Synergistic HNO3-H2SO4-NH3 upper tropospheric particle formation.

New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN)1-4. However, the precursor vapours that drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we show that nitric acid, sulfuric acid and ammonia form particles synergistically, at rates that are orders of magnitude faster than those from any two of the three components. The importance of this mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the upper troposphere over the Asian monsoon region5,6. Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements show that these CCN are also highly efficient ice nucleating particles-comparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNO3-H2SO4-NH3 nucleation in the upper troposphere and producing ice nucleating particles that spread across the mid-latitude Northern Hemisphere.

Rapid growth of new atmospheric particles by nitric acid and ammonia condensation.

A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog1,2, but how it occurs in cities is often puzzling3. If the growth rates of urban particles are similar to those found in cleaner environments (1-10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below -15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid-base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms4,5.

Protective effects of COVID-19 vaccination in splenectomized patients with immune thrombocytopenia.

Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID-19 vaccination on splenectomized patients with ITP during the COVID-19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID-19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow-up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID-19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05-0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04-0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04-0.67; p = 0.012). These findings indicate that COVID-19 vaccination plays a protective role in splenectomized patients with ITP.

IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities.

Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating innate immune signaling pathways to defend the host. Recent studies have revealed additional regulatory functions of STING beyond its innate immune-related activities, including the regulation of cellular metabolism, DNA repair, cellular senescence, autophagy and various cell deaths. These findings highlight the broader implications of STING in cellular physiology beyond its role in innate immunity. Currently, approximately 10 STING agonists have entered the clinical stage. Unlike inhibitors, which have a maximum inhibition limit, agonists have the potential for infinite amplification. STING signaling is a complex process that requires precise regulation of STING to ensure balanced immune responses and prevent detrimental autoinflammation. Recent research on the structural mechanism of STING autoinhibition and its negative regulation by adaptor protein complex 1 (AP-1) provides valuable insights into its different effects under physiological and pathological conditions, offering a new perspective for developing immune regulatory drugs. Herein, we present a comprehensive overview of the regulatory functions and molecular mechanisms of STING beyond innate immune regulation, along with updated details of its structural mechanisms. We discuss the implications of these complex regulations in various diseases, emphasizing the importance and feasibility of targeting the immunity-dependent or immunity-independent functions of STING. Moreover, we highlight the current trend in drug development and key points for clinical research, basic research, and translational research related to STING.

The discovery of novel and potent indazole NLRP3 inhibitors enabled by DNA-encoded library screening.

NLRP3 is an intracellular sensor protein that detects a broad range of danger signals and environmental insults. Its activation results in a protective pro-inflammatory response designed to impair pathogens and repair tissue damage via the formation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent secretory release of the pro-inflammatory cytokines IL-1ß and IL-18 as well as to gasdermin d-mediated pyroptotic cell death. Herein, we describe the discovery of a novel indazole series of high affinity, reversible inhibitors of NLRP3 activation through screening of DNA-encoded libraries and the potent lead compound 3 (BAL-0028, IC50 = 25 nM) that was identified directly from the screen. SPR studies showed that compound 3 binds tightly (KD range 104-123 nM) to the NACHT domain of NLRP3. A CADD analysis of the interaction of compound 3 with the NLRP3 NACHT domain proposes a binding site that is distinct from those of ADP and MCC950 and includes specific site interactions. We anticipate that compound 3 (BAL-0028) and other members of this novel indazole class of neutral inhibitors will demonstrate significantly different physical, biochemical, and biological properties compared to NLRP3 inhibitors previously identified.

HIO3-HIO2-Driven Three-Component Nucleation: Screening Model and Cluster Formation Mechanism.

Iodine oxoacids (HIO3 and HIO2)-driven nucleation has been suggested to efficiently contribute to new particle formation (NPF) in marine atmospheres. Abundant atmospheric nucleation precursors may further enhance HIO3-HIO2-driven nucleation through various multicomponent nucleation mechanisms. However, the specific enhancing potential (EP) of different precursors remains largely unknown. Herein, the EP-based screening model of precursors and enhancing mechanism of the precursor with the highest EP on HIO3-HIO2 nucleation were investigated. The formation free energies (ΔG), as critical parameters for evaluating EP, were calculated for the dimers of 63 selected precursors with HIO2. Based on the ΔG values, (1) a quantitative structure-activity relationship model was developed for evaluating ΔG of other precursors and (2) atmospheric concentrations of 63 (precursor)1(HIO2)1 dimer clusters were assessed to identify the precursors with the highest EP for HIO3-HIO2-driven nucleation by combining with earlier results for the nucleation with HIO3 as the partner. Methanesulfonic acid (MSA) was found to be one of the precursors with the highest EP. Finally, we found that MSA can effectively enhance HIO3-HIO2 nucleation at atmospheric conditions by studying larger MSA-HIO3-HIO2 clusters. These results augment our current understanding of HIO3-HIO2 and MSA-driven nucleation and may suggest a larger impact of HIO2 in atmospheric aerosol nucleation.

Nitrate Radicals Suppress Biogenic New Particle Formation from Monoterpene Oxidation.

Highly oxygenated organic molecules (HOMs) are a major source of new particles that affect the Earth's climate. HOM production from the oxidation of volatile organic compounds (VOCs) occurs during both the day and night and can lead to new particle formation (NPF). However, NPF involving organic vapors has been reported much more often during the daytime than during nighttime. Here, we show that the nitrate radicals (NO3), which arise predominantly at night, inhibit NPF during the oxidation of monoterpenes based on three lines of observational evidence: NPF experiments in the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN (European Organization for Nuclear Research), radical chemistry experiments using an oxidation flow reactor, and field observations in a wetland that occasionally exhibits nocturnal NPF. Nitrooxy-peroxy radicals formed from NO3 chemistry suppress the production of ultralow-volatility organic compounds (ULVOCs) responsible for biogenic NPF, which are covalently bound peroxy radical (RO2) dimer association products. The ULVOC yield of α-pinene in the presence of NO3 is one-fifth of that resulting from ozone chemistry alone. Even trace amounts of NO3 radicals, at sub-parts per trillion level, suppress the NPF rate by a factor of 4. Ambient observations further confirm that when NO3 chemistry is involved, monoterpene NPF is completely turned off. Our results explain the frequent absence of nocturnal biogenic NPF in monoterpene (α-pinene)-rich environments.

LncRNA MEG3 suppresses erastin-induced ferroptosis of chondrocytes via regulating miR-885-5p/SLC7A11 axis.

BACKGROUND: Ferroptosis is involved in osteoarthritis development; however, the roles of long noncoding RNAs (lncRNAs), including lncRNA MEG3, in the regulation of ferroptosis in osteoarthritis are still unclear. METHODS: In this study, qRT‒PCR and Western blotting assays were used to detect the expression of lncRNA MEG3, miR-885-5p, SLC7A11 and GPX4; MDA and CCK-8 assays were applied to analyse cellular MDA levels and cell viability, respectively. RESULT: Erastin elevated cellular MDA levels and decreased the viability of chondrocytes and the erastin-induced decline in cell viability was reversed by a ferroptosis inhibitor (ferrostatin-1). Erastin downregulated lncRNA MEG3, SLC7A11 and GPX4 and upregulated miR-885-5p. Silencing of lncRNA MEG3 increased miR-885-5p and downregulated SLC7A11 and GPX4 and further sensitized chondrocytes to erastin-induced ferroptosis. In contrast, overexpression of lncRNA MEG3 had opposite effects. Dual luciferase assays confirmed binding between lncRNA MEG3 and miR-885-5p and between miR-885-5p and the 3'UTR of SLC7A11. In the synovial fluids from patients with osteoarthritis compared with synovial fluids from normal controls, the RNA levels of lncRNA MEG3 and SLC7A11 were decreased and the miR-885-5p expression level was increased. CONCLUSION: Our findings indicated that lncRNA MEG3 overexpression alleviated ferroptosis in chondrocytes by affecting the miR-885-5p/SLC7A11 signalling pathway.

The Accuracy and Reliability of Automated Oscillometric Measurement of Ankle-Brachial Index in the Diagnosis of Peripheral Artery Disease.

BACKGROUND: Comparing the accuracy and reliability of ankle-brachial index (ABI) measured by an oscillometric device with the Doppler method in peripheral arterial disease (PAD). METHODS: 122 patients admitted to the department of interventional radiology with PAD were studied. ABI was measured with the 2 methods in random order. After excluding the inconclusive results, Doppler ABIs were compared with the oscillometric ABIs in each limb, the reliability was evaluated by intraclass correlation coefficient (ICC), and the accuracy and consistency were assessed by receiver operating characteristic curves and Bland-Altman method. RESULTS: In 122 patients (244 legs), 27 legs got inconclusive oscillometric results, 4 legs got inconclusive oscillometric and inconclusive dorsalis pedis artery Doppler results, 2 legs had oscillometric cuff pressure intolerance. Using Doppler ABI <0.9 as a diagnostic threshold, compared with the high Doppler ABI, oscillometric method had a sensitivity of 57.81%, a specificity of 95.18%, the ICC was 0.626 (95% confidence interval [CI]: 0.536-0.701), Bland-Altman method showed 11/211 (5.21%) difference points outside the 95% limits of agreement. Compared with the low Doppler ABI, oscillometric method had a sensitivity of 50.66%, a specificity of 98.31%, the ICC was 0.541(95% CI: 0.483-0.630), Bland-Altman method showed 11/211 (5.21%) difference points outside the 95% limits of agreement. Using 1.00 as the diagnostic threshold and considering error oscillometric results as abnormal ABIs, the sensitivity improved to 88.05% with high Doppler ABI and 81.42% with the low. CONCLUSIONS: The accuracy and reliability of oscillometric ABI in patients with PAD is unsatisfied, which makes it not suitable as an alternative method in clinic disease assessment. Using 1.0 as the ABI oscillometric threshold for PAD diagnosis can improve the diagnostic value.

Wave aberration corrections in PSF ellipticity measurements of astronomical telescopes using a multi-objective optimization.

The weak gravitational lensing (WGL) produces a shear effect on the observed galactic ellipticity that is much smaller than the endogenous ellipticity of the galaxy itself. Achieving such a high-level astronomical observation requires the superior performance of telescopes. To ensure the optical properties of telescopes to be competent in WGL detections, it is very necessary to measure point spread function (PSF) ellipticity of telescopes in labs. In this paper, a 2 m off-axis telescope that would be used to detect WGL in space is analyzed and studied. A collimator whose aperture is 2 m has been built to measure PSF ellipticity of the telescope. The wave aberrations of the collimator are roughly equal to those of the telescope, so they are important systematical errors and must be removed. However, it is difficult to precisely measure the wave aberrations of optical systems that have large apertures and long focal lengths. In addition, a 2 m flat mirror, which is indispensable to measure wave aberrations of optical systems, has significant surface errors. In this paper, a multi-objective optimization method is proposed to eliminate the effects of wave aberrations on PSF ellipticity measurements of the telescope. By constructing an equivalent model, the wave aberrations from collimators and flat mirrors can be corrected so that PSF ellipticity measurement error is reduced to within 0.01. Measurement accuracy of PSF ellipticity of the telescopes can be improved significantly.

Direct field evidence of autocatalytic iodine release from atmospheric aerosol.

Reactive iodine plays a key role in determining the oxidation capacity, or cleansing capacity, of the atmosphere in addition to being implicated in the formation of new particles in the marine boundary layer. The postulation that heterogeneous cycling of reactive iodine on aerosols may significantly influence the lifetime of ozone in the troposphere not only remains poorly understood but also heretofore has never been observed or quantified in the field. Here, we report direct ambient observations of hypoiodous acid (HOI) and heterogeneous recycling of interhalogen product species (i.e., iodine monochloride [ICl] and iodine monobromide [IBr]) in a midlatitude coastal environment. Significant levels of ICl and IBr with mean daily maxima of 4.3 and 3.0 parts per trillion by volume (1-min average), respectively, have been observed throughout the campaign. We show that the heterogeneous reaction of HOI on marine aerosol and subsequent production of iodine interhalogens are much faster than previously thought. These results indicate that the fast formation of iodine interhalogens, together with their rapid photolysis, results in more efficient recycling of atomic iodine than currently considered in models. Photolysis of the observed ICl and IBr leads to a 32% increase in the daytime average of atomic iodine production rate, thereby enhancing the average daytime iodine-catalyzed ozone loss rate by 10 to 20%. Our findings provide direct field evidence that the autocatalytic mechanism of iodine release from marine aerosol is important in the atmosphere and can have significant impacts on atmospheric oxidation capacity.

COF-SiO2@Fe3O4 Composite for Magnetic Solid-Phase Extraction of Pyrethroid Pesticides in Vegetables.

Pyrethroid pesticides (PYRs) have found widespread application in agriculture for the protection of fruit and vegetable crops. Nonetheless, excessive usage or improper application may allow the residues to exceed the safe limits and pose a threat to consumer safety. Thus, there is an urgent need to develop efficient technologies for the elimination or trace detection of PYRs from vegetables. Here, a simple and efficient magnetic solid-phase extraction (MSPE) strategy was developed for the simultaneous purification and enrichment of five PYRs in vegetables, employing the magnetic covalent organic framework nanomaterial COF-SiO2@Fe3O4 as an adsorbent. COF-SiO2@Fe3O4 was prepared by a straightforward solvothermal method, using Fe3O4 as a magnetic core and benzidine and 3,3,5,5-tetraaldehyde biphenyl as the two building units. COF-SiO2@Fe3O4 could effectively capture the targeted PYRs by virtue of its abundant π-electron system and hydroxyl groups. The impact of various experimental parameters on the extraction efficiency was investigated to optimize the MSPE conditions, including the adsorbent amount, extraction time, elution solvent type and elution time. Subsequently, method validation was conducted under the optimal conditions in conjunction with gas chromatography-mass spectrometry (GC-MS). Within the range of 5.00-100 µg·kg-1 (1.00-100 µg·kg-1 for bifenthrin and 2.5-100 µg·kg-1 for fenpropathrin), the five PYRs exhibited a strong linear relationship, with determination coefficients ranging from 0.9990 to 0.9997. The limits of detection (LODs) were 0.3-1.5 µg·kg-1, and the limits of quantification (LOQs) were 0.9-4.5 µg·kg-1. The recoveries were 80.2-116.7% with relative standard deviations (RSDs) below 7.0%. Finally, COF-SiO2@Fe3O4, NH2-SiO2@Fe3O4 and Fe3O4 were compared as MSPE adsorbents for PYRs. The results indicated that COF-SiO2@Fe3O4 was an efficient and rapid selective adsorbent for PYRs. This method holds promise for the determination of PYRs in real samples.

Impact of demographic factors on corneal donor recovery.

PURPOSE: Death-to-preservation time (DTP) is a commonly reported, but infrequently studied, measure of efficiency for the corneal tissue procurement process and is a key screening component for corneal tissue suitability for transplantation. It is unknown whether demographic factors such as race, age, or gender may affect DTP. METHODS: This retrospective cross-sectional study included all deceased-donor eye tissue collected by CorneaGen Eye Banks between June 1, 2012 and June 30, 2016. Exposure variables of race, age, and gender were independently analyzed with the outcome variable, DTP, using three simple linear regression analyzes. Associations were then confirmed by a multiple linear regression analysis within a single model. RESULTS: A total of 24,138 unique donors were identified from 48,207 donor eyes. Simple linear regression analysis showed that relative to White donors, Black and Hispanic donors were associated with a 2.40 h (95% CI 2.07-2.74 h, p < 0.001) and 2.48 h (95% CI 2.15-2.80 h, p < 0.001) longer mean DTP, respectively. DTP decreased with increasing age, at a rate of 30 min per every 10 years (95% CI 27-33 min, p < 0.001). Male donors were associated with a 35 min (95% CI 26-44 min, p < 0.001) longer DTP relative to female donors. A multiple linear regression confirmed the results of the three simple linear regressions. CONCLUSIONS: In a large cohort of corneal donors, non-White race, younger age, and male gender were associated with longer DTP.

Orthogonal Postsynthetic Copolymerization of Hydrogen-Bonded Organic Frameworks into a PolyHOF Membrane.

Hydrogen-bonded organic frameworks (HOFs) have shown promise in various fields; however, the construction of HOF/polymer hybrid membranes that can maintain both structural and functional integrity remains challenging. In this study, we here fabricated a new HOF (HOF-50) with reserved polymerizable allyl group via charge-assisted H-bonds between the carboxylate anion and amidinium, and subsequently copolymerized the HOF with monomers to construct a covalently bonded HOF/polymer hybrid (polyHOF) membrane. The resulting polyHOF membrane not only exhibits customizable mechanical properties and extreme stability, but also shows an exceptional ratiometric luminescent temperature-sensing function with very high sensitivity and visibility even when the lanthanide content is two orders of magnitude lower than that of the reported mixed-lanthanide metal-organic frameworks (MOFs) and lanthanide-doped covalent organic frameworks (COFs). This orthogonal postsynthesis copolymerization strategy may provide a general approach for preparing covalently connected HOF/polymer hybrid membranes for diverse applications.

Identification of immune-associated signatures and potential therapeutic targets for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) comprises a heterogeneous group of diseases with diverse aetiologies. It is characterized by increased pulmonary arterial pressure and right ventricular (RV) failure without specific drugs for treatment. Emerging evidence suggests that inflammation and autoimmune disorders are common features across all PAH phenotypes. This provides a novel idea to explore the characteristics of immunological disorders in PAH and identify immune-related genes or biomarkers for specific anti-remodelling regimens. In this study, we integrated three gene expression profiles and performed Gene Ontology (GO) and KEGG pathway analysis. CIBERSORT was utilized to estimate the abundance of tissue-infiltrating immune cells in PAH. The PPI network and machine learning were constructed to identify immune-related hub genes and then evaluate the relationship between hub genes and differential immune cells using ImmucellAI. Additionally, we implemented molecular docking to screen potential small-molecule compounds based on the obtained genes. Our findings demonstrated the density and distribution of infiltrating CD4 T cells in PAH and identified four immune-related genes (ROCK2, ATHL1, HSP90AA1 and ACTR2) as potential targets. We also listed 20 promising molecules, including TDI01953, pemetrexed acid and radotinib, for PAH treatment. These results provide a promising avenue for further research into immunological disorders in PAH and potential novel therapeutic targets.

Targeting ferroptosis attenuates podocytes injury and delays tubulointerstitial fibrosis in focal segmental glomerulosclerosis.

Ferroptosis is a non-apoptotic form of cell death, involved in chronic kidney diseases (CKD) and acute kidney injury (AKI), so far, the role of ferroptosis in focal segmental glomerulosclerosis (FSGS) remains largely unknown. We aimed to investigate the role of ferroptosis in FSGS, in this study, we found the reduced expression of GPX4 in podocytes, as well as tubular epithelial cells (TECs), from patients with FSGS. Treatment with ferrostatin-1 (Fer-1), a potent and selective ferroptosis inhibitor, significantly reduced proteinuria, prevented glomerulosclerosis, attenuated podocyte injury in ADR-induced FSGS murine model. As expected, ADR treatment caused downregulation of GPX4 in human podocytes, treatment with Fer-1 greatly blocked the downregulation of GPX4, restored the GSH level and attenuated cell death. Furthermore, Fer-1 treatment greatly delayed the development of tubulointerstitial fibrosis in ADR-induced FSGS murine model. Taken together, ferroptosis is involved in the pathogenesis of FSGS, targeting ferroptosis is a promising therapeutic option for patients with FSGS.

Synthesis of Ultrathin Topological Insulator ß-Ag2 Te and Ag2 Te/WSe2 -Based High-Performance Photodetector.

ß-Ag2 Te has attracted considerable attention in the application of electronics and optoelectronics due to its narrow bandgap, high mobility, and topological insulator properties. However, it remains a significant challenge to synthesize 2D Ag2 Te because of the non-layered structure of Ag2 Te. Herein, the synthesis of large-size, ultrathin single crystal topological insulator 2D Ag2 Te via the van der Waals epitaxial method for the first time is reported. The 2D Ag2 Te crystal exhibits p-type conduction behavior with high carrier mobility of 3336 cm2 V-1 s-1 at room temperature. Taking advantage of the high mobility and perfect electron structure of Ag2 Te, the Ag2 Te/WSe2 heterojunctions are fabricated via mechanical stacking and show an ultrahigh rectification ratio of 2 × 105 . Ag2 Te/WSe2 photodetector also exhibits self-driven properties with a fast response speed (40 µs/60 µs) in the near-infrared region. High responsivity (219 mA W-1 ) and light ON/OFF ratio of 6 × 105 are obtained under the photovoltaic mode. The overall performance of the Ag2 Te/WSe2 photodetector is significantly competitive among all reported 2D photodetectors. These results indicate that 2D Ag2 Te is a promising candidate for future electronic and optoelectronic applications.

The Controllable Synthesis of High-Quality Two-Dimensional Iron Sulfide with Specific Phases.

2D Fe-chalcogenides have drawn significant attention due to their unique structural phases and distinct properties in exploring magnetism and superconductivity. However, it remains a significant challenge to synthesize 2D Fe-chalcogenides with specific phases in a controllable manner since Fe-chalcogenides have multiple phases. Herein, a molecular sieve-assisted strategy is reported for synthesizing ultrathin 2D iron sulfide on substrates via the chemical vapor deposition method. Using a molecular sieve and tuning growth temperatures to control the partial pressures of precursor concentrations, hexagonal FeS, tetragonal FeS, and non-stoichiometric Fe7 S8 nanoflakes can be precisely synthesized. The 2D h-FeS, t-FeS, and Fe7 S8 have high conductivities of 5.4 × 105 S m-1 , 5.8 × 105 S m-1 , and 1.9 × 106 S m-1 . 2D tetragonal FeS shows a superconducting transition at 4 K. The spin reorientation at ≈30 K on the non-stoichiometric Fe7 S8 nanoflakes with ferrimagnetism up to room temperature has also been observed. The controllable synthesis of various phases of 2D iron sulfide may provide a route for synthesizing other 2D compounds with various phases.

Potent antitumor efficacy of human dental pulp stem cells armed with YSCH-01 oncolytic adenovirus.

BACKGROUND: Systemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug delivery due to their excellent tumor tropism, immunosuppressive modulatory effects, and paracrine effects. However, the potential of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy has not been investigated yet. METHODS: The stemness of hDPSCs was characterized by FACS analysis and Alizarin red staining, Oil Red O staining, and immunofluorescence assays. The biological fitness of hDPSCs loaded with oncolytic adenovirus YSCH-01 was confirmed by virus infection with different dosages and cell viability CCK-8 assays. Additionally, the expression of CAR receptor in hDPSCs was detected by qPCR assay. Tumor tropism of hDPSC loaded with YSCH-01 in vitro and in vivo was investigated by Transwell assays and living tumor-bearing mice imaging technology and immunohistochemistry, Panoramic scanning of frozen section slices assay analysis. Furthermore, the antitumor efficacy was observed through the different routes of YSCH-01/hPDSCs administration in SW780 and SCC152 xenograft models. The direct tumor cell-killing effect of YSCH-01/hDPSCs in the co-culture system was studied, and the supernatant of YSCH-01/hDPSCs inhibited cell growth was further analyzed by CCK-8 assays. RESULTS: hDPSCs were found to be susceptible to infection by a novel oncolytic adenovirus named YSCH-01 and were capable of transporting this virus to tumor sites at 1000 VP/cell infectious dosage in vitro and in vivo. Moreover, it was discovered that intraperitoneal injection of hDPSCs loaded with oncolytic adenovirus YSCH-01 exhibited potential anti-tumor effects in both SW780 and SCC152 xenograft models. The crucial role played by the supernatant secretome derived from hDPSCs loaded with YSCH-01 significantly exerted a specific anti-tumor effect without toxicity for normal cells, in both an active oncolytic virus and an exogenous protein-independent manner. Furthermore, the use of hDPSCs as a cell carrier significantly reduced the required dosage of virus delivery in vivo compared to other methods. CONCLUSIONS: These findings highlight the promising clinical potential of hDPSCs as a novel cell carrier in the field of oncolytic virus-based anti-cancer therapy.

Genome instability-related LINC02577, LINC01133 and AC107464.2 are lncRNA prognostic markers correlated with immune microenvironment in pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a leading cause of malignancy-related deaths worldwide, and the efficacy of immunotherapy on PAAD is limited. Studies report that long non-coding RNAs (lncRNAs) play an important role in modulating genomic instability and immunotherapy. However, the identification of genome instability-related lncRNAs and their clinical significance has not been investigated in PAAD. METHODS: The current study developed a computational framework for mutation hypothesis based on lncRNA expression profile and somatic mutation spectrum in pancreatic adenocarcinoma genome. We explored the potential of GInLncRNAs(genome instability-related lncRNAs) through co-expression analysis and function enrichment analysis. We further analyzed GInLncRNAs by Cox regression and used the results to construct a prognostic lncRNA signature. Finally, we analyzed the relationship between GILncSig (genomic instability derived 3-lncRNA signature) and immunotherapy. RESULTS: A GILncSig was developed using bioinformatics analyses. It could divide patients into high-risk and low-risk groups, and there was a significant difference in OS between the two groups. In addition, GILncSig was associated with genome mutation rate in pancreatic adenocarcinoma, indicating its potential value as a marker for genomic instability. The GILncSig accurately grouped wild type patients of KRAS into two risk groups. The prognosis of the low-risk group was significantly improved. GILncSig was significantly correlated with the level of immune cell infiltration and immune checkpoint. CONCLUSIONS: In summary, the current study provides a basis for further studies on the role of lncRNA in genomic instability and immunotherapy. The study provides a novel method for identification of cancer biomarkers related to genomic instability and immunotherapy.