Effect of Current Waveform on Microstructure Evolution and Mechanical Properties of GH4169 High-Temperature Alloy Tungsten Inert Gas Additive Manufacturing.

Direct current (DC) and pulsed DC tungsten inert gas (TIG) additive manufacturing processes were employed to fabricate GH4169 high-temperature alloy specimens. Upon comparing and analysing the two additive manufacturing methods, the evolution of microstructure and mechanical properties of the additively manufactured specimens were discussed. It provided a useful reference for the engineering application of pulsed DC TIG technology. The results showed that the overall forming process of the specimen was relatively stable under the DC TIG additive manufacturing and pulsed DC TIG additive manufacturing processes. The aspect ratio of the deposited layer of the pulsed DC-deposited specimen was relatively low, and the deposited layer of the pulsed DC specimen became flatter, which was conducive to maintaining the stability of the molten pool during the deposition process and improving forming accuracy. The microstructure distribution of the deposited layer from bottom to top was relatively uneven, with columnar dendrites in the bottom layer, cellular crystals in the middle layer, and equiaxed crystals in the top layer. Compared with the DC TIG additive manufacturing of GH4169 high-temperature alloy specimens, the Laves phase of the pulsed DC specimens was significantly reduced, which improved the plasticity and brittleness of the material.

Changes in stability, phytonutrients, 3-chloropropanol esters and glycidyl esters of peanut oil-based diacylglycerols during heat treatment.

Diacylglycerol (DAG) is generally considered one of the precursors of 3-chloropropanol esters (3-MCPDE) and glycidyl esters (GEs). This study aimed to evaluate static heating and stir-frying properties of peanut oil (PO) and PO based 58% and 82% DAG oils (PDAG-58 and PDAG-82). Observations revealed that, phytonutrient levels notably diminished during static heating, with PDAG exhibiting reduced oxidative stability, but maintaining a stability profile similar to PO over a short period. During stir-frying, 3-MCPDE content initially increased and then decreased whereas the opposite was observed for GEs. Furthermore, as temperature, and NaCl concentration increased, there was a corresponding increase in the levels of 3-MCPDE and GEs, although remained within safe limits. When used in suitable concentrations, these findings underscore the potential of DAG, as a nutritionally rich and oxidatively stable alternative to conventional cooking oils, promoting the use of DAG edible oil in heat-cooked food systems.

Mapping Endocytic Vesicular Acidification with a pH-Responsive DNA Nanomachine.

Mapping the endocytic vesicular acidification process is of prior importance to better understand the health and pathological processes of cells. Herein, by integrating a pH-sensitive i-motif and a pair of fluorescence resonance energy transfer (FRET) into a tetrahedral DNA framework (TDF), we develop a pH-responsive DNA nanomachine, allowing for efficient sensing of pH from 7.0 to 5.5 via the pH-triggered spatial proximity modulation of FRET. The inheriting endo-lysosome-targeting ability of TDF enables spatiotemporal tracking of endocytic vesicle acidification during the endosomal maturation process. Analysis of pH-dependent FRET response at single fluorescent spot level reveals the significant difference of endocytic vesicular acidification between normal and cancer cells. The performance of pH-responsive DNA nanomachine underlines its potential for studies on vesicle acidification-related pathologies as a universal platform.

Assessing oral and toothbrush microbial profiles among high-altitude individuals with and without periodontal disease: a case-control study.

BACKGROUND: Periodontitis is the sixth-most common disease worldwide. The oral microbiome composition and its association with Periodontal disease (PD) have been largely explored; however, limited studies have explored the microbial profiles of both oral and toothbrushes in patients with PD. Thus, this study aimed to ascertain the oral and toothbrushes microbial composition in high-altitude populations, hypothesizing that their correlation with periodontal health would differ from those at lower altitudes, potentially indicating links between environmental factors, microbial colonization patterns, and periodontal health in distinct geographic contexts. METHODS: In the present study, we enrolled 35 individuals including 21 healthy and 14 diagnosed with PD from the Lhasa region of Tibet, China. Saliva and toothbrush samples were collected from each participant to assess the association between toothbrush usage and oral microbiome with PD using 16 S rRNA gene-specific V3-V4 regions sequencing. To assess the oral and toothbrush microbiome composition and diversity and its possible link to PD. RESULTS: Significantly higher Alpha diversity (Shannon index) was observed between the PD group and PD toothbrushes (p = 0.00021) and between the PD group and Healthy toothbrushes (p = 0.00041). The predominant species were Proteobacteria, Bacteroidota, Firmicutes, Actinobacteria, and Fusobacteria, with genera Pseudomonas, Veillonella, Neisseria, Acinetobacter, and Haemophilus. In addition, PICRUST2 analysis unveiled 44 significant pathways differentiating the disease and healthy groups, along with 29 pathways showing significant differences between their respective toothbrush microbial profiles. The distinct oral and toothbrush microbial composition among high-altitude populations suggests potential adaptations to the challenges of high-altitude environments. CONCLUSION: This study emphasizes the importance of tailored dental care strategies, accounting for altitude and racial factors, to effectively manage periodontal health in these communities. Further research is warranted to investigate the specific microbial mechanisms and develop targeted interventions for optimizing oral health in populations across varying altitudes.

Natural small molecules synergize mesenchymal stem cells for injury repair in vital organs: a comprehensive review.

Mesenchymal stem cells (MSCs) therapy is a highly researched treatment that has the potential to promote immunomodulation and anti-inflammatory, anti-apoptotic, and antimicrobial activities. It is thought that it can enhance internal organ function, reverse tissue remodeling, and achieve significant organ repair and regeneration. However, the limited infusion, survival, and engraftment of transplanted MSCs diminish the effectiveness of MSCs-based therapy. Consequently, various preconditioning methods have emerged as strategies for enhancing the therapeutic effects of MSCs and achieving better clinical outcomes. In particular, the use of natural small molecule compounds (NSMs) as a pretreatment strategy is discussed in this narrative review, with a focus on their roles in regulating MSCs for injury repair in vital internal organs. Additionally, the discussion focuses on the future directions and challenges of transforming mesenchymal stem cell research into clinical applications.

Ultrafast Super-Resolution Imaging Exploiting Spontaneous Blinking of Static Excimer Aggregates.

Single-molecule localization methods have been popularly exploited to obtain super-resolved images of biological structures. However, the low blinking frequency of randomly switching emission states of individual fluorophores greatly limits the imaging speed of single-molecule localization microscopy (SMLM). Here we present an ultrafast SMLM technique exploiting spontaneous fluorescence blinking of cyanine dye aggregates confined to DNA framework nanostructures. The DNA template guides the formation of static excimer aggregates as a "light-harvesting nanoantenna", whereas intermolecular excitation energy transfer (EET) between static excimers causes collective ultrafast fluorescence blinking of fluorophore aggregates. This DNA framework-based strategy enables the imaging of DNA nanostructures with 12.5-fold improvement in speed compared to conventional SMLM. Further, we demonstrate the use of this strategy to track the movement of super-resolved DNA nanostructures for over 20 min in a microfluidic system. Thus, this ultrafast SMLM holds great potential for revealing the dynamic processes of biomacromolecules in living cells.

Analysis of Bending Deformation and Stress of 6063-T5 Aluminum Alloy Multi-Cavity Tube Filled with Liquid.

The production of aluminum alloy multi-lumen tubes primarily involves hot bending formation, a process where controlling thermal deformation quality is difficult. Specifically, the inner cavity wall of the tube is prone to bending instability defects under the bending stress field. To address these challenges in the bending deformation of aluminum alloy multi-lumen tubes, a multi-lumen liquid-filled bypass forming method is proposed in this paper. This study focuses on the 6063-T5 aluminum alloy double-lumen tube as the research object. The liquid-filled bending deformation behavior of the aluminum alloy double-lumen tube was investigated, and the deformation theory of the aluminum alloy double-lumen tube was studied. Through experimental and numerical simulation methods, the influence of support internal pressure, bending radius, and tube wall thickness on the liquid-filled bending deformation behavior of the double-lumen tube was examined. The results indicate that when the value of internal pressure was 7.5 MPa, the straightening of the outer wall was improved by 2.51%, the thinning rate of wall thickness was minimized, and the internal concave defect was effectively suppressed. The liquid-filled bending method provides a promising new approach for the integrated bending and forming of multi-lumen tubes.

Cancer-associated fibroblasts promote the malignant development of lung cancer through the FOXO1 protein/LIF signaling.

This paper aims to investigate the current situation of cancer related fibroblasts promoting malignant development of cancer through FOXO1 protein/LIF signal, and explore the strategy of cancer treatment. Recent studies have shown that the expression of the protein forkhead box O1 (FOXO1) is increased in CAFsCAFs (Cancer-associated fibroblasts). This led researchers to investigate whether FOXO1 is involved in the role of CAFs in lung cancer. The results of the study revealed that FOXO1 is indeed upregulated in CAFs, and it positively regulates the transcription of another protein called LIF. Notably, LIF is also upregulated in both CAFs and lung cancer cells. These changes in protein expression were associated with the overexpression of FOXO1 in CAFs. Conversely, silencing FOXO1 in CAFs suppressed their effects on cancer cells and transplanted tumors. The study revealed that the downregulation of LIFR in cancer cells abolished the impact of CAFs overexpressing FOXO1 on cancer cell behavior. This suggests that the FOXO1/LIF signaling pathway is involved in mediating the malignant development of lung cancer induced by CAFs.

Sophora subprostrate polysaccharide targets LncRNA MSTRG.5823.1 to suppress PCV2-mediated immunosuppression via TNF/NF-κB signaling.

Current evidence suggests that porcine circovirus type 2 (PCV2) infection induces immunosuppression in piglets. Sophora subprostrate polysaccharide (SSP) exhibits various pharmacological activities, including immunoregulatory, anti-inflammatory, antiviral, and antioxidant properties. However, the acts of lncRNAs in regulating the therapeutic effects of SSP on PCV2-infected RAW264.7 cells remains poorly understood. This study aimed to investigate the molecular mechanisms by which lncRNAs regulate PCV2-induced immunosuppression during SSP treatment. Our findings revealed that 1699 mRNAs, 373 lncRNAs, and 129 miRNAs were differentially expressed in PCV2-infected RAW264.7 cells. Additionally, 359 mRNAs, 271 lncRNAs, and 79 miRNAs exhibited differential expression in SSP-treated PCV2-infected RAW264.7 cells. GO and KEGG analyses indicated that the candidate genes were enriched in the TNF/NF-κB signaling pathway. Furthermore, based on GO and KEGG pathway analysis, a ceRNA network involving chemokine (C-X-C motif) ligand 2 (CXCL2), miR-217-x, and MSTRG.5823.1 was constructed. We demonstrated that lncRNA MSTRG.5823.1 localized to the cytoplasm. Moreover, we found that silencing or overexpressing lncRNA MSTRG.5823.1 significantly modulated PCV2-induced immunosuppression by regulating the activation of the TNF/NF-κB signaling pathway. Specifically, lncRNA MSTRG.5823.1 overexpression increased the expression of TNF/NF-κB signaling pathway-related genes and proteins in PCV2-infected RAW264.7 cells. Conversely, silencing lncRNA MSTRG.5823.1 decreased their expression. Rescue assays further revealed that the suppressive effects of miR-217-x overexpression on TNF/NF-κB signaling pathway-related genes and proteins could be reversed by MSTRG.5823.1 overexpression. These findings highlight the critical role of lncRNA MSTRG.5823.1 in PCV2 infection progression and suggest a new strategy for the prevention and treatment of PCV2 infection.

Genome-wide identification of the CAD gene family and functional analysis of putative bona fide CAD genes in tobacco (Nicotiana tabacum L.).

Cinnamyl alcohol dehydrogenase (CAD) plays a crucial role in lignin biosynthesis, and the gene family encoding various CAD isozymes has been cloned and characterized in numerous plant species. However, limited information regarding the CAD gene family in tobacco is currently available. In this study, we identified 10 CAD genes in Nicotiana tabacum, four in N. tomentosiformis, and six in N. sylvestris. The nucleotide and amino acid sequences of these tobacco CADs demonstrate high levels of similarity, whereas the putative protein sequences conservatively possessed two Zn2+ binding motifs and an NADP(H) cofactor binding motif. Both NtCAD1 and NtCAD2 had conservative substrate binding sites, similar to those possessed by bona fide CADs, and evidence from phylogenetic analysis as well as expression profiling supported their role as bona fide CADs involved in lignin biosynthesis. NtCAD1 has two paralogous genes, NtCAD1-1 and NtCAD1-2. Enzyme activity analysis revealed that NtCAD1-1 and NtCAD1-2 had a high affinity to coniferyl aldehyde, p-coumaryl aldehyde, and sinapyl aldehyde, whereas NtCAD2 preferred coniferyl aldehyde and p-coumaryl aldehyde as substrates. The kinetic parameter assay revealed that NtCAD1-2 functions as the most efficient enzyme. Downregulation of both NtCAD1-1 and NtCAD1-2 resulted in reddish-brown stems without significant changes in lignin content. Furthermore, NtCAD1-1, NtCAD1-2, and NtCAD2 showed distinct expression patterns in response to biotic and abiotic stresses, as well as different phytohormones. Our findings suggest that NtCAD1-1 and NtCAD1-2 are involved in lignin biosynthesis, with NtCAD1-2 also participating in both biological and abiotic stresses, whereas NtCAD2 plays a distinct role mainly in responding to biological and abiotic stresses in tobacco.

Seasonal quantification of the inter-city transport of PM2.5 in the Yangtze River Delta region of China based on a source-oriented chemical transport model and the Michaelis-Menten equation.

Regional transport plays a crucial role in the pollution of fine particulate matter (PM2.5) over the Yangtze River Delta region (YRD). A practical joint regional emission control strategy requires quantitative assessment of the contribution of regional transport. In this study, the contribution of inter-city transport to PM2.5 among the 41 cities in the YRD region were quantitatively estimated using a source-oriented chemical transport model, and then the relationship between the cumulative contribution of regional transport and the distance was examined using the Michaelis-Menten equation. The results show that the Michaelis-Menten equation is suitable to represent the relationship between the cumulative contribution and transport distance. The coefficient of determination (r2) of the fittings is greater than 0.9 in 71 % of the cases in the six subregions and four seasons in YRD. Two key parameters in the Michaelis-Menten eq. K1, indicating the maximum contribution of regional transport, and K2, indicating the distance to which the regional transport contribution reach half the maximum contribution, show substantial regional and seasonal variations. The average K1 is 73.6 %, with lower values observed in the northern part of the YRD and higher values in central Jiangsu. K2 is larger in northern Jiangsu, as well as central and southern Zhejiang. The local contribution in autumn and winter is lower than that in spring and summer in the northern part of the YRD. Particularly in northern Jiangsu, the local contribution reaches 90.4 % in summer but drops to 53.0 % in autumn and winter, illustrating significant impacts of regional transport to PM2.5 in autumn and winter in this area. K2 is larger on polluted days, compared to clean days, indicating greater contributions from regional transport to PM2.5 in YRD. The results can serve as a scientific foundation for implementing regional joint prevention and control measures in the YRD region.

Intracranial Aneurysms Managed by Parent Artery Reconstruction Using Tubridge Flow Diverter study: 1-year outcomes.

OBJECTIVE: Previous randomized controlled trials have reported a significantly higher occlusion rate of large and giant aneurysms when utilizing the Tubridge flow diverter (FD). In the present trial, the safety and efficacy of the Tubridge FD in treating unruptured internal carotid artery (ICA) or vertebral artery (VA) aneurysms were assessed in a real-world setting. METHODS: The Intracranial Aneurysms Managed by Parent Artery Reconstruction Using Tubridge Flow Diverter (IMPACT) study is a prospective, multicenter, single-arm clinical trial assessing the efficacy of the Tubridge FD in the management of unruptured aneurysms located in the ICA or VA. The primary endpoint was the complete occlusion (Raymond-Roy class 1) rate at the 1-year follow-up. The secondary endpoints included the technical success rate, the successful occlusion rate of the aneurysm, which is the degree of aneurysm embolization scored as Raymond-Roy class 1 or 2, major (> 50%) in-stent stenosis, and incidence of disabling stroke or neurological death associated with the target aneurysms. RESULTS: This study included 14 interventional neuroradiology centers, with 200 patients and 240 aneurysms. According to angiographic core laboratory assessment, 205 (85.4%) aneurysms were located in the ICA, 34 (14.2%) in the VA, and 1 (0.4%) in the middle cerebral artery. Additionally, 189 (78.8%) aneurysms were small (< 10 mm). At the 12-month follow-up, the total occlusion rate was 79.0% (166/210, 95% CI 72.91%-84.34%). Additionally, the occurrence of disabling stroke or neurological death related to the specified aneurysms was 1% (2/200). CONCLUSIONS: The 1-year results from the IMPACT trial affirm the safety record of use of the Tubridge FD in the treatment of intracranial aneurysms in real-world scenarios. These results reveal low morbidity and mortality rates of 3.5% and 1.5%, respectively. Furthermore, they provide evidence of the effectiveness of the Tubridge FD, as demonstrated by the complete occlusion achieved in 166 of 210 (79%) cases.

Continued Rise in Health Burden from Ambient PM2.5 in India under SSP Scenarios Until 2100 despite Decreasing Concentrations.

Forecasting alterations in ambient air pollution and the consequent health implications is crucial for safeguarding public health, advancing environmental sustainability, informing economic decision making, and promoting appropriate policy and regulatory action. However, predicting such changes poses a substantial challenge, requiring accurate data, sophisticated modeling methodologies, and a meticulous evaluation of multiple drivers. In this study, we calculate premature deaths due to ambient fine particulate matter (PM2.5) exposure in India from the 2020s (2016-2020) to the 2100s (2095-2100) under four different socioeconomic and climate scenarios (SSPs) based on four CMIP6 models. PM2.5 concentrations decreased in all SSP scenarios except for SSP3-7.0, with the lowest concentration observed in SSP1-2.6. The results indicate an upward trend in the five-year average number of deaths across all scenarios, ranging from 1.01 million in the 2020s to 4.12-5.44 million in the 2100s. Further analysis revealed that the benefits of reducing PM2.5 concentrations under all scenarios are largely mitigated by population aging and growth. These findings underscore the importance of proactive measures and an integrated approach in India to improve atmospheric quality and reduce vulnerability to aging under changing climate conditions.

Enhancing glioma-specific drug delivery through self-assembly of macrophage membrane and targeted polymer assisted by low-frequency ultrasound irradiation.

The blood-brain Barrier (BBB), combined with immune clearance, contributes to the low efficacy of drug delivery and suboptimal treatment outcomes in glioma. Here, we propose a novel approach that combines the self-assembly of mouse bone marrow-derived macrophage membrane with a targeted positive charge polymer (An-PEI), along with low-frequency ultrasound (LFU) irradiation, to achieve efficient and safe therapy for glioma. Our findings demonstrate the efficacy of a charge-induced self-assembly strategy, resulting in a stable co-delivery nanosystem with a high drug loading efficiency of 44.2 %. Moreover, this structure triggers a significant release of temozolomide in the acidic environment of the tumor microenvironment. Additionally, the macrophage membrane coating expresses Spyproteins, which increase the amount of An-BMP-TMZ that can evade the immune system by 40 %, while LFU irradiation treatment facilitates the opening of the BBB, allowing for enormously increased entry of An-BMP-TMZ (approximately 400 %) into the brain. Furthermore, after crossing the BBB, the Angiopep-2 peptide-modified An-BMP-TMZ exhibits the ability to selectively target glioma cells. These advantages result in an obvious tumor inhibition effect in animal experiments and significantly improve the survival of glioma-bearing mice. These results suggest that combining the macrophage membrane-coated drug delivery system with LFU irradiation offers a feasible approach for the accurate, efficient and safe treatment of brain disease.

Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer.

BACKGROUND: Lymph node (LN) staging in rectal cancer (RC) affects treatment decisions and patient prognosis. For radiologists, the traditional preoperative assessment of LN metastasis (LNM) using magnetic resonance imaging (MRI) poses a challenge. AIM: To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable LNs. METHODS: In this retrospective study, 270 LNs (158 nonmetastatic, 112 metastatic) were randomly split into training (n = 189) and validation sets (n = 81). LNs were classified based on pathology-MRI matching. Conventional MRI features [size, shape, margin, T2-weighted imaging (T2WI) appearance, and CE-T1-weighted imaging (T1WI) enhancement] were evaluated. Three radiomics models used 3D features from T1WI and T2WI images. Additionally, a nomogram model combining conventional MRI and radiomics features was developed. The model used univariate analysis and multivariable logistic regression. Evaluation employed the receiver operating characteristic curve, with DeLong test for comparing diagnostic performance. Nomogram performance was assessed using calibration and decision curve analysis. RESULTS: The nomogram model outperformed conventional MRI and single radiomics models in evaluating LNM. In the training set, the nomogram model achieved an area under the curve (AUC) of 0.92, which was significantly higher than the AUCs of 0.82 (P < 0.001) and 0.89 (P < 0.001) of the conventional MRI and radiomics models, respectively. In the validation set, the nomogram model achieved an AUC of 0.91, significantly surpassing 0.80 (P < 0.001) and 0.86 (P < 0.001), respectively. CONCLUSION: The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

Multi-targeted nanoarrays for early broad-spectrum detection of lung cancer based on blood biopsy of tumor exosomes.

Liquid biopsies utilizing tumor exosomes offer a noninvasive approach for cancer diagnosis. However, validation studies consistently report that in the early stages of cancer, the secretion of exosomes by cancer cells is relatively low, while bodily fluids exhibit a high abundance of other interfering biomolecules. Additionally, target mutations or differences in biomarker expression among various lung cancer subtypes may contribute to detection failures. In this study, we propose a targeted nanoarray-based early cancer diagnostic approach for multiple subtypes of lung cancer. The targeted nanoarray was constructed by modifying five targeting aptamers onto mesoporous silica nanoparticles through the conjugation between amino and carboxyl groups. The flow cytometry experiments demonstrated the specific recognition ability of the targeted nanoarray to tumor exosomes in PBS, even at biomarker expression levels as low as 1.5 %. Moreover, the TEM results indicated that the targeted nanoarray could isolate tumor exosomes in the blood of tumor-bearing mice. Furthermore, the targeted nanoarray could detect tumor exosomes in the blood of various lung cancer bearing mice, including at the early stages of cancer, which has just been established for 7 days. Overall, the targeted nanoarray represents a promising tool for the early detection of various subtypes of lung cancer.

[Retracted] Fe3O4­solamargine induces apoptosis and inhibits metastasis of pancreatic cancer cells.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the Transwell invasion assay data shown in Fig. 5B on p. 911 were strikingly similar to data that had appeared in a previously published paper written by different authors at a different research institute. In view of the fact that certain of the data in the above article had already appeared in a previously published paper, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 54: 905­915, 2019; DOI: 10.3892/ijo.2018.4637].

The potassium transporter TaNHX2 interacts with TaGAD1 to promote drought tolerance via modulating stomatal aperture in wheat.

Drought is a major global challenge in agriculture that decreases crop production. γ-Aminobutyric acid (GABA) interfaces with drought stress in plants; however, a mechanistic understanding of the interaction between GABA accumulation and drought response remains to be established. Here we showed the potassium/proton exchanger TaNHX2 functions as a positive regulator in drought resistance in wheat by mediating cross-talk between the stomatal aperture and GABA accumulation. TaNHX2 interacted with glutamate decarboxylase TaGAD1, a key enzyme that synthesizes GABA from glutamate. Furthermore, TaNHX2 targeted the C-terminal auto-inhibitory domain of TaGAD1, enhanced its activity, and promoted GABA accumulation under drought stress. Consistent with this, the tanhx2 and tagad1 mutants showed reduced drought tolerance, and transgenic wheat with enhanced TaNHX2 expression had a yield advantage under water deficit without growth penalty. These results shed light on the plant stomatal movement mechanism under drought stress and the TaNHX2-TaGAD1 module may be harnessed for amelioration of negative environmental effects in wheat as well as other crops.