Deciphering the Roles of Interfacial Amino Acids in Inter-Protein Charge Transport.

Elucidating charge transport (CT) through proteins is critical for gaining insights into ubiquitous CT chain reactions in biological systems and developing high-performance bioelectronic devices. While intra-protein CT has been extensively studied, crucial knowledge about inter-protein CT via interfacial amino acids is still absent due to the structural complexity. Herein, by loading cytochrome c (Cyt c) on well-defined peptide self-assembled monolayers to mimic the protein-protein interface, we provide a precisely controlled platform for identifying the roles of interfacial amino acids in solid-state CT via peptide-Cyt c junctions. The terminal amino acid of peptides serves as a fine-tuning factor for both the interfacial interaction between peptides and Cyt c and the immobilized Cyt c orientation, resulting in a nearly 10-fold difference in current through peptide-Cyt c junctions with varied asymmetry. This work provides a valuable platform for studying CT across proteins and contributes to the understanding of fundamental principles governing inter-protein CT.

Action and therapeutic targets of myosin light chain kinase, an important cardiovascular signaling mechanism.

The global incidence of cardiac diseases is increasing, imposing a substantial socioeconomic burden on healthcare systems. The pathogenesis of cardiovascular disease is complex and not fully understood, and the physiological function of the heart is inextricably linked to well-regulated cardiac muscle movement. Myosin light chain kinase (MLCK) is essential for myocardial contraction and diastole, cardiac electrophysiological homeostasis, vasoconstriction of vascular nerves and blood pressure regulation. In this sense, MLCK appears to be an attractive therapeutic target for cardiac diseases. MLCK participates in myocardial cell movement and migration through diverse pathways, including regulation of calcium homeostasis, activation of myosin light chain phosphorylation, and stimulation of vascular smooth muscle cell contraction or relaxation. Recently, phosphorylation of myosin light chains has been shown to be closely associated with the activation of myocardial exercise signaling, and MLCK mediates systolic and diastolic functions of the heart through the interaction of myosin thick filaments and actin thin filaments. It works by upholding the integrity of the cytoskeleton, modifying the conformation of the myosin head, and modulating innervation. MLCK governs vasoconstriction and diastolic function and is associated with the activation of adrenergic and sympathetic nervous systems, extracellular transport, endothelial permeability, and the regulation of nitric oxide and angiotensin II. Additionally, MLCK plays a crucial role in the process of cardiac aging. Multiple natural products/phytochemicals and chemical compounds, such as quercetin, cyclosporin, and ML-7 hydrochloride, have been shown to regulate cardiomyocyte MLCK. The MLCK-modifying capacity of these compounds should be considered in designing novel therapeutic agents. This review summarizes the mechanism of action of MLCK in the cardiovascular system and the therapeutic potential of reported chemical compounds in cardiac diseases by modifying MLCK processes.

Incremental burden on health-related quality of life, health service utilization and direct medical expenditures associated with cognitive impairment among non-institutionalized people with diabetes aged 65 years and older.

AIMS: To quantify the incremental health and economic burden associated with cognitive impairment (CI) among non-institutionalized people with diabetes ≥65 years in the United States. MATERIALS AND METHODS: Using 2016-2019 Medical Expenditure Panel Surveys data, we identified participants ≥65 years with diabetes. We used propensity score weighting to quantify the CI-associated incremental burden on health-related quality of life measured by the 12-item Short Form Survey (SF-12), including the mental component summary score, physical component summary score and health utility. We also compared the annual health service utilization and expenditures on ambulatory visits, prescriptions, home care, emergency room (ER), hospitalizations and total annual direct medical expenditures. RESULTS: We included 5094 adults aged ≥65 with diabetes, of whom 804 had CI. After propensity score weighting, CI was associated with a lower mental component summary score (-8.4, p < .001), physical component summary score (-5.2, p < .001) and health utility (-0.12, p < .001). The CI group had more ambulatory visits (+4.4, p = .004) and prescriptions (+9.9, p < .001), with higher probabilities of having home care (+11.3%, p < .001) and ER visits (+8.2%, p = .001). People with CI spent $5441 (p < .001) more annually, $2039 (p = .002) more on prescriptions, $2695 (p < .001) more on home care and $118 (p < .001) more on ER visits. There is no statistically significant difference in the utilization and expenditure of hospitalizations. CONCLUSION: CI was associated with worse health-related quality of life, higher health service utilization and expenditures. Our findings can be used to monitor the health and economic burden of CI in non-institutionalized older persons with diabetes.

Lipid Metabolic Disorders Induced by Organophosphate Esters in Silver Carp from the Middle Reaches of the Yangtze River.

The Yangtze River fishery resources have declined strongly over the past few decades. One suspected reason for the decline in fishery productivity, including silver carp (Hypophthalmichthys molitrix), has been linked to organophosphate esters (OPEs) contaminant exposure. In this study, the adverse effect of OPEs on lipid metabolism in silver carp captured from the Yangtze River was examined, and our results indicated that muscle concentrations of the OPEs were positively associated with serum cholesterol and total lipid levels. In vivo laboratory results revealed that exposure to environmental concentrations of OPEs significantly increased the concentrations of triglyceride, cholesterol, and total lipid levels. Lipidome analysis further confirmed the lipid metabolism dysfunction induced by OPEs, and glycerophospholipids and sphingolipids were the most affected lipids. Hepatic transcriptomic analysis found that OPEs caused significant alterations in the transcription of genes involved in lipid metabolism. Pathways associated with lipid homeostasis, including the peroxisome proliferator-activated receptor (PPAR) signal pathway, cholesterol metabolism, fatty acid biosynthesis, and steroid biosynthesis, were significantly changed. Furthermore, the affinities of OPEs were different, but the 11 OPEs tested could bind with PPARγ, suggesting that OPEs could disrupt lipid metabolism by interacting with PPARγ. Overall, this study highlighted the harmful effects of OPEs on wild fish and provided mechanistic insights into OPE-induced metabolic disorders.

Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults.

BACKGROUND: An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results. METHODS: We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020-May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. RESULTS: After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. CONCLUSIONS: Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection.

Effect of STING signaling on intestinal barrier damage in severe acute pancreatitis.

BACKGROUND: Patients with severe acute pancreatitis (SAP) have a compromised intestinal barrier with decreased barrier function and increased cell death. Intestinal epithelial cells (IECs) create a physicochemical barrier that anchors bacteria in the intestine. Recent studies have shown that the stimulator of interferons genes (STING) signaling pathway plays an important function in a number of inflammatory conditions. METHODS: The rat SAP model was established by retrograde injection of freshly prepared sodium taurocholate into the biliopancreatic duct. Serum amylase (AMY), lipase (LIPA), interleukin (IL)-6, interferon (IFN)-ß, tumor necrosis factor (TNF)-α, intestinal-type fatty acid binding protein (FABP2), diamine oxidase (DAO) and endotoxin (ET) levels were measured in rats. H&E staining was used to assess histological changes in the intestine and pancreas. The expression of intestinal epithelial cell tight junction (TJ) proteins and STING signaling pathway proteins and genes were measured by RT- PCR, Western blot and immunofluorescence staining were used to analyze. The expression of STING signaling pathway proteins in pancreas were measured by Western blot were used to analyze. TUNEL was used to detect IECs death. RESULTS: Upregulation of STING pathway-related proteins and genes occurred after sap-induced IECs. In addition, C-176 reduced serum AMY, LIPA, TNF-α, IL-6, INF-ß, FABP2, DAO and endotoxin levels and decreased pancreatic and intestinal histopathological injury in SAP rats; DMXAA aggravated serum AMY, LIPA, TNF-α, IL-6, INF-ß, FABP2, DAO and endotoxin levels and increased pancreatic and intestinal histopathological injury in SAP rats. CONLUSIONS: The results suggest that inhibition of STING signaling can alleviate IECs after SAP, and activation of STING signaling can aggravate IECs after SAP.

Base Pair Stacking Modulates Solid-State Charge Transport in DNA Hairpins.

Particular interest has been focused on modulation of solid-state charge transport (CT) in DNA. Nevertheless, it remains challenging to do so in a sensitive and predictive manner due to the lack of a definite relationship between DNA base pair stacking and DNA CT. The challenges can be mainly attributed to the ill-defined systems, which may lead to ambiguous and even contradictory conclusions. Here, we use DNA hairpins to construct the well-defined self-assembled monolayers. We reveal nearly positive-linear correlations between DNA conformation and CT in the DNA hairpins regulated with metal ion chelation and DNA sequence. The correlations have been confirmed by the solid-state current-voltage characteristics and circular dichroism in solution. The enhanced CT via metal ion chelated DNA hairpins is mainly from the improved DNA energy coupling to electrodes, not the almost unchanged energy barrier when Hg ion-induced DNA conformational switches toward the canonical B-form.

Healthcare Utilization and Mortality After Hospice Live Discharge Among Medicare Patients With and Without Alzheimer's Disease and Related Dementias.

BACKGROUND: Little is known about post-discharge outcomes among patients who were discharged alive from hospice. OBJECTIVE: To compare healthcare utilization and mortality after hospice live discharge among Medicare patients with and without Alzheimer's disease and related dementias (ADRD). DESIGN: Retrospective cohort study using Medicare claims data of a 20% random sample of Medicare fee-for-service (FFS) patients. PARTICIPANTS: A total of 153,696 Medicare FFS patients experienced live discharge from hospice between 2014 and 2019. MEASURES: Two types of burdensome transition (type 1: live discharge from hospice followed by hospitalization and subsequent hospice readmission; type 2: live discharge from hospice followed by hospitalization with the patient deceased in the hospital), acute care utilization, hospice readmission, and mortality in the 30 and 180 days after live discharge and between live discharge and death. RESULTS: Compared with non-ADRD patients, ADRD patients were less likely to experience burdensome transitions (type 1: adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.90-0.98; type 2: aOR, 0.70; 95% CI, 0.65-0.75), more likely to have ED visits (aOR, 1.05; 95% CI, 1.01-1.09), less likely to die (aOR, 0.71; 95% CI, 0.69-0.73), and less likely to be readmitted to hospice (aOR, 0.86; 95% CI, 0.84-0.89) 30 days after live discharge. Results of 180-day post-discharge outcomes were largely consistent with results of 30-day outcomes. Among patients who died as of December 31, 2019, ADRD patients were less likely to be hospitalized (aOR, 0.88; 95% CI, 0.85-0.92) and more likely to be readmitted to hospice (aOR, 1.12; 95% CI, 1.08-1.16) between live discharge and death. Significant racial/ethnicity disparities in acute care utilization and mortality after live discharge existed in both ADRD and non-ADRD groups. CONCLUSION: ADRD patients had lower mortality, a longer survival time, a lower rate of hospitalization, and an initially lower but gradually increasing rate of hospice readmission than non-ADRD patients after hospice live discharge. These different trajectories warrant further investigation of the eligibility of their initial hospice enrollment. Black patients had significantly worse outcomes after hospice live discharge compared with White patients.

Racial/Ethnic Disparities in Post-acute Sequelae of SARS-CoV-2 Infection in New York: an EHR-Based Cohort Study from the RECOVER Program.

BACKGROUND: Compared to white individuals, Black and Hispanic individuals have higher rates of COVID-19 hospitalization and death. Less is known about racial/ethnic differences in post-acute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: Examine racial/ethnic differences in potential PASC symptoms and conditions among hospitalized and non-hospitalized COVID-19 patients. DESIGN: Retrospective cohort study using data from electronic health records. PARTICIPANTS: 62,339 patients with COVID-19 and 247,881 patients without COVID-19 in New York City between March 2020 and October 2021. MAIN MEASURES: New symptoms and conditions 31-180 days after COVID-19 diagnosis. KEY RESULTS: The final study population included 29,331 white patients (47.1%), 12,638 Black patients (20.3%), and 20,370 Hispanic patients (32.7%) diagnosed with COVID-19. After adjusting for confounders, significant racial/ethnic differences in incident symptoms and conditions existed among both hospitalized and non-hospitalized patients. For example, 31-180 days after a positive SARS-CoV-2 test, hospitalized Black patients had higher odds of being diagnosed with diabetes (adjusted odds ratio [OR]: 1.96, 95% confidence interval [CI]: 1.50-2.56, q<0.001) and headaches (OR: 1.52, 95% CI: 1.11-2.08, q=0.02), compared to hospitalized white patients. Hospitalized Hispanic patients had higher odds of headaches (OR: 1.62, 95% CI: 1.21-2.17, q=0.003) and dyspnea (OR: 1.22, 95% CI: 1.05-1.42, q=0.02), compared to hospitalized white patients. Among non-hospitalized patients, Black patients had higher odds of being diagnosed with pulmonary embolism (OR: 1.68, 95% CI: 1.20-2.36, q=0.009) and diabetes (OR: 2.13, 95% CI: 1.75-2.58, q<0.001), but lower odds of encephalopathy (OR: 0.58, 95% CI: 0.45-0.75, q<0.001), compared to white patients. Hispanic patients had higher odds of being diagnosed with headaches (OR: 1.41, 95% CI: 1.24-1.60, q<0.001) and chest pain (OR: 1.50, 95% CI: 1.35-1.67, q < 0.001), but lower odds of encephalopathy (OR: 0.64, 95% CI: 0.51-0.80, q<0.001). CONCLUSIONS: Compared to white patients, patients from racial/ethnic minority groups had significantly different odds of developing potential PASC symptoms and conditions. Future research should examine the reasons for these differences.

Changes in racial and ethnic disparities in glucose-lowering drug utilization and glycated haemoglobin A1c in US adults with diabetes: 2005-2018.

AIM: To examine changes in racial and ethnic disparities in glucose-lowering drugs (GLD) use and glycated haemoglobin A1c in US adults with diabetes from 2005 to 2018. METHODS: We conducted pooled cross-sectional analysis using data from the 2005-2018 Medical Expenditure Panel Surveys, and the 2005-2018 National Health and Nutrition Examination Survey. Individuals ≥18 years with diabetes were included. Racial and ethnic disparities were measured in (a) newer non-insulin GLD use; (b) insulin analogue use; (c) non-insulin GLDs adherence; (d) insulin adherence; and (e) glucose management, along with (f) the proportion of the disparities explained by potential contributing factors. RESULTS: From 2005 to 2018, racial and ethnic disparities persisted in newer GLD use, non-insulin GLDs adherence, insulin analogue use and glucose management. In 2018, compared with non-Hispanic white adults, non-Hispanic black, Hispanic and other race/ethnicity groups had lower rates of using newer GLDs (adjusted risk ratio: 0.44, 0.52, 0.64, respectively; p < .05 for all) and insulin analogues (adjusted risk ratio: 0.93, 0.89, 0.95, respectively; p < .05 for all except other groups), lower non-insulin GLD adherence (proportion of days covered: -4.5%, -5.6%, -4.3%, respectively; p < .05 for all), higher glycated haemoglobin A1c (0.29%, 0.32%, 0.02%, respectively; p < .05 for all except other group), and similar insulin adherences. Socioeconomic and health status were the main contributors to these disparities. CONCLUSIONS: Our findings provide evidence of racial and ethnic disparities in newer GLD use and quality of care in glucose management. Our study results can inform decision-makers of the status of racial and ethnic disparities and identify ways to reduce these disparities.

Advancements and Challenges in Reductive Conversion of Carbon Dioxide via Thermo-/Photocatalysis.

Carbon dioxide (CO2) is the major greenhouse gas and also an abundant and renewable carbon resource. Therefore, its chemical conversion and utilization are of great attraction for sustainable development. Especially, reductive conversion of CO2 with energy input has become a current hotspot due to its ability to access fuels and various important chemicals. Nowadays, the controllable CO2 hydrogenation to formic acid and alcohols using sustainable H2 resources has been regarded as an appealing solution to hydrogen storage and CO2 accumulation. In addition, photocatalytic CO2 reduction to CO also provides a potential way to utilize this greenhouse gas efficiently. Besides direct CO2 hydrogenation, CO2 reductive functionalization integrates CO2 reduction with subsequent C-X (X = N, S, C, O) bond formation and indirect transformation strategies, enlarging the diverse products derived from CO2 and promoting CO2 reductive conversion into a new stage. In this Perspective, the progress and challenges of CO2 reductive conversion, including hydrogenation, reductive functionalization, photocatalytic reduction, and photocatalytic reductive functionalization are summarized and discussed along with the key issues and future trends/directions in this field. We hope this Perspective can evoke intense interest and inspire much innovation in the promise of CO2 valorization.

Dose-dependent early white matter alterations in patients with brain metastases after radiotherapy.

PURPOSE: Previous diffusion tensor imaging (DTI) studies have mainly focused on dose-dependent white matter (WM) alterations 1 month to 1 year after radiation therapy (RT) with a tract-average method. However, WM alterations immediately after RT are subtle, resulting in early WM alterations that cannot be detected by tract-average methods. Therefore, we performed a study with an along-tract method in patients with brain metastases to explore the early dose-response pattern of WM alterations after RT. METHODS: Sixteen patients with brain metastases underwent DTI before and 1-3 days after brain RT. DTI metrics, such as fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were calculated. Along-tract statistics were then used to resample WM fibre streamlines and generate a WM skeleton fibre tract. DTI metric alterations (post_RT-pre_RT DTI metrics) and the planned doses (max or mean doses) were mapped to 18 WM tracts. A linear fixed model was performed to analyse the main effect of dose on DTI metric alterations. RESULTS: AD alterations in the left hemispheric uncinated fasciculus (UNC_L) were associated with max doses, in which decreased AD alterations were associated with higher doses. CONCLUSION: Our findings may provide pathological insight into early dose-dependent WM alterations and may contribute to the development of max dose-constrained RT techniques to protect brain microstructure in the UNC_L.

Psychological distress as a risk factor for the efficacy of chemotherapy in advanced gastric cancer patients.

AIM: To assess the relationship between psychological distress and quality of life (QoL), cancer-related fatigue (CRF), and chemotherapy efficacy in advanced gastric cancer patients. METHODS: Advanced gastric cancer patients (39 with psychological distress and 35 without psychological distress) completed the Distress Thermometer (DT), QoL, and CRF test before receiving chemotherapy and assessed the efficacy after completing 2 courses of chemotherapy. RESULTS: Psychological distress was a significant factor in the efficacy of chemotherapy in advanced gastric cancer patients (χ2 = 6.324; p = 0.042). Compared to advanced gastric cancer patients with no psychological distress, advanced gastric cancer patients with psychological distress had a poorer QoL (50.41 ± 6.17 vs. 60.01 ± 7.94, t = - 5.882, p < 0.01) and more pronounced CRF (5.75 ± 1.16 vs. 3.22 ± 0.75, t = 11.231, p < 0.01) while receiving chemotherapy. FACT-G (p = 0.0035, r = - 0.4568), as well as PFS (p < 0.0001, r = 0.6599), correlated significantly with efficacy for patients in the psychological distress group. The FACT-G (p = 0.0134, r = - 0.4139) of patients in the no psychological distress group correlated significantly with efficacy. CONCLUSION: Psychological distress has a negative impact on QoL, CRF, and efficacy and may be a potential risk for the efficacy of palliative chemotherapy in advanced gastric cancer patients.

Ruan Jian Qing Mai's Formula Promotes Bone Marrow-Derived Mesenchymal Stem Cell Migration and Proliferation.

Objective: To investigate the response of (BM-MSCs) to the Ruan Jian Qing Mai formula (RJQM) in the treatment of atherosclerotic occlusion (ASO), and consequently promoting the development of collateral circulation and angiogenesis. Method: 35 male rats were randomly assigned to 6 experimental groups and A control group. 0.9% NaCl solution and 2.7, 5.4, 10.8, 16.2, 21.6, and 27 g × kg-1 × d-1 of RJQM formula were gavaged to the experimental groups twice a day for 8 days. After the last administration, medicated serum was prepared from the blood collected from the abdominal aorta. The human BM-MSCs were divided into an experimental group and a control group. A blank group of cells was added with a complete medium without rat serum; an experimental group of cells was added with the prepared drug-containing serum. Under hypoxic conditions, the drug-containing serum was used to treat BM-MSCs and/or endothelial cells of human umbilical vein (HUVECs). A Cell counting kit (CCK8) was used to detect cell proliferation. Western blot (WB) and quantitative real-time PCR (qPCR) were used to identify related genes expression. Results: The results of this study showed that the purity of the BM-MSCs was >95%. The drug-containing serum significantly rise in CCND1 expression (encoding cyclin D1) and MYC, especially when the concentration of medicated serum was 10.8 g × kg-1 × d-1. Treatment of either BM-MSCs or HUVECs alone or both with medicated serum aids in the spread of mesenchymal stem cells from the bone marrow to HUVECs. qPCR results showed that the mRNA expression of CCL2, CCL3, CCL25, IL8, IGF1, and PDGFB increased dramatically after treatment with medicated serum. The expression of the corresponding receptors for these up-regulated chemokines was detected in BM-MSCs, and it was found that CXCR1, CXCR4, CXCR7, and PDGFRB were up-regulated. Conclusion: This study provides a preliminary understanding of the mechanism of RJQM in the treatment of ASO.

Fault Diagnosis Method of Roadheader Bearing Based on VMD and Domain Adaptive Transfer Learning.

The roadheader is a core piece of equipment for underground mining. The roadheader bearing, as its key component, often works under complex working conditions and bears large radial and axial forces. Its health is critical to efficient and safe underground operation. The early failure of a roadheader bearing has weak impact characteristics and is often submerged in complex and strong background noise. Therefore, a fault diagnosis strategy that combines variational mode decomposition and a domain adaptive convolutional neural network is proposed in this paper. To start with, VMD is utilized to decompose the collected vibration signals to obtain the sub-component IMF. Then, the kurtosis index of IMF is calculated, with the maximum index value chosen as the input of the neural network. A deep transfer learning strategy is introduced to solve the problem of the different distributions of vibration data for roadheader bearings under variable working conditions. This method was implemented in the actual bearing fault diagnosis of a roadheader. The experimental results indicate that the method is superior in terms of diagnostic accuracy and has practical engineering application value.

Supramolecular Enhancement of Charge Transport through Pillar[5]arene-Based Self-Assembled Monolayers.

Intermolecular charge transport is one of the essential modes for modulating charge transport in molecular electronic devices. Supermolecules are highly promising candidates for molecular devices because of their abundant structures and easy functionalization. Herein, we report an efficient strategy to enhance charge transport through pillar[5]arene self-assembled monolayers (SAMs) by introducing cationic guests. The current density of pillar[5]arene SAMs can be raised up to about 2.1 orders of magnitude by inserting cationic molecules into the cavity of pillar[5]arenes in SAMs. Importantly, we have also observed a positive correlation between the charge transport of pillar[5]arene-based complex SAMs and the binding affinities of the pillar[5]arene-based complexation. Such an enhancement of charge transport is attributed to the efficient host-guest interactions that stabilize the supramolecular complexes and lower the energy gaps for charge transport. This work provides a predictive pattern for the regulation of intermolecular charge transport in guiding the design of next generation switches and functional sensors in supramolecular electronics.

Cost-Effective 2D Ultrathin Metal-Organic Layers with Bis-Metallic Catalytic Sites for Visible Light-Driven Photocatalytic CO2 Reduction.

As novel generated 2D materials, metal-organic layers (MOLs) have recently emerged as a potential platform for photocatalytic CO2 reduction reaction (PCO2 RR). Such 2D structures negate the blemish of low-density catalytic sites and low electron transmission efficiency on the surface of metal organic frameworks (MOFs), while retaining the advantage of low expenditure when using earth-abundant metal nodes and meritorious applicability in the PCO2 RR. Herein, it is reported that the 2D ultrathin layer material with bis-metallic catalytic sites (Ni-O metal node and the Ni-N metal site) from bidentate ligand 2,2'-bipyridine-5,5'-dicarboxylate (H2 bpydc) and nickel(II) remarkably boosts the visible light-driven PCO2 RR performance with a CO yield of 2400 mmol g-1 for 18 h and a selectivity up to 99 %. Consequently, the effects of morphology, catalytic sites and intrinsic properties on PCO2 RR efficiency have been investigated in detail. In this context, the ultrathin layer structure has been elucidated as the key point to facilitate electron transfer efficiency. Notably, the bis-metallic catalytic sites with reasonable distance between two adjacent metals presumably induce synergistic effect and offer a guiding ideology for further designing high performance photocatalysts.

Cost-Effective 2D Ultrathin Metal-Organic Layers with Bis-Metallic Catalytic Sites for Visible Light-Driven Photocatalytic CO2 Reduction.

Invited for the cover of this issue is the group of Liang-Nian He at Nankai University. The image depicts that 2D ultrathin metal organic layers (MOLs) with bis-metallic catalytic sites make an efficient photocatalyst resulting in efficient and selective visible-light-driven CO2 reduction. Read the full text of the article at 10.1002/chem.202201767.

Chronic Medication Nonadherence and Potentially Preventable Healthcare Utilization and Spending Among Medicare Patients.

BACKGROUND: The association between nonadherence to chronic medications and potentially preventable healthcare utilization and spending is largely unknown. OBJECTIVES: To examine the associations of chronic medication nonadherence with potentially preventable utilization and spending among patients who were prescribed diabetic medications, renin-angiotensin system antagonists (RASA) for hypertension, or statins for high cholesterol, and compare the associations by patient race/ethnicity and socioeconomic status. DESIGN: Retrospective cohort study. Medicare fee-for-service claims data from 2013 to 2016 for 177,881 patients. MEASURES: Medication nonadherence was defined as having a below 80% proportion of days covered in each 6-month interval after the index prescription. Potentially preventable utilization was measured by preventable emergency department visits and preventable hospitalizations. Potentially preventable spending was calculated as the geographically adjusted spending associated with preventable encounters. RESULTS: After adjustment for other patient characteristics, medication nonadherence was associated with a 1.7-percentage-point increase (95% confidence interval [CI]: 1.4 to 2.0 percentage points, p < 0.001) in the probability of preventable utilization among the diabetic medication cohort, a 1.7-percentage-point increase (95% CI: 1.5 to 1.9 percentage points, p < 0.001) among the RASA cohort, and a 1.0-percentage-point increase (95% CI: 0.8 to 1.1 percentage points, p < 0.001) among the statin cohort. Among patients with at least one preventable encounter, medication nonadherence was associated with $679-$898 increased preventable spending. The incremental probability of preventable utilization and incremental spending associated with nonadherence were higher among racial/ethnic minority and low socioeconomic groups. CONCLUSIONS: Improving medication adherence is a potential avenue to reducing preventable utilization and spending. Interventions are needed to address racial/ethnic and socioeconomic disparities.

Baseline haemoglobin A1c and the risk of COVID-19 hospitalization among patients with diabetes in the INSIGHT Clinical Research Network.

AIMS: To examine the association between baseline glucose control and risk of COVID-19 hospitalization and in-hospital death among patients with diabetes. METHODS: We performed a retrospective cohort study of adult patients in the INSIGHT Clinical Research Network with a diabetes diagnosis and haemoglobin A1c (HbA1c) measurement in the year prior to an index date of March 15, 2020. Patients were divided into four exposure groups based on their most recent HbA1c measurement (in mmol/mol): 39-46 (5.7%-6.4%), 48-57 (6.5%-7.4%), 58-85 (7.5%-9.9%), and ≥86 (10%). Time to COVID-19 hospitalization was compared in the four groups in a propensity score-weighted Cox proportional hazards model adjusting for potential confounders. Patients were followed until June 15, 2020. In-hospital death was examined as a secondary outcome. RESULTS: Of 168,803 patients who met inclusion criteria; 50,016 patients had baseline HbA1c 39-46 (5.7%-6.4%); 54,729 had HbA1c 48-57 (6.5-7.4%); 47,640 had HbA1c 58-85 (7.5^%-9.9%) and 16,418 had HbA1c ≥86 (10%). Compared with patients with HbA1c 48-57 (6.5%-7.4%), the risk of hospitalization was incrementally greater for those with HbA1c 58-85 (7.5%-9.9%) (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 1.06-1.34) and HbA1c ≥86 (10%) (aHR 1.40, 95% CI 1.19-1.64). The risk of COVID-19 in-hospital death was increased only in patients with HbA1c 58-85 (7.5%-9.9%) (aHR 1.29, 95% CI 1.06, 1.61). CONCLUSIONS: Diabetes patients with high baseline HbA1c had a greater risk of COVID-19 hospitalization, although association between HbA1c and in-hospital death was less consistent. Preventive efforts for COVID-19 should be focused on diabetes patients with poor glucose control.