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Under the acidic conditions (pH 4.0), the addition of wheat oligopeptides (WOPs) (25~100 g/L) decreased the thermal stability of purple sweet potato anthocyanins (PSPAs), but enhanced its antioxidant capacity, which increased with the rise of the additive amount. When the addition was 100 g/L, the DPPH, ABTS free radical scavenging capacity and FRAP total antioxidant capacity of PSPAs solution after in vitro simulated digestion were increased by 1.5 times, 34 times and 34%, respectively. After storage at 37 ℃ and 45 ℃ for 7 d, the antioxidant capacity did not change significantly, and it had stronger biological activity and higher stability than those of PSPAs. UV and fluorescence spectra showed that PSPAs can affected the redshift of absorption peak and fluorescence quenching at specific wavelength of WOPs at experimental concentration, which proved the interaction between WOPs and PSPAs. It can be seen from the above that WOPs have the potential to be applied in the development of acidic PSPAs beverages.

Abstract Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5′ end sequences derived from cap-snatching in influenza virus mRNA. Here, we report cryo-EM structures to characterize THOV polymerase RNA synthesis initiation and elongation. The structures demonstrate that THOV RNA transcription and replication are able to start with short dinucleotide primers and that the polymerase cap-snatching machinery is likely non-functional. Triggered by RNA synthesis, asymmetric THOV polymerase dimers can form without the involvement of host factors. We confirm that, distinctive from influenza viruses, THOV-polymerase RNA synthesis is weakly dependent of the host factors ANP32A/B/E in human cells. This study demonstrates varied mechanisms in RNA synthesis and host factor utilization among orthomyxoviruses, providing insights into the mechanisms behind thogotoviruses’ broad-infectivity range.

Central serous chorioretinopathy(CSC)is a common macular degeneration that primarily affects young patients. While the disease may resolve on its own to some extent, delayed or inadequate treatment can result in recurrence and progression to chronic CSC. This can lead to complications such as retinal pigment epithelium(RPE)atrophy and choroidal neovascularization, ultimately causing irreversible damage to central vision. Subthreshold micropulse laser photocoagulation(SMLP)is a type of laser therapy that differs from traditional lasers in that it does not cause damage or thermal injury to RPE cells and photoreceptors. SMLP has become widely used in clinical treatment of CSC due to its effectiveness, safety, and reproducibility, particularly in cases where verteporfin is not available in photodynamic therapy(PDT). The purpose of this review is to explain the mechanism of SMLP in CSC and summarize the effector cells, cytokines, and mechanisms of action involved in its treatment. This will provide a theoretical basis for promoting and rationalizing the use of SMLP in clinical practice.

To examine the prevalence of comorbidities in Chinese urticaria patients and assess medication use patterns across different ages (6–11 years, 12–17 years, above 18 years), a retrospective cohort study was performed in 192,647 urticaria patients within the Health Database. After 1:1 propensity score matching, 166,921 people were divided into the urticaria group and the control group, and the follow-up data were collected within 2 years. During the 12-month and 24-month follow-up period, significant comorbidities identified included allergic rhinitis and asthma, with distinct patterns observed across age groups. Chronic urticaria patients often have complications, such as allergic rhinitis, upper respiratory infection, oropharyngeal infection, and dental caries. The study underscores the need for age-specific treatment strategies in urticaria management.

Background: Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial growth factor receptor 2. However, it remains unclear whether vandetanib has therapeutic benefits in other lung diseases, particularly asthma. The present study investigated the pioneering use of vandetanib in the treatment of asthma.Methods:In vivo experiments including establishment of an asthma model, measurement of airway resistance measurement and histological analysis were used primarily to confirm the anticontractile and anti-inflammatory effects of vandetanib, while in vitro experiments, including measurement of muscle tension and whole-cell patch-clamp recording, were used to explore the underlying molecular mechanism.Results:In vivo experiments in an asthmatic mouse model showed that vandetanib could significantly alleviate systemic inflammation and a range of airway pathological changes including hypersensitivity, hypersecretion and remodeling. Subsequent in vitro experiments showed that vandetanib was able to relax the precontracted rings of the mouse trachea via calcium mobilization which was regulated by specific ion channels including VDLCC, NSCC, NCX and K+ channels.Conclusions: Taken together, our study demonstrated that vandetanib has both anticontractile and anti-inflammatory properties in the treatment of asthma, which also suggests the feasibility of using vandetanib in the treatment of asthma by reducing abnormal airway contraction and systemic inflammation.

We present the design of a Single Polarization Single Mode (SPSM) Terahertz Hollow-Core Anti-Resonant Waveguide (THz HC-ARW) by using multi-size semi-elliptical tubes (SETs) and high-resistance silicon layer. High single mode performance can be achieved by optimizing the structural parameters in the structure of the THz HC-ARW with multi-size SETs in the cladding. Numerical results indicate that the single mode bandwidth with High Order Mode Extinction Ratio (HOMER) above 100 reaches up to 420 GHz covering the frequency range from 0.82 THz to 1.24 THz, in which the loss of Fundamental Mode (FM) remains below 0.05 dB/m. To the best of our knowledge, this is the first instance of achieving low loss of FM under 0.05 dB/m and HOMER exceeding 100 within an exceptionally wide frequency bandwidth for a THz HC-ARW. On the basis of the above structure, a modified structure is proposed to further obtain single polarization characteristics by selectively coating a high-resistance silicon layer on the inner surface of one SET. When a high-resistance silicon layer with the thickness of 0.258 mm is coating on the inner surface of the biggest SET, a high polarization extinction ratio of 371 and a HOMER of 106 can be attained simultaneously at a frequency of 1 THz, thus only the X-polarization FM with low loss of 0.04 dB/m can propagate through the waveguide. This means SPSM can be achieved in the proposed modified structure.

Abstract Background Tyrosine kinase and phosphoinositide kinase pathways play important roles in asthma formation. As a dual tyrosine and phosphoinositide kinase inhibitor, PP121 has shown anticancer efficacy in multiple tumors. However, the study of PP121 in pulmonary diseases is still limited. Herein, we investigated the therapeutic activities of PP121 in asthma treatment. Methods Tension measurements and patch clamp recordings were made to investigate the anticontractile characteristics of PP121 in vitro. Then, an asthma mouse model was established to further explore the therapeutic characteristics of PP121 via measurement of respiratory system resistance, histological analysis and western blotting. Results We discovered that PP121 could relax precontracted mouse tracheal rings (mTRs) by blocking certain ion channels, including L-type voltage-dependent Ca2+ channels (L-VDCCs), nonselective cation channels (NSCCs), transient receptor potential channels (TRPCs), Na+/Ca2+ exchangers (NCXs) and K+ channels, and accelerating calcium mobilization. Furthermore, PP121 relieved asthmatic pathological features, including airway hyperresponsiveness, systematic inflammation and mucus secretion, via downregulation of inflammatory factors, mucins and the mitogen-activated protein kinase (MAPK)/Akt signaling pathway in asthmatic mice. Conclusion In summary, PP121 exerts dual anti-contractile and anti-inflammatory effects in asthma treatment, which suggests that PP121 might be a promising therapeutic compound and shed new light on asthma therapy.

Propane dehydrogenation (PDH) is a crucial approach for propylene production. However, commonly used CrOx–based catalysts have issues including easy sintering at elevated reaction temperatures and relying on high acidity supports. In this work, we develop a strategy, to strongly anchor and isolate active sites against their commonly observed aggregation during reactions, by taking advantage of the net trap effect in chromate intercalated Zn–Cr layered hydroxides as precursors. Furthermore, the intercalated chromate overcomes the collapse of traditional layered hydroxides during their transformation to metal oxide, thus exposing more available active sites. A joint fine modulation including crystal structure, surface acidity, specific surface area, and active sites dispersion is performed on the final mixed metal oxides for propane dehydrogenation. As a result, Zn1Cr2–CrO42−–MMO delivers attractive propane conversion (~27%) and propylene selectivity (>90%) as compared to other non–noble–metal–based catalysts.

BackgroundHay fever, characterized by seasonal allergic reactions, poses a significant health challenge. Existing therapies encompass standard drug regimens, biological agents, and specific immunotherapy. This study aims to assess and compare the effectiveness of anti-IgE (omalizumab), medication therapy, and subcutaneous immunotherapy (SCIT) for hay fever.MethodsConducted as a retrospective cohort study, this research involved 98 outpatient hay fever patients who underwent routine medication, omalizumab treatment, or SCIT before the onset of the spring pollen season. A follow-up was performed one month after the start of the pollen season. The comprehensive symptoms and drug scores were used to evaluate patients with different intervention methods, facilitating a comparative analysis of therapeutic outcomes.ResultsCompared with before treatment, the symptoms of patients treated with the three methods were all significantly relieved, and the medication score were significantly reduced. Patients treated with omalizumab demonstrated higher symptoms and medication scores than SCIT group before treatment, but similar scores after treatment, which were both lower than medicine treatment group. After treatment with omalizumab or SCIT, patients in both groups had significantly lower medication scores than the medication group and were close to no longer using medication for symptom relief. The mountain juniper-sIgE was significantly higher after treatment than before treatment in both medicine treatment group and omalizumab treatment group.ConclusionOmalizumab and SCIT offer superior effects than medication therapy in hay fever patients.

Long non-coding RNA (lncRNA) H19 is an extensively studied lncRNA that is related to numerous pathological changes. Our previous findings have documented that serum lncRNA H19 levels are decreased in patients with chronic kidney disorder and lncRNA H19 reduction is closely correlated with renal tubulointerstitial fibrosis, an essential step in developing end-stage kidney disease. Nonetheless, the precise function and mechanism of lncRNA H19 in renal tubulointerstitial fibrosis are not fully comprehended. The present work utilized a mouse model of unilateral ureteral obstruction (UUO) and transforming growth factor-β1 (TGF-β1)-stimulated HK-2 cells to investigate the possible role and mechanism of lncRNA H19 in renal tubulointerstitial fibrosis were investigated. Levels of lncRNA H19 decreased in kidneys of mice with UUO and HK-2 cells stimulated with TGF-β1. Up-regulation of lncRNA H19 in mouse kidneys remarkably relieved kidney injury, fibrosis and inflammation triggered by UUO. Moreover, the increase of lncRNA H19 in HK-2 cells reduced epithelial-to-mesenchymal transition (EMT) induced by TGF-β1. Notably, up-regulation of lncRNA H19 reduced lipid accumulation and triacylglycerol content in kidneys of mice with UUO and TGF-β1-stimulated HK-2 cells, accompanied by the up-regulation of long-chain acyl-CoA synthetase 1 (ACSL1). lncRNA H19 was identified as a sponge of microRNA-130a-3p, through which lncRNA H19 modulates the expression of ACSL1. The overexpression of microRNA-130a-3p reversed the lncRNA H19-induced increases in the expression of ACSL1. The suppressive effects of lncRNA H19 overexpression on the EMT, inflammation and lipid accumulation in HK-2 cells were diminished by ACSL1 silencing or microRNA-130a-3p overexpression. Overall, the findings showed that lncRNA H19 ameliorated renal tubulointerstitial fibrosis by reducing lipid deposition via modulation of the microRNA-130a-3p/ACSL1 axis.

Objective: This study aimed to solve the problem of the low utilization rate of mackerel and the single taste of fish chips. Methods: The specific volume, crispness, hardness, color, fat and acrylamide content of mackerel-yam fish chips made by frozen mackerel, starch and yam powder were determined to study the effects of different aging time, frying time, frying temperature and amount of yam powder on the quality of fish-chips. Results: With the extension of the aging time, the specific volume of the fish-chips gradually increased, when the aging time was 48 h, the specific volume reached 4.14 mL/g, and the hardness also gradually decreased. When the aging time was 48 h and 60 h, the hardness was 382.8 N and 371.5 N respectively. The brittleness first increased and then decreased with the increase of aging time, after 36 h, the brittleness of the fish stick had no significant difference. The best frying time of fish-chips was 40 s, at this time, its specific volume was 4.2 mL/g, its brittleness was 0.354 mm, and its hardness was 357.17 N; when the temperature reached 180 ℃, the specific volume and brittleness of the fish-chips did not change significantly. With the increasing amount of yam powder, the specific volume, hardness, and acrylamide of fish-chips gradually decreased and its brittleness gradually increased, whereas the fat content had no obvious regularity. Conclusion: The fish chips could meet the needs of the public and had potential development values.

Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can provide partial hearing sensation, but language development outcomes can vary, particularly for patients with inner ear malformations and/or cochlear nerve deficiency (IEM&CND). Currently, the peripheral auditory structure is evaluated through visual inspection of clinical imaging, but this method is insufficient for surgical planning and prognosis. The central auditory pathway is also challenging to examine in vivo due to its delicate subcortical structures. Previous attempts to locate subcortical auditory nuclei using fMRI responses to sounds are not applicable to patients with profound hearing loss as no auditory brainstem responses can be detected in these individuals, making it impossible to capture corresponding blood oxygen signals in fMRI. In this study, we developed a new pipeline for mapping the auditory pathway using structural and diffusional MRI. We used a fixel-based approach to investigate the structural development of the auditory-language network for profound SNHL children with normal peripheral structure and those with IEM&CND under 6 years old. Our findings indicate that the language pathway is more sensitive to peripheral auditory condition than the central auditory pathway, highlighting the importance of early intervention for profound SNHL children to provide timely speech inputs. We also propose a comprehensive pre-surgical evaluation extending from the cochlea to the auditory-language network, showing significant correlations between age, gender, Cn.VIII median contrast value, and the language network with post-implant qualitative outcomes.

With the rapid development of China’s economy and society, the core of national competitiveness has shifted from material elements to talents, systems, and innovation. Ultimately, it is a talent problem, that is, the problem of improving population quality. Only by striving to improve the quality of the population can we leverage our strong advantages in human resources and transform China from a populous country to a human capital powerhouse. Early childhood development and education are important ways and key links to improve population quality. This paper adopts literature research, empirical analysis, and quantitative analysis methods to conduct a comparative analysis of education programs in Eastern and Western countries around the topic of early childhood development education. The results indicate that the early childhood education and care (ECEC) policies and programs in Western countries have similar origins, both aimed at better protecting children, providing early education to children with special needs, and ensuring the social participation of mothers in the labor force. Although there are similarities in the formulation and implementation of program goals and policies, there are significant differences in other aspects. However, China’s early education faces problems such as insufficient local financial support, high costs, unequal access to opportunities, and significant differences in the quality of services. In the future, it is necessary to increase investment in early childhood development education, and the whole society should participate and carry out early childhood development education together.

It is generally believed that early childhood education primarily takes place in early education in-stitutions, where parents receive training to support their child’s education. Additionally, children’s literature is diverse, with a rich history and various genres. However, there is a lack of research regarding the influ-ence of the family environment and children’s literature on early childhood education, particularly in terms of quantifying this impact. To address this gap in knowledge, this study investigates the effects of the family environment and children’s literature on early childhood education. Specifically, the early childhood educa-tion group is divided into two categories: a parental guardianship group and an others guardianship group, depending on the relationship between the person receiving training from the parent school and the child. The study compares the developmental quotient, height, and weight of children in each group. Additionally, three types of children’s literature commonly used in kindergartens (nursery rhymes, children’s films, and picture book stories) are selected to analyze their educational value for children. The results indicate that early education is crucial for children’s physical and mental development, and parents should receive train-ing in different groups based on their role as guardians. Furthermore, children’s literature can enhance chil-dren’s perception of beauty and contribute to their emotional, linguistic, intellectual, and social development.

By using image analysis technology and automatic control technology, the artificial intelligence technology was applied to the detection of unsound wheat kernels. The automatic, rapid and nondestructive detection instrument for unsound wheat kernels was developed. Through the verification of accuracy, repeatability, stability, difference between two instruments and other related performance parameters, the results showed that the instrument had stable performance. The accuracy, repeatability, stability and difference between two instruments met the requirements of industry standards. The operation was simple, and the detection speed was fast. It can overcome the problems of strong subjectivity, poor repeatability and poor inspection consistency among different personnel with manual checking, achieving the automatic and rapid nondestructive testing of unsound wheat kernels, and meeting the testing demand of grain collection and storage enterprises, processing enterprises and inspection agencies.

The polyphenols and antioxidant activities of different mango cultivars were studied. Polyphenols from four commercial mango (Ivory, Yu, Zihua and Sannian) mango kernels were extracted, determined and analyzed statistically. The results showed that mango kernel contained abundant polyphenolic compounds and had good antioxidant activity. Among them, the content of polyphenol in Zihua mango kernel was the highest and its antioxidant activity was the strongest, followed by Ivory mango kernel and Sannian mango kernel, and that in Yu mango kernel was the worst. There were great differences in the extracts of mango kernels among the four cultivars, which were easy to distinguish, and there was a positive correlation between the determination indexes. Among them, total phenols and hydrolyzed tannins were significantly correlated with in vitro antioxidant activities (P

Polyphenols and dietary fiber can form complexes through their interactions. In order to investigate the interaction mechanism between polyphenols and dietary fibers, and the structure and morphology of complexes formed by them, this paper selected epigallocatechin gallate and oat β-glucan as the raw materials for the preparation of the complexes and their structural characterization. The results indicated that the formation of the complex of EGCG and oat β-glucan was related to the concentration and pH of EGCG, EGCG and oat β-glucan could form a complex with a particle size of 1.7 μm and a relatively uniform particle size (dispersion coefficient 0.38) in an aqueous solution with a mass ratio of 0.8:1 and pH5. Through transmission electron microscopy, the formation of regular spherical particles between EGCG and BG were clearly observed. Isothermal Titration Calorimetry (ITC) measurement was used to characterize the EGCG-BG complex. The binding mechanism at 25 °C clearly provided that the binding between EGCG and BG were mainly non-covalent interaction (such as hydrogen bonding and hydrophobic interaction). The above experimental results could indicate that EGCG and BG could spontaneously form a complex through non-covalent interactions. In summary, the findings of this study would provide a theoretical reference and research basis for the use of different polyphenol-oat β-glucan complexes as functional food ingredients or as bioactive materials.

Benzylisoquinoline alkaloids (BIAs) are a large family of plant natural products with important pharmaceutical applications. Sinomenium acutum is a medicinal plant from the Menispermaceae family and has been used to treat rheumatoid arthritis for hundreds of years. Sinomenium acutum contains more than 50 BIAs, and sinomenine is a representative BIA from this plant. Sinomenine was found to have preventive and curative effects on opioid dependence. Despite the broad applications of S. acutum, investigation on the biosynthetic pathways of BIAs from S. acutum is limited. In this study, we comprehensively analyzed the transcriptome data and BIAs in the root, stem, leaf, and seed of S. acutum. Metabolic analysis showed a noticeable difference in BIA contents in different tissues. Based on the study of the full-length transcriptome, differentially expressed genes, and weighted gene co-expression network, we proposed the biosynthetic pathways for a few BIAs from S. acutum, such as sinomenine, magnoflorine, and tetrahydropalmatine, and screened candidate genes involved in these biosynthesis processes. Notably, the reticuline epimerase (REPI/STORR), which converts (S)-reticuline to (R)-reticuline and plays an essential role in morphine and codeine biosynthesis, was not found in the transcriptome data of S. acutum. Our results shed light on the biogenesis of the BIAs in S. acutum and may pave the way for the future development of this important medicinal plant.

Abstract Background Rubiginones belong to the angucycline family of aromatic polyketides, and they have been shown to potentiate the vincristine (VCR)-induced cytotoxicity against VCR-resistant cancer cell lines. However, the biosynthetic gene clusters (BGCs) and biosynthetic pathways for rubiginones have not been reported yet. Results In this study, based on bioinformatics analysis of the genome of Streptomyces sp. CB02414, we predicted the functions of the two type II polyketide synthases (PKSs) BGCs. The rub gene cluster was predicted to encode metabolites of the angucycline family. Scale-up fermentation of the CB02414 wild-type strain led to the discovery of eight rubiginones, including five new ones (rubiginones J, K, L, M, and N). Rubiginone J was proposed to be the final product of the rub gene cluster, which features extensive oxidation on the A-ring of the angucycline skeleton. Based on the production profiles of the CB02414 wild-type and the mutant strains, we proposed a biosynthetic pathway for the rubiginones in CB02414. Conclusions A genome mining strategy enabled the efficient discovery of new rubiginones from Streptomyces sp. CB02414. Based on the isolated biosynthetic intermediates, a plausible biosynthetic pathway for the rubiginones was proposed. Our research lays the foundation for further studies on the mechanism of the cytochrome P450-catalyzed oxidation of angucyclines and for the generation of novel angucyclines using combinatorial biosynthesis strategies.

According to the requirements of GB/T 15000—2008 《Directives for the work of reference materials preparation》, the method of preparing reference materials for determination of wheat flour quality curve- stability time is established. High quality wheat flour, fully mixed and packed and without any additives, is used as raw materials. The uniformity and stability test and fixed value analysis of the stability time of the samples are carried out by Farinograph. The results show that the reference materials have good uniformity and stability under the storage condition with the temperature of 0 ℃ to 10 ℃ for 24 months. A cooperative certification is conducted with 11 qualified laboratories. The certification result of the reference material is 10.3 min and the expanded uncertainty is 0.6. The reference material conform to the technical requirements of the national standard sample development guidelines and can be used for the verification of wheat flour stability time test method and Farinograph, and it also has applications in the level assessment of laboratory personnel and the quality control of the detection process.

Bacteria could survive stresses by a poorly understood mechanism that contributes to the emergence of bacterial persisters exhibiting multidrug tolerance (MDT). Recently, Pseudoalteromonas rubra prpAT module was found to encode a toxin PrpT and corresponding cognate antidote PrpA. In this study, we first reported multiple individual and complex structures of PrpA and PrpT, which uncovered the high-resolution three-dimensional structure of the PrpT:PrpA2:PrpT heterotetramer with the aid of size exclusion chromatography-multi-angle light scattering experiments (SEC-MALS). PrpT:PrpA2:PrpT is composed of a PrpA homodimer and two PrpT monomers which are relatively isolated from each other and from ParE family. The superposition of antitoxin monomer structures from these structures highlighted the flexible C-terminal domain (CTD). A striking conformational change in the CTDs of PrpA homodimer depolymerized from homotetramer was provoked upon PrpT binding, which accounts for the unique PrpT-PrpARHH mutual interactions and further neutralizes the toxin PrpT. PrpA2–54-form I and II crystal structures both contain a doughnut-shaped hexadecamer formed by eight homodimers organized in a cogwheel-like form via inter-dimer interface dominated by salt bridges and hydrogen bonds. Moreover, PrpA tends to exist in solution as a homodimer other than a homotetramer (SEC-MALS) in the absence of flexible CTD. Multiple multi-dimers, tetramer and hexamer included, of PrpA2–54 mediated by the symmetric homodimer interface and the complicated inter-dimer interface could be observed in the solution. SEC-MALS assays highlighted that phosphate buffer (PB) and the increase in the concentration appear to be favorable for the PrpA2–54 oligomerization in the solution. Taken together with previous research, a model of PrpA2–54 homotetramer in complex with prpAT promoter and the improved mechanism underlying how PrpTA controls the plasmid replication were proposed here.

The receptor-binding domain (RBD) and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) play a crucial role in the entry and replication of viral particles, and co-targeting both of them could be an attractive approach for the treatment of SARS-CoV-2 infection by setting up a “double lock” in the viral lifecycle. However, few dual RBD/Mpro-targeting agents have been reported. Here, four novel RBD/Mpro dual-targeting peptides, termed as MRs 1-4, were discovered by an integrated virtual screening scheme combining molecular docking-based screening and molecular dynamics simulation. All of them possessed nanomolar binding affinities to both RBD and Mpro ranging from 14.4 to 39.2 nM and 22.5–40.4 nM, respectively. Further pseudovirus infection assay revealed that the four selected peptides showed >50% inhibition against SARS-CoV-2 pseudovirus at a concentration of 5 µM without significant cytotoxicity to host cells. This study leads to the identification of a class of dual RBD/Mpro-targeting agents, which may be developed as potential and effective SARS-CoV-2 therapeutics.

Cuproptosis is a newly discovered new mechanism of programmed cell death, and its unique pathway to regulate cell death is thought to have a unique role in understanding cancer progression and guiding cancer therapy. However, this regulation has not been studied in SKCM at present. In this study, data on Skin Cutaneous Melanoma (SKCM) patients were downloaded from the TCGA database. We screened the genes related to cuproptosis from the published papers and confirmed the lncRNAs related to them. We applied Univariate/multivariate and LASSO Cox regression algorithms, and finally identified 5 cuproptosis-related lncRNAs for constructing prognosis prediction models (VIM-AS1, AC012443.2, MALINC1, AL354696.2, HSD11B1-AS1). The reliability and validity test of the model indicated that the model could well distinguish the prognosis and survival of SKCM patients. Next, immune microenvironment, immunotherapy analysis, and functional enrichment analysis were also performed. In conclusion, this study is the first analysis based on cuproptosis-related lncRNAs in SKCM and aims to open up new directions for SKCM therapy.

Abstract Background Adult stem cells play an essential role in adult organ physiology and tissue repair and regeneration. While much has been learnt about the property and function of various adult stem cells, the mechanisms of their development remain poorly understood in mammals. Earlier studies suggest that the formation of adult mouse intestinal stem cells takes place during the first few weeks after birth, the postembryonic period when plasma thyroid hormone (T3) levels are high. Furthermore, deficiency in T3 signaling leads to defects in adult mouse intestine, including reduced cell proliferation in the intestinal crypts, where stem cells reside. Our earlier studies have shown that protein arginine methyltransferase 1 (PRMT1), a T3 receptor coactivator, is highly expressed during intestinal maturation in mouse. Methods We have analyzed the expression of PRMT1 by immunohistochemistry and studied the effect of tissue-specific knockout of PRMT1 in the intestinal epithelium. Results We show that PRMT1 is expressed highly in the proliferating transit amplifying cells and crypt base stem cells. By using a conditional knockout mouse line, we have demonstrated that the expression of PRMT1 in the intestinal epithelium is critical for the development of the adult mouse intestine. Specific removal of PRMT1 in the intestinal epithelium results in, surprisingly, more elongated adult intestinal crypts with increased cell proliferation. In addition, epithelial cell migration along the crypt-villus axis and cell death on the villus are also increased. Furthermore, there are increased Goblet cells and reduced Paneth cells in the crypt while the number of crypt base stem cells remains unchanged. Conclusions Our finding that PRMT1 knockout increases cell proliferation is surprising considering the role of PRMT1 in T3-signaling and the importance of T3 for intestinal development, and suggests that PRMT1 likely regulates pathways in addition to T3-signaling to affect intestinal development and/or homeostasis, thus affecting cell proliferating and epithelial turn over in the adult.

Although listed as endocrine disruptor compounds, atrazine (ATZ) is still used in large quantities in agricultural production. Here, alfalfa seedling was cultivated in hydroponic media to investigate the toxic effects of ATZ on alfalfa and accumulation of ATZ in tissues of different plant parts. Alfalfa had a strong upward translocation ability to ATZ. The stress response of alfalfa under ATZ stress was studied using metabolomic and transcriptomic techniques. S-adenosylmethionine, glutathione, 3-mercaptopyruvic acid, ornithine, and aminopropylcadaverine were significantly increased by ATZ in pathways mtr00270 and mtr00480. Several genes of cysteine synthase and spermidine synthase were significantly up-regulated by ATZ induction. They may be markers and genes with potential physiological functions of alfalfa in response to ATZ stress. In addition, using high resolution mass spectrometry, a total of five ATZ metabolites secreted from alfalfa roots were detected. Among them, acetylated deisopropylated ATZ was discovered for the first time. Hydroxylated ATZ and acetylated deethylated ATZ were more readily excreted by the root system. This study not only provides potential genes for the construction of engineering plants to remediate ATZ-contaminated soil, but also provides monitoring objects for the ecological research of ATZ metabolites.

ObjectiveThis meta-analysis comprehensively evaluated the association between hypertensive disorders in pregnancy (HDP) and the risk of developing chronic hypertension and the associations between specific types of HDP, including preeclampsia (PE) and gestational hypertension (GH), and the risk of developing chronic hypertension.DesignSystematic review and meta-analysis.Data SourcesThe PubMed, Embase and Cochrane Library databases were searched from inception to August 20, 2021.MethodsDepending on heterogeneity, the combined odds ratio (OR) of the 95% confidence interval (CI) was obtained with a random-effects or fixed-effects model. We used meta-regression analysis to explore the sources of heterogeneity. We analyzed the OR value after adjusting for age and BMI at recruitment, prepregnancy BMI, age at first delivery, and other factors. Additionally, we evaluated the results of the subgroup analysis by the year of publication (< 2016, ≥ 2016), study design, sample size (< 500, ≥ 500), region (North and South America, Europe, and other regions) and NOS score (< 7, ≥ 7).ResultsOur systematic review and meta-analysis comprehensively explored the relationships between HDP, GH, and PE and chronic hypertension. Twenty-one articles that included 634,293 patients were included. The results of this systematic review and meta-analysis suggested that women with a history of HDP are almost 3.6 times more likely to develop chronic hypertension than those without a history of HDP, women with a history of GH are almost 6.2 times more likely to develop chronic hypertension than those without a history of GH, and women with a history of PE are almost 3.2 times more likely to develop chronic hypertension than those without a history of PE. In addition, we further calculated the probability of developing chronic hypertension among patients with HDP or PE after adjusting for age and BMI at recruitment, prepregnancy BMI, age at first delivery, and other factors. The results suggested that women with a history of HDP are almost 2.47 times more likely to develop chronic hypertension than those without a history of HDP and that women with a history of PE are almost 3.78 times more likely to develop chronic hypertension than those without a history of PE. People in Asian countries are more likely to develop chronic hypertension after HDP or PE, while American people are not at high relative risk.ConclusionThese findings suggest that HDP, GH, and PE increase the likelihood of developing chronic hypertension. After adjustment for age and BMI at recruitment, prepregnancy BMI, age at first delivery, and other factors, patients with HDP or PE were still more likely to develop chronic hypertension. HDP may be a risk factor for chronic hypertension, independent of other risk factors. GH and PE, as types of HDP, may also be risk factors for chronic hypertension.Systematic Review Registration[www.ClinicalTrials.gov], identifier [CRD42021238599].

Rice protein is a high-quality plant-based protein source that is gluten-free, with high biological value and low allergenicity. However, the low solubility of rice protein not only affects its functional properties such as emulsification, gelling, and water-holding capacity but also greatly limits its applications in the food industry. Therefore, it is crucial to modify and improve the solubility of rice protein. In summary, this article discusses the underlying causes of the low solubility of rice protein, including the presence of high contents of hydrophobic amino acid residues, disulfide bonds, and intermolecular hydrogen bonds. Additionally, it covers the shortcomings of traditional modification methods and the latest compound improvement methods, compares various modification methods, and puts forward the best sustainable, economical, and environmentally friendly method. Finally, this article lists the uses of modified rice protein in dairy, meat, and baked goods, providing a reference for the extensive application of rice protein in the food industry.

This study investigated the effects of drying methods (hot air drying (HAD), microwave vacuum drying (MVD), and vacuum freeze drying (VFD)) on the rehydration performance (RP) of dried Lanzhou lily scales (LLS). Rehydration rate and water migration showed that MVD had the best RP, followed by VFD, while HAD had the worst. The results of additional morphology observation using scanning electron microscopy (SEM) and micro X-ray computed tomography (CT) imaging showed that both MVD and VFD created more channels in more porous structures, which facilitated their better RP than that by HAD. The results also revealed the spatial structure diversity (including pores, channels size, and internal network) of each dried Lanzhou lily scale group. In addition, studies analyzed how drying techniques affected the physiochemical properties of lily starch, including its water solubility, pasting profiles, and starch particle morphology. The findings indicated that when MVD was in operation, partial gelatinization in lily starch was brought about by thermal effects, allowing MVDS crystals to change from B-type to V-type and causing MVDS to have better water absorption ability. Consequently, despite the fact that MVD’s desiccated lilies have a lower porous structure and thinner channels than VFD’s, MVD has a higher RP than VFD.

Ultra-high-pressure jet processing (UHPJ) is a new non-thermal processing technique that can be employed for the homogenization and the sterilization of dairy products. However, the effects on dairy products are unknown when using UHPJ for homogenization and sterilization. Thus, this study aimed to investigate the effects of UHPJ on the sensory and curdling properties of skimmed milk and the casein structure in skimmed milk. Skimmed bovine milk was treated with UHPJ using different pressures (100, 150, 200, 250, 300 MPa) and casein was extracted by isoelectric precipitation. Subsequently, the average particle size, Zeta potential, contents of free sulfhydryl and disulfide bonds, secondary structure, and surface micromorphology were all used as evaluation indicators to explore the effects of UHPJ on the structure of casein. The results showed that with an increase of pressure, the free sulfhydryl group content changed irregularly, while the disulfide bond content increased from 1.085 to 3.0944 μmol/g. The content of α-helix and random coil in the casein decreased, while the β-sheet content increased at 100, 150, 200 MPa pressure. However, treatment with higher pressures of 250 and 300 MPa had the opposite effect. The average particle size of the casein micelles first decreased to 167.47 nm and then increased up to 174.63 nm; the absolute value of Zeta potential decreased from 28.33 to 23.77 mV. Scanning electron microscopy analysis revealed that the casein micelles had fractured into flat, loose, porous structures under pressure instead of into large clusters. After being ultra-high-pressure jet-processed, the sensory properties of skimmed milk and its fermented curd were analyzed concurrently. The results demonstrated that UHPJ could alter the viscosity and color of skimmed milk, shortening curdling time from 4.5 h to 2.67 h, and that the texture of the curd fermented with this skimmed milk could be improved to varying degrees by changing the structure of casein. Thus, UHPJ has a promising application in the manufacture of fermented milk due to its ability to enhance the curdling efficiency of skimmed milk and improve the texture of fermented milk.

Abstract The purpose of this article was to use finite element analysis (FEA) to study the relationship of tibial tunnel (TT) with fracture pattern and implants. A computed tomography scan of full-length tibia and fibula was obtained. Models were built after three-dimensional reconstruction. The corresponding plates and screws were constructed and assembled together with fracture models. FEA was performed and contourplots were output. The Von Mises stresses of nodes and displacements of elements were extracted. Student’s t test was used to compare the values of Von Mises stresses and displacements between corresponding models. Differences in Von Mises stresses and displacements of fragments and implants between models with and without TT were nearly all statistically significant. However, the displacements of fragments and implants for all models were

Background: Preeclampsia (PE) is a serious risk to the health of pregnant women and fetuses during pregnancy, and there is no effective treatment for this condition. Although many reports have confirmed the therapeutic effects of peptides in diseases, the role of peptides in PE remains poorly understood.Methods: A differentially expressed peptide in PE (AEDPPE) is derived from heat-shock protein beta-1 (HSPB1), amino acids 100 to 109 (DVNHFAPDEL), which we identified in a previous study. We synthesized AEDPPE and investigated its effect on HTR-8/SVneo cell function using a Cell Counting Kit-8, flow cytometric assay, and Transwell and wound-healing assays. Quantitative reverse transcription-PCR and ELISA were used to determine cytokine expression. Pull-down assay, mass spectrometry, Western blot analysis, and immunofluorescence were used to explore the potential targets and signaling pathways regulated by AEDPPE. Finally, we assessed the effect of AEDPPE in the lipopolysaccharide (LPS)-induced PE-like rat model.Results: AEDPPE significantly promoted the migration and invasion of HTR-8/SVneo cells, and it decreased the expression of interleukins 1 beta (IL-1β), interleukin 6 (IL-6), and interleukin 8 (IL-8). These functions performed by AEDPPE remained evident after injury to HTR-8/SVneo cells with tumor necrosis factor-alpha (TNF-α), and AEDPPE reversed the elevated sFlt-1/PlGF ratio induced by TNF-α. AEDPPE may exert these biological effects by binding to heat-shock protein 90β (HSP 90β) and, thus, affect the NF-κB signaling pathway. In an LPS-induced PE-like rat model, AEDPPE significantly improved PE symptoms and fetal rat outcomes.Conclusion: Our study showed that AEDPPE enhanced trophoblast migration and invasion and reduced inflammatory cytokine expression, and we hypothesized that these actions involved the NF-κB signaling pathway. The use of AEDPPE may thus develop into a novel modality in the treatment of PE.

The CoSiB/Pd multilayers with MgO/Pd underlayer were deposited by magnetron sputtering technique on the glass substrate. The effect of MgO underlayer's thickness t on perpendicular magnetic anisotropy of CoSiB/Pd multilayer was studied, and the thermal stability of multilayers with MgO/Pd underlayer was analyzed. The results show that the performance of PMA of samples improves due to the introduction of the MgO in the bottom layer through the analysis of anomalous Hall effect of samples, when the thickness t of MgO is 3.5 nm, the squareness of the sample is the best. The hysteresis loops of the best sample MgO(3.5 nm)/Pd(3 nm)/[CoSiB(0.5 nm)/Pd(0.8 nm)]2/Ta(2 nm) is tested, and the effective magnetic anisotropy constant(Keff) of the sample reaches 2.0×105 J/m3. The thermal stability analysis shows that the Keff reaches the maximum value 2.6×105 J/m3 at the annealing temperature of 200℃; the sample can still maintain good PMA performance, when the annealing temperature reaches 400℃.

The purpose of this study was to screen a bronchodilator from old drugs and elucidate the underlying mechanism. Paracetamol (acetaminophen) is a widely used analgesic and antipyretic drug. It has been reported that it inhibits the generation of prostaglandin and histamine, which play roles in asthma. These findings led us to explore whether paracetamol could be a potential bronchodilator. Paracetamol inhibited high K+- and acetylcholine (ACH)-induced precontraction of mouse tracheal and bronchial smooth muscles. Moreover, the ACH-induced contraction was partially inhibited by nifedipine (selective blocker of LVDCCs), YM-58483 (selective inhibitor of store-operated Ca2+ entry (SOCE), canonical transient receptor potential 3 (TRPC3) and TRPC5 channels) and Y-27632 (selective blocker of ROCK, a linker of the Ca2+ sensitization pathway). In single airway smooth muscle cells, paracetamol blocked the currents sensitive to nifedipine and YM-58483, and inhibited intracellular Ca2+ increases. In addition, paracetamol inhibited ACH-induced phosphorylation of myosin phosphatase target subunit 1 (MYPT1, another linker of the Ca2+ sensitization pathway). Finally, in vivo paracetamol inhibited ACH-induced increases of mouse respirator system resistance. Collectively, we conclude that paracetamol inhibits ASM contraction through blocking LVDCCs, SOCE and/or TRPC3 and/or TRPC5 channels, and Ca2+ sensitization. These results suggest that paracetamol might be a new bronchodilator. Keywords: Paracetamol, Airway smooth muscle, Canonical transient receptor potential channel, L-type voltage dependent Ca2+ channel, Store-operated Ca2+ channel, Ca2+ sensitization

In order to meet the requirements of the final quality control and real-time monitoring of rice milling degree during process, a detection technology which was objective and accurate and easy operation was studied by combination of the detection methods of whiteness and residual bran degree of rice.The results showed that the sensitivity of whiteness and residual bran degree could meet the requirements of production process.There was a significant negative linear relationship between whiteness and residual bran degree.In the actual production process, a model could be set between them and with the bran degree used as the final quality control index and the whiteness for real-time monitoring of rice processing.

56 representative wheat flour samples were detected by Farinograph, Extensograph, Alveograph and Glutograph-E respectively, and the relationship between rheological properties such as farinogram properties, tensile properties, alveogram characteristics and glutomatic properties of wheat flour dough were studied.The results showed that there were significant or extremely significant correlations among some indexes of these rheological properties, and some indicators had their own specificity.In order to improve the efficiency of research and detection, the appropriate indicators should be selected to evaluate the quality of wheat and flour according to the purpose of detection and the end-use of food.

Background: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease in China. Tubular injury contributes to the progression of DKD. Our study was conducted to explore the differential gene expression profiles between kidneys from patients with DKD and kidney living donors (LDs).Methods: In total, seven DKD and eighteen LD gene expression profiles from the GSE104954 dataset were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed in R with the limma package. DEGs were uploaded to the g:Profiler online database to explore the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Ingenuity pathway analysis (IPA) was carried out using online IPA software. Weighted gene co-expression network analysis (WGCNA) was performed using the WGCNA R package. By integrating DEGs and genes from the top 1 phenotype-gene associated module, we determined the hub gene. We next tested the hub gene, VCAN, in the GSE30122 dataset. We also validated the versican levels in human kidney tissues, explored immune cell type enrichment using an online database xCell, and investigated the correlation between cell types and VCAN expression.Results: A total of 563 DEGs was identified. A large number of pathways were involved in the immune response process according to the results of GO, KEGG, and IPA. Using WGCNA, we selected the lightcyan module in which genes showed the strongest correlation with the phenotype and smallest P-value. We also identified VCAN as a hub gene by integrating DEG analysis and WGCNA. Versican expression was upregulated in human diabetic kidney tissue. Moreover, versican was speculated to play a role in immune injury according to the enrichment of functions and signaling pathways. VCAN transcript levels correlate with the assembly of immune cells in the kidney.Conclusion: Immune processes played an essential role in DKD tubulointerstitium injury. The hub gene VCAN contributed to this process.

Head and neck paragangliomas (HNPGLs) are rare neoplasms that represent difficult treatment paradigms in neurotology. Germline mutations in genes encoding succinate dehydrogenase (SDH) are the cause of nearly all familial HNPGLs. However, the molecular mechanisms underlying tumorigenesis remain unclear. Mutational analysis identified 6 out of 14 HNPGLs harboring clinicopathologic SDH gene mutations. The SDHB gene was most frequently mutated in these patients, and western blot showed loss of SDHB protein in tumors with SDHB mutations. The paraganglioma cell line (PGL-626) was established from a sample that harbored a missense SDHB mutation (c.649C > T). Spectrometric analysis using tandem mass tags identified 151 proteins significantly differentially expressed in HNPGLs compared with normal nerves. Bioinformatics analyses confirmed the high level of enrichment of oxidative phosphorylation and metabolism pathways in HNPGLs. The mitochondrial complex subunits NDUFA2, NDUFA10, and NDUFA4, showed the most significantly increased expression and were localized predominantly in the cytoplasm of PGL-626 cells. The mitochondrial complex I inhibitor metformin exerted dose-dependent inhibitory effects on PGL-626 cells via cooperative down-regulation of NDUFA2, 4, and 10, with a significant decrease in the levels of reactive oxygen species and mitochondrial membrane potential. Further metabolomic analysis of PGL-626 cells showed that metabolites involved in central carbon metabolism in cancer and sphingolipid signaling pathways, pantothenate and CoA biosynthesis, and tryptophan and carbon metabolism were significantly altered after metformin treatment. Thus, this study provides insights into the molecular mechanisms underlying HNPGL tumorigenesis and identifies target correction of metabolic abnormalities as a novel therapeutic approach for this disease.

Aims: Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm, in which relapse due to drug resistance is the main cause for treatment failure and the disease progression. In this study, we aimed to investigate the molecular mechanism of KDM4C-dependent MALAT1/miR-328-3p/CCND2 axis in cytarabine (Ara-C) resistance in the context of AML. Methods: Bioinformatics analysis was performed to predict the targeting relationships among KDM4C, MALAT1, miR-328-3p, and CCND2 in AML, which were validated with chromatin immunoprecipitation and dual-luciferase reporter assay. Methylation-specific polymerase chain reaction was conducted to detect the methylation of MALAT1 promoter. After conducting gain- and loss-of-function assays, we investigated the effect of KDM4C on cell Ara-C resistance. A NOD/SCID mouse model was established to further investigate the roles of KDM4C/MALAT1/miR-328-3p/CCND2 in Ara-C resistant AML cells. Results: KDM4C expression was upregulated in AML. KDM4C upregulation promoted the demethylation in the promoter region of MALAT1 to increase its expression, MALAT1 targeted and inhibited miR-328-3p expression, enhancing the Ara-C resistance of HL-60/A. miR-328-3p targeted and suppressed the expression of CCND2 in HL-60/A to inhibit the Ara-C resistance. Mechanistically, KDM4C regulated miR-328-3p/CCND2 through MALAT1, resulting in Ara-C resistance in AML. Findings in an in vivo xenograft NOD/SCID mouse model further confirmed the contribution of KDM4C/MALAT1/miR-328-3p/CCND2 in the Ara-C resistant AML. Conclusion: Our study demonstrated that KDM4C may up-regulate MALAT1 expression, which decreases the expression of miR-328-3p. The downregulation of miR-328-3p increased the level of CCND2, which induced the Ara-C resistance in AML.

To gain insights into the roles of beneficial PGPR in controlling soil-borne disease, we adopted a metabolomics approach to investigate the beneficial impacts of P. polymyxa NSY50 on cucumber seedling roots under the pathogen of Fusarium oxysporum f. sp. cucumerinum (FOC). We found that NSY50 pretreatment (NSY50 + FOC) obviously reduced the production of reactive oxygen species (ROS). Untargeted metabolomic analysis revealed that 106 metabolites responded to NSY50 and/or FOC inoculation. Under FOC stress, the contents of root osmotic adjustment substances, such as proline and betaine were significantly increased, and dehydroascorbic acid and oxidized glutathione (GSH) considerably accumulated. Furthermore, the contents of free amino acids such as tryptophan, phenylalanine, and glutamic acid were also significantly accumulated under FOC stress. Similarly, FOC stress adversely affected glycolysis and the tricarboxylic acid cycles and transferred to the pentose phosphate pathway. Conversely, NSY50 + FOC better promoted the accumulation of α-ketoglutaric acid, ribulose-5-phosphate, and 7-phosphosodiheptanone compared to FOC alone. Furthermore, NSY50 + FOC activated GSH metabolism and increased GSH synthesis and metabolism-related enzyme activity and their encoding gene expressions, which may have improved redox homoeostasis, energy flow, and defense ability. Our results provide a novel perspective to understanding the function of P. polymyxa NSY50, accelerating the application of this beneficial PGPR in sustainable agricultural practices.

Gene expression is mediated by a series of regulatory proteins, i.e., transcription factors. Under different growth conditions, the transcriptional regulation of structural genes is associated with the recognition of specific regulatory elements (REs) in promoter DNA. The manner by which transcription factors recognize distinctive REs is a key question in structural biology. Previous research has demonstrated that Ino2p/Ino4p heterodimer is associated with the transcriptional regulation of phospholipid biosynthetic genes. Mechanistically, Ino2p/Ino4p could specifically recognize the inositol/choline-responsive element (ICRE), followed by the transcription activation of the phospholipid biosynthetic gene. While the promoter DNA sequence for Ino2p has already been characterized, the structural basis for the mutual interaction between Ino2p/Ino4p and their binding interface with promoter DNA remain relatively unexplored. Here, we have determined the crystalline structure of the Ino2pDBD/Ino4pDBD/DNA ternary complex, which highlights some residues (Ino2pHis12/Glu16/Arg20/Arg44 and Ino4pHis12/Glu16/Arg19/Arg20) associated with the sequence-specific recognition of promoter DNA. Our biochemical analysis showed that mutating these residues could completely abolish protein–DNA interaction. Despite the requirement of Ino2p and Ino4p for interprotein–DNA interaction, both proteins can still interact—even in the absence of DNA. Combined with the structural analysis, our in vitro binding analysis demonstrated that residues (Arg35, Asn65, and Gln69 of Ino2pDBD and Leu59 of Ino4pDBD) are critical for interprotein interactions. Together, these results have led to the conclusion that these residues are critical to establishing interprotein–DNA and protein–DNA mutual interactions.

Placenta-specific protein 9 (PLAC9) is a putative secretory protein that was initially identified in the placenta and is involved in cell proliferation and motility. Bioinformatics analyses revealed that PLAC9 is repressed in lung cancers (LCs), especially lung adenocarcinomas, compared to that in the paired adjacent normal tissues, indicating that PLAC9 might be involved in the pathogenesis of pulmonary diseases. To investigate the potential role of PLAC9 in the abnormal reprogramming of airway epithelial cells (AECs), a key cause of pulmonary diseases, we constructed a stable PLAC9-overexpressing human bronchial epithelial cell line (16HBE-GFP-Plac9). We utilized the proteomic approach isobaric tag for relative and absolute quantification (iTRAQ) to analyze the effect of PLAC9 on cellular protein composition. Gene ontology (GO) and pathway analyses revealed that GO terms and pathways associated with cell proliferation, cell cycle progression, and cell motility and migration were significantly enriched among the proteins regulated by PLAC9. Our in vitro results showed that PLAC9 overexpression reduced cell proliferation, altered cell cycle progression, and increased cell motility, including migration and invasion. Our findings suggest that PLAC9 inhibits cell proliferation through S phase arrest by altering the expression levels of cyclin/cyclin-dependent kinases (CDKs) and promotes cell motility, likely via the concerted actions of cyclins, E-cadherin, and vimentin. Since these mechanisms may underlie PLAC9-mediated abnormal human bronchial pathogenesis, our study provides a basis for the development of molecular targeted treatments for LCs.

The CoSiB/Pd multilayers with MgO/Pd underlayer were deposited by magnetron sputtering technique on the glass substrate. The effect of MgO underlayer's thickness t on perpendicular magnetic anisotropy of CoSiB/Pd multilayer was studied, and the thermal stability of multilayers with MgO/Pd underlayer was analyzed. The results show that the performance of PMA of samples improves due to the introduction of the MgO in the bottom layer through the analysis of anomalous Hall effect of samples, when the thickness t of MgO is 3.5 nm, the squareness of the sample is the best. The hysteresis loops of the best sample MgO(3.5 nm)/Pd(3 nm)/[CoSiB(0.5 nm)/Pd(0.8 nm)]2/Ta(2 nm) is tested, and the effective magnetic anisotropy constant(Keff) of the sample reaches 2.0×105 J/m3. The thermal stability analysis shows that the Keff reaches the maximum value 2.6×105 J/m3 at the annealing temperature of 200℃; the sample can still maintain good PMA performance, when the annealing temperature reaches 400℃.

Background: The great majority of sporadic vestibular schwannomas (VSs) are due to the mutations of the NF2 gene encoding merlin. Sporadic VSs exhibit variable growth patterns and only a small fraction of the tumours are fast-growing; however, the underlying mechanisms remain undefined. Methods: DNA sequencing and dosage analysis were used to identify the NF2 mutation status in sporadic schwannomas. The expression and sub-cellular localization of merlin and p53-MDM2 were assessed by immunoblotting, qRT-PCR and immunofluorescence. In vitro and in vivo studies were performed to reveal the effects of Nutlin-3 (a MDM2 inhibitor) and/or MG-132(a proteasome inhibitor) on schwannomas. The proliferation of schwannoma cells was assessed by CCK-8 assay, EdU staining and Flow cytometry analysis. Findings: Double genetic hits of NF2 tended to occur in fast-growing tumours, characterized by the absence of merlin. The deregulation of p53-MDM2 was demonstrated to mediate merlin-deficient tumour growth, characterized by a nuclear accumulation of stabilized MDM2, contributing to a nuclear export of p53 for degradation. Nutlin-3 blocked the proliferation of schwannoma cells via a cooperative recovery of merlin and p53, accompanied by the shuttling of both proteins from the cytoplasm to the nucleus. We further demonstrated a difference in the sensitivity to Nutlin-3 between schwannoma cells with and without merlin expression. Nutlin-3 combined with MG-132 narrowed this between-group difference and triggered stronger inhibitory effects on the growth of schwannomas through coordinated reactivation of p53. Interpretation: These findings present treatment strategies directed on the pathogenesis of sporadic schwannomas. Fund: National Natural Science Foundation of China. Keywords: Schwannomas, NF2, p53, Mechanisms, Treatment

Background: It has been reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis. However, their roles in ovarian cancer (OC) remain to be elucidated. The aim of this study was to uncover the function and underlying mechanisms of PCAT6 in OC.Methods: The expression pattern of PCAT6 in OC was analyzed in the GSE137238, GSE143897 and Gene Expression Profile Interactive Analysis (GEPIA) datasets. Kaplan–Meier Plotter online software was used for survival analysis. Loss-of-function assays and gain-of-function assays were used to assess the function of PCAT6 in OC development. Moreover, small-RNA sequencing, bioinformatic analysis, luciferase assays and rescue experiments were carried out to clarify the potential mechanism of PCAT6 in OC.Results: PCAT6 expression was significantly increased in OC tissues and positively correlated with advanced stages and with poor overall survival, progression-free survival and post-progression survival. Knockdown of PCAT6 in A2780 and SKOV3 cells inhibited OC cell proliferation, migration and invasion. In contrast, Overexpression of PCAT6 exerted the opposite effects on OC cells. Notably, PCAT6 bound to miR-143-3p and affected the expression of transforming growth factor (TGF)-β-activated kinase 1 (TAK1). Subsequent rescue assays confirmed that upregulation of miR-143-3p decreased the PCAT6 overexpression-induced promotion of proliferation, migration and invasion. Moreover, downregulation of miR-143-3p reversed the PCAT6 knockdown-induced inhibition of proliferation, migration, and invasion.Conclusions: Our findings demonstrate that PCAT6 plays an oncogenic role in OC and may be useful as a therapeutic target for OC.

We propose a novel porous-core photonic crystal fiber (PCF) consisting of asymmetrical rectangular air holes in the core and six-ring hexagonal lattice circular air holes in the cladding for achieving low-loss polarization terahertz transmission in a wide frequency range. By assuming TOPAS as the host material, the finite element method (FEM) is used to investigate its properties. The near-zero flattened dispersion of −0.01±0.02 ps/THz/cm is achieved over a frequency range of 1.0–2.0 THz, as well as a high birefringence of 7.1 × 10−2 which can be useful for polarization-maintaining applications. Also, critical parameters such as mode field distribution, effective material loss, confinement loss, and effective mode area are discussed in detail. Further, fabrication possibilities are discussed briefly by comparing recent work on similar waveguide structures.OCIS Codes: 040.2235 (Far infrared or terahertz), 060.4005 (Micro-structured fibers), 060.2420 (Fibers, polarization-maintaining), 160.5470 (Polymers).

An improved instantaneous frequency estimation algorithm for rotating machines based on a kernel-based fuzzy C-means clustering (KFCM) algorithm used in association with a spectral centroid algorithm is proposed in this study. The clustering algorithm is used first to discriminate the time-frequency points from the sources of the reference axis and other points. The discrete time-frequency points related to the instantaneous rotation frequency of the reference axis are then located based on the values of the time-frequency matrix elements; on the basis of these elements, the instantaneous rotation frequency is then estimated using a spectral centroid algorithm. It is demonstrated that this method effectively reduces the effects of interference and noise while achieving higher estimation precision. To validate the proposed method, numerical simulations of multi-component signals and crossover signals are performed. The results of these simulations indicate that the method can realize instantaneous frequency estimation with high precision, even when the numerical responses are contaminated by Gaussian white noise. In addition, when this method is used to analyze the vibration signal of rotating machinery in the situation of a run-up procedure, remarkable speed estimation results are obtained.

Characterized by abnormal smooth muscle contractility and airway inflammation, asthma is one of the most common airway diseases worldwide. Diacerein is a well-known anti-inflammatory drug, widely used in osteoarthritis. In current study, the innovative usage of diacerein in anti-contractile and anti-inflammatory treatment of asthma was studied. In vitro experiments including tension measurement and patch-clamp technique and in vivo experiments including establishment of mice model and measurement of respiratory resistance were applied to explore the role of diacerein in asthma. It turned out that agonist-precontracted mouse airway smooth muscle could be relaxed by diacerein via intracellular and extracellular calcium mobilization which was mediated by switched voltage-dependent L-type Ca2+ channels, non-selective cation channels, large-conductance Ca2+-activated K+ channel, and Na+/Ca2+ exchangers. Furthermore, diacerein could relieve bronchospasm and control airway inflammation in asthmatic mice via reduction of several inflammatory factors. Our studies elucidated the potential therapeutic property of diacerein in asthma treatment and the possible underlying mechanism. It also confirmed that new uses for already-approved drugs could be an important form of innovation.