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ObjectivesUnder the COVID-19 prevention and control policy, online learning has been widely used. The current study aimed to identify latent profiles of self-regulated learning in the context of online mathematics learning during the recurrent outbreak of COVID-19, and examine the mechanisms underlying the relationship between self-regulated learning and online mathematics learning engagement among Chinese junior high school students using variable-and person-centered approaches.MethodsA sample of 428 Chinese junior high school students (47.66% female) completed questionnaires on self-regulated learning, perceived academic control, and learning engagement. Mplus7.0 was used to analyze the latent classes of self-regulated learning. A mediation model was conducted using the software SPSS PROCESS macro.ResultsThree profiles of self-regulated learning were identified and named as low self-regulated learning (16.12%), medium self-regulated learning (43.23%), and high self-regulated learning (40.65%). In the mediating analysis, results of the variable-centered approach showed that perceived academic control mediated the effects of self-regulated learning on learning engagement. For the person-centered approach, we selected the low self-regulated learning type as the reference profile, and the analysis revealed that compared with the reference profile, perceived academic control partially mediated the link between the medium self-regulated learning profile and learning engagement; perceived academic control partially mediated the relationship between the high self-regulated learning profile and learning engagement.ConclusionThis study showed the heterogeneity in the online mathematics self-regulated learning patterns of Chinese junior high school students during the COVID-19 pandemic, revealing the internal mechanisms of Chinese junior high school students’ online mathematics learning engagement using variable-and person-centered approaches. Furthermore, the findings of the study have important implications for promoting online mathematics learning engagement among junior high students during the pandemic.

The relationship between metacognition and mindreading was investigated by examining how well one can monitor their own learning (Self) compared to another person’s learning (Other). Here, we used functional near-infrared spectroscopy (fNIRS) to systematically investigate the brain area activation during metacognition and mindreading. The evidence indicated that metacognition and mindreading are underpinned by distinct neural systems. Metacognition is associated with activation in brain regions important for memory retrieval, such as the fusiform gyrus, while mindreading is associated with activation in brain regions important for understanding and reasoning about others’ intentions, such as the right temporoparietal junction (rTPJ).

BackgroundLymphoma is a heterogeneous group of tumors in terms of morphological subtypes, molecular alterations, and management. However, data on circulating tumor DNA (ctDNA) mutated genes are limited. The purpose of this study was to investigate the features of the ctDNA mutated genes, the prognosis, and the association between the ctDNA mutated genes and the clinical parameters in lymphoma.MethodsDifferences in the ctDNA between the mutated genes and the prognosis of 59 patients with Hodgkin’s lymphoma (HL) (10.2%), germinal center B-cell–like lymphoma (GCB) (28.8%), nongerminal center B-cell–like lymphoma (non-GCB) (50.8%), and marginal zone lymphoma (MZL) (10.2%) were analyzed by next generation sequencing (NGS) targeting 121 lymphoma-relevant genes.ResultsGenetic alterations were identified in the ctDNA samples with a median of 6 variants per sample. The genetic variation of the ctDNA in the plasma was found to be significantly correlated with the clinical indices in lymphoma. The genetic heterogeneity of different lymphoma subtypes was clearly observed in the ctDNAs from HL, GCB, non-GCB, and MZL, confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas.ConclusionOur findings suggest that NGS-based ctDNA mutation analysis reveals genetic heterogeneity across lymphoma subtypes, with potential implications for discovering therapeutic targets, exploring genomic evolution, and developing risk-adaptive therapies.

Atom localization enables a high-precision imaging of the atomic position, which has provided vast applications in fundamental and applied science. In the present work, we propose a scheme for realizing two-dimensional off-axis atom localization in a three-level Λ system. Benefiting from the use of a hybrid coupling field, which consists of one Gaussian beam and one Laguerre–Gaussian beam, our scheme shows that the atoms can be localized at arbitrary position with high spatial resolution. Considering realistic experimental parameters, our numerical simulation predicts that the atoms can be precisely localized with a spatial resolution of ∼200 nm in the range of a radial distance of a few micrometers to the beam core. Our results provide a more flexible way to localize atoms in a two-dimensional system, possibly paving one-step closer to the nanometer scale atom lithography and ultraprecise microscopy.

Introduction: We investigated trends in the use of therapeutic drugs for pregnant patients with rheumatic diseases in nine Chinese cities (Beijing, Chengdu, Guangzhou, Harbin, Hangzhou, Shanghai, Shenyang, Tianjin, and Zhengzhou) to provide a reference for drug use in clinic. Methods: Outpatient prescription data for pregnant patients diagnosed with rheumatic diseases in nine cities across China in 2016-2021 were extracted from the Hospital Prescription Cooperation Project of the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association. A retrospective analysis was then performed, incorporating data on patient age, defined daily doses (DDDs), defined daily cost (DDC), and other metrics. Results: In 2016-2020, more than 70% of the pregnant patients diagnosed with rheumatic diseases in these nine cities were 25 to < 35 years of age. The most common rheumatic diseases during pregnancy were antiphospholipid antibody syndrome (APS) and systemic lupus erythematosus (SLE). In terms of the routine use of daily therapeutic drugs, the DDDs of low molecular weight heparins (LMWHs), glucocorticoids, and immunosuppressive agents dominated the top three. Intravenous immunoglobulin (IVIG) and tumor necrosis factor inhibitors (TNFi) have been used since 2019 and had been in the forefront of the DDC. Conclusion: The number and total cost of prescriptions for therapeutic drugs of pregnancy complicated by rheumatic diseases, have increased significantly over the study interval. Conventional therapeutic drugs, especially glucocorticoids, LMWHs, and hydroxychloroquine were the most widely used drugs in pregnant patients with rheumatic diseases. However, IVIG and TNFi, relatively high cost, have shown gradual increases in clinical use since 2019. [ABSTRACT FROM AUTHOR]

Easy of learning (EOL) judgments occur before active learning begins, and it is a prediction of how difficult it will be to learn new material in future learning. This study compared the amplitude of event-related potential (ERP) components and brain activation regions between high and low EOL judgments by adopting ERPs with a classical EOL judgment paradigm, aiming to confirm the ease-of-processing hypothesis. The results showed that (1) the magnitudes of EOL judgments are affected by encoding fluency cues, and the judgment magnitude increases with encoding fluency; (2) low EOL judgments are associated with higher N400 amplitude at the left superior frontal gyrus (SFG) and left middle frontal gyrus (MFG). High EOL judgments showed enlarged slow-wave (600–1,000 ms) potentials than low EOL judgments at the left medial temporal lobe (MTL), right ventromedial prefrontal cortex (VMPFC), and dorsolateral prefrontal cortex (DLPFC). Our results support the ease-of-processing hypothesis, particularly, by affirming that EOL judgments are affected by encoding fluency in two processing stages. N400 reflects the process of acquiring encoding fluency cues, while slow-wave indicates that individuals use encoding fluency cues for metacognitive monitoring.

Pancreatic lipase (PL) inhibitor therapy has been validated as an efficacious way for preventing and treating obesity and overweight. In the past few decades, porcine PL (pPL) is widely used as the enzyme source for screening the PL inhibitors, which generates a wide range of pPL inhibitors. By contrast, the efficacious inhibitors against human PL (hPL) are rarely reported. This study aims to discover the naturally occurring hPL inhibitors from edible herbal medicines (HMs) and to characterize the inhibitory mechanisms of the newly identified hPL inhibitors. Following the screening of the inhibition potentials of more than 100 HMs against hPL, Ampelopsis grossedentata extract (AGE) displayed the most potent hPL inhibition activity. After that, the major constituents in AGE were identified and purified, while their anti-hPL effects were assayed in vitro. The results clearly showed that two abundant constituents in AGE (dihydromyricetin and iso-dihydromyricetin) were moderate hPL inhibitors, while myricetin and quercetin were strong hPL inhibitors [half-maximal inhibitory concentration (IC50) values were around 1.5 μM]. Inhibition kinetic analyses demonstrated that myricetin and quercetin potently inhibited hPL-catalyzed near-infrared fluorogenic substrate of human pancreatic lipase (DDAO-ol) hydrolysis in a non-competitive inhibition manner, with Ki values of 2.04 and 2.33 μM, respectively. Molecular dynamics simulations indicated that myricetin and quercetin could stably bind on an allosteric site of hPL. Collectively, this study reveals the key anti-obesity constituents in AGE and elucidates their inhibitory mechanisms against hPL, which offers convincing evidence to support the anti-obesity and lipid-lowering effects of this edible herb.

Human carboxylesterase 2 (CES2), one of the most abundant hydrolases distributed in the small intestine, has been validated as a key therapeutic target to ameliorate the intestinal toxicity caused by irinotecan. This study aims to discover efficacious CES2 inhibitors from natural products and to characterize the inhibition potentials and inhibitory mechanisms of the newly identified CES2 inhibitors. Following high-throughput screening and evaluation of the inhibition potency of more than 100 natural products against CES2, it was found that the biflavones isolated from Ginkgo biloba displayed extremely potent CES2 inhibition activities and high specificity over CES1 (>1000-fold). Further investigation showed that ginkgetin, bilobetin, sciadopitysin and isoginkgetin potently inhibited CES2-catalyzed hydrolysis of various substrates, including the CES2 substrate-drug irinotecan. Notably, the inhibition potentials of four biflavones against CES2 were more potent than that of loperamide, a marketed anti-diarrhea agent used for alleviating irinotecan-induced intestinal toxicity. Inhibition kinetic analyses demonstrated that ginkgetin, bilobetin, sciadopitysin and isoginkgetin potently inhibited CES2-catalyzed fluorescein diacetate hydrolysis via a reversible and mixed inhibition manner, with Ki values of less than 100 nM. Ensemble docking and molecular dynamics revealed that these biflavones could tightly and stably bind on the catalytic cavity of CES2 via hydrogen bonding and π-π stacking interactions, while the interactions with CES1 were awfully poor. Collectively, this study reports that the biflavones isolated from Ginkgo biloba are potent and highly specific CES2 inhibitors, which offers several promising lead compounds for developing novel anti-diarrhea agent to alleviate irinotecan-induced diarrhea.

Dendrobium candidum is used as a traditional Chinese medicine and as a raw material in functional foods. D. candidum stems are green or red, and red stems are richer in anthocyanins. Light is an important environmental factor that induces anthocyanin accumulation in D. candidum. However, the underlying molecular mechanisms have not been fully unraveled. In this study, we exposed D. candidum seedlings to two different light intensities and found that strong light increased the anthocyanin content and the expression of genes involved in anthocyanin biosynthesis. Through transcriptome profiling and expression analysis, we identified a WD40-repeat transcription factor, DcTTG1, whose expression is induced by light. Yeast one-hybrid assays showed that DcTTG1 binds to the promoters of DcCHS2, DcCHI, DcF3H, and DcF3′H, and a transient GUS activity assay indicated that DcTTG1 can induce their expression. In addition, DcTTG1 complemented the anthocyanin deficiency phenotype of the Arabidopsis thaliana ttg1-13 mutant. Collectively, our results suggest that light promotes anthocyanin accumulation in D. candidum seedlings via the upregulation of DcTTG1, which induces anthocyanin synthesis-related gene expression.

Epilepsy is a complex neurological disorder characterized by recurrent and unprovoked seizures. Neuronal death process is implicated in the development of repetitive epileptic seizures. Therefore, cell death can be harnessed for ceasing seizures and epileptogenesis. Oxidative stress is regarded as a contributing factor of neuronal death activation and there is compelling evidence supporting antioxidants hold promise in abrogating seizure-related cell modality. Lapatinib, a well-known anti-cancer drug, has been traditionally reported to exert anti-tumor effect via modulating oxidative stress and a recent work illustrates the improvement of encephalomyelitis in rodent models after lapatinib treatment. However, whether lapatinib is beneficial for inhibiting neuronal death and epileptic seizure remains unknown. Here, we found that lapatinib remarkably prevented kainic acid (KA)-epileptic seizures in mice and ferroptosis, a newly defined cell death which is associated with oxidative stress, was involved in the neuroprotection of lapatinib. In the ferroptotic cell death model, lapatinib exerted neuroprotection via restoring glutathione peroxidase 4 (GPX4). Treatment with GPX4 inhibitor ras-selective lethal small molecule 3 (RSL3) abrogated its anti-ferroptotic potential. In a mouse model of KA-triggered seizure, it was also validated that lapatinib blocked GPX4-dependent ferroptosis. It is concluded that lapatinib has neuroprotective potential against epileptic seizures via suppressing GPX4-mediated ferroptosis.

Gastrointestinal stromal tumours (GISTs) are the most common human sarcomas and are typically located in the stomach or small intestine. Although circular RNAs (circRNAs) reportedly play vital roles in tumour oncogenesis and progression, the molecular basis of the aggressive tumour biology of these circRNAs in GISTs remains unclear. In this study, we applied SBC ceRNA microarrays to screen for tumour-specific circRNA profiles in GISTs and identified that a total of 5,770 circRNAs and 1,815 mRNAs were differentially expressed in GISTs. Three significantly differential circRNAs (circ_0069765, circ_0084097, and circ_0079471) and their host genes (KIT, PLAT, and ETV1) were also verified in 68 pairs of GISTs and adjacent normal gastrointestinal tissues by qRT-PCR. A GIST-specific circRNA-miRNA-mRNA regulatory network analysis demonstrated that the specific KIT-related regulatory networks involved the three circRNAs, the circRNA host genes and three miRNAs (miR-142-5p, miR-144-3p and miR-485-3p), which may be key regulators of GISTs that could serve as molecular biomarkers and potential therapeutic targets for this malignant disease.

Posttraumatic epilepsy (PTE) is a prevalent type of acquired epilepsy secondary to traumatic brain injury, and is characterized by repeated seizures. Traditional antiepileptic drugs have minimal response in preventing posttraumatic epileptic seizures. It is essential for the development of new therapeutic strategy. Our previous work disclosed a potent neuroprotective role of baicalein, a flavonoid extracted from Scutellaria baicalensis Georgi, against inherited epilepsy in rats. Whether baicalein has protective potential in posttraumatic epileptic seizures and the possible molecular mechanism remain elusive. Additionally, the brain is vulnerable to lipid peroxidation-induced damage due to high consumption of oxygen and abundant polyunsaturated fatty acids in neuronal membranes. Our present investigation aimed to elucidate whether baicalein exerts neuroprotective effects on posttraumatic epileptic seizures by inhibiting ferroptosis, a newly discovered lipid peroxidation-dependent cell death modality. We found that baicalein significantly reduced seizure score, number of seizures, and average seizure duration in an iron chloride (FeCl3)-induced PTE mouse model. The neuroprotective effect of baicalein was also validated in a ferric ammonium citrate (FAC)-induced HT22 hippocampal neuron damage model. Moreover, in vitro, baicalein could remarkably decrease ferroptotic indices (lipid reactive oxygen species, 4-hydroxynonenal, and prostaglandin endoperoxide synthase 2) and inhibit the expression of 12/15-lipoxygenase (12/15-LOX) in an iron-induced HT22 cell damage model. These findings were also validated in a mouse PTE model. It was concluded that baicalein exerted neuroprotective effects against posttraumatic epileptic seizures via suppressing ferroptosis and 12/15-LOX was likely to be involved in baicalein’s neuroprotection.

Early biomarkers of therapeutic responses can help optimize the treatment of metastatic colorectal cancers (mCRC). In this prospective exploratory study, we examined serial changes of plasma-circulating tumor DNA (ctDNA) in 41 mCRC patients receiving first-line chemotherapies and tested its association with treatment outcomes according to radiological assessments. Using next-generation sequencing technologies, we profiled somatic mutations in 50 cancer-related genes in ctDNA before each of the first four treatment cycles. We observed mutations in 95.7% of pre-treatment ctDNA samples. Using mutations of the maximal frequency in each pre-treatment plasma ctDNA sample as the candidate targets, we computed log2 fold changes of ctDNA levels between adjacent treatment cycles. We found that ctDNA reductions as early as prior to cycle 2 predicted responses after cycle 4. Log2 fold changes of ctDNA after cycle 1 (ctDNA log2 (C1/C0)) > −0.126 predicted progressive disease, with an accuracy of 94.6%. These patients also showed significantly worse progression-free survival than those with ctDNA log2 (C1/C0) ≤ −0.126 (median 2.0 vs. 9.0 months; P = 0.007). Together, the present exploratory study suggests that early changes in ctDNA levels detected via targeted sequencing are potential biomarkers of future treatment responses in mCRCs.

Varieties of Citrus are commercially important fruits that are cultivated worldwide and are valued for being highly nutritious and having an appealing flavor. Lignification of citrus fruit juice sacs is a serious physiological disorder that occurs during postharvest storage, for which the underlying transcriptional regulatory mechanisms remain unclear. In this study, we identified and isolated a candidate MYB transcription factor, CsMYB85, that is involved in the regulation of lignin biosynthesis in Citrus sinensis, which has homologs in Arabidopsis and other plants. We found that during juice sac lignification, CsMYB85 expression levels increase significantly, and therefore, suspected that this gene may control lignin biosynthesis during the lignification process. Our results indicated that CsMYB85 binds the CsMYB330 promoter, regulates its expression, and interacts with CsMYB308 in transgenic yeast and tobacco. A transient expression assay indicated that Cs4CL1 expression levels and lignin content significantly increased in fruit juice sacs overexpressing CsMYB85. At4CL1 expression levels and lignin content were also significantly increased in Arabidopsis overexpressing CsMYB85. We accordingly present convincing evidence for the participation of the CsMYB85 transcription factor in fruit juice sac lignification, and thereby provide new insights into the transcriptional regulation of this process in citrus fruits.

Transient gene expression systems using protoplasts have been widely used for rapid functional characterization of genes and high-throughput analysis in many model and crop species. Here, we describe a simplified and highly efficient root protoplast isolation and transient expression system in the model legumes Lotus japonicus and Medicago truncatula. Firstly, we presented an efficient protocol for isolating protoplasts from L. japonicus and M. truncatula roots. We then established an efficient transient expression system in these legumes root protoplasts. Using this protocol, the subcellular localization of two symbiosis related proteins (SYMRK and ERN1) were visualized in the plasma membrane and nuclei, respectively. Collectively, this efficient protoplast isolation and transformation protocol is sufficient for studies on protein subcellular localization, and should be suitable for many other molecular biology applications.

Introduction: To investigate the influences of time interval between multimodality therapies on survival for locally advanced gastric cancer (LAGC) patients, 627 patients were included in a retrospective study, and 350 who received neoadjuvant chemotherapy (NACT) based on SOX (S-1 plus Oxaliplatin)/XELOX (Capecitabine plus Oxaliplatin) treatment, radical surgery, and adjuvant chemotherapy (AC) from 2005.01 to 2018.06 were eligible for analyses. Methods: Three factors were used to assess influences, including time interval from NACT accomplishment to AC initiation (PECTI), time to surgery after NACT accomplishment (TTS), and time to adjuvant chemotherapy after surgery (TAC). Results: Concerning PECTIs, 99 (28.29%) experienced it within 9 weeks, 188 (53.71%) within 9-13 weeks, 63 (18.00%) over 13 weeks. Patients' 5-year overall survival (OS) significantly decreased as trichotomous PECTI increased (78.6% vs 66.7% vs 55.7%, P = .02). Analogously, there was a significant decrease for dichotomous TTS (within vs over 5 weeks) in OS (P = .03) and progression free survival (PFS) (P = .01) but not for dichotomous TAC (within vs over 6 weeks) in OS and PFS (P = .40). Through multivariate Cox analyses, patients with PECTI over 13 weeks had significantly worse OS (P = .03) and PFS (P = .02). Furthermore, extended TTS had significantly worse OS and PFS but insignificantly worse OS and PFS than extended TAC. Therefore, gastric patients receiving perioperative SOX/XELOX chemotherapy and surgery with extended PECTI over 9 weeks or TTS over 5 weeks would have a negative correlation with PFS and OS, and worse when PECTI over 13 weeks. Nomograms (including PECTI, ypT, ypN, Area Under Curve (AUC) = 0.81) could predict patient survival probability and guide intervention with net benefit. Discussion: In control of PECTI, TTS could be extended appropriately, and shortened TAC might make a remedy, and delayed TAC might be allowed when TTS was shortened. [ABSTRACT FROM AUTHOR]

BackgroundPreeclampsia (PE) is a hypertensive disorder of pregnancy that threatens the lives of millions of pregnant women and their babies worldwide. Without effective medications, there are thousands of maternal and child mortalities every year. Resveratrol (RSV), a non-flavonoid polyphenol extracted from multiple plants, has shown positive effects in treating hypertension, cardiovascular disorders, and even PE. This study aimed to explore the pharmacological mechanism of RSV in treating PE by using network pharmacology and bioinformatics.MethodsWith the use of multiple databases, 66 intersecting targets were obtained from the 347 putative targets of RSV and 526 PE-related genes. Then, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to investigate the functions of the intersecting targets. The protein–protein interaction network and target–pathway network were drawn and analyzed to illustrate the correlation between targets and pathways. Finally, molecular docking was conducted to calculate the binding energy between RSV and core targets.ResultsThe results showed that the core targets of RSV were IL6, TNF, IL1B, VEGFA, STAT3, and EGFR. There existed good binding between RSV and IL6, TNF, IL1B, VEGFA, and EGFR. In addition, we found that RSV mainly functioned in the AGE-RAGE and HIF-1 signaling pathways, which are associated with the occurrence and development of PE.ConclusionIn conclusion, our findings indicated that RSV has the effects of regulating angiogenesis and anti-inflammation and can be a candidate medicine for treating PE.

ObjectiveThis study investigated the prevalence of wrist injuries in 15 industries and different types of work in China. Study on the associated factors of wrist injuries provides a scientific basis for prevention and treatment of wrist diseases in occupational workers.MethodsA cross-sectional study of musculoskeletal symptoms of related practitioners in 15 industries, including automobile manufacturing, was conducted to retrieve worker demographic information, working wrist posture, and pain conditions. Multivariable binary logistic regression analyses were performed to identify factors associated with work-related musculoskeletal disorders (WMSDs).ResultsThe prevalence of wrist injuries among the study population was 13.2%. Toy manufacturing, animal husbandry, automobile manufacturing, shoe manufacturing, and biopharmaceutical manufacturing had the highest wrist injury rates at 29.1, 19.1, 14.9, 14.9, and 14.0%, respectively. Among the types of jobs, enamel workers (63.0%), butchers (43.6%), combers (32.5%), welders (31.3%), and scaffolders (26.5%) had the highest prevalence rates. Based on the final multivariate logistic regression analysis: female [odds ratios (OR) = 1.24; 95% confidence interval (CI), 1.15–1.35], 6–10 years of service (OR = 1.11; 95% CI, 1.03–1.18), >10 years of service (OR = 1.15; 95% CI, 1.06–1.25), frequent upward and downward flexion in wrist posture at work (OR = 1.81; 95% CI, 1.84–2.11), and frequent wrist placement on the edge of angular objects increased the OR of injury (OR = 1.52; 95% CI, 1.44–1.61). Need to squeeze objects tightly while working (OR = 1.72; 95% CI, 1.57–1.89), prolonged wrist flexion (OR = 1.86; 95% CI, 1.75–1.97), and work hand position above the shoulder for prolonged periods (OR = 1.11; 95% CI, 1.04–1.19) also suggested the relationship between these factors and the higher prevalence of wrist injury in the workers. The associated factor was physical activity (OR = 0.86; 95% CI, 0.80–0.94).ConclusionThis study suggested the relationship between these factors and the higher prevalence of wrist injury in the toy manufacturing, animal husbandry, automobile manufacturing, and shoe-making industries, enamel workers, butchers, and combers. And are work types that require special attention. Females, working age, physical activity, and abnormal posture of the wrist were factors significantly associated with WMSDs.