Neoadjuvant nivolumab plus bevacizumab therapy improves the prognosis of triple-negative breast cancer in humanized mouse models.

BACKGROUND: The combination of immune checkpoint inhibitors and anti-angiogenic agents has been proposed as a promising strategy to improve the outcome of advanced triple-negative breast cancer (TNBC). However, further investigation is warranted to elucidate the specific mechanisms underlying the effects of combination therapy and its potential as neoadjuvant therapy for early-stage TNBC. METHODS: In this study, we constructed humanized mouse models by engrafting the human immune system into severely immunodeficient mice and subsequently implanting TNBC cells into the model. The mice were treated with neoadjuvant combination therapy (bevacizumab combined with nivolumab), followed by in vivo imaging system to assess tumor recurrence and metastasis after surgery. The immune microenvironment of tumors was analyzed to investigate the potential mechanisms. Furthermore, we verified the impact of extending the interval before surgery or administering adjuvant therapy after neoadjuvant therapy on the prognosis of mice. RESULTS: Neoadjuvant combination therapy significantly inhibited tumor growth, prevented recurrence and metastasis by normalizing tumor vessels and inducing robust CD8+ T cell infiltration and activation in primary tumors (p < 0.001). In vivo experiments demonstrated that prolonging the interval before surgery or administering adjuvant therapy after neoadjuvant therapy did not enhance its efficacy. CONCLUSION: The preclinical study has demonstrated the therapeutic efficacy and mechanism of neoadjuvant combination therapy (nivolumab plus bevacizumab) in treating early TNBC.

Translation, cultural adaptation, and validation of the Chinese standardized outcomes in nephrology-hemodialysis fatigue (C-SONG-HD fatigue) scale: a study of Chinese patients undergoing hemodialysis.

OBJECTIVE: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale. METHODS: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. RESULTS: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. CONCLUSION: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients.

Cyanobacterial bioreporter of nitrate bioavailability in aquatic ecosystems.

The water eutrophication, resulting from the discharge of industrial and agricultural wastewater, leads to ecological degradation. However, to date, how to assess and manage the risks of water pollution, especially nitrogen pollution, remains a particularly noteworthy issue. Nitrate, the most important nitrogen compound, has become a bottleneck restricting total nitrogen management. The development of bioreporters monitoring nitrate pollution contributes to the estimation of water quality, especially the availability of nutrients. In this study, we obtained 9 bioreporters from 40 cyanobacterial derivatives which were constructed based on different hosts, copy numbers, and sensing elements and evaluated the performance of bioreporters. The results showed that single-celled Synechocystis was more sensitive to nitrate than filamentous Anabaena, that the reporter gene luxABCDE responded faster than sfgfp in most bioreporters, and that relatively medium-copy plasmid improved the performance of sensing elements. Nine bioreporters performed well in bioavailable nitrate detection, of which AD-AS-X and AR-NI-X, activated by nitrate repletion, had the shortest response time (2 h) and the widest response range (20-800 µM), respectively. Moreover, SR-GLN-SG, activated by nitrate deficiency, exhibited the best linear response (R2 = 0.998). After parameter optimization, exponential growth phase bioreporters, culture temperature of 30 °C, sample volume of 200 µL were determined as optimal monitoring conditions. We found that common water contaminants (copper, cadmium, and phosphorus) had no impact on the performance of bioreporters, indicating the stability of bioreporters. Six out of 9 bioreporters, especially the SR-NB-X, were highly effective in detecting the bioavailable nitrate in wastewater sample. This study provides valuable references for developing more cyanobacterial bioreporters and their practical application in nitrate detection.

Applications of mass spectrometry in cosmetic analysis: An overview.

Mass spectrometry (MS) is a crucial tool in cosmetic analysis. It is widely used for ingredient screening, quality control, risk monitoring, authenticity verification, and efficacy evaluation. However, due to the diversity of cosmetic products and the rapid development of MS-based analytical methods, the relevant literature needs a more systematic collation of information on this subject to unravel the true potential of MS in cosmetic analysis. Herein, an overview of the role of MS in cosmetic analysis over the past two decades is presented. The currently used sample preparation methods, ionization techniques, and types of mass analyzers are demonstrated in detail. In addition, a brief perspective on the future development of MS for cosmetic analysis is provided.

ZmmiR169q/ZmNF-YA8 is a module that homeostatically regulates primary root growth and salt tolerance in maize.

In response to salt stress, plants alter the expression of manifold gene networks, enabling them to survive and thrive in the face of adversity. As a result, the growth and development of plant roots could be drastically altered, with significant inhibition of the growth of root meristematic zones. Although it is known that root growth is primarily regulated by auxins and cytokinins, the molecular regulatory mechanism by which salt stress stunts root meristems remains obscure. In this study, we found that the ZmmiR169q/ZmNF-YA8 module regulates the growth of maize taproots in response to salt stress. Salt stress downregulates ZmmiR169q expression, allowing for significant upregulation of ZmNF-YA8, which, in turn, activates ZmERF1B, triggering the upregulation of ASA1 and ASA2, two rate-limiting enzymes in the biosynthesis of tryptophan (Trp), leading to the accumulation of auxin in the root tip, thereby inhibiting root growth. The development of the maize root is stymied as meristem cell division and meristematic zone expansion are both stifled. This study reveals the ZmmiR169q/ZmNF-YA8 module's involvement in maintaining an equilibrium in bestowing plant salt tolerance and root growth and development under salt stress, providing new insights into the molecular mechanism underlying the homeostatic regulation of plant development in response to salt stress.

Phosphatases maintain low catalytic activity of SGK1: DNA damage resets the balance in favor of phosphorylation.

The serum- and glucocorticoid-induced kinase 1 (SGK1) promotes cell survival under stress conditions and facilitates the emergence of drug resistance in cancer. The underlying mechanisms of these observations are not fully understood. In this study, we found that SGK1 activity is suppressed by the action of the S/T phosphatases PP5 and PP2A, which constantly dephosphorylate SGK1. Using newly developed anti-phospho SGK1 antibodies and inhibitors of phosphatases, we determined that the high degree of dephosphorylation is caused by two factors: the tendency of SGK1 to unfold, which makes it dependent on Hsp90 chaperone complexes composed of four proteins, Hsp90/CDC37/PP5/SGK1, and where the phosphatase PP5 persistently dephosphorylates SGK1 within the complex. SGK1 binding to PP2A regulatory subunits B55γ and B55δ brings PP2A catalytic subunit close to exposed SGK1 phosphoresidues. A further association of phosphorylated pS37-FAM122A-an endogenous inhibitor of PP2A-to the holoenzyme diminishes dephosphorylation of SGK1 mediated by PP2A. Our study also reveals that genotoxic stress can reverse the dominant impact of phosphatases over kinases by activating the DNA-dependent protein kinase, which enhances mTORC2 activity directed to SGK1. Thus, our results provide insight into a molecular pathway that enables SGK1 to gain phosphorylation and catalytic activity and promote cell survival, potentially diminishing the efficacy of cancer treatments. As the DNA damage response operates in many cancer cells and is further induced by chemotherapies, the findings of this study could have significant implications for the development of novel cancer therapies targeting SGK1.

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation.

Patients with eosinophilic asthma react well to conventional treatment of asthma while individualized therapy for non-eosinophilic endotypes have yet to be developed. Dysregulated sphingosine metabolites are associated with the pathophysiology of different asthma endotypes with their receptors involved. However, whether the sphingosine-1-phosphate receptor 4 (S1PR4) contributes to disease progression of asthma remains underappreciated. In this study, we demonstrated that sphingosine metabolism was disturbed in asthma while it could not be used to distinguish between different endotypes of asthma. S1PR4, a vital receptor of bioactive sphingosine metabolites and mainly expressed in macrophages, exhibited lower expression both in patients and experimental mice with neutrophilic airway inflammation. Additionally, S1pr4 deficiency aggravated the OVA/LPS-induced pulmonary inflammation in mice along with a significant up-regulation in M1 macrophage activation. Mechanistic studies showed that S1PR4 was strongly connected to bioactive oxylipins concurrent with bounding to formyl peptide receptor 2 to influence the phosphorylation of JNK and contributed to the macrophage M1 program, which in turn secreted amounts of inflammatory cytokines associated to the inflammatory response of neutrophilic asthma. Furthermore, treating mice with S1PR4 agonist CYM50308 was characterized by less pulmonary inflammatory infiltration. Our research indicates S1PR4 a promising therapeutic target for non-eosinophilic phenotypes of asthma.

Health-Promoting Activities and Associated Mechanisms of Polygonati Rhizoma Polysaccharides.

Polygonati Rhizoma, a typical homology of medicine and food, possesses remarkable anti-fatigue, anti-aging, metabolic regulatory, immunomodulatory, anti-inflammatory, neuroprotective, anti-diabetes, and anti-cancer effects. Among bioactive phytochemicals in Polygonati Rhizoma, polysaccharides play important roles in the health-promoting activities through the mechanisms mentioned above and potential synergistic effects with other bioactives. In this review, we briefly introduce the updated biosynthesis of polysaccharides, the purification method, the structure characterization, and food applications, and discuss in detail the biological activities of Polygonati Rhizoma polysaccharides and associated mechanisms, aiming at broadening the usage of Polygonati Rhizoma as functional food and medicine.

Molecular Characterization and Efficacy Evaluation of Transgenic Maize Harboring cry2Ab-vip3A-cp4epsps for Insect Resistance and Herbicide Tolerance.

Insect infestation and weed interference have a seriously negative impact on the growth, yield, and grain quality of maize. In this study, transgenic maize plants harboring three exogenous genes, cry2Ab, vip3A, and cp4epsps, that were constructed into a single T-DNA were developed for protection against insects and weeds. The transgene integration sites on the chromosomes in two transgenic maize events, CVC-1 and CVC-2, were determined using whole genome sequencing and specific PCR detection. As revealed by laboratory insect bioassays, these two transgenic events exhibited strong insecticidal toxicity against three major species of Lepidoptera insects, including Mythimna separata, Helicoverpa armigera, and Spodoptera frugiperda, with mortality rates exceeding 96%, 100%, and 100%, respectively, after six days of infestation. In addition, CVC-1 exhibited a high tolerance to glyphosate under field conditions. The successful expressions of cry2Ab, vip3A, and cp4epsps in various tissues at different developmental stages of CVC-1 were validated at the transcriptional and translational levels using quantitative real-time reverse transcription PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. These findings demonstrated that the transgenic maize CVC-1 developed using this triple gene construct has excellent insect resistance and herbicide tolerance, which may provide a valuable germplasm resource and data support for future maize breeding of insect and weed control.

MiR-199a-5p-containing macrophage-derived extracellular vesicles inhibit SMARCA4 and alleviate atherosclerosis by reducing endothelial cell pyroptosis.

BACKGROUND: Endothelial cell disturbance underpins a role in pathogenesis of atherosclerosis. Notably, accumulating studies indicate the substantial role of microRNAs (miRs) in atherosclerosis, and miR-199a-5p dysregulation has been associated with atherosclerosis and other cardiovascular disorders. However, the effect of miR-199a-5p on the phenotypes of endothelial cells and atherosclerosis remains largely unknown. METHODS: ApoE-/- male mice were fed with high-fat diet for detection of inflammation and aorta plaque area. Extracellular vesicles (EVs) were separated from THP-1-derived macrophage (THP-1-DM) that was treated by oxidized low-density lipoprotein, followed by co-culture with human aortic endothelial cells (HAECs). Ectopic expression and downregulation of miR-199a-5p were done in THP-1-DM-derived EVs to assess pyroptosis and lactate dehydrogenase (LDH) of HAECs. Binding relationship between miR-199a-5p and SMARCA4 was evaluated by luciferase activity assay. RESULTS: EVs derived from ox-LDL-induced THP-1-DM expedited inflammation and aorta plaque area in atherosclerotic mice. Besides, miR-199a-5p expression was reduced in EVs from ox-LDL-induced THP-1-DM, and miR-199a-5p inhibition facilitated HAEC pyroptosis and LDH activity. Moreover, miR-199a-5p targeted and restricted SMARCA4, and then SMARCA4 activated the NF-κB pathway by increasing PODXL expression in HAECs. CONCLUSION: EV-packaged inhibited miR-199a-5p from macrophages expedites endothelial cell pyroptosis and further accelerates atherosclerosis through the SMARCA4/PODXL/NF-κB axis, providing promising targets and strategies for the prevention and treatment of atherosclerosis.

The association between fibrinogen-to-albumin ratio (FAR) and adverse prognosis in patients with acute decompensated heart failure at different glucose metabolic states.

BACKGROUND: Circulating fibrinogen-to-albumin ratio (FAR) has been proposed as a novel inflammatory biomarker and a cardiovascular disease risk predictor. However, its prognostic value in patients with acute decompensated heart failure (ADHF) and different glycemic metabolic states remains ambiguous. METHODS: A total of 1031 hospitalized patients with ADHF from January 2018 to May 2021 were included in the study. The primary endpoints were the major adverse cardiac and cerebral events (MACCEs). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR obtained from restricted cubic spline function analysis. The Kaplan-Meier plots and three multivariate-adjusted Cox proportional hazard models were used to determine the association between FAR and the risk of developing MACCEs in patients with ADHF at different glycemic metabolic states. RESULTS: MACCEs occurred in 483 (46.8%) patients during a median follow-up time of 520 days. The optimal FAR cut-off value was 0.079. Upon analyzing the Kaplan-Meier plots, the incidence of MACCEs was significantly different between the FAR groups in all patients and patients with diabetes mellitus (p < 0.05). After adjusting for the confounding factors, the hazard ratio (HR) for MACCEs in the FAR-H group was 1.29 compared with the FAR-L group in all patients (Model 3: 95% CI 1.07-1.56, p = 0.007). Additionally, high FAR was associated with MACCEs in three multivariate Cox models (Model 1, HR = 1.52, 95% CI 1.17-1.96, p = 0.002; Model 2, HR = 1.46, 95% CI 1.13-1.89, p = 0.004; Model 3, HR = 1.48, 95% CI 1.14-1.92, p = 0.003) in DM patients. But no significant differences were found between the FAR groups for prediabetes mellitus (Pre-DM) and normal glucose regulation (NGR) using the three Cox models (all p-values were > 0.05). CONCLUSIONS: Elevated FAR was independently associated with poor prognosis in patients with ADHF and DM and thus could be used as a risk stratification tool and a potential therapeutic target in the future.

Increased expression of SYCP2 predicts poor prognosis in patients suffering from breast carcinoma.

Overexpression of synaptonemal complex protein-2 (SYCP2) has been identified in various human papillomavirus (HPV)-related carcinomas, whereas its significant role in breast carcinoma remains unclear. The aim of this study was to elucidate the prognostic value and potential function of SYCP2 in breast carcinoma. Herein, data for breast carcinoma patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas database (TCGA) were analyzed. The enrichment analysis of SYCP2 including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Friends, and GSEA was performed. Kaplan-Meier analysis, Cox regression, and receiver operating characteristic (ROC) curves were employed for determining the predictive value of SYCP2 on clinical outcomes in patients suffering from breast carcinoma. A nomogram was generated to predict the effect arising from SYCP2 on prognosis. The association analysis of SYCP2 gene expression and diverse immune infiltration levels was conducted through ssGSEA and ESTIMATE analysis, which consisted of dendritic cell (DC), neutrophil, eosinophil, macrophage, mast cell, NK cell, and other 18 cell subtypes. The results showed that SYCP2 expression was significantly elevated in breast carcinoma tissues as compared with that of normal tissues (p < 0.001). SYCP2 plays a certain role in pathways related to DNA methylation, keratinocyte differentiation, steroid hormone biosynthesis, and immune infiltration. The high expression of SYCP2 had a significant relationship to age, pathological type, ER expression, and PR expression (p < 0.001). Kaplan-Meier survival analysis showed that patients suffering from breast carcinoma characterized by high-SYCP2 expression had a poorer prognosis than patients with low-SYCP2 expression (p = 0.005). Univariate and multivariate Cox regression analyses revealed that SYCP2 had an independent relationship to overall survival (p = 0.049). Moreover, ROC curves suggested the significant diagnostic ability of SYCP2 for breast carcinoma, and as time went on, SYCP2 had more accurate prognostic efficacy. Furthermore, a high level of SYCP2 expression was found to have a relationship to poor prognosis of breast carcinoma in the subgroups of T3, N0, and M0, and infiltrating ductal carcinoma (HR > 1, p < 0.05). The calibration plot of the nomogram indicated that the SYCP2 model has an effective predictive performance for breast carcinoma patients. Conclusively, SYCP2 plays a vital role in the pathogenesis and progression of human breast carcinoma, so it may serve as a promising prognostic molecular marker of poor survival.

Association between serum pyrethroid insecticide levels and incident type 2 diabetes risk: a nested case-control study in Dongfeng-Tongji cohort.

Pyrethroid insecticides have been extensively used worldwide, but few studies explored the prospective association between pyrethroid exposure and incident type 2 diabetes (T2D). We conducted a nested case-control study of 2012 paired cases and controls, and measured eight pyrethroid insecticides in the baseline sera. We used conditional logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals, and constructed multiple-pollutant models to investigate the association of pyrethroid mixture with incident T2D risk. The median concentrations (detection rates) were 3.53 µg/L (92.45%), 0.52 µg/L (99.80%), 1.16 µg/L (90.61%) and 1.43 µg/L (99.95%) for permethrin, cypermethrin, fenvalerate, and deltamethrin, respectively. Compared to participants with serum fenvalerate levels in the first quartile, the multivariable-adjusted ORs of incident T2D were 1.20 (95% CI 0.86-1.67), 1.41 (0.97-2.05), and 2.29 (1.27-4.11) for the second, third and fourth quartile (P trend = 0.01). Spline analysis further confirmed the positive association between serum fenvalerate levels and incident T2D risk (P for overall association = 0.006). Furthermore, mixture models revealed a positive association of pyrethroid mixture with incident T2D risk, with serum fenvalerate ranked as the top contributor (proportion of relative contribution: > 70%). We found that high concentrations of serum pyrethroid insecticides were significantly associated with an increased risk of incident T2D. The elevated risk was largely explained by fenvalerate. Further investigations are urgently needed to confirm our findings and elucidate the underlying mechanisms, given the widespread use of pyrethroids and the global pandemic of diabetes.

Anticoagulation after transjugular intrahepatic portosystemic shunt for portal hypertension: A systematic review and meta analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is widely applied to decrease portal hypertension. Because of the lack of strong evidence, it is controversial whether anticoagulation should be performed after TIPS. This meta-analysis aimed to assess the safety and efficacy of anticoagulation for patients with portal hypertension following TIPS. METHODS: Studies making comparisons between combination treatment and TIPS alone were searched in China National Knowledge Infrastructure, Cochrane Library, PubMed, the Wan Fang electronic databases, and EMBASE, delivered between the earliest accessible date and September 4, 2021. The RevMan version 5.3 was applied to conduct all statistical analyses. I2 index statistic was used to assess heterogeneity. RESULTS: Five eligible studies were selected, and total 707 patients were enrolled. According to the meta-analysis, compared to TIPS alone, TIPS + anticoagulation led to much lower incidence of portal vein thrombosis (PVT; odds ratio [OR] = 0.39, 95% confidence interval [CI] 0.18-0.84, P = .02) as well as low heterogeneity (P = 0.36, I2 = 3%). Other index like the stent dysfunction rate (OR = 1.27, 95% CI 0.71-2.77, P = .42), bleeding rate (OR = 1.27, 95% CI 0.71-2.77, P = .42), and incidence of hepatic encephalopathy (OR = 0.87, 95% CI 0.56-1.36, P = .55) showed no statistical significance. CONCLUSIONS: In certain patients with portal hypertension, anticoagulation following TIPS may not be required. However, for patients who do not have a PVT before TIPS, post-TIPS anticoagulation can decrease the incidence of PVT. Nonetheless, further research is still required.

miR169o and ZmNF-YA13 act in concert to coordinate the expression of ZmYUC1 that determines seed size and weight in maize kernels.

MicroRNAs (miRNAs) play key regulatory roles in seed development and emerge as new key targets for engineering grain size and yield. The Zma-miRNA169 family is highly expressed during maize seed development, but its functional roles in seed development remain elusive. Here, we generated zma-miR169o and ZmNF-YA13 transgenic plants. Phenotypic and genetic analyses were performed on these lines. Seed development and auxins contents were investigated. Overexpression of maize miRNA zma-miR169o increases seed size and weight, whereas the opposite is true when its expression is suppressed. Further studies revealed that zma-miR169 acts by negatively regulating its target gene, a transcription factor ZmNF-YA13 that also plays a key role in determining seed size. We demonstrate that ZmNF-YA13 regulates the expression of the auxin biosynthetic gene ZmYUC1, which modulates auxin levels in the early developing seeds and determines the number of endosperm cells, thereby governing maize seed size and ultimately yield. Overall, our present study has identified zma-miR169o and ZmNF-YA13 that form a functional module regulating auxin accumulation in maize seeds and playing an important role in determining maize seed size and yield, providing a set of novel molecular tools for yield improvement in molecular breeding and genetic engineering.

ONOO- -mediated oxidative modification of extracellular matrix aggravates atherosclerosis by affecting biological behaviors of vascular smooth muscle cells.

Atherosclerosis (AS) is a principal contributor to stroke and coronary heart disease in humans characterized by chronic low-grade inflammation. The extracellular matrix (ECM) plays critical roles in regulating the function of arteries. However, the effect of changes in ECM on AS development is rarely studied. In this context, we intend to study the effect of oxidizing agent peroxynitrite (ONOO- )-mediated oxidization of ECM proteins on the biological behaviors of vascular smooth muscle cells (SMCs) and the development of AS. AS mouse models were established, and mouse coronary artery smooth muscle cells (MCASMCs) were cultured in vitro to derive ECM (SMC-ECM), which was obtained by deoxycholate (DOC)-based decellularization. Further, MCASMCs were subjected to the determination of ECM oxidative damage and ECM protein structure. Finally, roles of ONOO- -mediated oxidization of ECM in SMC adhesion and migration and in AS development were explored through Transwell assay, transcriptome sequencing, and gene enrichment analysis. High concentration of ONOO- was found in the serum of AS mice, and ONOO- could stimulate the development of AS. SMC-ECM with intact structure can be obtained in vitro by DOC treatment. Functionally, ONOO- -mediated oxidization destroyed the three-dimensional structure of SMC-ECM proteins, affected SMC adhesion and migration and promoted the absorption efficiency of lipids while reducing the efflux of cholesterol. In addition, the expression of inflammation- and oxidative stress-related genes was significantly increased in ECM subjected to ONOO- -mediated oxidization, thereby contributing to AS progression. ONOO- -mediated oxidative modification of ECM aggravates AS by affecting the biological behavior of SMCs.

Bidirectional Coupler Study for Chip-Based Spectral-Domain Optical Coherence Tomography.

A chip-based spectral-domain optical coherence tomography (SD-OCT) system consists of a broadband source, interferometer, and spectrometer. The optical power divider flatness in the interferometer's wavelength is crucial to higher signal-to-noise ratios. A Mach-Zehnder directional coupler (MZDC) structure could be utilized to smoothly maximize the splitting ratio of 50:50 on a silicon platform, with a sub-micrometer of decoupler optical path difference insensitive to the process variation up to 20 nanometers. However, the optical signal reflected from the reference and sample will go back to the same interferometer MZDC. The so-called bidirectional coupler MZDC will not illustrate a flat optical power response in the operating wavelength range but could still demonstrate at least 20 dB signal-to-noise ratio improvement in OCT after the echelle grating spectrum compensation is applied. For maintaining the axial resolution and sensitivity, the echelle grating is also insensitive to process shifts such as MZDC and could be further utilized to compensate a 3 dB bidirectional MZDC structure for a broad and flat 100 nm wavelength response in the interferometer-based on-chip SD-OCT.

A three-staged framework for measuring water supply resilience in rural China based on PLS-SEM.

China suffers from frequent large-scale earthquakes, posing a significant challenge to the development and integrity of its rural water supply system (RWSS). The earthquake resilience of water supply systems is understood to be a function of multifaceted factors, which are time- and space-dependent. Measuring the seismic-resilience of RWSS in China remains a challenge. This paper proposes a multi-stage comprehensive evaluation framework, focusing on the relationship between multi-dimensional factors and the seismic- resilience of RWSS in rural areas, across three stages: before, during and after earthquake events. This study comprises four steps: (1) Development of a multi-stage evaluation conceptual framework; (2) identification of seismic-resilience factors; (3) verification of the relationships between factors and stages; and (4) formation of the final evaluation framework. The relationship between multi-dimensional factors is confirmed by a method of triangulation through the quantitative analysis of PLS-SEM combined with the qualitative literature analysis, highlighting the causal approach of the resilience of RWSSs, so as to better understand the resilience state of each stage of disaster. Understanding these factors and their influence on the seismic capacity of RWSS will enable local authorities to recognize the existing advantages and disadvantages of these factors, so as to carry out better resilience practice in all stages of disasters.

The effects of extracellular vesicles derived from Krüppel-Like Factor 2 overexpressing endothelial cells on the regulation of cardiac inflammation in the dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is one of the common causes of heart failure. Myocardial injury triggers an inflammatory response and recruits immune cells into the heart. High expression of Krüppel-like factor 2 (KLF2) in endothelial cells (ECs) potentially exerts an anti-inflammatory effect. However, the role of extracellular vesicles (EVs) from KLF2-overexpressing ECs (KLF2-EVs) in DCM remains unclear. METHODS AND RESULTS: EVs were separated from the supernatant of KLF2-overexpressing ECs by gradient centrifugation. Mice were repeatedly administered low-dose doxorubicin (DOX) and then received KLF2-EVs through an intravenous injection. Treatment with KLF2-EVs prevented doxorubicin-induced left ventricular dysfunction and reduced the recruitment of Ly6high Mo/Mø in the myocardium. We used flow cytometry to detect Ly6high monocytes in bone marrow and spleen tissues and to elucidate the mechanisms underlying this beneficial effect. KLF2-EVs increased the retention of Ly6Chigh monocytes in the bone marrow but not in the spleen tissue. KLF2-EVs also significantly downregulated C-C chemokine receptor 2 (CCR2) protein expression in cells from the bone marrow. CONCLUSIONS: EVs derived from KLF2-overexpressing ECs reduced cardiac inflammation and ameliorated left ventricular dysfunction in DCM mice by targeting the CCR2 protein to inhibit Ly6Chigh monocyte mobilization from the bone marrow.

The Long-Term Change of Arrhythmias after Transcatheter Closure of Perimembranous Ventricular Septal Defects.

OBJECTIVES: To observe and analyze the long-term change of different types of arrhythmias after transcatheter closure of perimembranous ventricular septal defect (pmVSD). METHODS: We retrospectively collected the data of patients who underwent pmVSD closure in our institution from March 2002 to December 2010. RESULTS: One hundred thirty-nine patients met the inclusion criteria, of which 265 (25.5%) had early arrhythmia. They were classified into two categories: conduction abnormality (191/1039; 18.4%) and origin abnormality (94/1039; 9.0%), including 20 patients with both types of arrhythmias. The median follow-up time was 84.5 months, and 103 patients (103/191; 53.9%) with early conduction block got permanent arrhythmias, while only three patients (3/94; 3.2%) with early anomalous origin arrhythmias still had an abnormal electrocardiogram. Serious arrhythmias (28/1039; 2.7%), including II° atrioventricular block (AVB), III° AVB, and complete left bundle branch block (CLBBB), can appear immediately in the early postoperative period (21 patients) or in the late outset (seven patients) after several months or even years (6 months to 8.3 years). Twenty patients (20/21; 95.2%) with serious arrhythmia in the early postoperative period improved after early treatment, but six patients relapsed or worsened during follow-up. At the endpoint, severe arrhythmia persisted in 13 patients, of which four patients got permanent pacemaker implanted, and one patient with recurrent CLBBB died from heart failure. CONCLUSIONS: The probability of delayed CAVB or bundle branch block after VSD closure is low but often occurs several years after surgery. Therefore, long-term ECG follow-up should last for several years or even decades. Serious arrhythmias that appear early after transcatheter pmVSD closure may impose a risk of recurrence although they have been cured already. Close attention should be paid to the changes of cardiac function in patients with CLBBB after VSD closure, and the severity of such arrhythmia should be taken seriously and reexamined.