A Nano-Aggregatable Acedan Derivative for Clathrin-Mediated Cellular Uptake and Two-Photon Imaging of Diabetes-Associated Lipid Droplets.

Lipid droplets (LDs), the essential cytosolic fat storage organelles, have emerged as pivotal regulators of cellular metabolism and are implicated in various diseases. The noninvasive monitoring of LDs necessitates fluorescent probes with precise organelle selectivity and biocompatibility. Addressing this need, we have engineered a probe by strategically modifying the structure of a conventional two-photon-absorbing dipolar dye, acedan. This innovative approach induces nanoaggregate formation in aqueous environments, leading to aggregation-induced fluorescence quenching. Upon cellular uptake via clathrin-mediated endocytosis, the probe selectively illuminates within LDs through a disassembly process, effectively distinguishing LDs from the cytosol with exceptional specificity. This breakthrough enables the high-fidelity imaging of LDs in both cellular and tissue environments. In a pioneering investigation, we probed LDs in a diabetes model induced by streptozotocin, unveiling significantly heightened LD accumulation in cardiac tissues compared to other organs, as evidenced by TP imaging. Furthermore, our exploration of a lipopolysaccharide-mediated cardiomyopathy model revealed an LD accumulation during heart injury. Thus, our developed probe holds immense potential for elucidating LD-associated diseases and advancing related research endeavors.

Prostate cancer-induced endothelial-cell-to-osteoblast transition drives immunosuppression in the bone-tumor microenvironment through Wnt pathway-induced M2 macrophage polarization.

Immune checkpoint therapy has limited efficacy for patients with bone-metastatic castration-resistant prostate cancer (bmCRPC). To improve immunotherapy for bmCRPC, we aimed to identify the mechanism of bmCRPC-induced changes in the immune microenvironment. Among bmCRPC patients, higher levels of a 32-gene M2-like macrophage signature in bone metastasis samples correlated with shorter overall survival. Immunohistochemistry showed that CD206-positive (CD206+) macrophages were enriched in bmCRPC bone biopsy specimens compared with primary tumors or lymph node metastases. In preclinical osteogenic prostate cancer (Pca) xenograft models, CD206+ macrophages were recruited to areas with tumor-induced bone. RNA sequencing (RNAseq) analysis showed higher expression of an M2-like gene signature, with activated canonical and noncanonical Wnt pathways, in tumor-associated macrophages isolated from osteogenic tumors (bone-TAMs) than in TAMs isolated from nonosteogenic tumors (ctrl-TAMs). Mechanistic studies showed that endothelial cells (ECs) that had undergone EC-to-osteoblast (EC-to-OSB) transition, the precursors of tumor-induced OSBs, produced paracrine factors, including Wnts, CXCL14, and lysyl oxidase, which induced M2 polarization and recruited M2-like TAMs to the bone-tumor microenvironment (bone-TME). Bone-TAMs suppressed CD8+ T cells' proliferation and cytolytic activity, and these effects were partially reversed by treating bone-TAMs with Wnt inhibitors. Genetic or pharmacological inhibition of Pca-induced EC-to-OSB transition reduced the levels of M2-like macrophages in osteogenic tumors. Our study demonstrates that Pca-induced EC-to-OSB transition drives immunosuppression in the bone-TME, suggesting that therapies that reduce Pca-induced bone formation may improve immunotherapeutic outcomes for bmCRPC.

Bibliometric study of the application of the chicken embryo chorioallantoic membrane model in cancer research: the top 100 most cited articles.

The chicken embryo chorioallantoic membrane (CAM) model has played a crucial role in various aspects of cancer research. The purpose of this study is to help researchers clarify the research direction and prospects of the CAM model. A bibliometric analysis was conducted on the top 100 most cited articles on use of the CAM model in tumour research, retrieved from the Web of Science Core Collection database. Tools such as Bibliometrix, VOSviewer, CiteSpace and Excel were utilized for the visualization network analysis. The 100 articles analysed were mainly from the USA, China and European countries such as Germany and France. Tumour research involving CAM model experiments demonstrated reliability and scientific rigor (average citation count = 156.2). The analysis of keywords, topics and subject areas revealed that the applications of this model ranged from the biological characteristics of tumours to molecular mechanisms and signaling pathways, to recent developments in nanotechnology and clinical applications. Additionally, nude mouse experiments have been more frequently performed in recent years. We conclude that the CAM model is efficient, simple and cost-effective, and has irreplaceable value in various aspects of cancer research. In the future, the CAM model can further contribute to nanotechnology research.

Radium-223 Treatment Produces Prolonged Suppression of Resident Osteoblasts and Decreased Bone Mineral Density in Trabecular Bone in Osteoblast Reporter Mice.

Radium 223 (Ra-223) is an α-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been observed in patients treated with Ra-223. Both luciferase- or green fluorescence protein (GFP)-labeled osteoblast reporter mice were used to monitor the effect of Ra-223 on resident osteoblasts and normal bone structure. Upon Ra-223 treatment, 70% of resident osteoblasts were reduced within 2 days, and the osteoblast reduction lasted for at least 18 weeks without detectable recovery, as measured by in vivo bioluminescent imaging. In GFP-labeled osteoblast reporter mice, Ra-223 mainly reduced osteoblasts localized in the trabecular bone areas; the osteoblasts in the growth plates were less affected. Micro-computed tomography analyses showed that Ra-223 significantly reduced bone mineral density and bone microstructure in the trabecular area of femurs but not in the cortical bone. Tumor-induced bone was generated by inoculating osteogenic TRAMP-BMP4 prostate cancer cells into the mouse femurs; Ra-223 treatment significantly reduced tumor-induced osteoblasts. Our study shows that Ra-223 affects bone structures that are not involved in bone metastasis. Strategies that improve bone health may reduce fracture risk in patients receiving Ra-223.

Inner/Outer Side Chain Engineering of Non-Fullerene Acceptors for Efficient Large-Area Organic Solar Modules Based on Non-Halogenated Solution Processing in Air.

Achieving efficient and large-area organic solar modules via non-halogenated solution processing is vital for the commercialization yet challenging. The primary hurdle is the conservation of the ideal film-formation kinetics and bulk-heterojunction (BHJ) morphology of large-area organic solar cells (OSCs). A cutting-edge non-fullerene acceptor (NFA), Y6, shows efficient power conversion efficiencies (PCEs) when processed with toxic halogenated solvents, but exhibits poor solubility in non-halogenated solvents, resulting in suboptimal morphology. Therefore, in this study, the impact of modifying the inner and outer side-chains of Y6 on OSC performance is investigated. The study reveals that blending a polymer donor, PM6, with one of the modified NFAs, namely N-HD, achieved an impressive PCE of 18.3% on a small-area OSC. This modified NFA displays improved solubility in o-xylene at room temperature, which facilitated the formation of a favorable BHJ morphology. A large-area (55 cm2) sub-module delivered an impressive PCE of 12.2% based on N-HD using o-xylene under ambient conditions. These findings underscore the significant impact of the modified Y6 derivatives on structural arrangements and film processing over a large-area module at room temperature. Consequently, these results are poised to deepen the comprehension of the scaling challenges encountered in OSCs and may contribute to their commercialization.

Advances in an In Vitro Tuberculosis Infection Model Using Human Lung Organoids for Host-Directed Therapies.

The emergence of drug-resistant Mycobacterium tuberculosis (M.tb) has led to the development of novel anti-tuberculosis (anti-TB) drugs. Common methods for testing the efficacy of new drugs, including two-dimensional cell culture models or animal models, have several limitations. Therefore, an appropriate model representative of the human organism is required. Here, we developed an M.tb infection model using human lung organoids (hLOs) and demonstrated that M.tb H37Rv can infect lung epithelial cells and human macrophages (hMφs) in hLOs. This novel M.tb infection model can be cultured long-term and split several times while maintaining a similar number of M.tb H37Rv inside the hLOs. Anti-TB drugs reduced the intracellular survival of M.tb in hLOs. Notably, M.tb growth in hLOs was effectively suppressed at each passage by rifampicin and bedaquiline. Furthermore, a reduction in inflammatory cytokine production and intracellular survival of M.tb were observed upon knockdown of MFN2 and HERPUD1 (host-directed therapeutic targets for TB) in our M.tb H37Rv-infected hLO model. Thus, the incorporation of hMφs and M.tb into hLOs provides a powerful strategy for generating an M.tb infection model. This model can effectively reflect host-pathogen interactions and be utilized to test the efficacy of anti-TB drugs and host-directed therapies.

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Purpose: Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion: Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Exploring the accuracy of third-generation Nanopore Sequencing technology for detecting mycobacterium tuberculosis in patients with diabetes mellitus.

OBJECTIVE: To explore the diagnostic value of third-generation nanopore sequencing technology in patients with diabetes mellitus suspected of pulmonary tuberculosis. METHODS: Samples, including sputum and bronchoalveolar lavage fluid(BALF), were collected from patients with diabetes mellitus suspected of pulmonary tuberculosis who were admitted from October 2021 to August 2023. Nanopore sequencing, acid-fast bacilli (AFB) smear, mycobacterial solid culture, Xpert MTB/RIF, and DNA detection were performed, and their diagnostic efficacy was compared. RESULTS: Third-generation nanopore sequencing technology exhibited high accuracy in diagnosing pulmonary tuberculosis in patients with diabetes mellitus. Compared to traditional methods, nanopore sequencing showed significantly improved sensitivity (76.80 %), negative predictive value (30.40 %), coincidence (77.92 %), and diagnostic accuracy (AUC = 0.822). Combined detection with Xpert achieved the highest diagnostic performance, with increased sensitivity (81.20 %), positive predictive value (98.20 %), negative predictive value (35.00 %), coincidence (81.82 %), and AUC (0.843). Although acid-fast staining had limitations, its combination with nanopore sequencing improved screening effectiveness. CONCLUSION: Compared to established diagnostic modalities such as acid-fast staining, mycobacterial solid culture, Xpert MTB/RIF, and DNA detection, third-generation nanopore sequencing technology demonstrates a significant improvement in sensitivity for detecting suspected pulmonary tuberculosis in diabetic patients. Notably, the combined application of nanopore sequencing with Xpert testing offers a further enhancement in diagnostic accuracy.

Immunostimulatory Effects of Korean Mineral-Rich Seawaters on Cyclophosphamide-Induced Immunosuppression in Mice.

Deep seawater (DS), obtained from a depth over 200 m, has health benefits due to its rich nutrients and minerals, and intake of DS has shown diverse immunomodulatory effects in allergies and cancer. Therefore, the immunostimulatory effects of Korean mineral-rich seawaters were examined in a cyclophosphamide (CPA)-induced immunosuppression model. Three samples of Korean seawater, namely DS from the East Sea off the coasts of Pohang (PDS) and Uljin (UDS), and seawater from the West Sea off the coast of Boryeong (BS), were collected. The seawaters were abundant in several minerals (calcium, iron, zinc, selenium, etc.). Mice were orally administered the seawaters for 42 days, followed by CPA-induced immunosuppression. The CPA induction reduced the weight of the spleen and lymph nodes; however, the administration of seawaters increased the weight of the lymphoid organs, accompanied by stimulation of natural killer cells' activity and NF-kB-mediated cytokine production (IFNγ, TNFα, IL1ß, IL6, and IL12). The mouse-derived splenocytes showed lymphoproliferation without cytotoxicity in the seawater groups. Histopathological analysis revealed that the seawaters improved the CPA-induced atrophic changes by promoting lymphoproliferation in the spleen and lymph nodes. These results provide useful information for the use of Korean mineral-rich seawaters, particularly PDS and UDS, as alternative immunostimulants under immunosuppressive conditions.

Feasibility of remote-access and minimally invasive video-assisted approaches in lateral neck dissection for papillary thyroid carcinoma: A systematic review and network meta-analysis.

BACKGROUND: This study was conducted to evaluate the feasibility and surgical outcomes of minimally invasive video-assisted thyroidectomy (MIVAT) and three remote-access approaches, namely the robotic bilateral axillo-breast approach (BABA-R), endoscopic breast-chest approach (BCA-E), and robotic gasless transaxillary approach (GTAA-R) in lateral neck dissection for papillary thyroid carcinoma, compared with conventional transcervical approach (CTA). METHODS: The literature search was conducted in the PubMed, EMBASE, and Cochrane Library databases, covering the period January 2000 to February 2024. A systematic review and network meta-analysis were performed to compare surgical feasibility, safety, and oncologic outcomes between approaches. RESULTS: Fourteen articles on lateral neck dissection in patients with papillary thyroid carcinoma were included after systematic screening. The number of removed and metastatic lateral lymph nodes, the extent of lateral neck dissection, the rate of transient recurrent laryngeal nerve palsy and hypoparathyroidism, serum-stimulated thyroglobulin levels, and recurrence were not significantly different between the MIVAT and three remote-access approaches. Additionally, these were comparable to those of the CTA. However, the MIVAT and remote-access approaches took a longer operative time but provided superior cosmetic outcomes compared to the CTA. CONCLUSION: Lateral neck dissection using the MIVAT and three remote-access approaches was feasible and comparable to CTA in the number of lymph nodes removed, complications, stimulated thyroglobulin level, and recurrence. The MIVAT and remote-access approaches lasted longer but provided significantly superior cosmetic outcomes compared to the CTA.

Role of HIF-1α in the Responses of Tumors to Radiotherapy and Chemotherapy.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and NK cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells (MIDSCs), activation of regulatory T cells (Tregs), inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cranial Sutures in Northern Chinese Han Adults.

OBJECTIVES: To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. METHODS: The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. RESULTS: Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. CONCLUSIONS: The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.

Visfatin Facilitates VEGF-D-Induced Lymphangiogenesis through Activating HIF-1α and Suppressing miR-2277-3p in Human Chondrosarcoma.

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Lymphangiogenesis plays an essential role in cancer metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with VEGF-D generation and lymphangiogenesis in chondrosarcoma remains undetermined. Our results from clinical samples reveal that VEGF-D levels are markedly higher in chondrosarcoma patients than in normal individuals. Visfatin stimulation promotes VEGF-D-dependent lymphatic endothelial cell lymphangiogenesis. We also found that visfatin induces VEGF-D production by activating HIF-1α and reducing miR-2277-3p generation through the Raf/MEK/ERK signaling cascade. Importantly, visfatin controls chondrosarcoma-related lymphangiogenesis in vivo. Therefore, visfatin is a promising target in the treatment of chondrosarcoma lymphangiogenesis.

Lipid nanoparticle-encapsulated lncRNA DLX6-AS1 knockdown ameliorates cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis.

OBJECTIVE: Cerebral ischemia is a neurological disorder that leads to permanent disability. This research focuses on exploring the ameliorative effects of lipid nanoparticle (LNP)-encapsulated lncRNA DLX6-AS1 knockdown in cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis. METHODS: LNP-encapsulated lncRNA DLX6-AS1 was prepared. Cerebral ischemic injury mouse models were established utilizing middle cerebral artery occlusion (MCAO). The mice were treated by intravenous injection of LNP-encapsulated lncRNA DLX6-AS1. The neurological deficits, Inflammatory factor levels, pathological characteristics were observed. In vitro N2a cell oxygen and glucose deprivation (OGD) models were established, and the cells were treated with LNP-encapsulated lncRNA DLX6-AS1 or Nrf2 inhibitor (ML385). Cell viability and apoptosis were tested. DLX6-AS1, Nrf2, HO-1, and NLRP3 expression levels were assessed. RESULTS: LncRNA DLX6-AS1 levels were elevated in the brain tissues of mice with cerebral ischemic injury and OGD-induced N2a cells. LNP-encapsulated DLX6-AS1 siRNA (si-DLX6-AS1) improved neurological deficit scores, reduced the levels of inflammatory factors, improved brain tissue pathological damage, and raised the number of survival neurons in CA1. LNP-encapsulated si-DLX6-AS1 ameliorated the OGD-induced N2a cell viability decrease and apoptosis rate increase, and ML385 (Nrf2 inhibitor) reversed the ameliorative effects of LNP-encapsulated si-DLX6-AS1. In cerebral ischemic injury mice and OGD-induced N2a cells, Nrf2 and HO-1 levels were reduced and NLRP3 levels were increased. LNP-encapsulated si-DLX6-AS1 raised Nrf2 and HO-1 levels and reduced NLRP3 levels. Nrf2 inhibitor ML385 treatment reversed the ameliorative effects of LNP-encapsulated si-DLX6-AS1 on OGD-induced N2a cell viability and apoptosis. CONCLUSION: Lipid nanoparticle-encapsulated si-DLX6-AS1 ameliorates cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis.

Efficacy of live and inactivated recombinant Newcastle disease virus vaccines expressing clade 2.3.4.4b H5 hemagglutinin against H5N1 highly pathogenic avian influenza in SPF chickens, Broilers, and domestic ducks.

A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA).

A Brief Review of Anatomy Education in Korea, Encompassing Its Past, Present, and Future Direction.

Anatomy is a foundational subject in medicine and serves as its language. Hippocrates highlighted its importance, while Herophilus pioneered human dissection, earning him the title of the founder of anatomy. Vesalius later established modern anatomy, which has since evolved historically. In Korea, formal anatomy education for medical training began with the introduction of Western medicine during the late Joseon Dynasty. Before and after the Japanese occupation, anatomy education was conducted in the German style, and after liberation, it was maintained and developed by a small number of domestic anatomists. Medicine in Korea has grown alongside the country's rapid economic and social development. Today, 40 medical colleges produce world-class doctors to provide the best medical care service in the country. However, the societal demand for more doctors is growing in order to proactively address to challenges such as public healthcare issues, essential healthcare provision, regional medical service disparities, and an aging population. This study examines the history, current state, and challenges of anatomy education in Korea, emphasizing the availability of medical educators, support staff, and cadavers for gross anatomy instruction. While variations exist between Seoul and provincial medical colleges, each manages to deliver adequate education under challenging conditions. However, the rapid increase in medical student enrollment threatens to strain existing anatomy education resources, potentially compromising educational quality. To address these concerns, we propose strategies for training qualified gross anatomy educators, ensuring a sustainable cadaver supply, and enhancing infrastructure.

Novel Avian Influenza A(H5N6) Virus in Wild Birds, South Korea, 2023.

We isolated novel reassortant avian influenza A(H5N6) viruses containing genes from clade 2.3.4.4b H5N1 virus and low pathogenicity avian influenza viruses in carcasses of whooper swans and bean geese in South Korea during December 2023. Neuraminidase gene was from a clade 2.3.4.4b H5N6 virus infecting poultry and humans in China.

In-depth analysis of ambient air pollution changes due to the COVID-19 pandemic in the Asian Monsoon region.

The COVID-19 pandemic has given a chance for researchers and policymakers all over the world to study the impact of lockdowns on air quality in each country. This review aims to investigate the impact of the restriction of activities during the lockdowns in the Asian Monsoon region on the main criteria air pollutants. The various types of lockdowns implemented in each country were based on the severity of the COVID-19 pandemic. The concentrations of major air pollutants, especially particulate matter (PM) and nitrogen dioxide (NO2), reduced significantly in all countries, especially in South Asia (India and Bangladesh), during periods of full lockdown. There were also indications of a significant reduction of sulfur dioxide (SO2) and carbon monoxide (CO). At the same time, there were indications of increasing trends in surface ozone (O3), presumably due to nonlinear chemistry associated with the reduction of oxides of nitrogens (NOX). The reduction in the concentration of air pollutants can also be seen in satellite images. The results of aerosol optical depth (AOD) values followed the PM concentrations in many cities. A significant reduction of NO2 was recorded by satellite images in almost all cities in the Asian Monsoon region. The major reductions in air pollutants were associated with reductions in mobility. Pakistan, Bangladesh, Myanmar, Vietnam, and Taiwan had comparatively positive gross domestic product growth indices in comparison to other Asian Monsoon nations during the COVID-19 pandemic. A positive outcome suggests that the economy of these nations, particularly in terms of industrial activity, persisted during the COVID-19 pandemic. Overall, the lockdowns implemented during COVID-19 suggest that air quality in the Asian Monsoon region can be improved by the reduction of emissions, especially those due to mobility as an indicator of traffic in major cities.

Transcriptional regulation of Znt family members znt4, znt5 and znt10 and their function in zinc transport in yellow catfish (Pelteobagrus fulvidraco).

The study characterized the transcriptionally regulatory mechanism and functions of three zinc (Zn) transporters (znt4, znt5 and znt10) in Zn2+ metabolism in yellow catfish (Pelteobagrus fulvidraco), commonly freshwater fish in China and other countries. We cloned the sequences of znt4 promoter, spanning from -1217 bp to +80 bp relative to TSS (1297 bp); znt5, spanning from -1783 bp to +49 bp relative to TSS (1832 bp) and znt10, spanning from -1923 bp to +190 bp relative to TSS (2113 bp). In addition, after conducting the experiments of sequential deletion of promoter region and mutation of potential binding site, we found that the Nrf2 binding site (-607/-621 bp) and Klf4 binding site (-5/-14 bp) were required on znt4 promoter, the Mtf-1 binding site (-1674/-1687 bp) and Atf4 binding site (-444/-456 bp) were required on znt5 promoter and the Atf4 binding site (-905/-918 bp) was required on znt10 promoter. Then, according to EMSA and ChIP, we found that Zn2+ incubation increased DNA affinity of Atf4 to znt5 or znt10 promoter, but decreased DNA affinity of Nrf2 to znt4 promoter, Klf4 to znt4 promoter and Mtf-1 to znt5 promoter. Using fluorescent microscopy, it was revealed that Znt4 and Znt10 were located in the lysosome and Golgi, and Znt5 was located in the Golgi. Finally, we found that znt4 knockdown reduced the zinc content of lysosome and Golgi in the control and zinc-treated group; znt5 knockdown reduced the zinc content of Golgi in the control and zinc-treated group and znt10 knockdown reduced the zinc content of Golgi in the zinc-treated group. High dietary zinc supplement up-regulated Znt4 and Znt5 protein expression. Above all, for the first time, we revealed that Klf4 and Nrf2 transcriptionally regulated the activities of znt4 promoter; Mtf-1 and Atf4 transcriptionally regulated the activities of znt5 promoter and Atf4 transcriptionally regulated the activities of znt10 promoter, which provided innovative regulatory mechanism of zinc transporting in yellow catfish. Our study also elucidated their subcellular location, and regulatory role of zinc homeostasis in yellow catfish.