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Dendritic cells (DCs) are critical mediators of antigen priming and T-cell activation. Zymogen granule protein 16 (ZG16) is demonstrated as an anti-oncogene in T-cell mediated antitumor immunity, but its effect on DCs is largely unknown. Herein, we wonder whether ZG16 affects the activation of DCs in pancreatic cancer. Firstly, the increased ZG16 expression was observed during the maturation of DCs derived from mouse bone marrow or human peripheral blood. Then, overexpression of ZG16 or exogenous introduction of recombinant ZG16 protein induced the expression of MHC II, CD86, CD84, and CCR7 on the surface of DCs, thereby facilitating the secretion of proinflammatory mediators IL-1β, IL-6, TNF-α, and IL-12/p70, supporting the promoting effect of ZG16 on DC maturation. By establishing the subcutaneous and orthotopic mouse models of pancreatic cancer, we confirmed that intraperitoneal injection of recombinant ZG16 protein (Re-mZG16) could induce tumor regression by stimulating DC maturation and enhancing antitumor responses of CD4 + , CD8 + , PD-1 + , and Ctla4+ cells. Besides, Re-mZG16 in combination with gemcitabine showed a synergistic effect in the treatment of pancreatic cancer. Mechanistically, we demonstrated that ZG16 inhibited the ubiquitination and degradation of CD40, which depended on the lectin domain of ZG16. In conclusion, this study provided a novel insight into the role of ZG16-CD40 axis in DC-based immunotherapy for pancreatic cancer.

The sustainable construction of spirocyclic compounds is important to the scientific community and the pharmaceutical industries. Herein, we demonstrate a carbamoyl radical-initiated intramolecular dearomative spirocyclization to access the spiro-cyclohexadiene oxindoles under visible light irradiation, which constitutes the first example of accessing the I-substituted derivatives that facilitate diversified transformations. Additionally, the scalability, late-stage modification of drugs, and significant antitumor activity of the products demonstrate the novel spirocyclic synthesis platform for expediting drug development.

Topological superconductors (TSCs) offer a promising avenue for delving into exotic states of matter and fundamental physics. We propose a strategy for realizing high transition temperatures (high-Tc) in TSCs by leveraging nontrivial topology alongside a high carrier density near the Fermi level in metal-doped borophenes. We identified 39 candidates with exceptional thermodynamic stability from thousands of Be-intercalated borophenes (Be1–xBx) via extensive structural searches. Seven candidates exhibit high carrier densities, with B7Be2B7emerging as a particularly promising candidate. This nanosheet displays both type-I and type-II Dirac fermions, indicative of Z2topological metals, thereby positioning it as an ideal platform for high-TcTSCs. The high-density π electrons of B7Be2B7originating from type-II Dirac fermions, coupled with the out-of-plane vibrations of B and Be atoms, significantly enhance the electron–phonon coupling (λ = 1.42), resulting in a substantially high-Tcof 31.5 K. These findings underscore the potential of metal-doped borophenes as a cutting-edge material platform for achieving high-TcTSCs.

This study focuses on analyzing common fault types in photovoltaic (PV) modules, employing fault diagnosis methods based on machine learning technology to enhance the accuracy and efficiency of diagnosing faults in solar power systems. Initially, we collected relevant data from the solar power system and used data analysis techniques to identify system faults, designing a human-machine monitoring interface for practical application. Furthermore, the experimental results proved that the system could accurately identify eight major types of faults, including solar panel output circuits, energy storage batteries, maximum power point tracking (MPPT) controllers, inverters, dust accumulation, loosening of mounting rack screws, damage to the mounting rack foundation, and deformation of the mounting rack structure. Particularly in the detection of dust accumulation, we developed a new method of estimating power generation from multiple regression analysis (MRA), which closely aligns the estimated power output with the actual power output, highlighting the significant impact of dust accumulation on the efficiency of solar power systems. Next, by integrating voltmeters and support vector machines (SVM) into the solar PV array modules, we are able to quickly and accurately measure and locate short-circuit and open-circuit faults in bypass diodes. Ultimately, the proposed PV fault diagnosis strategy includes diagnostics for dust accumulation and mounting frame faults, making it particularly suitable for areas with severe air pollution and frequent earthquakes, providing a comprehensive fault diagnosis solution.

Appropriate O insertion in Ni can optimize the adsorption of *H and *OH, thereby enhancing HER/HOR activity. An O-Ni/WO2electrocatalyst with abundant oxygen-inserted Ni was successfully synthesized herein, and achieved excellent electrocatalytic HER/HOR kinetics.

Transcription factors respond to multilevel stimuli and co-occupy promoter regions of target genes to activate RNA polymerase (RNAP) in a cooperative manner. To decipher the molecular mechanism, here we report two cryo-electron microscopy structures of Anabaenatranscription activation complexes (TACs): NtcA-TAC composed of RNAP holoenzyme, promoter and a global activator NtcA, and NtcA–NtcB-TAC comprising an extra context-specific regulator, NtcB. Structural analysis showed that NtcA binding makes the promoter DNA bend by ∼50°, which facilitates RNAP to contact NtcB at the distal upstream NtcB box. The sequential binding of NtcA and NtcB induces looping back of promoter DNA towards RNAP, enabling the assembly of a fully activated TAC bound with two activators. Together with biochemical assays, we propose a ‘DNA looping’ mechanism of cooperative transcription activation in bacteria.

In this paper, the authors investigate the optimal per-claim reinsurance problem under the continuous-time framework to minimize the insurer’s ruin probability based on the Lundberg exponent. Considering reinsurance participants’ diversified risk preferences, the authors assume that the reinsurance premium is calculated by a combined premium principle, including the expected value premium principle and upper moment premium principle. Then, the authors derive the insurer’s optimal reinsurance strategy satisfying the principle of indemnity and the incentive compatibility condition in an infinite reinsurance space based on the point-wise optimization approach. Besides, the proposed work emphasizes the optimality and admissibility of the combination of the excess of loss reinsurance and its dual form when a piecewise reinsurance premium principle is considered. As a special case, the optimal reinsurance strategy under the expected value premium principle reduces to the classic result. Furthermore, the numerical analyses are provided to illustrate the effects of the main parameters on the maximal Lundberg exponent and the optimal reinsurance strategy.

As a medical system with a long history, traditional Chinese medicine (TCM) owns extremely rich and valuable experience and knowledge. In this paper, the granulation-based attribute partial ordered structure diagram (APOSD) is proposed to achieve knowledge discovery for spleen Yang deficiency syndrome in TCM. APOSD is discussed with the perspective of granular computing. Each layer of APOSD is viewed as a level of granularity and the nodes in APOSD layers are viewed as information granules. Granulation based generation method of APOSD reduces the complexity of the algorithm and can extract more comprehensive information from multi-level and multi-scale. The proposed method is testified through analysis of prescriptions of spleen Yang deficiency syndrome screening from the comprehensive database of TCM. Symptom patterns, import herbs and their relationship are extracted from different layers and clusters in generated APOSD. Compared with commonly used Apriori association rule analysis algorithm, the method proposed in this paper can not only extract herbs with high confidence but also extract herbs with specific effect, and the association relationships can also be shown on the generated APOSD.

Intangible cultural heritage is an important part of Chinese excellent traditional culture, and college dance teaching is paid more attention by researchers of physical education and computer technology. In order to help the inheritance and development of non-legacy culture in college dance teaching, this paper analyzes the influencing factors of wireless communication network in college dance teaching, constructs an interactive platform for non-legacy digital dance teaching based on wireless communication network technology, and applies it in the dance teaching process of a university in Henan province to highlight the role of wireless communication technology in dance teaching. The results show that the interactive platform can effectively reduce teachers' physical energy consumption and has certain reliability and practicality. Through artificial intelligence algorithm, the traditional dance teaching method has been changed, and a new exploration of non-legacy dance teaching has been realized.

Nemaline myopathy (NM) is a genetically and clinically heterogeneous disease that is diagnosed on the basis of the presence of nemaline rods on skeletal muscle biopsy. Although NM has typically been classified by causative genes, disease severity or prognosis cannot be predicted. The common pathologic end point of nemaline rods (despite diverse genetic causes) and an unexplained range of muscle weakness suggest that shared secondary processes contribute to the pathogenesis of NM. We speculated that these processes could be identified through a proteome-wide interrogation using a mouse model of severe NM in combination with pathway validation and structural/functional analyses. A proteomic analysis was performed using skeletal muscle tissue from the Nebconditional knockout mouse model compared with its wild-type counterpart to identify pathophysiologically relevant biological processes that might impact disease severity or provide new treatment targets. A differential expression analysis and Ingenuity Pathway Core Analysis predicted perturbations in several cellular processes, including mitochondrial dysfunction and changes in energetic metabolism and stress-related pathways. Subsequent structural and functional studies demonstrated abnormal mitochondrial distribution, decreased mitochondrial respiratory function, an increase in mitochondrial transmembrane potential, and extremely low ATP content in Nebconditional knockout muscles relative to wild type. Overall, the findings of these studies support a role for severe mitochondrial dysfunction as a novel contributor to muscle weakness in NM.

ACTA1encodes skeletal muscle-specific α-actin, which polymerizes to form the thin filament of the sarcomere. Mutations in ACTA1are responsible for approximately 30% of nemaline myopathy (NM) cases. Previous studies of weakness in NM have focused on muscle structure and contractility, but genetic issues alone do not explain the phenotypic heterogeneity observed in patients with NM or NM mouse models. To identify additional biological processes related to NM phenotypic severity, proteomic analysis was performed using muscle protein isolates from wild-type mice in comparison to moderately affected knock-in (KI) Acta1H40Yand the minimally affected transgenic (Tg) ACTA1D286GNM mice. This analysis revealed abnormalities in mitochondrial function and stress-related pathways in both mouse models, supporting an in-depth assessment of mitochondrial biology. Interestingly, evaluating each model in comparison to its wild-type counterpart identified different degrees of mitochondrial abnormality that correlated well with the phenotypic severity of the mouse model. Muscle histology, mitochondrial respiration, electron transport chain function, and mitochondrial transmembrane potential were all normal or minimally affected in the TgACTA1D286Gmouse model. In contrast, the more severely affected KI.Acta1H40Ymice displayed significant abnormalities in relation to muscle histology, mitochondrial respirometry, ATP, ADP, and phosphate content, and mitochondrial transmembrane potential. These findings suggest that abnormal energy metabolism is related to symptomatic severity in NM and may constitute a contributor to phenotypic variability and a novel treatment target.

This letter proposes a junction temperature (Tj) extraction method for the high-voltage thyristors with the cathode short-circuiting structure. It has been studied that the gate voltage Vgk under nontrigger current is a practical temperature-sensitive electrical parameter (TSEP), which can be used for online Tj monitoring by calibrating the linear relationship between the gate voltage Vgk under nontrigger current and Tj effect. The proposed TSEP does not affect the operating state of the thyristor and is suitable for complex operating conditions since it is extracted during off state. The total error in the Tj estimate obtained from the proposed TSEP is verified within ±2 °C by comparing with the Tj obtained from the traditional gate voltage VGK based TSEP during on state.

The difficulty of short-process bonded Nd–Fe–B magnet waste recycling lies in the effective removal of the cured polymer matrix while protecting the magnetic powder. In this study, the polymer matrix in bonded Nd–Fe–B magnet waste was destroyed using sodium hydroxide ethanol solution, and the effect of the recycling process on the magnetic powders was studied. The nonmagnetic polymer matrix was removed, while the magnetic phase was not destroyed. The carbon and oxygen contents of the recycled magnetic powders decreased by 92.96 and 89.30%, respectively, while the MS(saturation magnetization), Mr(remanence), and Hcj(coercivity) values of the recycled magnetic powders were 99.8, 98.5, and 95.9% of the original magnetic powders, respectively. The curing and decomposition processes of the polymer matrix were also analyzed. During the curing process, dicyandiamide and bisphenol A epoxy resin acted as bridges and skeletons, respectively, finally forming a thermosetting three-dimensional network structure. In the alkaline alcohol solution, the bridges and skeletons were destroyed by the free hydroxyl groups and free hydrogen radicals in ethanol, and small molecular products were dissolved in the solution.

Grain size determination is essential in producing and testing iron and steel materials. Grain size determination of martensitic steels usually requires etching with picric acid to reveal the prior austenite grain boundaries. However, picric acid is toxic and explosive and belongs to hazardous chemicals, which makes it difficult for laboratories and testing institutions to obtain. A new experimental method was developed to use Nital etchant instead of picric acid. The deep learning method was used to recognize the prior austenite grain boundaries in the etched martensite microstructure, and the grain size could be determined according to the recognition result. Firstly, the polished martensite specimen was etched twice with Nital etchant and picric acid, respectively, and the same position was observed using an optical microscope. The images of the martensitic structure and its prior austenite grain boundary label were obtained, and a data set was constructed. Secondly, based on this data set, a convolutional neural network model with a semantic segmentation function was trained, and the accuracy rate of the test set was 87.53%. Finally, according to the recognition results of the model, the grain size rating can be automatically determined or provide a reference for experimenters, and the difference between the automatic determination results and the measured results is about 0.5 level.

ABSTRACTAlthough 30% of international students who study in Australia are from China, there is a well-documented intellectual silence of Chinese students, the in-class silence of Chinese students in coursework degrees in particular. In response to the national policy and to provide insights into the international research education of Australia, this article reports on a study that examines the intellectual silence of research students from China enrolled in Master’s or doctoral degrees in five Australian universities. This qualitative study analysed semi-structured interviews with Australian research supervisors and Chinese research students, as well as research theses produced by Chinese research students. The intellectual silence of Chinese research students is examined through the lens of Qi’s concept – networked-hutong siwei. The results show that to adopt the networked-hutong siwei could provide a new perspective to reconsider the intellectual silence of Chinese research students by enhancing international students’ epistemological awareness of the interconnectedness of different intellectual resources and thus seeking theoretical and conceptual alternatives.

A differential carrier lifetime (DLT) measurement method with a measurement current as low as 0.1 mA, high noise immunity, and low measurement error has been proposed for the first time for electroluminescent light-emitting diodes (LEDs), which can also obtain the junction capacitance and differential resistance of LEDs. The method is based on the rate equation and phase-sensitive detection technology. The relationship between the DLT of red, green, and blue mini-LEDs and the injected current density was investigated with the proposed method. The DLT of the same LED decreases as the injected current density increases. The DLT of green mini-LEDs drops faster than that of blue mini-LEDs as the injected current density increases.

Dicing is an important process in the making of semiconductor chips. In recent years, high performance dicing technologies are badly needed for the new-generation wafers such as silicon carbide (SiC) and sapphire as those hard-to-machine brittle materials have posed great challenges for dicing. In this work, a novel bond metal, i.e., Ti-15/75Al binary alloy, was used to fabricate ultrathin diamond blades. The performance of the developed blades was assessed in the dicing of single crystal SiC. The blade using Ti-rich Ti15Al alloy (T-type) as bonding agent was found to produce lower dicing force, smaller chipping size, and higher removal ratio, in comparison to the blades using Al-rich Ti75Al (A-type) and conventional Cu-rich Cu20Sn alloys (C-type) as bond metals. The ground surface produced using the T-type blade was found to be smoother than those generated using the A- and C-type blades. The superior performance of the Ti-rich Ti15Al blade was attributed to the strong interfacial adhesion of diamond grits with the bond alloy. Such adhesion was established through forming titanium carbides at the interface, which helped retention of diamond grits during dicing. The strong adhesion also enabled the blade to possess a relatively high hardness and a sufficiently large porosity in bond matrix, both favored the material removal in the dicing of SiC.

Hidden natural products are representative of defensive strategies produced in vivoin diseased plants, a process that is induced by the plant immune system. The first transcriptome library of uninfected and pathogen infected Hibiscus tiliaceusstems was constructed by transcriptome sequencing technology, genes related to cadinene-type sesquiterpenoid biosynthesis were screened and combined with ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF-MS) analysis data, which indicated pathological tissue had potential to produce novel carbon skeletons of cadinane sesquiterpenoid dimers. Successfully, two cadinane-derived sesquiterpenoid dimers with unprecedented carbon skeletons, hibisceusanols A (1) and B (2) were isolated for the first time from the stems of H. tiliaceusinduced by plant-microbial interactions. Their structures and absolute configurations were unambiguously established by spectroscopy, advanced chemistry development (ACD) and electronic circular dichroism (ECD) methods. Compounds 1and 2exhibited significant antitumor activity in vitrowith half maximal inhibitory concentration (IC50) values of 2.3–7.2 µmol/L. The anticancer effect was generated viathe induction of HepG2 cell apoptosis by inhibiting the phosphatidylinositol 3-kinase (PI3K) pathway.

ABSTRACTLiver hepatocellular carcinoma (LIHC) is the most common type, comprising 75–85% of all liver malignancies. We investigated the roles of cleavage stimulation factor 2 (CSTF2) in LIHC and explored the underlying mechanisms. CSTF2 expression and its association with LIHC patient survival probability were analyzed with The Cancer Genome Atlas. CSTF2 expression in LIHC cells was assessed using western blot and quantitative real-time PCR. Alterations in CSTF2 expression were induced by cell transfection. Cell colony formation, apoptosis, proliferation, invasion, and migration were assessed using colony formation, flow cytometry, 5-ethynyl-2ʹ-deoxyuridine, and transwell assays. Pathway enrichment analysis was performed using gene set enrichment analysis (GSEA). The expression of apoptosis-, metastasis-, and pathway-associated factors was determined via western blot. The pathway rescue assay was further performed using 740Y-P or Wortmannin. CSTF2 upregulation was observed in LIHC tissues and cells. Patients with high CSTF2 expression had a lower probability of overall survival. CSTF2 overexpression enhanced colony formation, proliferation, invasion and migration, while repressing apoptosis in LIHC cells. GSEA revealed that CSTF2 was mainly enriched in the phosphatidylinositol 3′-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Western blot analysis proved that CSTF2 overexpression activated this pathway. CSTF2 knockdown yielded the opposite effects. 740Y-P, a PI3K activator, reversed the CSTF2 knockdown-triggered effects on cell proliferation, apoptosis, invasion, and migration. Moreover, Wortmannin, a PI3K inhibitor, also reversed the CSTF2 overexpression-induced effects on cell proliferation, apoptosis, invasion, and migration. These results indicated that CSTF2 overexpression might exacerbate the malignant phenotypes of LIHC cells via activation of PI3K/AKT/mTOR pathway.

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy characterized by profound skeletal muscle weakness, respiratory distress, and motor dysfunction. However, pathology is not limited to muscle and can be associated with life-threatening hepatic peliosis. Hepatobiliary disease has been reported in up to 17% of XLMTM patients but has not been extensively characterized. We report on five XLMTM patients who experienced intrahepatic cholestasis in their disease natural history, illustrating the need to further investigate these manifestations. These patients shared presentations that included pruritus, hypertransaminemia, and hyperbilirubinemia with normal gamma-glutamyl transferase, following infection or vaccination. Three patients who had genetic testing showed no evidence of genetic mutations associated with familial cholestasis. In one patient, progression to cirrhotic, decompensated liver disease occurred. Further investigations into the molecular pathomechanism underpinning these clinical observations in XLMTM patients will be important for informing patient care.

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy characterized by profound skeletal muscle weakness, respiratory distress, and motor dysfunction. However, pathology is not limited to muscle and can be associated with life-threatening hepatic peliosis. Hepatobiliary disease has been reported in up to 17% of XLMTM patients but has not been extensively characterized. We report on five XLMTM patients who experienced intrahepatic cholestasis in their disease natural history, illustrating the need to further investigate these manifestations. These patients shared presentations that included pruritus, hypertransaminemia, and hyperbilirubinemia with normal gamma-glutamyl transferase, following infection or vaccination. Three patients who had genetic testing showed no evidence of genetic mutations associated with familial cholestasis. In one patient, progression to cirrhotic, decompensated liver disease occurred. Further investigations into the molecular pathomechanism underpinning these clinical observations in XLMTM patients will be important for informing patient care.

Nine new dolabrane-type diterpenoids, notoscarins A–I (1–9), including an unprecedented 6,18-cyclo-dolabrane-type diterpenoid (1) obtained through intramolecular cyclization, two rare 19-nor-2-chloro-dolabrane diterpenoids (2and 3), six new related dolabrane-type diterpenoids (4–9), and one new butyrolactone derivative (10), were isolated from the Chinese liverwort Notoscyphus lutescens. The 6,18-cyclo-dolabrane and 19-nor-dolabrane carbon skeletons are reported for the first time. The structures of these compounds were determined on the basis of MS and NMR spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Preliminary bioassays showed that compounds 1–10exhibited moderate to weak quinone reductase-inducing activity in Hepa-1c1c7 cells.

Phenalenyls (PLYs) are important synthons in many functional and electronic materials, which often display favorable molecule-to-molecule overlap for electron or hole transport. They also serve as a prototype for π-stacking pancake bonding based on two-electron multicenter bonding (2e/mc). Unexpected near-doubling of the binding energy is obtained for the positively charged PLY2+dimer with an effect similar to that seen for the positively charged olympicenyl (OPY) radical dimer. This charge effect is reversed for the perfluorinated (PF) dimers, and the negatively charged perfluorinated (PF) dimers PF–PLY2–and PF-OPY2–become strongly bound. Long-range interactions reflect these differences. Also surprising is that in this case the pancake bonding corresponds to single-electron (1e/mc) or a three-electron (3e/mc) multicenter bonding in contrast to the 2e/mc bonding that occurs for the neutral radical dimers. The strong preference for a large intermolecular overlap is maintained in these charged dimers. Importantly, the preference for π-bonding in the charged dimers compared to σ-bonding is strongly enhanced relative to the neutral PLY dimers.

Purpose: Primary aldosteronism (PA) remains, to a large extent, an under-diagnosed disease. We aimed to develop and validate a novel clinical nomogram to predict PA based on routine biochemical variables including new ones, calcium-phosphorus product. Methods: Records from 806 patients with hypertension were randomly divided into 70% (n= 564) as the training set and the remaining 30% (n= 242) as the validation set. Predictors for PA were extracted to construct a nomogram model based on regression analysis of the training set. An internal validation was performed to assess the nomogram model’s discrimination and consistency using the area under the curve for receiver operating characteristic curves and calibration plots. The diagnostic accuracy was compared between nomogram and other known prediction models, using receiver operating characteristics (ROC) and decision curve analyses (DCA). Results: Female gender, serum potassium, serum calcium-phosphorus product, and urine pH were adopted as predictors in the nomogram. The nomogram resulted in an area under the curve of 0.73 (95% confidence interval: 0.68–0.78) in the training set and an area under the curve of 0.68 (0.59–0.75) in the validation set. Predicted probability and actual probability matched well in the nomogram (p> 0.05). Based on ROC and DCA, 21–70% threshold to predict PA in the nomogram model was clinically useful. Conclusions: We have developed a novel nomogram to predict PA in hypertensive individuals based on routine biochemical variables. External validation is needed to further demonstrate its predictive ability in primary care settings.

Hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR) have aroused great interest, but the high price of platinum group metals (PGMs) limits their development. The electronic reconstruction at the interface of a heterostructure is a promising strategy to enhance their catalytic performance. Here, MoO2/Ni heterostructure was synthesized to provide effective HER in an alkaline electrolyte and exhibit excellent HOR performance. Theoretical and experimental analyses prove that the electron density around the Ni atom is reduced. The electron density modulation optimizes the hydrogen adsorption and hydroxide adsorption free energy, which can effectively improve the activity of both HER and HOR. Accordingly, the prepared MoO2/Ni@NF catalyst reveals robust HER activity (η10= 50.48 mV) and HOR activity (j0= ∼1.21 mA cm–2). This work demonstrates an effective method to design heterostructure interfaces and tailor the surface electronic structure to improve HER/HOR performance.