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Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1β, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.

An optical type touch‐input flat panel is designed. The driving system is based on the passive pixel sensor (PPS) array with amorphous silicon (a‐Si) TFT technology. The embedded sensing structure of the optical sensor is using the a‐Si TFT phototransistor and four‐mask process architecture technology. This paper presents a primary optical pixel sensor circuit that utilizes hydrogenated amorphous silicon photo‐transistor sensor. The a‐Si TFT phototransistor sensor is high reliability by using Multi‐N+ layer in the a‐Si TFT structure.

The silk fibroin (SF)/ionic liquid (IL) based hydrogel is a kind of remarkable substrate for flexible devices because of its subzero-temperature elasticity, electrical conductivity, and water retention, although the procedure of the gelation is considered complex and time-consuming. In this work, we introduced an approximate method for the development of novel photo-cross-linked SF/IL hydrogel, that is, SF-IMA/PIL hydrogel via the modification of silk fibroin chain with 2-isocyanatoethyl methacrylate (SF-IMA) in a certain ionic liquid with an unsaturated double bond. The chemical cross-linking between methacrylated SF and IL was triggered by UV light, while the physical cross-linking of the hydrogel was attributed to the β-sheet formation of SF in SF-IMA/IL mixed solution. In addition to being a UV-induced three-dimensional (3D) printable one, the SF-IMA/PIL hydrogel performed significant ionic conductivity between room temperature and −50 °C and water retention within a wide range of relative humidity, which were the featured advantages as the ionic liquid involved. Moreover, the static and dynamic mechanical tests demonstrated that the hydrogel reserved its great elasticity at −50 °C and displayed its stiffness transition temperatures between −100 and −70 °C.

Because of the uncertainties of the input parameters in dynamic milling model, robust stability prediction is a technology to effectively avoid the occurrence of regenerative chatter. However, the existing robust stability prediction methods generally consider the potential interval of each input parameter as their uncertainty measurements directly, without taking into account the correlations between input parameters. In this regard, a novel robust stability prediction method considering the correlations between input parameters is proposed in this paper. To consider the correlations between input parameters, high-dimensional random variables composed of input parameters are constructed, and their probability density functions are estimated according to the observation data. Based on the obtained probability density functions, the confidence regions of these random variables are determined and used to describe the uncertainty boundaries of input parameters. The problem of judging the robust stability of milling at a given speed and axial depth is transformed into an optimization problem, and the confidence regions are used to construct the constraints for the optimization variable. The experimental results have shown that the robust stability boundary generated by the proposed method can effectively avoid the occurrence of regenerative chatter and ensure the stability of milling operation.

The polycrystalline diamond (PCD) tool will produce severe wear when cutting the bearing ring which is a ferrous metal material. In order to reduce the wear of the PCD tool and achieve higher quality bearing ring machining, the cutting parameters of turning bearing ring with low-temperature liquid carbon dioxide (CO2) assisted PCD tool was studied. In this paper, experiments were carried out based on the completed cryogenic cooling system. The experimental results show that the reference cutting temperature increases with the increase of feed rate and cutting speed. The optimal parameters extend the tool life by 2.5 times and make the cutting temperature more stable. The change in cutting speed has a more noticeable impact on the reference cutting temperature than the feed rate. The surface roughness of the workpiece increases with the increase in feed rate and cutting speed. The optimal parameters of feed rate and cutting speed reduce the surface roughness of the workpiece by 81.5 % and 45.8 %, respectively. The primary wear forms of the PCD tool are graphitization, diffusion wear, adhesion wear and tool edge breaking. The tool wear increases with the increase of feed rate and cutting speed. The optimal parameters of feed rate and cutting speed reduce flank wear of the PCD tool by 42.7 % and 47.8 %, respectively. Moreover, the technological parameters of feed rate and cutting speed are presented for reference in actual machining.

The change in ocean net surface heat flux plays an important role in the climate system. It is closely related to the ocean heat content change and ocean heat transport, particularly over the North Atlantic, where the ocean loses heat to the atmosphere, affecting the AMOC (Atlantic Meridional Overturning Circulation) variability and hence the global climate. However, the difference between simulated surface heat fluxes is still large due to poorly represented dynamical processes involving multiscale interactions in model simulations. In order to explain the discrepancy of the surface heat flux over the North Atlantic, datasets from nineteen AMIP6 and eight highresSST-present climate model simulations are analyzed and compared with the DEEPC (Diagnosing Earth’s Energy Pathways in the Climate system) product. As an indirect check of the ocean surface heat flux, the oceanic heat transport inferred from the combination of the ocean surface heat flux, sea ice, and ocean heat content tendency is compared with the RAPID (Rapid Climate Change-Meridional Overturning Circulation and Heat flux array) observations at 26°N in the Atlantic. The AMIP6 simulations show lower inferred heat transport due to less heat loss to the atmosphere. The heat loss from the AMIP6 ensemble mean north of 26°N in the Atlantic is about 10 W m−2less than DEEPC, and the heat transport is about 0.30 PW (1 PW = 1015W) lower than RAPID and DEEPC. The model horizontal resolution effect on the discrepancy is also investigated. Results show that by increasing the resolution, both surface heat flux north of 26°N and heat transport at 26°N in the Atlantic can be improved.

ALK-rearranged renal cell carcinoma (ALK-RCC) is rare, molecularly defined RCC subtype in the recently published fifth edition of World Health Organization classification of tumors. In this study, we described 9 ALK-RCCs from a clinicopathologic, immunohistochemical, and molecular genetic aspect, supporting and extending upon the observations by previous studies regarding this rare subgroup of RCC. There were 6 male and 3 female patients with ages ranging from 14 to 59 years (mean, 34.4 years). None of the patients had sickle cell trait. The diagnosis was based on radical or partial nephrectomy specimen for 8 patients and on biopsy specimen for 1. Tumor size ranged from 2.5 to 7.2 cm (mean, 2.8 cm). Follow-up was available for 6 of 9 patients (6-36 months); 5 had no tumor recurrence or metastasis and 1 developed lung metastasis at 24 months. The patient was subsequently treated with resection of the metastatic tumor followed by crizotinib-targeted therapy, and he was alive without tumor 12 months later. Histologically, the tumors showed a mixed growth of multiple patterns, including papillary, solid, tubular, tubulocystic, cribriform, and corded, often set in a mucinous background. The neoplastic cells had predominantly eosinophilic cytoplasm. Focally, clear cytoplasm with polarized nuclei and subnuclear vacuoles (n = 1), and pale foamy cytoplasm (n = 1) were observed on the tumor cells. The biopsied tumor showed solid growth of elongated tubules merging with bland spindle cells. Other common and uncommon features included psammomatous microcalcifications (n = 5), rhabdoid cells (n = 4), prominent intracytoplasmic vacuoles (n = 4), prominent chronic inflammatory infiltrate (n = 3), signet ring cell morphology (n = 2), and pleomorphic cells (n = 2). By immunohistochemistry, all 9 tumors were diffusely positive for ALK(5A4) and 4 of 8 tested cases showed reactivity for TFE3 protein. By fluorescence in situ hybridization analysis, ALKrearrangement was identified in all the 9 tumors; none of the tested tumors harbored TFE3rearrangement (0/4) or gains of chromosomes 7 and 17 (0/3). ALKfusion partners were identified by RNA-sequencing in all 8 cases analyzed, including EML4(n = 2), STRN(n = 1), TPM3(n = 1), KIF5B(n = 1), HOOK1(n = 1), SLIT1(n = 1), and TPM1(3′ UTR) (n = 1). Our study further expands the morphologic and molecular genetic spectrum of ALK-RCC.

Miniaturized components with High-Aspect-Ratio (HAR) have extensive applications in aerospace, biomedicine, and optical fields. However, the chip formation mechanism of HAR micro-structures is closely related to the machined surface quality and accuracy with insufficient attention at present. The minimum cutting thickness is changing in micro-milling, which leads to the transition from elastic deformation via elastic-plastic deformation to chip formation process. In this work, the chip formation mechanism of micro-structures with High-Aspect-Ratio is thoroughly studied considering the minimum cutting thickness, tool types and milling parameters from the theoretical and experimental perspective. Micro-milling experiments were carried out with single-edged PCD and two-fluted cemented carbide micro-milling cutters, and the chip characteristics and formation mechanism of HAR micro-grooves was further analyzed in detail. The quantitative evaluation of the top-burrs and comprehensive analysis of side-wall surface topography were conducted to investigate the influence of chip formation and chip removal on machined quality of HAR micro-grooves. The results suggest that the chip formation and characteristics of HAR micro-grooves has a significant relationship with the tool performance, milling parameters and side-wall limitation. The aspect-ratio has a negative impact on the effective chip removal which further promotes top-burr dimensions and reduces side-wall surface quality. Sharp micro-cutters with large chip space and exceptional wear-resistance are recommended for machining HAR micro-structures.

Diffuse midline glioma, H3 K27M-mutant (H3 K27M-mt DMG), is a rare and highly aggressive tumor that is more common in children than in adults. Few studies have compared the differences between pediatric and adult patients with this rare tumor. We here report our retrospective study of 94 adult and 70 pediatric cases of diffuse midline glioma. Surgical tumor samples were analyzed by routine histopathology and immunohistochemistry for H3 K27M, IDH1 R132H, ATRX, p53, OLIG2, glial fibrillary acidic protein, and Ki-67; Sanger sequencing for hot mutation spots in genes including H3F3A, HIST1H3B, IDH1, IDH2, TERT, and BRAF; and methylation-specific polymerase chain reaction for O6-methylguanine DNA methyltransferasepromoter methylation. The most frequent anatomic locations in adult and pediatric patients were the thalamus and brainstem, respectively. Molecular profiling revealed higher frequencies of ATRX loss and H3.3 mutation in adult than in pediatric H3 K27M-mt DMGs. TERTpromoter mutations and O6-methylguanine DNA methyltransferasepromoter methylation were not detected in pediatric patients but were present in a few adult patients. During the follow-up period, 93/122 patients (70.1%) died from the disease, with a median survival time of 10.5 months (range: 1 to 104 mo). Kaplan-Meier analyses demonstrated that the prognosis was better for adult patients than the pediatric cohort (P=0.0003). Multivariate analyses indicated that patient age, primary tumor size, status of ATRX expression, and Ki-67 index were independent prognosticators. The present study showed that there were differences between adult and pediatric H3 K27M-mt DMGs in terms of the anatomic location of tumor, molecular changes, and prognosis.

Laser ablation is demonstrated to be a competent approach to processing chemical vapor deposition (CVD) diamond which is admitted to own poor machinability and is accordingly arduous to machine using conventional techniques. Notwithstanding, initial laser absorption by defects typically precipitates undesirable ablation quality and an increment in internal defects. The strategy of metal-coating-assisted laser ablation, which applies a coating on the diamond prior to laser irradiation to curtail defects and advance the quality of the ablated surface, is proposed in this study. In addition, an absorptivity-based laser energy distribution model is established to evaluate surface roughness and ablation depth. It can be concluded that the metal coating prevents local graphitization during the early ablation stage. The laser ablation of Ti-coated diamond surfaces resulted in a maximum reduction in surface roughness of 42.6% and 53%, respectively, for 100 and 500 nm coating, in comparison to that with the uncoated surfaces. Besides, the ablation depth of the laser-ablated 500 nm coating surface abates and reaches 21% in comparison with the uncoated diamond, while the 100 nm coating has a negligible effect on the ablation depth. In summary, the application of thin coatings on diamond prior to laser ablation results in homogeneous graphitization and a better surface finish with a marginal reduction in ablation depth.

This study adopts an institutional approach in the case analysis of China's economic statecraft towards Brazil. In light of institutionalisation theory, it examines the institutional arrangements between Beijing and Brasilia for the purpose of facilitating bilateral economic cooperation and advancing strategic partnership. As a descriptive effort, it yields some preliminary findings: first, the institutionalisation of China's economic statecraft towards Brazil is incremental, driven largely by the desire for and belief in long-term planning; second, a set of norms, values, and principles is instituted alongside designated agencies, point persons, operational protocols, and exchange mechanisms, creating a form of institutional governance based on a multi-actor, multilevel, and network-based steering mode; third, governance remains so centralised that it falls short in empowering strategic participation; and, fourth and finally, Beijing's institution-building proves useful in the management of relations with Brazil, suggesting that economic statecraft may benefit from institutionalisation.

In a seminal 1994 book chapter, James E. Grunig and Todd Hunt proposed a four-stage model of public relations' evolution. They contended that these stages have developed - at least, [...]

This study surveyed 43 female practitioners in 4 varied Chinese cities. Respondents, mostly youthful, reported substantial career advancement. However, stereotyping by male colleagues apparently had hampered their progress. Guest relations took lots of respondents' time. Practitioners appeared to behave as technicians but think somewhat as managers when handling guest relations.

Graphic abstract:

A holographic three-dimensional (3D) display is a recognized and ideal 3D display technology. In the field of holographic research, cylindrical holography with the merit of 360° field of view (FOV) has recently become a hot issue, as it naturally solves the problem of limited FOV in planar holography. The recently proposed approximate phase compensation (APC) method successfully obtains larger FOV and fast generation of segment cylindrical hologram (SCH) in the visible light band. However, the FOV of SCH remains limited due to its intrinsic limitations, and, to our best knowledge, the issue has not been effectively addressed. In this paper, the restricted conditions are first analyzed for the generation of SCH by the APC method. Then, an FOV expansion method is proposed for realizing a large FOV holographic display by gapless splicing of multi-SCH. The proposed method can successfully obtain larger FOV cylindrical holograms and effectively eliminate the splicing gaps; its effectiveness is verified by the results of numerical simulation and optical experiments. Therefore, the proposed method can effectively solve the FOV limitation problem of the APC method for the generation of SCH in the visible band, realize a large FOV 3D display, and provide a useful reference for holographic 3D display.

SynopsisThe research problemThis paper examined whether firms’ decision to switch from the International Financial Reporting Standards (IFRS) to the new Generally Accepted Accounting Practice in the United Kingdom (New UK GAAP) affects their audit fees.MotivationThe New UK GAAP was introduced by the UK regulators to enhance the comparability of financial reports and to reduce the high financial reporting costs associated with IFRS. We aimed to provide evidence on whether the reduced frameworks of IFRS, like the New UK GAAP, are a more cost-effective option. Furthermore, only very few studies analyzed the impact of abandoning IFRS on audit fees, and these found inconsistent results using the public firm data. We aimed to extend the current literature by using the private firm data.The test hypothesesOur first set of hypotheses considered whether the switch from IFRS to the New UK GAAP is associated with audit fees. Our second hypothesis tested whether there is a difference in any such association between larger and smaller firms.Target populationWe focused on the UK private (i.e., nonlisted) firms that have previously voluntarily adopted the IFRS.Adopted methodologyWe used regression analyses, difference-in-differences (DID) analyses, various matching methods for robustness, and analyses of firms’ financial reports.AnalysesUsing the UK private (i.e., nonlisted) firm data for the period 2014–2019, we examined the impact of switching from IFRS to the New UK GAAP on audit fees. The data for regression and DID analyses were obtained from the FAME database. We also downloaded the financial reports of two firms from Companies House to analyze the differences in their reports before and after the switch to the New UK GAAP.FindingsWe found that firms’ decision to switch from IFRS to the New UK GAAP significantly reduced their audit fees, with larger firms experiencing an additional reduction in their audit fees following the switch. Through examining the real examples of firms’ financial reports, we found consistent evidence that firms turning away from IFRS did take advantage of the disclosure exemptions contained within the New UK GAAP, resulting in reduced disclosure, which may explain the reduced audit fees. Overall, our findings suggest that using full IFRS may still be burdensome for the sampled firms that previously voluntarily adopted the IFRS. The findings also imply that an accounting standard consistent with IFRS but requiring less disclosure, such as the New UK GAAP or the IFRS for Small and Medium-sized Entities, may be welcomed by practitioners and represents a useful alternative for standard setters.

AimsXp11 translocation renal cell carcinoma (RCC) is a distinctive subtype of RCC with TFE3(Transcription Factor Binding to IGHM Enhancer 3) gene rearrangement. The gross features in most Xp11 translocation RCCs closely resemble clear cell RCCs. In this study, we report six cases of Xp11 translocation RCCs with a unique multicystic architecture, reminiscent of multilocular cystic renal cell neoplasm of low malignant potential (MCRN-LMP).Methods and resultsMicroscopically, the renal mass was well circumscribed with multilocular cystic architecture. The cyst walls and septa were mostly lined by a single layer of cells with clear cytoplasm and low-grade nuclei, reminiscent of MCRN-LMP. Psammoma bodies were detected in four cases. One particular patient was misdiagnosed with benign cysts in local hospitals and led to second operation. Tumour cells were settled according to the track of the first surgical procedure. TFE3fluorescence in situ hybridization (FISH) assay confirmed the diagnosis of Xp11 translocation RCCs. FISH and RNA sequencing analyses confirmed MED15-TFE3gene fusion in all six cases. Respective patients were alive, without any recent evidence of disease recurrence and/or metastasis.ConclusionsHere, we introduce a relatively inertia-variant of Xp11 translocation RCC which mimics MCRN-LMP. The distinctive morphological condition is linked to MED15-TFE3gene fusion. In fact, renal neoplasms with morphological features of MCRN-LMP, especially those containing psammoma bodies, should be routinely evaluated for evidence of TFE3gene rearrangements.

A compound processing method of pulsed nanosecond laser, picosecond laser and precision grinding is proposed to fabricate large aspect ratio PCD micro-milling tools. The influence of picosecond laser parameters on the cutting edge is discussed. The optimal PCD tool with diameter of 0.5 mm, length-diameter ratio of 3 and a blunt radius of 3.5 μm is obtained. The cutting performance of the fabricated tool is investigated in the micro milling of oxygen-free copper.

Teratoma with malignant transformation is a rare type of malignant teratoma. In the present case, we describe a patient with salivary gland carcinoma (SGC) generating in mediastinal mature teratoma. Next-generation sequencing showed BRCA1 and KRAS somatic mutations, which might be associated with malignant transformation of the mediastinal mature teratomas. To our knowledge, the present case is the first report of coexistence of BRCA1 and KRAS mutations in mature cystic teratoma with malignant transformation to SGC. And the tumor showed a good response to chemotherapy with cisplatin and paclitaxel according to the transformed histology.

A schematic illustration of water-free alcohol lubrication.

Supplemental Digital Content is available in the text.Xp11 renal cell carcinoma (RCC) with different gene fusions may have different clinicopathologic features. We sought to identify variant fusions in TFEBtranslocation RCC. A total of 31 cases of TFEBRCCs were selected for the current study; MALAT1-TFEBfusion was identified in 25 cases (81%, 25/31) using fusion probes. The remaining 6 cases (19%, 6/31) were further analyzed by RNA sequencing and 5 of them were detected with TFEB-associated gene fusions, including 2 ACTB-TFEB, 1 EWSR1-TFEB, 1 CLTC-TFEB, and 1 potential PPP1R10-TFEB(a paracentric inversion of the TFEBgene, consistent with “negative” TFEBsplit FISH result, and advising a potential diagnostic pitfall in detecting TFEBgene rearrangement). Four of the 5 fusion transcripts were successfully validated by reverse transcription-polymerase chain reaction and Sanger sequencing. Morphologically, approximately one third (29%, 9/31) of TFEBRCCs showed typical biphasic morphology. The remaining two thirds of the cases (71%, 22/31) exhibited nonspecific morphology, with nested, sheet-like, or papillary architecture, resembling other types of renal neoplasms, such as clear cell RCC, Xp11 RCC, perivascular epithelioid cell tumor (PEComa), or papillary RCC. Although cases bearing a MALAT1-TFEBfusion demonstrated variable morphologies, all 9 cases featuring typical biphasic morphology were associated with MALAT1-TFEBgenotype. Accordingly, typical biphasic morphology suggests MALAT1-TFEBfusion, whereas atypical morphology did not suggest the specific type of fusion. Isolated or clustered eosinophilic cells were a common feature in TFEBRCCs, which may be a useful morphology diagnostic clue for TFEBRCCs. Clinicopathologic variables assessment showed that necrosis was the only morphologic feature that correlated with the aggressive behavior of TFEBRCC (P=0.004). In summary, our study expands the genomic spectrum and the clinicopathologic features of TFEBRCCs, and highlights the challenges of diagnosis and the importance of subtyping of this tumor by combining morphology and multiple molecular techniques.

The development of valuable theranostic agents for overcoming the blood–brain barrier (BBB) to achieve efficient imaging-guided glioma-targeting delivery of therapeutics remains a great challenge for personalized glioma therapy. We herein developed a novel functional star-shaped polyprodrug amphiphile (denoted as CPP-2) via a combination of successive reversible addition–fragmentation chain transfer (RAFT) polymerization and click functionalization. In a diluted solution, the star amphiphile existed as structurally stable unimolecular micelles, containing hydrophobic cores conjugated with reduction-responsive camptothecin prodrugs Camptothecin (CPT) prodrug monomer (CPTM) and a tertiary amine monomer (2-(diethylamine) ethyl methacrylate, DEA) and hydrophilic oligo-(ethylene glycol) monomethyl ether methacrylat (OEGMA) outer coronas covalently decorated with dual-targeting moieties Angiopep2 (ANG) and small magnetic resonance imaging (MRI) contrast agents DOTA-Gd. In vitro and in vivo data in this study demonstrated that the ANG-modified micelles were capable of efficiently penetrating the BBB and delivering loaded cargoes such as CPT and Gd3+contrast agents to glioma cells, leading to a considerably enhanced t1relaxivity as well as antiglioma efficacy. Simultaneously, the targeted antiglioma efficacy and noninvasive MR imaging for a visualized therapy were realized. These collective findings augured well for the star polyprodrug amphiphiles to be utilized as a novel theranostic platform for clinical application in glioma therapy.

In this study, the water-soluble products formed during the hydrothermal carbonization of glucose were analyzed by liquid chromatography (LC)–mass spectrometry (MS) and LC–MS2to determine the formulas and the possible structures of the main compounds. In addition to the well-known compounds of 3-deoxyglucosone, 5-hydroxymethylfurfural, and levulinic acid, the furanic compounds and the carbocyclic oxy-organics containing hydroxy group and carbonyl group with a molecular mass range between 170 and 260 Da were also identified. Both C–C coupling reaction and C–C cleavage reaction were proved to be involved during the formation of these carbocyclic oxy-organics, so they were proposed to be released via C–C cleavage of the primary polymers, which were formed by aldol condensation of the primary precursors formed during the degradation of glucose. The identification of these carbocyclic oxy-organics was indirect evidence that aldol condensation played a crucial role during the formation of hydrochar from carbonization of glucose.

Diamond is widely acknowledged as the hardest naturally occurring material. Nevertheless, when exposed to friction against ferrous metals, it is prone to graphitization or amorphization, which limits the utilization of its extremely high hardness and wear resistance. These issues have persisted for decades without an effective solution. Here, we report that a covalently bonded heterostructure with mixed-dimensional carbons as a high-performance solid lubricant could effectively reduce diamond surface friction and mechanochemical wear with excellent load capacity and durability. When subjected to dry friction and heavy loads (20–150 N), the heterostructure exhibited a notable improvement over pristine diamond with reduced friction coefficients and relative wear rates by 22–45 and 67–91%, respectively. Especially under a 20 N load, the relative wear rate was an order of magnitude lower than that of pristine diamond. Additionally, experiments and molecular dynamics simulations revealed that the heterostructure integrated the outstanding properties of diamond (three-dimensional (3D)), nanographite (3D), and graphene (two-dimensional (2D)), resulting in improved lubrication and antiwear performance that could not be achieved by the individual carbon materials. The findings in this work will be beneficial to overcome the ferrous metal forbidden zone of diamond and are expected to expand the applications of engineered diamond surfaces and graphite/graphene in tribology, mechanics, and electronic fields.

Processing microchannels inside laminated aluminum nitride high-temperature co-fired ceramics (AlN HTCC) packaging, a typical difficult-to-cut ceramic, can effectively solve the heat-dissipation problem of integrated chips used in smart skin. In order to improve the processing efficiency and quality of AlN, the machinability of AlN after laser chemical milling (LCM) was studied through the milling force, machined surface quality, surface defects, formation mechanism, and tool wear. This study established a milling force model that can predict the milling forces of AlN and analyses the reasons for the improvements in the milling force based on experimental data and predicted data. The results from the model and experiments demonstrated that the milling force of the laser chemical milling assisted micro milling (LCAMM) decreased by 85%–90% and 85%–95%, respectively, due to the amount of removal of a single edge was more uniform and the actual inclination angle increased during the cutting process in LCAMM. Moreover, the machined surface quality improved by 65%–76% after LCM because of less tool wear, fewer downward-propagating cracks generated during each feed, and the surface removal mode transformed from intergranular fracture to transgranular fracture, which effectively reducing tool wear and improving tool life. Finally, when feed per tooth and depth of cut were 0.4 μm/zand 5 μm, the optimal machined surface quality was obtained, with a roughness of 64.6 nm Therefore, milling after LCM can improve the machinability of AlN and providing a feasibility for the high-quality and efficient machining of microchannels.

Accurately monitoring tool wear during the cutting process is crucial for ensuring the precision manufacturing of components and enhancing machining efficiency. However, even under the same cutting conditions, there are differences in the feature distributions between offline data and online data, leading to poor monitoring effectiveness of traditional offline transfer learning algorithms. To effectively address this challenge, this paper proposes an innovative algorithm named MS-LARODTL (Multisource Lightweight Adaptive Replayed Online Deep Transfer Learning). In the MS-LARODTL algorithm, a lightweight convolution layer design is initially adopted, resulting in a reduction of 86.64 % in convolution time to enhance the algorithm's execution speed. Subsequently, online data features are replayed to adapt batch normalization layer parameters through a replay buffer, thereby improving the monitoring accuracy of the algorithm. Lastly, by replaying source data and online data features and leveraging Maximum Mean Discrepancy to align data features, the algorithm's monitoring accuracy is further enhanced. Experimental results distinctly demonstrate that the MS-LARODTL algorithm surpasses other multi-source transfer learning methods across all evaluation metrics on the self-constructed CNC milling dataset. These findings underscore the effectiveness and potential of the MS-LARODTL algorithm, emphasizing its importance in the design and application of tool wear monitoring algorithms.

It’s well known that N6-methyladenosine (m6A) modification is the most abundant modification in multiple RNA species. miRNAs play important roles in m6A modification and are closely related with occurrence and development of colorectal cancer (CRC). Thus, the aim of this study was to identify the prognostic value of m6A-related miRNAs and explore the correlation between the miRNAs and immune microenvironment in CRC. The differentially expressed m6A regulators and differentially expressed miRNAs between CRC tissues and adjacent normal tissues were identified based on TCGA dataset, and the m6A-related miRNAs were screened. The CRC patients from TCGA were randomized (1:1) into training set and validation set, and the risk score was established in the training set. Next, risk score was verified in the validation set and GSE92928 from GEO datasets. Besides, the relationship among tumor mutational burden, immune microenvironment and risk score were analyzed. What’s more, RT-qPCR were used to explore the expression levels of the miRNAs in risk score between SW480 and SW620. A total of 29 m6A-related miRNAs were screened out, and a 5-differentially expressed miRNAs risk score was established. Kaplan–Meier analysis and ROC curves revealed the risk score could predict the prognosis of CRC, accurately. Similarly, the patients in the high-risk group had shorter overall survival in GSE92928. The risk score was relevant with the tumor mutational burden and immune infiltration, and the expression of HAVCR2 was significant difference between 2 risk groups. The expression levels of miR-328-3p, miR-3934-5p, miR-664b-5p and miR-3677-3p were down-regulated in SW620 compared with SW480, only the expression level of miR-200c-5p was up-regulated in SW620. The findings provided the new insights into the correlation between miRNAs and m6A regulators. The m6A-related miRNAs could predict the prognosis of CRC and provide the valuable information of immunotherapy in CRC patients.

Fumarate hydratase (FH)–deficient renal cell carcinoma (RCC) is a rare and distinct subtype of renal cancer caused by FHgene mutations. FH negativity and s-2-succinocysteine (2SC) positivity on immunohistochemistry can be used to screen for FH-deficient RCC, but their sensitivity and specificity are not perfect. The expression of AKR1B10, an aldo-keto reductase that catalyzes cofactor-dependent oxidation-reduction reactions, in RCC is unclear. We compared AKR1B10, 2SC, and FH as diagnostic biomarkers for FH-deficient RCC. We included genetically confirmed FH-deficient RCCs (n = 58), genetically confirmed TFE3 translocation RCCs (TFE3-tRCC) (n = 83), clear cell RCCs (n = 188), chromophobe RCCs (n = 128), and papillary RCCs (pRCC) (n = 97). AKR1B10, 2SC, and FH were informative diagnostic markers. AKR1B10 had 100% sensitivity and 91.4% specificity for FH-deficient RCC. The nonspecificity of AKR1B10 was shown in 26.5% of TFE3-tRCCs and 21.6% of pRCCs. 2SC showed 100% sensitivity and 88.9% specificity. However, nonspecificity for 2SC was evident in multiple RCCs, including pRCC, TFE3-tRCC, clear cell RCCs, and chromophobe RCCs. FH was 100% specific but 84.5% sensitive. AKR1B10 served as a highly sensitive and specific diagnostic biomarker. Our findings suggest the value of combining AKR1B10 and 2SC to screen for FH-deficient RCC. AKR1B10+/2SC+/FH- cases can be diagnosed as FH-deficient RCC. Patients with AKR1B10+/2SC+/FH+ are highly suspicious of FH-deficient RCC and should be referred for FH genetic tests.

Hydrochars are solid byproducts formed during the liquid-phase biorefinery process and could be used to generate functional carbonaceous materials, but the detailed molecular structure and the formation mechanism are still unclear. Herein, the formation of hydrochars from liquid-phase carbonization of biomass-derived compounds including glucose, fructose, xylose, ribose, dihydroxyacetone (DHA), 5-hydroxymethylfurfural (HMF), furfural (FF), and pyruvaldehyde (PRV) in water and inert polar organic solvents ethyl acetate (EAC) and tetrahydrofuran (THF) was studied. The carbohydrates were found to generate hydrochars in both water and the organic solvents, while the HMF and FF could generate hydrochars only in water. The α-carbonyl aldehydes, including PRV, 3-deoxyglucosone, and 2,5-dioxo-6-hydroxyhexanal (DHH), formed during the decomposition of carbohydrates were proposed to be the key primary precursors for hydrochar formation. The molecular structures of the hydrochars were characterized by elemental analysis, Fourier transform infrared analysis, and solid-state 13C NMR analysis to confirm that the molecular formula of the hydrochars all could be approximately expressed as (C3H2O)n, and the molecular structures of the hydrochars all consisted of polyaromatic hydrocarbon, phenolic, furanic, and aliphatic framents and a small amount of carbonyl/carboxyl groups. The presence of the polyaromatic hydrocarbon and phenolic fragments in the hydrochars suggested that aldol condensation played a critical role for hydrochar formation. By regarding the aldol condensation of α-carbonyl aldehydes as the initial step for hydrochar formation, we deduced the polymerization routes of these α-carbonyl aldehydes and found that the α-carbonyl aldehydes all could undergo aldol condensation followed by acetal cyclization and etherification to form polymers (C3H2O)nrich in furanic framework or undergo aldol condensation followed by a 1,2-hydride shift, intramolecular aldol condensation, and dehydration to generate polymers (C3H2O)nrich in the phenolic framework. One molecular structure containing polyaromatic hydrocarbon, phenolic, furanic, and aliphatic fragments is proposed for the hydrochars.

Flexible perovskite solar cells (PSCs) have been quickly developed as the most promising candidates for low-cost photovoltaic technology. However, the bendable and foldable properties of PSCs induce the decrease of their efficiencies. In this paper, we report the design of a new kind of flexible PSCs with a sandwiched structure. The critical layer of the flexible device is designed at a neutral layer of the sandwiched structure, which is stress-free, no matter how the device bending is. During the bending test, sandwich-structured flexible PSCs showed extremely long bending lifetime, which is at least 5–8 times higher than that of generally reported devices. At the same time, the sandwiched structure works as the encapsulation effect. The flexible device with a sandwiched structure greatly improves the device’s long-term stability. Therefore, the designed sandwiched structure significantly promotes the bending ability and stability of flexible PSCs.

Unlike coherent imaging techniques, light field imaging uses incoherent (white light) illumination to generate a digital hologram of three-dimensional (3D) objects in real time. Multiple projections (or elemental images) of a 3D object are captured using a microlens array attached to a digital camera. Orthographic projection images (OPIs) can be synthesized from the recorded elemental images. The synthesized intensity-based OPIs are then multiplied by the corresponding phase functions and combined to form a digital hologram (also known as an integral hologram) of a 3D object under illumination. In this study, we analyze the performance of a synthesized integral hologram under low light imaging (photon-counting) conditions. The feasibility of this technique is verified experimentally by capturing the elemental images and subsequently generating orthographic projection images and by varying photon counts to reconstruct the digital holograms.

AimsHereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a newly recognised entity in the WHO 2016 classification defined as the germline mutation of FHgene. Fumaratehydratase-deficient renal cell carcinoma (FH-deficient RCC) is recommended for tumours with FH deficiency but lacking of genetic evidences of FHgermline mutation. In this study, we described the clinicopathological and molecular changes of 13 FH-deficient RCCs.Methods and resultsHistology features, clinicopathological data, radiology performance and outcomes were collected for each patient. Next-generation sequencing and DNA sequencing of FHgene were performed to examine FH mutations. The patient group included five females and eight males. Different morphological patterns of papillary, nested, adenoid, foam adenoid, cribriform, tubular, tubulocystic, cystic and loose oedema stroma were observed. Except typical big nuclei with or without eosinophilic nucleoli and perinucleolar halos, raisin-like, hobnail-like and even low-grade nuclei were also observed in these tumours. Eleven cases with high-grade nuclei showed disease progression or death, but no disease progression was detected in two cases with low-grade nuclei and eosinophilic cytoplasm. FH expression was absent in tumour cells except for case 11. Next-generation sequencing and DNA sequencing verified seven FH germline mutations and four somatic mutations out of 13 cases.ConclusionsFH-deficient RCC is a rare renal tumour and has a wide morphological spectrum. Most of the tumours had high-grade nuclei and were aggressive. However, we observed a morphological subtype of FH-deficient RCC with low-grade nuclei and eosinophilic cytoplasm, which might mainly occur in young women and show a relatively good prognosis.

The massive production and wide application of vanadium dioxide nanoparticles (VO2NPs) has raised safety concerns of VO2NPs exposure through various routes, especially viainhalation. To determine the pulmonary toxicity of VO2NPs in vitro, we report here on short-term (1 day) and long-term (20 days) comparative toxicity studies of VO2NPs (denoted as C-VO2, 20–30 nm) and VO2microparticles (denoted as M-VO2, ∼1 μm) on the lung cell line A549. Different toxic effects were observed under different durations of exposures to VO2particles. VO2particles induced cell growth inhibition and death in a dose- and size-dependent style after short-term exposure. The cell viability dropped when the concentration of C-VO2was 2.5 μg ml−1, C-VO2causing much more severe cell viability loss than M-VO2at the same concentration. For long-term exposure, the cell viability dropped to less than 50% after exposure to C-VO2at a dose of 0.2 μg ml−1, while cells exposed to M-VO2under the same conditions remained normal, confirming the higher toxicity of C-VO2than that of M-VO2. Moreover, the long-term exposure to C-VO2only inhibited the cell proliferation. We found that 0.05 μg ml−1was the highest non-toxic dose of C-VO2to A549 cells for long-term exposure. The dissolution of VO2contributed to the cytotoxicity of VO2. In addition, reactive oxygen species (ROS) generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation were observed in the cells after short-term exposure to VO2particles in the concentration range tested, indicating that the possible toxicological mechanism might be ROS generation and cell cycle arrest in the G0/G1 phase. ROS generation, mitochondrial damage, and inflammation in cells were also observed during the long-term exposure to C-VO2at concentrations of 0.1 μg ml−1and 0.2 μg ml−1, but the cells recovered after a subsequent 5 day recovery period. Our results show that there are significant differences between the short-term and long-term cytotoxicities of VO2.

On the morning of April 1, 2001, a U.S. EP-3 reconnaissance aircraft collided with a Chinese F-8 fighter plane off the coast of China's Hainan Island. This triggered a series [...]

Many critics view deontology(focusing largely on the merits of an action itself) and utilitarianism(evaluation of an action based on its projected consequences) as rival approaches to ethical decision making. This survey of public relations students at three universities in the United States and one each in Hong Kong and mainland China suggest that, as various theorists propose, many people adhere to both schools of thought, with utilitarianism being the dominant view overall. Furthermore, belief in both schools appears to correlate with high-minded ethical thinking as measured by assessments of several hypothetical ethical decisions. Implications for teaching are suggested.

In the conventional microlens-array-based light field imaging system, there is a trade-off between the angular and spatial resolutions. Light field reconstruction from images captured by focal plane sweeping, such as light field moment imaging (LFMI) and light field reconstruction with back projection (LFBP), can achieve high transverse resolution comparable to the modern camera sensor. However, the acquisition of a series of focal plane sweeping images along the optical axis is time consuming and requires fine alignment. Furthermore, different focal-plane-based light field reconstruction techniques require images with different characteristics. To solve these problems, we present an efficient approach for fast light field acquisition with precise focal plane sweeping capture by defocus modulation, rather than mechanical movement. Also, we verify the validity and the improvement of our system. With the controllable point spread function, we can capture images for light field reconstruction with both LFMI and LFBP. Otherwise, we quantitatively compare the two methods using images captured with the proposed systems.

Growth differentiation factor 15 (GDF15), a distant member of the transforming growth factor (TGF)-β family, is a secreted protein that circulates as a 25-kDa dimer. In humans, elevated GDF15 correlates with weight loss, and the administration of GDF15 to mice with obesity reduces body weight, at least in part, by decreasing food intake. The mechanisms through which GDF15 reduces body weight remain poorly understood, because the cognate receptor for GDF15 is unknown. Here we show that recombinant GDF15 induces weight loss in mice fed a high-fat diet and in nonhuman primates with spontaneous obesity. Furthermore, we find that GDF15 binds with high affinity to GDNF family receptor α–like (GFRAL), a distant relative of receptors for a distinct class of the TGF-β superfamily ligands. Gfral is expressed in neurons of the area postrema and nucleus of the solitary tract in mice and humans, and genetic deletion of the receptor abrogates the ability of GDF15 to decrease food intake and body weight in mice. In addition, diet-induced obesity and insulin resistance are exacerbated in GFRAL-deficient mice, suggesting a homeostatic role for this receptor in metabolism. Finally, we demonstrate that GDF15-induced cell signaling requires the interaction of GFRAL with the coreceptor RET. Our data identify GFRAL as a new regulator of body weight and as the bona fide receptor mediating the metabolic effects of GDF15, enabling a more comprehensive assessment of GDF15 as a potential pharmacotherapy for the treatment of obesity.

Light field reconstruction from images captured by focal plane sweeping can achieve high lateral resolution comparable to the modern camera sensor. This is impossible for the conventional micro-lenslet-based light field capture systems. However, the severe defocus noise and the low depth resolution limit its applications. In this paper, we analyze the defocus noise in the focal-plane-sweeping-based light field reconstruction technique, and propose a method to reduce the defocus noise. Both numerical and experimental results verify the proposed method.

Determining the axial position of the recorded object in digital holography is a crucial step for image reconstruction. When multiple discrete sections of a three-dimensional object are overlapping each other, this issue becomes more challenging. In this Letter, an autofocusing algorithm using the structure tensor and its eigenvalues is proposed. This method can extract the focal distance of each section for a multi-sectional object irrespective of whether the sections are overlapping or not. We validate the applicability of the proposed technique with synthesized and experimental data using two types of holographic systems.

Xp11 translocation renal cell carcinomas are characterized by several different translocations involving the TFE3gene. Tumors with different specific gene fusions may have different clinicopathological manifestations. Fewer than 10 renal cell carcinoma cases with NONO-TFE3have been described. Here we examined eight additional cases of this rare tumor using clinicopathological, immunohistochemical, and molecular analyses. The male-to-female ratio of our study cohort was 1:1, and the median age was 30 years. The most distinctive feature of the tumors was that they exhibited glandular/tubular or papillary architecture that was lined with small-to-medium cuboidal to high columnar cells with indistinct cell borders and an abundantly clear or flocculent eosinophilic cytoplasm. The nuclei were oriented toward the luminal surface and were round and uniform in shape, which resulted in the appearance of secretory endometrioid subnuclear vacuolization. The distinct glandular/tubular or papillary architecture was often accompanied by sheets of epithelial cells that presented a biphasic pattern. Immunohistochemically, all eight cases demonstrated moderate (2+) or strong (3+) positive staining for TFE3, CD10, RCC marker, and PAX-8. None of the tumors were immunoreactive for CK7, Cathepsin K, Melan-A, HMB45, Ksp-cadherin, Vimentin, CA9, 34βE12 or CD117. NONO-TFE3fusion transcripts were identified in six cases by RT-PCR. All eight cases showed equivocal split signals with a distance of nearly 2 signal diameters and sometimes had false-negative results. Furthermore, we developed a fluorescence in situhybridization (FISH) assay to serve as an adjunct diagnostic tool for the detection of the NONO-TFE3fusion gene and used this method to detect the fusion gene in all eight cases. Long-term follow-up (range, 10–102 months) was available for 7 patients. All 7 patients were alive with no evidence of recurrent disease or disease progression after their initial resection. This report adds to the known data regarding NONO-TFE3renal cell carcinoma.

Xp11 translocation renal cell carcinomas are characterized by several different translocations involving the TFE3 gene. Tumors with different specific gene fusions may have different clinicopathological manifestations. Fewer than 10 renal cell carcinoma cases with NONO-TFE3 have been described. Here we examined eight additional cases of this rare tumor using clinicopathological, immunohistochemical, and molecular analyses. The male-to-female ratio of our study cohort was 1:1, and the median age was 30 years. The most distinctive feature of the tumors was that they exhibited glandular/tubular or papillary architecture that was lined with small-to-medium cuboidal to high columnar cells with indistinct cell borders and an abundantly clear or flocculent eosinophilic cytoplasm. The nuclei were oriented toward the luminal surface and were round and uniform in shape, which resulted in the appearance of secretory endometrioid subnuclear vacuolization. The distinct glandular/tubular or papillary architecture was often accompanied by sheets of epithelial cells that presented a biphasic pattern. Immunohistochemically, all eight cases demonstrated moderate (2+) or strong (3+) positive staining for TFE3, CD10, RCC marker, and PAX-8. None of the tumors were immunoreactive for CK7, Cathepsin K, Melan-A, HMB45, Ksp-cadherin, Vimentin, CA9, 34βE12 or CD117. NONO-TFE3 fusion transcripts were identified in six cases by RT-PCR. All eight cases showed equivocal split signals with a distance of nearly 2 signal diameters and sometimes had false-negative results. Furthermore, we developed a fluorescence in situ hybridization (FISH) assay to serve as an adjunct diagnostic tool for the detection of the NONO-TFE3 fusion gene and used this method to detect the fusion gene in all eight cases. Long-term follow-up (range, 10–102 months) was available for 7 patients. All 7 patients were alive with no evidence of recurrent disease or disease progression after their initial resection. This report adds to the known data regarding NONO-TFE3 renal cell carcinoma.

Gamma-emitting radionuclide 99mTc is globally used for the diagnosis of various pathological conditions owing to its ideal single-photon emission computed tomography (SPECT) characteristics. However, the short half-life of 99mTc (T1/2= 6 h) makes it difficult to store or transport. Thus, the production of 99mTc is tied to its parent radionuclide 99Mo (T1/2= 66 h). The major production paths are based on accelerators and research reactors. The reactor process presents the potential for nuclear proliferation owing to its use of highly enriched uranium (HEU). Accelerator-based methods tend to use deuterium–tritium (D–T) neutron sources but are hindered by the high cost of tritium and its challenging operation. In this study, a new 99Mo production design was developed based on a deuterium–deuterium (D–D) gas dynamic trap fusion neutron source (GDT-FNS) and a subcritical blanket system (SBS) assembly with a low-enriched uranium (LEU) solution. GDT-FNS can provide a relatively high-neutron intensity, which is one of the advantages of 99Mo production. We provide a Monte Carlo-based neutronics analysis covering the calculation of the subcritical multiplication factor (ks) of the SBS, optimization design for the reflector, shielding layer, and 99Mo production capacity. Other calculations, including the neutron flux and nuclear heating distributions, are also provided for an overall evaluation of the production system. The results demonstrated that the SBS meets the nuclear critical safety design requirement (ks< 0.97) and maintained a high 99Mo production capacity. The proposed system can generate approximately 157 Ci 99Mo for a stable 24 h operation with a neutron intensity of 1 × 1014n/s, which can meet 50% of China’s demand in 2025.

Mutations of isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) genes have been identified as early molecular events in the development of astrocytomas and oligodendrogliomas. Data regarding the status and prevalence of IDH1/2mutations in Chinese patients are limited. Herein we report our data from West China Hospital, a major Chinese medical centre. IDH1(R132H) mutation was analysed by immunohistochemistry with the mutation-specific IDH1(R132H) antibody in 1011 patients, including 922 central nervous system (CNS) tumours and 89 non-neoplastic CNS lesions, and PCR-based direct sequencing of IDH1/2gene mutation in 570 of these samples. Correlation with clinicopathological features and immunohistochemical expression of p53, EGFR, PTEN and Ki-67 was examined. Our data showed that IDH1/2mutation was present in oligodendrogliomas, anaplastic oligodendrogliomas, diffuse or anaplastic astrocytomas, and glioblastomas, with decreasing frequency, but not in other types of CNS tumours or non-neoplastic lesions examined. IDH1(R132) mutation was most frequent in oligodendrogliomas (57/62, 91.9%), with IDH1(R132H) mutation as the most frequent mutation form. Only one case for each of the rare mutations (R132C, R132G, R132L, and R132S) was identified in the 570 samples analysed by sequencing. Younger age, low expression of p53 and low Ki-67 index were significantly correlated with IDH1mutation status (p=0.000). All tumours with IDH1(R132) mutations were supratentorial, with frontal lobe as the most frequent site for IDH-mutated gliomas. Only three IDH2(R172) mutation cases were detected in this series. Univariate survival analysis in 459 glioma patients with diffusely infiltrating gliomas showed that IDH1mutations as well as the more classical prognosticators (age, WHO grade, p53 and Ki-67 index) were of prognostic significance. Multivariate analysis by Cox proportional hazard regression model demonstrated that lack of IDH1mutation was an independent prognostic factor for both progression-free survival [relative risk (RR)=2.450, 95% confidence interval (CI)=1.351–4.444] and disease-specific survival (RR=2.489, 95%CI=1.155–5.363).

The cutting force is a critical parameter in machining. The measured data is impacted by noise created from machining environment and data acquisition equipment. It can decrease the fitting quality of the cutting forces at high frequencies which constitutes the main concern of this study. This paper presents an optimized fit of the cutting forces model in the frequency domain in milling. The optimization process is performed by means of the minimization of the error function defined by the difference between the measured and predicted Fast Fourier Transformations of the force. The number of harmonics affects the deviation of the fit, so this study evaluates the optimal number of harmonics for the determination of the force coefficients in the fitting model of 2-fluted mills. A comprehensive set of parameters are investigated to define optimal parameter selection. The results show the ability to fit cutting forces with reduced harmonics, leading to a lower deviation of the fit and a potential improvement in computation time. The shifted linear model presents a better fit, particularly at high material removal rates. The results at the small tool diameter have shown poor quality of the fit, especially at low material removal rates. The proposed optimization method has potential applications in the industry for fast force prediction, leading to improved machining performance.