Transcriptomic profiling of lung fibroblasts in silicosis: Regulatory roles of Nrf2 agonists in a mouse model.

Silicosis is an occupational disease caused by long-term inhalation of free silica, resulting in a significant global health burden. Its pathogenesis remains unclear, and there is no effective treatment. Proliferative and activated myofibroblasts play a key role in the development of silicosis. Traditional studies have focused on fibroblast proliferation and collagen secretion, neglecting their functional heterogeneity. With the advancement of omics research, more pathogenic fibroblast subgroups and their functions have been identified. In this study, we applied transcriptomics to analyze gene changes in primary lung fibroblasts during silicosis development using a mouse model. Our results indicate that DEGs are enriched in collagen secretion, ECM synthesis, leukocyte migration, and chemotaxis functions. Altered core genes are associated with immune cell recruitment and cell migration. Nrf2 agonists, known for anti-inflammatory and antioxidant properties, have shown potential therapeutic effects in fibrotic diseases. However, their effects on fibroblasts in silicosis are not fully understood. We used four common Nrf2 agonists to study gene expression changes in lung fibroblasts at the transcriptome level, combined with histopathological and biochemical methods, to investigate their effects on silicosis in mice. Results show that Nrf2 agonists can exert anti-silicosis fibrosis functions by downregulating genes like Fos and Egr1, involved in cell differentiation, proliferation, and inflammation. In conclusion, this study suggests that inflammation-related co-functions of fibroblasts may be a potential mechanism in silicosis pathogenesis. Targeting Nrf2 may be a promising strategy to alleviate oxidative stress and inflammation in silicosis.

Enhanced mitochondrial fluorescence imaging through confinement fluorescence effect within a rigid silicon suboxide network.

Fluorescence imaging technology has emerged as a powerful tool for studying intricate mitochondrial morphology within living cells. However, the need for fluorophores with stable fluorescence intensity and low phototoxicity poses significant challenges, particularly for long-term live-cell mitochondrial monitoring. To address this, we introduce the confinement fluorescence effect (CFE) into the design of fluorophores. This strategy involves confining small-molecule fluorophores within a silicon suboxide network structure of nanoparticles (CEF-NPs), which restricts molecular rotation, resulting in the suppression of non-radiative transition and the isolation of encapsulated fluorophores from surrounding quenching factors. CFE-NPs (SY2@SiOx) exhibit exceptional properties, such as high fluorescence intensity (80-fold) and reduced phototoxicity (0.15-fold). Furthermore, the TPP + -functionalized CFE-NPs (SY2@SiOxTPP) demonstrated efficacy in mitochondrial imaging and mitochondrial dynamics monitoring. Biochemistry assays indicated that SY2@SiOxTPP exhibits significantly lower phototoxicity to mitochondrial functions compared to both small-molecule fluorophore and commercial Mito Tracker. This approach allows for the long-term dynamic monitoring of mitochondrial morphological changes through fluorescence imaging, without impairing mitochondrial functionality.

S-CDK-regulated bipartite interaction of Mcm10 with MCM is essential for DNA replication.

Mcm10 plays an essential role in the activation of replicative helicase CMG through the cell cycle-regulated interaction with the prototype MCM double hexamer in Saccharomyces cerevisiae. In this study, we reported that Mcm10 is phosphorylated by S-phase cyclin-dependent kinases (S-CDKs) at S66, which enhances Mcm10--MCM association during the S phase. S66A single mutation or even deletion of whole N-terminus (a.a. 1-128) only causes mild growth defects. Nevertheless, S66 becomes indispensable in the absence of the Mcm10 C-terminus ((a.a. 463-571), the major MCM-binding domain. Using a two-degron strategy to efficiently deplete Mcm10, we show that mcm10-S66AΔC has a severe defect in proceeding into the S phase. Notably, both lethality and S-phase deficiency can be rescued by artificially tethering mcm10-S66AΔC to MCM. These findings illustrate how the Mcm10-MCM association is regulated as a crucial event in DNA replication initiation.

Strong Pairing Originated from an Emergent Z_{2} Berry Phase in La_{3}Ni_{2}O_{7}.

The recent discovery of high-temperature superconductivity in La_{3}Ni_{2}O_{7} offers a fresh platform for exploring unconventional pairing mechanisms. Starting with the basic argument that the electrons in d_{z^{2}} orbitals nearly form local moments, we examine the effect of the Hubbard interaction U on the binding strength of Cooper pairs based on a single-orbital bilayer model with intralayer hopping t_{∥} and interlayer superexchange J_{⊥}. By extensive density matrix renormalization group calculations, we observe a remarkable enhancement in binding energy as much as 10-20 times larger with U/t_{∥} increasing from 0 to 12 at J_{⊥}/t_{∥}∼1. We demonstrate that such a substantial enhancement stems from a kinetic-energy-driven mechanism. Specifically, a Z_{2} Berry phase will emerge at large U due to the Hilbert space restriction (Mottness), which strongly suppresses the mobility of single particle propagation as compared to U=0. However, the kinetic energy of the electrons (holes) can be greatly restored by forming an interlayer spin-singlet pairing, which naturally results in a superconducting state even for relatively small J_{⊥}. An effective hard-core bosonic model is further proposed to estimate the superconducting transition temperature at the mean-field level.

Efficient Formaldehyde Gas Sensing Performance via Promotion of Oxygen Vacancy on In-Doped LaFeO3 Nanofibers.

Perovskite oxide LaFeO3(LFO) emerges as a potential candidate for formaldehyde (HCHO) detection due to its exceptional electrical conductivity and abundant active metal sites. However, the sensitivity of the LFO sensor needs to be further enhanced. Herein, a series of LaxIn1-xFeO3 (x = 1.0, 0.9, 0.8, and 0.7) nanofibers (LxIn1-xFO NFs) with different ratios of La/In were obtained via the electrospinning method followed by a calcination process. Among all these LxIn1-xFO NFs sensors, the sensor based on the L0.8In0.2FO NFs possessed the maximum response value of 18.8 to 100 ppm HCHO at the operating temperature of 180 °C, which was 4.47 times higher than that based on pristine LFO NFs (4.2). Furthermore, the L0.8In0.2FO NFs sensor also exhibited a rapid response/recovery time (2 s/22 s), exceptional repeatability, and long-term stability. This excellent gas sensing performance of the L0.8In0.2FO NFs can be attributed to the large number of oxygen vacancies induced by the replacement of the A-site La3+ by In3+, the large specific surface area, and the porous structure. This research presents an approach to enhance the HCHO gas sensing capabilities by adjusting the introduced oxygen vacancies through the doping of A-sites in perovskite oxides.

Albumins constrainting the conformation of mitochondria-targeted photosensitizers for tumor-specific photodynamic therapy.

Tumor ablation Preclinical organelle-targeted phototherapies have effectively achieved tumor photoablation for regenerative biomedical applications in cancer therapies. However, engineering effective phototherapy drugs with precise tumor-localization targeting and organelle direction remains challenging. Herein, we report a albumins constrainting mitochondrial-targeted photosensitizer nanoparticles (PSs@BSAs) for tumor-specific photodynamic therapy. X-ray crystallography elucidates the two-stage assembly mechanism of PSs@BSAs. Femtosecond transient absorption spectroscopy and quantum mechanical calculations reveal the implications of conformational dynamics at the excited state. PSs@BSAs can efficiently disable mitochondrial activity, and further disrupt tumor angiogenesis based on the photodynamic effect. This triggers a metabolic and oxidative stress crisis to facilitate photoablation of solid tumor and antitumor metastasis. The study fully elucidates the interdisciplinary issues of chemistry, physics, and biological interfaces, thereby opening new horizons to inspire the engineering of organelle-targeted tumor-specific photosensitizers for biomedical applications.

Gene Therapy for Inflammatory Cascade in Intrauterine Injury with Engineered Extracellular Vesicles Hybrid Snail Mucus-enhanced Adhesive Hydrogels.

Early hyper-inflammation caused by intrauterine injury triggered subsequent intrauterine adhesion (IUA). STAT1-mediated M1 macrophages are confirmed to secrete pro-inflammatory cytokines to accelerate inflammatory cascade and IUA formation by multi-omics analysis and experimental verification. However, clinically used hyaluronic acid (HA) hydrogels are prone to slip out of injury sites due to poor bio-adhesion properties. Therefore, there are still challenges in applying hydrogels for M1 macrophage intervention in IUA treatment. Herein, an engineered extracellular vesicles (EVs) hybrid snail mucus (SM)-enhanced adhesive hydrogels to improve bio-adhesion property is fabricated and M1 macrophage intervention through targeting delivery and STAT1 silencing is achieved. First, inspired by the high bio-adhesion capacity of SM, SM and gelatin methacrylate (GelMA) solution are mixed to construct GelMA/SM (GS) hydrogel. Then, folic acid-modified extracellular vesicles (FA-EVs) are synthesized for targeting the delivery of STAT1-siRNA. Upon injection of FA-EVs hybrid GS hydrogel into the uterine cavity, a protective hydrogel layer forms on the surface of injury sites and sustains the release of STAT1-siRNA-loaded FA-EVs to curtail M1 macrophages generation through inhibiting STAT1 phosphorylation, resulting in reduction of myofibroblasts activation and collagen deposition. In addition, the pregnancy rate and the number of fetuses in rats treated with this hydrogel were much higher than those in other groups, suggesting that the hydrogel could promote functional endometrial regeneration and restore fertility. Overall, this study presents a promising strategy for employing FA-EVs hybrid adhesive hydrogel with superior bio-adhesion properties and M1 macrophage targeting delivery for IUA treatment and uterus recovery.

Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein.

Ultraviolet (UV) radiation is the primary extrinsic factor in skin aging, contributing to skin photoaging, actinic keratosis (AK), and even squamous cell carcinoma (SCC). Currently, the beneficial role of mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) in cutaneous wound healing has been widely reported, but the field of photoaging remains to be explored. Our results suggested that human umbilical cord MSC-derived sEVs (hucMSC-sEVs) intervention could effectively alleviate skin photoaging phenotypes in vivo and in vitro, including ameliorating UV-induced histopathological changes in the skin and inhibiting oxidative stress and collagen degradation in dermal fibroblasts (DFs). Mechanistically, pretreatment with hucMSC-sEVs reversed UVA-induced down-regulation of pregnancy zone protein (PZP) in DFs, and achieved photoprotection by inhibiting matrix metalloproteinase-1 (MMP-1) expression and reducing DNA damage. Clinically, a significant decrease in PZP in AK and SCC in situ samples was observed, while a rebound appeared in the invasive SCC samples. Collectively, our findings reveal the effective role of hucMSC-sEVs in regulating PZP to combat photoaging and provide new pre-clinical evidence for the potential development of hucMSC-sEVs as an effective skin photoprotective agent.

Transcriptomics analyses combined with intestinal microorganism survey suggest Resveratrol (RSV) anti-aging and anti-oxidant effects in silkworm (Bombyx mori).

The growing elderly population presents a significant concern, with the prolongation of life expectancy, aging diseases are becoming increasingly common. Resveratrol (RSV) has emerged as a promising compound for disease prevention. However, the effect of RSV on lifespan extension in different organisms, particularly the model organism silkworm, remains inconsistent. We conducted aging experiments using silkworm (B. mori) and employed transcriptomics to investigate the therapeutic effects of RSV on lifespan extension and healthy lifespan in silkworms. RSV increased the survival rate by 8.57 %-12.12 % and enhanced the antioxidant capacity of silkworms. Transcriptomic analysis demonstrated that genes in signaling pathways such as AMPK and FoxO were significantly upregulated. 16SrRNA sequencing of gut contents showed an increase in beneficial bacterial strains under the action of RSV. This study aims to enhance our understanding of lifespan regulation mechanisms using the silkworm model and provide new targets for anti-aging antioxidants research to delay the onset of age-related diseases.

Mindfulness and academic procrastination among Chinese adolescents: a moderated mediation model.

Background: While previous studies have linked mindfulness to reduced academic procrastination, the mechanisms involved remain under-explored. This study deepens the understanding by investigating how learning vigor mediates the mindfulness and procrastination relationship, and how harsh parenting influences this mediation. Methods: This study, adopting a positivist research approach, utilized a cross-sectional design. Data were collected from 800 students at three middle schools in Henan Province, China, through cluster random sampling. This approach yielded 800 questionnaires. The participants sequentially completed four questionnaires: the Mindfulness Attention Awareness Scale, the Utrecht Work Engagement Scale-Student, the Aitken Procrastination Inventory, and the Harsh Parenting Questionnaire. After removing 67 invalid questionnaires due to incomplete responses and patterned answers, a total of 733 valid questionnaires were obtained, with 53.3% girls and an average age of 13.12 years (SD = 1.01), leading to an effectiveness rate of 91.63%. Upon data collection, SPSS 26.0 software was used for correlation analysis, mediation analysis, and moderated mediation analysis to assess the relationships between variables. Results: (1) Mindfulness negatively predicts academic procrastination; (2) Learning vigor serves as a mediator in the relationship between mindfulness and academic procrastination; and (3) Harsh parenting moderates the relationship between mindfulness and learning vigor. Specifically, the positive impact of mindfulness on learning vigor is more pronounced in individuals experiencing lower levels of harsh parenting compared to those with higher levels. Conclusion: This study reveals that mindfulness significantly protects against academic procrastination in adolescents, with 52.27% of this effect mediated by increased learning vigor. Additionally, it shows that high levels of harsh parenting weaken mindfulness's positive impact on learning vigor, tempering its overall protective influence on procrastination. These insights, which apply Trait Activation Theory to educational psychology, not only deepen our understanding of the dynamics between mindfulness and procrastination but also have important implications for addressing academic procrastination in Chinese adolescents.

An Efficient SM9 Aggregate Signature Scheme for IoV Based on FPGA.

With the rapid development of the Internet of Vehicles (IoV), the demand for secure and efficient signature verification is becoming increasingly urgent. To meet this need, we propose an efficient SM9 aggregate signature scheme implemented on Field-Programmable Gate Array (FPGA). The scheme includes both fault-tolerant and non-fault-tolerant aggregate signature modes, which are designed to address challenges in various network environments. We provide security proofs for these two signature verification modes based on a K-ary Computational Additive Diffie-Hellman (K-CAA) difficult problem. To handle the numerous parallelizable elliptic curve point multiplication operations required during verification, we utilize FPGA's parallel processing capabilities to design an efficient parallel point multiplication architecture. By the Montgomery point multiplication algorithm and the Barrett modular reduction algorithm, we optimize the single-point multiplication computation unit, achieving a point multiplication speed of 70776 times per second. Finally, the overall scheme was simulated and analyzed on an FPGA platform. The experimental results and analysis indicate that under error-free conditions, the proposed non-fault-tolerant aggregate mode reduces the verification time by up to 97.1% compared to other schemes. In fault-tolerant conditions, the proposed fault-tolerant aggregate mode reduces the verification time by up to 77.2% compared to other schemes. When compared to other fault-tolerant aggregate schemes, its verification time is only 28.9% of their consumption, and even in the non-fault-tolerant aggregate mode, the verification time is reduced by at least 39.1%. Therefore, the proposed scheme demonstrates significant advantages in both error-free and fault-tolerant scenarios.

The effect of simulated problem learning in nursing ethics on moral sensitivity, empathy and critical thinking of nursing students: A quasi-experimental study.

AIM: Compare the effects of Simulation with problem-based learning (SPBL) and Problem-based learning (PBL) in nursing ethics education on nursing students' moral sensitivity, empathy, critical thinking, test scores and teaching satisfaction. BACKGROUND: Promoting nursing students' individual and ethical and abilities through education is an essential way to improve their ethical performance and build trustful relationship with patients. Despite significant efforts in this area, few have evaluated the effectiveness of Simulation with problem-based learning and Problem-based learning as applied to nursing ethics education. DESIGN: A quasi-experimental design based on a non-equivalent control group pre-test/post-test. METHODS: A quasi-experimental design was used. Participants were 161 undergraduate nursing students from two levels of a university, 88 subjects in the experimental group were taught using Simulation with problem-based learning and 73 subjects in the control group were taught using Problem-based learning. A pre-test, post-test and questionnaire were used to assess the effectiveness of student nursing ethics education. χ2 test was used to examine group differences in students' characteristics and satisfaction with teaching post-intervention. Student's t-test was used to assess group differences in scale scores and test scores. RESULTS: Compared to the pre-test, empathy as well as critical thinking were significantly higher in the PBL group (P<0.05), but there was no significant change in moral sensitivity (P>0.05); moral sensitivity, empathy and critical thinking were significantly higher in the SPBL group (P<0.05). Moreover, this study also showed that improvement in moral sensitivity, empathy, critical thinking and grades was more significant in the SPBL group of nursing students compared to the PBL group (P<0.05) and no statistically significant difference was found between the two groups in terms of teaching satisfaction (P>0.05). CONCLUSION: The use of Simulation with problem-based learning in nursing ethics education has a positive impact on nursing students' competency development and knowledge acquisition. Nurse educators should consider this teaching method and promote change to increase the effectiveness of nursing ethics education.

Finite-element analysis of different fixation types after Enneking II + III pelvic tumor resection.

The current primary treatment approach for malignant pelvic tumors involves hemipelvic prosthesis reconstruction following tumor resection. In cases of Enneking type II + III pelvic tumors, the prosthesis necessitates fixation to the remaining iliac bone. Prevailing methods for prosthesis fixation include the saddle prosthesis, ice cream prosthesis, modular hemipelvic prosthesis, and personalized prosthetics using three-dimensional printing. To prevent failure of hemipelvic arthroplasty protheses, a novel fixation method was designed and finite element analysis was conducted. In clinical cases, the third and fourth sacral screws broke, a phenomenon also observed in the results of finite element analysis. Based on the original surgical model, designs were created for auxiliary dorsal iliac, auxiliary iliac bottom, auxiliary sacral screw, and auxiliary pubic ramus fixation. A nonlinear quasi-static finite element analysis was then performed under the maximum load of the gait cycle, and the results indicated that assisted sacral dorsal fixation significantly reduces stress on the sacral screws and relative micromotion exceeding 28 µm. The fixation of the pubic ramus further increased the initial stability of the prosthesis and its interface osseointegration ability. Therefore, for hemipelvic prostheses, incorporating pubic ramus support and iliac back fixation is advisable, as it provides new options for the application of hemipelvic tumor prostheses.

Artificial intelligence with mass spectrometry-based multimodal molecular profiling methods for advancing therapeutic discovery of infectious diseases.

Infectious diseases, driven by a diverse array of pathogens, can swiftly undermine public health systems. Accurate diagnosis and treatment of infectious diseases-centered around the identification of biomarkers and the elucidation of disease mechanisms-are in dire need of more versatile and practical analytical approaches. Mass spectrometry (MS)-based molecular profiling methods can deliver a wealth of information on a range of functional molecules, including nucleic acids, proteins, and metabolites. While MS-driven omics analyses can yield vast datasets, the sheer complexity and multi-dimensionality of MS data can significantly hinder the identification and characterization of functional molecules within specific biological processes and events. Artificial intelligence (AI) emerges as a potent complementary tool that can substantially enhance the processing and interpretation of MS data. AI applications in this context lead to the reduction of spurious signals, the improvement of precision, the creation of standardized analytical frameworks, and the increase of data integration efficiency. This critical review emphasizes the pivotal roles of MS based omics strategies in the discovery of biomarkers and the clarification of infectious diseases. Additionally, the review underscores the transformative ability of AI techniques to enhance the utility of MS-based molecular profiling in the field of infectious diseases by refining the quality and practicality of data produced from omics analyses. In conclusion, we advocate for a forward-looking strategy that integrates AI with MS-based molecular profiling. This integration aims to transform the analytical landscape and the performance of biological molecule characterization, potentially down to the single-cell level. Such advancements are anticipated to propel the development of AI-driven predictive models, thus improving the monitoring of diagnostics and therapeutic discovery for the ongoing challenge related to infectious diseases.

Urolithin A attenuates hexavalent chromium-induced small intestinal injury by modulating PP2A/Hippo/YAP1 pathway.

Hexavalent chromium (Cr(VI)) exposure has been linked with gastrointestinal toxicity, whereas the molecular pathways and key targets remain elusive. Computational toxicology analysis predicted the correlation between protein phosphatase 2A (PP2A) and genes regarding Cr(VI)-induced intestinal injury. Here, we generated a mouse model with intestinal epithelium-specific knock out of Ppp2r1a (encoding PP2A Aα subunit) to investigate the mechanisms underlying Cr(VI)-induced small intestinal toxicity. Heterozygous (HE) mice and matched WT littermates were administrated with Cr(VI) at 0, 5, 20, and 80 mg/l for 28 successive days. Cr(VI) treatment led to crypt hyperplasia, epithelial cell apoptosis, and intestinal barrier dysfunction, accompanied by the decline of goblet cell counts and Occludin expression in WT mice. Notably, these effects were aggravated in HE mice, indicating that PP2A Aα deficiency conferred mice with susceptibility to Cr(VI)-induced intestinal injury. The combination of data analysis and biological experiments revealed Cr(VI) exposure could decrease YAP1 phosphorylation at Ser127 but increase protein expression and activity, together with elevated transcriptional coactivator with PDZ-binding motif protein driving epithelial crypt cells proliferation following damage, suggesting the involvement of Hippo/YAP1 signaling pathway in Cr(VI)-induced intestinal toxicity. Nevertheless, the enhanced phosphorylation of YAP1 in HE mice resulted in proliferation/repair defects in intestinal epithelium, thereby exacerbating Cr(VI)-induced gut barrier dysfunction. Notably, by molecular docking and further studies, we identified urolithin A, a microbial metabolite, attenuated Cr(VI)-induced disruption of intestinal barrier function, partly by modulating YAP1 expression and activity. Our findings reveal the novel molecular pathways participated in Cr(VI)-caused small intestinal injury and urolithin A could potentially protect against environmental hazards-induced intestinal diseases.

Vinpocetine alleviates the abdominal aortic aneurysm progression via VSMCs SIRT1-p21 signaling pathway.

Abdominal aortic aneurysm (AAA) is a degenerative disease that caused mortality in people aged >65. Senescence plays a critical role in AAA pathogenesis. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. Our Previous study found cyclic nucleotide phosphodiesterase 1C (PDE1C) exacerbate AAA through aggravate vascular smooth muscle cells (VSMCs) senescence by downregulating Sirtuin1 (SIRT1) expression and activity. Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation, it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA. This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice. In addition, the elastin degradation, MMP (matrix metalloproteinase) activity, macrophage infiltration, ROS production, collagen fibers remodeling, and VSMCs senescence were decreased in AAA treated with vinpocetine. While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice. Accordingly, we revealed that vinpocetine suppressed migration, proliferation, and senescence in VSMCs. Moreover, vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy. In conclusion, this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.

Identifying and validating the roles of the cuproptosis-related gene DKC1 in cancer with a focus on esophageal carcinoma.

BACKGROUND: Esophageal cancer is a common malignancy of the digestive tract. Despite remarkable advancements in its treatment, the overall prognosis for patients remains poor. Cuproptosis is a form of programmed cell death that affects the malignant progression of tumors. This study aimed to examine the impact of the cuproptosis-associated gene DKC1 on the malignant progression of esophageal cancer. METHODS: Clinical and RNA sequencing data of patients with esophageal cancer were extracted from The Cancer Genome Atlas (TCGA). Univariate Cox regression analysis was used to identify the differentially expressed genes related to cuproptosis that are associated with prognosis. We then validated the difference in the expression of DKC1 between tumor and normal tissues via three-dimensional multiomics difference analysis. Subsequently, we investigated the association between DKC1 expression and the tumor microenvironment by employing the TIMER2.0 algorithm, which was further validated in 96 single-cell datasets obtained from the TISCH database. Additionally, the functional role of DKC1 in pancarcinoma was assessed through GSEA. Furthermore, a comprehensive pancancer survival map was constructed, and the expression of DKC1 was verified in various molecular subtypes. By utilizing the CellMiner, GDSC, and CTRP databases, we successfully established a connection between DKC1 and drug sensitivity. Finally, the involvement of DKC1 in the progression of esophageal cancer was investigated through in vivo and in vitro experiments. RESULTS: In this study, we identified a copper death-related gene, DKC1, in esophageal cancer. Furthermore, we observed varying levels of DKC1 expression across different tumor types. Additionally, we conducted an analysis to determine the correlation between DKC1 expression and clinical features, revealing its association with common cell cycle pathways and multiple metabolic pathways. Notably, high DKC1 expression was found to indicate poor prognosis in patients with various tumors and to influence drug sensitivity. Moreover, our investigation revealed significant associations between DKC1 expression and the expression of molecules involved in immune regulation and infiltration of lymphocyte subtypes. Ultimately, the increased expression of DKC1 in esophageal cancer tissues was verified using clinical tissue samples. Furthermore, DKC1-mediated promotion of esophageal cancer cell proliferation and migration was confirmed through both in vitro and in vivo experiments. Additionally, it is plausible that DKC1 may play a role in the regulation of cuproptosis. CONCLUSION: In this study, we conducted a systematic analysis of DKC1 and its regulatory factors and experimentally validated its excellent diagnostic and prognostic abilities in various cancers. Further research indicated that DKC1 may reshape the tumor microenvironment (TME), highlighting the potential of DKC1-based cancer treatment and its usefulness in predicting the response to chemotherapy.

SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma.

Calcium channel blockers are emerging as a new generation of attractive anticancer drugs. SKF96365, originally thought to be a store-operated calcium entry (SOCE) inhibitor, is now often used as a TRPC channel blocker and is widely used in medical diagnostics. SKF96365 has shown antitumor effects on a variety of cancer cell lines. The objective of this study was to investigate the anticancer effect of SKF96365 on esophageal cancer in vivo and in vitro. Cell Counting Kit-8 (CCK-8) and colony formation were used to test the proliferation inhibition of SKF96365 on cell lines. Western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect cell apoptosis rates. In addition, we demonstrated the antitumor effect of SKF96365 in vivo in xenografted mice. As a result, SKF96365 significantly inhibited the proliferation of K510, K30, and EC9706 in vitro. SKF96365 induces apoptosis in three cell lines through the poly(adenosine diphosphate-ribose) polymerase (PARP), caspase-9, and BCL-2 pathways in a dose-dependent and time-dependent manner. Moreover, SKF96365 treatment also induced apoptosis and inhibited tumor growth in nude mice. The calcium channel TRPC1 was significantly downregulated by SKF96365. Autophagy was also induced during the treatment of SKF96365. In summary, SKF96365 induces apoptosis (PARP, caspase-9, and BCL-2) and autophagy (LC3-A/B) by inhibiting TRPC1 in esophageal cancer cells, thereby inhibiting tumor growth.

Adherence to PRISMA-A and reporting was suboptimal in meta-analysis abstracts on drug efficacy for tumors: a literature survey.

OBJECTIVES: To assess the reporting of meta-analysis abstracts on drug efficacy for tumors in terms of adherence to Preferred Reporting Items for Systematic Reviews and Meta-analyses for Abstracts (PRISMA-A) and identify the potential factors associated with adherence to PRISMA-A. STUDY DESIGN AND SETTING: A total of 3,211 eligible meta-analysis abstracts were assessed using a checklist adapted from the PRISMA-A statement. Adherence to PRISMA-A was analyzed by the total PRISMA-A score and adherence rate (AR). The independent samples t-test was performed to compare the difference of the total scores between two groups with different characteristics, and the analysis of variance or Kruskal-Wallis test was used among multiple groups. The Pearson's correlation coefficient was used to measure the correlation between the word count and the total PRISMA-A score. RESULTS: The mean total score was 8.11 (±1.76) and the AR was 57.94%. The items with lower AR were funding (AR = 0.93%), registration (AR = 3.86%), and risk of bias (AR = 7.85%). Meta-analyses published after the release of PRISMA-A showed better adherence to PRISMA-A. Compared to unstructured abstracts, structured abstracts had a higher AR for each item in PRISMA-A. There was a positive correlation between the word count of abstract and the total PRISMA-A score (r = 0.358, P < .001). CONCLUSION: Adherence to PRISMA-A was suboptimal in meta-analysis abstracts on drug efficacy for tumors, despite the improvement after the release of PRISMA-A. Various measures should be implemented to improve compliance with PRISMA-A and enhance the reporting of meta-analysis abstracts, including journal endorsement of PRISMA-A, requirement of stricter adherence to PRISMA-A, relaxation of abstract word limits, etc. PLAIN LANGUAGE SUMMARY: Meta-analysis is the statistical method used to compare and synthesize the results of studies on the same result research problem. It is integral in guiding evidence-based decision making in clinical practice. However, crucial information is frequently inadequately documented in meta-analysis abstracts, thereby reducing their significance for readers. And there has been a lack of published research evaluating the reporting of meta-analysis abstracts in the field of drug efficacy for tumors. The objectives of our study were (1) to assess the reporting of meta-analysis abstracts on drug efficacy for tumors in terms of adherence to Preferred Reporting Items for Systematic Reviews and Meta-analyses for Abstracts (PRISMA-A); and (2) to identify factors that might influence adherence to PRISMA-A. Our study reveals that meta-analyses published after the release of PRISMA-A showed better adherence to PRISMA-A, although there is still large room for improvement. Compared to unstructured abstracts, structured abstracts received the higher adherence rate (AR) for each item in PRISMA-A. There was a positive correlation between the word counts of abstract and the total PRISMA-A scores. Our study suggests that more efforts are still needed to improve the adherence to PRISMA-A in meta-analysis abstracts on drug efficacy for tumors. The journal editors should endorse PRISMA-A to authors, appropriately relax the word limit for abstracts, and provide authors with the writing template for structured abstracts.

Identification of differentially expressed tumour-related genes regulated by UHRF1-driven DNA methylation.

Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an epigenetic regulator that plays critical roles in tumours. However, the DNA methylation alteration patterns driven by UHRF1 and the related differentially expressed tumour-related genes remain unclear. In this study, a UHRF1-shRNA MCF-7 cell line was constructed, and whole-genome bisulfite sequencing and RNA sequencing were performed. The DNA methylation alteration landscape was elucidated, and DNA methylation-altered regions (DMRs) were found to be distributed in both gene bodies and adjacent regions. The DMRs were annotated and categorized into 488 hypermethylated/1696 hypomethylated promoters and 1149 hypermethylated/5501 hypomethylated gene bodies. Through an integrated analysis with the RNA sequencing data, 217 methylation-regulated upregulated genes and 288 downregulated genes were identified, and these genes were primarily enriched in nervous system development and cancer signalling pathways. Further analysis revealed 21 downregulated oncogenes and 15 upregulated TSGs. We also showed that UHRF1 silencing inhibited cell proliferation and migration and suppressed tumour growth in vivo. Our study suggested that UHRF1 and the oncogenes or TSGs it regulates might serve as biomarkers and targets for breast cancer treatment.