Low-sugar universal mRNA vaccine against coronavirus variants with deletion of glycosites in the S2 or stem of SARS-CoV-2 spike messenger RNA (mRNA).

Since the outbreak of Severe Acute Respiratory Syndrome Virus-2 (SARS-CoV-2) in 2019, more than 15 million spike protein sequences have been identified, raising a new challenge for the development of a broadly protective vaccine against the various emerging variants. We found that the virus, like most other human viruses, depends on host-made glycans to shield the conserved epitopes on spike protein from immune response and demonstrated that deletion of the glycan shields exposed highly conserved epitopes and elicited broadly protective immune responses. In this study, we identified 17 conserved epitopes from 14 million spike protein sequences and 11 of the conserved epitopes are in the S2 domain, including the six most conserved epitopes in the stem region. We also demonstrated that deletion of the glycosites in the spike messenger RNA (mRNA) S2 domain or the stem region exposed the highly conserved epitopes and elicited broadly protective immune responses, particularly CD-8+ T cell response against various SARS-CoV-2 variants, and other human coronaviruses including MERS, SARS viruses, and those causing common cold.

Glycosite-deleted mRNA of SARS-CoV-2 spike protein as a broad-spectrum vaccine.

Development of the messenger RNA (mRNA) vaccine has emerged as an effective and speedy strategy to control the spread of new pathogens. After vaccination, the mRNA is translated into the real protein vaccine, and there is no need to manufacture the protein in vitro. However, the fate of mRNA and its posttranslational modification inside the cell may affect immune response. Here, we showed that the mRNA vaccine of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein with deletion of glycosites in the receptor-binding domain (RBD) or especially the subunit 2 (S2) domain to expose more conserved epitopes elicited stronger antibody and CD8+ T cell responses with broader protection against the alpha, beta, gamma, delta, and omicron variants, compared to the unmodified mRNA. Immunization of such mRNA resulted in accumulation of misfolded spike protein in the endoplasmic reticulum, causing the up-regulation of BiP/GRP78, XBP1, and p-eIF2α to induce cell apoptosis and strong CD8+ T cell response. In addition, dendritic cells (DCs) incubated with S2-glysosite deleted mRNA vaccine increased class I major histocompatibility complex (MHC I) expression. This study provides a direction for the development of broad-spectrum mRNA vaccines which may not be achieved with the use of expressed proteins as antigens.

Interference with sphingosine kinase-1 reduces the hydrogen peroxide-induced oxidative stress damage in melanocytes through four and a half LIM domains 2.

Vitiligo is featured by manifestation of white maculae and primarily results from oxidative stress. Sphingosine kinase-1 (SPHK1) participates in oxidative stress. This paper was devised to explore the role of SPHK1 in vitiligo and to disclose the mechanism. PIG1 cell viability was appraised utilizing cell counting kit-8 assay while Western blot detected SPHK1 and four and a half LIM domains 2 (FHL2). The transduction efficacy of small interfering RNA (siRNA)-SPHK1, siRNA-FHL2 and pcDNA3.1 plasmid overexpressing FHL2 (Ov-FHL2) was checked using Western blot. Flow cytometry detected cell apoptotisis. Western blot detected mitochondrial cytochrome c (Mit-Cyt-c) and cytosolic cytochrome c (Cyto-Cyt-c). Dichloro-dihydro-fluorescein diacetate (DCFH-DA) detected reactive oxygen species (ROS) activity while oxidative stress markers were evaluated using corresponding assay kits. SPHK1 expression was discovered to be increased in hydrogen peroxide (H2O2)-challenged PIG1 cells and SPHK1 interference alleviated H2O2-challenged viability damage, apoptosis, oxidative stress and FHL2 expression in PIG1 cells. FHL2 depletion could suppress viability damage, apoptosis and oxidative stress in H2O2-challenged PIG1 cells. Rescue experiments demonstrated that the suppressive impacts of SPHK1 deficiency on PIG1 cell viability, apoptosis and oxidative stress induced by H2O2 were offset by FHL2 overexpression. Collectively, SPHK1 knockdown protected against vitiligo via the regulation of FHL2.

Evolving from Didactic to Dialogic: How to Improve Faculty Development and Support Faculty Developers by Using Action Research.

Problem: Since competency-based medical education has gained widespread acceptance to guide curricular reforms, faculty development has been regarded as an indispensable element to make these programs successful. Faculty developers have striven to design and deliver myriad of programs or workshops to better prepare faculty members for fulfilling their teaching roles. However, how faculty developers can improve workshop delivery by researching their teaching practices remains underexplored. Intervention: Action research aims to understand real world practices and advocates for formulation of doable plans through cycles of investigations, and ultimately contributes to claims of knowledge and a progression toward the goal of practice improvement. This methodology aligns with the aim of this study to understand how I could improve a faculty development workshop by researching my teaching practices. Context: In 2016, we conducted four cycles of action research in the context of mini-Clinical Evaluation Exercise (mini-CEX) workshops within a faculty development program aiming for developing teaching and assessment competence in faculty members. We collected multiple sources of qualitative data for thematic analysis, including my reflective journal, field notes taken by a researcher-observer, and post-workshop written reflection and feedback in portfolio from fourteen workshop attendees aiming to develop faculty teaching and assessment competence. Impact: By doing action research, I scrutinized each step as an opportunity for change, enacted adaptive practice and reflection on my teaching practices, and formulated action plans to transform a workshop design through each cycle. In so doing, my workshop evolved from didactic to dialogic with continuous improvement on enhanced engagement, focused discussion and participant empowerment through a collaborative inquiry into feedback practice. Moreover, these processes of action research also supported my growth as a faculty developer. Lessons Learned: The systematic approach of action research serves as a vehicle to enable faculty developers to investigate individual teaching practices as a self-reflective inquiry, to examine, rectify, and transform processes of program delivery, and ultimately introduce themselves as agents for change and improvement.

Oral rhabdomyosarcoma, a rare malignant tumor mimicking an endodontic-periodontal lesion in an adult patient: a case report.

BACKGROUND: According to previous research, 2.8% of lesions clinically identified as endodontic pathosis were ultimately diagnosed as non-endodontic periapical lesions via histopathology, and 3.7% of these non-endodontic periapical lesions were malignant neoplasms. Rhabdomyosarcoma, a malignant tumor most commonly observed in children, is uncommon in the oral cavity. CASE PRESENTATION: This is a report of a rare case of embryonal rhabdomyosarcoma in a 41-year-old female, in which the lesion was in the maxillary gingiva. The biopsy reports confirmed the diagnosis of embryonal rhabdomyosarcoma. The wide excision of the tumor, free flap reconstruction, chemotherapy, and radiotherapy were performed. Clinical, radiological, and histopathological and management aspects of the neoplasm were also discussed. CONCLUSIONS: This case report aimed to create awareness that rhabdomyosarcoma is one of the differential diagnoses of periapical lesions.

A lectin from Crenomytilus grayanus as a probe for the detection of widespread cancerous and metastatic cells.

A novel Gal-binding lectin from mussels (Crenomytilus grayanus, CGL) with 6 binding sites in the dimeric structure has been previously shown to have antifungal, anticancer, and antibacterial activities. In this study, a glycan array was used to confirm that CGL recognizes a range of non-reducing end α- or ß-linked Gal glycans on normal cells but not sialic acid-capped glycans. This finding suggests that CGL has potential in the tumor detection due to the hyper-sialylation present in cell surface glycans from cancer cells. To evaluate the feasibility of this possibility, we labeled CGL with biotin and then mixed it with streptavidin-horseradish peroxidase (HRP) to create a CGL-biotin-SP complex as a probe for use in enzyme-linked lectin assays. CGL-biotin-SP successfully distinguished not only HeLa cells and de-sialylated HeLa cells that mimic normal cell surface glycans but also lung and breast cancer cells with different metastatic abilities. This work provides the insights into a new Gal-binding lectin by establishing its specificity and also demonstrates practical applications in cancer diagnosis greater than other reported lectins.

Mechanism of Antigen Presentation and Specificity of Antibody Cross-Reactivity Elicited by an Oligosaccharide-Conjugate Cancer Vaccine.

Polysaccharides have been successfully used as immunogens for the development of vaccines against bacterial infection; however, there are no oligosaccharide-based vaccines available to date and no previous studies of their processing and presentation. We reported here the intracellular enzymatic processing and antigen presentation of an oligosaccharide-conjugate cancer vaccine prepared from the glycan of Globo-H (GH), a globo-series glycosphingolipid (GSL). This oligosaccharide-conjugate vaccine was shown to elicit antibodies against the glycan moieties of all three globo-series GSLs that are exclusively expressed on many types of cancer and their stem cells. To understand the specificity and origin of cross-reactivity of the antibodies elicited by the vaccine, we found that the vaccine is first processed by fucosidase 1 in the early endosome of dendritic cells to generate a common glycan antigen of the GSLs along with GH for MHC class II presentation. This work represents the first study of oligosaccharide processing and presentation and is expected to facilitate the design and development of glycoconjugate vaccines based on oligosaccharide antigens.

Effective Organotin-Mediated Regioselective Functionalization of Unprotected Carbohydrates.

Regioselective functionalization of unprotected carbohydrates at a secondary OH group in the presence of primary OH groups based on the commonly used organotin-mediated reaction has been improved. We found that the preactivation of the dibutylstannylene acetal intermediate with tetrabutylammonium bromide in toluene is a key to the improved condition for the efficient, high-yielding, and regioselective tosylation, benzoylation, or benzylation of unprotected carbohydrates. The counteranion of tetrabutylammonium ion with a weak coordination ability plays a crucial role in the improved regioselective reactions. A convenient access to the intermediates of synthetic value is also demonstrated in the organotin-mediated regioselective tosylation of unprotected carbohydrates, followed by the nucleophilic inversion reaction to give sulfur-containing and azide-modified carbohydrates.

Striving to thrive or striving to survive: Professional identity constructions of medical trainees in clinical assessment activities.

CONTEXT: Assessment plays a key role in competence development and the shaping of future professionals. Despite its presumed positive impacts on learning, unintended consequences of assessment have drawn increasing attention in the literature. Considering professional identities and how these can be dynamically constructed through social interactions, as in assessment contexts, our study sought to understand how assessment influences the construction of professional identities in medical trainees. METHODS: Within social constructionism, we adopted a discursive, narrative approach to investigate the different positions trainees narrate for themselves and their assessors in clinical assessment contexts and the impact of these positions on their constructed identities. We purposively recruited 28 medical trainees (23 students and five postgraduate trainees), who took part in entry, follow-up and exit interviews of this study and submitted longitudinal audio/written diaries across nine-months of their training programs. Thematic framework and positioning analyses (focusing on how characters are linguistically positioned in narratives) were applied using an interdisciplinary teamwork approach. RESULTS: We identified two key narrative plotlines, striving to thrive and striving to survive, across trainees' assessment narratives from 60 interviews and 133 diaries. Elements of growth, development, and improvement were identified as trainees narrated striving to thrive in assessment. Neglect, oppression and perfunctory narratives were elaborated as trainees narrated striving to survive from assessment. Nine main character tropes adopted by trainees with six key assessor character tropes were identified. Bringing these together we present our analysis of two exemplary narratives with elaboration of their wider social implications. CONCLUSION: Adopting a discursive approach enabled us to better understand not only what identities are constructed by trainees in assessment contexts but also how they are constructed in relation to broader medical education discourses. The findings are informative for educators to reflect on, rectify and reconstruct assessment practices for better facilitating trainee identity construction.

The RNA binding protein Quaking represses splicing of the Fibronectin EDA exon and downregulates the interferon response.

Quaking (QKI) controls RNA metabolism in many biological processes including innate immunity, where its roles remain incompletely understood. To illuminate these roles, we performed genome scale transcriptome profiling in QKI knockout cells with or without poly(I:C) transfection, a double-stranded RNA analog that mimics viral infection. Analysis of RNA-sequencing data shows that QKI knockout upregulates genes induced by interferons, suggesting that QKI is an immune suppressor. Furthermore, differential splicing analysis shows that QKI primarily controls cassette exons, and among these events, we noted that QKI silences splicing of the extra domain A (EDA) exon in fibronectin (FN1) transcripts. QKI knockout results in elevated production and secretion of FN1-EDA protein, which is a known activator of interferons. Consistent with an upregulation of the interferon response in QKI knockout cells, our results show reduced production of dengue virus-2 and Japanese encephalitis virus in these cells. In conclusion, we demonstrate that QKI downregulates the interferon system and attenuates the antiviral state.

Unmasking the Resolution-Throughput Tradespace of Focused-Ion-Beam Machining.

Focused-ion-beam machining is a powerful process to fabricate complex nanostructures, often through a sacrificial mask that enables milling beyond the resolution limit of the ion beam. However, current understanding of this super-resolution effect is empirical in the spatial domain and nonexistent in the temporal domain. This article reports the primary study of this fundamental tradespace of resolution and throughput. Chromia functions well as a masking material due to its smooth, uniform, and amorphous structure. An efficient method of in-line metrology enables characterization of ion-beam focus by scanning electron microscopy. Fabrication and characterization of complex test structures through chromia and into silica probe the response of the bilayer to a focused beam of gallium cations, demonstrating super-resolution factors of up to 6 ± 2 and improvements to volume throughput of at least factors of 42 ± 2, with uncertainties denoting 95% coverage intervals. Tractable theory models the essential aspects of the super-resolution effect for various nanostructures. Application of the new tradespace increases the volume throughput of machining Fresnel lenses by a factor of 75, enabling the introduction of projection standards for optical microscopy. These results enable paradigm shifts of sacrificial masking from empirical to engineering design and from prototyping to manufacturing.

Development and utilization of microsatellite markers to assess genetic variation coupled with modelling range shifts of Dodonaea viscosa (L.) Jacq. in isolated Taita Hills and Mount Kenya forests.

BACKGROUND: Understanding genetic variation is critical for the protection and maintenance of fragmented and highly disturbed habitats. The Taita Hills of Kenya are the northernmost part of the Eastern Arc Mountains and have been identified as one of the world's top ten biodiversity hotspots. Over the past century the current forests in the Taita Hills have become highly fragmented. In order to appraise the influence of anthropological disturbance and fragmentation on plant species in these mountains, we studied the genetic variation and population structure of Dodonaea viscosa (L.) Jacq. (Sapindaceae), using newly developed microsatellite (SSR) markers, combined with ecological niche modelling analyses (ENMs). METHODS AND RESULTS: We utilized the Illumina paired-end technology to sequence D. viscosa's genome and developed its microsatellite markers. In total, 646,428 sequences were analyzed, and 49,836 SSRs were identified from 42,638 sequences. A total of 18 out of 25 randomly selected primer pairs were designed to test polymorphism among 92 individuals across eight populations. The average observed heterozygosity and expected heterozygosity ranged from 0.119 to 0.982 and from 0.227 to 0.691, respectively. Analysis of molecular variance (AMOVA) revealed 78% variance within populations and only 20% among the eight populations. According to ENM results, D. viscosa's suitable habitats have been gradually reducing since the last glacial maximum (LGM), and the situation will worsen under the extreme pessimist scenario of (representative concentration pathway) RCP 8.5. Moreover, genetic diversity was significantly greater in larger fragments. CONCLUSIONS: In the present study, we successfully developed and tested SSR markers for D. viscosa. Study results indicate that fragmentation would constitute a severe threat to plant forest species. Therefore, urgent conservation management of smaller fragmented patches is necessary to protect this disturbed region and maintain the genetic resources.

Cardiac autonomic neuropathy predicts diabetic retinopathy progression in Asian population with type 2 diabetes mellitus.

PURPOSE: To investigate the role of cardiac autonomic neuropathy (CAN), vascular condition, and sensory function in diabetic retinopathy (DR) progression. METHODS: This 3-year cohort study conducted in a community hospital included 4850 patients over 20 with type 2 diabetes mellitus. Participants were assessed in 2017 at baseline and were followed up in 2020. Patients were divided into two groups based on whether they had DR progression or not and were compared using the chi-square test or two-sample t-test. Beta coefficient and odds ratio (OR) with 95% confidence intervals were calculated using binary logistic regression. The receiver operating characteristic (ROC) curve of various independent variables for DR progression was provided with C-statistics. RESULTS: Abnormal hemoglobin A1c (HbA1c) level/variation, estimated glomerular filtration rate, urine albumin-to-creatinine ratio, R-R interval variation, standard deviation of the average NN intervals, autonomic nervous system function, power of high-frequency (HF) bands, balance, cardio-ankle vascular index (CAVI), and warm stimulation (WS) were associated with DR progression. Average HbA1c, HF, and proliferative diabetic retinopathy were independent factors for patients developing DR progression. The top three areas under the curve of ROCs were HF + baseline DR grading, WS + baseline DR grading, and CAVI + baseline DR grading. These variable combinations were the most reliable predictors of DR progression. CONCLUSION: CAN, abnormal vascular condition, and sensory function are associated with DR progression. The combination of HF, WS, and CAVI with baseline DR grading provides the most accurate predictive model for DR progression. Early detection of these factors is important to prevent DR progression.

Improving transitional care through online communication skills training.

BACKGROUND: As the aging population is increasing significantly, the communication skills training (CST) on transitional care (TC) is insufficient. AIMS: This study aimed to test the effectiveness of an intervention (the online TC CST [OTCCST] and TC) through the perspectives of healthcare providers (HCPs), older patients, and family members. METHODS: A total of 38 HCPs caring for older patients were randomized to the experimental (n = 18) or control groups (n = 20), and 84 pairs of patients and family members were enrolled (experimental: n = 42 vs. control: n = 42). The primary outcome was HCP communication confidence; while secondary outcomes included patient quality of life (QoL), activities of daily living (ADL), rehospitalization counts, and family caregiving burden. Data were collected from HCPs using a scale measuring confidence in communicating with patients. Patient outcomes were assessed using the McGill QoL Questionnaire-Revised and Barthel Index. Family members were assessed with the Caregiver Burden Inventory. Rehospitalization counts were tracked for 3 months post-discharge. Data were analyzed using multiple regression analysis. RESULTS: Experimental group HCPs showed a significant improvement in communication confidence over the control group (p = 0.0006). Furthermore, experimental group patients had significantly fewer rehospitalization counts within 3-month post-discharge (p < 0.05). However, no significant group differences were found in patient QoL and ADL nor in family caregiver burden. CONCLUSION: The OTCCST can effectively improve HCP communication confidence, and the combination of OTCCST and TC can reduce rehospitalization counts for older patients. The OTCCST allows HCPs to learn asynchronously at their convenience, ideal for continuing education, especially during the COVID-19 pandemic.

Signaling pathway of globo-series glycosphingolipids and ß1,3-galactosyltransferase V (ß3GalT5) in breast cancer.

The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, and Globo-H specifically expressed on cancer cells are found to correlate with tumor progression and metastasis, but the functional roles of these GSLs and the key enzyme ß1,3-galactosyltransferase V (ß3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Here we show that the expression of ß3GalT5 significantly correlates with tumor progression and poor survival in patients, and the globo-series GSLs in breast cancer cells form a complex in membrane lipid raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) which then interact with AKT and receptor-interacting protein kinase (RIP), respectively. Knockdown of ß3GalT5 disrupts the complex and induces apoptosis through dissociation of RIP from the complex to interact with the Fas death domain (FADD) and trigger the Fas-dependent pathway. This finding provides a link between SSEA3/SSEA4/Globo-H and the FAK/CAV1/AKT/RIP complex in tumor progression and apoptosis and suggests a direction for the treatment of breast cancer, as demonstrated by the combined use of antibodies against Globo-H and SSEA4.

Simple Advanced Preparation Method for Improving the Thickness Stability of Powder Thickening Agents in Dysphagia Management.

Texture modification of foods by using thickening agents is a routine practice for assessing and treating dysphagic patients. However, a powder-thickened fluid's viscosity might change over time, and little has been proposed to overcome this inconsistency. This study aimed to evaluate variations in the thickness of a fluid thickened with a common xanthan gum-based powder and to explore the feasibility of a simple advanced preparation method for thickened liquids to improve thickness stability. Thickened fluids with concentrations of 1.0 g/100 mL, 0.7 g/100 mL, and 0.5 g/100 mL were prepared from both freshly opened and previously opened thickening powders. Fluid thickness was measured every 10 min in a series of International Dysphagia Diet Standardization Initiative flow tests. A significant time-dependent decline in thickness was observed for all three concentrations in both groups, namely those prepared with freshly opened and previously opened thickening powders, and the shortest periods to achieve a stable viscosity after liquid preparation for the two groups were 80 and 70 min, respectively. On diluting the thickened liquids from the base liquid, which was prepared at a concentration of 1.0 g/100 mL and stored at room temperature for 90 min, no significant time-dependent thickness changes were observed over the following 60 min. The simple protocol of preparing the thickest "base" liquid in advance and then diluting it to the desired thickness resulted in a consistent liquid thickness, with the prepared liquids ready to be clinically applied and consumed, with high stability within 60 min.

The actin depolymerizing factor destrin serves as a negative feedback inhibitor of smooth muscle cell differentiation.

We have previously shown that several components of the RhoA signaling pathway control smooth muscle cell (SMC) phenotype by altering serum response factor (SRF)-dependent gene expression. Because our genome-wide analyses of chromatin structure and transcription factor binding suggested that the actin depolymerizing factor, destrin (DSTN), was regulated in a SMC-selective fashion, the goals of the current study were to identify the transcription mechanisms that control DSTN expression in SMC and to test whether it regulates SMC function. Immunohistochemical analyses revealed strong and at least partially SMC-selective expression of DSTN in many mouse tissues, a result consistent with human data from the genotype-tissue expression (GTEx) consortium. We identified several regulatory regions that control DSTN expression including a SMC-selective enhancer that was activated by myocardin-related transcription factor-A (MRTF-A), recombination signal binding protein for immunoglobulin κ-J region (RBPJ), and the SMAD transcription factors. Indeed, enhancer activity and endogenous DSTN expression were upregulated by RhoA and transforming growth factor-ß (TGF-ß) signaling and downregulated by inhibition of Notch cleavage. We also showed that DSTN expression was decreased in vivo by carotid artery injury and in cultured SMC cells by platelet-derived growth factor-BB (PDGF-BB) treatment. siRNA-mediated depletion of DSTN significantly enhanced MRTF-A nuclear localization and SMC differentiation marker gene expression, decreased SMC migration in scratch wound assays, and decreased SMC proliferation, as measured by cell number and cyclin-E expression. Taken together our data indicate that DSTN is a negative feedback inhibitor of RhoA/SRF-dependent gene expression in SMC that coordinately promotes SMC phenotypic modulation. Interventions that target DSTN expression or activity could serve as potential therapies for atherosclerosis and restenosis.NEW & NOTEWORTHY First, DSTN is selectively expressed in SMC in RhoA/SRF-dependent manner. Second, a SMC-selective enhancer just upstream of DSTN TSS harbors functional SRF, SMAD, and Notch/RBPJ binding elements. Third, DSTN depletion increased SRF-dependent SMC marker gene expression while inhibiting SMC migration and proliferation. Taken together, our data suggest that DSTN is a critical negative feedback inhibitor of SMC differentiation.

Selective Luminescence Response of a Zero-Dimensional Hybrid Antimony(III) Halide to Solvent Molecules: Size-Effect and Supramolecular Interactions.

Zero-dimensional (0D) metal halides with solid-state luminescence switching (SSLS) have attracted attention as sensors and luminescent anticounterfeiting. Herein, selective solvent molecule response and accordingly luminescence switching were discovered in 0D [EtPPh3]2[SbCl5] (1, EtPPh3 = ethyltriphenylphosphonium). More than a dozen kinds of solvent molecules have been tested to find out the selection rule for molecule absorption in 1, which is demonstrated to be the size effect of guest molecules. Confirmed by crystal structural analysis, only the solvents with molecular volume less than 22.3 Å3 could be accommodated in 1 leading to the solvatochromic photoluminescence (PL). The mechanism of solvatochromic PL was also deeply studied, which was found to be closely related to the supramolecular interactions between solvent molecules and the host material. Different functional groups of the solvent molecule can affect its strength of hydrogen bonding with [SbCl5]2-, which is crucial for the distortion level of [SbCl5]2- unit and thus results in not only distinct solvatochromic PL but also distinct thermochromic PL. In addition, they all show typical self-trapped exciton triplet emissions. The additional supramolecular interactions from guest molecules can enhance the photoluminescence quantum yield to be as high as 95%.

Drivers for the poor air quality conditions in North China Plain during the COVID-19 outbreak.

China's lockdown to control COVID-19 brought significant declines in air pollutant emissions, but haze was still a serious problem in North China Plain (NCP) during late-January to mid-February of 2020. We seek the potential causes for the poor air quality in NCP combining satellite data, ground measurements and model analyses. Efforts to constrain COVID-19 result in a drop-off of primary gaseous pollutants, e.g., -42.4% for surface nitrogen dioxide (NO2) and -38.9% for tropospheric NO2 column, but fine particulate matter (PM25) still remains high and ozone (O3) even increases sharply (+84.1%). Stagnant weather during COVID-19 outbreak, e.g., persistent low wind speed, frequent temperature inversion and wind convergence, is one of the major drivers for the poor air quality in NCP. The surface PM2.5 levels vary between -12.9~+15.1% in NCP driven by the varying climate conditions between the years 2000 and 2020. Besides, the persistent PM2.5 pollution might be maintained by the still intensive industrial and residential emissions (primary PM2.5), and increased atmospheric oxidants (+26.1% for ozone and +29.4% for hydroxyl radical) in response to the NO2 decline (secondary PM2.5). Further understanding the nonlinear response between atmospheric secondary aerosols and NOx emissions is meaningful to cope with the emerging air pollution problems in China.

Understanding the lived experiences of medical learners in a narrative medicine course: a phenomenological study.

BACKGROUND: Reflection and various approaches to foster reflection have been regarded as an indispensable element in enhancing professional practice across different disciplines. With its inherent potential to engage learners in reflection and improvement, narrative medicine has been adopted in various settings. However, the relevance and effectiveness of reflection remains underexplored in the context of narrative medicine, specifically in regard to the concern about variability of learner acceptance and the way learners really make sense of these reflective activities. This study aimed to explore what medical learners experience through narrative medicine and the meanings they ascribe to the phenomenon of this narrative-based learning. METHODS: Using a transcendental phenomenology approach, twenty medical learners were interviewed about their lived experiences of taking a narrative medicine course during their internal medicine clerkship rotation. Moustakas' phenomenological analysis procedures were applied to review the interview data. RESULTS: Six themes were identified: feeling hesitation, seeking guidance, shifting roles in narratives, questioning relationships, experiencing transformation, and requesting a safe learning environment. These themes shaped the essence of the phenomenon and illustrated what and how medical learners set out on a reflective journey in narrative medicine. These findings elucidate fundamental elements for educators to consider how narrative approaches can be effectively used to engage learners in reflective learning and practice. CONCLUSION: Adopting Moustakas' transcendental phenomenology approach, a better understanding about the lived experiences of medical learners regarding learning in narrative medicine was identified. Learner hesitancy should be tackled with care by educators so as to support learners with strategies that address guidance, relationship, and learning environment. In so doing, medical learners can be facilitated to develop reflective capabilities for professional and personal growth.