The role of P3H family in cancer: implications for prognosis, tumor microenvironment and drug sensitivity.

Introduction: Prolyl 3-hydroxylases (P3H) are crucial enzymes in collagen biosynthesis and are known to be involved in a variety of physiological processes. However, their specific roles in cancer progression, modulation of the tumor microenvironment (TME), and impact on patient prognosis remain areas that require further investigation. Methods: The investigation involved a comprehensive analysis of expression profiles and clinical data obtained from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. This included the assessment of genetic variation, gene expression, and the prognostic significance of P3H family genes. P3H scores were calculated using various databases and R-based tools, followed by correlation analyses with the TME, immune cell infiltration, drug sensitivity and immunotherapy.Variations in P3H gene expression patterns were observed across different tumor types and prognoses, suggesting that most genes within the family were risk factors, especially P3H1 and P3H4. The P3H score was associated with immune infiltration and drug resistance. Notably, individuals with elevated expression of P3H2, P3H3, and CRTAP exhibited higher resistance to multiple anti-tumor drugs. Results: P3H family proteins play diverse roles in cancer progression, significantly impacting patient prognosis and the effectiveness of immunotherapy. Conclusions: The P3H score, identified as a potential biomarker for evaluating TME, holds promise in guiding precision medicine strategies.

Synthesis, Structure and Antibacterial Activity of Two Novel Coordination Polymers Based on N,N'-bis(4-carbozvlbenzvl)-4-aminotoluene and Heterocyclic Ligand against S. aureus.

As the use of antibiotics increases, the increasing resistance of bacteria is the main reason for the reduced efficiency of antibacterial drugs, making the research of new antibacterial materials become new hot spot. In this article, two novel coordination polymers (CPs), namely, [Cd2(L)2(bibp)2]n (1) and [Ni(L)(bib)]n (2), where H2L = N,N'-bis(4-carbozvlbenzvl)-4-aminotoluene, bibp = 4,4'-bis(imidazol-1-yl)biphenyl, and bib = 1,3-bis(1-imidazoly)benzene, have been synthesized under solvothermal and hydrothermal condition. Structural clarification was performed through infrared spectrum and single-crystal X-ray diffraction analysis, while thermal analysis and XRD technology were used for the performance assessment of compounds 1 and 2. In addition, antibacterial performance experiments showed that compounds 1 and 2 have certain selectivity in their antibacterial properties and have good antibacterial properties against S. aureus. As the concentration of the compound increases, the inhibitory effect gradually strengthens, and when the concentration of the compound reaches 500 µg/mL and 400 µg/mL, the concentration of the S. aureus solution no longer increases and has been completely inhibited.

Dilute RuCo Alloy Synergizing Single Ru and Co Atoms as Efficient and CO-Resistant Anode Catalyst for Anion Exchange Membrane Fuel Cells.

Ruthenium (Ru) is considered a promising candidate catalyst for alkaline hydroxide oxidation reaction (HOR) due to its hydrogen binding energy (HBE) like that of platinum (Pt) and its much higher oxygenophilicity than that of Pt. However, Ru still suffers from insufficient intrinsic activity and CO resistance, which hinders its widespread use in anion exchange membrane fuel cells (AEMFCs). Here, we report a hybrid catalyst (RuCo)NC+SAs/N-CNT consisting of dilute RuCo alloy nanoparticles and atomically single Ru and Co atoms on N-doped carbon nanotubes The catalyst exhibits a state-of-the-art activity with a high mass activity of 7.35 A mgRu-1. More importantly, when (RuCo)NC+SAs/N-CNT is used as an anode catalyst for AEMFCs, its peak power density reaches 1.98 W cm-2, which is one of the best AEMFCs properties of noble metal-based catalysts at present. Moreover, (RuCo)NC+SAs/N-CNT has superior long-time stability and CO resistance. The experimental and density functional theory (DFT) results demonstrate that the dilute alloying and monodecentralization of the exotic element Co greatly modulates the electronic structure of the host element Ru, thus optimizing the adsorption of H and OH and promoting the oxidation of CO on the catalyst surface, and then stimulates alkaline HOR activity and CO tolerance of the catalyst.

Association between Metabolic Score for Visceral Fat and the risk of hypertension in different ethnic groups: a prospective cohort study in Southwest China.

Objective: Visceral adipose tissue assessment holds significant importance in hypertension prevention. This study aimed to explore the association between the Metabolic Score for Visceral Fat (METS-VF), a new indicator based on laboratory and anthropometry measures, and hypertension risk and to further investigate the association between the METS-VF and the risk of hypertension in different ethnic groups. Methods: In this study, a total of 9,280 people from 48 townships in 12 districts (counties) of Guizhou Province were selected for the survey using a multistage cluster random sampling method, and 5,127 cases were finally included in the analysis after excluding those with missing relevant data, losing visits, dying at follow-up, those who suffered from hypertension at baseline, and those whose information on the outcome of hypertension was not clear. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) between METS-VF and incident hypertension, and an accelerated failure time (AFT) model was applied to analyze the association between METS-VF and the onset time of hypertension. Results: The total person-years (PYs) of the 5,127 subjects were 36,188.52 years, and the median follow-up time was 6.64 years. During follow-up, 1,127 patients were newly diagnosed with hypertension, and the incidence density was 31.14/1,000 PYs. After adjusting for multivariables, compared with the METS-VF first (Q1), the third (Q3) and fourth (Q4) groups of the METS-VF increased by 29.9% and 61.5%, respectively (HR = 1.299 [1.061, 1.590] and 1.615 [1.280, 2.036]). The risk of hypertension increased with higher METS-VF values (HR = 1.323 [1.167, 1.500], ptrend < 0.001). In the Han Chinese population, Q2 and Q3 increased the risk of hypertension (HR = 1.459 [1.111, 1.917], 1.999 [1.417, 2.718]), and the onset of hypertension was advanced by 0.653 (ß = -0.653 (-0.930, -0.375]) years for per 1 unit increase in METS-VF. However, these associations were not found in ethnic minorities. Conclusion: METS-VF was significantly positively associated with the risk of hypertension, and the association was different among ethnic groups.

Alcohol consumption and accelerated biological ageing in middle-aged and older people: A longitudinal study from two cohorts.

BACKGROUND AND AIMS: The relationship between alcohol consumption and age-related diseases is inconsistent. Biological age (BA) serves as both a precursor and a predictor of age-related diseases; however, longitudinal associations between alcohol consumption and BA in middle-aged and older people remain unclear. We measured whether there was a longitudinal association between drinking frequency and pure alcohol intake with BA among middle-aged and older people. DESIGN AND SETTING AND PARTICIPANTS: This study involved two prospective cohort studies, set in Southwestern China and the United Kingdom. A total of 8046 participants from the China Multi-Ethnic Cohort study (CMEC) and 5412 participants from the UK Biobank (UKB), aged 30-79 years, took part, with complete data from two waves of clinical biomarkers. MEASUREMENTS: BA was calculated by the Klemera Doubal's method. Accelerated BA equalled BA minus chronological age. Drinking frequency and pure alcohol intake were obtained through self-reported questionnaires. Drinking frequency in the past year was classified as current non-drinking, occasional (monthly drinking) and regular (weekly drinking). FINDINGS: Compared with consistent current non-drinkers, more frequent drinkers [CMEC: ß = 0.46, 95% confidence interval (CI) = 0.13-0.80; UKB: ß = 0.65, 95% CI = 0.01-1.29)], less frequent drinkers (CMEC: ß = 0.62, 95% CI = 0.37-0.87; UKB: ß = 0.54, 95% CI = -0.01-1.09), consistent occasional drinkers (CMEC: ß = 0.51, 95% CI = 0.23-0.79; UKB: ß = 0.63, 95% CI = 0.13-1.13) and consistent regular drinkers (CMEC: ß = 0.56, 95% CI = 0.17-0.95; UKB: ß = 0.46, 95% CI = 0.00-0.91) exhibited increased accelerated BA. A non-linear relationship between pure alcohol intake and accelerated BA was observed among consistent regular drinkers. CONCLUSIONS: In middle-aged and older people, any change in drinking frequency and any amount of pure alcohol intake seem to be positively associated with acceleration of biological ageing, compared with maintaining abstinence.

Predicting lung function decline in cystic fibrosis: the impact of initiating ivacaftor therapy.

BACKGROUND: Modulator therapies that seek to correct the underlying defect in cystic fibrosis (CF) have revolutionized the clinical landscape. Given the heterogeneous nature of lung disease progression in the post-modulator era, there is a need to develop prediction models that are robust to modulator uptake. METHODS: We conducted a retrospective longitudinal cohort study of the CF Foundation Patient Registry (N = 867 patients carrying the G551D mutation who were treated with ivacaftor from 2003 to 2018). The primary outcome was lung function (percent predicted forced expiratory volume in 1 s or FEV1pp). To characterize the association between ivacaftor initiation and lung function, we developed a dynamic prediction model through covariate selection of demographic and clinical characteristics. The ability of the selected model to predict a decline in lung function, clinically known as an FEV1-indicated exacerbation signal (FIES), was evaluated both at the population level and individual level. RESULTS: Based on the final model, the estimated improvement in FEV1pp after ivacaftor initiation was 4.89% predicted (95% confidence interval [CI]: 3.90 to 5.89). The rate of decline was reduced with ivacaftor initiation by 0.14% predicted/year (95% CI: 0.01 to 0.27). More frequent outpatient visits prior to study entry and being male corresponded to a higher overall FEV1pp. Pancreatic insufficiency, older age at study entry, a history of more frequent pulmonary exacerbations, lung infections, CF-related diabetes, and use of Medicaid insurance corresponded to lower FEV1pp. The model had excellent predictive accuracy for FIES events with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.83 to 0.84) for the independent testing cohort and 0.90 (95% CI: 0.89 to 0.90) for 6-month forecasting with the masked cohort. The root-mean-square errors of the FEV1pp predictions for these cohorts were 7.31% and 6.78% predicted, respectively, with standard deviations of 0.29 and 0.20. The predictive accuracy was robust across different covariate specifications. CONCLUSIONS: The methods and applications of dynamic prediction models developed using data prior to modulator uptake have the potential to inform post-modulator projections of lung function and enhance clinical surveillance in the new era of CF care.

Population Structure and Genetic Diversity of the Toona ciliata (Meliaceae) Complex Assayed with Chloroplast DNA Markers.

Toona ciliata is a deciduous or semi-deciduous tree species and belongs to the Toona genus of the Meliaceae family. Owing to low natural regeneration and over-exploitation, the species is listed as an endangered species at level II in China and its conservation has received increasing concern. Here, we sampled 447 individuals from 29 populations across the range-wide distribution of the T. ciliata complex in China and assessed their genetic variation using two chloroplast DNA markers. The results showed that the overall haplotype diversity and nucleotide diversity per site were high at h = 0.9767 and π = 0.0303 for the psbA-trnH fragment and h= 0.8999 and π = 0.0189 for the trnL-trnL fragment. Phylogenetic analysis supported the division of the natural distribution of T. ciliata complex into western and eastern regions. The genetic diversity was higher in the western region than in the eastern region, showing significant phylogeographic structure. Genetic differentiation among populations was moderate (Φst=42.87%), and the effects of isolation by distance (IBD) were significant. A neutrality test and mismatch distribution analysis indicated that the distribution of the T. ciliata complex generally did not expand, although a few local populations could likely expand after bottleneck effects. The overall results were complementary to and consolidated previous studies using mitochondrial and nuclear DNA markers. We finally discussed strategies for the genetic conservation of the T. ciliata complex.

Enhanced Carbon-Carbon Coupling at Interfaces with Abrupt Coordination Number Changes.

Cu-catalyzed electrochemical CO2 reduction reaction (CO2RR) produces multi-carbon (C2+) chemicals with considerable selectivities and activities, yet required high overpotentials impede its practical application. Here, we design interfaces with abrupt coordination number (CN) changes that greatly reduce the applied potential for achieving high C2+ Faradaic efficiency (FE). Encouraged by the mechanistic finding that the coupling between *CO and *CO(H) is the most probable C-C bond formation path, we use Cu2O- and Cu-phthalocyanine-derived Cu (OD-Cu and PD-Cu) to build the interface. Using operando X-ray absorption spectroscopy (XAS), we find that the Cu CN of OD-Cu is ~11, favoring CO* adsorption, while the PD-Cu has a COH*-favorable CN of ~4. Operando Raman spectroscopy revealed that the interfaces with abrupt CN changes promote *OCCOH formation. As a result, the designed catalyst achieves a C2+ FE of 85±2 % at 220 mA cm-2 in a zero-gap CO2 electrolyzer. An improvement of C2+ FE by 3 times is confirmed at the low potential regime where the current density is 60-140 mA cm-2, compared to bare OD-Cu. We report a 45-h stable CO2RR operation at 220 mA cm-2, producing a C2+ product FE of ~80 %.

Low-coordination Nanocrystalline Copper-based Catalysts through Theory-guided Electrochemical Restructuring for Selective CO2 Reduction to Ethylene.

Revealing the dynamic reconstruction process and tailoring advanced copper (Cu) catalysts is of paramount significance for promoting the conversion of CO2 into ethylene (C2H4), paving the way for carbon neutralization and facilitating renewable energy storage. In this study, we initially employed density functional theory (DFT) and molecular dynamics (MD) simulations to elucidate the restructuring behavior of a catalyst under electrochemical conditions and delineated its restructuring patterns. Leveraging insights into this restructuring behavior, we devised an efficient, low-coordination copper-based catalyst. The resulting synthesized catalyst demonstrated an impressive Faradaic efficiency (FE) exceeding 70 % for ethylene generation at a current density of 800 mA cm-2. Furthermore, it showed robust stability, maintaining consistent performance for 230 hours at a cell voltage of 3.5 V in a full-cell system. Our research not only deepens the understanding of the active sites involved in designing efficient carbon dioxide reduction reaction (CO2RR) catalysts but also advances CO2 electrolysis technologies for industrial application.

In situ copper faceting enables efficient CO2/CO electrolysis.

The copper (Cu)-catalyzed electrochemical CO2 reduction provides a route for the synthesis of multicarbon (C2+) products. However, the thermodynamically favorable Cu surface (i.e. Cu(111)) energetically favors single-carbon production, leading to low energy efficiency and low production rates for C2+ products. Here we introduce in situ copper faceting from electrochemical reduction to enable preferential exposure of Cu(100) facets. During the precatalyst evolution, a phosphate ligand slows the reduction of Cu and assists the generation and co-adsorption of CO and hydroxide ions, steering the surface reconstruction to Cu (100). The resulting Cu catalyst enables current densities of > 500 mA cm-2 and Faradaic efficiencies of >83% towards C2+ products from both CO2 reduction and CO reduction. When run at 500 mA cm-2 for 150 hours, the catalyst maintains a 37% full-cell energy efficiency and a 95% single-pass carbon efficiency throughout.

Durable CO2 conversion in the proton-exchange membrane system.

Electrolysis that reduces carbon dioxide (CO2) to useful chemicals can, in principle, contribute to a more sustainable and carbon-neutral future1-6. However, it remains challenging to develop this into a robust process because efficient conversion typically requires alkaline conditions in which CO2 precipitates as carbonate, and this limits carbon utilization and the stability of the system7-12. Strategies such as physical washing, pulsed operation and the use of dipolar membranes can partially alleviate these problems but do not fully resolve them11,13-15. CO2 electrolysis in acid electrolyte, where carbonate does not form, has therefore been explored as an ultimately more workable solution16-18. Herein we develop a proton-exchange membrane system that reduces CO2 to formic acid at a catalyst that is derived from waste lead-acid batteries and in which a lattice carbon activation mechanism contributes. When coupling CO2 reduction with hydrogen oxidation, formic acid is produced with over 93% Faradaic efficiency. The system is compatible with start-up/shut-down processes, achieves nearly 91% single-pass conversion efficiency for CO2 at a current density of 600 mA cm-2 and cell voltage of 2.2 V and is shown to operate continuously for more than 5,200 h. We expect that this exceptional performance, enabled by the use of a robust and efficient catalyst, stable three-phase interface and durable membrane, will help advance the development of carbon-neutral technologies.

Tea consumption and attenuation of biological aging: a longitudinal analysis from two cohort studies.

Background: The biological aging process can be modified through lifestyle interventions to prevent age-related diseases and extend healthspan. However, evidence from population-based studies on whether tea consumption could delay the biological aging process in humans remains limited. Methods: This study included 7931 participants aged 30-79 years from the China Multi-Ethnic Cohort (CMEC) Study and 5998 participants aged 37-73 years from the UK Biobank (UKB) who participated in both the baseline and first follow-up surveys. Tea consumption information was collected through questionnaires. Biological age (BA) acceleration was calculated using clinical biomarkers and anthropometric measurements based on the Klemera Doubal method (KDM). Change-to-change analyses were performed to estimate the associations between changes in tea consumption status and changes in BA acceleration using multiple linear models. Follow-up adjusted for baseline analyses were further conducted to examine the prospective exposure-response relationship between tea consumption and BA acceleration among individuals with constant tea consumption status. Findings: During a median follow-up of 1.98 (1.78, 2.16) years in the CMEC and 4.50 (3.92, 5.00) years in the UKB, tea consumption was consistently associated with attenuated BA acceleration in both cohorts. Transitioning from nondrinking to tea-drinking was associated with decreased BA acceleration (CMEC: ß = -0.319, 95% CI: -0.620 to -0.017 years; UKB: ß = -0.267, 95% CI: -0.831 to 0.297 years) compared to consistent nondrinking. Even stronger associations were found in consistent tea drinkers. The exposure-response relationship suggested that consuming around 3 cups of tea or 6-8 g of tea leaves per day may offer the most evident anti-aging benefits. Interpretation: Tea consumption was associated with attenuated BA acceleration measured by KDM, especially for consistent tea drinkers with moderate consumption. Our findings highlight the potential role of tea in developing nutrition-oriented anti-aging interventions and guiding healthy aging policies. Funding: National Natural Science Foundation of China (Grant No. 82273740).

Role of metabolic risk factors in the relationship between ambient fine particulate matter and depressive symptoms: Evidence from a longitudinal population study.

BACKGROUND: There is growing evidence indicating a connection between fine particulate matter (PM2.5) and depressive symptoms. Metabolic risk factors are critical determinants of depressive symptoms. However, the mediating role of these factors on the association between PM2.5 and depressive symptoms remains elusive. We aimed to investigate whether and to what extent metabolic risk factors mediated the link between long-term PM2.5 exposure and depressive symptoms. METHODS: This study comprised 7794 individuals aged between 30 and 79 years who participated in two waves of the on-site surveys in the China Multi-Ethnic Cohort. Ambient PM2.5 concentrations were assessed utilizing a random forest method based on satellite data. We employed the Patient Health Questionnaire-9 to assess depressive symptoms at wave 2, and the overall as well as three sub-domain symptom scores (emotional, neurovegetative, and neurocognitive symptoms) were calculated. Three metabolic risk factors, including hypertension, diabetes, and dyslipidemia, were considered. Mediation analyses were conducted to assess the indirect effects of PM2.5 on depressive symptoms through metabolic risk factors. RESULTS: We found a positive association between chronic exposure to ambient PM2.5 and overall depressive symptoms as well as the three sub-domains. In mediation analyses, metabolic risk factors partially mediated the associations of PM2.5 on depressive symptoms. The natural indirect effects (RR, 95% CI) of PM2.5 on overall, emotional, neurovegetative, and neurocognitive symptoms mediated through metabolic risk factors were 1.004(1.001, 1.007), 1.004 (1.001, 1.008), 1.004 (1.001, 1.007), and 1.003(0.999, 1.007), respectively. Larger indirect effects were found in elderly participants (mediated proportion, 29.3%), females (13.3%), and people who did not consume alcohol (19.6%). CONCLUSIONS: Metabolic risk factors may act as mediators in the relationship between chronic PM2.5 exposure and depression. Treatment of metabolic risk factors may be an opportunity to reduce the burden of depression caused by long-term exposure to PM2.5.

Hypoconnectivity of the Amygdala in Patients with Low-Back-Related Leg Pain Linked to Individual Mechanical Pain Sensitivity: A Resting-State Functional MRI Study.

Purpose: To explore resting-state functional connectivity (rsFC) of the amygdala in patients with low-back-related leg pain (LBLP). Patients and Methods: For this prospective study, a total of 35 LBLP patients and 30 healthy controls (HCs) were included and underwent functional MRI and clinical assessments. Then, patients with LBLP were divided into acute LBLP (aLBLP) and chronic LBLP (cLBLP) subgroups. We further evaluated the between-group rsFC differences using left and right amygdala seeds in a whole-brain voxel analysis strategy. Finally, we performed correlation analysis between the rsFC values of altered regions and clinical indices. Results: Compared to HCs, hypoconnectivity of the amygdala was observed in LBLP patients (P < 0.01, with correction). The amygdala's rsFC pattern was different between aLBLP and cLBLP patients: decreased the amygdala's FC to the right putamen, to the right paracentral lobule (PCL), or to the right posterior temporal lobe in aLBLP patients, while right amygdala to the bilateral anterior cingulate cortex (ACC) and the left postcentral gyrus (PoCG) in cLBLP patients. Correlation analysis showed that lower rsFC of the left amygdala to the right PCL was correlated with the von Frey filament (vF) test values of the left lumbar (p = 0.025) and right lumbar (p = 0.019) regions, and rsFC of the right amygdala to the left PoCG was correlated with lower vF test values of the left lumbar (p = 0.017), right lumbar spine (p = 0.003); to right PoCG was correlated with calf (p = 0.015); the rsFC of the right amygdala to bilateral ACC was negatively correlated with the pain rating index (p = 0.003). Conclusion: LBLP patients showed amygdala hypoconnectivity, and the altered pattern of amygdala rsFC was different in the acute and chronic phases. Moreover, the amygdala hypoconnectivity was related to individual mechanical sensitivity (vF test) in LBLP patients.

Application of a Metal Cobalt Based on 4,6-Bis(imidazol-1-yl)isophthalicacid Metal-Organic -Framework Materials in Photocatalytic CO2 Reduction, Antibacterial, and Dye Adsorption.

In this paper, the reported MOF ([Co(bimip)(H2O)0.5]·0.5H2O) was employed in photocatalytic CO2 reduction, antibacterial, and dye adsorption experiments. The photocatalytic activity of the MOF for CO2 reduction was systematically investigated. The high average CO generation rate of 3421.59 µmol·g-1·h-1 after 12 h confirms the efficient photocatalytic CO2 reduction ability of the MOF. At the same time, the MOF can completely inhibit the growth of S. aureus and C. albicans within 24 h when its concentration reaches 400 µg/mL and 500 µg/mL, respectively. The MOF has an adsorption capacity for CR. The adsorption rate was 83.42% at 60 min, and the adsorption capacity of the MOF for CR reached 500.00 mg·g-1.

Near-Atomic-Scale Superfine Alloy Clusters for Ultrastable Acidic Hydrogen Electrocatalysis.

As a commercial electrode material for proton-exchange membrane water electrolyzers and fuel cells, Pt-based catalysts still face thorny issues, such as insufficient mass activity, stability, and CO tolerance. Here, we construct a bifunctional catalyst consisting of Pt-Er alloy clusters and atomically dispersed Pt and Er single atoms, which exhibits excellent activity, durability, and CO tolerance of acidic hydrogen evolution and oxidation reactions (HER and HOR). The catalyst possesses a remarkably high mass activity and TOF for HER at 63.9 times and 7.2 times more than that of Pt/C, respectively. More impressively, it can operate stably in the acidic electrolyte at 1000 mA cm-2 for more than 1200 h, thereby confirming its potential for practical applications at the industrial current density. In addition, the catalyst also demonstrates a distinguished HOR performance and outstanding CO tolerance. The synergistic effects of active sites give the catalyst exceptional activity for the hydrogen reaction, while the introduction of Er atoms greatly enhances its stability and CO tolerance. This work provides a promising idea for designing low-Pt-loading acidic HER electrocatalysts that are durable at ampere-level current densities and for constructing HOR catalysts with high CO tolerance.

Near index matching enables solid diffractive optical element fabrication via additive manufacturing.

Diffractive optical elements (DOEs) have a wide range of applications in optics and photonics, thanks to their capability to perform complex wavefront shaping in a compact form. However, widespread applicability of DOEs is still limited, because existing fabrication methods are cumbersome and expensive. Here, we present a simple and cost-effective fabrication approach for solid, high-performance DOEs. The method is based on conjugating two nearly refractive index-matched solidifiable transparent materials. The index matching allows for extreme scaling up of the elements in the axial dimension, which enables simple fabrication of a template using commercially available 3D printing at tens-of-micrometer resolution. We demonstrated the approach by fabricating and using DOEs serving as microlens arrays, vortex plates, including for highly sensitive applications such as vector beam generation and super-resolution microscopy using MINSTED, and phase-masks for three-dimensional single-molecule localization microscopy. Beyond the advantage of making DOEs widely accessible by drastically simplifying their production, the method also overcomes difficulties faced by existing methods in fabricating highly complex elements, such as high-order vortex plates, and spectrum-encoding phase masks for microscopy.

Cytological DNA methylation for cervical cancer screening: a validation set.

Background: In a previous training set with a case-controlled design, cutoff values for host EPB41L3 and JAM3 gene methylation were obtained for the detection of cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+). This validation trial was conducted to evaluate the role of DNA methylation in screening for CIN2+ by cervical cytology among unselected participants. Methods: From June 1, 2019, to September 1, 2019, in our study center, we collected liquid-based samples from cervical swabs for methylation assays and hrHPV testing in eligible patients. The primary endpoint was the diagnostic accuracy of DNA methylation and hrHPV genotyping for CIN2+ according to confirmed histology results. Results: Among 307 participants, compared with hrHPV testing, the methylation assay for CIN2+ had lower sensitivity (68.7% versus 86.1%, p=0.002) but higher specificity (96.7% versus 0.696, p<0.001). The methylation assay also had favorable sensitivity and specificity in patients with negative hrHPV testing (56.3% and 96.9%) and in patients with cervical adenocarcinoma (73.7% and 92.7%). DNA methylation had higher specificity than the hrHPV assay (100.0% versus 44.4%, p<0.001) for identifying residual CIN2+ in patients without residual lesions. Positive cervical DNA methylation was associated with a diagnostic probability of endometrial carcinoma (odds ratio 15.5 [95% confidence interval 4.1-58.6]) but not of ovarian epithelial carcinoma (1.4 [0.3-6.5]). Conclusions: The host EPB41L3 and JAM3 gene methylation assay in cervical cytology had favorable diagnostic accuracy for CIN2+ and was highly specific for residual CIN2+ lesions The methylation assay is a promising triage tool in hrHPV+ women, or even an independent tool for cervical cancer screening. The methylation status in cervical cytology could also serve as a prognostic biomarker. Its role in detecting endometrial carcinomas is worthy of further exploration.

Promoting CO2 Electroreduction to Multi-Carbon Products by Hydrophobicity-Induced Electro-Kinetic Retardation.

Advancing the performance of the Cu-catalyzed electrochemical CO2 reduction reaction (CO2 RR) is crucial for its practical applications. Still, the wettable pristine Cu surface often suffers from low exposure to CO2 , reducing the Faradaic efficiencies (FEs) and current densities for multi-carbon (C2+ ) products. Recent studies have proposed that increasing surface availability for CO2 by cation-exchange ionomers can enhance the C2+ product formation rates. However, due to the rapid formation and consumption of *CO, such promotion in reaction kinetics can shorten the residence of *CO whose adsorption determines C2+ selectivity, and thus the resulting C2+ FEs remain low. Herein, we discover that the electro-kinetic retardation caused by the strong hydrophobicity of quaternary ammonium group-functionalized polynorbornene ionomers can greatly prolong the *CO residence on Cu. This unconventional electro-kinetic effect is demonstrated by the increased Tafel slopes and the decreased sensitivity of *CO coverage change to potentials. As a result, the strongly hydrophobic Cu electrodes exhibit C2+ Faradaic efficiencies of ≈90 % at a partial current density of 223 mA cm-2 , more than twice of bare or hydrophilic Cu surfaces.