CD169+ Skin Macrophages Function as a Specialized Subpopulation in Promoting Psoriasis-like Skin Disease in Mice.

Skin macrophages are critical to maintain and restore skin homeostasis. They serve as major producers of cytokines and chemokines in the skin, participating in diverse biological processes such as wound healing and psoriasis. The heterogeneity and functional diversity of macrophage subpopulations endow them with multifaceted roles in psoriasis development. A distinct subpopulation of skin macrophages, characterized by high expression of CD169, has been reported to exist in both mouse and human skin. However, its role in psoriasis remains unknown. Here, we report that CD169+ macrophages exhibit increased abundance in imiquimod (IMQ) induced psoriasis-like skin lesions. Specific depletion of CD169+ macrophages in CD169-ditheria toxin receptor (CD169-DTR) mice inhibits IMQ-induced psoriasis, resulting in milder symptoms, diminished proinflammatory cytokine levels and reduced proportion of Th17 cells within the skin lesions. Furthermore, transcriptomic analysis uncovers enhanced activity in CD169+ macrophages when compared with CD169- macrophages, characterized by upregulated genes that are associated with cell activation and cell metabolism. Mechanistically, CD169+ macrophages isolated from IMQ-induced skin lesions produce more proinflammatory cytokines and exhibit enhanced ability to promote Th17 cell differentiation in vitro. Collectively, our findings highlight the crucial involvement of CD169+ macrophages in psoriasis development and offer novel insights into the heterogeneity of skin macrophages in the context of psoriasis.

Time-varying impacts of green credit on carbon productivity in China: New evidence from a non-parametric panel data model.

In the context of global climate change threatening human survival, and in a post-pandemic era that advocates for a global green and low-carbon economic recovery, conducting an in-depth analysis to assess whether green finance can effectively support low-carbon economic development from a dynamic perspective is crucial. Unlike existing research, which focuses solely on the average effects of green credit (GC) on carbon productivity (CP), we introduce a non-parametric panel data model to investigate GC's impact on CP across 30 provinces in China from 2003 to 2021, verifying a significant time-varying effect. Specifically, during the first phase (2003-2008), GC negatively impacted CP. In the second phase (2009-2014), this negative influence gradually diminished and transformed into a positive effect. In the third phase (2015-2021), GC continued to positively influence CP, although this effect became insignificant during the pandemic. Further subgroup analysis reveals that in the regions with low environmental regulations, GC did not significantly boost CP throughout the sample period. In contrast, in the regions with high environmental regulations, GC's positive effect persisted in the mid to late stages of the sample period. Additionally, compared to the regions with low levels of marketization, the impact of GC on CP was more pronounced in highly marketized regions. This indicates that the promoting effect of GC on CP depends on strong support from environmental regulations and well-functioning market mechanisms. By adopting a non-parametric approach, this study reveals variations in the impact of GC on CP across different stages and under the influence of the pandemic shock, offering new insights into the relationship between GC and China's CP.

Med23 deficiency reprograms the tumor microenvironment to promote lung tumorigenesis.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. We previously found that Mediator complex subunit 23 (MED23) is important for the tumourigenicity of lung cancer cells with hyperactive Ras activity in vitro, although the in vivo function of MED23 in lung tumourigenesis remains to be explored. METHODS: In this study, we utilized well-characterized KrasG12D-driven non-small cell lung cancer mouse model to investigate the role of MED23 in lung cancer. The lung tumour progression was evaluated by H&E and IHC analysis. Western blotting and qRT-PCR assays were performed to detect changes in gene expression. Immune cells were analyzed by FACS technology. RNA-seq and reporter assays were conducted to explore the mechanism. RESULTS: We observed that lung epithelial Med23 deletion by adeno-Cre resulted in a significant increase in KrasG12D tumour number and size, which was further verified with another mouse model with Med23 specifically deleted in alveolar type II cells. Mice with lung-specific Med23 deficiency also exhibited accelerated tumourigenesis, and a higher proliferation rate for tumour cells, along with increased ERK phosphorylation. Notably, the numbers of infiltrating CD4+ T cells and CD8+ T cells were significantly reduced in the lungs of Med23-deficient mice, while the numbers of myeloid-derived suppressor cells (MDSCs) and Treg cells were significantly increased, suggesting the enhanced immune escape capability of the Med23-deficient lung tumours. Transcriptomic analysis revealed that the downregulated genes in Med23-deficient lung tumour tissues were associated with the immune response. Specifically, Med23 deficiency may compromise the MHC-I complex formation, partially through down-regulating B2m expression. CONCLUSIONS: Collectively, these findings revealed that MED23 may negatively regulate Kras-induced lung tumourigenesis in vivo, which would improve the precise classification of KRAS-mutant lung cancer patients and provide new insights for clinical interventions.

Potential drug targets for asthma identified in the plasma and brain through Mendelian randomization analysis.

Background: Asthma is a heterogeneous disease, and the involvement of neurogenic inflammation is crucial in its development. The standardized treatments focus on alleviating symptoms. Despite the availability of medications for asthma, they have proven to be inadequate in controlling relapses and halting the progression of the disease. Therefore, there is a need for novel drug targets to prevent asthma. Methods: We utilized Mendelian randomization to investigate potential drug targets for asthma. We analyzed summary statistics from the UK Biobank and then replicated our findings in GWAS data by Demenais et al. and the FinnGen cohort. We obtained genetic instruments for 734 plasma and 73 brain proteins from recently reported GWAS. Next, we utilized reverse causal relationship analysis, Bayesian co-localization, and phenotype scanning as part of our sensitivity analysis. Furthermore, we performed a comparison and protein-protein interaction analysis to identify causal proteins. We also analyzed the possible consequences of our discoveries by the given existing asthma drugs and their targets. Results: Using Mendelian randomization analysis, we identified five protein-asthma pairs that were significant at the Bonferroni level (P < 6.35 × 10-5). Specifically, in plasma, we found that an increase of one standard deviation in IL1R1 and ECM1 was associated with an increased risk of asthma, while an increase in ADAM19 was found to be protective. The corresponding odds ratios were 1.03 (95% CI, 1.02-1.04), 1.00 (95% CI, 1.00-1.01), and 0.99 (95% CI, 0.98-0.99), respectively. In the brain, per 10-fold increase in ECM1 (OR, 1.05; 95% CI, 1.03-1.08) and PDLIM4 (OR, 1.05; 95% CI, 1.04-1.07) increased the risk of asthma. Bayesian co-localization found that ECM1 in the plasma (coloc.abf-PPH4 = 0.965) and in the brain (coloc.abf-PPH4 = 0.931) shared the same mutation with asthma. The target proteins of current asthma medications were found to interact with IL1R1. IL1R1 and PDLIM4 were validated in two replication cohorts. Conclusion: Our integrative analysis revealed that asthma risk is causally affected by the levels of IL1R1, ECM1, and PDLIM4. The results suggest that these three proteins have the potential to be used as drug targets for asthma, and further investigation through clinical trials is needed.

Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases.

BACKGROUND: RNA N6-methyladenosine (m6A) regulators are considered post-transcriptional regulators that affect several biological functions, and their role in immunity, in particular, is emerging. However, the role of m6A regulators in respiratory allergic diseases remains unclear. Therefore, we aimed to investigate the role of key m6A regulators in mediating respiratory allergic diseases and immune microenvironment infiltration characteristics. METHODS: We downloaded gene expression profiles of respiratory allergies from the Gene Expression Omnibus (GEO) database and we performed hierarchical clustering, difference analysis, and construction of predictive models to identify hub m6A regulators that affect respiratory allergies. Next, we investigate the underlying biological mechanisms of key m6A regulators by performing PPI network analysis, functional enrichment analysis, and immune microenvironment infiltration analysis. In addition, we performed a drug sensitivity analysis on the key m6A regulator, hoping to be able to provide some implications for clinical medication. RESULTS: In this study, we identified four hub m6A regulators that affect the respiratory allergy and investigated the underlying biological mechanisms. In addition, studies on the characteristics of immune microenvironment infiltration revealed that the expression of METTL14, METTL16, and RBM15B correlated with the infiltration of the mast and Th2 cells in respiratory allergy, and METTL16 expression was found to be significantly negatively correlated with macrophages for the first time (R = -0.53, P < 0.01). Finally, a key m6A regulator, METTL14, was screened by combining multiple algorithms. In addition, by performing a drug sensitivity analysis on METTL14, we hypothesized that it may play an important role in the improvement of allergic symptoms in the upper and lower airways with topical nasal glucocorticoids. CONCLUSIONS: Our findings suggest that m6A regulators, particularly METTL14, play a crucial role in the development of respiratory allergic diseases and the infiltration of immune cells. These results may provide insight into the mechanism of action of methylprednisolone in treating respiratory allergic diseases.

Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1G2032R and ALKG1202R.

Clinical treatment by FDA-approved ROS1/ALK inhibitor Crizotinib significantly improved the therapeutic outcomes. However, the emergence of drug resistance, especially driven by acquired mutations, have become an inevitable problem and worsened the clinical effects of Crizotinib. To combat drug resistance, some novel 2-aminopyridine derivatives were designed rationally based on molecular simulation, then synthesised and subjected to biological test. The preferred spiro derivative C01 exhibited remarkable activity against CD74-ROS1G2032R cell with an IC50 value of 42.3 nM, which was about 30-fold more potent than Crizotinib. Moreover, C01 also potently inhibited enzymatic activity against clinically Crizotinib-resistant ALKG1202R, harbouring a 10-fold potency superior to Crizotinib. Furthermore, molecular dynamic disclosed that introducing the spiro group could reduce the steric hindrance with bulky side chain (Arginine) in solvent region of ROS1G2032R, which explained the sensitivity of C01 to drug-resistant mutant. These results indicated a path forward for the generation of anti Crizotinib-resistant ROS1/ALK dual inhibitors.

Utilization of commercial collagens for preparing well-differentiated human beta cells for confocal microscopy.

Introduction: With technical advances, confocal and super-resolution microscopy have become powerful tools to dissect cellular pathophysiology. Cell attachment to glass surfaces compatible with advanced imaging is critical prerequisite but remains a considerable challenge for human beta cells. Recently, Phelps et al. reported that human beta cells plated on type IV collagen (Col IV) and cultured in neuronal medium preserve beta cell characteristics. Methods: We examined human islet cells plated on two commercial sources of Col IV (C6745 and C5533) and type V collagen (Col V) for differences in cell morphology by confocal microscopy and secretory function by glucose-stimulated insulin secretion (GSIS). Collagens were authenticated by mass spectrometry and fluorescent collagen-binding adhesion protein CNA35. Results: All three preparations allowed attachment of beta cells with high nuclear localization of NKX6.1, indicating a well-differentiated status. All collagen preparations supported robust GSIS. However, the morphology of islet cells differed between the 3 preparations. C5533 showed preferable features as an imaging platform with the greatest cell spread and limited stacking of cells followed by Col V and C6745. A significant difference in attachment behavior of C6745 was attributed to the low collagen contents of this preparation indicating importance of authentication of coating material. Human islet cells plated on C5533 showed dynamic changes in mitochondria and lipid droplets (LDs) in response to an uncoupling agent 2-[2-[4-(trifluoromethoxy)phenyl]hydrazinylidene]-propanedinitrile (FCCP) or high glucose + oleic acid. Discussion: An authenticated preparation of Col IV provides a simple platform to apply advanced imaging for studies of human islet cell function and morphology.

A Novel and Highly Selective Epidermal Growth Factor Receptor Inhibitor, SMUZ106, for the Treatment of Glioblastoma.

Targeting the epidermal growth factor receptor (EGFR) is one of the potential ways to treat glioblastoma (GBM). In this study, we investigate the anti-GBM tumor effects of the EGFR inhibitor SMUZ106 in both in vitro and in vivo conditions. The effects of SMUZ106 on the growth and proliferation of GBM cells were explored through MTT and clone formation experiments. Additionally, flow cytometry experiments were conducted to study the effects of SMUZ106 on the cell cycle and apoptosis of GBM cells. The inhibitory activity and selectivity of SMUZ106 to the EGFR protein were proved by Western blotting, molecular docking, and kinase spectrum screening methods. We also conducted a pharmacokinetic analysis of SMUZ106 hydrochloride following i.v. or p.o. administration to mice and assessed the acute toxicity level of SMUZ106 hydrochloride following p.o. administration to mice. Subcutaneous and orthotopic xenograft models of U87MG-EGFRvIII cells were established to assess the antitumor activity of SMUZ106 hydrochloride in vivo. SMUZ106 could inhibit the growth and proliferation of GBM cells, especially for the U87MG-EGFRvIII cells with a mean IC50 value of 4.36 µM. Western blotting analyses showed that compound SMUZ106 inhibits the level of EGFR phosphorylation in GBM cells. It was also shown that SMUZ106 targets EGFR and presents high selectivity. In vivo, the absolute bioavailability of SMUZ106 hydrochloride was 51.97%, and its LD50 exceeded 5000 mg/kg. SMUZ106 hydrochloride significantly inhibited GBM growth in vivo. Furthermore, SMUZ106 inhibited the activity of U87MG-resistant cells induced by temozolomide (TMZ) (IC50: 7.86 µM). These results suggest that SMUZ106 hydrochloride has the potential to be used as a treatment method for GBM as an EGFR inhibitor.

Association of CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients.

Aim: To evaluate the association between CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation. Materials & methods: High performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentrations. First-generation sequencing was performed to detect gene polymorphisms. Results: Voriconazole concentrations of normal metabolizers were significantly higher than those of intermediate (p < 0.05) and ultrafast (p < 0.001) metabolizers. Patients with ABCC2 GG and GA genotypes exhibited significantly lower voriconazole concentrations compared with patients with the AA genotype (p < 0.05). Conclusion: These results demonstrate a significant association between voriconazole concentrations and the CYP2C19 phenotype in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation.

Losartan attenuates upstream vasculopathy in a modified piglet model of pulmonary vein stenosis: contribution of the Hippo pathway.

Background: Diffuse pulmonary vein stenosis (PVS) is an intractable congenital heart disease for which the underlying mechanism remains unclear. In this study, we investigated the effect of losartan and the role of the Hippo pathway in PVS. Methods: A total of 19 neonatal piglets were divided into 3 groups: a sham group (n=7), a banded group (n=6) with the left upper pulmonary vein and common trunk of both lower pulmonary veins banded, and a losartan group (n=6) with losartan treatment (1 mg/kg/d) after the banding operation. After 8 weeks, the piglets underwent hemodynamic measurement and harvesting. The upstream pulmonary veins were collected for histological staining and molecular biological analysis. Losartan and/or angiotensin II (stepwise concentrations from 0.1 to 100 µmol/L) were added to a human umbilical vein endothelial cell culture to investigate the potential mechanism in vitro. Results: The modified model demonstrated the main characteristics of patients with PVS, including pulmonary hypertension and intimal hyperplasia in the upstream veins. Upregulation of yes-associated protein (YAP) and angiotensin II type 1 receptor was observed in the neointima (P<0.01). Losartan treatment improved the pathological changes in piglets and decreased YAP expression in the neointima (P<0.01). In vitro, losartan suppressed angiotensin II-induced cell proliferation by inhibiting dephosphorylation and nuclear translocation of YAP in human umbilical vein endothelial cells (P<0.05). Conclusions: Losartan treatment ameliorates intimal hyperplasia and inhibits YAP activation. The activation of the Hippo-YAP pathway is involved in the vasculopathy of progressive PVS. These findings may contribute to the development of new approaches for treating PVS.

Deficiency of astrocyte CysLT1R ameliorates depression-like behaviors in mice by modulating glutamate synaptic transmission.

Our previous study suggests that hippocampal cysteinyl leukotriene receptor 1 (CysLT1R) could be involved in depression. Herein we hypothesize that CysLT1R may regulate depression by affecting synaptic glutamate cycling based on existence of CysLT1R in the astrocytes that participate in occurrence of depression. We found that CysLT1R expression was significantly increased in the astrocyte of chronic unpredictable mild stress (CUMS)-induced depression-like mice, CysLT1R astrocyte-specific conditional knockout (AcKO) significantly improved depression-like behaviors, as indicated by decreased immobility time in the forced swimming test and tail suspension test and increased sucrose preference in the sucrose preference test, and knockdown of CysLT1R in the astrocyte of dentate gyrus (DG), the region with the most significant increase of CysLT1R in the astrocyte of depression-like mice, produced similar effects. Correspondingly, overexpression of CysLT1R in the astrocyte of DG induced depression-like behaviors in mice. The further study showed that CysLT1R AcKO ameliorated synaptic plasticity impairment, as reflected by increased synapse, LTP and PSD95, and promoted glutamate transporter 1 (GLT-1) expression by inhibiting NF-κB p65 nuclear translocation mediated by ß-arestin2 and clatrhin, subsequently decreased glutamate in synaptic cleft and GluN2B on postsynaptic membrane in depression-like mice. The present study also showed that GLT-1 agonist or NF-κB inhibitor ameliorated depressive-like behaviors induced by overexpression of the astrocyte CysLT1R of DG. Our study demonstrated that astrocyte CysLT1R regulated depression by modulating glutamate synaptic transmission, suggesting that CysLT1R could be a potential target for developing novel drugs of anti-depression.

CD169+ subcapsular sinus macrophage-derived microvesicles are associated with light zone follicular dendritic cells.

Follicular dendritic cells (FDCs) are a specialized type of stromal cells that exclusively reside in B-cell follicles. When inflammation occurs, the FDC network is reorganized to support germinal center (GC) polarization into the light zone (LZ) and dark zone (DZ). Despite the indispensable role of FDCs in supporting humoral responses, the FDC regulatory requirements remain incompletely defined. In this study, we unexpectedly observed an accumulation of CD169+ subcapsular sinus macrophage (SSM)-derived microvesicles (MVs) in the B-cell zone, which were tightly associated with the FDC network. Interestingly, a selective deposition of CD169+ MVs was detected in both GC LZ FDCs in secondary follicles and on predetermined LZ FDCs in primary follicles. The ablation of CD169+ MVs, resulting from SSM depletion, resulted in significantly decreased expression of LZ-related genes in FDCs. In addition, we found that CD169+ MVs could colocalize with fluorescently tagged antigen-containing immune complexes (ICs), supporting a possible role of CD169+ MVs in transporting antigens to the FDC network. Thus, our data reveal intimate crosstalk between FDCs and SSMs located outside B-cell follicles via SSM-released MVs, providing a novel perspective on the mechanisms underlying the regulation of FDC maturation and polarization.

Orbits of charged particles trapped in a dipole magnetic field.

Motion of a test charged particle in a dipole magnetic field can be reduced to a two degree-of-freedom Hamiltonian system due to the axisymmetry of the dipole field. We carried out a systematic study of orbits of low-energy trapped charged particles in the dipole field via calculation of their Lyapunov characteristic exponents (LCEs) with random initial conditions in the four-dimensional phase space. Since there is at most one positive LCE, these orbits are classified as chaotic ones with one positive LCE and quasi-periodic ones with vanishing LCEs. The dependence of the fraction of quasi-periodic orbits in the phase space on the particle energy is given, which reveals a discrete spectrum, confirming the results of earlier studies. It is also found that most quasi-periodic orbits are confined near the equatorial plane and away from the dipole except for some at very low energies, while chaotic ones are ergodic. The distribution of the maximum LCE (mLCE) appears to vary gradually in the phase space and chaotic orbits with very low values of the mLCE wander near quasi-periodic orbits for a significant amount of time before merging into the sea of chaos.

Lipid Droplets' Role in the Regulation of ß-Cell Function and ß-Cell Demise in Type 2 Diabetes.

During development of type 2 diabetes (T2D), excessive nutritional load is thought to expose pancreatic islets to toxic effects of lipids and reduce ß-cell function and mass. However, lipids also play a positive role in cellular metabolism and function. Thus, proper trafficking of lipids is critical for ß cells to maximize the beneficial effects of these molecules while preventing their toxic effects. Lipid droplets (LDs) are organelles that play an important role in the storage and trafficking of lipids. In this review, we summarize the discovery of LDs in pancreatic ß cells, LD lifecycle, and the effect of LD catabolism on ß-cell insulin secretion. We discuss factors affecting LD formation such as age, cell type, species, and nutrient availability. We then outline published studies targeting critical LD regulators, primarily in rat and human ß-cell models, to understand the molecular effect of LD formation and degradation on ß-cell function and health. Furthermore, based on the abnormal LD accumulation observed in human T2D islets, we discuss the possible role of LDs during the development of ß-cell failure in T2D. Current knowledge indicates that proper formation and clearance of LDs are critical to normal insulin secretion, endoplasmic reticulum homeostasis, and mitochondrial integrity in ß cells. However, it remains unclear whether LDs positively or negatively affect human ß-cell demise in T2D. Thus, we discuss possible research directions to address the knowledge gap regarding the role of LDs in ß-cell failure.

Innovation and green total factor productivity in China: a linear and nonlinear investigation.

The empirical conclusions regarding the influence of innovation on green total factor productivity (GTFP) are relatively mixed. Based on China's provincial panel data from 1999 to 2015, this paper uses the number of patent applications to measure regional innovation capacity, and comprehensively examines the linear and nonlinear effects of innovation on GTFP. Our results show that innovation plays a leading role in promoting GTFP growth in China in general. However, two different types of patents, invention patents, and non-invention patents have heterogeneous impacts on China's green growth under the difference of innovation level. Additionally, the relationship between innovation and China's GTFP also differs significantly before and after 2009. A further nonlinear effect analysis based on a panel threshold model reveals that the impact of innovation on GTFP is higher with the rise of human capital, knowledge stock, and financial development. However, only the appropriate environmental regulation stringency is conducive to promoting the influence of innovation on China's green growth. Overall, our findings contribute to a better understanding regarding the impact of innovation on GTFP in China.

Oriented Localization of Surgical Tools by Location Encoding.

Surgical tool localization is the foundation to a series of advanced surgical functions e.g. image guided surgical navigation. For precise scenarios like surgical tool localization, sophisticated tools and sensitive tissues can be quite close. This requires a higher localization accuracy than general object localization. And it is also meaningful to know the orientation of tools. To achieve these, this paper proposes a Compressive Sensing based Location Encoding scheme, which formulates the task of surgical tool localization in pixel space into a task of vector regression in encoding space. Furthermore with this scheme, the method is able to capture orientation of surgical tools rather than simply outputting horizontal bounding boxes. To prevent gradient vanishing, a novel back-propagation rule for sparse reconstruction is derived. The back-propagation rule is applicable to different implementations of sparse reconstruction and renders the entire network end-to-end trainable. Finally, the proposed approach gives more accurate bounding boxes as well as capturing the orientation of tools, and achieves state-of-the-art performance compared with 9 competitive both oriented and non-oriented localization methods on a mainstream surgical image dataset: m2cai16-tool-locations. A range of experiments support our claim that regression in CSLE space performs better than traditionally detecting bounding boxes in pixel space.

Modified Nuss procedure with a novel steel bar in patients with pectus excavatum post-congenital heart surgery.

OBJECTIVES: Pectus excavatum (PE) can be secondary in patients who underwent sternotomy for cardiac surgery. Retrosternal adhesions increase the complexity and risk of traditional Nuss repair. Thus, we summarized the outcomes of our modified Nuss procedure using a newly designed bar. METHODS: A retrospective analysis was performed on 35 patients who underwent modified PE repair after open heart surgery from January 2011 to July 2019. The surgery was performed using a novel bar with no need for intraoperative reshaping and rotation, assisted by thoracoscopy and subxiphoid incision when necessary. RESULTS: There were 19 males and 16 females with a median age of 5.3 years (interquartile range, 4.1-10.9) at PE repair. All patients underwent the modified procedure uneventfully with no death. The median operating time was 70 min. Twenty-nine (82.9%) patients required subxiphoid incision assistance. There was 1 case (2.8%) with unexpected sternotomy due to intraoperative bleeding. The median length of postoperative hospital stay was 4 days. During the median 3.5 years of follow-up, no bar dislocation was found and 30 (85.7%) patients had their bars removed with no recurrence recorded. After PE repair, the Haller index improved significantly (2.6 ± 0.4 vs 4.9 ± 1.3, P < 0.05) and further decreased till the time of bar removal (2.5 ± 0.4 vs 2.6 ± 0.4, P < 0.05). All patients were satisfied with the cosmetic outcome. CONCLUSIONS: The novel bar can be placed and removed easily with a low rate of adverse events. This modified Nuss procedure seems to be a safe, effective and convenient approach for the management of PE after cardiac surgery.

The Behavioral Role of Digital Economy Adaptation in Sustainable Financial Literacy and Financial Inclusion.

The basic aim of this research was to investigate the impact of the behavioral biases on financial inclusion in Pakistan while considering the moderating effect of financial literacy in this relation, in the context of behavioral perspective. This study focused on the significant behavioral phenomenon, including self-control, optimism, herding, and loss aversion with a perspective of the digital economy. To test the proposed hypothesis, the primary data collection method was used. A structured questionnaire was designed to collect data from 102 individual households through the convenience sampling technique. SmartPLS was used to analyze collected data. This study found the negative impact of self-control, optimism, and herding on financial inclusion. In contrast, loss aversion contributes to the uplift of financial inclusion in Pakistan. Similarly, financial literacy proved to have a decreasing effect on financial inclusion because of religious concerns. The moderation effect of financial literacy was also significantly positive except for loss aversion. The behavioral phenomenon proved to have a significant impact on financial inclusion. This research shows that individual households who do not use developed technological services and products from formal financial inclusion can overcome the behavioral biases that hinder them from making informed financial decisions. This research work will significantly help households use financial services to improve their standard of living and overall long-term financial well-being. This research is essential because many households are not using bank services and have low financial knowledge in Pakistan. The key contribution of this research study is that it found the relation between behavioral factors and financial inclusion. Financial literacy also has a moderating effect on their relations.

Yiqi Jiemin decoction alleviates allergic rhinitis in a guinea pig model by suppressing inflammation, restoring Th1/Th2 balance, and improving cellular metabolism.

We investigated the mechanisms underlying the therapeutic effects of Yiqi Jiemin decoction (YJD), a traditional Chinese medicine (TCM), in the ovalbumin (OVA)-induced allergic rhinitis (AR) model in guinea pigs. YJD significantly decreased infiltration of mast cells and eosinophils into the nasal mucosa of AR model guinea pigs. YJD also increased expression of TGF-ß in the nasal mucosa, restored the balance of Th1/Th2 immune cell responses, and decreased serum levels of various pro-inflammatory mediators, including histamine (HA), neuropeptide Y (NPY), acetylcholine (ACH), norepinephrine and immunoglobulin E (IgE). Metabolic analyses using liquid chromatography coupled with high-resolution mass spectrometry revealed that YJD improved cellular metabolism in AR model guinea pigs and increased serum levels of glycocholic acid while decreasing levels 1-palmitoyl lysophosphatidic acid. RNA-sequencing analysis identified BPIFB2 as a potential diagnostic biomarker and therapeutic target for AR. Functional enrichment analyses showed that YJD significantly inhibited cytokine secretion pathways in AR model guinea pigs. These findings demonstrate that YJD protects against OVA-induced AR in guinea pigs by suppressing inflammation in the nasal mucosa, restoring Th1/Th2 balance, and improving cellular metabolism.