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Abstract Meniscus‐derived stem cells (MeSCs) are a potential cell source for meniscus tissue engineering. The stark morphological and structural changes of meniscus tissue during development indicate the complexity of MeSCs at different tissue regions and stages of development. In this study, we characterized and compared postnatal rat meniscus tissue and MeSCs at different tissue regions and stages of development. We observed that the rat meniscus tissue exhibited marked changes in tissue morphology during development, with day 7 being the most representative time point of different developmental stages. All rat MeSCs displayed typical stem cell characteristics. Rat MeSCs derived from day 7 inner meniscus tissue exhibited the highest self‐renewal capacity, cell proliferation, differentiation potential toward various mesenchymal lineage and the highest expression levels of chondrogenic genes and proteins. Transplantation of rat MeSCs derived from day 7 inner meniscus tissue promoted neo‐tissue formation and effectively protected joint surface cartilage in vivo. Our results demonstrated for the first time that rat MeSCs are not necessarily better at earlier developmental stages, and that rat MeSCs derived from day 7 inner meniscus tissue may be a superior cell source for effective meniscus regeneration and articular cartilage protection. This information could make a significant contribution to human meniscus tissue engineering in the future. Stem Cells Translational Medicine 2019;8:1318&1329

Abstract We describe a patient with Castleman's disease with TAFRO syndrome and concurrent Sjögren's syndrome and investigate whether the autoimmune process may have accelerated the onset of her Castleman's disease. Patient was treated with R‐CVP therapy with remission of symptoms although there is no current standard treatment.

Metabolic engineering of cyanobacteria has received much attention as a sustainable strategy to convert CO2 to various longer carbon chain fuels. Pinene has become increasingly attractive since pinene dimers contain high volumetric energy and have been proposed to act as potential aircraft fuels. However, cyanobacteria cannot directly convert geranyl pyrophosphate into pinene due to the lack of endogenous pinene synthase. Herein, we integrated the gene encoding Abies grandis pinene synthase into the model cyanobacterium Synechococcus sp. PCC 7002 through homologous recombination. The genetically modified cyanobacteria achieved a pinene titer of 1.525 ± 0.l45 mg L−1 in the lab-scale tube photobioreactor with CO2 aeration. Specifically, the results showed a mixture of α- and β-pinene (∼33:67 ratio). The ratio of β-pinene in the product was significantly increased compared with that previously reported in the engineered Escherichia coli. Furthermore, we investigated the photoautotrophic growth performances of Synechococcus overlaid with different concentrations of dodecane. The work demonstrates that the engineered Synechococcus is a suitable potential platform for β-pinene production.

ABSTRACT Biological nitrogen fixation is an energy-intensive process that contributes significantly toward supporting life on this planet. Among nitrogen-fixing organisms, cyanobacteria remain unrivaled in their ability to fuel the energetically expensive nitrogenase reaction with photosynthetically harnessed solar energy. In heterocystous cyanobacteria, light-driven, photosystem I (PSI)-mediated ATP synthesis plays a key role in propelling the nitrogenase reaction. Efficient light transfer to the photosystems relies on phycobilisomes (PBS), the major antenna protein complexes. PBS undergo degradation as a natural response to nitrogen starvation. Upon nitrogen availability, these proteins are resynthesized back to normal levels in vegetative cells, but their occurrence and function in heterocysts remain inconclusive. Anabaena 33047 is a heterocystous cyanobacterium that thrives under high light, harbors larger amounts of PBS in its heterocysts, and fixes nitrogen at higher rates compared to other heterocystous cyanobacteria. To assess the relationship between PBS in heterocysts and nitrogenase function, we engineered a strain that retains large amounts of the antenna proteins in its heterocysts. Intriguingly, under high light intensities, the engineered strain exhibited unusually high rates of nitrogenase activity compared to the wild type. Spectroscopic analysis revealed altered PSI kinetics in the mutant with increased cyclic electron flow around PSI, a route that contributes to ATP generation and nitrogenase activity in heterocysts. Retaining higher levels of PBS in heterocysts appears to be an effective strategy to enhance nitrogenase function in cyanobacteria that are equipped with the machinery to operate under high light intensities. IMPORTANCE The function of phycobilisomes, the large antenna protein complexes in heterocysts has long been debated. This study provides direct evidence of the involvement of these proteins in supporting nitrogenase activity in Anabaena 33047, a heterocystous cyanobacterium that has an affinity for high light intensities. This strain was previously known to be recalcitrant to genetic manipulation and, hence, despite its many appealing traits, remained largely unexplored. We developed a genetic modification system for this strain and generated a ΔnblA mutant that exhibited resistance to phycobilisome degradation upon nitrogen starvation. Physiological characterization of the strain indicated that PBS degradation is not essential for acclimation to nitrogen deficiency and retention of PBS is advantageous for nitrogenase function.

Programmed cell death ligand 1 (PD-L1) is widely expressed in a variety of human tumors, and inhibition of the PD-L1/PD-1 pathway represents one of the most promising therapy for many types of cancer. However, the physiological function of PD-L1 in tissue development is still unclear, although PD-L1 mRNA is abundant in many tissues. To address this puzzle, we investigated the function of PD-L1 in mammary gland development. Interestingly, we found that PD-L1 is enriched in protein C receptor (Procr)-expressing mammary stem cells (MaSCs), and PD-L1-expressing mammary basal cells (PD-L1+ basal cells) exhibit robust mammary regeneration capacity in transplantation assay. The lineage tracing experiment showed that PD-L1+ cells can differentiate into all lineages of mammary epithelium cells, suggesting that PD-L1+ basal cells have the activities of MaSCs. Furthermore, PD-L1 deficiency significantly impairs mammary development and reduces mammary regeneration capacity of mammary basal cells, suggesting that PD-L1 is not only enriched in MaSCs but also improves activities of MaSCs. In summary, these results demonstrated that PD-L1 is enriched in MaSCs and promotes mammary gland development and regeneration. Mechanistically, our data indicated that PD-L1 expression is induced by continuous activation of Wnt/ß-catenin signaling. In conclusion, these results demonstrated that PD-L1 is a marker of MaSCs, and PD-L1 is essential for mammary development. Our study provides novel insight into the physiological functions of PD-L1 in tissue development.

Aedes aegypti

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune diseases of the connective tissues, characteristic of the presentation of keratoconjunctivitis sicca and xerostomia. A cardinal pathogenetic feature of SS is B-cell hyperactivity, which has invited efforts on optimal B-cell targeted therapy, whereas conventional corticosteroids and disease-modifying antirheumatic drugs (DMARDs) are restricted to symptomatic relief. As per the first EULAR recommendation for pSS patients published in 2020, regimens with monoclonal antibodies targeting B cells may be initiated in patients with severe, refractory systemic disease, notably rituximab (RTX), a mouse-derived monoclonal antibody that targets CD20 antigen and contributes to B-cell depletion. Nonetheless, the data available from clinical trials with RTX are often controversial. Despite the lack of promising results from two large RCTs, several positive clinical efficacies were demonstrated. This current review addressed the efficacy and safety of clinical trials available and elucidated the potential of RTX on the immune system, especially B and T cells. Furthermore, plausible explanations for the discrepancy in clinical data were also presented.

Non-essential proteins for viral replication affect host cell metabolism, while the function of the UL43 protein of herpes simplex virus 1 (HSV-1) is not clear. Herein, we performed a comprehensive microarray analysis of HUVEC cells infected with HSV-1 and its UL43-deficient mutant and found significant variation in genes associated with cellular energy metabolic pathways. The localization of UL43 protein in host cells and how it affects cellular energy metabolism pathways were further investigated. Internalization analysis showed that the UL43 protein could be endocytosis-mediated by YPLF motif (aa144–147) and localized to mitochondria. At the same time, more ATP was produced by coupling with mitochondrial small G protein ARF-like 2 (ARL2) GTPase, which triggered the phosphorylation of ANT1 (SLC25A4) to affect the opening degree of mitochondrial permeability transition pore (mPTP), and significantly promoted the aerobic oxidation and oxidative phosphorylation of glucose. Our study shows that UL43 mediates the improvement of host cell metabolism after HSV-1 infection. Additionally, UL43 protein could be a valuable ATP-stimulating factor for mammalian cells.

This paper aims to study the natural heat dissipation capacity of a hydraulic tank during its miniaturization revolution. A theoretical model of heat dissipation was built up on the basis of experimental analysis. Then, the natural heat dissipation power was deduced and shown to be relevant. Influencing factors were analyzed, which were the oil height proportion, design proportion, volume, material type, and wall thickness. The results showed that the heat dissipation power is proportional to the height of the oil in the tank. The power increases with the height proportional coefficient k2, while it first decreases and then increases with the length proportional coefficient k1. The lengthwise coefficient obviously has a more significant effect. The influence degree of reduction methods on natural heat dissipation is in the following order: length reduction > equal proportion reduction > height reduction > width reduction. Additionally, when the thermal conductivity λ is greater than 10 W/(m·K), the material and wall thickness of the tank slightly influence the heat dissipation capacity; otherwise, the influence is evident.

The slow proliferation rate and poor osteodifferentiation ability of inflammatory periodontal membrane stem cells extracted from periodontitis tissues (i-PDLSCs) account for poor efficiency in treating inflammatory bone loss. Exosomes reportedly have inducible and relatively stable components, allowing them to promote inflammatory bone repair, but obtaining i-PDLSCs exosomes with the ability to promote osteodifferentiation is challenging. In the present study, i-PDLSCs were extracted from periodontal membrane tissues of patients with severe periodontitis, and in vitro induction with gallic acid (GA) significantly promoted the proliferative activity of i-PDLSCs at a concentration of 10 mM, with TC0 of 11.057 mM and TC50 of 67.56 mM for i-PDLSCs. After mRNA sequencing, we found that GA could alleviate oxidative stress in i-PDLSCs and increase its mitochondrial membrane potential and glucose aerobic metabolism level, thus promoting the osteodifferentiation of i-PDLSCs. After exosomes of i-PDLSCs after GA induction (i-EXO-GA) were isolated by differential centrifugation, we found that 200 ug/mL of i-EXO-GA could remarkably promote the osteodifferentiation of i-PDLSCs. Overall, our results suggest that GA induction can enhance the proliferation and osteodifferentiation in primary cultures of i-PDLSCs in vitro, mediated by alleviating oxidative stress and glycometabolism levels in cells, which further influences the osteodifferentiation-promoting ability of i-EXO-GA. Overall, we provide a viable cell and exosome induction culture method for treating inflammatory alveolar defects associated with periodontitis.

As one of the most abundant insect orders on earth, most Hemipteran insects are phytophagous, with the few hematophagous exceptions falling into two families: Cimicidae, such as bed bugs, and Reduviidae, such as kissing bugs. Many of these blood-feeding hemipteran insects are known to be realistic or potential disease vectors, presenting both physical and psychological risks for public health. Considerable researches into the interactions between hemipteran insects such as kissing bugs and bed bugs and their human hosts have revealed important information that deepens our understanding of their chemical ecology and olfactory physiology. Sensory mechanisms in the peripheral olfactory system of both insects have now been characterized, with a particular emphasis on their olfactory sensory neurons and odorant receptors. This review summarizes the findings of recent studies of both kissing bugs (including Rhodnius prolixus and Triatoma infestans) and bed bugs (Cimex lectularius), focusing on their chemical ecology and peripheral olfactory systems. Potential chemosensation-based applications for the management of these Hemipteran insect vectors are also discussed.

The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.

While formative assessment is recognised as a powerful strategy to improve student learning in mainstream education, less is known about its use in special schools. This study investigates how teachers’ Personal Practice Assessment Theories (PPATs) affect their formative assessment practices in the special school context with the support of e-books. A case study was conducted with three Chinese teachers working with lower primary students who exhibit mild levels of intellectual disability. Data were collected through classroom observations and interviews. The findings reveal that the interaction between teachers’ PPATs and the use of e-books affect teachers assessment goals, and the way they elicit, interpret and respond to assessment information. This study contributes to the understanding of how e-learning technology can be used to facilitate meaningful formative assessment in the special education context.

Background: Cryptococcal pneumonia is an uncommon lesion in immune-competent adults. Histological evidence of Cryptococcus neoformans is a gold criterion for diagnosis. Here we report a case firstly misdiagnosed as tuberculosis from a lung biopsy. Methods: Chest computed tomography (CT) scan and CT-guided puncture were performed for diagnosis and blood tests explored for the latent etiology. Results: Chest CT scan images showed multiple nodules in the left peripheral lower lobe. Histopathology demonstrated multiple granulomatous inflammatory response lacking evidence of Cryptococcus neoformans, acid-fast staining was negative, serum cryptococcal antigen was positive. Conclusions: Serum cryptococcal antigen has high specificity in cryptococcal pneumonia. [ABSTRACT FROM AUTHOR]

Tilapias are important aquaculture species. Male-biased sexual size dimorphism is very common and males are preferred for aquaculture in tilapia. However, the mechanisms underlying sexual dimorphism remain to be elucidated. One hundred and thirty-six sex-biased genes, of which 23 were male-biased and 113 were female-biased, were identified via reanalysis of a muscle transcriptome data using the latest reference genome assembly. These genes were mapped to KEGG pathways that are related to somatic cell metabolism, growth and differentiations, such as MAPK, FoxO4 and metabolism pathways as well as developmental processes responsible for skeletal muscle development. Pathways related to cell growth and proliferations such as MAPK signaling pathways are upregulated in males while pathways regulating cell division such as FoxO4 are upregulated in females. Sex-biased genes in tilapia skeletal muscle have higher evolution rates (dN/dS) compared to unbiased genes. Female-biased and male-biased genes showed 17.4% and 13.5% higher dN/dS, respectively, compared to unbiased genes. Our results suggest that some of the male and female sex-biased genes were under selection pressures. Three SNPs located in the promoter region of one sex-biased gene RASGRF1 on LG1 were associated with bodyweight differences in the hybrid tilapia. These sex-biased genes identified in this study may serve as candidate genes for future functional analysis on sexual size dimorphism and for developing DNA markers for selecting fast-growing saline tilapia in aquaculture. Keywords: Sexual dimorphism, Body size, RNA-Seq, Tilapia, Aquaculture, Evolution

Abstract Understanding the distribution and composition of soil microbes in bare patches is a critical step to improving ecological remediation. The effects of different vegetative restoration types on soil microbes within semi‐arid bare patches remain unclear. Here, we evaluated the distribution of soil fungi and bacteria among different ecological restoration types at the southern Taihang Mountains. Analysis of variance showed that the chemical properties of soil with vegetation cover have higher nutrient quality than those of the exposed soil. The results also suggested that vegetative restoration significantly improved the diversity and the richness of the soil fungal and bacterial communities. Sequencing results showed that Ascomycota and Basidiomycota were the main soil fungal communities, whereas Proteobacteria, Acidobacteria, and Actinobacteria were the main soil bacterial communities. There were significant relationships between the contents of moisture, organic matter and organic carbon and the soil fungal/bacterial communities. Venn and network diagrams indicated that the vegetative restoration types largely influenced the soil fungi and weakly influenced the soil bacteria in the bare patches. This study discusses the importance of vegetative restoration in the ecological remediation of bare patches. These findings provide effective references for soil restorative measures, water conservation, and bare‐spot reduction at the southern Taihang Mountains in future.

Long duty hours have been associated with significant medical errors, adverse events, and physician “burn-out”. An innovative night float (NF) system has been implemented in our internal medicine program to reduce the negative effects of long duty hours associated with conventional full-call systems. However, concerns remain if this would result in inadequate training for interns. We developed a structured questionnaire to assess junior doctors’ perceptions of the NF system compared to full calls, in areas of patient safety, medical training, and well-being. Ninety-seven (71%) of the 137 doctors polled responded. Ninety-one (94%) felt the NF system was superior to the full call system. A strong majority felt NF was beneficial for patient safety compared to full call (94% vs. 2%, p

This study was conducted in order to identify the presence of four synthetic phenolic antioxidants (SPAs): propyl gallate (PG), tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) in various food stuffs that are commonly consumed in Malaysia. The identification method was optimized and validated before it was applied to the analyses of eighty three food samples which include chewing gum, chili sauce, cereal-based snack food, noodles, potato snack, cereal breakfast, oat, biscuit, cookie, coffee, junk food, seaweed, nut, chocolate, apple juice, orange juice and blackcurrant juice. Twenty nine food samples contained SPAs either singly or in combination. The chromatography conditions such as elution method, flow rate and wavelength were optimized. Good linearity ranges (1–300 mgL–1) were found for all the four phenolic antioxidants. RSD for repeatability and reproducibility ranged from 0.15–0.84% for both precision analyses. LOD and LOQ ranged from 0.02–0.67 and 0.06–2.03 mgL–1, respectively. Recoveries of the four SPAs ranged from 80.4 to 119.0% when selected food items spiked at 10, 50, and 100 mgL–1.

Abstract Background Exosomes from cancer cells or immune cells, carrying bio-macromolecules or microRNAs (miRNAs), participate in tumor pathogenesis and progression by modulating microenvironment. Our study aims to investigate the role of these microRNA-501-3p (miR-501-3p) containing exosomes derived from tumor-associated macrophage (TAM) in the progression of pancreatic ductal adenocarcinoma (PDAC). Methods Firstly, the function of TAM recruitment in PDAC tissues was assessed, followed by identification of the effects of M2 macrophage-derived exosomes on PDAC cell activities and tumor formation and metastasis in mice. In silico analysis was conducted to predict differentially expressed genes and regulatory miRNAs related to PDAC treated with macrophages, which determined miR-501-3p and TGFBR3 for subsequent experiments. Next, gain- and loss-of-function experiments were performed to examine their role in PDAC progression with the involvement of the TGF-β signaling pathway. Results TAM recruitment in PDAC tissues was associated with metastasis. Highly expressed miR-501-3p was observed in PDAC tissues and TAM-derived exosomes. Both M2 macrophage-derived exosomes and miR-501-3p promoted PDAC cell migration and invasion, as well as tumor formation and metastasis in nude mice. MiR-501-3p was verified to target TGFBR3. PDAC cells presented with down-regulated TGFBR3, which was further decreased in response to M2 macrophage treatment. TGF-β signaling pathway activation was implicated in the promotion of miR-501-3p in PDAC development. The suppression of macrophage-derived exosomal miR-501-3p resulted in the inhibition of tumor formation and metastasis in vivo. Conclusion M2 macrophage-derived exosomal miR-501-3p inhibits tumor suppressor TGFBR3 gene and facilitates the development of PDAC by activating the TGF-β signaling pathway, which provides novel targets for the molecular treatment of PDAC.

It remains a challenge to obtain high-resolution structures of molecules smaller than 200 kDa using single particle cryo-EM. Here, the authors apply the Cs-corrector-VPP coupled cryo-EM and solve structures of the 52 kDa streptavidin (SA) protein at near-atomic resolution.

Objective To analyze the clinical characteristics and treatment experience of Vitamin B12 (VB12) defi⁃ cient patients with recurrent aphthous ulcers (RAU) to improve the clinical efficacy. Methods A retrospective analysis was performed on 15 cases of recurrent oral ulcers from January 2016 to September 2018. The causes were analyzed ac⁃ cording to the patients’clinical characteristics. Results In total, 15 patients with RAU had no remission after routine immunotherapy. Further clinical examination suggested that vitamin B12 levels were reduced. The erythrocyte mean cor⁃ puscular volume (MCV) was significantly increased, and the average number of red blood cells (RBC) and hemoglobin (Hb) levels were decreased. RAU disappeared after vitamin B12 supplementation. Routine blood work showed that the MCV returned to the normal range, which was statistically significant compared with the pretreatment MCV (P < 0.001). Vitamin B12 serum levels were significantly higher (P < 0.001) than those before treatment. Conclusion When the main manifestation of vitamin B12 deficiency is recurrent oral ulcer symptoms, dentists should examine the lesions care⁃ fully, inquire about the medical history in detail, and perform further serological tests when necessary to avoid the over⁃ use of immunosuppressive drugs for treatment.

Abstract. Background:. Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several studies show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nω-nitro-L-arginine methyl ester (L-NAME) PE-like mouse model in our previous study. This study aimed to investigate the effect of mTOR signaling pathway in PE-like model treated with Pra. Methods:. Pregnant mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from gestational 7th to 18th day. Giving Pra (L-NAME + Pra, Control + Pra, n = 8) or normal saline (NS; L-NAME + NS, Control + NS, n = 8) from gestational 8th to 18th day, the mice were sacrificed on day 18 and their liver and placental tissues were collected. Then the activation of mTOR and its substrates in the liver and placenta were detected. And the association between mTOR activation and serum free fatty acid (FFA) levels and the expression of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) were evaluated using Pearson correlation test. Differences between groups were analyzed using independent t-test or one-way analysis of variance (ANOVA). Results:. Both in the maternal liver and placenta, the activation of mTOR protein and its effect on substrates increased significantly in the L-NAME + NS group and decreased significantly in the L-NAME + Pra group. The p-mTOR/mTOR protein ratio decreased in the L-NAME + Pra group significantly than that in the L-NAME + NS group both in liver and placenta (liver: 0.74 ± 0.08 vs. 0.85 ± 0.06, t = 2.95, P

The deep neural network is similar to the biological neural network, so it has the ability of high efficiency and accurate extraction of the deep hidden features of information, can learn multiple layers of abstract features, and can learn more about cross-domain, multi-source and heterogeneous content information. This paper presents an extraction feature based on multi-user-project combined deep neural network, self-learning and other advantages to achieve the model of personalized information. This model does deep neural network self-learning and extraction based on the input multi-source heterogeneous data characteristics，fuses collaborative filtering wide personalization to generate candidate sets, and then through two times of model self-learning produces a sort set. Finally，it can achieve accurate, real-time, and personalized recommendations. The experimental results show that the model can self-learn and extract the user′s implicit feature well, and it can solve the problems of sparse and new items of traditional recommendation system to some extent, and realize more accurate, real-time and personalized recommendation.

Abstract Background Prostate cancer (PCa) is one of the most common cancers in male worldwide. Oxidative stress has been recognized as one of the driving signals pathologically linked to PCa progression. Nevertheless, the association of oxidative stress with PCa progression remains unclear. Methods Western blot, q-RT-PCR and bioinformatics analyses were used to examine PAGE4 expression. Comet assay and Annexin V/ PI dual staining assay were performed to investigate DNA damage and cell death under oxidative stress. Mouse xenograft model of PCa cells was established to verify the role of PAGE4 in vivo. Transcriptomic analysis was performed to investigate the underlying mechanism for the function of PAGE4 under oxidative stress. Western blot assay was conducted to determine the status of MAPK pathway. Immunohistochemistry was used to identify protein expression of PAGE4 in tumor tissues. Results In this study, we found that PAGE4 expression was increased in PCa cells under oxidative stress condition. PAGE4 overexpression protected PCa cells from oxidative stress-inducing cell death by reducing DNA damage. PAGE4 overexpression promoted PCa cells growth in vivo. Mechanistically, PAGE4 promoted the survival of prostate cancer cells through regulating MAPK pathway which reflected in decreasing the phosphorylation of MAP2K4, JNK and c-JUN but increasing phosphorylation of ERK1/2. Conclusion Our findings indicate that PAGE4 protects PCa cells from DNA damage and apoptosis under oxidative stress by modulating MAPK signalling pathway. PAGE4 expression may serve as a prognostic biomarker for clinical applications.

As an unconventional realization of topological orders with an exotic interplay of topology and geometry, fracton (topological) orders feature subextensive topological ground-state degeneracy and subdimensional excitations that are movable only within a certain subspace. It has been known, in the exactly solvable three-dimensional X-cube model that universally represents the type-I fracton orders, that mobility constraints on subdimensional excitations originate from the absence of spatially deformable stringlike operators. To unveil the interplay of topology and geometry, in this paper, we study the dynamical signature in the X-cube model in the presence of external Zeeman fields via large-scale quantum Monte Carlo simulation and stochastic analytic continuation. We compute both real-space correlation functions and dynamic structure factors of subdimensional excitations (i.e., fractons, lineons, and planons) in the fracton phase and their evolution into the trivial paramagnetic phase by increasing external fields. We find, in the fracton phase, that the correlation functions and the spectral functions show clear anisotropy exactly caused by the underlying mobility constraints. On the other hand, the external fields successfully induce quantum fluctuations and offer mobility to excitations along the subspace allowed by mobility constraints. These numerical results provide the evolution of a dynamical signature of subdimensional particles in fracton orders, indicating that the mobility constraints on local dynamical properties of subdimensional excitations are deeply related to the existence of fracton topological order. The results will also be helpful in potential experimental identifications in spectroscopy measurements such as neutron scattering and nuclear magnetic resonance.

To investigate the main modes of interannual variation of chlorophyll-a (Chla) with seasonal evolution and its variation cycle in the North Indian Ocean based on satellite-derived products during 1998–2016, a season-reliant empirical orthogonal function (S-EOF) analysis and power spectrum analysis based on Fourier transform are applied in the study. The first three dominate modes reveal distinct Chla variability, as the S-EOF1 features by one dipole pattern have a negative anomaly in the central western Indian Ocean and a positive anomaly off the Java–Sumatra coasts, which is mainly synchronously associated with the climate indices of the positive Indian Ocean dipole (IOD) and eastern Pacific El Nino (EP-El Niño). The S-EOF2 indicates a tripolar structure with positive anomalies located in the central Indian Ocean surrounded by two negative anomalies, which is one year behind a positive IOD and EP-El Niño event. The S-EOF3 exhibits a different dipole distribution, with a positive anomaly in the central west and a negative anomaly in the southeast, synchronized or lagging behind the central Pacific El Nino (CP-El Niño). Moreover, regarding the correlation between the main modes of interannual variation and the IOD and El Nino events, the dynamic parameters (such as SST, SLA, rain, and wind) of the tropical Indo-Pacific Ocean are discussed using time-delay correlation and linear regression analysis to explain the key factors and possible influencing mechanism of the joint seasonal and interannual variations of Chla in the northern Indian Ocean.

The purpose of the study was to examine the social-ecological factors associated with diabetic self-management compliance among elders with diabetes in China. A total of 2,586 rural elderly residents who were 60-years-old or above participated in the survey. Socio-demographic factors, social support, healthcare accessibility and health risk factors were measured, along with self-reported medication and blood glucose monitoring data. Among the 117 individuals with diabetes, the medication compliance rate was 79.49%. The elderly who had high economic status were more likely to meet medication treatment compliance. Only 58.97% of study participants monitored blood glucose once a month. Younger age (

Starch and sucrose metabolism plays a crucial role in the formation and development of bulbs in bulbous plants. However, these mechanisms remain unclear and unexplored in the corms of Freesia hybrida. Herein, we investigated the dynamics of the major form of carbohydrates and related enzyme activities and profiled the transcriptome of freesia corms at four developmental stages with the aim to reveal the relation between the expression of genes involved in the metabolism of carbohydrates and the accumulation of carbohydrates in corm developmental stages for further exploring the mechanism on the starch and sucrose metabolism regulating the formation and development of corms in F. hybrida. The content of starch, sucrose and soluble sugars followed an overall upward trend across the corm developmental stages. Activities of the adenosine diphosphoglucose pyrophosphorylase, starch branching enzyme and β-amylase generally followed the pattern of the starch and sucrose levels. Activities of sucrose phosphate synthase increased from corm formation till the initial swelling stage and subsequently reached a plateau. Activities of invertase and sucrose synthase peaked at the later rapid swelling stage. These suggested that the starch and sucrose dynamics paralleled corm swelling under the action of metabolic enzymes. A total of 100,999 unigenes were assembled in the transcriptomic analysis, and 44,405 unigenes of them were annotated. Analysis based on Clusters of Orthologous Groups suggested that carbohydrate transport and metabolism (9.34% of the sequences) was prominent across the corm developmental process. In total 3,427 differentially expressed genes (DEGs) were identified and the enrichment analysis detected starch and sucrose metabolism as a critical pathway in corm development, especially at the rapid swelling stage. Further, DEGs encoding key carbohydrate-metabolizing enzymes were identified and correlated to enzyme activities and carbohydrate accumulation. The results construct a valuable resource pool for further molecular-level studies, which are helpful for metabolic regulation of carbohydrates and improvement in F. hybrida.

This study investigates the alteration in function and number of circulating endothelial progenitor cells (EPCs) in patients with aortic dissection (AD), compared with hypertensive patients, and its possible mechanism. Thirty-four patients with acute aortic dissection (AAD) and 20 patients with primary hypertension were involved. Flow cytometry analysis was performed to detect the number of CD34+/KDR+ cells, and acetylated low density lipoprotein (ac-LDL) and lectin fluorescent staining method was applied to test the number of cultured EPCs. In addition, EPC migration and proliferation were measured, and plasma interleukin 6 (IL-6) and interleukin 17 (IL-17) levels were investigated. The number of circulating EPCs in the AAD group was lower than that in the non-AD group, and the proliferation and migration of circulating EPCs in the AAD group were lower than that in the non-AD group. In addition, the number, proliferation, and migration of circulating EPCs were significantly inversely correlated with the aortic dissection detection risk score (ADD-RS). More importantly, increased plasma IL-6 and IL-17 level was found in the AAD group, and the two inflammatory factors were inversely associated with the function and number of circulating EPCs in the AAD group. We first demonstrated that the number and function of circulating EPCs are reduced in the AAD group, which may be partly related to upregulated plasma IL-6 and IL-17. Our study provides novel insight on the underlying mechanism and potential therapeutic target of AAD.

Tendon harbors a cell population that possesses stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity, commonly referred to as tendon stem/progenitor cells (TSPCs). Various techniques have been employed to study how TSPCs are implicated in tendon development, homeostasis and healing. Recent advances in single-cell analysis have enabled much progress in identifying and characterizing distinct subpopulations of TSPCs, which provides a more comprehensive view of TSPCs function in tendon biology. Understanding the mechanisms of physiological and pathological processes regulated by TSPCs, especially a particular subpopulation, would greatly benefit treatment of diseased tendons. Here, we summarize the current scientific literature on the various subpopulations of TSPCs, and discuss how TSPCs can contribute to tissue homeostasis and pathogenesis, as well as examine the key modulatory signaling pathways that determine stem/progenitor cell state. A better understanding of the roles that TSPCs play in tendon biology may facilitate the development of novel treatment strategies for tendon diseases.

To investigate aqueous metabolic profiles in Vogt-Koyanagi-Harada (VKH) and Behcet’s disease (BD), we applied ultra-high-performance liquid chromatography equipped with quadrupole time-of flight mass spectrometry in aqueous humor samples collected from these patients and controls. Metabolite levels in these three groups were analyzed by univariate logistic regression. The differential metabolites were subjected to subsequent pathway analysis by MetaboAnalyst. The results showed that both partial-least squares discrimination analysis and hierarchical clustering analysis showed specific aqueous metabolite profiles when comparing VKH, BD, and controls. There were 28 differential metabolites in VKH compared to controls and 29 differential metabolites in BD compared to controls. Amino acids and fatty acids were the two most abundant categories of differential metabolites. Furthermore, pathway enrichment analysis identified several perturbed pathways, including pantothenate and CoA biosynthesis when comparing VKH with the control group, and D-arginine and D-ornithine metabolism and phenylalanine metabolism when comparing BD with the control group. Aminoacyl-tRNA biosynthesis was altered in both VKH and BD when compared to controls. Our findings suggest that amino acids metabolism as well as two fatty acids, palmitic acid and oleic acid, may be involved in the pathogenesis of BD and VKH.

Objectives Having to access life-sustaining treatment during the emerging COVID-19 outbreak has placed patients with cancer at an especially vulnerable position notwithstanding their immunocompromised condition. The present study aimed to elucidate cancer patients’ and their caregivers’ experiences during this outbreak.Design Face-to-face semistructured interviews were conducted.Setting A tertiary cancer care facility.Participants 16 patients with cancer and 14 caregivers. Inclusions criteria were: (A) diagnosed with cancer, (B) receiving active treatment or follow-ups, (C) aged 21 years and above and (D) fluent in English or Mandarin.Results Thematic analysis was conducted. Five themes were identified: heightened sense of threat, impact on healthcare experience, responsibility falls on oneself, striving for normalcy and sense of safety and trust. Heightened threat of COVID-19 was more pronounced in patients and linked to vulnerability and fear, uncertainty and actions of socially irresponsible others. Dominant in their healthcare experience was prioritising cancer and treatment amidst heightened threat and anticipatory worry about treatment disruptions. Both noted on the importance of taking responsibility for one’s health, with caregivers reporting a reinforced sense of duty towards patients. They strived to maintain normalcy by viewing COVID-19 as beyond personal control, downplaying and living life as usual. Their resolve was supported by a sense of safety from the actions of authorities, hospitals and trust towards healthcare providers.Conclusions Cancer intensifies threat and the emotional impact of COVID-19 and may trigger specific concerns related to treatment. Psychoeducation interventions led by healthcare providers over digital platforms could help address cancer-specific concerns and support patients and caregivers during the pandemic.

Fusobacterium nucleatum is an anaerobic oral commensal organism that is often associated with inflammatory bowel disease, adverse pregnancy outcomes, respiratory tract infections, and Lemierre’s syndrome. Rheumatoid arthritis is often associated with pleuropulmonary manifestations including noninfectious pleural effusions and interstitial lung disease. We present a case of a 47-year-old man with progressive rheumatoid arthritis on immunosuppressive therapy who was found to have a left-sided pleural effusion, thought secondary to possible pneumonia, and was treated with levofloxacin and methylprednisolone. He presented a month later and was found to have a large left-sided thick-walled fluid collection found to be an empyema. A chest tube was placed, and fluid culture grew Fusobacterium nucleatum. The patient was successfully treated with intrapleural fibrinolytic therapy and amoxicillin-clavulanic acid.

Exosomes, as the main group of extracellular vesicles, are biologically active lipid-bilayer vesicles that are naturally released from different types of normal or tumor cells. These vesicles play an important role in intercellular communication and influence the extracellular environment and the immune system. Emerging evidence demonstrates that cancer-derived exosomes are enriched in immunosuppressive proteins, such as the programmed death-ligand 1 (PD-L1). PD-L1 and its receptor programmed cell death protein 1 (PD-1) are the key immune checkpoint molecules that promote tumor progression via negative regulation of immune responses. PDL-1 is highly expressed on the surface of tumor cells and binds to PD-1 on the surface of activated T cells, leading to suppression of T cells, which consequently enables cancer cells to escape antitumor immunity. Currently, there are several Food and Drug Administration-approved monoclonal antibodies blocking PD-1/PD-L1 interaction, which are clinically used for cancer treatment. However, despite impressive treatment outcomes, some patients show poor response to PD-1/PD-L1 blockade. Of note, tumor-derived exosomes containing PD-L1 can recapitulate the effect of cell-surface PD-L1. There is evidence that reveals a significant association between levels of circulating exosomal PD-L1 and rate of response to anti-PD-1/PD-L1 antibody therapy. The present article reviews the role of exosomal PDL-1 in the therapeutic resistance to anti-PD-1/PD-L1 treatment. Importantly, it is suggested that the removal of exosomal PDL-1 could serve as a therapeutic adjuvant for enhancing the efficacy of anti-PD-1/PD-L1 therapy in patients with cancer.

Droughts and floods have occurred frequently in the Lower Mekong River Basin in recent years. Obtaining the evapotranspiration (ET) in the basin helps people to better understand water cycle and water resources. In this study, we retrieved and validated ET in the Lower Mekong Basin over multiple years (from 2008 to 2017) using remote sensing products. Based on the retrieval ET, we analyzed the spatial-temporal variation of ET and influencing factors at the monthly, seasonal, and inter-annual scale respectively. The results revealed that the overall variation trend of ET at annual scale slightly increased during 2008 to 2017, with the highest annual ET being 1198 mm/year in 2015 and the lowest annual ET being 949 mm/year in 2008. At the seasonal scale, ET in the rainy season was lower than the dry season; at the monthly scale, March had the highest monthly ET (101 mm/month) while July had the lowest monthly ET (73 mm/month). Spatial analyzing showed that ET in the margin of this region was higher (with on average about 1250 mm/year) and lower in the middle (with on average about 840 mm/year), and monthly ET changed mostly in forest areas with the difference of 60 mm/month. Influencing analyzing results showed that ET was mainly driven by solar radiation and near-surface temperature, and precipitation had an inhibitory effect on ET in the rainy season months. The study also showed that forests in the basin are very sensitive to solar radiation, with a correlation coefficient of 0.89 in March (the month with the highest ET) and 0.45 in July (the month with the lowest ET).

Cryptocurrencies can be considered as mathematical money. As the most famous cryptocurrency, the Bitcoin price forecasting model is one of the popular mathematical models in financial technology because of its large price fluctuations and complexity. This paper proposes a novel ensemble deep learning model to predict Bitcoin’s next 30 min prices by using price data, technical indicators and sentiment indexes, which integrates two kinds of neural networks, long short-term memory (LSTM) and gate recurrent unit (GRU), with stacking ensemble technique to improve the accuracy of decision. Because of the real-time updates of comments on social media, this paper uses social media texts instead of news websites as the source data of public opinion. It is processed by linguistic statistical method to form the sentiment indexes. Meanwhile, as a financial market forecasting model, the model selects the technical indicators as input as well. Real data from September 2017 to January 2021 is used to train and evaluate the model. The experimental results show that the near-real time prediction has a better performance, with a mean absolute error (MAE) 88.74% better than the daily prediction. The purpose of this work is to explain our solution and show that the ensemble method has better performance and can better help investors in making the right investment decision than other traditional models.

Background: Triptolide (TP) is a major active component of colquhounia root tablet, which has been long been used in China to treat diabetic nephropathy (DN) due to its marked anti‑inflammatory, antiproteinuric, and podocyte‑protective effects. Methods: This study investigated the anti-proteinuria activity and related signaling cascade of TP in DN by utilizing a network pharmacology and molecular docking approach. Results: From the GeneCard, DisGeNET, and National Center for Biotechnology Information Gene databases, 1458 DN targets were obtained and input together with 303 TP targets into Venny2.1.0 for mapping and comparing. In total, 113 common targets of TP and DN were obtained, of which 7 targets were found to play an important role through theoretical inhibitory constant analysis. The common targets were further analyzed by Kyoto Encyclopedia of Genes and Genomes to identify the pathways related to the therapeutic effect of TP on DN. Among them, the seven targets were found to play key roles in six signaling pathways. The molecular docking results also showed TP had good binding ability to the seven targets. Conclusions: Analysis of the common targets and key pathways showed that TP can improve DN via its anti-nephritis, anti-renal fibrosis, antioxidant, and podocyte-protective effects, which might elucidate the mechanism by which TP improves renal function and reduces proteinuria in DN.

Using the daily electric power load and meteorological data over the period from January 2006 to September 2010 in Beijing, the general features of the electric power load and the main factors affecting this load have been analysed. The results indicate that winter and summer are the two peak power consumption seasons in each year. This finding could be mainly attributed to the consumption of energy for urban residential cooling or heating. In the summer, the daily minimum temperature was most closely correlated with the maximum power load (correlation co-efficient of 0.65, significant at the 0.1% level); the primary effect of temperature on the maximum power load varied largely from 376 to 858 MW °C −1, and it increased sharply when the daily minimum temperature was higher than 24 °C or the daily maximum temperature was higher than 32 °C. In the winter, the daily maximum temperature was most closely correlated with the power load (−0.45, 0.1% significance), and the primary effect varied from 109 to 391 MW °C −1. However, the relationship between the power load and the temperature was more complicated in the winter: this relationship varied during the central heating period and its pre- and post-periods. Moreover, the temperature humidity index (THI) could explain more of the variance in the daily maximum power load than any single temperature factor in the summer, while the wind-chill temperature index (WCT) did not contribute to this variance in the winter. Finally, due to the rapid urbanization of Beijing, the power load and the priamry effect increased each year. Copyright © 2012 Royal Meteorological Society [ABSTRACT FROM AUTHOR]