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Abstract Background Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. Methods This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. Results The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn’t affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. Conclusions RFID tag witnessing doesn’t negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist’s confidence.

Objectives: To analyze the methodology, evidence, recommendations, quality, and implementation of traditional Chinese patent medicine (CPM) guidelines. Methods: We retrieved clinical application guidelines of CPM published from 2019 to 2022. Independent screening and data extraction were performed by two evaluators. The basic information about the guidelines, including evidence and recommendations, were extracted and statistically analyzed. Quality and implementation were evaluated using the Implementation Evaluation Tool and Appraisal of Guidelines for Research & Evaluation (AGREE) II. Results: In total, 29 guidelines were analyzed, including 262 recommendations and 2308 references. All the CPM guidelines followed the principle of “evidence as a core, consensus as a supplement, and experience as a reference'' and the methods provided by WHO Handbook. An average of 89 references were cited in each guideline and 8 in each recommendation. Randomized controlled trials and systematic reviews constituted 89 % and 0.9 %, respectively, of all references. Low or very low-quality evidence characterized 74.5 % and weak recommendations characterized 83.6 %. Of all recommendations, 13.7 % were based on expert consensus, and 9.5 % of strong recommendations were based on low or very low-quality evidence. The AGREE II scores for each domain were: scope and purpose (79.63 %) and editorial independence (79.27 %), followed by clarity of presentation (72.59 %), stakeholder involvement (69.99 %), rigor of development (53.97 %) and applicability (5.11 %). The implementation quality of most guidelines was either high (44.8 %) or moderate (55.2 %). Conclusions: The results for CPM guidelines were impressive in terms of methodology, quality, and implementation. However, confidence in CPM recommendations was downgraded by low quality of evidence.

Delirium is an acute, global cognitive disorder syndrome, also known as acute brain syndrome, characterized by disturbance of attention and awareness and fluctuation of symptoms. Its incidence is high among critically ill patients. Once patients develop delirium, it increases the risk of unplanned extubation, prolongs hospital stay, increases the risk of nosocomial infection, post-intensive care syndrome-cognitive impairment, and even death. Therefore, it is of great importance to understand how delirium occurs and to reduce the incidence of delirium in critically ill patients. This paper reviews the potential pathophysiological mechanisms of delirium in critically ill patients, with the aim of better understanding its pathophysiological processes, guiding the formulation of effective prevention and treatment strategies, providing a basis for clinical medication.

Abstract Background The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. Methods R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. Results MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. Conclusion This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.

Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an A5cla cluster from Penicillium sp. MYA5, derived from the Arctic plant Dryas octopetala, is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F (1) and six known clavatols (2–7), were isolated from Penicillium sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds 1–7. Compounds 1 and 2 demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 μM, respectively. Compound 6 exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 4.0 μg/mL and 4.0 μg/mL, respectively. Additionally, compounds 1, 5, and 6 also showed potential iron-binding ability.

Abstract High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2− and triple-negative breast cancer (TNBC). Among HR+HER2− breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2− or TNBC who may not benefit from NACT. HR+HER2− breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A–H (1–8), and two new eudesmane-type sesquiterpenes, eutypellaolides I–J (9–10), along with four known 12,8-eudesmanolide compounds 11–14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 μg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 μM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 μM, respectively.

Sedum jinglanii, a new species of Crassulaceae from Mount Danxia in Guangdong, China, is described and illustrated. Phylogenetic analysis based on the internal transcribed spacer (ITS) region of nrDNA suggests that the new species belongs to S. sect. Sedum sensu Fu and Ohba (2001) in the “Flora of China”, and is sister to a clade comprising S. alfredi and S. emarginatum with high support values (SH-aLRT = 84, UFBS = 95) but is distantly related to S. baileyi. The new species is morphologically similar to S. alfredi but it can be distinguished from the latter in its opposite leaves (vs. alternate leaves), its usually wider leaves (0.4–1.2 cm vs. 0.2–0.6 cm), its usually shorter petals (3.4–4.5 mm vs. 4–6 mm), its shorter nectar scales (0.4–0.5 mm vs. 0.5–1 mm), its shorter carpels (1.5–2.6 mm vs. 4–5 mm), and its shorter styles (0.6–0.9 mm vs. 1–2 mm). The new species can be easily distinguished from S. emarginatum which both have opposite leaves by its short, erect or ascending rhizome (vs. long and prostrate rhizome in the latter), shorter petals (3.4–4.5 mm vs. 6–8 mm) and shorter carpels (1.5–2.6 mm vs. 4–5 mm). It can also be easily distinguished from S. baileyi by its short, erect or ascending rhizome (vs. long and prostrate rhizome) and its shorter style (0.6–0.9 mm vs. 1–1.5 mm).

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3–H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N–O fragment donor.

Summary: Tubulointerstitial abnormalities contribute to the progression of diabetic kidney disease (DKD). However, the underlying mechanism of the pathobiology of tubulointerstitial disease is largely unknown. Here, we showed that MYCT1 expression was downregulated in in vitro and in vivo DKD models. Adeno-associated virus (AAV)-Myct1 significantly attenuated renal dysfunction and tubulointerstitial fibrosis in diabetic db/db mice and downregulated Sp1 transcription and TGF-β1/SMAD3 pathway activation. In human proximal tubular epithelial cells, high glucose-induced high expression of SP1 and TGF-β1/SMAD3 pathway activation as well as overaccumulation of extracellular matrix (ECM) were abrogated by MYCT1 overexpression. Mechanistically, the binding of VDR to the MYCT1 promoter was predicted and confirmed using dual-luciferase reporter and ChIP analysis. VDR transcriptionally upregulates MYCT1. Our data reveal MYCT1 as a new and potential therapeutic target in treating DKD.

AIM:To evaluate the efficacy and safety of femtosecond laser assisted phacoemulsification combined with Ahmed glaucoma drainage valve implantation in the treatment of cataract complicated with refractory glaucoma.METHODS: Retrospective case-control study. From October 2019 to October 2021, 53 cataract patients(53 eyes)with refractory glaucoma were divided into 26 cases(26 eyes)in the femtosecond laser assisted cataract surgery(FLACS)group and 27 cases(27 eyes)in the conventional phacoemulsification surgery(CPCS)group according to their voluntary choice. The two groups underwent FLACS and CPCS combined with Ahmed glaucoma drainage valve implantation separately. The differences of intraoperative phacoemulsification energy(CDE), effective phacoemulsification time(EPT)and the changes of the number of anti glaucoma drugs before and after operation were compared between the two groups, and the effects of improving best corrected visual acuity(BCVA), reducing intraocular pressure, the degree of damage to corneal endothelial cells, the surgical complications and success rate were observed and compared between the two groups in different follow-up periods(1d,1wk, 1 and 3mo).RESULTS: The intraoperative CDE and EPT in FLACS group were significantly lower than those in CPCS group(t=8.50, 5.16; P

Context Obesity, one of the major public health problems worldwide, has attracted increasing attention. Ginsenoside Rb1 is the most abundant active component of Panax ginseng C.A.Mey (Araliaceae) and is reported to have beneficial effects on obesity and diabetes. However, the mechanisms by which Rb1 regulates obesity remain to be explored.Objective This paper intends to further explore the mechanism of Rb1 in regulating obesity.Materials and methods The C57BL/6 obese mice were divided into two groups: the control (CTR) and Rb1. The CTR group [intraperitoneally (ip) administered with saline] and the Rb1 group (ip administered with Rb1, 40 mg/kg/d) were treated daily for four weeks. In vitro, Rb1 (0, 10, 20, 40 μM) was added to differentiated C2C12 cells and Rb1 (0, 20, 40 μM) was added to 3T3-L1 cells. After 24 h, total RNA and protein from C2C12 cells and 3T3-L1 cells were used to detect myostatin (MSTN) and fibronectin type III domain-containing 5 (FNDC5) expression.Results Rb1 reduced the body weight and adipocyte size. Improved glucose tolerance and increased basic metabolic activity were also found in Rb1 treated mice. MSTN was downregulated in differentiated C2C12 cells, 3T3-L1 cells and adipose tissues upon Rb1 treatment. FNDC5 was increased after Rb1 treatment. However, MSTN overexpression attenuated Rb1-mediated decrease accumulation of lipid droplets in differentiated 3T3-L1 adipocytes.Discussion & Conclusions Rb1 may ameliorate obesity in part through the MSTN/FNDC5 signalling pathway. Our results showed that Rb1 can be used as an effective drug in the treatment of human obesity.

Glycocalyx is located outside the vascular endothelial cells playing an important role in vascular homeostasis. However, lacking efficient detection methods is one of the biggest obstacles to study the glycocalyx. In this study, three dehydration methods were used to compare the preservation of HUVEC, aorta and kidney glycocalyx by transmission electron microscope. The chemical pre-fixation was performed by lanthanum nitrate staining, and the mice aorta and renal glycocalyx were prepared by different dehydration methods such as ethanol gradient, acetone gradient and low temperature dehydration. HUVEC glycocalyx was prepared by acetone gradient and low temperature dehydration. Low temperature dehydration method preserves HUVEC and mice aortic glycocalyx completely, which had a certain thickness and presented a needle-like structure. But for mice kidney, the acetone gradient dehydration preparation method could better preserve the glycocalyx integrity than other two methods. In conclusion, low temperature dehydration method is suitable for HUVEC and aortic glycocalyx preservation, acetone gradient dehydration method is more suitable for kidney glycocalyx preservation.

An aryl iodide catalyzed intramolecular oxidative transformation of diphenylpropanamide derivatives is described that can readily afford the C–N/C–O coupling products in a single step. The speed of the 1,3-aryl iodide migration process determines the diversity of target compound generation in this reaction. This straightforward approach can be performed with the use of inexpensive and readily available catalyst, transition-metal-free, mild conditions and good functional group tolerance.

Pulmonary hypertension (PH) is featured by pulmonary vascular and cardiac remodeling. Rehabilitation exercise can improve patients’ quality of life. We previously pinpointed a potential glutamine metabolism dysfunction in PH. Hence, we aim to investigate whether rehabilitation exercise could mitigate right ventricular and pulmonary vascular remodeling and its effect on glutaminase (GLS). We collected clinical indicators of PH patients and analyzed their correlation with GLS. Rehabilitation exercise (moderate intensity swimming exercise) was performed in monocrotaline-induced PH (MCT-PH) rats. We found that plasma GLS1 level in patients was lower than healthy subjects, and it was negatively correlated with end-systolic stage eccentricity index, right atrial transverse dimension and right atrial longitudinal dimension. MCT-PH rats displayed pulmonary vascular remodeling and right ventricular hypertrophy. Compared to control rats, higher levels of GLS1 and GLS2 mRNA in lung and lower levels of these two isoforms of GLS in right ventricle (RV) were displayed in MCT-PH rats. After swimming exercise, GLS mRNA levels in the lung and RV were significantly upregulated, and the cross-sectional area of right ventricular cardiomyocytes was significantly decreased although the percentage of pulmonary arteriolar medial wall thickness was not significantly changed. Therefore, we hold the opinion that plasma GLS1 level was decreased in PH. The transcriptional levels of GLS1 and GLS2 were increased in the lung tissues in PH, but were decreased in the RV tissues. Meanwhile, the changes of GLS levels indicated the pulmonary vascular and right ventricular remodeling. Whereas moderate intensity swimming exercise might improve the right ventricular remodeling by regulating the levels of GLS.

The large population movement during the Spring Festival travel in China can considerably accelerate the spread of epidemics, especially after the relaxation of strict control measures against COVID-19. This study aims to assess the impact of population migration in Spring Festival holiday on epidemic spread under different scenarios. Using inter-city population movement data, we construct the population flow network during the non-holiday time as well as the Spring Festival holiday. We build a large-scale metapopulation model to simulate the epidemic spread among 371 Chinese cities. We analyze the impact of Spring Festival travel on the peak timing and peak magnitude nationally and in each city. Assuming an R0 (basic reproduction number) of 15 and the initial conditions as the reported COVID-19 infections on 17 December 2022, model simulations indicate that the Spring Festival travel can substantially increase the national peak magnitude of infection. The infection peaks arrive at most cities 1–4 days earlier as compared to those of the non-holiday time. While peak infections in certain large cities, such as Beijing and Shanghai, are decreased due to the massive migration of people to smaller cities during the pre-Spring Festival period, peak infections increase significantly in small- or medium-sized cities. For a less transmissible disease (R0 = 5), infection peaks in large cities are delayed until after the Spring Festival. Small- or medium-sized cities may experience a larger infection due to the large-scale population migration from metropolitan areas. The increased disease burden may impose considerable strain on the healthcare systems in these resource-limited areas. For a less transmissible disease, particular attention needs to be paid to outbreaks in large cities when people resume work after holidays.

Rhizosphere microbial communities play important roles in facilitating or inhibiting the establishment of exotic species. Since some invasive plants interact with soil microbial communities such as rhizosphere bacteria, changes triggered by rhizosphere bacteria may alter competitive interactions between exotic and native plants. This study compared the Bacillus cereus content in soils with different degrees of Ageratina adenophora invasion, and investigated the effects of A. adenophora allelochemicals on B. cereus growth and soil characteristics and the feedback effects of B. cereus on A. adenophora growth. Bacillus cereus content in the rhizosphere of A. adenophora increased with intensification of the invasion process, and newly invaded soil contained almost twice as much bacteria as noninvaded soil. When rhizosphere soil was added to the root exudates of A. adenophora, the contents of B. cereus were twice as much as the control, except on the first day. Certain soil parameters increased significantly, such as ammonium nitrogen (NH4+-N) and available phosphorus (AP), which were increased by 41 and 27%, respectively. Soil treatment with B. cereus promoted the degradation of two allelochemicals from the rhizosphere of A. adenophora, amorpha-4,7(11)-dien-8-one and 6-hydroxy-5-isopropy1-3,8-dimethyl-4a,5,6,7,8,8a-hexahydraphthalen-2(1H)-one, to varying degrees; and increased the germination rate by 50%, root length by 117%, shoot length by 48% and fresh weight by 81% for A. adenophora compared to those of untreated soil. Our results confirmed that the invasion of A. adenophora will promote an increase of B. cereus, a beneficial rhizosphere bacterium, which in turn induces a positive feedback effect on A. adenophora.

Adjuvants are used to increase the strength, quality, and duration of the immune response of vaccines. Neutrophils are the first immune cells that arrive at the injection site and can release DNA fibers together with granular proteins, so-called neutrophil extracellular traps (NETs), to entrap microbes in a sticky matrix of extracellular chromatin and microbicidal agents. Similar extracellular structures were also released by macrophages, mast cells, and eosinophils and are now generalized as “ETs.” Here we demonstrated that Alum adjuvant stimulation led to peritoneal cells swarming and ET release in vitro. Moreover, compared to antigen stimulation alone, ET release was significantly increased after stimulation with antigen-mixed adjuvants and in a time- and dose-dependent manner. In vivo, we were able to monitor and quantify the continuous changes of the ET release in the same fish by using the small animal in vivo imaging instrument at different times during the early stages after intraperitoneal immunization. The results showed that the fluorescence signal of ETs in the peritoneum increased from 0 to 12 h after injection and then gradually decreased. The fluorescence signals came from extracellular DNA fibers, which are sensitive to DNase I and confirmed by microscopy of peritoneal fluid ex vivo. In summary, this study introduced a new method for detecting ETs in the peritoneum of fish in vivo and indicated that ET formation is involved in the immune response at the early stage after intraperitoneal immunization to vaccines.

The Three Gorges Project (TGP) has changed the flow-sediment process in the middle Yangtze River. For navigation purposes, there is an urgent need to study the changes of the river regime over a long-term period and the shoal-channel evolution over different seasons since the completion of the TGP. Based on analysis of the measured data and the results of a two-dimensional mathematical model, the changes of the river regime and river bed evolution in the Yaojian reach downstream of the TGP were studied. Results show that a high sediment transport flux helps to keep the main flow in the North Branch, while a low sediment transport flux helps to keep the main flow in the South Branch. Thus, the main branch will not change in the near future because of the low sediment transport load. In this study, the flow-sediment process adjusted by the TGP was restored to the conditions before the TGP, and the river bed evolution under the adjusted and non-adjusted flow-sediment conditions was calculated. After the completion of the TGP, the reservoir storage accelerated the flood recession process and decreased the erosion by 11.9% under the flow-sediment conditions in 2010, and the deposition in the flood season decreased by 56.4%.

The objective of the study was to assess the association between changes in plasma follicle-stimulating hormone (FSH) and the potential effect on idiopathic pulmonary arterial hypertension (IPAH) in male patients. A total of 116 male patients with IPAH and 53 healthy controls were included from XX Hospital. Plasma FSH concentration was assessed in all participants. Receiver operating characteristic curves were used to assess the mortality risk. Kaplan–Meier curve and Cox regression analyses were used to predict the value of FSH on the survival rate of male IPAH patients. The plasma FSH concentration in the IPAH group was significantly higher than that in the control group ( p = .017). Nonsurvivors had significantly higher levels of FSH than survivors ( p < .0001). FSH levels were positively correlated with World Health Organization Functional Class, mean pulmonary artery pressure, and pulmonary vascular resistance (PVR; p = .023, p < .0001, and p < .0001, respectively) and negatively correlated with 6-min walk distance (6MWD) and cardiac output (CO; p = .004 and p = .010). Cox regression model analysis showed that the levels of FSH were also the independent factors of mortality in male IPAH patients ( p < .0001). The IPAH patients with higher FSH levels had higher PVR, lower 6MWD, CO, and a lower survival rate ( p = .042, p = .003, p = .029, and p < .0001, respectively). Therefore, we identified that increased FSH levels were associated with disease severity in male patients with IPAH and independently predicted risk of disease and poor survival rate.

A cascade 6-endo-dig cyclization reaction was developed for the switchable synthesis of halogen and non-halogen-functionalized pyrazolo[3,4-b]pyridines from 5-aminopyrazoles and alkynyl aldehydes via C≡C bond activation with silver, iodine, or NBS. In addition to its wide substrate scope, the reaction showed good functional group tolerance as well as excellent regional selectivity. This new protocol manipulated three natural products, and the arylation, alkynylation, alkenylation, and selenization of iodine-functionalized products. These reactions demonstrated the potential applications of this new method.

Objective To determine if plasma exosomal microRNAs (miRNAs) can predict survival in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods The study enrolled patients with IPAH that underwent right heart catheterization. Plasma was collected and exosomal miRNAs were extracted. Exosomes were evaluated using transmission electron microscopy, Western blot analysis and particle size distribution analysis. MiRNAs were evaluated using a miRNA microarray and validated using real-time polymerase chain reaction. Results This study included 12 patients with IPAH in the study group and 48 patients with IPAH in the validation group. The mean ± SD follow-up duration was 60.3 ± 35.4 months in the overall cohort. The levels of miR-596 were higher in the nonsurvivors compared with the survivors. The levels of miR-596 significantly correlated with survival time, mean right atrial pressure, pulmonary vascular resistance (PVR) and cardiac index. High levels of miR-596 and PVR were significantly associated with poor overall survival. Multivariate analysis demonstrated that exosomal miR-596 (hazard ratio [HR] = 2.119; 95% confidence interval [CI] 1.402, 3.203) and PVR (HR = 1.146; 95% CI 1.010, 1.300) were independent predictors of survival. Conclusions High levels of plasma exosomal miR-596 were significantly associated with disease severity and poor prognosis of patients with IPAH.

MYCT1, a target of c-Myc, inhibits laryngeal cancer cell migration, but the underlying mechanism remains unclear. In the study, we detected differentially expressed genes (DEGs) from laryngeal cancer cells transfected by MYCT1 using RNA-seq (GSE123275). DEGs from head and neck squamous cell carcinoma (HNSCC) were first screened by comparison of transcription data from the Gene Expression Omnibus (GSE6631) and the Cancer Genome Atlas (TCGA) datasets using weighted gene co-expression network analysis (WGCNA). GO and KEGG pathway analysis explained the functions of the DEGs. The DEGs overlapped between GSE6631and TCGA datasets were then compared with ours to find the key DEGs downstream of MYCT1 related to the adhesion and migration of laryngeal cancer cells. qRT-PCR and Western blot were applied to validate gene expression at mRNA and protein levels, respectively. Finally, the cell adhesion, migration, and wound healing assays were to check cell adhesion and migration abilities, respectively. As results, 39 overlapping genes were enriched in the GSE6631 and TCGA datasets, and most of them revealed adhesion function. Thirteen of 39 genes including COL6 members COL6A1, COL6A2, and COL6A3 were overlapped in GSE6631, TCGA, and GSE123275 datasets. Similar to our RNA-seq results, we confirmed that COL6 is a target of MYCT1 in laryngeal cancer cells. We also found that MYCT1 inhibited the adhesion and migration of laryngeal cancer cells via COL6. These indicate that COL6 is a potential target of MYCT1 and participates the adhesion and migration of laryngeal cancer cells, which provides an important clue for further study on how MYCT1 regulating COL6 in laryngeal cancer progression.

Translocation and assembly module (TAM) is a protein channel known to mediate the secretion of virulence factors during pathogen infection. Edwardsiella tarda is a Gram-negative bacterium that is pathogenic to a wide range of farmed fish and other hosts including humans. In this study, we examined the function of the two components of the TAM, TamA and TamB, of E. tarda (named tamAEt and tamBEt, respectively). TamAEt was found to localize on the surface of E. tarda and be recognizable by TamAEt antibody. Compared to the wild type, the tamA and tamB knockouts, TX01ΔtamA and TX01ΔtamB, respectively, were significantly reduced in motility, flagella formation, invasion into host cells, intracellular replication, dissemination in host tissues, and inducing host mortality. The lost virulence capacities of TX01ΔtamA and TX01ΔtamB were restored by complementation with the tamAEt and tamBEt genes, respectively. Furthermore, TX01ΔtamA and TX01ΔtamB were significantly impaired in the ability to survive under low pH and oxidizing conditions, and were unable to maintain their internal pH balance and cellular structures in acidic environments, which led to increased susceptibility to lysozyme destruction. Taken together, these results indicate that TamAEt and TamBEt are essential for the virulence of E. tarda and required for E. tarda to survive under stress conditions.

Abstract Bat virus host shifts can result in the spread of diseases with significant effects. The rabies virus (RABV) is able to infect almost all mammals and is therefore a useful model for the study of host shift mechanisms. Carnivore RABVs originated from two historical host shifts from bat viruses. To reveal the genetic pathways by which bat RABVs changed their host tropism from bats to carnivores, we investigated the second permanent bat-to-carnivore shift resulting in two carnivore variants, known as raccoon RABV (RRV) and south-central skunk RABV (SCSKV). We found that their glycoprotein (G) genes are the result of recombination between an American bat virus and a carnivore virus. This recombination allowed the bat RABV to acquire the head of the G-protein ectodomain of the carnivore virus. This region is involved in receptor recognition and binding, response to changes in the pH microenvironment, trimerization of G proteins, and cell-to-cell transmission during the viral infection. Therefore, this recombination event may have significantly improved the variant’s adaptability to carnivores, altering its host tropism and thus leading to large-scale epidemics in striped skunk and raccoon.

Extracellular enzymes, initiating the degradation of organic macromolecules, are important functional components of marine ecosystems. Measuring in situ seawater extracellular enzyme activity (EEA) can provide fundamental information for understanding the biogeochemical cycling of organic matter in the ocean. Here we investigate the patterns of EEA and the major factors affecting the seawater EEA of Chinese marginal seas. The geographic distribution of EEA along a latitudinal transect was examined and found to be associated with dissolved organic carbon. Compared with offshore waters, inshore waters had higher enzyme activity. All the tested substrates were hydrolyzed at different rates and phosphatase, β-glucosidase and protease contributed greatly to summed hydrolysis rates. For any particular enzyme activity, the contribution of dissolved to total EEA was strongly heterogenous between stations. Comparisons of hydrolysis rates of the polymers and their corresponding oligomers suggest that molecule size does not necessarily limit the turnover of marine organic matter. In addition, several typical enzyme-producing clades, such as Bacteroidetes, Planctomycetes, Chloroflexi, Roseobacter, Alteromonas, and Pseudoalteromonas, were detected in the in situ environments. These enzyme-producing clades may be responsible for the production of different enzymes. Overall, each enzyme was found to flexibly respond to environmental conditions and were linked to microbial community composition. It is likely that this activity will profoundly affect organic matter cycling in the Chinese marginal seas.

[This corrects the article DOI: 10.1371/journal.pone.0098047.].

In view of the anatomical and physiological barrier of the ocular surface and the intraocular structure, the conventional ophthalmic agents cannot efficiently reach the lesion site. Currently, the different types of nanomaterials possess great advantages in delivering drugs due to their characteristics of small size, easy preparation, degradability, strong targeting and less irritation to biological tissue. As drug delivery carriers, nanomaterials have been widely used in ocular drug delivery so as to treat different types of eye diseases. In this paper, the applications of nanomaterials as drug delivery carriers in treating eye diseases are briefly reviewed.

In the Formosa cold seep of the South China Sea (SCS), large amounts of methane and sulfide hydrogen are released from the subseafloor. In this study, we systematically investigated the microbial communities in the seawater–sediment interface of Formosa cold seep using high-throughput sequencing techniques including amplicon sequencing based on next-generation sequencing and Pacbio amplicon sequencing platforms, and metagenomics. We found that Sulfurovum dominated the microbial communities in the sediment–seawater interface, including the seawater close to the seepage, the surface sediments, and the gills of the dominant animal inhabitant (Shinkaia crosnieri). A nearly complete 16S rRNA gene sequence of the dominant operational taxonomic units (OTUs) was obtained from the Pacbio sequencing platforms and classified as OTU-L1, which belonged to Sulfurovum. This OTU was potentially novel as it shared relatively low similarity percentages (Sulfurovum was assembled using the binning technique based on metagenomic data. Genome analysis suggested that Sulfurovum sp. in this region may fix carbon by the reductive tricarboxylic acid (rTCA) pathway, obtain energy by oxidizing reduced sulfur through sulfur oxidizing (Sox) pathway, and utilize nitrate as electron acceptors. These results demonstrated that Sulfurovum probably plays an important role in the carbon, sulfur, and nitrogen cycles of the Formosa cold seep of the SCS. This study improves our understanding of the diversity, distribution, and function of sulfur-oxidizing bacteria in deep-sea cold seep.

Seven inorganic amendment materials were added into arsenic (As) contaminated soil at a rate of 0.5% (w/w); the materials used were sepiolite, red mud, iron grit, phosphogypsum, ferrihydrite, iron phosphate, and layered double oxides (LDO). Plant growth trials using rape (edible rape, Brassia campestris L.) as a bio-indicator are commonly used to assess As bioavailability in soils. In this study, B. campestris was grown in a contaminated soil for 50 days. All of the inorganic amendments significantly inhibited the uptake of As by B. campestris. Following soil treatment with the seven aforementioned inorganic ammendments, the As concentrations in the edible parts of B. campestris were reduced by 28.6, 10.5, 8.7, 31.0, 47.4, 25.3, and 28.8%, respectively, as compared with the plants grown in control soil. The most effective amendment was ferrihydrite, which reduced As concentration in B. campestris from 1.84 to 0.97 mg kg−1, compared to control. Furthermore, ferrihydrite-treated soils had a remarkable decrease in both non-specifically sorbed As and available-As by 67 and 20%, respectively, comparing to control. Phosphogypsum was the most cost-effective amendment and it showed excellent performance in reducing the water soluble As in soils by 31% and inhibiting As uptake in B. campestris by 21% comparing to control. Additionally, obvious differences in As transfer rates were observed in the various amendments. The seven amendment materials used in this study all showed potential reduction of As bioavailability and influence on plant growth and other biological processes still need to be further explored in the long term.

Pseudomonas fluorescens is a common bacterial pathogen to a wide range of aquaculture animals including various species of fish. In this study, we employed proteomic analysis and identified filamentous hemagglutinin (FHA) as an iron-responsive protein secreted by TSS, a pathogenic P. fluorescens isolate. In vitro study showed that compared to the wild type, the fha mutant TSSfha (i) exhibited a largely similar vegetative growth profile but significantly retarded in the ability of biofilm growth and producing extracellular matrix, (ii) displayed no apparent flagella and motility, (iii) was defective in the attachment to host cells and unable to form self-aggregation, (iv) displayed markedly reduced capacity of hemagglutination and surviving in host serum. In vivo infection analysis revealed that TSSfha was significantly attenuated in the ability of dissemination in fish tissues and inducing host mortality, and that antibody blocking of the natural FHA produced by the wild type TSS impaired the infectivity of the pathogen. Furthermore, when introduced into turbot as a subunit vaccine, recombinant FHA elicited a significant protection against lethal TSS challenge. Taken together, these results indicate for the first time that P. fluorescens FHA is a key virulence factor essential to multiple biological processes associated with pathogenicity.

Bactericidal/permeability-increasing protein (BPI) is an important factor of innate immunity that in mammals is known to take part in the clearance of invading Gram-negative bacteria. In teleost, the function of BPI is unknown. In the present work, we studied the function of tongue sole (Cynoglossus semilaevis) BPI, CsBPI. We found that CsBPI was produced extracellularly by peripheral blood leukocytes (PBL). Recombinant CsBPI (rCsBPI) was able to bind to a number of Gram-negative bacteria but not Gram-positive bacteria. Binding to bacteria led to bacterial death through membrane permeabilization and structural destruction, and the bound bacteria were more readily taken up by PBL. In vivo, rCsBPI augmented the expression of a wide arrange of genes involved in antibacterial and antiviral immunity. Furthermore, rCsBPI enhanced the resistance of tongue sole against bacterial as well as viral infection. These results indicate for the first time that a teleost BPI possesses immunoregulatory effect and plays a significant role in antibacterial and antiviral defense.

BACKGROUND: In the clinic, variations in circadian rhythm are evident in patients with cardiovascular disease, and the risk of cardiovascular events increases when rhythms are disrupted. In this study, we focused on the role of the circadian gene period2 (per2) in mobilization and function of endothelial progenitor cells (EPCs) in vitro and in vivo after myocardial infarction (MI) in mice. METHODS AND RESULTS: MI was produced by surgical ligation of the left anterior descending coronary artery in mice with and without per2 deficiency. Trans-thoracic echocardiography was used to evaluate cardiac function in mice. Per2-/- mice with MI showed decreased cardiac function and increased infarct size. The number of CD34+ cells and capillary density were decreased in the myocardium of per2-/- mice on immunohistochemistry. Flow cytometry revealed decreased number of circulating EPCs in per2-/- mice after MI. In vitro, per2-/- EPCs showed decreased migration and tube formation capacity under hypoxia. Western blot analysis revealed inhibited activation of extracellular signal-regulated kinase and Akt signaling in the bone marrow of per2-/- mice and inhibited PI3K/Akt expression in per2-/- EPCs under hypoxia. CONCLUSIONS: Per2 modulates EPC mobilization and function after MI, which is important to recovery after MI in mice.

BACKGROUND:It has been demonstrated that Tongxinluo (TXL), a traditional Chinese medicine compound, improves ischemic heart disease in animal models via vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). The present study aimed to investigate whether TXL protects against pressure overload-induced heart failure in mice and explore the possible mechanism of action. METHODS AND RESULTS:Transverse aortic constriction (TAC) surgery was performed in mice to induce heart failure. Cardiac function was evaluated by echocardiography. Myocardial pathology was detected using hematoxylin and eosin or Masson trichrome staining. We investigated cardiomyocyte ultrastructure using transmission electron microscopy. Angiogenesis and oxidative stress levels were determined using CD31 and 8-hydroxydeoxyguanosine immunostaining and malondialdehyde assay, respectively. Fetal gene expression was measured using real-time PCR. Protein expression of VEGF, phosphorylated (p)-VEGF receptor 2 (VEGFR2), p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p-eNOS, heme oxygenase-1 (HO-1), and NADPH oxidase 4 (Nox4) were measured with western blotting. Twelve-week low- and high-dose TXL treatment following TAC improved cardiac systolic and diastolic function and ameliorated left ventricular hypertrophy, fibrosis, and myocardial ultrastructure derangement. Importantly, TXL increased myocardial capillary density significantly and attenuated oxidative stress injury in failing hearts. Moreover, TXL upregulated cardiac nitrite content and the protein expression of VEGF, p-VEGFR2, p-PI3K, p-Akt, p-eNOS, and HO-1, but decreased Nox4 expression in mouse heart following TAC. CONCLUSION:Our findings indicate that TXL protects against pressure overload-induced heart failure in mice. Activation of the VEGF/Akt/eNOS signaling pathway might be involved in TXL improvement of the failing heart.