on pyrolysis in a furnace or in oleylamine/HDA yielded tetragonal CuInSe2. The morphology and composition of nanostructures were investigated by pXRD, SEM, TEM and EDX analysis. The band gap of the CuInSe2 nanostructures, obtained from pyrolysis in HDA and OA has been deduced from DRS as 1.85 and 1.86 eV, respectively.

A compact and portable 99Mo-99 mTc generator based on solvent-extraction, mimic to the conventional 99Mo-99 mTc alumina column generator is much-needed commodity for use in hospital radiopharmacy setup. The present study includes the development of a portable, simple and low cost 99Mo/99 mTc-generator based on MEK solvent extraction technique to obtain a very high concentration of no-carrier added (nca) 99 mTc solution, where low specific activity 99Mo source is obtained through 98Mo(n, γ)99Mo reaction in a research reactor. The unit is intended for operation under the conditions of medical radiological laboratories. Technical trials showed that the mean time of preparation of sodium [99mTc] pertechnetate radiopharmaceutical did not exceed 15 min. The quality and yield of 99 mTc-pertechnetate is upto the mark for formulation of radiopharmaceuticals.

More than half of patients diagnosed with renal cell carcinoma (RCC) are age 65 or older. However, older patients are often unable to meet eligibility criteria for clinical trial enrollment due to multiple factors, such as comorbidities and polypharmacy, which leads to under-representation of this population in clinical trials. Given this, efficacy data from the registration trials may not apply to older patients. Our objective was to evaluate the efficacy of first-line and salvage-line treatment in older patients, and compare efficacy between older and younger patients with metastatic RCC (mRCC).Pivotal phase three clinical trials for first-line and salvage-line treatments were included if they reported overall survival (OS) or progression-free survival (PFS) results stratified by age (/≥65 years). The meta-analysis of OS and PFS stratified by age/≥65 years was conducted in the context of Bayesian hierarchical log-linear models with both within and between study variance components.In the first-line setting, data suggests that Nivolumab plus Ipilimumab is the most efficacious treatment for older patients (PFS hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.23-1.45, probability best 39.7%). In the salvage-line setting, Cabozantinib is likely the most efficacious therapy for older patients (PFS HR 0.15, 95% CI 0.08-0.28, probability best 77.2%). Evidence suggests that the majority of first-line treatments have worse efficacy in older patients compared to younger patients.For older patients, first-line Nivolumab plus Ipilimumab and salvage-line Cabozantinib may offer the best survival outcomes. Most first-line drugs for mRCC have inferior performance in older patients compared to their younger counterparts.

The emergence of multi-drug resistant bacteria due to the misuse of antibiotics and inadequate development of antibiotic drugs is a global threat to human health. Recent development in materials research caused the emergence of nanomaterials with promising bactericidal properties. Carbon based nanomaterials like graphene and graphene oxide(GO) have appealed researchers for antimicrobial properties, although some researchers claimed that they promote bacteria growth. To address the conflict, authors performed experiments to study the influence of GO and reduced GO(rGO) on gram positive Staphylococcus aureus and gram negative Pseudomonas aeruginosa bacteria. GO restricts S. aureus and P. aeruginosa cell growth by 93.7% and 48.6% whereas, percentage inhibition by rGO are 67.7% and 93.3% respectively. GO destructs bacteria by cell membrane damage through chemical reaction whereas, rGO induce mechanical stress and pierce the cell membrane. Shape and type of bacteria act as the controlling factors in determining the bactericidal efficacy of the nanomaterials.