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As we all know, it is difficult to deal with the weak boundary and noisy images by using local or global image information. Therefore, this paper proposes a signed pressure force function for image segmentation by combining global and local image information. First, the global and local gray fitted terms are given by using the global and local region information of the image respectively. Then, the global and local terms are linearly combined to construct a mixed signed pressure force function. Finally, the balloon force function is redefined to adaptively change the contour curve evolution rate of the level set. The numerical simulation results show that the proposed algorithm can not only accurately segment weak boundary and multi-target images, but also has a fast segmentation speed and a certain robustness to the noise.

Objectives: The aim of this study was to measure the P-wave dispersion(PWD) in the ECG of patients with pulmonary arterial hypertension(PAH). Methods: A total of 103 PAH patients were collected, including 55 patients related with CHD and 44 patients with IPAH. In addition, 30 CHD patients without PAH (nPAH-CHD group) and 30 healthy controls (HCG group) were collected as control. Patients in the PAH group were categorized into the low-risk group (30 cases), moderate-risk group (53 cases) and high-risk group (20 cases), followed by comparison of PWD difference between groups. The ROC curve was used to evaluate the diagnostic efficacy of PWD on PAH-CHD and IPAH. Results: The levels of PWD and Pmax in PAH-CHD and IPAH group were significantly higher than those in nPAH-CHD and HCG group (PConclusion: PWD might be an effective ECG indicator for PAH, which might be used as a relatively economical and easily accessible indicator for PAH patients to assist in early diagnosis, disease severity assessment and prognosis evaluation.

Design and optimization of well spacing is a key indicator for evaluating the development effect of shale gas reservoirs. On the basis of theoretical understanding, and after the verification by analogy, numerical simulation, and economic evaluation, a complete workflow from inter-well interference simulation and dynamic data diagnosis to multi-well production simulation and well spacing optimization was formed. First, a pressure detection boundary propagation model is established to simulate the response degree of inter-well interference under different connected conditions. Second, inter-well interference is identified and diagnosed depending on the inter-well interference response behaviors and the interpretation of performance data from gas wells. Third, taking the geological interpretation and dynamic analysis results as basic parameters, a multi-well numerical model for volume fracturing in gas reservoirs is established to simulate the production performance of gas field, and then well spacing is optimized in combination with the net present value model. The application in the Ning 201 well block in the Changning National Shale Gas Demonstration Area has shown that a smaller well spacing can allow a premature inter-well interference and also the enhancement of recovery in the entire block. Given the current fracturing scale and parameter system, the well spacing of 300–400 m can be optimized to 260–320 m, that is, the number of wells per unit area increases by 20%–30%. As a result, the recovery percent of reserves in the block increase by about 10%. The net present value of the block rises, but the corresponding optimal well spacing does not change, with the production period.

Cochlear nerve deficiency (CND) is often combined with modiolar deficiency-type inner ear malformations, which cause variable cochlear implantation (CI) outcomes. We aimed to assess the postoperative development of auditory and speech perception in CND patients with modiolar deficiency-type malformations after 3 years of follow-up to determine the factors correlated with CI outcomes.Sixty-seven CND patients with modiolar deficiency-type malformations who underwent CI surgery were retrospectively reviewed. Modiolar deficiency-type malformations included common cavity (CC), cochlear hypoplasia (CH) (including CH-I and CH-II) and incomplete partition-I (IP-I). Categorical auditory performance (CAP) and the infant-toddler meaningful auditory integration scale (MAIS) were used to assess auditory ability. The speech intelligibility rating (SIR) and meaningful use of speech scale (MUSS) were used to assess the speech intelligibility of these CI patients. The CI outcomes were evaluated at 0, 12, 24 and 36 months after implant activation.All patients demonstrated improvements in auditory ability and speech intelligibility after CI. There were no significant differences in CI outcomes at any time point according to the malformation type. The number of nerve bundles within the internal auditory canal (IAC) showed significant differences at 12, 24 and 36 months after CI (p0.05). Patients with one nerve bundle had relatively poor CI outcomes.CND patients with modiolar deficiency-type malformations showed continuous improvement in auditory and speech abilities after CI. Compared with malformations, the number of nerve bundles should be given more attention when selecting the side for CI.

Toxic effects of excessive manganese (Mn) from occupational or environmental exposure cause harm to human health. Excessive Mn exposure is intimately associated with neurodegeneration and cognitive dysfunction. Inflammatory responses mediated by microglia are essential contributors to the pathogenesis of Mn-induced neurotoxicity. Inhibition of microglia-mediated inflammation has been shown to alleviate Mn-induced neurotoxicity. Sesamol, derived from sesame, has neuroprotective properties in various disease models, including neurological diseases. Whether sesamol protects against Mn-induced neurological injuries has not been determined. Here, both in vivo and in vitro Mn exposure models were established to address the beneficial effects of sesamol on Mn-induced neurotoxicity. We showed that administration of sesamol mitigated learning and memory deficits of mice treated by Mn. Furthermore, sesamol reduced Mn-induced microglial activation and the expression of proinflammatory mediators (TNF-α, iNOS, and Cxcl10), while exerting a marginal effect on anti-inflammation and microglial phagocytosis. Mn exposure activated the microglial cGAS-STING pathway and sesamol inhibited this pathway by reducing the phosphorylation of STING and NF-κB, concomitantly decreasing IFN-α and IFN-β synthesis. In summary, our novel results indicated that sesamol exerted its protective effects on Mn-induced neuroinflammation and cognitive impairment via the microglial cGAS-STING/NF-κB pathway, providing evidence that sesamol may serve as an effective therapeutic for preventing and treating Mn-induced neurotoxicity.

To compare the core indexes of cardiopulmonary exercise test (CPET) in the patients with coronary artery disease and combining anxiety and/or depression, and to explore the effect of the emotional disorder with "anxiety and/or depression" on cardiopulmonary function and exercise tolerance in patients with coronary artery disease.A total of 255 patients with stable coronary artery disease and 302 patients without coronary artery disease were selected as subjects. According to the results of anxiety and depression scale, they were divided into a control group (Peak oxygen uptake, anaerobic domain, peak metabolic equivalent, and peak heart rate in all coronary artery disease groups were significantly lower than those in the control group, while peak systolic pressure and heart rate reserve were significantly increased (allThe cardiopulmonary function and exercise tolerance is significantly decreased in the coronary artery disease combined with anxiety and depression patients; there is a declining trend in the cardiopulmonary function and exercise tolerance in the simple anxiety or simple depression patients. Simple anxiety, simple depression and simple anxiety combined with depression don't cause a negative impact on cardiopulmonary function and exercise tolerance in non-coronary artery disease control population.

Talker sex and spatial cues can facilitate segregation of competing speech. However, the spectrotemporal degradation associated with cochlear implants (CIs) can limit the benefit of talker sex and spatial cues. Acoustic hearing in the nonimplanted ear can improve access to talker sex cues in CI users. However, it's unclear whether the CI can improve segregation of competing speech when maskers are symmetrically placed around the target (i.e., when spatial cues are available), compared with acoustic hearing alone. The aim of this study was to investigate whether a CI can improve segregation of competing speech by individuals with unilateral hearing loss.Speech recognition thresholds (SRTs) for competing speech were measured in 16 normal-hearing (NH) adults and 16 unilaterally deaf CI users. All participants were native speakers of Mandarin Chinese. CI users were divided into two groups according to thresholds in the nonimplanted ear: (1) single-sided deaf (SSD); pure-tone thresholds25 dB HL at all audiometric frequencies, and (2) Asymmetric hearing loss (AHL; one or more thresholds25 dB HL). SRTs were measured for target sentences produced by a male talker in the presence of two masker talkers (different male or female talkers). The target sentence was always presented via loudspeaker directly in front of the listener (0°), and the maskers were either colocated with the target (0°) or spatially separated from the target at ±90°. Three segregation cue conditions were tested to measure masking release (MR) relative to the baseline condition: (1) Talker sex, (2) Spatial, and (3) Talker sex + Spatial. For CI users, SRTs were measured with the CI on or off.Binaural MR was significantly better for the NH group than for the AHL or SSD groups ( P0.001 in all cases). For the NH group, mean MR was largest with the Talker sex + spatial cues (18.8 dB) and smallest for the Talker sex cues (10.7 dB). In contrast, mean MR for the SSD group was largest with the Talker sex + spatial cues (14.7 dB), and smallest with the Spatial cues (4.8 dB). For the AHL group, mean MR was largest with the Talker sex + spatial cues (7.8 dB) and smallest with the Talker sex (4.8 dB) and the Spatial cues (4.8 dB). MR was significantly better with the CI on than off for both the AHL ( P = 0.014) and SSD groups ( P0.001). Across all unilaterally deaf CI users, monaural (acoustic ear alone) and binaural MR were significantly correlated with unaided pure-tone average thresholds in the nonimplanted ear for the Talker sex and Talker sex + spatial conditions ( P0.001 in both cases) but not for the Spatial condition.Although the CI benefitted unilaterally deaf listeners' segregation of competing speech, MR was much poorer than that observed in NH listeners. Different from previous findings with steady noise maskers, the CI benefit for segregation of competing speech from a different talker sex was greater in the SSD group than in the AHL group.

We aimed to analyse the reasons behind the need for cochlear implant revision surgeries, as well as the rate at which they occur, to reduce the revision surgery rate for non-device failures. We also aimed to elucidate the cumulative survival and device survival rates in different age groups. This retrospective single cohort study reviewed 4563 cochlear implant surgeries and 119 revision surgeries performed at a tertiary referral hospital in China between 1996 and 2019. Kaplan–Meier curves were used to calculate the cumulative survival and device survival rates. The revision surgery rate was 2.61%. The reasons for revision included device (73.1%) and non-device (26.9%) failures. The most common reasons were hard device (47.1%) and non-device failure (28.6%). The 10- and 20-year cumulative survival rates were 96.8% and 96.7%, respectively. Younger children were more likely to undergo a second surgery. This study is the longest study about revision surgery in China. Cochlear implantation is a reliable treatment. It has a low complication rate in patients with sensorineural hearing loss. Children have a higher revision rate than adults. Doctors should be aware of each complication and perform the appropriate procedure.

Ionic rectifier membranes or devices generate uni-directional ion transport to convert an alternating current (AC) ion current input into stored energy or direct current (DC) in the form of ion/salt gradients. Electrochemical experiments 80 years ago were conducted on biological membrane rectifier systems, but today a plethora of artificial ionic rectifier types has been developed and electroanalytical tools are employed to explore mechanisms and performance. This overview focuses on microscale ionic rectifiers with a comparison to nano- and macroscale ionic rectifiers. The potential is surveyed for applications in electrochemical analysis, desalination, energy harvesting, electrochemical synthesis, and in selective ion extraction.

Sclerotinia sclerotiorum is a devastating plant pathogen that causes substantial losses in various agricultural crops. Although plants have developed some well-known defense mechanisms against invasive fungi, much remains to be learned about plant responses to fungal pathogens. In this study, we investigated how S. sclerotiorum infection affects plant primary and secondary metabolism in the model plant Arabidopsis thaliana. Our results showed that soluble sugar and amino acid content changed significantly in A. thaliana leaves upon fungal colonization, with a decrease in sucrose and an increase in mannitol, attributed to fungal biosynthesis. Furthermore, the jasmonate signaling pathway was rapidly activated by S. sclerotiorum infection, and there was a striking accumulation of antifungal metabolites such as camalexin, p-coumaroyl agmatine, feruloyl agmatine, and Nδ-acetylornithine. On the other hand, the characteristic defense compounds of the Brassicaceae, the glucosinolates, were not induced in A. thaliana infected by S. sclerotiorum. Our study provides a better understanding of how A. thaliana primary and secondary metabolism is modified during infection by a fungal pathogen like S. sclerotiorum that has both hemibiotrophic and necrotrophic stages.

Patients with Chronic rhinosinusitis with nasal polyps and asthma (CRSwAS) are highly heterogenous in severity and prognosis. The clinical phenotypes and inflammatory endotypes of CRSwAS and the association with outcomes of endoscopic sinus surgery (ESS) have not been fully studied yet.We aimed to find out the clinical phenotypes of CRSwAS and explore their relationship with ESS outcome using cluster analysis.We recruited 103 consecutive adult CRSwAS patients who had undergone ESS and been followed up for more than one year. For cluster analysis, we collected the data of 63 variables pertaining to demographic characteristics, preoperative disease status, surgical techniques, postoperative medical treatment and outcomes. Eosinophilic CRS was defined as ≥10 eosinophils/high power field (HPF), sinus CT was evaluated by Lund-Mackay sinus CT score (LM score).We screened out 92 eligible patients and 13 preoperative variables for BIRCH cluster analysis. CRSwAS patients were divided into four clusters with distinct ESS outcomes: Cluster 1, characterized by aspirin-exacerbated respiratory disease (AERD), eosinophilic CRS, high preoperative LM score, moderate to severe asthma, uncontrolled CRS after ESS; Cluster 2, characterized by female dominant (66.67%), non-AERD, eosinophilic CRS, high preoperative LM score, moderate to severe asthma, uncontrolled CRS after ESS; Cluster 3, characterized by female dominant (95.83%), non-eosinophilic CRS, low preoperative LM score, moderate asthma, controlled CRS after ESS; Cluster 4, characterized by male only, smoker, non-eosinophilic CRS, low preoperative LM score, mild asthma, controlled CRS after ESS.CRSwAS has distinct clusters, each corresponding to unique clinical and inflammatory characteristics and ESS outcomes.

Ultradeep carbonate gas reservoirs are a major resource of interest in clean energy development, and complex pore structures and reservoir conditions with high-temperatures and pressures are great ...

Vision and language understanding is one of the most fundamental and difficult tasks in Multimedia Intelligence. Simultaneously Visual Question Answering (VQA) is even more challenging since it requires complex reasoning steps to the correct answer. To achieve this, Neural Module Network (NMN) and its variants rely on parsing the natural language question into a module layout (i.e., a problem-solving program). In particular, this process follows a feedforward encoder-decoder pipeline: the encoder embeds the question into a static vector and the decoder generates the layout. However, we argue that such conventional encoder-decoder neglects the dynamic nature of question comprehension (i.e., we should attend to different words from step to step) and per-module intermediate results (i.e., we should discard module performing badly) in the reasoning steps. In this paper, we present a novel NMN, called Self-Adaptive Neural Module Transformer (SANMT), which adaptively adjusts both of the question feature encoding and the layout decoding by considering intermediate Q&A results. Specifically, we encode the intermediate results with the given question features by a novel transformer module to generate dynamic question feature embedding which evolves over reasoning steps. Besides, the transformer utilizes the intermediate results from each reasoning step to guide subsequent layout arrangement. Extensive experimental evaluations demonstrate the superiority of the proposed SANMT over NMN and its variants on four challenging benchmarks, including CLEVR, CLEVR-CoGenT, VQAv1.0, and VQAv2.0 (on average the relative improvement over NMN are 1.5, 2.3, 0.7 and 0.5 points with respect to accuracy).

Understanding and controlling the swimming direction of a synthetic nano- and micromotor holds fundamental and applied significance. Here, we focus on platinum-containing Janus colloids that catalytically decompose H

Background The importance of multidisciplinary team (MDT) centred on pregnant women with pulmonary hypertension (PH) has been highlighted. However, rare studies have explored its effects on pregnancy outcomes. This study seeks to investigate whether and how the MDT has an effect on the treatment and outcomes of PH pregnant women. Methods A pre- and post-intervention study was conducted based on an interrupted time series design to compare the treatment and outcomes of patients with PH before (pre-MDT) and after (post-MDT) implementation of the MDT. PH was defined as pulmonary artery systolic pressure (sPAP) ≥ 35 mmHg measured by echocardiography or right heart catheterization and sPAP at 35–60 mmHg and over 60 mmHg was defined as mild and severe PH, respectively. All results were analyzed by T-tests, Chi square tests or Fisher exact test and two-sided p value Results 149 pregnancies were found in 143 women with PH. Overall, 46 pregnancies were elective abortions, remaining 49 and 54 pregnancies completing delivery in the pre-MDT group and post-MDT group, respectively. Five (10.2%) mother and seven (8.6%) neonatal died in the former, while no maternal deaths but 1.9% neonatal death occurred in the latter. In subgroup analysis, maternal and fetal/neonatal complications were higher in patients with severe PH and World Health Organization functional class (WHO FC) III/IV and all maternal deaths occurred in class III/IV women. In pre-MDT and post-MDT groups, there were 8 and 22 pregnant women receiving the pulmonary-specific therapy and completing delivery, respectively. The percentage of heart failure and urgent cesarean of pre-MDT group was higher than the post-MDT group (30.6% vs. 12.9%, p = 0.02; 40.8% vs. 14.8%, p = 0.01, respectively). Conclusion Implementing the MDT decreased the rate of urgent caesarean section and heart failure in patients with PH and no maternal deaths occurred in the post-MDT group. Pregnant women with severe PH and WHO FC III/IV might have a poor prognosis, whereas the use of pulmonary-specific therapy might improve outcomes of pregnancy.

Micro-hole voltammetry exhibiting rectified current-voltage curves was performed in hydrochloric acid by varying the lengths and the diameters of the micro-holes on one end of which a Nafion film was mounted. Some voltammetric properties were compared with those in NaCl solution. The voltammograms were composed of two line-segments, the slope of one segment being larger than the other. They were controlled by electric migration partly because of the linearity of the voltammograms and partly the independence of the scan rates. Since the low conductance which appeared in the current from the hole to the Nafion film was proportional to the cross section area of the hole and the inverse of the length of the hole, it should be controlled by the geometry of the hole. The conductance of the hydrogen ion in the Nafion film was observed to be smaller than that in the bulk, because the transport rate of hydrogen ion by the Grotthuss mechanism was hindered by the destruction of hydrogen bonds in the film. In contrast, the conductance for the current from the Nafion to the hole, enhancing by up to 30 times in magnitude from the opposite current, was controlled by the cell geometry rather than the hole geometry except for very small holes. A reason for the enhancement is a supply of hydrogen ions from the Nafion to increase the concentration in the hole. The concentration of the hydrogen ion was five times smaller than that of sodium ion because of the blocking of transport of the hydrogen ion in the Nafion film. However, the rectification ratio of H+ was twice as large as that of Na+.

Background Acute myeloid leukemia (AML) is one of the most common hematological diseases in adults. The overall survival rate remains unsatisfactory. It is urgent to identify potential prognostic biomarkers and develop new molecular therapeutic strategies for AML. Signal transducer and activator of transcription (STAT) is a family of genes that encode intracellular transcription factors. STATs are associated with leukemogenesis, cellular transformation, and cell cycle in AML. Methods We used sequencing data and clinical data from The Cancer Genome Atlas (TCGA) and ONCOMINE to identify expression difference, gene variability and correlation as well as prognostic effects of STAT genes in AML patients. Then, we verified the expression difference of STAT6 between healthy control and AML patients and its prognostic impact in Gene Expression Omnibus (GEO) database and our own recruited cohort. Results The mRNA level of STAT6 was increased in AML patients among TCGA, GEO and ONCOMINE public datasets and was found to be an independent risk factor of overall survival in all AML patients and patients who only received chemotherapy by multivariate analysis. In our study, STAT6 mRNA level was markedly up-regulated in AML patients (n=105) compared to healthy donor (n=39) (P=0.0435) as a validated cohort. Patients that only received chemotherapy in high STAT6 group showed significantly lower overall survival (OS) (P=0.0055). Conclusion STAT6 expression was increased in AML patients. STAT6 was found to be an adverse prognosis factor in AML patients, especially those who only received chemotherapy treatments.

Right heart failure and right ventricular (RV) remodeling were the main reason for mortality of pulmonary hypertension (PH) patients. Apolipoprotein AV (ApoA5) is a key regulator of plasma triglyceride and have multifunction in several target organs. We detected decreased ApoA5 in serum of patients with PH and both in serum and RV of monocrotaline-induced PH model. Exogenously, overexpression ApoA5 by adenovirus showed protective effects on RV failure and RV fibrosis secondary to PH. In addition, in vitro experiments showed ApoA5 attenuated the activation of fibroblast induced by transforming growth factor β1 and synthesis and secretion of extracellular matrix by inhibiting focal adhesion kinase-c-Jun N-terminal kinase-Smad3 pathway. Finally, we suggest that ApoA5 may potentially be a pivotal target for RV failure and fibrosis secondary of PH.

Since the research direction of supercapacitors (SC) has been deviated from the principle of causing capacitance, the revisit may be a future task in exploiting electric power storage. SC have been developed by applying ionic properties in order to enhance heterogeneity of ionic distributions. However, SC belong to double-layer capacitances (DLC), which are caused by orientation of solvent dipoles without any direct relation to ionic properties. DLC are always complicated with ion-independent characteristics such as frequency dispersion, voltage dependence, and participation in redox reactions, whereas these complications have not yet been considered in development of SC. Especially, pseudo capacitances should be examined through isolating the contribution of DLC from the redox properties.

Brassicales plants produce glucosinolates and myrosinases that generate toxic isothiocyanates conferring broad resistance against pathogens and herbivorous insects. Nevertheless, some cosmopolitan fungal pathogens, such as the necrotrophic white mold Sclerotinia sclerotiorum, are able to infect many plant hosts including glucosinolate producers. Here, we show that S. sclerotiorum infection activates the glucosinolate-myrosinase system, and isothiocyanates contribute to resistance against this fungus. S. sclerotiorum metabolizes isothiocyanates via two independent pathways: conjugation to glutathione and, more effectively, hydrolysis to amines. The latter pathway features an isothiocyanate hydrolase that is homologous to a previously characterized bacterial enzyme, and converts isothiocyanate into products that are not toxic to the fungus. The isothiocyanate hydrolase promotes fungal growth in the presence of the toxins, and contributes to the virulence of S. sclerotiorum on glucosinolate-producing plants., Some plants produce toxic isothiocyanates that protect them against pathogens. Here, Chen et al. show that the plant pathogenic fungus Sclerotinia sclerotiorum converts isothiocyanates into non-toxic compounds via glutathione conjugation and, more effectively, via hydrolysis to amines using an isothiocyanate hydrolase.

The design of powerful, more biocompatible microrobots calls for faster catalytic reactions. Here we demonstrate a two-fold increase in the speed of photocatalytic TiO2-metal Janus micromotors via a Au/Ag bi-layered coating. Electrochemical measurements show that such a bimetallic coating is a better photocatalyst than either metal alone. Similarly, an additional sputtered Ag layer could also significantly increase the speed of Pt-PS or TiO2-Pt micromotors, suggesting that applying bimetallic coatings is a generalizable strategy in the design of faster catalytic micromotors.

In nature, plant-insect interactions occur in complex settings involving multiple trophic levels, often with multiple species at each level.

Excessive manganese (Mn) exposure gives rise to various neurological disorders, including motor dysfunction and cognitive impairment. Microglia-mediated neuroinflammation plays an essential role in the pathogenesis of Mn neurotoxicity. However, the underlying mechanisms have not been fully clarified. Immunoproteasome is a specialized proteasome. Recent studies have shown that immunoproteasome, especially catalytic subunit PSMB8, is highly associated with various neurological diseases. Whether PSMB8 is involved in Mn-neurotoxicity is still unknown. In this study, in vivo and in vitro models were established, and our data showed that Mn exposure upregulated the expression and activity of PSMB8. Selective inhibition of PSMB8 mitigated neuroinflammation with reduced microglial activation and fewer TNF-α, iNOS, and CCL12 production in Mn-treated mice and BV2 cells. Learning and memory tests and Golgi staining further confirmed that inhibition of PSMB8 alleviated Mn-induced recognition memory impairments and synapse deficits. Besides, we found that blocking of PERK signaling inhibited Mn-induced elevation of PSMB8. And inhibition of PSMB8 reduced the phosphorylation of NF-κB p65. Together, our data demonstrated that PSMB8 played an essential role in microglia-mediated neuroinflammation upon Mn exposure, and the underlying mechanisms may be via PERK/NF-κB pathways. These results provide a novel target for the prevention and treatment of Mn-neurotoxicity.

Elucidating the interplay of stress and geometry is a fundamental scientific question arising in multiple fields. In this work, we investigate the geometric frustration of crystalline caps confined on the sphere in both elastic and plastic regimes. Based on the revealed quasi-conformal ordering, we discover the partial, but uniform screening of the substrate curvature by the induced curvature underlying the inhomogeneous lattice. This scenario is fundamentally different from the conventional screening mechanism based on topological defects. In the plastic regime, the yield of highly stressed caps leads to fractures with featured morphologies not found in planar systems. We also demonstrate the strategy of engineering stress and fractures by vacancies. These results advance our general understanding on the organization and adaptivity of geometrically-frustrated crystalline order., Comment: 6 pages, 4 figures

Studies indicate that viruses could spread across species, but it is difficult to know when and where such small probability events occur because it is almost impossible to design an observational study on the whole landscape.We did a comprehensive analysis on the National Center for Biotechnology Information database and tried to find the time, place, and host that the viruses stayed in their long evolutionary history.Public databases are helpful to understand the risk of virus infection in humans and also a cost-effective method for monitoring public health and safety events.

A compact silicon on-chip wavelength triplexer engineered by double bridged subwavelength gratings (BSWGs) is proposed based on cascaded symmetric directional couplers (SDCs). The SDC consists of a pair of symmetric and identical BSWGs with another SWG waveguide implemented in the middle of the SDC section. It functions well provided that the coupling lengths can match even or odd times of beat lengths of the three wavelengths. Relying on deliberately tailoring the structural dimensions of SWGs at different positions of SDC, the two lowest-mode refractive indices and beat lengths can be efficiently tuned, drastically reducing device footprint. The results show a total device length of 42.2 µm, which is ∼ 10 % of its conventional counterpart based on SDCs. An insertion loss (IL) lower than 0.67 dB, reflection loss (RL) below − 21.4 d B , and extinction ratio (ER) as high as 34.5 dB are also obtained in the results. The bandwidths around wavelength bands and fabrication tolerances to dimensional variations are investigated and analyzed. The field evolutions for the three injected wavelength bands are presented.

IEEE TBME manuscript

Introduction In many critical illnesses including burn injury (BI), muscle wasting (MW) with mitochondrial dysfunction (MD) leads to poor prognosis. Disturbed mitochondria can normally be turned over by autophagic degradation of mitochondria (mitophagy). We have previously observed that BI causes disturbed mitophagy response in skeletal muscles both in vivo and in the cultured myocytes, a potential mechanism for BI-induced MD. These previous findings have lead to the expectation that augmenting mitophagy will rescue mitochondrial functions and can help treating the BI-induced MW and MD. There have been, however, limited research tools to specifically intervene (or augment) mitophagy. In the current study, we have established mitophagy-compromised cell strains by CRISPR/Cas9-mediated knocking out of BNIP3L, a pivotal molecule mediating parkin-independent mitophagy induction. Deferiprone (DFP), a recently established mitophagy inducer, had previously been known to exert cellular and organ protective functions, but the mechanisms of its beneficial effects were not investigated in detail. Nor has its efficacy been tested on BI-induced MD. Methods First, whether DFP stimulated mitophagy induction causes translocation of mitophagy markers into mitochondrial fraction, was tested by Western Blotting on the WT C2C12 cells against Parkin/PINK1- and BNIP3L- pathway molecules. Next we established BNIP3L knockout C2C12 myoblast cell like by CRISPR/Cas9-mediated gene deletion. Using both WT and BNIP3L knockout (KO) cell lines incubated in the BI or SB serum (from 30% rat burn at 3PBD) with or without DFP treatment, we tested whether DFP can rescue BI-induced upregulation of mitochondria-derived superoxide (SO) using MitoSOX staining. Results In WT C2C12 cells, mitophagy stimulation by DFP caused robust increase of the protein amount of BNIP3L in the mitochondrial fraction, but Parkin/PINK1 did not. KO completely abolished both basal and stimulated increase of BNIP3L. BI serum caused significant elevation of mitochondrial SO in WT myocytes ( >20 fold of SB), which was ameliorated by DFP-stimulated mitophagy augmentation (95% reduction). In KO C2C12 cells, however, DFP-induced SO reduction in BI serum was completely abolished, suggesting that DFP-mediated mitochondrial protection against BI was through augmenting mitophagy via BNIP3L pathway. Conclusions By using BNIP3L KO C2C12 myocytes, mitochondrial protective role of BNIP3L-mediated mitophagy against BI-induced stress was demonstrated for the first time. Previously reported cellular and organ protective functions of DFP is likely through activation of this pathway. Augmentation of mitophagy will be a promising therapeutic approach in protecting BI-induced MW and MD.