Atomic Imaging of Multi-Dimensional Ruddlesden-Popper Interfaces in Lead-Halide Perovskites.

Ruddlesden-Popper (RP) interface with defined stacking structure will fundamentally influence the optoelectronic performances of lead-halide perovskite (LHP) materials and devices. However, it remains challenging to observe the atomic local structures in LHPs, especially for multi-dimensional RP interface hidden inside the nanocrystal. In this work, the advantages of two imaging modes in scanning transmission electron microscopy (STEM), including high-angle annular dark field (HAADF) and integrated differential phase contrast (iDPC) STEM, are successfully combined to study the bulk and local structures of inorganic and organic/inorganic hybrid LHP nanocrystals. Then, the multi-dimensional RP interfaces in these LHPs are atomically resolved with clear gap and blurred transition region, respectively. In particular, the complex interface by the RP stacking in 3D directions can be analyzed in 2D projected image. Finally, the phase transition, ion missing, and electronic structures related to this interface are investigated. These results provide real-space evidence for observing and analyzing atomic multi-dimensional RP interfaces, which may help to better understand the structure-property relation of LHPs, especially their complex local structures.

Endovascular thrombectomy for acute ischemic stroke in elderly patients with large ischemic cores.

BACKGROUND: Understanding the benefits and risks of endovascular therapy (EVT) is crucial for elderly patients with large ischemic cores, as the combination of advanced age and extensive brain infarction may negatively impact clinical outcomes. METHODS: The study retrospectively analyzed clinical outcomes for elderly stroke patients (age ≥ 70) with large ischemic cores (Alberta Stroke Program Early CT Score [ASPECTS] < 6 or ischemic cores ≥ 70 ml) in the anterior circulation using data from our prospective database between June 2018 and January 2022. The effectiveness and risks of EVT in those patients were investigated, with the primary outcome being fair outcome (modified Rankin Scale, mRS ≤ 3). RESULTS: Among 182 elderly patients with large ischemic core volume (120 in the EVT group and 62 in the non-EVT group), 20.9% (38/182, 22.5% in the EVT group vs. 17.7% in the non-EVT group) achieved a fair outcome. Meanwhile, 49.5% (90/182, 45.8% in the EVT group vs. 56.5% in the non-EVT group) of them died at 3 months. The benefits of EVT numerically exceeded non-EVT treatment for those aged ≤ ~ 85 years or with a mismatch volume ≥ ~ 50 ml. However, after adjustment, EVT was associated with an increased risk of symptomatic intracranial hemorrhage (aOR 4.24, 95%CI 1.262-14.247). CONCLUSIONS: This study highlights the clinical challenges faced by elderly patients with large infarctions, resulting in poor outcomes at 3 months. EVT may still provide some benefits in this population, but it also carries an increased risk of intracranial hemorrhage.

Implication of m6A Methylation Regulators in the Immune Microenvironment of Bronchopulmonary Dysplasia.

N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of bronchopulmonary dysplasia (BPD) remains poorly characterized. Thus, the purpose of this investigation was to evaluate the effects of m6A RNA methylation regulators on the development of BPD. BPD-related transcriptome data were downloaded from the GEO database. Differentially expressed m6A methylation regulators between BPD and control group were identified. Consensus clustering was conducted for the classification of BPD and association between clusters and BPD phenotypes were explored. Analysis of differentially expressed genes (DEGs) and immune-related DEGs was performed. The GSEA, GO and KEGG analyses were used to interpret the functional enrichments. The composition of immune cell subtypes in BPD subsets was predicted by CIBERSORT analysis. Compared with the control group, expression of most m6A regulators showed significant alteration, especially for IGF2BP1/2/3. BPD was classified into 2 subsets, and cluster 1 was correlated with severe BPD. Furthermore, the results of functional enrichment analyses showed a disturbed immune-related signaling pathway. Based on CIBERSORT analysis, we found that the proportion of immune cell subsets changed between cluster 1 and cluster 2. Our study revealed the implication of m6A methylation regulators in the development of BPD, which might provide a novel insight for the diagnosis and treatment of BPD.

Activable Nano-Immunomodulator Assembled from π-Extended Naphthalenediimide for Precision Photothermal Immunotherapy.

A nano-immunomodulator (R-NPT NP) comprising a tumor microenvironment (TME) activable resiquimod (R848) and a π-extended NIR-absorbing naphthophenanthrolinetetraone (NPT) has been engineered for spatiotemporal controlled photothermal immunotherapy. R-NPT NP demonstrated excellent photostability, while R848 promoted synergistic immunity as a toll-like receptor 7/8 (TLR7/8) agonist. Upon accumulation at the tumor site, R-NPT NP released R848 in response to redox metabolite glutathione (GSH), triggering dendritic cell (DC) activation. The photothermal effect endowed by R-NPT NP can ablate tumors directly and trigger immunogenic cell death to augment immunity after photoirradiation. The synergistic effect of GSH-liable TLR7/8 agonist and released immunogenic factors leads to a robust evocation of systematic immunity through promoted DC maturation and T cell infiltration. Thus, R-NPT NP with photoirradiation achieved 99.3 % and 98.2 % growth inhibition against primary and distal tumors, respectively.

AtINO80 represses photomorphogenesis by modulating nucleosome density and H2A.Z incorporation in light-related genes.

Photomorphogenesis is a critical developmental process bridging light-regulated transcriptional reprogramming with morphological changes in organisms. Strikingly, the chromatin-based transcriptional control of photomorphogenesis remains poorly understood. Here, we show that the Arabidopsis (Arabidopsis thaliana) ortholog of ATP-dependent chromatin-remodeling factor AtINO80 represses plant photomorphogenesis. Loss of AtINO80 inhibited hypocotyl cell elongation and caused anthocyanin accumulation. Both light-induced genes and dark-induced genes were affected in the atino80 mutant. Genome-wide occupancy of the H2A.Z histone variant and levels of histone H3 were reduced in atino80 In particular, AtINO80 bound the gene body of ELONGATED HYPOCOTYL 5 (HY5), resulting in lower chromatin incorporations of H2A.Z and H3 at HY5 in atino80 Genetic analysis revealed that AtINO80 acts in a phytochrome B- and HY5-dependent manner in the regulation of photomorphogenesis. Together, our study elucidates a mechanism wherein AtINO80 modulates nucleosome density and H2A.Z incorporation and represses the transcription of light-related genes, such as HY5, to fine tune plant photomorphogenesis.

Real-Space Imaging of the Node-Linker Coordination on the Interfaces between Self-Assembled Metal-Organic Frameworks.

Surface and interface, with unique local characteristics different from bulk structure, are of great significance in various applications of metal-organic frameworks (MOFs), which should be studied by real-space imaging methods, such as electron microscopy. However, it is still challenging to atomically resolve these local structures in MOFs, because they are even more sensitive to electron irradiation. Here, we use integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM) to achieve the atomic imaging of both the metal nodes and organic linkers in UiO-66 (Zr) nanocrystals and their assembly. After adding acetic acid, we modulate the whole process of MOF assembly and observe the organic linkers at both the surfaces and twin interfaces in the chemically assembled UiO-66 (Zr) crystals by the iDPC-STEM. These results bring us a deeper understanding on the role of acid modulators that promote the MOF assembly by generating the missing-linker defects on the crystal surface.

The Hyperdense middle cerebral artery sign is associated with poor leptomeningeal collaterals in acute ischemic stroke: a retrospective study.

BACKGROUND: The hyperdense middle cerebral artery sign (HMCAS) is an early radiological marker to provide an early diagnosis and to identify ischemia. As reported, HMCAS is associated with heavy clot burden. Moreover, a heavy clot burden may cause obstruction of the orifices of arteries for leptomeningeal collateral flows and can lead to severe clinical conditions. However, the direct relationship between HMCAS and collateral flows remains unclear. Therefore, we explored the association between HMCAS and leptomeningeal collaterals in patients with acute ischemic stroke. METHODS: Consecutive ischemic stroke patients were enrolled from January 2015 to April 2021. HMCAS appearance and collateral status were detected by multimodal computed tomography at admission. Logistic regression analyses helped to identify the association between HMCAS, collateral flows and stroke severity. RESULTS: In 494 included patients, 180 (36.4%) presented with HMCAS. Ipsilateral collaterals were not seen or less prominent in patients with HMCAS (P < 0.001). The HMCAS appearance was significantly associated with less collaterals (odds ratio 5.17, 95% confidence interval 3.27-8.18, P < 0.001), internal carotid artery + M1/M1 occlusion, the initial stroke severity and follow-up outcomes. Subgroup analyses further confirmed HMCAS as an indicator of poor collaterals in ischemic stroke (all P values < 0.05). CONCLUSIONS: HMCAS is associated with poor leptomeningeal collaterals, the stroke severity and a poor neurological outcome. Therefore, the HMCAS appearance can act as an early warning sign for healthcare professionals to be alert for poor collateral flows and poor neurological outcomes in ischemic stroke patients with middle cerebral artery occlusion.

GSK-3ß inhibition protects human nucleus pulposus cell against oxidative stress-inducing apoptosis through mitochondrial pathway.

BACKGROUND: Oxidative stress in the intervertebral disc leads to nucleus pulposus (NP) degeneration by inducing cell apoptosis. However, the molecular mechanisms underlying this process remain unclear. Increasing evidence indicates that GSK-3ß is related to cell apoptosis induced by oxidative stress. In this study, we explored whether GSK-3ß inhibition protects human NP cell against apoptosis under oxidative stress. METHODS AND RESULTS: Immunofluorescence staining was used to show the expression of GSK-3ß in human NP cells (NPCs). Flow cytometry, mitochondrial staining and western blot (WB) were used to detect apoptosis of treated NPCs, changes of mitochondrial membrane potential and the expression of mitochondrial apoptosis-related proteins using GSK-3ß specific inhibitor SB216763. Co-Immunoprecipitation (Co-IP) was used to demonstrate the interaction between GSK-3ß and Bcl-2. We delineated the protective effect of GSK-3ß specific inhibitor SB216763 on human NPCs apoptosis induced by oxidative stress in vitro. Further, we showed SB216763 exert the protective effect by preservation of the mitochondrial membrane potential and inhibition of caspase 3/7 activity during oxidative injury. The detailed mechanism underlying the antiapoptotic effect of GSK-3ß inhibition was also studied by analyzing mitochondrial apoptosis pathway in vitro. CONCLUSIONS: We concluded that the GSK-3ß inhibitor SB216763 protected mitochondrial membrane potential to delay nucleus pulposus cell apoptosis by inhibiting the interaction between GSK-3ß and Bcl-2 and subsequently reducing cytochrome c(Cyto-C) release and caspase-3 activation. Together, inhibition of GSK-3ß using SB216763 in NPCs may be a favorable therapeutic strategy to slow intervertebral disc degeneration.

Calcium channel blockers versus other classes of drugs for hypertension.

BACKGROUND: This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated. OBJECTIVES: To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events. SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions. SELECTION CRITERIA: Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years. DATA COLLECTION AND ANALYSIS: Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information. MAIN RESULTS: This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased  major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence). AUTHORS' CONCLUSIONS: For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.

Relationship Between Body Temperature and Early Neurological Deterioration after Endovascular Thrombectomy for Acute Ischemic Stroke with Large Vessel Occlusion.

BACKGROUND: Early neurological deterioration (END) after endovascular thrombectomy (EVT) is strongly associated with poor prognosis in patients with large vessel occlusion. The relationship between body temperature and END after EVT is unknown, which we aimed to investigate in this study. METHODS: END was defined as an increase of four or more points on the National Institutes of Health Stroke Scale score compared with the baseline assessment within 24 h. Logistic regression and restricted cubic spline models were used to assess the relationship between body temperature and END. RESULTS: Among 7741 consecutive patients with ischemic stroke, 406 patients with large vessel occlusion who underwent EVT were enrolled. In total, 88 (21.7%) patients developed END. Logistic regression showed that the maximum body temperature within 24 h (odds ratio [OR] = 1.97 per °C, 95% confidence interval [CI] 1.17-3.32, p = 0.010) was independently associated with END. This association was nonlinear and J shaped (p for nonlinearity = 0.010), and the risk of END increased when the maximum body temperature within 24 h was lower or higher than 37.0 °C. Fever burden is also independently associated with END (OR = 1.06 per °C × hour, 95% CI 1.01-1.11, p = 0.012). In addition, the timing of fever onset was independently associated with END, and the highest risk of END was associated with fever onset within 6 h after EVT (OR = 3.92, 95% CI 1.25-12.27, p = 0.019). CONCLUSIONS: In summary, there is a J-shaped association between the maximum body temperature within 24 h after EVT and END. Moreover, the risk of END differed according to the timing of fever onset.

Calcium channel blockers versus other classes of drugs for hypertension.

BACKGROUND: This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated. OBJECTIVES: To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events. SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions. SELECTION CRITERIA: Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years. DATA COLLECTION AND ANALYSIS: Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information. MAIN RESULTS: This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased  major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence). AUTHORS' CONCLUSIONS: For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.

Development and utility of a close contact information management system for the COVID-19 pandemic.

BACKGROUND: Since the outbreak started in 2019, COVID-19 pandemic has a significant global impact. Due to the highly infective nature of SARS-CoV-2, the COVID-19 close contacts are at significant risk of contracting COVID-19. China's experience in successfully controlling COVID-19 emphasized the importance of managing close contacts because this strategy helps to limit potential infection sources, prevent the unconscious spread of COVID-19 and thus control this pandemic. As a result, to understand and consider the management of close contacts may be beneficial to other countries. However, managing close contacts is challenging owing to the huge number of close contacts and a lack of appropriate management tools and literature references. METHODS: A new system called the COVID-19 Close Contact Information Management System was developed. Here we introduced the design, use, improvement and achievements of this system. RESULTS: This system was designed from the standpoint of the Centers for Disease Control and Prevention in charge of managing close contacts. Two main functions and eight modules/themes were ultimately formed after two development stages. The system introduces what information need to be collected in the close contact management. Since the system allows information flow across cities, the geographical distance and administrative regional boundaries are no longer obstacles for managing close contacts, which promotes the management of each close contact. Moreover, when this system is used in conjunction with other data tools, it provides data assistance for understanding the COVID-19 characteristics and formulating targeted COVID-19 control policies. To date, the system has been widely used in Guangdong Province for over 1 year and has recorded tens of thousands of pieces of data. There is sufficient practical experience to suggest that the system is capable of meeting the professional work requirements for close contact management. CONCLUSIONS: This system provides a new way to manage close contacts and restrict the spread of COVID-19 by combining information technology with disease prevention and control strategies in the realm of public health. We hope that this system will serve as an example and guide for those anticipating similar work in other countries in response to current and future public health incidents.

Protective Effects of L-Theanine on IPEC-J2 Cells Growth Inhibition Induced by Dextran Sulfate Sodium via p53 Signaling Pathway.

L-theanine is a nonprotein amino acid found in tea leaves and has been widely used as a safe food additive in beverages or foods because of its varied bioactivities. The aim of this study was to reveal the in vitro gastrointestinal protective effects of L-theanine in DSS-induced intestinal porcine enterocyte (IPEC-J2) cell models using molecular and metabolic methods. Results showed that 2.5% dextran sulfate sodium (DSS) treatment inhibited the cell proliferation of IPEC-J2 and blocked the normal operation of the cell cycle, while L-theanine pretreatment significantly preserved these trends to exert protective effects. L-theanine pre-treatment also up-regulated the EGF, CDC2, FGF2, Rb genes and down-regulated p53, p21 proliferation-related mRNA expression in DSS-treated cells, in accompany with p53 signaling pathway inhibition. Meanwhile, metabolomics analysis revealed that L-theanine and DSS treated IPEC-J2 cells have different metabolomic profiles, with significant changes in the key metabolites involved in pyrimidine metabolism and amino acid metabolism, which play an important role in nucleotide metabolism. In summary, L-theanine has a beneficial protection in DSS-induced IPEC-J2 cells via promoting proliferation and regulating metabolism disorders.

The MdXTHB gene is involved in fruit softening in 'Golden Del. Reinders' (Malus pumila).

BACKGROUND: Fruit softening is a major determinant of commercial value and shelf life. A transcriptomic analysis of 'Golden Delicious' and 'Golden Del. Reinders' (a bud mutation of 'Golden Delicious' that readily softens) apple fruit was conducted during storage. RESULTS: A comparative analysis of the obtained expression profiles of fruit between two cultivars identified 1345 upregulated and 3475 downregulated differentially expressed genes (DEGs). The DEGs identified were associated with cellular processes and carbohydrate metabolism and were especially enriched in cell-wall-related genes. Among the cell-wall-related genes, the xyloglucan endotransglucosylase/hydrolases (XTH) gene MdXTHB was significantly upregulated and exhibited high expression levels in 'Golden Del. Reinders' fruit, which had a lower level of firmness relative to 'Golden Delicious'. Overexpression of MdXTHB in both 'Golden Delicious' and 'Fuji', which typically maintain high levels of firmness in storage, exhibited faster rates of softening and an earlier peak of ethylene production than empty-vector-infiltrated fruit did. CONCLUSION: The results of this study indicate that MdXTHB potentially promotes apple fruit softening by degrading the fruit cell wall. This result is also useful to designing further experiments on the molecular regulation of fruit softening in apple. © 2020 Society of Chemical Industry.

The impact of COVID-19 pandemic on headache symptoms and drug withdrawal among patients with medication overuse headache: a cross-sectional study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) bring about a range of psychological distress and symptom deterioration to headache patients especially to some migraineurs. Compared to migraineurs or normal control, medication overuse headache (MOH) patients are more likely to experience a worse psychological distress and poorer outcome in non-COVID-19 time. However, in COVID-19 pandemic, whether MOH patients would have greater physical and mental symptom deterioration or worse relief of headache symptoms and medications overuse remained unclear. We aim to investigate the impact of COVID-19 on MOH patients to guide for a better management in this study. METHODS: We enrolled MOH patients who were diagnosed and treated at headache clinic of West China Hospital. Information of the pre-pandemic 3 months period and COVID-19 pandemic period was collected. Univariate and multivariate logistic regression were performed to identify independent factors associated with changes in headache symptoms and drug withdrawal. RESULTS: Seventy-eight MOH patients were enrolled into the study ultimately. In comparison to pre-pandemic period, fewer MOH patients reported decreased headache days, intensity and days with acute medications per month during the pandemic. Available access to regular prophylactic medications was significantly associated with a reduction of at least 50% in headache days and decrease in headache intensity per month with respective odds ratios of 39.19 (95% CI 3.75-409.15, P = 0.002) and 10.13 (95% CI 2.33-44.12, P = 0.002). Following abrupt withdrawal and high educational level were both significant factors in decreasing headache intensity. Male sex was significantly associated with decrease in days with acute medication per month during the pandemic (odds ratios 4.78, 95%CI 1.44-15.87, P = 0.011). CONCLUSIONS: Our findings reflect that MOH patients experienced a worse relief of headache symptoms and drug withdrawal during the pandemic. Available access to regular prophylactic medications was the significant independent factor for improvement of headache symptoms. Male sex was significantly associated with decreased days with acute medications per month.

A Nature-Inspired Metal-Organic Framework Discriminator for Differential Diagnosis of Cancer Cell Subtypes.

Metabolic glycan labeling (MGL) followed by bioorthogonal chemistry provides a powerful tool for tumor imaging and therapy. However, selectively metabolic labeling of cells or tissues of interest remains a challenge. Particularly, owing to tumor heterogeneity including tumor subtypes and interpatient heterogeneity, it is far more difficult to realize tumor-cell-selective metabolic labeling for precise diagnosis. Inspired by nature, we designed azidosugar-functionalized metal-organic frameworks camouflaged with cancer cell membranes to accomplish cancer-cell-selective MGL in vivo. With abundant receptors, this biomimetic platform not only selectively targets homotypic cells but also realizes different breast cancer subtype-selective MGL. Moreover, the endo/lysosomal-escaped ZIF-8 can make azidosugar escape from lysosomes and accelerate its metabolic incorporation. This strategy also takes advantage of cancer-tissue-derived cell membranes, which may have huge potential for personalized diagnosis and therapy.

Self-Protecting Biomimetic Nanozyme for Selective and Synergistic Clearance of Peripheral Amyloid-ß in an Alzheimer's Disease Model.

Clearance of peripheral amyloid-ß (Aß) has been demonstrated to be promising for overcoming the blood-brain barrier (BBB) hurdle to eliminate brain-derived Aß associated with Alzheimer's disease (AD). Even so, current developed therapeutic assays for clearance of peripheral Aß are still facing challenges on how to avoid interference of certain biological molecules and prevent triggering the activation of immune responses and blood clotting. Here, a biomimetic nanozyme (CuxO@EM-K) with augmented protein adsorption resistance, minimized immunogenicity, and enhanced biocompatibility is designed and synthesized. The CuxO@EM-K is made of CuxO nanozyme wrapped with modified 3xTg-AD mouse erythrocyte membrane with Aß-targeting pentapeptide KLVFF. KLVFF serves as Aß-specific ligand that works together with erythrocyte membrane to selectively capture Aß in the blood. Meanwhile, the erythrocyte membrane coating prevents protein coronas formation and thus retains Aß-targeting ability of CuxO@EM-K in biological fluids. More importantly, the CuxO core with multiple antioxidant enzyme-like activities stabilizes the outer erythrocyte membrane and simultaneously mitigates Aß-induced membrane oxidative damage, which enables the extended systemic circulation indispensable for adsorbing Aß. In vivo studies demonstrate that CuxO@EM-K not only reduces Aß burden in the blood and brain but also ameliorates memory deficits in the widely used 3xTg-AD mouse model. Moreover, CuxO@EM-K shows no apparent toxicity in 3xTg-AD mice. Overall, this work provides an example for developing biocompatible and synergistic clearance of peripheral Aß associated with AD.

A sensitive and rapid "off-on" fluorescent probe for the detection of esterase and its application in evaluating cell status and discrimination of living cells and dead cells.

The discrimination of living and dead cells shows great importance in the development of biology, pathology, medicine, and pharmacology research. Herein, we synthesized a simple benzothiazole-based probe, EP, which was characterized via1H NMR (hydrogen nuclear magnetic resonance) spectroscopy, 13C NMR (carbon nuclear magnetic resonance) spectroscopy and HRMS (high-resolution mass spectroscopy). The fluorescence changes in response to esterase were characterized via fluorescence spectroscopy. EP exhibited a 70-fold fluorescence enhancement in the presence of esterase and possessed a very low limit of detection (4.73 × 10-5 U mL-1). EP also showed high selectivity to esterase compared to other biological species. Bright fluorescence appeared in living cells, which was activated by esterase when incubated with EP. In paraformaldehyde or H2O2 pretreated cells, the fluorescence became very weak since esterase became inactive in these cells. In summary, the EP probe can monitor esterase activity both in vitro and in living cells and can be used to evaluate the health status of cells and discriminate living and dead cells effectively.

Alleviation of drought stress and the physiological mechanisms in Citrus cultivar (Huangguogan) treated with methyl jasmonate.

The role of exogenous methyl jasmonate (MeJA) in alleviating drought stress was investigated on Huangguogan. Except for intercellular CO2 concentration, MeJA had little effect on net photosynthetic rate, stomatal conductance, and transpiration rate under drought stress. Compared with drought stress, MeJA significantly alleviated the decrease of chlorophyll content. However, chlorophyll a/b ratio was significantly increased. MeJA significantly increased proline and soluble sugar contents, significantly decreased the O2 -· and H2O2 levels, and increased SOD and POD activities. In addition, the MDA content of drought stress was the highest of all treatments. MeJA significantly reduced MDA content in drought-stressed Huangguogan leaves. Although the Ascorbic acid (AsA) contents of 500 and 1000 mg L-1 MeJA treatments were lower than that of 250 mg L-1 MeJA, but all concentration of MeJA treatments delayed the decline of AsA content. Therefore, MeJA could induce drought stress tolerance by increasing the osmotic adjustment substances and antioxidant activities.

Camera calibration for anamorphic lenses with three-dimensional targets.

Anamorphic lenses, with different optical powers along the tangential plane and the sagittal plane, are calibrated in this paper. The imaging model for anamorphic lenses is introduced. Compared with the pinhole model, it has two more intrinsic parameters: the anamorphic distance and the anamorphic angle. The anamorphic lens has two optical centers: one is in the tangential plane and the other is in the sagittal plane. The distance between the two optical centers is the anamorphic distance. The anamorphic angle refers to the angle between the camera coordinates and the pixel coordinates in the CCD plane. Formulas determining the initial value of the anamorphic distance are provided. Two experiments are conducted for the anamorphic lens calibration. As a comparison, the anamorphic lens is calibrated using the anamorphic imaging model and the pinhole model, respectively. The calibration accuracy can be improved remarkably if the anamorphic imaging model is applied, and calibrated results for the anamorphic distance and the anamorphic angle are very stable for different positions of the calibration target, which shows the validity and effectiveness of the anamorphic imaging model for anamorphic lens calibration.