Search

Stroke ranks as the second most significant contributor to mortality worldwide and is a major factor in disability. Ischemic strokes account for 71% of all stroke incidences globally. The foremost approach to treating ischemic stroke prioritizes quick reperfusion, involving methods such as intravenous thrombolysis and endovascular thrombectomy. These techniques can reduce disability but necessitate immediate intervention. After cerebral ischemia, inflammation rapidly arises in the vascular system, producing pro-inflammatory signals that activate immune cells, which in turn worsen neuronal injury. Following reperfusion, an overload of intracellular iron triggers the Fenton reaction, resulting in an excess of free radicals that cause lipid peroxidation and damage to cellular membranes, ultimately leading to ferroptosis. The relationship between inflammation and ferroptosis is increasingly recognized as vital in the process of cerebral ischemia-reperfusion (I/R). Inflammatory processes disturb iron balance and encourage lipid peroxidation (LPO) through neuroglial cells, while also reducing the activity of antioxidant systems, contributing to ferroptosis. Furthermore, the lipid peroxidation products generated during ferroptosis, along with damage-associated molecular patterns (DAMPs) released from ruptured cell membranes, can incite inflammation. Given the complex relationship between ferroptosis and inflammation, investigating their interaction in brain I/R is crucial for understanding disease development and creating innovative therapeutic options. Consequently, this article will provide a comprehensive introduction of the mechanisms linking ferroptosis and neuroinflammation, as well as evaluate potential treatment modalities, with the goal of presenting various insights for alleviating brain I/R injury and exploring new therapeutic avenues.

Facial expression recognition (FER) plays a crucial role in affective computing, enhancing human-computer interaction by enabling machines to understand and respond to human emotions. Despite advancements in deep learning, current FER systems often struggle with challenges such as occlusions, head pose variations, and motion blur in natural environments. These challenges highlight the need for more robust FER solutions. To address these issues, we propose the Attention-Enhanced Multi-Layer Transformer (AEMT) model, which integrates a dual-branch Convolutional Neural Network (CNN), an Attentional Selective Fusion (ASF) module, and a Multi-Layer Transformer Encoder (MTE) with transfer learning. The dual-branch CNN captures detailed texture and color information by processing RGB and Local Binary Pattern (LBP) features separately. The ASF module selectively enhances relevant features by applying global and local attention mechanisms to the extracted features. The MTE captures long-range dependencies and models the complex relationships between features, collectively improving feature representation and classification accuracy. Our model was evaluated on the RAF-DB and AffectNet datasets. Experimental results demonstrate that the AEMT model achieved an accuracy of 81.45% on RAF-DB and 71.23% on AffectNet, significantly outperforming existing state-of-the-art methods. These results indicate that our model effectively addresses the challenges of FER in natural environments, providing a more robust and accurate solution. The AEMT model significantly advances the field of FER by improving the robustness and accuracy of emotion recognition in complex real-world scenarios. This work not only enhances the capabilities of affective computing systems but also opens new avenues for future research in improving model efficiency and expanding multimodal data integration.

Artificial intelligence (AI) has made significant progress in the medical field in the last decade. The AI-powered analysis methods of medical images and clinical records can now match the abilities of clinical physicians. Due to the challenges posed by the unique group of fetuses and the dynamic organ of the heart, research into the application of AI in the prenatal diagnosis of congenital heart disease (CHD) is particularly active. In this review, we discuss the clinical questions and research methods involved in using AI to address prenatal diagnosis of CHD, including imaging, genetic diagnosis, and risk prediction. Representative examples are provided for each method discussed. Finally, we discuss the current limitations of AI in prenatal diagnosis of CHD, namely Volatility, Insufficiency and Independence (VII), and propose possible solutions.

For over 170 years, general anesthesia has played a crucial role in clinical practice, yet a comprehensive understanding of the neural mechanisms underlying the induction of unconsciousness by general anesthetics remains elusive. Ongoing research into these mechanisms primarily centers around the brain nuclei and neural circuits associated with sleep-wake. In this context, two sophisticated methodologies, optogenetics and chemogenetics, have emerged as vital tools for recording and modulating the activity of specific neuronal populations or circuits within distinct brain regions. Recent advancements have successfully employed these techniques to investigate the impact of general anesthesia on various brain nuclei and neural pathways. This paper provides an in-depth examination of the use of optogenetic and chemogenetic methodologies in studying the effects of general anesthesia on specific brain nuclei and pathways. Additionally, it discusses in depth the advantages and limitations of these two methodologies, as well as the issues that must be considered for scientific research applications. By shedding light on these facets, this paper serves as a valuable reference for furthering the accurate exploration of the neural mechanisms underlying general anesthesia. It aids researchers and clinicians in effectively evaluating the applicability of these techniques in advancing scientific research and clinical practice.

Jujube (Ziziphus jujuba var. jujuba Mill.) and sour jujube (Z. jujuba var. spinosa (Bunge) Hu ex H.F.Chow.) are economically, nutritionally, and ecologically significant members of the Rhamnaceae family. Despite their importance, insufficient research on their genetics and habitats has impeded effective conservation and utilization. To address this knowledge gap, we conducted plastome sequencing, integrated distribution data from China, and assessed genetic diversity and suitable habitat. The plastomes of both species exhibited high conservation and low genetic diversity. A new-found 23 bp species-specific Indel in the petL-petG enabled us to develop a rapid Indel-based identification marker for species discrimination. Phylogenetic analysis and dating illuminated their genetic relationship, showing speciation occurred 6.9 million years ago, in a period of dramatic global temperature fluctuations. Substantial variations in suitable climatic conditions were observed, with the mean temperature of the coldest quarter as the primary factor influencing distributions (−3.16°C–12.73°C for jujube and −5.79°C to 4.11°C for sour jujube, suitability exceeding 0.6). Consequently, distinct conservation strategies are warranted due to differences in suitable habitats, with jujube having a broader distribution and sour jujube concentrated in Northern China. In conclusion, disparate habitats and climatic factors necessitate tailored conservation approaches. Comparing genetic diversity and developing rapid species-specific primers will further enhance the sustainable utilization of these valuable species.

Background: Small extracellular vesicles (sEVs) mediate intercellular communication in the tumor microenvironment (TME) and contribute to the malignant transformation of tumors, including unrestricted growth, metastasis, or therapeutic resistance. However, there is a lack of agents targeting sEVs to overcome or reverse tumor chemotherapy resistance through sEVs-mediated TME reprogramming.Methods: The paclitaxel (PTX)-resistant A549T cell line was used to explore the inhibitory effect of alpha-hederin on impeding the transmission of chemoresistance in non-small cell lung cancer (NSCLC) through the small extracellular vesicles (sEVs) pathway. This investigation utilized the CCK-8 assay and flow cytometry. Transcriptomics, Western blot, oil red O staining, and targeted metabolomics were utilized to evaluate the impact of alpha-hederin on the expression of signaling pathways associated with chemoresistance transmission in NSCLC cells before and after treatment. In vivo molecular imaging and immunohistochemistry were conducted to assess how alpha-hederin influences the transmission of chemoresistance through the sEVs pathway. RT-PCR was employed to examine the expression of miRNA and lncRNA in response to alpha-hederin treatment.Results: The resistance to PTX chemotherapy in A549T cells was overcome by alpha-hederin through its dependence on sEV secretion. However, the effectiveness of alpha-hederin was compromised when vesicle secretion was blocked by the GW4869 inhibitor. Transcriptomic analysis for 463 upregulated genes in recipient cells exposed to A549T-derived sEVs revealed that these sEVs enhanced TGFβ signaling and unsaturated fatty acid synthesis pathways. Alpha-hederin inhibited 15 types of unsaturated fatty acid synthesis by reducing the signaling activity of the sEVs-mediated TGFβ/SMAD2 pathway. Further, we observed that alpha-hederin promoted the production of three microRNAs (miRNAs, including miR-21-5p, miR-23a-3p, and miR-125b-5p) and the sorting to sEVs in A549T cells. These miRNAs targeted the TGFβ/SMADs signaling activity in sEVs-recipient cells and sensitized them to the PTX therapy.Conclusion: Our finding demonstrated that alpha-hederin could sensitize PTX-resistant NSCLC cells by sEV-mediated multiple miRNAs accumulation, and inhibiting TGFβ/SMAD2 pathways in recipient cells.

Coastal fishery systems are vital for both the environment and the economy, and at present, they face heightened vulnerability due to global climate change and natural disasters. A clearer understanding of the challenges that the system presents can be obtained by examining the vulnerabilities of fishery systems. This study employed a vulnerability scoping diagram framework and a multi-indicator approach combined with the entropy weight method for assigning weights to systematically evaluate the vulnerabilities of fishery systems in China’s coastal provinces. The spatiotemporal variation characteristics of vulnerability were analyzed and characterized, and the primary obstacles that affect vulnerability are discussed. The findings suggest that China’s coastal provinces’ fishery systems display vulnerability in terms of both time and space. From a temporal perspective, Liaoning, Hebei, and Shandong provinces exhibited an increasing trend in vulnerability, while Tianjin, Jiangsu, Zhejiang, Shanghai, Fujian, Guangdong, Guangxi, and Hainan showed decreasing trends. From a spatial perspective, Hainan and Liaoning’s fishery systems exhibited extremely high vulnerability in most years. In contrast, Tianjin consistently experienced extremely low vulnerability in most years. From the perspective of obstacles, the main factor was the funding for the extension of aquaculture technology, and this remained the primary obstacle factor across all years. The findings are significant for enhancing our understanding of vulnerability in fishery systems and for strengthening disaster prevention and mitigation measures. The results provide robust support for the improvement of management and the protection of fishery systems.

Magnetic microrobots are ideal for medical applications owing to their deep tissue penetration, precise control, and flexible movement. After decades of development, various magnetic microrobots have been used to achieve medical functions such as targeted delivery, cell manipulation, and minimally invasive surgery. This review introduces the research status and latest progress in the design and control systems of magnetic medical microrobots from a system integration perspective and summarizes the advantages and limitations of the research to provide a reference for developers. Finally, the future development direction of magnetic medical microrobot design and control systems are discussed.

ContextSeveral observational studies have found that hypothyroidism is associated with diabetes and its microvascular complications. However, the cause and effect have not been clarified.ObjectiveThe aim of the study was to examine the causality of such associations by a Mendelian randomization study.MethodsTwo-sample Mendelian randomization analysis was conducted to investigate the associations. Summary statistics for hypothyroidism were from the UK Biobank, and diabetes and its microvascular complications were from the largest available genome-wide association studies. MR–Egger, weighted median, inverse variance weighted, simple mode and weighted mode were used to examine the causal associations, and several sensitivity analyses were used to assess pleiotropy.ResultsInverse variance weighted estimates suggested that hypothyroidism was associated with type 1 diabetes and type 1 diabetes with renal complications (β= 9.059926, se= 1.762903, P = 2.76E-07 and β= 10.18375, se= 2.021879, P = 4.73E-07, respectively) but not type 2 diabetes and type 2 diabetes with renal complications. In addition, hypothyroidism was positively associated with severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy (β= 8.427943, se= 2.142493, P = 8.36E-05 and β= 3.100939, se= 0.74956, P=3.52E-05, respectively).ConclusionsThe study identified the causal roles of hypothyroidism in diabetes and its microvascular complications. Hypothyroidism can lead to type 1 diabetes, type 1 diabetes with renal complications, severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy.

BackgroundThe role of the microbiota-gut-brain axis in Parkinson’s disease (PD) has received increasing attention. Although gender differences are known to an essential role in the epidemiology and clinical course of PD, there are no studies on the sex specificity of the microbiota-gut-brain axis in the development and progression of PD.MethodsFresh fecal samples from 24 PD patients (13 males, 11 females) were collected for metagenomic sequencing. The composition and function of the gut microbiota were analyzed by resting-state functional magnetic resonance imaging (fMRI). Gender-dependent differences in brain ALFF values and their correlation with microbiota were further analyzed.ResultsThe relative abundance of Propionivibrio, Thermosediminibacter, and Flavobacteriaceae_noname was increased in male PD patients. LEfse analysis showed that Verrucomicrobial, Akkermansiaceae, and Akkermansia were dominant in the males. In female patients, the relative abundance of Propionicicella was decreased and Escherichia, Escherichia_coli, and Lachnospiraceae were predominant. The expression of the sesquiterpenoid and triterpenoid biosynthesis pathways was increased in male PD patients and was statistically different from females. Compared to the Male PD patients, female patients showed decreased ALFF values in the left inferior parietal regions, and the relative abundance of Propionivibrio was positively correlated with the regional ALFF values.ConclusionOur study provides novel clinical evidence of the gender-specific relationship between gut microbiota alterations and brain function in PD patients, highlighting the critical role of the microbiota-gut-brain axis in gender differences in PD.

Recently, COVID-19 pandemic, locust plague, drought and conflict have seriously affected the development of agriculture in Africa, which make Africa countries difficultly to achieve the Sustainable Development Goals (SDGs) 1 and 2. As the cornerstone of agricultural development, technological progress has made brilliant contributions to achieving food security and nutrition improvement in African countries. And as the largest economic and trade partner of Africa, analyzing the agricultural technology gap between China and African countries and exploring optimal paths also has great significance for achieving SDGs 8 and 9. Therefore, the paper used the Meta-frontier SBM model to measure the agricultural technology gap between China and African countries from 2003 to 2019, and explores sources of the gap. On this basis, 24 African countries were taken as samples to identify multiple paths for narrowing the technology gap between China and Africa with the help of the configuration analysis method of the fuzzy-set qualitative comparative analysis (fsQCA). The results showed that the overall agricultural technology gap between China and Africa was narrowing, which was mainly caused by the reduction of pure technical inefficiency. However, sources of technology gap in African countries with different economic development levels were different. Configuration analysis found that agricultural technology innovation and institutional environment were the key conditional variables to narrow the agricultural technology gap between China and Africa. Five paths had been formed around two key conditional variables, and further summarized into three driving modes: “technology-environment” driving mode, “technology-organization” driving mode and “organization-environment” driving mode. Furthermore, this paper explored the multiple concurrent causality of narrowing the technology gap, which overcomes the deficiency of using regression methods. The paper highlights the importance of enhancing the integration of technical, organizational, and environmental conditions in African countries to collectively advance agricultural scientific and technological progress

BackgroundWhile psychosocial problems and their related factors in men who have sex with men (MSM) have been well documented in developed countries, there are still not many studies addressing this issue in China and the results are inconsistent. This study aimed to assess the prevalence of loneliness and depressive symptoms among MSM, examine their associated factors, and investigate potential factors moderating the link between depressive symptoms and loneliness.MethodsA cross-sectional study was conducted in Taizhou of Zhejiang Province in China between April and November 2021. Loneliness was assessed using the 3-item UCLA Loneliness Scale (UCLA-3), and depressive symptoms were measured using the Patient Health Questionaire-9 (PHQ-9). Data from 655 MSM were eligible for analysis. Logistic regression models were used to examine the associations between independent variables and the outcomes of loneliness and depression. The interaction terms were added in the models to assess the moderating effects.ResultsOf the MSM sample, 13.28 and 7.48% perceived loneliness and reported moderate-to-severe depressive symptoms, respectively. We found that participants who experienced loneliness were more likely to have younger age (OR 0.44, 95% CI 0.21, 0.93, 15–32 years as reference group), low social support (OR 3.60, 95% CI 2.14, 6.04), low self-esteem (OR 3.03, 95% CI 1.45, 6.32) and moderate-to-severe depressive symptoms (OR 5.45, 95% CI 2.66, 11.15). The participants with moderate-to-severe depressive symptoms were more likely to have low self-esteem (OR 6.78, 95% CI 3.08, 14.95) and feelings of loneliness (OR 5.51, 95% CI 2.66, 11.40). Stratified analyzes showed that the magnitude of the associations between depressive symptoms and loneliness varied in MSM with different age, marital status, and self-esteem.ConclusionOur study suggests that we need to pay attention to feelings of loneliness and depressive symptoms and their closely associated factors such as social support and self-esteem among MSM in China. The MSM who were young, not married, and had low self-esteem were especially vulnerable to the impact of depressive symptoms on loneliness.

BackgroundHalf of the population of non-small cell lung cancer (NSCLC) patients are older than 70 years and have limited therapeutic options due to poor tolerance and being excluded in most clinical trials. Anlotinib hydrochloride, a novel oral multi-target tyrosine kinase inhibitor, has been approved for the standard third-line treatment for NSCLC in China. Herein we report an elderly NSCLC patient without any driver gene mutations who was undergoing anlotinib as a front-line treatment and who achieved long-term survival.Case summaryThe 77-year-old male patient was admitted to the hospital for chest tightness after engaging in physical activity for a week. The patient has been diagnosed with stage IIIB driver gene-negative squamous cell lung carcinoma. After that, he was treated with anlotinib for 2 years and 10 months from the first diagnosis until the last disease progression. Briefly, anlotinib combined with platinum-based chemotherapy was performed as the first-line therapy over six cycles. After 6 more cycles of anlotinib monotherapy maintenance, disease progression occurred. Then, anlotinib combined with tegafur was administered as a salvage treatment, and the disease was controlled again. After 29 cycles of anlotinib combined with tegafur regimens, the disease progressed finally. The patient achieved a total of 34 months of progression-free survival after anlotinib was used as the front-line treatment. He is still alive with a good performance status now (performance status score: 1).ConclusionThis patient achieved long-term survival using anlotinib as a front-line regimen combined with chemotherapy.

Microtubules are essential for regulating cell morphogenesis, plant growth, and the response of plants to abiotic stresses. TPX2 proteins are the main players determining the spatiotemporally dynamic nature of the MTs. However, how TPX2 members respond to abiotic stresses in poplar remains largely unknown. Herein, 19 TPX2 family members were identified from the poplar genome and analyzed the structural characteristics as well as gene expression patterns. All TPX2 members had the conserved structural characteristics, but exhibited different expression profiles in different tissues, indicating their varying roles during plant growth. Additionally, several light, hormone, and abiotic stress responsive cis-acting regulatory elements were detected on the promoters of PtTPX2 genes. Furthermore, expression analysis in various tissues of Populus trichocarpa showed that the PtTPX2 genes responded differently to heat, drought and salt stress. In summary, these results provide a comprehensive analysis for the TPX2 gene family in poplar and an effective contribution to revealing the mechanisms of PtTPX2 in the regulatory network of abiotic stress.

BackgroundUlcerative colitis (UC) is a chronic autoimmune-related disease that causes inflammation of the intestine. Ankylosing spondylitis (AS) is a common extraintestinal complication of UC involving the sacroiliac joint. However, the pathogenesis of AS secondary to UC has not been studied. This study aimed to investigate the shared pathways and potential common biomarkers of UC and AS.MethodsMicroarray data downloaded from the Gene Expression Omnibus (GEO) database were used to screen differentially expressed genes (DEGs) in the UC and AS datasets. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules related to UC and AS. Shared genes were then further analyzed for functional pathway enrichment. Next, the optimal common biomarker was selected using SVM-RFF and further validated using two independent GEO datasets. Finally, immune infiltration analysis was used to investigate the correlation of immune cell infiltration with common biomarkers in UC and AS.ResultsA total of 4428 and 2438 DEGs in UC and AS, respectively, were screened. Four modules were identified as significant for UC and AS using WGCNA. A total of 25 genes overlapped with the strongest positive and negative modules of UC and AS. KEGG analysis showed these genes may be involved in the mitogen-activated protein kinase (MAPK) signaling pathway. GO analysis indicated that these genes were significantly enriched for RNA localization. PAN3 was selected as the optimal common biomarker for UC and AS. Immune infiltration analysis showed that the expression of PAN3 was correlated with changes in immune cells.ConclusionThis study first explored the common pathways and genetic diagnostic markers involved in UC and AS using bioinformatic analysis. Results suggest that the MAPK signaling pathway may be associated with both pathogeneses and that PAN3 may be a potential diagnostic marker for patients with UC complicated by AS.

BackgroundThe trend towards low fertility and low mortality is prominant worldwide. The accelerating ageing and the pressure on public pensions are making the “dependent pattern of old-age support”, which relies on family and government, unsustainable. It is urgent for people to change their mindset about ageing and to develop a sense of “relying on themselves for oldage support”.MethodsThis study incorporates the commercial pension insurance, formal care and the attitude towards independent old-age support pattern into the framework of “independent pattern of old-age support”, using the probit regression model and instrumental variables approach to examine the impact of internet use on old-age support patterns of middleaged and older people based on the CGSS 2012–2018 five-period data.ResultsThe more frequent internet use increased the likelihood of purchasing commercial pension insurance, accepting formal care, and endorsing independence in later life. The internet can promote the acceptance of independent pattern of old-age support by delivering information and facilitating social interaction.DiscussionConsistent with previous research, this study finds that internet use can promote the purchase of commercial pension insurance. There are no relevant studies on the impact of internet use on formal care and attitude towards independent old-age support pattern. Our finding provides important empirical and theoretical references for ageing countries to further transform old-age support patterns.

Warburg effect is characterized by excessive consumption of glucose by the tumor cells under both aerobic and hypoxic conditions. This metabolic reprogramming allows the tumor cells to adapt to the unique microenvironment and proliferate rapidly, and also promotes tumor metastasis and therapy resistance. Metabolic reprogramming of tumor cells is driven by the aberrant expression and activity of metabolic enzymes, which results in the accumulation of oncometabolites, and the hyperactivation of intracellular growth signals. Recent studies suggest that tumor-associated metabolic remodeling also depends on intercellular communication within the tumor microenvironment (TME). Small extracellular vesicles (sEVs), also known as exosomes, are smaller than 200 nm in diameter and are formed by the fusion of multivesicular bodies with the plasma membrane. The sEVs are instrumental in transporting cargoes such as proteins, nucleic acids or metabolites between the tumor, stromal and immune cells of the TME, and are thus involved in reprogramming the glucose metabolism of recipient cells. In this review, we have summarized the biogenesis and functions of sEVs and metabolic cargos, and the mechanisms through they drive the Warburg effect. Furthermore, the potential applications of targeting sEV-mediated metabolic pathways in tumor liquid biopsy, imaging diagnosis and drug development have also been discussed.

Cerium dioxide (CeO2, ceria) has long been regarded as one of the key materials in modern catalysis, both as a support and as a catalyst itself. Apart from its well-established use (three-way catalysts and diesel engines), CeO2 has been widely used as a cocatalyst/catalyst in energy conversion and storage applications. The importance stems from the oxygen storage capacity of ceria, which allows it to release oxygen under reducing conditions and to store oxygen by filling oxygen vacancies under oxidizing conditions. However, the nature of the Ce active site remains not well understood because the degree of participation of f electrons in catalytic reactions is not clear in the case of the heavy dependence of catalysis theory on localized d orbitals at the Fermi energy EF. This review focuses on the catalytic applications in energy conversion and storage of CeO2-based nanostructures and discusses the mechanisms for several typical catalytic reactions from the perspectives of electronic properties of CeO2-based nanostructures. Defect engineering is also summarized to better understand the relationship between catalytic performance and electronic properties. Finally, the challenges and prospects of designing high efficiency CeO2-based catalysts in energy storage and conversion have been emphasized.

IntroductionSepsis is a common clinical syndrome and nearly 20% of all deaths are related to sepsis. As an important part of the body, bone homeostasis disorders are closely related to inflammatory response, but the correlation between bone homeostasis and sepsis, sepsis shock was unknown. The objective of this study was to explore the relation of bone homeostasis on sepsis and sepsis shock.MethodsIn this retrospective cohort study, patients were enrolled between April 2018 and May 2022 from Beijing Chaoyang hospital. Primary outcomes were serum indicators reflected bone homeostasis, such as cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I), tartrate-resistant acid phosphatase 5b (TRACP-5b) and piezo-type mechanosensitive ion channel component 1 (PIEZO1).ResultsThe data were analyzed retrospectively. among 88 evaluable patients, 45 were sepsis (19 were sepsis shock) and 43 were non-sepsis. There was no significant difference in age, gender, BMI, combination diseases, operation time, intraoperative blood loss, and hospital stay. Patients with sepsis or sepsis shock had higher serum CTX-I, TRACP-5b, PIEZO1 (p < 0.05). Spearman’s rank correlation test showed that CTX-I, TRACP-5b, PIEZO1 and the three together (CTX-I + TRACP-5b + PIEZO1) had strong correlation with sepsis or sepsis shock (p < 0.05). The receiver operating characteristic curve (ROC) and precision-recall curve (PRC) showed that these indicators could predict the occurrence of sepsis or sepsis shock (p < 0.05). Besides, decision curve analysis (DCA) and interventions avoided curve (IAC) displayed a high net benefit of bone homeostasis disorders indicators on sepsis or sepsis shock. Kaplan–Meier survival curves revealed that sepsis or shock patients with high value indicators (>0.47227) had a higher mortality (p < 0.05).ConclusionBone homeostasis disorders could increase the mortality of sepsis and sepsis shock patients.

The genus Coptis belongs to the Ranunculaceae family, containing 15 recognized species highly diverse in morphology. It is a conspicuous taxon with special evolutionary position, distribution pattern and medicinal value, which makes it to be of great research and conservation significance. In order to better understand the evolutionary dynamics of Coptis and promote more practical conservation measures, we performed plastome sequencing and used the sequencing data in combination with worldwide occurrence data of Coptis to estimate genetic diversity and divergence times, rebuild biogeographic history and predict its potential suitable distribution area. The average nucleotide diversity of Coptis was 0.0067 and the hotspot regions with the highest hypermutation levels were located in the ycf1 gene. Coptis is most likely to have originated in North America and Japanese archipelago and has a typical Eastern Asian and North American disjunct distribution pattern, while the species diversity center is located in Mid-West China and Japan. The crown age of the genus is estimated at around 8.49 Mya. The most suitable climatic conditions for Coptis were as follows: precipitation of driest quarter > 25.5 mm, annual precipitation > 844.9 mm and annual mean temperature -3.1 to 19 °C. The global and China suitable area shows an upward trend in the future when emission of greenhouse gases is well controlled, but the area, especially in China, decreases significantly without greenhouse gas policy interventions. The results of this study provide a comprehensive insight into the Coptis evolutionary dynamics and will facilitate future conservation efforts.

Stem cell therapy is a promising treatment for knee osteoarthritis, but few bibliometric studies have been performed on the subject. Bibliometric analysis is helpful for identifying the most influential studies in a specific field and can evaluate the global research trends in stem cell therapy for knee osteoarthritis. The Web of Science Core Collection was searched for publications from 2001 to 2021. Publication performance was analyzed using several bibliometric parameters, including VOSviewer, to identify the research landscape of trends in topics, and CiteSpace was investigated to identify the keywords that have the strongest citation bursts. From 2001 to 2021, in total, 1,345 publications explored the research on stem cells in knee osteoarthritis. The United States contributed the largest number of publications and at the top list of international collaborations. Tokyo Medical and Dental University ranked first among institutions in the overall number of articles and citations. The journal of Osteoarthritis and Cartilage had the largest number of publications. Sekiya Ichiro was the most cited author, with 32 articles. The keywords with the most frequent occurrence were “osteoarthritis,” “mesenchymal stem cells,” and “cartilage,” in descending order of frequency. “fibroblast growth factor” and “extracellular vesicle” were the first and last searched theme terms, respectively. The number of publications on stem cells for knee osteoarthritis stays growing. Cartilage repair and paracrine function are current research hotspots for the stem cell therapy mechanism. Stem cell therapy has gradually advanced from basic research to the clinical application stage.

Spinal cord injury (SCI) is a devastating central nervous system disease, caused by physical traumas. With the characteristic of high disability rate, catastrophic dysfunction, and enormous burden on the patient’s family, SCI has become a tough neurological problem without efficient treatments. Contemporarily, the pathophysiology of SCI comprises complicated and underlying mechanisms, in which oxidative stress (OS) may play a critical role in contributing to a cascade of secondary injuries. OS substantively leads to ion imbalance, lipid peroxidation, inflammatory cell infiltration, mitochondrial disorder, and neuronal dysfunction. Hence, seeking the therapeutic intervention of alleviating OS and appropriate antioxidants is an essential clinical strategy. Previous studies have reported that traditional Chinese medicine (TCM) has antioxidant, anti-inflammatory, antiapoptotic and neuroprotective effects on alleviating SCI. Notably, the antioxidant effects of some metabolites and compounds of TCM have obtained numerous verifications, suggesting a potential therapeutic strategy for SCI. This review aims at investigating the mechanisms of OS in SCI and highlighting some TCM with antioxidant capacity used in the treatment of SCI.

Natural rubber (NR) is an essential industrial raw material widely used in our life. Hevea brasiliensis (Reyan7-33-97) is an economic plant producing natural rubber. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators in numerous biological processes while the characterization and analysis of lncRNAs in Hevea brasiliensis are still largely unrevealed. We integrated the transcriptome datasets from multiple tissues to identify rubber lncRNAs. As a result, 12,029 lncRNAs were found and characterized with notably distinctive features such as longer exon, lower expression levels and GC content, and more tissue specificity in comparison with mRNAs. We discovered thousands of tissue-specific lncRNAs in rubber root, latex, bark, leaf, flower, and seed tissues. The functional enrichment result reveals that tissue-specific lncRNAs are potentially referred to particular functions of tissues, while the non-tissue specific is related to the translation and metabolic processes. In the present study, a comprehensive lncRNA dataset was identified and its functional profile in Hevea brasiliensis was explored, which provides an annotation resource and important clues to understand the biological functions of lncRNAs in Hevea brasiliensis.

Ecological priority and green development have become the main theme of the times in China. The policy performance evaluation of ecological protection needs to quantitatively identify the changes of ecosystem quality and services firstly. This paper constructed the analytical framework driven by ecological protection policy of “Goal-oriented—Policy driven—Ecological quality–Service improvement”, and used multi-source data to establish the evaluation approach of “ecosystem quality-ecosystem services-ecosystem services value”. This study took Lishui as a case study to confirm the framework proposed. The results show that the ecosystem quality of Lishui has been steadily improved in recent 10 years. The overall quality of ecosystem services such as vegetation oxygen release, carbon sequestration, pollution removal, cooling service, humidification regulation and water conservation service has been improved by a range of 2%–6%. The value of ecological products has increased from 143.28 billion CNY in 2009 to 150.23 billion CNY in 2019. Lishui has implemented the development concept of “ecological civilization”, and the policies of ecological restoration or land remediation have changed land use and ecosystem quality, which was the main driving force for the improvement of ecological quality and the main promotion of ecological products value. The methods and results can provide insight into the impact of land policies on ecosystem services and decisions that support for further optimizing land ecological protection policies.

BackgroundElectrocardiography (ECG) plays a very important role in various cardiovascular diseases and elevated D-dimer in serum associated with thrombosis. In patients with coronavirus disease 2019 (COVID-19), immense pieces of evidence showed that ECG abnormalities or elevated D-dimer in serum occurred frequently. However, it remains unclear whether ECG abnormalities combined with elevated D-dimer could be a new risk predictor in patients with COVID-19.Methods and resultsThis retrospective cohort study enrolled 416 patients with COVID-19 at Wuhan Tongji Hospital from 1 February to 20 March 2020. ECG manifestations, D-dimer levels, and in-hospital deaths were recorded for all patients. Logistic regression analysis was performed to examine the association between ECG manifestations and in-hospital mortality in patients with elevated D-dimer levels. In patients hospitalized for COVID-19, ST-T abnormalities (34.3%) were the most frequent ECG manifestations, whereas sinus tachycardia (ST) (13.3%) and atrial arrhythmias with rapid rhythms (8.5%) were the two most common cardiac arrhythmias. Compared to severely ill patients with COVID-19, ST-T abnormalities, ST and atrial arrhythmias (p

Establishing a portable diagnostic method for identifying plant pathogens is essential to prevent the spread of plant disease, especially in field and customs inspections. Leptosphaeria maculans (L. maculans) is an aggressive fungus, which causes severe phoma stem canker of Brassica napus, responsible for major yield losses of oilseed rape worldwide. In this study, CRISPR/Cas12a-based detection system and recombinase polymerase amplification (RPA) technique were employed to develop a rapid and sensitive detection method for identifying L. maculans. The involved RPA pre-amplification and CRISPR/Cas12a cleavage confer considerable sensitivity and selectivity, which can be finished within 45 min with a LOD of 4.7 genomic DNA copies. This detection system was further developed to two portable platforms, i.e., one-pot lateral flow detection and all-in-one chip lateral flow assay (AOCLFA), which integrates the lyophilized recombinase polymerase amplification (RPA) reagents and lyophilized Cas12a cleavage reagents in one tube or chip. The developed portable platforms have flexible portability and simple operation for the detection of L. maculans from plant tissues in the field. The proposed portable suitcase containing the minimum equipment, regents, and AOCLFA meets the practical needs of rapid on-site disease screening of plant fungi, port quarantine, or pathogen spreading control.

BackgroundAutism spectrum disorder (ASD) is a severe public health concern, and Gastrointestinal (GI) symptoms are becoming more common among co-morbidities. The evidence has to be updated depending on differences in different parts of the world. This systematic review and meta-analysis aimed to better understand the existing epidemiological condition and help make health-related decisions.MethodsSearches in PubMed, Web of Science, Embase databases are limited to 14 March 2022. We reviewed the global prevalence of ASD and the prevalence of GI in people with ASD. Data were extracted by two independent researchers. Literature quality assessment using the National Institutes of Health Study Quality Assessment Tool.ResultsWe discovered that the global pooled prevalence of ASD was 98/10,000 (95% confidence interval, 95%CI: 81/10,000–118/10,000, I2 = 99.99%, p < 0.001), with 48.67% (95%CI: 43.50 −53.86, I2 = 99.51%) of individuals with ASD reporting GI symptoms. Based on the subgroup analyses, we found a higher prevalence of ASD in males (90/10,000, 95%CI: 71/10,000–112/10,000, I2 = 99.99%) than females (21/10,000, 95%CI: 15/10,000–27/10,000, I2 = 99.99%). Prevalence of pooling is higher in developing countries (155/10,000, 95% CI: 111/10,000–204/10,000, I2 = 99.87%) than in developed countries (85/10,000, 95%CI: 67/10,000-105/10,000, I2 = 99.99%).ConclusionThe global prevalence of ASD and the prevalence of GI symptoms in ASD are both significant. The prevalence of ASD is much higher in men than in women. Further attention to ASD and its related comorbidities will be required in the future to inform coping strategy adaptation.

Leaf rolling is an important agronomic trait in wheat (Triticum aestivum L.). Moderate leaf rolling keeps leaves upright and maintains the relatively normal photosynthesis of plants under drought stress. However, the molecular mechanism of wheat leaf rolling remains unclear. Here, we identified a candidate gene TaMYB5-3A that regulates leaf rolling by using a genome-wide association study (GWAS) in a panel of 323 wheat accessions. Phenotype analysis indicated that the leaves of tamyb5 mutants were flatter than that of the wild type under drought condition. A nucleotide variation in the TaMYB5-3A coding region resulted in a substitution of Thr to Lys, which corresponds to two alleles SNP-3A-1 and SNP-3A-2. The leaf rolling index (LRI) of the SNP-3A-1 genotype was significantly lower than that of the SNP-3A-2 genotype. In addition, TaMYB5-3A alleles were associated with canopy temperature (CT) in multiple environments. The CT of the SNP-3A-1 genotype was lower than that of the SNP-3A-2 genotype. Gene expression analysis showed that TaMYB5-3A was mainly expressed in leaves and down-regulated by PEG and ABA treatment. TaMYB5 induces TaNRL1 gene expression through the direct binding to the AC cis-acting element of the promoter of the target gene, which was validated by EMSA (electrophoretic mobility shift assay). Our results revealed a crucial molecular mechanism in wheat leaf rolling and provided the theoretical basis and a gene resource for crop breeding.

BackgroundBiomarkers that predict the efficacy of first-line tyrosine kinase inhibitors (TKIs) are pivotal in epidermal growth factor receptor (EGFR) mutant advanced lung adenocarcinoma. Imaging-based biomarkers have attracted much attention in anticancer therapy. This study aims to use the machine learning method to distinguish EGFR mutation status and further explores the predictive role of EGFR mutation-related radiomics features in response to first-line TKIs.MethodsWe retrospectively analyzed pretreatment CT images and clinical information from a cohort of lung adenocarcinomas. We entered the top-ranked features into a support vector machine (SVM) classifier to establish a radiomics signature that predicted EGFR mutation status. Furthermore, we identified the best response-related features based on EGFR mutant-related features in first-line TKI therapy patients. Then we test and validate the predictive effect of the best response-related features for progression-free survival (PFS).ResultsSix hundred ninety-two patients were enrolled in building radiomics signatures. The 13 top-ranked features were input into an SVM classifier to establish the radiomics signature of the training cohort (n = 514), and the predictive score of the radiomics signature was assessed on an independent validation group with 178 patients and obtained an area under the curve (AUC) of 74.13%, an F1 score of 68.29%, a specificity of 79.55%, an accuracy of 70.79%, and a sensitivity of 62.22%. More importantly, the skewness-Low (≤0.882) or 10th percentile-Low group (≤21.132) had a superior partial response (PR) rate than the skewness-High or 10th percentile-High group (p < 0.01). Higher skewness (hazard ratio (HR) = 1.722, p = 0.001) was also found to be significantly associated with worse PFS.ConclusionsThe radiomics signature can be used to predict EGFR mutation status. Skewness may contribute to the stratification of disease progression in lung cancer patients treated with first-line TKIs.

The lack of regenerative capacity of neurons leads to poor prognoses for some neurological disorders. The use of small molecules to directly reprogram somatic cells into neurons provides a new therapeutic strategy for neurological diseases. In this review, the mechanisms of action of different small molecules, the approaches to screening small molecule cocktails, and the methods employed to detect their reprogramming efficiency are discussed, and the studies, focusing on neuronal reprogramming using small molecules in neurological disease models, are collected. Future research efforts are needed to investigate the in vivo mechanisms of small molecule-mediated neuronal reprogramming under pathophysiological states, optimize screening cocktails and dosing regimens, and identify safe and effective delivery routes to promote neural regeneration in different neurological diseases.

Purpose: This study aimed to compare the performance of radiomics and deep learning in predicting EGFR mutation status in patients with lung cancer based on PET/CT images, and tried to explore a model with excellent prediction performance to accurately predict EGFR mutation status in patients with non-small cell lung cancer (NSCLC).Method: PET/CT images of 194 NSCLC patients from Xijing Hospital were collected and divided into a training set and a validation set according to the ratio of 7:3. Statistics were made on patients’ clinical characteristics, and a large number of features were extracted based on their PET/CT images (4306 radiomics features and 2048 deep learning features per person) with the pyradiomics toolkit and 3D convolutional neural network. Then a radiomics model (RM), a deep learning model (DLM), and a hybrid model (HM) were established. The performance of the three models was compared by receiver operating characteristic (ROC) curves, sensitivity, specificity, accuracy, calibration curves, and decision curves. In addition, a nomogram based on a deep learning score (DS) and the most significant clinical characteristic was plotted.Result: In the training set composed of 138 patients (64 with EGFR mutation and 74 without EGFR mutation), the area under the ROC curve (AUC) of HM (0.91, 95% CI: 0.86–0.96) was higher than that of RM (0.82, 95% CI: 0.75–0.89) and DLM (0.90, 95% CI: 0.85–0.95). In the validation set composed of 57 patients (32 with EGFR mutation and 25 without EGFR mutation), the AUC of HM (0.85, 95% CI: 0.77–0.93) was also higher than that of RM (0.68, 95% CI: 0.52–0.84) and DLM (0.79, 95% CI: 0.67–0.91). In all, HM achieved better diagnostic performance in predicting EGFR mutation status in NSCLC patients than two other models.Conclusion: Our study showed that the deep learning model based on PET/CT images had better performance than radiomics model in diagnosing EGFR mutation status of NSCLC patients based on PET/CT images. Combined with the most statistically significant clinical characteristic (smoking) and deep learning features, our hybrid model had better performance in predicting EGFR mutation types of patients than two other models, which could enable NSCLC patients to choose more personalized treatment schemes.

Purpose: To assess the significance of mutation mutual exclusion information in the optimization of radiomics algorithms for predicting gene mutation.Methods: We retrospectively analyzed 258 non-small cell lung cancer (NSCLC) patients. Patients were randomly divided into training (n = 180) and validation (n = 78) cohorts. Based on radiomics features, radiomics score (RS) models were developed for predicting KRAS proto-oncogene mutations. Furthermore, a composite model combining mixedRS and epidermal growth factor receptor (EGFR) mutation status was developed.Results: Compared with CT model, the PET/CT radiomics score model exhibited higher AUC for predicting KRAS mutations (0.834 vs. 0.770). By integrating EGFR mutation information into the PET/CT RS model, the AUC, sensitivity, specificity, and accuracy for predicting KRAS mutations were all elevated in the validation cohort (0.921, 0.949, 0.872, 0.910 vs. 0.834, 0.923, 0.641, 0.782). By adding EGFR exclusive mutation information, the composite model corrected 64.3% false positive cases produced by the PET/CT RS model in the validation cohort.Conclusion: Integrating EGFR mutation status has potential utility for the optimization of radiomics models for prediction of KRAS gene mutations. This method may be used when repeated biopsies would carry unacceptable risks for the patient.

ObjectiveAs COVID-19 persists around the world, it is necessary to explore the long-term mental health effects in COVID-19 survivors. In this study, we investigated the mental health outcomes of survivors of COVID-19 at 6 and 12 months postdiagnosis.MethodsPosttraumatic stress disorder (PTSD checklist for the DSM-5, PCL-5), depression (PHQ-9), anxiety (Generalized Anxiety Disorder Scale, GAD-7), resilience (Connor-Davidson Resilience Scale, CD-RISC-10), perceived social support (PSSS), personality traits (Chinese Big Five Personality Inventory-15, CBF-PI-15), and sociodemographic information were examined among 511 survivors of COVID-19 (48.1%, females; Mage = 56.23 years at first assessment) at 6 and 12 months postdiagnosis. The data were analyzed with Wilcoxon signed rank tests and multivariable logistic regression models.ResultsThe prevalence of anxiety, depression, and posttraumatic stress disorder (PTSD) at 6 and 12 months after diagnosis was 13.31% and 6.26%; 20.35% and 11.94%; and 13.11% and 6.07%, respectively. The risk factors for all symptoms were as follows: higher neuroticism; lower openness, extraversion, agreeableness, and resilience; greater life disruptions due to COVID-19; poorer living standards; and increased symptoms of PTSD or depression at 6 months postdiagnosis.ConclusionThe mental health of COVID-19 survivors improved between 6 and 12 months postdiagnosis. Mental health workers should pay long-term attention to this group, especially to survivors with risk factors.

BackgroundPrimary tumor of the inferior vena cava is a rare tumor, which arises from the smooth muscle of vascular walls. Surgery appears the only curative treatment. However, the optimal surgical methods and surgical management are not well-studied. In this article, we reviewed the successful treatment experience of patients in our center who had resection of primary tumor of the inferior vena cava and reviewed the relevant literature.MethodsFour cases of patients who undergoing initial resection of primary tumors of the inferior vena cava from September 2017 to August 2021 in the Second Affiliated Hospital of Nanchang University were screened and followed up. They were discussed and cases reported in this field were reviewed.ResultsAmong the four patients, three of them were female. The median age of the disease is 53.75 years (range 45–60 years). After surgical treatment, tumors were removed in all patients, and some patients had reconstruction of inferior vena cava. There were no disease-specific deaths, no serious complications, and no recurrence during follow-up in these cases.ConclusionsCareful preoperative examination, correct surgical treatment methods, and multidisciplinary collaboration can lead to safe and successful operations, which improve the survival rate of patients.

ObjectiveTo assess a novel eyelid pressure measurement device and study the relationship between eyelid pressure and ocular surface parameters of moderate-to-severe dry eye disease (DED).MethodsThe present study included 70 eyes of 35 moderate-to-severe DED patients. All subjects were subjected to the following examinations for DED assessment: Ocular Surface Disease Index (OSDI) questionnaire, tear meniscus height (TMH), lipid layer thickness (LLT), number of partial blink (PB), total blink (TB) and partial blink rate (PBR), fluorescein tear breakup time (FBUT), corneal fluorescein staining (CFS), lid margin abnormality, meibum expression assessment (meibum score), meibomian gland dropout (MGd) and Schirmer I test. Pressure of the upper eyelid was measured thrice with the novel pressure measurement device. Repeatability of the device was evaluated by intraclass correlation coefficient (ICC). Safety of the device was evaluated by observing ocular adverse reactions of each subject prior to measurement, at day 1 and day 7 following measurement. Correlations between eyelid pressure and ocular surface parameters of moderate-to-severe DED were analyzed by using Pearson correlation coefficient and Kendall's tau-b correlation coefficient.ResultsICC of the measurement results in our study was 0.86. There was no abnormality presenting in all subjects recorded prior to measurement, 1 and 7 days following measurement. The eyelid pressure was significantly correlated with PBR (r = 0.286, P = 0.016), FBUT (r = −0.331, P = 0.005), CFS (r = 0.528, P = 0.000), lid margin abnormality (r = 0.408, P = 0.011) and MGd (r = 0.226, P = 0.016) in moderate-to-severe DED patients, but not significantly correlated with OSDI score (r = 0.016, P = 0.912), TMH (r = −0.002, P = 0.988), meibum score (r = −0.196, P = 0.317), LLT (r = 0.114, P = 0.346), PB (r = 0.116, P = 0.338), TB (r = 0.074, P = 0.544), meibum score (r = −0.196, P = 0.317) and Schirmer I test (r = 0.028, P = 0.821).ConclusionThe novel pressure measurement device exhibited good repeatability and safety in measuring eyelid pressure. Significant correlations were noted between the eyelid pressure and PBR, FBUT, CFS, lid margin abnormality and MGd in moderate-to-severe DED. The measurement of eyelid pressure combined with ocular surface parameters may be valuable for the assessment of DED.

Background: Left ventricular noncompaction (LVNC) is a rare cardiomyopathy, long QT syndrome (LQTS) is a rare ion channel disease, and simultaneous occurrence of both is even rarer. Further clinical reports and studies are needed to identify the association between LVNC and LQTS and the underlying mechanism.Methods and Results: A 26-year-old primigravida was referred at 25 weeks gestation for prenatal echocardiography due to fetal bradycardia detected during the routine ultrasound examination. The echocardiographic findings were consistent with biventricular noncompaction cardiomyopathy (BVNC) with pulmonary stenosis and suspected LQTS. After detailed counseling, the couple decided to terminate the pregnancy, and subsequent postmortem examination confirmed BVNC and pulmonary stenosis. Then, A trio (fetus and the parents) whole-exome sequencing (WES) and copy number variation sequencing (CNV-seq) were performed. CNV-seq identified no aneuploidy or pathogenic CNV. A de novo missense variant in KCNH2 (NM_000238.3:c.1847A > G,p.Tyr616Cys) was identified by WES. This KCNH2 missense mutation was classified as pathogenic according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology variant interpretation guidelines.Conclusion: We report the first prenatal case of KCNH2 mutation presenting with LVNC combined with bradycardia and second-degree 2:1 atrioventricular block. Importantly, this case reminds clinicians to systematically search ion channel gene mutations in patients with LVNC and arrhythmia.

Objectives: To evaluate the effect of astaxanthin in the treatment of mild-to-moderate dry eye disease (DED) in middle-aged and elderly patients.Methods: 120 eyes of 60 middle-aged and elderly patients with mild-to-moderate DED were enrolled in this prospective, one-group, quasi-experimental study. Six milligram Astaxanthin tablets (Weihong Haematococcus Pluvialis Astaxanthin, Hangzhou Xinwei Low Carbon Technology R&D Co., Ltd., China) were administered orally, twice daily for 30 ± 2 days. History of eye diseases, treatment, systemic disease, and medication before the test were recorded. In addition, the ocular surface disease index (OSDI) questionnaire, non-invasive tear break-up time (NIBUT), fluorescein break-up time (FBUT), corneal fluorescein staining (CFS) score, eyelid margin signs, meibomian gland (MG) expressibility, meibum quality, meibomian gland dropout (MGDR), Schirmer I test (SIt), tear meniscus height (TMH), bulbar conjunctiva congestion degree, blink frequency, incomplete blink rate, and thickness of tear film lipid layer were collected before treatment, 2 weeks after the initiation of treatment, and at the end of treatment. Visual acuity (VA), intraocular pressure (IOP), anterior segment, fundus, discomfort symptoms and other adverse reactions were also monitored throughout the study to assess the safety.Results: OSDI score, NIBUT, BUT, CFS score, eyelid margin signs, MG expressibility, meibum quality, and blink frequency improved significantly to varying degrees after treatment compared with those before the treatment (P < 0.05), while TMH, SIt, conjunctival congestion, the thickness of tear film lipid layer, MGDR, incomplete blink rate, VA and IOP did not differ (P > 0.05).Conclusions: Oral administration of astaxanthin improves the symptoms and signs of middle-aged and elderly patients with mild-to-moderate DED.

Hypercholesterolemia and carotid atherosclerosis contribute to the etiology of stroke. However, there has been a lack of appropriate comorbid animal models incorporating some of the ubiquitous characteristics that precede strokes. Curcumin is a natural active polyphenolic compound extracted from the rhizoma of Curcuma longa L. which possesses comprehensive bioactivities. The present study aimed to evaluate whether neurobehavioral deficits, neuroendocrine-immune dysregulations and cerebral microcirculation dysfunction, are part of the initial stages of cerebral ischemia in individuals suffering from carotid atherosclerosis resulting from a high cholesterol diet (HCD) and if they could be tested using a comorbid animal model. Furthermore, the utility of this model will be examined following the administration of curcumin. Adult wild-type SD rats were fed a regular diet or HCD and supplemented with either vehicle or curcumin for 4 weeks. Carotid injury was induced by an air-drying endothelial denudation method at the end of the second week. Plasma cholesterol, carotid pathomorphology, neurobehavioral tests, and neuroendocrine-immune parameters were measured. We found higher plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), intima and media (I/M) ratio, but lower high-density lipoprotein-cholesterol (HDL-C), spatial learning and memory capacity impairment, elevated NPY expression in the hypothalamus, increased plasma concentration of leptin, upregulated TNF-α, IL-1β, and CRP in the circulation as well as TNF-α and IL-1β in the cerebral cortex, plus enhanced ICAM-1, VCAM-1, and E-selectin in cerebral microvessels in HCD-fed model rats. All these alterations were ameliorated by curcumin. These results suggest that a comorbid rat model was effectively developed by HCD and carotid injury.

The plant microbiome is a key determinant of health and productivity. However, it is still difficult to understand the structural composition of the bacterial and fungal microbiomes of diseased and healthy plants, especially the spatial dynamics and phylogenies of endophytic and rhizosphere microbial communities. We studied the differentiation and variability in the rhizosphere and endosphere microbiomes of healthy and diseased cotton from north and south of the Tianshan Mountains using the methods of PCR-based high-throughput sequencing and real-time quantitative PCR. The endophytic and rhizosphere bacterial abundances in the diseased plants were greater than those of healthy plants. The numbers of endophytic and rhizosphere fungi associated with diseased plants were greater than those associated healthy plants (p < 0.05). Endophytic and rhizosphere bacteria did not share common OTUs. The dominant rhizosphere bacteria were Proteobacteria (29.70%), Acidobacteria (23.14%), Gemmatimonadetes (15.17%), Actinobacteria (8.31%), Chloroflexi (7.99%), and Bacteroidetes (5.15%). The dominant rhizosphere fungi were Ascomycota (83.52%), Mortierellomycota (7.67%), Basidiomycota (2.13%), Chytridiomycota (0.39%), and Olpidiomycota (0.08%). The distribution of dominant bacteria in different cotton rhizosphere soils and roots differed, with the dominant bacteria Pseudomonas (15.54%) and Pantoea (9.19%), and the dominant fungi Alternaria (16.15%) and Cephalotrichum (9.10%) being present in the greatest numbers. At sampling points in different ecological regions, the total numbers of cotton endophytic and rhizosphere microbiome OTUs from southern to northern Xinjiang showed an increasing trend. There were significant differences in the composition and diversity of rhizosphere microbes and endophytes during the entire cotton growth period and in representative ecological regions (p < 0.01), whereas rhizosphere microbes and endophytes showed no significant differences among the four growth periods and in representative ecological regions. RB41, H16, Nitrospira, and Sphingomonas play important roles in the microbial ecology of cotton rhizosphere soil. Pseudomonas accounted for a large proportion of the microbes in the cotton rhizosphere soil. This study provides an in-depth understanding of the complex microbial composition and diversity associated with cotton north and south of the Tianshan Mountains.

Background: Most studies on mental health problems caused by COVID-19 crisis in children were limited to the period of home quarantine. It remained unclear what adverse impact of the psychosocial stressors caused by school reopening, as well as the transitions in daily activities and social interactions had on mental health in children.Methods: A total of 6400 students in primary schools were enrolled in a cross-sectional study conducted in East China, between June 26 and July 6, 2020, when schools reopened. Children’s mental health status was assessed by the parent version of Strengths and Difficulties Questionnaire (SDQ). Ultimately, data on a total of 6017 children with completed information on mental health, psychosocial stressors, daily activities, and social interactions were eligible for analysis. The associations of mental health with psychosocial stressors, daily activities, and social interactions were determined by ordinal logistic regression models. Stratified analyses were conducted according to grade, gender, school level, area, and caregiver–child relationship to further observe the effects of stressors on mental status.Results: The prevalence of borderline, moderately abnormal, and prominently abnormal scores were 7.16, 3.34, and 1.96% for total difficulties, and 13.83, 13.45, and 17.85% for prosocial behavior, respectively. Children with psychological stressors had a significantly higher risk of being in a worse category of mental health status, with the maximum adjusted OR of 7.90 (95% CI 3.33–18.75) in those definitely afraid of inadaptation to study and life styles. Time used in home work and computer games was positively related to mental health problems, while physical exercises and frequency of communication with others was negatively related. The effects of psychological stressors on total difficulties were more evident in middle-high grade students (OR = 7.52, 95% CI 4.16–8.61), boys (OR = 6.95, 95% CI 4.83–8.55), those who lived in Taizhou (OR = 7.62, 95% CI 4.72–8.61) and with poor caregiver–child relationship (OR = 7.79, 95% CI 2.26–8.65).Conclusion: Emotional and behavioral difficulties, especially less prosocial behavior, were prevalent in primary school children after schools reopened. The Chinese government, communities, schools, and families need to provide more effective support for students’ transition back into the school building and address emotional and behavioral problems for children with difficulties.

Background and Aims: The relationships between blood lipid levels and obesity and cognitive impairment have not been fully determined. Considering that the lipid accumulation product (LAP) is a composite index of blood lipid levels and obesity, we investigated the relationships between LAP levels at baseline and cognitive decline over 4 years.Methods: A total of 983 subjects (≥40 years) from a longitudinal cohort in a village of Xi’an, China, who completed the baseline survey were followed-up for 4 years. All participants underwent face-to-face interviews and cognitive assessments at baseline and at the 4-year follow-up. The Mini-Mental State Examination (MMSE) was used to assess cognitive function, and an MMSE score dropping ≥ 2 points from baseline was defined as cognitive decline. The relationships between LAP and cognitive decline were analyzed by linear regression models.Results: During the 4-year follow-up, 172 patients exhibited cognitive decline (17.5%). Univariate analysis showed that the rate of change in MMSE score was significantly different between the low-LAP group and the high-LAP group (t = −2.26, p = 0.024). Multiple linear regression indicated that a high LAP was positively associated with cognitive decline (β = 0.564, p = 0.012). Stratified multivariate analysis showed that LAP was positively associated with cognitive decline in the normal blood pressure female subgroup (β = 1.29, p = 0.002) but not in the high blood pressure group or the male group.Conclusions: High LAP is associated with cognitive decline in females with normal blood pressure but not in those with high blood pressure or males. This indicates that the relationships between blood lipid levels and obesity and cognitive impairment may be affected by blood pressure and sex.

To investigate the prevalence of emotional and behavioral problems (EBPs) among children during the COVID-19 post-pandemic in China; examine associations between COVID-19-related knowledge and precautions and problems in children, and explore the potential explanatory value of the mental health status of caregivers on any associations observed. Based on a cross-sectional design, caregivers of 6,017 children from 12 primary schools in Shanghai and Taizhou, China, were invited to complete an online survey from June 26 to July 6, 2020. EBPs of the children were assessed using the Strengths and Difficulties Questionnaire (SDQ), while the emotional problems of caregivers were assessed using the Depression Anxiety Stress Scales-21 (DASS-21). Structural equation modeling was employed to estimate the direct and indirect associations (explained by the emotional problems of caregivers) between COVID-19-related knowledge and precautions and the EBPs among children. The overall prevalence of EBPs in the sample was 12.5%, and 5.3% of them had a high or very high SDQ total difficulties score during the COVID-19 post-pandemic. After adjustment for covariates, higher COVID-19-related knowledge (β = −0.83; P < 0.001) and precautions (β = −0.80; P < 0.001) were significantly associated with lower SDQ total difficulties score among children. There was an explanatory effect of emotional problems of caregivers on the aforementioned associations, which explained 31% and 41% of the total effect, respectively. Higher levels of knowledge and precautions of COVID-19 were associated with lower EBPs among children, and the relationship was partially explained by the emotional problems in caregivers. It may be beneficial to improve pandemic-related prevention education and adopt psychological interventions toward the emotional status of caregivers for the psychological health of children.

Wheat is one of the staple food crops. The utilization of elite genetic resources to develop resource-efficient wheat varieties is an effective approach to deal with the challenges of climate change and population growth. WRKY transcription factors (TFs) are multifaceted regulators of plant growth and development and response to environmental stress. The previous studies have shown that TaWRKY51 positively regulates the development of lateral roots, while its roles in agronomic trait development are not clear, and there is no functional marker for molecular breeding. To bridge the gap, we cloned the three members of TaWRKY51 and found they were highly expressed in the roots and flag leaves at the flowering stage and were induced by the multiple abiotic stresses and phytohormones. The highest expression level was observed in TaWRKY51-2D, followed by TaWRKY51-2A and -2B. The two haplotypes/alleles for each member were identified in the natural populations, and functional markers were developed accordingly. The association assays revealed that Hap-2A-I was an elite haplotype for the large spike, Hap-2B-II and allele-G were favorable haplotypes/alleles for long root. However, only Hap-2A-I was selected for wheat breeding in China. The results of transgenic experiments showed that the rice lines overexpressing TaWRKY51 had large panicle, high thousand-grain-weight, and more crown and lateral roots, which further confirmed the results of association analysis. In short, TaWRKY51 is a positive regulator of the root architecture and grain yield (GY) contributing traits. The elite gene resources and functional markers may be utilized in the marker-assisted selection for high-yield breeding in wheat.

Objectives: To establish and validate a nomogram integrating radiomics signatures from ultrasound and clinical factors to discriminate between benign, borderline, and malignant serous ovarian tumors.Materials and methods: In this study, a total of 279 pathology-confirmed serous ovarian tumors collected from 265 patients between March 2013 and December 2016 were used. The training cohort was generated by randomly selecting 70% of each of the three types (benign, borderline, and malignant) of tumors, while the remaining 30% was included in the validation cohort. From the transabdominal ultrasound scanning of ovarian tumors, the radiomics features were extracted, and a score was calculated. The ability of radiomics to differentiate between the grades of ovarian tumors was tested by comparing benign vs borderline and malignant (task 1) and borderline vs malignant (task 2). These results were compared with the diagnostic performance and subjective assessment by junior and senior sonographers. Finally, a clinical-feature alone model and a combined clinical-radiomics (CCR) model were built using predictive nomograms for the two tasks. Receiver operating characteristic (ROC) analysis, calibration curve, and decision curve analysis (DCA) were performed to evaluate the model performance.Results: The US-based radiomics models performed satisfactorily in both the tasks, showing especially higher accuracy in the second task by successfully discriminating borderline and malignant ovarian serous tumors compared to the evaluations by senior sonographers (AUC = 0.789 for seniors and 0.877 for radiomics models in task one; AUC = 0.612 for senior and 0.839 for radiomics model in task 2). We showed that the CCR model, comprising CA125 level, lesion location, ascites, and radiomics signatures, performed the best (AUC = 0.937, 95%CI 0.905–0.969 in task 1, AUC = 0.924, 95%CI 0.876–0.971 in task 2) in the training as well as in the validation cohorts (AUC = 0.914, 95%CI 0.851–0.976 in task 1, AUC = 0.890, 95%CI 0.794–0.987 in task 2). The calibration curve and DCA analysis of the CCR model more accurately predicted the classification of the tumors than the clinical features alone.Conclusion: This study integrates novel radiomics signatures from ultrasound and clinical factors to create a nomogram to provide preoperative diagnostic information for differentiating between benign, borderline, and malignant ovarian serous tumors, thereby reducing unnecessary and risky biopsies and surgeries.

Abscisic acid (ABA), one of phytohormones, plays an important regulatory role in plant growth and development. ABA receptor PYL4 (pyrabactin resistance 1-like 4) was previously detected to be involved in plant response to a variety of stresses. TaPYL4 overexpression could enhance wheat (Triticum aestivum) drought resistance. In order to further investigate TaPYL4’s role in regulating development of other major agronomic traits in wheat, genes of TaPYL4-2A, TaPYL4-2B, and TaPYL4-2D were cloned from wheat, respectively. Polymorphism analysis on TaPYL4 sequences revealed that encoding regions of the three genes were highly conserved, without any SNP (single nucleotide polymorphism) presence. However, nine SNPs and four SNPs were identified in the promoter regions of TaPYL4-2A and TaPYL4-2B, respectively. Functional molecular markers were developed based on these polymorphisms, which were then used to scan a natural population of 323 common wheat accessions for correlation analysis between genotype and the target phenotypic traits. Both TaPYL4-2A and TaPYL4-2B markers were significantly correlated with plant growth-related traits under multiple environments (well-watered, drought and heat stress treatments). The additive effects of TaPYL4-2A and TaPYL4-2B were verified by the combinational haplotype (Hap-AB1∼Hap-AB4) effects determined from field data. Cis-acting elements were analyzed in the promoters of TaPYL4-2A and TaPYL4-2B, showing that a TGA-element bound by ARFs (auxin response factors) existed only in Hap-2A-1 of TaPYL4-2A. Gene expression assays indicated that TaPYL4-2A was constitutively expressed in various tissues, with higher expression in Hap-2A-1 genotypes than in Hap-2A-2 materials. Notably, TaARF4 could act as TaPYL4-2A transcription activator in Hap-2A-1 materials, but not in Hap-2A-2 genotypes. Analysis of geographic distribution and temporal frequency of haplotypes indicated that Hap-AB1 was positively selected in wheat breeding in China. Therefore, TaPYL4-2A and TaPYL4-2B could be a valuable target gene in wheat genetic improvement to develop the ideal plant architecture.

Objective: This study was conducted in order to investigate the association of matrix metalloproteinase (MMP)-9 levels with phenotypes of moyamoya disease (MMD).Methods: This study included plasma samples from 84 MMD patients. The clinical variables of these patients were reviewed from the medical record. The serum concentration of tight junction, adherens junction proteins, and MMPs (MMP-2 and MMP-9) was determined using the ELISA method. Patients with hemorrhagic-onset MMD were compared with those with ischemic-onset MMD.Results: Compared with pediatric patients, the expression of MMP-9 was significantly higher, while the MMP-2 and vascular endothelial-cadherin were lower in adult patients. In adult subgroup analysis, hemorrhagic MMD patients exhibited significantly higher serum concentrations of MMP-9 compared with ischemic MMD patients. The ROC curve identified that a baseline serum MMP-9 level >1,011 ng/ml may be associated with spontaneous hemorrhage in adult MMD patients with 70.37% sensitivity and 71.88% specificity [area under curve (AUC), 0.73; 95% CI 0.597–0.864; P = 0.003]. A late Suzuki stage (>4) (OR 4.565, 95% CI 1.028–20.280, P = 0.046) and serum concentrations of MMP-9 >1,011 ng/ml (OR 7.218, 95% CI 1.826–28.533, P = 0.005) are risk predictors of hemorrhages in MMD patients. Hemorrhagic-type MMD patients had higher serum levels of MMP-9 and BBB permeability compared with ischemic-type MMD patients. Adult MMD patients had higher serum levels of MMP-9 and BBB permeability compared with pediatric patients.Conclusions: MMP-9 might serve as a biomarker for hemorrhage prediction in MMD. Serum MMP-9 level >1,011 ng/ml is an independent risk factor of MMD hemorrhagic strokes.

The morphology and the regulation of cortical pattern associated with the cell size, division, and phylogenetic position of a new hypotrichous ciliate, Quadristicha subtropica n. sp. collected from a freshwater pond in southern China, were investigated. Quadristicha subtropica n. sp. is characterized as follows: size in vivo 60–115 μm × 25–45 μm; 19–21 adoral membranelles; buccal cirrus near anterior end of endoral and paroral; cirrus IV/3 at about level of buccal vertex; right marginal row begins ahead of buccal vertex; 11–16 right and 12–19 left marginal cirri; and dorsal cilia about 5 μm long. The basic morphogenetic process in Q. subtropica n. sp. is consistent with that of the type species, Quadristicha setigera. Phylogenetic analyses based on small subunit ribosomal DNA sequence data reveal that the systematic position of Q. subtropica n. sp. is rather unstable with low support values across the tree and the genus Quadristicha is not monophyletic.

Objectives: Amyloid-β (Aβ) deposition in the brain is the hallmark of Alzheimer’s disease (AD) pathology. Hypertension is a risk factor for AD, but the effects of hypertension on Aβ deposition are not fully determined. Considering peripheral Aβ closely relates to Aβ deposition in the brain, we investigated the relationships between blood pressure (BP) level and plasma Aβ concentrations.Methods: One-thousand and sixty-nine participants (age above 45) from a village in the suburbs of Xi’an, China were enrolled. Questionnaires and validated Chinese versions of the Mini-Mental State Examination (MMSE) were used to collect information about vascular risk factors and assess cognition function. The apolipoprotein E (ApoE) genotype was detected using PCR and sequencing. Plasma Aβ levels were measured using ELISA. The associations between BP and plasma Aβ levels were analyzed by using multivariate linear regression.Results: Plasma Aβ1–40 level was higher in high BP group than that in normal BP group (53.34 ± 8.50 pg/ml vs. 51.98 ± 8.96 pg/ml, P = 0.013), in high SBP group than that in normal SBP group (53.68 ± 8.69 pg/ml vs. 51.88 ± 8.80 pg/ml, P = 0.001) and in high MABP group than that in normal MABP group (54.05 ± 8.78 pg/ml vs. 52.04 ± 8.75 pg/ml, P = 0.001). After controlling for the confounding factors, SBP (b = 0.078, P < 0.001), DBP (b = 0.090, P = 0.008) and MABP (b = 0.104, P < 0.001) correlated with plasma Aβ1–40 level positively in ApoE ε4 non-carriers, but not ApoE ε4 carriers.Conclusions: Elevated BP levels were associated with increased plasma Aβ1–40 levels in middle-aged and elderly ApoE ε4 non-carriers.

Periodontitis is a chronic, destructive disease of periodontal tissues caused by multifaceted, dynamic interactions. Periodontal bacteria and host immunity jointly contribute to the pathological processes of the disease. The dysbiotic microbial communities elicit an excessive immune response, mainly by polymorphonuclear neutrophils (PMNs). As one of the main mechanisms of PMN immune response in the oral cavity, neutrophil extracellular traps (NETs) play a crucial role in the initiation and progression of late-onset periodontitis. NETs are generated and released by neutrophils stimulated by various irritants, such as pathogens, host-derived mediators, and drugs. Chromatin and proteins are the main components of NETs. Depending on the characteristics of the processes, three main pathways of NET formation have been described. NETs can trap and kill pathogens by increased expression of antibacterial components and identifying and trapping bacteria to restrict their spread. Moreover, NETs can promote and reduce inflammation, inflicting injuries on the tissues during the pro-inflammation process. During their long-term encounter with NETs, periodontal bacteria have developed various mechanisms, including breaking down DNA of NETs, degrading antibacterial proteins, and impacting NET levels in the pocket environment to resist the antibacterial function of NETs. In addition, periodontal pathogens can secrete pro-inflammatory factors to perpetuate the inflammatory environment and a friendly growth environment, which are responsible for the progressive tissue damage. By learning the strategies of pathogens, regulating the periodontal concentration of NETs becomes possible. Some practical ways to treat late-onset periodontitis are reducing the concentration of NETs, administering anti-inflammatory therapy, and prescribing broad-spectrum and specific antibacterial agents. This review mainly focuses on the mechanism of NETs, pathogenesis of periodontitis, and potential therapeutic approaches based on interactions between NETs and periodontal pathogens.