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The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons.sup.1. The atmospheric concentration of trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s.sup.2. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased.sup.3,4. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown.sup.3. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 [plus or minus] 3.0 ([plus or minus]1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010. Emissions from eastern China account for approximately 40 to 60 per cent of the global rise in emissions of trichlorofluoromethane (CFC-11), which may be a result of new production and use., Author(s): M. Rigby [sup.1] , S. Park [sup.2] , T. Saito [sup.3] , L. M. Western [sup.1] , A. L. Redington [sup.4] , X. Fang [sup.5] , S. Henne [sup.6] [...]

Multivesicular bodies are key endosomal compartments implicated in cellular quality control through their degradation of membrane-bound cargo proteins 1-3 . The ATP-consuming ESCRT protein machinery mediates the capture and engulfment of membrane-bound cargo proteins through invagination and scission of multivesicular-body membranes to form intraluminal vesicles 4,5 . Here we report that the plant ESCRT component FREE1 6 forms liquid-like condensates that associate with membranes to drive intraluminal vesicle formation. We use a minimal physical model, reconstitution experiments and in silico simulations to identify the dynamics of this process and describe intermediate morphologies of nascent intraluminal vesicles. Furthermore, we find that condensate-wetting-induced line tension forces and membrane asymmetries are sufficient to mediate scission of the membrane neck without the ESCRT protein machinery or ATP consumption. Genetic manipulation of the ESCRT pathway in several eukaryotes provides additional evidence for condensate-mediated membrane scission in vivo. We find that the interplay between condensate and machinery-mediated scission mechanisms is indispensable for osmotic stress tolerance in plants. We propose that condensate-mediated scission represents a previously undescribed scission mechanism that depends on the physicomolecular properties of the condensate and is involved in a range of trafficking processes. More generally, FREE1 condensate-mediated membrane scission in multivesicular-body biogenesis highlights the fundamental role of wetting in intracellular dynamics and organization., (© 2024. The Author(s).)

N6-methyladenosine (m6A) modification is one of the most prevalent forms of epigenetic modification and plays an important role in the development of degenerative diseases such as osteoarthritis (OA). However, the evidence concerning the role of m6A modification in OA is insufficient. Here, m6A modification was increased in human OA cartilage and degenerated chondrocytes. Among all of the m6A enzymes, the expression of the demethylase fat mass and obesity-associated protein (FTO) decreased dramatically. Conditional knockout of FTO in chondrocytes accelerates OA progression. FTO transcription is regulated by runt-related transcription factor-1 (RUNX1). Reduced FTO elevates m6A modification at the adenosine N6 position in SMAD family member 2 (SMAD2) mRNA, whose stability is subsequently modulated by the recruited m6A reader protein YTH N6-methyladenosine RNA binding protein F2 (YTHDF2). Collectively, these findings reveal the function and mechanism of the m6A family member FTO in OA progression. Therefore, reducing m6A modification to increase SMAD2 stability by activating FTO might be a potential therapeutic strategy for OA treatment., (© 2024. The Author(s).)

Due to the excellent mechanical, chemical, and electrical properties of third-generation semiconductor silicon carbide (SiC), pressure sensors utilizing this material might be able to operate in extreme environments with temperatures exceeding 300 °C. However, the significant output drift at elevated temperatures challenges the precision and stability of measurements. Real-time in situ temperature monitoring of the pressure sensor chip is highly important for the accurate compensation of the pressure sensor. In this study, we fabricate platinum (Pt) thin-film resistance temperature detectors (RTDs) on a SiC substrate by incorporating aluminum oxide (Al 2 O 3 ) as the transition layer and utilizing aluminum nitride (AlN) grooves for alignment through microfabrication techniques. The composite layers strongly adhere to the substrate at temperatures reaching 950 °C, and the interface of the Al 2 O 3 /Pt bilayer remains stable at elevated temperatures of approximately 950 °C. This stability contributes to the excellent high-temperature electrical performance of the Pt RTD, enabling it to endure temperatures exceeding 850 °C with good linearity. These characteristics establish a basis for the future integration of Pt RTD in SiC pressure sensors. Furthermore, tests and analyses are conducted on the interfacial diffusion, surface morphological, microstructural, and electrical properties of the Pt films at various annealing temperatures. It can be inferred that the tensile stress and self-diffusion of Pt films lead to the formation of hillocks, ultimately reducing the electrical performance of the Pt thin-film RTD. To increase the upper temperature threshold, steps should be taken to prevent the agglomeration of Pt films., (© 2024. The Author(s).)

Pressure overload-induced cardiac hypertrophy is a common cause of heart failure (HF), and emerging evidence suggests that excessive oxidized lipids have a detrimental effect on cardiomyocytes. However, the key regulator of lipid toxicity in cardiomyocytes during this pathological process remains unknown. Here, we used lipidomics profiling and RNA-seq analysis and found that phosphatidylethanolamines (PEs) and Acsl4 expression are significantly increased in mice with transverse aortic constriction (TAC)-induced HF compared to sham-operated mice. In addition, we found that overexpressing Acsl4 in cardiomyocytes exacerbates pressure overload‒induced cardiac dysfunction via ferroptosis. Notably, both pharmacological inhibition and genetic deletion of Acsl4 significantly reduced left ventricular chamber size and improved cardiac function in mice with TAC-induced HF. Moreover, silencing Acsl4 expression in cultured neonatal rat ventricular myocytes was sufficient to inhibit hypertrophic stimulus‒induced cell growth. Mechanistically, we found that Acsl4-dependent ferroptosis activates the pyroptotic signaling pathway, which leads to increased production of the proinflammatory cytokine IL-1β, and neutralizing IL-1β improved cardiac function in Acsl4 transgenic mice following TAC. These results indicate that ACSL4 plays an essential role in the heart during pressure overload‒induced cardiac remodeling via ferroptosis-induced pyroptotic signaling. Together, these findings provide compelling evidence that targeting the ACSL4-ferroptosis-pyroptotic signaling cascade may provide a promising therapeutic strategy for preventing heart failure., (© 2024. The Author(s).)

This study aims to uncover the molecular mechanisms underlying pediatric kidney stone formation induced by renal calcium deposition by utilizing high-throughput sequencing data to reveal the regulation of PINK1 by MyoD1. We performed transcriptome sequencing on peripheral blood samples from healthy children and children with kidney stones to obtain differentially expressed genes (DEGs). Genes related to mitochondrial oxidative stress were obtained from the Genecards website and intersected with DEGs to obtain candidate target genes. Additionally, we conducted protein-protein interaction (PPI) analysis using the STRING database to identify core genes involved in pediatric kidney stone disease (KSD) and predicted their transcription factors using the hTFtarget database. We assessed the impact of MyoD1 on the activity of the PINK1 promoter using dual-luciferase reporter assays and investigated the enrichment of MyoD1 on the PINK1 promoter through chromatin immunoprecipitation (ChIP) experiments. To validate our hypothesis, we selected HK-2 cells and established an in vitro kidney stone model induced by calcium oxalate monohydrate (COM). We evaluated the expression levels of various genes, cell viability, volume of adherent crystals in each group, as well as mitochondrial oxidative stress in cells by measuring mitochondrial membrane potential (Δψm), superoxide dismutase (SOD) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) content. Mitochondrial autophagy was assessed using mtDNA fluorescence staining and Western blot analysis of PINK1-related proteins. Apoptosis-related proteins were evaluated using Western blot analysis, and cell apoptosis was measured using flow cytometry. Furthermore, we developed a rat model of KSD and assessed the expression levels of various genes, as well as the pathologic changes in rat renal tissues using H&E and von Kossa staining, transmission electron microscopy (TEM), and the expression of creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) to evaluate the mitochondrial oxidative stress in vivo (through measurement of Δψm, SOD activity, ROS, and MDA content). Mitochondrial autophagy was evaluated by Western blot analysis of PINK1-associated proteins. Apoptosis-related proteins were detected using Western blot analysis, and cellular apoptosis was examined using cell flow cytometry and TUNEL staining. Bioinformatics analysis revealed that the PINK1 gene is upregulated and vital in pediatric kidney stone patients. Our in vitro and in vivo experiments demonstrated that silencing PINK1 could inhibit kidney stone formation by suppressing mitochondrial oxidative stress both in vitro and in vivo. We identified MyoD1 as an upstream transcription factor of PINK1 that contributes to the occurrence of pediatric kidney stones through the activation of PINK1. Our in vivo and in vitro experiments collectively confirmed that silencing MyoD1 could inhibit mitochondrial oxidative stress, mitochondrial autophagy, and cellular apoptosis in a rat model of kidney stones by downregulating PINK1 expression, consequently suppressing the formation of kidney stones. In this study, we discovered that MyoD1 may promote kidney stone formation and development in pediatric patients by transcriptionally activating PINK1 to induce mitochondrial oxidative stress., (© 2024. The Author(s).)

China ranks 160 out of 180 countries in terms of ecological efficiency, with an EPI score of 28.40 and a 10-year average change in score of 11.40. This article examines the impact of green finance and China's natural resources on regional ecological efficiency using the Tobit regression model. The study uses the average yearly exchange rate to normalize dollar-related values and GDP to 2012 RMB using the price deflator. Variables used as explanatory tools include green financing, the availability of natural resources, and regional eco-efficiency. The results of the study imply that natural resources in eastern region of China are better managed as and have avoided the resource curse as compared to central and western regions. Resources temporarily support area economic and social growth. However, resource agglomeration locks many elements in the resource industry and degrades regional industrial development, generating environmental and social difficulties that may hinder regional economic progress. Given that Foreign Direct Investment (FDI) increases regional eco-efficiency after accounting for adjustment. The FDI positively correlated with ecological efficiency in the east zone, while central and western zones have negative correlations. The industrial development of the nation negatively impacts ecological efficiency in the East, Midwest, and West regions. Western results are distinctive, with ecological efficiency and regional economic growth frequently going hand in hand., (© 2024. The Author(s).)

Algin oligosaccharides have been applied in diverse industries and could be innovative synthesized by alginate-degrading bacteria. For enhance the alginate degradation efficiency to produce more algin oligosaccharides, a mutant strain (Cobetia sp. cqz5-12-M1) was obtained through the complex mutagenesis using UV and the alkylating agent 1-methyl-3-nitro-1-nitrosoguanidine. The enzyme activity of the fermentation supernatant of mutant exhibited a significant 38.09% (53.98 ± 0.69 U/mL) increase, and its optimal growth conditions were determined as: 5 g/L sodium alginate, 5 g/L yeast powder, 30 g/L NaCl, 2 g/L K 2 HPO 4 , 2 g/L KH 2 PO 4 , 1 g/L MgSO 4 •7H 2 O, 0.01 g/L FeSO 4 •7H 2 O, pH 6.5, and 34 ℃. Moreover, its optimal degradation conditions were identified as: 5 g/L sodium alginate, 5 g/L yeast powder, 30 g/L NaCl, 2 g/L K 2 HPO 4 , 2 g/L KH 2 PO 4 , 1 g/L MgSO 4 •7H 2 O, 0.01 g/L FeSO 4 •7H 2 O, pH 6.5, 31 ℃ and 72 h, yielding an enzyme activity of 120.98 ± 1.40 U/mL in the fermentation supernatant. Conclusive experiments on reagent tolerance revealed the growth of the mutant strain was significantly inhibited by 3% hydrogen peroxide, 5% carbolic acid, and 10 mg/mL gatifloxacin. Additionally, the alginate degradation capacity of mutant strain was highly significantly inhibited by 75% ethanol and all tested antibiotics., (© 2024. The Author(s).)

Cuproptosis is characterized by lipoylated protein aggregation and loss of iron-sulfur (Fe-S) proteins, which are crucial for a wide range of important cellular functions, including DNA replication and damage repair. Sirt2 and sirt4 are lipoamidases that remove the lipoyl moiety from lipoylated proteins using nicotinamide adenine dinucleotide (NAD + ) as a cofactor. However, to date, it is not clear whether nicotinamide mononucleotide (NMN), a precursor of NAD + , affects cellular sensitivity to cuproptosis. Therefore, in the current study, cuproptosis was induced by the copper (Cu) ionophore elesclomol (Es) in HeLa cells. It was also found that Es/Cu treatment increased cellular DNA damage level. On the other hand, NMN treatment partially rescued cuproptosis in a dose-dependent manner, as well as reduced cellular DNA damage level. In addition, NMN upregulated the expression of Fe-S protein POLD1, without affecting the aggregation of lipoylated proteins. Mechanistic study revealed that NMN increased the expression of sirt2 and cellular reduced nicotinamide adenine dinucleotide phosphate (NADPH) level. Overexpression of sirt2 and sirt4 did not change the aggregation of lipoylated proteins, however, sirt2, but not sirt4, increased cellular NADPH levels and partially rescued cuproptosis. Inhibition of NAD + kinase (NADK), which is responsible for generating NADPH, abolished the rescuing function of NMN and sirt2 for Es/Cu induced cell death. Taken together, our results suggested that DNA damage is a characteristic feature of cuproptosis. NMN can partially rescue cuproptosis by upregulating sirt2, increase intracellular NADPH content and maintain the level of Fe-S proteins, independent of the lipoamidase activity of sirt2., (© 2024. The Author(s).)

To increase the efficiency of phytoremediation to clean up heavy metals in soil, assisted with alternating current (AC) electric field technology is a promising choice. Our experiments utilized the hyperaccumulator Sedum alfredii Hance and the fast-growing, high-biomass willow (Salix sp.). We investigated the efficiency of AC field combined with S. alfredii-willow intercropping for removing Cd from soils with different pH values. In the AC electric field treatment with S. alfredii-willow intercropping, the available Cd content in acidic soil increased by 50.00% compared to the control, and in alkaline soil, the increase was 100.00%. Furthermore, AC electric field promoted Cd uptake by plants in both acidic and alkaline soils, with Cd accumulation in the aboveground increased by 20.52% (P < 0.05) and 11.73%, respectively. In conclusion, the integration of AC electric fields with phytoremediation demonstrates significant favorable effectiveness., (© 2024. The Author(s).)

Chromosome instability (CIN) and subsequent aneuploidy are prevalent in various human malignancies, influencing tumor progression such as metastases and relapses. Extensive studies demonstrate the development of chemoresistance in high-CIN tumors, which poses significant therapeutic challenges. Given the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma (CRC), here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC cells. By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC. Subsequent analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these drugs. We further revealed the critical role of BCL-XL in the viability of high-CIN CRC cells. In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Mounting evidence showed that HER2-Low breast cancer patients could benefit from the novel anti-HER2 antibody-drug conjugates (ADCs) treatment, which pointed the way towards better therapy for HER2-Low patients. The purpose of this study was to describe the clinicopathological features, along with chemotherapeutic effects and survival outcomes of HER2-Low and HER2-Zero in TNBC who received neoadjuvant chemotherapy (NACT). We retrospectively evaluated 638 triple-negative breast cancer patients who were treated with neoadjuvant chemotherapy between August 2014 and August 2022. Pathologic complete response (pCR) and survival outcomes were analyzed in HER2-Low cohort, HER2-Zero cohort and the overall patients, respectively. In the entire cohort, 342 (53.6%) patients were HER2-Low and 296 (46.4%) patients were HER2-Zero. No significant difference was found between HER2-Low and HER2-Zero patients based on all the clinical-pathological characteristics. 143 cases (22.4%) achieved pCR after NACT in the overall TNBC patients. The pCR rate of the HER2-Low patients and the HER2-Zero patients was 21.3% and 23.6%, respectively, exhibiting no statistical difference (p = 0.487). The survival of pCR group after NACT significantly improved compared to non-pCR group either in HER2-Low patients or in HER2-Zero patients. Although we found that patients with HER2-Low had longer DFS than patients with HER2-Zero, there was no considerable difference (p = 0.068). However, HER2-Low patients had a dramatically longer OS than HER2-Zero patients (p = 0.012). The data from present study confirmed the clinical importance of HER2-Low expression in TNBC. Further effort is needed to determine whether HER2-Low could be a more favorable prognostic marker for individual treatment., (© 2024. The Author(s).)

Circulating cell-free DNA (cfDNA) in the peripheral blood is a promising biomarker for cancer diagnosis and prognosis. Somatic mutations identified in cancers have been used to detect therapeutic targets for clinical transformation and individualize drug selection, while germline variants can predict a patient's risk of developing cancer and drug sensitivity. However, no platform has been developed to analyze, calculate, integrate, and friendly visualize these pan-cancer cfDNA mutations deeply. In this work, we performed panel sequencing encompassing 1,115 cancer-related genes across 16,659 cancer patients, spanning 27 cancer types. We detected 496 germline variants in leukocytes and 11,232 somatic mutations in the cfDNA of all patients. CPGV (Cancer Peripheral blood Gene Variations), a database constructed from this dataset, is the first pan-cancer cfDNA database that encompasses somatic mutations, germline variants, and further comparative analyses of mutations across different cancer types. It bears great promise to serve as a valuable resource for cancer research., (© 2024. The Author(s).)

As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor (ACE2-OE) that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. Interferon-lambda was upregulated in cells with low-level infection while the NF-kB inhibitor alpha gene (encoding IkBa) was consistently upregulated in infected cells, and its expression positively correlated with infection levels. Confocal microscopy showed more IkBa expression in infected than bystander cells, but found concurrent nuclear translocation of NF-kB that IkBa usually prevents. Overexpressing a nondegradable IkBa mutant reduced NF-kB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and underscore that the strength of the NF-kB feedback loop in infected cells controls viral replication., (© 2024. The Author(s).)

Here, we present the whole genome sequence of Bt S2160-1, a potential alternative to the mosquitocidal model strain, Bti. One chromosome genome and four mega-plasmids were contained in Bt S2160-1, and 13 predicted genes encoding predicted insecticidal crystal proteins were identified clustered on one plasmid pS2160-1p2 containing two pathogenic islands (PAIs) designed as PAI-1 (Cry54Ba, Cry30Ea4, Cry69Aa-like, Cry50Ba2-like, Cry4Ca1-like, Cry30Ga2, Cry71Aa-like, Cry72Aa-like, Cry70Aa-like, Cyt1Da2-like and Vpb4C1-like) and PAI-2 (Cyt1Aa-like, and Tpp80Aa1-like). The clusters appear to represent mosquitocidal toxin islands similar to pathogenicity islands. Transcription/translation of 10 of the 13 predicted genes was confirmed by whole-proteome analysis using LTQ-Orbitrap LC-MS/MS. In summary, the present study identified the existence of a mosquitocidal toxin island in Bacillus thuringiensis, and provides important genomic information for understanding the insecticidal mechanism of B. thuringiensis., (© 2024. The Author(s).)

Wheat straw returning is a common agronomic measure in the farmland. Understanding organic carbon transformation is of great significance for carbon budget under the premise of widespread distribution of cadmium (Cd) contaminated soils. An incubation experiment was conducted to assess the influence of Cd contamination on the decomposition and accumulation of total organic carbon (TOC) as well as the composition and abundance of bacterial communities in eight soil types with wheat straw addition. The results showed that inhibition of Cd contamination on microbially mediated organic carbon decomposition was affected by soil types. The lower cumulative C mineralization and higher TOC content could be observed in the acidic soils relative to that in the alkaline soils. The content of Cd in soil exhibits different effects on the inhibition in decomposition of TOC. The high dosage level of Cd had stronger inhibitory impact due to its high toxicity. The decomposition of TOC was restricted by a reduction in soil bacterial abundance and weakening of bacterial activities. Redundancy analysis (RDA) indicated that Proteobacteria and Gemmatimonadetes were abundant in alkaline Cd-contaminated soils with wheat straw addition, while Bacteroidetes dominated cumulative C mineralization in acidic Cd-contamination soils. Moreover, the abundance of predicted functional bacteria indicated that high-dose Cd-contamination and acid environment all inhibited the decomposition of TOC. The present study suggested that pH played an important role on carbon dynamics in the Cd-contaminated soils with wheat straw addition., (© 2024. The Author(s).)

Accurate penetration rate prediction enhances rock-breaking efficiency and reduces disc cutter damage in tunnel boring machine (TBM) construction. However, this process faces significant challenges such as the high uncertainty of ground conditions and the complexity of maintaining optimal TBM operation in long and large tunnels. To address these challenges, we propose TCN-SENet++, a novel hybrid multistep real-time penetration rate prediction model that combines a temporal convolutional network (TCN) and a squeeze-and-excitation (SENet) block for aided tunneling. This study aims to demonstrate the application of TCN-SENet++, as well as other models such as RNN, LSTM, GRU, and TCN, for TBM penetration rate prediction. The model was developed using actual datasets collected from the Yin-Song diversion project. We employ a 30-s time step to predict the future time steps of the penetration rate (1st, 3rd, 5th, 7th, and 9th). The features that influence the penetration rate, such as the cutterhead torque, thrust, and cutterhead power, were considered. A comparative analysis using the mean absolute error and mean squared error revealed that the TCN-SENet++ model outperformed the other models, including RNN, LSTM, GRU, TCN, and TCN-SENet+. In comparison, TCN-SENet++ achieved average MSE reductions of 18%, 6%, 3%, 1%, and 2%, respectively. The TCN-SENet++ model demonstrated fewer errors in the new project, validating its effectiveness and suitability for real-time penetration rate prediction in TBM construction., (© 2024. The Author(s).)

In the rapidly evolving landscape of Internet of Things (IoT), Zigbee networks have emerged as a critical component for enabling wireless communication in a variety of applications. Despite their widespread adoption, Zigbee networks face significant security challenges, particularly in key management and network resilience against cyber attacks like distributed denial of service (DDoS). Traditional key rotation strategies often fall short in dynamically adapting to the ever-changing network conditions, leading to vulnerabilities in network security and efficiency. To address these challenges, this paper proposes a novel approach by implementing a reinforcement learning (RL) model for adaptive key rotation in Zigbee networks. We developed and tested this model against traditional periodic, anomaly detection-based, heuristic-based, and static key rotation methods in a simulated Zigbee network environment. Our comprehensive evaluation over a 30-day period focused on key performance metrics such as network efficiency, response to DDoS attacks, network resilience under various simulated attacks, latency, and packet loss in fluctuating traffic conditions. The results indicate that the RL model significantly outperforms traditional methods, demonstrating improved network efficiency, higher intrusion detection rates, faster response times, and superior resource management. The study underscores the potential of using artificial intelligence (AI)-driven, adaptive strategies for enhancing network security in IoT environments, paving the way for more robust and intelligent Zigbee network security solutions., (© 2024. The Author(s).)

The response of cardiac fibroblast proliferation to detrimental stimuli is one of the main pathological factors causing heart remodeling. Reactive oxygen species (ROS) mediate the proliferation of cardiac fibroblasts. However, the exact molecular mechanism remains unclear. In vivo, we examined the oxidative modification of miRNAs with miRNA immunoprecipitation with O 8 G in animal models of cardiac fibrosis induced by Ang II injection or ischemia‒reperfusion injury. Furthermore, in vitro, we constructed oxidation-modified miR-30c and investigated its effects on the proliferation of cardiac fibroblasts. Additionally, luciferase reporter assays were used to identify the target of oxidized miR-30c. We found that miR-30c oxidation was modified by Ang II and PDGF treatment and mediated by excess ROS. We demonstrated that oxidative modification of G to O 8 G occurred at positions 4 and 5 of the 5' end of miR-30c (4,5-oxo-miR-30c), and this modification promoted cardiac fibroblast proliferation. Furthermore, CDKN2C is a negative regulator of cardiac fibroblast proliferation. 4,5-oxo-miR-30c misrecognizes CDKN2C mRNA, resulting in a reduction in protein expression. Oxidized miR-30c promotes cardiac fibroblast proliferation by mismatch mRNA of CDKN2C., (© 2024. The Author(s).)

In response to the global trend of climate change, it is important to accurately quantify emissions of fully fluorinated greenhouse gases (FFGHGs, referring to SF 6 /NF 3 /CF 4 /C 2 F 6 /C 3 F 8 /c-C 4 F 8 here). Atmospheric observation-based top-down methods and activity-based bottom-up methods are usually used together to estimate FFGHG emissions at the global and regional levels. In this work, emission gaps at global and regional levels are discussed among top-down studies, between the top-down and bottom-up FFGHG emissions, and among bottom-up emissions. Generally, trends and magnitudes of individual FFGHG emissions among top-down estimates are close to each other within the uncertainties. However, global bottom-up inventories show discrepancies in FFGHG emissions among each other in trends and magnitudes. The differences in emission magnitudes are up to 93%, 90%, 88%, 83%, 87%, and 85% for SF 6 , NF 3 , CF 4 , C 2 F 6 , C 3 F 8 , and c-C 4 F 8 , respectively. Besides, we reveal the insufficient regional TD studies and the lack of atmospheric observation data/stations especially in areas with potential FFGHG emissions. We make recommendations regarding the best practices for improving our understanding of these emissions, including both top-down and bottom-up methods., (© 2024. The Author(s).)

To investigate the associations between corneal curvature (CC) and other anterior segment biometrics in young myopic adults. In this retrospective multi-center study, 7893 young myopic adults were included. CC and other anterior segment biometrics were measured by Scheimpflug imaging (Pentacam). CC was defined as SimK at central 3 mm area, and other anterior segment biometrics included white-to-white corneal diameter (WTW), central corneal thickness (CCT), corneal volume (CV) at 3 mm, 5 mm, and 7 mm area, anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), anterior corneal eccentricity (ACE) and asphericity (ACAP), posterior corneal eccentricity (PCE) and asphericity (PCAP), anterior chamber depth (ACD), and anterior chamber volume (ACV). Univariate regression analyses were used to assess the associations between CC and other anterior segment biometrics, and multivariate regression analyses were further performed to adjusted for age, gender and spherical equivalent. CC was higher in patients of female gender and higher myopia (all P < 0.05). Eyes in higher CC quartiles had lower WTW, thinner CCT, lower CV at 3 mm and 5 mm, lower ACD, and lower ACV (all P < 0.001), but had larger ACA, larger PCA, less PCE and less PCAP (all P < 0.001), compared to eyes in lower CC quartiles. The trends of CV at 7 mm, ACE and ACAP were inconsistent in different CC quartiles. After adjusting for age, gender and spherical equivalent with multivariate linear regression, CC was positively correlated to CV at 7 mm (β s  = 0.069), ACA (β s  = 0.194), PCA (β s  = 0.187), ACE (β s  = 0.072), PCAP (β s  = 0.087), and ACD (β s  = 0.027) (all P < 0.05), but was negatively correlated to WTW (β s  = - 0.432), CCT (β s  = - 0.087), CV-3 mm (β s  = - 0.066), ACAP (β s  = - 0.043), PCE (β s  = - 0.062), and ACV (β s  = - 0.188) (all P < 0.05). CC was associated with most of the other anterior segment biometrics in young myopic adults. These associations are important for better understanding of the interactions between different anterior segment structures in young myopic patients, and are also useful for the exploration of the pathogenesis of myopia., (© 2024. The Author(s).)

Synthetic data generation is being increasingly used as a privacy preserving approach for sharing health data. In addition to protecting privacy, it is important to ensure that generated data has high utility. A common way to assess utility is the ability of synthetic data to replicate results from the real data. Replicability has been defined using two criteria: (a) replicate the results of the analyses on real data, and (b) ensure valid population inferences from the synthetic data. A simulation study using three heterogeneous real-world datasets evaluated the replicability of logistic regression workloads. Eight replicability metrics were evaluated: decision agreement, estimate agreement, standardized difference, confidence interval overlap, bias, confidence interval coverage, statistical power, and precision (empirical SE). The analysis of synthetic data used a multiple imputation approach whereby up to 20 datasets were generated and the fitted logistic regression models were combined using combining rules for fully synthetic datasets. The effects of synthetic data amplification were evaluated, and two types of generative models were used: sequential synthesis using boosted decision trees and a generative adversarial network (GAN). Privacy risk was evaluated using a membership disclosure metric. For sequential synthesis, adjusted model parameters after combining at least ten synthetic datasets gave high decision and estimate agreement, low standardized difference, as well as high confidence interval overlap, low bias, the confidence interval had nominal coverage, and power close to the nominal level. Amplification had only a marginal benefit. Confidence interval coverage from a single synthetic dataset without applying combining rules were erroneous, and statistical power, as expected, was artificially inflated when amplification was used. Sequential synthesis performed considerably better than the GAN across multiple datasets. Membership disclosure risk was low for all datasets and models. For replicable results, the statistical analysis of fully synthetic data should be based on at least ten generated datasets of the same size as the original whose analyses results are combined. Analysis results from synthetic data without applying combining rules can be misleading. Replicability results are dependent on the type of generative model used, with our study suggesting that sequential synthesis has good replicability characteristics for common health research workloads., (© 2024. The Author(s).)

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions., (© 2024. The Author(s).)

SULF1 has been implicated in a number of malignancies. The function of SULF1 in gastric cancer is disputed. The objective of this study was to examine the role and underlying molecular mechanisms of SULF1 in the context of gastric cancer. We found that the expression of SULF1 was increased in gastric cancer, especially in cancer-associated fibroblasts. The overexpression of SULF1 was found to be significantly correlated with unfavorable prognosis among individuals diagnosed with gastric cancer. Functionally, cancer-associated fibroblasts-derived SULF1 served as a oncogenic molecule which facilitated gastric cancer cells metastasis and CDDP resistance. Mechanistically, SULF1 regulated the communication between gastric cancer cells and cancer-associated fibroblasts in tumor microenvironment as a signaling molecule. Cancer-associated fibroblasts-secreted SULF1 interfered with the interaction between TGF-β1 and TGFBR3 by combining with TGFBR3 on gastric cancer cell membrane, subsequently activated TGF-β signaling pathway. In conclusion, our findings have presented novel approaches for potential treatment and prognosis prediction in individuals diagnosed with gastric cancer through the targeting of the CAFs-SULF1-TGFBR3-TGF-β1 signaling axis., (© 2024. The Author(s).)

Large language models (LLMs) have the potential to transform our lives and work through the content they generate, known as AI-Generated Content (AIGC). To harness this transformation, we need to understand the limitations of LLMs. Here, we investigate the bias of AIGC produced by seven representative LLMs, including ChatGPT and LLaMA. We collect news articles from The New York Times and Reuters, both known for their dedication to provide unbiased news. We then apply each examined LLM to generate news content with headlines of these news articles as prompts, and evaluate the gender and racial biases of the AIGC produced by the LLM by comparing the AIGC and the original news articles. We further analyze the gender bias of each LLM under biased prompts by adding gender-biased messages to prompts constructed from these news headlines. Our study reveals that the AIGC produced by each examined LLM demonstrates substantial gender and racial biases. Moreover, the AIGC generated by each LLM exhibits notable discrimination against females and individuals of the Black race. Among the LLMs, the AIGC generated by ChatGPT demonstrates the lowest level of bias, and ChatGPT is the sole model capable of declining content generation when provided with biased prompts., (© 2024. The Author(s).)

This study aimed to assess pulmonary changes at 6-month follow-up CT and predictors of pulmonary residual abnormalities and fibrotic-like changes in COVID-19 pneumonia patients in China following relaxation of COVID restrictions in 2022. A total of 271 hospitalized patients with COVID-19 pneumonia admitted between November 29, 2022 and February 10, 2023 were prospectively evaluated at 6 months. CT characteristics and Chest CT scores of pulmonary abnormalities were compared between the initial and the 6-month CT. The association of demographic and clinical factors with CT residual abnormalities or fibrotic-like changes were assessed using logistic regression. Follow-up CT scans were obtained at a median of 177 days (IQR, 170-185 days) after hospital admission. Pulmonary residual abnormalities and fibrotic-like changes were found in 98 (36.2%) and 39 (14.4%) participants. In multivariable analysis of pulmonary residual abnormalities and fibrotic-like changes, the top three predictive factors were invasive ventilation (OR 13.6; 95% CI 1.9, 45; P < .001), age > 60 years (OR 9.1; 95% CI 2.3, 39; P = .01), paxlovid (OR 0.11; 95% CI 0.04, 0.48; P = .01) and invasive ventilation (OR 10.3; 95% CI 2.9, 33; P = .002), paxlovid (OR 0.1; 95% CI 0.03, 0.48; P = .01), smoker (OR 9.9; 95% CI 2.4, 31; P = .01), respectively. The 6-month follow-up CT of recent COVID-19 pneumonia cases in China showed a considerable proportion of the patients with pulmonary residual abnormalities and fibrotic-like changes. Antivirals against SARS-CoV-2 like paxlovid may be beneficial for long-term regression of COVID-19 pneumonia., (© 2024. The Author(s).)

The interactions between white-to-white corneal diameter (WTW) and other ocular biometrics are important for planning of refractive surgery and understanding of ocular structural changes in myopia, but such interactions are rarely investigated in young myopic adults. This is a retrospective study involving 7893 young myopic adults from five centers. WTW and other ocular biometrics were measured by Pentacam. The ocular biometrics included anterior corneal curvature (AK) and posterior corneal curvature (PK), central corneal thickness (CCT) and corneal volume (CV), anterior and corneal eccentricity and asphericity, anterior corneal astigmatism (ACA) and posterior corneal astigmatism, anterior chamber depth (ACD), and anterior chamber volume (ACV). The ocular biometrics were compared among eyes of different WTW quartiles. Multivariate linear regression was used to assess the linear associations between WTW and other ocular biometrics adjusting for age, gender and spherical equivalent. In eyes of different WTW quartiles, other ocular biometrics were also significantly different (all P < 0.05). After adjusting for age, gender and spherical equivalent, WTW was positively correlated to AK (β = 0.26 to 0.29), ACA (β = 0.13), anterior corneal asphericity (β = 0.05), PK (β = 0.33 to 0.34), posterior corneal asphericity (β = 0.13), ACD (β = 0.29), and ACV (β = 40.69), and was negatively correlated to CCT (β = - 6.83), CV (β = - 0.06 to - 0.78), anterior corneal eccentricity (β = - 0.035), and posterior corneal eccentricity (β = - 0.14) (all P < 0.001). In conclusion, we found that in young myopic adults, larger WTW was associated with thinner corneal thickness, flatter corneal curvature, more anterior corneal toricity, less corneal eccentricity and asphericity, and broader anterior chamber. Our findings may fill in the gap of literature, and help us better understand how the anterior segment structures interact with the WTW in myopia., (© 2024. The Author(s).)

The ITER project is one of the largest international cooperative scientific projects in the world, aiming to verify the feasibility of magnetic confinement controlled nuclear fusion technology and provide a technical basis for the subsequent construction of fusion energy power stations. The success or failure of ITER will greatly affect the commercialization process of fusion energy. The probabilistic safety assessment (PSA) was a powerful means to evaluate the risk and reliability of nuclear facility and achieved great success in safety assessment of fission power plants. Based on this, the PSA progress for ITER was proposed in this paper. And the in-vessel leakage accident was investigated to verify the effectiveness of proposed method. The result shows the maximum possible radiological consequences of ITER in-vessel leakage accident of ITER is 1.6E-3 mSv, and the frequencies of this consequence is 1.63E-8/year. The reason of this consequence was also discussed in this paper. Those result could provide some valuable reference for radiation risk assessment and safety supervision of fusion commercial reactor in the nuclear future., (© 2024. The Author(s).)

Chironomids are one of the most abundant aquatic insects and are widely distributed in various biological communities. However, the lack of high-quality genomes has hindered our ability to study the evolution and ecology of this group. Here, we used Nanopore long reads and Hi-C data to produce two chromosome-level genomes from mixed genomic data. The genomes of Smittia aterrima (SateA) and Smittia pratorum (SateB) were assembled into three chromosomes, with sizes of 78.45 Mb and 71.56 Mb, scaffold N50 lengths of 25.73 and 23.53 Mb, and BUSCO completeness of 98.5% and 97.8% (n = 1,367), 5.68 Mb (7.24%) and 1.94 Mb (2.72%) of repetitive elements, and predicted 12,330 (97.70% BUSCO completeness) and 11,250 (97.40%) protein-coding genes, respectively. These high-quality genomes will serve as valuable resources for comprehending the evolution and environmental adaptation of chironomids., (© 2024. The Author(s).)

To evaluate the impact of copublication on hypertension-related clinical practice guidelines' citation, we searched the Web of Science Core Collection and guide.medlive.cn until 31 December 2017 using the terms "hypertension" and "guideline". The copublished group was matched with the noncopublished group at a 1:2 ratio. Primary outcomes were total citations and citations within the first five years after publication. Secondary outcomes included the adjusted impact factor ratio (excluding copublished guidelines) to the actual impact factor of the journal. Altmetric scores were compared using Altmetric explorer data. 21 copublished and 42 noncopublished guidelines were included. The copublished group had higher median current total citations [387.0 (90.0, 1806.0) vs 70.5 (23.25, 158.25)], and higher median citations at one, two, three, four, and five years [7.0 (0.5, 58.5) vs 1.0 (0.0, 5.5), 33.0 (14.0, 142.0) vs 5.5 (1.75, 26.25), 46.0 (24.5, 216.0) vs 10.5 (3, 25.75), 50.0 (19.0, 229.0) vs 9.0 (3.0, 19.0), 52.0 (13.5, 147.0) vs 7.0 (2.0, 20.0), all p < 0.05]. The adjusted IF analysis showed that if they had not copublished the guidelines, 10 of 24 and 11 of 24 journals would have had a lower IF in the first and second years. Median altmetric scores were significantly higher for copublished guidelines [38.5 (9.5, 90.5) vs 3.5 (1.0, 9.0)] (p < 0.05). Copublication is associated with a higher citation frequency of hypertension guidelines and may increase the journal IF. Positive impacts extend beyond academia, benefiting society through broader guideline application and dissemination. This facilitates broader application of guidelines and promotes their dissemination. We conducted a retrospective cohort study to demonstrate how copublication promotes the dissemination of hypertension guidelines., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

To explore the correlation between tear LT-a, pterygium status, and dry eye indicators. We established a diagnostic model to evaluate active pterygium. A retrospective study was conducted between June 2021 and June 2023 on 172 patients, comprising 108 men and 64 women. The study analyzed LT-a and various ocular parameters in all participants. The data was collected using Excel software and analyzed using SPSS 25.0 statistical software and Medcalc. We made a nomogram diagnostic model to different diagnosed the state of pterygium. This study found that pterygium has progressive eye surface damage during the active state. There was no significant difference in dry eye indicators between the two groups. However, the concentration of LT-a in the active group was significantly lower than that in the inactive group (P < 0.001). We observed that increased pterygium grade corresponded to a worse ocular surface condition. In addition, LT-a was significantly positively correlated with disease duration, but negatively correlated with age, pterygium size, active pterygium state, and LLT value. The optimal intercept value for evaluating active pterygium in Lt-a was ≤ 0.49 dg/ml. We screened three variables for evaluating active pterygium through Single and Multiple regression analysis: LT-a grading, pterygium size, and congestion score. Finally, we made a reliable diagnostic nomogram model. Pterygium development triggers immune inflammation. Our model based on LT-a identifies active pterygium for personalized treatment options and new research directions., (© 2024. The Author(s).)

The contribution of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) is crucial for nitrogen transformation. The effects of four organic amendments (OAs) plus urea on soil nitrogen transformation and the contribution of the ammonia-oxidizing microbial community were investigated using an incubation experiment. The OAs plus urea treatments included pig manure plus urea (PM + U), wheat straw plus urea (WS + U), compost plus urea (CP + U) and improved-compost plus urea (IC + U), while no OAs and urea amended control was noted as CK. The abundance and composition of AOA and AOB were determined using high through-put sequencing. Compared with CK, the OA plus urea treatments significantly enhanced the amount of total mineralized nitrogen released during the incubation process. After incubation, the highest mineralized nitrogen and net nitrogen mineralization was under the PM + U treatment and the lowest was in the WS + U treatment. In conclusion, among all OA plus urea treatments, the microbial biomass nitrogen content was the highest in WS + U treatment and dissolved organic nitrogen content was the highest with the PM + U treatment. Additionally, the abundance of AOB was inhibited in comparison to that of AOA; however, AOB contributed more to nitrification than AOA. Soil NO 3 - -N and dissolved organic nitrogen were the principal components influencing the distribution of AOA and AOB. The result illustrated that the OAs plus urea, especially PM plus urea promoted mineralization to produce more dissolved organic nitrogen and NH4 + -N, thus accelerating the growth of AOB to strengthen nitrification in soil., (© 2023. The Author(s).)

Salt stress is one unfavorable factor of global climate change that adversely affects rice plant growth and yield. To identify novel salt-tolerant genes and new varieties of salt-tolerant rice, a better understanding of the molecular regulation mechanism of salt tolerance in rice is needed. In this study we used transcriptome analyses to examine changes in gene expression of salt-tolerant and salt-sensitive rice plants. The salt-tolerant cultivar HH11 and salt-sensitive cultivar IR29 were treated with 200 mM NaCl solution for 0 h, 6 h, 24 h and 48 h at the three leaf stage. Physiological parameters and transcriptome were measured and analyzed after each treatment. Activity of SOD and POD, as well as the MDA and protein content of the two rice cultivars generally increased with increasing time of exposure to NaCl. Meanwhile, the APX activity first increased, then decreased in both cultivars, with maximum values seen at 6 h for IR29 and at 24 h for HH11. The GR and GPX activity of HH11 were stronger than that of IR29 in response to salt stress. The H 2 O 2 content first increased at 0-6 h, then decreased at 6-24 h, and then increased again at 24-48 h under salt stress. Compared with IR29, SOD, POD and APX activity of HH11 was more sluggish in response to salt stress, reaching the maximum at 24 h or 48 h. The MDA, H 2 O 2 and proline content of HH11 was lower than that of IR29 under salt stress. Relative to untreated HH11 plants (0 h) and those exposed to salt for 6 h, 24 h, and 48 h (H0-H6, H0-H24 and H0-H48), 7462, 6363 and 6636, differentially expressed genes (DEGs), respectively, were identified. For IR29, the respective total DEGs were 7566, 6075 and 6136. GO and KEGG enrichment analysis showed that metabolic pathways related to antioxidative responses and osmotic balance played vital roles in salt stress tolerance. Sucrose and starch metabolism, in addition to flavonoid biosynthesis and glutathione metabolism, showed positive responses to salt stress. Expression of two SPS genes (LOC&#95;Os01g69030 and LOC&#95;Os08g20660) and two GST genes (LOC&#95;Os06g12290 and LOC&#95;Os10g38740) was up-regulated in both HH11 and IR29, whereas expression of LOC&#95;Os09g12660, a glucose-1-phosphate adenylyltransferase gene, and two SS genes (LOC&#95;Os04g17650 and LOC&#95;Os04g24430) was up-regulated differential expression in HH11. The results showed that HH11 had more favorable adjustment in antioxidant and osmotic activity than IR29 upon exposure to salt stress, and highlighted candidate genes that could play roles in the function and regulation mechanism of salt tolerance in rice., (© 2023. The Author(s).)

Thiotepa/carmustine (TT-BCNU) is a commonly used autologous transplant (ASCT) conditioning regimen for primary DLBCL of the CNS (PCNSL). The total thiotepa dose varies among TT-BCNU recipients, with some centers administering a total dose of 20 mg/kg, while others using 10 mg/kg. We retrospectively assessed the impact of thiotepa dose intensity on ASCT outcomes in 218 adult PCNSL patients who underwent a first ASCT with TT-BCNU conditioning and received either a total thiotepa dose of 10 mg/kg (TT-10 group; N = 90), or 20 mg/kg (TT-20 group; N = 128). The median follow-up of survivors was 22 months. The cumulative incidence of 1-year non-relapse mortality (NRM) for TT-10 and TT-20 cohorts were 6% (95%CI = 2-12%) vs. 4% (95%CI = 1-8%), respectively (p = 0.66). The 3-year cumulative incidence of relapse (15% vs. 13%; p = 0.67), progression-free survival (PFS) (71% vs. 80%; p = 0.25) and overall survival (OS) (79% vs. 83%; p = 0.56) were similar in the TT-10 and TT-20 groups, respectively. On multivariate analysis compared to TT-10, the TT-20 cohort was not associated with significantly different risk of NRM (Hazard ration [HR] = 0.77; p = 0.64), relapse/progression (HR = 0.87; p = 0.74), PFS (HR = 0.80; p = 0.48) or OS (HR = 1.10; p = 0.80). In conclusion thiotepa dose-intensity in TT-BCNU conditioning does not impact ASCT outcomes of PCNSL patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

High grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH) represents an uncommon B-cell lymphoma (BCL) with aggressive clinical courses and poor prognosis. Despite revolutionary therapeutic advances in BCL, there has been limited treatment progress in HGBCL-DH, thus necessitating additional therapeutic strategies for HGBCL-DH. This study demonstrated that the BET antagonist INCB057643 synergized with the XPO1 inhibitors (selinexor and eltanexor) to decrease cell viability and increase cell apoptosis in HGBCL-DH cells with or without TP53 mutations. As anticipated, the combined treatment of INCB057643 with selinexor slowed tumor growth and reduced the tumor burden in TP53-mutated HGBCL-DH xenografts. Mechanistically, MYC functional inhibition was a potential molecular mechanism underlying the synergy of the combined INCB057643 and selinexor treatment in HGBCL-DH cells independent of TP53 mutation status. In TP53 mutated HGBCL-DH cells, inducing DNA damage and impairing the DNA damage response (DDR) were involved in the therapeutic interaction of the combined regimen. In TP53 wild-type cells, the molecular mechanism was linked with upregulation of p53 levels and activation of its targeted pathways, rather than dysregulation of the DDR. Collectively, we might provide a potential promising combination therapy regimen for the management of HGBCL-DH. Clinical evaluations are warranted to confirm this conclusion., (© 2023. The Author(s).)

Mice have emerged as a widely employed model for investigating various retinal diseases. However, the availability of comprehensive datasets capturing the entire developmental and aging stages of the mouse retina, particularly during the elderly period, encompassing integrated lncRNA and mRNA expression profiles, is limited. In this study, we assembled a total of 18 retina samples from mice across 6 distinct stages of development and aging (5 days, 3 weeks, 6 weeks, 10 weeks, 6 months, and 15 months) to conduct integrated lncRNA and mRNA sequencing analysis. This invaluable dataset offers a comprehensive transcriptomic resource of mRNA and lncRNA expression profiles during the natural progression of retinal development and aging. The discoveries stemming from this investigation will significantly contribute to the elucidation of the underlying molecular mechanisms associated with various retinal diseases, such as congenital retinal dysplasia and retinal degenerative diseases., (© 2023. Springer Nature Limited.)

To explore the genetic characteristics of systemic juvenile rheumatoid arthritis (sJRA) and type 1 diabetes mellitus (T1D). The microarray data of sJRA and T1D from Gene Expression Omnibus (GEO) were analyzed. The shared differentially expressed genes (SDEGs) were identified by the Meta-analysis, and genes of extracellular proteins were identified. Then, transcription factors (TFs) and their target genes in SDEGs were obtained by comparing databases from HumanTFDB, and hTFtarget. After that, functional enrichment analyses of the previously identified gene sets were performed by metascape tool. Finally, immune infiltration was analysed by CIBERSORT. We found 175 up-regulated and 245 down-regulated SDEGs, and by constructing a TFs-targeted SDEGs network, 3 key TFs (ARID3A, NEF2, RUNX3) were screened. Functional enrichment analyses and immune infiltration results suggested not only the adaptive immune system but also the innate immune system, and signaling pathways like JAK-STAT are important in the pathogenesis of sJRA and T1D, involving biological processes such as CD4 T cell functions and neutrophil degranulation. This work suggests that innate immune abnormalities also play important roles in sJRA and T1D, CD4 T cell functions, neutrophil degranulation and the JAK-STAT pathway may be involved. The regulatory roles of ARID3A, NEF2, and RUNX3 in this network need to be further investigated., (© 2023. Springer Nature Limited.)

Nocturia is a manifestation of systemic diseases, in which chronic kidney disease (CKD) is an independent predictor of nocturia due to its osmotic diuretic mechanism. However, to our knowledge, previous studies have not examined the association between nocturia and estimated glomerular filtration rate (eGFR). The purpose of this study was to assess the association between nocturia exposure and eGFR in the general US population. This study presents a cross-sectional analysis of the general US population enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. To account for potential confounding factors, linear regression analysis was conducted to investigate the association between nocturia and eGFR. Stratified analyses and interaction tests were employed to examine the variables of interest. Additionally, sensitivity analyses were conducted across diverse populations. A total of 12,265 individuals were included in the study. After controlling for confounding factors, the results of the linear regression analysis indicated that a single increase in nocturnal voiding frequency was associated with a decrease in eGFR by 2.0 mL/min/1.73 m 2 . In comparison to individuals with a nocturnal urinary frequency of 0, those who voided 1, 2, 3, 4, and ≥ 5 times at night experienced a decrease in eGFR by 3.1, 5.4, 6.4, 8.6 and 4.0 mL/min/1.73 m 2 , respectively. Nocturia was found to be associated with a decreased eGFR of 4 mL/min/1.73 m 2 when compared to individuals without nocturia. The sensitivity analysis yielded consistent findings regarding the association between nocturia and eGFR in both CKD and non-CKD populations, as well as in hypertensive and non-hypertensive populations. Nevertheless, inconsistent conclusions were observed across various prognostic risk populations within the CKD context. The presence of nocturia and heightened frequency of nocturnal urination have been found to be associated with a decline in eGFR., (© 2023. Springer Nature Limited.)

Demineralized dentin matrix (DDM) is an osteoconductive and osteoinductive material that has been successfully used in sinus floor augmentation and alveolar ridge augmentation in clinical applications. It releases bone morphogenetic proteins (BMPs) and other growth factors, making DDM a suitable grafting material. However, the granular particle of DDM makes it difficult to anchor into the bone defect area. The aim of this study was to investigate the biological effects and osteoinductivity of the combination of DDM and Fibrin Glue (FG) at an optimal ratio on bone healing from a critical bone defect in an animal model. The mouse osteoblastic cell line (MC3T3-E1) was co-cultured with various ratios of DDM and FG to examine their effects on osteoblast proliferation and differentiation, as indicated by alkaline phosphatase (ALP) activity, osteocalcin (OC) production and mineralized nodules formation. The optimal ratio was then chosen for further study with a rabbit calvarial defective model, in which they were implanted with DDM or DDM-FG1 (1 g: 0.1 ml) and DDM-FG2 (1 g: 0.5 ml) compounds, or left blank for 2, 4, 8 and 12 weeks to investigate soft tissue and new bone regeneration. Micro-CT and histology analysis were used to evaluate the total grafting properties according to the different healing periods. The result from in vitro studies demonstrated that the ratio of 1:0.1 induced more ALP activity and mineralized nodules, while the ratio of 1: 0.5 (DDM-FG combined) induced more osteocalcin (OC) at specific time points. In the animal model, the 3D new bone volume in all DDM-FG treatment groups was significantly greater than that in the blank group at 2, 4, 8 and 12 weeks. Furthermore, the new bone volume was greater in DDM-FG2 when compared to the other groups during the early weeks of the healing period. In histological analysis, clusters of osteoblasts were formed adjacent to the DDM particles, and newly formed bone was observed in all groups, suggesting an osteoinductive property of DDM. Moreover, the greater new collagen synthesis observed at 4 weeks suggested that early bone healing was induced in the DDM-FG2 group. This study demonstrated that at an optimal ratio, the DDM-FG compound enhances osteogenic activities and bone regeneration., (© 2023. Springer Nature Limited.)

The neutron capture cross section of [Formula: see text]Ta is relevant to s-process of nuclear astrophysics, extraterrestrial samples analysis in planetary geology and new generation nuclear energy system design. The [Formula: see text]Ta([Formula: see text]) cross section had been measured between 1 eV and 800 keV at the back-streaming white neutron facility (Back-n) of China spallation neutron source(CSNS) using the time-of-flight (TOF) technique and [Formula: see text] liquid scintillator detectors. The experimental results are compared with the data of several evaluated libraries and previous experiments in the resolved and unresolved resonance region. Resonance parameters are extracted using the R-Matrix code SAMMY in the 1-700 eV region. The astrophysical Maxwell average cross section(MACS) from kT = 5 to 100 keV is calculated over a sufficiently wide range of neutron energies. For the characteristic thermal energy of an astrophysical site, at kT = 30keV the MACS value of [Formula: see text]Ta is 834 ± 75 mb, which shows an obvious discrepancy with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS) recommended value 766 ± 15 mb. The new measurements strongly constrain the MACS of [Formula: see text]Ta([Formula: see text]) reaction in the stellar s-process temperatures., (© 2023. Springer Nature Limited.)

Experiencing a social threat, such as social exclusion, is a painful event. In contrast to previous studies providing insight into the processing of a single short-termed threat, we exposed healthy individuals to the simultaneous onset of different social threats. This approach allowed us to track whether these threats are processed independently-or whether they interact in a common system. Using a virtual ball-throwing game (Cyberball), electrophysiological (event-related brain potentials, ERPs) and behavioral (self-reports) responses were collected. We assigned undergraduates to three experimental groups: single threat exclusion (n = 24), single threat loss of control (n = 26), and joint onset of both threats (dual-threat, n = 25). Self-reports indicated an increase in threats (i.e., in perceived exclusion and loss-of-control) in the latter group. The ERPs disentangled the neural responses to each threat: In the dual-threat group, the amplitudes of the P3 responses to exclusionary and intervention events were enhanced. This indicates that individuals are sensitized to each of the threats when the other threat is present simultaneously. Our findings support the theoretical notion of a common cognitive system responding to violations in subjective expectations., (© 2023. The Author(s).)

Ligamentum flavum hypertrophy (LFH) is the main physiological and pathological mechanism of lumbar spinal canal stenosis (LSCS). The specific mechanism for LFH has not been completely clarified. In this study, bioinformatic analysis, human ligamentum flavum (LF) tissues collection and analysis, and in vitro and in vivo experiments were conducted to explore the effect of decorin (DCN) on LFH pathogenesis. Here, we found that TGF-β1, collagen I, collagen III, α-SMA and fibronectin were significantly upregulated in hypertrophic LF samples. The DCN protein expression in hypertrophic LF samples was higher than that in non-LFH samples, but the difference was not significant. DCN inhibited the expression of TGF-β1-induced fibrosis-associated proteins in human LF cells, including collagen I, collagen III, α-SMA, and fibronectin. ELISAs showed that TGF-β1 can upregulate PINP and PIIINP in the cell supernatant, and this effect was inhibited after DCN administration. Mechanistic studies revealed that DCN suppressed TGF-β1-induced fibrosis by blocking the TGF-β1/SMAD3 signaling pathway. In addition, DCN ameliorated mechanical stress-induced LFH in vivo. In summary, our findings indicated that DCN ameliorated mechanical stress-induced LFH by antagonizing the TGF-β1/SMAD3 signaling pathway in vitro and in vivo. These findings imply that DCN is a potential therapeutic candidate for ligamentum flavum hypertrophy., (© 2023. The Author(s).)

Background: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear., Methods: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks., Results: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention., Conclusions: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety., Impact: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The family Chironomidae is represented by seven subfamilies in China, among which Chironominae and Orthocladiinae are the most diverse. To gain a better understanding of the architecture and evolution of the mitogenomes of Chironomidae, we sequenced mitogenomes of twelve species (including two published species) of the two subfamilies Chironominae and Orthocladiinae, and comparative mitogenomic analyses were performed. Thus, we identified highly conserved genome organization of twelve species with regard to genome content, nucleotide and amino acid composition, codon usage, and gene characteristics. The K a /K s values of most protein-coding genes were far smaller than 1, indicating that these genes were evolving under purifying selection. Phylogenetic relationships between the family Chironomidae were reconstructed using 23 species representing six subfamilies, based on protein-coding genes and rRNAs using Bayesian Inference and Maximum Likelihood. Our results suggested the following relationship within the Chironomidae: (Podonominae + Tanypodinae) + (Diamesinae + (Prodiamesinae + (Orthocladiinae + Chironominae))). This study contributes to the mitogenomic database of Chironomidae, which will be significant for studing the mitogenome evolution of Chironomidae., (© 2023. The Author(s).)

Clear cell renal cell carcinoma (ccRCC) is a main subtype of renal cancer, and advanced ccRCC frequently has poor prognosis. Many studies have found that lipid metabolism influences tumor development and treatment. This study was to examine the prognostic and functional significance of genes associated with lipid metabolism in individuals with ccRCC. Using the database TCGA, differentially expressed genes (DEGs) associated with fatty acid metabolism (FAM) were identified. Prognostic risk score models for genes related to FAM were created using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Our findings demonstrate that the prognosis of patients with ccRCC correlate highly with the profiles of FAM-related lncRNAs (AC009166.1, LINC00605, LINC01615, HOXA-AS2, AC103706.1, AC009686.2, AL590094.1, AC093278.2). The prognostic signature can serve as an independent predictive predictor for patients with ccRCC. The predictive signature's diagnostic effectiveness was superior to individual clinicopathological factors. Between the low- and high-risk groups, immunity research revealed a startling difference in terms of cells, function, and checkpoint scores. Chemotherapeutic medications such lapatinib, AZD8055, and WIKI4 had better outcomes for patients in the high-risk group. Overall, the predictive signature can help with clinical selection of immunotherapeutic regimens and chemotherapeutic drugs, improving prognosis prediction for ccRCC patients., (© 2023. The Author(s).)

In vitro maturation of porcine oocytes is characterized by asynchronous cytoplasmic and nuclear maturation, leading to less competent oocytes supporting embryo development. The purpose of this study was to evaluate the combined effect of rolipram and cilostamide as cyclic Adenine monophosphate (cAMP) modulators to find the maximum cAMP levels that temporarily arrest meiosis. We determined the optimal time to maintain functional gap junction communication during pre-in vitro maturation to be four hours. Oocyte competence was evaluated by the level of glutathione, reactive oxygen species, meiotic progression, and gene expression. We evaluated embryonic developmental competence after parthenogenetic activation and somatic cell nuclear transfer. The combined treatment group showed significantly higher glutathione and lower reactive oxygen species levels and a higher maturation rate than the control and single treatment groups. Cleavage and blastocyst formation rates in parthenogenetic activation and somatic cell nuclear transfer embryos were higher in two-phase in vitro maturation than in the other groups. The relative levels of BMP15and GDF9 expression were increased in two-phase in vitro maturation. Somatic cell nuclear transfer blastocysts from two-phase in vitro maturation oocytes showed a lower level of expression of apoptotic genes than the control, indicating better pre-implantation developmental competence. The combination of rolipram and cilostamide resulted in optimal synchrony of cytoplasmic and nuclear maturation in porcine in vitro matured oocytes and there by enhanced the developmental competence of pre-implantation embryos., (© 2023. The Author(s).)

Our previous study has shown that ATP action on P2X7R could be the second signal to induce the onset of gouty arthritis. However, the functional changes of P2X7R single nucleotide polymorphisms (SNPs) on the effects of ATP-P2X7R-IL-1β signaling pathway and uric acid remained unknown. We aimed to investigate the association between the functional change of P2X7R containing the Ala 348 to Thr polymorphisms (rs1718119) and the pathogenesis of gout. First, 270 gout patients and 70 hyperuricemic patients (without gout attack history in recent 5 years) were recruited for genotyping. In addition, the changes of ATP-induced pore formation were assessed in HEK-293T cells overexpressing different mutants in P2RX7, and the effects on P2X7R-NLRP3-IL-1β pathway activation were explored in P2RX7 overexpression THP-1 cells. The risk allele for gout was A at rs1718119, and the AA and AG genotypes exhibited a higher risk of gout. Furthermore, Ala 348 to Thr mutants increased P2X7-dependent ethidium + bromide uptake, upregulated IL-1β and NLRP3 levels as compared to the wild-type. We suggest that genetic polymorphisms of P2X7R containing the Ala 348 to Thr are associated with the increased risk of gout, showing an enhanced gain-of-function effect on the development of this disease., (© 2023. The Author(s).)

Microelectromechanical system (MEMS) pressure sensors based on silicon are widely used and offer the benefits of miniaturization and high precision. However, they cannot easily withstand high temperatures exceeding 150 °C because of intrinsic material limits. Herein, we proposed and executed a systematic and full-process study of SiC-based MEMS pressure sensors that operate stably from -50 to 300 °C. First, to explore the nonlinear piezoresistive effect, the temperature coefficient of resistance (TCR) values of 4H-SiC piezoresistors were obtained from -50 to 500 °C. A conductivity variation model based on scattering theory was established to reveal the nonlinear variation mechanism. Then, a piezoresistive pressure sensor based on 4H-SiC was designed and fabricated. The sensor shows good output sensitivity (3.38 mV/V/MPa), accuracy (0.56% FS) and low temperature coefficient of sensitivity (TCS) (-0.067% FS/°C) in the range of -50 to 300 °C. In addition, the survivability of the sensor chip in extreme environments was demonstrated by its anti-corrosion capability in H 2 SO 4 and NaOH solutions and its radiation tolerance under 5 W X-rays. Accordingly, the sensor developed in this work has high potential to measure pressure in high-temperature and extreme environments such as are faced in geothermal energy extraction, deep well drilling, aeroengines and gas turbines., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)