Platform-independent estimation of human physiological time from single blood samples.

Abundant epidemiological evidence links circadian rhythms to human health, from heart disease to neurodegeneration. Accurate determination of an individual's circadian phase is critical for precision diagnostics and personalized timing of therapeutic interventions. To date, however, we still lack an assay for physiological time that is accurate, minimally burdensome to the patient, and readily generalizable to new data. Here, we present TimeMachine, an algorithm to predict the human circadian phase using gene expression in peripheral blood mononuclear cells from a single blood draw. Once trained on data from a single study, we validated the trained predictor against four independent datasets with distinct experimental protocols and assay platforms, demonstrating that it can be applied generalizably. Importantly, TimeMachine predicted circadian time with a median absolute error ranging from 1.65 to 2.7 h, regardless of systematic differences in experimental protocol and assay platform, without renormalizing the data or retraining the predictor. This feature enables it to be flexibly applied to both new samples and existing data without limitations on the transcriptomic profiling technology (microarray, RNAseq). We benchmark TimeMachine against competing approaches and identify the algorithmic features that contribute to its performance.

Feasibility and Acceptability of an Internet of Things-Enabled Sedentary Behavior Intervention: Mixed Methods Study.

BACKGROUND: Encouraging office workers to break up prolonged sedentary behavior (SB) at work with regular microbreaks can be beneficial yet challenging. The Internet of Things (IoT) offers great promise for delivering more subtle and hence acceptable behavior change interventions in the workplace. We previously developed an IoT-enabled SB intervention, called WorkMyWay, by applying a combination of theory-informed and human-centered design approaches. According to the Medical Research Council's framework for developing and evaluating complex interventions such as WorkMyWay, process evaluation in the feasibility phase can help establish the viability of novel modes of delivery and identify facilitators and barriers to successful delivery. OBJECTIVE: This study aims to evaluate the feasibility and acceptability of the WorkMyWay intervention and its technological delivery system. METHODS: A mixed methods approach was adopted. A sample of 15 office workers were recruited to use WorkMyWay during work hours for 6 weeks. Questionnaires were administered before and after the intervention period to assess self-report occupational sitting and physical activity (OSPA) and psychosocial variables theoretically aligned with prolonged occupational SB (eg, intention, perceived behavioral control, prospective memory and retrospective memory of breaks, and automaticity of regular break behaviors). Behavioral and interactional data were obtained through the system database to determine adherence, quality of delivery, compliance, and objective OSPA. Semistructured interviews were conducted at the end of the study, and a thematic analysis was performed on interview transcripts. RESULTS: All 15 participants completed the study (attrition=0%) and on average used the system for 25 tracking days (out of a possible 30 days; adherence=83%). Although no significant change was observed in either objective or self-report OSPA, postintervention improvements were significant in the automaticity of regular break behaviors (t14=2.606; P=.02), retrospective memory of breaks (t14=7.926; P<.001), and prospective memory of breaks (t14=-2.661; P=.02). The qualitative analysis identified 6 themes, which lent support to the high acceptability of WorkMyWay, though delivery was compromised by issues concerning Bluetooth connectivity and factors related to user behaviors. Fixing technical issues, tailoring to individual differences, soliciting organizational supports, and harnessing interpersonal influences could facilitate delivery and enhance acceptance. CONCLUSIONS: It is acceptable and feasible to deliver an SB intervention with an IoT system that involves a wearable activity tracking device, an app, and a digitally augmented everyday object (eg, cup). More industrial design and technological development work on WorkMyWay is warranted to improve delivery. Future research should seek to establish the broad acceptability of similar IoT-enabled interventions while expanding the range of digitally augmented objects as the modes of delivery to meet diverse needs.

A minimal model of peripheral clocks reveals differential circadian re-entrainment in aging.

The mammalian circadian system comprises a network of endogenous oscillators, spanning from the central clock in the brain to peripheral clocks in other organs. These clocks are tightly coordinated to orchestrate rhythmic physiological and behavioral functions. Dysregulation of these rhythms is a hallmark of aging, yet it remains unclear how age-related changes lead to more easily disrupted circadian rhythms. Using a two-population model of coupled oscillators that integrates the central clock and the peripheral clocks, we derive simple mean-field equations that can capture many aspects of the rich behavior found in the mammalian circadian system. We focus on three age-associated effects that have been posited to contribute to circadian misalignment: attenuated input from the sympathetic pathway, reduced responsiveness to light, and a decline in the expression of neurotransmitters. We find that the first two factors can significantly impede re-entrainment of the clocks following perturbation, while a weaker coupling within the central clock does not affect the recovery rate. Moreover, using our minimal model, we demonstrate the potential of using the feed-fast cycle as an effective intervention to accelerate circadian re-entrainment. These results highlight the importance of peripheral clocks in regulating the circadian rhythm and provide fresh insights into the complex interplay between aging and the resilience of the circadian system.

A Two-Step Simulated Annealing Algorithm for Spectral Data Feature Extraction.

To address the shortcomings in many traditional spectral feature extraction algorithms in practical application of low modeling accuracy and poor stability, this paper introduces the "Boruta algorithm-based local optimization process" based on the traditional simulated annealing algorithm and proposes the "two-step simulated annealing algorithm (TSSA)". This algorithm combines global optimization and local optimization. The Boruta algorithm ensures that the feature extraction results are all strongly correlated with the dependent variable, reducing data redundancy. The accuracy and stability of the algorithm model are significantly improved. The experimental results show that compared with the traditional feature extraction method, the accuracy indexes of the inversion model established by using the TSSA algorithm for feature extraction were significantly improved, with the determination coefficient R2 of 0.9654, the root mean square error (RMSE) of 3.6723 µg/L, and the mean absolute error (MAE) of 3.1461 µg/L.

TRIM28 regulates sprouting angiogenesis through VEGFR-DLL4-Notch signaling circuit.

Sprouting angiogenesis is a highly coordinately process controlled by vascular endothelial growth factor receptor (VEGFR)-Notch signaling. Here we investigated whether Tripartite motif-containing 28 (TRIM28), which is an epigenetic modifier implicated in gene transcription and cell differentiation, is essential to mediate sprouting angiogenesis. We observed that knockdown of TRIM28 ortholog in zebrafish resulted in developmental vascular defect with disorganized and reduced vasculatures. Consistently, TRIM28 knockdown inhibited angiogenic sprouting of cultured endothelial cells (ECs), which exhibited increased mRNA levels of VEGFR1, Delta-like (DLL) 3, and Notch2 but reduced levels of VEGFR2, DLL1, DLL4, Notch1, Notch3, and Notch4.The regulative effects of TRIM28 on these angiogenic factors were partially mediated by hypoxia-inducible factor 1 α (HIF-1α) and recombination signal-binding protein for immunoglobulin kappa J region (RBPJκ). In vitro DNA-binding assay showed that TRIM28 knockdown increased the association of RBPJκ with DNA sequences containing HIF-1α-binding sites. Moreover, the phosphorylation of TRIM28 was controlled by VEGF and Notch1 through a mechanism involving RBPJκ-dual-specificity phosphatase (DUSP)-p38 MAPK, indicating a negative feedback mechanism. These findings established TRIM28 as a crucial regulator of VEGFR-Notch signaling circuit through HIF-1α and RBPJκ in EC sprouting angiogenesis.

TRIM28 and TRIM27 are required for expressions of PDGFRß and contractile phenotypic genes by vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) in the normal arterial media continually express contractile phenotypic markers which are reduced dramatically in response to injury. Tripartite motif-containing proteins are a family of scaffold proteins shown to regulate gene silencing, cell growth, and differentiation. We here investigated the biological role of tripartite motif-containing 28 (TRIM28) and tripartite motif-containing 27 (TRIM27) in VSMCs. We observed that siRNA-mediated knockdown of TRIM28 and TRIM27 inhibited platelet-derived growth factor (PDGF)-induced migration in human VSMCs. Both TRIM28 and TRIM27 can regulate serum response element activity and were required for maintaining the contractile gene expression in human VSMCs. At the same time, TRIM28 and TRIM27 knockdown reduced the expression of PDGF receptor-ß (PDGFRß) and the phosphorylation of its downstream signaling components. Immunoprecipitation showed that TRIM28 formed complexes with TRIM27 through its N-terminal RING-B boxes-Coiled-Coil domain. Furthermore, TRIM28 and TRIM27 were shown to be upregulated and mediate the VSMC contractile marker gene and PDGFRß expression in differentiating human bone marrow mesenchymal stem cells. In conclusion, we identified that TRIM28 and TRIM27 cooperatively maintain the endogenous expression of PDGFRß and contractile phenotype of human VSMCs.

Optimal adjustment of the human circadian clock in the real world.

Which suggestions for behavioral modifications, based on mathematical models, are most likely to be followed in the real world? We address this question in the context of human circadian rhythms. Jet lag is a consequence of the misalignment of the body's internal circadian (~24-hour) clock during an adjustment to a new schedule. Light is the clock's primary synchronizer. Previous research has used mathematical models to compute light schedules that shift the circadian clock to a new time zone as quickly as possible. How users adjust their behavior when provided with these optimal schedules remains an open question. Here, we report data collected by wearables from more than 100 travelers as they cross time zones using a smartphone app, Entrain. We find that people rarely follow the optimal schedules generated through mathematical modeling entirely, but travelers who better followed the optimal schedules reported more positive moods after their trips. Using the data collected, we improve the optimal schedule predictions to accommodate real-world constraints. We also develop a scheduling algorithm that allows for the computation of approximately optimal schedules "on-the-fly" in response to disruptions. User burnout may not be critically important as long as the first parts of a schedule are followed. These results represent a crucial improvement in making the theoretical results of past work viable for practical use and show how theoretical predictions based on known human physiology can be efficiently used in real-world settings.

Homogeneous electrochemical biosensor for microRNA based on enzyme-driven cascaded signal amplification strategy.

Infectious diseases are a long-standing and severe global public health problem. The rapid diagnosis of infectious diseases is an urgent need to solve this problem. MicroRNA (miRNA) plays an important role in the intervention of some infectious diseases and is expected to become a potential biomarker for the diagnosis and prognosis of infectious diseases. It is of great significance to develop rapid and sensitive methods for detecting miRNA for effective control of infectious diseases. In this study, a simple and highly sensitive homogeneous electrochemical method for microRNAs using enzyme-driven cascaded signal amplification has been developed. In the presence of target miRNA, the reaction system produced plenty of MB-labeled single-nucleotide fragments (MB-MF) containing a few negative charges, which can diffuse to the negative surface of the ITO electrode easily, so an obvious electrochemical signal enhancement was obtained. Without the target, MB-HP contains a relatively large amount of negative charges due to the phosphates on the DNA chain, which cannot be digested by the enzyme and cannot diffuse freely to the negatively charged ITO electrode, so only a small signal was detected. The enhanced electrochemical response has a linear relationship with the logarithm of miRNA concentration in the range of 10 fM to 10 nM and the limit of detection as low as 3.0 fM. Furthermore, the proposed strategy showed the capability of discriminating single-base mismatch and performed eligibly in the analysis of miRNA in cell lysates, exhibiting great potential for disease diagnosis and biomedical research. Graphical abstract.

Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells.

Mitochondria are dynamic organelles that are able to change their morphology and cellular distribution by either fission or fusion. However, the molecular mechanisms controlling mitochondrial dynamics in vascular endothelial cells (ECs) remain largely unknown. In this study, we observed that knockdown of microtubule-associated tumor suppressor 1 (MTUS1) in ECs inhibited tube formation and migration, accompanied with decreased promigratory signalings. We showed that MTUS1 was localized in the outer membrane of mitochondria in ECs. Knockdown of MTUS1 disturbed the elongated mitochondrial network and induced the formation of perinuclear clusters of mitochondria. Importantly, mitochondrial motility and fusion were suppressed, whereas generation of reactive oxygen species was increased in MTUS1 knockdown ECs. Mechanistically, we showed that the N-terminal coiled-coil domain of MTUS1 interacted with the mitochondrial membrane proteins, mitofusin-1 and mitofusin-2, to maintain mitochondrial morphology in ECs. This study illustrated a novel role of MTUS1 in mitochondrial morphology and EC angiogenic responses.-Wang, Y., Huang, Y., Liu, Y., Li, J., Hao, Y., Yin, P., Liu, Z., Chen, J., Wang, Y., Wang, N., Zhang, P. Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells.

NR6A1 regulates lipid metabolism through mammalian target of rapamycin complex 1 in HepG2 cells.

BACKGROUND: Lipogenesis is required for the optimal growth of many types of cancer cells, it is shown to control the biosynthesis of the lipid bilayer membrane during rapid proliferation and metastasis, provides cancer cells with signaling lipid molecules to support cancer development and make cancer cells more resistant to oxidative stress-induced cell death. Though multiple lipogenic enzymes have been identified to mediate this metabolic change, how the expression of these lipogenic enzymes are transcriptionally regulated remains unclear. METHODS: Gain- and loss-of-function experiments were conducted to assess the role of transcriptional repressor, nuclear receptor sub-family 6, group A, member 1 (NR6A1) in HepG2 cells. RT-qPCR method was performed to investigate target gene of NR6A1. Western blot was employed to determine the mechanisms by which NR6A1 regulates lipid accumulation in HepG2 cells. RESULTS: We provide evidence that NR6A1 is a novel regulator of lipid metabolism in HepG2 cells. NR6A1 knockdown can increase lipid accumulation as well as insulin-induced proliferation and migration of HepG2 cells. The lipogenic effect correlated well with the expression of lipogenic genes, including fatty acid synthase (FAS), diglyceride acyltransferase-2 (DGAT2), malic enzyme 1 (ME1), microsomal triglyceride transfer protein (MTTP) and phosphoenolpyruvate carboxykinase (PEPCK). NR6A1 knockdown also increased the expression of carnitine palmitoyltransferase 1A (CPT1a), the rate-limiting enzyme in fatty acid oxidation. Furthermore, NR6A1 knockdown induced lipid accumulation through mammalian target of rapamycin complex 1 (mTORC1), but not mTORC2. Moreover, siRNA-mediated knockdown of NR6A1 increased expression of insulin receptor (INSR) and potentitated insulin-induced phosphorylation of mTOR and AKT partly via miR-205-5p in HepG2 cells. CONCLUSIONS: These findings provide important new insights into the role of NR6A1 in the lipogenesis in HepG2 cells. .

Digital Interventions to Reduce Sedentary Behaviors of Office Workers: Scoping Review.

BACKGROUND: There is a clear public health need to reduce office workers' sedentary behaviors (SBs), especially in the workplace. Digital technologies are increasingly being deployed in the workplace to measure and modify office workers' SBs. However, knowledge of the range and nature of research on this topic is limited; it also remains unclear to what extent digital interventions have exploited the technological possibilities. OBJECTIVE: This study aimed to investigate the technological landscape of digital interventions for SB reduction in office workers and to map the research activity in this field. METHODS: Terms related to SB, office worker, and digital technology were applied in various combinations to search Cochrane Library, Joanna Briggs Institute Database of Systematic Reviews, MEDLINE, PsycARTICLES, PsycINFO, Scopus, Association for Computing Machinery Digital Library, Engineering index Compendex, and Google Scholar for the years 2000 to 2017. Data regarding the study and intervention details were extracted. Interventions and studies were categorized into development, feasibility and/piloting, evaluation, or implementation phase based on the UK Medical Research Council (MRC) framework for developing and evaluating complex interventions. A novel framework was developed to classify technological features and annotate technological configurations. A mix of quantitative and qualitative approaches was used to summarize data. RESULTS: We identified 68 articles describing 45 digital interventions designed to intervene with office workers' SB. A total of 6 common technological features had been applied to interventions with various combinations. Configurations such as "information delivery and mediated organizational and social support" and "digital log and automated tailored feedback" were well established in evaluation and implementation studies; in contrast, the integration of passive data collection, connected devices, and ATF or scheduled prompts was mostly present in development and piloting research. CONCLUSIONS: This review is the first to map and describe the use of digital technologies in research on SB reduction in office workers. Interdisciplinary collaborations can help to maximize the potential of technologies. As novel modes of delivery that capitalize on embedded computing and electronics, wireless technologies have been developed and piloted in engineering, computing, and design fields, efforts can be directed to move them to the next phase of evaluation with more rigorous study designs. Quality of research may be improved by fostering conversations between different research communities and encouraging researchers to plan, conduct, and report their research under the MRC framework. This review will be particularly informative to those deciding on areas where further research or development is needed and to those looking to locate the relevant expertise, resources, and design inputs when designing their own systems or interventions.

Tripartite motif-containing 28 bridges endothelial inflammation and angiogenic activity by retaining expression of TNFR-1 and -2 and VEGFR2 in endothelial cells.

Angiogenesis and inflammation are regarded as important factors in the pathogenesis of chronic inflammation, cancer, and wound healing. Recent studies have supported prior evidence that common signaling pathways are involved in angiogenesis and inflammatory responses; however, key factors controlling both processes remain unclear. Although tripartite motif-containing (TRIM)-28 is known to have an immunosuppressive role in immune cells, its expression level and role in endothelial cells (ECs) are still unclear. In this study, we investigated the role of TRIM28 in inflammatory responses and angiogenic activity of ECs for the first time. We showed that TRIM28 is the most abundant TRIM family member and is localized in nuclei of ECs. Small interfering RNA-mediated knockdown of TRIM28 strikingly suppressed expression of TNF receptor (TNFR)-1 and -2, decreased TNF-α-induced phosphorylation of IKKα/ß and IκBα and degradation of IκBα and nuclear translocation of p65, and suppressed basal level and TNF-α-induced expression of chemokines and adhesion molecules, including VCAM-1, IL-6, ICAM-1, E-selectin, and monocyte chemoattractant protein (MCP)-1. Unexpectedly, IL-8 was potentiated by TRIM28 knockdown in ECs in an NF-κB-inducing kinase-dependent manner. Meanwhile, knockdown of TRIM28 inhibited expression of VEGF receptor 2 and suppressed VEGF-induced proliferation and tube formation by ECs. Finally, knockdown of TRIM28 suppressed recruitment of ECs in vivo in a murine synthetic basement membrane model. In summary, we found that TRIM28 acts as a central factor in controlling endothelial inflammatory responses and angiogenic activities by retaining expression of TNFR-1 and -2 and VEGF receptor 2 in ECs.-Wang, Y., Li, J., Huang Y., Dai, X., Liu, Y., Liu, Z., Wang, Y., Wang, N., Zhang, P. Tripartite motif-containing 28 bridges endothelial inflammation and angiogenic activity by retaining expression of TNFR1 and -2 and VEGFR2 in endothelial cells.

A motif from Lys216 to Lys222 in human BUB3 protein is a nuclear localization signal and critical for BUB3 function in mitotic checkpoint.

Human BUB3 is a key mitotic checkpoint factor that recognizes centromeric components and recruits other mitotic checkpoint molecules to the unattached kinetochore. The key amino acid residues responsible for its localization are not yet defined. In this study, we identified a motif from Lys(216) to Lys(222) in BUB3 as its nuclear localization signal. A BUB3 mutant with deletion of this motif (Del216-222) was found to localize to both the cytoplasm and the nucleus, distinct from the exclusively nuclear distribution of wild-type BUB3. Further analysis revealed that residues Glu(213), Lys(216), Lys(217), Lys(218), Tyr(219), and Phe(221), but not Lys(222), contribute to nuclear localization. Interestingly, the nuclear localization signal was also critical for the kinetochore localization of BUB3. The deletion mutant Del216-222 and a subtle mutant with four residue changes in this region (E213Q/K216E/K217E/K218E (QE)) did not localize to the kinetochore efficiently or mediate mitotic checkpoint arrest. Protein interaction data suggested that the QE mutant was able to interact with BUB1, MAD2, and BubR1 but that its association with the centromeric components CENP-A and KNL1 was impaired. A motif from Leu(61) to Leu(65) in CENP-A was found to be involved in the association of BUB3 and CENP-A in cells; however, further assays suggested that CENP-A does not physically interact with BUB3 and does not affect BUB3 localization. Our findings help to dissect the mechanisms of BUB3 in mitotic checkpoint signaling.

Comparison of two platinum-containing chemotherapy regimens in the treatment of advanced cervical cancer with concurrent chemoradiotherapy.

OBJECTIVE: The present study aims to compare the efficacy and side effects of a platinum-containing combination regimen and platinum single-drug concurrent chemoradiotherapy (CCRT) in patients with advanced cervical cancer (CC) and to understand the prognostic factors in patients with CC. METHODS: A total of 108 cases of CC treated in Wenzhou Central Hospital were retrospectively selected. Patients in the monotherapy (single-drug) group received external pelvic radiotherapy (RT) and platinum-based single-drug chemotherapy (CT). Patients in the combined group received external pelvic RT and platinum-containing CT. The efficacy, CCRT time, 3-year survival rate after treatment and side effects were compared between the two groups, and the prognostic factors were analysed. RESULTS: The total effective rate was 74.07% in the monotherapy group and 72.22% in the combined group (p = .828). The incidences of myelosuppression, gastrointestinal reaction and abnormal liver function in the grades III-IV combined group were significantly higher than those in the monotherapy group (p < .001; p = .236; p = .022). Furthermore, the CCRT time was significantly longer in the combined group than in the monotherapy group, and the 3-year overall survival (OS) was 81.48% in the monotherapy group and 79.63% in the combined group (p = .643; p = .808). The older the age was, the higher the serum squamous cell carcinoma antigen (SCC-Ag) value before treatment and the shorter the progression-free survival time. In addition, the older the adenocarcinoma (AC) was, the shorter the OS. CONCLUSION: The efficacy of the two regimens in the treatment of advanced CC was similar. However, the side effects increased significantly during combined treatment. PROGNOSTIC FACTORS: A higher patient age, having an AC and stage of IIIa and a high SCC-Ag value before treatment resulted in a relatively low survival rate.

Exploring Effects of a Nostalgic Storytelling Virtual Reality Experience Beyond Hedonism.

In this study, we tested the effect of a nostalgic storytelling virtual reality (VR) experience (vs. a text-reading neutral VR experience as the comparison condition) on state-level eudaimonic well-being and explored the underlying mediating mechanisms. In a within-subject experimental design, all 31 participants experienced both versions of the VR in pseudorandomized and counterbalanced order. Compared with the text-reading VR experience, the nostalgic storytelling VR resulted in significantly higher hedonic and eudaimonic entertainment media gratifications (aka. media enjoyment and media appreciation, respectively), social connectedness, and state-level well-being. Moreover, the relationship between VR and well-being was serially mediated by the level of state nostalgia and eudaimonic media gratifications. That is, the nostalgic storytelling VR was found to evoke state nostalgia, which led to a greater appreciation of the VR experience; this appreciation, in turn, contributed to increased state-level well-being. Implications of the study findings for future research and practice are discussed.

A combination of cuproptosis and lncRNAs predicts the prognosis and tumor immune microenvironment in cervical cancer.

BACKGROUND: Cuproptosis induces proteotoxic stress and eventually leads to cell death. However, the relationship between cuproptosis and lncRNAs in cervical cancer has not been fully elucidated. Therefore, we aim to explore the association among lncRNAs, cuproptosis and clinical features in cervical cancer. METHODS: RNA sequencing, genetic mutations, and clinical data of CESC patients were obtained from TCGA. Cuproptosis-associated genes were gathered. WGCNA was used to cluster important modules, and KEGG, GO, GSEA and GSVA were used to explore functional and pathway enrichment. The association between immune microenvironment and cuproptosis-related lncRNAs was performed by using cibersort algorithm and other platforms, including XCELL, TIMER, QUANTISEQ, MCPCOUNTER and EPIC. Fluorescence quantitative PCR was employed to detect the expression of LINC01833 and LINC02321, and CCK-8 and cell scratch assays were used to assess cell proliferation and migration capabilities after LINCRNA interference. RESULTS: 202 upregulated and 45 downregulated lncRNAs were selected. The survival analysis showed that there was a statistically significant difference in survival rates between the high-risk and low-risk groups. The prognosis of tumour mutation burden and the degree of immune infiltration were differed noticeably between the high-risk and low-risk groups. BHG712, TL-2-105, FR-180204, Masitinib, TAK-715, ODI-027, JW-7-24-2, and OSI-930 had substantially higher IC50 values in the high-risk group. Notably, we found AL360178.1 was associated with RNF44 E3 ubiquitin ligase expression. In cervical cancer cell lines, LINC01833 and LINC02321 displayed significant upregulation. Efficient siRNA transfection led to a decreased expression of LINC01833 and LINC02321. This knockdown significantly hindered both cell proliferation and migration capabilities in cervical cancer cells compared to the negative control. CONCLUSION: In conclusion, we constructed five cuprotosis-related lncRNA prognostic models, which may be new tumor therapeutic targets for the prevention and treatment of cervical cancer.

Preparation of Fe-HMOR with a Preferential Iron Location in the 12-MR Channels for Dimethyl Ether Carbonylation.

As the Brønsted acid sites in the 8-membered ring (8-MR) of mordenite (MOR) are reported to be the active center for dimethyl ether (DME) carbonylation reaction, it is of great importance to selectively increase the Brønsted acid amount in the 8-MR. Herein, a series of Fe-HMOR was prepared through one-pot hydrothermal synthesis by adding the EDTA-Fe complex into the gel. By combining XRD, FTIR, UV-Vis, Raman and XPS, it was found that the Fe atoms selectively substituted for the Al atoms in the 12-MR channels because of the large size of the EDTA-Fe complex. The NH3-TPD and Py-IR results showed that with the increase in Fe addition from Fe/Si = 0 to 0.02, the Brønsted acid sites derived from Si-OH-Al in the 8-MR first increased and then decreased, with the maximum at Fe/Si = 0.01. The Fe-modified MOR with Fe/Si = 0.01 showed the highest activity in DME carbonylation, which was three times that of HMOR. The TG/DTG results indicated that the carbon deposition and heavy coke formation in the spent Fe-HMOR catalysts were inhibited due to Fe addition. This work provides a practical way to design a catalyst with enhanced catalytic performance.

Biodegradation of phthalate acid esters and whole-genome analysis of a novel Streptomyces sp. FZ201 isolated from natural habitats.

Di-n-butyl phthalate (DBP) is one of the most extensively used phthalic acid esters (PAEs) and is considered to be an emerging, globally concerning pollutant. The genus Streptomyces holds promise as a degrader of various organic pollutants, but PAE biodegradation mechanisms by Streptomyces species remain unsolved. In this study, a novel PAE-degrading Streptomyces sp. FZ201 isolated from natural habitats efficiently degraded various PAEs. FZ201 had strong resilience against DBP and exhibited immediate degradation, with kinetics adhering to a first-order model. The comprehensive biodegradation of DBP involves de-esterification, ß-oxidation, trans-esterification, and aromatic ring cleavage. FZ201 contains numerous catabolic genes that potentially facilitate PAE biodegradation. The DBP metabolic pathway was reconstructed by genome annotation and intermediate identification. Streptomyces species have an open pangenome with substantial genome expansion events during the evolutionary process, enabling extensive genetic diversity and highly plastic genomes within the Streptomyces genus. FZ201 had a diverse array of highly expressed genes associated with the degradation of PAEs, potentially contributing significantly to its adaptive advantage and efficiency of PAE degradation. Thus, FZ201 is a promising candidate for remediating highly PAE-contaminated environments. These findings enhance our preliminary understanding of the molecular mechanisms employed by Streptomyces for the removal of PAEs.

Mechanistic insights into the effects of diuron exposure on Alexandrium pacificum.

Diuron (N-(3,4-dichlorophenyl)-N,N­dimethylurea, DCMU), a ureic herbicide, is extensively used in agriculture to boost crop productivity; however, its extensive application culminates in notable environmental pollution, especially in aquatic habitats. Therefore, the present study investigated the effect of diuron on the dinoflagellate Alexandrium pacificum, which is known to induce harmful algal blooms (HAB), and its potential to biodegrade DCMU. Following a four-day DCMU exposure, our results revealed that A. pacificum proficiently assimilated DCMU at concentrations of 0.05 mg/L and 0.1 mg/L in seawater, attaining a complete reduction (100 % efficiency) after 96 h for both concentrations. Moreover, evaluations of paralytic shellfish toxins content indicated that cells subjected to higher DCMU concentrations (0.1 mg/L) exhibited reductions of 73.4 %, 86.7 %, and 75 % in GTX1, GTX4, and NEO, respectively. Exposure to DCMU led to a notable decrease in A. pacificum's photosynthetic efficacy, accompanied by increased levels of reactive oxygen species (ROS) and suppressed cell growth, with a growth inhibition rate of 41.1 % at 72 h. Proteomic investigations pinpointed the diminished expression levels of specific proteins like SxtV and SxtW, linked to paralytic shellfish toxins (PSTs) synthesis, as well as key proteins associated with Photosystem II, namely PsbA, PsbD, PsbO, and PsbU. Conversely, proteins central to the cysteine biosynthesis pathways exhibited enhanced expression. In summary, our results preliminarily resolved the molecular mechanisms underlying the response of A. pacificum to DCMU and revealed that DCMU affected the synthesis of PSTs. Meanwhile, our data suggested that A. pacificum has great potential in scavenging DCMU.

Attachment anxiety and cyberbullying victimization in college students: the mediating role of social media self-disclosure and the moderating role of gender.

Backgrounds and purpose: Cyberbullying is a globally prevalent social problem that threatens the wellbeing of young people. Despite a rising call for more research focused on cyberbullying victims, our understanding of the psychological and behavioral risk factors associated with cyberbullying victimization (CV) remains limited, especially among the Chinese population. However, such information is crucial for identifying potential victims and planning targeted educational and protective interventions. In this paper, we report an empirical investigation into how attachment anxiety (AA), social media self-disclosure (SMSD), and gender interplay with each other to influence CV. Methods: Cross-sectional survey data from 845 Chinese college students (Female = 635, Mage = 18.7) were analyzed in SPSS PROCESS using Haye's macro with the bootstrap method. Results: Our data support a moderated mediation model. First, SMSD partially mediates the positive relationship between AA and CV, which suggests individuals with high AA tend to engage in risky and excessive self-disclosure behavior on social media, which, in turn, expose them to an increased risk of cyberbullying. Second, gender moderates the direct AA-CV path and the second stage of the mediation path, making the effect of AA on CV appear more direct in males (i.e., not mediated by SMSD) and more indirect (i.e., fully mediated through SMSD) in females. Conclusion: The results contribute to an ongoing endeavor to better understand the psychological and behavioral mechanisms underlying CV and develop effective strategies to identify and protect vulnerable individuals.