Direct Photocatalytic Methane Oxidation to Formaldehyde by N Doping Co-Decorated Mixed Crystal TiO2.

In this paper, N-doped TiO2 mixed crystals are prepared via direct calcination of TiN for highly selective oxidation of CH4 to HCHO at room temperature. The structures of the prepared TiO2 samples are characterized to be N-doped TiO2 of anatase and rutile mixed crystals. The crystal structures of TiO2 samples are determined by XRD spectra and Raman spectra, while N doping is demonstrated by TEM mapping, ONH inorganic element analysis, and high-resolution XPS results. Significantly, the production rate of HCHO is as high as 23.5 mmol·g-1·h-1 with a selectivity over 90%. Mechanism studies reveal that H2O is the main oxygen source and acts through the formation of ·OH. DFT calculations indicate that the construction of a mixed crystal structure and N-doping modification mainly act by increasing the adsorption capacity of H2O. An efficient photocatalyst was prepared by us to convert CH4 to HCHO with high yield and selectivity, greatly promoting the development of the photocatalytic CH4 conversion study.

Gradient matters via filament diameter-adjustable 3D printing.

Gradient matters with hierarchical structures endow the natural world with excellent integrity and diversity. Currently, direct ink writing 3D printing is attracting tremendous interest, and has been used to explore the fabrication of 1D and 2D hierarchical structures by adjusting the diameter, spacing, and angle between filaments. However, it is difficult to generate complex 3D gradient matters owing to the inherent limitations of existing methods in terms of available gradient dimension, gradient resolution, and shape fidelity. Here, we report a filament diameter-adjustable 3D printing strategy that enables conventional extrusion 3D printers to produce 1D, 2D, and 3D gradient matters with tunable heterogeneous structures by continuously varying the volume of deposited ink on the printing trajectory. In detail, we develop diameter-programmable filaments by customizing the printing velocity and height. To achieve high shape fidelity, we specially add supporting layers at needed locations. Finally, we showcase multi-disciplinary applications of our strategy in creating horizontal, radial, and axial gradient structures, letter-embedded structures, metastructures, tissue-mimicking scaffolds, flexible electronics, and time-driven devices. By showing the potential of this strategy, we anticipate that it could be easily extended to a variety of filament-based additive manufacturing technologies and facilitate the development of functionally graded structures.

Reversible strain-promoted DNA polymerization.

Molecular strain can be introduced to influence the outcome of chemical reactions. Once a thermodynamic product is formed, however, reversing the course of a strain-promoted reaction is challenging. Here, a reversible, strain-promoted polymerization in cyclic DNA is reported. The use of nonhybridizing, single-stranded spacers as short as a single nucleotide in length can promote DNA cyclization. Molecular strain is generated by duplexing the spacers, leading to ring opening and subsequent polymerization. Then, removal of the strain-generating duplexers triggers depolymerization and cyclic dimer recovery via enthalpy-driven cyclization and entropy-mediated ring contraction. This reversibility is retained even when a protein is conjugated to the DNA strands, and the architecture of the protein assemblies can be modulated between bivalent and polyvalent states. This work underscores the utility of using DNA not only as a programmable ligand for assembly but also as a route to access restorable bonds, thus providing a molecular basis for DNA-based materials with shape-memory, self-healing, and stimuli-responsive properties.

Viperin inhibits interferon-γ production to promote Mycobacterium tuberculosis survival by disrupting TBK1-IKKε-IRF3-axis and JAK-STAT signaling.

OBJECTIVES AND DESIGN: As an interferon-inducible protein, Viperin has broad-spectrum antiviral effects and regulation of host immune responses. We aim to investigate how Viperin regulates interferon-γ (IFN-γ) production in macrophages to control Mycobacterium tuberculosis (Mtb) infection. METHODS: We use Viperin deficient bone-marrow-derived macrophage (BMDM) to investigate the effects and machines of Viperin on Mtb infection. RESULTS: Viperin inhibited IFN-γ production in macrophages and in the lung of mice to promote Mtb survival. Further insight into the mechanisms of Viperin-mediated regulation of IFN-γ production revealed the role of TANK-binding kinase 1 (TBK1), the TAK1-dependent inhibition of NF-kappa B kinase-epsilon (IKKε), and interferon regulatory factor 3 (IRF3). Inhibition of the TBK1-IKKε-IRF3 axis restored IFN-γ production reduced by Viperin knockout in BMDM and suppressed intracellular Mtb survival. Moreover, Viperin deficiency activated the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, which promoted IFN-γ production and inhibited Mtb infection in BMDM. Additionally, a combination of the anti-TB drug INH treatment in the absence of Viperin resulted in further IFN-γ production and anti-TB effect. CONCLUSIONS: This study highlights the involvement of TBK1-IKKε-IRF3 axis and JAK-STAT signaling pathways in Viperin-suppressed IFN-γ production in Mtb infected macrophages, and identifies a novel mechanism of Viperin on negatively regulating host immune response to Mtb infection.

Pure optical twist with zero net torque.

In photonic systems, bilayer or multilayer systems exhibit numerous exciting phenomena induced by twisting. Thus, it is highly desired to explore the twisting effect by engineering the light-matter interactions. Optical torque, an important means in optical micromanipulation, can rotate micro-objects in various ways, enabling a wide range of promising applications. In this study, we present an interesting phenomenon called "pure optical twist" (POT), which emerges when a bilayer structure with specific symmetry is illuminated by counter-propagating lights with opposite spin and/or orbital angular momentum. Remarkably, this leads to zero net optical torque but yet possesses an interesting mechanical effect of bilayer system twisting. The crucial determinant of this phenomenon is the rotational symmetries of each layer, which govern the allowed azimuthal channels of the scattered wave. When the rotational symmetries do not allow these channels to overlap, no resultant torque is observed. Our work will encourage further exploration of the twisting effect through engineered light-matter interactions. This opens up the possibility of creating twisted bilayer systems using optical means, and constructing a stable bilayer optical motor that maintains identical rotation frequencies for both layers.

ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human ß-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.

Radiotherapy Resistance of 3D Bioprinted Glioma via ITGA2/p-AKT Signaling Pathway.

Due to the inherent radiation tolerance, patients who suffered from glioma frequently encounter tumor recurrence and malignant progression within the radiation target area, ultimately succumbing to treatment ineffectiveness. The precise mechanism underlying radiation tolerance remains elusive due to the dearth of in vitro models and the limitations associated with animal models. Therefore, a bioprinted glioma model is engineered, characterized the phenotypic traits in vitro, and the radiation tolerance compared to 2D ones when subjected to X-ray radiation is assessed. By comparing the differential gene expression profiles between the 2D and 3D glioma model, identify functional genes, and analyze distinctions in gene expression patterns. Results showed that 3D glioma models exhibited substantial alterations in the expression of genes associated with the stromal microenvironment, notably a significant increase in the radiation tolerance gene ITGA2 (integrin subunit A2). In 3D glioma models, the knockdown of ITGA2 via shRNA resulted in reduced radiation tolerance in glioma cells and concomitant inhibition of the p-AKT pathway. Overall, 3D bioprinted glioma model faithfully recapitulates the in vivo tumor microenvironment (TME) and exhibits enhanced resistance to radiation, mediated through the ITGA2/p-AKT pathway. This model represents a superior in vitro platform for investigating glioma radiotherapy tolerance.

ZNFX1 promotes AMPK-mediated autophagy against Mycobacterium tuberculosis by stabilizing Prkaa2 mRNA.

Tuberculosis has the highest mortality rate worldwide for a chronic infectious disease caused by a single pathogen. RNA-binding proteins (RBPs) are involved in autophagy - a key defense mechanism against Mycobacterium tuberculosis (M. tuberculosis) infection - by modulating RNA stability and forming intricate regulatory networks. However, the functions of host RBPs during M. tuberculosis infection remain relatively unexplored. Zinc finger NFX1-type containing 1 (ZNFX1), a conserved RBP critically involved in immune deficiency diseases and mycobacterial infections, is significantly upregulated in M. tuberculosis-infected macrophages. Here, we aimed to explore the immunoregulatory functions of ZNFX1 during M. tuberculosis infection. We observed that Znfx1 knockout markedly compromised the multifaceted immune responses mediated by macrophages. This compromise resulted in reduced phagocytosis, suppressed macrophage activation, increased M. tuberculosis burden, progressive lung tissue injury, and chronic inflammation in M. tuberculosis-infected mice. Mechanistic investigations revealed that the absence of ZNFX1 inhibited autophagy, consequently mediating immune suppression. ZNFX1 critically maintained AMPK-regulated autophagic flux by stabilizing protein kinase AMP-activated catalytic subunit alpha 2 mRNA, which encodes a key catalytic α subunit of AMPK, through its zinc finger region. This process contributed to M. tuberculosis growth suppression. These findings reveal a function of ZNFX1 in establishing anti-M. tuberculosis immune responses, enhancing our understanding of the roles of RBPs in tuberculosis immunity and providing a promising approach to bolster antituberculosis immunotherapy.

How enlightened self-interest guided global vaccine sharing benefits all: A modeling study.

Background: Despite consensus that vaccines play an important role in combatting the global spread of infectious diseases, vaccine inequity is still a prevalent issue due to a deep-seated mentality of self-priority. We aimed to evaluate the existence and possible outcomes of a more equitable global vaccine distribution and explore a concrete incentive mechanism that promotes vaccine equity. Methods: We designed a metapopulation epidemiological model that simultaneously considers global vaccine distribution and human mobility, which we then calibrated by the number of infections and real-world vaccination records during the coronavirus disease 2019 (COVID-19) pandemic from March 2020 to July 2021. We explored the possibility of the enlightened self-interest incentive mechanism, which comprises improving one's own epidemic outcomes by sharing vaccines with other countries, by evaluating the number of infections and deaths under various vaccine sharing strategies using the proposed model. To understand how these strategies affect the national interests, we distinguished imported from local cases for further cost-benefit analyses that rationalise the enlightened self-interest incentive mechanism behind vaccine sharing. Results: The proposed model accurately reproduces the real-world cumulative infections for both global and regional epidemics (R2>0.990), which can support the following evaluations of different vaccine sharing strategies: High-income countries can reduce 16.7 (95% confidence interval (CI) = 8.4-24.9, P < 0.001) million infection cases and 82.0 (95% CI = 76.6-87.4, P < 0.001) thousand deaths on average by more actively sharing vaccines in an enlightened self-interest manner, where the reduced internationally imported cases outweigh the threat from increased local infections. Such vaccine sharing strategies can also reduce 4.3 (95% CI = 1.2-7.5, P < 0.01) million infections and 7.0 (95% CI = 5.7-8.3, P < 0.001) thousand deaths in middle- and low-income countries, effectively benefiting the whole global population. Lastly, the more equitable vaccine distribution could help largely reduce the global mobility reduction needed for pandemic control. Conclusions: The incentive mechanism of enlightened self-interest we explored here could motivate vaccine equity by realigning the national interest to more equitable vaccine distributions. The positive results could promote multilateral collaborations in global vaccine redistribution and reconcile conflicted national interests, which could in turn benefit the global population.

Protocol for Development and Validation of Multivariable Prediction Models for Chronic Postsurgical Pain Following Video-Assisted Thoracic Surgery.

Purpose: Chronic postsurgical pain (CPSP) is a common complication after thoracic surgery and associated with long-term adverse outcomes. This study aims to develop two prediction models for CPSP after video-assisted thoracic surgery (VATS). Methods and Analysis: This single-center prospective cohort study will include a total of 500 adult patients undergoing VATS lung resection (n = 350 for development and n = 150 for external validation). Patients will be enrolled continuously at The First Affiliated Hospital of Soochow University in Suzhou, China. The cohort for external validation will be recruited in another time period. The outcome is CPSP, which is defined as pain with the numerical rating scale score of 1 or higher 3 months after VATS. Univariate and multivariable logistic regression analyses will be performed to develop two CPSP prediction models based on patients' data of postoperative day 1 and day 14, respectively. For internal validation, we will use the bootstrapping validation technique. For external validation, the discrimination capability of the models will be assessed using the area under the receiver operating characteristic curve, and the calibration will be evaluated using the calibration curve and Hosmer-Lemeshow goodness-of-fit statistic. The results will be presented in model formulas and nomograms. Conclusion: Based on the development and validation of the prediction models, our results contribute to early prediction and treatment of CPSP after VATS. Trial Registration: Chinese Clinical Trial Register (ChiCTR2200066122).

miR-21-5p Inhibits the Proliferation, Migration, and Invasion of Glioma by Targeting S100A10.

S100A10, a member of the S100 protein family, is upregulated in multiple human malignancies and plays a key role in regulating tumor progression. This study aimed to reveal the underlying mechanism by which S100A10 in regulates the proliferation, migration, and invasion of glioma. The expression and clinical information data of S100A10 were downloaded from public databases (TCGA, CGGA, and GEPIA2). S100A10 expression levels in glioma tumor tissues and adjacent nontumor tissues were compared by immunohistochemistry (IHC). The functional roles of S100A10 in glioma were assessed by cell counting kit-8 (CCK-8) cell proliferation assay, wound healing assay, transwell assay, and flow cytometry. miRDB and double luciferase assay were used to predict and identify potential S100A10 mRNA-complementary miRNAs, and the roles of miR-21-5p in glioma cell were examined by targeted knockdown or overexpression miR-21-5p in glioma cell lines. We found that S100A10 was overexpressed in glioma tissues and predicted a worse prognosis. S100A10 knockdown significantly inhibited glioma cell proliferation, invasion, and migration. Furthermore, we demonstrated that miR-21-5p inhibits glioma proliferation, migration, and invasion by targeting S100A10. This study showed S100A10 was a new prognostic predictor among glioma patients and provided new insights into the pathogenesis of gliomas, suggesting that miR-21-5p /S100A10 axis may serve as a valuable therapeutic target for glioma.

The E3 ligase HERC5 promotes antimycobacterial responses in macrophages by ISGylating the phosphatase PTEN.

Innate immune signaling in macrophages during viral infection is regulated by ISGylation, the covalent attachment of the ubiquitin-like protein interferon-stimulated gene 15 (ISG15) to protein targets. Here, we explored the role of ISGylation in the macrophage response to infection with Mycobacterium tuberculosis. In human and mouse macrophages, the E3 ubiquitin ligases HERC5 and mHERC6, respectively, mediated the ISGylation of the phosphatase PTEN, which promoted its degradation. The decreased abundance of PTEN led to an increase in the activity of the PI3K-AKT signaling pathway, which stimulated the synthesis of proinflammatory cytokines. Bacterial growth was increased in culture and in vivo when human or mouse macrophages were deficient in the major E3 ISG15 ligase. The findings expand the role of ISGylation in macrophages to antibacterial immunity and suggest that HERC5 signaling may be a candidate target for adjunct host-directed therapy in patients with tuberculosis.

Cisatracurium besylate rescues Mycobacterium Tuberculosis-infected macrophages from necroptosis and enhances the bactericidal effect of isoniazid.

OBJECTIVE: Tuberculosis is the leading killer among the chronic single-source infectious diseases. Mycobacterium tuberculosis can induce necrotic-dominant multiple modes of cell death in macrophages, which accelerates bacterium dissemination and expands tissue injury in host lungs. Mining drugs to counteract Mycobacterium tuberculosis-induced cell death would be beneficial to tuberculosis patients. METHODS: In this study, the protective drug was screened out from the FDA-approved drug library in Mycobacterium tuberculosis-infected macrophages with CCK-8 assay. The death mode regulated by the drug was identified using transcriptomic sequencing, cytomorphological observation, and in the experimental mouse Mycobacterium tuberculosis-infection model. The functional mechanism was explored using western blot, co-immunoprecipitation, and DARTS assay. The intracellular bacterial survival was detected using colony forming unit assays. RESULTS: Cisatracurium besylate was identified to be highly protective for the viability of macrophages during Mycobacterium tuberculosis infection via inhibiting necroptosis. Cisatracurium besylate prevented RIPK3 to be associated with the executive molecule MLKL for forming the necroptotic complex, resulting in the inhibition of MLKL phosphorylation and pore formation on cell membrane. However, Cisatracurium besylate did not interfere with the association between RIPK3 with its upstream kinase RIPK1 or ZBP1 but regulated RIPK3 autophosphorylation. Moreover, Cisatracurium besylate significantly inhibited the expansion of intracellular Mycobacterium tuberculosis both in vitro and in vivo, which also displayed a strong auxiliary bacteriostatic effect to support the therapeutic efficacy of isoniazid and rifampicin, the first-line anti-tubercular drugs. CONCLUSION: Cisatracurium besylate performs anti-Mycobacterium tuberculosis and anti-necroptotic roles, which potentiates its application to be an adjuvant drug for antituberculosis therapy to assist the battle against drug-resistant tuberculosis.

Morphology-dependent resonance induced optical forces in a multiple-sphere system.

Optical fields and forces can be greatly enhanced for a microparticle when the whispering gallery modes (WGMs) are excited. In this paper, by solving the scattering problem using the generalized Mie theory, the morphology-dependent resonances (MDRs) and resonant optical forces derived from the coherent coupling of WGMs are investigated in multiple-sphere systems. When the spheres approach each other, the bonding and antibonding modes of MDRs emerge and correspond to the attractive and repulsive forces, respectively. More importantly, the antibonding mode is good at propagating light forward, while the optical fields decay rapidly for the bonding mode. Moreover, the bonding and antibonding modes of MDRs in the PT-symmetric system can persist only when the imaginary part of the refractive index is small enough. Interestingly, it is also shown that for a PT-symmetric structure, only a minor imaginary part of the refractive index is required to generate a significant pulling force at MDRs, making the whole structure move against the light propagation direction. Our work deepens the understanding of the collective resonance behavior of multiple spheres and paves the way for potential applications in particle transportation, non-Hermitian systems, integrated optical devices, etc.

Disheveled3 enhanced EMT and cancer stem-like cells properties via Wnt/ß-catenin/c-Myc/SOX2 pathway in colorectal cancer.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis and drug-resistance. Disheveled3 (DVL3) is involved in malignant behaviors of cancer. However, the role and potential mechanism of DVL3 remain elusive in EMT and CSLCs of colorectal cancer (CRC). METHODS: UALCAN and PrognoScan databases were employed to evaluate DVL3 expression in CRC tissues and its correlation with CRC prognosis, respectively. Transwell, sphere formation and CCK8 assay were used to assess metastasis, stemness and drug sensitivity of CRC cells, respectively. Western blotting and dual luciferase assay were performed to analyze the protein expression and Wnt/ß-catenin activation, respectively. Lentiviral transfection was used to construct the stable cell lines. Animal studies were performed to analyze the effect of silencing DVL3 on tumorigenicity and metastasis of CRC cells in vivo. RESULTS: DVL3 was overexpressed in CRC tissues and several CRC cell lines. DVL3 expression was also higher in CRC tissues with lymph node metastasis than tumor tissues without metastasis, and correlated with poor prognosis of CRC patients. DVL3 positively regulated the abilities of migration, invasion and EMT-like molecular changes in CRC cells. Moreover, DVL3 promoted CSLCs properties and multidrug resistance. We further identified that Wnt/ß-catenin was crucial for DVL3-mediated EMT, stemness and SOX2 expression, while silencing SOX2 inhibited DVL3-mediated EMT and stemness. Furthermore, c-Myc, a direct target gene of Wnt/ß-catenin, was required for SOX2 expression and strengthened EMT and stemness via SOX2 in CRC cells. Finally, knockdown of DVL3 suppressed tumorigenicity and lung metastasis of CRC cells in nude mice. CONCLUSION: DVL3 promoted EMT and CSLCs properties of CRC via Wnt/ß-catenin/c-Myc/SOX2 axis, providing a new strategy for successful CRC treatment.

3,4-Enhanced Polymerization of Isoprene Catalyzed by Side-Arm Tridentate Iminopyridine Iron Complex with High Activity: Optimization via Response Surface Methodology.

3,4-Enhanced polymerization of isoprene catalyzed by late transition metal with high activity remains one of the great challenges in synthetic rubber chemistry. Herein, a library of [N, N, X] tridentate iminopyridine iron chloride pre-catalysts (Fe 1-4) with the side arm were synthesized and confirmed by the element analysis and HRMS. All the iron compounds served as highly efficient pre-catalysts for 3,4-enhanced (up to 62%) isoprene polymerization when 500 equivalent MAOs were utilized as co-catalysts, delivering the corresponding high-performance polyisoprenes. Furthermore, optimization via single factor and response surface method, it was observed that the highest activity was obtained by complex Fe 2 with 4.0889 × 107 g·mol(Fe)-1·h-1 under the following conditions: Al/Fe = 683; IP/Fe = 7095; t = 0.52 min.

Healthy Cities, A comprehensive dataset for environmental determinants of health in England cities.

This paper presents a fine-grained and multi-sourced dataset for environmental determinants of health collected from England cities. We provide health outcomes of citizens covering physical health (COVID-19 cases, asthma medication expenditure, etc.), mental health (psychological medication expenditure), and life expectancy estimations. We present the corresponding environmental determinants from four perspectives, including basic statistics (population, area, etc.), behavioural environment (availability of tobacco, health-care services, etc.), built environment (road density, street view features, etc.), and natural environment (air quality, temperature, etc.). To reveal regional differences, we extract and integrate massive environment and health indicators from heterogeneous sources into two unified spatial scales, i.e., at the middle layer super output area (MSOA) and the city level, via big data processing and deep learning. Our data holds great promise for diverse audiences, such as public health researchers and urban designers, to further unveil the environmental determinants of health and design methodology for a healthy, sustainable city.

LINP1 represses unfolded protein response by directly inhibiting eIF2α phosphorylation to promote cutaneous squamous cell carcinoma.

BACKGROUND: Endoplasmic reticulum stress (ER stress) may destroy endoplasmic reticulum homeostasis (ER homeostasis) and leads to programmable cell death. Unfolded protein response (UPR) originally stimulated by ER stress is critical for the survival of tumor cells through trying to re-establish ER homeostasis as an adaption to harsh microenvironment. However, mechanisms involving key regulators in modulating UPR remain underexplored. METHODS: The expression of LINP1 in cutaneous squamous cell carcinoma (cSCC) tissues and cell lines was assessed. Subsequently, LINP1 was knocked out, knocked down or overexpressed in cSCC cells. CCK-8 assays, colony forming assays, transwell migration assays and invasiveness measurement by matrigel-coated transwell were performed to examine the role of LINP1 in cSCC development through gain-of-function and loss-of-function experiments. Transcriptomic sequencing (RNA-Seq) was conducted and indicated the key downstream signaling events regulated by LINP1 including UPR and apoptosis signaling. Furthermore, the direct interaction between LINP1 and eIF2α to modulate UPR and apoptosis was confirmed by RNA pulldown, RNA immunoprecipitation (RIP), ChIP-qPCR and in vitro phosphorylation assays. RESULTS: In this study, LncRNA in non-homologous end joining pathway 1 (LINP1) was identified to be one of the top ten highest-expressed LncRNAs in cSCC, the second most common cancer in the world. Functional studies using in vitro and in vivo models revealed that LINP1 functions as an oncogene to promote cell proliferation, colony formation, migration and invasiveness while inhibiting cell apoptosis in cSCC. Transcriptomic sequencing after knockdown of LINP1 indicated LINP1 negatively regulates UPR-related pathways involving key effectors for activating UPR and the apoptosis following the prolonged UPR. Mechanistic study showed LINP1 physically interacts with eIF2α to inhibit its phosphorylation for avoiding unmitigated UPR. Loss of LINP1 followed by enhanced eIF2α phosphorylation led to overactivated UPR and induced DDIT3 expression, contributing to ER stress-induced apoptosis and suppression of cSCC development. CONCLUSIONS: Our findings demonstrate a novel regulatory hierarchy of UPR by demonstrating LINP1 as a critical modulator for eIF2α phosphorylation and a suppressor of UPR-mediated apoptosis, which suggests a novel therapeutic target for cSCC treatment.

Viperin deficiency promotes dendritic cell activation and function via NF-kappaB activation during Mycobacterium tuberculosis infection.

OBJECTIVES AND DESIGN: Dendritic cells (DCs) are one of the key immune cells in bridging innate and adaptive immune response against Mycobacterium tuberculosis (Mtb) infection. Interferons (IFNs) play important roles in regulating DC activation and function. Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (Viperin) is one of the important IFN-stimulated genes (ISGs), and elicits host defense against infection. METHODS: We investigated the effects and mechanisms of Viperin on DC activation and function using Viperin deficient bone marrow-derived dendritic cells (BMDCs) during Mtb infection. RESULTS: Viperin deficiency enhanced phagocytic activity and increased clearance of Mtb in DCs, produced higher abundance of NO, cytokine including interleukin-12 (IL-12), Tumor necrosis factor-α (TNF-α), IL-1ß, IL-6 and chemokine including CXCL1, CXCL2 and CXCL10, elevated MHC I, MHC II and co-stimulatory molecules expression, and enhanced CD4+ and CD8+ T cell responses. Mechanistically, Viperin deficiency promoted DC activation and function through NF-κB p65 activation. NF-κB p65 inhibitor prevented cytokine and chemokine production, and co-stimulatory molecules expression promoted by Viperin deficiency. CONCLUSIONS: These results suggest that Mtb induced Viperin expression could impair the activation of host defense function of DCs and DC-T cell cross talk during Mtb infection. This research may provide a potential target for future HDT in TB therapy.

Evaluation and Projection of Surface PM2.5 and Its Exposure on Population in Asia Based on the CMIP6 GCMs.

This paper evaluates the historical simulated surface concentrations of particulate matter small than 2.5 µm in diameter (PM2.5) and its components (black carbon (BC), dust, SO4, and organic aerosol (OA)) in Asia, which come from Coupled Model Intercomparison Project Phase 6 (CMIP6). In addition, future projected changes of surface PM2.5 and its components, as well as their exposure to population, under the different Shared Socioeconomic Pathway (SSP) scenarios are also provided. Results show that the simulated spatial distribution of surface PM2.5 concentrations is consistent with the Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA-2) and Socioeconomic Data and Applications Center (SEDAC). The model spreads are small/large over the regions with low/high climatic mean surface PM2.5 concentrations, i.e., Northern Asia/Saudi Arabia, Iran, and Xinjiang Province of China. The multi-model ensemble of CMIP6 reproduces the main features of annual cycles and seasonal variations in Asia and its sub-regions. Under the scenarios of SSP1-2.6, SSP2-4.5, and SSP5-8.5, compared to the present-day period of 1995-2014, annual mean surface PM2.5 concentrations are projected to decrease in Asia, with obvious differences among the scenarios. Meanwhile, the magnitudes and timings of changes at the regional scale are quite different, with the largest decreases in South Asia (SAS). Under SSP3-7.0, the increase of surface PM2.5 concentrations in SAS is the largest, with the increase value of 8 µg/m3 in 2050; while under SSP370-lowNTCF, which assumes stronger levels of air quality control measures relative to the SSP3-7.0, the decreases of surface PM2.5 concentrations in SAS, East Asia (EAS) and Southeast Asia (SEAS) are the largest. The characteristics of seasonal trends are consistent with that of the annual trend. The trends in the concentrations of surface PM2.5 and its components are similar. The population-weighted average values of surface PM2.5 concentrations are projected to decrease in Central Asia (CAS), EAS, North Asia (NAS), and SEAS, and it indicates that the surface PM2.5 concentrations over the most populated area of Asia will decrease. In SAS, because of its large population, the impact of air pollutants on human health is still disastrous in the future. In summary, the surface PM2.5 concentrations over the most area of Asia will decrease, which is beneficial to air quality and human health; under SSP370-lowNTCF, the reduction of short-lived climate forcers (SLCFs) will further improve air quality.