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Strobilanthes sarcorrhiza, a folk medicine from China, is known to treat kidney deficiency and lumbago. However, its protective effects and mechanisms against diabetic nephropathy (DN) remain unclear. This study aimed to investigate the effects and mechanisms of Strobilanthes sarcorrhiza root phenolic extract (CTS) on streptozotocin (STZ)-induced DN in mice. Firstly, the constituents in CTS were characterized by UPLC-QTOF-MS. Thirty-three constituents were identified, including 12 phenylethanoid glycosides and their derivatives, 14 phenylpropanoid glycosides derivatives, 6 polyphenols derivatives, and 1 other constituent. Then, utilizing the identified constituents of CTS, network pharmacology was used to anticipate potential pathways against DN. Thirty-two out of thirty-three constituents showed anti-DN activity; their mechanism of action was significantly linked to tumor-, glycosylation-, metabolism-related pathways, etc. Furthermore, the effectiveness of CTS against DN and its in vivo mechanism was assessed by combining immunohistochemistry, untargeted metabolomics, biochemical evaluation, and histopathological examination. The findings showed that CTS improved blood glucose and lipid levels in diabetic mice, reduced serum levels of ALT, CREA, UREA, IL-1ß, and IL-17, decreased pathological damage and fibrosis in kidney tissue, and lowered the protein expression of VEGF, Laminin, TNF-α, and NF-κB in kidney tissue. Metabolomics results indicated that CTS alleviated DN mainly by regulating glycerophospholipid metabolism. To the best of our knowledge, this study is the first to report that Strobilanthes sarcorrhiza attenuates DN, potentially through the inhibition of the NF-κB pathway, leading to a reduction in the inflammatory response and fibrosis of renal tissue. These findings suggest that Strobilanthes sarcorrhiza could be a promising therapeutic agent for DN.
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Covalent organic frameworks (COFs) incorporating oligo(phenylenevinylene) units have shown promise in enhancing photocatalytic hydrogen evolution. This study presents a series of linear oligo(phenylenevinylene)-based COFs with various ratios of ß-ketoenamine to imine linkages. The COFs-950-OMe are crystalline, exhibiting higher surface area compared to amorphous COFs-950, due to the introduction of methoxy side groups.
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BACKGROUND: Electrocardiograms (ECGs) and angiographic features indicative of acute atrial infarction (AAI) often go unnoticed and are under-recognized in clinical practice. METHODS: In this retrospective observational study, we analyzed the data of 3981 out of 9803 patients (40.61%) who were referred to our hospital for angiography and/or percutaneous coronary intervention due to acute coronary syndrome (ACS). These patients were diagnosed with acute ST segment elevation myocardial infarction (AMI) affecting the inferior, posterior, and/or right ventricular regions. RESULTS: Of the 3981 patients, 270 (6.78%) had involvement of the main coronary atrial branch meeting the angiographic criteria for AAI. Among the 270 patients identified, the right coronary artery was diagnosed as the infarct-related artery (IRA) in 187 patients (group R), while the left circumflex artery was the IRA in 83 patients (group L). The incidence of PR-segment deviation was similar between the two groups (65.2% in group R vs. 66.3% in group L, pâ¯= 0.870), as was occurrence of atrial tachyarrhythmia (67.4% vs. 55.4%, pâ¯= 0.059). The prevalence of P wave morphology abnormalities (29.9% vs. 49.4%, pâ¯= 0.005) and sinus bradycardia or arrest (25.1% vs. 66.3%, pâ¯< 0.001) was significantly lower in Group R than in Group L. CONCLUSION: Acute atrial infarction represents a distinct yet frequently overlooked clinical entity. Clinicians should consider the potential for atrial arrhythmias, thromboembolism, hemodynamic instability, and atrial rupture when diagnosing AAI.
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Fatigue failure is one of the most common fracture modes of structural materials in the industrial field. The study of material fatigue mechanisms and methods for predicting fatigue life has always been of significant interest to researchers due to the abrupt and catastrophic failure mode. In recent decades, the performance and functionality of scanning electron microscopy (SEM) have been continuously improved and expanded. Based on this, the development of in situ fatigue testing in SEM has been rapidly developed. This technology plays a crucial role in providing insights into the deformation behavior of materials under fatigue. Keeping this in view, a comprehensive review of the development and application methods of in situ SEM fatigue testing technology is provided here. The development of in situ SEM fatigue testing devices is provided in brief overview, and the application and research progress of this technology in some representative metal structural materials (nickel-based single-crystal superalloys, steel, aluminum alloys and additive manufacturing materials) are analyzed in detail. Moreover, the perspectives on evaluating fatigue damage, particularly about small cracks and the plastic accumulations fatigue behavior, are presented in this study, utilizing the latest advancements in in situ SEM fatigue testing. Remarks about the present and outlook for future work to be done are then provided.
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Cyclodextrin-based polyrotaxanes (CD-PRs) are gaining attention for their dynamic sliding rings along the polymer axis, enabling various applications in molecular shuttles, drug delivery, and durable polymers with slidable cross-links. However, the conventional synthesis of CD-PRs with tunable threading ratios is typically laborious, time-consuming, and complicated, which limits their scalability and cost-effectiveness. Herein, we highlight the great potential of planetary centrifugal mixing, a process that significantly accelerates and simplifies the initial synthesis of polypseudorotaxanes (PPRs), followed by a thiol-ene click reaction as an efficient end-capping reaction for the synthesis of PRs. Notably, PRs synthesized with glutathione (GSH) as the end-capping reagent are in a metastable state, where GSH act as a molecular bumper that significantly prevent de-threading of α-CD rings at room temperature. Moreover, the rate of ring de-threading can be precisely controlled by heating, enabling the preparation of metastable PRs with tunable threading ratios over a wide range. The developed strategy is of great significance to the efficient synthesis of CD-PRs, thus marking a significant step towards their practical application in advanced functional materials and devices.
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Campylobacter jejuni is recognized as a significant foodborne pathogen, and recent studies have indicated a rising trend of aminoglycosides resistance gene aph(2â³)-If among C. jejuni isolates from food-producing animals in China. However, systematic information about aph(2â³)-If-positive C. jejuni from food-producing animals and other sources worldwide based on whole-genome analysis remains a knowledge gap. In this study, we aimed to analyze the worldwide distribution, genetic environment and phylogenetic tree of aph(2â³)-If by utilizing Whole Genome Sequencing (WGS) data obtained, coupled with information in the GenBank database. A total of 160C. jejuni isolates in the GenBank database and 14C. jejuni isolates in our laboratory carrying aph(2â³)-If gene were performed for further analysis. WGS analysis revealed the global distribution of aph(2â³)-If among C. jejuni from 6 countries. Multilocus Sequence Typing(MLST) results indicated that 70 STs were involved in the dissemination of aph(2â³)-If, with ST10086 being the predominant ST. Whole-genome Multilocus Sequence Typing(wg-MLST) analysis according to times, countries, and origins of C. jejuni isolation further demonstrated a close relationship between aph(2â³)-If carrying C. jejuni isolates from farm and food. The findings also revealed the existence of 32 distinct types of genetic environments surrounding aph(2â³)-If among these isolates. Notably, Type 30, characterized by the arrangement ISsag10-deoD-ant(9)-hp-hp-aph(2â³)-If, emerged as the predominant genetic environment. In conclusion, our analysis provides the inaugural perspective on the worldwide distribution of aph(2â³)-If. This resistance gene demonstrates horizontal transferability and regional diffusion in a clonal pattern. The close association observed among aph(2â³)-If-positive C. jejuni strains isolated from poultry, food, and clinical environments underscores the potential for zoonotic transmission from these isolates.
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Aminoglicosídeos , Antibacterianos , Infecções por Campylobacter , Campylobacter jejuni , Farmacorresistência Bacteriana , Tipagem de Sequências Multilocus , Filogenia , Campylobacter jejuni/genética , Campylobacter jejuni/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Aminoglicosídeos/farmacologia , Animais , Antibacterianos/farmacologia , Infecções por Campylobacter/microbiologia , Infecções por Campylobacter/veterinária , Infecções por Campylobacter/epidemiologia , Sequenciamento Completo do Genoma , Humanos , Prevalência , China , Microbiologia de Alimentos , Testes de Sensibilidade MicrobianaRESUMO
Polyhalogenated carbazoles (PHCZs), an emerging persistent halogenated organic pollutant, have been detected in the environment. However, our understanding of PHCZs in the ocean remains limited. In this study, 47 seawater samples (covering 50 - 4000 m) and sediment samples (49 surface and 3 cores) were collected to investigate the occurrence and spatial distribution patterns of carbazole and its halogenated derivants (CZDs) in the Western Pacific Ocean. In seawater, the detection frequencies of CZ (97.87%) and 3-CCZ (57.45%) were relatively high. In addition, the average concentration of ΣPHCZs in the upper water (< 150 m, 0.23 ± 0.21 ng/L) was significantly lower than that in the deep ocean (1000 - 4000 m, 0.65 ± 0.56 ng/L, P < 0.05), which may indicate the vertical transport of PHCZs in the marine environment. The concentration of ΣCZDs in surface sediment ranges from 0.46 to 6.48 ng/g (mean 1.54 ng/g), among which CZ and 36-CCZ were the predominant components. Results from sediment cores demonstrate a noteworthy negative correlation between the concentration of CZDs and depth, indicating the ongoing natural degradation process occurring in sediment cores over a long period. This study offers distinctive insights into the occurrence, composition, and vertical features of CZDs in oceanic environments.
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BACKGROUND: While the development of CT imaging technique has brought cognition of in vivo organs, the resolution of CT images and their static characteristics have gradually become barriers of microscopic tissue research. PURPOSE: Previous research used the finite element method to study the airflow and gas exchange in the alveolus and acinar to show the fate of inhaled aerosols and studied the diffusive, convective, and sedimentation mechanisms. Our study combines these techniques with CT scan simulation to study the mechanisms of respiratory movement and its imaging appearance. METHODS: We use 3D fluid-structure interaction simulation to study the movement of an ideal alveolus under regular and forced breathing situations and ill alveoli with different tissue elasticities. Additionally, we use the Monte Carlo algorithm within the OpenGATE platform to simulate the computational CT images of the dynamic process with different designated resolutions. The resolutions show the relationship between the kinematic model of the human alveolus and its imaging appearance. RESULTS: The results show that the alveolus and the wall thickness can be seen with an image resolution smaller than 15.6 µm. With ordinary CT resolution, the alveolus is expressed with four voxels. CONCLUSIONS: This is a preliminary study concerning the imaging appearance of the dynamic alveolus model. This technique will be used to study the imaging appearance of the dynamic bronchial tree and the lung lobe models in the future.
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Pulmão , Alvéolos Pulmonares , Humanos , Pulmão/diagnóstico por imagem , Alvéolos Pulmonares/diagnóstico por imagem , Respiração , Aerossóis , Tomografia Computadorizada por Raios X , Simulação por ComputadorRESUMO
Covalent organic frameworks (COFs) have shown great advantages as photocatalysts for hydrogen evolution. However, the effect of linkage geometry and type of linkage on the extent of π-electron conjugation in the plane of the framework and photocatalytic properties of COFs remains a significant challenge. Herein, two Kagome (kgm) topologic oligo(phenylenevinylene)-based COFs are designed and synthesized for boosting photocatalytic hydrogen evolution via a "two in one" strategy. Under visible light irradiation, COF-954 with 5 wt% Pt as cocatalyst exhibits high hydrogen evolution rate (HER) of 137.23 mmol g-1 h-1 , outperforming most reported COF-based photocatalysts. More importantly, even in natural seawater, COF-954 shows an average HER of 191.70 mmol g-1 h-1 under ultraviolet-visible (UV-vis) light irradiation. Additionally, the water-drainage experiments indoors and outdoors demonstrate that 25 and 8 mL hydrogen gas could be produced in 80 min under UV-vis light and natural sunlight, respectively, corresponding to a high HER of 167.41 and 53.57 mmol h-1 g-1 . This work not only demonstrates an effective design strategy toward highly efficient COF-based photocatalysts, but also shows the great potential of using the COF-based photocatalysts for photocatalytic hydrogen evolution.
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The demand for respiratory disease and dynamic breathing studies has continuously driven researchers to update the pulmonary bronchial tree's morphology model. This study aims to construct a bronchial tree morphology model efficiently and effectively with practical algorithms. We built a performance index system using failure branch rate, volume ratio, and coefficient of variation of terminal volumes to evaluate the model performance. We optimized the parameter settings and found the best options to build the morphology model, and we constructed a 14th-generation bronchial tree model with a decent performance index. The dimensions of our model closely matched published data from anatomic in vitro measurements. The proposed model is adjustable and computable and will be used in future dynamic breathing simulations and respiratory disease studies.
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BACKGROUND: Ovarian cancer has been a worldwide health burden for women and its progression is highly hypoxia-independent. Here, we investigated the exact mechanisms by which hypoxia contributes to the malignant progression of ovarian cancer. METHOD: MTT, transwell, colony formation, and scratch wound healing assays were carried out for cellular functions. The underlying mechanism by which hypoxia functions was explored by RNA-seq, enrichment analysis, western blotting, qRT-PCR, flow cytometry, ChIP, luciferase reporter, and ELISA. Finally, animal experiments including the xenograft model and tumor metastasis model were constructed to validate the role of SLC2A12 in vivo. RESULTS: Hypoxia treatment promoted the cell proliferation, mobility, and colony growth abilities of the two ovarian cancer cell lines HO-8910 and A2780. RNA-seq and enrichment analysis showed that SLC2A12 was hyper-expressed under hypoxia condition and it may be related to glutathione and lipid metabolism. Besides, the expression of SLC2A12 was negatively correlated with overall survival. Hypoxia suppressed ferroptosis by SLC2A12 because silencing SLC2A12 declined the cell viability of HO-8910 and A2780 cells under hypoxia conditions, while the ferroptosis inhibitor ferrostatin-1 (Fer-1) breached that result and upregulated the expression of glutathione peroxidase 4 (GPX4). Moreover, hypoxia increased the expression of hypoxia inducible factor 1 A (HIF-1A), and the accumulated HIF-1A binds to hypoxia inducible factor 1 B (HIF1B) to form HIF-1 complex, then promoted the binding of hypoxic response elements (HRE) to SLC2A12 promoter by HIF-1/HRE signal. Subsequently, SLC2A12 regulated glutathione metabolism and in turn inhibited ferroptosis. The animal experiments indicated that silencing SLC2A12 could significantly inhibit tumor growth and metastasis in vivo. CONCLUSION: Hypoxia promoted ovarian cancer progression by upregulating SLC2A12 and then regulating glutathione metabolism to inhibit ferroptosis.
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Ferroptose , Proteínas Facilitadoras de Transporte de Glucose , Neoplasias Ovarianas , Animais , Feminino , Humanos , Linhagem Celular Tumoral , Ferroptose/genética , Glutationa , Hipóxia , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Ovarianas/patologia , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismoRESUMO
In this work, one-dimensional TiO2 nanotube arrays are coupled with a covalent organic framework (COF) thin film with a controlled thickness to form a three-dimensional heterojunction, which exhibits a 3.3-fold higher hydrogen evolution rate than that of TiO2, and becomes active for CO2 conversion, compared to the bare COF. Such high activity results from the large difference in Fermi levels forming an internal electric field at the interface.
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Strong and ductile adhesives often undergo both interfacial and cohesive failure during the debonding process. Herein, we report a rare self-reinforcing polyurethane adhesive that shows the different phenomenon of only interfacial failure yet still exhibiting superior adhesive strength and toughness. It is synthesized by designing a hanging adhesive moiety, hierarchical H-bond moieties, and a crystallizable soft segment into one macromolecular polyurethane. The former hanging adhesive moiety allows the hot-melt adhesive to effectively associate with the target substrate, providing sufficient adhesion energy; the latter hierarchical H-bond moieties and a crystallizable soft segment cooperate to enable the adhesive to undergo large lap-shear deformations through sacrificing weak bonds and mechano-responsive strength through the fundamental mechanism of strain-induced crystallization. As a result, this polyurethane adhesive can keep itself intact during the debonding process while still withstanding a high lap-shear strength and dissipating tremendous stress energy. Its adhesive strength and work of debonding are as high as 11.37 MPa and 10.32 kN m-1, respectively, outperforming most reported tough adhesives. This self-reinforcing adhesive is regarded as a new member of the family of strong and ductile adhesives, which will provide innovative chemical and structural inspirations for future conveniently detachable yet high-performance adhesives.
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To exploit the potential of our newly developed three-dimensional (3D) dimerized acceptors, a series of chlorinated 3D acceptors (namely CH8-3/4/5) were reported by precisely tuning the position of chlorine (Cl) atom. The introduction of Cl atom in central unit affects the molecular conformation. Whereas, by replacing fluorinated terminal groups (CH8-3) with chlorinated terminal groups (CH8-4 and CH8-5), the red-shift absorption and enhanced crystallization are achieved. Benefiting from these, all devices received promising power conversion efficiencies (PCEs) over 16 % as well as decent thermal/photo-stabilities. Among them, PM6:CH8-4 based device yielded a best PCE of 17.58 %. Besides, the 3D merits with multi alkyl chains enable their versatile processability during the device preparation. Impressive PCEs of 17.27 % and 16.23 % could be achieved for non-halogen solvent processable devices prepared in glovebox and ambient, respectively. 2.88â cm2 modules also obtained PCEs over 13 % via spin-coating and blade-coating methods, respectively. These results are among the best performance of dimerized acceptors. The decent performance of CH8-4 on small-area devices, modules and non-halogen solvent-processed devices highlights the versatile processing capability of our 3D acceptors, as well as their potential applications in the future.
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OBJECTIVE: To investigate the prevalence of a tet(A) gene variant and its role in developing high-level tigecycline resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates. METHODS: The mechanism of high-level tigecycline resistance in CRKP mediated by a tet(A) variant was explored by induction experiments, antimicrobial susceptibility testing, whole-genome sequencing and bioinformatics analysis. The amplification and overexpression of the tet(A) variant were measured by the determination of sequencing depth, gene copy numbers, and qRT-PCR. RESULTS: A high rate (62.1%, 998/1607) of tet(A) variant carriage was observed among 1607 CRKP clinical isolates from Henan Province, China. High-level tigecycline resistance could rapidly develop by the amplification of the tet(A) variant in these isolates. The analysis of the raw sequencing data and the plasmid mapping depth revealed that the ΔtnpA homologous sequence of Tn1721 supports the amplification of the region that harbours the tet(A) variant by forming a large number of repeat arrays through translocatable units (TUs). Moreover, the epidemiological analysis of tet(A) variant-carrying structures among 1607 clinical CRKPs showed that the TU structure is widely present. CONCLUSION: The presence of a tigecycline resistance-mediating tet(A) variant in CRKP clinical isolates represents a greater health concern than initially thought and should be monitored consistently.
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Three-dimensional covalent organic frameworks (3D COFs) have been of great interest due to their inherent numerous open sites and pore confinement effect. However, it has remained challenging to build 3D frameworks via interdigitation (also known as inclined interpenetration) by generating an entangled network formed by multiple 2D layers inclined with respect to each other. Herein, we report the first case of constructing a 3D COF, termed COF-904, through interdigitating 2D hcb nets, which was formed via [3+2] imine condensation reactions by the use of 1,3,5-triformylbenzene and 2,3,5,6-tetramethyl-1,4-phenylenediamine. The single-crystal structure of COF-904 is solved, and the locations of all non-hydrogen atoms are determined by 3D electron diffraction with a resolution up to 0.8 Å. These results not only broaden the strategy for achieving 3D COFs via interdigitation but also demonstrate that structurally complex extended frameworks can arise from simple molecules.
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Covalent organic frameworks (COFs) have gained significant attention as key photocatalysts for efficient solar light conversion into hydrogen production. Unfortunately, the harsh synthetic conditions and intricate growth process required to obtain highly crystalline COFs greatly hinder their practical application. Herein, we report a simple strategy for the efficient crystallization of 2D COFs based on the intermediate formation of hexagonal macrocycles. Mechanistic investigation suggests that the use of 2,4,6-triformyl resorcinol (TFR) as the asymmetrical aldehyde build block allows the equilibration between irreversible enol-to-keto tautomerization and dynamic imine bonds to produce the hexagonal ß-ketoenamine-linked macrocycles, the formation of which could provide COFs with high crystallinity in half hour. We show that COF-935 with 3â wt % Pt as cocatalyst exhibit a high hydrogen evolution rate of 67.55â mmol g-1 h-1 for water splitting when exposed to visible light. More importantly, COF-935 exhibits an average hydrogen evolution rate of 19.80â mmol g-1 h-1 even at a low loading of only 0.1â wt % Pt, which is a significant breakthrough in this field. This strategy would provide valuable insights into the design of highly crystalline COFs as efficient organic semiconductor photocatalysts.
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Aim: Steam pop (SP) during radiofrequency catheter ablation (RFCA) for pulmonary vein isolation (PVI) may cause cardiac perforation, which may require drainage and emergent thoracotomy or even lead to death. Data investigating the timely detection of the occurrence of "silent" or "nonaudible" SP events are limited. Methods and Results: A total of 516 consecutive atrial fibrillation (AF) patients who underwent index PVI were included in this retrospective observational study. The duration, power, impedance, temperature, and contact force (CF) of RFCA were continually monitored and recorded throughout the procedure. A total of 15 (2.9%) audible SP events occurred in 14 patients; 2 of the patients developed pericardial tamponade, 1 patient underwent drainage, and 1 patient underwent emergent thoracotomy. The time from RFCA initiation to the occurrence of audible SP was 19.4 ± 6.9 s. Abrupt temperature change occurred in 13 (86.7%) of the 15 SP events, of which 8 (53.3%) exhibited an abrupt temperature rise of 2.3 ± 1.0°C, 5 (33.3%) exhibited an abrupt temperature drop of 2.3 ± 1.3°C, and 2 (13.3%) exhibited no discernible temperature change. Conclusions: In conclusion, simultaneously recorded spike potentials and abrupt impedance rise with concomitant temperature and/or CF change could be a feasible method for the timely detection of the occurrence of audible, "silent," or "nonaudible" SP events, particularly in regions where the risk of perforation may be of concern.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Temperatura , Vapor , Impedância Elétrica , Potenciais de Ação , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Resultado do TratamentoRESUMO
Imine-linked covalent organic frameworks (COFs) have been extensively studied in photocatalysis because of their easy synthesis and excellent crystallinity. The effect of imine-bond orientation on the photocatalytic properties of COFs, however, is still rarely studied. Herein, we report two novel COFs with different orientations of imine bonds using oligo(phenylenevinylene) moieties. The COFs showed similar structures but great differences in their photoelectric properties. COF-932 demonstrated a superior hydrogen evolution performance compared to COF-923 when triethanolamine was used as the sacrificial agent. Interestingly, the use of ascorbic acid led to the protonation of the COFs, further altering the direction of electron transfer. The photocatalytic performances were increased to 23.4 and 0.73â mmol g-1 h-1 for protonated COF-923 and COF-932, respectively. This study provides a clear strategy for the design of imine-linked COF-based photocatalysts and advances the development of COFs.
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OBJECTIVE: To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. METHODS: A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. RESULTS: The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. CONCLUSION: Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.