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Background Occupational noise exposure was related to cardiovascular disease, of which dyslipidemia was an important inducement. This study investigated the relationship between occupational noise exposure and dyslipidemia. Methods Four hundred ninety-two occupational noise-exposed workers and 664 non-exposed workers were recruited to conduct environmental noise tests and personal occupational physical examinations. A lasso-logistic regression model was used to estimate the relative risk of dyslipidemia. A restricted cubic spline was used to estimate the association between noise exposure years and dyslipidemia after adjusting for potential confounding factors. Results A crude association was observed between the occupational noise exposure (75–85 dB(A)) and dyslipidemia. After adjusting for confounding factors, there was a non-linear relationship between noise exposure years and dyslipidemia (P for non-linearity =0.01). Workers exposed to 75–85 dB(A) for 11 to 24.5 years had a higher risk of dyslipidemia than non-exposed workers. Conclusions A positive and non-linear exposure-response relationship was found in workers exposed to 75–85 dB(A) whose exposure years were between 11 and 24.5. Workers had the highest risk of dyslipidemia when exposed for 13.5 years.

Modern vehicles rely on the Controller Area Network (CAN) for inter-module communication, yet its inherent lack of security exposes it to cyber-attacks that can compromise vehicle safety. Among these, stealthy attacks, such as masquerade and sophisticated injection attacks, are particularly pernicious as they mimic normal traffic patterns, evading many conventional detection systems. To address this critical challenge, this paper introduces DriveShield, a novel unsupervised intrusion detection framework designed to unmask such evasive threats. The core of DriveShield is its unique approach to adversarial spatiotemporal feature learning. It begins by fusing granular time-interval data with physical signal data to create a rich, comprehensive representation of network behavior. This fused data is then fed into an adversarial autoencoder, which is trained not only to precisely reconstruct normal data but also to fool a discriminator. This adversarial process compels the model to learn the intricate, underlying distribution of legitimate traffic, making it highly sensitive to subtle anomalies that signal an attack. Extensive experiments on public CAN datasets demonstrate that DriveShield significantly outperforms state-of-the-art methods, especially in its ability to identify complex, stealthy attacks. This research provides a robust defense mechanism for in-vehicle networks, advancing the state of automotive cybersecurity against modern, adaptive threats.

Previous studies have demonstrated that bis-(3',5')-cyclic diguanosine monophosphate (bis-3',5'-c-di-GMP) is a ubiquitous second messenger employed by bacteria. Here, we report that 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) controls the important biological functions, quorum sensing (QS) signaling systems and virulence in Ralstonia solanacearum through the transcriptional regulator RSp0980. This signal specifically binds to RSp0980 with high affinity and thus abolishes the interaction between RSp0980 and the promoters of target genes. In-frame deletion of RSp0334, which contains an evolved GGDEF domain with a LLARLGGDQF motif required to catalyze 2',3'-cGMP to (2',5')(3',5')-cyclic diguanosine monophosphate (2',3'-c-di-GMP), altered the abovementioned important phenotypes through increasing the intracellular 2',3'-cGMP levels. Furthermore, we found that 2',3'-cGMP, its receptor and the evolved GGDEF domain with a LLARLGGDEF motif also exist in the human pathogen Salmonella typhimurium . Together, our work provides insights into the unusual function of the GGDEF domain of RSp0334 and the special regulatory mechanism of 2',3'-cGMP signal in bacteria. Nucleotide second messengers are employed by many bacterial species to regulate various cellular processes. Here, the authors demonstrate that 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) controls the important biological functions and virulence in Ralstonia solanacearum by abolishing the interaction between a transcriptional regulator and the promoters of target genes.

Phosphodiesterase 2 (PDE2) has been regarded as a novel target for the treatment of Alzheimer’s disease (AD). In this study, we obtained (R)-LZ77 as a hit compound with moderate PDE2 inhibitory activity (IC50 = 261.3 nM) using a high-throughput virtual screening method based on molecular dynamics. Then, we designed and synthesized 28 dihydropyranopyrazole derivatives as PDE2 inhibitors. Among them, compound (+)-11h was the most potent PDE2 inhibitor, with an IC50 value of 41.5 nM. The molecular docking of PDE2-(+)-11h reveals that the 4-(trifluoromethyl)benzyl)oxyl side chain of the compound enters the H-pocket and forms strong hydrophobic interactions with L770/L809/F862, which improves inhibitory activity. The above results may provide insight for further structural optimization of highly potent PDE2 inhibitors and may lay the foundation for their use in the treatment of AD.

Background: Lung cancer is an aggressive disease with rapid progression and a high rate of metastasis, leading to a significantly poor prognosis for many patients. While chemotherapy continues to serve as a cornerstone treatment for a large proportion of lung cancer patients, expanding preclinical and clinical evidence indicates that chemotherapy may promote tumor metastasis and cause side effects. Methods: We develop an injectable bait-and-hook hydrogel (BH-gel) for targeted tumor cell eradication, which embedded doxorubicin liposomes as cytotoxic agents and CXCL12 as a chemoattractant to capture and kill tumor cells. The hydrogel backbone was formed through covalent cross-linking between PVA and borax. In vitro, we investigated tumor recruitment and the antitumor effects in A549 cells. In vivo, we explored the anti-metastatic and antitumor activities against lung cancer. Results: BH-gel retained CXCL12 within its three-dimensional porous architecture for gradual release, effectively recruiting tumor cells. In contrast, blank hydrogel failed to achieve this. After encapsulation in BH-gel, the therapeutic efficacy of doxorubicin liposomes for tumor eradication was markedly improved, significantly reducing metastatic tumor presence to near-undetectable levels, while also resulting in notable reductions in cardiotoxicity and hepatotoxicity. Notably, BH-gel adhered well to tissues and exhibited exceptional electrical conductivity, which may be further developed into a real-time tumor monitoring system, facilitating timely therapeutic adjustments. Conclusions: BH-gel utilizes CXCL12 as a bait to recruit and entrap tumor cells in a three-dimensional porous matrix and subsequently kill them with embedded doxorubicin liposomes, thereby tackling the issue of metastatic spread. This bait-and-hook strategy has significant implications for the field of anti-metastasis medicine and shows considerable potential for clinical application.

Atopic dermatitis (AD) is the most common heterogeneous skin disease. Currently, effective primary prevention approaches that hamper the occurrence of mild to moderate AD have not been reported. In this work, the quaternized β-chitin dextran (QCOD) hydrogel was adopted as a topical carrier system for topical and transdermal delivery of salidroside for the first time. The cumulative release value of salidroside reached ~82% after 72 h at pH 7.4, while in vitro drug release experiments proved that QCOD@Sal (QCOD@Salidroside) has a good, sustained release effect, and the effect of QCOD@Sal on atopic dermatitis mice was further investigated. QCOD@Sal could promote skin repair or AD by modulating inflammatory factors TNF-α and IL-6 without skin irritation. The present study also evaluated NIR-II image-guided therapy (NIR-II, 1000–1700 nm) of AD using QCOD@Sal. The treatment process of AD was monitored in real-time, and the extent of skin lesions and immune factors were correlated with the NIR-II fluorescence signals. These attractive results provide a new perspective for designing NIR-II probes for NIR-II imaging and image-guided therapy with QCOD@Sal.

Chaperonins mediate protein folding in a cavity formed by multisubunit rings. The human CCT has eight non-identical subunits and the His147Arg mutation in one subunit, CCT5, causes neuropathy. Knowledge is scarce on the impact of this and other mutations upon the chaperone's structure and functions. To make progress, experimental models must be developed. We used an archaeal mutant homolog and demonstrated that the His147Arg mutant has impaired oligomeric assembly, ATPase activity and defective protein homeostasis functions. These results establish for the first time that a human chaperonin gene defect can be reproduced and studied at the molecular level with an archaeal homolog. The major advantage of the system, consisting of rings with eight identical subunits, is that it amplifies the effects of a mutation as compared with the human counterpart, in which just one subunit per ring is defective. Therefore, the slight deficit of a non-lethal mutation can be detected and characterized.

作为蓬勃发展的空间大地测量技术, InSAR和北斗/GNSS在地表形变监测中具有独特优势。应用两种手段开展综合测量, 可充分利用其互补性, 实现北斗/GNSS高时间分辨率与InSAR高空间分辨率的有机统一。本文首先介绍了InSAR与北斗/GNSS监测地表形变的基本原理, 重点探讨了InSAR研究在20余年内的理论发展; 其次综述了InSAR与北斗/GNSS技术集成及数据融合研究的最新进展; 然后总结分析了当前地表形变监测应用所面临的关键问题及挑战; 最后对InSAR与北斗/GNSS综合测量方法的发展趋势进行了展望。

P237; 多时相InSAR技术具有探测大范围毫米级地表形变的能力,已被广泛应用于地面沉降监测.近几年,应用多时相InSAR技术监测以高铁为代表的大尺度人造线状地物形变备受关注.本文将C波段SAR数据用于高铁沿线路基形变监测,应用相位稳定性分析和改进的StaMPS技术来增加相干性点的密度和形变参数解算的稳定性.采用研究区时间跨度为21个月的47景Sentinel-1A数据,对连(云港)盐(城)高铁及其沿线区域进行多时相InSAR分析,并利用同时期连续的北斗导航卫星系统(BeiDou navigation satellite system,BDS)观测数据对线性沉降速率和时序位移分别进行监测分析,进而对比验证二者的沉降监测结果.研究结果表明:利用C波段的Sentinel-1A数据能够获取毫米级的线性形变速率和时序位移序列,InSAR与BDS二者平均时序位移均方根误差为3.8 mm,与BDS监测结果相比取得很好的一致性,且连盐高铁线路整体表现稳定.

Jasmonates play a number of diverse roles in plant defense and development. CORONATINE INSENSITIVE1 (COI1), an F-box protein essential for all the jasmonate responses, interacts with multiple proteins to form the SCFCOI¹ E3 ubiquitin ligase complex and recruits jasmonate ZIM-domain (JAZ) proteins for degradation by the 26S proteasome. To determine which protein directly binds to jasmonoyl-isoleucine (JA-Ile)/coronatine (COR) and serves as a receptor for jasmonate, we built a high-quality structural model of COI1 and performed molecular modeling of COI1-jasmonate interactions. Our results imply that COI1 has the structural traits for binding JA-Ile or COR. The direct binding of these molecules with COI1 was further examined using a combination of molecular and biochemical approaches. First, we used the immobilized jasmonate approach to show that the COI1 protein in crude leaf extracts can bind to the jasmonate moiety of JA-Ile. Second, we employed surface plasmon resonance technology with purified COI1 and JAZ1 protein to reveal the interaction among COI1, JA-Ile, and JAZ1. Finally, we used the photoaffinity labeling technology to show the direct binding of COR with purified insect-expressed COI1. Taken together, these results demonstrate that COI1 directly binds to JA-Ile and COR and serves as a receptor for jasmonate.