Unintentional emissions of polychlorinated naphthalenes in China: Sources, composition, and historical trends.

Polychlorinated naphthalenes (PCNs) are detrimental to human health and the environment. With the commercial production of PCNs banned, unintentional releases have emerged as a significant environmental source. However, relevant information is still scarce. In this study, provincial emissions for eight PCNs homologues from 37 sources in the Chinese mainland during the period of 1960-2019 were estimated based on a source-specific and time-varying emission factor database. The results showed that the total PCNs emissions in 2019 reached 757.0 kg with Hebei ranked at the top among all the provinces and iron & steel industry as the biggest source. Low-chlorinated PCNs comprised 90% of emissions by mass, while highly chlorinated PCNs dominated in terms of toxicity, highlighting divergent priorities for mitigating emissions and safeguarding human health. The emissions showed an overall upward trend from 1960 to 2019 driven by emission increase from iron & steel industry in terms of source, and from North China and East China in terms of geographic area. Per-capita emissions followed an inverted U-shaped environmental Kuznets curve while emission intensities decreased with increasing per-capita Gross Domestic Product (GDP) following a nearly linear pattern when log-transformed.

CATSPER2 and SPEF2 are potential molecular markers for boar sperm quality: a population association study.

PURPOSE: This study investigates the role of cation channel sperm associated 2 (CATSPER2) and sperm flagella 2 (SPEF2) genes in boar spermatogenesis, focusing on their association with sperm quality traits in boars. METHODS: Utilizing targeted next-generation sequencing, we identified and genotyped two polymorphisms in CATSPER2 (rs341636020G > A, rs326912346G > T) and three variants in SPEF2 (rs320839956A > G, rs334209514C > A, rs325319860C > T) across three boar breeds (Duroc, n = 181; Landrace, n = 87; Large White, n = 52). RESULTS: Our results confirmed the presence of the specified single nucleotide polymorphisms (SNPs), adhering to association study criteria. In CATSPER2, significant associations were detected between rs341636020G > A and sperm curvilinear velocity (VCL) in Duroc and Landrace boars, and between rs326912346G > T and straight velocity (VSL) in Duroc and Large White boars. For SPEF2, rs320839956A > G was significantly linked to sperm viability in Duroc and Landrace and to sperm concentration (SCON) in Large White boars. Additionally, rs334209514C > A and rs325319860C > T showed significant associations with SCON and VCL respectively, in Doruc and Landrace boars. CONCLUSIONS: Overall, our findings suggest that CATSPER2 and SPEF2 SNPs significantly impact boar sperm quality traits. These genetic markers have the potential to enhance boar fertility through selective breeding programs, contributing to the optimization of reproductive performance in pigs.

A multifunctional DNA tetrahedron for imaging, gene therapy, and chemotherapy-phototherapy combination: Binding affinity and anticancer activity.

Imaging, silencing cancer-related microRNA, and chemotherapy-phototherapy (CTPT) combination therapy are crucial for cancer diagnosis and drug resistance overcoming. In this study, we designed a multifunctional DNA tetrahedron (MB-MUC1-TD) for the targeted delivery of combined daunorubicin (DAU) + toluidine blue O (TBO). The detection limit of miRNA-21 was determined to be 0.91 nM. The intercalation of DAU and TBO into MB-MUC1-TD was proved by spectroscopic and calorimetric methods. The thermodynamic parameters for the interactions of DAU and/or TBO with MB-MUC1-TD confirmed high drug loading. The first addition of TBO in the ternary system achieved a higher loading of both drugs and a more stable complex structure. Deoxyribonuclease I (DNase I) accelerated the release of DAU and/or TBO loaded in MB-MUC1-TD. Confocal laser scanning microscope demonstrated that MB-MUC1-TD exhibited good imaging ability for miRNA-21 to accurately identify cancer cells, and DAU/TBO was predominantly distributed within the nucleus of cancer cells. In vitro cytotoxicity showed better gene therapy efficacy of MB on MCF-7 cells, better biocompatibility of loaded DAU and TBO on LO2 cells, and stronger synergistic cytotoxicity of DAU + TBO on MCF-7/ADR cells. This study may establish a theoretical foundation for co-loading CTPT combination drugs based on multifunctional DNA nanostructures.

Revealing the performance of aerotolerant anodes for electroactive nitrification/denitrification and current production under coexistence of oxygen and nitrate conditions.

The coexistence of oxygen and/or nitrate at anode usually affects the biofilm activities of traditional anaerobic anode, thereby deteriorating wastewater treatment performance of microbial fuel cells (MFCs). Improving the aerotolerant responses of anode biofilms is a challenge for field application. In this study, we report that using the electroactive nitrifying/denitrifying inoculum and air-cathode expansion could fabricate the aerotolerant anode biofilms (AAB) under affordable nitrate stress (90 ± 5 mg/L). The highest average removal efficiencies were 99% for chemical oxygen demand (COD), NH4+-N and total nitrogen. The highest average current output of 0.69 mA and power density of 290 mW/m2 were obtained. The average current was confirmed to be reduced 10%-78% but the power density remained almost stable except the quart-air-cathodes MFC by increasing dissolved oxygen concentration with expansion of the air-cathode area. The higher oxygen concentration also contributed to oxidation of ammonium through electroactive autotrophic nitrification. The facultative anaerobic bacteria including Thauera, Microsillaceae, Shinella, Blastocatellaceae, Rhodobacter, Comamonadaceae, Caldilineaceae were enriched, which forms the AAB to remove nitrogen and produce current. Therefore, an easy-to-use method to fabricate AAB is evaluated to realize practical applications of MFCs in wastewater treatment.

Single-cell RNA-sequencing reveals anti-tumor potency of CD56+ NK cells and CD8+ T cells in humanized mice via PD-1 and TIGIT co-targeting.

In solid tumors, the exhaustion of natural killer (NK) cells and cytotoxic T cells in the immunosuppressive tumor microenvironment poses challenges for effective tumor control. Conventional humanized mouse models of hepatocellular carcinoma-patient-derived xenografts (HCC-PDX) encounter limitations in NK-cell infiltration, hindering studies on NK-cell immunobiology. Here, we introduce an improved humanized mouse model with restored NK-cell reconstitution and infiltration in HCC-PDX, coupled with single-cell RNA-sequencing (scRNA-seq) to identify potential anti-HCC treatments. A single administration of adeno-associated virus carrying human interleukin-15 reinstated persistent NK-cell reconstitution and infiltration in HCC-PDX in humanized mice. ScRNA-seq revealed NK-cell and T-cell subpopulations with heightened PDCD1 and TIGIT levels. Notably, combination therapy with anti-PD-1 and anti-TIGIT antibodies alleviated HCC burden in humanized mice, demonstrating NK cell-dependent efficacy. Bulk-RNA sequencing analysis also revealed significant alterations in the tumor transcriptome that may contribute to further resistance after combination therapy, warranting further investigations. As an emerging strategy, ongoing clinical trials with anti-PD-1 and anti-TIGIT antibodies provide limited data. The improved humanized mouse HCC-PDX model not only sheds light on the pivotal role of NK cells but also serves as a robust platform for evaluating safety and anti-tumor efficacy of combination therapies and other potential regimens, complementing clinical insights.

TRIB3 knockdown increases the sensitivity of clear cell renal cell carcinoma to sunitinib by inducing ferroptosis.

Sunitinib resistance presents a significant challenge in the treatment of clear cell renal cell carcinoma (ccRCC). The role of TRIB3, a newly identified oncogene, in tumor drug resistance has been widely studied. However, the mechanism by which TRIB3 contributes to sunitinib resistance in ccRCC has not been previously explored. This study aimed to investigate the mechanism through which TRIB3 regulates ferroptosis to increase the susceptibility of ccRCC to sunitinib treatment. Bioinformatics analysis and experimental validation revealed that TRIB3 is significantly upregulated in ccRCC tissues and is associated with poor prognosis. Knockdown of TRIB3 using siRNA transfection inhibited the proliferation and migration of ccRCC cells and induced ferroptosis. Following sunitinib treatment, TRIB3 knockdown increased cell sensitivity to sunitinib, enhanced the suppressive impact of sunitinib, and augmented sunitinib-induced ferroptosis. This study demonstrated that TRIB3 knockdown induces ferroptosis by targeting the SLC7A11/GPX4 pathway and enhances therapeutic efficacy of sunitinib for ccRCC, providing new insights and potential strategies to overcome the challenge of sunitinib resistance in ccRCC.

Ambroxol hydrochloride spray (Luo Runchang®) in the treatment of acute respiratory infectious diseases: a prospective, multicenter, open label, randomized controlled study.

Purpose: Cough and sputum are the most common clinical symptoms of acute respiratory tract infection. Ambroxol is a mucolytic expectorant commonly used in clinical practice. This study aimed to evaluate the efficacy, safety, and compliance of ambroxol hydrochloride spray (Luo Runchang ®) for the treatment of acute respiratory tract diseases in children. Methods: This was a multicenter, open-labeled, randomized controlled study. The experimental group received ambroxol hydrochloride oral sprays, and the control group received ambroxol hydrochloride oral solutions. The primary endpoint was the change in cough symptom scores from baseline. Secondary endpoints include changes in cough severity score, quality of life, adherence, and adverse events. Results: A total of 154 subjects were randomized and included in the analysis. The mean change of total cough symptom score of the spray group at the end of treatment was -4.7 (1.54) compared to -4.2 (1.62) in the solution group (P = 0.0005). The mean change of cough severity score was -5.7 (2.09) in the spray group compared to -5.2(2.04) in the solution group (P = 0.012). Quality of life scores significantly improved in the spray group (P < 0.0001) compared to the oral solution group. Medication adherence markers were significantly better in the spray group (P < 0.0001). The incidence of adverse events in the experimental group (1.33%) was lower than that in the control group (6.33%), but the difference between the groups was not statistically significant. Conclusion: Ambroxol hydrochloride spray significantly improved cough symptom score, cough severity score, and quality of life score compared to ambroxol hydrochloride oral solution.

Influence of deposition conditions on performance of Ni3S2 as the bifunctional electrocatalyst in alkaline solutions by galvanostatic deposition.

The electrodeposition method is a popular synthesis method due to its low cost, simplicity, and short synthesis time. In addition, this synthesis route results in the preparation of a self-supporting electrocatalyst, which eliminates the use of binders and ultimately facilitates the durability as well as the activity of the catalyst. In this work, a series of Ni3S2/Ni mesh electrodes are prepared by galvanostatic deposition at different deposition current densities and times. The morphology, microstructure, and elemental composition distribution of these obtained electrodes are characterized, and the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performance of the series of Ni3S2/Ni meshes are tested. The results show that the Ni3S2/Ni mesh electrodes electrodeposited at 30 mA cm-2 for 1200 s have superior electrochemical performance for HER and OER. The overpotentials of Ni3S2/Ni mesh 30 mA cm-2-1200 s are 236 and 244 mV for HER and OER, respectively, at a current density of 10 mA cm-2. In addition, the Tafel slopes for HER and OER are 113 mV dec-1 and 176 mV dec-1, respectively. This research provides some valuable insights into the use of the electrodeposition method for the fabrication of electrocatalysts.

Characterization and mechanism of phthalic acid esters bioaccumulation in dominant mangrove fish at different habitats in the mangrove ecosystem of Dongzhai Harbor, China.

With the wide application of phthalic acid esters (PAEs) in the manufacturing of plastic products, a large number of PAEs were discharged into marine ecosystem and accumulated in fish, which has posed a serious threat to marine ecological environment and fishery resources. However, the bioaccumulation of PAEs in fish in mangrove ecosystem, the most productive marine ecosystem, has not been well characterized. In this study, dominant fish and their potential food sources (including particulate organic matter (POM), sedimentary organic matter (SOM), Metapenaeus ensis (Shrimp) and Oreochromis (Ore)) were collected from Dongzhai Harbor, a typical mangrove ecosystem. The concentrations of nine PAEs in fish and their potential food sources were determined. Then stable nitrogen and carbon isotope analysis, combined with a new Bayesian mixing model (MixSIMMR) was used to quantify the diet compositions of fish and elucidate the effect of dietary habit on PAEs bioaccumulation in fish. The results indicated that the median concentration of ∑9PAEs in fish was 1119 µg/kg ww, positioning it at a moderate to low level in comparison to other regions. di-n-butyl phthalate (DBP) and diisononyl ortho-phthalate (DINP) were the dominant PAEs in fish. The PAEs concentration in demersal fish was significantly higher than that of pelagic fish, which may be attributed to the substantial contributions of shrimp (28.5 %) and POM (25.3 %) to the diet of demersal fish. This study provided new insights on the bioaccumulation of PAEs in dominant mangrove fish and confirmed that habitat preferences and food sources could significantly influence the bioaccumulation of PAEs in fish.

Analysis of the therapeutic effect of pestle needle & EEG biofeedback and methylphenidate in the treatment of attention deficit and hyperactivity disorder.

OBJECTIVE: This research aimed to analyze the therapeutic effect of pestle needle combined with electroencephalogram (EEG) biofeedback and methylphenidate in the treatment of attention deficit and hyperactivity disorder (ADHD) in children. METHODS: Seventy-eight children with ADHD were selected and randomized into a control group and an observation group (n = 39). The control group received EEG biofeedback and methylphenidate treatment, while the observation group received pestle needle therapy on this basis. Both groups received continuous treatment for 3 months. The clinical efficacy, scores of Conners Parents Symptom Questionnaire (PSQ), Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), Pittsburgh Sleep Quality Index (PSQI), EEG θ/ß changes in values, serum indicators such as adrenocorticotropic hormone (ACTH) and cortisol (CORT), and incidence of adverse reactions were compared in two groups. RESULTS: The total effective rate of the observation group was 92.31% (36/39), which was higher than the control group's 69.23% (27/39) (P < 0.05). After treatment, reduced PSQ scores, PSQI scores, EEG θ/ß values, and ACTH levels while elevated IVA-CPT and CORT levels were observed in both groups; the observation group had the best improvement effect after treatment (P < 0.05). CONCLUSION: Pestle needle combined with EEG biofeedback and methylphenidate in the treatment of ADHD children can elevate the IVA-CPT score, improve EEG waves, sleep quality, regulate serum indicators such as ACTH and CORT, reduce behavioral problem scores, and have high efficacy and safety.

Spatially Covariant Image Registration With Text Prompts.

Medical images are often characterized by their structured anatomical representations and spatially inhomogeneous contrasts. Leveraging anatomical priors in neural networks can greatly enhance their utility in resource-constrained clinical settings. Prior research has harnessed such information for image segmentation, yet progress in deformable image registration has been modest. Our work introduces textSCF, a novel method that integrates spatially covariant filters and textual anatomical prompts encoded by visual-language models, to fill this gap. This approach optimizes an implicit function that correlates text embeddings of anatomical regions to filter weights. textSCF not only boosts computational efficiency but can also retain or improve registration accuracy. By capturing the contextual interplay between anatomical regions, it offers impressive interregional transferability and the ability to preserve structural discontinuities during registration. textSCF's performance has been rigorously tested on intersubject brain magnetic resonance imaging (MRI) and abdominal computerized tomography (CT) registration tasks, outperforming existing state-of-the-art models in the MICCAI Learn2Reg 2021 challenge and leading the leaderboard. In abdominal registrations, textSCF's larger model variant improved the Dice score by 11.3% over the second-best model, while its smaller variant maintained similar accuracy but with an 89.13% reduction in network parameters and a 98.34% decrease in computational operations.

Microplastic pollution in tropical coral reef ecosystems from the coastal South China Sea and their impacts on corals in situ.

Coral reefs possess extremely high ecological value in tropical and subtropical waters worldwide. Microplastics as emerging and pervasive pollutants pose a great threat to the health of coral ecosystems. However, in situ studies on microplastics pollution and its impacts in coral ecosystems globally are limited. The occurrence characteristics of microplastics in the environment mediums and reef-dwelling organisms were investigated in coral reef areas from the southern Hainan Island, and the impacts of microplastics on corals in situ were evaluated in this study. Average microplastics abundance was 9.48 items L-1 in seawater, 190.00 items kg-1 in sediment, 0.36 items g-1 in coral, 1.50 items g-1 in shellfish, 0.48 items g-1 in fish gill, and 1.71 items g-1 in fish gastrointestinal tract. The prevalent microplastics in the above samples were characterized as being less than 1000 µm in size, fibrous, and transparent, with predominant polymer types as polyethylene terephthalate, polypropylene, polyethylene, and rayon. The microplastic enrichment capacity of different corals varied (Pocillopora > Acropora > Sinularia). Notably, microplastics were more abundant on the surface of corals compared to their interiors, with distinct characteristics observed, including larger-sized (>500 µm) and fiber-shaped polyethylene terephthalate microplastics on the surface and smaller-sized (20-200 µm) fragmented polyethylene microplastics within coral interiors. Furthermore, the investigation showed species-specific impacts of microplastics on corals in situ, including photosynthetic activity of photosymbionts and antioxidant and immune activities of corals. Furthermore, the ecological risks of microplastics were minor across most environmental media in the studied areas, with exceptions in the bottom seawater and surface sediment of YLW, which exhibited extreme and medium risk levels, respectively. Coral risk levels were generally medium, except for dangerous levels in DDH and high levels in LHT. The potential sources of microplastics in the marginal reefs of southern Hainan Island were primarily tourism, residential, and fishing activities.

Intelligent response micelles with high andrographolide loading for the effective treatment of atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory disease which associated with a maladaptive immune response driven by macrophages. In the development of AS, macrophages have gradually become new therapeutic targets due to their involvement in numerous inflammatory-related pathological processes in AS. However, despite significant breakthroughs in the development of macrophages targeting nanocarriers, unsatisfactory drug loading, and inexact drug release limited the development of nano-therapy. Therefore, developing a high drug-loading nanocarrier that can accurately release drugs at AS lesions is quite essential. Herein, we optimized double moieties coupled mPEG-PLA copolymer micelles via phenylboronic acid (PBA)-terminated on the hydrophobic chain and cRGD coupled in hydrophilic chain to enhance AS therapy. The micelles loaded with andrographolide (AND) exhibited advanced drug loading capacity, as PBA could form a reversible boronic ester with AND at physiological pH. The cRGD-modified AND-loaded micelles (RPPPA) could be efficaciously internalized by macrophages and efficiently prevent macrophages from differentiating to foam cells. After intravenous administration, RPPPA could accumulate in plaques and exert therapeutic effects. The optimistic therapeutic results of atherosclerosis were shown in RPPPA, included the fewer plaques, a smaller necrotic core, a more stabilized fibrous cap, and lower macrophages and MMP-9, compared with the control group. To sum up, the proposed encouraging therapy can contribute to high drug loading, exact target, and precise drug release as well as reduce inflammation for AS treatment.

The root strategy of the C4 grasses tends to be 'do-it-yourself'.

Root resource acquisition strategies play a crucial role in understanding plant water uptake and drought adaptation. However, the interrelationships among mycorrhizal associations, root hair development, and fine root strategies, as well as the disparities between C3 and C4 grasses, remain largely unknown. A pot experiment was conducted to determine leaf gas exchange, root morphology, root hair, mycorrhizal fungi, and biomass allocation of three C4 grasses and four C3 grasses, common species of grasslands in Northeast China, under the control and drought conditions. Compared to the C3 grasses, the C4 grasses increased specific surface area by decreasing tissue density, yet exhibited root hair factor at only 21 % of the C3 grasses. Under the drought conditions, the C4 grasses exhibited more intense and extensive adjustments in root traits, characterized by shifts toward a more conservative morphology with increased root diameter and tissue density, as well as reduced mycorrhizal colonization rates. These adaptations led to a decrease in root absorptive function, which was compensated in the C4 grasses by greater root biomass partitioning and root hair factor. Variances in root strategies between plants functional groups were closely related to leaf photosynthetic rate, water and nitrogen use efficiency. We observed that the C4 grasses prefer direct acquisition of soil resources through the fine root pathway over the root hair or mycorrhizal pathway, suggesting a 'do-it-yourself' approach. These findings provide valuable insights into how plant communities of different photosynthetic types might respond to future climate change.

Flood simulation using LISFLOOD and inundation effects: A case study of Typhoon In-Fa in Shanghai.

Urban flooding threatens residents and their property, necessitating timely and accurate flood simulations to enhance prevention measures. However, as a megacity, Shanghai presents a complex underlying surface that proves challenging to assess accurately in existing studies. To simulate the dynamic flooding caused by Typhoon In-Fa in Shanghai from July 23rd to 28th 2021, we employed the LISFLOOD hydrodynamic model with multi-source data and validated the flooded area using the S1FLOOD deep learning model with Sentinel-1 satellite imagery. Based on simulated flood results and a flood depth classification system, we quantified the impacts of flood inundation on population, land use, and buildings. Key findings include: (1) The most severe flooding period in Shanghai occurred on July 25th and 26th 2021. (2) The LISFLOOD model effectively captured the extent of inundation, with the very-high flood depth zone covering 98.07 % of the area identified as flooded by the S1FLOOD and Sentinel-1. (3) Peak-affected individuals were recorded on July 25th 2021. (4) Farmland experienced the most extensive flooding among land use types, while residential buildings were notably affected among building types. Our study reconstructed the spatiotemporal dynamics of Typhoon In-Fa-induced flooding in Shanghai. We mapped the spatial extent and water depths, revealing the dynamic impacts of inundation on population, land use, and buildings across urban areas. This comprehensive framework for flood simulation and inundation impact analysis offers a valuable approach to improve urban flood emergency response.

A Strategy Involving Microporous Microneedles Integrated with CAR-TREM2-Macrophages for Scar Management by Regulating Fibrotic Microenvironment.

Dipeptidyl peptidase 4 (DPP4) positive fibroblasts play a pivotal role in scar development following skin injury. Heterogeneous vascular endothelial cells (ECs) within scarred areas retain the capacity to drive tissue regeneration and repair. Simultaneously, TREM2 macrophages play a crucial role in the progression and resolution of fibrosis by engaging in mutual regulation with ECs. However, effective strategies to inhibit scar formation through multi-factor regulation of the scar microenvironment remain a challenge. Here, CAR-TREM2-macrophages (CAR-TREM2-Ms) capable of targeting DPP4+ fibroblasts and modulating ECs subtype within the scar microenvironment are engineered to effectively prevent scarring. Hydrogel microporous microneedles (mMNs) are employed to deliver CAR-TREM2-Ms, which can effectively alleviate scar. Single-cell transcriptome sequencing (scRNA-seq) analysis reveals that CAR-TREM2-Ms can modify ECs fibrotic phenotype and regulate fibrosis by suppressing the profibrotic gene leucine-rich-alpha-2-glycoprotein 1 (Lrg1). In vitro experiments further demonstrate that CAR-TREM2-Ms improve the scar microenvironment by phagocytosing DPP4+ fibroblasts and suppressing TGFß secretion. This, in turn, inhibits the phenotypic conversion of LRG1 ECs and provides multifactorial way of alleviating scars. This study uncovers the evidence that mMNs attached to CAR-TREM2-Ms may exert vital influences on skin scarring through the regulation of the skin scar microenvironment, providing a promising approach for treating posttraumatic scarring.

Longxuetongluo Capsule alleviate ischemia/reperfusion induced cardiomyocyte apoptosis through modulating oxidative stress and mitochondrial dysfunction.

BACKGROUND: Chinese dragon's blood, the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen., is widely used to treat cardiovascular and cerebrovascular diseases in China. Longxuetongluo Capsule (LTC) is a total phenolic compound extracted from Chinese dragon's blood, currently used in treating ischemic stroke. Myocardial injury can be aggravated after reperfusion of ischemic myocardium, which is called myocardial ischemia-reperfusion injury (MIRI), and the mechanism of MIRI is complex. However, the exact effect and mechanism of LTC on MIRI are still unclear. We explore the effect of LTC on alleviating MIRI based on mitochondrial dysfunction and oxidative stress. AIM OF THE STUDY: To explore the cardioprotective mechanism of LTC against MIRI. MATERIALS AND METHODS: A rat MIRI model was constructed through ligation of the left anterior descending coronary artery, and LTC was given continuously for 28 days before surgery. The H9c2 cardiomyocyte injury model was induced by oxygen-glucose deprivation/reperfusion (OGD/R), and LTC was given 24 h before OGD. Myocardial ischemia areas were detected with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cardiac histopathological changes were detected with hematoxylin-eosin (HE) staining. And biochemical indexes were detected with serum biochemical kit. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining and flow cytometry were used to detect apoptosis. Fluorescent probes were used to observe reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), Ca2+and other indexes. MitoTracker staining and immunofluorescence were used to observe the morphology of mitochondria and translocation of dynamin-related protein 1 (Drp1). Finally, immunohistochemistry and Western blotting were used to examine the expression of proteins related to apoptosis, mitochondrial fission and fusion and oxidative stress. RESULTS: LTC could ameliorate cardiac pathological changes, decrease myocardial infarct area and the content or level of relevant serum cardiac enzymes, indicating that LTC could alleviate MIRI. Meanwhile, LTC could inhibit cardiomyocyte apoptosis via regulating apoptosis-related protein expression, and it could restore mitochondrial morphology, maintain ΔΨm, inhibit mitochondrial ROS generation and Ca2+ accumulation, increase the expression of mitochondrial fusion protein 2 (Mfn2), decrease the level of phosphorylation dynamin-related protein 1 (p-Drp1), and regulate ATP synthesis, thereby significantly ameliorating mitochondrial dysfunction. Moreover, LTC significantly reduced the expression of NADPH oxidase 2 (NOX2), NADPH oxidase 4 (NOX4) and neutrophil cytosolic factor 2 (NOXA2/p67phox), and reduced ROS production. CONCLUSION: The study demonstrated that LTC could inhibit MIRI induced cardiomyocyte apoptosis by inhibiting ROS generation and mitochondrial dysfunction, and these fundings suggested that LTC can be used to alleviate MIRI, which provides a potential therapeutic approach for future treatment of MIRI.

Generation Potential and Kinetics of Gaseous Hydrocarbons from Upper Paleozoic Carboniferous Benxi Formation Mudstone in Ordos Basin, China.

Industrial quantities of tight gas from the Carboniferous Benxi Formation have been found in the southern Ordos Basin. The source and contributions from mudstone and coal in the Benxi Formation to the tight gas are still unclear, and the hydrocarbon generation potential and kinetics of the Benxi Formation mudstone have rarely been reported, which has halted resource evaluation of tight gas. Confined pyrolysis experiments were performed to determine the yields and kinetic parameters for gaseous hydrocarbon formation for a representative sample of a Benxi Formation mudstone from the Ordos Basin, with a hydrogen index (HI) of 137 mg/g TOC and T max of 434 °C. The maximum yield of C1-C5 hydrocarbons is 143 mg/g TOC. For samples with similar HI, Upper Paleozoic mudstone samples might have a higher total gas generation potential than Upper Paleozoic coal samples because of the more reducing environment during mudstone deposition, which is beneficial for the preservation of sedimentary lipids. Even though the HI of Upper Paleozoic coals is apparently higher than that of Upper Paleozoic mudstones, they have a similar late gas generation potential. Basin modeling shows that the amount of natural gas generated from Benxi Formation mudstone increases southward. Coaly source rocks from the Ordos Basin with a lower oil generation potential have more negative δ13C1 values when the vitrinite reflectance is lower than 1.4-1.7%. This phenomenon might be related to the more negative δ13C of wet gas or the small hydrocarbon molecules incorporated into the kerogen compared with the components generating primary cracking gases. This study deepens the understanding of gaseous hydrocarbons generated from mudstone and coal in transitional depositional environments and provides the key parameters for tight gas resources in this area.

SLAMF1 as a novel molecule mediating the causal association between rheumatoid arthritis and interstitial lung disease: A Mendelian randomization study combined with transcriptomics and in vivo validation.

BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common complication of rheumatoid arthritis (RA) that result in significant morbidity and mortality. Understanding the molecular mechanisms underlying RA-ILD is crucial for effective prevention. This study aims to identify the specific molecule that mediate the causal association between RA and ILD, as well as to explore its potential mechanisms in the pathogenesis of RA-ILD. METHODS: Using two-sample Mendelian randomization (MR) analyses, we investigated the causal relationship among 16,987 blood genes, RA and ILD. Subsequently, a two-step MR technique was employed to identify significant genes that mediate the association between RA and ILD, and to quantify their proportion of mediation effect. To validate the genes as mediators, the replication MR analysis was conducted and the in vivo experiment was performed using an established animal model of RA-ILD. Furthermore, integrated bioinformatic analyses were conducted to elucidate the specific biological functions of the determined mediator in pathogenesis of RA-ILD. RESULTS: Nine genes, namely MAPK8IP2, TAF11, SLAMF1, DAB2IP, GLUL, SLC4A10, PRSS35, NFX1, and PLK3, were identified as mediators. Among them, SLAMF1 was validated as the most significant mediator, accounting for 4.693% of the mediating effect on the causal relationship between RA and ILD. Upregulated mRNA expression of SLAMF1 was observed in the animal model of RA-ILD compared to controls. Bioinformatic analyses revealed that SLAMF1 was overexpressed in patients with lung fibrosis and correlated with a poor prognosis. Specifically, SLAMF1 was found to be predominantly overexpressed in T cells in lung tissues of patients with lung fibrosis. Additionally, the functional role of SLAMF1 was associated with multiple immune cell infiltrations and the biological process of extracellular matrix synthesis in pulmonary tissues from patients with lung fibrosis. CONCLUSION: SLAMF1 may play a crucial role as a molecular mediator in the causal association between RA and ILD, and participate in multiple mechanisms underlying the pathogenesis of RA-ILD. This research provides insights into how the development of RA influences the risk of ILD and offers potential interventional targets against RA-ILD.