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Intelligent manufacturing, defined as the integration of manufacturing with modern information technologies such as 5G, digitalization, networking, and intelligence, has grown in popularity as a means of boosting the productivity, intelligence, and flexibility of traditional manufacturing processes. The steel industry is a necessary support for modern life and economic development, and the Chinese steel industry’s capacity has expanded to roughly half of global production. However, the Chinese steel industry is now confronted with high labor costs, massive carbon emissions, a low level of intelligence, low production efficiency, and unstable quality control. Therefore, China’s steel industry has launched several large-scale intelligent manufacturing initiatives to improve production efficiency, product quality, manual labor intensity, and employee working conditions. Unfortunately, there is no comprehensive overview of intelligent manufacturing in China’s steel industry. We began this research by summarizing the construction goals and overall framework for intelligent manufacturing of the steel industry in China. Following that, we offered a brief review of intelligent manufacturing for China’s steel industry, as well as descriptions of two typical intelligent manufacturing models. Finally, some major technologies employed for intelligent production in China’s steel industry were introduced. This research not only helps to comprehend the development model, essential technologies, and construction techniques of intelligent manufacturing in China’s steel industry, but it also provides vital inspiration for the manufacturing industry’s digital and intelligence updates and quality improvement.

Background Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemotherapy-elicited exosomes in regulating chemoresistance is poorly understood. Methods Using commercial kits, serum exosomes were extracted from patients before neoadjuvant chemotherapy, after one cycle of chemotherapy and after four cycles of chemotherapy consisting of doxorubicin (DOX) and paclitaxel (PTX). Their miRNAs were sequenced, and the correlation between the sequencing results and chemotherapy effects was further verified by RT-qPCR using patient serum exosomes. Cell Counting Kit-8 (CCK-8) was used to detect chemosensitivity. Stemness was assessed by CD44+/CD24- population analysis and mammosphere formation assays. Chromatin immunoprecipitation (ChIP) experiments were performed to verify the binding of signal transducer and activator of transcription 3 (STAT3) to the promoter of miRNAs. Results Here, we provide clinical evidence that chemotherapy-elicited exosomal miR-378a-3p and miR-378d are closely related to the chemotherapy response and that exosomes produced by BC cells after stimulation with DOX or PTX deliver miR-378a-3p and miR-378d to neighboring cells to activate WNT and NOTCH stemness pathways and induce drug resistance by targeting Dickkopf 3 (DKK3) and NUMB. In addition, STAT3, which is enhanced by zeste homolog 2 (EZH2), bound to the promoter regions of miR-378a-3p and miR-378d, thereby increasing their expression in exosomes. More importantly, chemotherapeutic agents combined with the EZH2 inhibitor tazemetostat reversed chemotherapy-elicited exosome-induced drug resistance in a nude mouse tumor xenograft model. Conclusion This study revealed a novel mechanism of acquired chemoresistance whereby chemotherapy activates the EZH2/STAT3 axis in BC cells, which then secrete chemotherapy-elicited exosomes enriched in miR-378a-3p and miR-378d. These exosomes are absorbed by chemotherapy-surviving BC cells, leading to activation of the WNT and NOTCH stem cell pathways via the targeting of DKK3 and NUMB and subsequently resulting in drug resistance. Therefore, blocking this adaptive mechanism during chemotherapy may reduce the development of chemotherapy resistance and maximize the therapeutic effect.

Despite being predicted to be a thermodynamically equilibrium structure, the absence of direct experimental evidence of hexagonally close-packed spherical phase in single-component block copolymers raises uncomfortable concerns regarding the existing fundamental phase principles. This work presents a robust approach to regulate the phase behavior of linear block copolymers by deliberately breaking molecular symmetry, and the hexagonally close-packed lattice is captured in a rigorous single-component system. A collection of discrete A 1 BA 2 triblock copolymers is designed and prepared through an iterative growth method. The precise chemical composition and uniform chain length eliminates inherent size distribution and other molecular defects. Simply by tuning the relative chain length of two end A blocks, a rich array of ordered nanostructures, including Frank−Kasper A15 and σ phases, are fabricated without changing the overall chemistry or composition. More interestingly, hexagonally close-packed spherical phase becomes thermodynamically stable and experimentally accessible attributed to the synergistic contribution of the two end blocks. The shorter A blocks are pulled out from the core domain into the matrix to release packing frustration, while the longer ones stabilize the ordered spherical phase against composition fluctuation that tends to disrupt the lattice. This study adds a missing puzzle piece to the block copolymer phase diagram and provides a robust approach for rational structural engineering. Although hexagonally close packed structures are predicted, obtaining direct experimental evidence has been a challenge. Here, the authors report direct evidence for this phaseby regulation of phase behaviour by deliberate breaking of molecular symmetry.

A total of 96 isolates were obtained from 375 segments, isolated from the healthy roots, stems, leaves, hypocotyls and flowers of Bruguiera sexangula (Lour.) Poir. collected at the Dong Zhai Gang Mangrove Garden on Hainan Island, and 20 independent representative isolates were identified using a combination of morphological and molecular approaches. The most frequent endophytic fungal species isolated were Diaporthe phaseolorum (relative frequency = 31.2%). The Shannon–Wiener diversity and Simpson’s diversity index both showed that stems possessed the highest diversity compared to the other tissues estimated. Ethyl acetate extracts and the isolated metabolites were tested for antimicrobial activity using the serial dilution technique and for antioxidant activity using 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) radical-scavenging capacity assays, respectively. The fungal isolate HL18 (Gelasinospora endodonta) cultured on Czapek’s agar (CA) displayed a broad spectrum of antimicrobial activities and was significantly active against Escherichia coli (MIC = 0.0625 mg ml−1). Antioxidant assays showed that most of the fungal isolates (60.0%) exhibited some degree of antioxidant capacity (%RSA > 50%). The stain HL14 (Pestalotiopsis mangiferae) grown on potato dextrose agar (PDA) exhibited the highest DPPH and ABTS radical-scavenging capability with IC50 values of 0.717 ± 0.012 mg ml−1 and 0.787 ± 0.027 mg ml−1, respectively. Furthermore, five known secondary metabolites 1–5 were isolated and identified from HL-14. Compounds 1 and 5 exhibited weak antioxidant activity.

To present a rare case of cryptococcal pericarditis with unexplained multiple lymphadenopathies in an immunocompetent patient. Fungal pericarditis is an uncommon infection that may result from hematogenous dissemination, direct extension, or iatrogenic inoculation. Cryptococcal pericarditis typically occurs in immunocompromised hosts and is exceedingly rare in immunocompetent individuals. We describe a case of cryptococcal pericarditis with multiple lymphadenopathies in an immunocompetent patient. A 40-year-old male with no underlying disease or history of high-risk behaviors presented with chronic cough and sputum production. Imaging revealed bilateral pulmonary lesions, widespread lymphadenopathy, and pericardial effusion. Serum and pericardial fluid cryptococcal antigen tests were positive. HIV testing (fourth-generation antigen/antibody ELISA) was negative, and immunologic evaluation was unremarkable. Pericardiocentesis drained 585 mL of effusion. The patient was treated with intravenous antifungal therapy with fluconazole (0.4 g daily) for 1 week, followed by oral fluconazole for 4 months. Follow-up echocardiography performed 2 weeks after discharge revealed no significant pericardial effusion, whereas a subsequent at 4 months after discharge demonstrated a small residual effusion. The patient's cough and sputum production had also improved. Throughout the hospitalization and post-discharge period, the patient was able to maintain normal physical activity without functional limitations. This report presents a rare case of cryptococcal pericarditis with unexplained multiple lymphadenopathies in an immunocompetent patient, highlighting that fungal infection should be considered even in immunocompetent hosts with pericarditis.

Demethylincisterol A3 (Sdy-1), a highly degraded sterol that we previously isolated from Chinese mangrove Rhizophora mucronata endophytic Pestalotiopsis sp. HQD-6, exhibits potent antitumor activity towards a variety of cancer cells. In this study, we further verified that Sdy-1 effectively inhibited the proliferation and migration of human liver (HepG2) and cervical cancer (HeLa) cells in vitro and it can induce cell apoptosis and arrest the cell cycle in the G1-phase. Mechanistically, we demonstrated that Sdy-1 executes its function via inhibition of the Wnt/β-catenin signaling pathway. Sdy-1 may not inhibit the Wnt signaling pathway through the cascade reaction from upstream to downstream, but directly acts on β-catenin to reduce its transcription level, thereby reducing the level of β-catenin protein and further reducing the expression of downstream related proteins. The possible interaction between Sdy-1 and β-catenin protein was further confirmed by molecular docking studies. In the nude mouse xenograft model, Sdy-1 can also significantly inhibit tumor growth. These results indicated that Sdy-1 is an efficient inhibitor of the Wnt signaling pathway and is a promising antitumor candidate for therapeutic applications.

Overwhelming evidence points to an aberrant Wnt/β-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone isolated from the endophytic fungus Phomopsis asparagi DHS-48 obtained from mangrove plant Rhizophora mangle via chemical epigenetic manipulation of the culture, has demonstrated effective anti-tumor properties, with an obscure action mechanism. The objective of the current study was to explore the efficacy of DD-9 on HepG2 and HeLa cancer cells and its functional mechanism amid the Wnt/β catenin signaling cascade. Isolation of DD-9 was carried out using various column chromatographic methods, and its structure was elucidated with 1D NMR. The cytotoxicity of DD-9 on HepG2 and HeLa cells was observed with respect to the proliferation, clonality, migration, invasion, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade. We found that DD-9 treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in HepG2 and HeLa cells. The subsequent experiments in vitro implied that DD-63 could significantly suppress the tumor clonality, metastases, and induced apoptosis, and that it arrested the cell cycle at the G0/G1 phase of HepG2 and HeLa cells. Dual luciferase assay, Western blot, and immunofluorescence assay showed that DD-9 could dose-dependently attenuate the Wnt/β-catenin signaling by inhibiting β-catenin transcriptional activity and abrogating β-catenin translocated to the nucleus; down-regulating the transcription level of β-catenin-stimulated Wnt target gene and the expression of related proteins including p-GSK3-β, β-catenin, LEF1, Axin1, c-Myc, and CyclinD1; and up-regulating GSK3-β expression, which indicates that DD-9 stabilized the β-catenin degradation complex, thereby inducing β-catenin degradation and inactivation of the Wnt/β-catenin pathway. The possible interaction between DD-9 and β-catenin and GSK3-β protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-β-mediated crosstalk with the Wnt/β-catenin signaling axis, providing insights into the mechanism for the potency of DD-9 on hepatocellular and cervical cancer.

Limited data are available on applying circulating tumor DNA (ctDNA) in metastatic triple-negative breast cancer (mTNBC) patients. Here, we investigated the value of ctDNA for predicting the prognosis and monitoring the treatment response in mTNBC patients. We prospectively enrolled 70 Chinese patients with mTNBC who had progressed after [less than or equal to]2 lines of chemotherapy and collected blood samples to extract ctDNA for 457-gene targeted panel sequencing. ctDNA profiling provides insight into the mutational landscape of mTNBC and may reliably predict the prognosis and treatment response of mTNBC patients.

Background Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. Methods A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. Results The C-index of nomogram1was 0.708 (95%CI: 0.673–0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606–0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690–0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691–0.813; AUC: 0.784, 95%CI: 0.709–0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. Conclusions Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.

Three new cytochalasins, phomoparagins A-C (1–3), along with five known analogs (4–8), were isolated from Phomopsis asparagi DHS-48, a mangrove-derived endophytic fungus. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD techniques. Notably, 1 possessed an unprecedented 5/6/5/8/5-fused pentacyclic skeleton. These compounds were tested for their inhibitory activity against concanavalin A (ConA)/lipopolysaccharide (LPS)-induced spleen lymphocyte proliferation and calcineurin (CN) enzyme. Several metabolites (2 and 4–6) exhibited fascinating inhibitory activities with a relatively low toxicity. Furthermore, 2 was demonstrated to inhibit ConA-stimulated activation of NFAT1 dephosphorylation and block NFAT1 translocation in vitro, subsequently inhibiting the transcription of interleukin-2 (IL-2). Our results provide evidence that 2 may, at least partially, suppress the activation of spleen lymphocytes via the CN/NFAT signaling pathway, highlighting that it could serve as an effective immunosuppressant that is noncytotoxic and natural.