Puerarin Alleviates Experimental Autoimmune Thyroiditis by Regulating Macrophages.

Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, predominantly affecting women. Although the pathogenesis of HT is incompletely understood, some studies have found that macrophage polarization plays a role. Puerarin is a soy isoflavone compound that has anti-inflammatory and immunomodulatory effects and regulates macrophage immune activity. This study aimed to verify the therapeutic effect of puerarin on HT and explored its regulatory effect on macrophage polarization imbalance in HT. Through bioinformatics analysis and molecular biology methods, it was found that macrophages increased significantly in HT patients and model mice. Immunological staining showed that puerarin intervention could reduce tissue inflammatory cell infiltration. Molecular biological examination displayed that puerarin could inhibit local and systemic inflammation levels, and the expression of marker thyroglobulin and thyroid peroxidase Abs. In vivo experimental results indicated that puerarin regulated macrophage polarity and reduced inflammatory damage, possibly by inhibiting the pyroptosis signaling pathway. In vivo macrophage clearance experiments demonstrated that puerarin relied on macrophages to exert its mechanism of action in treating HT. The results of this study indicate that macrophages are important mediators in the development of HT, and puerarin can regulate macrophage polarity and inflammatory status to provide thyroid tissue protection, which provides a new idea for the treatment of HT.

Common Driving Forces of Provincial-Level Greenhouse Gas and Air Pollutant Emissions in China.

By developing a filtering framework and a sector-level multi-regional input-output structural decomposition model, this study identifies key common emission sources, motivation sources, and inter-provincial emission flows of both GHGs and air pollutants and reveals the key driving forces of changes in different emissions from 2012 to 2017. Results show that key common emission sources are electricity sector, non-metallic mineral products, and smelting and processing of metals in Shandong and Hebei. However, key common motivation sources are the construction sectors in Guangdong, Henan, Jiangsu, Zhejiang, and Shandong. The key inflow regions include Guangdong and Zhejiang and key outflow regions include Jiangsu and Hebei. The emission reductions are attributed to the emission intensity effect of the construction sector; contrastingly, the emission increase is from the investment scale of the construction sector. Here, Jiangsu could be a key target for future emission reduction because of its high absolute emissions and low past reduction. The scale of investment in construction might be a significant factor in reducing emissions in Shandong and Guangdong. Henan and Zhejiang could concentrate on sound new building planning and resource recycling.

Parent-Adolescent Conflict, Peer Victimization, and Internet Gaming Disorder Among Chinese Adolescents: The Moderating Effect of OXTR Gene rs53576 Polymorphism.

Despite growing evidence that parent-adolescent conflict positively correlates with Internet gaming disorder (IGD) among adolescents, its underlying mediating and moderating mechanisms have yet to be thoroughly examined. Based on the social development model and gene-environment interaction perspective, this study investigates whether the indirect association of parent-adolescent conflict, which impacts adolescent IGD through peer victimization, was moderated by the oxytocin receptor (OXTR) gene rs53576 polymorphism. Overall, 673 Chinese adolescents (Meanage = 12.81 years; SD = 0.48 years; 54% boys) were included in this study. The participants completed questionnaires concerning parent-adolescent conflict, peer victimization, and IGD, and genomic DNA was extracted from each participant's saliva and buccal cells. The findings indicated that peer victimization mediated the link between parent-adolescent conflict and IGD among adolescents. The OXTR gene rs53576 polymorphism also moderated this indirect link. Specifically, the indirect effect of parent-adolescent conflict on adolescent IGD through peer victimization was significant for adolescents with AA homozygotes. However, it was non-significant for adolescents with GA and GG genotypes. This research simultaneously considers the roles of family, peers, and genetics in adolescent IGD. Furthermore, it provides beneficial information to customize interventions for adolescent IGD prevention.

Synthesis and Biological Evaluation of Novel 2-Amino-1,4-Naphthoquinone Amide-Oxime Derivatives as Potent IDO1/STAT3 Dual Inhibitors with Prospective Antitumor Effects.

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) have emerged as significant targets in the tumor microenvironment for cancer therapy. In this study, we synthesized three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives and identified them as dual inhibitors of IDO1 and STAT3. The representative compound NK3 demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC50 = 0.06 µM), leading to its selection for further investigation. The direct interactions between compound NK3 and IDO1 and STAT3 proteins were confirmed through surface plasmon resonance analysis. A molecular docking study of compound NK3 revealed key interactions between NK3 and IDO1, with the naphthoquinone-oxime moiety coordinating with the heme iron. In the in vitro anticancer assay, compound NK3 displayed potent antitumor activity against selected cancer cell lines and effectively suppressed nuclear translocation of STAT3. Moreover, in vivo assays conducted on CT26 tumor-bearing Balb/c mice and an athymic HepG2 xenograft model revealed that compound NK3 exhibited potent antitumor activity with low toxicity relative to 1-methyl-L-tryptophan (1-MT) and doxorubicin (DOX). Overall, these findings provided evidence that the dual inhibitors of IDO1 and STAT3 may offer a promising avenue for the development of highly effective drug candidates for cancer therapy.

FLCN-regulated miRNAs suppressed reparative response in cells and pulmonary lesions of Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé Syndrome (BHDS) characterised by skin fibrofolliculomas, kidney tumour and pulmonary cysts/pneumothorax is caused by folliculin (FLCN) germline mutations. The pathology of both neoplasia and focused tissue loss of BHDS strongly features tissue-specific behaviour of the gene. Isolated cysts/pneumothorax is the most frequent atypical presentation of BHDS and often misdiagnosed as primary spontaneous pneumothorax (PSP). Deferential diagnosis of BHDS with isolated pulmonary presentation (PSP-BHD) from PSP is essential in lifelong surveillance for developing renal cell carcinoma. METHODS: The expression profiles of microRNAs (miRNAs) in cystic lesions of PSP-BHD and PSP were determined via microarray. The selected upregulated miRNAs were further confirmed in the plasma of an expanded cohort of PSP-BHD patients by reverse transcription quantitative PCR (RT-qPCR). Their diagnostic accuracy was evaluated. Moreover, the cellular functions and targeted signalling pathways of FLCN-regulated miRNAs were assessed in various cell lines and in the lesion tissue contexts. RESULTS: Cystic lesions of PSP-BHD and PSP showed different miRNAs profiles with a significant upregulation of miR-424-5p and let-7d-5p in PSP-BHD. The combination of the two effectively predicted BHDS patients. In vitro studies revealed a suppressive effect of FLCN on miR-424-5p and let-7d-5p expressions specifically in lung epithelial cells. The ectopic miRNAs triggered epithelial apoptosis and epithelial transition of mesenchymal cells and suppressed the reparative responses in cells and tissues with FLCN deficiency. CONCLUSION: The upregulation of miR-424-5p and let-7d-5p by FLCN deficiency occurred in epithelial cells and marked the PSP-BHD condition, which contributed to a focused degenerative pathology in the lung of PSP-BHD patients.

Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer.

OBJECTIVE: To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes. DESIGN: We performed metagenome-wide association studies on faecal samples from 74 patients with CRC and 54 controls from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls. RESULTS: Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I-II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC. CONCLUSIONS: We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal samples.

Changes to pollutants and carbon emission multipliers in China 2007-2012: An input-output structural decomposition analysis.

This study performed an input-output structural decomposition analysis on changes in COD, ammonia nitrogen, SO2, NOx, soot and dust, industrial solid waste, and CO2 emission multipliers for 41 final products over the period 2007-2012 in China. The results show that during the examined period, emission multipliers were, in general, decreasing. The main driver of this was technical effects. The effects that made a significant contribution were concentrated in eight sectors: coal mining and washing; metals mining and quarrying; food and tobacco products; paper printing manufacturing; the chemical industry; non-metallic mineral products; metal smelting and rolling processing; and electricity, heat production, and supply. Moreover, the technical effects presented an obvious spillover. Although the contribution of the structural effects was far less than the technical ones, there were still some structural adjustments that led to significant synergistic mitigation. For example, the decrease in the direct demand of the agriculture products, electricity, and heat for food and tobacco products commonly reduced SO2, NOx, and CO2. In addition, four technical effects and most of the structural effects with high efficiency made small contributions. More than one third of the structural effects that showed obvious contributions played a positive role.

Chemical constituents from the tubers of Scirpus yagara and their anti-inflammatory activities.

A new natural compound, dehydrophyllodulcin (1) was isolated from the tubers of Scirpus yagara, together with 11 known compounds. Among them, compounds 2, 5-8, and 10-12 were isolated from this plant for the first time. (1)H NMR, (13)C NMR, and 2D NMR data of compound 1 are first reported in this article, though it was synthesized in 1996. The structures of all compounds were determined by comprehensive analyses of their spectroscopic data and compared with literature information. Moreover, the anti-inflammatory effects of compounds 1, 3, 4, 6, and 9 against inflammatory cytokines production in Lipopolysaccharide - or Pam3csk4-stimulated macrophage RAW264.7 cells were evaluated by Enzyme-linked immunosorbent assay. And these compounds significantly inhibited the tumor necrosis factor (TNF)-α, interleukin (IL)-6 productions in RAW264.7 cells, with IC50 values less than 20 µM.

Establish Albumin-creatinine Ratio Reference Valueof Adults in the Rural Area of Hebei Province.

Objective To establish albumin-creatinine ratio (ACR) reference value of the rural population in Hebei province.Methods This study enrolled 5154 participants. By excluding subjects with hypertension, diabetes, dyslipidemia, cardiovascular and cerebrovascular diseases, kidney diseases, and overweight condition, as well as those with an estimated glomerular filtration rate (eGFR)<60 ml/(min·1.73 m2), apparently healthy subjects (1168) were selected. Urine albumin was measured by using the immunoturbidimetic method, serum creatinine was measured by using Jaffe's kinetic method on a morning spot-urine sample, and ACR was calculated. The 95th percentile of ACR in the healthy subjects was used as the normal upper limit.Results The normal upper limit of ACR was 28.71 mg/g (3.25 mg/mmol) for males and 31.85 mg/g (3.60 mg/mmol) for females. Based on this ACR reference value, the age-gender standardized prevalence of albuminuria in the rural areas of Hebei province was 12.9%.Conclusion The ACR reference value in the rural of Hebei province is higher than that of the Western population.

Toll-like receptor 2/4 heterodimer mediates inflammatory injury in intracerebral hemorrhage.

OBJECTIVE: Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH)-induced secondary brain injury. However, the upstream events that initiate inflammatory responses following ICH remain elusive. Our previous studies suggested that Toll-like receptor 4 (TLR4) may be the upstream signal that triggers inflammatory injury in ICH. In addition, recent clinical findings indicated that both TLR2 and TLR4 may participate in ICH-induced brain injury. However, it is unclear how TLR2 functions in ICH-induced inflammatory injury and how TLR2 interacts with TLR4. METHODS: The role of TLR2 and TLR2/TLR4 heterodimerization in ICH-induced inflammatory injury was investigated in both in vivo and in vitro models of ICH. RESULTS: TLR2 mediated ICH-induced inflammatory injury, which forms a heterodimer with TLR4 in both in vivo and in vitro models of ICH. Hemoglobin (Hb), but not other blood components, triggered inflammatory injury in ICH via assembly of TLR2/TLR4 heterodimers. MyD88 (myeloid differentiation primary response gene 88), but not TRIF (Toll/IR-1 domain-containing adaptor protein inducing interferon-beta), was required for ICH-induced TLR2/TLR4 heterodimerization. Mutation of MyD88 Arg196 abolished the TLR2/TLR4 heterodimerization. INTERPRETATION: Our results suggest that a novel TLR2/TLR4 heterodimer induced by Hb initiates inflammatory injury in ICH. Interfering with the assembly of the TLR2/TLR4 heterodimer may be a novel target for developing effective treatment of ICH.

Determination of sparstolonin B by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry: application to pharmacokinetic study of sparstolonin B in rat plasma.

Sparstolonin B (SsnB), a spontaneous isocoumarin compound isolated from the tuber of Scirpus yagara Ohwi. (Cyperaceae), possesses potent anti-inflammatory and antitumor activity. In the present study, a rapid and simple UHPLC/MS/MS method for determination of SsnB in rat plasma was developed and validated. Plasma samples were pretreated by liquid-liquid extraction with ethyl acetate containing rhein as an internal standard and separated on a C18 column at 35 °C, with a gradient mobile phase consisting of acetonitrile and water containing 0.2% (v/v) formic acid within 2.1 min. MS/MS detection was accomplished in multiple reaction monitoring mode with negative electrospray ionization. The precursor-product ion transitions were m/z 266.9 [M-H](-) → m/z 211.0 for SsnB and m/z 283.2 [M-H](-) → m/z 239.0 for IS. The intra- and inter-day precision (RSD) was <8.98% and the accuracy (RE) ranged from -7.40 to 4.50%. The extraction recoveries ranged from 96.28 to 97.30%. The pharmacokinetic parameters were calculated using Win Nonlin53 software. The absolute bioavailability of SsnB was estimated to be 6.98%. The proposed method was successfully applied to a pharmacokinetic study of SsnB in rats after intravenous administration with a dose of 0.5 mg/kg and oral administration at a dose of 5 mg/kg.

Is extra-pleura Nuss procedure more secure and effective?

PURPOSE: To compare total extra-pleura Nuss procedure with classical Nuss, and evaluate the efficacies and safety of thoracoscopic total extra-pleural approach of Nuss procedure for correction of pectus excavatum in children. METHODS: We managed 69 patients with pectus excavatum from July 2006 to October 2012. Of the 69 patients, 40 underwent thoracoscopic total extra-pleural approach of Nuss (group A), and 29 underwent classical Nuss procedure (group B). In group A, there were 29 boys and 11 girls, and the mean age was 6.4 (ranged from 3.5 to 14.5). Under thoracoscopic guidance, an extra-pleural tunnel was created using a blunt dissector via a right thoracic incision. A steel bar was inserted in the entirely extra-pleural tunnel. The bar was turned and fixed as in standard Nuss procedure. In group B, there were 20 boys and 9 girls, and the mean age was 5.9 (ranged from 4 to 11) years. Under thoracoscopic guidance, a blunt dissector was inserted into pleura cavity directly via a right thoracic incision. It was a standard Nuss procedure. RESULTS: The operations were completed successfully in all patients. None of the children developed pneumothorax or injuries to the pericardium, heart or lungs. The operating time was 42.0 ± 5.3 and 43.4 ± 6.0 min in group A and B, respectively, and the difference was not significant (p = 0.306). Compared to group B, the postoperative hospital stay of group A was shorter (4.0 ± 1.1 vs 5.2 ± 1.2 days, p = 0.001). The outcomes of both groups were similar (97.5% in group A vs 93.8% in group B, p = 0.377) but pain time was shorter, and time of taking painkiller was less than those of group B (2.6 ± 0.8 vs 4.1 ± 1.0 days, p = 0.001; 1.1 ± 0.6 vs 1.8 ± 0.9 time, p = 0.008). No patients in group A developed subcutaneous emphysema or pleural irritation, while 5 patients in group B showed the symptoms (p = 0.004). All patients were followed-up for 4-30 months (mean 20.2). During the follow-up, none of the children had pulmonary infection or dislocation of the steel board or fixation instruments before the bar was removed. 69 patients removed their bar after a 24-month period on average. According to Nuss' postoperative assessment criteria, one patient in group B was fair. The other patients were all excellent or good. CONCLUSIONS: Extra-pleura Nuss procedure under thoracoscopic guidance is a safe and less traumatic procedure for the correction of pectus excavatum. It is not only superior in postoperative recovery and pleural cavity protection, but also results in fewer complications than the intrapleural procedures.

Multi-model comparison of the economic and energy implications for China and India in an international climate regime.

This paper presents a modeling comparison on how stabilization of global climate change at about 2 °C above the pre-industrial level could affect economic and energy systems development in China and India. Seven General Equilibrium (CGE) and energy system models on either the global or national scale are soft-linked and harmonized with respect to population and economic assumptions. We simulate a climate regime, based on long-term convergence of per capita carbon dioxide (CO2) emissions, starting from the emission pledges presented in the Copenhagen Accord to the United Nations Framework Convention on Climate Change and allowing full emissions trading between countries. Under the climate regime, Indian emission allowances are allowed to grow more than the Chinese allowances, due to the per capita convergence rule and the higher population growth in India. Economic and energy implications not only differ among the two countries, but also across model types. Decreased energy intensity is the most important abatement approach in the CGE models, while decreased carbon intensity is most important in the energy system models. The reduction in carbon intensity is mostly achieved through deployment of carbon capture and storage, renewable energy sources and nuclear energy. The economic impacts are generally higher in China than in India, due to higher 2010-2050 cumulative abatement in China and the fact that India can offset more of its abatement cost though international emission trading.

Distinct compositions and functions of circulating microbial DNA in the peripheral blood compared to fecal microbial DNA in healthy individuals.

The crucial function of circulating microbial DNA (cmDNA) in peripheral blood is gaining recognition because of its importance in normal physiology and immunity in healthy individuals. Evidence suggests that cmDNA in peripheral blood is derived from highly abundant, translocating gut microbes. However, the associations with and differences between cmDNA in peripheral blood and the gut microbiome remain unclear. We collected blood, urine, and fecal samples from volunteers to compare their microbial information via 16S rDNA sequencing. The results revealed that, compared with gut microbial DNA, cmDNA in peripheral blood was associated with reduced diversity and a distinct microbiota composition. The cmDNA in the blood reflects the biochemical processes of microorganisms, including synthesis, energy conversion, degradation, and adaptability, surpassing that of fecal samples. Interestingly, cmDNA in blood showed a limited presence of DNA from anaerobes and gram-positive bacteria, which contrast with the trend observed in fecal samples. Furthermore, analysis of cmDNA revealed traits associated with mobile elements and potential pathologies, among others, which were minimal in stool samples. Notably, cmDNA analysis indicated similarities between the microbial functions and phenotypes in blood and urine samples, although greater diversity was observed in urine samples. Source Tracker analysis suggests that gut microbes might not be the main source of blood cmDNA, or a selective mechanism allows only certain microbial DNA into the bloodstream. In conclusion, our study highlights the composition and potential functions associated with cmDNA in peripheral blood, emphasizing its selective presence; however, further research is required to elucidate the mechanisms involved.IMPORTANCEOur research provides novel insights into the unique characteristics and potential functional implications of circulating microbial DNA (cmDNA) in peripheral blood. Unlike other studies that analyzed sequencing data from fecal or blood microbiota in different study cohorts, our comparative analysis of cmDNA from blood, urine, and fecal samples from the same group of volunteers revealed a distinct blood-specific cmDNA composition. We discovered a decreased diversity of microbial DNA in blood samples compared to fecal samples as well as an increased presence of biochemical processes microbial DNA in blood. Notably, we add to the existing knowledge by documenting a reduced abundance of anaerobes and gram-positive bacteria in blood compared to fecal samples according to the analysis of cmDNA and gut microbial DNA, respectively. This observation suggested that a potential selective barrier or screening mechanism might filter microbial DNA molecules, indicating potential selectivity in the translocation process which contrasts with the traditional view that cmDNA primarily originates from random translocation from the gut and other regions. By highlighting these differences, our findings prompt a reconsideration of the origin and role of cmDNA in blood circulation and suggest that selective processes involving more complex biological mechanisms may be involved.

Sublingual immunotherapy for experimental allergic conjunctivitis in a murine model induced by Dermatophagoides farinae allergen.

BACKGROUND: Sublingual immunotherapy (SLIT) is a clinically effective treatment in allergic conjunctivitis (AC); however, the mechanism of the underlying pharmacodynamics remains unclear. Here, we investigate the efficacy and the mechanism of a sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine AC model. METHODS: A murine model of AC caused by Der f extract was developed in BALB/c mice by repeated application of allergen. Sensitized mice were SLIT treated by Der f drops and subsequently analyzed for AC symptoms, histopathological and immunological parameters. RESULTS: In this study, Der f extract successfully induced the symptoms of AC in BALB/c mice. In these sensitized mice, clinical symptoms (scratching behavior, lacrimation, conjunctival hyperemia and edema), immunological and histopathological findings (inflammatory cell infiltration) were very similar to those in human AC. SLIT treatment of sensitized mice markedly reduced the clinical and histopathological symptoms and decreased the expression levels of total immunoglobulin E (IgE), Der f-specific IgE and T helper cell 2 (Th2) cytokine interleukin-4, with a significant increase in Der f-specific IgG4 and Th1 cytokine interferon-γ. CONCLUSIONS: SLIT with Der f drops is a potentially effective means of immunotherapy for Der f-induced AC by modulating the Th2-biased allergic immune response.

A new di-O-prenylated flavone from an actinomycete Streptomyces sp. MA-12.

A new di-O-prenylated flavone, named 7,3'-di-(γ,γ-dimethylallyloxy)-5-hydroxy-4'-methoxyflavone (1), was isolated from the culture broth of the endophytic actinomycete Streptomyces sp. MA-12 isolated from the root of the semi-mangrove plant Myoporum bontioides A. Gray. The structure of 1 was determined by comprehensive spectroscopic methods, including 1D and 2D NMR experiments (COSY, HMQC, and HMBC). Primary bioassays showed that 1 at concentration of 0.25 mM had moderate inhibitory activity against three plant pathogenic fungi including Colletotrichum musae, Gibberella zeae (Schweinitz) Petch, and Penicillium citrinum Thom.

Three-dimensional stability analysis of tunnel face based on unified strength theory.

The impact of cyclic footage and intermediate principal stress on the stability of the tunnel-face area are analyzed in this study using the theory of limit analysis. The study introduces the unified strength theory and proposes three-dimensional logarithmic spiral failure modes with corresponding velocity fields. The influence of various parameters on the tunnel-face area stability is analyzed, and it is found that when the internal friction angle is less than 30°, the internal friction angle parameters should be improved first to enhance stability, while when the internal friction angle is greater than 30°, cohesion should be prioritized. When using the double shear uniform strength theory in the tunnel-face area, the intermediate principal stress can improve the stability of the tunnel face. Results show that Mohr-Coulomb criterion calculations are conservative in the good surrounding ground, but no similar conclusion has been obtained for the poor surrounding ground, and specific problems must be analyzed during construction.

Learning adaptability facilitates self-regulated learning at school: the chain mediating roles of academic motivation and self-management.

Studies have demonstrated that learning adaptability has emerged as an important factor for students' utilization of self-regulated learning for successful learning, but how this association occurred is not clear yet. This study aimed to clarify the mechanism of the relationship between learning adaptability and self-regulated learning by investigating the chain mediating roles of academic motivation and self-management of 787 junior high school students under the "double reduction" background. The results showed that (1) learning adaptability had significant positive effects on junior high school students' self-regulated learning and (2) academic motivation and self-management played independent and accumulative mediating roles in the relationship between learning adaptability and self-regulated learning. These findings help to understand how to support students in successfully coping with the new challenges brought by educational reform and promote effective adjustment to challenges, including the "double reduction." The key contribution of this study is to provide new insights into the literature that academic motivation and self-management separately and sequentially mediate the learning adaptability, self-regulated learning links, and learning adaptability is effective driver of self-regulated learning in the population of junior high school students.

Puerarin alleviates sleep disorders in aged mice related to repairing intestinal mucosal barrier.

More and more evidence suggests that puerarin, a potential remedy for gut inflammation, may have an ameliorative effect on sleep disturbances. However, the relationship between puerarin and sleep disruption has not been extensively researched. This study aims to explore the role and mechanisms of puerarin in improving sleep disorders. We established a light-induced sleep disorder model in mice and assessed the effects of puerarin on cognitive behavior using open field and water maze tests. Pathological detection demonstrated that sleep disturbances resulted in observable damage to the liver, lung, and kidney. Puerarin reversed multi-organ damage and inflammation. Further, puerarin activated paneth cells, resulting in increased lysozyme and TGF-ß production, and stimulating intestinal stem cell proliferation. Puerarin also effectively inhibited the expression of F4/80, iNOS, TNF-α, and IL-1ß in the small intestine, while it increased Chil3, CD206, and Arg-1 levels. Moreover, puerarin treatment significantly decreased P-P65, TLR4, Bcl-xl, and cleaved caspase-3 protein levels while increasing barrier protein levels, including ZO-1, Occludin, Claudin 1 and E-cadherin suggesting a reduction in inflammation and apoptosis in the gut. Overall, puerarin diminished systemic inflammation, particularly intestinal inflammation, and enhanced intestinal barrier integrity in mice with sleep disorders. Our findings suggest a potential new therapeutic pathway for sleep disorders.

A burns and COVID-19 shared stress responding gene network deciphers CD1C-CD141- DCs as the key cellular components in septic prognosis.

Differential body responses to various stresses, infectious or noninfectious, govern clinical outcomes ranging from asymptoma to death. However, the common molecular and cellular nature of the stress responsome across different stimuli is not described. In this study, we compared the expression behaviors between burns and COVID-19 infection by choosing the transcriptome of peripheral blood from related patients as the analytic target since the blood cells reflect the systemic landscape of immune status. To this end, we identified an immune co-stimulator (CD86)-centered network, named stress-response core (SRC), which was robustly co-expressed in burns and COVID-19. The enhancement of SRC genes (SRCs) expression indicated favorable prognosis and less severity in both conditions. An independent whole blood single-cell RNA sequencing of COVID-19 patients demonstrated that the monocyte-dendritic cell (Mono-DC) wing was the major cellular source of SRC, among which the higher expression of the SRCs in the monocyte was associated with the asymptomatic COVID-19 patients, while the quantity-restricted and function-defected CD1C-CD141-DCs were recognized as the key signature which linked to bad consequences. Specifically, the proportion of the CD1C-CD141-DCs and their SRCs expression were step-wise reduced along with worse clinic conditions while the subcluster of CD1C-CD141-DCs from the critical COVID-19 patients was characterized of IFN signaling quiescence, high mitochondrial metabolism and immune-communication inactivation. Thus, our study identified an expression-synchronized and function-focused gene network in Mono-DC population whose expression status was prognosis-related and might serve as a new target of diagnosis and therapy.