Quercetin and Kaempferol inhibit HMC-1 activation via SOCE/NFATc2 signaling and suppress hippocampal mast cell activation in lipopolysaccharide-induced depressive mice.

OBJECTIVE AND DESIGN: Mast cells (MCs), as the fastest immune responders, play a critical role in the progression of neuroinflammation-related diseases, especially in depression. Quercetin (Que) and kaempferol (Kae), as two major diet-derived flavonoids, inhibit MC activation and exhibit significant antidepressant effect due to their anti-inflammatory capacity. The study aimed to explore the mechanisms of inhibitory effect of Que and Kae on MC activation, and whether Que and Kae suppress hippocampal mast cell activation in LPS-induced depressive mice. SUBJECTS AND TREATMENT: In vitro assays, human mast cells (HMC-1) were pretreated with Que or Kae for 1 h, then stimulated by phorbol 12-myristate 13-acetate (PMA) and 2,5-di-t-butyl-1,4-benzohydroquinone (tBHQ) for 3 h or 12 h. In vivo assays, Que or Kae was administered by oral gavage once daily for 14 days and then lipopolysaccharide (LPS) intraperitoneally injection to induce depressive behaviors. METHODS: The secretion and expression of TNF-α were determined by ELISA and Western blotting. The nuclear factor of activated T cells (NFAT) transcriptional activity was measured in HMC-1 stably expressing NFAT luciferase reporter gene. Nuclear translocation of NFATc2 was detected by nuclear protein extraction and also was fluorescently detected in HMC-1 stably expressing eGFP-NFATc2. We used Ca2+ imaging to evaluate changes of store-operated calcium entry (SOCE) in HMC-1 stably expressing fluorescent Ca2+ indicator jGCamP7s. Molecular docking was used to assess interaction between the Que or Kae and calcium release-activated calcium modulator (ORAI). The  hippocampal mast cell accumulation and activation  were detected by toluidine blue staining and immunohistochemistry with ß-tryptase. RESULTS: In vitro assays of HMC-1 activated by PtBHQ (PMA and tBHQ), Que and Kae significantly decreased expression and secretion of TNF-α. Moreover, NFAT transcriptional activity and nuclear translocation of NFATc2 were remarkably inhibited by Que and Kae. In addition, the Ca2+ influx mediated by SOCE was suppressed by Que, Kae and the YM58483 (ORAI inhibitor), respectively. Importantly, the combination of YM58483 with Que or Kae had no additive effect on the inhibition of SOCE. The molecular docking also showed that Que and Kae both exhibit high binding affinities with ORAI at the same binding site as YM58483. In vivo assays, Que and Kae significantly reversed LPS-induced depression-like behaviors in mice, and inhibited hippocampal mast cell activation  in LPS-induced depressive mice. CONCLUSIONS: Our results indicated that suppression of SOCE/NFATc2 pathway-mediated by ORAI channels may be the mechanism of inhibitory effect of Que and Kae on MC activation, and also suggested Que and Kae may exert the antidepressant effect through suppressing hippocampal mast cell activation.

Increasing the scan-efficiency of pulmonary imaging at 0.55 T using iterative concomitant field and motion-corrected reconstruction.

PURPOSE: To develop an iterative concomitant field and motion corrected (iCoMoCo) reconstruction for isotropic high-resolution UTE pulmonary imaging at 0.55 T. METHODS: A free-breathing golden-angle stack-of-spirals UTE sequence was used to acquire data for 8 min with prototype and commercial 0.55 T MRI scanners. The data was binned into 12 respiratory phases based on superior-inferior navigator readouts. The previously published iterative motion corrected (iMoCo) reconstruction was extended to include concomitant field correction directly in the cost function. The reconstruction was implemented within the Gadgetron framework for inline reconstruction. Data were retrospectively reconstructed to simulate scan times of 2, 4, 6, and 8 min. Image quality was assessed using apparent SNR and image sharpness. The technique was evaluated in healthy volunteers and patients with known lung pathology including coronavirus disease 2019 infection, chronic granulomatous disease, lymphangioleiomyomatosis, and lung nodules. RESULTS: The technique provided diagnostic-quality images, and image quality was maintained with a slight loss in SNR for simulated scan times down to 4 min. Parenchymal apparent SNR was 4.33 ± 0.57, 5.96 ± 0.65, 7.36 ± 0.64, and 7.87 ± 0.65 using iCoMoCo with scan times of 2, 4, 6, and 8 min, respectively. Image sharpness at the diaphragm was comparable between iCoMoCo and reference images. Concomitant field corrections visibly improved the sharpness of anatomical structures away from the isocenter. Inline image reconstruction and artifact correction were achieved in <5 min. CONCLUSION: The proposed iCoMoCo pulmonary imaging technique can generate diagnostic quality images with 1.75 mm isotropic resolution in less than 5 min using a 6-min acquisition, on a 0.55 T scanner.

CKR-1 orchestrates two motor states from a single motoneuron in C. elegans.

Neuromodulation is pivotal in modifying neuronal properties and motor states. CKR-1, a homolog of the cholecystokinin receptor, modulates robust escape steering and undulation body bending in C. elegans. Nevertheless, the mechanisms through which CKR-1 governs these motor states remain elusive. We elucidate the head motoneuron SMD as the orchestrator of both motor states. This regulation involves two neuropeptides: NLP-12 from DVA enhances undulation body curvature, while NLP-18 from ASI amplifies Ω-turn head curvature. Moreover, synthetic NLP-12 and NLP-18 peptides elicit CKR-1-dependent currents in Xenopus oocytes and Ca2+ transients in SMD neurons. Notably, CKR-1 shows higher sensitivity to NLP-18 compared to NLP-12. In situ patch-clamp recordings reveal CKR-1, NLP-12, and NLP-18 are not essential for neurotransmission at C. elegans neuromuscular junction, suggesting that SMD independently regulates head and body bending. Our studies illustrate that a single motoneuron SMD utilizes a cholecystokinin receptor CKR-1 to integrate two motor states.

Prevalence, Transmission and Genetic Diversity of Pyrazinamide Resistance Among Multidrug-Resistant Mycobacterium tuberculosis Isolates in Hunan, China.

Background: China is a country with a burden of high rates of both TB and multidrug-resistant TB (MDR-TB). However, published data on pyrazinamide (PZA) resistance are still limited in Hunan province, China. This study investigated the prevalence, transmission, and genetic diversity of PZA resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Hunan province. Methods: Drug susceptibility testing (DST) with the Bactec MGIT 960 PZA kit and pyrazinamidase (PZase) testing were conducted on all 298 MDR clinical isolates. Moreover, 24-locus MIRU-VNTR and DNA sequencing of pncA, rpsA, and panD genes were conducted on 180 PZA-resistant (PZA-R) isolates. Results: The prevalence of PZA resistance among MDR-TB strains reached 60.4%. Newly diagnosed PZA-R TB patients and clustered isolates with identical pncA, rpsA, and panD mutations showed that transmission of PZA-R isolates played a significant role in the formation of PZA-R TB. Ninety-eight mutation patterns were observed in the pncA among 180 PZA-R isolates, and seventy-one (72.4%) were point mutations. Twenty-four of these mutations are new, including 2 base substitutions (V93G and T153S) and 22 nucleotide deletions or insertions. The W119C was found in PZA-S isolates, on the other hand, F94L and V155A mutations were found in both PZA resistant and susceptible isolates with positive PZase activity, indicating that they were not associated with PZA resistance. This is not entirely in line with the WHO catalogue. Ten novel rpsA mutations were found in 10 PZA-R isolates, which all combined with mutations in pncA. Thus, it is unpredictable whether these mutations in rpsA can impact PZA resistance. No panD mutation was found in all PZA-R isolates. Conclusion: DNA sequencing of pncA and PZase activity testing have great potential in predicting PZA resistance.

Development of therapeutic monoclonal antibodies against DKK1 peptide-HLA-A2 complex to treat human cancers.

BACKGROUND: Targeted immunotherapy with monoclonal antibodies (mAbs) is an effective and safe method for the treatment of malignancies. Development of mAbs with improved cytotoxicity, targeting new and known tumor-associated antigens, therefore continues to be an active research area. We reported that Dickkopf-1 (DKK1) is a good target for immunotherapy of human cancers based on its wide expression in different cancers but not in normal tissues. As DKK1 is a secreted protein, mAbs binding directly to DKK1 have limited effects on cancer cells in vivo. METHODS: The specificity and antibody-binding capacity of DKK1-A2 mAbs were determined using indirect ELISA, confocal imaging, QIFIKIT antibody-binding capacity and cell surface binding assays. The affinity of mAbs was determined using a surface plasmon resonance biosensor. A flow cytometry-based cell death was performed to detect tumor cell apoptosis. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays were used to evaluate the ability of DKK1-A2 mAbs to mediate ADCC and CDC activities against tumor cells in vitro. Flow cytometry data were collected with an FACSymphony A3 cell analyzer and analyzed with FlowJo V.10.1 software. Human cancer xenograft mouse models were used to determine the in vivo therapeutic efficacy and the potential safety and toxicity of DKK1-A2 mAbs. In situ TUNEL assay was performed to detect apoptosis in tumors and mouse organs. RESULTS: We generated novel DKK1-A2 mAbs that recognize the DKK1 P20 peptide presented by human HLA-A*0201 (HLA-A2) molecules (DKK1-A2 complexes) that are naturally expressed by HLA-A2+DKK1+ cancer cells. These mAbs directly induced apoptosis in HLA-A2+DKK1+ hematologic and solid cancer cells by activating the caspase-9 cascade, effectively lysed the cancer cells in vitro by mediating CDC and ADCC and were therapeutic against established cancers in their xenograft mouse models. As DKK1 is not detected in most human tissues, DKK1-A2 mAbs neither bound to or killed HLA-A2+ blood cells in vitro nor caused tissue damage in tumor-free or tumor-bearing HLA-A2-transgenic mice. CONCLUSION: Our study suggests that DKK1-A2 mAbs may be a promising therapeutic agent to treat human cancers.

First report of leaf blight caused by Alternaria alternata on Lactuca indica in China.

Lactuca indica, an annual or biennial herbaceous plant, is widespread in valleys, shrubland, ditches, hillside meadows or fields (Wang et al. 2003). In China, it is widely used as medicine and high protein feed for herbivorous animal husbandry. In July 2022, leaf blight on L. indica was observed at Zhejiang Normal University (29°8'4″N, 119°37'54″E) in Jinhua City, Zhejiang Province, China. 70% of the 87 plants investigated were infected. Small brown spots with a yellow halos first appeared on the leaves, then became irregular necrotic spots until the entire leaf wilted and fell off. To identify the pathogen, four symptomatic leaves were collected and disinfected according to Wang et al. 2023. Then they were transferred onto potato dextrose agar (PDA), and incubated at 28°C for 7 days. To obtain the pure culture, the marginal mycelium was transferred to a new PDA plate. The colony of the isolated LPB-1 was light gray and regularly round at the early stage, and then changed to dark gray and villous. The back of the culture plate appeared sooty black. The conidia of the isolated fungi (n=50) were in chains, brown, obclavate, ovoid or ellipsoid, with an average size of 29.09 µm long and 6.41 µm wide, with 0 to 3 longitudinal and 1 to 7 transverse septa. These cultural and morphological characteristics were consistent with those of Alternaria alternata (Simmons 2007). To identify the strain, internal transcribed spacer (ITS) region, RNA polymerase Ⅱ second largest subunit (RPB2), and translation elongation factor 1-alpha (TEF1-α) genes were amplified with the primers ITS1/ITS4 (White et al. 1990), RPB2-5F/RPB2-7cR (Liu et al. 1999) and EF1-728F/EF1-986R (Carbone & Kohn 1999). The RPB2 (OP909715), TEF-1α (OP909714), and ITS (OP776880) were 99 to 100% identical to those of A. alternata (GenBank accession nos. MZ170963.1, MK605900.1, and MK605895.1 for RPB2 sequences; ON951981.1, KJ008702.1, and MK672900.1 for TEF-1α sequences; OP850817.1, OP811328.1, and OP740510.1 for ITS sequences). In addition, the phylogenetic analysis also showed that the stain LPB-1 was A. alternata. To complete Koch's postulates, the conidial suspension (1×108 conidia/mL) were spray-inoculated on healthy leaves of three mature L. indica plants with sterile water as a control. All plants were incubated at 28 ℃ in a greenhouse with 12-h-light/12-h-dark photoperiod and approximately 70% humidity (Li et al. 2019). Fourteen days after incubation, the inoculated leaves showed symptoms similar to those of naturally infected leaves, while the controls remained asymptomatic. The pathogen reisolated from the inoculated leaves had the same morphological characteristics and molecular identification results as the original isolate. All the results shown above indicated that A. alternata was responsible for the leaf blight of L. indica. As far as we know, this is the first report of leaf blight caused by Alternaria alternata on Lactuca indica in China. The identification of the pathogen could provide relevant information for the establishment of methods to control the disease.

Concurrent measurement of perfusion parameters related to small blood vessels and cerebrospinal fluid circulation in the human brain using dynamic dual-spin-echo perfusion MRI.

Accumulating evidence from recent studies has indicated the importance of studying the interaction between the microvascular and lymphatic systems in the brain. To date, most imaging methods can only measure blood or lymphatic vessels separately, such as dynamic susceptibility contrast (DSC) MRI for blood vessels and DSC MRI-in-the-cerebrospinal fluid (CSF) (cDSC MRI) for lymphatic vessels. An approach that can measure both blood and lymphatic vessels in a single scan offers advantages such as a halved scan time and contrast dosage. This study attempts to develop one such approach by optimizing a dual-echo turbo-spin-echo sequence, termed "dynamic dual-spin-echo perfusion (DDSEP) MRI". Bloch simulations were performed to optimize the dual-echo sequence for the measurement of gadolinium (Gd)-induced blood and CSF signal changes using a short and a long echo time, respectively. The proposed method furnishes a T1-dominant contrast in CSF and a T2-dominant contrast in blood. MRI experiments were performed in healthy subjects to evaluate the dual-echo approach by comparing it with existing separate methods. Based on simulations, the short and long echo time were chosen around the time when blood signals show maximum difference between post- and pre-Gd scans, and the time when blood signals are completely suppressed, respectively. The proposed method showed consistent results in human brains as previous studies using separate methods. Signal changes from small blood vessels occurred faster than from lymphatic vessels after intravenous Gd injection. In conclusion, Gd-induced signal changes in blood and CSF can be detected simultaneously in healthy subjects with the proposed sequence. The temporal difference in Gd-induced signal changes from small blood and lymphatic vessels after intravenous Gd injection was confirmed using the proposed approach in the same human subjects. Results from this proof-of-concept study will be used to further optimize DDSEP MRI in subsequent studies.

Modified Xiaoyao San reverses lipopolysaccharide-induced depression-like behavior through suppressing microglia M1 polarization via enhancing autophagy involved in PI3K/Akt/mTOR pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Xiaoyao San (MXYS), a clinical empirical modified formula based on famous traditional Chinese herbal prescription Xiaoyao San, according to the "yu syndrome" theory of traditional Chinese medicine. MXYS has been shown to be an excellent effective therapy for depression patients in clinic, but the antidepressant mechanisms remain unclear. AIM OF THE STUDY: A growing body of evidence indicates the microglia autophagy and M1 polarized microglia (proinflammatory phenotype)-mediated neuroinflammation act critical roles in the pathogenesis of depression. This study aimed to investigate whether MXYS exerts antidepressant efficacy through inhibition of M1 polarized microglia-mediated neuroinflammation and modulation of autophagy involved in PI3K/Akt/mTOR pathway. MATERIALS AND METHODS: In present research, the lipopolysaccharide (LPS)-induced depressive mice and LPS-stimulated N9 microglia cell line were utilized. Behavioral tests (sucrose preference, tail suspension and open field tests) were carried out to evaluate the antidepressant effect of MXYS. The neuronal damage was measured by Nissl's staining in LPS-treated mice. The proinflammatory cytokine levels, the autophagic markers, microglia M1 polarization as well as the PI3K/Akt/mTOR pathway related proteins of MXYS treatment were analyzed by ELISA kits, Western blot and immunofluorescence staining in vivo and vitro. Finally, the influence of autophagy antagonist (3-MA) on the protective effect of MXYS-containing serum in the LPS-stimulated N9 microglia was investigated. RESULTS: Treatment of LPS-induced depressive mice with MXYS significantly reversed depression-like behaviors, accompanied by reduction of proinflammatory cytokine levels (TNF-α, IL-1ß) and amelioration of neuronal damage in prefrontal cortex. MXYS suppressed microglia M1 polarization and promoted autophagy in prefrontal cortex and LPS-stimulated N9 cells. Importantly, the remarkable inhibitory effect of the MXYS-medicated serum on microglia M1 polarization was blocked by autophagy antagonist 3-MA in LPS-stimulated N9 cells. Meanwhile, the MXYS treatment exhibited an excellent inhibition effect of PI3K/Akt/mTOR pathway in vivo and vitro. CONCLUSION: Our research suggests that the antidepressant effect of MXYS in LPS-induced depressive mice may be related to alleviate neuroinflammation through suppression of microglia M1 polarization via enhancing autophagy involved in inactivation of the PI3K/Akt/mTOR pathway.

Knowledge, attitudes, and practice related to the prone positioning of patients among intensive care unit nurses working in COVID-19 units: A cross-sectional study in China.

BACKGROUND: An increasing number of studies persistently demonstrate that prone position ventilation can significantly improve the oxygenation index and blood oxygen saturation for most patients (70-80%) with acute respiratory distress syndrome (ARDS). Studies have also shown that the awake prone position was both safe and effective in helping patients with coronavirus disease 2019 (COVID-19) breathe spontaneously. However, the prone position is not widely adopted when treating patients with COVID-19 or ARDS from other causes. Basic knowledge, positive attitudes, and correct practices among the nursing staff are necessary to increase the use of prone positions, reduce the incidence of complications associated with prone positions, and improve the quality and safety of health care. AIM: This study aimed to investigate the knowledge, attitudes, and practice of prone positioning of patients among intensive care unit (ICU) nurses working in COVID-19 units and provide suggestions for improvement. STUDY DESIGN: ICU nurses were recruited from two designated tertiary hospitals for COVID-19 treatment in Shanghai, China, in April 2022, using convenience sampling. A questionnaire survey focusing on the dimensions of knowledge, attitudes, and practice of the prone position with 42 items, was conducted. RESULTS: A total of 132 ICU nurses participated. The scores on the overall questionnaire and the dimensions of knowledge, attitudes, and practice of prone position were 167.28 (95% CI, 161.70-172.86), 78.35 (95% CI, 76.04-80.66), 32.08 (95% CI, 31.51-32.65), and 56.85 (95% CI, 52.42-61.28) respectively. The overall average score was 79.66% (95% CI, 0.77-0.82). The results of multiple linear regression analysis showed that prior experience in treating patients with COVID-19 and professional titles were related to the level of knowledge, attitudes, and practice of prone position. CONCLUSIONS: The ICU nurses strongly believed in the effectiveness of prone positioning, but their knowledge and practice levels need improvement. The experience in treating patients with COVID-19 and professional titles were related to the level of knowledge, attitudes, and practice of prone position. Nursing managers should ensure that ICU nurses are well trained in prone positioning and help enhance the knowledge and attitudes toward prone positioning to promote its widespread use. RELEVANCE TO CLINICAL PRACTICE: Clinical guidelines and in-service training modules need to be developed to promote the use of prone positioning and reduce prone position-related complications.

Inhibition of ferroptosis through regulating neuronal calcium homeostasis: An emerging therapeutic target for Alzheimer's disease.

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, generates a serious threat to the health of the elderly. The AD brain is microscopically characterized by amyloid plaques and neurofibrillary tangles. There are still no effective therapeutic drugs to restrain the progression of AD though much attention has been paid to exploit AD treatments. Ferroptosis, a type of programmed cell death, has been reported to promote the pathological occurrence and development of AD, and inhibition of neuronal ferroptosis can effectively improve the cognitive impairment of AD. Studies have shown that calcium (Ca2+) dyshomeostasis is closely related to the pathology of AD, and can drive the occurrence of ferroptosis through several pathways, such as interacting with iron, and regulating the crosstalk between endoplasmic reticulum (ER) and mitochondria. This paper mainly reviews the roles of ferroptosis and Ca2+ in the pathology of AD, and highlights that restraining ferroptosis through maintaining the homeostasis of Ca2+ may be an innovative target for the treatment of AD.

Visual Analysis of Psychological Resilience Research Based on Web of Science Database.

Background: The importance of psychological resilience that people show in coping with stress and adversity is prominent, but few studies have used rigorous bibliometric tools to analyze the knowledge structure and distribution of psychological resilience research. Objective: The purpose of this study was to sort out and summarize the previous studies on psychological resilience by using bibliometrics. Specifically, the time distribution of psychological resilience research was determined by publication trend, the power distribution was determined by the distribution of countries, authors, institutions and journals, the hot research spots were analyzed according to the results of keyword cluster analysis, and the research frontier was explored according to the results of burst keywords. Methods: CiteSpace5.8.R3 was used to analyze the literatures on psychological resilience collected in Web of Science core Collection database from January 1, 2010, to June 16, 2022. Results: A total of 8462 literatures were included after screening. Research on psychological resilience has been on the rise in recent years. The United States had made a high contribution in this field. Robert H Pietrzak, George A Bonanno, Connor KM and others were highly influential. J Pers Soc Psychol has the highest citation frequency and centrality. The research hot spots focus on five aspects: study on psychological resilience related to COVID-19 pandemic, influencing factors of psychological resilience, psychological resilience related to PTSD, study on psychological resilience of special population, and the molecular biology and genetic basis of psychological resilience. Psychological resilience related to COVID-19 pandemic was the most cutting-edge research aspect. Conclusion: The current situation and trend of psychological resilience research were found in this study, which may be used to identify more hot issues and explore new research directions in this field.

Study on the hepatotoxicity and potential mechanism of gefitinib based on CYP450 in mice and AML12 cells.

OBJECTIVES: Gefitinib is mainly used for the treatment of non-small-cell lung cancer. Hepatotoxicity is one of the main side effects of gefitinib, and seriously affects the treatment process of the disease. However, the hepatotoxicity mechanism of gefitinib remains unclear. METHODS: The hepatotoxicity of different doses of gefitinib was investigated in mice and AML-12 cells, and the possible correlation of hepatotoxicity with CYP450 was analysed. KEY FINDINGS: The toxic effects of gefitinib were confirmed by the increased liver index, decreased body weight and survival rate, injured liver function and histopathology followed 16 days of oral administration. Gefitinib (400 mg/kg) upregulated the hepatic mRNA expression of CYP1A1 and downregulated the CYP2D9 and CYP2D10 in mice. Furthermore, we verified that gefitinib produced cytotoxicity on AML-12 cells in a dose and time-dependent manner, and confirmed that gefitinib (20 µM) induced cell apoptosis, upregulated mRNA expression of CYP1A1 and downregulated CYP2D9 and CYP2D10. Pearson correlation analysis also showed that the hepatotoxicity of gefitinib was positively correlated with CYP1A1 and negatively correlated with CYP2D9 and CYP2D10. CONCLUSIONS: Our results suggested that the hepatotoxicity gefitinib may be associated with CYP1A1, CYP2D9 and CYP2D10. These findings will contribute to a better understanding of the mechanism of gefitinib hepatotoxicity.

Study on the mechanisms of action of berberine combined with fluconazole against fluconazole-resistant strains of Talaromyces marneffei.

Talaromyces (Penicillium) marneffei (T. marneffei) is a thermally dimorphic fungus that can cause opportunistic systemic mycoses. Our previous study demonstrated that concomitant use of berberine (BBR) and fluconazole (FLC) showed a synergistic action against FLC-resistant T. marneffei (B4) in vitro. In this paper, we tried to figure out the antifungal mechanisms of BBR and FLC in T. marneffei FLC-resistant. In the microdilution test, the minimum inhibitory concentration (MIC) of FLC was 256 µg/ml before FLC and BBR combination, and was 8 µg/ml after combination, the partial inhibitory concentration index (FICI) of B4 was 0.28. After the treatments of BBR and FLC, the studies revealed that (i) increase reactive oxygen species (ROS), (ii) reduce ergosterol content, (iii) destroy the integrity of cell wall and membrane, (iv) decrease the expression of genes AtrF, MDR1, PMFCZ, and Cyp51B however ABC1 and MFS change are not obvious. These results confirmed that BBR has antifungal effect on T. marneffei, and the combination with FLC can restore the susceptibility of FLC-resistant strains to FLC, and the reduction of ergosterol content and the down-regulation of gene expression of AtrF, Mdr1, PMFCZ, and Cyp51B are the mechanisms of the antifungal effect after the combination, which provides a theoretical basis for the application of BBR in the treatment of Talaromycosis and opens up new ideas for treatment of Talaromycosis.

Choroidal layer segmentation in OCT images by a boundary enhancement network.

Morphological changes of the choroid have been proved to be associated with the occurrence and pathological mechanism of many ophthalmic diseases. Optical Coherence Tomography (OCT) is a non-invasive technique for imaging of ocular biological tissues, that can reveal the structure of the retinal and choroidal layers in micron-scale resolution. However, unlike the retinal layer, the interface between the choroidal layer and the sclera is ambiguous in OCT, which makes it difficult for ophthalmologists to identify with certainty. In this paper, we propose a novel boundary-enhanced encoder-decoder architecture for choroid segmentation in retinal OCT images, in which a Boundary Enhancement Module (BEM) forms the backbone of each encoder-decoder layer. The BEM consists of three parallel branches: 1) a Feature Extraction Branch (FEB) to obtain feature maps with different receptive fields; 2) a Channel Enhancement Branch (CEB) to extract the boundary information of different channels; and 3) a Boundary Activation Branch (BAB) to enhance the boundary information via a novel activation function. In addition, in order to incorporate expert knowledge into the segmentation network, soft key point maps are generated on the choroidal boundary, and are combined with the predicted images to facilitate precise choroidal boundary segmentation. In order to validate the effectiveness and superiority of the proposed method, both qualitative and quantitative evaluations are employed on three retinal OCT datasets for choroid segmentation. The experimental results demonstrate that the proposed method yields better choroid segmentation performance than other deep learning approaches. Moreover, both 2D and 3D features are extracted for statistical analysis from normal and highly myopic subjects based on the choroid segmentation results, which is helpful in revealing the pathology of high myopia. Code is available at https://github.com/iMED-Lab/Choroid-segmentation.

Cardiac Arrhythmia after COVID-19 Vaccination versus Non-COVID-19 Vaccination: A Systematic Review and Meta-Analysis

AimsCardiac arrhythmia is a rare complication after vaccination. Recently, reports of arrhythmia after COVID-19 vaccination have increased. Whether the risk for cardiac arrhythmia is higher with COVID-19 vaccines than with non-COVID-19 vaccines remains controversial. This meta-analysis explored the incidence of arrhythmia after COVID-19 vaccination and compared it with the incidence of arrhythmia after non-COVID-19 vaccination. MethodsWe searched the MEDLINE, Scopus, Cochrane Library, and Embase databases for English-language studies reporting the incidence of arrhythmia (the primary endpoint) after vaccination from January 1, 1947 to October 28, 2022. Secondary endpoints included incidence of tachyarrhythmia and all-cause mortality. Subgroup analyses were conducted to evaluate the incidence of arrhythmia by age (children [<18 years] versus adults [[≥]18 years]), vaccine type (mRNA COVID-19 vaccine versus non-mRNA COVID-19 vaccine; individual non-COVID-19 vaccines versus COVID-19 vaccine), and COVID-19 vaccine dose (first versus second versus third). Random-effects meta-analyses were performed, and the intrastudy risk for bias and the certainty of evidence were evaluated. This study was registered with PROSPERO (CRD42022365912). ResultsThe overall incidence of arrhythmia from 36 studies (1,528,459,662 vaccine doses) was 291.8 (95% CI 111.6-762.7) cases per million doses. The incidence of arrhythmia was significantly higher after COVID-19 vaccination (2263.4 [875.4-5839.2] cases per million doses; 830,585,553 doses, 23 studies) than after non-COVID-19 vaccination (9.9 [1.3-75.5] cases per million doses; 697,874,109 doses, 14 studies; P<0.01). Compared with COVID-19 vaccines, the influenza, pertussis, human papillomavirus, and acellular pertussis vaccines were associated with a significantly lower incidence of arrhythmia. The incidence of tachyarrhythmia was significantly higher after COVID-19 vaccination (4367.5 [1535.2-12,360.8] cases per million doses; 1,208,656 doses, 15 studies) than after non- COVID-19 vaccination (25.8 [4.5-149.4] cases per million doses; 179,822,553 doses, 11 studies; P<0.01). Arrhythmia was also more frequent after the third dose of COVID-19 vaccine (19,064.3 [5775.5-61,051.2] cases per million doses; 7968 doses, 3 studies) than after the first dose (3450.9 [988.2-11,977.6] cases per million doses; 41,714,762 doses, 12 studies; P=0.05) or second dose (2262.5 [2205.9-2320.7] cases per million doses; 34,540,749 doses, 10 studies; P<0.01). All-cause mortality was comparable between the COVID-19 and non-COVID-19 vaccination groups. ConclusionsThe overall risk for arrhythmia after COVID-19 vaccination was relatively low, although it was higher in COVID-19 vaccine recipients than in non-COVID-19 vaccine recipients. This increased risk should be evaluated along with other important factors, such as the incidence of local outbreaks and the risk for arrhythmia due to COVID infection itself, when weighing the safety and efficacy of COVID-19 vaccines.

First report of bacterial wilt disease caused by Pantoea agglomerans on the ornamental perennial Oxalis articulata in China.

Oxalis articulata is now widely cultivated in China as an ornamental species, and thus found in abundance in agricultural farms, gardens, and lawns. In December 2021, some severely infected Oxalis articulata were observed at many places at Zhejiang Normal University (29°8'4″N, 119°37'54″E) in Jinhua City, Zhejiang Province, China. Yellow was first observed on the margin of the leaves, leading to light brown and wilting at a later stage. To identify the pathogen, symptomatic leaves were collected and cut into small pieces, surface disinfected in 1% sodium hypochlorite solution for 3 min, followed by 75% alcohol for 0.5 min, then rinsed in sterile distilled water thrice. Then they were transferred onto Luria-Bertani medium and incubated at 28°C for 3 days. The colonies were round, yellow, viscous and smooth, which was consistent with the characteristics of Pantoea agglomerans (Li et al. 2020; Zhang et al. 2022). The bacteria tested gram-negative, negative for indole test and Voges-Proskauer reaction, and positive for methyl red reaction, lysine decarboxylase and ornithine decarboxylase. In addition, the bacteria can utilize D-xylose, sorbitol, adonitol, and glucose, but can't utilize raffinose, urea, and Simmons. Meanwhile the bacteria can not produce H2S, and can not produce gas from D-glucose as well. These results of physiological and biochemical characteristics were consistent with those of Pantoea agglomerans (Gavini et al. 1989). To identify the strain, the 16S rDNA gene fragment was amplified by polymerase chain reaction (PCR) using universal primers 8F and 1510R, and sequenced. The BLAST results indicated that the 16S rDNA sequence of the strain OAPB-1, deposited under GenBank accession LC709256, showed 99.93% (1376/1377) and 99.49% (1370/1377) identity to the corresponding sequence of Pantoea agglomerans FC2948 (MH532498.1) and the type strain Pantoea agglomerans DSM 3493 (AJ233423) respectively. The Neighbor-Joining phylogenetic tree generated using MEGA11 indicated that it formed a clade with the other P. agglomerans. Furthermore, the phylogenetic analysis based on sequences of housekeeping genes (atpD, rpoB and infB; GenBank accession LC722492 to LC722494) showed the same result. Based on the above results, the strain OAPB-1 from Zhejiang was identified as P.agglomerans. To test the Koch's postulates, bacterial suspensions (2×108CFU/mL) were injected into the middle of healthy leaves of mature plants with sterile water as a control. Then the plants were placed at 28°C in a light incubator with 12-h-light/12-h-dark photoperiod and approximately 60% humidity. Leaves in the inoculated group showed symptoms similar to those observed on the naturally infected leaves, while leaves in the control group showed no symptoms. The pathogen was reisolated from inoculated leaves, and its morphological characteristics and molecular identification results were consistent with those of the original isolate. P. agglomerans is a bacterium associated with plants, and also infects humans and animals (Dutkiewicz et al. 2016). In China, it has been reported to infect many kinds of plants (Fan et al. 2022; Guo et al. 2020; Han et al. 2020; Li et al. 2020; She et al. 2019; Zhang et al. 2022). As far as we know, this is the first report of P. agglomerans causing bacterial wilt on Oxalis articulata in China. These results further expand the range of plants that can be infected by P. agglomerans, and help to establish an effective control strategy against the disease.

Cryptotanshinone Alleviates Oxidative Stress and Reduces the Level of Abnormally Aggregated Protein in Caenorhabditis elegans AD Models.

Alzheimer's disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from Salvia castanea. It is found that it can alleviate AD-like features associated with Aß1-42 toxicity in muscle cells as well as neuronal cells of Caenorhabditis elegans (C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of sod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aß monomers and highly toxic oligomers in C. elegans while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of hsp-16.2 and downregulated the expression of ace-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.

Visualized analysis of research on helicopter emergency medical service.

BACKGROUND: Numerous studies have confirmed that helicopter emergency medical services (HEMS) play a positive role in prehospital care. However, few studies have used rigorous bibliometric tools to analyze the knowledge structure and distribution of HEMS research. OBJECTIVES: The purpose of this study was to use bibliometric methods to conduct a quantitative and qualitative analysis of the HEMS-related literature and to determine the research status and hotspots of HEMS research. METHODS: CiteSpace was used for bibliometric analysis of the HEMS-related literature retrieved from the Web of Science database from 1989 to 2021. RESULTS: A total of 1378 HEMS-related literature were included. Collaboration among countries, authors, and institutions needs to be strengthened. The topics in HEMS research have mainly focused on the effectiveness of helicopter emergency medical services for trauma patients and the comparison of transport effectiveness between helicopters and ground emergency medical services on trauma patient transport. Research over the past 10 years has mainly focused on the application of HEMS in patients with trauma, myocardial infarction, cerebral apoplexy, application of tracheal intubation technology in HEMS, and advanced airway management. In recent years, HEMS research trends have mainly included out-of-hospital cardiac arrest, and transport. CONCLUSIONS: CiteSpace was used to visualize and analyze the HEMS-related literature, which visually reflected the research status and hot spots, providing references for the topic selection and development direction of HEMS research.

A dominant set-informed interpretable fuzzy system for automated diagnosis of dementia.

Dementia is an incurable neurodegenerative disease primarily affecting the older population, for which the World Health Organisation has set to promoting early diagnosis and timely management as one of the primary goals for dementia care. While a range of popular machine learning algorithms and their variants have been applied for dementia diagnosis, fuzzy systems, which have been known effective in dealing with uncertainty and offer to explicitly reason how a diagnosis can be inferred, sporadically appear in recent literature. Given the advantages of a fuzzy rule-based model, which could potentially result in a clinical decision support system that offers understandable rules and a transparent inference process to support dementia diagnosis, this paper proposes a novel fuzzy inference system by adapting the concept of dominant sets that arise from the study of graph theory. A peeling-off strategy is used to iteratively extract from the constructed edge-weighted graph a collection of dominant sets. Each dominant set is further converted into a parameterized fuzzy rule, which is finally optimized in a supervised adaptive network-based fuzzy inference framework. An illustrative example is provided that demonstrates the interpretable rules and the transparent reasoning process of reaching a decision. Further systematic experiments conducted on data from the Open Access Series of Imaging Studies (OASIS) repository, also validate its superior performance over alternative methods.