Metabolomics research on treatment of primary liver cancer with Cortex Juglandis Mandshuricae on LC-MS/MS technology.

Diethylnitrosamine (DEN) was applied to create the primary liver cancer (PLC) animal model. In the study, the normal group, model group, cyclophosphamide (CTX) group, Cortex Juglandis Mandshuricae (CJM) extract group, myricetin group and myricitrin group were divided. LC-MS/MS technology was applied to determine the metabolites of liver tissue samples from different locations (nodular and non-nodular parts of liver tissue) in each group of rats. Through metabolomics research, the connection and difference of anti-PLC induced by the CJM extract, myricetin and myricitrin was analyzed. The surface of the liver tissues of rats in the model group was rough, dimly colored, inelastic, on which there were scattered gray white cancer nodules and blood stasis points. The number of cancer nodules was significantly reduced, and the degree of cell malignancy was low, but there were some inflammatory cell infiltrations, necrosis area and karyokinesis in the CJM extract group, myricetin group, myricitrin group and CTX group. The result of metabolic research indicated that 45 potential biomarkers of the PLC were found, as gamma-aminoisobutyrate, taurochenodeoxycholate, xanthurenic acid, etc. There were 22 differential metabolites in the CTX group, 16 differential metabolites in the CJM extract group, 14 differential metabolites in the myricetin group, 14 differential metabolites in the myricitrin group.

Single-Nucleus Transcriptomic Atlas of Human Pericoronary Epicardial Adipose Tissue in Normal and Pathological Conditions.

BACKGROUND: Pericoronary epicardial adipose tissue (EAT) is a unique visceral fat depot that surrounds the adventitia of the coronary arteries without any anatomic barrier. Clinical studies have demonstrated the association between EAT volume and increased risks for coronary artery disease (CAD). However, the cellular and molecular mechanisms underlying the association remain elusive. METHODS: We performed single-nucleus RNA sequencing on pericoronary EAT samples collected from 3 groups of subjects: patients undergoing coronary bypass surgery for severe CAD (n=8), patients with CAD with concomitant type 2 diabetes (n=8), and patients with valvular diseases but without concomitant CAD and type 2 diabetes as the control group (n=8). Comparative analyses were performed among groups, including cellular compositional analysis, cell type-resolved transcriptomic changes, gene coexpression network analysis, and intercellular communication analysis. Immunofluorescence staining was performed to confirm the presence of CAD-associated subclusters. RESULTS: Unsupervised clustering of 73 386 nuclei identified 15 clusters, encompassing all known cell types in the adipose tissue. Distinct subpopulations were identified within primary cell types, including adipocytes, adipose stem and progenitor cells, and macrophages. CD83high macrophages and FOSBhigh adipocytes were significantly expanded in CAD. In comparison to normal controls, both disease groups exhibited dysregulated pathways and altered secretome in the primary cell types. Nevertheless, minimal differences were noted between the disease groups in terms of cellular composition and transcriptome. In addition, our data highlight a potential interplay between dysregulated circadian clock and altered physiological functions in adipocytes of pericoronary EAT. ANXA1 (annexin A1) and SEMA3B (semaphorin 3B) were identified as important adipokines potentially involved in functional changes of pericoronary EAT and CAD pathogenesis. CONCLUSIONS: We built a complete single-nucleus transcriptomic atlas of human pericoronary EAT in normal and diseased conditions of CAD. Our study lays the foundation for developing novel therapeutic strategies for treating CAD by targeting and modifying pericoronary EAT functions.

DeTAL: Open-Vocabulary Temporal Action Localization with Decoupled Networks.

Pre-trained visual-language (ViL) models have demonstrated good zero-shot capability in video understanding tasks, where they were usually adapted through fine-tuning or temporal modeling. However, in the task of open-vocabulary temporal action localization (OV-TAL), such adaption reduces the robustness of ViL models against different data distributions, leading to a misalignment between visual representations and text descriptions of unseen action categories. As a result, existing methods often strike a trade-off between action detection and classification. Aiming at this issue, this paper proposes DeTAL, a simple but effective two-stage approach for OV-TAL. DeTAL decouples action detection from action classification to avoid the compromise between them, and the state-of-the-art methods for close-set action localization can be handily adapted to OV-TAL, which significantly improves the performance. Meanwhile, DeTAL can easily tackle the scenario where action category annotations are unavailable in the training dataset. In the experiments, we propose a new cross-dataset setting to evaluate the zero-shot capability of different methods. And the results demonstrate that DeTAL outperforms the state-of-the-art methods for OV-TAL on both THUMOS14 and ActivityNet1.3. Code and data are publicly available at https://github.com/vsislab/DeTAL.

The effects of demand-resource relationship on work-family conflict under Chinese culture: a cross-sectional study.

Chinese work and lifestyle are undergoing dramatic changes caused by constantly changing technology and new policies. The demand-resource dynamic relationship, which leads to work-family conflict (WFC), has become increasingly complicated. However, very little is known about the combined effects of different factors from work and family spheres on WFC. This study aims to explore (1) the discrepancy between fit and misfit, (2) the discrepancy of the different degrees of fit, and (3) the discrepancy of the different degrees of misfit from two perspectives: work demand-family resource and work resource-family demand. Data were collected from 745 individuals in China and analyzed using polynomial regression and response surface. The results demonstrate that individuals having low work demand-high family resources experience the lowest WFC, and the fit between work demands and family resources impacts the conflict in a U way. Similarly, high work resource-low family demand results in the lowest WFC; however, the fit between work resources and family demands has negative effects on the conflict. This study took factors from both family and work domains into consideration and explored the effect of their interaction on WFC. By examining the dynamic relationship between demands and resources, adjustments can be made in both domains simultaneously, providing more flexible guidance for management practices that reduce WFC.

Targeting estrogen mediated CYP4F2/CYP4F11-20-HETE metabolic disorder decelerates tumorigenesis in ER+ breast cancer.

Purpose: As the most common subset of breast cancer (BC), estrogen receptor positive (ER+) BC accounting for 80% of cases, has become a global public health concern. The female hormone estrogen (E2) unequivocally drives ER + breast malignancies. The reasons that estrogen affects BC development has long been considered, yet further study remains to be conducted of the molecular events in the E2-estrogen receptor α (ERα) signaling pathway in ER + BC progression, especially lipid metabolism, so providing more options for tailored and individualized therapy. Our aim is to find out new targets and clinical biomarkers for ER + breast cancer treatment from the perspective of lipid metabolism. Methods: Lipid metabolomics profiling was used to examine the membrane phospholipid stimulated by E2. Clinical BC samples were used to assess the association of CYP4F2, CYP4F11 expression with clinicopathological characteristics and patient outcomes. Some inhibitors of main enzymes in AA metabolism were used combined with E2 to assess roles of CYP4F2/CYP4F11 in the progression of ER + BC. CYP4F2, CYP4F11 overexpression and knockdown BC cell lines were employed to examine the effects of CYP4F2, CYP4F11 on cellular proliferation, apoptosis and tumor growth. Western blotting, qPCR, Immunohistochemical staining and flow cytometry were also conducted to determine the underlying mechanisms related to CYP4F2, CYP4F11 function. Results: The activation of the CYP450 signaling pathway in arachidonic acid metabolism contributed to ER + BC tumorigenesis. In ER + BC, CYP4F2 and CYP4F11 overexpression induced by E2 could promote cancer cell proliferation and resistance to apoptosis by producing the metabolite 20-HETE and activating the antiapoptotic protein Bcl-2. CYP4F2 and CYP4F11 elevation correlates with poorer overall survival and disease-free survival in ER + BC patients. Conclusion: CYP4F2, CYP4F11 and their metabolite 20-HETE could serve as effective prognostic markers and attractive therapeutic targets for novel anticancer drug development about ER + BC.

The GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment in pancreatic cancer.

The immunosuppressive microenvironment caused by several intrinsic and extrinsic mechanism has brought great challenges to the immunotherapy of pancreatic cancer. We identified GFPT2, the key enzyme in hexosamine biosynthesis pathway (HBP), as an immune-related prognostic gene in pancreatic cancer using transcriptome sequencing and further confirmed that GFPT2 promoted macrophage M2 polarization and malignant phenotype of pancreatic cancer. HBP is a glucose metabolism pathway leading to the generation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is further utilized for protein O-GlcNAcylation. We confirmed GFPT2-mediated O-GlcNAcylation played an important role in regulating immune microenvironment. Through cellular proteomics, we identified IL-18 as a key downstream of GFPT2 in regulating the immune microenvironment. Through CO-IP and protein mass spectrum, we confirmed that YBX1 was O-GlcNAcylated and nuclear translocated by GFPT2-mediated O-GlcNAcylation. Then, YBX1 functioned as a transcription factor to promote IL-18 transcription. Our study elucidated the relationship between the metabolic pathway of HBP in cancer cells and the immune microenvironment, which might provide some insights into the combination therapy of HBP vulnerability and immunotherapy in pancreatic cancer.

Preparation of nano-silver containing black phosphorus based on quaternized chitosan hydrogel and evaluating its effect on skin wound healing.

Hydrogels with favorable biocompatibility and antibacterial properties are essential in postoperative wound hemorrhage care, facilitating rapid wound healing. The present investigation employed electrostatic adsorption of black phosphorus nanosheets (BPNPs) and nano­silver (AgNPs) to cross-link the protonated amino group NH3+ of quaternized chitosan (QCS) with the hydroxyl group of hyaluronic acid (HA). The electrostatic interaction between the two groups resulted in the formation of a three-dimensional gel network structure. Additionally, the hydrogel containing AgNPs deposited onto BPNPs was assessed for its antibacterial properties and effects on wound healing. Hydrogel demonstrated an outstanding drug-loading capacity and could be employed for wound closure. AgNPs loaded on the BPNPs released silver ions and exhibited potent antibacterial properties when exposed to 808 nm near-infrared (NIR) radiation. The ability of the hydrogel to promote wound healing in an acute wound model was further evaluated. The BPNPs were combined with HA and QCS in the aforementioned hydrogel system to improve adhesion, combine the photothermal and antibacterial properties of the BPNPs, and promote wound healing. Therefore, the reported hydrogels displayed excellent biocompatibility and hold significant potential for application in the field of tissue engineering for skin wound treatment.

Effective reduction on flame soot via plasma coupled with carbon dioxide.

This study explored the impact of non-thermal plasma and CO2 on the flame soot characteristics within the diffusion flames. We analyzed on flame structures that were diluted with either CO2 or N2, temperature distributions, and soot characteristics, both in the presence and absence of plasma. Due to the higher specific heat capacity of CO2 compared to N2, the optical observations consistently showed lower temperatures in flames diluted with CO2 as compared to those diluted with N2. The inclusion of plasma and carbon dioxide resulted in the lowest soot concentration, indicating that plasma coupled with CO2 has a synergistic inhibitory effect on soot emissions. The findings revealed that when CO2 was used to dilute the flames and the oxygen concentration was low, the soot nanostructure appeared amorphous. Raman results showed that the level of graphitization observed in soot particles from CO2 dilution flames was lower than that from N2 dilution flames. In the presence of plasma and CO2, the soot obtained exhibited the shortest fringe length and the highest fringe tortuosity. Significant correlations were observed between the nanostructure of soot and its reactivity. The combined application of plasma and CO2 proved to be effective in reducing the soot carbonization degree.

Resolving the heterogeneous tumour microenvironment in cardiac myxoma through single-cell and spatial transcriptomics.

BACKGROUND: Cardiac myxoma (CM) is the most common (58%-80%) type of primary cardiac tumours. Currently, there is a need to develop medical therapies, especially for patients not physically suitable for surgeries. However, the mechanisms that shape the tumour microenvironment (TME) in CM remain largely unknown, which impedes the development of targeted therapies. Here, we aimed to dissect the TME in CM at single-cell and spatial resolution. METHODS: We performed single-cell transcriptomic sequencing and Visium CytAssist spatial transcriptomic (ST) assays on tumour samples from patients with CM. A comprehensive analysis was performed, including unsupervised clustering, RNA velocity, clonal substructure inference of tumour cells and cell-cell communication. RESULTS: Unsupervised clustering of 34 759 cells identified 12 clusters, which were assigned to endothelial cells (ECs), mesenchymal stroma cells (MSCs), and tumour-infiltrating immune cells. Myxoma tumour cells were found to encompass two closely related phenotypic states, namely, EC-like tumour cells (ETCs) and MSC-like tumour cells (MTCs). According to RNA velocity, our findings suggest that ETCs may be directly differentiated from MTCs. The immune microenvironment of CM was found to contain multiple factors that promote immune suppression and evasion, underscoring the potential of using immunotherapies as a treatment option. Hyperactive signals sent primarily by tumour cells were identified, such as MDK, HGF, chemerin, and GDF15 signalling. Finally, the ST assay uncovered spatial features of the subclusters, proximal cell-cell communication, and clonal evolution of myxoma tumour cells. CONCLUSIONS: Our study presents the first comprehensive characterisation of the TME in CM at both single-cell and spatial resolution. Our study provides novel insight into the differentiation of myxoma tumour cells and advance our understanding of the TME in CM. Given the rarity of cardiac tumours, our study provides invaluable datasets and promotes the development of medical therapies for CM.

Effect of Continuous Positive Airway Pressure on Incident Frailty in Elderly Patients with Obstructive Sleep Apnea: A Study Based on Propensity Score Matching.

Background: The concomitant rise in the prevalence of obstructive sleep apnea (OSA) and frailty among the elderly population has been linked to an increase in mortality rates. Despite continuous positive airway pressure (CPAP) being the gold standard treatment for OSA, its impact on incident frailty remains inadequately explored. Methods: In this cohort study, we analyzed data from 1290 patients diagnosed with OSA, aged 60 years and older. A subset of 71 patients who demonstrated high adherence to CPAP therapy were categorized as the CPAP group. Propensity score matching (PSM) was employed at a 1:4 ratio, matching for variables such as age, gender, body mass index (BMI), and sleep apnea-hypopnea index (AHI), to establish a non-CPAP group for comparison. The FRAIL scale was utilized to evaluate the frailty status of participants. Logistic regression analysis examined the relationship between CPAP therapy and incident frailty, as well as its individual components, in elderly patients with OSA. Results: During a median follow-up period of 52 months, incident frailty was observed in 70 patients (19.7%). Patients with OSA receiving CPAP therapy exhibited a lower incidence of frailty compared to those not receiving CPAP (11.26% vs 21.83%, P=0.045). In the multivariate model, CPAP therapy was significantly correlated with a reduced risk of incident frailty (OR = 0.36, 95% CI, 0.15-0.88; P = 0.025). Subcomponent analyses revealed that CPAP was associated with a lower risk of fatigue (OR=0.35, 95% CI, 0.19-0.63; P < 0.001), resistance (OR = 0.32, 95% CI, 0.14-0.74; P=0.008), and weight loss (OR = 0.38, 95% CI, 0.19-0.75; P = 0.007). Conclusion: CPAP therapy was associated with a reduced risk of incident frailty among elderly patients with OSA.

Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) belongs to the category of intestinal wind, anal ulcer, abdominal mass and other diseases in traditional Chinese medicine (TCM). Floris Sophorae Powder (F.S), is a classical prescription is recorded in Puji Benshi Fang for the treatment of intestinal carbuncle. It has been incorporated into the prescriptions for the treatment of intestinal diseases and achieved remarkable results in modern medicine. However, the mechanism of F.S in the treatment of colorectal cancer remains unclear and requires further study. AIM OF THE STUDY: To investigate F.S in treating CRC and clarify the underlying mechanism. MATERIALS AND METHODS: This study was based on Dextran Sulfate Sodium Salt (DSS) combined with Azoxymethane (AOM) induced CRC mouse model to clarify the pharmacological effects of F.S. The serum metabolomics was used to study the mechanism of action, and the chemical composition of F.S was found by UPLC-Q-TOF-MS. The rationality of serm metabolomics results was verified through the clinical target database of network pharmacology, and the upstream and downstream targets of related pathways were found. The mechanism pathway was verified by Western blot to clarify its mechanism of action. RESULTS: In vivo pharmacological experiments showed that F.S inhibited tumor growth and improved hematochezia. The vital signs of mice in the high-dose F.S group approached to those in the control group. A total of 43 differential metabolites were found to be significantly changed by serum metabolomics. F.S could modulate and recover most of the differential metabolites, which proved to be closely related to the KRAS/MEK-ERK signaling pathway. A total of 46 compounds in F.S were identified, and the rationality of serm metabolic pathway was verified by network pharmacology. Western blot results also verified that the expression of KRAS, E2F1, p-MEK and p-ERK were significantly decreased after F.S treatment. CONCLUSION: Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.

Suppression of pancreatic cancer proliferation through TXNIP-mediated inhibition of the MAPK signaling pathway.

Thioredoxin-interacting protein (TXNIP) is a crucial thioredoxin-binding protein that is recognized as a tumor suppressor in diverse malignancies, such as breast cancer, lung cancer, hepatocellular carcinoma, and thyroid cancer. However, the specific role and molecular mechanisms of TXNIP in the pathogenesis and progression of pancreatic cancer cells have not been determined. In this study, we investigate the relationship between TXNIP expression and overall survival prognosis in pancreatic cancer patients. Mechanistic studies are conducted to reveal the role of TXNIP in pancreatic cancer cell proliferation, migration, and regulation during malignancy. Our findings indicate that patients with high TXNIP expression have a more favorable prognosis. In vitro experiments with pancreatic cell lines show that overexpression of TXNIP suppresses the proliferation and migration of pancreatic cancer cells. Furthermore, we find that TXNIP inhibits the activation of the MAPK signaling pathway, thereby decreasing the malignant potential of pancreatic cancer. In conclusion, our study reveals TXNIP as a promising new predictive marker and therapeutic target for pancreatic cancer.

Structural analysis of global mineral governance system from the perspective of country.

The uneven spatial distribution of mineral resources necessitates the construction of mature global mineral governance system to ensure rational allocation of mineral resources. To this end, it is essential to analyze the structure of the global mineral governance system to provide a theoretical basis for the construction. The governance actor is the crucial element in driving the governance process, and country serves as the most central actor. Therefore, clarifying the roles and statuses of different countries in the governance system will be helpful to analyze the structure of the governance system. In the context of advancing globalization, a complex cooperative relationship has been presented between countries based on international organizations. Thus, we establish a national cooperation network based on the principle of the co-existence of countries in international organizations, to quantify these relationships between countries and identify the role and status of different countries, as well as the country communities in the cooperation network, by combining the characteristics of the countries in the network with the actual performance in the organizations. The research findings are as follow: (1) The UK, Germany, France, Sweden, and Canada play pivotal roles in promoting international cooperation as well as leading governance in the governance system. (2) Emerging economies are more actively engaged in these organizations and can promote international cooperation, but lack the capacity to assume leadership roles in governance. (3) The U.S. and China have a stronger ability to lead than to cooperate in the governance system. (4) Most African and South American countries, as well as some European nations, are marginalized in the governance system. (5) Countries with the same needs and similar economic and political conditions belong to the same community: The European countries and the U.S., consumer with a high level of economic and political development but low mineral resource endowment are in the first community. Canada, Australia, and certain African and South American countries, producers with high mineral resource endowments are in the second community. Most African and South American countries with lower levels of economic and political development are in the third group.

YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia†.

Genomic integrity is critical for sexual reproduction, ensuring correct transmission of parental genetic information to the descendant. To preserve genomic integrity, germ cells have evolved multiple DNA repair mechanisms, together termed as DNA damage response. The RNA N6-methyladenosine is the most abundant mRNA modification in eukaryotic cells, which plays important roles in DNA damage response, and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) is a well-acknowledged N6-methyladenosine reader protein regulating the mRNA decay and stress response. Despite this, the correlation between YTHDF2 and DNA damage response in germ cells, if any, remains enigmatic. Here, by employing a Ythdf2-conditional knockout mouse model as well as a Ythdf2-null GC-1 mouse spermatogonial cell line, we explored the role and the underlying mechanism for YTHDF2 in spermatogonial DNA damage response. We identified that, despite no evident testicular morphological abnormalities under the normal circumstance, conditional mutation of Ythdf2 in adult male mice sensitized germ cells, including spermatogonia, to etoposide-induced DNA damage. Consistently, Ythdf2-KO GC-1 cells displayed increased sensitivity and apoptosis in response to DNA damage, accompanied by the decreased SET domain bifurcated 1 (SETDB1, a histone methyltransferase) and H3K9me3 levels. The Setdb1 knockdown in GC-1 cells generated a similar phenotype, but its overexpression in Ythdf2-null GC-1 cells alleviated the sensitivity and apoptosis in response to DNA damage. Taken together, these results demonstrate that the N6-methyladenosine reader YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia, which provides novel insights into the mechanisms underlying spermatogonial genome integrity maintenance and therefore contributes to safe reproduction.

Branched-chain amino acid catabolic defect promotes α-cell proliferation via activating mTOR signaling.

Elevated circulating level of branched-chain amino acids (BCAAs) is closely related to the development of type 2 diabetes. However, the role of BCAA catabolism in various tissues in maintaining glucose homeostasis remains largely unknown. Pancreatic α-cells have been regarded as amino acid sensors in recent years. Therefore, we generated α-cell specific branched-chain alpha-ketoacid dehydrogenase E1α subunit (BCKDHA) knockout (BCKDHA-αKO) mice to decipher the effects of BCAA catabolism in α-cells on whole-body energy metabolism. BCKDHA-αKO mice showed normal body weight, body fat, and energy expenditure. Plasma glucagon level and glucose metabolism also remained unchanged in BCKDHA-αKO mice. Whereas, the deletion of BCKDHA led to increased α-cell number due to elevated cell proliferation in neonatal mice. In vitro, only leucine among BCAAs promoted aTC1-6 cell proliferation, which was blocked by the agonist of BCAA catabolism BT2 and the inhibitor of mTOR Rapamycin. Like Rapamycin, BT2 attenuated leucine-stimulated phosphorylation of S6 in αTC1-6 cells. Elevated phosphorylation level of S6 protein in pancreatic α-cells was also observed in BCKDHA-αKO mice. These results suggest that local accumulated leucine due to defective BCAA catabolism promotes α-cell proliferation through mTOR signaling, which is insufficient to affect glucagon secretion and whole-body glucose homeostasis.

Effect of Oroxylum indicum on hepatocellular carcinoma via the P53 and VEGF pathways based on microfluidic chips.

BACKGROUND: Hepatocellular carcinoma (HCC), abbreviated as liver cancer, is one of the most common cancers in clinics. HCC has a wider spread and higher incidence due to its high malignancy and metastasis. In HCC, effective strategies to block cancer cell migration, invasion, and neovascularization need to be further studied. Consumption of flavonoid-rich Oroxylum indicum (OI) has been associated with multiple beneficial effects, including anti-inflammatory and anticancer properties, but the potential effects on HCC have not been thoroughly investigated. OBJECTIVE: In this study, we aimed to reveal the effect of OI on HCC and its potential mechanism through microfluidic technology. METHODS: We designed microfluidic chips for cell migration, invasion, and neovascularization to evaluate the effect of OI on HepG2 cells. To further explore the mechanism of its anti-liver cancer action, the relevant signaling pathways were studied by microfluidic chips, RT‒qPCR and immunofluorescence techniques. Compared to the control group, cell migration, invasion, and angiogenesis were significantly reduced in each administration group. According to the P53 and VEGF pathways predicted by network pharmacology, RT‒qPCR and immunofluorescence staining experiments were conducted. RESULTS: The results showed that OI upregulated the expression of Bax, P53 and Caspase-3 and downregulated the expression of Bcl-2 and MDM2. It has been speculated that OI may directly or indirectly induce apoptosis of HepG2 cells by regulating apoptosis-related genes. OI blocks the VEGF signaling pathway by downregulating the expression levels of VEGF, HIF-1α and EGFR and inhibits the migration and invasion of HepG2 cells and the formation of new blood vessels. CONCLUSION: Our findings suggest that OI may inhibit the migration, invasion, and neovascularization of HepG2 cells, and its regulatory mechanism may be related to the regulation of the P53 and VEGF pathways.

Knockdown of TACC3 inhibits tumor cell proliferation and increases chemosensitivity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant digestive tract tumor with limited clinical treatments. Transforming acidic coiled-coil-containing protein 3 (TACC3) is a component of the centrosome axis and a member of the TACC family, which affect mitosis and regulate chromosome stability and are involved in tumor development and progression. However, the role of TACC3 in PDAC remains elusive. In this study, by exploiting the TCGA database, we found that high TACC3 expression in PDAC is associated with poor prognosis. shRNA-mediated TACC3 knockdown caused S phase arrest of the cell cycle and inhibited proliferation in PDAC cell lines. Through RNA sequencing and protein co-immunoprecipitation combined with mass spectrometry, KIF11 was identified as a protein that interacts with TACC3. TACC3 stabilizes and regulates KIF11 protein expression levels in PDAC cells through physical interaction. Knockdown of TACC3 or KIF11 resulted in abnormal spindle formation during cell division both in vitro and in vivo. Pharmacological inhibition of TACC3 or KIF11 can suppress tumor cell proliferation and promote apoptosis. Our studies further demonstrated that high expression of TACC3 and KIF11 mediated the resistance of PDAC to gemcitabine, and deficiency of TACC3 or KIF11 increased the sensitivity of PDAC cells to chemotherapy. In conclusion, our study reveals the fundamental role of TACC3 expression in PDAC cell proliferation and chemoresistance, suggesting that TACC3 can be used as a molecular marker to evaluate the prognosis of PDAC.

Spatiotemporal gait characteristics during single- and dual-task walking are associated with the burden of cerebral small vessel disease.

Introduction: Gait impairment is a common symptom among individuals with cerebral small vessel disease (CSVD). However, performance differences between single-task walking (STW) and dual-task walking (DTW) among individuals with CSVD remain unclear. Therefore, we aimed to examine differences in gait characteristics during STW and DTW as well as the association between gait performance and neuroimaging markers. Methods: We enrolled 126 older individuals with CSVD. The speed, cadence, stride length, stride time, and their dual-task cost (DTC) or variability were measured under the STW, motor-cognitive DTW (cognitive DTW), and motor-motor DTW (motor DTW) conditions. We examined neuroimaging features such as white matter hyperintensities (WMHs), lacunes, microbleeds, and total burden. Further, we analysed the association of neuroimaging markers with gait performance, including gait variability and DTC. Results: Almost all spatiotemporal characteristics, as well as their DTCs or variabilities, showed significant among-group differences according to disease severity in the cognitive DTW condition; however, relatively lesser differences were observed in the STW and motor DTW conditions. The total CSVD burden score was moderately correlated with all the spatial parameters, as well as their DTCs or variabilities, in the cognitive DTW condition. Moreover, WMHs showed a correlation with speed, stride time, and cadence, as well as their DTCs, in the cognitive DTW condition. Furthermore, lacunes showed a moderate correlation with speed, stride length, and the DTC of speed, whilst microbleeds were only related to the DTC of stride length in the cognitive DTW condition. Neuroimaging biomarkers were not correlated with spatiotemporal parameters in STW and motor DTW conditions after Bonferroni correction. Moreover, the correlation coefficient between the total CSVD burden score and gait parameters was greater than those of other biomarkers. Discussion: Parameters in the cognitive DTW condition are more appropriate than those in the motor DTW condition for the evaluation of gait abnormalities in patients with CSVD. Moreover, the total CSVD burden score might have better predictive utility than any single neuroimaging marker. Patients with CSVD, especially those with moderate-to-severe disease, should concentrate more on their gait patterns and reduce the load of secondary cognitive tasks whilst walking in daily life.

A Strain Transfer Model for Detection of Pitting Corrosion and Loading Force of Steel Rebar with Distributed Fiber Optic Sensor.

Steel rebar corrosion is one of the predominant factors influencing the durability of marine and offshore reinforced concrete structures, resulting in economic loss and the potential threat to human safety. Distributed fiber optic sensors (DFOSs) have gradually become an effective method for structural health monitoring over the past two decades. In this work, a strain transfer model is developed between a steel rebar and a DFOS, considering pitting-corrosion-induced strain variation in the steel rebar. The Gaussian function is first adopted to describe the strain distribution near the corrosion pit of the steel rebar and then is substituted into the governing equation of the strain transfer model, and the strain distribution in the DFOS is analytically obtained. Tensile tests are also conducted on steel rebars with artificially simulated corrosion pits, which are used to validate the developed model. The results show that the Gaussian function can be used to describe the strain variation near a corrosion pit with a depth less than 50% of the steel rebar diameter, and the strain distribution in the DFOS analytically determined based on the developed strain transfer model agrees well with the tensile test results. The corrosion pit depth and loading force in the steel rebars estimated based on the proposed model agree well with the actual values, and therefore, the developed strain transfer model is effective in detecting pitting corrosion and loading force in steel rebars.

Elucidating Interfacial Dynamics of Ti-Al Systems Using Molecular Dynamics Simulation and Markov State Modeling.

Due to their remarkable mechanical and chemical properties, Ti-Al-based materials are attracting considerable interest in numerous fields of engineering, such as automotive, aerospace, and defense. With their low density, high strength, and resistance to corrosion and oxidation, these intermetallic alloys and metal-compound composites have found diverse applications. However, additive manufacturing and heat treatment of Ti-Al alloys frequently lead to brittleness and severe formation of defects. The present study delves into the interfacial dynamics of these Ti-Al systems, particularly focusing on the behavior of Ti and Al atoms in the presence of TiAl3 grain boundaries under experimental heat treatment conditions. Using a combination of molecular dynamics and Markov state modeling, we scrutinize the kinetic processes involved in the formation of TiAl3. The molecular dynamics simulation indicates that at the early stage of heat treatment, the predominating process is the diffusion of Al atoms toward the Ti surface through the TiAl3 grain boundaries. Markov state modeling identifies three distinct dynamic states of Al atoms within the Ti/Al mixture that forms during the process, each exhibiting a unique spatial distribution. Using transition time scales as a qualitative measure of the rapidness of the dynamics, it is observed that the Al dynamics is significantly less rapid near the Ti surface compared to the Al surface. Put together, the results offer a comprehensive understanding of the interfacial dynamics and reveal a three-stage diffusion mechanism. The process initiates with the premelting of Al, proceeds with the prevalent diffusion of Al atoms toward the Ti surface, and eventually ceases as the Ti concentration within the mixture progressively increases. The insights gained from this study could contribute significantly to the control and optimization of manufacturing processes for these high-performing Ti-Al-based materials.