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Podoplanin (PDPN) promotes platelet aggregation and activation by interacting with C-type lectin-like receptor 2(CLEC-2) on platelets. The interaction between the upregulated PDPN and platelet CLEC-2 stimulates venous thrombosis. PDPN was identified as a risk factor for coagulation and thrombosis in inflammatory processes. Hypercoagulability is defined as the tendency to develop thrombosis according to fibrinogen and/or D dimer levels. Nephrotic syndrome is also considered to be a hypercoagulable state. The aim of this study is to investigate the association of soluble PDPN/CLEC-2 with hypercoagulability in nephrotic syndrome. Thirty-five patients with nephrotic syndrome and twenty-seven healthy volunteers were enrolled. PDPN, CLEC-2 and GPVI concentrations were tested by enzyme-linked immunosorbent assay (ELISA). Patients with nephrotic syndrome showed higher serum levels of PDPN and GPVI in comparison to healthy controls ( P 5.88 ng/ml, the risk of hypercoagulability was significantly increased in nephrotic syndrome (OR = 22.79, 95% CI 5.92-87.69, P

A common strategy for the functional interpretation of genome-wide association study (GWAS) findings has been the integrative analysis of GWAS and expression data. Using this strategy, many association methods (e.g., PrediXcan and FUSION) have been successful in identifying trait-associated genes via mediating effects on RNA expression. However, these approaches often ignore the effects of splicing, which can carry as much disease risk as expression. Compared to expression data, one challenge to detect associations using splicing data is the large multiple testing burden due to multidimensional splicing events within genes. Here, we introduce a multidimensional splicing gene (MSG) approach, which consists of two stages: 1) we use sparse canonical correlation analysis (sCCA) to construct latent canonical vectors (CVs) by identifying sparse linear combinations of genetic variants and splicing events that are maximally correlated with each other; and 2) we test for the association between the genetically regulated splicing CVs and the trait of interest using GWAS summary statistics. Simulations show that MSG has proper type I error control and substantial power gains over existing multidimensional expression analysis methods (i.e., S-MultiXcan, UTMOST, and sCCA+ACAT) under diverse scenarios. When applied to the Genotype-Tissue Expression Project data and GWAS summary statistics of 14 complex human traits, MSG identified on average 83%, 115%, and 223% more significant genes than sCCA+ACAT, S-MultiXcan, and UTMOST, respectively. We highlight MSG's applications to Alzheimer's disease, low-density lipoprotein cholesterol, and schizophrenia, and found that the majority of MSG-identified genes would have been missed from expression-based analyses. Our results demonstrate that aggregating splicing data through MSG can improve power in identifying gene-trait associations and help better understand the genetic risk of complex traits.

Obtaining reliable and detailed energy consumption information about building service (BS) systems is an essential prerequisite for identifying energy-saving potential and improving energy efficiency of a building. Therefore, in recent years, energy sub-metering systems have been widely implemented in public buildings in China. A majority of electrical systems and equipment can be directly metered. However, in actual sub-metering systems, the terminal units of heating, ventilation and air conditioning (HVAC) systems, such as fan coils, air handling units and so on, are often mixed with the lighting-plug circuit. This mismatch between theoretical sub-metering systems and actual electricity supply circuits constitutes a lot of challenges in BS system management and control optimization. This study proposed an indirect method to disaggregate the energy consumption of HVAC terminal units from mixed sub-metering data based on the CART algorithm. This method was demonstrated in two buildings in Shanghai. The case study results show that the weighted mean absolute percentage errors (WMAPE) are within 5% and 15% during working hours in the cooling and heating seasons, respectively.

Solar radiation has important impacts on buildings such as for cooling/heating load forecasting, energy consumption forecasting, and multi-energy complementary optimization. Two types of solar radiation data are commonly used in buildings: radiation data in typical meteorological years and measured radiation data from meteorological stations, both of which are types of historical data. However, it is difficult to predict the hourly global solar radiation, which affects the application of relevant prediction models in practical engineering. Most existing methods for predicting hourly global solar radiation have issues such as difficulty in obtaining input parameters or complex data processing, which limits their practical engineering applications. This study proposed a simplified method to accurately predict the hourly horizontal solar radiation using extraterrestrial solar radiation, weather types, cloud cover, air temperature, relative humidity, and time as the input parameters. The back-propagation network, support vector machine, and light gradient boosting machine (LightGBM) models were used to establish the prediction model, and Shapley additive explanations were used to analyze the relationship between the input variables and the prediction results to simplify the structure of the prediction model. Taking Lanzhou New District in Gansu Province as an example, the results showed that the LightGBM model performed the best, with the root mean square error of 126.1 W/m2. Shapley additive explanations analysis showed that weather type was not a significant factor in the LightGBM model. Therefore, the weather type was removed from the LightGBM model and the root mean square error was 135.2 W/m2. The results showed that extra-terrestrial radiation and limited weather forecast parameters can be used to predict hourly global solar radiation with satisfactory prediction results.

Online customer reviews (OCRs) are the real feelings of customers in the process of using products, which have great reference value for potential customers’ purchase decisions. However, it is difficult for consumers to extract helpful information from very large numbers of OCRs. To support consumers’ purchase decisions, this paper proposes a hybrid method to rank alternative products through OCRs. In this method, we use the fine-grained Bidirectional Encoder Representation from Transformers (BERT) model for aspect-level sentiment analysis (SA) and convert SA results of sub-criteria into a corresponding interval intuitionistic fuzzy number, accurately extracting customer satisfaction in OCRs and reducing the errors caused by different amounts of OCRs. Furthermore, in order to obtain the ranking results of products, the subjective and objective weights are combined to determine weight of feature. Subsequently, an improved interval intuitionistic fuzzy VIKOR method is proposed to rank mobile games. Finally, we conduct a case study and make some comparisons, which show that our method can reduce the complexity of accurately obtaining consumers’ personal preferences and help consumers make more accurate decisions.

Due to the complexity and uncertainty of decision-making circumstances, it is difficult to provide an accurate compensation cost in strategic weight manipulation, making the compensation cost uncertain. Simultaneously, the change in the attribute weight is also accompanied by risk, which brings a greater challenge to manipulators’ decision making. However, few studies have investigated the risk aversion behavior of manipulators in uncertain circumstances. To address this research gap, a robust risk strategic weight manipulation approach is proposed in this paper. Firstly, mean-variance theory (MVT) was used to characterize manipulators’ risk preference behavior, and a risk strategic weight manipulation model was constructed. Secondly, the novel robust risk strategic weight manipulation model was developed based on the uncertainty caused by the estimation error of the mean and covariance matrix of the unit compensation cost. Finally, a case of emergency facility location was studied to verify the feasibility and effectiveness of the proposed method. The results of the sensitivity analysis and comparative analysis show that the proposed method can more accurately reflect manipulators’ risk preference behavior than the deterministic model. Meanwhile, some interesting conclusions are revealed.

Bovine lactoferrin (bLf) is a multifunctional glycoprotein and a good candidate for producing diverse bioactive peptides, which are easily lost during over-digestion. Accordingly, the effects of laccase-mediated pectin–ferulic acid conjugate (PF) and transglutaminase (TG) on improving the production of bLf active peptides by in vitro gastrointestinal digestion were investigated. Using ultra-high-performance liquid chromatography tandem mass spectroscopy (UPLC-MS-MS), the digests of bLf alone, PF-encapsulated bLf complex (LfPF), and TG-treated LfPF complex (LfPFTG) produced by conditioned in vitro gastric digestion (2000 U/mL pepsin, pH 3.0, 37 °C, 2 h) were identified with seven groups of active peptide-related fragments, including three common peptides (VFEAGRDPYKLRPVAAE, FENLPEKADRDQYEL, and VLRPTEGYL) and four differential peptides (GILRPYLSWTE, ARSVDGKEDLIWKL, YLGSRYLT, and FKSETKNLL). The gastric digest of LfPF contained more diverse and abundant detectable peptides of longer lengths than those of bLf and LfPFTG. After further in vitro intestinal digestion, two active peptide-related fragments (FEAGRDPYK and FENLPEKADRDQYE) remained in the final digest of LfPFTG; one (EAGRDPYKLRPVA) remained in that of bLf alone, but none remained in that of LfPF. Conclusively, PF encapsulation enhanced the production of bLf active peptide fragments under the in vitro gastric digestion applied. TG treatment facilitated active peptide FENLPEKADRDQYE being kept in the final gastrointestinal digest.

Monkeypox virus is a double-stranded DNA virus species that causes disease in humans and mammals. It is a zoonotic virus belongs the genus Orthopoxviral, the family of Poxviridae, associated with the smallpox virus in many aspects. The first human case of monkeypox was reported throughout the Democratic Republic of Congo in 1970. In April 2022, several cases were recorded in widespread regions of Africa, the Northern and western hemispheres. The current review spotlights taxonomic classification, clinical presentations during infection, and the pathogenicity of the monkeypox virus in humans. Furthermore, the current review also highlights different diagnostics used for virus detection.

Monkeypox is a serious public health issue in tropical and subtropical areas. Antivirals that target monkeypox proteins might lead to more effective and efficient therapy. The F13 protein is essential for the growth and maturation of the monkeypox virus. F13 inhibition might be a viable therapeutic target for monkeypox. The in silico fragment-based drug discovery method for developing antivirals may provide novel therapeutic options. In this study, we generated 800 compounds based on tecovirimat, an FDA-approved drug that is efficacious at nanomolar quantities against monkeypox. These compounds were evaluated to identify the most promising fragments based on binding affinity and pharmacological characteristics. The top hits from the chemical screening were docked into the active site of the F13 protein. Molecular dynamics simulations were performed on the top two probable new candidates from molecular docking. The ligand–enzyme interaction analysis revealed that the C2 ligand had lower binding free energy than the standard ligand tecovirimat. Water bridges, among other interactions, were shown to stabilize the C2 molecule. Conformational transitions and secondary structure changes in F13 protein upon C2 binding show more native three-dimensional folding of the protein. Prediction of pharmacological properties revealed that compound C2 may be promising as a drug candidate for monkeypox fever. However, additional in vitro and in vivo testing is required for validation.

Occupancy, which refers to the occupant count in this paper, is one of the main factors affecting the energy consumption of commercial buildings. It is important for both building managers and energy simulation engineers to understand how an entire building’s energy consumption varies with different occupancy levels in the process of building automation systems or in assessments of building performance with benchmarking lines. Because commercial buildings usually have large scales, complex layouts and a large number of people, it is a challenge to simulate the relationships between an entire building’s energy consumption and occupancy. This study proposes a fast method for calculating the influence of occupancy on the energy consumption of commercial buildings with different building layouts and existing occupancies. Other occupant behaviors, such as the opening of windows and adjustment of shading devices, are comprehensively reflected in two basic building parameters: the balance point temperature and the total heat transmission coefficient of the building. This new method can be easily used to analyze how building energy varies with occupancy without a physical building’s energy model. An office building in Shanghai is taken as a case study to validate the proposed method. The results show that the coefficient of determination R2 between the calculated value and actual value is 0.86, 0.8 and 0.71 for lighting, cooling and heating energy, respectively, which is suitable in engineering applications.

Autophagy is an evolutionarily conserved cellular recycling process that maintains cellular homeostasis. Despite extensive research in endocrine contexts, the role of autophagy in ovarian and testicular steroidogenesis remains elusive. The significant role of autophagy in testosterone production suggests potential treatments for conditions like oligospermia and azoospermia. Further, influence of autophagy in folliculogenesis, ovulation, and luteal development emphasizes its importance for improved fertility and reproductive health. Thus, investigating autophagy in gonadal cells is clinically significant. Understanding these processes could transform treatments for endocrine disorders, enhancing reproductive health and longevity. Herein, we provide the functional role of autophagy in testicular and ovarian steroidogenesis to date, highlighting its modulation in testicular steroidogenesis and its impact on hormone synthesis, follicle development, and fertility therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Influenza A(H1N1)pdm09 viruses have undergone rapid evolution, and in recent years the complementary and antagonistic effects of HA and NA have gathered more attentions; however, the effects of co-occurring mutations in HA and NA on the patients’ clinical characteristics are still poorly understood. In this study, we analyzed molecular epidemiology and evolution of A(H1N1) pdm09, explored co-occurring mutations of HA and NA, and investigated effect of co-occurring mutations on patients’ clinical features. Methods A(H1N1)pdm09 was confirmed by reverse transcription-polymerase chain reaction. HA and NA genes were sequenced and phylogenetically analyzed. Clinical characteristics of the co-occurring mutations were analyzed statistically. Results By analyzing the HA and NA gene sequences of 33 A(H1N1)pdm09 viruses during the 2015–2017 influenza season, we found that all the viruses shared high similarities to each other and the HA genes of these viruses exclusively belonged to subclade 6B.1A. Several unreported substitutions in HA and NA proteins were observed, furthermore, co-occurring mutations of HA-V169T, A278S, E508G, D518E and NA-V67I were detected in 30.3% (10/33) A(H1N1)pdm09 virus strains when comparing with vaccine strains A/California/07/2009 and A/Michigan/45/2015 (H1N1). Sore throat was significantly associated with co-occurring mutations in HA and NA of A(H1N1)pdm09 (χ2, P

Circular RNAs (circRNAs) are non-coding single-stranded covalently closed circular RNA, mainly produced by reverse splicing of exons of precursor mRNAs (pre-mRNAs). The characteristics of high abundance, strong specificity, and good stability of circRNAs have been discovered. A large number of studies have reported its various functions and mechanisms in biological events, such as the occurrence and development of cancer. In this review, we focus on the classification, characterization, biogenesis, functions of circRNAs, and the latest advances in cancer research. The development of circRNAs as biomarkers in cancer diagnosis and treatment also provides new ideas for studying circRNAs research.

BackgroundAs a common clinical superficial fungal infection, the diagnosis of onychomycosis relies on clinical features, traditional KOH direct microscopy and fungal culture. In recent years, dermoscopy has been widely used in the diagnosis and treatment of infectious diseases and has provided new options for the diagnosis of onychomycosis.ObjectiveTo evaluate the value of dermoscopy in the clinical diagnosis of onychomycosis and to explore the relationship between each clinical subtype and the dermoscopic pattern.MethodsA retrospective study of 114 cases of clinically suspected onychomycosis was conducted to compare the differences between dermoscopy and fungal pathogenic examination (microscopy and culture) in the diagnostic sensitivity of onychomycosis and to analyze the relationship between nine common dermoscopic modalities and clinical subtypes of onychomycosis.ResultsAmong the 114 proposed patients, 87 nails with positive fluorescent staining microscopy and/or positive fungal cultures were diagnosed as onychomycosis. The sensitivity and specificity of dermatoscopy, using the mycological findings as a reference, were 86.21 and 33.33%, respectively. The incidence of common dermatoscopic patterns in the 87 nails with confirmed onychomycosis was as follows: white flocculation in 76 cases (87.35%), longitudinal nail pattern in 72 cases (82.76%), jagged changes in the distal nail plate in 69 cases (79.31%) and yellow staining in 46 cases (52.87%), these four patterns were more commonly seen in the distal lateral subungual onychomycosis and total dystrophic onychomycosis, but there was no statistical difference in the positive dermatoscopic pattern between these two types (P > 0.05).ConclusionDermoscopy can be an important aid in the diagnosis of onychomycosis, especially when fungal microscopy or culture is not appropriate, but this method is still not a substitute for fungal microscopy and culture.

Abstract Background Numerous studies have clarified that family socioeconomic status (SES) is positively associated with health. However, the mechanism of family SES on health needs to be further investigated from a social epidemiological perspective. This study aims to analyze the relationships among family SES, family social capital, and adult general health and tests whether gender-based differences exist in the relationship between family social capital and general health. Methods A cross-sectional survey was used to collect data from 4187 representative households in six Chinese provinces. Family SES was conceptualized based on household income, family education, and family occupational status. Family social capital was measured by using family cohesion and health-related family support. General health was assessed by using five general health perception items of the Health Survey Short Form. Structural equation modeling (SEM) was applied to examine the relationships among family SES, family social capital, and general health, and a linear regression model was used to test gender-based differences. Results The SEM showed that the direct effects of family SES, family cohesion, and health-related family support on health were 0.08 (P 0.05). Conclusions The results provide strong support for the positive association between family SES, family social capital, and adult health. Family intervention programs should focus on establishing a harmonious family relationship to mobilize family support, particularly for the families with low cohesion and low SES.

Abstract Background Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingolipids and produced by sphingosine kinases (SphK1 and SphK2). SphK1/S1P pathway is implicated in the progression of chronic kidney disease. However, the role of SphK1/S1P pathway in renal injury in hypertension has not been reported. This study tested the hypothesis that SphK1/S1P pathway mediates the kidney damage in DOCA-salt hypertensive mice. Methods Male wild type (WT) C57BL6 and SphK1 knockout (KO) mice were subjected to unilateral nephrectomy, subcutaneous implant containing 50 mg of deoxycorticosterone acetate (DOCA) and 1% NaCl drinking water for 7 weeks. At the end of experiments, blood pressure data, 24 h urine and kidney samples were collected. Renal mRNA levels of SphK1 were measured by real-time RT-PCR. Markers for fibrogenesis and immune cell infiltration in kidneys were detected using Western blot and immunohistochemistray analysis, respectively. The glomerular morphological changes were examined in kidney tissue slides stained with Periodic-Acid Schiff. Four groups were studied: wild type control (WT-C), WT-DOCA, KO-C and KO-DOCA. Results The renal SphK1 mRNA expression was significantly upregulated in WT-DOCA mice, whereas this upregulation of renal SphK1 mRNA was blocked in KO-DOCA mice. There was no difference in DOCA-salt-induced hypertension between WT and KO mice. The urinary albumin was increased in both DOCA-salt groups. However, the albuminuria was significantly lower in KO-DOCA than in WT-DOCA group. There were increases in glomerulosclerosis indices in both DOCA-salt groups, whereas the increases were also significantly lower in KO-DOCA than in WT-DOCA mice. Renal protein levels of α-smooth muscle actin were upregulated in both DOCA-salt groups, but the increase was significant lower in KO-DOCA than in WT-DOCA group. The increased staining areas of collagen detected by Sirius Red-staining in kidney tissue sections were also attenuated in KO-DOCA compared with WT-DOCA mice. In contrast, the increased infiltration of CD43+ (a T cell marker) or CD68+ (a macrophage marker) cells in DOCA-salt kidneys showed no significant difference between WT-DOCA and KO-DOCA mice. Conclusions SphK1/S1P signaling pathway mediates kidney damage in DOCA-salt hypertensive mice independent of blood pressure and immune modulation.

Invasive Aspergillosis (IA) has increased significantly in recent years in which about 90% is caused by Aspergillus fumigatus, and the mortality rate is on the rise. Its treatment has become a common problem clinically. Calcineurin (CaN) plays an important role in the morphogenesis and toxicity of Aspergillus fumigatus, making it an attractive antifungal target. Although the Calcineurin inhibitors FK506 and cyclosporine A have successfully applied in modern transplantation medicine, the systemic toxic and side effects of the two drugs have greatly limited their clinical antifungal applications. Previous studies have shown that CaN of the Aspergillus fumigatus is localized at the top and division of hyphae, and interactions of CaN with cbpA are closely related to the PxIxIT motif. The functioning of CaN is closely related to the PxIxIT motif. Calcineurin substrates or target proteins such as Crz1, SIm1, SIm2, Hph1, and CbpA all contain similar PxIxIT motifs, and similar motifs are present in the Aspergillus fumigatus KpsF gene sequence. We can find KpsF gene in the Aspergillus fumigatus genome through bioinformatics methods, which contains a similar motif in its sequence. Therefore, we can speculate that this motif may interact with Calcineurin, further illustrate the specific mechanism of pathogenesis of CaN in Aspergillus fumigatus, which will help us to have a deeper understanding of the pathogenesis of invasive aspergillosis and provide new ideas for us. By completing the construction of the Aspergillus fumigatus KpsF gene-deficient strain and over-exp strain, we found that the KpsF gene over-exp strain of Aspergillus fumigatus is significantly different from that of the control strain in morphology, and is different from the cbpA in calcium ion regulation. In the low concentration of Ca2+, KpsF may be involved in the negative feedback regulation of Calcineurin, and this negative feedback regulation is inhibited under the condition of high concentration Ca2+. Keywords: Aspergillus fumigatus, PxIxIT gene, KpsF gene, Calcineurin, Gene mutation

Abstract Rural–urban migration is a defining feature of socio‐economic change in contemporary China. It is estimated that internal migrants in China account for 20% of its population of 1.39 billion, providing manpower to the expanding urban industries. Yet internal migrants have long faced barriers to accessing health and other social services in urban destinations, and the migration process may expose them to novel health risks and inequities. Based on the analysis of policy documents and associated material, this article reviews the historical development of health policy in China in relation to internal migrants, identifying elements of continuity and change in the policy agenda and the ways in which migrants have been framed in policy formulations. Against this background, remaining gaps in the current policy framework and implementation challenges are discussed.

Objective. To explore the features and diagnostic value of computed tomography (CT) imaging in cases of thymic cysts. Methods. A total of 24 cases of the thymic cysts (confirmed by postoperative pathology) were retrospectively analyzed. The location, morphology, and density of the thymic cysts were summarized, and the changes in CT value of the region of interest (ROI) in the thymic cysts between noncontrast enhanced and enhanced chest scans were compared and classified. Results. The average long-axis dimension was 17.50 ± 6.00 mm, the CT value range across the 24 cases was 5–81 HU, and the average CT value of the noncontrast enhanced scans was 39.75 ± 20.66 HU. The CT value in the noncontrast enhanced scan was >20 HU in 79% of the sample cases. The CT value in the ROI of the thymic cysts under enhanced scan showed a significant decrease in 15 cases, a significant increase in 5 cases, and an insignificant change in 4 cases. Conclusion. The CT values of the thymic cysts in the enhanced scans were generally lower than in the noncontrast enhanced scans, which might be a valuable finding for thymic cysts diagnosis.

Recently, the consensus model of group decision-making in uncertain circumstances has received extensive attention. Existing models focus on either minimum cost (maintain the total budget) or maximum utility (improve satisfaction). Based on the minimum cost consensus model, a new multicriteria robust minimum cost consensus model with utility preference is proposed in this paper. Firstly, considering the inherent uncertainty of input data, the unit adjustment cost of experts is described under three robust scenarios. Subsequently, a cost consensus model that expresses the views of decision-makers in a variety of uncertain preference forms such as utility function and Gaussian distribution is proposed. Finally, through the application in emergency decision-making, the cost model and the utility model were compared and analyzed to verify the effectiveness and superiority of the proposed model.

Objective. At present, renal injury caused by sepsis seriously endangers the health of patients. Our paper proposed to study the protective effects of meloxicam (Mel) in sepsis-induced acute kidney injury (SAKI) and the underlying mechanisms. Methods. The in vitro and in vivo models of SAKI were established using lipopolysaccharide (LPS). Mel was injected intraperitoneally at 60 mg/kg into male C57BL/6 mice 4 hours before LPS injection (10 mg/kg). The HK-2 cells were treated with LPS (1 μg/mL) and Mel (40 μM). The renal function and renal pathological changes as well as renal inflammation and apoptosis were detected in SAKI mice. The inflammation and apoptosis of HK-2 cells induced by LPS were also detected. Results. The treatment of Mel significantly decreased the elevated levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in SAKI mice. In addition, the results of HE staining suggested that Mel significantly reduced kidney damage in SAKI mice. Consistently, Mel reduced the expression of LPS-induced kidney injury markers (NGAL and KIM-1). Moreover, LPS induced the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the kidney, which can be reduced by Mel. Furthermore, Mel effectively reduced the number of apoptotic cells and inhibited the expression of proapoptotic-related proteins (cleaved Caspase-3 and Bax) but increased the antiapoptotic-related protein (Bcl-2) in the kidneys of SAKI mice. Mechanistically, Mel inhibited the phosphorylation of P65 but induced the phosphorylation of AKT and the expression of glycoprotein B of nonmetastatic melanoma (GPNMB). However, knocking down GPNMB can eliminate the anti-inflammatory and antiapoptotic effects of Mel. Conclusion. Mel alleviated sepsis-induced kidney injury by inhibiting kidney inflammation and apoptosis via upregulating GPNMB.

PurposeNormative data on the growth and development of the upper airway across the sexes is needed for the diagnosis and treatment of congenital and acquired respiratory anomalies and to gain insight on developmental changes in speech acoustics and disorders with craniofacial anomalies.MethodsThe growth of the upper airway in children ages birth to 5 years, as compared to adults, was quantified using an imaging database with computed tomography studies from typically developing individuals. Methodological criteria for scan inclusion and airway measurements included: head position, histogram-based airway segmentation, anatomic landmark placement, and development of a semi-automatic centerline for data extraction. A comprehensive set of 2D and 3D supra- and sub-glottal measurements from the choanae to tracheal opening were obtained including: naso-oro-laryngo-pharynx subregion volume and length, each subregion's superior and inferior cross-sectional-area, and antero-posterior and transverse/width distances.ResultsGrowth of the upper airway during the first 5 years of life was more pronounced in the vertical and transverse/lateral dimensions than in the antero-posterior dimension. By age 5 years, females have larger pharyngeal measurement than males. Prepubertal sex-differences were identified in the subglottal region.ConclusionsOur findings demonstrate the importance of studying the growth of the upper airway in 3D. As the lumen length increases, its shape changes, becoming increasingly elliptical during the first 5 years of life. This study also emphasizes the importance of methodological considerations for both image acquisition and data extraction, as well as the use of consistent anatomic structures in defining pharyngeal regions.

This study investigated the effects of a novel antibacterial film based on chitosan, carboxymethyl cellulose, sodium alginate, tea polyphenols, ascorbic acid, and tangelo peel extract on the postharvest quality and reactive oxygen species metabolism of tangelo fruit during storage. The composite film significantly reduced the fruit decay rate and weight loss, delayed the reduction in total soluble solids and titratable acidity, and retained fruit firmness and the appearance of tangelo fruit during storage. Furthermore, the composite film effectively reduced the fruit respiration rate, inhibited the increase in cell-membrane permeability, markedly reduced the generation of superoxide anion, hydrogen peroxide, and malondialdehyde, and enhanced the activity of the antioxidant enzymes superoxide dismutase, catalase, and ascorbate peroxidase. The composite film also reduced losses of the nonenzymatic antioxidants ascorbic acid and glutathione. Overall, the chitosan-based composite antibacterial film effectively maintained the quality of tangelo fruit during storage, enhanced ROS scavenging capacity and antioxidant properties, and then reduced the rot rate of postharvest tangelo.

Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Nanotechnology-based medicinal approaches deliver valuable cargos targeting molecular and cellular processes with greater safety, efficacy, and specificity than traditional approaches. CNS diseases include a wide range of brain ailments connected to short- and long-term disability. They affect millions of people worldwide and are anticipated to become more common in the coming years. Nanotechnology-based brain therapy could solve the BBB problem. This review analyzes nanomedicine’s role in medication delivery; immunotherapy, chemotherapy, and gene therapy are combined with nanomedicines to treat CNS disorders. We also evaluated nanotechnology-based approaches for CNS disease amelioration, with the intention of stimulating the immune system by delivering medications across the BBB.

The newly identified porcine Kobuvirus (PKV) has raised concerns owing to its association with diarrheal symptom in pigs worldwide. The process involving the emergence and global spread of PKV remains largely unknown. Here, the origin, genetic diversity, and geographic distribution of PKV were determined based on the available PKV sequence information. PKV might be derived from the rabbit Kobuvirus and sheep were an important intermediate host. The most recent ancestor of PKV could be traced back to 1975. Two major clades are identified, PKVa and PKVb, and recombination events increase PKV genetic diversity. Cross-species transmission of PKV might be linked to interspecies conserved amino acids at 13–17 and 25–40 residue motifs of Kobuvirus VP1 proteins. Phylogeographic analysis showed that Spain was the most likely location of PKV origin, which then spread to pig-rearing countries in Asia, Africa, and Europe. Within China, the Hubei province was identified as a primary hub of PKV, transmitting to the east, southwest, and northeast regions of the country. Taken together, our findings have important implications for understanding the evolutionary origin, genetic recombination, and geographic distribution of PKV thereby facilitating the design of preventive and containment measures to combat PKV infection.

Lung cancer is one of the 10 most common cancers in the world, which seriously affects the normal life and health of patients. According to the investigation report, the 3-year survival rate of patients with lung cancer is less than 20%. Heredity, the environment, and long-term smoking or secondhand smoke greatly promote the development and progress of the disease. The mechanisms of action of the occurrence and development of lung cancer have not been fully clarified. As a new type of gas signal molecule, hydrogen sulfide (H2S) has received great attention for its physiological and pathological roles in mammalian cells. It has been found that H2S is widely involved in the regulation of the respiratory system and digestive system, and plays an important role in the occurrence and development of lung cancer. H2S has the characteristics of dissolving in water and passing through the cell membrane, and is widely expressed in body tissues, which determines the possibility of its participation in the occurrence of lung cancer. Both endogenous and exogenous H2S may be involved in the inhibition of lung cancer cells by regulating mitochondrial energy metabolism, mitochondrial DNA integrity, and phosphoinositide 3-kinase/protein kinase B co-pathway hypoxia-inducible factor-1α (HIF-1α). This article reviews and discusses the molecular mechanism of H2S in the development of lung cancer, and provides novel insights for the prevention and targeted therapy of lung cancer.

We consider an optimization problem on the maximal magnitude of angular acceleration of the output-links of a commercially available center-driven linkage system (CDLS) for vehicle wipers on windshield. The purpose of this optimization is to improve the steadiness of a linkage system without weakening its normal function. Thus this optimization problem is considered under the assumptions that the frame of the fixed links of linkage system is unchanged and that the input-link rotates at the same constant angular speed with its length unchanged. To meet the usual requirements for vehicle wipers on windshield, this optimization problem must be solved subject to 10 specific constraints. We expect that optimizing the maximal magnitude of angular acceleration of the output-links of a linkage system would also be helpful for reducing the amplitudes of sound waves of wiper noise. We establish the motion model of CDLS and then justify this model with ADAMS. We use a “Differential Evolution” type method to search for the minimum of an objective function subject to 10 constraints for this optimization problem. Our optimization computation shows that the maximal magnitude of angular acceleration of both output-links of this linkage system can be reduced by more than 10%.

Background: Circular RNAs (circRNAs) play a key role in regulating the drug resistance of numerous human tumors. However, whether circKRT17 involves in the osimertinib resistance of lung adenocarcinoma (LUAD) remains undetermined. Methods: Relative mRNA/circRNA and protein levels were detected by qRT-PCR and western blotting. Localization of circKRT17 and YAP1 was determined by FISH and immunofluorescence staining. Cell growth and apoptosis were evaluated using colony formation, EdU assays, and flow cytometry. The N6-methyladenosine (m6A) modification was analyzed by MeRIP. The interplay between EIF4A3 and circKRT17 or YAP1 was verified by RNA pull-down or/and RIP assays. Subcutaneous tumor growth was monitored in nude mice, and Ki-67 and TUNEL staining were carried out to evaluate cell proliferation and apoptosis, respectively. Results: CircKRT17 and METTL3 were elevated in osimertinib-insensitive LUAD tissues and cells. Knockdown of circKRT 17 and METTL3 increased the sensitivity of LUAD cells to osimertinib. Knockdown of METTL3 decreased the expression of circKRT17 by inhibiting m6A modification. CircKRT17 promoted the stability and nuclear transportation of YAP1 by recruiting EIF4A3 in LUAD cells. Overexpression of YAP1 abolished the impacts of circKRT17 knockdown on the osimertinib sensitivity of LUAD cells. CircKRT17 knockdown increased the repressive effects of osimertinib on tumor growth in vivo by inhibiting YAP1 signaling. Conclusion: METTL3 initiated the m6A modification of circKRT17, thus promoting osimertinib resistance of LUAD by enhancing YAP1 stability through EIF4A4 recruitment.

Gymnodimines (GYMs) are a group of fast-acting phycotoxins and their toxicological effects on human beings are still unclear due to the lack of sufficiently well-characterized large quantities of purified toxins for toxicology studies. In this study, a certified reference material (CRM) of GYM-A was prepared from the dinoflagellate Karenia selliformis, followed by multi-step chromatography separation and purification. Subsequently, the stability of GYM-A in methanolic media was evaluated at different temperature (−20, 4, and 20 °C) and pH (3, 5, and 7) conditions for 8 months, and the conversion products of GYM-A were explored by liquid chromatography–high resolution mass spectrometry (LC-HRMS). The results show that the stability of GYM-A decreased with increasing temperature and pH values. The GYM-A was stable during storage at −20 °C regardless of pH, but it decreased rapidly (81.8% ± 9.3%) at 20 °C in pH 7 solution after 8 months. Moreover, the concentrations of GYM-A did not significantly change at all temperatures in solutions with pH 3 (p > 0.05). It is recommended that GYM-A should be stored at low temperature (≤−20 °C) and pH (≤3) conditions for long-term storage in aqueous methanolic media. In addition, two conversion products of GYM-A, tentatively named as GYM-K (m/z 540) and GYM-L (m/z 524), were identified in the samples stored at high levels of pH and temperature. Based on the LC-HRMS data, the hypothetical chemical structures of both converting derivatives were proposed. A useful strategy for long-term storage of GYM-A CRM in aqueous methanolic media was suggested and two hypothesized conversion products of GYM-A were discovered in this study.