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Abstract Objectives Good’s syndrome (GS) is a rare secondary immunodeficiency which is characterized by hypogammaglobulinemia and thymoma. This study aims to investigate the expression and distribution of B cells in thymoma tissue, given that B cells had been found to be reduced or absent in peripheral blood or bone marrow. Methods This study retrospectively analyzed thymoma tissues from 5 GS patients at the First Affiliated Hospital of Wenzhou Medical University and Zhejiang Provincial People’s Hospital. Tissues from 20 patients with simple thymoma were used as controls. Immunohistochemistry analyses were performed to detect the markers CD19, CD20, PAX5 and CD138 to evaluate the expression of B cells or plasma cells. Results Compared to the control group, 4 GS patients exhibited a complete absence of B cells in their thymoma tissue, while 1 GS patient exhibited a notable reduction in B cells. The expression levels of CD19, CD20 and PAX5 in the thymoma tissues of GS patients were dramatically lower than those in the control group (0 vs. 85%, 20 vs. 85%, 20 vs. 85%, respectively; P 0.05). Conclusion This is the first report of B cell deficiency in 5 thymoma tissues of GS patients.

Abstract Background Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor–node–metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck–lymph node radiotherapy in patients with NPC. Methods Overall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression. Results DECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73–0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively. Conclusion Quantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool.

Objective: To investigate the protective effect of Scutellaria baicalensis extract on ultraviolet (UVA)-induced photoaging in a fibroblast cell line (NIH3T3). Methods: The cellular photoaging model was established by UVA irradiation, and the protective effects of Scutellaria baicalensis extract on photoaging fibroblasts were investigated using CCK-8 assay, β-galactosidase staining, DAPI staining, and immunofluorescence staining. Results: Scutellaria baicalensis extract significantly promoted cell proliferation and migration of NIH3T3 cells (P

Abstract This paper highlights the need for intelligent analysis of students’ behavioral states in physical education tasks. The hand-ring inertial data is used to identify students’ motion sequence states. First, statistical feature extraction is performed based on the acceleration and angular velocity data collected from the bracelet. After completing the filtering and noise reduction of the data, we perform feature extraction by Back Propagation Neural Network (BPNN) and use the sliding window method for analysis. Finally, the classification capability of the model sequence is enhanced by the Hidden Markov Model (HMM). The experimental results indicate that the classification accuracy of student action sequences in physical education exceeds 96% after optimization by the HMM method. This provides intelligent means and new ideas for future student state recognition in physical education and teaching reform.

ABSTRACT The difficulty in detecting viable but non-culturable (VBNC) Salmonella by culture-dependent methods poses a risk to food safety. In our study, we applied a viability test to Salmonella following a lethal treatment and to flour samples inoculated with Salmonella to evaluate the effectiveness of viability polymerase chain reaction (PCR). Our findings revealed that the combination of both ddPCR and qPCR with those DNA-intercalating dyes could quantify viable cells at low concentrations when the plate counting method failed to detect them post-inactivation. Prolonged UV exposure did not induce cell membrane disruption, as confirmed with PMA-ddPCR, with insignificant differences in gene copies. However, samples exposed to DyeTox13 and DyeTox13 + EMA showed lower gene copy numbers, implying that enzymatic activity was decreased by UV exposure duration. In addition, temperature-dependent survival in flour revealed uniform decay rates and D values (time required for a 1 log reduction) of DNA in untreated samples across various temperatures. By contrast, different decay rates were observed with DNA-intercalating dyes (DyeTox13 and DyeTox13 + EMA), showing faster metabolic activity loss at higher temperatures in flour. The decay rates and D values, determined through plate counting and those DNA-intercalating dyes, indicated the potential presence of VBNC Salmonella. A strong correlation between DyeTox13 dyes and the plate counting method suggested DyeTox13 as a rapid alternative for detecting Salmonella in flour. The ddPCR with DNA-intercalating dyes could effectively evaluate Salmonella viability, facilitating more precise monitoring of VBNC in food.IMPORTANCESalmonella, a major foodborne pathogen, poses significant risks, particularly to vulnerable groups like infants, older people, and the immunocompromised. Accurate detection is vital for public health and food safety, given its potential to cause severe and life-threatening symptoms. Our study demonstrated digital polymerase chain reaction (ddPCR) with DNA-intercalating dyes for identifying the different physiological statuses of Salmonella. Also, the application of ddPCR with DNA-intercalating dyes offers quantification of viable cells post-disinfection as an alternative method in food. Utilizing ddPCR and DNA-intercalating dyes, we enhanced the detection of VBNC Salmonella, a form often undetectable by conventional methods. This innovative approach could significantly improve the precision and efficiency of detection for viable Salmonella. By providing deeper insights into its transmission potential, our method is a critical tool in preventing outbreaks and ensuring the safety of food products. This research contributes substantially to global efforts in controlling foodborne illnesses and safeguarding public health.

When measurement equipment for marine refractive index is calibrated, the existing calibration methods have problems such as low quantity, high price, and complicated operation. Based on the existing empirical model of seawater refractive index, the dynamic range of the corresponding refractive index was calculated with reference to the dynamic range of temperature and salinity in the range of 0–2 000 m in the South China Sea. This paper also proposed an equipment calibration method for measuring seawater refractive index based on distilled water. The distilled water medium was selected, and within the dynamic range of refractive index suitable for marine measurement, a refractive index measurement experiment with a temperature interval of 0.1 °C was carried out. By comparing with the theoretical interpolation value of the Tilton empirical model, the accuracy of the theoretical value obtained by the empirical model was verified, and a credible data set was selected for the subsequent calibration and application of the equipment for measuring seawater refractive index based on distilled water.

The study of underwater vehicle wake detection is of significant importance within the field of target detection, localisation, and tracking of underwater vehicles. Given that propellers are the propellers of modern ships and underwater vehicles, the propeller wake field represents the principal target source for wake detection in underwater vehicles. The objective of this paper is to propose a method for measuring the wake of an underwater propeller based on a position-sensitive detector. A theoretical model of the relationship between the laser spot displacement and the change in the refractive index of the wake field is established on the basis of the principle of laser beam deflection. A prototype experimental setup for underwater propeller wake measurement was constructed based on the aforementioned optical measurement method. Furthermore, the simulation of the propeller wake flow field with strong density stratification and linear density stratification was conducted based on the experimental setup. Furthermore, experiments were conducted to detect the flow field of a propeller wake. The experimental results indicate that the wake dissipation times of the propeller in a strong density-stratified water environment are approximately 800 s and 750 s. Following the stabilisation of the wake field density, the laser spot position is observed to be stable at 0.341 mm and 0.441 mm, respectively, with a corresponding refractive index change of 2.99 × 10−6 RIU (refractive index unit) and 3.87 × 10−6 RIU, respectively. These experimental results are found to be in general agreement with the simulation results of the propeller wake field. A comparison of the experimental wake measurements based on the device with the wake measurements based on a CTD (conductivity–temperature–depth) device reveals a consistent trend. The realisation of this detection technique is of great significance for the advancement of research in the field of optical detection of underwater vehicle wake streams.

The seawater refractive index is an essential parameter in ocean observation, making its high-precision measurement necessary. This can be effectively achieved using a position-sensitive detector-based measurement system. However, in the actual measurement process, the impact of the jitter signal measurement error on the results cannot be ignored. In this study, we theoretically analysed the causes of long jitter signals during seawater refractive index measurements and quantified the influencing factors. Through this analysis, it can be seen that the angle between the two windows in the seawater refractive index measurement area caused a large error in the results, which could be effectively reduced by controlling the angle to within 2.06°. At the same time, the factors affecting the position-sensitive detector’s measurement accuracy were analysed, with changes to the background light, the photosensitive surface’s size, and the working environment’s temperature leading to its reduction. To address the above factors, we first added a 0.9 nm bandwidth, narrow-band filter in front of the detector’s photosensitive surface during system construction to filter out any light other than that from the signal light source. To ensure the seawater refractive index’s measuring range, a position-sensitive detector with a photosensitive surface size of 4 mm × 4 mm was selected; whereas, to reduce the working environment’s temperature variation, we partitioned the measurement system. To validate the testing error range of the optimised test system, standard seawater samples were measured under the same conditions, showing a reduction in the measurement system’s jitter signal from 0.0022 mm to 0.0011 mm, before and after optimisation, respectively, as well as a reduction in the refractive index’s deviation. The experimental results show that the refractive index of seawater was effectively reduced by adjusting the measurement system’s optical path and structure.

Abstract Background Intracranial extraventricular ependymoma (IEE) is an ependymoma located in the brain parenchyma outside the ventricles. IEE has overlapping clinical and imaging characteristics with glioblastoma multiforme (GBM) but different treatment strategy and prognosis. Therefore, an accurate preoperative diagnosis is necessary for optimizing therapy for IEE. Methods A retrospective multicenter cohort of IEE and GBM was identified. MR imaging characteristics assessed with the Visually Accessible Rembrandt Images (VASARI) feature set and clinicopathological findings were recorded. Independent predictors for IEE were identified using multivariate logistic regression, which was used to construct a diagnostic score for differentiating IEE from GBM. Results Compared to GBM, IEE tended to occur in younger patients. Multivariate logistic regression analysis identified seven independent predictors for IEE. Among them, 3 predictors including tumor necrosis rate (F7), age, and tumor‐enhancing margin thickness (F11), demonstrated higher diagnostic performance with an Area Under Curve (AUC) of more than 70% in distinguishing IEE from GBM. The AUC was 0.85, 0.78, and 0.70, with sensitivity of 92.98%, 72.81%, and 96.49%, and specificity of 65.50%, 73.64%, and 43.41%, for F7, age, and F11, respectively. Conclusion We identified specific MR imaging features such as tumor necrosis and thickness of enhancing tumor margins that could help to differentiate IEE from GBM. Our study results should be helpful to assist in diagnosis and clinical management of this rare brain tumor.

Abstract Although solar exposure is necessary for human health, phototoxicology induced by excessive UVB and UVA radiation, which involves sunburns, skin aging and even tumorigenesis, has been widely researched. Sunscreen is one of the most important ways to protect skin from UV phototoxic damage. As well as inorganic and organic UV filters, some natural products or plant extracts with aromatic rings in their structures, such as flavonoids or polyphenols, can absorb UV to reduce sunburn, acting as a natural UV filter; they also show antioxidant or/and anti‐inflammatory activity. This could explain why, although there are no officially approval natural commercial sun‐filters, more and more commercial sunscreen products containing plant extracts are available on the market. Here we summarize articles focusing on natural UV filters from plant published in the last 6 years, selecting the most significant data in order to better understand the photoprotective activity of natural products and extracts from plants, including their major constituents and main biological effects, methods for evaluating UV radiation resistance, anti‐UV radiation experimental models and anti‐UV radiation mechanisms.

The refractive index of seawater is one of the essential parameters in ocean observation, so it is necessary to achieve high-precision seawater refractive index measurements. In this paper, we propose a method for measuring the refractive index of seawater, based on a position-sensitive detector (PSD). A theoretical model was established to depict the correlation between laser spot displacement and refractive index change, utilizing a combination of a position-sensitive detector and laser beam deflection principles. Based on this optical measurement method, a seawater refractive index measurement system was established. To effectively enhance the sensitivity of refractive index detection, a focusing lens was incorporated into the optical path of the measuring system, and simulations were conducted to investigate the impact of focal length on refractive index sensitivity. The calibration experiment of the measuring system was performed based on the relationship between the refractive index of seawater and underwater pressure (depth). By measuring laser spot displacement at different depths, changes in displacement, with respect to both refractive index and depth, were determined. The experimental results demonstrate that the system exhibits a sensitivity of 9.93×10−9 RIU (refractive index unit), and the refractive index deviation due to stability is calculated as ±7.54×10−9 RIU. Therefore, the feasibility of this highly sensitive measurement of seawater refractive index is verified. Since the sensitivity of the refractive index measurement of this measurement system is higher than the refractive index change caused by the wake of underwater vehicles, it can also be used in various applications for underwater vehicle wake measurement, as well as seawater refractive index measurement, such as the motion state monitoring of underwater navigation targets such as AUVs and ROVs.

Seawater density is an important physical property in oceanography that affects the accuracy of calculations such as gravity fields and tidal potentials and the calibration of acoustic and optical oceanographic sensors. In related studies, constant density values are frequently used, which can introduce significant errors. Therefore, this study employs a basic convolutional neural network model to construct a comprehensive model showing the seawater density distribution across the globe. The model takes into account depth, latitude, longitude, and month as inputs. Numerous real seawater datasets were used to train the model, and it has been shown that the model has an absolute mean error and root mean square error of less than 1 kg/m3 in 99% of the test set samples. The model effectively demonstrates the influence of input parameters on the distribution of seawater density. In this paper, we present a newly developed global model for distributing seawater density which is both comprehensive and accurate, surpassing previous models. The utilization of the model presented in this paper for estimating seawater density can minimize errors in theoretical ocean models and serve as a foundation for designing and analyzing ocean exploration systems.

Abstract Background Acute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI. Methods Metabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays. Results DM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered. Conclusion This study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI. Graphical Abstract

Background: The transfer of mitochondria from healthy mesenchymal stem cells (MSCs) to injured MSCs has been shown to have potential therapeutic benefits for neural cell post-ischemic stroke. Specifically, functional mitochondria can perform their normal functions after being internalized by stressed cells, leading to host cell survival. However, while this approach shows promise, there is still a lack of understanding regarding which neural cells can internalize functional mitochondria and the regulatory mechanisms involved. To address this gap, we investigated the ability of different neural cells to internalize exogenous functional mitochondria extracted from MSCs.Methods: Functional mitochondria (F-Mito) isolated from umbilical cord derived-MSCs (UCMSCs) were labeled with lentivirus of HBLV-mito-dsred-Null-PURO vector. The ability of stressed cells to internalize F-Mito was analyzed using a mouse (C57BL/6 J) middle cerebral artery occlusion (MCAO) model and an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model. The cell viability was measured by CCK-8 kit. Time-course of intracellular ROS levels in stressed cells were analyzed by DCFH-DA staining after OGD/R and F-Mito treatment. MitoSOX, Mitotracker and WGA labeling were used to assess the relationship between ROS levels and the uptake of F-Mito at the single-cell level. Pharmacological modulation of ROS was performed using acetylcysteine (ROS inhibitor).Results: Our findings demonstrate that neurons and endothelial cells are more effective at internalizing mitochondria than astrocytes, both in vitro and in vivo, using an ischemia-reperfusion model. Additionally, internalized F-Mito decreases host cell reactive oxygen species (ROS) levels and rescues survival. Importantly, we found that the ROS response in stressed cells after ischemia is a crucial determinant in positively mediating the internalization of F-Mito by host cells, and inhibiting the generation of ROS chemicals in host cells may decrease the internalization of F-Mito. These results offer insight into how exogenous mitochondria rescue neural cells via ROS response in an ischemic stroke model. Overall, our study provides solid evidence for the translational application of MSC-derived mitochondria as a promising treatment for ischemic stroke.

Abstract Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy‐M‐Exo) is developed via fusing tumor‐derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the reserved tumor antigens and endogenous danger signals in the hybrid nanovaccine activated antigen presenting cells (APCs) elicited a robust T‐cell response. Moreover, the nanovaccine Hy‐M‐Exo displayed good therapeutic efficacy in a mouse model of HNSCC. These results indicated that Hy‐M‐Exo is of high clinical value to serve as a feasible strategy for antitumor immunotherapy.

Abstract Objective Since 2011, noninvasive prenatal testing (NIPT) has undergone rapid expansion, with both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this testing tool are lacking. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations in order to inform pre- and post-test counseling, pre/perinatal decision making, and medical risk assessment/management. Methods This retrospective study included women referred for invasive prenatal diagnosis to confirm positive NIPT results between January 2017 and December 2020. Prenatal diagnosis testing, including karyotyping, chromosomal microarray analysis (CMA) were performed. Positive predictive values (PPVs) were calculated. Results In total, 468 women were recruited. The PPVs for trisomies 21, 18, and 13 were 86.1%, 57.8%, and 25.0%, respectively. The PPVs for rare chromosomal abnormalities (RCAs) and copy number variants (CNVs) were 17.0% and 40.4%, respectively. The detection of sex chromosomal aneuploidies (SCAs) had a PPV of 20% for monosomy X, 23.5% for 47,XXX, 68.8% for 47,XXY, and 62.5% for 47,XYY. The high-risk groups had a significant increase in the number of true positive cases compared to the low- and moderate-risk groups. Conclusions T13, monosomy X, and RCA were associated with lower PPVs. The improvement of cell-free fetal DNA screening technology and continued monitoring of its performance are important.

The refractive index measurement of seawater has proven significance in oceanography, while an optical heterodyne interferometer is an important, highly accurate, tool used for seawater refractive index measurement. However, for practical seawater refractive index measurement, the refractive index of seawater needs to be monitored for long periods of time, and the influence of drift error on the measurement results for these cases cannot be ignored. This paper proposes a drift error compensation algorithm based on wavelet decomposition, which can adaptively separate the background from the signal, and then calculate the frequency difference to compensate for the drift error. It is suitable for unstable signals, especially signals with large differences between the beginning and the end, which is common in actual seawater refractive index monitoring. The authors identify that the primary cause of drift error is the frequency instability of the acousto-optic frequency shifter (AOFS), and the actual frequency difference was measured through experimentation. The frequency difference was around 0.1 Hz. Simulation experiments were designed to verify the effectiveness of the algorithm, and the standard deviation of the optical length of the results was on the scale of 10−8 m. Liquid refractive index measurement experiments were carried out in a laboratory, and the measurement error was reduced from 36.942% to 0.592% after algorithm processing. Field experiments were carried out regarding seawater refractive index monitoring, and the algorithm-processing results are able to match the motion of the target vehicle. The experimental data were processed with different algorithms, and, according to the comparison of the results, the proposed algorithm performs better than other existing drift error elimination algorithms.

Abstract Paroxysmal nocturnal hemoglobinuria is a clonal disease caused by PIG-A mutation of hematopoietic stem cells. At present, there is no suitable PNH animal model for basic research, therefore, it is urgent to establish a stable animal model. We constructed a Pig-a conditional knock-out mice model by ES targeting technique and Vav-iCre. The expressions of GPI and GPI-AP were almost completely absent in CKO homozygote mice, and the proportion of the deficiency remained stable from birth. In CKO heterozygote mice, the proportion of the deficiency of GPI and GPI-AP was partially absent and decreased gradually from birth until it reached a stable level at 3 months after birth and remained there for life. Compared with normal C57BL/6N mice and Flox mice, pancytopenia was found in CKO homozygous mice, and leukopenia and anemia were found in CKO heterozygotes mice. Meanwhile, in CKO mice, the serum LDH, TBIL, IBIL, complement C5b-9 levels were increased, and the concentration of plasma FHb was increased. Hemosiderin granulosa cells can be seen more easily in the spleens of CKO mice. What’s more, CKO mice had stable transcription characteristics. In conclusion, our mouse model has stable GPI-deficient and mild hemolysis, which may be an ideal in vivo experimental model for PNH.

Abstract Neoantigens derived from mutant proteins in tumour cells could elicit potent personalized anti‐tumour immunity. Nevertheless, the layout of vaccine vehicle and synthesis of neoantigen are pivotal for stimulating robust response. The power of synthetic biology enables genetic programming bacteria to produce therapeutic agents under contol of the gene circuits. Herein, we genetically engineered bacteria to synthesize fusion neoantigens, and prepared bacteria derived vesicles (BDVs) presenting the neoantigens (BDVs‐Neo) as personalized therapeutic vaccine to drive systemic antitumour response. BDVs‐Neo and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were inoculated subcutaneously within hydrogel (Gel), whereas sustaining release of BDVs‐Lipopolysaccharide (LPS) and GM‐CSF recruited the dendritic cells (DCs). Virtually, Gel‐BDVs‐Neo combined with the programmed cell death protein 1 (PD‐1) antibody intensively enhanced proliferation and activation of tumour‐infiltrated T cells, as well as memory T cell clone expansion. Consequently, BDVs‐Neo combining with checkpoint blockade therapy effectively prevented tumour relapse and metastasis.

In order to investigate and develop functional foods of marine origin with hypoglycemic activity, Enteromorpha prolifera polysaccharide–Zn(II) (EZ) complex was first prepared by marine resourced E. prolifera polysaccharide (EP) and ZnSO4 and their anti-diabetes activities against high-sugar and high-fat-induced diabetic mice were evaluated. The detailed structural characterization of EZ was elucidated by UV-Vis spectroscopy, infrared spectroscopy, and monosaccharide composition determination. The pharmacological research suggests that EZ has a potent hypoglycemic effect on high-sugar and high-fat-induced diabetic mice by inhibiting insulin resistance, improving dyslipidemia, decreasing inflammatory status, repairing pancreas damage, as well as activating the IRS/PI3K/AKT signaling pathway and regulating GLUT2 gene expression. At the same time, microbiota analysis indicates that a high dose of EZ could enhance the abundance of dominant species, such as Staphylococcaceae, Planococcaceae, Muribaculaceae, Aerococcaceae, and Lacrobacillaceae, in intestinal microbiota distribution. Thus, EZ could be considered as a potential candidate for developing an ingredient of functional foods for Zn(II) supplements with hypoglycemic activity.

Abstract Long noncoding RNAs (lncRNAs) and their crosstalks with other RNAs have been revealed to be closely related to tumorigenesis and development, but their role in invasive pituitary adenoma (IPA) remains largely unclear. In our study, LINC00473 was identified as the most upregulated lncRNA in IPA by whole transcriptome RNA sequencing (RNA-Seq). Further, its related signaling pathway LINC00473/miR-502-3p/KMT5A was obtained by constructing a competing endogenous RNA (ceRNA) regulatory network. Their expression in IPA and non-invasive pituitary adenoma (NIPA) tissues was verified by qRT-PCR. Then the effects and mechanisms of LINC00473 and its ceRNA network on the proliferation of pituitary adenoma (PA) cells were confirmed by gene overexpression or silencing techniques combined with CCK-8 assay, EdU staining, flow cytometry assay, and double luciferase reporter gene assay in PA cell lines AtT-20 and GT1-1 in vitro and in a xenograft model in vivo. LINC00473 is overexpressed in IPA and can promote PA cells proliferation. Mechanistically, overexpression of LINC00473 restricts miR-502-3p through the ceRNA mechanism, upregulates KMT5A expression, and promotes the expression of cyclin D1 and CDK2, which is conducive to the cell cycle process, thereby promoting the proliferation of PA cells, involving IPA progression.

Abstract Background Little is known about whether the influence of glycemic variability on arrhythmia is related to age in type 2 diabetes mellitus (T2DM). Therefore, we aimed to compare the association between glycemic variability and arrhythmia in middle-aged and elderly T2DM patients. Methods A total of 107 patients were divided into two groups: elderly diabetes mellitus group (EDM, n = 73) and middle-aged diabetes mellitus group (MDM, n = 34). The main clinical data, continuous glucose monitoring (CGM) and dynamic ECG reports were collected. The parameters including standard deviation of blood glucose (SDBG), largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), absolute means of daily differences (MODD), time in range (TIR), time below range (TBR), time above range (TAR), coefficient of variation (CV) were tested for glycemic variability evaluation. Results In terms of blood glucose fluctuations, MAGE (5.77 ± 2.16 mmol/L vs 4.63 ± 1.89 mmol/L, P = 0.026), SDBG (2.39 ± 1.00 mmol/L vs 2.00 ± 0.82 mmol/L, P = 0.048), LAGE (9.53 ± 3.37 mmol/L vs 7.84 ± 2.64 mmol/L, P = 0.011) was significantly higher in EDM group than those of MDM group. The incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat were significantly higher in EDM group compared with the MDM group (all P

A rapid, sensitive, selective, and accurate HPLC–MS/MS method was developed and validated for the simultaneous determination of chlorogenic acid, naucleactonin C, khaephuoside A 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside in rat plasma and tissues after oral administration of Nauclea officinalis extracts. Chloramphenicol was used as an internal standard (IS). The plasma and tissue samples were extracted by protein precipitation with methanol-ethyl acetate (1 : 1, v/v) including 0.1% (v/v) formic acid. The chromatographic separation was achieved by using an C18 column with gradient elution using mobile phase, which consisted of 0.1% formic acid water (A) and acetonitrile (B) and the flow rate of 0.8 mL/min. Mass spectrometric detection was performed in multiple reaction monitoring (MRM) mode utilizing electrospray ionization (ESI) in negative mode. The developed method exhibited good linearity (determination coefficients, R2 ≥ 0.9849), and the lower limits of quantification were 2, 5, 5, and 25 ng/mL for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside. The intraday and interday precisions (relative standard deviation, RSD) were less than 12.65%, while the accuracy was ranged from 86.31 to 114.17%. The recovery rate were 51.85–97.06%, 75.99–106.68%, 77.46–105.35%, and 68.36–103.75% for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside the matrix effects were 50.17–116.62%, 86.75–115.99%, 45.79–87.44%, and 51.60–92.34% for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside in different matrix. The developed method was successfully applied to a pharmacokinetic study and tissue distribution of four compounds in rats after oral administration of Nauclea officinalis extracts.

Background: Several complex cellular and gene regulatory processes are involved in peripheral nerve repair. This study uses bioinformatics to analyze the differentially expressed genes (DEGs) in the satellite glial cells of mice following sciatic nerve injury. Methods: R software screens differentially expressed genes, and the WebGestalt functional enrichment analysis tool conducts Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analysis. The Search Tool for the Retrieval of Interacting Genes/Proteins constructs protein interaction networks, and the cytoHubba plug-in in the Cytoscape software predicts core genes. Subsequently, the sciatic nerve injury model of mice was established and the dorsal root ganglion satellite glial cells were isolated and cultured. Satellite glial cells-related markers were verified by immunofluorescence staining. Real-time polymerase chain reaction assay and Western blotting assay were used to detect the mRNA and protein expression of Sox9 in satellite glial cells. Results: A total of 991 DEGs were screened, of which 383 were upregulated, and 508 were downregulated. The GO analysis revealed the processes of biosynthesis, negative regulation of cell development, PDZ domain binding, and other biological processes were enriched in DEGs. According to the KEGG pathway analysis, DEGs are primarily involved in steroid biosynthesis, hedgehog signaling pathway, terpenoid backbone biosynthesis, American lateral skeleton, and melanoma pathways. According to various cytoHubba algorithms, the common core genes in the protein–protein interaction network are Atf3, Mmp2, and Sox9. Among these, Sox9 was reported to be involved in the central nervous system and the generation and development of astrocytes and could mediate the transformation between neurogenic and glial cells. The experimental results showed that satellite glial cell marker GS were co-labeled with Sox9; stem cell characteristic markers Nestin and p75NTR were labeled satellite glial cells. The mRNA and protein expression of Sox9 in satellite glial cells were increased after sciatic nerve injury. Conclusions: In this study, bioinformatics was used to analyze the DEGs of satellite glial cells after sciatic nerve injury, and transcription factors related to satellite glial cells were screened, among which Sox9 may be associated with the fate of satellite glial cells.

Mindfulness-based cognitive therapy (MBCT) has been increasingly recognized as effective in different mental illnesses, but these effects are limited in schizophrenia. For patients with schizophrenia, stigma is one of the most negative factors that affects treatment, rehabilitation and social function. This research aimed to determine the effects of MBCT on stigma in patients with schizophrenia. In total, 62 inpatients with schizophrenia were recruited and randomly assigned to the experimental group or control group. The experimental group received an 8-week MBCT intervention, and the control group were treated as usual. Link's Stigma Scales (with three subscales, including perceived devaluation-discrimination (PDD), stigma-coping orientation, and stigma-related feeling), Five Facet Mindfulness Questionnaire (FFMQ), and Insight and Treatment Attitudes Questionnaire (ITAQ) were used to collect data before and after intervention. After intervention, the post-test score of PDD, stigma-coping orientation, FFMQ, and ITAQ were significantly different between the experimental group and the control group. In the experimental group, the PDD and stigma-coping orientation scores significantly decreased, and FFMQ and ITAQ scores increased remarkably (P < 0.05). In addition, correlation analysis revealed a significant negative correlation between mindfulness and stigma. MBCT was effective in reducing stigma in patients with schizophrenia, which mainly manifested as changes in the patients' perception of stigma as well as the withdrawal and avoidance caused by schizophrenia. Enhancing mindfulness will help reduce the stigma level. MBCT is worthy of promotion and application in patients with schizophrenia.

Background and objectiveStroke is a major contributor to the global burden of disease. Although numerous modifiable risk factors (RF) for stroke have been identified, some remain unexplained. Increasing studies have investigated stroke risk in arthritis, but their results are inconsistent. We aimed to synthesize, quantify, and compare the risk of stroke for the major types of arthritis in cohort studies by using a systematic review and meta-analysis approach.MethodsWe searched Chinese and English databases to identify relevant studies from inception to April 30, 2020. Only studies adjusting at least for age and sex were included. We calculated pooled effect estimates for relative risk (RR) and 95% confidence interval (CI) and identified potential sources of heterogeneity and publication bias.ResultsA total of 1,348 articles were retrieved, and after an preliminary screening of titles and abstracts, 69 were reviewed for full text, and finally, 32 met the criteria for meta-analysis. Stroke risk in arthritis was significantly increased in studies adjusting for age and sex (RR = 1.36, 95% CI: 1.27-1.46) and for at least one traditional risk factor (RR = 1.40, 95% CI: 1.28-1.54). The results of studies stratified by stroke subtype were consistent with the main finding (ischemic stroke: RR = 1.53, 95% CI: 1.32-1.78; hemorrhagic stroke: RR = 1.45, 95% CI: 1.15-1.84). In subgroup analysis by arthritis type, stroke risk was significantly increased in rheumatoid arthritis (RR = 1.38, 95% CI: 1.29-1.48), ankylosing spondylitis (RR = 1.49, 95% CI: 1.25-1.77), psoriatic arthritis (RR = 1.33, 95% CI: 1.22-1.45), and gout (RR = 1.40, 95% CI: 1.13-1.73) but not osteoarthritis (RR = 1.03, 95% CI: 0.91-1.16). Age and sex subgroup analyses indicated that stroke risk was similar by sex (women: RR = 1.47, 95% CI: 1.31-1.66; men: RR = 1.44, 95% CI: 1.28-1.61); risk was higher with younger age (ConclusionsStroke risk was increased in multiple arthritis and similar between ischemic and hemorrhagic stroke. Young patients with arthritis had the highest risk.

Colorectal cancer (CRC) has two major subtypes, microsatellite instability (MSI) and microsatellite stability (MSS) based on the genomic instability. In this study, using computational programs, we identified 9 master transcription factors (TFs) based on epigenomic profiling in MSS CRC samples. Notably, unbiased gene set enrichment analysis (GSEA) showed that several master TFs were strongly associated with immune-related functions in TCGA MSS CRC tissues, such as interferon gamma (IFN-γ) and interferon alpha (IFN-α) responses. Focusing to the top candidate, ASCL2, we found that CD8+ T cell infiltration was low in ASCL2 overexpressed MSS CRC samples. Compared with other gastrointestinal (GI) cancers (gastric cancer, MSI CRC, and esophageal cancer), ASCL2 is specifically upregulated in MSS CRC. Moreover, we identified 28 candidate genes in IFN-γ and IFN-α response pathways which were negatively correlated with ASCL2. Together, these results link transcriptional dysregulation with the immune evasion in MSS CRC, which may advance the understanding of immune resistance and contribute to developing novel treatments of MSS CRC.

Abstract Background Hemophilia B (HB) is an X‐linked recessive inherited bleeding disorder caused by mutations in the F9 gene that lead to plasma factor IX deficiency. To identify the causative mutations in HB, a molecular analysis of HB pedigrees in China was performed. Methods Using next‐generation sequencing (NGS) and an in‐house bioinformatics pipeline, 76 unrelated HB pedigrees were analyzed. The mutations identified were validated by comparison with the results of Sanger sequencing or Multiplex Ligation‐dependent Probe Amplification assays. The pathogenicity of the causative mutations was classified following the American College of Medical Genetics and Genomics guidelines. Results The mutation detection rate was 94.74% (72/76) using NGS. Of the 76 HB pedigrees analyzed, 59 causative variants were found in 72 pedigrees, with 38 (64.41%) missense mutations, 9 (15.25%) nonsense mutations, 2 (3.39%) splicing mutations, 5 (8.47%) small deletions, 4 (6.78%) large deletions, and 1 intronic mutation (1.69%). Of the 59 different F9 mutations, 10 were novel: c.190T>G, c.199G>T, c.290G>C, c.322T>A, c.350_351insACAATAATTCCTA, c.391+5delG, c.416G>T, c.618_627delAGCTGAAACC, c.863delA, and c.1024_1027delACGA. Of these 10 novel mutations, a mosaic mutation, c.199G>T(p.Glu67Ter), was identified in a sporadic HB pedigree. Using in‐silico analysis, these novel variants were predicted to be disease‐causing. However, no potentially causative mutations were found in the F9 coding sequences of the four remaining HB pedigrees. In addition, two HB pedigrees carrying additional F8/F9 mutations were discovered. Conclusion The identification of these mutations enriches the spectrum of F9 mutations and provides further insights into the pathogenesis of HB in the Chinese population.

The limited availability of nitrogen (N) is a fundamental challenge for many crop plants. We have hypothesized that the relative crop photosynthetic rate (P) is exponentially constrained by certain plant-specific enzyme activities, such as ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), NADP-glyceraldehyde-3-phosphate dehydrogenase (NADP-G3PDH), 3-phosphoglyceric acid (PGA) kinase, and chloroplast fructose-1,6-bisphosphatase (cpFBPase), in Triticum aestivum and Oryza sativa. We conducted a literature search to compile information from previous studies on C3 and C4 crop plants, to examine the photosynthetic rate responses to limited leaf [N] levels. We found that in Zea mays, NADP-malic enzyme (NADP-ME), PEP carboxykinase (PCK), and Rubisco activities were positively correlated with P. A positive correlation was also observed between both phosphoenolpyruvate carboxylase (PEPC) and Rubisco activity with leaf [N] in Sorghum bicolor. Key enzyme activities responded differently to P in C3 and C4 plants, suggesting that other factors, such as leaf [N] and the stage of leaf growth, also limited specific enzyme activities. The relationships followed the best fitting exponential relationships between key enzymes and the P rate in both C3 and C4 plants. It was found that C4 species absorbed less leaf [N] but had higher [N] assimilation rates (Arate) and higher maximum photosynthesis rates (Pmax), i.e., they were able to utilize and invest more [N] to sustain higher carbon gains. All C3 species studied herein had higher [N] storage (Nstore) and higher absorption of [N], when compared with the C4 species. Nstore was the main [N] source used for maintaining photosynthetic capacity and leaf expansion. Of the nine C3 species assessed, rice had the greatest Pmax, thereby absorbing more leaf [N]. Elevated CO2 (eCO2) was also found to reduce the leaf [N] and Pmax in rice but enhanced the leaf [N] and N use efficiency of photosynthesis in maize. We concluded that eCO2 affects [N] allocation, which directly or indirectly affects Pmax. These results highlight the need to further study these physiological and biochemical processes, to better predict how crops will respond to eCO2 concentrations and limited [N].

Autoimmune thyroid disease (AITD) and type 1 diabetes mellitus (T1DM) are two common autoimmune diseases that can occur concomitantly. In general, patients with diabetes have a high risk of AITD. It has been proposed that a complex genetic basis together with multiple nongenetic factors make a variable contribution to the pathogenesis of T1DM and AITD. In this paper, we summarize current knowledge in the field regarding potential pathogenic factors of T1DM and AITD, including human leukocyte antigen, autoimmune regulator, lymphoid protein tyrosine phosphatase, forkhead box protein P3, cytotoxic T lymphocyte-associated antigen, infection, vitamin D deficiency, and chemokine (C-X-C motif) ligand. These findings offer an insight into future immunotherapy for autoimmune diseases.

This dataset presents the mitochondrial genome variants associated with oncocytic tumors. These data were obtained by Sanger sequencing of the whole mitochondrial genomes of oncocytic tumors and the adjacent normal tissues from 32 patients. The mtDNA variants are identified after compared with the revised Cambridge sequence, excluding those defining haplogroups of our patients. The pathogenic prediction for the novel missense variants found in this study was performed with the Mitimpact 2 program.

Abstract Noninvasive prenatal testing of common aneuploidies has become routine over the past decade, but testing of monogenic disorders remains a challenge in clinical implementation. Most recent studies have inherent limitations, such as complicated procedures, a lack of versatility, and the need for prior knowledge of parental genotypes or haplotypes. To overcome these limitations, a robust and versatile next‐generation sequencing‐based cell‐free DNA (cfDNA) allelic molecule counting system termed cfDNA barcode‐enabled single‐molecule test (cfBEST) is developed for the noninvasive prenatal diagnosis (NIPD) of monogenic disorders. The accuracy of cfBEST is found to be comparable to that of droplet digital polymerase chain reaction (ddPCR) in detecting low‐abundance mutations in cfDNA. The analytical validity of cfBEST is evidenced by a β‐thalassemia assay, in which a blind validation study of 143 at‐risk pregnancies reveals a sensitivity of 99.19% and a specificity of 99.92% on allele detection. Because the validated cfBEST method can be used to detect maternal‐fetal genotype combinations in cfDNA precisely and quantitatively, it holds the potential for the NIPD of human monogenic disorders.

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