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Naphthalene (Nap) and its derivatives, including 1-methylnaphthalene (1-MN) and 2-methylnaphthalene (2-MN), serve as prominent intermediate volatile organic compounds (IVOCs) and contribute to the formation of secondary organic aerosol (SOA). In this study, the Community Multiscale Air Quality (CMAQ) model coupled with detailed emissions and reactions of these compounds was utilized to examine their roles in the formation of SOA and other secondary pollutants in the Yangtze River Delta (YRD) region during summer. Significant underestimations of Nap and MN concentrations (by 79 % and 85 %) were observed at the Taizhou site based on the model results using the default emissions. Constrained by the observations, anthropogenic emissions of Nap and MN in the entire region were multiplied by 5 and 7, respectively, to better capture the evolution of pollutants. The average concentration of Nap reached 25 ppt (parts per trillion) in the YRD, with Nap contributing 4.1 % and 8.1 % (up to 12.6 %) of total aromatic emissions and aromatic-derived secondary organic carbon (SOC), respectively. The concentrations of 1-MN and 2-MN were relatively low, averaging 2 and 5 ppt, respectively. Together, they accounted for only 2.4 % of the aromatic-derived SOC. The impacts of Nap and MN oxidation on ozone and radicals were insignificant at regional scales but were not negligible when considering daily fluctuations in locations with high emissions of Nap and MN. This study highlights the significant roles of Nap and MN in the formation of SOA, which may pose environmental risks and result in adverse health effects.

Volatile organic compounds (VOCs) play a crucial role in the formation of tropospheric ozone (O3) and secondary organic aerosols. VOC emissions are generally considered to have larger uncertainties compared to other pollutants, such as sulfur dioxide and fine particulate matter (PM2.5). Although predictions of O3 and PM2.5 have been extensively evaluated in air quality modeling studies, there has been limited reporting on the evaluation of VOCs, mainly due to a lack of routine VOC measurements at multiple sites. In this study, we utilized VOC measurements from the “Towards an Air Toxic Management System in China” (ATMSYC) project at 28 sites across China and assessed the predicted VOC concentrations using the Community Multiscale Air Quality (CMAQ) model with the widely used Multi-resolution Emission Inventory for China (MEIC). The ratio of predicted to observed total VOCs was found to be 0.74 ± 0.40, with underpredictions ranging from 2.05 to 50.61 ppbv (5.77 % to 85.40 %) at 24 sites. A greater bias in VOC predictions was observed in industrial cities in the north and southwest, such as Jinan, Shijiazhuang, Lanzhou, Chengdu, and Guiyang. In terms of different VOC components, alkanes, alkenes, non-naphthalene aromatics (ARO2MN), alkynes, and formaldehyde (HCHO) had prediction-to-observation ratios of 0.53 ± 0.38, 0.51 ± 0.48, 0.31 ± 0.38, 0.41 ± 0.47, and 1.21 ± 1.61, respectively. Sensitivity experiments were conducted to assess the impact of the VOC prediction bias on O3 predictions. While emission adjustments improved the model performance for VOCs, resulting in a change in the ratio of total VOCs to 0.86 ± 0.47, they also exacerbated O3 overprediction relative to the base case by 0.62 % to 6.27 % across the sites. This study demonstrates that current modeling setups and emission inventories are likely to underpredict VOC concentrations, and this underprediction of VOCs contributes to lower O3 predictions in China.

Ozone (O3) has become a significant air pollutant in China in recent years. O3 abatement is challenging due to the nonlinear response of O3 to precursors nitrogen oxides (NOx) and volatile organic compounds (VOCs). Photochemical indicators are widely used to estimate the O3–NOx–VOC sensitivity, and this has important policy implications. However, the effectiveness of the indicators has seldom been evaluated. This study examined the applications of four indicators that include the ratio of the production rates of H2O2 and HNO3 (PH2O2/PHNO3), HCHO/NO2, HCHO/NOy, and reactive nitrogen (NOy) in the Yangtze River Delta (YRD) with localized thresholds. The overall accuracy was high (>92 %) for all indicators and not significantly reduced with different simulation periods or in different locations of the region. By comparing with the O3 isopleths, it was found that HCHO/NO2 and HCHO/NOy showed the most consistency, whereas PH2O2/PHNO3 (NOy) tended to underestimate (overestimate) the positive response of O3 to NOx. Additionally, PH2O2/PHNO3 was less likely to attribute the O3 formation to mixed sensitivity than the other indicators, and this demonstrated a preference for a single-pollutant control strategy. This study also revealed that the details in the methodology used to derive the threshold values impacted the results, and this may produce uncertainties in the application of photochemical indicators.

Abstract Gravitational‐wave high‐energy Electromagnetic Counterpart All‐sky Monitor (GECAM) is a space‐borne instrument dedicated to monitoring high‐energy transients, including Terrestrial Gamma‐ray Flashes (TGFs) and Terrestrial Electron Beams (TEBs). We implemented a TGF/TEB search algorithm for GECAM, with which 147 bright TGFs, 2 typical TEBs and 2 special TEB‐like events are identified during an effective observation time of ∼9 months. We show that, with gamma‐ray and charged particle detectors, GECAM can effectively identify and distinguish TGFs and TEBs, and measure their temporal and spectral properties in detail. A very high TGF‐lightning association rate of ∼80% is obtained between GECAM and GLD360 in east Asia region.

Carbon dioxide is considered an inert gas that rarely participates in atmospheric chemical reactions. Nonetheless, we show here that CO2 is involved in some important photo-oxidation reactions in the atmosphere through the formation of carbonate radicals (CO3⚫-). This potentially active intermediate CO3⚫- is routinely overlooked in atmospheric chemistry concerning its effect on sulfate formation. The present work demonstrates that the SO2 uptake coefficient is enhanced by 17 times on mineral dust particles driven by CO3⚫-. Importantly, upon irradiation, mineral dust particles are speculated to produce gas-phase carbonate radical ions when the atmospherically relevant concentration of CO2 presents, thereby potentially promoting external sulfate aerosol formation and oxidative potential in the atmosphere. Employing a suite of laboratory investigations of sulfate formation in the presence of carbonate radicals on the model and authentic dust particles, ground-based field measurements of sulfate and (bi)carbonate ions within ambient PM, together with density functional theory (DFT) calculations for single electron transfer processes in terms of CO3⚫--initiated S(IV) oxidation, a novel role of carbonate radical in atmospheric chemistry is elucidated.

Abstract Background The American Thyroid Association published revised guidelines in 2015 on the management of differentiated thyroid cancer in adults. One of the key changes introduced in the revision proposes that diagnostic biopsy be based on ultrasound findings (i.e. size and nodule characteristics). The overall effect of these changes results in fewer nodules requiring biopsy. This study was conducted to determine if the changes to the guidelines will result in overlooked thyroid cancers, specifically malignancies with aggressive characteristics measuring between 1 and 1.49 cm. Methods Patients (n = 2083) with thyroid nodules who underwent total or subtotal/hemi thyroidectomy with or without neck dissection by a single surgeon between 2006 and 2016 were retrospectively enrolled. Demographic information and nodule characteristics were collected for all patients. Ultrasonography and final pathology reports were reviewed for patients with thyroid nodules between the sizes of 1–1.49 cm (n = 155). Results 45% (n = 70) of patients with nodules between 1 and 1.49 cm were “low suspicion” nodules according to ultrasound. 47 of these nodules contained malignancies on final histopathological examination, 100% of which were of the papillary subtype. 21% (n = 10) of these malignant nodules demonstrated extrathyroidal extension and 34% (n = 16) were associated with regional metastases. Conclusions Reliance on sonographic patterns alone could result in missed cancer diagnoses in patients with thyroid nodules measuring between 1 and 1.49 cm. Moreover, a portion of these malignancies may be associated with aggressive features. The effect of this finding on long-term outcomes is unclear.

Nowadays, multiple-view stereo satellite imagery has become a valuable data source for digital surface model generation and 3D reconstruction. In 2016, a well-organized multiple view stereo publicly benchmark for commercial satellite imagery has been released by the John Hopkins University Applied Physics Laboratory, USA. This benchmark motivates us to explore the method that can generate accurate digital surface models from a large number of high resolution satellite images. In this paper, we propose a pipeline for processing the benchmark data to digital surface models. As a pre-procedure, we filter all the possible image pairs according to the incidence angle and capture date. With the selected image pairs, the relative bias-compensated model is applied for relative orientation. After the epipolar image pairs’ generation, dense image matching and triangulation, the 3D point clouds and DSMs are acquired. The DSMs are aligned to a quasi-ground plane by the relative bias-compensated model. We apply the median filter to generate the fused point cloud and DSM. By comparing with the reference LiDAR DSM, the accuracy, the completeness and the robustness are evaluated. The results show, that the point cloud reconstructs the surface with small structures and the fused DSM generated by our pipeline is accurate and robust.

High resolution, optical satellite sensors are boosted to a new era in the last few years, because satellite stereo images at half meter or even 30cm resolution are available. Nowadays, high resolution satellite image data have been commonly used for Digital Surface Model (DSM) generation and 3D reconstruction. It is common that the Rational Polynomial Coefficients (RPCs) provided by the vendors have rough precision and there is no ground control information available to refine the RPCs. Therefore, we present two relative orientation methods by using corresponding image points only: the first method will use quasi ground control information, which is generated from the corresponding points and rough RPCs, for the bias-compensation model; the second method will estimate the relative pointing errors on the matching image and remove this error by an affine model. Both methods do not need ground control information and are applied for the entire image. To get very dense point clouds, the Semi-Global Matching (SGM) method is an efficient tool. However, before accomplishing the matching process the epipolar constraints are required. In most conditions, satellite images have very large dimensions, contrary to the epipolar geometry generation and image resampling, which is usually carried out in small tiles. This paper also presents a modified piecewise epipolar resampling method for the entire image without tiling. The quality of the proposed relative orientation and epipolar resampling method are evaluated, and finally sub-pixel accuracy has been achieved in our work.

Photogrammetry is currently in a process of renaissance, caused by the development of dense stereo matching algorithms to provide very dense Digital Surface Models (DSMs). Moreover, satellite sensors have improved to provide sub-meter or even better Ground Sampling Distances (GSD) in recent years. Therefore, the generation of DSM from spaceborne stereo imagery becomes a vivid research area. This paper presents a comprehensive study about the DSM generation of high resolution satellite data and proposes several methods to implement the approach. The bias-compensated Rational Polynomial Coefficients (RPCs) Bundle Block Adjustment is applied to image orientation and the rectification of stereo scenes is realized based on the Project-Trajectory-Based Epipolarity (PTE) Model. Very dense DSMs are generated from WorldView-2 satellite stereo imagery using the dense image matching module of the C/C++ library LibTsgm. We carry out various tests to evaluate the quality of generated DSMs regarding robustness and precision. The results have verified that the presented pipeline of DSM generation from high resolution satellite imagery is applicable, reliable and very promising.

Cellulolytic plate bacteria are considered to be the major drivers of litter decomposition and play critical roles in soil conditioning and nutrient cycling. With the goal to identify strategies used by soil cellulolytic bacteria to overcome nitrogen limitation characteristic of saline-sodic grasslands, cellulolytic strains were isolated from the soil of such habitats in northeast China and their abilities to fix nitrogen were evaluated. Sequencing of the 16S rRNA gene indicated that Streptomyces strains were the most abundant cellulolytic microorganisms in this saline-sodic soil. Most of the isolates exhibited extracellular carboxymethyl cellulase (CMCase) and xylanase activities. Importantly, all the cellulolytic isolates from grassland soils with various vegetation types demonstrated nitrogen-fixing activities ranging from 10.80 to 33.36 nmol C2H4·h-1 ·ml-1 . The cellulolytic isolates also exhibited indole-3-acetic (IAA) acid production abilities ranging from 2.40 to 80.69 μg·ml-1 . These findings provided the first evidence that cellulolytic bacteria likely adapted to the low-nitrogen saline-sodic grassland soils with the acquisition of nitrogenfixing abilities [ABSTRACT FROM AUTHOR]

AIM: Gene expression profiles for intervertebral disc (IVD) cells treated with different osmolarities were compared to identify key genes associated with intervertebral disc diseases. MATERIALS AND METHODS: Microarray data was downloaded from Gene Expression Omnibus (GEO) database and pre-processed using package of R. Gene co-expression was determined with Pearson correlation coefficient. Interaction networks were established with the protein-protein interaction (PPI) information obtained from Human Protein Reference Database (HPRD database) for the two conditions: isosmoticity and hyperosmosis, and then a comparative analysis was done to identify disease-related genes. The functional annotation was performed for these genes using network ontology analysis (NOA), which also confirmed the effectiveness of this method. RESULTS: A total of 45 feature genes were obtained through comparing 7 samples treated under isosmotic conditions and 9 high osmotic conditions. Biological processes and molecular functions were then revealed by NOA. CONCLUSIONS: A range of disease-related genes were obtained, which might serve as the potential biomarkers or drug targets. More works are needed to further elucidate their roles in the development of intervertebral disc diseases like intervertebral disc herniation. [ABSTRACT FROM AUTHOR]

Synthetic methods were developed for the synthesis of the 3-(4-substituted phenyl)-2-5-(substituted phenyl)thiazol-2-yltropanes (4a−s). The compounds were evaluated for their monoamine transporter binding and monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. In general, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin and norepinephrine transporters (SERT and NET, respectively) and greater 3Hdopamine uptake inhibition potency relative to 3Hserotonin and 3Hnorepinephrine uptake inhibition. Several compounds were DAT selective relative to the SERT and NET in the monoamine transporter binding assays. The most potent and selective analog in the functional monoamine uptake inhibition test was 3-(4-methylphenyl-2-5-(3-nitrophenyl)thiazol-2-yltropane (4p). [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer (EC) represents a serious health concern among women globally. Excessive activation of the protooncogene c-Myc (c-Myc) is associated with the proliferation and stemness of EC cells. Phosphocholine (PC), which is synthesized by choline kinase alpha (CHKA) catalysis, is upregulated in EC tumor tissues. The present study aimed to investigate the effect of PC accumulation on EC cells and clarify the relationship between PC accumulation and c-Myc activity in EC., Methods: The c-Myc and CHKA expression in EC tumor tissues were examined using immunohistochemistry. Cell Counting Kit-8 assay, colony formation assay, flow cytometry, western blotting, BrdU staining, and tumorsphere formation assay were used to assess the effect of PC accumulation on EC cells. The mechanism by which PC accumulation inhibits c-Myc was evaluated using RNA-sequencing. Patient-derived organoid (PDO) models were utilised to explore the preclinical efficacy of PC against EC cells., Results: PC accumulation suppressed EC cell proliferation and stemness by inhibiting the activation of the mammalian target of rapamycin (mTOR)-c-Myc signaling. PC accumulation promoted excessive reactive oxygen species production, which reduced the expression of GTPase HRAS. This, in turn, inhibited the mTOR-c-Myc axis and induced EC cell apoptosis. Finally, PC impeded proliferation and downregulated the expression of the mTOR-MYC signaling in EC PDO models., Conclusions: PC accumulation impairs the proliferation ability and stem cell characteristics of EC cells by inhibiting the activated mTOR-c-Myc axis, potentially offering a promising strategy to enhance the efficacy of EC clinical therapy through the promotion of PC accumulation in tumor cells., Competing Interests: Declarations. Conflict of interests: The authors declare that they have no competing interests. The authors alone are responsible for the content and writing of this article. Figures were created with BioRender ( https://biorender.com/ , accessed on November 10th, 2024). Ethical approval and consent to participate: The acquisition and use of human specimens were in concordance with the International Ethical Guidelines for Research Involving Human Subjects, as stated in the Helsinki Declaration, and were approved by the Medical Ethics Committee of Guangzhou Women and Children’s Medical Center (No.: 202019001). The EC tumor tissue samples were collected after obtaining signed informed consent from the participants. The use of endometrial cancer tissue microarray was approved by the Ethics Committee of Shanghai Outdo Biotech Company (No.: SHYJS-CP-1504005). The animals experiments were approved by the Guangzhou Women and Children’s Medical Center Animal Welfare and Ethics Committee (KTDW-2024-00480). Consent for publication: Not applicable., (© 2024. The Author(s).)

Curcumin, the main active compound in turmeric, has garnered significant interest for its wide range of pharmacological properties. In this study, CiteSpace was used to visually analyze curcumin-related publications to elucidate the current landscape and explore emerging frontiers in curcumin research. In total, 23,184 publications on curcumin from January 1, 2014, to December 31, 2023, were scrutinized. The analysis revealed that publication volume consistently increased over time. The top 10 countries contributed 90.87% of the publications, highlighting the global significance of curcumin research. China generated 31.34% of the total corpus due to its strong research capabilities and traditional medicine culture. The top 10 institutions contributed 11.21% of the articles, revealing notable collaborations. Among the prolific authors, Amirhossein Sahebkar produced 246 publications, whereas Preetha Anand garnered the most citations. Keyword analysis revealed prevalent trends such as "fabrication", "combination", "extract", "natural products", "colorectal cancer", and "resveratrol". Reference analysis emphasized research on therapeutic and modulatory effects, anticancer potential, and interdisciplinary topics, such as molecular biology, chemistry, and nutrition. More importantly, we simplified cluster relationships by selecting the top 30% of cluster dependency paths. For instance, the references within the #1 polymeric micelle cite literature from the #2 anticancer potential, #3 modulatory effect, and #4 therapeutic effect, indicating that clusters 2, 3, and 4 serve as knowledge foundations for cluster 1. This interconnectedness highlights how the information in these clusters can contribute to the knowledge of curcumin in various studies. This study provides an overview of the research trends and critical themes related to curcumin, offering insights for future research directions and emphasizing the interdisciplinary and global scope of curcumin research., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Lai et al.)

The ecological risks of biodegradable microplastics (BMPs) to soil ecosystems have received increasing attention. This study investigates the impacts of polylactic acid microplastics (PLA-MPs) and polybutylene adipate terephthalate microplastics (PBAT-MPs) on soil properties of black soil (BS) and fluvo-aquic soil (FS) under three water conditions including dry (Dry), flooded (FL), and alternate wetting and drying (AWD). The results show that BMPs exhibited more evident aging under Dry and AWD conditions compared to FL condition. However, BMPs aging under FL condition induced more substantial changes in soil properties, especially dissolved organic carbon (DOC) concentrations, than under Dry and AWD conditions. BMPs also increased the humification degree of soil dissolved organic matter (DOM), particularly in BS. Metagenomic analysis of PBAT-MPs treatments showed different changes in microbial community structure depending on soil moisture. Under Dry conditions, PBAT-MPs enhance the ammonium-producing process of soil microbial communities. Genes related to N nitrification and benzene degradation were enriched under AWD conditions. In contrast, PBAT-MPs do not change the abundance of genes related to the N cycle under FL conditions but significantly reduce genes related to benzene degradation. This reduction in benzene degradation genes under FL condition might potentially slow down the degradation of PBAT-MPs, and could lead to temporary accumulation of benzene-related intermediates. These findings highlight the complex interactions between BMPs, soil properties, and microbial communities, emphasizing the need for comprehensive evaluations of BMPs' environmental impacts under varying soil water conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Eclipta prostrata (Linn.) is a traditional medicinal Chinese herb that displays multiple biological activities, such as encompassing immunomodulatory, anti-inflammatory, anti-tumor, liver-protective, antioxidant, and lipid-lowering effects. Ecliptasaponin A (ESA), a pentacyclic triterpenoid saponin isolated from Eclipta prostrata (Linn.), has been demonstrated to exert superior anti-inflammatory activity against many inflammatory disorders., Aim of the Study: Inflammation plays a critical role in acute myocardial infarction (AMI). This study aims to explore the treatment effects of ESA in AMI, as well as the underlying mechanism., Methods: An AMI mouse model was established in mice via left anterior descending coronary artery (LAD) ligation. After surgery, ESA was injected at doses of 0.5, 1.25, and 2.5 mg/kg, respectively. Myocardial infarction size, cardiomyocyte apoptosis and cardiac echocardiography were studied. The potential mechanism of action of ESA was investigated by RNA-seq, Western blot, surface plasmon resonance (SPR), molecular docking, and immunofluorescence staining., Results: ESA treatment not only significantly reduced myocardial infarct size, decreased myocardial cell apoptosis, and inhibited inflammatory cell infiltration, but also facilitated to improve cardiac function. RNA-seq and Western blot analysis proved that ESA treatment-induced differential expression genes mainly enriched in HMGB1/TLR4/NF-κB pathway. Consistently, ESA treatment resulted into the down-regulation of IL-1β, IL-6, and TNF-α levels after AMI. Furthermore, SPR and molecular docking results showed that ESA could bind directly to HMGB1, thereby impeding the activation of the downstream TLR4/NF-κB pathway. The immunofluorescence staining and Western blot results at the cellular level also demonstrated that ESA inhibited the activation of the HMGB1/TLR4/NF-κB pathway in H9C2 cells., Conclusion: Our study was the first to demonstrate a cardiac protective role of ESA in AMI. Mechanism study indicated that the treatment effects of ESA are mainly attributed to its anti-inflammatory activity that was mediated by the HMGB1/TLR4/NF-κB pathway., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aims to develop a sustained release patch for bisoprolol (BSP) to address the issue of blood pressure fluctuations caused by traditional dosing methods, ensuring continuous drug release and efficient utilization. Long-chain saturated fatty acids (C 6 -C 12 ) were chosen as counterions to precisely control BSP's permeation rate in the patch formulation, and the ion-pairing strategy's mechanism in drug delivery was thoroughly investigated. Molecular docking results revealed significant differences in the adsorption capacities of different ion pairs in the stratum corneum (SC) and epidermis, directly influencing their residence times and thereby regulating BSP's passive diffusion rate. Particularly, the BSP-C 10 ion pair successfully reduced BSP's permeation rate to one-third of its baseline. To enhance drug delivery efficiency and reduce costs, chemical permeation enhancers (CPEs) are typically added to sustained release patches. In contrast to traditional static analyses based on cumulative permeation, this study utilized ATR-FTIR dynamic detection of isopropyl myristate (IPM) as a preferred enhancer, studying its disruptive effects on the skin barrier during drug delivery. The study observed that during drug delivery, the interaction between IPM and skin lipids follows a U-shaped trend: initially increasing, then decreasing, with the peak occurring at 10 h. Similarly, the drug delivery rate displays a comparable pattern. The addition of IPM as CPE increased the patch utilization rate from 39.8 ± 4.31 to 79.8 ± 7.27%. This strategy aims to rapidly reduce blood pressure in the initial phase with subsequent weakening of IPM disruption, allowing the ion-pairing strategy to dominate drug delivery control and maintain stable long-term therapeutic effects. Pharmacokinetic studies demonstrated that the newly developed BSP sustained release patch maintains stable blood drug concentrations, reduces burst release effects, increases bioavailability to 84.679%, doubles MRT 0- t , halves C max , and significantly reduces the occurrence of blood pressure fluctuations.

Tandospirone(Tan) is a commonly used drug for anxiety treatment. However, it has a significant first-pass effect and needs to be taken three times a day. To increase the bioavailability of the drug and reduce the number of administrations, this work amid to prepare a Tan patch that can be administered once a day by using the strategy of therapeutic deep eutectic solvent(THEDES) in cooperation with chemical permeation enhancer(CPE). In this study, four organic acids and five permeation enhancers were selected, and the optimized formulation was obtained by single-factor investigation and Box-Behnken design. The optimized formulation could significantly enhance drug loading by 2.5-fold and skin permeation up to 586.6 ± 17 μg/cm 2 in rats. Based on pharmacokinetic results, compared to oral administration, the drug exhibited a substantially elevated bioavailability, registering a 17-fold increase(from 3.01 % to 52.17 %), alongside a 10-fold rise in the mean residence time(MRT). Meanwhile, the patch was not irritating. The results of the mechanistic study showed that levulinic acid(LeA) acted as a bridge to increase the interaction between the Tan and the matrix and inhibited the crystallization of the drug in the patch, and THEDES together with CPE improved the matrix fluidity and skin permeability. This study provides a reference for the joint application of THEDES and CPEs in patch development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Given the genetic and clinical overlap observed between schizophrenia and depression, the present study was to identify the similarities and differences in serum metabolic profiles between patients with schizophrenia and depression. Global metabolomics research methods based on UHPLC-QTOF-MS/MS were performed. A total of 113 and 118 differential metabolites were screened and identified in depression and schizophrenia groups, respectively, as compared to health control; among those, 94 differential metabolites were shared by both. Pathway analysis indicated arginine and proline metabolism, alanine, aspartate, and glutamate metabolism were two significant metabolic pathways both in depression and schizophrenia groups as compared with health control groups, respectively. Similarly, 77 differential metabolites were identified between depression and schizophrenia groups, in which, serum N-acetylglutamine and isovalerylglycine levels showed significant differences between patients with depression and schizophrenia with p values less than 0.001 and without significant outliers. Sphingolipid metabolism was identified as a significant metabolic pathway distinguishing between depression and schizophrenia groups based on pathway analysis. Conclusively, common alterations in arginine and proline metabolism, alanine, aspartate, and glutamate metabolism were observed in patients with schizophrenia and depression; whereas differences in serum N-acetylglutamine and isovalerylglycine levels as well as sphingolipid metabolism were discovered between the two categories of patients., (© 2024 John Wiley & Sons Ltd.)

Protein arginine methyltransferase 5 (PRMT5) is a type II PRMT enzyme that plays an important role in protein formation. PRMT5 is widely distributed in the nucleus and is involved in regulating a variety of biological processes, including gene transcription, signaling, and cell proliferation. PRMT5 regulates the function and stability of histones through methylation, affecting important cellular activities such as cell cycle regulation, DNA repair, and RNA processing. Studies have shown that PRMT5 is overexpressed in a variety of tumors and is closely related to the occurrence and development of tumors. In recent years, several PRMT5 inhibitors have entered clinical trials for the treatment of various cancers. In view of their importance, this paper reviews the first generation of PRMT5 inhibitors obtained by high-throughput screening, virtual screening, lead compound optimization and substitution modification, as well as novel PRMT5 inhibitors obtained by PROTAC technology and by synthetic lethal principle. Finally, by comparing the differences between the first generation and the second generation, the challenges and future development directions of PRMT5 inhibitors are discussed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal re­lationships which may be considered as potential competing interests: Guisen Zhao reports financial support was provided by National Natural Science Foundation of China. Guisen Zhao reports a relationship with National Natural Science Foundation of China that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (Ratio Hep/Port , Ratio Peri/Hep , and Ratio Port/Peri ) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher Ratio Peri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher Ratio Port/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

Wang, Liping, Gang Fu, Ruijuan Han, Peijia Fan, Jing Yang, Kerui Gong, Zhijun Zhao, Chunyang Zhang, Kai Sun, and Guo Shao. MALAT1 and NEAT1 are neuroprotective during hypoxic preconditioning in the mouse hippocampus possibly by regulation of NR2B. High Alt Med Biol. 25:285-294, 2024. Background: The regulation of noncoding ribonucleic acid (ncRNA) has been shown to be involved in cellular and molecular responses to hypoxic preconditioning (HPC), a situation created by the induction of sublethal hypoxia in the brain. The ncRNAs metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and nuclear paraspeckle assembly transcript 1 (NEAT1) are abundantly expressed in the brain, where they regulate the expression of various genes in nerve cells. However, the exact roles of MALAT1 and NEAT1 in HPC are not fully understood. Methods: A mouse model of acute repeated hypoxia was used as a model of HPC, and MALAT1 and NEAT1 levels in the hippocampus were measured using real-time polymerase chain reaction (PCR). The mRNA and protein levels of N -methyl-d-aspartate receptor subunit 2 B (NR2B) in the mouse hippocampus were measured using real-time PCR and western blotting, respectively. HT22 cells knocked-down for MALAT1 and NEAT1 were used for in vitro testing. Expression of NR2B, which is involved in nerve cell injury under ischemic and hypoxic conditions, was also evaluated. The levels of spectrin and cleaved caspase-3 in MALAT1 and NEAT1 knockdown HT22 cells under oxygen glucose deprivation/reperfusion (OGD/R) were determined by western blotting. Results: HPC increased the expression of MALAT1 and NEAT1 and decreased the expression of NR2B mRNA in the mouse hippocampus ( p < 0.05). Knockdown of MALAT1 and NEAT1 increased both NR2B mRNA and protein levels nearly twofold and caused damage under OGD/R conditions in HT22 cells ( p < 0.05). Conclusion: MALAT1 and NEAT1 exert neuroprotective effects by influencing the expression of NR2B.

Biodegradable microplastics (BMPs) may impact the environmental fate and ecotoxicity of Cd, but the effect mechanism in soil-plant system remain poorly understood. This study investigated the impact of BMPs (poly(lactic acid) (PLA) and poly(butylene adipate terephthalate) (PBAT) microplastics) on the Cd toxicity, translocation, transformation, and metabolome in lettuce (Lactuca sativa L.) by pot experiments. The results show that co-exposure to BMPs and Cd synergistically inhibited the shoot growth. 0.2 % PLA MPs enhanced but 2.5 % PLA MPs inhibited the photosynthesis; however, the dose of PBAT MPs was negatively correlated with the content of chlorophyll a. Moreover, the presence of 2.5 % PBAT MPs increased the nitrate content of leaves by 9.5 % compared to single Cd exposure. The partial least squares path model (PLS-PM) indicates that BMPs exacerbated the inhibitory effects of Cd on lettuce growth. PLA MPs enhanced K, Ca, Cu, and Zn accumulation in root stele, whereas PBAT MPs promoted Fe and Mn enrichment in epidermis. Furthermore, co-exposure resulted in higher inorganic and water-soluble Cd proportions in shoots. PLA MPs elevated Cd contents in cell wall fractions of both roots and shoots, while PBAT MPs increased Cd contents in shoot cell walls and root cells and soluble Cd ratio in shoots. BMPs enhanced Cd toxicity and bioaccumulation by downregulating the expression of ABC transporters and phenylpropanoid biosynthesis pathways, and the relative abundance of related metabolites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Biodegradable plastics (BPs) are regarded as ecomaterials and are emerging as a substitute for traditional non-degradable plastics. However, the information on the interaction between biodegradable microplastics (BMPs) and cadmium (Cd) in agricultural soil is still limited. Here, lettuce plants were cultured in BMPs (polylactic acid (PLA) MPs and poly(butylene-adipate-co-terephthalate) (PBAT) MPs) and Cd co-polluted soil for 35 days. The results show that diffusive gradient in thin films technique (DGT) but not diethylenetriaminepentaacetic acid (DTPA) extraction method greatly improved the prediction reliability of Cd bioavailability in non-rhizosphere soil treated with BMPs (R 2  = 0.902). BMPs increased the Cd bioavailability in non-rhizosphere soil indirectly by decreasing soil pH, cation exchange capacity (CEC), and dissolved organic carbon (DOC), rather than by directly adsorbing Cd on their surface. PLA MPs incubated in rhizosphere soil showed more considerable degradation with extremely obvious cavities and the fracture of ester functional groups on their surface than PBAT MPs. BMPs could provide ecological niches to colonize and induce microorganisms associated with BMPs' degradation to occupy a more dominant position. In addition, Cd only affected the composition and function of microbial communities in soil but not on BMPs. However, co-exposure to BMPs and Cd significantly reduced the degrees of co-occurrence network of fungal communities on PLA MPs and PBAT MPs by 37.7% and 26.7%, respectively, compared to single exposure to BMPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hydroxycarboxylic acid receptor 3 (HCAR3), a class A G-protein-coupled receptor, is an important cellular energy metabolism sensor with a key role in the regulation of lipolysis in humans. HCAR3 is deeply involved in many physiological processes and serves as a valuable target for the treatment of metabolic diseases, tumors, and immune diseases. Here, we report four cryoelectron microscopy (cryo-EM) structures of human HCAR3-Gi1 complexes with or without agonists: the endogenous ligand 3-hydroxyoctanoic acid, the drug niacin, the highly subtype-specific agonist compound 5c (4-(n-propyl)amino-3-nitrobenzoic acid), and the apo form. Together with mutagenesis and functional analyses, we revealed the recognition mechanisms of HCAR3 for different agonists. In addition, the key residues that determine the ligand selectivity between HCAR2 and HCAR3 were also illuminated. Overall, these findings provide a structural basis for the ligand recognition, activation, and selectivity and G-protein coupling mechanisms of HCAR3, which contribute to the design of HCAR3-targeting drugs with high efficacy and selectivity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Osteoarthritis (OA) is a degenerative joint disorder characterized by progressive cartilage degradation. Excessive oxidative stress (OS), inflammatory responses, extracellular matrix breakdown, and cellular senescence of chondrocytes play crucial roles in the pathological development of OA. Currently, curing OA remains a significant challenge. In this study, we aimed to elucidate the protective effects of Annexin A1 protein Mimetic Peptide (Ac2-26) against tumor necrosis factor-α (TNF-α)-induced damage in CHON-001 chondrocytes by assessing cellular senescence, OS, and the expression levels of matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4. Our results show that Ac2-26 mitigated the reduction of telomerase activity and the exacerbation of cellular senescence induced by TNF-α in CHON-001 chondrocytes. Treatment with TNF-α led to decreased expression of the human telomerase reverse transcriptase gene and increased expression of the telomeric repeat-binding factor 2 gene, which were reversed by Ac2-26 treatment. The TNF-α-induced increases in the gene and protein expressions of p53 and p16 were restored by Ac2-26 in a dose-dependent manner. Additionally, we found that TNF-α caused elevations in the mRNA and protein levels of MMP-13 and ADAMTS-4, which were reduced by Ac2-26 in a dose-dependent fashion. Furthermore, TNF-α triggered the activation of nuclear factor κ-B (NF-κB) by increasing the levels of phosphorylated NF-κB p65 and the luciferase activity of NF-κB. Notably, Ac2-26 alleviated OS by reducing mitochondrial reactive oxygen species levels and promoting the activation of NF-E2-related factor 2 (Nrf2) in TNF-α-challenged CHON-001 chondrocytes. Silencing Nrf2 abolished the Ac2-26-induced activation of NF-κB and cellular senescence in CHON-001 chondrocytes. Collectively, these findings offer new insights into the potential therapeutic use of Ac2-26 for treating OA., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

Often, chemical reactions are markedly accelerated in microdroplets compared with the corresponding bulk phase. While identifying the precise causative factors remains challenging, the interfacial electric field (IEF) and partial solvation are the two widely proposed factors, accounting for the acceleration or turning on of many reactions in microdroplets. In sharp contrast, this combined computational and experimental study demonstrates that these two critical factors have a negligible effect on promoting a model Diels-Alder (DA) reaction between cyclopentadiene and acrylonitrile in water microdroplets. Instead, the acceleration of the DA reaction appears to be driven by the effect of confinement and the concentration increase caused by evaporation. Quantum chemical calculations and ab initio molecular dynamics simulations coupled with enhanced sampling techniques predict that the air-water interface exhibits a higher free-energy barrier of this reaction than the bulk, while external electric fields marginally reduce the barrier. Remarkably, the catalytic capability of the IEF at the water microdroplet surface is largely hampered by its fluctuating character. Mass spectrometric assessment of the microdroplet reaction corroborates these findings, suggesting that the DA reaction is not facilitated by the IEF as increasing the spray potential suppresses the DA products by promoting substrate oxidation. While the DA reaction exhibits a surface preference in water microdroplets, the same reaction tends to occur mainly within the core of the acetonitrile microdroplet, suggesting that the partial solvation is not necessarily a critical factor for accelerating this reaction in microdroplets. Moreover, experiments indicate that the rapid evaporation of microdroplets and subsequent reagent enrichment within the accessible confined volume of microdroplets caused the observed acceleration of the DA reaction in water microdroplets.

Head and neck (H&N) cancers are among the most prevalent types of cancer worldwide, and [18F]F-FDG PET/CT is widely used for H&N cancer management. Recently, the diffusion model has demonstrated remarkable performance in various image-generation tasks. In this work, we proposed a 3D diffusion model to accurately perform H&N tumor segmentation from 3D PET and CT volumes. The 3D diffusion model was developed considering the 3D nature of PET and CT images acquired. During the reverse process, the model utilized a 3D UNet structure and took the concatenation of PET, CT, and Gaussian noise volumes as the network input to generate the tumor mask. Experiments based on the HECKTOR challenge dataset were conducted to evaluate the effectiveness of the proposed diffusion model. Several state-of-the-art techniques based on U-Net and Transformer structures were adopted as the reference methods. Benefits of employing both PET and CT as the network input as well as further extending the diffusion model from 2D to 3D were investigated based on various quantitative metrics and the uncertainty maps generated. Results showed that the proposed 3D diffusion model could generate more accurate segmentation results compared with other methods. Compared to the diffusion model in 2D format, the proposed 3D model yielded superior results. Our experiments also highlighted the advantage of utilizing dual-modality PET and CT data over only single-modality data for H&N tumor segmentation.

Background: Cognitive fusion MRI-guided targeted biopsy (cTB) has been widely used in the diagnosis of prostate cancer (PCa). However, cTB relies heavily on the operator's experience and confidence in MRI readings. Our objective was to compare the cancer detection rates of MRI artificial intelligence-guided cTB (AI-cTB) and routine cTB and explore the added value of using AI for the guidance of cTB., Methods: This was a prospective, single-institution randomized controlled trial (RCT) comparing clinically significant PCa (csPCa) and PCa detection rates between AI-cTB and cTB. A total of 380 eligible patients were randomized to the AI-cTB group (n = 191) or the cTB group (n = 189). The AI-cTB group underwent AI-cTB plus systematic biopsy (SB) and the cTB group underwent routine cTB plus SB. The primary outcome was the detection rate of csPCa. The reference standard was the pathological results of the combination of TB (AI-cTB/cTB) and SB. Comparisons of detection rates of csPCa and PCa between groups were performed using the chi-square test or Fisher's exact test., Results: The overall csPCa and PCa detection rates of the whole inclusion cohort were 58.8% and 61.3%, respectively. The csPCa detection rates of TB combined with SB in the AI-cTB group were significantly greater than those in the cTB group at both the patient level (58.64% vs. 46.56%, p = 0.018) and per-lesion level (61.47% vs. 47.79%, p = 0.004). Compared with cTB, the AI-cTB could detect a greater proportion of patients with csPCa at both the per-patient level (69.39% vs. 49.71%, p < 0.001) and per-lesion level (68.97% vs. 48.57%, p < 0.001). Multivariate logistic analysis indicated that compared with the cTB, the AI-cTB significantly improved the possibility of detecting csPCa (p < 0.001)., Conclusions: AI-cTB effectively improved the csPCa detection rate. This study successfully integrated AI with TB in the routine clinical workflow and provided a research paradigm for prospective AI-integrated clinical studies., Trial Registration: ClinicalTrials.gov, NCT06362291., Competing Interests: Declarations Ethics approval and consent to participate The study was reviewed and approved by the institutional review board of Peking University First Hospital (2023IR27). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Diabetic retinopathy (DR) is a leading cause of blindness globally. Buyang Huanwu decoction (BHD) is a traditional Chinese medicine for treating DR, but its therapeutic mechanisms are not fully understood. This study aimed to elucidate and validate the underlying mechanisms of BHD in DR treatment through network pharmacology and in vitro experiments. We identified active compounds in BHD and their associated targets using the TCMSP and SwissTargetPrediction. DR-related targets were sourced from GeneCards, NCBI, and OMIM databases. The protein-protein interaction (PPI) network and enrichment analyses were employed to predict common targets and pathways. Subsequent molecular docking and in vitro experiments, including cell viability assays, RT-qPCR, flow cytometry, and Western blot, were conducted to validate the anti-DR mechanism of BHD. Network pharmacology identified paeoniflorin as a key active compound in BHD for treating DR, with VEGFA emerging as a central target. Molecular docking suggested a strong binding affinity between paeoniflorin and VEGFA. In vitro experiments confirmed that paeoniflorin attenuated high glucose-induced increases in cell viability, migration, apoptosis, and inflammatory cytokine expression in retinal pigment epithelial cells. The therapeutic effect of paeoniflorin was primarily mediated through the downregulation of VEGFA expression. Our study demonstrates that paeoniflorin, a key active compound in BHD, effectively mitigates DR by downregulating VEGFA expression and reducing high glucose-induced cellular alterations, thereby highlighting its potential as a therapeutic agent for DR., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Altered reward processing has been repeatedly reported in Internet gaming disorder (IGD). However, it remains unclear whether these changes are linked to the severity of addictive symptoms or the extent of gaming experience. This study examined the neurophysiological responses regarding reward anticipation and consummation in individuals at different levels of gaming (including 22 casual gamers, 31 regular gamers, and 27 individuals with IGD) through a monetary incentive delay task. Three event-related potential components during reward anticipation-cue-related P300 (Cue-P3), contingent negative variation, and stimulus-preceding negativity (SPN)-and two during reward consummation-feedback-related negativity and feedback-related P300 (FB-P3)-were measured. We found that IGD individuals exhibited greater Cue-P3 but lower SPN amplitude compared to casual gamers, while regular gamers fell between the two without significant differences. Regressions indicated that more extensive gaming experience, rather than the severity of the symptoms, primarily contributed to the increased Cue-P3 in IGD. No group differences were found during reward consummation. Our results highlight disrupted reward anticipation processing in IGD, characterized by increased attention bias toward reward cues (Cue-P3) but diminished cognitive resources for reward anticipation (SPN) and emphasize the role of gaming experience in increased attention bias in IGD., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms., Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations., Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking., Conclusion: Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.