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BackgroundLung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer (NSCLC), remains a pervasive global public health concern. Disulfidoptosis, a nascent form of regulated cell death (RCD), presents an emerging field of inquiry. Currently, investigations into disulfidoptosis are in their initial stages. Our undertaking sought to integrate single-cell RNA sequencing (scRNA-seq) in conjunction with traditional bulk RNA sequencing (bulk RNA-seq) methodologies, with the objective of delineating genes associated with disulfidoptosis and subsequently prognosticating the clinical outcomes of LUAD patients.MethodsInitially, we conducted an in-depth examination of the cellular composition disparities existing between LUAD and normal samples using scRNA-seq data sourced from GSE149655. Simultaneously, we scrutinized the expression patterns of disulfidoptosis-associated gene sets across diverse cell types. Subsequently, leveraging the bulk RNA-seq data, we formulated disulfidoptosis-related prognostic risk signatures (DRPS) employing LASSO-Cox regression. This was accomplished by focusing on genes implicated in disulfidoptosis that exhibited differential expression within endothelial cells (ECs). Sequentially, the robustness and precision of the DRPS model were rigorously verified through both internal and external validation datasets. In parallel, we executed single-cell trajectory analysis to delve into the differentiation dynamics of ECs. Concluding our study, we undertook a comprehensive investigation encompassing various facets. These included comparative assessments of enrichment pathways, clinicopathological parameters, immune cell abundance, immune response-associated genes, impacts of immunotherapy, and drug predictions among distinct risk cohorts.ResultsThe scrutiny of scRNA-seq data underscored discernible disparities in cellular composition between LUAD and normal samples. Furthermore, disulfidoptosis-associated genes exhibited marked discrepancies within endothelial cells (ECs). Consequently, we formulated the Disulfidoptosis-Related Prognostic Signature (DRPS) to facilitate prognostic prediction. The prognostic nomogram based on the risk score effectively demonstrated DRPS’s robust capacity to prognosticate survival outcomes. This assertion was corroborated by rigorous assessments utilizing both internal and external validation sets, thus affirming the commendable predictive accuracy and enduring stability of DRPS. Functional enrichment analysis shed light on the significant correlation of DRPS with pathways intrinsic to the cell cycle. Subsequent analysis unveiled correlations between DRPS and gene mutations characteristic of LUAD, as well as indications of an immunosuppressive status. Through drug prediction, we explored potential therapeutic agents for low-risk patients. Concluding our investigation, qRT-PCR experiments confirmed the heightened expression levels of EPHX1, LDHA, SHC1, MYO6, and TLE1 in lung cancer cell lines.

While understanding the long-term slip rate of active normal faults is essential for the comprehensive assessment of seismic activity, it is difficult due to the absence of age control in the erosional bedrock region. The preserved sequence of wave-cut platforms in granite allows exploration of the long-term slip rate in the footwall of some normal faults. We investigated wave-cut platforms in the southern Pearl River Delta (PRD), a coastal delta transected by the seismically active Littoral Fault Zone (LFZ) in the northern South China Sea, to derive slip rates and their impacts on the seismic hazard potential. We mapped a flight of four wave-cut platforms (T1–T4), dated the T2 and T4 platforms by 10Be cosmogenic nuclide dating, and used the absolute age to correlate the un-dated platform to global sea-level highstands. Our results allocate the ages of 128 ka, 197 ka, and 239 ka to the upper three wave-cut platforms and yield temporally various uplift rates ranging from 0.30 to 0.38 mm/a during 239–128 ka to 0.09 mm/a since 128 ka. A decrease in the uplift rate, which coincided with a decreased subsidence rate within the PRD in previous work, implied a weakened differential uplift onshore of the LFZ system. Our findings infer that the transgression event occurred as early as marine isotope stage (MIS) 7 in the PRD, consistent with the view that Pleistocene sedimentation began in MIS 5 or earlier in the PRD.

Background: Numerous studies have revealed that the long non-coding RNA LINC00662 is irregularly expressed in various cancers, as well as is correlated with cancer development and progression. Nevertheless, the clinical value of LINC00662 remains controversial. Hence, we explored the correlation of LINC00662 with cancer prognosis through meta-analysis and bioinformatics analysis.Methods: From the beginning through 12 March 2022, we searched for correlational studies on Web of Science, Embase, PubMed and The Cochrane Library. We used pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) to determine the significance of studies on survival outcomes and clinicopathological aspects in human cancers. Additionally, the Gene Expression Profiling Interactive Analysis (GEPIA) database was employed to confirm our findings.Results: Our meta-analysis of 14 studies comprising a total of 960 cancer patients revealed that LINC00662 overexpression was correlated with poor overall survival (HR = 1.91, 95% CI 1.49–2.45, p < 0.001) in cancer patients and relapse-free survival (HR = 2.12, 95% CI 1.19–3.76, p = 0.010) in hepatocellular carcinoma patients. The correlation between LINC00662 and OS was further supported by the results of subgroup analyses according to cancer type, follow-up time, HR availability, and NOS score. In addition, LINC00662 overexpression predicted advanced tumor stage (OR = 4.23, 95% CI 2.50–7.17, p < 0.001), larger tumor size (OR = 1.49, 95% CI 1.11–1.99, p = 0.008), earlier lymph node metastasis (OR = 2.40, 95% CI 1.25–4.59, p = 0.008), and earlier distant metastasis (OR = 4.78, 95% CI 2.57–8.88, p < 0.001). However, there were no statistically significant differences in age (OR = 1.16, 95% CI 0.90–1.51, p = 0.246), gender (OR = 1.10, 95% CI 0.79–1.53, p = 0.578), or differentiation grade (OR = 1.53, 95% CI 0.71–3.33, p = 0.280).Conclusion: LINC00662 expression upregulation is associated with poor prognosis and advanced clinicopathological features in patients with multiple tumors. LINC00662 may serve as a biomarker for the diagnosis and treatment of patients with tumors.

The arc-shaped tectonic belt, located in the northeastern margin of the Tibetan Plateau, is one of the leading edges of the plateau’s outward growth and uplift expansion, with a large number of active faults and frequent seismic activity. Researchers have carried out numerous studies on active faults in this region, and a wealth of reliable basic data has been accumulated. However, integrating multidisciplinary data to establish a 3D geometrical structure model that is concerned about seismogenic tectonics and can be tested, has become the key to restricting the regional seismic hazard evaluation. Based on a series of published active tectonic research, we analyze in detail the surface and deep coupling relationships of the major active faults in this region and establish three sets of 3D fault structure models, which are built respectively by active fault mapping and dip angles (the V1 model), 7 magnetotelluric profiles and 7 auxiliary profiles (the V2 model), and multi-source data (the V3 model) and continuously close to the real geological facts. From the model perspective, it is suggested that the controversial Haiyuan fault is a crustal-scale left-slip fault and the shape of the Liupanshan fault reflects the absorption of the left-slip component of the Haiyuan fault. Comparing the same fault plane of these three models, we find that the V3 model is more consistent with geological facts, showing that by assisting the multi-source data 3D geological modeling technique we can establish a 3D geological model closest to the real regional structure. Finally, combining the V3 model, the fault segmentation, and the empirical formulas of the moment magnitude-rupture parameters, we segment the faults and calculate the potential moment magnitudes of the major active faults in the study region. The faults with relatively higher seismic hazards are the Liupanshan fault, the southeastern segment of the Xiangshan-Tianjingshan fault, the westernmost segment of the Haiyuan fault, and the West Qinling fault, of which the estimated potential moment magnitudes are generally more than 7.0. Our study provides a referenced 3D geological model for exploring the deep structures of the region, regional geological research, and earthquake disaster prevention.

The Qilian Shan, located in the northeastern Tibetan Plateau, is an intraplate orogenic belt that underwent several episodes of fold and thrust deformation, particularly during the Mesozoic and Cenozoic. However, the deformation styles and relationships between the basin and mountains remain controversial. Therefore, in the current study, we conducted detailed field mapping of the sedimentary basins in Sunan and Huangcheng, and observed three episodes of compressive tectonic activity. We also restored a deformed section to determine the shortening rate of the Cretaceous sedimentary Sunan Basin. The first thrust episode, during the Paleogene, involved a southwestward thrust motion, comprising the Yumu Shan and Gaizhangdaban thrust systems. The second Neogene episode involved the northeastern thrust belt in the northern Qilian Shan, which comprises the Northern Qilian thrust system. The third episode produced NW-trending strike-slip activity that became the major tectonic deformation style; thus, the entire block rotated clockwise. Additionally, the restored section revealed that the Cretaceous strata have been shortened by ∼3.56%. Collectively, these results indicate that the Sunan and Huangcheng area on the northeastern Tibetan Plateau is influenced by the far-field effects of the collision between the Indian and Asian continents, as well as the effects of intraplate orogenic processes related to the collision of the Alashan Block and the Qilian Shan. Therefore, the current study has defined the deformation style in the northeastern Qilian Shan region, so we wish to give a clarification of the tectonic evolution and forecast the tectonic propagation in the Qilian Shan region.

The COVID-19 outbreak has affected the lives of people across the globe. To investigate the mental impact of COVID-19 and to respond to the call of researchers for the use of unobtrusive and intensive measurement in capturing time-sensitive psychological concepts (e.g., affect), we used big data methods to investigate the impact of COVID-19 by analyzing 348,933 tweets that people posted from April 1, 2020 to April 24, 2020. The dataset covers 2,231 working adults, who are from 454 counties across 48 states in the United States. In this study, we theorize the similarity and dissimilarity between COVID-19 and other common stressors. Similar to other stressors, pandemic severity negatively influenced the well-being of people by increasing negative affect. However, we did not find an influence of pandemic severity on the positive affect of the people. Dissimilar to other stressors, the protective factors for people during COVID-19 are not common factors that make people resilient to stress and they echo the unique experience during COVID-19. Moreover, we analyzed the text content of 348,933 tweets through Linguistic Inquiry Word Count (LIWC) and word cloud analysis to further reveal the psychological impact of COVID-19 and why the protective factors make people resilient to the mental impact of COVID-19. These exploratory analyses revealed the specific emotions that people experienced and the topics that people are concerned about during the pandemic. The theoretical and practical implications are discussed.

Background: Although mainstream guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in patients following transcatheter aortic valve replacement (TAVR), it is not evidence-based. We aim to investigate the safety and efficacy of DAPT vs. single antiplatelet therapy (SAPT) after TAVR, and review updated evidence.Methods: We systematically searched PubMed, Embase, and Cochrane for studies comparing DAPT to SAPT after TAVR from inception to November 30, 2020. The primary outcome was major adverse cardiac and cerebrovascular events, including all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke, and major or life-threatening bleeding (LTB). Subgroup analysis was performed according to study type (randomized control trials vs. observational studies) using a fixed-effects model. The quality of evidence was assessed by two scoring systems and GRADE (Grading of Recommendations Assessment, Development, and Evaluation).Results: Twelve studies of 20,766 patients were included in our meta-analysis. Compared with SAPT, DAPT was associated with an increased risk for combined life threatening and major bleeding [OR 1.73 (1.19–2.51), p = 0.004] after TAVR. Such a difference was largely driven by major bleeding [OR 2.29 (1.68–3.11), p < 0.001]. There were no significant differences on major adverse cardiovascular events (MACE) [OR 1.19 (0.99–1.44), p = 0.07], cardiovascular mortality [OR 1.46 (0.93–2.30), p = 0.10], and stroke [OR 0.97 (0.80–1.16), p = 0.71].Conclusions: Compared with SAPT, post-TAVR DAPT was associated with increased risks of major or life-threatening bleeding without additional benefits of reducing thrombotic events. Future guidelines for post-TAVR antiplatelet strategy are expected to be updated as new high-quality evidence emerges.Systematic Review Registration: PROSPERO, Identifier: CRD42021230075.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare autosomal dominant hereditary cancer syndrome characterized by a predisposition to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). It is known to be caused by germline mutations of the fumarate hydratase (FH) gene, which encodes an enzyme component of the citric acid cycle and catalyzes the conversion of fumarate to L-malate. Currently, there is no standardized treatment for HLRCC, which may be due in part to a lack of understanding of the underlying mechanisms. Here, the underlying molecular mechanisms by which the inactivation of FH causes HLRCC are discussed. Additionally, potential therapeutic pharmacological strategies are also summarized to provide new perspectives for the prevention and treatment of HLRCC.

Background and AimAtractyloside (ATR), a mitochondrial uncoupler, is known for its specific inhibition of mitochondrial oxidative phosphorylation. Previous studies have reported that moderate mitochondrial uncoupling effect is beneficial to increase the decomposition and clearance of hepatic lipid, prevent the occurrence of fatty liver diseases. Moreover, the beneficial effects of mitochondrial uncouplers on type 2 diabetes and metabolic syndromes have been consistently observed. The present study investigated the effect of ATR on steatosis level of HepG2 cells treated with free fatty acid (FFA).MethodsIntracellular triglyceride level and Oil Red O staining were assessed, the mitochondrial adaptation and ADP/ATP ratio were analyzed, the protein level of AMPK, mTOR and LC3B, autophagic flux, and the co-localization of LC3B with lipid droplets was performed.ResultsATR treatment inhibited the activity of mitochondrial respiratory chain complexes I and IV, decreased the mitochondrial membrane potential, and increased the ADP/ATP ratio in the FFA-treated cells. Furthermore, ATR increased the gene expression and protein level of LC3B and promoted the autophagic flux processing from early autophagosome to late autolysosome by increasing the protein level of AMPKα and decreasing the protein level of mTOR. An increased number of autophagosomes (LC3B) was also observed in the lipid droplets. ATR treatment accelerated lipid degradation in the FFA-treated cells, and the lowest lipid content was observed in the cell group with 7.5 μM ATR.ConclusionLow concentrations (2.5, 5, and 7.5 μM) of ATR treatment could activate autophagy to accelerate the degradation of TGs in steatosis HepG2 cells; the mechanism may be related to the activation of the AMPK/mTOR pathway induced by the increased ADP/ATP ratio. In addition, the ideal concentration of ATR for improving steatotic HepG2 cells was 7.5 μM.

The aim of this study was to improve the utilization of rice straw as forage in ruminants by investigating the degradation pattern of rice straw in the dairy cow rumen. Ground up rice straw was incubated in situ in the rumens of three Holstein cows over a period of 72 h. The rumen fluid at 0 h and the rice straw at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 h were collected for analysis of the bacterial community and the degradation of the rice straw. The bacterial community and the carbohydrate-active enzymes in the rumen fluid were analyzed by metagenomics. The diversity of bacteria loosely and tightly attached to the rice straw was investigated by scanning electron microscopy and Miseq sequencing of 16S rRNA genes. The predominant genus in the rumen fluid was Prevotella, followed by Bacteroides, Butyrivibrio, unclassified Desulfobulbaceae, Desulfovibrio, and unclassified Sphingobacteriaceae. The main enzymes were members of the glycosyl hydrolase family, divided into four categories (cellulases, hemicellulases, debranching enzymes, and oligosaccharide-degrading enzymes), with oligosaccharide-degrading enzymes being the most abundant. No significant degradation of rice straw was observed between 0.5 and 6 h, whereas the rice straw was rapidly degraded between 6 and 24 h. The degradation then gradually slowed between 24 and 72 h. A high proportion of unclassified bacteria were attached to the rice straw and that Prevotella, Ruminococcus, and Butyrivibrio were the predominant classified genera in the loosely and tightly attached fractions. The composition of the loosely attached bacterial community remained consistent throughout the incubation, whereas a significant shift in composition was observed in the tightly attached bacterial community after 6 h of incubation. This shift resulted in a significant reduction in numbers of Bacteroidetes and a significant increase in numbers of Firmicutes. In conclusion, the degradation pattern of rice straw in the dairy cow rumen indicates a strong contribution by tightly attached bacteria, especially after 6 h incubation, but most of these bacteria were not taxonomically characterized. Thus, these bacteria should be further identified and subjected to functional analysis to improve the utilization of crop residues in ruminants.