Kinetics and Thermodynamics Study on Removal of Cr(VI) from Aqueous Solutions Using Acid-Modified Banana Peel (ABP) Adsorbents.

Banana peel waste is abundant and can be utilized as a low-cost adsorbent for removing toxic Cr (VI) from wastewater. The acid modification of banana peels significantly enhances their adsorption capacity for Cr (VI). An adsorbent was prepared by treating banana peel powder with 50% H2SO4 at 50 °C for 24 h. The acid treatment increased the surface area of the adsorbent from 0.0363 to 0.0507 m2/g. The optimum adsorbent dose was found to be 1 g/L for the complete removal of Cr (VI) from 100 ppm solutions. The adsorption capacity was 161 mg/g based on the Langmuir isotherm model. The adsorption kinetics followed a pseudo-second order model. Increasing the temperature from 20 to 50 °C increased the initial adsorption rate but had a minor effect on the equilibrium adsorption capacity. Thermodynamics studies showed that the process was spontaneous and endothermic. The activation energy was estimated as 24.5 kJ/mol, indicating physisorption. FTIR analyses before and after adsorption showed the involvement of hydroxyl, carbonyl and carboxyl groups in binding the Cr (VI). The Cr (VI) was reduced to Cr (III), which then bound to functional groups on the adsorbent. Desorption under acidic conditions could recover 36% of the adsorbed Cr as Cr (III). No desorption occurred at a neutral pH, indicating irreversible adsorption. Overall, acid-modified banana peel is an efficient, low-cost and eco-friendly adsorbent for removing toxic Cr (VI) from wastewater.

Prediction of upcoming urinary tract infection after intracerebral hemorrhage: a machine learning approach based on statistics collected at multiple time points.

Purpose: Accurate prediction of urinary tract infection (UTI) following intracerebral hemorrhage (ICH) can significantly facilitate both timely medical interventions and therapeutic decisions in neurocritical care. Our study aimed to propose a machine learning method to predict an upcoming UTI by using multi-time-point statistics. Methods: A total of 110 patients were identified from a neuro-intensive care unit in this research. Laboratory test results at two time points were chosen: Lab 1 collected at the time of admission and Lab 2 collected at the time of 48 h after admission. Univariate analysis was performed to investigate if there were statistical differences between the UTI group and the non-UTI group. Machine learning models were built with various combinations of selected features and evaluated with accuracy (ACC), sensitivity, specificity, and area under the curve (AUC) values. Results: Corticosteroid usage (p < 0.001) and daily urinary volume (p < 0.001) were statistically significant risk factors for UTI. Moreover, there were statistical differences in laboratory test results between the UTI group and the non-UTI group at the two time points, as suggested by the univariate analysis. Among the machine learning models, the one incorporating clinical information and the rate of change in laboratory parameters outperformed the others. This model achieved ACC = 0.773, sensitivity = 0.785, specificity = 0.762, and AUC = 0.868 during training and 0.682, 0.685, 0.673, and 0.751 in the model test, respectively. Conclusion: The combination of clinical information and multi-time-point laboratory data can effectively predict upcoming UTIs after ICH in neurocritical care.

Predicting visual recovery in pituitary adenoma patients post-endoscopic endonasal transsphenoidal surgery: Harnessing delta-radiomics of the optic chiasm from MRI.

OBJECTIVES: To investigate whether morphological changes after surgery and delta-radiomics of the optic chiasm obtained from routine MRI could help predict postoperative visual recovery of pituitary adenoma patients. METHODS: A total of 130 pituitary adenoma patients were retrospectively enrolled and divided into the recovery group (n = 87) and non-recovery group (n = 43) according to visual outcome 1 year after endoscopic endonasal transsphenoidal surgery. Morphological parameters of the optic chiasm were measured preoperatively and postoperatively, including chiasmal thickness, deformed angle, and suprasellar extension. Delta-radiomics of the optic chiasm were calculated based on features extracted from preoperative and postoperative coronal T2-weighted images, followed by machine learning modeling using least absolute shrinkage and selection operator wrapped with support vector machine through fivefold cross-validation in the development set. The delta-radiomic model was independently evaluated in the test set, and compared with the combined model that incorporated delta-radiomics, significant clinical and morphological parameters. RESULTS: Postoperative morphological changes of the optic chiasm could not significantly be used as predictors for the visual outcome. In contrast, the delta-radiomics model represented good performances in predicting visual recovery, with an AUC of 0.821 in the development set and 0.811 in the independent test set. Moreover, the combined model that incorporated age and delta-radiomics features of the optic chiasm achieved the highest AUC of 0.841 and 0.840 in the development set and independent test set, respectively. CONCLUSIONS: Our proposed machine learning models based on delta-radiomics of the optic chiasm can be used to predict postoperative visual recovery of pituitary adenoma patients. CLINICAL RELEVANCE STATEMENT: Our delta-radiomics-based models from MRI enable accurate visual recovery predictions in pituitary adenoma patients who underwent endoscopic endonasal transsphenoidal surgery, facilitating better clinical decision-making and ultimately improving patient outcomes. KEY POINTS: • Prediction of the postoperative visual outcome for pituitary adenoma patients is important but challenging. • Delta-radiomics of the optic chiasm after surgical decompression represented better prognostic performances compared with its morphological changes. • The proposed machine learning models can serve as novel approaches to predict visual recovery for pituitary adenoma patients in clinical practice.

Structure-Activity Relationships of Metal-Based Inhibitors of the Mitochondrial Calcium Uniporter.

The mitochondrial calcium uniporter (MCU) is a transmembrane protein that is responsible for mediating mitochondrial calcium (mCa2+ ) uptake. Given this critical function, the MCU has been implicated as an important target for addressing various human diseases. As such, there has a been growing interest in developing small molecules that can inhibit this protein. To date, metal coordination complexes, particularly multinuclear ruthenium complexes, are the most widely investigated MCU inhibitors due to both their potent inhibitory activities as well as their longstanding use for this application. Recent efforts have expanded the metal-based toolkit for MCU inhibition. This concept paper summarizes the development of new metal-based inhibitors of the MCU and their structure-activity relationships in the context of improving their potential for therapeutic use in managing human diseases related to mCa2+ dysregulation.

A Fluorogenic Inhibitor of the Mitochondrial Calcium Uniporter.

Inhibitors of the mitochondrial calcium uniporter (MCU) are valuable tools for studying the role of mitochondrial Ca2+ in various pathophysiological conditions. In this study, a new fluorogenic MCU inhibitor, RuOCou, is presented. This compound is an analogue of the known MCU inhibitor Ru265 that contains fluorescent axial coumarin carboxylate ligands. Upon aquation of RuOCou and release of the axial coumarin ligands, a simultaneous increase in its MCU-inhibitory activity and fluorescence intensity is observed. The fluorescence response of this compound enabled its aquation to be monitored in both HeLa cell lysates and live HeLa cells. This fluorogenic prodrug represents a potential theranostic MCU inhibitor that can be leveraged for the treatment of human diseases related to MCU activity.

Carboxylate-Capped Analogues of Ru265 Are MCU Inhibitor Prodrugs.

The mitochondrial calcium uniporter (MCU) is a transmembrane protein that resides on the inner membrane of the mitochondria and mediates calcium uptake into this organelle. Given the critical role of mitochondrial calcium trafficking in cellular function, inhibitors of this channel have arisen as tools for studying the biological relevance of this process and as potential therapeutic agents. In this study, four new analogues of the previously reported Ru-based MCU inhibitor [ClRu(NH3)4(µ-N)Ru(NH3)4Cl]Cl3 (Ru265) are reported. These compounds, which bear axial carboxylate ligands, are of the general formula [(RCO2)Ru(NH3)4(µ-N)Ru(NH3)4(O2CR)]X3, where X = NO3- or CF3SO3- and R = H (1), CH3 (2), CH2CH3 (3), and (CH2)2CH3 (4). These complexes were fully characterized by IR spectroscopy, NMR spectroscopy, and elemental analysis. X-ray crystal structures of 1 and 3 were obtained, revealing the expected presence of both the linear Ru(µ-N)Ru core and axial formate and propionate ligands. The axial carboxylate ligands of complexes 1-4 are displaced by water in buffered aqueous solution to give the aquated compound Ru265'. The kinetics of these processes were measured by 1H NMR spectroscopy, revealing half-lives that span 5.9-9.9 h at 37 °C. Complex 1 with axial formate ligands underwent aquation approximately twice as fast as the other compounds. In vitro cytotoxicity and mitochondrial membrane potential measurements carried out in HeLa and HEK293T cells demonstrated that none of these four complexes negatively affects cell viability or mitochondrial function. The abilities of 1-4 to inhibit mitochondrial calcium uptake in permeabilized HEK293T cells were assessed and compared to that of Ru265. Fresh solutions of 1-4 are approximately 2-fold less potent than Ru265 with IC50 values in the range of 14.7-19.1 nM. Preincubating 1-4 in aqueous buffers for longer time periods to allow for the aquation reactions to proceed increases their potency of mitochondrial uptake inhibition to match that of Ru265. This result indicates that 1-4 are aquation-activated prodrugs of Ru265'. Finally, 1-4 were shown to inhibit mitochondrial calcium uptake in intact, nonpermeabilized cells, revealing their value as tools and potential therapeutic agents for mitochondrial calcium-related disorders.

An Anticancer Rhenium Tricarbonyl Targets Fe-S Cluster Biogenesis in Ovarian Cancer Cells.

Target identification remains a critical challenge in inorganic drug discovery to deconvolute potential polypharmacology. Herein, we describe an improved approach to prioritize candidate protein targets based on a combination of dose-dependent chemoproteomics and treatment effects in living cancer cells for the rhenium tricarbonyl compound TRIP. Chemoproteomics revealed 89 distinct dose-dependent targets with concentrations of competitive saturation between 0.1 and 32 µM despite the broad proteotoxic effects of TRIP. Target-response networks revealed two highly probable targets of which the Fe-S cluster biogenesis factor NUBP2 was competitively saturated by free TRIP at nanomolar concentrations. Importantly, TRIP treatment led to a down-regulation of Fe-S cluster containing proteins and upregulated ferritin. Fe-S cluster depletion was further verified by assessing mitochondrial bioenergetics. Consequently, TRIP emerges as a first-in-class modulator of the scaffold protein NUBP2, which disturbs Fe-S cluster biogenesis at sub-cytotoxic concentrations in ovarian cancer cells.

Probing the Drug Dynamics of Chemotherapeutics Using Metasurface-Enhanced Infrared Reflection Spectroscopy of Live Cells.

Infrared spectroscopy has drawn considerable interest in biological applications, but the measurement of live cells is impeded by the attenuation of infrared light in water. Metasurface-enhanced infrared reflection spectroscopy (MEIRS) had been shown to mitigate the problem, enhance the cellular infrared signal through surface-enhanced infrared absorption, and encode the cellular vibrational signatures in the reflectance spectrum at the same time. In this study, we used MEIRS to study the dynamic response of live cancer cells to a newly developed chemotherapeutic metal complex with distinct modes of action (MoAs): tricarbonyl rhenium isonitrile polypyridyl (TRIP). MEIRS measurements demonstrated that administering TRIP resulted in long-term (several hours) reduction in protein, lipid, and overall refractive index signals, and in short-term (tens of minutes) increase in these signals, consistent with the induction of endoplasmic reticulum stress. The unique tricarbonyl IR signature of TRIP in the bioorthogonal spectral window was monitored in real time, and was used as an infrared tag to detect the precise drug delivery time that was shown to be closely correlated with the onset of the phenotypic response. These results demonstrate that MEIRS is an effective label-free real-time cellular assay capable of detecting and interpreting the early phenotypic responses of cells to IR-tagged chemotherapeutics.

Differentiation between Germinoma and Craniopharyngioma Using Radiomics-Based Machine Learning.

For the tumors located in the anterior skull base, germinoma and craniopharyngioma (CP) are unusual types with similar clinical manifestations and imaging features. The difference in treatment strategies and outcomes of patients highlights the importance of making an accurate preoperative diagnosis. This retrospective study enrolled 107 patients diagnosed with germinoma (n = 44) and CP (n = 63). The region of interest (ROI) was drawn independently by two researchers. Radiomic features were extracted from contrast-enhanced T1WI and T2WI sequences. Here, we established the diagnosis models with a combination of three selection methods, as well as three classifiers. After training the models, their performances were evaluated on the independent validation cohort and compared based on the index of the area under the receiver operating characteristic curve (AUC) in the validation cohort. Nine models were established and compared to find the optimal one defined with the highest AUC in the validation cohort. For the models applied in the contrast-enhanced T1WI images, RFS + RFC and LASSO + LDA were observed to be the optimal models with AUCs of 0.91. For the models applied in the T2WI images, DC + LDA and LASSO + LDA were observed to be the optimal models with AUCs of 0.88. The evidence of this study indicated that radiomics-based machine learning could be potentially considered as the radiological method in the presurgical differential diagnosis of germinoma and CP with a reliable diagnostic performance.

Photochemistry and in vitro anticancer activity of Pt(IV)Re(I) conjugates.

The photophysical and photochemical properties of two Pt(IV)Re(I) conjugates were studied via both experimental and computational methods. Both conjugates exhibit modest photocytotoxicity against ovarian cancer cells. X-ray fluorescence microscopy showed that Pt and Re colocalize in cells whether they had been irradiated or not. This work demonstrates the potential of photoactivated multilimetallic agents for combating cancer.

Systematically altering the lipophilicity of rhenium(I) tricarbonyl anticancer agents to tune the rate at which they induce cell death.

Rhenium-based anticancer agents have arisen as promising alternatives to conventional platinum-based drugs. Based on previous studies demonstrating how increasing lipophilicity improves drug uptake within the cell, we sought to investigate the effects of lipophilicity on the anticancer activity of a series of six rhenium(i) tricarbonyl complexes. These six rhenium(i) tricarbonyl structures, called Re-Chains, bear pyridyl imine ligands with different alkyl chains ranging in length from two to twelve carbons. The cytotoxicities of these compounds were measured in HeLa cells. At long timepoints (48 h), all compounds are equally cytotoxic. At shorter time points, however, the compounds with longer alkyl chains are significantly more active than those with smaller chains. Cellular uptake studies of these compounds show that they are taken up via both passive and active pathways. Collectively, these studies show how lipophilicity affects the rate at which these Re compounds induce their biological activities.