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Achieving superior ductility, microstructure, and strength simultaneously in tailor-welded blanks remains challenging. To address this, pre-aging blanks before friction stir welding was proposed. Systematic studies were conducted on the microstructure, ductility, and post-aging strength of pre-aged 2219 aluminium alloy after friction stir welding. Uniaxial tensile tests evaluated the ductility of tailor-welded blanks at room and cryogenic temperatures, along with their mechanical properties after artificial aging. Microstructural characterization and Vickers hardness measurements elucidated the strengthening mechanisms between the welded region and base material. No abnormal grain growth was observed in the welded region post pre-aging welding; instead, a finer grain structure prevailed. Ductility of the tailor-welded blanks initially increased and then decreased with increasing rotational speed. Excellent elongations, 27.8% at room temperature and 32.4% at cryogenic temperatures, were obtained at a rotational speed of 1300 rpm, reaching 91.5% of the base material. This attributed to the finer grain boundary strengthening in the welded regions. After artificial aging, a joint efficiency of 93.5% was achieved, owing to effective compensation of the reduction in precipitation strengthening caused by the welded heat input through finer grain strengthening. This approach represents a novel method for preparing ultrawide blanks for forming integral large-sized aluminum alloy components.

Temperature and pressure have a significant impact on friction in aluminum alloy ultra-low temperature forming. In this paper, cryogenic strip drawing test (CSDT), morphologies analysis and microstructure characterization were used for friction mechanism investigation of aluminum alloy under different temperatures and pressures. The findings indicated that the coefficient of friction (COF) first increased and then decreased as pressure increased. From 2 to 10 MPa, the lowest COF was observed at −190 °C. The formation of fine deformation microstructure enhanced surface material plasticity and resistance to deformation leading to reduced adhesive friction or plowing friction, resulting in low COF at high-pressure and ultra-low temperature. Furthermore, higher temperatures and pressures increased the adhesion, which was detrimental to prolonging the service life of die.

Abstract The monkeypox virus (MPXV) is a zoonotic DNA virus that belongs to the poxvirus family. Conventional laboratory methods for detecting MPXV are complex and expensive, making them unsuitable for detecting the virus in regions with limited resources. In this study, we using the Helicase dependent amplification (HDA) method and the Recombinase polymerase amplification (RPA) technique in combination with the lateral flow test (LFT), together with a self-designed qPCR technique for the detection of the MPXV specific conserved fragment F3L, to compare the sensitivity and specificity of the three assays. By analyzing the sensitivity detection results using Probit, it can be seen that the limit of detection (LOD) of the HDA-LFT detection target is 9.86 copies/µL (95% confidence interval, CI 7.52 copies/µL lower bound), the RPA-LFT detection target is 6.97 copies/µL (95% CI 3.90 copies/µL lower bound), and the qPCR detection target is 479.24 copies/mL (95% CI 273.81 copies/mL lower bound). The specificity test results showed that the specificity of the three methods mentioned above was higher than 90% in detecting pseudoviruses of the same genus of MPXV. The simple, highly sensitive, and specific MPXV assay developed in this study is anticipated to provide a solid foundation for future applications in the early screening, diagnosis, and evaluation of the efficacy of MPXV. This is the first time the HDA-LFT assay has been utilized to detect MPXV infection.

Abstract Broad use of lightweight aluminium alloy parts in automobile manufacturing, aerospace, electronic communication, and rail transit is mainly formed through deep drawing process. Deep drawing friction is a key boundary condition for controlling the forming quality of aluminium alloy parts. However, due to the oxidation and adhesion tendency of aluminium alloys, the tribological situations of aluminium alloy deep drawing (AADD) system is more complicated than those of traditional deep drawing of steel sheets. Therefore, the study of AADD friction is essential for manufacturing high-performance aluminium alloy parts. Herein, aiming to provide a valuable reference for researchers in related fields, a comprehensive review of AADD friction is provided, including friction mechanism, influencing factors, friction measurement, friction model, friction simulation, and lubrication-free friction control. Finally, a brief conclusion and several current challenges were discussed.

Abstract Background The prevalence of preterm birth has been rising, and there is a paucity of nationwide data on the perinatal characteristics and neonatal outcomes of twin deliveries of very preterm infants (VPIs) in China. This study compared the perinatal characteristics and outcomes of singletons and twins admitted to neonatal intensive care units (NICUs) in China. Methods The study population comprised all infants born before 32 weeks in the Chinese Neonatal Network (CHNN) between January 2019 and December 2019. Three-level and population-average generalized estimating equation (GEE)/alternating logistic regression (ALR) models were used to determine the association of twins with neonatal morbidities and the use of NICU resources. Results During the study period, there were 6634 (71.2%) singletons and 2680 (28.8%) twins, with mean birth weights of 1333.70 g and 1294.63 g, respectively. Twins were significantly more likely to be delivered by caesarean section (p

Abstract Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are currently the main methods of GC screening, and treatment relies on surgical resection or chemotherapy. However, traditional examination and treatment methods are more harmful to patients and less sensitive and accurate. A minimally invasive method to respond to GC early screening, prognosis monitoring, treatment efficacy, and drug resistance situations is urgently needed. As a result, liquid biopsy techniques have received much attention in the clinical application of GC. The non-invasive liquid biopsy technique requires fewer samples, is reproducible, and can guide individualized patient treatment by monitoring patients' molecular-level changes in real-time. In this review, we introduced the clinical applications of circulating tumor cells, circulating free DNA, circulating tumor DNA, non-coding RNAs, exosomes, and proteins, which are the primary markers in liquid biopsy technology in GC. We also discuss the current limitations and future trends of liquid biopsy technology as applied to early clinical biopsy technology.

In light of the significance of regulatory authorities and the rising demand for information disclosure, a vast amount of information on food safety news reports is readily accessible on the Internet. The extraction of such information for precise classification and provision of appropriate safety alerts based on their respective categories has emerged as a challenging problem for academic research. Given that most food safety-related events in news reports comprise lengthy text, the pre-trained language models currently employed for text analysis are generally limited in their capability to handle long documents. This paper proposes a long-text classification model utilising hierarchical Transformers. We categorise information in long documents into two distinct types: (1) multiple text chunks meeting the length constraint and (2) essential sentences within long documents, such as headings, paragraph start and end sentences, etc. Initially, our proposed model utilises the text chunks as input to the BERT model. Then, it concatenates the output of the BERT model with the important sentences from the document and use them as input to the Transformer model for feature transformation. Finally, we utilise a classifier for food safety news classification. We conducted several comparative experiments with various commonly used text classification models on a dataset constructed from publicly available information on food regulatory websites. Our proposed method outperforms existing methods, establishing itself as the leading approach in terms of performance.

The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment; however, biocompatibility and targeted penetration of these nanomaterials remain as limitations, which lead to serious side effects and significantly narrow the scope of their application. The self-assembly of intermediate filaments with arginine–glycine–aspartate (RGD) peptide (RGD-IFP) was triggered by the hydrophobic cationic molecule 7-amino actinomycin D (7-AAD) to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment. The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes, ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA. It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential, but also potent antitumor therapeutic effects in vivo. The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.

Summary: Ever since the catalytic hairpin assembly (CHA) circuit has been highlighted as a powerful nucleic acid detection tool, nucleic acid detection methods based on CHA have been widely studied. However, the detection sensitivity of CHA-based methods is insufficient. The relatively high background signals resulting from the spontaneous reaction between the two hairpin probes is one of the major reasons for limiting the sensitivity of CHA. In this study, we established that the addition of deoxynucleotide triphosphates (dNTPs) to the reaction system can significantly reduce the background leakage of CHA. The dNTPs-CHA, coupled with a fluorescence lateral flow assay strip, is used for the rapid and highly sensitive detection of miRNA. It is capable of reliably detecting miRNA in serum samples down to a limit of 100 aM, which is an improvement in the lower detection limit by nearly five orders of magnitude compared to that of the pure CHA.

The deformation and effective die quenching are critical to ensure the final dimensional accuracy and strength of the thick-walled curved components in hot forming-quenching integrated process. The deformation behavior of an Al–Cu–Mg alloy plate during bending-quenching process was thus analyzed at different temperatures and die clearances. The strengthening behavior along thickness and radial directions was evaluated under different heating and die quenching conditions. The strengthening mechanism was revealed by microstructure observation. It is found that the smaller die clearance and higher heating temperature contribute to improve the dimensional accuracy. The water-cooled die quenching can ensure the effective quenching of a bended specimen with 25 mm in thickness, being at the strengthening level of peak aging. And, the effective quenching thickness reaches 50 mm at least. Dynamic recovery is the main restoration mechanism in the integrated process. The hardness reduces while air cooling due to the formation of coarse S precipitates with average size exceeding 750 nm. Finally, a large-size tapered thick plate component with superior dimensional accuracy was successfully fabricated under the guidance of the obtained results.

The hybridization chain reaction (HCR) is widely used for biosensing. However, HCR does not provide the required sensitivity. In this study, we reported a method to improve the sensitivity of HCR by dampening the cascade amplification. First, we designed a biosensor based on HCR, and an initiator DNA was used to trigger the cascade amplification. Optimization of the reaction was then performed, and the results showed that the limit of detection (LOD) for the initiator DNA was about 2.5 nM. Second, we designed a series of inhibitory DNAs to dampen the HCR cascade amplification, and DNA dampeners (50 nM) were applied in the presence of the DNA initiator (50 nM). One of the DNA dampeners (D5) showed the best inhibitory efficiency of greater than 80%. This was further applied at concentrations ranging from 0 nM to 10 nM to prohibit the HCR amplification caused by a 2.5 nM initiator DNA (the limit of detection for this initiator DNA). The results showed that 0.156 nM of D5 could significantly inhibit the signal amplification (p

Recently, the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was reported to be involved in the pathogenesis of several cancers, including human colorectal cancer (CRC). However, the molecular basis for cancer initiation, development, and progression remains unclear. In this study, we observe that upregulated PVT1 is associated with poor prognosis and bad clinicopathological features of CRC patients. In vitro means of PVT1 loss in a CRC cell line inhibit cell proliferation, migration, and invasion. Furthermore, dual-luciferase reporter and RNA pull-down assays indicated that PVT1 binds to miR-16-5p, which has been shown to play strong tumor suppressive roles in CRC. Targeted loss of miR-16-5p partially rescues the suppressive effect induced by PVT1 knockdown. Vascular endothelial growth factor A (VEGFA), a direct downstream target of miR-16-5p, was suppressed by PVT1 knockdown in CRC cells. Overexpression of VEGFA is known to modulate the AKT signaling cascade by activating vascular endothelial growth factor receptor 1 (VEGFR1). We, therefore, show that PVT1 loss combined with miR-16-5p overexpression reduces tumor volume maximally when propagated within a mouse xenograft model. We conclude that the PVT1-miR-16-5p/VEGFA/VEGFR1/AKT axis directly coordinates the response in CRC pathogenesis and suggest PVT1 as a novel target for potential CRC therapy.

The chromosomal homologies of human (Homo sapiens—HSA) and Trachypithecus phayrei (TPH—Phayre’s leaf-monkey, family Cercopithecidae) have previously been studied by using classical chromosome staining/banding and fluorescence in situ hybridization (FISH) from the 1970s to 1990s. In this study, we carried out molecular cytogenetics applying human multicolor banding (MCB), locus-specific, and human heterochromatin-specific probes to establish the first detailed chromosomal map of TPH, which was not available until now. Accordingly, it was possible to precisely determine evolutionary-conserved breakpoints (ECBs) and the orientation of evolutionary-conserved segments compared to HSA. It could be shown that five chromosomes remained completely unchanged between these two species, and 16 chromosomes underwent only intrachromosomal changes. In addition, 50 ECBs that failed to be resolved in previous reports were exactly identified and characterized in this study. It could also be shown that 43.5% of TPH centromere positions were conserved and 56.5% were altered compared to HSA. Interestingly, 82% ECBs in TPH corresponded to human fragile sites. Overall, this study is an essential contribution to future studies and reviews on chromosomal evolution in Cercopithecidae.

Affective understanding of language is an important research focus in artificial intelligence. The large-scale annotated datasets of Chinese textual affective structure (CTAS) are the foundation for subsequent higher-level analysis of documents. However, there are very few published datasets for CTAS. This paper introduces a new benchmark dataset for the task of CTAS to promote development in this research direction. Specifically, our benchmark is a CTAS dataset with the following advantages: (a) it is Weibo-based, which is the most popular Chinese social media platform used by the public to express their opinions; (b) it includes the most comprehensive affective structure labels at present; and (c) we propose a maximum entropy Markov model that incorporates neural network features and experimentally demonstrate that it outperforms the two baseline models.

Hydroxyurea (HU) is a widely used pharmacological therapy for sickle cell disease (SCD). However, replication stress caused by HU has been shown to inhibit premeiotic S-phase DNA, leading to reproductive toxicity in germ cells. In this study, we administered the therapeutic doses of HU (i.e., 25 and 50 mg/kg) to male mice to explore whether replication stress by HU affects pachytene spermatocytes and causes the abnormalities of homologous chromosomes pairing and recombination during prophase I of meiosis. In comparison with the control group, the proportions of spermatocyte gaps were significantly different in the experimental groups injected with 25 mg/kg (p < 0.05) and 50 mg/kg of HU (p < 0.05). Moreover, the proportions of unrepaired double-stranded breaks (DSBs) observed by γH2AX staining also corresponded to a higher HU dose with a greater number of breaks. Additionally, a reduction in the counts of recombination foci on the autosomal SCs was observed in the pachytene spermatocytes. Our results reveal that HU has some effects on synaptonemal complex (SC) formation and DSB repair which suggest possible problems in fertility. Therefore, this study provides new evidence of the mechanisms underlying HU reproductive toxicity.

Abstract Background Grb2-associated binder 2 (Gab2) is a scaffolding protein that serves as a critical signaling amplifier downstream of tyrosine kinase receptors. Our previous study has shown that Gab2 induces epithelial-to-mesenchymal transition (EMT) and promotes metastasis in colorectal cancer (CRC). However, the role of Gab2 in CRC growth and angiogenesis remains unclear. Methods The expression of vascular endothelial growth factor (VEGF) in different colorectal tissues was detected by immunohistochemistry and qRT-PCR to evaluate its correlation with Gab2. Lentiviral vectors bearing Gab2 gene and its small interfering RNAs were constructed and transfected into CRC cell lines. The effects of Gab2 on the cell proliferation in vitro and tumorigenesis in vivo, were examined via CCK‑8 assay, colony formation assay as well as tumorigenicity assay respectively. Moreover, to assess its potential role in tumor growth and angiogenesis, the expression of Ki67, CD34 and vascular endothelial growth factor receptor-2 (VEGFR2) were detected by immunohistochemistry in CRC cells tumors. Finally, we evaluated the impact of Gab2 on the expression of c-Myc and VEGF, and the probable effect of mechanistic targeted extracellular signal-regulated kinase (ERK) pathway in suppressing tumor growth and angiogenesis. Results Up-regulation of Gab2 expression was found to be positively correlated with VEGF in CRC tissues. Exogenous expression of Gab2 obviously promoted, whereas silencing of Gab2 inhibited, proliferation and clone formation of human CRC cells in vitro. Of note, Gab2 enhanced tumorigenesis and tumor growth in mouse xenografts with high Ki67 expression, and led to an increased vessel density with strong CD34 and VEGFR2 activity. In addition, elevated Gab2 expression obviously up-regulated the expression of VEGF, and stimulated the activation of its downstream genes, ERK1/2 and c-Myc in CRC cells. Instead, down-regulated Gab2 expression significantly reduced the levels of VEGF, and inhibited the transduction of ERK/c-Myc pathway. Finally, we revealed that mechanistic target of mitogen-activated protein kinase (MEK) could attenuate Gab2-induced tumor growth and angiogenesis via altering VEGF and c-Myc levels. Conclusions The results from our study suggest that Gab2 promotes intestinal tumor growth and angiogenesis through upregulation of VEGF expression mediated by the MEK/ERK/c-Myc pathway.

The emergence of drug-resistant bacteria emphasizes the urgent need for novel antibiotics. The antimicrobial peptide TS shows extensive antibacterial activity in vitro and in vivo, especially in gram-negative bacteria; however, its antibacterial mechanism is unclear. Here, we find that TS without hemolytic activity disrupts the integrity of the outer bacterial cell membrane by displacing divalent cations and competitively binding lipopolysaccharides. In addition, the antimicrobial peptide TS can inhibit and kill E. coli by disintegrating the bacteria from within by interacting with bacterial DNA. Thus, antimicrobial peptide TS’s multiple antibacterial mechanisms may not easily induce bacterial resistance, suggesting use as an antibacterial drug to be for combating bacterial infections in the future.

The deformation behavior of a 2024 aluminum alloy sheet at elevated temperatures was studied by uniaxial hot tensile tests over the nominal initial strain rate range of 0.001⁻0.1 s−1 and temperature range of 375⁻450 °C. In order to analyze the deformation behavior with higher accuracy, a digital image correlation (DIC) system was applied to determine the strain distribution during hot tensile tests. Local stress-strain curves for different local points on the specimens were calculated. The strain rate evolution of each point during the tensile tests was investigated under different deformation conditions. Then, an improved Fields⁻Backofen (FB) model, taking into account the local strain rate evolution instead of the fixed strain rate, was proposed to describe the constitutive behaviors. It has been found that obvious non-uniform strain distribution occurred when the true strain was larger than 0.3 during hot tensile tests. The strain rate distribution during deformation was also non-uniform. It showed increasing, steady, and decreasing variation tendencies for different points with the increasing of strain, which led to the local flow stress being different at different local points. The flow stresses predicted by the improved FB model showed good agreement with experimental results when the strain rate evolutions of local points during tensile tests were considered. The prediction accuracy was higher than that of traditional FB models.

Comparative cytogenetic analysis in New World Monkeys (NWMs) using human multicolor banding (MCB) probe sets were not previously done. Here we report on an MCB based FISH-banding study complemented with selected locus-specific and heterochromatin specific probes in four NWMs and one Old World Monkey (OWM) species, i.e. in Alouatta caraya (ACA), Callithrix jacchus (CJA), Cebus apella (CAP), Saimiri sciureus (SSC), and Chlorocebus aethiops (CAE), respectively. 107 individual evolutionary conserved breakpoints (ECBs) among those species were identified and compared with those of other species in previous reports. Especially for chromosomal regions being syntenic to human chromosomes 6, 8, 9, 10, 11, 12 and 16 previously cryptic rearrangements could be observed. 50.4% (54/107) NWM-ECBs were colocalized with those of OWMs, 62.6% (62/99) NWM-ECBs were related with those of Hylobates lar (HLA) and 66.3% (71/107) NWM-ECBs corresponded with those known from other mammalians. Furthermore, human fragile sites were aligned with the ECBs found in the five studied species and interestingly 66.3% ECBs colocalized with those fragile sites (FS). Overall, this study presents detailed chromosomal maps of one OWM and four NWM species. This data will be helpful to further investigation on chromosome evolution in NWM and hominoids in general and is prerequisite for correct interpretation of future sequencing based genomic studies in those species.

Cryogenic medium pressure forming has been developed to form the complex-shaped tubular components, in which the needed shape and tube diameter directly determine the complex evolution of biaxial stress in bulging process. The superposition of biaxial stress and cryogenic temperature complicates the deformation behaviors, especially for the final fracture and bulging limit, which determine the forming quality of components. Therefore, the effects of tube geometry on failure orientation and fracture strain of Al-Mg-Si alloy tubes under cryogenic biaxial stress were elucidated, by utilizing cryogenic free bulging with different length-diameter ratios. The failure orientations and corresponding damage modes under different bulging geometric conditions were revealed. The influence mechanism of tube geometry and temperature on the failure mode was analyzed theoretically. A fracture model was established to predict the fracture strain in cryogenic bulging. The failure mode changes from circumferential cracking to axial cracking with the decreasing length-diameter ratio, owing to the stress sequence reversal induced by the significant nonlinearity of the stress path under a small length-diameter ratio. The failure mode can inverse under a larger length-diameter ratio of 1.0 at -196 °C because of the enhanced nonlinearity, which is promoted by the improved plasticity at cryogenic temperature. The established model based on the more accurate assessment of hardening ability during deformation can accurately predict the fracture strain with an average deviation of 10.6% at different temperatures. The study can guide deformation analysis and failure prediction in the cryogenic forming of aluminum alloy tubular parts. [ABSTRACT FROM AUTHOR]