Carbon Dioxide-Mediated Desalination.

Conventional desalination membrane technologies, although offer portable drinking water, are still energy-intensive processes. This paper proposes a potentially new approach for performing water desalination and purification by utilizing the reversible interaction of carbon dioxide (CO2) with nucleophilic amines─reminiscent of the Solvay process. Based on our model studies with small molecules, CO2-responsive amphiphilic insoluble diamines were prepared, characterized, and applied in the formation of soda and ammonium chloride upon exposure to ambient CO2 (1 atm), thus removing chloride ions from model and real seawater. This ion-exchange process and separation of chloride from the aqueous phase are spontaneous in the presence of CO2 without the need for external energy sources. We demonstrate a flow system to envisage energy-efficient CO2-mediated desalination and simultaneous carbon capture and sequestration.

Impact of Chart-Derived Frailty Index on 1-Year Mortality After Radical Cystectomy in 1004 Patients with Bladder Cancer.

BACKGROUND: Radical cystectomy is a major urological procedure with high morbidity and mortality. The chart-derived frailty index (CFI), a measure of preoperative frailty, can be calculated by using demographic and routine laboratory variables. We assessed the impact of CFI on 1-year mortality after radical cystectomy. METHODS: This retrospective study included patients with bladder cancer who underwent radical cystectomy between 2007 and 2021. The CFI was calculated as the sum of the presence of the following parameters: age > 70 years, body mass index < 18.5 kg/m2, hematocrit < 35%, albumin < 3.4 g/dL, and creatinine > 2.0 mg/dL. Patients were divided into those with low (0-2) and high (3-5) CFI. The 1-year, all-cause and cancer-specific mortalities after radical cystectomy were evaluated. RESULTS: Of the 1004 patients, 914 (91.0%) had a low CFI and 90 (9.0%) had a high CFI. The 1-year, all-cause mortality in the low and high CFI groups was 12.0% and 27.8%, respectively (P < 0.001). Multivariate Cox regression analysis revealed that high CFI (P < 0.001), tumor stage (P = 0.003), and red blood cell transfusion amount (P < 0.001) were significantly associated with 1-year, all-cause mortality after radical cystectomy. Kaplan-Meier survival analysis demonstrated significantly different 1-year, all-cause and cancer-specific mortalities after radical cystectomy between patients with a high CFI and those with a low CFI (log-rank test, both P < 0.001). CONCLUSIONS: High CFI is associated with higher 1-year mortality after radical cystectomy, suggesting that the CFI can effectively predict mortality after radical cystectomy.

Comparison of the Intrableb Characteristics of Anterior Segment Optical Coherence Tomography Imaging in Trabeculectomy according to Amniotic Membrane Transplantation.

INTRODUCTION: The purpose of this study was to compare the characteristics of filtering bleb with anterior segment optical coherence tomography (AS-OCT) according to amniotic membrane transplantation (AMT). METHODS: One hundred and sixteen eyes of 103 glaucoma patients who underwent trabeculectomy with (AMT group; 85 eyes) or without AMT (control group; 31 eyes) were included. Intrableb parameters were evaluated with AS-OCT. Surgical success was defined as an intraocular pressure (IOP) ≤18 mm Hg and IOP reduction ≥20% without medication at the time of AS-OCT examination. Logistic regression analyses were performed to determine factors associated with IOP control. RESULTS: In the eyes with successful IOP control, the fluid-filled space area, score, and height were greater for the AMT group than the control group (all ps < 0.001), while stripping layer thickness was greater and bleb wall reflectivity was lower for the control group than the AMT group (all ps < 0.001). Surgical success in the AMT group was associated with greater fluid-filled space score, lower bleb wall reflectivity, and microcyst formation (odds ratio [OR] = 8.016, 0.913, and 16.202, respectively, all ps ≤ 0.041). Lower bleb wall reflectivity alone was associated with surgical success in the control group (OR = 0.815, p = 0.019). CONCLUSION: The extent of the fluid-filled space was associated with successful IOP control after trabeculectomy with AMT. Hyporeflective bleb wall was associated with successful IOP control in AMT and control groups.

Neck Extension and Intraocular Pressure Elevation During Palatoplasty in a Patient with Patau Syndrome and Congenital Glaucoma: A Case Report.

Patau syndrome (trisomy 13) is a severe disorder associated with multiple systemic defects. Patau syndrome is commonly associated with ocular abnormalities but rarely associated with congenital glaucoma. To obtain a better surgical view, palatoplasty requires neck extension during surgery. The intraocular pressure (IOP) of patients with Patau syndrome can increase owing to the neck extension position while undergoing palatoplasty, particularly in those with congenital glaucoma. Here, we describe a case with increased IOP measured using a rebound tonometer during palatoplasty in a pediatric patient with Patau syndrome and congenital glaucoma. This case shows that it may be important to reduce the degree of neck extension and shorten the operation time to minimize any increase in the IOP during palatoplasty in pediatric patients with Patau syndrome accompanied by congenital glaucoma.

An ETS-NOCV-based computational strategies for the characterization of concerted transition states involving CO2.

Due to the presence of both a slightly acidic carbon and a slightly basic oxygen, carbon dioxide is often involved in concerted transition states (TSs) with two (or more) different molecular events interlaced in the same step. The possibility of isolating and quantitatively evaluating each molecular event would be important to characterize and understand the reaction mechanism in depth. This could be done, in principle, by measuring the relevant distances in the optimized TS, but often distances are not accurate enough, especially in the presence of many simultaneous processes. Here, we have applied the Extended Transition State-Natural Orbital for Chemical Valence-method (ETS-NOCV), also in combination with the Activation Strain Model (ASM) and Energy Decomposition Analysis (EDA), to separate and quantify these molecular events at the TS of both organometallic and organic reactions. For the former, we chose the decomposition of formic acid to CO2 by an iridium catalyst, and for the latter, a CO2 -mediated transamidation and its chemical variations (hydro- and aminolysis of an ester) as case studies. We demonstrate that the one-to-one mapping between the "molecular events" and the ETS-NOCV components is maintained along the entire lowest energy path connecting reactants and products around the TS, thus enabling a detailed picture on the relative importance of each interacting component. The methodology proposed here provides valuable insights into the effect of different chemical substituents on the reaction mechanism and promises to be generally applicable for any concerted TSs.

Cooperative Asymmetric Cation-Binding Catalysis.

Asymmetric cation-binding catalysis in principle enables the use of (alkali) metal salts, otherwise insoluble in organic solvents, as reagents and effectors in enantioselective reactions. However, this concept has been a formidable challenge due to the difficulties associated with creating a highly organized chiral environment for cations and anions simultaneously. Over the last four decades, various chiral crown ethers have been developed as cation-binding phase-transfer catalysts and examined in asymmetric catalysis. However, the limited ability of chiral crown ethers to generate soluble reactive anions in a confined chiral cage offers a restricted reaction scope and unsatisfactory chirality induction. To address the constraints of monofunctional chiral crown ethers as cation-binding catalysts, it is therefore desirable to develop a cooperative cation-binding catalyst possessing secondary binding sites for anions, which enables the generation of a reactive anion within a chiral cage of a catalyst. This account summarizes our design, development, and applications of chiral BINOL-based oligoethylene glycols (oligoEGs) as a new type of bifunctional cation-binding catalyst. We initially found that achiral oligoEGs were efficient promoters in nucleophilic fluorination with potassium fluoride. Thereby, we hypothesized that, by breaking the closed cyclic ether unit of chiral crown ethers, the free terminal -OH groups could activate the electrophiles by hydrogen bonding whereas the ether oxygens could act as the Lewis base to coordinate metal ions, thus generating soluble anions in a confined chiral cage. This hypothesis was realized by synthesizing a series of chiral variants of oligoEGs by connecting two 3,3'-disubstituted-BINOL units with glycol linkers. Readily available BINOL-based chiral oligoEGs enabled numerous asymmetric transformations out of the reach of chiral monofunctional crown ether catalysts. We have demonstrated that this new type of bifunctional cation-binding catalysts can generate a soluble fluoride anion from alkali metal fluorides, which can be a versatile chiral promoter for diverse asymmetric catalytic reactions, kinetic resolution (selectivity factor of up to ∼2300), asymmetric protonation, Mannich reactions, tandem cyclization reactions, and the isomerization of allylic alcohols and hemithioacetals. We have also successfully utilized our chiral oligoEG catalysts along with alkali metal salts of carbon- and heteroatom-based nucleophiles, respectively, for asymmetric Strecker reactions and the asymmetric synthesis of chiral aminals. The power of our cooperative cation-binding catalysis was exemplified by kinetic resolution reactions of secondary alcohols, achieving highly enantioselective catalysis with only <1 ppm loading of an organocatalyst with high TOFs (up to ∼1300 h-1 at 1 ppm catalyst loading). The broadness and generality of our cooperative asymmetric cation-binding catalysis can be ascribed, in a similar fashion, to active-site architectures of enzymes using allosteric interactions, highly confined chiral cages formed by the incorporation of alkali metal salts in the catalyst polyether chain backbone, and the cooperative activation of reacting partners by hydrogen-bonding and ion-ion interactions. Confining reactive components in such a chiral binding pocket leads to enhanced reactivity and efficient transfer of the stereochemical information.

Carbon dioxide enhances sulphur-selective conjugate addition reactions.

Sulphur-selective conjugate addition reactions play a central role in synthetic chemistry and chemical biology. A general tool for conjugate addition reactions should provide high selectivity in the presence of competing nucleophilic functional groups, namely nitrogen nucleophiles. We report CO2-mediated chemoselective S-Michael addition reactions where CO2 can reversibly control the reaction pHs, thus providing practical reaction conditions. The increased chemoselectivity for sulphur-alkylation products was ascribed to CO2 as a temporary and traceless protecting group for nitrogen nucleophiles, while CO2 efficiently provide higher conversion and selectivity sulphur nucleophiles on peptides and human serum albumin (HSA) with various electrophiles. This method offers simple reaction conditions for cysteine modification reactions when high chemoselectivity is required.

The microbiomes of the eyelid and buccal area of patients with uveitic glaucoma.

BACKGROUND: The microbiome could trigger inflammation leading to epigenetic changes and is involved in the pathophysiology of eye diseases; however, its effect on uveitic glaucoma (UG) has not been fully investigated. This study analysed the differences in eyelid and buccal microbiomes in patients with UG using next-generation sequencing. METHODS: The eyelid and buccal specimens of 34 UG and 25 control patients were collected. The taxonomic composition of the microbiome was obtained via 16S ribosomal DNA sequencing. Diversity and differential gene expression analyses (DEG) determined taxon differences between the microbiomes of UG and control groups. RESULTS: In both the eyelid and buccal microbiomes, alpha-diversity was lower in UG patients than controls, while beta-diversity in patients with UG was higher than in controls. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment of Paenibacillus and Dermacoccus (p-value, 1.31e-6 and 1.55e-7, respectively) and depletion of Morganella and Lactococcus (p-value, 6.26e-12 and 2.55e-6, respectively) in patients with UG. In the buccal microbiome, taxa such as Lactococcus was significantly depleted (p-value, 1.31e-17), whereas Faecalibacterium was enriched in patients with UG (p-value, 6.12e-8). CONCLUSIONS: The eyelid and buccal microbiomes in patients with UG differ from controls, which raises concerns surrounding environmental influences on the pathogenesis of UG. The reduced Lactococcus in the eyelid and buccal area suggest that microbiota dysbiosis is associated with UG.

Mode of action of quinoline antimalarial drugs in red blood cells infected by Plasmodium falciparum revealed in vivo.

The most widely used antimalarial drugs belong to the quinoline family. Their mode of action has not been characterized at the molecular level in vivo. We report the in vivo mode of action of a bromo analog of the drug chloroquine in rapidly frozen Plasmodium falciparum-infected red blood cells. The Plasmodium parasite digests hemoglobin, liberating the heme as a byproduct, toxic to the parasite. It is detoxified by crystallization into inert hemozoin within the parasitic digestive vacuole. By mapping such infected red blood cells with nondestructive X-ray microscopy, we observe that bromoquine caps hemozoin crystals. The measured crystal surface coverage is sufficient to inhibit further hemozoin crystal growth, thereby sabotaging heme detoxification. Moreover, we find that bromoquine accumulates in the digestive vacuole, reaching submillimolar concentration, 1,000-fold more than that of the drug in the culture medium. Such a dramatic increase in bromoquine concentration enhances the drug's efficiency in depriving heme from docking onto the hemozoin crystal surface. Based on direct observation of bromoquine distribution in the digestive vacuole and at its membrane surface, we deduce that the excess bromoquine forms a complex with the remaining heme deprived from crystallization. This complex is driven toward the digestive vacuole membrane, increasing the chances of membrane puncture and spillage of heme into the interior of the parasite.

Anomaly Detection Based on Time Series Data of Hydraulic Accumulator.

Although hydraulic accumulators play a vital role in the hydraulic system, they face the challenges of being broken by continuous abnormal pulsating pressure which occurs due to the malfunction of hydraulic systems. Hence, this study develops anomaly detection algorithms to detect abnormalities of pulsating pressure for hydraulic accumulators. A digital pressure sensor was installed in a hydraulic accumulator to acquire the pulsating pressure data. Six anomaly detection algorithms were developed based on the acquired data. A threshold averaging algorithm over a period based on the averaged maximum/minimum thresholds detected anomalies 2.5 h before the hydraulic accumulator failure. In the support vector machine (SVM) and XGBoost model that distinguish normal and abnormal pulsating pressure data, the SVM model had an accuracy of 0.8571 on the test set and the XGBoost model had an accuracy of 0.8857. In a convolutional neural network (CNN) and CNN autoencoder model trained with normal and abnormal pulsating pressure images, the CNN model had an accuracy of 0.9714, and the CNN autoencoder model correctly detected the 8 abnormal images out of 11 abnormal images. The long short-term memory (LSTM) autoencoder model detected 36 abnormal data points in the test set.

The lymphocyte/monocyte ratio and red blood cell transfusion during radical retropubic prostatectomy.

PURPOSE: Despite improvements of strategy in radical retropubic prostatectomy, blood loss is still a major concern. The lymphocyte/monocyte (LM) ratio is a prognostic indicator for various diseases. We identified the risk factors, including the LM ratio, for red blood cell (RBC) transfusion during radical retropubic prostatectomy. METHODS: This retrospective study assessed patients who underwent radical retropubic prostatectomy between March 2009 and December 2020. To determine the risk factors for RBC transfusion, a multivariate logistic regression analysis was conducted. A receiver operating characteristic (ROC) curve analysis was also performed. Postoperative outcomes, including acute kidney injury (AKI), hospitalization duration, and intensive care unit (ICU) admission, were also evaluated. RESULTS: Among 1302 patients, 158 patients (12.1%) received an intraoperative RBC transfusion. Multivariate logistic regression analysis demonstrated that the risk factors for RBC transfusion were the LM ratio, hemoglobin, 6% hydroxyethyl starch amount, and positive surgical margin. The area under the ROC curve of LM ratio was 0.706 (cut-off = 4.3). The LM ratio at ≤ 4.3 was significantly related to transfusion in multivariate-adjusted analysis (odds ratio = 4.598, P < 0.001). AKI and ICU admission were significantly higher, and the hospitalization duration was significantly longer in patients with RBC transfusion. CONCLUSIONS: The LM ratio was a risk factor for RBC transfusion in radical retropubic prostatectomy. The optimal cut-off value of the LM ratio to predict transfusion was 4.3. RBC transfusion was associated with poor postoperative outcomes. Therefore, our results suggest that the LM ratio provide useful information on RBC transfusion in radical retropubic prostatectomy.

Preoperative bullae and subsequent pneumothorax in 6605 patients who underwent robotic prostatectomy.

PURPOSE: Robotic prostatectomy is the most common surgical approach for treating prostate cancer. Patients undergoing robotic prostatectomy may have bullae, which may rupture leading to pneumothorax. We evaluated the incidence of pneumothorax due to preoperative bullae rupture in robotic prostatectomy. METHODS: A large retrospective study of patients who underwent robotic prostatectomy between 2009 and 2021 was conducted. Bullae were detected using chest computed tomography. Pneumothorax was detected using a chest X-ray. The primary outcome was the incidence of pneumothorax due to bullae rupture. Secondary outcomes were the prevalence of preoperative bullae and the evaluation of postoperative outcomes, including length of hospital stay, intensive care unit admission rate, and prolonged intensive care unit stay (> 2 days). RESULTS: A total of 6605 patients were included. The prevalence of preoperative bullae was 3.0% (196/6,605). There was no incidence of pneumothorax due to bullae rupture. No significant difference in the incidences of pneumothorax between patients with and without bullae (0/196 vs. 2/6,409, P > 0.999) was observed. In addition, length of hospital stay, intensive care unit admission rate, and prolonged intensive care unit stay were not significantly different between the two groups. Kaplan-Meier analysis showed that there was no significant difference in lengths of hospital stay between the two groups (log-rank test, P > 0.999). CONCLUSION: In our cohort, there was no incidence of pneumothorax following robotic prostatectomy in patients with preoperative bullae. This result could help in the management of patients with prostate cancer with bullae.

CO2 -Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions*.

Thermodynamic and kinetic control of a chemical process is the key to access desired products and states. Changes are made when a desired product is not accessible; one may manipulate the reaction with additional reagents, catalysts and/or protecting groups. Here we report the use of carbon dioxide to accelerate cyanohydrin synthesis under neutral conditions with an insoluble cyanide source (KCN) without generating toxic HCN. Under inert atmosphere, the reaction is essentially not operative due to the unfavored equilibrium. The utility of CO2 -mediated selective cyanohydrin synthesis was further showcased by broadening Kiliani-Fischer synthesis under neutral conditions. This protocol offers an easy access to a variety of polyols, cyanohydrins, linear alkylnitriles, by simply starting from alkyl- and arylaldehydes, KCN and an atmospheric pressure of CO2 .

A CO2-Catalyzed Transamidation Reaction.

Transamidation reactions are often mediated by reactive substrates in the presence of overstoichiometric activating reagents and/or transition metal catalysts. Here we report the use of CO2 as a traceless catalyst: in the presence of catalytic amounts of CO2, transamidation reactions were accelerated with primary, secondary, and tertiary amide donors. Various amine nucleophiles including amino acid derivatives were tolerated, showcasing the utility of transamidation in peptide modification and polymer degradation (e.g., Nylon-6,6). In particular, N,O-dimethylhydroxyl amides (Weinreb amides) displayed a distinct reactivity in the CO2-catalyzed transamidation versus a N2 atmosphere. Comparative Hammett studies and kinetic analysis were conducted to elucidate the catalytic activation mechanism of molecular CO2, which was supported by DFT calculations. We attributed the positive effect of CO2 in the transamidation reaction to the stabilization of tetrahedral intermediates by covalent binding to the electrophilic CO2.

Differences in the eyelid and buccal microbiome of glaucoma patients receiving long-term administration of prostaglandin analog drops.

PURPOSE: To investigate the differences in the eyelid and buccal microbiomes between patients receiving long-term prostaglandin analogs for open-angle glaucoma (PG-OAG) and naïve-OAG patients by using metagenomics. METHODS: Eyelid and buccal samples were collected from 30 PG-OAG and 32 naïve-OAG patients. The taxonomic composition of the microbiome was obtained via 16S rRNA gene sequencing, operational taxonomic unit analysis, and diversity analysis. Differential gene expression analysis (DEG) and Bland-Altman (MA) plots were used to determine taxon differences between the microbiomes of PG-OAG and naïve-OAG patients. RESULTS: The eyelid microbiome showed marginally significant differences, while the alpha-diversity of the buccal microbiome showed significant differences between PG-OAG and naïve-OAG patients. However, the beta-diversity of both eyelid and buccal microbiomes was higher in PG-OAG patients than in naïve-OAG patients. The MA plot showed cluster differences in the eyelid microbiome. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment of Azomonas, Pseudomonas, and Granulicatella in PG-OAG patients over naïve-OAG patients, as well as significant depletion of Delftia and Rothia. In the buccal microbiome in PG-OAG patients, taxa such as Rikenella and Stenotrophomonas were significantly enriched. CONCLUSION: Our findings suggest that the eyelid microbiome differs between PG-OAG and naïve-OAG patients, raising concerns regarding the eyelid environment in patients receiving these drugs. The overexpressed microbiome in the eyelid area suggests that microbiota may change after the administration of glaucoma medications in OAG.

Homocoupling Reactions of Azoles and Their Applications in Coordination Chemistry.

Pyrazole, a member of the structural class of azoles, exhibits molecular properties of interest in pharmaceuticals and materials chemistry, owing to the two adjacent nitrogen atoms in the five-membered ring system. The weakly basic nitrogen atoms of deprotonated pyrazoles have been applied in coordination chemistry, particularly to access coordination polymers and metal-organic frameworks, and homocoupling reactions can in principle provide facile access to bipyrazole ligands. In this context, we summarize recent advances in homocoupling reactions of pyrazoles and other types of azoles (imidazoles, triazoles and tetrazoles) to highlight the utility of homocoupling reactions in synthesizing symmetric bi-heteroaryl systems compared with traditional synthesis. Metal-free reactions and transition-metal catalyzed homocoupling reactions are discussed with reaction mechanisms in detail.

Asymmetric Aminalization via Cation-Binding Catalysis.

Asymmetric cation-binding catalysis, in principle, can generate "chiral" anionic nucleophiles, where the counter cations are coordinated within chiral environments. Nitrogen nucleophiles are intrinsically basic, therefore, its use as nucleophiles is often challenging and limiting the scope of the reaction. Particularly, a formation of configurationally labile aminal centers with alkyl substituents has been a formidable challenge due to the enamine/imine equilibrium of electrophilic substrates. Herein, we report enantioselective nucleophilic addition reactions of potassium phthalimides to Boc-protected alkyl- and aryl-substituted α-amido sulfones. In situ generated imines smoothly reacted with the nitrogen nucleophiles to corresponding aminals with good to excellent enantioselectivitiy under mild reaction conditions. In addition, transformation of aminal products gave biologically relevant pyrrolidinone-fused hexahydropyrimidine scaffold with excellent stereoselectivity and good yield.

Relationship between corneal biomechanical properties and structural biomarkers in patients with normal-tension glaucoma: a retrospective study.

BACKGROUND: We evaluated the relationships between corneal biomechanical properties and structural parameters in patients with newly diagnosed, untreated normal-tension glaucoma (NTG). METHODS: All subjects were evaluated using an Ocular Response Analyzer (ORA) measuring corneal hysteresis (CH) and the corneal resistance factor (CRF). Central corneal thickness (CCT), Goldmann applanation tonometric (GAT) data, axial length, and the spherical equivalent (SE), were also measured. Confocal scanning laser ophthalmoscopy was performed with the aid of a Heidelberg retina tomograph (HRT III). We sought correlations between HRT parameters and different variables including CCT, CH, and the CRF. Multiple linear regression analysis was performed to identify significant associations between corneal biomechanical properties and optic nerve head parameters. RESULTS: We enrolled 95 eyes of 95 NTG patients and 93 eyes of 93 normal subjects. CH and the CRF were significantly lower in more advanced glaucomatous eyes (P = 0.001, P = 0.008, respectively). The rim area, rim volume, linear cup-to-disc ratio (LCDR), and mean retinal nerve fiber layer (RNFL) thickness were significantly worse in more advanced glaucomatous eyes (P < 0.001, P < 0.001, P < 0.001, and P = 0.001). CH was directly associated with rim area, rim volume, and mean RNFL thickness (P = 0.012, P = 0.028, and P = 0.043) and inversely associated with LCDR (P = 0.015), after adjusting for age, axial length, CCT, disc area, GAT data, and SE. However, in normal subjects, there were no significant associations between corneal biomechanical properties and HRT parameters. CONCLUSIONS: A lower CH is significantly associated with a smaller rim area and volume, a thinner RNFL, and a larger LCDR, independent of disc size, corneal thickness, intraocular pressure, and age.