Search

Abstract Background Monosaccharide transporter (MST) family, as a carrier for monosaccharide transport, plays an important role in carbon partitioning and widely involves in plant growth and development, stress response, and signaling transduction. However, little information on the MST family genes is reported in maize (Zea mays), especially in response to abiotic stresses. In this study, the genome-wide identification of MST family genes was performed in maize. Result A total of sixty-six putative members of MST gene family were identified and divided into seven subfamilies (including SPT, PMT, VGT, INT, pGlcT, TMT, and ERD) using bioinformatics approaches, and gene information, phylogenetic tree, chromosomal location, gene structure, motif composition, and cis-acting elements were investigated. Eight tandem and twelve segmental duplication events were identified, which played an important role in the expansion of the ZmMST family. Synteny analysis revealed the evolutionary features of MST genes in three gramineous crop species. The expression analysis indicated that most of the PMT, VGT, and ERD subfamilies members responded to osmotic and cadmium stresses, and some of them were regulated by ABA signaling, while only a few members of other subfamilies responded to stresses. In addition, only five genes were induced by NaCl stress in MST family. Conclusion These results serve to understand the evolutionary relationships of the ZmMST family genes and supply some insight into the processes of monosaccharide transport and carbon partitioning on the balance between plant growth and development and stress response in maize.

Climate anomalies have significant impacts on forest productivity and tree mortality worldwide, leading to ecological disturbances. Understanding the climate-growth relationship and species-specific responses to climate and drought events are crucial for developing effective conservation strategies for tree growth. However, studies on such issues are scarce in the Qinling Mountains (QLM), a significant geo-ecological boundary for climate, vegetation distribution, and river systems in China. This study focuses on the southern slope of the QLM, where we developed tree-ring-width chronologies for Pinus tabulaeformis Carr. and Tsuga chinensis Pritz. in the same habitat, and analyzed their response to climate and two extreme drought events. Both species were found to have a positive correlation with temperature, but their responses to precipitation and scPDSI differed. Specifically, P. tabulaeformis showed a negative correlation with precipitation and scPDSI, while T. chinensis exhibited a positive correlation with precipitation. These differences in response may be attributed to species-specific preferences and interspecific competition between the two coniferous species. Results of the 31-year sliding correlation analysis and K-S test analysis, which aimed to explore the dynamic relationship between chronologies and their most limiting climate factors, demonstrated that both P. tabulaeformis and T. chinensis have experienced a qualitative change in their response patterns to certain climatic factors. Under the backdrop of warming climate, the response of P. tabulaeformis to the maximum temperatures from June to September of the previous year has diminished to a non-response; the response to precipitation from July to September of the previous year, although still significantly negatively correlated, has seen a decrease in significance. In contrast, T. chinensis has exhibited an increasing sensitivity to precipitation from September of the previous year to June of the current year. Study on resistance (Rt), recovery (Rc), and resilience (Rs) of tree growth to drought events revealed that P. tabuliformis and T. chinensis did not exhibit a negative response to the transient drought event in 1933 AD. However, when faced with the prolonged and severe drought event in 1941–1944 AD, both species experienced a decline in growth. It was observed that T. chinensis displayed weaker drought tolerance compared to P. tabuliformis and was more susceptible to the negative impacts of drought conditions. These findings suggest that forest management in the context of climate change should be species-specific, and more effort is needed for species with weaker drought resistance in the QLM, such as T. chinensis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic diseases caused by a combination of many factors, including genetics, environment, and immunity. AAV is characterized by predominantly small-vessel involvement and has a variety of clinical manifestations. Small-vessel lesions of the kidneys and lungs are common, and lesions of medium-sized arteries may also present, but the involvement of large arteries and their primary branches is very rare. This report delineates two instances of AAV with large arterial involvement, one case presenting with lesions of the aortic valve and the other with lesions of the pulmonary artery. The first case involved a 57-year-old man with no underlying diseases. Transthoracic echocardiography showed thickening of the left and right coronary valves of the aortic valve with enhanced echogenicity, moderate echogenic masses were seen on both valve leaflets, and the leaflets had restricted opening and poor closure. Blood tests showed positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-myeloperoxidase (MPO) antibodies. The patient's aortic valve thickening virtually disappeared after treatment with hormones combined with immunosuppressive agents. The second case involved a 60-year-old woman whose transthoracic echocardiography and CT (computed tomography) angiography of the pulmonary arteries showed wall thickening of the main pulmonary artery and the proximal left and right pulmonary arteries, leading to luminal stenosis. Blood tests showed positive cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA) and anti-proteinase 3 (PR 3) antibodies. The patient's pulmonary artery wall thickening reduced after receiving hormones in combination with immunosuppression but she died of heart failure during subsequent treatment. The patient had been diagnosed with tuberculosis six months earlier and had been poorly treated with anti-tuberculosis therapy. The involvement of large arteries in AAV is a rare and critical condition with rapid progression and a high mortality rate. Early recognition of this type of AAV and aggressive immunosuppressive therapy may facilitate the reversal of the vascular lesion and a reduction in the risk of patient death.

Abstract Protein function annotation has been one of the longstanding issues in biological sciences, and various computational methods have been developed. However, the existing methods suffer from a serious long-tail problem, with a large number of GO families containing few annotated proteins. Herein, an innovative strategy named AnnoPRO was therefore constructed by enabling sequence-based multi-scale protein representation, dual-path protein encoding using pre-training, and function annotation by long short-term memory-based decoding. A variety of case studies based on different benchmarks were conducted, which confirmed the superior performance of AnnoPRO among available methods. Source code and models have been made freely available at: https://github.com/idrblab/AnnoPRO and https://zenodo.org/records/10012272

Abstract Background Despite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets. Methods We collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis. Results The bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption. Conclusions These results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels.

AbstractContext Zi Xue Powder (ZXP) is a traditional formula for the treatment of fever. However, the potential mechanism of action of ZXP remains unknown.Objective This study elucidates the antipyretic characteristics of ZXP and the mechanism by which ZXP alleviates fever.Materials and methods The key targets and underlying fever-reducing mechanisms of ZXP were predicted using network pharmacology and molecular docking. The targets of ZXP anti-fever active ingredient were obtained by searching TCMSP, STITCH and HERB. Moreover, male Sprague-Dawley rats were randomly divided into four groups: control, lipopolysaccharide (LPS), ZXP (0.54, 1.08, 2.16 g/kg), and positive control (acetaminophen, 0.045 g/kg); the fever model was established by intraperitoneal LPS injection. After the fever model was established at 0.5 h, the rats were administered treatment by gavage, and the anal temperature changes of each group were observed over 10 h after treatment. After 10 h, ELISA and Western blot analysis were used to further investigate the mechanism of ZXP.Results Network pharmacology analysis showed that MAPK was a crucial pathway through which ZXP suppresses fever. The results showed that ZXP (2.16 g/kg) decreased PGE2, CRH, TNF-a, IL-6, and IL-1β levels while increasing AVP level compared to the LPS group. Furthermore, the intervention of ZXP inhibited the activation of MAPK pathway in LPS-induced fever rats.Conclusions This study provides new insights into the mechanism by which ZXP reduces fever and provides important information and new research ideas for the discovery of antipyretic compounds from traditional Chinese medicine.

Tuina is a treatment method in traditional Chinese medicine which has analgesic effects and effectively alleviates the symptoms of neuropathic pain (NP). Transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin type 1 (TRPA1) play major roles in transmitting nociceptive sensory signals in the nociceptive primary sensory dorsal root ganglion (DRG) nerve. The nitric oxide (NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) pathway exerts both nociceptive and antinociceptive effects in various chronic pain models. TRPV1 and TRPA1 mediate the influx of calcium, which stimulates the generation of NO. Subsequently, NO activates the NO/cGMP/protein kinase G (PKG) signaling pathway, thereby improving hyperalgesia. In the present study, oa rat model of NP with minor chronic constriction injury (CCI) of the right sciatic nerve of NP was established. The results of behavioral testing showed that, after a one-time tuina intervention, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were prolonged to varying degrees in the tuina group compared with the model group. Similarly, the expression of TRPV1, TRPA1, NO, soluble guanylate cyclase β (sGCβ), cGMP, and PKG1 was significantly decreased in the DRG of the tuina and tuina + TRPV1/TRPA1 antagonist group was significantly decreased. These findings suggest that the tuina intervention can effectively improve the symptoms of thermal and mechanical allodynia caused by peripheral nerve injuries. Tuina exerts immediate analgesic effects through the TRPV1/TRPA1-NO-cGMP-PKG signaling pathway.

PurposeThe current study designed a unique type of corneal topography evaluation method based on deep learning and traditional image processing algorithms. The type of corneal topography of patients was evaluated through the segmentation of important medical zones and the calculation of relevant medical indicators of orthokeratology (OK) lenses.MethodsThe clinical data of 1,302 myopic subjects was collected retrospectively. A series of neural network-based U-Net was used to segment the pupil and the treatment zone in the corneal topography, and the decentration, effective defocusing contact range, and other indicators were calculated according to the image processing algorithm. The type of corneal topography was evaluated according to the evaluation criteria given by the optometrist. Finally, the method described in this article was used to evaluate the type of corneal topography and compare it with the type classified by the optometrist.ResultsWhen the important medical zones in the corneal topography were segmented, the precision and recall of the treatment zone reached 0.9587 and 0.9459, respectively, and the precision and recall of the pupil reached 0.9771 and 0.9712. Finally, the method described in this article was used to evaluate the type of corneal topography. When the reviewed findings based on deep learning and image processing algorithms were compared to the type of corneal topography marked by the professional optometrist, they demonstrated high accuracy with more than 98%.ConclusionThe current study provided an effective and accurate deep learning algorithm to evaluate the type of corneal topography. The deep learning algorithm played an auxiliary role in the OK lens fitting, which could help optometrists select the parameters of OK lenses effectively.

Abstract Background Myopia control interventions, such as defocus incorporated multiple segments (DIMS) spectacle lenses, have been adopted in school-aged children to reduce the prevalence of myopia and its complications. This study aimed to investigate the effect of DIMS spectacle lenses on subfoveal choroidal thickness (SfChT) over a period of two years, as the choroidal response to myopic control is a crucial factor in exploring its potential effect on predicting myopia progression. Methods This study involved a secondary analysis of our previous randomized clinical trial. Myopic school-aged children aged 8–13 years were recruited in a two-year study investigating the effect of DIMS spectacle lenses on myopia progression. The treated group received DIMS spectacle lenses (n = 78), while the control group was treated with a pair of single vision (SV) spectacle lenses (n = 80). SfChT was monitored at 1 week, 1, 3, 6, 12, 18 and 24 months post lens wear using spectral-domain optical coherence tomography and a custom made auto-segmentation algorithm utilizing convolutional neural networks. Results SfChT increased significantly after one week of DIMS spectacle lens wear compared to those wearing SV spectacle lenses (adjusted mean change relative to baseline ± SEM at one week; DIMS vs. SV, 6.75 ± 1.52 µm vs. − 3.17 ± 1.48 µm; P

Abstract The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquire early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogram and reverse the immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells of healthy donors or metastatic female breast cancer patients, induce robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a promising therapy for solid tumors.

ABSTRACT: Two PPG1000 based temperature-sensitive magnetic ionic liquid were synthesized and characterized. The temperature-sensitive magnetic ionic liquid aqueous biphasic system combined with HPLC was applied for the continuous enrichment and trace analysis of tetracycline antibiotics (TC) in bovine milk for the first time. High enrichment factors were achieved and the detection was highly sensitive. The trace analysis of TC was rapid, free of organic solvent, recyclable and magnetically assisted for phase separation. Under optimum conditions, wide linear ranges of 0.25–300 ng/mL for all TC, high enrichment factors of 217.7–231.4, good precisions with relative standard deviation in the range of 0.74–3.97%, very low limits of detection of 0.031–0.067 ng/mL, limits of quantification of 0.103–0.223 ng/mL, and good recoveries of 94.28–99.76% were acquired for the proposed analytical method. Real milk analysis was satisfactory. This developed analytical method is showing great potential for trace analysis of targeted analytes in foods and drinks.

Drug discovery and development affects various aspects of human health and dramatically impacts the pharmaceutical market. However, investments in a new drug often go unrewarded due to the long and complex process of drug research and development (R&D). With the advancement of experimental technology and computer hardware, artificial intelligence (AI) has recently emerged as a leading tool in analyzing abundant and high-dimensional data. Explosive growth in the size of biomedical data provides advantages in applying AI in all stages of drug R&D. Driven by big data in biomedicine, AI has led to a revolution in drug R&D, due to its ability to discover new drugs more efficiently and at lower cost. This review begins with a brief overview of common AI models in the field of drug discovery; then, it summarizes and discusses in depth their specific applications in various stages of drug R&D, such as target discovery, drug discovery and design, preclinical research, automated drug synthesis, and influences in the pharmaceutical market. Finally, the major limitations of AI in drug R&D are fully discussed and possible solutions are proposed.

The shales of the Taiyuan Formation and Shanxi Formation in the North China Basin have good prospects for shale gas exploration and development. In this study, Well KP1 at the northern margin of the North China Basin was used as the research object for rock mineral, organic geochemical, and elemental geochemical analyses. The results show that brittle minerals in the shales of the Taiyuan Formation and Shanxi Formation are relatively rare (50%). The average TOC content is 3.68%. The organic matter is mainly mixed and sapropelic. The source rocks of the Taiyuan Formation and Shanxi Formation are mainly felsic, and the tectonic background lies in the continental island arc area. The primary variables that influenced the enrichment of organic materials during the sedimentary stage of the Taiyuan Formation were paleosalinity and paleoproductivity. Paleosalinity acted as the primary regulator of organic matter enrichment during the sedimentary stage of the Shanxi Formation.

Abstract Background Breast cancer (BC) is the most common malignancy affecting women. It is vital to explore sensitive biological markers to diagnose and treat BC patients. Recent studies have proved that long noncoding RNAs (lncRNAs) were involved in breast tumor progression. Nonetheless, whether lncRNA prostate cancer‐associated transcript 19 (PCAT19) impacts BC development remains unknown. Methods We performed various bioinformatic analyses, including machine learning models to identify critical regulatory lncRNAs affecting prognosis in BC. The in situ hybridization (ISH) assay was carried out to confirm the expression levels of lncRNA PCAT19 in tissue specimens. MTT assay, wound healing assay, and transwell assay were performed to investigate PCAT19's impact on proliferation, migration, and invasion of BC cells. Mouse xenografts were used to examine the proliferation‐inhibiting function of PCAT19 in vivo. Results Among the prognosis‐associated lncRNAs, PCAT19 predicted a favorable prognosis in BC. Patients with high expression levels of PCAT19 had a lower clinical stage and less lymph node metastasis. The PCAT19‐related genes were enriched in signaling pathways involved in tumor development, indicating PCAT19 was an essential regulator of BC. Using the ISH assay, we confirmed the expression level of lncRNA PCAT19 in human BC tissues was lower than normal breast tissues. Moreover, the knockdown of PCAT19 further confirmed its inhibiting ability in BC cell proliferation. Correspondingly, overexpressing PCAT19 reduced tumor size in mouse xenografts. Conclusions Our study demonstrated that lncRNA PCAT19 suppressed the development of BC. PCAT19 might be a promising prognostic biomarker, which provides new insights into risk stratification for BC patients.

Nourishing Yin and Moistening Dryness Formula (NYMD) is a functional food known for its ability to nourish Yin and relieve constipation symptoms. However, the specific molecular mechanism by which it improves Yin-deficiency constipation (YC) is not well understood. This study used metabolomics, network pharmacology, and experimental validation to investigate the effect mechanism of NYMD on YC. Metabolomics analysis identified 34 YC-specific metabolites, while HPLC-Q-TOF/MS confirmed 33 major components of NYMD. Network pharmacology predicted that NYMD may regulate the PI3K/AKT signaling pathway in treating YC. Experimental validation through Western Blot and apoptosis assay confirmed that NYMD inhibits colon cell apoptosis through the PI3K/AKT signaling pathway, alleviating YC. Further confirmation was obtained by blocking the pathway using the PI3K inhibitor LY294002. These findings highlight the PI3K/AKT pathway as the primary mechanism of NYMD to improve YC. This study has significant implications for YC treatment, NYMD development, and its comprehensive utilization.

Lipoprotein (a) [Lp (a)] is a complex polymorphic lipoprotein consisting of one low-density lipoprotein particle with one molecule of apolipoprotein B100 and another apolipoprotein (a) linked by a disulfide bond. In recent years, due to its causal role in premature atherosclerotic cardiovascular diseases and calcified aortic stenosis, Lp (a) has attracted more and more attention. Our study aimed to illustrate the trend of Lp (a) research in atherosclerosis (AS) through bibliometric analysis. The Science Citation Index-Expanded was used to locate Lp (a) and AS studies published between December 1, 2012 and December 1, 2022. VOSviewer and CiteSpace bibliometric software packages were used to analyze literature information. LP (a) has seen an overall increase in annual publications. The United States had the highest number of publications worldwide, with 192 publications. The University of California, San Diego, has contributed significantly to Lp (a) with 29 publications and led research collaboration. In the past few decades, there has been close collaboration between countries or regions, institutions, and authors. In addition, the European Heart Journal was the most cited, followed by the Journal of Lipid Research and AS with 2033, 1096, and 806 citations, respectively. Recent studies were on genes and lipid-lowering therapies. Our study comprehensively evaluated the research status and trends of Lp (a) in AS worldwide for the first time and provided a valuable reference for clinical researchers.

To explore the crystalline arrangement of the alloy and the processes involving iron (Fe) precipitation, we employed molecular dynamics simulation with a cooling rate of 2 × 1010 for Cu100-XFeX (where X represents 1%, 3%, 5%, and 10%) alloy. The results reveal that when the Fe content was 1%, Fe atoms consistently remained uniformly distributed as the temperature of the alloy decreased. Further, there was no Fe atom aggregation phenomenon. The crystal structure was identified as an FCC-based Cu crystal, and Fe atoms existed in the matrix in solid solution form. When the Fe content was 3%, Fe atoms tended to aggregate with the decreasing temperature of the alloy. Moreover, the proportion of BCC crystal structure exhibited no obvious changes, and the crystal structure remained FCC-based Cu crystal. When the Fe content was between 5% and 10%, the Fe atoms exhibited obvious aggregation with the decreasing temperature of the alloy. At the same time, the aggregation phenomenon was found to be more significant with a higher Fe content. Fe atom precipitation behaviour can be delineated into three distinct stages. The initial stage involves the gradual accumulation of Fe clusters, characterised by a progressively stable cluster size. This phenomenon arises due to the interplay between atomic attraction and the thermal motion of Fe-Fe atoms. In the second stage, small Fe clusters undergo amalgamation and growth. This growth is facilitated by non-diffusive local structural rearrangements of atoms within the alloy. The third and final stage represents a phase of equilibrium where both the size and quantity of Fe clusters remain essentially constant following the crystallisation of the alloy.

The small-scale linear information in galaxy samples typically lost during nonlinear growth can be restored to a certain level by the density field reconstruction, which has been demonstrated for improving the precision of the baryon acoustic oscillation (BAO) measurements. As proposed in the literature, a joint analysis of the power spectrum before and after the reconstruction enables an efficient extraction of information carried by high-order statistics. However, the statistics of the postreconstruction density field are difficult to model. In this work, we circumvent this issue by developing an accurate emulator for the prereconstructed, postreconstructed, and cross-power spectra ( ${P}_{\mathrm{pre}}$ , P _post , P _cross ) up to k = 0.5 h Mpc ^−1 based on the Dark Quest N -body simulations. The accuracy of the emulator is at the percent level; namely, the error of the emulated monopole and quadrupole of the power spectra is less than 1% and 10% of the ground truth, respectively. A fit to an example power spectrum using the emulator shows that the constraints on cosmological parameters get largely improved using ${P}_{\mathrm{pre}}$ + P _post + P _cross with ${k}_{\max }=0.25\,h\,{\mathrm{Mpc}}^{-1}$ , compared to that derived from ${P}_{\mathrm{pre}}$ alone; namely, the constraints on (Ω _m , H _0 , σ _8 ) are tightened by ∼41%–55%, and the uncertainties of the derived BAO and RSD parameters ( α _⊥ , α _∣∣ , f σ _8 ) shrink by ∼28%–54%, respectively. This highlights the complementarity among ${P}_{\mathrm{pre}}$ , P _post , and P _cross , which demonstrates the efficiency and practicability of a joint ${P}_{\mathrm{pre}}$ , P _post , and P _cross analysis for cosmological implications.

In this work, a novel numerical method for studying the influence of gas types on drag reduction by microbubble injection is presented. Aimed at the microbubble drag reduction (MBDR) process for different types of gases, the mass transfer velocity of different types of gases in the gas–liquid phase is defined by writing a user-defined function (UDF), which reflected the influence of gas solubility on the drag reduction rate. An Eulerian multiphase flow model and the Realizable k−ε turbulence model are used for numerical calculation. The population balance model is used to describe the coalescence and breakup phenomena of the microbubble groups. Henry’s theorem is used to calculate the equilibrium concentration of the microbubble mixed flow. The interphase mass transfer rate of the microbubble injection process for different types of gases is studied by using permeation theory. The local mass fraction of the mixed flow is solved by the component transport equation. It is found that the larger the solubility of the gas, the lower the efficiency of MBDR. When the volume flow rate of the same type of gas is the same but the injection speed is different, the larger the solubility of the gas is, the greater the difference in the drag reduction ratio.

Markov chain Monte Carlo (MCMC) stands out as an effective method for tackling Bayesian inverse problems. However, when dealing with computationally expensive forward models and high-dimensional parameter spaces, the challenge of repeated sampling becomes pronounced. A common strategy to address this challenge is to construct an inexpensive surrogate of the forward model, which cuts the computational cost of individual samples. While the Gaussian process (GP) is widely used as a surrogate modeling strategy, its applicability can be limited when dealing with high-dimensional input or output spaces. This paper presents a novel approach that combines the analysis of variance (ANOVA) decomposition method with Gaussian process regression to handle high-dimensional Bayesian inverse problems. Initially, the ANOVA method is employed to reduce the dimension of the parameter space, which decomposes the original high-dimensional problem into several low-dimensional sub-problems. Subsequently, principal component analysis (PCA) is utilized to reduce the dimension of the output space on each sub-problem. Finally, a Gaussian process model with a low-dimensional input and output is constructed for each sub-problem. In addition to this methodology, an adaptive ANOVA-GP-MCMC algorithm is proposed, which further enhances the adaptability and efficiency of the method in the Bayesian inversion setting. The accuracy and computational efficiency of the proposed approach are validated through numerical experiments. This innovative integration of ANOVA and Gaussian processes provides a promising solution to address challenges associated with high-dimensional parameter spaces and computationally expensive forward models in Bayesian inference.

Accurate crop mapping is critical for agricultural applications. Although studies have combined deep learning methods and time-series satellite images to crop classification with satisfactory results, most of them focused on supervised methods, which are usually applicable to a specific domain and lose their validity in new domains. Unsupervised domain adaptation (UDA) was proposed to solve this limitation by transferring knowledge from source domains with labeled samples to target domains with unlabeled samples. Particularly, multi-source UDA (MUDA) is a powerful extension that leverages knowledge from multiple source domains and can achieve better results in the target domain than single-source UDA (SUDA). However, few studies have explored the potential of MUDA for crop mapping. This study proposed a MUDA crop classification model (MUCCM) for unsupervised crop mapping. Specifically, 11 states in the U.S. were selected as the multi-source domains, and three provinces in Northeast China were selected as individual target domains. Ten spectral bands and five vegetation indexes were collected at a 10-day interval from time-series Sentinel-2 images to build the MUCCM. Subsequently, a SUDA model Domain Adversarial Neural Network (DANN) and two direct transfer methods, namely, the deep neural network and random forest, were constructed and compared with the MUCCM. The results indicated that the UDA models outperformed the direct transfer models significantly, and the MUCCM was superior to the DANN, achieving the highest classification accuracy (OA>85%) in each target domain. In addition, the MUCCM also performed best in in-season forecasting and crop mapping. This study is the first to apply a MUDA to crop classification and demonstrate a novel, effective solution for high-performance crop mapping in regions without labeled samples.

Abstract Background The coronavirus disease 2019 (COVID‐19) pandemic has had an unprecedented impact on the healthcare system, economy, and society. Studies have reported that COVID‐19 may cause various neurologic symptoms, including cognitive impairment. We aimed to assess the causal effect of COVID‐19 on neurodegenerative diseases using two‐sample Mendelian randomization (MR) study. Methods Genetic variants were obtained from genome‐wide association studies (GWAS) summary‐level data and meta‐analyses. We used the inverse variance–weighted (IVW) method as the primary analysis to estimate causal effects. Sensitivity analyses were performed to make the conclusions more robust and reliable. Results We found that the COVID‐19 infection phenotype was associated with a higher risk of AD and inverse associated with the risk of ALS and MS. The hospitalized COVID‐19 phenotype was associated with the risk of AD and wasn't associated with ALS and MS. We also found that the severe COVID‐19 (main analysis) phenotype was associated with the AD outcome from UK biobank datasets but was not associated with other outcomes. The severe COVID‐19 infection phenotype, the severe COVID‐19 (subtype analysis) phenotype and the hospitalization risk of COVID‐19 were not associated with each outcome. Conclusion This MR study suggests a potential association between genetically predicted COVID‐19 and a higher risk of AD and a reduced risk of ALS and MS. Further elucidations of this association and underlying mechanisms may inform public health messages to prevent COVID‐19 and AD.

Abstract Background The lack of social support for adults with epilepsy (AWEs) is receiving increased attention, as it may result in low quality of life. This study was aimed to confirm the demographic characteristics of and clinical factors associated with social support for AWEs. Methods AWEs were consecutively recruited from our hospital. The 10-term Social Support Rating Scale (SSRS) was used to measure social support. A linear regression analysis with stepwise selection was performed to analyze the independent variables associated with social support for AWEs. Results In total, 165 AWEs were consecutively included in the present study. Linear regression analysis showed that the marital status (t = -3.550, β = -0.272, P = 0.001), the age at onset (t = 2.545, β = 0.192, P = 0.012), and the QOLIE-31 score (t = 3.144, β = 0.221, P = 0.002) were independent variables associated with social support for AWEs. Conclusions Our findings suggest that the poor social support is associated with childhood onset of epilepsy and the unmarried status. This study also confirmed a negative influence of low social support on quality of life in AWEs.

Abstract Objectives The association between insomnia and quality of life (QOL) in epilepsy is poorly understood and may involve interactive variables. We aimed to investigate whether and how insomnia, levels of depression and anxiety symptoms interact to influence QOL in people with epilepsy (PWE). Methods A consecutive cohort of 179 PWE was enrolled. We collected data on insomnia, levels of depression and anxiety symptoms, and QOL. The Insomnia Severity Index (ISI), Depression Inventory for Epilepsy (NDDI-E), Generalized Anxiety Disorder-7 (GAD-7), and QOL in Epilepsy Inventory (QOLIE-31) were used. The direct, indirect, and total effects of insomnia on QOL were estimated based on a moderated mediation model. Results Depression symptom levels mediated the association between insomnia and QOL (B = 0.09 SE = 0.03, p = 0.01). Depression symptom levels accounted for 34.7% of the total effect of insomnia on QOL. The mediating effect of depression symptom levels was positively moderated by anxiety symptom levels (B = 0.09, SE = 0.03, p = 0.01). Conclusion The effect of insomnia on QOL can be partially explained by the mediation of depression symptom levels. Additionally, improving anxiety symptoms may attenuate the indirect effect of insomnia on QOL through depression symptom levels.

Abstract Background There were limited studies investigating treatments of septic cardiomyopathy (SCM), which is a common complication during sepsis. A septic rat model created by cecal ligation and puncture (CLP) was used to investigate the effects of diminazene aceturate (DIZE) in SCM. Methods A total of 151 Wistar rats were randomly assigned into the sham, CLP, or CLP + DIZE group. Data evaluated postoperatively at 6, 12, 24, and 48 hours included: cardiac function; plasma concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6, angiotensin-(1–7) [Ang-(1–7)], angiotensin II (AngII), troponin I, and brain natriuretic peptide; expression levels of myocardial Ang-(1–7), angiotensin-converting enzyme (ACE), ACE2, and angiotensin type 1 and Mas receptors; and histological changes. Results We found that the CLP + DIZE group had a lower mortality compared to the CLP group (38.5% versus 61.5%) within 48 h postoperatively, although without statistical significance. In contrast to the sham group, the CLP group had decreased cardiac functions, increased myocardial injuries, and higher TNF-α levels, which were ameliorated in the CLP + DIZE group. Furthermore, administration of DIZE could reverse the decreases of myocardial Ang-(1–7) and ACE2 expressions in the CLP group, which finally minimized the myocardial microstructure disruptions. Conclusions It was concluded that DIZE could mitigate the development of SCM and preserve cardiac function during sepsis possibly by interfering with the renin-angiotensin system through promoting myocardial ACE2 expression and restoring local Ang-(1–7) levels.

Over the past fifty years, the distribution patterns of C4 species, across large spatial scales, are largely ignored. Here, we endeavored to examine patterns in the taxonomic and phylogenetic diversity of species with C4 photosynthetic pathways across the broad spatial extent of China and relate those to climatic gradients. We built a database of all plants with the C4 photosynthetic pathway in China. We analyzed the geographic distributions, taxonomic diversity, phylogenetic diversity, and phylogenetic structure of all C4 species, as well as the three families with the most C4 species (Poaceae, Amaranthaceae and Cyperaceae), and compared their values along temperature and precipitation gradients at two scales—the level of the province and at the 100 x 100 km grid cell. We found 644 C4 plants (belonging to 23 families 165 genera) in China, with Poaceae (57%), Amaranthaceae (17%), Cyperaceae (13%) accounting for the majority of species. Standardized effect size values of phylogenetic distances were negative overall, indicating that C4 species showed a phylogenetic clustering pattern. Southern China had the highest species richness and the highest degree of phylogenetic clustering. C4 tended to be more phylogenetically over-dispersed in regions with colder and/or drier climates, but more clustered in warmer and/or wetter climates. Patterns within individual families were more nuanced. The distribution of C4 species and its phylogenetic structure across China was constrained by temperature and precipitation. C4 species showed a phylogenetic clustering pattern across China, while different families showed more nuanced responses to climate variation, suggesting a role for evolutionary history.

Common carotid artery (CCA) pseudoaneurysm is a rare clinical disorder. CCA pseudoaneurysm that occurs with a carotid-esophageal fistula and causes massive upper gastrointestinal bleeding is especially uncommon but can be life-threatening. Accurate diagnosis and prompt managements are essential to save lives. Here, we report a case of a 58-year-old female who presented with dysphagia and throat pain after accidental ingestion of a chicken bone. The patient presented with active upper gastrointestinal bleeding which quickly developed into hemorrhage shock. Imaging studies confirmed a diagnosis of right CCA pseudoaneurysm and carotid-esophageal fistula. The patient had a satisfactory recovery after a right CCA balloon occlusion, right CCA pseudoaneurysm excision, and right CCA and esophageal repairs. We present and discuss this case here to remind physicians to rule out rare causes of upper gastrointestinal bleeding. A multidisciplinary approach is commonly required to achieve satisfactory outcomes in these cases.

Swine acute diarrhea syndrome coronavirus (SADS-CoV), a member of the family Coronaviridae and the genus Alphacoronavirus, primarily affects piglets under 7 days old, causing symptoms such as diarrhea, vomiting, and dehydration. It has the potential to infect human primary and passaged cells in vitro, indicating a potential risk of zoonotic transmission. In this study, we successfully generated and purified six monoclonal antibodies (mAbs) specifically targeting the spike protein of SADS-CoV, whose epitope were demonstrated specificity to the S1A or S1B region by immunofluorescence assay and enzyme-linked immunosorbent assay. Three of these mAbs were capable of neutralizing SADS-CoV infection on HeLa-R19 and A549. Furthermore, we observed that SADS-CoV induced the agglutination of erythrocytes from both humans and rats, and the hemagglutination inhibition capacity and antigen–antibody binding capacity of the antibodies were assessed. Our study reveals that mAbs specifically targeting the S1A domain demonstrated notable efficacy in suppressing the hemagglutination phenomenon induced by SADS-CoV. This finding represents the first instance of narrowing down the protein region responsible for SADS-CoV-mediated hemagglutination to the S1A domain, and reveals that the cell attachment domains S1A and S1B are the main targets of neutralizing antibodies.

BackgroundThe association between iron status and obesity-related traits is well established by observational studies, but the causality is uncertain. In this study, we performed a two-sample bidirectional Mendelian randomization analysis to investigate the causal link between iron status and obesity-related traits.MethodsThe genetic instruments strongly associated with body mass index (BMI), waist-hip ratio (WHR), serum ferritin, serum iron, transferrin saturation (TSAT), and total iron-binding capacity (TIBC) were obtained through a series of screening processes from summary data of genome-wide association studies (GWAS) of European individuals. We used numerous MR analytical methods, such as inverse-variance weighting (IVW), MR-Egger, weighted median, and maximum likelihood to make the conclusions more robust and credible, and alternate methods, including the MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis to evaluate the horizontal pleiotropy and heterogeneities. In addition, the MR-PRESSO and RadialMR methods were utilized to identify and remove outliers, eventually achieving reduced heterogeneity and horizontal pleiotropy.ResultsThe results of IVW analysis indicated that genetically predicted BMI was associated with increased levels of serum ferritin (β: 0.077, 95% CI: 0.038, 0.116, P=1.18E-04) and decreased levels of serum iron (β: -0.066, 95% CI: -0.106, -0.026, P=0.001) and TSAT (β: -0.080, 95% CI: -0.124, -0.037, P=3.08E-04), but not associated with the levels of TIBC. However, the genetically predicted WHR was not associated with iron status. Genetically predicted iron status were not associated with BMI and WHR.ConclusionsIn European individuals, BMI may be the causative factor of serum ferritin, serum iron, and TSAT, but the iron status does not cause changes in BMI or WHR.

The identification of protein–protein interaction (PPI) sites is essential in the research of protein function and the discovery of new drugs. So far, a variety of computational tools based on machine learning have been developed to accelerate the identification of PPI sites. However, existing methods suffer from the low predictive accuracy or the limited scope of application. Specifically, some methods learned only global or local sequential features, leading to low predictive accuracy, while others achieved improved performance by extracting residue interactions from structures but were limited in their application scope for the serious dependence on precise structure information. There is an urgent need to develop a method that integrates comprehensive information to realize proteome-wide accurate profiling of PPI sites. Herein, a novel ensemble framework for PPI sites prediction, EnsemPPIS, was therefore proposed based on transformer and gated convolutional networks. EnsemPPIS can effectively capture not only global and local patterns but also residue interactions. Specifically, EnsemPPIS was unique in (a) extracting residue interactions from protein sequences with transformer and (b) further integrating global and local sequential features with the ensemble learning strategy. Compared with various existing methods, EnsemPPIS exhibited either superior performance or broader applicability on multiple PPI sites prediction tasks. Moreover, pattern analysis based on the interpretability of EnsemPPIS demonstrated that EnsemPPIS was fully capable of learning residue interactions within the local structure of PPI sites using only sequence information. The web server of EnsemPPIS is freely available at http://idrblab.org/ensemppis.

This study presented recently reprocessed multi-channel seismic data and multi-beam bathymetric map to reveal the geomorphology and stratigraphic architecture of the Yongle isolated carbonate platform in the Xisha Archipelago, northwestern South China Sea. Our results show that the upper slope angles of Yongle carbonate platform exceed 10° and even reach to ∼32.5° whereas the lower slope angles vary from .5° to 5.3°. The variations of slope angles show that margins of Yongle Atoll belong to escarpment (bypass) margins to erosional (escarpment) margins. The interior of carbonate platform is characterized by sub-parallel to parallel, semi-continuous to continuous reflectors with medium-to high-amplitude and low-to medium-frequency. The platform shows a sub-flat to flat-topped shape in its geometry with aggradation and backstepping occurring on the platform margins. According to our seismic-well correlation, the isolated carbonate platform started forming in Early Miocene, grew during Early to Middle Miocene, and subsequently underwent drowning in Late Miocene, Pliocene and Quaternary. Large-scale submarine mass transport deposits are observed in the southeastern and southern slopes of Yongle Atoll to reshape the slopes since Late Miocene. The magmatism and hydrothermal fluid flow pipes around the Yongle Atoll have been active during 10.5–2.6 Ma. Their activity might intensify dolomitization of the Xisha isolated carbonate platforms during Late Miocene to Pliocene. Our results further suggest that the Yongle carbonate platform is situated upon a pre-existing fault-bounded block with a flat pre-Cenozoic basement rather than a large scale volcano as previously known and the depth of the basement likely reached to 1400 m, which is deeper than the well CK-2 suggested.

Immunogenic cell death (ICD) is a form of regulated cell death that elicits immune response. Common inducers of ICD include cancer chemotherapy and radiation therapy. A better understanding of ICD might contribute to modify the current regimens of anti-cancer therapy, especially immunotherapy. This study aimed to identify ICD-related prognostic gene signatures in breast cancer (BC). An ICD-based gene prognostic signature was developed using Lasso-cox regression and Kaplan-Meier survival analysis based on datasets acquired from the Cancer Genome Atlas and Gene Expression Omnibus. A nomogram model was developed to predict the prognosis of BC patients. Gene Set Enrichment Analysis (GESA) and Gene Set Variation Analysis (GSVA) were used to explore the differentially expressed signaling pathways in high and low-risk groups. CIBERSORT and ESTIMATE algorithms were performed to investigate the difference of immune status in tumor microenvironment of different risk groups. Six genes (CALR, CLEC9A, BAX, TLR4, CXCR3, and PIK3CA) were selected for construction and validation of the prognosis model of BC based on public data. GSEA and GSVA analysis found that immune-related gene sets were enriched in low-risk group. Moreover, immune cell infiltration analysis showed that the immune features of the high-risk group were characterized by higher infiltration of tumor-associated macrophages and a lower proportion of CD8+ T cells, suggesting an immune evasive tumor microenvironment. We constructed and validated an ICD-based gene signature for predicting prognosis of breast cancer patients. Our model provides a tool with good discrimination and calibration abilities to predict the prognosis of BC, especially triple-negative breast cancer (TNBC).

BackgroundIn general, medical staff who work in nuclear medicine should be entirely safe in their professional environment. Nevertheless, we already know that the working environment of the nuclear medicine staff is not completely safe due to the handling of high amounts of radionuclides for diagnostic and therapy applications, which is especially relevant for 131I (as a non-sealed source).PurposeThe goal of this study was to assess the inhaled 131I thyroid dose in nuclear medicine workers and to introduce a simple method for internal exposure monitoring.MethodsUsing 2-IN*2-in NaI (Tl) scintillation spectrometer and its supporting software (InSpector Maintenance Utility and Genie 2000), from 2019 to 2021, internal thyroid irradiation monitoring, an internal thyroid irradiation monitoring investi A NaI (Tl) scintillation spectrometer and its sugation was carried out for 3 consecutive years, between 2019 and 2021, in staff members of nuclear medicine departments engaged with iodine therapy.Results131I activity was found highest in the thyroid of nuclear medicine workers involved with the manual packaging and delivery of the radioisotope, while it was not detected in staff members involved with the automatic packaging and drug delivery. The activity range was found to be 30.00 ± 6.60–6070.00 ± 1335.40 Bq for the exposed personnel, and the estimated dose was 0.05–6.77 mSv. In 2021, three workers had an annual equivalent dose above 5 mSv.ConclusionBy monitoring the thyroid 131I in staff members of the nuclear medicine department, it was found that there are 131I internal occupational exposure risks. The best solution is automatic packaging and drug delivery.

Emissions of agricultural machines during tillage processes played an important role in severe seasonal pollution events in agricultural areas in China and cannot be ignored. In this study, the CO, NOX, HC and PM2.5 emissions of agricultural machines during real-world tillage processes were tested using a portable emission measurement system (PEMS), and their fuel-based and tillage area-based emission factors were calculated. The CO, NOX, HC and PM2.5 emissions were influenced by emission standards, engine rated power, tillage processes and crops. Only the CO, HC and PM2.5 fuel-based emission factors were reduced from China 0 to China II. For China III agricultural machines, the fuel-based emission factors were higher during plowing and tilling than during harvesting. The tillage area-based CO, NOX, HC and PM2.5 emission factors of corn tillage process were 11.85 ± 8.30, 53.21 ± 48.80, 3.46 ± 3.14 and 1.64 ± 1.33 kg/km2, respectively. The tillage area-based CO, NOX, HC and PM2.5 emission factors of wheat tillage process were 19.69 ± 21.50, 79.98 ± 63.22, 3.90 ± 2.96 and 1.61 ± 2.43 kg/km2, respectively. The tillage area-based emission factors of China III agricultural machines during plowing and tilling were higher than those during harvesting. The fuel consumption per unit tillage area can be used to provide a reference for the interconversion of the two emission factors in future studies. By comparing the fuel-based emission factors in this study with those in the Guidelines and other studies, we observed that the CO, HC and PM2.5 emissions of agricultural machines with corresponding emission standards may be overestimated and the NOX emissions may be underestimated in areas where wheat and corn are mainly grown. Moreover, the pollutant emissions of agricultural machines were regionally different. These results could help elucidate the pollution contribution of agricultural machines in China.

Abstract Ectopic activation during early acute regional ischemia may initiate fatal reentrant arrhythmias. However, the origin of this ectopy remains poorly understood. Studies suggest that systolic stretch arising from dyskinesia in ischemic tissue may cause ectopic depolarization due to cardiac mechanosensitivity. The aim of this study was to investigate the link between mechanical stretch and ectopic electrical activation during early acute regional ischemia. We used a recently developed optical mapping technique capable of simultaneous imaging of mechanical deformation and electrical activation in isolated hearts. Eight domestic swine hearts were prepared in left ventricular working mode (LVW), in which the left ventricle was loaded and contracting. In an additional eight non‐working (NW) hearts, contraction was pharmacologically suppressed with blebbistatin and the left ventricle was not loaded. In both groups, the left anterior descending coronary artery was tied below the first diagonal branch. Positive mechanical stretch (bulging) during systole was observed in the ischemic zones of LVW, but not NW, hearts. During ischemia phase 1a (0–15 min post‐occlusion), LVW hearts had more ectopic beats than NW hearts (median: 19, interquartile range: 10–28 vs. median: 2, interquartile range: 1–6; p = 0.02); but the difference during phase 1b (15–60 min post‐occlusion) was not significant (median: 27, interquartile range: 22–42 vs. median: 16, interquartile range: 12–31; p = 0.37). Ectopic beats arose preferentially from the ischemic border zone in both groups (p

A series of lockdown measures in response to the Corona Virus Disease 2019 (COVID-19) outbreak resulted in a drop in anthropogenic emissions and changes in concentrations of PM2.5 and O3. Backward trajectories analysis, cluster analysis, potential source contribution function (PSCF) and concentration weighted trajectory (CWT) technologies were conducted to reveal the characteristics and potential source areas of pollutants in Beijing before the COVID-19 outbreak (BCO period), during the outbreak (COB period) and after the outbreak (ACO period), as well as the contemporaneous period in 2019 (CCO period), which is critical for exploring the efficient control measures and making policy. The results indicated that despite the significant reduction in anthropogenic emissions during the epidemic, the PM2.5 concentrations increased by 1.0% caused by unfavorable meteorological conditions. O3 concentrations increased by 174.8% compared to that during the BCO period due to the increased temperature and inappropriate precursor reduction ratios. A considerable decrease of NO3- in PM2.5 was observed under the influence of significant reductions in vehicle emissions during the lockdown. The cluster analysis revealed that short-range transport played a significant role in the accumulation of local PM2.5 pollution, while long-range northwest airflows contributed more to O3 accumulation, and weakened as the season changed. The PSCF and CWT analysis demonstrated that potential source areas of PM2.5 were mostly located in the central and southern Hebei, the southwestern Shandong in the CCO period, and expanded to central Inner Mongolia and northern Shanxi in the COB period. These areas were highly compatible with the high emission areas of the emission inventory statistics. After the outbreak, the source areas of O3 were centered in the Beijing-Tianjin-Hebei region and Shandong province, with a radial dispersion in all directions, while they were distributed in the central Mongolia and Inner Mongolia during the other periods.

BackgroundRadical antegrade modular pancreatosplenectomy (RAMPS) has been proven to improve R0 resection and lymph harvest in treating patients with distal pancreatic cancer. The development of minimally invasive surgery has advantages in postoperative recovery. Therefore, minimally invasive (MI-) RAMPS may combine the advantages of both benefits to improve survival. Nevertheless, evidence to validate the safety and efficacy of MI-RAMPS is limited.Method/DesignThe MIRROR trial will be the first multicenter prospective randomized clinical trial to investigate the outcome of MI-RAMPS. The hypothesis is that MI-RAMPS is superior in postoperative recovery. The primary outcome is the length of postoperative stay. Based on the hypothesis and primary outcome, the sample size is 250 patients (125 participants in each group). The trial will investigate factors related to surgical safety, short-term outcome, pathological assessment, and survival as secondary outcomes.ConclusionThis study will offer a relatively higher level of evidence to further illustrate the accessibility and benefits of MI-RAMPS for the treatment of distal pancreatic cancer.Clinical Trial RegistrationClinicaltrials.gov, NCT03770559.

Fibrinogen is reportedly associated with neurodegenerative diseases (NDs), but the underlying causality remains controversial. Using Mendelian randomization (MR), this study aimed to assess the causal association between fibrinogen and Alzheimer’s disease (AD), Parkinson’s disease (PD), and Lewy body dementia (LBD). Genetic variants associated with fibrinogen and γ-fibrinogen were selected and used as instrumental variables. The effect estimates of the main analysis were obtained by inverse-variance weighting (IVW), complemented by sensitivity analyses to verify model assumptions, and multivariable MR was conducted to control for potential pleiotropic effect. Two-step MR was performed to assess the causal association through mediators. The main analysis suggested no causal association between genetically predicted plasma fibrinogen and γ-fibrinogen levels and the risk of AD, PD, and LBD. The effect estimates did not change in the follow-up sensitivity analyses and MVMR. However, the two-step MR analysis provides evidence that fibrinogen may contribute to the risk of AD via CRP levels. There was an inverse effect of adult height levels on the risk of AD. Our results support the effects of fibrinogen on the risk of AD through increasing plasma CRP levels. Our study found no evidence to support the effects of genetically determined fibrinogen and γ-fibrinogen levels on the risk of PD and LBD. Additionally, our findings suggested an inverse association between genetically determined adult height levels and the risk of AD. Future studies are needed to elucidate the underlying mechanisms and their clinical applications.

After its initial outbreak in 2019, the 2019 novel coronavirus disease (COVID-19) remains a global health concern. COVID-19 is well known for causing severe respiratory pathology, but it can also cause a variety of extra-pulmonary manifestations. Among them, myocardial injury has received substantial attention because it is usually associated with poor prognosis and mortality, thus emphasizing the importance of monitoring and managing myocardial injury in patients with COVID-19. Myocarditis has received attention as a complication of myocardial injury during and after the onset of COVID-19. Here, to aid in clinical decision-making, we present a narrative review on COVID-19- associated myocardial injury and myocarditis, discussing clinical evidence, pathogenesis, diagnostic tools, and therapeutic strategies.

ObjectiveTo investigate the relapse rate and study the factors that may predict the subsequent relapse in anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis in Northeast China.MethodsIn the retrospective cohort study, we consecutively enrolled patients with anti-N1MDAR, anti-GABABR and anti-LGI1 encephalitis between March 2015 and November 2021. The patients were followed up for at least 6 months. The outcome variable was a binary variable of relapse or not. Predictors of relapse were identified.ResultsA total of 100 patients were enrolled. Relapse occurred in 26 (26%) patients after a median follow-up of 18 months since the first event. The relapse rates of anti - NMDAR, anti - GABABR and anti - LGI1 encephalitis were 25%, 33.3%, and 28.6%, respectively. The multivariable analysis results suggested that immunotherapy delay at the acute phase was independently associated with an increased risk of relapse in total patients (HR = 2.447, 95% CI = 1.027 - 5.832; P = 0.043). Subgroup analysis results showed that antibody titer was associated with the likelihood of relapse in anti-LGI1 encephalitis. The higher the concentration, the more likely it was for patients to have relapse (p=0.019).ConclusionThe general relapse rate of anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis was 26%. The risk of subsequent relapse was elevated in those with delayed immunotherapy in the first episode. In subgroup of anti-LGI1 encephalitis, higher antibody titer was the risk factors of relapse. Thus, timely and aggressive immunotherapy may be beneficial for patients to prevent subsequent relapse.

The randomized controlled study investigated the impacts of immediate peri-operative Intermittent pneumatic compression (IPC) on hemodynamic indicators in patients undergoing laparoscopic gynecologic surgery. Patients scheduled for elective laparoscopic gynecologic surgery were randomized to control (IPC not used), pre-operative IPC, post-operative IPC, and peri-operative IPC (performed both before and after surgery) groups. Systolic blood pressure (SBP), mean blood pressure (MBP) cardiac output (CO), heart rate (HR) and systemic vascular resistance (SVR) were measured at different time points. The results showed that SBP changes not obviously over time in the control and peri-operative IPC group. Compared with values before surgery, the pre-operative IPC group had a lower SBP (P

Lung infection is a common complication induced by stroke and seriously affects the prognosis and life quality of patients. However, effective therapeutic strategies are still lacking. In the present study, the herb formula GCis was confirmed to prevent pulmonary infection induced by intracerebral hemorrhage (ICH). The animal model of lung infection induced by ICH, GCis (Ginseng Radix et Rhizoma, Aconiti Lateralis Radix Praeparata, and Cistanches Herba) was orally administrated every day for 7 days. Lung microbial biomass and pathological results showed that the GCis formula pretreatment significantly reduced lung bacterial biomass and alleviated pathological abnormalities. These results indicated that the GCis formula has a clear pharmacological effect on preventing lung infection induced by ICH. Immunosuppression induced by ICH seemed to be the main mechanism of lung infection. Our results showed that the spleen and thymus indexes, WBC, and LY% contents were significantly increased in the GCis formula group. Moreover, bone marrow cells were further analyzed by transcriptome sequencing, and GO and KEGG enrichment analysis results showed that immune function was the main pathway enriched by differential genes after GCis formula intervention. More importantly, our results showed that GCis pretreatment had no significant effect on the mRNA expression of IL-1β, IL-6, and TNF-α in the brain. These results indicated that the GCis formula could enhance immunity after ICH. The intestinal barrier function was further investigated in the present study, considering the origin of the source of infection. Our results showed that the mRNA expressions of intestinal ZO-1, SIgA, and MUC2 were significantly increased, villi structure was intact, inflammatory cell infiltration was reduced, and goblet cell number was increased after GCis formula treatment. These results suggest that the GCis formula can enhance the intestinal mucosal immune barrier. This study provides a herb formula (GCis) that could enhance peripheral immunity and intestinal mucosal immune barrier to prevent pulmonary infection induced by ICH. It would be beneficial in the prevention of severe clinical infections.

Cucurbitacins have a variety of bioactivities, such as anticancer, anti-inflammatory, antidepressant-like, and antiviral effects, but their pharmacological effect in ulcerative colitis (UC) has not been reported until now. Thus, this study aims to investigate the preventive effects of Xuedan sustained release pellets (XSPs) on UC rats and the underlying mechanisms. XSPs were prepared by extracting cucurbitacins from Hemsleya. Experimental UC rats were induced by the intake of 4% dextran sulfate sodium (DSS) for a week and treated with different doses of XSP (0.95, 1.90, and 3.8 mg/kg). The body weight, colon length, disease activity index (DAI), and histological changes of colonic tissue were measured. In addition, the expressions of pro-inflammatory cytokines were detected by using the enzyme-linked immunosorbent assay. Pathways involved in the intestinal inflammation were targeted by RNA-sequencing. Moreover, the changes of gut microbial diversity and composition were analyzed by the 16SrNA analysis and the contents of short-chain fatty acids (SCFAs) were detected by GC-MS. The results revealed that XSP intervention greatly restored the weight loss and colonic shortening (p < 0.05) and reduced the raised DAI scores, myeloperoxidase, and nitric oxide activities in UC in rats (p < 0.05). XSP administration also downregulated the protein levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α. Notably, it was found that XSP considerably suppressed the activation of the MAPK signaling pathway. In addition, XSP treatment improved the balance of gut microbiota that was disturbed by DSS. The beneficial bacteria Lachnospiraceae_NK4A136 group and Lactobacillus at the genus level significantly increased in the XSP group, which had decreased with the use of DSS (p < 0.05). Pathogenic bacteria including Escherichia–Shigella and Bacteroides in UC in rats were reduced by XSP intervention. Furthermore, XSP significantly elevated the production of SCFAs in UC in rats (p < 0.05). These alterations in inflammatory status were accompanied with changes in gut microbiota diversity and SCFA production. In conclusion, XSP exhibited protective effects against DSS-induced UC in rats. XSP treatment decreased inflammation via modulation of gut microbiota composition and SCFA production.

Abstract We introduce a new computational method named EMeth to estimate cell type proportions using DNA methylation data. EMeth is a reference-based method that requires cell type-specific DNA methylation data from relevant cell types. EMeth improves on the existing reference-based methods by detecting the CpGs whose DNA methylation are inconsistent with the deconvolution model and reducing their contributions to cell type decomposition. Another novel feature of EMeth is that it allows a cell type with known proportions but unknown reference and estimates its methylation. This is motivated by the case of studying methylation in tumor cells while bulk tumor samples include tumor cells as well as other cell types such as infiltrating immune cells, and tumor cell proportion can be estimated by copy number data. We demonstrate that EMeth delivers more accurate estimates of cell type proportions than several other methods using simulated data and in silico mixtures. Applications in cancer studies show that the proportions of T regulatory cells estimated by DNA methylation have expected associations with mutation load and survival time, while the estimates from gene expression miss such associations.

In order to improve the mechanical properties, nutritional value and fresh-keeping ability of conventional sodium alginate edible composite membranes, a new type of edible composite film was prepared by adding water-blocking agent carnauba wax, plasticizer glycerin, antioxidant and nutritional enhancer sodium ascorbate on a basis of traditional sodium alginate composite film. In this study, the physical, mechanical and structural properties of different film components were investigated. The results showed the components did not simply combine, but produced interaction forces which improved the stability and mechanical properties of composite film. When the amount of calcium ascorbate was 0.4%, the water vapor transmittance of the composite film reached a minimum of 0.65 g·mm/(cm2·d·kPa), and the tensile strength and elongation at break reached the maximum, which were 398.64 MPa and 17.93%, respectively. Additionally, the sodium alginate-carnauba wax film exhibited better performance on the preservation of fresh-cut apples. Compared with other composite films, the color and hardness of fresh-cut apples coated with this composite film were better maintained, and the losses of titration acid content and soluble solid content were reduced. Moreover, the weight loss rate, increase in polyphenol oxidase activity and total colony count were inhibited. All results determined that the edible film has good application value in the field of fresh-cut fruit preservation, which provides a theoretical basis for further research on edible film.

The sintering behaviour and microwave dielectric properties of LiCaPO4 ceramic synthesized by the solid-state reaction method have been investigated, and the vibration property has been discussed with the help of the first principle calculation. Characterisation methods include X-ray diffraction, scanning electron microscopy, network analysis, differentia-thermal and thermo-mechanical analysis, and Raman spectrometry. The increasing sintering temperature results in the formation of the second phase. The composite ceramic with two phases (LiCaPO4 and Ca3(PO4)2) has formed when sintered at 950 °C, 2.99 g/cm3 for density, 20.09 for ɛr and tanδ = 0.008 at 8 GHz.

ObjectiveWe aimed to investigate the mortality rate and identify the predictors of death in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis.MethodsPatients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were recruited from the Neurology Department of the First Hospital of Jilin University from March 2015 to November 2021. The primary outcome variable was a binary variable of death vs. survival. The potential risk factors for mortality were evaluated. The mortality rates were determined, and the independent predictors of death were identified using multivariable logistic regression analysis.ResultsA total of 100 hospitalized patients with anti-NMDAR, anti-LGI1, or anti-GABABR encephalitis were included in the final analysis. Fifteen patients (15%) died during a median follow-up period of 18 months. The mortality rates were 10% for anti-NMDAR encephalitis, 2.8% for anti-LGI1 encephalitis, and 41.7% for anti-GABABR encephalitis. The multivariable analysis results showed that older age at onset [adjusted odds ratio (OR) = 1.017, 95% confidence interval (CI) = 1.009–1.136; p = 0.023] was independently associated with an increased risk of death. Antibody type was also associated with mortality. Patients with anti-GABABR encephalitis had 13.458-fold greater odds of dying than patients with anti-LGI1 encephalitis (adjusted OR = 13.458, 95% CI = 1.270–142.631; p = 0.031).ConclusionThe general mortality rate of anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis was 15%. Age at onset and type of autoimmune encephalitis antibody were independent predictors of death in these patients.

Objective: We aimed to determine the prevalence of social isolation and associated factors among adults with epilepsy in northeast China.Methods: A cohort of consecutive patients with epilepsy (PWE) from the First Hospital of Jilin University (Changchun, China) was recruited. Demographic and clinical data for each patient were collected during a face-to-face interview. Social isolation was measured using the Berkman-Syme Social Network Index (SNI), and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Quality of Life in Epilepsy Inventory (QOLIE-31) were also administered. Multivariate logistic regression analyses were used to determine the factors associated with social isolation in PWE.Results: A total of 165 patients were included in the final analysis. The mean SNI score was 2.56 (SD: 1.19), and 35 patients (21.2%) were socially isolated. In multivariate logistic regression analysis, higher depressive symptom levels (OR = 1.15, 95% CI: 1.003–1.318, P = 0.045) and poorer quality of life (OR = 0.967, 95% CI: 0.935–0.999, P = 0.047) emerged as independent factors associated with social isolation in PWE.Conclusion: Social isolation is common and occurs in approximately one-fifth of PWE. Social isolation is significantly associated with depressive symptoms and poor quality of life in PWE. Patients need to be encouraged to actively integrate with others and reduce social isolation, which may help improve their quality of life.