Hypoxia Pathways in Parkinson's Disease: From Pathogenesis to Therapeutic Targets.

The human brain is highly dependent on oxygen, utilizing approximately 20% of the body's oxygen at rest. Oxygen deprivation to the brain can lead to loss of consciousness within seconds and death within minutes. Recent studies have identified regions of the brain with spontaneous episodic hypoxia, referred to as "hypoxic pockets". Hypoxia can also result from impaired blood flow due to conditions such as heart disease, blood clots, stroke, or hemorrhage, as well as from reduced oxygen intake or excessive oxygen consumption caused by factors like low ambient oxygen, pulmonary diseases, infections, inflammation, and cancer. Severe hypoxia in the brain can manifest symptoms similar to Parkinson's disease (PD), including cerebral edema, mood disturbances, and cognitive impairments. Additionally, the development of PD appears to be closely associated with hypoxia and hypoxic pathways. This review seeks to investigate the molecular interactions between hypoxia and PD, emphasizing the pathological role of hypoxic pathways in PD and exploring their potential as therapeutic targets.

Insecticide susceptibility in a planthopper pest increases following inoculation with cultured Arsenophonus.

Facultative vertically transmitted symbionts are a common feature of insects that determine many aspects of their hosts' phenotype. Our capacity to understand and exploit these symbioses is commonly compromised by the microbes unculturability and consequent lack of genetic tools, an impediment of particular significance for symbioses of pest and vector species. Previous work had established that insecticide susceptibility of the economically important pest of rice, the brown planthopper Nilaparvata lugens, was higher in field-collected lineages that carry Ca. Arsenophonus nilaparvatae. We established Ca. A. nilaparvatae into cell-free culture and used this to establish the complete closed genome of the symbiont. We transformed the strain to express GFP and reintroduced it to N. lugens to track infection in vivo. The symbiont established vertical transmission, generating a discrete infection focus towards the posterior pole of each N. lugens oocyte. This infection focus was retained in early embryogenesis before transition to a diffuse somatic infection in late N. lugens embryos and nymphs. We additionally generated somatic infection in novel host species, but these did not establish vertical transmission. Transinfected planthopper lines acquired the insecticide sensitivity trait, with associated downregulation of the P450 xenobiotic detoxification system of the host. Our results causally establish the role of the symbiont in increasing host insecticide sensitivity with implications for insecticide use and stewardship. Furthermore, the culturability and transformation of this intracellular symbiont, combined with its ease of reintroduction to planthopper hosts, enables novel approaches both for research into symbiosis and into control of insect pest species.

Spherical harmonics-based deep learning achieves generalized and accurate diffusion tensor imaging.

Diffusion tensor imaging (DTI) is a prevalent magnetic resonance imaging (MRI) technique, widely used in clinical and neuroscience research. However, the reliability of DTI is affected by the low signal-to-noise ratio inherent in diffusion-weighted (DW) images. Deep learning (DL) has shown promise in improving the quality of DTI, but its limited generalization to variable acquisition schemes hinders practical applications. This study aims to develop a generalized, accurate, and efficient DL-based DTI method. By leveraging the representation of voxel-wise diffusion MRI (dMRI) signals on the sphere using spherical harmonics (SH), we propose a novel approach that utilizes SH coefficient maps as input to a network for predicting the diffusion tensor (DT) field, enabling improved generalization. Extensive experiments were conducted on simulated and in-vivo datasets, covering various DTI application scenarios. The results demonstrate that the proposed SH-DTI method achieves advanced performance in both quantitative and qualitative analyses of DTI. Moreover, it exhibits remarkable generalization capabilities across different acquisition schemes, centers, and scanners, ensuring its broad applicability in diverse settings.

Cancer-associated fibroblast-secreted exosomal miR-454-3p inhibits lipid metabolism and ferroptosis in breast cancer by targeting ACSL4.

Cancer-associated fibroblasts (CAFs) participate in the development of the tumor microenvironment through the secretion of exosomes. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an essential component of ferroptosis. However, the regulatory mechanism of ACSL4 in breast cancer remains unexplored. The study aimed to determine the influence of exosomal miR-454-3p from CAFs on lipid metabolism and ferroptosis. CAF-derived exosomes (CAF-exo) were isolated from breast cancer tissue of breast cancer patients and characterized using transmission electron microscopy (TEM) and Western blot. Luciferase reporter assay and RNA immunoprecipitation (RIP) were used to demonstrate the relationship between miR-454-3p and ACSL4. Cell viability and ferroptosis-related markers were detected by CCK-8 and Western blot. Malondialdehyde (MDA), glutathione (GSH), and iron levels were detected. Reverse transcription-quantitative PCR (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to assess miR-454-3p expression. miR-454-3p and ACSL4 levels were abnormally expressed in breast cancer tissues. CAF-exo significantly enhanced cell viability and GSH levels and suppressed MDA, and iron levels. CAF-exo upregulated ferroptosis suppressor protein 1 (FSP1) and glutathione peroxidase 4 (GPX4) expression, and reduced ACSL4 levels. miR-454-3p was strongly expressed in CAF-exo, and exosomal miR-454-3p suppressed lipid metabolism and ferroptosis in breast cancer cells. The effects of miR-454-3p inhibitor on lipid metabolism and ferroptosis were eliminated by ACSL4 knockdown. CAF-secreted exosomal miR-454-3p inhibited lipid metabolism and ferroptosis by targeting ACSL4 in breast cancer. This study revealed a novel molecular mechanism that offers a potential therapeutic intervention in breast cancer treatment.

Nrf2 inhibits M1 macrophage polarization to ameliorate renal ischemia-reperfusion injury through antagonizing NF-κB signaling.

Renal ischemia-reperfusion injury (IRI) is a condition that arises from a sudden interruption of the blood flow to the kidney for a period of time followed by restoration of the blood supply. This process contributes to acute kidney injury (AKI), increases morbidity and mortality, and is a major risk factor for chronic kidney disease (CKD). Nuclear factor erythroid-derived 2-like 2 (Nrf2) has been shown to exhibit strong anti-oxidative and anti-inflammatory effects, which are reciprocally regulated by the pro-inflammatory actions of nuclear factor-kappa B (NF-κB) signaling. In this study, we established a model of AKI caused by renal IRI in mice lacking the Nrf2 gene (KO-Nrf2) and mice pre-injected with ML385 (Nrf2 inhibitor). In addition, LPS- or IL-4-induced M1- or M2-type polarized macrophages (RAW264.7), respectively, were also treated with Nrf2 activation and inhibition. The results demonstrated a more pronounced activation of the NF-κB signaling pathway in the Nrf2 inhibition model, accompanied by a more severe inflammatory effect. In cultured macrophages and renal IRI mice, Nrf2 inhibition activated M1 macrophage polarization, thereby increasing the release of proinflammatory cell factors (iNOS and TNF-α) and aggravating renal IRI. Notably, the inhibitory effect of Nrf2 on M1 macrophage polarization was related to the downregulation of the NF-κB signaling pathway activity, resulting in partial relief of renal IRI. Consequently, our findings indicated that Nrf2 inhibits M1 macrophage polarization to ameliorate renal IRI through antagonizing NF-κB signaling. Targeted activation of Nrf2 may be one of the important strategies for renal IRI treatment.

Disentangling the impact of motion artifact correction algorithms on functional near-infrared spectroscopy-based brain network analysis.

Significance: Functional near-infrared spectroscopy (fNIRS) has been widely used to assess brain functional networks due to its superior ecological validity. Generally, fNIRS signals are sensitive to motion artifacts (MA), which can be removed by various MA correction algorithms. Yet, fNIRS signals may also undergo varying degrees of distortion due to MA correction, leading to notable alternation in functional connectivity (FC) analysis results. Aim: We aimed to investigate the effect of different MA correction algorithms on the performance of brain FC and topology analyses. Approach: We evaluated various MA correction algorithms on simulated and experimental datasets, including principal component analysis, spline interpolation, correlation-based signal improvement, Kalman filtering, wavelet filtering, and temporal derivative distribution repair (TDDR). The mean FC of each pre-defined network, receiver operating characteristic (ROC), and graph theory metrics were investigated to assess the performance of different algorithms. Results: Although most algorithms did not differ significantly from each other, the TDDR and wavelet filtering turned out to be the most effective methods for FC and topological analysis, as evidenced by their superior denoising ability, the best ROC, and an enhanced ability to recover the original FC pattern. Conclusions: The findings of our study elucidate the varying impact of MA correction algorithms on brain FC analysis, which could serve as a reference for choosing the most appropriate method for future FC research. As guidance, we recommend using TDDR or wavelet filtering to minimize the impact of MA correction in brain network analysis.

Bionic Optimization Design and Fatigue Life Prediction of a Honeycomb-Structured Wheel Hub.

The wheel hub is an important component of the wheel, and a good hub design can significantly improve vehicle handling, stability, and braking performance, ensuring safe driving. This article optimized the hub structure through morphological aspects, where reducing the hub weight contributed to enhanced fuel efficiency and overall vehicle performance. By referencing honeycombed structures, a bionic hub design is numerically simulated using finite element analysis and response surface optimization. The results showed that under the optimization of the response surface analytical model, the maximum stress of the optimized bionic hub was 109.34 MPa, compared to 119.77 MPa for the standard hub, representing an 8.7% reduction in maximum stress. The standard hub weighs 34.02 kg, while the optimized hub weight was reduced to 29.89 kg, a decrease of 12.13%. A fatigue analysis on the optimized hub indicated that at a stress of 109.34 MPa, the minimum load cycles were 4.217 × 105 at the connection point with the half-shaft, meeting the fatigue life requirements for commercial vehicle hubs outlined in the national standard GB/T 5334-2021.

Tanshinone IIA Loaded Inhaled Polymer Nanoparticles Alleviate Established Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by chronic, progressive scarring of the lung parenchyma, leading to an irreversible decline in lung function. Apart from supportive care, there is currently no specific treatment available to reverse the disease. Based on the fact that tanshinone IIA (TAN) had an effect on protecting against TGF-ß1-induced fibrosis through the inhibition of Smad and non-Smad signal pathways to avoid myofibroblasts activation, this study reported the development of the inhalable tanshinone IIA-loaded chitosan-oligosaccharides-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CPN@TAN) for enhancing the pulmonary delivery of tanshinone IIA to treat pulmonary fibrosis. The CPN@TAN with a size of 206.5 nm exhibited excellent in vitro aerosol delivery characteristics, featuring a mass median aerodynamic diameter (MMAD) of 3.967 ± 0.025 µm and a fine particle fraction (FPF) of 70.516 ± 0.929%. Moreover, the nanoparticles showed good stability during atomization and enhanced the mucosal penetration capabilities. The results of confocal spectroscopy confirmed the potential of the nanoparticles as carriers that facilitated the uptake of drugs by NIH3T3, A549, and MH-S cells. Additionally, the nanoparticles demonstrated good in vitro biocompatibility. In a mouse model of bleomycin-induced pulmonary fibrosis, noninvasive inhalation of aerosol CPN@TAN greatly suppressed collagen formation and facilitated re-epithelialization of the destroyed alveolar epithelium without causing systemic toxicity compared with intravenous administration. Consequently, our noninvasive inhalation drug delivery technology based on polymers may represent a promising paradigm and open the door to overcoming the difficulties associated with managing pulmonary fibrosis.

Gα13 controls pharyngeal endoderm convergence by regulating E-cadherin expression and RhoA activation.

Pharyngeal endoderm cells undergo convergence and extension (C&E), which is essential for endoderm pouch formation and craniofacial development. Our previous work implicates Gα13/RhoA-mediated signaling in regulating this process, but the underlying mechanisms remain unclear. Here, we have used endoderm-specific transgenic and Gα13 mutant zebrafish to demonstrate that Gα13 plays a crucial role in pharyngeal endoderm C&E by regulating RhoA activation and E-cadherin expression. We showed that during C&E, endodermal cells gradually establish stable cell-cell contacts, acquire apical-basal polarity and undergo actomyosin-driven apical constriction, which are processes that require Gα13. Additionally, we found that Gα13-deficient embryos exhibit reduced E-cadherin expression, partially contributing to endoderm C&E defects. Notably, interfering with RhoA function disrupts spatial actomyosin activation without affecting E-cadherin expression. Collectively, our findings identify crucial cellular processes for pharyngeal endoderm C&E and reveal that Gα13 controls this through two independent pathways - modulating RhoA activation and regulating E-cadherin expression - thus unveiling intricate mechanisms governing pharyngeal endoderm morphogenesis.

Microstructural and functional substrates underlying dispositional greed and its link with trait but not state impulsivity.

The interplay between personality traits and impulsivity has long been a central theme in psychology and psychiatry. However, the potential association between Greed Personality Traits (GPT) and impulsivity, encompassing both trait and state impulsivity and future time perspective, remains largely unexplored. To address these issues, we employed questionnaires and an inter-temporal choice task to estimate corresponding trait/state impulsivity and collected multi-modal neuroimaging data (resting-state functional imaging: n = 430; diffusion-weighted imaging: n = 426; task-related functional imaging: n = 53) to investigate the underlying microstructural and functional substrates. Behavioral analyses revealed that GPT mediated the association between time perspective (e.g., present fatalism) and trait impulsivity (e.g., motor impulsivity). Functional imaging analyses further identified that brain activation strengths and patterns related to delay length, particularly in the dorsomedial prefrontal cortex, superior parietal lobule, and cerebellum, were associated with GPT. Moreover, individuals with similar levels of greed exhibited analogous spontaneous brain activity patterns, predominantly in the Default Mode Network (DMN), Fronto-Parietal Network (FPN), and Visual Network (VIS). Diffusion imaging analysis observed specific microstructural characteristics in the spinocerebellar/pontocerebellar fasciculus, internal/external capsule, and corona radiata that support the formation of GPT. Furthermore, the corresponding neural activation pattern, spontaneous neural activity pattern, and analogous functional couplings among the aforementioned brain regions mediated the relationships between time perspective and GPT and between GPT and motor impulsivity. These findings provide novel insights into the possible pathway such as time perspective → dispositional greed → impulsivity and uncover their underlying microstructural and functional substrates.

Indole alleviates nonalcoholic fatty liver disease in an ACE2-dependent manner.

Indole is a microbial metabolite produced by the gut microbiota through the degradation of dietary tryptophan, known for its well-established anti-inflammatory and antioxidant properties. In this study, we collected fecal samples from mice fed a high-fat diet (HFD) and those on a standard diet (SD), then conducted 16S rRNA sequencing to analyze their gut microbiota. The analysis revealed distinct differences in the dominant bacterial species between the two groups, with a significant decrease in indole-producing probiotics in the HFD mice compared to the SD group. Then we administered oral indole treatment to male C57BL/6J mice with HFD-induced NAFLD and observed a significant improvement in hepatic steatosis and inflammation. Notably, indole alleviated the HFD-induced decline in serum Angiotensin-(1-7) [Ang-(1-7)] levels and Angiotensin-Converting Enzyme 2 (ACE2) expression. To further investigate the role of indole and ACE2 in NAFLD, we conducted experiments using ACE2 knockout (ACE2KO) mice that were also induced with HFD-induced NAFLD and treated with indole. Interestingly, the protective effects of indole were compromised in the absence of ACE2. In HepG2 cells, indole similarly stimulated ACE2 expression and, in an ACE2-dependent manner, reduced ROS generation, maintained mitochondrial membrane potential stability, and increased SIRT3 expression. In summary, our results highlight the formation of a biologically active gut-liver axis between the gut microbiota and the liver through the tryptophan metabolite indole, which mitigates NAFLD in an ACE2-dependent manner. Elevating dietary tryptophan and increasing indole levels may represent an effective approach for preventing and treating NAFLD.

Unveiling the role of uranium in enhancing the transformation of antibiotic resistance genes.

Transformation represents one of the most important pathways for the horizontal transfer of antibiotic resistance genes (ARGs), which enables competent bacteria to acquire extracellular ARGs from the surrounding environment. Both heavy metals and irradiation have been demonstrated to influence the bacterial transformation process. However, the impact of ubiquitously occurring radioactive heavy metals on the transformation of ARGs remains largely unknown. Here, we showed that a representative radioactive nuclide, uranium (U), at environmental concentrations (0.005-5 mg/L), improved the transformation frequency of resistant plasmid pUC19 into Escherichia coli by 0.10-0.85-fold in a concentration-dependent manner. The enhanced ARGs transformation ability under U stress was demonstrated to be associated with reactive oxygen species (ROS) overproduction, membrane damage, and up-regulation of genes related to DNA uptake and recombination. Membrane permeability and ROS production were the predominant direct and indirect factors affecting transformation ability, respectively. Our findings provide valuable insight into the underlying mechanisms of the impacts of U on the ARGs transformation process and highlight concerns about the exacerbated spread of ARGs in radioactive heavy metal-contaminated ecosystems, especially in areas with nuclear activity or accidents.

Novel analgesic peptide derived from Cinobufacini injection suppressing inflammation and pain via ERK1/2/COX-2 pathway.

Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient's life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1ß) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.

Theranostic Nanoplatform Based on Polydopamine-Coated Magnetic Mesoporous Silicon for Precise Cancer Triplex Nanotherapy and Multimodal Imaging.

Although targeted therapy has revolutionized oncotherapy, engineering a versatile oncotherapy nanoplatform integrating both diagnostics and therapeutics has always been an intractable challenge to overcome the limitations of monotherapy. Herein, a theranostics platform based on DI/MP-MB has successfully realized the fluorescence detection of disease marker miR-21 and the gene/photothermal/chemo triple synergetic cancer therapy, which can trace the tumor through photothermal and fluorescence dual-mode imaging and overcome the limitations of monotherapy to improve the treatment efficiency of tumors. DI/MP-MB was prepared by magnetic mesoporous silicon nanoparticles (M-MSNs) loaded with doxorubicin (Dox) and new indocyanine green (IR820), and subsequently coating polydopamine as a "gatekeeper", followed by the surface adsorbed with molecular beacons capable of targeting miR-21 for responsive imaging. Under the action of enhanced permeability retention and external magnetic field, DI/MP-MB were targeted and selectively accumulated in the tumor. MiR-21 MB hybridized with miR-21 to form a double strand, which led to the desorption of miR-21 MB from the polydopamine surface and the fluorescence recovery to realize gene silencing and fluorescence imaging for tracking the treatment process. Meanwhile, with the response to the near-infrared irradiation and the tumor's microacid environment, the outer layer polydopamine will decompose, releasing Dox and IR820 to realize chemotherapy and photothermal therapy. Finally, the ability of DI/MP-MB to efficiently suppress tumor growth was comprehensively assessed and validated both in vitro and in vivo. Noteworthily, the excellent anticancer efficiency by the synergistic effect of gene/photothermal/chemo triple therapy of DI/MP-MB makes it an ideal nanoplatform for tumor therapy and imaging.

New triple therapy for the diagnosis of CKD-MBD: a cross-sectional study in Shanxi province.

OBJECTIVES: To seek a triple combination of biomarkers for early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and to explore the diagnostic efficacy of ß2-microglobulin, parathyroid hormone and blood urea nitrogen in chronic kidney disease-mineral and bone metabolic disorder. PARTICIPANTS: We collected medical records of 864 patients with chronic kidney disease (without direct contact with patients) and divided them into two groups based on the renal bone disease manifestations of all patients. PRIMARY AND SECONDARY OUTCOME MEASURES: There were 148 and 716 subjects in the Chronic kidney disease-mineral and bone metabolic disorder and the control groups, respectively. The aggregated data included basic information and various clinical laboratory indicators, such as blood lipid profile, antibody and electrolyte levels, along with renal function-related indicators. RESULTS: It was observed that most renal osteopathy occurs in the later stages of chronic kidney disease. In the comparison of two clinical laboratory indicators, 16 factors were selected for curve analysis and compared. We discovered that factors with high diagnostic values were ß2-microglobulin, parathyroid hormone and blood urea nitrogen. CONCLUSIONS: The triple combination of ß2-microglobulin+parathyroid hormone+blood urea nitrogen indicators can play the crucial role of a sensitive indicator for the early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and in preventing or delaying the progress of chronic kidney disease-mineral and bone metabolic disorder.

Suicidal ideation in medical students of Hebei province: prevalence and associated factors.

Objectives: This study investigated the prevalence of suicidal ideation (SI) among Chinese medical students and its associated risk factors. Methods: A total of 6643 medical students (2383 males/4260 females) were recruited from a medical college in Hebei Province, China. Demographic data were collected via a self-administered questionnaire. The Childhood Trauma Questionnaire Short Form (CTQ-SF) was used to evaluate childhood maltreatment (CM), and the Adolescent Self-Rating Life Events Checklist (ASLEC) was used to evaluate the stressful life events. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation (BSSI). Univariate and multivariate logistic regression models were used to analyze the factors affecting SI. Results: The prevalence of SI in medical students was 11.5% (763/6643). Multivariate logistic regression analysis revealed that SI was significantly associated with younger age, a female sex, being lovelorn, being introverted, experiencing CM during childhood, and experiencing stressful life events within the past 12 months. Of the five subtypes of CM, emotional abuse may have the strongest effect on SI (OR=2.76, 95% CI: 1.72-4.42). The joint effects of CM and stressful life events were significantly associated with an increased risk of SI (OR=5.39, 95% CI: 4.15-6.98). Conclusion: The prevalence of SI among medical students is high, and medical students who have experienced CM and stressful life events have a higher tendency towards SI. Screening for both CM and stressful life events may be an effective way of identifying individuals at high risk of SI.

Erratum to "Characterization of a predictive signature for tumor microenvironment and immunotherapy response in hepatocellular carcinoma involving neutrophil extracellular traps" [Heliyon Volume 10, issue 10, May 2024, article e30827].

[This corrects the article DOI: 10.1016/j.heliyon.2024.e30827.].

Novel genotypes and phenotypes in Snijders Blok-Campeau syndrome caused by CHD3 mutations.

Background: Snijders Blok-Campeau syndrome (SNIBCPS) is a rare genetic disorder characterized by facial abnormalities, hypotonia, macrocephaly, and global developmental delay (GDD) caused by mutations in CHD3 gene. There is limited information on SNIBCPS and few studies on its pathogenic gene CHD3. Methods: We utilized whole-exome sequencing, in vitro minigene splicing assay analysis, and construction of protein models to validate the suspected pathogenic mutation. In addition, the PubMed database was searched using the keywords "Snijders Blok-Campeau syndrome," "CHD3," or "SNIBCPS" to summarize the gene mutations and clinical phenotypic characteristics of children with SNIBCPS. Results: We identified a non-frameshift variant c.3592_c.3606delGCCAAGAGAAAGATG, a splice site variant c.1708-1G>T, and two missense variants, c. 2954G>C (p.Arg985Pro) and c.3371C>T (p.A1124V), in CHD3 variants with SNIBCPS. Importantly, the c.3592_c.3606delGCCAAGAGAAAGATG, c.1708-1G>T, and c.3371C > T (p.A1124V) loci were not reported, and the children in this study also had phenotypic features of unibrow, transverse palmar creases, tracheal bronchus, and hypomelanosis of Ito (HI). The c.1708-1G>T classical splicing mutation leads to abnormal shearing of mRNA, forming a truncated protein that ultimately affects gene function. Conclusion: Our findings have expanded the spectrum of genetic variants and clinical features in children with SNIBCPS. Splicing analysis of CHD3 is an important method to understand the pathogenesis of spliced cells.

The Impact of Death Education on College 'Students' Sense of Meaning in Life and Ability to Cope with Death.

Purpose: This study aims to assess the impact of death education on college students' sense of meaning in life and ability to cope with death. Method: A questionnaire survey was conducted among a randomly selected sample of 320 undergraduate students from a specific city. The survey, administered through the paper questionnaire, collected data on students' demographic characteristics, their awareness of death, and their demand for death education. Linear regression analysis was performed to identify factors influencing the demand for death education and assess its impact on college students' attitudes towards death, sense of meaning in life, and coping abilities. Results: The results revealed that participants' personality traits and family status significantly influenced their need for death education (P < .05). The overall score for death education needs among participants was (37.40±6.57). Notably, the statement "I think death education can help me understand death" received the highest mean rating (3.85), while the statement "I think death education will help me engage in nursing work in the future" received the lowest mean rating (3.55). Personal factors such as personality, family status, being an only child, and family experiences with serious illness were found to impact college students' demand for death education (P < .05). Post-death education, significant differences were observed in scores related to death fear and escape acceptance dimensions (P < .05). Moreover, there were statistically significant improvements in students' sense of meaning in life, quality of life, and life goals following death education (P < .05). Additionally, all dimensions of death coping ability showed higher scores after death education (P < .05). Factors such as current psychological state, being an only child, family experiences with serious illness, and attendance at funerals were found to be statistically significant in relation to college students' sense of meaning in life (P < .05). Multiple regression analysis indicated that the sense of meaning in life was influenced by the current psychological state and family experiences with serious illness (P < .05). Conclusion: The study highlights the importance of integrating death education into college curriculums to address students' fear of death and enhance their appreciation of life. Providing death education can help students develop a healthier perspective on death, improve their well-being, reduce avoidance attitudes towards death-related events, and strengthen their sense of meaning in life and ability to cope with death. These findings emphasize the need for educational institutions to implement comprehensive death education programs, considering individual factors such as personality and family background, and contribute to the development of effective educational policies and curricula.

Integrated analysis of genes shared between type 2 diabetes mellitus and osteoporosis.

Background: The relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OP) has been widely recognized in recent years, but the mechanism of interaction remains unknown. The aim of this study was to investigate the genetic features and signaling pathways that are shared between T2DM and OP. Methods: We analyzed the GSE76894 and GSE76895 datasets for T2DM and GSE56815 and GSE7429 for OP from the Gene Expression Omnibus (GEO) database to identify shared genes in T2DM and OP, and we constructed coexpression networks based on weighted gene coexpression network analysis (WGCNA). Shared genes were then further analyzed for functional pathway enrichment. We selected the best common biomarkers using the least absolute shrinkage and selection operator (LASSO) algorithm and validated the common biomarkers, followed by RT-PCR, immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA) to validate the expression of these hub genes in T2DM and OP mouse models and patients. Results: We found 8,506 and 2,030 DEGs in T2DM and OP, respectively. Four modules were identified as significant for T2DM and OP using WGCNA. A total of 19 genes overlapped with the strongest positive and negative modules of T2DM and OP. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed these genes may be involved in pantothenate and CoA biosynthesis and the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and renin-angiotensin system signaling pathway. The LASSO algorithm calculates the six optimal common biomarkers. RT-PCR results show that LTB, TPBG, and VNN1 were upregulated in T2DM and OP. Immunofluorescence and Western blot show that VNN1 is upregulated in the pancreas and bones of T2DM model mice and osteoporosis model mice. Similarly, the level of VNN1 in the sera of patients with T2DM, OP, and T2DM and OP was higher than that in the healthy group. Conclusion: Based on the WGCNA and LASSO algorithms, we identified genes and pathways that were shared between T2DM and OP. Both pantothenate and CoA biosynthesis and the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and renin-angiotensin systems may be associated with the pathogenesis of T2DM and OP. Moreover, VNN1 may be a potential diagnostic marker for patients with T2DM complicated by OP. This study provides a new perspective for the systematic study of possible mechanisms of combined OP and T2DM.