Phase stability diagram, self-similar structures, and multistability in a free-running VCSEL with a small misalignment between the phase and amplitude anisotropies.

We report on the global dynamics of a free-running vertical-cavity surface-emitting laser (VCSEL) with misalignment between the linear phase and amplitude anisotropies due to the fact that this case might occur in practice caused unintentionally by minor manufacturing variations or design, in virtue of high-resolution phase stability diagrams, where two kinds of self-similar structures are revealed. Of interest is that the Arnold tongue cascades covered by multiple distinct periodicities are discovered for the first time in several scenarios specified in the free-running VCSEL, to the best of our knowledge. Additionally, we also uncover the existence of multistability through the basin of the attraction, as well as the eyes of anti-chaos and periodicity characterized by fractal. The findings may shed new light on interesting polarization dynamics of VCSELs, and also open the possibility to detect the above-mentioned structures experimentally and develop some potential applications.

Extreme events in two laterally-coupled semiconductor lasers.

Rogue waves (RWs) are extreme and rare waves that emerge unexpectedly in many natural systems and their formation mechanism and prediction have been extensively studied. Here, we numerically demonstrate the appearance of extreme events (EEs) for the first time, to the best of our knowledge, in the chaotic regimes of a two-element coupled semiconductor laser array. Based on coupled-mode theory, we characterize the occurrence of EEs by calculating the probability distribution, which confirms the RW-type feature of the intensity pulses, i.e., non-Gaussian distribution. Combining with the results of the 0-1 test for chaos, we confirm that EEs originate from deterministic nonlinearities in coupled semiconductor laser systems. We show that EEs can be predicted with a long anticipation time. Furthermore, simulation results manifest that the occurrence probability of EEs can be flexibly tuned by tailoring the coupling parameter space. With the help of two-dimension maps, the effects of key parameters, i.e., the waveguide structure and the pump level, on the formation of EEs are discussed systematically. This work provides a new platform for the research of EEs in a highly integrated structure and opens up a novel investigation field for coupled semiconductor laser arrays.

Process optimization for fermented siwu decoction by multi-index-response surface method and exploration of the effects of fermented siwu decoction on the growth, immune response and resistance to Vibrio harveyi of Pacific white shrimp (Litopenaeus vannamei).

The purpose of this study was to explore the optimal fermentation technology of Chinese herbal medicine formula-Siwu Decoction and the effects of fermented Siwu Decoction (FSW) on the growth performance, immune response, intestinal microflora and anti microbial ability of Litopenaeus vannamei. Response to surface methodology (RSM) was used to optimize the fermentation process of Siwu Decoction. The optimal fermentation conditions were obtained as follows: inoculation amount of mixed strains was 4.5%, fermentation time was 36 h, and the ratio of material to liquid was 20%. A total of 1260 shrimps were selected and divided into seven groups, three in parallel in each group. The dietary level of each group was as follows: Control （No additions）, USW1 (0.2% unfermented herbal medicine), USW2 (0.5% unfermented herbal medicine), USW3 (0.8% unfermented herbal medicine), FSW1 (0.2% fermented herbal medicine), FSW2 (0.5% fermented herbal medicine), FSW3 (0.8% fermented herbal medicine). The immune response and antioxidant defense ability of hemocytes and intestine were measured at 21 and 42 days of feeding and the intestinal flora and growth performance were measured at 42 days of feeding, after that, a 7-day challenge test against Vibrio harveyi was conducted. The results showed that fermented Siwu Decoction significantly improved the growth performance and body composition of Litopenaeus vannamei; significantly increased the total number of hemocytes, phagocytic activity, antibacterial activity and bacteriolytic activity of Litopenaeus vannamei, and improved the antioxidant activity of Litopenaeus vannamei; the addition of fermented Siwu Decoction significantly increased the gene expression level of hemocytes and intestinal tract of Litopenaeus vannamei, and improved the antioxidant activity of Litopenaeus vannamei. The abundance of Bacillus increased, while the abundance of Vibrio decreased. After Vibrio harveyi challenge, the cumulative mortality of FSW group was significantly lower than that of control group. Fermented Siwu Decoction may be a potential physiological enhancer in aquaculture, and can be widely used in aquaculture.

Wedelolactone ameliorates Pseudomonas aeruginosa-induced inflammation and corneal injury by suppressing caspase-4/5/11/GSDMD-mediated non-canonical pyroptosis.

Pseudomonas aeruginosa (P. aeruginosa) keratitis, a worldwide leading cause of corneal perforation and blindness, which is associated with contact lens usage. Increasing evidence has indicated that pyroptosis, a novel proinflammatory programmed cell death, is linked with ocular diseases, little is known about the role of noncanonical pyroptosis in microbial keratitis. Here, we first indicated the involvement of noncanonical pyroptosis in P. aeruginosa keratitis and investigated whether wedelolactone (WDL), a major active component of Eclipta prostrate known to target caspase-11, could alleviate P. aeruginosa keratitis development. We found the expression of caspase-4/5/11 and cleaved GSDMD in corneas of P. aeruginosa keratitis patients, animal models and lipopolysaccharide (LPS)-induced primary cultured human corneal keratocytes (piHCKs) were increased. Combining ciprofloxacin with WDL significantly ameliorated the severity of P. aeruginosa keratitis, as manifested by decreased inflammatory responses and reduced corneal epithelial defects. Consistent with these findings, WDL also dose-dependently alleviated LPS-induced noncanonical pyroptosis by reversing the increased expression of caspase-4/5 and GSDMD in piHCKs. In summary, our results demonstrated that by targeting the activation of caspase-4/5/11, wedelolactone inhibited the development of P. aeruginosa keratitis and suppressed the release of proinflammatory cytokines. Wedelolactone may be a promising anti-inflammatory candidate to combat P. aeruginosa keratitis.

Effect of dietary Xiao-Chaihu-Decoction on growth performance, immune response, detoxification and intestinal microbiota of pacific white shrimp (Litopenaeus vannamei).

Xiao-Chaihu-Decoction (XCHD), a classical traditional Chinese medicine with diverse biological activities, is widely applied to prevent and treat many human diseases. Effects of dietary XCHD on growth performance, immune response, detoxification system, intestinal microbiota and resistance against aflatoxin B1(AFB1) of Litopenaeus vannamei was studied. Four isonitrogenous and isolipidic diets were formulated to contain 0, 1, 2, and 5 g/kg (control, XCHD1, XCHD2 and XCHD3) of XCHD, respectively. Seven hundred and eighty shrimp (1.16 ± 0.09 g) were assigned randomly to 12 tanks (400 L, three tanks each group, 65 shrimp in each tank) for 6 weeks. After sampling, 25 shrimp from each tank were selected for a 2-week AFB1 (2500 µg/kg) challenge experiment. The results indicated that the final weight, weight gain and specific growth rate in XCHD2 and XCHD3 groups were significantly increased compared to control. The protease, amylase, superoxide dismutase (SOD), glutathione s-transferase (GST), sulfotransferase (SULT) activities, total antioxidant capacity (T-AOC) and glutathione (GSH) contents in hepatopancreas were significantly increased in XCHD3 groups and the expressions of immune-related genes (Toll, Dorsal and Cru) in hepatopancreas were significantly up-regulated in XCHD2 and XCHD3 groups. High-throughput sequencing analysis revealed that the abundance of Proteobacteria decreased and the abundances of Bacteroidetes increased in XCHD2 and XCHD3 groups. Additionally, AFB1 challenge experiments showed that AFB1 caused histological damage to the hepatopancreas and significantly increased the levels of malondialdehyde (MDA) and protein carbonylation (PC) in hepatopancreas as well as the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Nevertheless, XCHD could effectively alleviated the growth toxicity, immunosuppression and macromolecular damage caused by AFB1 to shrimp by inhibiting the Phase I enzyme and enhancing Phase II enzyme and antioxidant system.

Transcriptome profiling based on protein-protein interaction networks provides a set of core genes for understanding the immune response mechanisms of the egg-protecting behavior in Octopus ocellatus.

Protection via of the immune system is indispensable to the life of organisms. Within an immune network, problems with a given link will affect the normal life activities of the organism. Octopus ocellatus is cephalopod widely distributed throughout the world's oceans. Because of its unique nervous system and locomotive organs, research on this species has gradually increased in recent years. Many immune response mechanisms associated with behaviors of O. ocellatus are still unclear. Moreover, as a factor affecting the normal growth of O. ocellatus, egg protection has rarely been considered in previous behavioral studies. In this study, we analyzed the transcriptome profile of gene expression in O. ocellatus larvae, and identified 5936 differentially expressed genes (DEGs). GO and KEGG enrichment analyses were used to search for immune-related DEGs. Protein-protein interaction networks were constructed to examine the interactions between immune-related genes. Fifteen hub genes involved in multiple KEGG signaling pathways or with multiple protein-protein interaction relationships were obtained and verified by quantitative RT-PCR. We first studied the effects of egg protection on the immunity of O. ocellatus larvae by means of protein-protein interaction networks, and the results provide valuable genetic resources for understanding the immunity of invertebrate larvae. The data serve as a foundation for further research on the egg-protecting behavior of invertebrates.

The Interface between Nanoenergy and Self-Powered Electronics.

In recent decades, nanogenerators based on several techniques such as triboelectric effects, piezoelectric effects, or other mechanisms have experienced great developments. The nanoenergy generated by nanogenerators is supposed to be used to overcome the problem of energy supply problems for portable electronics and to be applied to self-powered microsystems including sensors, actuators, integrated circuits, power sources, and so on. Researchers made many attempts to achieve a good solution and have performed many explorations. Massive efforts have been devoted to developing self-powered electronics, such as self-powered communication devices, self-powered human-machine interfaces, and self-powered sensors. To take full advantage of nanoenergy, we need to review the existing applications, look for similarities and differences, and then explore the ways of achieving various self-powered systems with better performance. In this review, the methods of applying nanogenerators in specific circumstances are studied. The applications of nanogenerators are classified into two categories, direct utilization and indirect utilization, according to whether a treatment process is needed. We expect to offer a line of thought for future research on self-powered electronics.

Phase-field study of the effects of the multi-controlling parameters on columnar dendrite during directional solidification in hexagonal materials.

The growth of hexagonal columnar dendrite during directional solidification with respect to the multi-controlling parameters such as anisotropy, cooling rate, temperature gradient and orientation angle were investigated by a quantitative phase-field method, respectively. The simulation results show that the increase of anisotropy, cooling rate and temperature gradient can accelerate the solidification velocity of columnar dendrites. Among them, the cooling rate has the most significant effect on the solidification velocity of columnar dendrite. In contrast, the solidification velocity of columnar dendrite slows down with the increase of the orientation angle. Meanwhile, the primary dendrite spacing decreases with the increase of cooling rates and temperature gradient, and the primary dendrite arms are smooth. The primary dendrite spacing increases with the increase of anisotropy and orientation angle, which provides space for the development of secondary dendrite arms. In addition, the effects of cooling rate and temperature gradient on the solid volume fraction were also studied.

Integrated bioinformatic analysis reveals YWHAB as a novel diagnostic biomarker for idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is a severe cardiovascular disease that is a serious threat to human life. However, the specific diagnostic biomarkers have not been fully clarified and candidate regulatory targets for IPAH have not been identified. The aim of this study was to explore the potential diagnostic biomarkers and possible regulatory targets of IPAH. We performed a weighted gene coexpression network analysis and calculated module-trait correlations based on a public microarray data set (GSE703) and six modules were found to be related to IPAH. Two modules which have the strongest correlation with IPAH were further analyzed and the top 10 hub genes in the two modules were identified. Furthermore, we validated the data by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent sample set originated from our study center. Overall, the qRT-PCR results were consistent with most of the results of the microarray analysis. Intriguingly, the highest change was found for YWHAB, a gene encodes a protein belonging to the 14-3-3 family of proteins, members of which mediate signal transduction by binding to phosphoserine-containing proteins. Thus, YWHAB was subsequently selected for validation. In congruent with the gene expression analysis, plasma 14-3-3ß concentrations were significantly increased in patients with IPAH compared with healthy controls, and 14-3-3ß expression was also positively correlated with mean pulmonary artery pressure ( R 2 = 0.8783; p < 0.001). Taken together, using weighted gene coexpression analysis, YWHAB was identified and validated in association with IPAH progression, which might serve as a biomarker and/or therapeutic target for IPAH.

Soluble ST2 for Prediction of Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction Receiving Primary PCI.

Soluble suppression of tumorigenicity 2 (sST2), a biomarker representing myocardial fibrosis and inflammation, has been applied in risk stratification of patients with myocardial infarction (MI). However, whether primary PCI (PPCI) will eliminate the predictive value of sST2 in STEMI patients has not been well studied. Here, we conducted a prospective clinical trial to evaluate the correlation between sST2 and prognosis in STEMI patients undergoing PPCI. sST2 levels were measured in 295 STEMI patients (60.2 ± 10.8 years) at admission using a high sensitivity assay. Baseline sST2 levels were significantly associated with heart function, biomarkers of inflammation, and myocardial injury. During a 12-month follow-up, 19 patients had major adverse cardiovascular events (MACEs). Greater sST2 was continuously associated with a higher risk of incident MACEs. Such association remained even after adjusting for other risk factors in a multivariate Cox analysis. A baseline sST2 level in the highest quartile (≥ 58.7 ng/mL) was independently associated with mortality (HR: 5.01, 95%CI: 1.02-16.30, P = 0.048). More incident heart failure was seen in the group with greater sST2, however, the association was not significant after adjustment. Therefore, baseline sST2 may be useful to predict MACEs, especially mortality, in STEMI patients receiving PPCI.

Clinical characteristics and long-term prognosis of spontaneous coronary artery dissection: A single-center Chinese experience.

BACKGROUND AND OBJECTIVE: Spontaneous coronary artery dissection (SCD) remains a rare and important cause of coronary artery disease (CAD). The purpose of this study was to describe the clinical and angiographic features in SCD and to evaluate the treatment and long-term prognosis of this condition in China. METHODS: This retrospective cohort study included 118 Chinese patients with SCD confirmed by coronary angiography. Clinical and angiographic features, treatment modalities and outcomes of SCD were estimated. RESULTS: The overall prevalence of SCD was 0.15%. Age was 57 ± 10 years; 86% patients were men; 75% presented with acute coronary syndrome (ACS); 72% had concomitant atherosclerotic CAD. SCD often affected right coronary artery (RCA) and caused a short dissection (< 20mm). A conservative therapy was used in 28% of patients and revascularization in 72% (percutaneous coronary intervention [PCI] 57%; coronary artery bypass grafting [CABG] 15%). Only one patient died during hospitalization due to multiple organ failure after CABG. During a median follow-up of 43 months (range, 1 - 158 months), 32 patients had a new-onset ACS, 9 received revascularization (7 PCI and 2 CABG), and 8 died. The Kaplan-Meier estimated 12-year rates of freedom from cardiac death and ACS were both higher in revascularization versus conservative therapy (78% versus 57%; P = 0.023; 48% versus 25%, P = 0.014). No significant difference was found in freedom from revascularization between the two therapies. CONCLUSIONS: In China, SCD was usually associated with atherosclerosis and predominantly affected male population. SCD often affected RCA and caused a short dissection. In-hospital mortality rate was low regardless of therapeutic strategy. However, a significantly better long-term prognosis was observed in the revascularization compared with conservative therapy.

Plasma Resistin Levels in Patients with Acute Aortic Dissection: A Propensity Score-Matched Observational Case-Control Study.

BACKGROUND The aim of this observational case-control study was to compare the levels of plasma resistin between patients with acute aortic dissection and matched controls, and to use propensity score matching (PSM) to reduce case selection bias and clinical confounders. MATERIAL AND METHODS With the use of PSM, this study included 43 pairs of patients with acute aortic dissection (type-A and type-B dissection) and matched controls. Plasma resistin levels and other laboratory parameters were compared between the two groups, including white blood cell (WBC) count, glucose, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-dimer. The correlations between resistin and other laboratory parameters were evaluated in patients with acute aortic dissection. RESULTS Following PSM adjustment for clinical variables, including age, sex, body mass index, smoking, alcohol drinking, hypertension, diabetes mellitus, coronary heart disease and stroke, plasma resistin levels were significantly increased in patients with acute aortic dissection when compared with controls (35.2±13.8 vs. 18.4±9.1 ng/ml) (p<0.001). WBC counts, and levels of glucose, hs-CRP, IL-6, TNF-α and D-dimer were also significantly increased in the patients with aortic dissection compared with the control group. After adjustment for these variables, the association between plasma resistin levels and acute aortic dissection remained significant (OR, 1.114; 95% CI, 1.036-1.224) (p<0.001). Plasma resistin levels was positively correlated with WBC count (r=0.368, p=0.015), hs-CRP (r=0.359, p=0.022), IL-6 (r=0.306, p=0.046) and TNF-α levels (r=0.315, p=0.040) in patients with acute aortic dissection. CONCLUSIONS Acute aortic dissection is associated with elevated levels of plasma resistin and other pro-inflammatory cytokines. Plasma resistin levels is positively associated with other pro-inflammatory cytokines in acute aortic dissection.

Ursodeoxycholic Acid Attenuates Acute Aortic Dissection Formation in Angiotensin II-Infused Apolipoprotein E-Deficient Mice Associated with Reduced ROS and Increased Nrf2 Levels.

BACKGROUND/AIMS: Acute aortic dissection (AAD) is characterized by excessive smooth muscle cell (SMC) loss, extracellular matrix (ECM) degradation and inflammation. In response to certain stimulations, oxidative stress is activated and regulates apoptosis and inflammation. Excessive apoptosis promotes aortic inflammation and degeneration, leading to AAD formation. This study aimed to clarify role of oxidative stress in the pathogenesis of AAD and whether the antioxidant ursodeoxycholic acid (UDCA) attenuates AAD formation. METHODS: Angiotensin II (Ang II) was infused in 8-months male ApoE-/- mice for one week to establish a model of AAD. UDCA (10 mg/kg/day) was administered via intragastric gavage for 3 consecutive days before AngII infusion and also during the AngII infusion for another consecutive 7 days. RESULTS: Ang II-infusion resulted in the incidence of AAD at a rate of 35% (13/37) and UDCA markedly reduced the incidence of AAD to 16% (6/37), accompanied with reduced maximal aortic diameter measured at the suprarenal region of the abdominal aorta. Additionally, UDCA pretreatment prevented Ang II induced generations of reactive oxygen species (ROS) and apoptosis of vascular smooth muscle cells (VSMCs) both in vivo and in. vitro Mechanistically, we found UDCA markedly increased Nrf2 expression in VSMCs and prevented Ang II induced expression of NADPH subunits (p47, p67 and gp91) in Nrf2-dependent manner and rescued the activity of redox enzymes (Cu/Zn-SOD, Mn-SOD and CAT), thereby inhibiting apoptosis of VSMCs. CONCLUSION: These results demonstrate that UDCA prevented AAD formation by reducing apoptosis of VSMCs caused by oxidative stress in Nrf2 dependent manner and suggest that UDCA might have clinical potential to suppress AAD formation.

CYP2J2 Overexpression Increases EETs and Protects Against HFD-Induced Atherosclerosis in ApoE-/- Mice.

AIMS: The aim of the present study was to investigate how cytochrome P450 (CYP)2J2-derived epoxyeicosatrienoic acids (EETs) regulate the AKT1 and FOXO1 and BIM pathway and protect against endothelial apoptosis in the development and progression of atherosclerosis. METHODS AND RESULTS: Recombinant adeno-associated virus (rAAV)-mediated CYP2J2 overexpression increased EET levels and prevented high-fat diet-induced atherosclerosis in ApoE mice, which was associated with reduced vascular apoptosis. We also observed that CYP2J2 overexpression suppressed the weight gain induced by a high-fat diet. In vitro CYP2J2 overexpression increased EET levels, subsequently preventing tumor necrosis factor-α-induced apoptosis in human umbilical vein endothelial cells (HUVECs), which contributed to the pathogenesis of atherosclerosis. We observed that AKT1 suppressed BIM expression and apoptosis by inhibiting the function of FOXO1 in cultured HUVECs. Furthermore, we found that CYP2J2 overexpression and its metabolic products, EETs, suppressed tumor necrosis factor-α-induced apoptosis through AKT1 and FOXO1 and BIM dependent signaling in HUVECs. CONCLUSIONS: In summary, we identified a novel molecular mechanism for CYP2J2-derived EETs to protect against atherosclerosis.

Hybrid Approach to Management of Complex Aortic Arch Pathologies: A Single-Center Experience in China.

BACKGROUND: The purpose of this study is to summarize a single-center experience and midterm outcomes of a combined supra-aortic debranching and thoracic endovascular aortic repair (TEVAR) for hybrid operation on patients with complex aortic arch disease. METHODS: From 2012 to 2015, 43 consecutive patients (37 male and 6 females) who underwent a hybrid operation for complex aortic arch disease were retrospectively analyzed. Of the 43 patients, 12 were diagnosed with type A aortic dissection (AD), 27 with complicated type B AD involving the aortic arch, 2 with aortic arch aneurysm, and 2 with type A penetrating atherosclerosis ulcer. RESULTS: The patients' mean age was 52.3 ± 11.3 years. Hybrid operation was technically successful in all patients. The overall 30-day mortality and in-hospital mortality rates were 2.3% (1 of 43), with 1 patient dying at days 18 of severe aspiration pneumonia after procedure. Thirty-day paraplegia and stroke were 0%. Complication included 1 newly onset renal insufficiency and type II endoleak. After a median follow-up of 15 months (range, 6-26 months), the overall mortality was 7.1% (3 of 42), with Kaplan-Meier survival estimate of 91% at 1 year. Only one late death was considered aorta-related. computed tomography (CT) scanning was performed at 6 months and annually thereafter, and 2 patients were observed with type Ib endoleak and type II endoleak, respectively. For the patient with type Ib endoleak, distal extension was performed successfully. No late extra-anatomic bypass occlusion and stent-graft migration were found on CT scans or ultrasound. CONCLUSIONS: These initial results suggest that hybrid operation with supra-aortic debranching, and TEVAR is an acceptable treatment option for patients with complex aortic arch disease. Short-term and midterm outcomes are acceptable. Further research with large sample size and long-term follow-up is needed.

Impact of admission serum total cholesterol level on in-hospital mortality in patients with acute aortic dissection.

OBJECTIVE: To find out the association between serum total cholesterol (TC) on admission and in-hospital mortality in patients with acute aortic dissection (AAD). METHODS: From January 2007 to January 2014, we enrolled 1492 consecutive AAD patients with serum TC measured immediately on admission. Baseline characteristics and in-hospital mortality were compared between the patients with serum TC above and below the median (4.00 mmol/L). Propensity score matching (PSM) was used to account for known confounders in the study. Cox proportional hazard model was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) for admission serum TC levels. RESULTS: With the use of PSM, 521 matched pairs of patients with AAD were yielded in this analysis due to their similar propensity scores. Patients with admission serum TC < 4.00 mmol/L, as compared with those with admission serum TC ≥ 4.00 mmol/L, had higher in-hospital mortality (11.7% vs. 5.8%; HR, 2.06; 95% CI, 1.33-3.19, P = 0.001). Stratified analysis according to Stanford classification showed that the inverse association between admission serum TC and in-hospital mortality was observed in patients with Type-A AAD (24.0% vs. 11.3%; HR, 2.18; 95% CI, 1.33 - 3.57, P = 0.002) but not in those with Type-B AAD (3.8% vs. 2.2%; HR, 1.71; 95% CI, 0.67 - 4.34, P = 0.261). CONCLUSIONS: Lower serum TC level on admission was strongly associated with higher in-hospital mortality in patients with Type-A AAD.

The EH domain-containing protein, EdeA, is involved in endocytosis, cell wall integrity, and pathogenicity in Aspergillus fumigatus.

Endocytosis has been extensively studied in yeasts, where it plays crucial roles in growth, signaling regulation, and cell-surface receptor internalization. However, the biological functions of endocytosis in pathogenic filamentous fungi remain largely unexplored. In this study, we aimed to functionally characterize the roles of EdeA, an ortholog of the Saccharomyces cerevisiae endocytic protein Ede1, in Aspergillus fumigatus. EdeA was observed to be distributed as patches on the plasma membrane and concentrated in the subapical collar of hyphae, a localization characteristic of endocytic proteins. Loss of edeA caused defective hyphal polarity, reduced conidial production, and fewer sites of endocytosis initiations than that of the parental wild type. Notably, the edeA null mutant exhibited increased sensitivity to cell wall-disrupting agents, indicating a role for EdeA in maintaining cell wall integrity in A. fumigatus. This observation was further supported by the evidence showing that the thickness of the cell wall in the ΔedeA mutant increased, accompanied by abnormal activation of MpkA, a key component in the cell wall integrity pathway. Additionally, the ΔedeA mutant displayed increased pathogenicity in the Galleria mellonella wax moth infection model, possibly due to alterations in cell wall morphology. Site-directed mutagenesis identified the conserved residue E348 within the third EH (Eps15 homology) domain of EdeA as crucial for its subcellular localization and functions. In conclusion, our results highlight the involvement of EdeA in endocytosis, hyphal polarity, cell wall integrity, and pathogenicity in A. fumigatus. IMPORTANCE: Aspergillus fumigatus is a significant human pathogenic fungus known to cause invasive aspergillosis, a disease with a high mortality rate. Understanding the basic principles of A. fumigatus pathogenicity is crucial for developing effective strategies against this pathogen. Previous research has underscored the importance of endocytosis in the infection capacity of pathogenic yeasts; however, its biological function in pathogenic mold remains largely unexplored. Our characterization of EdeA in A. fumigatus sheds light on the role of endocytosis in the development, stress response, and pathogenicity of pathogenic molds. These findings suggest that the components of the endocytosis process may serve as potential targets for antifungal therapy.

High-frequency rTMS of the left dorsolateral prefrontal cortex for post-stroke depression: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis investigated the therapeutic efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) for treatment of post-stroke depression (PSD). METHODS: Ten articles with 266 patients in rTMS group and 258 patients in control group were included. The primary outcome was performed to examine the efficacy of rTMS for PSD. Secondary outcomes of response rates and remission rates and subgroup analyses were further explored. RESULTS: Our meta-analysis revealed a significant pooled effect size (the standard mean difference (SMD) was -1.45 points (95% CI, -2.04 to -0.86; p < 0.00001)). The odds ratio (OR) of the response rate and remission rate were 8.41 (95% CI, 2.52-28.12, p = 0.0005) and 6.04 (95% CI, 1.5-24.39, p = 0.01). Moreover, rTMS treatment for PSD patients in subacute phase and targeting the left DLPFC at 5-cm anterior to the left motor hotspot or the midpoint of the middle frontal gyrus showed significant antidepressant effect. In addition, the Hamilton Depression Rating Scale (HAMD) was sensitive to detect depressive changes in patients. CONCLUSIONS: Our meta-analysis elucidated that the application of high-frequency rTMS over the left DLPFC was an effective treatment alternative for PSD. SIGNIFICANCE: Our meta-analysis may help to develop more reasonable treatment strategies in clinical practice for PSD patients.

Phycosphere bacterial disturbance of Saccharina japonica caused by white rot disease relates to seawater nutrients.

In mid-November 2021, there were large areas of white rot disease on cultivated Saccharina japonica in Rongcheng City, China, and diseases were undetected on Sargassum horneri and Porphyra yezoensis. The disturbance direction of bacterial community in the phycosphere after disease outbreak and the relationship with seawater nutrients remain unclear. Here, in situ studies of bacterial community in the non-diseased and diseased areas (Shawo and Dongchu islands) and seawater nutrient levels were carried out. 16S rRNA sequencing showed that the bacterial richness of the studied seaweeds increased in the diseased area. Only in S. japonica, Algitalea outcompeted abundant primary bacteria with probiotic relationships to the host of the non-diseased area, and dominated in the diseased area (17.6% of the total abundance). Nitrogen and phosphorus levels in seawater were 57.8% and 19.6% higher in the non-diseased area than those in the diseased area, respectively, and were strongly correlated with the phycosphere bacteria at the family level of S. japonica. There was no difference in potential pathogenicity between the two areas, while positive signal communications decreased, and nitrogen cycle, chemoheterotrophy, and cellulolysis increased in the diseased area compared to the non-diseased area. Overall, white rot disease caused a structural disturbance in phycosphere bacterial community of S. japonica that related to seawater nutrient levels. Enriched degraders and altered bacterial community functions may exacerbate the disease. This evaluation will provide information for white rot disease management to prevent and mitigate the occurrence of S. japonica outbreaks.

Safety profile of intravenous digoxin in Chinese patients with acute heart failure with reduced ejection fraction: a small-scale prospective cohort study.

Background: Adverse effects of intravenous digoxin vary from patients and disease status, which should be closely monitored. Aims: To explore the safety profile of intravenous digoxin in acute heart failure with reduced ejection fraction (HFrEF) among Chinese patients. Methods: A clinical prospective, single-center, single-arm, open-label exploratory clinical trial was performed in patients with acute HFrEF at Wuhan Asia Heart Hospital. A fixed dose of 0.5 mg digoxin was used intravenously once per day for 3 days. The normalized dosage of digoxin (NDD), toxic serum digoxin concentration (SDC), and adverse reactions of intravenous digoxin were recorded. Results: A total of 40 patients were recruited in the study. The SDC increased from 1.03 ± 0.34 ng/mL to 1.95 ± 0.52 ng/mL during treatment. 50% (20/40) patients reached a toxic SDC of 2.0 ng/mL, and toxic effects were seen in 30% (12/40) patients. Estimated glomerular filtration rate (eGFR) < 60 mL/min [HR: 5.269; 95% CI: 1.905-14.575, p = 0.001], NDD ≥7 µg/kg [HR: 3.028; 95% CI: 1.119-8.194, p = 0.029], and ischemic cardiomyopathy [HR: 2.658; 95% CI: 1.025-6.894, p = 0.044] were independent risk factors for toxic SDC. Toxic SDC was effectively identified [area under the receiver operating characteristic (ROC) curve = 0.85, p < 0.001] using this model, and patients would have a higher risk of toxicity with more risk factors. Conclusion: Intravenous digoxin of 0.5 mg was safe and effective for initial dose but not suitable for maintenance treatment in Chinese patients with acute HFrEF. Patients who had lower eGFR, received higher NDD, and had ischemic cardiomyopathy should be closely monitored to avoid digoxin toxicity.