Effect of acute concurrent exercise training and the mediating role of lactate on executive function: An ERP study.

Both acute aerobic (AE) and resistance exercise (RE) have been acknowledged to be effective methods in enhancing executive function and brain-related P3 amplitudes. Nevertheless, the effect of acute concurrent exercise training (CET), combining both AE and RE, on executive function remains subject to speculation. Moreover, investigation of the mechanisms that underlie improvements in executive function would facilitate scientific understanding. Notably, lactate has emerged as a candidate among several potential mechanisms. Therefore, the main aim of the present study was to investigate the effect of acute CET on the cognitive flexibility dimension of executive function using behavioural and neuro-electric measures. A secondary aim was to determine the mediating effect of blood lactate in the acute exercise-executive function relationship. Seventy-eight young adults (38 women, 40 men; 22.8 ± 1.8 years) were randomly assigned to one of the following groups: CET, AE, or reading control (RC). Cognitive flexibility was evaluated using the Task-Switching Test and its derived electroencephalography (EEG) was assessed immediately prior to and following each treatment. Fingertip lactate assays were taken prior to, at the midpoint, and after each treatment. Both acute CET and AE shortened response time regardless of test conditions when compared to the RC group. Greater P3 amplitude was observed following CET in the heterogeneous condition and under AE in the switch condition. A significant mediation of blood lactate for response time emerged in both the CET and AE groups for the heterogeneous and switch conditions. The blood lactate mediation was not reflected in P3 amplitude. The present findings suggest that acute CET leads to positive behavioural and neuro-electric alterations of cognitive flexibility, and its effect is similar to AE. Additionally, blood lactate serves as a mediator of the effects of acute exercise on executive function from a behavioural, but not neuro-electric standpoint.

Acute high-intensity interval exercise improves food-related cognition in young adults with obesity: An ERP study.

Purpose Cognitive function, particularly food-related cognition, is critical for maintaining a healthy weight and preventing the acceleration of obesity. High-Intensity Interval Exercise (HIIE) is an increasingly popular form of exercise and has been shown to improve physical fitness and cognitive function. However, there is limited research on the effects and underlying mechanisms of HIIE on general and food-related cognition among adults with obesity. The aim of the current study was to examine the influence of a single bout of HIIE on food-related cognition among young adults with obesity. Methods Fifteen young men with obesity (BMI = 33.88 ± 4.22, age = 24.60 ± 5.29 years) were recruited. Participants took part in a HIIE condition consisting of 30 minutes of stationary cycle exercise (5-min warm-up, 20-min HIIE and 5-min cool down), and a control session consisting of a time and attention-matched period of sedentary rest in a counterbalanced order. Behavioral (reaction time and accuracy) and event-related potential measures (P3 and the late positive potential, LPP) elicited during a food-related Flanker task were measured after the HIIE and control session. Results Shorter response times were observed following HIIE, regardless of congruency or picture type, with no change in accuracy. Increased P3 and LPP amplitudes were observed following HIIE relative to the control session. Conclusion The findings suggest a single bout of HIIE has a beneficial effect on general and food-related cognition among young adults with obesity, with increased recruitment of cognitive resources to support cognitive control. Future research is warranted to examine the dose-response relationship between acute bouts or longer participation in HIIE on food-related cognition in obesity.

Clostridium innocuum, an emerging pathogen that induces lipid raft-mediated cytotoxicity.

Clostridium innocuum is an emerging spore-forming anaerobe that is often observed in Clostridioides difficile-associated inflammatory bowel disease (IBD) exacerbations. Unlike C. difficile, C. innocuum neither produces toxins nor possesses toxin-encoding genetic loci, but is commonly found in both intestinal and extra-intestinal infections. Membrane lipid rafts are composed of dynamic assemblies of cholesterol and sphingolipids, allowing bacteria to gain access to cells. However, the direct interaction between C. innocuum and lipid rafts that confers bacteria the ability to disrupt the intestinal barrier and induce pathogenesis remains unclear. In this study, we investigated the associations among nucleotide-binding oligomerization domain containing 2 (NOD2), lipid rafts, and cytotoxicity in C. innocuum-infected gut epithelial cells. Our results revealed that lipid rafts were involved in C. innocuum-induced NOD2 expression and nuclear factor (NF)-κB activation, triggering an inflammatory response. Reducing cholesterol by simvastatin significantly dampened C. innocuum-induced cell death, indicating that the C. innocuum-induced pathogenicity of cells was lipid raft-dependent. These results demonstrate that NOD2 mobilization into membrane rafts in response to C. innocuum-induced cytotoxicity results in aggravated pathogenicity.

Study of Atomic Layer Deposition Nano-Oxide Films on Corrosion Protection of Al-SiC Composites.

In recent years, aluminum matrix composites (AMCs) have attracted attention due to their promising properties. However, the presence of ceramic particles in the aluminum matrix renders AMCs a high corrosion rate and makes it challenging to use traditional corrosion protection methods. In this study, atomic layer deposition (ALD) techniques were used to deposit HfO2, ZrO2, TiO2, and Al2O3 thin films on AMC reinforced with 20 vol.% SiC particles. Our results indicate that the presence of micro-cracks between the Al matrix and SiC particles leads to severe micro-crack-induced corrosion in Al-SiC composites. The ALD-deposited films effectively enhance the corrosion resistance of these composites by mitigating this micro-crack-induced corrosion. Among these four atomic-layer deposited films, the HfO2 film exhibits the most effective reduction in the corrosion current density of Al-SiC composites in a 1.5 wt% NaCl solution from 1.27 × 10-6 A/cm2 to 5.89 × 10-11 A/cm2. The electrochemical impedance spectroscopy (EIS) investigation shows that HfO2 deposited on Al-SiC composites has the largest Rp value of 2.0 × 1016. The HfO2 film on Al-SiC composites also exhibits effective inhibition of pitting corrosion, remaining at grade 10 even after 96 h of a salt spray test.

Acute effect of combined exercise with aerobic and resistance exercises on executive function.

Objective: Recent studies indicate that acute exercise, whether aerobic exercise (AE) or resistance exercise (RE), improves cognitive function. However, the effects on cognitive function of combined exercise (CE), involving both AE and RE in an exercise session, remain unknown. The aim of this study was to investigate the effects of acute CE on cognitive function. Design: Within-subject design with counterbalancing. Methods: Fifteen healthy men with a sedentary lifestyle in the previous three months were recruited. The participants were assessed for muscular fitness after performing four upper body exercises for a 10-repetition maximum and underwent a submaximal aerobic fitness assessment for V̇O2peak and corresponding workload (watts). They were then assigned to a CE, RE, or sitting control (SC) session in counterbalanced order and were assessed with the Stroop Color and Word Test (SCWT) after each session. Results: Acute CE led to a significantly shorter response time compared to SC (p < .05) in the SCWT, wherein there were no significant differences between acute CE and RE (p = 1.00). Additionally, no significant differences in the accuracy rate were observed across the different sessions (ps > .05). Conclusion: A single session of moderate-intensity CE improved response time in the SCWT, comparable to RE. CE shows promise for enhancing cognitive function, warranting further research on its benefits and other exercise modalities.

DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 main protease inhibitors.

The development of SARS-CoV-2 main protease (Mpro) inhibitors for the treatment of COVID-19 has mostly benefitted from X-ray structures and preexisting knowledge of inhibitors; however, an efficient method to generate Mpro inhibitors, which circumvents such information would be advantageous. As an alternative approach, we show here that DNA-encoded chemistry technology (DEC-Tec) can be used to discover inhibitors of Mpro. An affinity selection of a 4-billion-membered DNA-encoded chemical library (DECL) using Mpro as bait produces novel non-covalent and non-peptide-based small molecule inhibitors of Mpro with low nanomolar Ki values. Furthermore, these compounds demonstrate efficacy against mutant forms of Mpro that have shown resistance to the standard-of-care drug nirmatrelvir. Overall, this work demonstrates that DEC-Tec can efficiently generate novel and potent inhibitors without preliminary chemical or structural information.

Effects of acute moderate-intensity exercise on executive function in children with preterm birth: A randomized crossover study.

BACKGROUND: Acute exercise appears to promote executive function (EF) in children. However, the effect of acute exercise on EF in children with preterm birth (PB) remains unclear. OBJECTIVE: To investigate whether acute moderate-intensity exercise improves EF in children with PB. METHODS: Twenty child participants with PB (age = 10.95 ± 1.19 years, birth age = 31.71 ± 3.64 weeks) completed exercise and control sessions in a randomized crossover design. In the exercise session, participants completed a 30-minute period of moderate-intensity aerobic exercise. In the control session, participants watched a video for appropriately 30 min. Following each session immediately, inhibitory control, an aspect of EF, was assessed with the Numerical Stroop task. RESULTS: Response time (RT) for the Stroop's incongruent condition was shorter after the exercise session than after the control session. However, no differences were observed in RT for the congruent condition. Accuracy rate (ACC) in both congruent and incongruent conditions did not differ between exercise and control session. CONCLUSION: The findings support the beneficial effect of acute exercise on executive function (EF) in children with PB, particularly in terms of improving inhibitory control.

Dual-Ion Co-intercalation Mechanism on a Na2V6O16·3H2O Cathode with a Commercial-Level Mass Loading for Aqueous Zinc-Ion Batteries with High Areal Capacity.

A proton (H+) and zinc ion (Zn2+) co-insertion model is put forward in this study to elucidate the capacity origin of an aqueous zinc ion battery (ZIB) based on a heavily loaded (∼15 mg cm-2) cathode, which consists of Na2V6O16·3H2O (NVO) embedded particularly in the macropores of activated carbon cloth (ACC), coupled with a highly stable Zn/In anode. The confinement effect of these porous channels not only prevents the detachment of NVO from ACC but also well mitigates its volume change resulting from H+ and Zn2+ co-intercalation, which collectively render the stability of NVO/ACC markedly enhanced. Moreover, the bicontinuous structure of NVO/ACC, as a result of the self-interlacing of intrapore NVO, which is first engineered into the nanobelts, and their interlocking with the carbon fibers of ACC, simultaneously giving rise to a solid and a holey framework, is favorable to the electron and ion transport throughout the entire electrode. The synergistic effect of such facile charge transfer kinetics and the high packing density of NVO in the cathode endows ZIBs with not only a good rate performance but also an exceptional areal capacity amounting to 4.6 mAh cm-2, far surpassing those reported for additional vanadium-based counterparts reported in the literature.

DNA-Compatible Nitro Reduction and Synthesis of Benzimidazoles.

A key factor for productive DNA-encoded libraries is the chemical diversity of the small molecule moiety attached to an encoding DNA oligomer. The library structure diversity is often limited to DNA-compatible chemical reactions in aqueous media. Herein, we describe a facile process for reducing aryl nitro groups to aryl amines by using sodium dithionite (Na2S2O4). The new protocol offers simple operation and circumvents the pyrophoric potential of the conventional method (Raney nickel). The utility of this method is demonstrated by the versatile synthesis of benzimidazoles on DNA.

Idiopathic Multicentric Castleman Disease with Strikingly Elevated IgG4 Concentration in the Serum and Abundant IgG4-Positive Cells in the Tissue: A Case Report.

Idiopathic multicentric Castleman disease (iMCD) can be challenging to distinguish clinically and histopathologically from Immunoglobulin G4-related disease (IgG4RD). A 73-year-old man was referred to a rheumatologist for suspected autoimmune-related polyclonal hypergammaglobulinemia. The patient had a history of multiple lymphadenopathies in the neck for over 20 years. Laboratory data showed elevated serum immunoglobulin G4 (IgG4) levels, hypergammaglobulinemia, high C-reactive protein (CRP) levels, marked anemia, and positivity for several autoantibodies. Additionally, imaging studies revealed multiple enlarged lymph nodes and multifocal, ill-defined, small patchy opacities over the lung. Biopsies of the neck lymph node and right lung revealed typical features of multicentric Castleman disease (MCD). Immunohistochemical staining was negative for human herpesvirus-8 (HHV-8) in both lymph nodes and the right lung, sub-classified as iMCD, whereas the IgG4/IgG ratio was >40%, which raised the suspicion of IgG4RD. However, serological cytokine analysis demonstrated an increased interleukin-6 (IL-6) level, alongside systemic inflammatory and histopathological features, distinguishing MCD from IgG4RD in this patient. The patient was treated with short-term glucocorticoids and regular infusion of an anti-IL-6 receptor monoclonal antibody (tocilizumab), with satisfactory clinical and radiographic responses. Notably, differentiating MCD from IgG4RD is crucial for optimal treatment. Clinical and pathological features may assist in distinguishing between these two diseases.

Bacillus licheniformis-fermented products and enramycin differentially modulate microbiota and antibiotic resistome in the cecal digesta of broilers.

Since antibiotic resistance is a global health issues, the use of antibiotics in animal feed for growth promotion has been restricted in many countries. Bacillus licheniformis probiotic is a potential alternative to antibiotics for increasing poultry performance. Through metagenomic sequencing, this study investigated the effects of B. licheniformis-fermented products (BLFPs) and enramycin on the microbial community composition and antibiotic resistance gene (ARG) distribution in the cecal digesta of broilers at the age of 35 d. In total, 144 one-day-old male broiler chicks (Ross 308) were randomly assigned to 4 dietary treatments as follows: basal diet (control [C] group), basal diet plus 10 mg/kg enramycin (E group), basal diet plus 1 g/kg BLFPs (L group), and basal diet plus 3 g/kg BLFPs (H group), with 6 replicate cages per treatment group and 6 birds per cage. The results indicated that the cecal alpha diversity (richness and evenness) of bacterial species was higher in the H group than in the C group. Principal coordinate analysis of microbiota and the ARG composition indicated clear differences among the cecal samples of the groups. In the cecal digesta, the abundance of active bacteria associated with probiotic properties, such as Lactobacillus crispatus and Akkermansia muciniphila, was higher in the H group than in the other groups. Enramycin treatment promoted the expression of peptide (bcrA), glycopeptide (vanRI), and lincosamide (lsaE) resistance genes but inhibited the expression of aminocoumarin (parY) and pleuromutilin (TaeA) resistance genes. BLFP (1 and 3 g/kg) treatment suppressed the expression of aminoglycoside (ANT(6)-Ib), streptogramin (vatB), and peptide (ugd) resistance genes but enhanced the expression of macrolide (efrA) and aminocoumarin (novA) resistance genes. The abundance of peptide resistance genes in Bacteroides spp. was lower in the H group than in the C group. The abundance of lincosamide resistance genes in Lactobacillus spp. was higher in the E group than in the other groups. These results demonstrated that differential changes in the structure of 3 g/kg BLFPs and enramycin-induced cecal microbial communities accompany changes in the abundance of bacterial hosts carrying specific ARGs in the cecal microbiota of broilers.

Removal of chlorine-contaminated groundwater by two-stage ozonation and biostimulation methods.

Trichloroethene (TCE) contamination is a critical environmental hazard, and the substrate options for its biostimulated remediation are limited. This study applied an ozonation-and-biostimulation process to remove TCE from groundwater. The substrate used, denoted as Transferred Energy Element (TEE), was composed of natural organic materials and had a low viscosity (2.914 cP). Ten batch experiments were conducted through the application of micro-nano bubbles (MNBs) and substrates (TEE and EOS® [emulsified oil substrate]). MNBs with an average diameter of 157.5-180.8 nm effectively degraded TCE and dichloroethane within 6 min. Biostimulation using the TEE substrate effectively degraded both TCE and vinyl chloride pollutants and reached a steady state after 25 days. The two-stage dechlorination procedure with MNB treatment as the first stage enhanced TCE removal via biostimulation. MNBs reduced the TCE concentration in the first 20 min, but increased the chloride (Cl-) concentration over the following five days (∼80 mg/L). The procedure with biostimulation as the first stage and 20 min ozonation as the second stage reduced the Cl- concentration by ∼10 mg/L. The Cl- concentrations rebounded after day 25 in the EOS environment. X-ray diffraction revealed that the released Na+ from the TEE settled with Cl- as minerals in the soil. The novel two-stage method for TCE removal was found to be more effective than solo MNB treatment or biostimulation.

Dry dechlorination of solid-derived fuels obtained from food waste and polyvinyl chloride.

Solid-recovered fuels (SRFs) with low chlorine (Cl) contents are urgently needed, particularly considering the limited availability of energy resources globally. Two main sources of chlorinated pollution in municipal solid wastes, namely food waste and polyvinyl chloride (PVC), were used as raw materials for SRF production. These materials were dechlorinated using alkaline adsorbents (calcium hydroxide (Ca(OH)2) and sodium bicarbonate (NaHCO3)), yielding five sample SRFs. The SRFs had low heating values (LHVs) of 14.10-15.12 MJ/kg. The alkaline adsorbents were introduced during dry dechlorination, which increased the LHVs by 8.4 MJ/g. Approximately 50 % of the total Cl content was transformed into the liquid and gaseous phases after incineration of the SRF. The PVC content was increased to increase the amount of gaseous Cl produced. Conversely, the yields of liquid and solid Cl increased when the FW content was increased. Among alkaline adsorbents, Ca(OH)2 exhibited better adsorption performance than NaHCO3. Upon mixing ~15 wt% of Ca(OH)2 with the SRFs, the highest Cl removal efficiency (77 %) in the gaseous phase was achieved. Over 90 % of the total Cl content was converted into solid-phase calcium chloride and sodium chloride by the alkaline adsorbents. The total cost of the SRF was US$85.48/t, of which labor and electricity costs accounted for 50 % and 25 %, respectively.

Efficacy and safety of cervicothoracic epidural blood patch for patients with spontaneous intracranial hypotension.

BACKGROUND: Epidural blood patch (EBP) is a generally effective treatment for spontaneous intracranial hypotension (SIH) caused by cerebrospinal fluid (CSF) leakage through the spinal dura mater. It is still unclear; however, whether application near the leakage site (targeted EBP) is more effective than distal application (untargeted EBP). Further, EBP targeted to high thoracic or cervical spine levels is infrequent due to greater technical requirements and potential complications. Here, we examined the safety and efficacy of EBP applied to high thoracic or cervical spine levels. METHODS: We retrospectively reviewed the clinical and outcome data of 13 patients receiving cervical or high thoracic EBP for SIH. All patients were referred by neurologists following poor response to conservative treatment and presented with persistent headache aggravated by orthostatic changes. RESULTS: Neuroimaging confirmed CSF leakage and targeted EBP resulted in immediate pain improvement. Repeated injections provided additional improvement for patients with recurrent headache. No serious adverse events were documented during follow-up. CONCLUSION: Based on recent studies and our clinical experience, we conclude that EBP targeted to the high thoracic and cervical spine is safe and effective for early-stage SIH.

High-Intensity Post-Stroke Rehabilitation Is Associated with Lower Risk of Pressure Ulcer Development in Patients with Stroke: Real-World Evidence from a Nationwide, Population-Based Cohort Study.

Background and Objectives: Multiple factors are associated with pressure ulcer (PU) development, including limited mobility following stroke. We performed a nationwide cohort study to investigate the impact of rehabilitation intensity on the incidence of post-stroke PU. Materials and Methods: Data of patients diagnosed with stroke between 2000 and 2012 were collected from the 2000 Longitudinal Health Insurance Database (Taiwan). Based on the number of rehabilitation sessions attended within 90 days of discharge, the rehabilitation intensity was classified as low, medium, or high. After adjusting for sociodemographic factors and comorbidities, the Cox proportional hazards model evaluated the risk of PU development during the 12-year follow-up period. Kaplan−Meier curves were used to estimate the cumulative incidence of PUs. Results: Our study included 18,971 patients who had their first episode of stroke. Of these, 9829 (51.8%) underwent rehabilitation therapy after discharge. Female patients and patients with a National Institutes of Health Stroke Scale (NIHSS) score >13 points, who commenced high-intensity post-stroke rehabilitation after discharge had a significantly lower risk of PU development than those who underwent low-intensity post-stroke rehabilitation after discharge. Cumulative survival analysis showed a significantly lower cumulative incidence of PU during the 12-year follow-up period in the high-intensity rehabilitation group. Conclusion: Compared with low-intensity post-stroke rehabilitation, high-intensity post-stroke rehabilitation after discharge from hospital is associated with a lower risk of post-stroke PU development, especially in female stroke patients and patients with a NIHSS score >13 points. High-intensity rehabilitation is also associated with a significantly lower cumulative incidence of PU events during the 12-year follow-up period.

Novel and Efficient Quantitative Posterior-Circulation-Structure-Based Scale via Noncontrast CT to Predict Ischemic Stroke Prognosis: A Retrospective Study.

(1) Background: Posterior circulation ischemic stroke has high mortality and disability rates and requires an early prediction prognosis to provide the basis for an interventional approach. Current quantitative measures are only able to accurately assess the prognosis of patients using magnetic resonance imaging (MRI). However, it is difficult to obtain MRI images in critically urgent cases. Therefore, the development of a noncontrast CT-based rapid-assist tool is needed to enhance the value of the clinical application. (2) Objective: This study aimed to develop an auxiliary-annotating noncontrast CT-efficient tool, which is based on a deep learning model, to provide a quantitative scale and the prognosis of posterior circulation ischemic stroke patients. (3) Methods: A total of 31 patients with posterior circulation ischemic stroke, diagnosed in the stroke registry at the Tri-Service General Hospital from November 2019 to July 2020, were included in the study, with a total of 578 CT images collected from noncontrast CT and MRI that were ≤ 3 days apart. A 5-fold cross validation was used to develop an image segmentation model to identify nine posterior circulation structures, and intersection over union (IoU) was used to assess the ability of the model to identify each structure. A quantitative score was integrated to assess the importance of the proportion of ischemic lesions in each posterior circulation structure, and the ROC curve was compared with the semiquantitative score for prognostic power. The prognoses of the patients were defined into two groups of 18 patients. An mRS score of 0-2 at discharge was defined as a good prognosis, while an mRS score of 3-6 was deemed to be a poor prognosis. (4) Results: The performance of the image segmentation model for identifying the nine posterior circulation structures in noncontrast CT images was evaluated. The IoU of the left cerebellum was 0.78, the IoU of the right cerebellum was 0.79, the IoU of the left occipital lobe was 0.74, the IoU of the right occipital lobe was 0.68, the IoU of the left thalamus was 0.73, the IoU of the right thalamus was 0.75, the IoU of the medulla oblongata was 0.82, and the IoU of the midbrain was 0.83. The prognostic AUC of posterior circulation patients predicted using a quantitative integrated score was 0.74, which was significantly higher than that of the pc-ASPECTS (AUC = 0.63, p = 0.035), with a sensitivity of 0.67 and a specificity of 0.72. (5) Conclusions: In this study, a deep learning model was used to develop a noncontrast CT-based quantitative integrated score tool, which is an effective tool for clinicians to assess the prognosis of posterior circulation ischemic stroke.

Highly Efficient Recovery of H2 from Industrial Waste by Sunlight-Driven Photoelectrocatalysis over a ZnS/Bi2S3/ZnO Photoelectrode.

Hydrogen (H2) fuel production from hazardous contaminants is not only of economic importance but also of significance for the environment and health. Hydrogen production is exemplified in this work by using bismuth sulfide (Bi2S3) sandwiched in between zinc sulfide (ZnS) and zinc oxide (ZnO) as dual-heterojunction photoelectrode to photoelectrochemically extract H2 from sulfide- and sulfite-containing wastewater, which is emitted in enormous quantities from the petrochemical industries. The H2 evolution rate over the ZnS/Bi2S3/ZnO photoelectrode under solar illumination amounts to 112.8 µmol cm-2 h-1, of which the photocurrent density in the meantime reaches 10.7 mA cm-2, by far exceeding those reported for additional Bi2S3-based counterparts in the literature. Such superior performance is ascribed on one hand to the broadband sunlight-harvesting ability of Bi2S3 that gives rise to respectable photoexcited electron-hole pairs. These photogenerated charge carriers are subsequently rectified by the built-in electric field at the ZnS/Bi2S3 and Bi2S3/ZnO heterojunctions to flow in the opposite directions to well circumvent the recombination losses and, most importantly, in turn contribute substantially to the H2 evolution reaction.

Design and construction of a stereochemically diverse piperazine-based DNA-encoded chemical library.

Here we report the successful construction of a novel, stereochemically diverse DNA-Encoded Chemical Library (DECL) by utilizing 24 enantiomerically pure trifunctional 2, 6- di-substituted piperazines as central cores. We introduce the concept of positional diversity by placing the DNA attachment at either of two possible sites on the piperazine scaffold. Using a wide range of building blocks, a diverse library of 77 million compounds was produced. Cheminformatic analysis demonstrates that this library occupies a wide swath of chemical space, and that the piperazine scaffolds confers different shape diversity compared to the commonly used triazine core.

Defective Indium Tin Oxide Forms an Ohmic Back Contact to an n-Type Cu2O Photoanode to Accelerate Charge-Transfer Kinetics for Enhanced Low-Bias Photoelectrochemical Water Splitting.

In significant contrast to the tremendous research efforts mostly geared to addressing the severe hole accumulation at the back contact of a p-type Cu2O photocathode with a fluorine-doped tin oxide (FTO) substrate, sluggish electron transfer from an n-type Cu2O photoanode to a tin-doped indium oxide (ITO) substrate has been largely overlooked. To tackle this issue that has been reported to largely limit the photoelectrochemical performance of n-type Cu2O photoanodes at a low bias, the present contribution puts forward a strategy to introduce oxygen vacancies into the ITO substrate via an unprecedented yet facile electrochemical approach. Such defect engineering turns out to decrease the work function of the ITO substrate, which in turn approaches the conduction band extremum of n-Cu2O to highly efficiently extract the photoexcited electrons therein. Moreover, the dendritic growth of n-Cu2O is, in the meantime, interfered by the oxygen vacancy manifested as pinholes distributed over the ITO substrate, which is thereby crystallized into several small grains with augmented surface roughness that is in favor of the injection of the photoexcited hole into the electrolyte. Such facile interfacial charge-transfer kinetics leads to a significant cathodic shift amounting to 200 mV of the onset potential to 0 VAg/AgCl, whereat the n-Cu2O photoanode deposited on the defective ITO substrate delivers the maximum photocurrent density reaching 2 mA cm-2 and, more significantly, its applied bias photon-to-current efficiency (ABPE) reaches 1.1%, which is among the highest performance reported to date for a variety of state-of-the-art metal oxide-based photoanodes in the literature.

DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 Mpro inhibitors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition constant [Ki] = 20 nM). CDD-1713, a smaller two-building-block analog (MW = 353.3 g/mol) of CDD-1714, is a reversible covalent inhibitor of Mpro (Ki = 45 nM) that binds in the protease pocket, has specificity over human proteases, and shows in vitro efficacy in a SARS-CoV-2 infectivity model. Subsequently, key regions of CDD-1713 that were necessary for inhibitory activity were identified and a potent (Ki = 37 nM), smaller (MW = 323.4 g/mol), and metabolically more stable analog (CDD-1976) was generated. Thus, screening of DNA-encoded chemical libraries can accelerate the discovery of efficacious drug-like inhibitors of emerging viral disease targets.