Mechanism of Action of Antitumor Au(I) N-Heterocyclic Carbene Complexes: A Computational Insight on the Targeting of TrxR Selenocysteine.

The targeting of human thioredoxin reductase is widely recognized to be crucially involved in the anticancer properties of several metallodrugs, including Au(I) complexes. In this study, the mechanism of reaction between a set of five N-heterocyclic carbene Au(I) complexes and models of the active Sec residue in human thioredoxin reductase was investigated by means of density functional theory approaches. The study was specifically addressed to the kinetics and thermodynamics of the tiled process by aiming at elucidating and explaining the differential inhibitory potency in this set of analogous Au(I) bis-carbene complexes. While the calculated free energy profile showed a substantially similar reactivity, we found that the binding of these Au(I) bis-carbene at the active CysSec dyad in the TrxR enzyme could be subjected to steric and orientational restraints, underlining both the approach of the bis-carbene scaffold and the attack of the selenol group at the metal center. A new and detailed mechanistic insight to the anticancer activity of these Au(I) organometallic complexes was thus provided by consolidating the TrxR targeting paradigm.

Age represents the main driver of surgical decision making in patients candidate to radical cystectomy.

BACKGROUND AND OBJECTIVES: Age might influence the choice of surgical approach, type of urinary diversion (UD) and lymph node dissection (LND) in patients candidate to radical cystectomy (RC) for urothelial bladder cancer (UBC). Similarly, age may enhance surgical morbidity and worsen perioperative outcomes. We tested the impact of age (octogenarian vs. younger patients) on surgical decision making and peri- and postoperative outcomes of RC. METHODS: Non-metastatic muscle-invasive UBC patients treated with RC at 18 high-volume European institutions between 2006 and 2021 were identified and stratified according to age (≥80 vs. <80 years). Intraoperative Complications Assessment and Reporting with Universal Standards and European Association of Urology guidelines recommendations were accomplished in collection and reporting of, respectively, intraoperative and postoperative complications. Multivariable logistic regression models (MVA) tested the impact of age on outcomes of interest. Sensitivity analyses after 1:3 propensity score matching were performed. RESULTS: Of 1955 overall patients, 251 (13%) were ≥80-year-old. Minimally invasive RC was performed in 18% and 40% of octogenarian and younger patients, respectively (p < 0.001). UD without bowel manipulation (ureterocutaneostomy, UCS) was performed in 31% and 7% of octogenarian and younger patients (p < 0.001). LND was delivered to 81% and 93% of octogenarian and younger patients (p < 0.001). At MVA, age ≥80 years independently predicted open approach (odds ratio [OR]: 1.55), UCS (OR: 3.70), and omission of LND (OR: 0.41; all p ≤ 0.02). Compared to their younger counterparts, octogenarian patients experienced higher rates of intraoperative (8% vs. 4%, p = 0.04) but not of postoperative complications (64% vs. 61%, p = 0.07). At MVA, age ≥80 years was not an independent predictor of length of stay, intraoperative or postoperative transfusions and complications, and readmissions (all p values >0.1). These results were replicated in sensitivity analyses. CONCLUSIONS: Age ≥80 years does not independently portend worse surgical outcomes for RC. However, octogenarians are unreasonably more likely to receive open approach and UCS diversion, and less likely to undergo LND.

Immediate radical cystectomy versus BCG immunotherapy for T1 high-grade non-muscle-invasive squamous bladder cancer: an international multi-centre collaboration.

PURPOSE: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). METHODS: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. RESULTS: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). CONCLUSION: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.

A Fully Linear Response G0W0 Method That Scales Linearly up to Tens of Thousands of Cores.

We present a G0W0 approach that is based on the evaluation of the linear response of the actions of the G0 and W0 operators. In this way we avoid sums over empty one-particle orbitals and do not have to explicitly develop the screened Coulomb interaction W0 on a dedicated basis. For a given orbital, the self-energy is found by summing terms relative to a set of points in the real-space simulation cell. This permits us to easily control the ratio of the accuracy to the computational cost. A trivial parallelization strategy allows strong linear scaling up to tens of thousands of computing cores.

Retzius-Sparing versus Standard Robot-Assisted Radical Prostatectomy: A Comparative Prospective Study of Nearly 500 Patients.

PURPOSE: We compared standard robot-assisted radical prostatectomy and Retzius-sparing robot-assisted radical prostatectomy in a multicenter study using prospective patient reported outcome measures of functional recovery and quality of life plus standard pentafecta outcomes. MATERIALS AND METHODS: Patient and physician reported data on 483 patients who underwent robot-assisted radical prostatectomy and Retzius-sparing robot-assisted radical prostatectomy from August 2017 to April 2020 by 3 experienced surgeons had been prospectively collected. Perioperative and pentafecta outcomes were analyzed using SPSS software. Patient reported outcome measures for urinary function, erectile function and quality of life were reported at baseline and at 7 days and 1, 3, 6, 9 and 12 months postoperatively. RESULTS: A total of 201 patients underwent robot-assisted radical prostatectomy and 282 had Retzius-sparing robot-assisted radical prostatectomy. Patient and tumor characteristics were similar except for fewer low risk and more intermediate risk disease in robot-assisted radical prostatectomy vs Retzius-sparing robot-assisted radical prostatectomy (p <0.001). High risk disease was similar between groups (p=0.071). Immediate urinary continence was higher in Retzius-sparing robot-assisted radical prostatectomy group (70.4% vs 58.1%, p=0.02), with less nocturnal enuresis prevalence (p=0.011) and bother (p=0.009) with no significant differences afterwards. A better quality of life (p=0.004) was reported 1 week after surgery. No other differences in functional or quality of life outcomes, perioperative parameters, complications or margin rates were found. CONCLUSIONS: Retzius-sparing robot-assisted radical prostatectomy is associated with better immediate continence than anterior robot-assisted radical prostatectomy with no differences in longer-term functional recovery, quality of life or other important outcomes. The overall similarity in outcomes between groups lends support to the view that the surgical technique matters less than the surgeon performing it.

Artificial photosynthesis: photoanodes based on polyquinoid dyes onto mesoporous tin oxide surface.

Dye-sensitized photoelectrochemical cells represent an appealing solution for artificial photosynthesis, aimed at the conversion of solar light into fuels or commodity chemicals. Extensive efforts have been directed towards the development of photoelectrodes combining semiconductor materials and organic dyes; the use of molecular components allows to tune the absorption and redox properties of the material. Recently, we have reported the use of a class of pentacyclic quinoid organic dyes (KuQuinone) chemisorbed onto semiconducting tin oxide as photoanodes for water oxidation. In this work, we investigate the effect of the SnO2 semiconductor thickness and morphology and of the dye-anchoring group on the photoelectrochemical performance of the electrodes. The optimized materials are mesoporous SnO2 layers with 2.5 µm film thickness combined with a KuQuinone dye with a 3-carboxylpropyl-anchoring chain: these electrodes achieve light-harvesting efficiency of 93% at the maximum absorption wavelength of 533 nm, and photocurrent density J up to 350 µA/cm2 in the photoelectrochemical oxidation of ascorbate, although with a limited incident photon-to-current efficiency of 0.075%. Calculations based on the density functional theory (DFT) support the role of the reduced species of the KuQuinone dye via a proton-coupled electron transfer as the competent species involved in the electron transfer to the tin oxide semiconductor. Finally, a preliminary investigation of the photoelectrodes towards benzyl alcohol oxidation is presented, achieving photocurrent density up to 90 µA/cm2 in acetonitrile in the presence of N-hydroxysuccinimide and pyridine as redox mediator and base, respectively. These results support the possibility of using molecular-based materials in synthetic photoelectrochemistry.

Partial versus radical nephrectomy in very elderly patients: a propensity score analysis of surgical, functional and oncologic outcomes (RESURGE project).

PURPOSE: To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor. PATIENTS AND METHODS: A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM). RESULTS: A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p < 0.01). PN was not correlated with OM (HR = 0.71; p = 0.56), OCM (HR = 0.74; p = 0.5), and showed a protective trend for CSM (HR = 0.19; p = 0.05). PN was found to be a protective factor for surgical CKD (HR = 0.28; p < 0.01) and worsening of eGFR in patients with baseline CKD. Retrospective design represents a limitation of this analysis. CONCLUSIONS: Adoption of PN in very elderly patients with localized renal tumor does not compromise oncological outcomes, and it allows better functional preservation at mid-term (3-year) follow-up, relative to RN. Whether this functional benefit translates into a survival benefit remains to be determined.

Urology in the Time of Coronavirus: Reduced Access to Urgent and Emergent Urological Care during the Coronavirus Disease 2019 Outbreak in Italy.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has put a substantial burden on the Italian healthcare system, resulting in the restructuring of hospitals to care for COVID-19 patients. However, this has likely impacted access to care for patients experiencing other conditions. We aimed to quantify the impact of COVID-19 on access to care for patients with urgent/emergent urological conditions throughout Italy. MATERIALS AND METHODS: A questionnaire was sent to 33 urological units in the AGILE consortium, asking clinicians to report on the number of urgent/emergent urological patients seen and/or undergoing surgery over a 3-week period during the peak of the COVID-19 outbreak and a reference week prior to the outbreak. ANOVA and linear regression models were used to quantify these changes. RESULTS: Data from 27 urological centres in Italy showed a decrease from 956 patients/week seen just prior to the outbreak to 291 patients/week seen by the end of the study period. There was a difference in the number of patients with urgent/emergent urological disease seen within/during the different weeks (all p values < 0.05). A significant decrease in the number of patients presenting with haematuria, urinary retention, urinary tract infection, scrotal pain, renal colic, or trauma and urgent/emergent cases that required surgery was reported (all p values < 0.05). CONCLUSION: In Italy, during the COVID-19 outbreak there has been a decrease in patients seeking help for urgent/emergent urological conditions. Restructuring of hospitals and clinics is mandatory to cope with the COVID-19 pandemic; however, the healthcare system should continue to provide adequate levels of care also to patients with other conditions.

Assessing perioperative, functional and oncological outcomes of patients with imperative versus elective indications for robot-assisted partial nephrectomy: Results from a high-volume center.

OBJECTIVE: To determine the impact of imperative or elective indications on the perioperative, functional and oncological outcomes of patients undergoing robot-assisted partial nephrectomy. METHODS: Between June 2006 and September 2016, data of patients who underwent robot-assisted partial nephrectomy at the Onze-Lieve-Vrouwziekenhuis Hospital in Aalst, Belgium, were retrospectively reviewed from a prospectively collected database. Only patients with non-metastatic, clinical T1-T2 graded tumors were included. Perioperative, functional and oncological outcomes were recollected. A comparative analysis was carried out after dividing patients into two groups: those who underwent robot-assisted partial nephrectomy for an elective indication (group 1, n = 194), and for an imperative indication (group 2, n = 57) caused by a solitary kidney (n = 20), impaired renal function (n = 2) or both (n = 35). RESULTS: Patients in group 2 were older (74 vs 71 years, P < 0.001), and had a higher Charlson Comorbidity Index (P < 0.001) and American Society of Anesthesiologists score (P < 0.001). No differences were observed concerning laterality, sex, preoperative aspects and dimensions used for an anatomical score or clinical stage. Surgical outcomes considering estimated blood loss, surgical time, ischemia time and transfusion rate showed no significant difference between groups. The complication rate according to Clavien-Dindo showed no difference between groups (P = 0.6). No difference was found between groups with regard to percentage decrease of estimated glomerular filtration rate (7.4 vs 4.8%, P < 0.15). CONCLUSIONS: Robot-assisted partial nephrectomy can be safely and effectively carried out by experienced surgeons in a high-volume center with similar perioperative, functional and oncological outcomes for both elective or imperative indications.

Robotic Assisted Simple Prostatectomy versus Holmium Laser Enucleation of the Prostate for Lower Urinary Tract Symptoms in Patients with Large Volume Prostate: A Comparative Analysis from a High Volume Center.

PURPOSE: We report a comparative analysis of robotic assisted simple prostatectomy vs holmium laser enucleation of the prostate in patients who had benign prostatic hyperplasia with a large volume prostate (greater than 100 ml). MATERIALS AND METHODS: A total of 81 patients underwent robotic assisted simple prostatectomy and 45 underwent holmium laser enucleation of the prostate in a 7-year period. Patients were preoperatively assessed with transrectal ultrasound and uroflowmetry. Functional parameters were assessed postoperatively during followup. Perioperative outcomes included operative time, postoperative hemoglobin, catheterization time and hospitalization. Complications were reported according to the Clavien-Dindo classification. RESULTS: Compared to the holmium laser enucleation group, patients treated with prostatectomy were significantly younger (median age 69 vs 74 years, p = 0.032) and less healthy (Charlson comorbidity index 2 or greater in 62% vs 29%, p = 0.0003), and had a lower rate of suprapubic catheterization (23% vs 42%, p = 0.028) and a higher preoperative I-PSS (International Prostate Symptom Score) (25 vs 21, p = 0.049). Both groups showed an improvement in the maximum flow rate (15 vs 11 ml per second, p = 0.7), and a significant reduction in post-void residual urine (-73 vs -100 ml, p = 0.4) and I-PSS (-20 vs -18, p = 0.8). Median operative time (105 vs 105 minutes, p = 0.9) and postoperative hemoglobin (13.2 vs 13.8 gm/dl, p = 0.08) were similar for robotic assisted prostatectomy and holmium laser enucleation, respectively. Median catheterization time (3 vs 2 days, p = 0.005) and median hospitalization (4 vs 2 days, p = 0.0001) were slightly shorter in the holmium laser group. Complication rates were similar with no Clavien grade greater than 3 in either group. CONCLUSIONS: Our results from a single center suggest comparable outcomes for robotic assisted simple prostatectomy and holmium laser enucleation of the prostate in patients with a large volume prostate. These findings require external validation at other high volume centers.

Chlorine Incorporation in the CH3NH3PbI3 Perovskite: Small Concentration, Big Effect.

The role of chlorine doping in CH3NH3PbI3 represents an important open issue in the use of hybrid perovskites for photovoltaic applications. In particular, even if a positive role of chlorine doping on perovskite film formation and on material morphology has been demonstrated, an inherent positive effect on the electronic and photovoltaic properties cannot be excluded. Here we carried out periodic density functional theory and Car-Parrinello molecular dynamics simulations, going down to ∼1% doping, to investigate the effect of chlorine on CH3NH3PbI3. We found that such a small doping has important effects on the dynamics of the crystalline structure, both with respect to the inorganic framework and with respect to the cation libration motion. Together, we observe a dynamic spatial localization of the valence and conduction states in separated spatial material regions, which takes place in the 10-1 ps time scale and which could be the key to ease of exciton dissociation and, likely, to small charge recombination in hybrid perovskites. Moreover, such localization is enhanced by chlorine doping, demonstrating an inherent positive role of chlorine doping on the electronic properties of this class of materials.

Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer.

Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC) is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC) instillation in patients with high-risk recurrent NMIBC. MATERIALS AND METHODS: Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT) system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel). The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria) score system. RESULTS: Mean age was 72 (32-87) years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period). 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3%) were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. CONCLUSIONS: BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

Electronic and optical properties of MAPbX3 perovskites (X = I, Br, Cl): a unified DFT and GW theoretical analysis.

Materials engineering is a key for the enhancement of photovoltaics technology. This is particularly true for the novel class of perovskite solar cells. Accurate theoretical modelling can help establish general trends of behavior when addressing structural changes. Here, we consider the effects due to halide substitution in organohalide CH3NH3PbX3 perovskites exploring the halide series with X = Cl, Br, I. For this task, we use accurate DFT and GW methods including spin-orbit coupling. We find the expected band gap increase when moving from X = I to Cl, in line with the experimental data. Most notably, the calculated absorption coefficients for I, Br and Cl are nicely reproducing the behavior reported experimentally. A common feature of all the simulated band structures is a significant Rashba effect. This is similar for MAPbI3 and MAPbBr3 while MAPbCl3 shows in general a reduced Rashba interaction coefficient. Finally, a monotonic increase of the exciton reduced masses is calculated when moving from I to Br to Cl, in line with the stronger excitonic character of the lighter perovskite halides.

Cation-induced band-gap tuning in organohalide perovskites: interplay of spin-orbit coupling and octahedra tilting.

Organohalide lead perovskites have revolutionized the scenario of emerging photovoltaic technologies. The prototype MAPbI3 perovskite (MA = CH3NH3(+)) has dominated the field, despite only harvesting photons above 750 nm (∼1.6 eV). Intensive research efforts are being devoted to find new perovskites with red-shifted absorption onset, along with good charge transport properties. Recently, a new perovskite based on the formamidinium cation ((NH2)2CH(+) = FA) has shown potentially superior properties in terms of band gap and charge transport compared to MAPbI3. The results have been interpreted in terms of the cation size, with the larger FA cation expectedly delivering reduced band-gaps in Pb-based perovskites. To provide a full understanding of the interplay among size, structure, and organic/inorganic interactions in determining the properties of APbI3 perovskites, in view of designing new materials and fully exploiting them for solar cells applications, we report a fully first-principles investigation on APbI3 perovskites with A = Cs(+), MA, and FA. Our results evidence that the tetragonal-to-quasi cubic structural evolution observed when moving from MA to FA is due to the interplay of size effects and enhanced hydrogen bonding between the FA cations and the inorganic matrix altering the covalent/ionic character of Pb-I bonds. Most notably, the observed cation-induced structural variability promotes markedly different electronic and optical properties in the MAPbI3 and FAPbI3 perovskites, mediated by the different spin-orbit coupling, leading to improved charge transport and red-shifted absorption in FAPbI3 and in general in pseudocubic structures. Our theoretical model constitutes the basis for the rationale design of new and more efficient organohalide perovskites for solar cells applications.

Penile fracture: retrospective analysis of our case history with long-term assessment of the erectile and sexological outcome.

OBJECTIVES: To review the cases of patients with suspected penile fracture and asses erectile and sexological outcomes. MATERIALS AND METHODS: from 1987 to 2013 presented to the Urology Clinic of Trieste and at the AIED of Pordenone a total of 41 cases that were divided into two groups according to the timing of treatment: 18 patients with anamnestic diagnosis of penile fracture treated nonimmediately and 23 patients treated immediately after the trauma. For all patients we evaluated the type of treatment adopted, the occurrence of complications and reoperations and the follow-up. The erectile function was also evaluated through the IIEF, as well as the psychological impact of the trauma on social and sex life, using a psycho- sexological questionnaire. RESULTS: Among patients treated immediately after the trauma 14 were subjected to surgery. About a year after surgery, penile curvature was reported in 1 patient, pain in 3 patients, urinary disorders in 1 patient, while none reported erectile dysfunction (ED). Out of these, only 3 patients underwent reoperation. Among those treated conservatively 1 patient reported curvature, 1 patient reported pain and none reported ED. Among patients who were admitted at a later date, 14 reported curvature and 4 reported pain whereas urinary disorders were reported in 1 and ED in 4 patients. From a psychological point of view, the trauma caused in most cases a fear of new trauma and of repercussions on erectile function and sensitivity. CONCLUSIONS: The diagnosis is mainly clinical; however, radiological investigation is essential to confirm the diagnosis, assess the site and extent of the trauma and possible urethral involvement, so as to plan the most appropriate treatment. In addition, immediate treatment leads to better long-term results, with a lower incidence of ED and penile curvature. Psychologically, penile trauma intensifies the fear of reoccurrence; it decreases, however, with the passage of time.

Diruthenium Paddlewheel Complexes Attacking Proteins: Axial versus Equatorial Coordination.

Metallodrugs are an important group of medicinal agents used for the treatment of various diseases ranging from cancers to viral, bacterial, and parasitic diseases. Their distinctive features include the availability of a metal centre, redox activity, as well as the ability to multitarget. Diruthenium paddlewheel complexes are an intensely developing group of metal scaffolds, which can securely coordinate bidentate xenobiotics and transport them to target tissues, releasing them by means of substitution reactions with biomolecular nucleophiles. It is of the utmost importance to gain a complete comprehension of which chemical reactions happen with them in physiological milieu to design novel drugs based on these bimetallic scaffolds. This review presents the data obtained in experiments and calculations, which clarify the chemistry these complexes undergo once administered in the proteic environment. This study demonstrates how diruthenium paddlewheel complexes may indeed embody a new paradigm in the design of metal-based drugs of dual-action by presenting and discussing the protein metalation by these complexes.

The binding of diruthenium (II,III) and dirhodium (II,II) paddlewheel complexes at DNA/RNA nucleobases: Computational evidences of an appreciable selectivity toward the AU base pairs.

Multiple medicinal strategies involve modifications of the structure of DNA or RNA, which disrupt their correct functioning. Metal complexes with medicinal effects, also known as metallodrugs, are among the agents intended specifically for the attack onto nucleosides. The diruthenium (II,III) and dirhodium (II,II) paddlewheel complexes constitute promising dual acting drugs due to their ability to release the therapeutically active bridging ligands upon their substitution by endogenous ligands. In this paper, we study the structure and the stability of the complexes formed by the diruthenium (II,III) and dirhodium (II,II) paddlewheel complexes coordinated in axial positions with the DNA/RNA nucleobases or base pairs, assuming the attainable metalation at all the accessible pyridyl nitrogens. Dirhodium complexes coordinate at the pyridyl nitrogens more strongly than the diruthenium complexes. On the other hand, we found that the diruthenium scaffold binds more selectively to nucleobase targets. Furthermore, we reveal a tighter coordination of diruthenium complex at the adenine-uracil base pair, compared to adenine-thymine, hence constituting a scarce instance of RNA-selectivity. We envision that the here reported computational outcomes may pace future experiments addressing the binding of diruthenium and dirhodium paddlewheel complexes at either single nucleobases or DNA/RNA fragments.

Trifurcated Splitting of Water Droplets on Engineered Lithium Niobate Surfaces.

Controlled splitting of liquid droplets is a key function in many microfluidic applications. In recent years, various methodologies have been used to accomplish this task. Here, we present an optofluidic technique based on an engineered surface formed by coating a z-cut iron-doped lithium niobate crystal with a lubricant-infused layer, which provides a very slippery surface. Illuminating the crystal with a light spot induces surface charges of opposite signs on the two crystal faces because of the photovoltaic effect. If the light spot is sufficiently intense, millimetric water droplets placed near the illuminated spot split into two charged fragments, one fragment being trapped by the bright spot and the other moving away from it. The latter fragment does not move randomly but rather follows one of three well-defined trajectories separated by 120°, which reflect the anisotropic crystalline structure of Fe:LiNbO3. Numerical simulations explain the behavior of water droplets in the framework of the forces induced by the interplay of pyroelectric, piezoelectric, and photovoltaic effects, which originate simultaneously inside the illuminated crystal. Such a synergetic effect can provide a valuable feature in applications that require splitting and coalescence of droplets, such as chemical microreactors and biological encapsulation and screening.

Photoelectrochemical C-H Activation Through a Quinacridone Dye Enabling Proton-Coupled Electron Transfer.

Dye-sensitized photoanodes for C-H activation in organic substrates are assembled by vacuum sublimation of a commercially available quinacridone (QNC) dye in the form of nanosized rods onto fluorine-doped tin oxide (FTO), TiO2 , and SnO2 slides. The photoanodes display extended absorption in the visible range (450-600 nm) and ultrafast photoinduced electron injection (<1 ps, as revealed by transient absorption spectroscopy) of the QNC dye into the semiconductor. The proton-coupled electron-transfer reactivity of QNC is exploited for generating a nitrogen-based radical as its oxidized form, which is competent in C-H bond activation. The key reactivity parameter is the bond-dissociation free energy (BDFE) associated with the N⋅/N-H couple in QNC of 80.5±2.3 kcal mol-1 , which enables hydrogen atom abstraction from allylic or benzylic C-H moieties. A photoelectrochemical response is indeed observed for organic substrates characterized by C-H bonds with BDFE below the 80.5 kcal mol-1 threshold, such as γ-terpinene, xanthene, or dihydroanthracene. This work provides a rational, mechanistically oriented route to the design of dye-sensitized photoelectrodes for selective organic transformations.

Holmium Laser Enucleation of the Prostate vs Robot-Assisted Simple Prostatectomy for Lower Urinary Tract Symptoms in Patients with Extremely Large Prostates ≥200 cc: A Comparative Analysis.

Introduction and Objectives: Robot-assisted simple prostatectomy (RASP) and holmium laser enucleation of the prostate (HoLEP) are both well-established, minimally invasive surgical treatment options for lower urinary tract symptoms caused by benign prostatic enlargement. We have reported the first comparative analysis of both techniques in patients with prostates of ≥200 cc. Materials and Methods: Between 2009 and 2020 a total of 53 patients with a prostate volume of ≥200 cc were surgically treated at OLV Hospital Aalst (Belgium): 31 underwent RASP and 22 underwent HoLEP. Preoperative and postoperative assessments included uroflowmetry with maximum urinary flow rate (Qmax) and postvoid residual volume (PVR), as well as the International Prostate Symptom Score (IPSS) and quality of life (IPSS-QoL). The complication rates were evaluated according to the Clavien-Dindo Classification. Results: Patients treated with RASP had significantly larger prostate volumes compared with HoLEP (median 226 cc vs 204.5 cc, p = 0.004). After a median follow-up of 14 months, both groups showed a significant improvement in the maximum flow rate (+10.60 mL/s vs +10.70 mL/s, p = 0.724) and a reduction of the IPSS score (-12.50 vs -9, p = 0.246) as well as improvement of the QoL (-3 vs -3, p = 0.880). Median operative time was similar in both groups (150 minutes vs 132.5 minutes, p = 0.665). The amount of resected tissue was lower in the RASP group (134.5 g vs 180 g, p = 0.029) and there was no significant difference in postoperative prostate-specific antigen (1.2 ng/mL vs 0.8 ng/mL, p = 0.112). Despite a similar median catheterization time (3 days vs 2 days, p = 0.748), the median hospitalization time was shorter in the HoLEP group (4 days vs 3 days, p = 0.052). Complication rates were similar in both groups (32% vs 36%, p = 0.987). Conclusion: Our results suggest similar outcomes for RASP and HoLEP in patients with very large prostates ≥200 cc. These findings will require external validation at other high-volume centers.