Learning pathways composed of core subjects with features of reducing cognitive load have better learning outcomes.

BACKGROUND: Changing the course duration or timing of subjects in learning pathways would influence medical students' learning outcomes. Curriculum designers need to consider the strategy of reducing cognitive load and evaluate it continuously. Our institution underwent gradual curricular changes characterized by reducing cognitive load since 2000. Therefore, we wanted to explore the impact of this strategy on our previous cohorts. METHODS: This cohort study explored learning pathways across academic years of more than a decade since 2000. Eight hundred eighty-two medical students between 2006 and 2012 were included eventually. Learning outcomes included an average and individual scores of subjects in different stages. Core subjects were identified as those where changes in duration or timing would influence learning outcomes and constitute different learning pathways. We examined whether the promising learning pathway defined as the pathway with the most features of reducing cognitive load has higher learning outcomes than other learning pathways in the exploring dataset. The relationship between features and learning outcomes was validated by learning pathways selected in the remaining dataset. RESULTS: We found nine core subjects, constituting four different learning pathways. Two features of extended course duration and increased proximity between core subjects of basic science and clinical medicine were identified in the promising learning pathway 2012, which also had the highest learning outcomes. Other pathways had some of the features, and pathway 2006 without such features had the lowest learning outcomes. The relationship between higher learning outcomes and cognitive load-reducing features was validated by comparing learning outcomes in two pathways with and without similar features of the promising learning pathway. CONCLUSION: An approach to finding a promising learning pathway facilitating students' learning outcomes was validated. Curricular designers may implement similar design to explore the promising learning pathway while considering potential confounding factors, including students, medical educators, and learning design of the course.

Rational Design of Triazinone Derivatives with Low Bee Toxicity Based on the Binding Mechanism of Neonicotinoids to Apis mellifera.

Bees, one of the most vital pollinators in the ecosystem and agriculture, are currently threatened by neonicotinoids. To explore the molecular mechanisms of neonicotinoid toxicity to bees, the different binding modes of imidacloprid, thiacloprid, and flupyradifurone with nicotinic acetylcholine receptor (nAChR) α1ß1 and cytochrome P450 9Q3 (CYP9Q3) were studied using homology modeling and molecular dynamics simulations. These mechanisms provided a basis for the design of compounds with a potential low bee toxicity. Consequently, we designed and synthesized a series of triazinone derivatives and assessed their bioassays. Among them, compound 5a not only displayed substantially insecticidal activities against Aphis glycines (LC50 = 4.40 mg/L) and Myzus persicae (LC50 = 6.44 mg/L) but also had low toxicity to Apis mellifera. Two-electrode voltage clamp recordings further confirmed that compound 5a interacted with the M. persicae nAChR α1 subunit but not with the A. mellifera nAChR α1 subunit. This work provides a paradigm for applying molecular toxic mechanisms to the design of compounds with low bee toxicity, thereby aiding the future rational design of eco-friendly nicotinic insecticides.

Using machine learning to identify key subject categories predicting the pre-clerkship and clerkship performance: 8-year cohort study.

BACKGROUND: Medical students need to build a solid foundation of knowledge to become physicians. Clerkship is often considered the first transition point, and clerkship performance is essential for their development. We hope to identify subjects that could predict the clerkship performance, thus helping medical students learn more efficiently to achieve high clerkship performance. METHODS: This cohort study collected background and academic data from medical students who graduated between 2011 and 2019. Prediction models were developed by machine learning techniques to identify the affecting features in predicting the pre-clerkship performance and clerkship performance. Following serial processes of data collection, data preprocessing before machine learning, and techniques and performance of machine learning, different machine learning models were trained and validated using the 10-fold cross-validation method. RESULTS: Thirteen subjects from the pre-med stage and 10 subjects from the basic medical science stage with an area under the ROC curve (AUC) >0.7 for either pre-clerkship performance or clerkship performance were found. In each subject category, medical humanities and sociology in social science, chemistry, and physician scientist-related training in basic science, and pharmacology, immunology-microbiology, and histology in basic medical science have predictive abilities for clerkship performance above the top tertile. Using a machine learning technique based on random forest, the prediction model predicted clerkship performance with 95% accuracy and 88% AUC. CONCLUSION: Clerkship performance was predicted by selected subjects or combination of different subject categories in the pre-med and basic medical science stages. The demonstrated predictive ability of subjects or categories in the medical program may facilitate students' understanding of how these subjects or categories of the medical program relate to their performance in the clerkship to enhance their preparedness for the clerkship.

Centimeter-Sized Single Crystals of Tetrahedral Manganese (II) Halide Hybrids for Wide-Color Gamut Backlighting Displays.

Phosphors with narrow-band green emissions and high photoluminescent quantum efficiency (PLQY) are significantly required for backlighting displays with wider color gamut. In this work, two centimeter-sized manganese (II) halide single crystals TMG2 MnCl4 and TMG2 MnBr4 (TMG = 1,1,3,3-tetramethylguanidine) are synthesized, exhibiting bright narrow-band green emissions with high PLQYs up to 62% and 90%, respectively. The narrow-band green light emission is located at 520 nm with a full-width at half-maximum (FWHM) of only 57 nm. The photoluminescence mechanisms of two single crystals are elaborated. Two white-light-emitting diodes for backlighting displays (BD-WLEDs) based on them are fabricated, exhibiting the widest color gamut of 122% National Television Standards Committee (NTSC), and a luminous efficacy reached ≈93 lm W-1 with excellent luminescence stability at high temperatures. These properties indicate the potential applications of tetrahedral manganese (II) hybrids in wide-color gamut backlighting displays.

Target-Based Design, Synthesis, and Biological Evaluation of Novel 1,2,4-Triazolone Derivatives as Potential nAChR Modulators.

Novel agrochemicals have been successfully developed using target-based drug design (TBDD). To discover a novel, efficient, and highly selective nicotinic insecticide candidate, we developed a unified pharmacological model using TBDD by studying the binding modes of 11 nicotinic acetylcholine receptor (nAChR) modulators with acetylcholine binding protein (AChBP) targets for the first time. This model was used to design and develop a series of 1,2,4-triazolone derivatives. Bioassays demonstrated excellent insecticidal activities against Aphis glycines of compounds 4k (LC50 = 4.95 mg/L) and 4q (LC50 = 3.17 mg/L), and low toxicities to Apis mellifera. Additionally, compound 4q was stably bound to Aplysia californica AChBP, which was consistent with the pharmacological model obtained via molecular docking and molecular dynamics simulations. Therefore, compound 4q could be a potential lead candidate targeting nAChR. The explicit pharmacological model of nAChR modulators with Ac-AChBP in this study may facilitate the future rational design of eco-friendly nicotinic insecticides.

Erythropoietin-mediated IL-17 F attenuates sepsis-induced gut microbiota dysbiosis and barrier dysfunction.

Septic gut damage is critical in the progression of sepsis and multiple organ failure, characterized by gut microbiota dysbiosis and epithelium deficiency in the gut barrier. Recent studies highlight the protective effects of Erythropoietin (EPO) on multiple organs. The present study found that EPO treatment significantly alleviated the survival rate, suppressed inflammatory responses, and ameliorated intestine damage in mice with sepsis. EPO treatment also reversed sepsis-induced gut microbiota dysbiosis. The protective role of EPO in the gut barrier and microbiota was impaired after EPOR knockout. Notably, we innovatively demonstrated that IL-17 F screened by transcriptome sequencing could ameliorate sepsis and septic gut damage including gut microbiota dysbiosis and barrier dysfunction, which was verified by IL-17 F-treated fecal microbiota transplantation (FMT) as well. Our findings highlight the protection effects of EPO-mediated IL-17 F in sepsis-induced gut damage by alleviating gut barrier dysfunction and restoring gut microbiota dysbiosis. EPO and IL-17 F may be potential therapeutic targets in septic patients.

Two Novel Two-Dimensional Organic-Inorganic Hybrid Lead Halides with Broadband Emission for White-Light-Emitting Diodes.

Low-dimensional organic-inorganic metal halides (LOMHs) recently have attracted much attention due to their tunable crystal structures and excellent photoelectric properties. The configuration and arrangement of organic cations in LOMHs have significant effect on the structure of inorganic frameworks and luminescence properties. In this work, we systematically explored the "spatial effect" and "hydrogen bonding effect" of organic cations on the structure and properties of LOMHs, by synthesizing three LOMHs including (N-AD)PbCl4, (N-AD)2Pb2Br7, and (N-AD)4Pb3I12 (N-AD: N-acetylethylenediamine, C4H10N2O). Specifically, (110)-oriented two-dimensional (N-AD)PbCl4 and (N-AD)2Pb2Br7 with manifest blue-white emissions, originating from the free excitons (FEs) and self-trapped excitons (STEs), respectively. The UV-pumped light-emitting diode (LED)-based on (N-AD)2Pb2Br7 was prepared, and the highest color rendering index (CRI) and correlated color temperature (CCT) were up to 80 and 4484 K, respectively. This proves its potential application in solid-state lighting.

One-Dimensional Organic-Inorganic Lead Bromide Hybrids with Excitation-Dependent White-Light Emission Templated by Pyridinium Derivatives.

Organic-inorganic hybrid metal halides have attracted widespread attention due to their excellent tunability and versatility. Here, we have selected pyridinium derivatives with different substituent groups or substitution positions as the organic templating cations and obtained six 1D chain-like structures. They are divided into three types: type I (single chain), type II (double chain), and type III (triple chain), with tunable optical band gaps and emission properties. Among them, only (2,4-LD)PbBr3 (2,4-LD = 2,4-lutidine) shows an exciton-dependent emission phenomenon, ranging from strong yellow-white to weak red-white light. By comparing its photoluminescence spectrum with that of its bromate (2,4-LD)Br, it is found that the strong yellow-white emission at 534 nm mainly came from the organic component. Furthermore, through a comparison of the fluorescence spectra and lifetimes of (2,4-LD)PbBr3 and (2-MP)PbBr3 (2-MP = 2-methylpyridine) with similar structures at different temperatures, we confirm that the tunable emission of (2,4-LD)PbBr3 comes from different photoluminescent sources corresponding to organic cations and self-trapped excitons. Density functional theory calculations further reveal that (2,4-LD)PbBr3 has a stronger interaction between organic and inorganic components compared to (2-MP)PbBr3. This work highlights the importance of organic templating cations in hybrid metal halides and the new functionalities associated with them.

Stimulus Design for Visual Evoked Potential Based Brain-Computer Interfaces.

Visual stimuli design plays an important role in brain-computer interfaces (BCIs) based on visual evoked potentials (VEPs). Variations in stimulus parameters have been shown to affect both decoding accuracy and subjective perception experience, implying the need for a trade-off in design. In this study, we comprehensively and systematically compared various combinations of amplitude contrast and spectral content parameters in the stimulus design to quantify their impact on decoding performance and subject comfort. Specifically, three parameters were investigated: 1) contrast level, 2) temporal pattern (periodic steady-state or pseudo-random code-modulated), and 3) frequency range. We collected electroencephalogram (EEG) data and subjective perception ratings from ten subjects and evaluated the decoding accuracy and subject comfort rating for different combinations of the stimulus parameters. Our results indicate that while high-frequency steady-state VEP (SSVEP) stimuli were rated the most comfortable, they also had the lowest decoding accuracy. Conversely, low-frequency SSVEP stimuli were rated the least comfortable but had the highest decoding accuracy. Standard and high-frequency M-sequence code-modulated VEPs (c-VEPs) produced intermediates between the two. We observed a consistent trade-off relationship between decoding accuracy and subjective comfort level across all parameters. Based on our findings, we offer c-VEP as a preferable stimulus for achieving reliable decoding accuracy while maintaining a reasonable level of comfortability.

Re-examining the governance effect of China's environmental protection tax.

China has long exercised environmental control through the imposition of sewage charges. The start of the environmental protection tax on January 1, 2018, means that China has entered a new phase of environmental control. Unlike many previous studies on the role of environmental taxes at the firm level, this paper examines whether environmental taxes affect pollution emissions by influencing the behavioral choices of micro-actors. This paper first reviews the Pyrrhic tax, the Porter hypothesis, and the "double dividend effect." We then construct provincial panel data for 30 provinces in China from 2012 to 2019 as a sample, use the environmental protection tax as a natural experiment to evaluate the policy of this environmental protection tax using propensity score matching and difference-in-differences model, investigate the intermediate transmission mechanism of the policy implementation, and then analyze the differences in policy effects between provinces with different levels of economic development. The increased tax burden in 2018 led to a general reduction in provincial pollution emissions in which technological innovation by various groups, including firms and universities, had a mediating role.

I-line photolithographic metalenses enabled by distributed optical proximity correction with a deep-learning model.

High pattern fidelity is paramount to the performance of metalenses and metasurfaces, but is difficult to achieve using economic photolithography technologies due to low resolutions and limited process windows of diverse subwavelength structures. These hurdles can be overcome by photomask sizing or reshaping, also known as optical proximity correction (OPC). However, the lithographic simulators critical to model-based OPC require precise calibration and have not yet been specifically developed for metasurface patterning. Here, we demonstrate an accurate lithographic model based on Hopkin's image formulation and fully convolutional networks (FCN) to control the critical dimension (CD) patterning of a near-infrared (NIR) metalens through a distributed OPC flow using i-line photolithography. The lithographic model achieves an average ΔCD/CD = 1.69% due to process variations. The model-based OPC successfully produces the 260 nm CD in a metalens layout, which corresponds to a lithographic constant k1 of 0.46 and is primarily limited by the resolution of the photoresist. Consequently, our fabricated NIR metalens with a diameter of 1.5 mm and numerical aperture (NA) of 0.45 achieves a measured focusing efficiency of 64%, which is close to the calculated value of 69% and among the highest reported values using i-line photolithography.

Effect of cellulase and lactic acid bacteria on the fermentation quality, carbohydrate conversion, and microbial community of ensiling oat with different moisture contents.

Oat (Avena sativa L.) is one of the most widely cultivated crops used as forage. The aim of this study was to evaluate the effects of cellulase and Lactobacillus plantarum interactions with different moisture contents on oat ensiling. Oats with three moisture contents were treated with nothing (C), cellulase (CE), lactic acid bacteria (LP), or CE+LP and ensiled for 30 and 60 days. Compared with the control, LP and CE treatments increased crude protein and lactic acid concentrations and reduced the pH and ammonia nitrogen/total nitrogen (NH3-N/TN) ratios of silages. The addition of CE improved lignocellulosic degradation, compared with approximately 67% (LD) and 81% moisture content (HD) ensiling, CE (CE, CE+LP) ensiling in the approximately 75% moisture content (MD) group retained higher water-soluble carbohydrate, glucose, sucrose and fructose concents. The LP and CE inoculations significantly reduced the microbial community diversity, and lower values for the observed species, ACE, Chao1, and Shannon indices compared with CK-treated samples. Additives inhibited the growth of unfavorable bacteria (such as Clostridium) and increased the abundances of lactic acid bacteria (LAB); the maximum increases in the Lactiplantibacillus abundance were obtained in the LP- and CE+LP-treated samples, improving the microbial community structure in silage. In summary, adding LP and CE effectively improved the oat fermentation quality, and better performances in ensiling oat and lignocellulose degradation were obtained with LP and CE combinations, especially for the MD group of silages that were ensiled for 60 days. The addition of CE and LP at the appropriate moisture content might be helpful for producing high-quality oat silage, and also provide a simple and feasible method to enhance the effects of bacteria and enzymes.

Medical students' self-assessed efficacy and satisfaction with training on endotracheal intubation and central venous catheterization with smart glasses in Taiwan: a non-equivalent control-group pre- and post-test study

PURPOSE: Endotracheal intubation and central venous catheterization are essential procedures in clinical practice. Simulation-based technology such as smart glasses has been used to facilitate medical students' training on these procedures. We investigated medical students' self-assessed efficacy and satisfaction regarding the practice and training of these procedures with smart glasses in Taiwan. METHODS: This observational study enrolled 145 medical students in the 5th and 6th years participating in clerkships at Taipei Veterans General Hospital between October 2020 and December 2021. Students were divided into the smart glasses or the control group and received training at a workshop. The primary outcomes included students' pre- and post-intervention scores for self-assessed efficacy and satisfaction with the training tool, instructor's teaching, and the workshop. RESULTS: The pre-intervention scores for self-assessed efficacy of 5th- and 6th-year medical students in endotracheal intubation and central venous catheterization procedures showed no significant difference. The post-intervention score of self-assessed efficacy in the smart glasses group was better than that of the control group. Moreover, 6th-year medical students in the smart glasses group showed higher satisfaction with the training tool, instructor's teaching, and workshop than those in the control group. CONCLUSION: Smart glasses served as a suitable simulation tool for endotracheal intubation and central venous catheterization procedures training in medical students. Medical students practicing with smart glasses showed improved self-assessed efficacy and higher satisfaction with training, especially for procedural steps in a space-limited field. Simulation training on procedural skills with smart glasses in 5th-year medical students may be adjusted to improve their satisfaction.

Design, Synthesis and Bioactivity of Novel Low Bee-Toxicity Compounds Based on Flupyrimin.

Neonicotinoids are important insecticides for controlling aphids in agriculture. Growing research suggested that neonicotinoid insecticides are a key factor causing the decline of global pollinator insects, such as bees. Flupyrimin (FLP) is a novel nicotinic insecticide with unique biological properties and no cross-resistance, and is safe for pollinators. Using FLP as the lead compound, a series of novel compounds were designed and synthesized by replacing the amide fragment with a sulfonamideone. Their structures were confirmed by 1H NMR, 13C NMR and HRMS spectra. Bioassay results showed that compound 2j had good insecticidal activity against Aphis glycines with an LC50 value of 20.93 mg/L. Meanwhile, compound 2j showed significantly lower acute oral and contact toxicity to Apis mellifera. In addition, compound 2j interacted well with the protein in insect acetylcholine binding protein (AChBP). The molecular docking on honeybee nicotinic acetylcholine receptor (nAChR) indicated that the sulfonamide group of compound 2j did not form a hydrogen bond with Arg173 of the ß subunit, which conforms to the reported low bee-toxicity conformation. In general, target compound 2j can be regarded as a bee-friendly insecticide candidate.

A single-center, cross-sectional study of cross-professional faculties' perception to virtual class under different scenarios: A stepwise approach.

BACKGROUND: Virtual teaching in medical education is rising with the increased need caused by the recent pandemic. However, evaluations of the perception of clinical teachers across professions for setting a virtual class in different teaching scenarios are limited. This study aims to identify cross-professional clinical teachers' perception of virtual classes and the acceptability of the virtual class-specific checklist for setting a virtual class. METHODS: We conducted a cross-sectional study to investigate clinical teachers' need to set and teach a virtual class and then designed a virtual class-specific checklist with five essential steps and a related training program in July 2021. After the training, 186 participants were randomly enrolled in October 2021 to evaluate their perceptions about setting virtual classes and the acceptability of the virtual class-specific checklist using an online assessment questionnaire. RESULTS: In our institution, the number of faculty-led virtual classes has recently been on the increase. Our study revealed that most teachers agreed that virtual classes could break space and time limitations, but that the Internet environment could affect the fluency of the virtual class. They further agreed that the essential five steps in the checklist should vary depending on the type of teaching scenario. Most clinical teachers, with the exception of those who teach in the operating room, considered the operating room as the most difficult scenario for setting virtual classes. CONCLUSION: Faculty training for setting virtual classes is essential, and the essential virtual class-specific five steps are suitable for different teachers and teaching scenarios. However, the virtual class-specific checklist should be further adjusted according to the limitations caused by emerging innovative virtual teaching technology.

Identification of a potentially novel LncRNA-miRNA-mRNA competing endogenous RNA network in pulmonary arterial hypertension via integrated bioinformatic analysis.

AIMS: Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disease with a cancer-like phenotype. Competing endogenous RNA (ceRNA) networks extensively involve in its pathological processes. But rare ceRNA networks and profound molecular mechanisms have been revealed in PAH. The aim of this study was to illuminate the ceRNA networks in PAH. MATERIALS AND METHODS: In this work, we have chosen the idiopathic PAH as an example. GSE15197 (mRNA) and GSE56914 (miRNA) from the Gene Expression Omnibus (GEO) were selected to explore key genes and novel ceRNA networks in PAH by a series of integrated bioinformatic analysis. To be more scientific, a part of pairs in identified ceRNA network were detected in hypoxia-induced HPASMCs. And the dual-luciferase assay was performed to certify the relationship between miRNAs and mRNAs. KEY FINDINGS: Totally, 311 differentially expressed genes (DEGs) were identified and functional enrichment analysis illuminated that the majority of DEGs were enriched in proliferation, anti-apoptosis, inflammation and cancer-related pathways. And 10 hub genes were determined via Cytohubba after PPI network construction. Sequentially, with stepwise reverse prediction and pan-cancer co-expression analysis from mRNA to LncRNA in TargetScan, miRNet, ENCORI (Starbase V3.0) databases, a crucially ceRNA network was identified including 14 LncRNAs, 2 miRNAs, and 3 mRNAs. Further, in hypoxia-induced HPASMCs, the alterations of mRNAs, miRNAs and LncRNAs and their relationship were in accordance with the results we identified. SIGNIFICANCE: Consequently, the unique hub genes and ceRNA network we proposed may advance our understanding of the molecular mechanisms in PAH.

Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner.

In inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

Exosomal miR-211 contributes to pulmonary hypertension via attenuating CaMK1/PPAR-γaxis.

AIM: Exsomes play a significant role in increasing pathophysiological processes by delivering their content. Recently, a variety of studies have showed exosomal microRNAs (miRNAs) are involved in pulmonary hypertension (PH) notably. In this study, we found that exosomal miR-211 was overexpressed in hypoxia-induced PH rats but its intrinsic regulation was unclear. Therefore, our aim was to reveal the underlying mechanism which overexpressed exosomal miR-211 targeted in the development of PH. METHODS: 18 male SD rats were randomly divided into normoxia and hypoxia group, housed in normal or hypoxic chamber for 3 weeks respectively. Then, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance(PVR), right ventricular hypertrophy index(RV/(LV + S)), the percentage of medial wall area (WA%) and the percentage of medial wall thickness (WT%) were measured. Expression of miR-211 in exosomes was detected by qRT-PCR. Expression of Ca2+/calmodulin-dependent kinase1(CaMK1)and peroxisome proliferator-activated receptors-γ(PPAR-γ)in lung tissue were detected by Western blot(WB); After miR-211 overexpressed exosomes were injected to rats through caudal vein, mPAP, PVR, RV/(LV + S), WA% and WT% were also measured. Sequentially, hypoxia rats were injected with lentivirus riched in miR-211 inhibitor via tail vein, and PH-related indicators were measured. In vitro, after miR-211 was positively or negatively regulated in pulmonary arterial smooth muscle cell (PASMC) by plasmid transfection, proliferation of PASMC was detected by CCK8, as well as the expression of CaMK1 and PPAR- γ. Further, the relationship between CaMK1 and miR-211 was verified by Dual-Luciferase assay. And the regulatory relationship of CaMK1/PPAR- γ aixs was demonstrated in PASMC. RESULTS: Evident increases of mPAP, PVR, RVHI, WT% and WA% were observed with hypoxia administration. And the concentration of plasma exosomes in hypoxia rats was increased and positively correlated with the above indexes. miR-211 in exosomes of PH was upregulated while the expression of CaMK1 and PPAR-γ decreased in lung tissues. Further, injection of exosomes overexpressed with miR-211 demonstrated that exosomal miR-211 aggravated PH while inhibition of miR-211 attenuated PH in rats. In vitro, overexpression of miR-211 promoted the proliferation of PASMC and inhibited expression of CaMK1 and PPAR-γ in PASMC. And Dual-luciferase assay demonstrated that CaMK1 was a downstream gene of miR-211. Plasmid transfection experiments indicated that CaMK1 can promote PPAR-γ expression. CONCLUSION: Exosomal miR-211 promoted PH via inhibiting CaMK1/PPAR-γ axis, promoting PASMC proliferation in rats.

Composite Cartilage-osseous-mucosal Nasoseptal Flap for Reconstruction after Near Total Rhinectomy.

BACKGROUND: Reconstruction of full thickness nasal defects usually requires different donor sites for the external skin envelope, structural elements, and internal nasal lining. In this paper we present a novel single site method for dual inner lining and skeleton repair for full thickness nasal defects with a composite nasoseptal flap and extended pedicle dissection. METHODS: A 72-year-old male presented with a T4b melanoma involving the nasal dorsum and left upper lateral cartilage. Following full thickness resection, reconstruction was performed with a nasoseptal flap (NSF) with attached septal cartilage and vomer in conjunction with a paramedian forehead flap. Extended pedicle dissection into the pterygopalatine fossa allowed the NSF to fully cover the defect. RESULTS: The nasal defect was fully corrected. There was no evidence of flap compromise or nasal valve stenosis at 1 month, 2 month, and 1 year follow-up visits. CONCLUSIONS: We present here the first successful application of a composite cartilage-osseous-mucosal NSF for multilayered nasal reconstruction. In appropriate patients, this technique may obviate the need for flaps or grafts from extranasal sources, limiting donor site morbidity.

Innate Immune Functions of Astrocytes are Dependent Upon Tumor Necrosis Factor-Alpha.

Acute inflammation is a key feature of innate immunity that initiates clearance and repair in infected or damaged tissues. Alternatively, chronic inflammation is implicated in numerous disease processes. The contribution of neuroinflammation to the pathogenesis of neurological conditions, including infection, traumatic brain injury, and neurodegenerative diseases, has become increasingly evident. Potential drivers of such neuroinflammation include toll-like receptors (TLRs). TLRs confer a wide array of functions on different cell types in the central nervous system (CNS). Importantly, how TLR activation affects astrocyte functioning is unclear. In the present study, we examined the role of TLR2/4 signaling on various astrocyte functions (i.e., proliferation, pro-inflammatory mediator production, regulatory mechanisms, etc) by stimulating astrocytes with potent exogenous TLR2/4 agonist, bacterial lipopolysaccharide (LPS). Newborn astrocytes were derived from WT, Tnfα-/-, Il1α-/-/Il1ß-/-, and Tlr2-/-/Tlr4-/- mice as well as Sprague Dawley rats for all in vitro studies. LPS activated mRNA expression of different pro-inflammatory cytokines and chemokines in time- and concentration-dependent manners, and upregulated the proliferation of astrocytes based on increased 3H-thymidine update. Following LPS-mediated TLR2/4 activation, TNF-α and IL-1ß self-regulated and modulated the expression of pro-inflammatory cytokines and chemokines. Polyclonal antibodies against TNF-α suppressed TLR2/4-mediated upregulation of astrocyte proliferation, supporting an autocrine/paracrine role of TNF-α on astrocyte proliferation. Astrocytes perform classical innate immune functions, which contradict the current paradigm that microglia are the main immune effector cells of the CNS. TNF-α plays a pivotal role in the LPS-upregulated astrocyte activation and proliferation, supporting their critical roles in in CNS pathogenesis.