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As a substitute for brominated flame retardants, organophosphate flame retardants (OPFRs) have become a global concern due to their high toxicity and bioaccumulation. To paint an overall picture of OPFRs in the global environment, the present study develops a gridded global emission inventory of OPFRs on a spatial resolution of 1 × 1° from 2010 to 2020. Revealing a 3.31% average annual increase in emissions, totaling 21,324.42 tons. The production process is the primary source, accounting for 55.43% of emissions, with consumption processes making up the rest. Major sources are in Asia, North America, and Europe. The inventory is verified by implementing emission data into a global atmospheric transport model to predict OPFR concentrations in the global environment and comparing modeled concentrations with field sampled data. The results indicate that the inventory is reliable except for the pristine polar region, where the emission inventory and modeled concentrations underestimate OPFR levels in the atmosphere, likely resulting from ignorance of chemical reactions and the secondary derivative of parent OPFRs during their global long-distance atmospheric transport in the model. This comprehensive data set aids in formulating OPFR emission control policies and assessing health risks.

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BACKGROUND: This study investigates how metabolic/bariatric surgery (MBS) affects thyroid hormone (TH) levels and TH resistance in obese euthyroid individuals, focusing on their correlation with changes in body composition. METHODS: We included 470 obese individuals and 118 controls for baseline assessment, and 125 obese patients receiving MBS for longitudinal study. Data on body composition and thyroid function were collected. Correlations between baseline and changes in thyroid function and body composition were assessed. RESULTS: In the obese group, thyroid stimulating hormone (TSH), free triiodothyronine (fT3) levels, and thyroid feedback quantile-based index (TFQI) were elevated and significantly decreased post-MBS, along with visceral fat area (VFA) and body fat percentages, while skeletal muscle mass (SMM) percentage increased. Preoperative partial correlation analysis adjusted for age and sex revealed that TSH positively correlated with VFA (r=0.109, P=0.019), body fat percentage (r=0.114, P=0.013), and negatively correlated with SMM percentage (r=-0.104, P=0.024). Similar correlations were observed between central TH resistance indices and body composition, but no significant correlations were found in the control group. Post-MBS, decreased TSH positively correlated with decreased VFA (r=0.251, P=0.006) and increased SMM percentage (r=0.233, P=0.011). While reductions in VFA and body fat percentage were linked to improved central thyroid hormone resistance, a decrease in peripheral TH conversion was noted. CONCLUSIONS: MBS significantly impacts thyroid function and TH resistance, with notable correlations to changes in body composition.

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Silicon heterojunction (SHJ) solar cells have set world-record efficiencies among single-junction silicon solar cells, accelerating their commercial deployment. Despite these clear efficiency advantages, the high costs associated with low-temperature silver pastes (LTSP) for metallization have driven the search for more economical alternatives in mass production. 2D transition metal carbides (MXenes) have attracted significant attention due to their tunable optoelectronic properties and metal-like conductivity, the highest among all solution-processed 2D materials. MXenes have emerged as a cost-effective alternative for rear-side electrodes in SHJ solar cells. However, the use of MXene electrodes has so far been limited to lab-scale SHJ solar cells. The efficiency of these devices has been constrained by a fill factor (FF) of under 73%, primarily due to suboptimal charge transport at the contact layer/MXene interface. Herein, a silver nanowire (AgNW)-assisted Ti3C2Tx MXene electrode contact is introduced and explores the potential of this hybrid electrode in industry-scale solar cells. By incorporating this hybrid electrode into SHJ solar cells, 9.0 cm2 cells are achieved with an efficiency of 24.04% (FF of 81.64%) and 252 cm2 cells with an efficiency of 22.17% (FF of 76.86%), among the top-performing SHJ devices with non-metallic electrodes to date. Additionally, the stability and cost-effectiveness of these solar cells are discussed.

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BACKGROUND: A sclerosing epithelioid fibrosarcoma (SEF) is a rare malignant fibroblastic soft tissue tumor that rarely occurs in intra-abdominal organs. A case of a SEF in the pancreatic head is reported herein, including its clinical manifestations, preoperative imaging features, gross specimen and pathological findings. CASE SUMMARY: A 33-year-old male patient was admitted to Peking Union Medical College Hospital in December 2023 due to a one-year history of intermittent upper abdominal pain and the discovery of a pancreatic mass. The patient underwent an enhanced computed tomography scan of the abdomen, which revealed a well-defined, round mass with clear borders and calcifications in the pancreatic head. The mass exhibited progressive, uneven mild enhancement, measuring approximately 6.6 cm × 6.3 cm. The patient underwent laparoscopic pylorus-preserving pancreaticoduodenectomy. Postoperative pathological examination revealed that the lesion was consistent with a SEF. At the 3-month postoperative follow-up, the patient did not report any short-term complications, and there were no signs of tumor recurrence. CONCLUSION: SEFs are rare malignant fibrous soft tissue tumors. SEFs rarely develop in the pancreas, and its preoperative diagnosis depends on imaging findings, with confirmation depending on pathological examination and immunohistochemistry. Currently, only four cases of pancreatic SEF have been reported in studies written in English. This case is the first reported case of a pancreatic SEF by a clinical physician.

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Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy.

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We report on the efficient generation of intense terahertz radiation from the organic crystal N-benzyl-2-methyl-4-nitroaniline pumped by chirped Ti:sapphire femtosecond laser pulses. The THz energy and spectrum as a function of the pump fluence and duration of the chirped laser pulses are studied systematically. For the appropriate positively chirped pump pulses, a significant boost in the THz generation efficiency by a factor of around 2.5 is achieved, and the enhancement of high-frequency components (>1 THz) shortens the THz pulse duration. Via complete characterization of THz properties and transmitted laser spectra, this nonlinear behavior is attributed to the extended effective interaction length for phase matching as a result of the self-phase modulation of the intense pump laser pulses. Numerical calculations well reproduce the experimental observation. Our results demonstrate a robust, efficient, strong-field (up to several MV/cm) THz source using the common sub-10 mJ and sub-100 fs Ti:sapphire laser systems without optical parametric amplifiers.

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The unprecedented habitat fragmentation or loss has threatened the existence of many species. Therefore, it is essential to understand whether and how these species can pace with the environmental changes. Recent advantages in landscape genomics enabled us to identify molecular signatures of adaptation and predict how populations will respond to changing environments, providing new insights into the conservation of species. Here, we investigated the pattern of neutral and putative adaptive genetic variation and its response to changing environments in a tertiary relict tree species, Taxus cuspidata Sieb. et Zucc, which is distributed in northeast China and adjacent regions. We investigated the pattern of genetic diversity and differentiation using restriction site-associated DNA sequencing (RAD-seq) and seven nuclear microsatellites (nSSRs) datasets. We further explored the endangered mechanism, predicted its vulnerability in the future, and provided guidelines for the conservation and management of this species. RAD-seq identified 16,087 single nucleotide polymorphisms (SNPs) in natural populations. Both the SNPs and nSSRs datasets showed high levels of genetic diversity and low genetic differentiation in T. cuspidata. Outlier detection by F ST outlier analysis and genotype-environment associations (GEAs) revealed 598 outlier SNPs as putative adaptive SNPs. Linear redundancy analysis (RDA) and nonlinear gradient forest (GF) showed that the contribution of climate to genetic variation was greater than that of geography, and precipitation played an important role in putative adaptive genetic variation. Furthermore, the genetic offset and risk of non-adaptedness (RONA) suggested that the species at the northeast edge may be more vulnerable in the future. These results suggest that although the species has maintained high current genetic diversity in the face of recent habitat loss and fragmentation, future climate change is likely to threaten the survival of the species. Temperature (Bio03) and precipitation (Prec05) variables can be potentially used as predictors of response of T. cuspidata under future climate. Together, this study provides a theoretical framework for conservation and management strategies for wildlife species in the context of future climate change.

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Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.

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This study investigated the influence of photoaging on a nanoscale metal-organic framework (MOF), truncated rhombic dodecahedron nano-zeolitic imidazolate framework-8 (nZIF-8), focusing on its oxidative stress, inflammation, and implications for pulmonary diseases. We observed significant photodegradation-induced transformations in nZIF-8, characterized by a reduction in particle size from 200.5 to 101.4 nm and notable structural disintegration after prolonged exposure to simulated solar radiation. This alteration resulted in a marked decrease in oxidative cytotoxicity in BEAS-2B cells, which was attributed to changes in surface properties and reduced reactive oxygen species (ROS) production. Gene expression analysis further revealed a decrease in cytotoxic and inflammatory responses, which potentially lowers the risk of chronic obstructive pulmonary disease (COPD). Aged nZIF-8 also showed diminished capacity to induce pro-inflammatory cytokines and influence COPD-related gene expression, reducing its potential to exacerbate COPD pathogenesis. Our findings highlight the critical need for comprehensive safety evaluations of these materials, while considering their long-term environmental and biological impacts. The diminished cytotoxicity and inflammatory potential of aged nZIF-8 highlighted its enhanced suitability for broader applications, indicating that photoaging may lead to safer and more sustainable material utilization.

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Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the western blot data shown for the MMP­9 experiment in Fig. 4 on p. 1493 were strikingly similar to the western blots shown for the total­Akt experiments in Fig. 6 on p. 1494. After having re­examined their original data files, the authors realized that Fig. 6 had been inadvertently assembled incorrectly. The revised version of Fig. 6, containing the correct data for the total­Akt experiments, is shown below. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 31: 1489­1497, 2014; DOI: 10.3892/or.2013.2961].

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BACKGROUND: This study aimed to use artificial intelligence (AI) to integrate various radiological and clinical pathological data to identify effective predictors of contralateral cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC) and to establish a clinically applicable model to guide the extent of surgery. METHODS: This prospective cohort study included 603 patients with PTC from three centers. Clinical, pathological, and ultrasonographic data were collected and utilized to develop a machine learning (ML) model for predicting CCLNM. Model development at the internal center utilized logistic regression along with other ML algorithms. Diagnostic efficacy was compared among these methods, leading to the adoption of the final model (random forest). This model was subject to AI interpretation and externally validated at other centers. RESULTS: CCLNM was associated with multiple pathological factors. The Delphian lymph node metastasis ratio, ipsilateral cervical lymph node metastasis number, and presence of ipsilateral cervical lymph node metastasis were independent risk factors for CCLNM. Following feature selection, a Delphian lymph node-CCLNM (D-CCLNM) model was established using the Random forest algorithm based on five attributes. The D-CCLNM model demonstrated the highest area under the curve (AUC; 0.9273) in the training cohort and exhibited high predictive accuracy, with AUCs of 0.8907 and 0.9247 in the external and validation cohorts, respectively. CONCLUSIONS: We developed a new, effective method that uses ML to predict CCLNM in patients with PTC. This approach integrates data from Delphian lymph nodes and clinical characteristics, offering a foundation for guiding surgical decisions, and is conveniently applicable in clinical settings.

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(+)4-cholesten-3-one has been proved to have potential wound healing effect in the process of wound regeneration. This study aimed to evaluate the effect of (+)4-cholesten-3-one/sodium alginate/gelatin on skin injury and reveal its potential molecular mechanism. First, we prepared sodium alginate/gelatin hydrogel (SA/Gel hydrogel) with different ratios and tested their characteristics. Based on these results, different concentrations of (+)4-cholesten-3-one were added into SA/Gel hydrogel. A full-thickness skin injury model was successfully established to evaluate wound healing activityin vivo. HE staining and Masson staining were used to evaluate the thickness of granulation tissue and collagen deposition level. Immunohistochemical staining and immunofluorescence staining were applied to detect the level of revascularization and proliferation in each group of wounds. Western blot, quantitative-PCR and immunofluorescence staining were used to detect the expression of proteins related to Wnt/ß-catenin signaling pathway in each group of wounds.In vitroresults showed that the hydrogel not only created a 3D structure for cell adhesion and growth, but also exhibited good swelling ability, excellent degradability and favorable bio-compatibility. Most importantly,in vivoexperiments further indicated that (+)4-cholesten-3-one/SA/Gel hydrogel effectively enhanced wound healing. The effectiveness is due to its superior abilities in accelerating healing process, granulation tissue regeneration, collagen deposition, promoting angiogenesis, tissue proliferation, as well as fibroblast activation and differentiation. The underlying mechanism was related to the Wnt/ß-catenin signaling pathway. This study highlighted that (+)4-cholesten-3-one/SA/Gel hydrogel holds promise as a wound healing dressing in future clinical applications.

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BACKGROUND: Idiopathic ventricular arrhythmias (IVAs) arising from different portions of the communicating vein of the left ventricular summit (summit-CV) are not a rare phenomenon. Whereas its electrocardiographic (ECG) and electrophysiological characteristics are not fully investigated. OBJECTIVE: This study aimed to identify distinct ECG and electrophysiological features of IVAs originating from different portions of summit-CV. METHODS: Nineteen patients confirmed arising from summit-CV were included in this study. RESULTS: The 19 patients were divided into proximal and distal portion groups based on their target sites in summit-CV. In the proximal portion group, 100% (11/11) VAs showed dominant negative (rs or QS) waves in lead I, while in the distal portion group, 87.5% (7/8) showed dominant positive waves (R, Rs or r) (p < 0.000). In lead V1, 100% (11/11) of the proximal portion group showed dominant positive waves (R or Rs), while 62.50% (5/8) of the distal portion group showed positive and negative bidirectional or negative waves (RS or rS) (p < 0.005). RI>4mV, SI<3.5mV, RV1<13mV, SV1>3.5mV, RI/SI>0.83, and RV1/SV1< 2.6 indicated a distal portion of summit-CV with the predictive value of 0.909, 1.000, 0.653, 0.972, 0.903, 0.966, respectively. A more positive wave in lead I and a more negative wave in lead V1 indicated more distal origin in summit-CV. Target sites in proximal and distal summit-CV groups showed similar electrophysiological characteristics during mapping. CONCLUSIONS: There were significant differences in ECG characteristics of VAs at different portions of summit-CV, which could aid pre-procedure planning and facilitate radiofrequency catheter ablation (RFCA) procedures.

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The bacterium Pseudomonas aeruginosa is an exceptionally resilient opportunistic pathogen, presenting formidable challenges for treatment due to its proclivity for developing drug resistance. To address this predicament, we have devised a self-assembled supramolecular antibiotic known as dHTSN1@pHPplus, which can circumvent the drug resistance mechanism of Pseudomonas aeruginosa and effectively combat Pseudomonas aeruginosa infection by impeding the secretion of key virulence factors through the inhibition of the type III secretion system while simultaneously mobilizing immune cells to eradicate Pseudomonas aeruginosa. Furthermore, dHTSN1@pHPplus was ingeniously engineered with infection-targeting capabilities, enabling it to selectively concentrate precisely at the site of infection. As anticipated, the administration of dHTSN1@pHPplus exhibited a remarkable therapeutic efficacy in combating dual resistance to Meropenem and imipenem in a mouse model of P. aeruginosa lung infection. The results obtained from metagenomic detection further confirmed these findings, demonstrating a significant reduction in the proportion of Pseudomonas aeruginosa compared to untreated mice with Pseudomonas aeruginosa-infected lungs. Additionally, no notable acute toxicity was observed in the acute toxicity experiments. The present study concludes that the remarkable efficacy of dHTSN1@pHPplus in treating drug-resistant P. aeruginosa infection confirms its immense potential as a groundbreaking antibiotic agent for combating drug-resistant P. aeruginosa.

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COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, CFP-1, that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5. By using this platform, we identified 2-aminothiazole-4-carboxylic acids as new CSN5 inhibitors, which inhibited CSN5 but slightly downregulated PD-L1 in cancer cells. Furthermore, through the integration of deep learning-enabled virtual screening, we discovered that shikonins are nanomolar CSN5 inhibitors, which can upregulate PD-L1 in HCT116 cells. The binding modes of these structurally distinct inhibitors with CSN5 were explored by using microsecond-scale molecular dynamics simulations and tryptophan quenching assays.

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Anxiety disorders are prevalent chronic psychological disease with complex pathogenic mechanisms. Current anxiolytics have limited efficacy and numerous side effects in many anxiety patients, highlighting the urgent need for new therapies. Recent research has been focusing on nutritional supplements, particularly amino acids, as potential therapies for anxiety disorders. Among these, L-Cysteine plays a crucial role in various biological processes. L-Cysteine exhibits antioxidant properties that can enhance the antioxidant functions of the central nervous system (CNS). Furthermore, metabolites of L-cysteine, such as glutathione and hydrogen sulfide have been shown to alleviate anxiety through distinct molecular mechanisms. Long-term administration of L-Cysteine has anxiolytic, antidepressant, and memory-improving effects. L-Cysteine depletion can lead to increased oxidative stress in the brain. This review delves into the potential mechanisms of L-Cysteine and its main products, glutathione (GSH) and hydrogen sulfide (H2S) in the management of anxiety and related diseases.

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Immunotherapy for pancreatic ductal carcinoma (PDAC) remains disappointing due to the repressive tumor microenvironment and T cell exhaustion, in which the roles of interferon-stimulated genes were largely unknown. Here, we focused on a typical interferon-stimulated gene, GBP4, and investigated its potential diagnostic and therapeutic value in pancreatic cancer. Expression analysis on both local samples and public databases indicated that GBP4 was one of the most dominant GBP family members present in the PDAC microenvironment, and the expression level of GBP4 was negatively associated with patient survival. We then identified DNA hypo-methylation in regulatory regions of GBP4 in PDAC, and validated its regulatory role on GBP4 expression via performing targeted methylation using dCas9-SunTag-DNMAT3A-sgRNA-targeted methylation system on selected DNA locus. After that, we investigated the downstream functions of GBP4, and chemotaxis assays indicated that GBP4 overexpression significantly improved the infiltration of CD8+T cells, but also induced upregulation of immune checkpoint genes and T cell exhaustion. Lastly, in vitro T cell killing assays using primary organoids suggested that the PDAC samples with high level of GBP4 expression displayed significantly higher sensitivity to anti-PD-1 treatment. Taken together, our studies revealed the expression patterns and epigenetic regulatory mechanisms of GBP4 in pancreatic cancer and clarified the effects of GBP4 on T cell exhaustion and antitumor immunology.

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Automatically identifying abnormal behaviors of caged laying hens in a thermal environment improves manual management efficiency. It also provides reference indicators for breeding heat-tolerant hens. In this study, we propose a deep learning-based method for automatic recognition and evaluation of typical heat stress behaviors in hens. We developed a lightweight object detection algorithm, YOLO-HGP, based on the YOLOv8n as the baseline model. YOLO-HGP achieves Precision (P), Recall (R), and mean average precision (mAP) of 95.952%, 94.127%, and 97.667%, respectively, effectively detecting typical heat stress behaviors in hens. Compared to the original YOLO v8n, YOLO-HGP improves R, and mAP by 6.257%, and 1.963%, respectively. The FLOPs (floating point operations) and parameter count of YOLO-HGP are 4.3G and 1.729M, reducing by 47.56% and 42.58% compared to the original model. Additionally, we introduce the "ORC-ratio" (The ratio of the combined frequency of open-beak breathing and retching behaviors to the frequency of closed-beak behaviors.) as an evaluation indicator for the frequency of typical heat stress behaviors in hens and combine it with the Hybrid-SORT multiobject tracking algorithm to achieve tracking detection of individual hens. The study demonstrates that the proposed model effectively identifies and quantitatively evaluates typical behaviors of hens in a thermal environment, providing an effective approach for the automated recognition of heat stress behaviors in hens.