Exploring The Factors Of Sleep Quality: An Integrated Analysis Of Data From Questionnaires And Environmental Sensor Data

Sleep quality plays a crucial role in human health, but its determinants remain incompletelyunderstood. This integrated analysis investigates the relationships of demographic characteristics, living habits, as well as psychological factors on sleep quality. It also ranks the importance of sleep discomfort and examines the effect of bedroom air quality on sleep quality. Results showed stress had a significant negative correlation (r = -0.66) with sleep quality. Furthermore, nocturnal bathroom usage was the most influential predictor, contributing approximately 17.5% to sleep quality ratings using random forest classification. Air quality measures, including carbon dioxide (CO2) levels, temperature, relative humidity, and particulate matter (PM2.5), demonstrated no significant impact on sleep quality. This research builds a stepstone for more precise sleep intervention by looking at the interaction of impacting factors and creates methods to generate new features from real-time air quality sensor data

Current Evidence and Future Directions of PCSK9 Inhibition

Recent scientific and therapeutic advances in proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition have opened a chapter in the management of hypercholesterolemia, especially in patients who are inadequately controlled on or intolerant to statins. The two PCSK9 monoclonal antibodies, evolocumab and alirocumab, reduce LDL cholesterol by 60% and improve cardiovascular outcomes when taken in addition to statin therapy. More recently, inclisiran, a silencing RNA (siRNA) that inhibits translation of PCSK9 mRNA, demonstrated LDL cholesterol reduction by 45–50% with the advantage of dramatically reduced dose frequency. Other modes of PCSK9 inhibition include small molecule antagonists, vaccines, CRISPR gene editing, and antagonism at various steps of translation, and post-translational processing

Stromal-Derived NRG1 Enables Oncogenic KRAS Bypass in Pancreas Cancer

Activating KRAS mutations (KRAS*) in pancreatic ductal adenocarcinoma (PDAC) drive anabolic metabolism and support tumor maintenance. KRAS* inhibitors show initial antitumor activity followed by recurrence due to cancer cell-intrinsic and immune-mediated paracrine mechanisms. Here, we explored the potential role of cancer-associated fibroblasts (CAFs) in enabling KRAS* bypass and identified CAF-derived NRG1 activation of cancer cell ERBB2 and ERBB3 receptor tyrosine kinases as a mechanism by which KRAS*-independent growth is supported. Genetic extinction or pharmacological inhibition of KRAS* resulted in up-regulation of ERBB2 and ERBB3 expression in human and murine models, which prompted cancer cell utilization of CAF-derived NRG1 as a survival factor. Genetic depletion or pharmacological inhibition of ERBB2/3 or NRG1 abolished KRAS* bypass and synergized with KRA

SOX on Tumors, a Comfort or a Constraint?

The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes the physiological function of the SOX family and their multiple roles in tumors, with a focus on the relationship between the SOX family and TIME, aiming to propose their potential role in cancer and promising methods for treatment

Liver-targeting MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan

Commercial gadolinium (Gd)-based contrast agents (GBCAs) play important role in clinical diagnostic of hepatocellular carcinoma, but their diagnostic efficacy remained improved. As small molecules, the imaging contrast and window of GBCAs is limited by low liver targeting and retention. Herein, we developed a liver-targeting gadolinium (Ⅲ) chelated macromolecular MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan, namely, CS-Ga-(Gd-DTPA)n, to improve hepatocyte uptake and liver retention. Compared to Gd-DTPA and non-specific macromolecular agent CS-(Gd-DTPA)n, CS-Ga-(Gd-DTPA)n showed higher hepatocyte uptake, excellent cell and blood biocompatibility in vitro. Furthermore, CS-Ga-(Gd-DTPA)n also exhibited higher relaxivity in vitro, prolonged retention and better T1-weighted signal enhancement in liver. At 10 days post-injection of CS-Ga-(Gd-DTPA)n at a dose of 0.03 mM Gd/Kg, Gd had a little accumulation in liver with no liver function damage. The good performance of CS-Ga-(Gd-DTPA)n gives great confidence in developing liver-specifc MRI contrast agents for clinical translation

Transcription Factor BACH1 in Cancer: Roles, Mechanisms, and Prospects for Targeted Therapy

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap \u27n\u27 Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic

Spatiotemporal dynamic of subtropical forest carbon storage and its resistance and resilience to drought in China

Subtropical forests are rich in vegetation and have high photosynthetic capacity. China is an important area for the distribution of subtropical forests, evergreen broadleaf forests (EBFs) and evergreen needleleaf forests (ENFs) are two typical vegetation types in subtropical China. Forest carbon storage is an important indicator for measuring the basic characteristics of forest ecosystems and is of great significance for maintaining the global carbon balance. Drought can affect forest activity and may even lead to forest death and the stability characteristics of different forest ecosystems varied after drought events. Therefore, this study used meteorological data to simulate the standardized precipitation evapotranspiration index (SPEI) and the Biome-BGC model to simulate two types of forest carbon storage to quantify the resistance and resilience of EBF and ENF to drought in the subtropical region of China. The results show that: 1) from 1952 to 2019, the interannual drought in subtropical China showed an increasing trend, with five extreme droughts recorded, of which 2011 was the most severe one; 2) the simulated average carbon storage of the EBF and ENF during 1985-2019 were 130.58 t·hm-2 and 78.49 t·hm-2, respectively. The regions with higher carbon storage of EBF were mainly concentrated in central and southeastern subtropics, where those of ENF mainly distributed in the western subtropic; 3) The median of resistance of EBF was three times higher than that of ENF, indicating the EBF have stronger resistance to extreme drought than ENF. Moreover, the resilience of two typical forest to 2011 extreme drought and the continuous drought events during 2009 - 2011 were similar. The results provided a scientific basis for the response of subtropical forests to drought, and indicating that improve stand quality or expand the plantation of EBF may enhance the resistance to drought in subtropical China, which provided certain reference for forest protection and management under the increasing frequency of drought events in the future

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead