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The ways in which learning environments are spatially conceived have undergone a significant transformation from "space" as "a realm without meaning" into "place" as "a meaningful location." In this context, the relevance of online interactions and the significance of online space and place in facilitating positive learning are worth exploration. Drawing on a nationwide survey involving 1010 international students at 41 Chinese HEIs in the COVID-19 pandemic, this research applied k-means cluster analyses which produced a typology of international students' perceived online educational environments and another typology of their online interpersonal interactions. The logistic regression results indicated the predictive power of both typologies on ability development. The discussion highlights the importance of considering spatial dimensions of international students' online learning. Promoting international students' online interactions and supporting inclusive, engaging learning experiences require both space for hosting and place enabling intercultural learning. The research holds implications for the sustainable development of online international education in the post-COVID-19 era.

The research investigated the influences of international students' perceived online learning environments, self-efficacy, and online interaction on their online learning achievement, as measured by these students' self-reported development of "generic skills," "research capacities," and "Chinese proficiency and global abilities." Data were generated by a nationwide survey involving 1,010 international students across disciplines at 41 universities in China. The SEM analysis showed that among all factors directly and positively supporting international students' learning achievement, the two online environmental factors, i.e. "accessibility" to online learning resources and opportunities for "knowledge acquisition," presented the strongest effects. The mediation analysis showed that through interaction, environmental "interactivity" had significant and positive indirect influences on learning achievement; and through self-efficacy, "knowledge acquisition" had significant and positive indirect influences on learning achievement. The SEM analysis also revealed a significant negative influence of environmental "flexibility" on international students' "generic skill" development. Possible explanations for the results were proposed. Implications of the results were discussed to support the sustainable development of online international education.

Abstract Objectives Wild soybean (Glycine soja), the ancestor of domesticated soybean, retains a higher level of genetic diversity and adaptability to harsh environments, making it highly valuable for breeding. Here, we re-sequenced 69 wild soybean individuals collected by the Shandong Academy of Agricultural Sciences and identified 1,613,162 high-quality SNPs which not only enriches our understanding of the genetic structure of wild soybean, but also provides valuable resources for further genomic research and genetic improvement of soybean. Data description In this study, we collected 69 wild soybean accessions from Shandong Province, China, and performed re-sequencing on the DNBSEQ platform, followed by SNPs identification. We then integrated ADMIXTURE, neighbor-joining tree, and principal component analysis to illustrate population characteristics. The results showed that these wild soybean accessions could be divided into three distinct subpopulations, exhibiting significant genetic differences.

BackgroundCircadian rhythm disruption is typical in Parkinson’s disease (PD) early stage, and it plays an important role in the prognosis of the treatment effect in the advanced stage of PD. There is growing evidence that circadian rhythm genes can influence development of PD. Therefore, this study explored specific regulatory mechanism of circadian genes (C-genes) in PD through bioinformatic approaches.MethodsDifferentially expressed genes (DEGs) between PD and control samples were identified from GSE22491 using differential expression analysis. The key model showing the highest correlation with PD was derived through WGCNA analysis. Then, DEGs, 1,288 C-genes and genes in key module were overlapped for yielding differentially expressed C-genes (DECGs), and they were analyzed for LASSO and SVM-RFE for yielding critical genes. Meanwhile, from GSE22491 and GSE100054, receiver operating characteristic (ROC) was implemented on critical genes to identify biomarkers, and Gene Set Enrichment Analysis (GSEA) was applied for the purpose of exploring pathways involved in biomarkers. Eventually, immune infiltrative analysis was applied for understanding effect of biomarkers on immune microenvironment, and therapeutic drugs which could affect biomarkers expressions were also predicted. Finally, we verified the expression of the genes by q-PCR.ResultsTotally 634 DEGs were yielded between PD and control samples, and MEgreen module had the highest correlation with PD, thus it was defined as key model. Four critical genes (AK3, RTN3, CYP4F2, and LEPR) were identified after performing LASSO and SVM-RFE on 18 DECGs. Through ROC analysis, AK3, RTN3, and LEPR were identified as biomarkers due to their excellent ability to distinguish PD from control samples. Besides, biomarkers were associated with Parkinson’s disease and other functional pathways.ConclusionThrough bioinformatic analysis, the circadian rhythm related biomarkers were identified (AK3, RTN3 and LEPR) in PD, contributing to studies related to PD treatment.

IntroductionThe programmed cell death (PCD) plays a key role in the development and progression of lung adenocarcinoma. In addition, immune-related genes also play a crucial role in cancer progression and patient prognosis. However, further studies are needed to investigate the prognostic significance of the interaction between immune-related genes and cell death in LUAD.MethodsIn this study, 10 clustering algorithms were applied to perform molecular typing based on cell death-related genes, immune-related genes, methylation data and somatic mutation data. And a powerful computational framework was used to investigate the relationship between immune genes and cell death patterns in LUAD patients. A total of 10 commonly used machine learning algorithms were collected and subsequently combined into 101 unique combinations, and we constructed an immune-associated programmed cell death model (PIGRS) using the machine learning model that exhibited the best performance. Finally, based on a series of in vitro experiments used to explore the role of PSME3 in LUAD.ResultsWe used 10 clustering algorithms and multi-omics data to categorize TCGA-LUAD patients into three subtypes. patients with the CS3 subtype had the best prognosis, whereas patients with the CS1 and CS2 subtypes had a poorer prognosis. PIGRS, a combination of 15 high-impact genes, showed strong prognostic performance for LUAD patients. PIGRS has a very strong prognostic efficacy compared to our collection. In conclusion, we found that PSME3 has been little studied in lung adenocarcinoma and may be a novel prognostic factor in lung adenocarcinoma.DiscussionThree LUAD subtypes with different molecular features and clinical significance were successfully identified by bioinformatic analysis, and PIGRS was constructed using a powerful machine learning framework. and investigated PSME3, which may affect apoptosis in lung adenocarcinoma cells through the PI3K/AKT/Bcl-2 signaling pathway.

The initial investment for a buried pipe system using soil as a seasonal thermal storage medium is costly and not suitable for small rural buildings. To promote the cost-effective heating in rural areas, this study proposes a novel seasonal thermal storage system utilizing water and soil as thermal storage medium with copper rods to enhance thermal transfer between water tank and the surrounding soil. An experimental platform was established to discuss the temperature variation characteristics and investigate the thermal performance under different operating modes and experimental parameters. The results show that the temperature of the soil without copper rods is linearly related to the depth, while the highest temperature at the end of the copper rods occurs at the middle depth. The soil with short copper rods exhibits the most rapid thermal storage response and a relatively shorter thermal extraction response time. Intermittent operation can significantly enhance the thermal extraction rate and outlet temperature of the thermal storage unit, whereas the energy storage efficiency decreases with the extension of the downtime. The soil contribution rate of the thermal storage unit is influenced by the operational duration, initial temperature of the water tank and outdoor ambient temperature.

We have previously reported that the expression of miR-34c-5p was up-regulated during acupuncture treatment in the setting of a cerebral ischemia/reperfusion injury (CIRI), indicating that miR-34c-5p plays an important role in healing from a CIRI-induced brain injury. This study sought to evaluate the effects of acupuncture on miR-34c-5p expression and autophagy in the forward and reverse directions using a rat focal cerebral ischemia/reperfusion model. After 120 minutes of middle cerebral artery occlusion and reperfusion, rats were treated with acupuncture at the ''Dazhui'' (DU20), ''Baihui'' (DU26) and ''Renzhong'' (DU14) points. Neurologic function deficit score, cerebral infarct area ratio, neuronal apoptosis and miR-34c-5p expression were evaluated 72 hr after treatment. The autophagy agonist RAPA and the antagonist 3MA were used to evaluate the neuro protective effects of autophagy-mediated acupuncture. We found that acupuncture treatment improved autophagy in the brain tissue of CIRI rats. Acupuncture reversed the negative effects of 3MA on CIRI, and acupuncture combined with RAPA further enhanced autophagy. We also found that acupuncture could increase miR-34c-5p expression in hippocampal neurons after ischemia/reperfusion. Acupuncture and a miR-34c agomir were able to enhance autophagy, improve neurologic deficits, and reduce the cerebral infarct area ratio and apoptosis rate by promoting the expression of miR-34c-5p. Silencing miR-34c resulted in a significantly reduced activating effect of acupuncture on autophagy and increased apoptosis, neurologic deficit symptoms, and cerebral infarct area ratio. This confirms that acupuncture can upregulate miR-34c-5p expression, which is beneficial in the treatment of CIRI.

Abstract Background Laser-assisted hatching (LAH) stands as the predominant technique for removing the zona pellucida (ZP) in embryos, primarily consisting of two methods: drilling laser-assisted hatching (D-LAH) and thinning laser-assisted hatching (T-LAH). Presently, both methods have limitations, and their comparative efficacy for embryo implantation and clinical pregnancy remains uncertain. Aim Evaluate the impact of D-LAH and T-LAH on clinical pregnancy rates within assisted reproductive technology (ART). Methods We systematically searched electronic databases including PubMed, Web of Science, and Cochrane Library until July 20, 2022. This study encompassed observational studies and randomized controlled trials (RCTs). A 95% confidence interval (CI) was utilized for assessing the risk ratio (RR) of pregnancy outcomes. The level of heterogeneity was measured using I2 statistics, considering a value exceeding 50% as indicative of substantial heterogeneity. Results The meta-analysis scrutinized 9 studies involving 2405 clinical pregnancies from D-LAH and 2239 from T-LAH. Findings suggested no considerable variation in the clinical pregnancy rates between the two techniques (RR = 0.93, 95% CI: 0.79–1.10, I2 = 71%, P = 0.41). Subgroup analyses also revealed no substantial differences. However, D-LAH exhibited a notably higher occurrence of singleton pregnancies compared to T-LAH (RR = 2.28, 95% CI: 1.08–4.82, I2 = 89%, P = 0.03). There were no noteworthy distinctions observed in other secondary outcomes encompassing implantation rate, multiple pregnancies, ongoing pregnancy, miscarriage, premature birth, and live birth. Conclusion Both the primary findings and subgroup analyses showed no marked variance in clinical pregnancy rates between D-LAH and T-LAH. Therefore, patients with varying conditions should select their preferred LAH technique after assessing their individual situation. However, due to the restricted number of studies involved, accurately gauging the influence of these laser techniques on clinical outcomes is challenging, necessitating further RCTs and high-quality studies to enhance the success rate of ART. Trial registration PROSPERO: CRD42022347066.

IntroductionGeranylgeranyltransferase Subunit Beta (RABGGTB) was expressed at higher levels in patients with Amyotrophic lateral sclerosis (ALS) compared with healthy controls. This study aims to observe the expression of RABGGTB in different cells from patients with ALS and different diseases.MethodsIn this case–control study, we collected peripheral blood from patients with ALS and healthy controls, and compared the expression of RABGGTB in natural killer cells (NK), T cells and B cells between patients with ALS and healthy controls by flow cytometry. And compared the expression of RABGGTB in monocytes and monocyte-derived macrophages from patients with ALS, Parkinson’s disease (PD), acute cerebrovascular disease (ACVD), and healthy controls by flow cytometry and immunofluorescence. Then flow cytometry was used to detect the expression of RABGGTB in monocytes from SOD1G93A mice and WT mice.ResultsThe expression of RABGGTB was not significantly changed in NK cells, cytotoxic T cells (CTL), helper T cells (Th), regulatory T cells (Treg), and B cells from patients with ALS compared to healthy controls. And the expression of RABGGTB in monocytes and monocyte-derived macrophages was higher in the ALS group than in the PD, ACVD and control group. The expression of RABGGTB was significantly higher in monocytes of SOD1G93A mice compared to WT mice.ConclusionThese findings suggest that RABGGTB expression was increased in monocytes and monocyte-derived macrophages from patients with ALS, not in NK, CTL, Th, Treg, and B cells. Future studies are needed to find the clinical implication of RABGGTB in ALS.

Primary hepatic lymphoma (PHL) is rare, and its early diagnosis is difficult. This article presents a primary hepatic non-Hodgkin’s lymphoma (NHL) case report. A 52-year-old woman was admitted to the hospital due to a fever. After undergoing laboratory examination, contrast-enhanced computed tomography (CT), ultrasound, and contrast-enhanced ultrasound (CEUS), only CEUS suggested malignancy. Then, the patient underwent a laparoscopic liver biopsy, which diagnosed NHL. Previous studies have shown that hepatic lymphoma is a hypoglycemic tumor, and the enhanced CT and magnetic resonance imaging (MRI) scans are mostly mildly intensified. At the same time, the two-dimensional and color Doppler ultrasonography are mostly atypical. CEUS has unique advantages in displaying micro-vessels, which can be helpful in the diagnosis of primary hepatic lymphoma.

GCN1 is a highly conserved protein present widely across eukaryotes. As an upstream activator of protein kinase GCN2, GCN1 plays a pivotal role in integrated stress responses, such as amino acid starvation and oxidative stress. Through interaction with GCN2, GCN1 facilitates the activation of GCN2, thus initiating downstream signaling cascades in response to cellular stressors. In these contexts, the activation of GCN2 necessitates the presence and action of GCN1. Notably, GCN1 also operates as a ribosome collision sensor, contributing significantly to the translation quality control pathway. These discoveries offer valuable insights into cellular responses to internal stresses, vital for maintaining cellular homeostasis. Additionally, GCN1 exhibits the ability to regulate the cell cycle and suppress inflammation, among other processes, independently of GCN2. Our review outlines the structural characteristics and biological functions of GCN1, shedding light on its significant involvement in the onset and progression of various cancer and non-cancer diseases. Our work underscores the role of GCN1 in the context of drug therapeutic effects, hinting at its potential as a promising drug target. Furthermore, our work delves deep into the functional mechanisms of GCN1, promising innovative avenues for the diagnosis and treatment of diseases in the future. The exploration of GCN1's multifaceted roles not only enhances our understanding of its mechanisms but also paves the way for novel therapeutic interventions. The ongoing quest to unveil additional functions of GCN1 holds the promise of further enriching our comprehension of its mode of action.

Abstract Artificial intelligence (AI)-assisted PET imaging is emerging as a promising tool for the diagnosis of Parkinson’s disease (PD). We aim to systematically review the diagnostic accuracy of AI-assisted PET in detecting PD. The Ovid MEDLINE, Ovid Embase, Web of Science, and IEEE Xplore databases were systematically searched for related studies that developed an AI algorithm in PET imaging for diagnostic performance from PD and were published by August 17, 2023. Binary diagnostic accuracy data were extracted for meta-analysis to derive outcomes of interest: area under the curve (AUC). 23 eligible studies provided sufficient data to construct contingency tables that allowed the calculation of diagnostic accuracy. Specifically, 11 studies were identified that distinguished PD from normal control, with a pooled AUC of 0.96 (95% CI: 0.94–0.97) for presynaptic dopamine (DA) and 0.90 (95% CI: 0.87–0.93) for glucose metabolism (18F-FDG). 13 studies were identified that distinguished PD from the atypical parkinsonism (AP), with a pooled AUC of 0.93 (95% CI: 0.91 − 0.95) for presynaptic DA, 0.79 (95% CI: 0.75–0.82) for postsynaptic DA, and 0.97 (95% CI: 0.96–0.99) for 18F-FDG. Acceptable diagnostic performance of PD with AI algorithms-assisted PET imaging was highlighted across the subgroups. More rigorous reporting standards that take into account the unique challenges of AI research could improve future studies.

Abstract Background Stroke stands as the second leading cause of death worldwide. Currently, extensive research has been conducted on stroke risk factors. However, when stroke patients contend with multiple risk factors, the impact on clinical indicators remains uncertain. Objectives This study seeks to investigate potential significant variations among distinct ranges of clinical indicators in instances where stroke patients experience multiple risk factors and various ischemic stroke subtypes. Material and methods The research encompassed 440 stroke patients admitted to the First People's Hospital of Wenling City, Zhejiang Province, China. These patients were classified based on the type and quantity of risk factors and subtypes of ischemic stroke they presented. The χ2 test was employed to assess the relationship between the risk of comorbid diseases and clinical indicators in stroke patients. Results The results of our study have underscored a significant correlation between various comorbid risk factors in stroke patients and the patients' age (P

Nowadays, presynaptic dopaminergic positron emission tomography, which assesses deficiencies in dopamine synthesis, storage, and transport, is widely utilized for early diagnosis and differential diagnosis of parkinsonism. This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism. We conducted a thorough literature search using reputable databases such as PubMed and Web of Science. Selection criteria involved identifying peer-reviewed articles published within the last 5 years, with emphasis on their relevance to clinical applications. The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis. Moreover, when employed in conjunction with other imaging modalities and advanced analytical methods, presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker. This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion. In summary, the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials, ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

Abstract Parkinson’s disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and deposits of α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) is involved in various diseases, including inflammatory bowel disease and neurodegenerative diseases; however, its precise role in PD remains unclear. Here, we investigated the neuroprotective role of MLKL inhibition or ablation against primary neuronal cells and human iPSC-derived midbrain organoids induced by toxic α-Synuclein preformed fibrils (PFFs). Using a mouse model (Tg-Mlkl −/− ) generated by crossbreeding the SNCA A53T synuclein transgenic mice with MLKL knockout (KO)mice, we assessed the impact of MLKL deficiency on the progression of Parkinsonian traits. Our findings demonstrate that Tg-Mlkl −/− mice exhibited a significant improvement in motor symptoms and reduced phosphorylated α-synuclein expression compared to the classic A53T transgenic mice. Furthermore, MLKL deficiency alleviated tyrosine hydroxylase (TH)-positive neuron loss and attenuated neuroinflammation by inhibiting the activation of microglia and astrocytes. Single-cell RNA-seq (scRNA-seq) analysis of the SN of Tg-Mlkl −/− mice revealed a unique cell type-specific transcriptome profile, including downregulated prostaglandin D synthase (PTGDS) expression, indicating reduced microglial cells and dampened neuron death. Thus, MLKL represents a critical therapeutic target for reducing neuroinflammation and preventing motor deficits in PD.

IntroductionLimited knowledge exists regarding the impact of paternal smoking and alcohol exposure on the development of allergic rhinitis in offspring. Our study aimed to investigate the potential association between preconception paternal smoking and alcohol exposure and the likelihood of children allergic rhinitis.MethodsA retrospective case-control study of 556 prepubertal children aged 3–12 years was performed. The participants were 278 children with allergic rhinitis and 278 healthy controls matched for age and gender. Self-administered questionnaires were distributed and collected on-site, focusing on various factors related to the children's fathers, mothers, and the children themselves during the first year of life and the past 12 months, from March to October 2022.ResultsMultivariate analysis demonstrated that paternal smoking, paternal alcohol consumption prior to conception, paternal allergic diseases, children with a family history of allergies, maternal allergic diseases and pregnancy complications were identified as independent risk factors for allergic rhinitis in their offspring. Moreover, after considering confounding factors, it was observed that paternal smoking exceeding 5 cigarettes per day in the year preceding pregnancy and exceeding 11 years significantly elevated the likelihood of allergic rhinitis in children (OR = 2.009 and 2.479, respectively). Furthermore, the consumption of alcohol by the father at intervals of less than one month in the year prior to pregnancy and a duration of alcohol consumption exceeding 11 years prior to pregnancy are both associated with a significantly increased risk of allergic rhinitis in children (OR = 2.005 and 3.149, respectively).ConclusionsPaternal smoking and alcohol consumption prior to conception contribute to an increased risk of allergic rhinitis in children, with the risk being dependent on the dosage and duration of exposure. Therefore, it is important to not only focus on personal and maternal environmental exposures when considering the occurrence risk of allergic rhinitis in children, but also to consider paternal detrimental exposures prior to conception.

IntroductionAutism spectrum disorder (ASD) is a neurological condition that is marked by deficits in social interaction, difficulty expressing oneself, lack of enthusiasm, and stereotypical conduct. The TOMATIS training method is an effective music therapy for children with ASD for its individually developed programs to improve behavioral deficits.MethodsThe research employed both longitudinal and crosssectional designs.ResultsIn the cross-sectional study, the experimental group showed significant improvement in symptoms after TOMATIS training compared to the control group of children with ASD. The results validated the effect of TOMATIS treatment for ASD-related deficits, including perceptual-motor, attentional, social, and emotional issues.DiscussionASD’s auditory hypersensitivity hampers social information processing, but TOMATIS enhances cochlear frequency selectivity, aiding in capturing relevant auditory stimuli. In addition, the longitudinal study confirmed these findings, which proved TOMATIS training effective in clinically treating ASD. This study focused on audiometric indicators and behavioural improvement, elucidating the mechanisms behind the training’s success. Behavioral improvements might stem from TOMATIS’ frequency selectivity, reshaping auditory organ-cortical feedback loops to filter interference and focus on valid information.

Abstract Multiple evidence indicates that perinatal factors make impact on immune development and affect offspring allergic rhinitis (AR) risk. In this systematic review and meta-analysis, we examined available published studies to clarify the relationship between cesarean section (C-section) and offspring AR in children. To explore the relationship between C-section, especially the special attention was paid to different cesarean delivery mode, and the risk of AR in children. Articles were searched using PubMed, Web of Science, EMBASE, Cochrane Library, China knowledge Network, Wanfang, and China Science and Technology Journal databases. A meta-analysis of 22 studies published before August 1, 2022, which included 1,464,868 participants, was conducted for statistical analysis with RevMan5.4. The correlation strength between C-section and offspring AR was determined by combining odds ratio (OR) and 95% confidence interval (95% CI). Meta-regression and subgroup analyses were used to explore potential sources of heterogeneity. Publication bias was detected using the funnel chart and Egger tests. Meta-analysis revealed that there was a significant correlation between C-section and children AR (OR = 1.19, 95% CI: 1.12–1.27, P

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3–5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.

Advancements in understanding the pathogenesis mechanisms underlying gastrointestinal diseases, encompassing inflammatory bowel disease, gastrointestinal cancer, and gastroesophageal reflux disease, have led to the identification of numerous novel therapeutic targets. These discoveries have opened up exciting possibilities for developing gene therapy strategies to treat gastrointestinal diseases. These strategies include gene replacement, gene enhancement, gene overexpression, gene function blocking, and transgenic somatic cell transplantation. In this review, we introduce the important gene therapy targets and targeted delivery systems within the field of gastroenterology. Furthermore, we provide a comprehensive overview of recent progress in gene therapy related to gastrointestinal disorders and shed light on the application of innovative gene-editing technologies in treating these conditions. These developments are fueling a revolution in the management of gastrointestinal diseases. Ultimately, we discuss the current challenges (particularly regarding safety, oral efficacy, and cost) and explore potential future directions for implementing gene therapy in the clinical settings for gastrointestinal diseases.

AIM: To investigate the prevalence of color vision deficiency (CVD) among college students and their quality of life (QoL) in a Chinese college. METHODS: This cross-sectional study was performed in Sichuan University in Chengdu, China. The questionnaire containing participants' demographic data, as well as CVD related QoL was distributed to students who were screened as CVD [by Color Vision Examination Plates (Version 6)] in 2022 freshman entrance examination. Color blindness QoL (CBQoL) and utility analysis were used to evaluate the QoL of CVD students. RESULTS: There were 381 of 17 303 (2.20%) students screened as CVD, including 368 (4.11%) males and 13 (0.16%) females. A total of 317 students completed the questionnaire, the response rate was 83.20%. Only 166 participants (52.3%) knew they have CVD before the physical examination for college entrance examination, while a total of 145 participants (45.74%) hoped to be diagnosed earlier. The medians of CBQoL score and utility were 5.85 (range 2.2-6) and 1 (range 0-1), respectively. The proportions of students whose QoL is affected by CVD were 67.63% (211/312) and 42.27% (134/317) measured by CBQoL and utility analysis respectively. CONCLUSION: The prevalence of CVD in males is much higher than that in females. The time when CVD students first became aware of their CVD is relatively late. The QoL of the study population is quite high, while a large proportion of students' QoL are affected by CVD. It is suggested that as a congenital defect, CVD screening in China should be earlier, and appropriate guidance and support are needed for CVD patients to help them better adapt to life, study, and work.

The CO2 sequestration capacity evaluation of reservoirs is a critical procedure for carbon capture, utilization, and storage (CCUS) techniques. However, calculating the sequestration amount for CO2 flooding in low-permeability reservoirs is challenging. Herein, a method combining numerical simulation technology with artificial intelligence is proposed. Based on the typical geological and fluid characteristics of low-permeability oil reservoirs in the Liaohe oilfield, the CMG 2020 version software GEM module is used to establish a model for CO2 flooding and sequestration. Meanwhile, a calculation method for the effective sequestration coefficient of CO2 is established. We systematically study the sequestration rules in low-permeability reservoirs under varying conditions of permeability, reservoir temperature, and initial reservoir pressure. The results indicate that, as the permeability and sequestration pressure of the reservoir increase, oil recovery gradually increases. The proportion of structurally bound sequestration volume increases from 55% to 60%. Reservoir temperature has minimal impact on both the recovery rate and the improvement in sequestration efficiency. Sequestration pressure primarily improves sequestration efficiency by increasing the dissolution of CO2 in the remaining oil and water. The calculation chart for the effective sequestration coefficient, developed using artificial intelligence algorithms under multi-factor conditions, enables accurate and rapid evaluation of the sequestration potential and the identification of favorable sequestration areas in low-permeability reservoirs. This approach provides valuable technical support for CO2 flooding and sequestration in pilot applications.

Powdery mildew is a fungal disease devastating to crops, causing significant quality and yield loss. As one of the most important fruits in the world, melon also is damaged by powdery mildew. The present study investigated the effect of powdery mildew on the photosynthetic parameters and leaf microstructure of melons, the ultrastructure of the leaf surface, photosynthetic index, chlorophyll content, yield, and quality index of five thick-skinned and differently shaped melon varieties. The net photosynthetic rate, transpiration rate, leaf water use efficiency, and chlorophyll levels were significantly (p < 0.05) higher in Kangbing F3800 plants compared to the other four varieties. In the case of powdery mildew infection, the total number of stomata in the upper and lower epidermis was particularly high in the Zhongtian No. 8 and Zhongtianxueqiong varieties, respectively. The stomatal length and width were highest in the upper epidermis of Zhongtian No. 12 leaves and in the lower epidermis of Zhongtian No. 8 leaves compared to the other varieties. The total yield and meat thickness were significantly (p < 0.05) higher in the Zhongtianxueqiong variety than the others, along with the low edge sugar content. Overall, powdery mildew impacted differently the photosynthetic and leaf surface characteristics of the five melon varieties. Kangbing F3800 emerged as the most resistant variety, making it the preferred choice for introducing and promoting thick-skinned melon varieties in the Ningxia Hui Autonomous Region of China.

Abstract Plant-derived exosome-like nanoparticles (PDENs) have been paid great attention in the treatment of ulcerative colitis (UC). As a proof of concept, we isolated and identified Portulaca oleracea L-derived exosome-like nanoparticles (PELNs) from edible Portulaca oleracea L, which exhibited desirable nano-size (~ 160 nm) and a negative zeta potential value (-31.4 mV). Oral administration of PELNs effectively suppressed the expressions of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1β) and myeloperoxidase (MPO), increased levels of the anti-inflammatory cytokine (IL-10), and alleviated acute colitis in dextran sulfate sodium (DSS)-induced C57 mice and IL-10−/− mice. Notably, PELNs exhibited excellent stability and safety within the gastrointestinal tract and displayed specific targeting to inflamed sites in the colons of mice. Mechanistically, oral administration of PELNs played a crucial role in maintaining the diversity and balance of gut microbiota. Furthermore, PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which might activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells. This activation downregulated Zbtb7b expression, leading to the reprogramming of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells). In conclusion, our findings highlighted the potential of orally administered PELNs as a novel, natural, and colon-targeted agent, offering a promising therapeutic approach for managing UC. Graphic abstract Schematic illustration of therapeutic effects of oral Portulaca oleracea L -derived natural exosome-like nanoparticles (PELNs) on UC. PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells leading to downregulate the expression of Zbtb7b, reprogram of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells), and decrease the levels of pro-inflammatory cytokines.

Abstract The organoids represent one of the greatest revolutions in the biomedical field in the past decade. This three-dimensional (3D) micro-organ cultured in vitro has a structure highly similar to that of the tissue and organ. Using the regeneration ability of stem cells, a 3D organ-like structure called intestinal organoids is established, which can mimic the characteristics of real intestinal organs, including morphology, function, and personalized response to specific stimuli. Here, we discuss current stem cell-based organ-like 3D intestinal models, including understanding the molecular pathophysiology, high-throughput screening drugs, drug efficacy testing, toxicological evaluation, and organ-based regeneration of inflammatory bowel disease (IBD). We summarize the advances and limitations of the state-of-the-art reconstruction platforms for intestinal organoids. The challenges, advantages, and prospects of intestinal organs as an in vitro model system for precision medicine are also discussed. Key applications of stem cell-derived intestinal organoids. Intestinal organoids can be used to model infectious diseases, develop new treatments, drug screens, precision medicine, and regenerative medicine.

Objective:. Computed tomography pulmonary angiography (CTPA) parameters are valuable for predicting pulmonary hypertension (PH) in patients with pulmonary embolism (PE). However, few studies have used the coronary sinus ostium area (CSOA), derived from CTPA, to detect PH. This study aimed to compare the prognostic values of the CSOA, coronary sinus ostium diameter (CSOD), and right ventricular (RV)/left ventricular (LV) ratio for PH. Methods:. This study retrospectively analyzed 78 patients (mean age, (51.94 ± 12.33) years; 53.8% male) with acute PE confirmed by CTPA at the Sixth and Eighth Medical Centers of the People’s Liberation Army General Hospital between June 2018 and June 2020. Patients were categorized into 2 groups using a pulmonary artery systolic pressure (PASP) cut-off of 30 mmHg. CTPA parameters were compared between these groups. Results:. Patients with PASP >30 mmHg (n = 22) had a larger CSOA, CSOD, RV diameter, RV/LV ratio, and inferior vena cava diameter compared with patients with PASP ≤30 mmHg (n = 56). The CSOA had an area under the receiver-operating characteristic curve (AUC, 0.84; 95% confidence interval (CI), 0.74–0.94; P < 0.001) similar to that of the RV/LV ratio (AUC, 0.85; 95%CI, 0.73–0.99; P < 0.001), while that of the CSOD was smaller (AUC, 0.66; 95%CI, 0.51–0.81; P < 0.05). Conclusion:. Both CSOA and CSOD demonstrated a good ability to predict PH, while CSOA better predicted PASP >30 mmHg.

The increasing heating demand calls for a correspondingly augmented heating capacity of the primary heating network. However, due to the restriction of existing pipes, the heating capacity can be finitely increased. Therefore, based on the organic Rankine cycle (ORC) and vapor compression cycle (VCC), a novel thermal station is proposed to realize self-augmented heating capacity. Based on laws of thermodynamics, the mathematical model is constructed, and the dynamic performances of power generation and self-augmented heating capacity are analyzed. Results show that the supply water temperature of the primary heating network greatly influences the power generation performance. The self-sufficient electricity can achieve approximately 2000 h, accounting for 61.70% of the heating period. Additionally, the proposed thermal station can flexibly reduce the return water temperature of the primary heating network to 20 °C, thereby achieving self-augmented heating capacity. The self-augmented heating capacity rate can reach 53.56%. Therefore, the proposed thermal station demonstrates excellent self-augmented heating capacity, which provides a new path for satisfying the ever-increasing heating demand.

In recent years, research on the mechanism of bone destruction in rheumatoid arthritis (RA) has remained in the initial stages, and the mechanism has not been fully elucidated to date. Recent studies have shown that long noncoding RNAs (lncRNAs) participate in RA bone destruction via autophagy, but the specific regulatory mechanism of lncRNA-mediated autophagy is unclear. Therefore, in this article, we review the mechanisms of lncRNA-mediated autophagy in fibroblast-like synoviocytes and chondrocytes in RA bone destruction. We explain that lncRNAs mediate autophagy and participate in many specific pathological processes of RA bone destruction by regulating signalling pathways and the expression of target genes. Specific lncRNAs can be used as markers for molecular diagnosis, mechanistic regulation, treatment and prognosis of RA.

Abstract Bacteria form a highly complex ecosystem in the gastrointestinal (GI) tract. In recent years, mounting evidence has shown that bacteria can release nanoscale phospholipid bilayer particles that encapsulate nucleic acids, proteins, lipids, and other molecules. Extracellular vesicles (EVs) are secreted by microorganisms and can transport a variety of important factors, such as virulence factors, antibiotics, HGT, and defensive factors produced by host eukaryotic cells. In addition, these EVs are vital in facilitating communication between microbiota and the host. Therefore, bacterial EVs play a crucial role in maintaining the GI tract’s health and proper functioning. In this review, we outlined the structure and composition of bacterial EVs. Additionally, we highlighted the critical role that bacterial EVs play in immune regulation and in maintaining the balance of the gut microbiota. To further elucidate progress in the field of intestinal research and to provide a reference for future EV studies, we also discussed the clinical and pharmacological potential of bacterial EVs, as well as the necessary efforts required to understand the mechanisms of interaction between bacterial EVs and gut pathogenesis.

Abstract Objective The purpose of this study was to provide evidence for early life care by meta-analyzing the relationship between infection during pregnancy and up to 2 years of age and the risk of subsequent allergic rhinitis (AR). Methods Published studies up to April 2022 were systematically searched in PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang Database, and VIP. Literature screening, including quality assessment, was performed, and the effect values (OR, HR, RR) and 95% confidence intervals (95% CI) of infection during pregnancy and up to 2 years of age and allergic rhinitis were extracted from each qualified study. Results In total, 5 studies with a sample size of 82,256 reported the relationship between infection during pregnancy and offspring AR. Meta-analysis showed that maternal infection during pregnancy was associated with an increased risk of childhood AR in offspring (OR = 1.34, 95% CI: 1.08–1.67). Altogether, 13 studies with a sample size of 78,426 reported evidence of an association between infection within 2 years of age and subsequent AR in children. A pooled meta-analysis of all studies showed that early infection within 2 years of age was closely associated with childhood AR (OR = 1.25, 95% CI: 1.12–1.40), especially upper respiratory tract infection (OR = 1.32, 95% CI: 1.06–1.65) and gastrointestinal infections (OR = 1.37, 95% CI: 1.01–1.86), but ear infection showed similar results in the cohort study (OR = 1.13, 95% CI: 1.04–1.22). Conclusion Current evidence suggests that infection during pregnancy, early upper respiratory infection, gastrointestinal infections and ear infection within 2 years of age would increase the risk of AR in children. Therefore, the prevention of infection during pregnancy and in infancy and young children needs to be emphasized.

Hepatocellular carcinoma (HCC), ranking as the seventh most prevalent cancer worldwide, poses a significant health challenge. Actinidia chinensis Planch Root extracts (acRoots), a traditional Chinese medicine, has exhibited promising inhibitory effects on the proliferation, invasion, and migration of various cancer cell types. Nevertheless, its specific impact and underlying mechanisms concerning HCC remain unclear. This research aimed to elucidate the anticancer properties and potential molecular mechanisms of acRoots in the HepG2 and LM3 cell lines. Our findings demonstrate that acRoots effectively hampers the in vitro proliferation, migration, and invasion of HCC cells. Furthermore, acRoots induces apoptosis and autophagy by impeding the AKT/mTOR signaling pathway, with its inhibitory effects on cells being restored under AKT activator induction. This study, for the first time, elucidates that acRoots can suppress HepG2 and LM3 cell proliferation by blocking the Akt/mTOR pathway, thereby activating apoptosis and autophagy. These results underscore the potential of acRoots as a promising antitumor agent for HCC.

Summary: Background: Progressive supranuclear palsy (PSP) is a primary 4-repeat tauopathy with diverse clinical phenotypes. Previous post-mortem studies examined tau deposition sequences in PSP, but in vivo scrutiny is lacking. Methods: We conducted [18F]Florzolotau tau positron emission tomography (PET) scans on 148 patients who were clinically diagnosed with PSP and 20 healthy controls. We employed the Subtype and Stage Inference (SuStaIn) algorithm to identify PSP subtype/stage and related tau patterns, comparing clinical features across subtypes and assessing PSP stage-clinical severity association. We also evaluated functional connectivity differences among subtypes through resting-state functional magnetic resonance imaging. Findings: We identified two distinct subtypes of PSP: Subtype1 and Subtype2. Subtype1 typically exhibits a sequential progression of the disease, starting from subcortical and gradually moving to cortical regions. Conversely, Subtype2 is characterized by an early, simultaneous onset in both regions. Interestingly, once the disease is initiated, Subtype1 tends to spread more rapidly within each region compared to Subtype2. Individuals categorized as Subtype2 are generally older and exhibit less severe dysfunctions in areas such as cognition, bulbar, limb motor, and general motor functions compared to those with Subtype1. Moreover, they have a more favorable prognosis in terms of limb motor function. We found significant correlations between several clinical variables and the identified PSP SuStaIn stages. Furthermore, Subtype2 displayed a remarkable reduction in functional connectivity compared to Subtype1. Interpretation: We present the evidence of distinct in vivo spatiotemporal tau trajectories in PSP. Our findings can contribute to precision medicine advancements for PSP. Funding: This work was supported by grants from the National Natural Science Foundation of China (number 82272039, 81971641, 82021002, and 92249302); Swiss National Science Foundation (number 188350); the STI2030-Major Project of China (number 2022ZD0211600); the Clinical Research Plan of Shanghai Hospital Development Center of China (number SHDC2020CR1038B); and the National Key R&D Program of China (number 2022YFC2009902, 2022YFC2009900), the China Scholarship Council (number 202006100181); the Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198).

Abstract Cancer is one of the most fatal diseases for decades. Aggregation‐induced emission luminogens (AIEgens) have been recently used as molecular imaging or therapeutic agents in cancers, due to the advantages of large Stokes shift, high quantum yield, great biocompatibility, and strong photostability. AIEgens can specifically target different types of cancer via diverse targeting strategies. AIEgen‐based fluorescence imaging, especially near‐infrared imaging, demonstrated deep penetration and suitable signal‐to‐noise ratio, which allows reliable in vivo cancer imaging. Combined with other imaging modalities, AIEgen‐based multimodal imaging could provide multidimensional cancer hallmarks from different perspectives. In addition, AIEgen‐based phototherapy can be used for photodynamic therapy and photothermal therapy, which facilitate ablation of cancer cells with good biosafety and high therapeutic effects in vivo. AIEgens nanoparticles fabricated with some specific chemicals, drugs, or siRNA, could display synergistic therapeutic effects for cancers. This paper comprehensively describes the current status and future perspectives of AIEgens, which have showed a great potential for the future preclinical and clinical translation on in vivo molecular imaging and theranostics in cancer.

Inflammatory bowel disease (IBD) encompasses a collection of idiopathic diseases characterized by chronic inflammation in the gastrointestinal (GI) tract. Patients diagnosed with IBD often experience necessitate long-term pharmacological interventions. Among the multitude of administration routes available for treating IBD, oral administration has gained significant popularity owing to its convenience and widespread utilization. In recent years, there has been extensive evaluation of the efficacy of orally administered herbal medicinal products and their extracts as a means of treating IBD. Consequently, substantial evidence has emerged, supporting their effectiveness in IBD treatment. This review aimed to provide a comprehensive summary of recent studies evaluating the effects of herbal medicinal products in the treatment of IBD. We delved into the regulatory role of these products in modulating immunity and maintaining the integrity of the intestinal epithelial barrier. Additionally, we examined their impact on antioxidant activity, anti-inflammatory properties, and the modulation of intestinal flora. By exploring these aspects, we aimed to emphasize the significant advantages associated with the use of oral herbal medicinal products in the treatment of IBD. Of particular note, this review introduced the concept of herbal plant-derived exosome-like nanoparticles (PDENs) as the active ingredient in herbal medicinal products for the treatment of IBD. The inclusion of PDENs offers distinct advantages, including enhanced tissue penetration and improved physical and chemical stability. These unique attributes not only demonstrate the potential of PDENs but also pave the way for the modernization of herbal medicinal products in IBD treatment.

Here, the authors show that the glycosylceramide synthesis inhibitor and FDA approved drug Eliglustat inhibits autophagic degradation of TRAF3 which is a key step for osteoclast differentiation and thereby improves myeloma bone lesions.