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Abstract Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Objective: Identification of heavy menstrual bleeding (HMB) cases in primary care settings is often done by using pictorial blood assessment charts (PBAC). The study aims to highlight the challenge of assessing blood loss, to develop a standardized method to efficiently customize a patient-reported pictorial chart, to validate the tool produced with our proposed method, and to demonstrate the feasibility of using PBACs in settings where resources are scarce. Materials and methods: Using blood samples and feedback from 21 women aged 30–51 years, we followed guidelines suggested in the literature, developed a method to produce PBACs for regular, long and night sizes, and had 9 participants testuse them. Linear regression analysis was performed to determine the correlation between participants’ scores and menstrual blood weight. Results: The study demonstrated the feasibility of customizing product-sensitive and size-specific pictorial charts by adopting essential steps including collecting menstrual blood with menstrual cups, employing fluid application techniques, and using sanitary pads as icons for easy identification. Linear regression analyses of score versus blood weight showed that the recorded blood weight was around 95% of the scored values (R2 = 0.9428, 0.947, and 0.9508, respectively; p

Background Fibrotic metabolic dysfunction-associated steatohepatitis (MASH) is a condition at risk of progressing to advanced liver disease. We examined whether an innovative exhaled nitric oxide (eNO) breath test (BT) can accurately diagnose fibrotic MASH without requiring blood tests.Methods One hundred and forty-seven patients with MASH were recruited, and all tests were undertaken within 1 week of recruitment. With fibrotic MASH (NAS ≥ 4 and fibrosis stage ≥ 2) as the main outcome indicator, the diagnostic efficacy of eNO in identifying fibrotic MASH was compared to other validated models for advanced fibrosis requiring venesection, namely FAST, Agile 3+, and FIB-4 scores.Results The mean age was 40.36 ± 12.28 years, 73.5% were men. Mean body mass index was 28.83 ± 4.31 kg/m2. The proportion of fibrotic MASH was 29.25%. The area under the receiver operating curve for eNO in diagnosing fibrotic MASH was 0.737 [95% CI 0.650–0.823], which was comparable to FAST (0.751 [0.656–0.846]), Agile 3+ (0.764 [0.670–0.858]), and FIB-4 (0.721 [0.620-0.821]) (all DeLong test p > 0.05). A cut-off of eNO 13.5 ppb provided a specificity of 91.3% and a positive predictive value of 65.4% for ruling-in fibrotic MASH. Sensitivity analyses demonstrated that the diagnostic efficacy of eNO was similar across characteristics such as age. Moreover, adding vibration-controlled transient elastography-LSM (liver stiffness measurement) reduced the uncertainty interval from 46.9% to 39.5%.Conclusions The eNO-BT is a promising simple test for non-invasively identifying fibrotic MASH, and its performance is further improved by adding LSM measurement.

Abstract Early and accurate diagnosis of ear deformities in newborns is crucial for an effective non-surgical correction treatment, since this commonly seen ear anomalies would affect aesthetics and cause mental problems if untreated. It is not easy even for experienced physicians to diagnose the auricular deformities of newborns and the classification of the sub-types, because of the rich bio-metric features embedded in the ear shape. Machine learning has already been introduced to analyze the auricular shape. However, there is little publicly available datasets of ear images from newborns. We released a dataset that contains quality-controlled photos of 3,852 ears from 1,926 newborns. The dataset also contains medical diagnosis of the ear shape, and the health data of each newborn and its mother. Our aim is to provide a freely accessible dataset, which would facilitate researches related with ear anatomies, such as the AI-aided detection and classification of auricular deformities and medical risk analysis.

Extracellular HSP90α (eHSP90α) is a promoter of tumor development and malignant progression. Patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC), have generally shown 5~10-fold increases in serum/plasma eHSP90α levels. In this study, we developed a humanized antibody HH01 to target eHSP90α and evaluated its anticancer efficacy. HH01, with novel complementarity-determining regions, exhibits high binding affinity toward HSP90α. It recognizes HSP90α epitope sites 235AEEKEDKEEE244 and 251ESEDKPEIED260, with critical amino acid residues E237, E239, D240, K241, E253, and K255. HH01 effectively suppressed eHSP90α-induced invasive and spheroid-forming activities of colorectal cancer and PDAC cell lines by blocking eHSP90α’s ligation with the cell-surface receptor CD91. In mouse models, HH01 potently inhibited the tumor growth of PDAC cell grafts/xenografts promoted by endothelial-mesenchymal transition-derived cancer-associated fibroblasts while also reducing serum eHSP90α levels, reflecting its anticancer efficacy. HH01 also modulated tumor immunity by reducing M2 macrophages and reinvigorating immune T-cells. Additionally, HH01 showed low aggregation propensity, high water solubility, and a half-life time of >18 days in mouse blood. It was not cytotoxic to retinal pigmented epithelial cells and showed no obvious toxicity in mouse organs. Our data suggest that targeting eHSP90α with HH01 antibody can be a promising novel strategy for PDAC therapy.

为了探究我国3个储粮生态区的大豆存储质量变化周期，指导不同储粮生态区大豆保质技术措施，收集了相关储存库点2014—2016年大豆品质数据，考察了大豆储存过程中粗脂肪酸值、蛋白质溶解比率的变化，分析了大豆品质指标与粗脂肪酸值、蛋白质溶解比率的相关性。结果发现：区域储存温度对大豆粗脂肪酸值影响较为明显，对蛋白质溶解比率影响较弱；在第五区中温高湿区储存大豆，其粗脂肪酸值增长与损伤粒、热损伤粒的增加及储存时间的延长有一定关系，蛋白质溶解比率与热损伤粒有一定的关系。综上，合理控制大豆的损伤粒、热损伤粒比例，对于控制其粗脂肪酸值和蛋白质溶解比率有较明显作用。 In order to explore the changing cycle of soybean storage quality in three grain storage ecological regions in China and guide the technical measures of soybean quality preservation in different grain storage ecological regions. Soybean quality data from relevant storage points during 2014-2016 were collected, the changes in crude fat acid value and protein solubility ratio during storage of soybeans were examined, and the correlations between soybean quality indexes and crude fat acid value, protein solubility ratio were analyzed. The results showed that regional storage temperature had obvious effect on crude fat acid value of soybean, but had little effect on protein solubility ratio. Storing soybeans in the fifth areas with moderate temperature and high humidity had a certain relationship with the increase of crude fat acid value and the increase of damaged grains, heat damaged grains, and storage time. There was a certain relationship between protein solubility ratio and heat damaged grains. In conclusion, reasonable control of damaged grain ratio and heat damaged grain ratio of soybean has obvious effect on controlling crude fat acid value and protein solubility ratio.

Abstract Background Air pollution is a key public health factor with the capacity to induce diseases. The risk of ischemia heart disease (IHD) in those suffering from systemic lupus erythematosus (SLE) from air pollution exposure is ambiguous. This study aimed to: (1) determine the hazard ratio (HR) of IHD after the first-diagnosed SLE and (2) examine the effects of air pollution exposure on IHD in SLE for 12 years. Methods This is a retrospective cohort study. Taiwan’s National Health Insurance Research Database and Taiwan Air Quality Monitoring data were used in the study. Cases first diagnosed with SLE in 2006 cases without IHD were recruited as the SLE group. We randomly selected an additional sex-matched non-SLE cohort, four times the size of the SLE cohort, as the control group. Air pollution indices by residence city per period were calculated as the exposure. Life tables and Cox proportional risk models of time-dependent covariance were used in the research. Results This study identified patients for the SLE group (n = 4,842) and the control group (n = 19,368) in 2006. By the end of 2018, the risk of IHD was significantly higher in the SLE group than in the control group, and risks peaked between the 6th and 9th year. The HR of incidence IHD in the SLE group was 2.42 times that of the control group. Significant correlations with risk of developing IHD were noted for sex, age, CO, NO2, PM10, and PM2.5, of which PM10 exposure had the highest risk of IHD incidence. Conclusions Subjects with SLE were at a higher risk of IHD, especially those in the 6th to 9th year after SLE diagnosis. The advanced cardiac health examinations and health education plan should be recommended for SLE patients before the 6th year after SLE diagnosed.

The medium effects of nucleons and equation of state (EOS) are two important issues in low-intermediate energy nuclear physics. In laboratory, the medium effects of nucleons and EOS can be learned by comparing the heavy ion collisions (HICs) with the transport model simulations. Up to now, the main challenges are to find sensitive probes for learning the medium effects of nucleons, such as the effective mass for proton and neutron, and to improve the reliability of the extraction of the medium effects of nucleons and EOS by comparing the transport model calculations with experimental data. To improve the reliability of the comparisons, it is necessary to use the same conditions as those used in experiments, such as angle cut or energy bins for measured particles or fragments, and centrality of the reaction. The angle cut and energy bins can be easily realized in the calculations. However, the centrality of HICs can not be used directly as an input in the simulations, since the centrality of HICs does not correspond to a specific value of the impact parameter. Another, the impact parameter used in the transport model simulations can not be directly measured in experiments. Thus, reconstructing the impact parameter distribution from the centrality of HIC observables is necessary for simulating HICs and comparing with data in a reasonable way. In this work, we first investigate the fluctuation mechanism in low-intermediate energy HICs. Our calculations show that the initial statistical fluctuations and random nucleon-nucleon scattering are two origins of inherent fluctuations. The fluctuation mechanism leads the observables to be distributed over a wide range even with the same inputs, such as a fixed value of impact parameter, beam energy, EOS, nucleon-nucleon scattering cross section, etc. On the other hand, a fixed or certain value of observables maps to the input variables over a wide range. If a machine learning is used to map the values of observables to the distribution of input physics variables, a novel algorithm should be proposed. For model-independently reconstructing impact parameter distributions with two-dimensional observables, we propose a method by combining an unsupervised machine learning K-means algorithm with Bayesian method. After fitting the conditional probability density distributions of the reduced multiplicity M0 and the total transverse momentum of the light fragment ptott0 at given impact parameters, the probability density function of the impact parameters at given observable is obtained. The events are automatically sorted by using the K-means algorithm, and then a Bayesian method is used to reconstruct the impact parameter distributions for the events selected by certain values of observables. Furthermore, we use the convolutional neural network (CNN) and forward neural network (FNN) to distinguish two Skyrme parameter sets, such as SkM* and SLy4, from the data generated by ImQMD. The two parameter sets have different signs of the effective mass splitting. The two-dimensional observables, such as the longitudinal and transverse kinetic momentum distributions of neutron and proton, and neutron/proton energy spectra are selected to train the CNN and FNN, respectively. Our calculations show that CNN can distinguish two sets from two-dimensional observables with an accuracy of 81% for 132Sn+124Sn system at the beam energy of 200 MeV/nucleon. FNN can distinguish two sets from neutron/proton energy spectra with an accuracy better than 93%. These studies accumulate the experience on the determination of effective mass splitting distribution with the data in the future.

This study represents a primary investigation centered on screening six marine fungi, Emericellopsis maritima, Engyodontium album, Hypomontagnella monticulosa, Hortaea werneckii, Trichoderma harzianum, and Aspergillus sp.7, associated with the red algae Pterocladiella capillacea, which was collected from Chao-Jin Park in Keelung, Taiwan, as potential immunostimulants for shrimp aquaculture. Recognizing the imperative for novel strategies to combat pathogen resistance arising from the use of antibiotics and vaccines in aquaculture, this study aimed to evaluate the metabolomic profile, antioxidant capabilities, and antibacterial properties of marine fungi. The antibacterial activity of the fungal extract was evaluated against five major aquaculture pathogens: Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Enterobacter aeruginosa, and Vibrio parahaemolyticus. The viability and cytotoxicity of marine fungal extracts were preliminarily evaluated using brine shrimps before assessing cytotoxicity, growth performance, immune efficacy, and disease resistance in white shrimp. The present study demonstrated that total phytochemical analysis correlated with antioxidant activity. Emericellopsis maritima and Trichoderma harzianum exhibited the strongest DPPH antioxidant scavenging activities of half-maximal inhibitory concentration (IC50) 16.5 ± 1.2 and 12.2 ± 2.6, which are comparable to ascorbic acid. LC-HDMSE analysis of the marine fungal extracts identified more than 8000 metabolites mainly classified under the superclass level of organic oxygen compounds, Organoheterocyclic compounds, Phenylpropanoids and polyketides, alkaloid and derivatives, benzenoids, lignans and neolignans, lipid and lipid-like molecules, nucleotides and nucleosides, organic nitrogen compounds, and organic acids and derivatives. Overall, our study significantly contributes to the advancement of sustainable practices by exploring alternative antimicrobial solutions and harnessing the bioactive potential inherent in marine endophytic fungi. In conclusion, our study advances our comprehension of fungal communities and their applications and holds promise for the development of effective and environmentally friendly approaches for enhancing shrimp health and productivity.

Abstract The newly proposed term “metabolic dysfunction-associated fatty liver disease” (MAFLD) is replacing the old term “non-alcoholic fatty liver disease” (NAFLD) in many global regions, because it better reflects the pathophysiology and cardiometabolic implications of this common liver disease. The proposed change in terminology from NAFLD to MAFLD is not simply a single-letter change in an acronym, since MAFLD is defined by a set of specific and positive diagnostic criteria. In particular, the MAFLD definition specifically incorporates within the classification recognized cardiovascular risk factors. Although convincing evidence supports a significant association between both NAFLD and MAFLD, with increased risk of CVD morbidity and mortality, neither NAFLD nor MAFLD have received sufficient attention from the Cardiology community. In fact, there is a paucity of scientific guidelines focusing on this common and burdensome liver disease from cardiovascular professional societies. This Perspective article discusses the rationale and clinical relevance for Cardiologists of the newly proposed MAFLD definition.

ObjectiveMalignant transformation of mature ovarian teratoma is a rare phenomenon, mainly occurring in postmenopausal period. Squamous cell carcinoma accounts for 80% of all malignant transformations. Sarcoma transformation is much less common and tends to imply a poorer prognosis and aggressiveness.Case reportWe report a case of undifferentiated sarcoma with squamous cell carcinoma in a mature cystic teratoma of the ovary in a 36-year-old woman. The tumor shows epithelial and stromal components. This is a unique report of a benign teratoma of the ovary with malignant transformation, showing epithelial and sarcomatous components. This young woman presented with abdominal distension and a rapidly enlarging ovario-derived pelvic mass with a slightly elevated CA199 tumor marker of 115.9 U/ml. The woman underwent transabdominal excision of the left ovarian cyst on October 20, 2020. During the operation, rapid freezing pathological examination did not indicate malignancy. The postoperative paraffin pathology revealed undifferentiated sarcoma with squamous cell carcinoma (from mature cystic teratoma malignancy), and she finally received comprehensive staging surgery. Postoperative paraffin pathology showed no residual cancer in uterus and other tissues, and all lymph nodes were negative. The patient was finally diagnosed with ovarian malignant tumor IC1 stage (high-grade spindle cell sarcoma complicated with squamous cell carcinoma). Chemotherapy was completed three times after surgery, and no signs of recurrence were found after follow-up.ConclusionThe preoperative diagnosis and intraoperative rapid freezing examination of malignant transformation of mature teratoma of ovary are challenging.

Abstract Background The World Health Organization in recent years has emphasized reducing the possibility of unnecessary interventions in natural childbirth, but little is known about the accuracy of non-invasive methods when assessing the progress of labor. This paper presents a literature review to assess strategies that support non-invasive methods for labor during the first stage. It evaluates the available evidence to provide the most suitable assessments and predictions that objectively identify the progress of low-risk labor during the first stage of labor. Methods A search for relevant literature was conducted using the electronic databases of PubMed, CINAHL, Web of Sciences, the Cochrane Library, Scopus, Medline (OVID), and CEPS, with publications up to November 2021. Records were screened against pre-specified inclusion/exclusion criteria and the potential papers from Google Scholar were examined to identify additional papers that may have been missed. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to appraise the methodological quality of the included studies. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Two independent investigators extracted the review’s characteristics, and discrepancies were resolved by consensus. This review calculated individual and pooled sensitivity, specificity, and positive predictive values, which were exported to STATA (version 14; Stata Corp., College Station, TX) to represent the performance of diagnostic testing. Results Our search returned 2283 reports of which 13 fulfilled the inclusion criteria, accounting for 2594 women. The subjects were divided into groups according to the diagnostic tests used to assess the progress of their labor, including appearance assessment and sonographic imaging parameters (head perineum distance, HPD; angle of progression, AOP, and other parameters). HPD pooled sensitivity was 0.74 (0.65–0.82), and specificity was 0.77 (0.69–0.84). The pooled diagnostic odds ratio (DOR) was 8.21 (4.67–14.41) and 10.34 (5.02–21.27), respectively. The results of subgroup analysis showed that the summary sensitivity and specificity were of medium accuracy overall. The quality of evidence as assessed with GRADE was low. Conclusion Vaginal examination is an intrinsic element in the use of the partogram, while transperineal ultrasound can also be used as an auxiliary tool. However, the presence of publication bias within the parameters of ultrasound indicates that the diagnostic performance may be overestimated. Thus, randomized controlled trials or large-scale prospective cohort studies are necessary.

ObjectiveTo explore spatio-temporal clustering of Vibrio parahaemolyticus detection rate among reported foodborne disease cases in Zhejiang province and to provide evidence to surveillance and prevention of foodborne disease in the region. MethodsThe data on Vibrio parahaemolyticus detection among foodborne disease cases reported by 101 sentinel hospitals in Zhejiang province during 2016 – 2017 were collected from provincial reporting system for foodborne disease monitoring. Descriptive statistics analysis, spatial analysis and spatio-temporal scanning statistics were performed on the data obtained. ResultsAmong 43386 and 33407 specimens from foodborne diarrhoea cases in 2016 and 2017, 1978 and 1346 were positive for Vibrio parahaemolyticus, with the detection rate of 4.56 % and 4.03 %. The Vibrio parahaemolyticus detection rate was the highest in August during a year and the detection rate was higher in adult cases, especially in those aged 26 – 35 years. Obvious temporal and spatial clustering of Vibrio parahaemolyticus detection rate were identified, with spatial clustering in 3 regions in 2016 and another 3 regions in 2017 and temporal clustering during August – October of 2016 and July – October of 2017, respectively． ConclusionAmong reported foodborne disease cases in Zhejiang province, the Vibrio parahaemolyticus detection rate is of uneven age and seasonal distribution and the detection rate is also of obvious spatial and temporal clustering.

Abstract Background Pubic symphysis diastasis (PSD) hinders the connection between bilateral ischia and pubic bones, resulting in instability of the anterior pelvic ring. PSD exceeding 25 mm is considered disruptions of the symphyseal and unilateral/bilateral anterior sacroiliac ligaments and require surgical intervention. The correct choice of fixation devices is of great significance to treat PSD. This study aimed to evaluate the construct stability and implant performance of seven fixation methods to treat PSD using finite element analysis. Methods The intact skeleton-ligament pelvic models were set as the control group. PSD models were simulated by removing relevant ligaments. To enhance the stability of the posterior pelvic ring, a cannulated screw was applied in the PSD models. Next, seven anterior fixation devices were installed on the PSD models according to standard surgical procedures, including single plates (single-Plate group), single plates with trans-symphyseal cross-screws (single-crsPlate group), dual plates (dual-Plate group), single cannulated screws, dual crossed cannulated screws (dual-canScrew group), subcutaneous plates (sub-Plate group), and subcutaneous pedicle screw-rod devices (sub-PedRod group). Compression and torsion were applied to all models. The construct stiffness, symphyseal relative micromotions, and von Mises stress performance were recorded and analyzed. Results The construct stiffness decreased dramatically under PSD conditions. The dual-canScrew (154.3 ± 9.3 N/mm), sub-Plate (147.1 ± 10.2 N/mm), and sub-PedRod (133.8 ± 8.0 N/mm) groups showed better ability to restore intact stability than the other groups (p

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine that presents clinically with abdominal pain, mucopurulent stools, and posterior urgency. The lesions of UC are mainly concentrated in the rectal and colonic mucosa and submucosa. For patients with mild to moderate UC, the best pharmacological treatment includes glucocorticoids, immunosuppressants, antibiotics, and biologics, but the long-term application can have serious toxic side effects. Currently, nearly 40% of UC patients are treated with herbal natural products in combination with traditional medications to reduce the incidence of toxic side effects. Flavonoid herbal natural products are the most widely distributed polyphenols in plants and fruits, which have certain antioxidant and anti-inflammatory activities. Flavonoid herbal natural products have achieved remarkable efficacy in the treatment of UC. The pharmacological mechanisms are related to anti-inflammation, promotion of mucosal healing, maintenance of intestinal immune homeostasis, and regulation of intestinal flora. In this paper, we summarize the flavonoid components of anti-ulcerative colitis and their mechanisms reported in the past 10 years, to provide a basis for rational clinical use and the development of new anti-ulcerative colitis drugs.

Abstract Background Shrimp aquaculture has suffered huge economic losses over the past decade due to the outbreak of acute hepatopancreatic necrosis disease (AHPND), which is mainly caused by the bacteria Vibrio parahaemolyticus (V. parahaemolyticus) with the virulence pVA1 plasmid, which encodes a secretory photorhabdus insect-related (Pir) toxin composed of PirA and PirB proteins. The Pir toxin mainly attacks the hepatopancreas, a major metabolic organ in shrimp, thereby causing necrosis and loss of function. The pandemic of antibiotic-resistant strains makes the impact worse. Methods Mild pyrolysis of a mixture of polysaccharide dextran 70 and the crosslinker 1,8-diaminooctane at 180 ℃ for 3 h to form carbonized nanogels (DAO/DEX-CNGs) through controlled cross-linking and carbonization. The multifunctional therapeutic CNGs inherit nanogel-like structures and functional groups from their precursor molecules. Results DAO/DEX-CNGs manifest broad-spectrum antibacterial activity against Vibrio parahaemolyticus responsible for AHPND and even multiple drug-resistant strains. The polymer-like structures and functional groups on graphitic-carbon within the CNGs exhibit multiple treatment effects, including disruption of bacterial membranes, elevating bacterial oxidative stress, and neutralization of PirAB toxins. The inhibition of Vibrio in the midgut of infected shrimp, protection of hepatopancreas tissue from Pir toxin, and suppressing overstimulation of the immune system in severe V. parahaemolyticus infection, revealing that CNGs can effectively guard shrimp from Vibrio invasion. Moreover, shrimps fed with DAO/DEX-CNGs were carefully examined, such as the expression of the immune-related genes, hepatopancreas biopsy, and intestinal microbiota. Few adverse effects on shrimps were observed. Conclusion Our work proposes brand-new applications of multifunctional carbon-based nanomaterials as efficient anti-Vibrio agents in the aquatic industry that hold great potential as feed additives to reduce antibiotic overuse in aquaculture. Graphical Abstract

Red and blue light illumination has been reported to significantly affect plantlet growth. Potato is an important food and feed crop in the world and potato plantlet cultured in vitro plays an important role in potato production. However, few studies have documented the effects of red and blue light on the growth of potato plantlets revealed at the transcriptome level. The objective of this study was to determine the growth and physiological responses of potato plantlets cultured in vitro under monochromatic red (RR), monochromatic blue (BB) as well as combined red and blue (RB) LEDs using the RNA-Seq technique. In total, 3150 and 814 differentially expressed genes (DEGs) were detected in potato plantlets under RR and BB, respectively, compared to RB (used as control). Compared to the control, the DEGs enriched in “photosynthesis” and “photosynthesis-antenna proteins” metabolic pathways were up-regulated and down-regulated by BB and RR, respectively, which might be responsible for the increases and decreases of maximum quantum yield (Fv/Fm), photochemical quantum yield (ϕPSII), photochemical quenching (qp) and electron transfer rate (ETR) in BB and RR, respectively. Potato plantlets exhibited dwarfed stems and extended leaves under BB, whereas elongated stems and small leaves were induced under RR. These dramatically altered plantlet phenotypes were associated with variable levels of endogenous plant hormones gibberellin (GAs), indoleacetic acid (IAA) and cytokinins (CKs), as assessed in stems and leaves of potato plantlets. In addition, monochromatic red and blue LEDs trigged the opposite expression profiles of DEGs identified in the “plant hormone signal transduction” metabolic pathway, which were closely related to the endogenous plant hormone levels in potato plantlets. Our results provide insights into the responses of potato plantlets cultured in vitro to red and blue LEDs at the transcriptomic level and may contribute to improvements in the micro-propagation of potato plantlets cultured in vitro from the light spectrum aspect.

Abstract Background To evaluate the prognosis of acute cerebral infarction at 1-year follow-up in different circulation infarctions. Methods Clinical data of 858 consecutive patients with acute cerebral infarction were collected. Of the 858 cases, 21 (2.45%) were lost to follow-up and 837 completed follow-up and thus were enrolled in this study. At 1-year follow-up, death or moderate-to-severe dysfunction (modified Rankin Scale (mRS) ≥ 3 points) was regarded as the poor prognostic endpoint. Univariate analysis and multivariate logistic stepwise regression analysis were performed to assess the prognosis. The prediction probability of indicators was obtained for the multivariate model, and the receiver operating characteristic curve was delineated to calculate the area under the curve (AUC) to predict the fitness of the model. Results The older the age, the greater the probability of a poor prognosis. Patients with previous diabetes and cerebral infarction had a poor prognosis. The higher the National Institutes of Health Stroke Scale and mRS scores and the lower the Barthel index at admission, the worse the prognosis of the patients. The longer the hospital stay, the worse the prognosis of the patients. The prognosis of different circulation infarctions was different. The AUC of the multivariate model was AUC = 0.893, and the 95% confidence interval was 0.870–0.913, indicating a good fit. The prognosis of anterior circulation infarction (ACI) was worse than that of posterior circulation infarction (PCI) (P 0.05). Conclusions Diabetes, the Barthel index at admission and previous cerebral infarction are poor prognostic factors of acute cerebral infarction. The prognosis of ACI is worse than that of PCI. Different factors affect the prognosis of different circulatory system infarctions.

ObjectiveGastric-type mucinous carcinoma (GAS), as a rare subtype of mucinous adenocarcinoma, accounts for approximately 1%–3% of cervical adenocarcinoma. It was considered as a new type of cervical mucinous adenocarcinoma by the World Health Organization (WHO) in 2014. GAS represents more aggressive disease than does usual type endocervical adenocarcinoma (UEA).Case reportA case of cervical adenocarcinoma with an abnormal increase of CA199 in a 50-year-old Chinese woman was reported. Our patient presented with abnormal vaginal discharge and combined with elevated Ca199 at the value of 2,729 U/mL. Imaging examinations showed no abnormalities. Diagnostic conical resection suggested cervical adenocarcinoma in situ. Post-operative pathology confirmed mucinous cervical adenocarcinoma (considering gastric type), infiltrating cervical interstitial >2/3, involving the deep myometrium, accompanied by vascular carcinoma infiltration and lymph node metastasis.The patients received an extensive hysterectomy and post-operative adjuvant chemoradiotherapy. The chemotherapy regimen was paclitaxel, combined with platinum. After 20 months of follow-up, the patient showed no signs of recurrence.ConclusionPreoperative diagnosis of cervical adenocarcinoma is insidious and can be easily misdiagnosed. For patients with high preoperative Ca199, the possibility of GAS should be kept open.

BackgroundSublingual immunotherapy (SLIT) has been proved to be an effective and safe treatment for allergic asthma (AS) in children. Nonetheless, several issues regarding SLIT remain to be resolved, including the information about optimal administration timing.MethodsA total of 163 AS children aged 4-13 years were enrolled and randomized into the morning dosing (MD) group and the evening dosing (ED) group. Participants received SLIT with Dermatophagoides farinae drops between 7:00 a. m. and 9:00 a.m. (for the MD group) or between 8:00 p. m. and 10:00 p.m. (for the ED group). The total asthma symptom score (TASS), total asthma medicine score (TAMS), Asthma Control Questionnaire (ACQ), forced expiratory volume in one second (FEV1), FEV1/forced volume vital capacity (FVC), fractional exhaled nitric oxide (FeNO) and adverse events (AEs) were assessed at baseline, 0.5 and 1 year during the 1-year SLIT.ResultsAfter 1 year, 62 patients in the MD group and 63 patients in the ED group completed the entire study. The clinical efficacy, pulmonary function and FeNO in both groups improved significantly at 0.5 and 1 year (p < 0.001). Compared to the MD group, the ED group showed significant lower ACQ score at 0.5 year (p < 0.001) and lower FeNO at 1 year (p < 0.05). No significant difference between two groups was observed in AE rate (p > 0.05). All AEs occurred in the first month, with no systemic AEs reported.Conclusion1-year house dust mite (HDM) SLIT is effective and well-tolerated in AS children regardless of administration time. SLIT dosing in the evening might enhance the asthma control level and reduce FeNO level compared with SLIT dosing in the morning.

Abstract Objective To study the effect of an early childhood education machine on sedation and analgesia in children after cardiothoracic surgery. Methods A prospective randomized controlled study was conducted in a provincial hospital in China. Fifty-two patients (aged from 1 to 5 years) underwent cardiothoracic surgery (including: ventricular septal defect, patent ductus arteriosus, atrial septal defect, pulmonary stenosis, pulmonary sequestration and congenital cystic adenomatoid lung malformation) were divided into the study group (n = 26) and the control group (n = 26). The patients in the study group underwent intervention with an early childhood education machine (uniform type) in addition to routine standard treatment and nursing, while the patients in the control group only received routine standard treatment and nursing. Richmond agitation sedation score (RASS) and face, legs, activity, cry, consolability (FLACC) score of all of the patients were evaluated, and the negative emotions (self-rating anxiety scale (SAS) score and self-rating depression scale (SDS) score) of the parents of the two groups were compared. Results There was no significant difference in the general clinical data between the two groups. The RASS and FLACC scores in the study group were significantly lower than those in the control group, and the SAS and SDS scores of the parents in the study group were significantly lower than those in the control group. Conclusion The application of an early childhood education machine for children after cardiothoracic surgery can effectively reduce postoperative agitation, improve sedation and analgesia of the patients, and ease the pessimistic mood of the patients’ parents.

White spot syndrome virus (WSSV) is a very large dsDNA virus. The accepted shape of the WSSV virion has been as ellipsoidal, with a tail-like extension. However, due to the scarcity of reliable references, the pathogenesis and morphogenesis of WSSV are not well understood. Here, we used transmission electron microscopy (TEM) and cryogenic electron microscopy (Cryo-EM) to address some knowledge gaps. We concluded that mature WSSV virions with a stout oval-like shape do not have tail-like extensions. Furthermore, there were two distinct ends in WSSV nucleocapsids: a portal cap and a closed base. A C14 symmetric structure of the WSSV nucleocapsid was also proposed, according to our Cryo-EM map. Immunoelectron microscopy (IEM) revealed that VP664 proteins, the main components of the 14 assembly units, form a ring-like architecture. Moreover, WSSV nucleocapsids were also observed to undergo unique helical dissociation. Based on these new results, we propose a novel morphogenetic pathway of WSSV.

BackgroundEndolymphatic hydrops (EH) is considered as the pathological correlate of Menière’s disease (MD) and cause of hearing loss. The mechanism of EH, remaining unrevealed, poses challenges for formalized clinical trials.ObjectiveThis study aims to investigate the development of hearing loss, as well as the effect of dehydration treatment on EH animal models.MethodsIn this study, different severity EH animal models were created. The laser Doppler vibrometer (LDV) and auditory brainstem responses (ABR) were used to study the effects of EH and the dehydration effects of mannitol. The LDV was used to measure the vibration of the round window membrane (RWM) reflecting the changes in inner ear impedance. ABR was used to evaluate the hearing changes. Furthermore, tissue section and scanning electron microscopy (SEM) observations were used to analyze the anatomical change to the cochlea and outer hair cells.ResultsThe RWM vibrations decreased with the severity of EH, indicating an increase in the cochlear impedance. The dehydration therapy lowered the impedance to restore acoustic transduction in EH 10- and 20-day animal models. Simultaneously, the ABR thresholds increased in EH models and were restored after dehydration. Moreover, a difference in the hearing was found between ABR and LDV results in severe EH animal models, and the dehydration therapy was less effective, indicating a sensorineural hearing loss (SNHL).ConclusionEndolymphatic hydrops causes hearing loss by increasing the cochlear impedance in all tested groups, and mannitol dehydration is an effective therapy to restore hearing. However, SNHL occurs for the EH 30-day animal models, limiting the effectiveness of dehydration. Our results suggest the use of dehydrating agents in the early stage of EH.

To ensure the safety of the workers in the fire danger of the blind coal roadway and reduce the economic losses caused by fire, the combination method of theoretical analysis and practical experience is used to analyze the cause of blind coal roadway fire and summarize the fire characteristics. This paper expounds the technical measures for emergency firefighting and the safety protection measures for combat personnel on site under three different fire conditions of the blind coal roadway. From the four aspects of living space, air duct protection, real-time monitoring and rescue environment, this paper focuses on the rescue technical measures for the trapped people in the blind coal roadway fire, which provides the reference for fire prevention and control of coal enterprises in China, so as to achieve the maximum control of human casualties and economic losses caused by the fire accident in the blind coal roadway.

Objective To ensure the newly admitted patients with non-COVID-19 infection to be well protected through setting up buffer quarantine area in designated hospitals. Methods For safety of the admission of patients with infectious diseases in Yichang Third People's Hospital, a buffer quarantine area was set up,pathway for outpatient and emergency patients entering management process of diagnosis and treatment was established. Through the outpatient pre-screening and triage, the non-COVID-19 and COVID-19 patients were preliminarily identified. Newly admitted patients with non-coronavirus infectious diseases were managed in separated rooms. Then they were divided into specialized infectious disease areas through a six-day health monitoring and standardized screening. Results The establishment and operation of the buffer quarantine area ensured the regular treatment of patients with other infectious diseases during the COVID-19 pandemic, and prevented cross-infection to medical staff and other patients. At the same time, by buffering and isolating the ward, centralized treatment reduced the investment of human resources and protective materials, which was more conducive to standardized management. Conclusions The setting up of the centralized management of the buffer quarantine area can protect the patients with other infectious diseases and provide them with qualified treatment.

Abstract Background Dentine hypersensitivity (DH) could occur or intensify after non-surgical periodontal therapy because of the exposure of dentine tubules, but currently no gold standard exists to treat DH. It has been demonstrated that nano-sized particles presented potential for dentine tubules blocking and remineralization. This randomized controlled trial aimed to investigate the efficacy of dentifrice containing nano-carbonate apatite (n-CAP) in reducing dentine hypersensitivity (DH) after non-surgical periodontal therapy. Methods 48 periodontitis patients with DH were included in this clinical trial. After non-surgical periodontal therapy, patients included were randomized to test and control group and the respective dentifrices were applied at chairside, after which they were instructed to brush teeth with the allocated dentifrices twice a day at home. Periodontal parameters were recorded at baseline and the last follow-up. DH was measured by air-blast test and recorded by visual analogue scale (VAS) and Schiff sensitivity scale at baseline, after polishing (0 week) and 2/4/6 weeks. Results 45 participants completed the follow-up. Periodontal parameters were improved and comparable between groups. Significant reduction in DH was observed in both groups at all time-points compared to baseline in terms of VAS and Schiff score. The test group achieved significantly greater relief from hypersensitivity compared with the control group after 4-week at-home use (for change of VAS, test group: 2.27 ± 2.47 versus control group: 1.68 ± 2.24, p = 0.036; for change of Schiff, test group: 0.94 ± 0.92 versus control group: 0.61 ± 0.83, p

Light spectrum plays an important role in regulating the growth and development of in vitro cultured potato (Solanum tuberosum L.) plantlets. The status of potato plantlets at the end of in vitro stage influences the minituber production after transplanting. With 100 µmol m−2 s−1 total photosynthetic photon flux density (PPFD), a light spectrum study of 100% red light emitting diodes (LEDs) light spectrum (RR), 100% blue LEDs light spectrum (BB), 65% red+35% blue LEDs light spectrum (RB), and 45% red+35% blue+20% green LEDs light spectrum (RBG) providing illumination at the in vitro cultured stage of potato plantlets for 4 weeks using fluorescent lamp as control (CK) was performed to investigate the effects of LEDs light spectrum on the growth, leaf anatomy, and chloroplast ultrastructure of potato plantlets in vitro as well as the minituber yield after 2 months transplanting in the greenhouse. Compared to CK, RB and RBG promoted the growth of potato plantlets in vitro with increased stem diameter, plantlet fresh weight, plantlet dry weight, and health index. Furthermore, BB induced the greatest stem diameter as well as the highest health index in potato plantlets in vitro. Root activity, soluble protein, and free amino acid were also significantly enhanced by BB, whereas carbohydrates were improved by RR. In addition, thickness of leaf, palisade parenchyma and spongy parenchyma was significantly increased by BB and RBG. Chloroplasts under BB and RBG showed well-developed grana thylakoid and stroma thylakoid. Unexpectedly, distinct upper epidermis with greatest thickness was induced and palisade parenchyma and spongy parenchyma were arranged neatly in RR. After transplanting in the greenhouse for 2 months, potato plantlets in vitro from BB, RB, and RBG produced high percentage of large size tuber. BB improved fresh and dry weights of the biggest tuber but decreased tuber number per plantlet. In addition, RBG increased tuber number as well as tuber fresh and dry weight slightly. Our results suggested monochromatic blue LEDs as well as combined red, blue or/and green LEDs light spectrum were superior to fluorescent lamp spectrum in micropropagation of potato plantlets. Therefore, the application of RBG was suitable; BB and RB could be used as alternatives.

This study is conducted to explore the association between health behaviors and the COVID-19 vaccination based on the risk compensation concept among health-care workers in Taizhou, China. We conducted a self-administered online survey to estimate the health behaviors among the staff in a tertiary hospital in Taizhou, China, from May 18 to 21 May 2021. A total of 592 out of 660 subjects (89.7%) responded to the questionnaire after receiving an e-poster on WeChat. Subjects who had been inoculated with the COVID-19 vaccine were asked to mention the differences in their health behaviors before and after the vaccination. The results showed that there were no statistical differences in health behaviors between vaccinated and unvaccinated groups, except in terms of the type of gloves they used (62.8% in the vaccinated group and 49.2% in the unvaccinated group, p = .048). Subjects who received earlier COVID-19 vaccinations exhibited better health behaviors (22.40% increased for duration of wearing masks (P = .007), 25.40% increased for times of washing hands (P = .01), and 20.90% increased for times of wearing gloves (P = .01)). Subjects also revealed better health behaviors (washing hands, wearing gloves, and wearing masks) after vaccination compared to that before. In conclusion, concept of risk compensation was not applied in our findings. The health behaviors did not reduce after the COVID-19 vaccination, which even may improve health behaviors among health-care workers in the hospital setting.

Acute gastrointestinal illness (AGI) is a prevalent public health concern worldwide. This study investigated the magnitude, distribution and burden of self-reported AGI among residents of Zhejiang Province, China. A face-to-face household survey was conducted using a multi-stage stratified random sampling method in 10 counties in Zhejiang Province between July 2018 and June 2019. In total, 12,021 participants were recruited. The prevalence of AGI 28 days after standardization was 1.8% (95% confidence interval (CI), 1.6-2.1), with an incidence rate of 0.24 episodes of AGI per person-year and an estimated 14 million cases of AGI in Zhejiang Province. Univariate and multivariable analyses showed a higher AGI prevalence among people who performed housework and were unemployed in summer and autumn among respondents living in western or northern cities (p < 0.05). More than 50% of AGI cases were attributed to the consumption of contaminated food. The disease burden caused by AGI in Zhejiang Province was approximately 975 million Chinses yuan (CNY). These results indicated that the disease burden of AGI in Zhejiang Province should be addressed and highlights the need for an improved active surveillance system of foodborne diseases to assess the impact of AGI on society and health.

Abstract Background Endothelial-to-mesenchymal transition (EndoMT) can provide a source of cancer-associated fibroblasts which contribute to desmoplasia of many malignancies including pancreatic ductal adenocarcinoma (PDAC). We investigated the clinical relevance of EndoMT in PDAC, and explored its underlying mechanism and therapeutic implication. Methods Expression levels of 29 long non-coding RNAs were analyzed from the cells undergoing EndoMT, and an EndoMT index was proposed to survey its clinical associations in the PDAC patients of The Cancer Genome Atlas database. The observed clinical correlation was further confirmed by a mouse model inoculated with EndoMT cells-involved PDAC cell grafts. In vitro co-culture with EndoMT cells or treatment with the conditioned medium were performed to explore the underlying mechanism. Because secreted HSP90α was involved, anti-HSP90α antibody was evaluated for its inhibitory efficacy against the EndoMT-involved PDAC tumor. Results A combination of low expressions of LOC340340, LOC101927256, and MNX1-AS1 was used as an EndoMT index. The clinical PDAC tissues with positive EndoMT index were significantly correlated with T4-staging and showed positive for M2-macrophage index. Our mouse model and in vitro cell-culture experiments revealed that HSP90α secreted by EndoMT cells could induce macrophage M2-polarization and more HSP90α secretion to promote PDAC tumor growth. Furthermore, anti-HSP90α antibody showed a potent therapeutic efficacy against the EndoMT and M2-macrophages-involved PDAC tumor growth. Conclusions EndoMT cells can secrete HSP90α to harness HSP90α-overproducing M2-type macrophages to promote PDAC tumor growth, and such effect can be targeted and abolished by anti-HSP90α antibody.

AIM: To investigate the secretion levels of serum tumor markers neuron specific enolase(NSE), glycoprotein antigen CA153 and CA199 in patients with retinoblastoma(RB).METHODS: Data of 42 RB patients who received chemotherapy at Shenzhen People's Hospital between October 2017 and October 2019 were collected. The RB group was regrouped according to early and mid-term/advanced stages, and single/double eye involvement, the levels of serum tumor markers were compared between these subgroups and different genders.RESULTS: The levels of tumor markers NSE, CA153 and CA199 in the advanced group were higher than those in the early and mid-term groups(49.69±18.45ng/mL vs 36.18±14.92ng/mL, 22.38±12.03U/mL vs 15.10±8.32U/mL, 46.44±18.76U/mL vs 30.21±24.03U/mL, P0.05).CONCLUSION: Serum NSE, CA153 and CA199 are significantly increased in advanced group than early and mid-term group, and they are of great significance in the diagnosis and treatment of RB. The difference between NSE in single and double eyes is worthy of further study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or 10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Electrodes with high conductivity and flexibility are crucial to the development of flexible lithium-ion batteries. In this study, three-dimensional (3D) LiFePO4 and Li4Ti5O12 fiber membrane materials were prepared through electrospinning and directly used as self-standing electrodes for lithium-ion batteries. The structure and morphology of the fibers, and the electrochemical performance of the electrodes and the full battery were characterized. The results show that the LiFePO4 and Li4Ti5O12 fiber membrane electrodes exhibit good rate and cycle performance. In particular, the all-fiber-based gel-state battery composed of LiFePO4 and Li4Ti5O12 fiber membrane electrodes can be charged/discharged for 800 cycles at 1C with a retention capacity of more than 100 mAh·g−1 and a coulombic efficiency close to 100%. The good electrochemical performance is attributed to the high electronic and ionic conductivity provided by the 3D network structure of the self-standing electrodes. This design and preparation method for all-fiber-based lithium-ion batteries provides a novel strategy for the development of high-performance flexible batteries.

AIM: To investigate the effect and binocular alignment of unilateral recession-resection(R-R)procedure in patients with insufficient convergence intermittent exotropia(IXT).METHODS: Totally 45 patients with insufficient convergence IXT were operated with unilateral R-R procedure. Binocular alignment was accessed 1d postoperative and 2wk postoperative. Statistical analysis was performed on squint at different time points.RESULTS: All 45 patients with insufficient convergence IXT were operated with unilateral R-R procedure. On the 1st day after surgery, an overcorrection of 8.27±7.17PD at distance and 2.40±8.86PD at near were seen. On the 2wk after surgery. An under correction of 1.18±6.98PD at distance and 4.36±7.83PD at near were seen. Within 2wk after surgery, the average exo-drift at distance was 9.45±6.40PD, and at near was 6.77±7.92PD. There was statistically significant difference between exo-drift at distance and near, and a positive correlation was discovered. The difference of near-distance squint at postoperative(3.18±5.60PD)was significantly lower than that of preoperative(7.65±6.55PD), and there was a positive correlation between them.CONCLUSION: Unilateral R-R procedure is appropriate for patients with insufficient convergence IXT. An appropriate increase of medial rectus strengthening can reduce postoperative near-distance squint difference and does not change the tension of medial rectus and lateral rectus. There was a synchronized exo-drift both at distance and near. The postoperative exo-drift at distance was 10PD and we believe a 10PD overcorrection shortly after operation may be beneficial to the long-term binocular alignment.

White spot syndrome virus (WSSV) has been reported to cause severe economic loss in the shrimp industry. With WSSV being a large virus still under investigation, the 3D structure of its assembly remains unclear. The current study was planned to clarify the 3D structures of WSSV infections in the cell nucleus of red swamp crayfish (Procambarus clarkii). The samples from various tissues were prepared on the seventh day post-infection. The serial sections of the intestinal tissue were obtained for electron tomography after the ultrastructural screening. After 3D reconstruction, the WSSV-associated structures were further visualized, and the expressions of viral proteins were confirmed with immuno-gold labeling. While the pairs of sheet-like structures with unknown functions were observed in the nucleus, the immature virions could be recognized by the core units of nucleocapsids on a piece of the envelope. The maturation of the particle could include the elongation of core units and the filling of empty nucleocapsids with electron-dense materials. Our observations may bring to light a possible order of WSSV maturation in the cell nucleus of the crayfish, while more investigations remain necessary to visualize the detailed viral–host interactions.

Shrimp farming is an important economic activity. However, due to the spread of pathogens, shrimp aquaculture is becoming increasingly difficult. Many studies have confirmed that white spot syndrome virus (WSSV) recombinant proteins can inhibit viral infection. Among them, VP53 recombinant protein has been found to reduce mortality upon WSSV challenge. This study was conducted in Kaohsiung, Taiwan and reports the first field feeding trial to demonstrate that WSSV recombinant proteins can improve shrimp survival rates at a farming scale. Prior to the feeding trial, the shrimp were confirmed to be slightly infected with WSSV, Vibrio parahaemolyticus strains causing acute hepatopancreatic necrosis disease (AHPND), non-AHPND V. parahaemolyticus strains, and Enterocytozoon hepatopenaei (EHP), which are common pathogens that shrimp farmers often face. The shrimp were then divided into two groups: a control group (C group) fed with a commercial diet and a protein group (P group) fed with the same commercial feed with VP53 recombinant protein. Our findings indicated that the survival rate and expression of immune genes of the P group were higher than those of the C group. The intestinal microbiota of the two groups were also analysed. Collectively, our results confirmed that the recombinant WSSV envelope protein derivative can be used as an effective anti-virus biological agent in shrimp farms.

Summary: Specific recording, labeling, and spatiotemporal manipulating neurons are essential for neuroscience research. In this study, we developed a tripartite spatiotemporal gene induction system in C. elegans, which is based on the knockout of two transcriptional terminators (stops in short) by two different recombinases FLP and CRE. The recombinase sites (loxP and FRT) flanked stops after a ubiquitous promoter terminate transcription of target genes. FLP and CRE, induced by two promoters of overlapping expression, remove the stops (subsequent FLP/CRE-out). The system provides an ''AND'' gate strategy for specific gene expression in single types of cell(s). Combined with an inducible promoter or element, the system can control the spatiotemporal expression of genes in defined cell types, especially in cells or tissues lacking a specific promoter. This tripartite FLP/CRE-out gene expression system is a simple, labor- and cost-saving toolbox for cell type-specific and inducible gene expression in C. elegans.

Background: Oral commensals contribute to microbe-host symbiosis in periodontal homeostasis, and Porphyromonas gingivalis (P. gingivalis) as the keystone pathogen critically accounts for the shift of symbiosis to dysbiosis and periodontal destruction. Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome-mediated interleukin-1β (IL-1β) is significantly involved in periodontal diseases, and notably P. gingivalis enables to modulate the induction and expression of NLRP3. Whereas, the exact mechanism by which NLRP3 inflammasome is regulated in response to commensal and pathogenic bacteria remains unclear.Methods: To examine the expression of IL-1β and NLRPs inflammasome in tissues with severe chronic periodontitis, and further investigate how Caspase-4-dependent non-canonical NLRP3 inflammasome pathways functioned during the interactions of Streptococcus mitis (S. mitis) and P. gingivalis with human THP-1 cells.Results: IL-1β and NLRP3, NLRP6, NLRP12, and absent in melanoma 2 (AIM2) inflammasomes are highly expressed in gingival tissues with severe chronic periodontitis. In human THP-1 cells, P. gingivalis activates the synthesis and secretion of IL-1β to higher levels than S. mitis. Importantly, NLRP3-, Caspase-1-, and Caspase-4-siRNA knockdown THP-1 cells treated with P. gingivalis exhibited a lower expression level of IL-1β as compared to the control cells. In addition, silencing of either CASP4 or CASP1 can lead to a concurrent or reciprocal decrease in the expression of the other. Of note, the IL-1β induction is not affected in the S. mitis-treated THP-1 cells with the silence of NLRP3, Caspase-1, and Caspase-4 genes.Conclusion: NLRP3/Caspase-4 and NLRP3/Caspase-1 dependent IL-1β production may crucially contribute to the dysregulated immuno-inflammatory response in periodontal pathogenesis.

Anoplin is an amphipathic, α-helical bioactive peptide from wasp venom. In recent years, pharmaceutical and organic chemists discovered that anoplin and its derivatives showed multiple pharmacological activities in antibacterial, antitumor, antifungal, and antimalarial activities. Owing to the simple and unique structure and diverse biological activities, anoplin has attracted considerable research interests. This review highlights the advances in structural modification, biological activities, and the outlook of anoplin in order to provide a basis for new drug design and delivery.

PurposeTo compare macular choroidal thickness of idiopathic epiretinal membrane (ERM) and fellow eyes, and before and after vitrectomy in terms of the morphological features on spectral-domain optical coherent tomography (SD-OCT).MethodsEighty-four patients with unilateral idiopathic ERM were involved. Patients were categorized into: Group 1, ERM without membrane contraction; Group 2, ERM with membrane contraction and retinal folding; and Group 3, ERM with membrane contraction and macular edema. Twenty-two patients received surgical removal of ERM. Choroidal thickness was compared between ERM and fellow eyes, and before and after treatment.ResultsMean choroidal thickness was significantly greater in ERM eyes than in fellow eyes (234.4 ± 22.5 vs 220.6 ± 20.8 μm; PConclusionsMembrane contraction contributed to the increase in choroidal thickness in idiopathic ERM patients. This finding may help to elucidate the pathophysiologic features of idiopathic ERM as well as the response to treatment in these patients.

Insufficient compactness of rockfill materials may potentially cause excessive deformation of a concrete face rockfill dam (CFRD), thus resulting in cracking of the face slab and leakage of the dam body, thereby requiring reinforcement treatment. To date, there are no effective measures in strengthening rockfill materials. In this study, self-compacting mortar (SCM) was applied to the Shibaozhai CFRD in Gansu Province, China, to test the effectiveness of grouting reinforcement. Simultaneously, an indoor triaxial shear test was conducted to investigate the changes in the mechanical properties of rockfill materials before and after the grouting reinforcement. The on-site test results showed that the rockfill reached the desired porosity after grouting and grouting reinforcement enhanced the cementation degree of rockfill materials while maintaining uninterrupted drainage capacity, which met the requirements of rockfill grouting for the face rockfill dam. The results of the triaxial shear test indicated that the cohesive force of the rockfill materials rose by 3.95 times and the modulus increased by 7.24 times after grouting reinforcement，significantly enhancing the mechanical and deformation properties of the rockfill. An increase in the content of coarse particles was shown to enhance the stability of cementitious structures, which leads to a better skeleton effect and thereby raises the effectiveness of the grouting reinforcement. The rockfill materials also exhibited strain-softening characteristics following the grouting reinforcement. The research showed that grouting reinforcement technology is suitable for managing the deformation of high CFRDs or reinforcing ill rockfill dams.

Abstract Smart structures with manipulatable properties are highly demanded in many fields. However, there is a critical challenge in the pursuit of transparent windows that allow optical waves (wavelength of µm–nm) for transmitting while blocking microwave (wavelength of cm) in terms of absorbing electromagnetic energy, specifically for meeting the frequency requirement for the 5th generation (5G) mobile networks. For fundamentally establishing novel manipulatable microwave absorbing structures, here, new polymeric aqueous gels as both optically transparent materials and microwave absorbing materials are demonstrated, in which polar networks play significant roles in attenuating electromagnetic energy. By manipulating the hydrogen bonding networks, the resulting optically transparent solid‐state gels are able to offer the capabilities for absorbing microwaves. Interestingly, such gels can be switched into an optically opaque state via converting the amorphous state into a polycrystal state when the temperature is decreased. Such ionic conductive gels can endow the assembled sandwich windows with effective microwave absorbing capability in the range of 15–40 GHz, covering a branch of 5G frequency bands. The results highlight a new strategy for using ionic conductive gels to design and fabricate manipulatable microwave stealth structures for various applications.

M2-polarization and the tumoricidal to tumor-promoting transition are commonly observed with tumor-infiltrating macrophages after interplay with cancer cells or/and other stroma cells. Our previous study indicated that macrophage M2-polarization can be induced by extracellular HSP90α (eHSP90α) secreted from endothelial-to-mesenchymal transition-derived cancer-associated fibroblasts. To extend the finding, we herein validated that eHSP90α-induced M2-polarized macrophages exhibited a tumor-promoting activity and the promoted tumor tissues had significant increases in microvascular density but decreases in CD4+ T-cell level. We further investigated the signaling pathways occurring in eHSP90α-stimulated macrophages. When macrophages were exposed to eHSP90α, CD91 and toll-like receptor 4 (TLR4) functioned as the receptor/co-receptor for eHSP90α binding to recruit interleukin (IL)-1 receptor-associated kinases (IRAKs) and myeloid differentiation factor 88 (MyD88), and next elicited a canonical CD91/MyD88–IRAK1/4–IκB kinase α/β (IKKα/β)–nuclear factor-κB (NF-κB)/interferon regulatory factor 3 (IRF3) signaling pathway. Despite TLR4-MyD88 complex-associated activations of IKKα/β, NF-κB and IRF3 being well-known as involved in macrophage M1-activation, our results demonstrated that the CD91-TLR4-MyD88 complex-associated IRAK1/4−IKKα/β−NF-κB/IRF3 pathway was not only directly involved in M2-associated CD163, CD204, and IL-10 gene expressions but also required for downregulation of M1 inflammatory cytokines. Additionally, Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) were recruited onto MyD88 to induce the phosphorylation and activation of the transcription factor signal transducer and activator of transcription-3 (STAT-3). The JAK2/TYK2−STAT-3 signaling is known to associate with tumor promotion. In this study, the MyD88−JAK2/TYK2−STAT-3 pathway was demonstrated to contribute to eHSP90α-induced macrophage M2-polarization by regulating the expressions of M1- and M2-related genes, proangiogenic protein vascular endothelial growth factor, and phagocytosis-interfering factor Sec22b.

Abstract Because of the exclusion for the patients more than 75 years (very elderly patients) in many clinical trials of esophageal cancer (EC), there is no consensus on prognosis and treatment for this population. We aim to evaluate the outcomes and aging‐related prognostic factors of definitive radiotherapy (RT) for very elderly EC patients. We retrospectively analyzed 149 very elderly EC patients consecutively treated between January 2015 and June 2016 by definitive intensity‐modulated radiotherapy (IMRT) with or without chemotherapy. The clinical outcome and toxicities were assessed, and the potential prognostic factors, such as nutritional risk index (NRI) and neutrophil–lymphocyte ratio (NLR), were analyzed statistically. The median follow‐up time for survivors was 22.5 months. The 2‐year overall survival (OS), local–regional failure‐free survival (LRFFS), and distant metastasis‐free survival (DMFS) were 51.6%, 54.7%, and 85.2%, respectively. Independent predictors for poorer OS were higher American Joint Committee on Cancer (AJCC) stage, lower NRI, and higher NLR value before RT. Meanwhile, the total dose (cutoff value 60 Gy) of planning gross tumor volume (PGTV) and chemotherapy was also identified as independent prognostic indicator for LRFFS and DMFS, respectively. 72 patients had treatment failure and 58 (80.6%), 6 (8.3%), and 18 (25.0%) patients had experienced local, regional, and distant failure, respectively. Few severe toxicities were observed. The conservative definitive RT with modern technique was effective for very elderly EC patients in short term with low rate and tolerable toxicities. Local residue or recurrence was the most common failure pattern. The aging‐related prognostic factors concerned nutrition and immune, such as NRI and NLR before RT, should be considered for use in future clinical practice.

The risk factors for symptoms of depression in pregnant women are still unclear. The current crosssectional study examined the mindfulness stress-buffering hypothesis as a possible mediating and moderating mechanism of stress and anxiety. Two hundred and thirty-three women who were pregnant at more than 13 gestational weeks completed questionnaires designed to measure stress, anxiety, and depression. SPSS PROCESS macro 3.5 software was used to test the mediation model, in which anxiety was the moderated mediation model variable, and mindfulness was the moderator variable. The current study found that mindfulness directly, and indirectly via anxiety, moderated the effect of stress on depression, with a threshold of 146.95 and 144.60, respectively. Mindfulness levels above these thresholds reduced the use of labor anesthesia and promoted exclusive breastfeeding. This finding suggests that health professionals should pay attention to the mindfulness learning needs of participants when designing mindfulness programs. Achieving high mindfulness scores will help participants fight stress, lower anxiety, and reduce symptoms of depression. In addition, it can also help women adapt to labor pains and promote exclusive breastfeeding behaviors. [ABSTRACT FROM AUTHOR]

We investigated whether phycoerythrin (PE), a pigment sourced from marine algae, could act as an immunomodulatory agent in whiteleg shrimp (Litopenaeus vannamei). To this end, PE was extracted and purified from a PE-rich macroalgae, Colaconema sp. Our in vitro analysis demonstrated that PE enhanced prophenoloxidase and phagocytosis activity but inhibited the production of reactive oxygen species in hemocytes. Additionally, the PE signal could be detected using an in vivo imaging system after its injection into the ventral sinus of the cephalothorax of whiteleg shrimp. The expression profiles of fourteen immune-related genes were monitored in hemocytes from whiteleg shrimp injected with 0.30 μg of PE per gram of body weight, and crustin, lysozyme, penaiedin 4, and anti-lipopolysaccharide factor showed up-regulated post-stimulation. The induction of immune genes and enhancement of innate immune parameters by PE may explain the higher survival rates for shrimp that received different doses of PE prior to being challenged with Vibrio parahaemolyticus or white spot syndrome virus compared to controls. Combined, these results show that PE from Colaconema sp. can differentially stimulate the immune response of whiteleg shrimp in vitro and in vivo and could potentially be used as an immunomodulator in shrimp culture.

The shrimp aquaculture industry has encountered many diseases that have caused significant losses, with the most serious being white spot syndrome (WSS). Until now, no cures, vaccines, or drugs have been found to counteract the WSS virus (WSSV). The purpose of this study was to develop an oral delivery system to transport recombinant proteinaceous antigens into shrimp. To evaluate the feasibility of the oral delivery system, we used white shrimp as the test species and maggots as protein carriers. The results indicated that the target protein was successfully preserved in the maggot, and the protein was detected in the gastrointestinal tract of the shrimp, showing that this oral delivery system could deliver the target protein to the shrimp intestine, where it was absorbed. In addition, the maggots were found to increase the total haemocyte count and phenoloxidase activity of the shrimp, and feeding shrimp rVP24-fed maggots significantly induced the expression of penaeidins 2. In the WSSV challenge, the survival rate of rVP24-fed maggots was approximately 43%. This study showed that maggots can be used as effective oral delivery systems for aquatic products and may provide a new method for aquatic vaccine delivery systems.

Abstract Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders.