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Abstract Background Mesenchymal stem cells (MSCs) have been proposed to treat osteoarthritis (OA) for many years. However, clinical outcomes have been inconsistent due to biological variation between patients, differences in tissue source and preparation of the MSCs, and type of donor (e.g. allogenic versus autologous). Here, we test the hypothesis that inconsistent clinical outcomes are related to variations in the stemness and senescence of the injected autologous adipose-derived (AD) MSCs. Methods In the prospective randomized trial, 45 knee OA patients were divided into two groups: Group 1 (n = 22) patients treated with high tibial osteotomy (HTO) alone and Group 2 (n = 23) patients treated with HTO followed by intra-articular injection of autologous AD-MSCs (HTO + AD-MSCs). MRI and X-ray were performed pre-operation and 12 months post-operation. WOMAC and VAS score were collected four times, every 6 months over a 24-month follow-up. We observed the proliferation and stemness of AD-MSCs selected from the 5 patients showing the most improvement and from the 5 patients with the least improvement, and completed further in vitro experiments including beta-galactosidase activity, reactive oxygen species and bioinformatic analysis. Results The results showed that patients treated with HTO + AD-MSCs had a significant reduction in knee OA severity as compared to patients treated with HTO alone. Moreover, we discovered that proliferation and colony forming efficiency of AD-MSCs selected from the 5 patients showing the most improvement performed significantly better than cells selected from the 5 patients with the least improvement. AD-MSCs from the patients with the most improvement also had lower amounts of senescent cells and intracellular reactive oxygen species. Conclusions Clinical outcomes of autologous AD-MSCs therapy in knee osteoarthritis are correlated with stem cell stemness and senescence. Our study highlights emerging opportunities and trends in precision medicine that could potentially improve autologous MSC-based therapies.

A high-resolution meteorological dataset (≤10 km) over the Tibetan Plateau (TP) is the foundation for investigating and predicting the weather and climate over Asia. The TP Subregional Dynamical Downscaling (TPSDD) dataset is a newly developed high-spatial-temporal resolution gridded dataset for land‒air exchange processes and lower atmospheric structure studies over the whole TP region, taking the climate characteristics of each TP subregion into consideration. The dataset spans from 1981 to 2020, covering the TP with a temporal resolution of 2 hr and spatial resolution of 10 km. Meteorological elements of the dataset include near-surface land–air exchange parameters, such as downward/upward longwave/shortwave radiation flux, sensible heat flux, latent heat flux, etc. In addition, the vertical distributions of 3-dimensional wind, temperature, humidity, and pressure from the surface to the lower stratosphere are also included. Independent evaluations were conducted to verify the performance of the TPSDD dataset by comparing TPSDD/reanalysis with surface and vertical observations through the calculation of statistical parameters. The results demonstrate the accuracy and superiority of this dataset against reanalysis data, which provides great potential for future climate change research.

Objective This study aimed to compare infection, aseptic loosening, revision, operation time, function scores, and the radiographic radiolucent line (RLL) between cementless and cemented fixation in total knee arthroplasty (TKA). Methods Articles reporting the outcomes of cemented and cementless TKA were searched in Medline, EMBASE, Web of Science, and the Cochrane Library. The search was conducted from articles published from January 1996 to May 2024. Odds Ratios (OR) and confidence intervals (CI) were used to measure the results. Cochrane Collaboration’s Review Manager software was used to perform the meta-analysis. Results Sixteen randomized controlled trials containing 2358 participants were included in this meta-analysis. Pooled data found that, in TKA, there were no significant differences between cemented fixation and cementless fixation for a prosthesis in infection, aseptic loosening and revision. The subgroup analysis and sensitivity analysis results of the knee society score (KSS) showed a significant difference favoring cementless fixation in a follow-up of less than 5 years (MD = −2.30, 95%CI –3.85 -0.74, p = .001) while favoring cemented fixation in a follow-up over 5 years (MD = 2.79, 95%CI 0.95 4.63, p = .003). The operation time of cementless was less than that of cemented (MD = 12.03, 95%CI 8.30 15.77, p < .00001). No significant difference was detected in knee society function score, Western Ontario and McMaster Universities osteoarthritis index, and RLL. There was no heterogeneity across studies ( p > .1), and most studies have a low risk of bias. Conclusions Within a follow-up period of less than 5 years, cementless TKA had better KSS, while over 5 years, KSS was better in cemented TKA, and cementless TKA required less operation time.

Abstract The significant role of the cathodic binder in modulating mass transport within the catalyst layer (CL) of fuel cells is essential for optimizing cell performance. This investigation focuses on enhancing the membrane electrode assembly (MEA) through the utilization of a short‐side‐chain perfluoro‐sulfonic acid (SSC‐PFSA) ionomer as the cathode binder, referred to as SSC‐MEA. This study meticulously visualizes the distinctive interpenetrating networks of ionomers and catalysts, and explicitly clarifies the triple‐phase interface, unveiling the transport‐friendly microstructure and transport mechanisms inherent in SSC‐MEA. The SSC‐MEA exhibits advantageous microstructural features, including a better‐connected ionomer network and well‐organized hierarchical porous structure, culminating in superior mass transfer properties. Relative to the MEA bonded by long‐side‐chain perfluoro‐sulfonic acid (LSC‐PFSA) ionomer, noted as LSC‐MEA, SSC‐MEA exhibits a notable peak power density (1.23 W cm−2), efficient O2 transport, and remarkable proton conductivity (65% improvement) at 65 °C and 70% relativity humidity (RH). These findings establish crucial insights into the intricate morphology‐transport‐performance relationship in the CL, thereby providing strategic guidance for developing highly efficient MEA.

Wear is the key issue hindering the further application of titanium alloy. The aim of this work was to explore the strengthening mechanisms for the wear properties of Ti–15Mo alloys via laser powder bed fusion (LPBF) by the La2O3 addition. The results showed that the grain of LPBF-fabricated Ti–15Mo/La2O3 composites was obviously refined after La2O3 addition by heterogeneous nucleation and inhibited grain growth. The average grain size of Ti–15Mo/(0.2 wt%, 0.4 wt%, 0.6 wt% and 0.8 wt%) La2O3 composites is 11.75 μm, 10.85 μm, 10.39 μm, and 9.99 μm, respectively. The wear rate of Ti–15Mo/(0.2 wt% - 0.8 wt%) La2O3 composites is 1.5916 × 10−4mm3N−1m−1, 1.2885 × 10−4mm3N−1m−1, 0.6821 × 10−4mm3N−1m−1 and 0.6063 × 10−4mm3N−1m−1, respectively. Thanks to the combined effect of fine grain strengthening, grain boundary strengthening, precipitation strengthening, dispersion strengthening and dislocation strengthening, the wear resistance of the obtained sample exceeds that of the LPBF-fabricated Ti–15Mo sample more than five times and that of the LPBF-fabricated CP-Ti sample more than ten times.

Changes in wetland ecosystems have a critical impact on the local ecology and species diversity. Different development scenarios and policies are key factors influencing their changes. Therefore, we studied changes of wetlands in the middle Yangtze River basin (MYRB) in 2001–2020, and a patch-generated land use simulation (PLUS) model and random forest (RF) method were applied to predict and analyze the changes under different scenarios in the MYRB in the future (i.e.2035–2095). The results indicated that: (1) The regions with high wetland proportions were concentrated in the central and eastern MYRB in 2001–2020, with a 1.5% decrease in overall wetland area; (2) The RF could simulate the future ecological quality with training and testing accuracies of 0.98 and 0.92, respectively; (3) Remote Sensing Ecological Index (RSEI) less than 0.5 in the central and eastern regions and 13.3% reduction in the northwest in the SSP245 scenario. In general, the study provides a basis for future regional studies of ecosystem quality and provides data to support wetland conservation and management.

The bionic-inspired Ti–15Mo gradient porous structures were fabricated by selective laser melting (SLM) for the first time in this work. The compression-compression fatigue behavior of functional gradient Ti–15Mo porous structures is investigated, with emphasis on understanding the relationship between fatigue performance and microstructure. The microstructure of the samples was analyzed both before and after fatigue, and correlated with the fatigue performance. During cyclic deformation, the pillars exhibited a non-uniform local stress distribution, primarily attributed to the disparity of gradient density distribution. Fatigue cracks typically initiate at the place with the defects and subsequently propagate until structural damage occurs. Fatigue ratcheting effect occurs throughout the entire fatigue process while the fatigue damage typically initiates at a later stage in the fatigue process. The results indicated that the fatigue performance of the lateral gradient (LG) structure was superior to that of the homogeneous structure, while the vertical gradient (VG) structure exhibited the poorest fatigue performance.

The microstructure evolution of near β-Ti alloys with initially lamellar and equiaxed microstructures subjected to dynamic loading was investigated. Results showed that during high strain rate compression, shear failure is more likely to occur in equiaxed microstructure. Owing to temperature rise and stress concentration, the lamellar α phase in adiabatic shear band (ASB) zone was recrystallized and re-melted, while the equiaxed α phase transformed in strip-shaped following the propagating direction of adiabatic shear band. During high strain rate loading, the twinning transfer was observed between β matrix and α phase, which demonstrates that twinning is the dominant deformation mode to accommodate plastic deformation.

Abstract Distributed photovoltaics in living environment harvest the sunlight in different incident angles throughout the day. The development of planer solar cells with large light-receiving angle can reduce the requirements in installation form factor and is therefore urgently required. Here, thin film organic photovoltaics with nano-sized phase separation integrated in micro-sized surface topology is demonstrated as an ideal solution to proposed applications. All-polymer solar cells, by means of a newly developed sequential processing, show large magnitude hierarchical morphology with facilitated exciton-to-carrier conversion. The nano fibrilar donor-acceptor network and micron-scale optical field trapping structure in combination contributes to an efficiency of 19.06% (certified 18.59%), which is the highest value to date for all-polymer solar cells. Furthermore, the micron-sized surface topology also contributes to a large light-receiving angle. A 30% improvement of power gain is achieved for the hierarchical morphology comparing to the flat-morphology devices. These inspiring results show that all-polymer solar cell with hierarchical features are particularly suitable for the commercial applications of distributed photovoltaics due to its low installation requirement.

In this work, laser powder bed fusion (LPBF) technology was used to fabricate pure nickel components, and the densification behavior and microstructure of pure nickel with different energy densities were investigated. The results indicate that for LPBF-fabricated pure nickel components, the relative density reaches a peak of 98.76% at an energy density of 101 J/mm 3 . With the increase of energy density, a large number of pores appear inside the grains, and the grains grow epitaxially along the building direction within multiple molten pools, pores gradually disappear after undergoing remelting at the edges of the melting tracks. Among these, competitive inward growth of columnar crystals may be the main cause of dislocations and new grain generation. The grains are primarily distributed along the Ni (111) or Ni (110) orientations, and with the increase of energy density, the grains with these two orientations increase. The surface energy follows the sequence of Ni (220) > Ni (200) > Ni (111). Due to the stacking of the oriented main layer and the oriented sub-layer in the building direction, the sample with higher energy density exhibits a strong Ni {110} texture, accompanied by increased tensile properties.

Bones are vital for anchoring muscles, tendons, and ligaments, serving as a fundamental element of the human skeletal structure. However, our understanding of bone development mechanisms and the maintenance of bone homeostasis is still limited. Extracellular signal-related kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, plays a critical role in the pathogenesis and progression of various diseases, especially neoplasms. Recent studies have highlighted ERK5’s significant role in both bone development and bone-associated pathologies. This review offers a detailed examination of the latest research on ERK5 in different tissues and diseases, with a particular focus on its implications for bone health. It also examines therapeutic strategies and future research avenues targeting ERK5.

BackgroundHypoxia and metabolism are closely correlated with the progression of cancer. We aimed to construct a combined hypoxia- and metabolism-related genes (HMRGs) prognostic signature to predict survival and immunotherapy responses in patients with clear cell renal cell carcinoma (ccRCC).MethodsThe RNA-seq profiles and clinical data of ccRCC were acquired from the TCGA and the ArrayExpress (E-MTAB-1980) databases. Least absolute shrinkage and selection operator (LASSO) and univariate and multivariate Cox regression analyses were applied to establish a prognostic signature. The E-MTAB-1980 cohort was selected for validation. The effectiveness and reliability of the signature were further evaluated by Kaplan–Meier (K-M) survival and time-dependent receiver operating characteristic (ROC) curves. Further analyses, including functional enrichment, ssGSEA algorithm, CIBERSORT algorithm, and expression of immune checkpoints, were explored to investigate immune status and immunotherapy responses.ResultsWe constructed a prognostic eight-gene signature with IRF6, TEK, PLCB2, ABCB1, TGFA, COL4A5, PLOD2, and TUBB6. Patients were divided into high-risk and low-risk groups based on the medium-risk score. The K-M analysis revealed that patients in the high-risk group had an apparently poor prognosis compared to those in the low-risk group in the TCGA (p < 0.001) and E-MTAB-1980 (p < 0.005). The area under ROC curve (AUC) of the prognostic signature was 0.8 at 1 year, 0.77 at 3 years, and 0.78 at 5 years in the TCGA, respectively, and was 0.82 at 1 year, 0.74 at 3 years, and 0.75 at 5 years in the E-MTAB-1980, respectively. Independent prognostic analysis confirmed the risk score as a separate prognostic factor in ccRCC patients (p < 0.001). The results of ssGSEA showed not only a high degree of immune cell infiltration but also high scores of immune-related functions in the high-risk group. The CIBERSORT analysis further confirmed that the abundance of immune cells was apparently different between the two risk groups. The risk score was significantly correlated with the expression of cytotoxic T lymphocyte-associated antigen-4 (CTLA4), lymphocyte-activation gene 3 (LAG3), and programmed cell death protein 1 (PD-1).ConclusionThe HMRGs signature could be used to predict clinical prognosis, evaluate the efficacy of immunotherapy, and guide personalized immunotherapy in ccRCC patients.

Abstract Hydrogen energy as the next‐generation clean energy carrier has attracted the attention of both academic and industrial fields. A key limit in the current stage is the operation temperature of hydrogen fuel cells, which lies in the slow development of high‐temperature and high‐efficiency proton exchange membranes. Currently, much research effort has been devoted to this field, and very innovative material systems have been developed. The authors think it is the right time to make a short summary of the high‐temperature proton exchange membranes (HT‐PEMs), the fundamentals, and developments, which can help the researchers to clearly and efficiently gain the key information. In this paper, the development of key materials and optimization strategies, the degradation mechanism and possible solutions, and the most common morphology characterization techniques as well as correlations between morphology and overall properties have been systematically summarized.

Abstract Background Most patients with insufficient bone mass suffer from severe horizontal or vertical bone defects in oral implant surgery. The purpose of this study was to compare the bone regeneration effects of titanium meshes with different porosity in the treatment of bone defects. Methods Nine beagle dogs were equally divided into three groups based on execution time. Three months after the extraction of the first to fourth premolars of the mandible, three bone defects were randomly made in the mandible. Bone particles and three kinds of three-dimensional (3D) printed titanium nets with different porosities (low porosity group (LP), 55%; medium porosity group (MP), 62%; and high porosity group (HP), 68%) were replanted in situ. The beagles were killed 4, 8, and 12 weeks after surgery. Formalin-fixed specimens were embedded in acrylic resin. The specimens were stained with micro-CT, basic fuchsin staining, and toluidine blue staining. Results Micro-CT analysis showed that the trabecular thickness, trabecular number, and bone volume fraction of the HP group were higher than those of the other two groups. Moreover, the trabecular separation of the HP group decreased slightly and was lower than that of the MP and LP groups. Histological staining analysis showed that the trabecular number in the HP group was higher than in the other two groups at 8 and 12 weeks, and the bone volume fraction of the HP was higher than that in the other two groups at 12 weeks. Moreover, the trabecular thickness of the MP was higher than that of the LP group at 12 weeks and the trabecular separation was lower in the HP group at 4 and 8 weeks. The differences were statistically significant (p

Atmospheric ducts could disturb radar detection and radio communication in the Arctic and risk increasing human activities under Arctic warming. It is an urgent need to understand atmospheric ducts in the Arctic, with distinct atmospheric systems and environment. This study attempts to analyze the surface atmospheric ducts over Svalbard, as a critical region in the Arctic Ocean, and discuss the relation to atmospheric and oceanic conditions, based on observation and reanalysis data. The results show an occurrence of 12.6 percent, mean strength of 1.30 MU, and mean depth of 13 m for the surface duct in Svalbard winter from December 2018 to February 2020. The surface duct is characterized as two types: T-type ducts mainly constructed by temperature inversion and H-type ducts constructed by a humidity gradient. The T-type duct dominates the surface duct in Svalbard winter, with an appearance percentage of 80 percent, indicating an importance of temperature inversion in surface duct construction. The surface duct is closely related to atmospheric and oceanic conditions in Svalbard winter, because the T-type duct occurs in colder, drier, and northeasterly weather and the H-type duct occurs in warmer, wetter, and southeasterly weather with higher sea surface temperature.

Full automation of manufacturing is strongly desired to improve the productivity. Autonomous optimization of the cutting conditions in the end milling operation is one of the challenges in achieving this goal. This paper proposes a system for optimization of the cutting conditions based on Deep Q-Network (DQN), which is a kind of deep reinforcement learning. An end mill is used as an agent and the end milling simulation is employed to provide the environment in the proposed system. Geometric information of interference state between tool and workpiece in the simulation is considered as the state of the environment and acceleration of feed rate is the action for the agent to take. The action is optimized by DQN to maximize the accumulated reward given from the environment, which evaluates how good the scenario of action is. Therefore, the cutting conditions can be optimized according to the defined reward function. We performed three case studies to verify our proposed method, in which the cutting torque is controlled to be a specified value. The objective was successfully achieved regardless of differences in the end milling scenario. The obtained results strongly suggested a fact that the reinforcement learning is a promising solution to autonomous optimization of the cutting conditions.

BackgroundOxidative stress plays a significant role in the tumorigenesis and progression of tumors. We aimed to develop a prognostic signature using oxidative stress-related genes (ORGs) to predict clinical outcome and provide light on the immunotherapy responses of clear cell renal cell carcinoma (ccRCC).MethodsThe information of ccRCC patients were collected from the TCGA and the E-MTAB-1980 datasets. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) were conducted to screen out overall survival (OS)-related genes. Then, an ORGs risk signature was built by multivariate Cox regression analyses. The performance of the risk signature was evaluated with Kaplan-Meier (K-M) survival. The ssGSEA and CIBERSORT algorithms were performed to evaluate immune infiltration status. Finally, immunotherapy responses was analyzed based on expression of several immune checkpoints.ResultsA prognostic 9-gene signature with ABCB1, AGER, E2F1, FOXM1, HADH, ISG15, KCNMA1, PLG, and TEK. The patients in the high risk group had apparently poor survival (TCGA: p < 0.001; E-MTAB-1980: p < 0.001). The AUC of the signature was 0.81 at 1 year, 0.76 at 3 years, and 0.78 at 5 years in the TCGA, respectively, and was 0.8 at 1 year, 0.82 at 3 years, and 0.83 at 5 years in the E-MTAB-1980, respectively. Independent prognostic analysis proved the stable clinical prognostic value of the signature (TCGA cohort: HR = 1.188, 95% CI =1.142-1.236, p < 0.001; E-MTAB-1980 cohort: HR =1.877, 95% CI= 1.377-2.588, p < 0.001). Clinical features correlation analysis proved that patients in the high risk group were more likely to have a larger range of clinical tumor progression. The ssGSEA and CIBERSORT analysis indicated that immune infiltration status were significantly different between two risk groups. Finally, we found that patients in the high risk group tended to respond more actively to immunotherapy.ConclusionWe developed a robust prognostic signature based on ORGs, which may contribute to predict survival and guide personalize immunotherapy of individuals with ccRCC.

Recently, severe plastic deformation of alloys under cold conditions has been experimentally investigated to develop refined microstructures. The present study proposed to demonstrate the feasibility of applying cold deformation to a β-solution treated near β-Ti alloy. To be specific, the evolution of microstructure and mechanical properties of a β-solution treated near β-Ti alloy subjected to unidirectional 20% cold rolling were investigated. Results showed that long cracks formed in the 20% cold rolled sample. Meanwhile, two types of deformation-inducted α′ martensite have been observed in cold-rolled β matrix, namely, acicular α′ martensite with an orientation relationship of (12¯10)α′//(111)β with β matrix, and deformed (irregular shape) α′ martensite without coordinating orientation relationship. The formation of cracks was mainly related to the pre-existing α′ plate, and the micro-crack was prone to occur in α′ plates and propagate to β matrix. The microstructure characteristics result in poor ductility and low ultimate strength in the cold-rolled sample. Lastly, the lattice distortion and {101¯2}1¯011 α′-twinning were also characterized in the deformed α′ plates.

Magnolol is a chemically defined and active polyphenol extracted from magnolia plants possessing anti-allergic activity, but its low solubility and rapid metabolism dramatically hinder its clinical application. To improve the therapeutic effects, magnolol-encapsulated polymeric poly (DL-lactide-co-glycolide)–poly (ethylene glycol) (PLGA-PEG) nanoparticles were constructed and characterized. The prophylactic and therapeutic efficacy in a chronic murine model of OVA-induced asthma and the mechanisms were investigated. The results showed that administration of magnolol-loaded PLGA-PEG nanoparticles significantly reduced airway hyperresponsiveness, lung tissue eosinophil infiltration, and levels of IL-4, IL-13, TGF-β1, IL-17A, and allergen-specific IgE and IgG1 in OVA-exposed mice compared to their empty nanoparticles-treated mouse counterparts. Magnolol-loaded PLGA-PEG nanoparticles also significantly prevented mouse chronic allergic airway mucus overproduction and collagen deposition. Moreover, magnolol-encapsulated PLGA-PEG nanoparticles showed better therapeutic effects on suppressing allergen-induced airway hyperactivity, airway eosinophilic inflammation, airway collagen deposition, and airway mucus hypersecretion, as compared with magnolol-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles or magnolol alone. These data demonstrate the protective effect of magnolol-loaded PLGA-PEG nanoparticles against the development of allergic phenotypes, implicating its potential usefulness for the asthma treatment.

BackgroundAt present, androgen deprivation therapy (ADT) is still the standard regimen for patients with metastatic and locally advanced prostate cancer (PCa). The level of androgen receptor splice variant-7 (AR-V7) in men with castration-resistant prostate cancer (CRPC) has been reported to be elevated compared with that in patients diagnosed with hormone-sensitive prostate cancer (HSPC).AimHerein, we performed a systematic review and cumulative analysis to evaluate whether the expression of AR-V7 was significantly higher in patients with CRPC than in HSPC patients.MethodsThe commonly used databases were searched to identify the potential studies reporting the level of AR-V7 in CRPC and HSPC patients. The association between CRPC and the positive expression of AR-V7 was pooled by using the relative risk (RR) with the corresponding 95% confidence intervals (CIs) under a random-effects model. For detecting the potential bias and the heterogeneity of the included studies, sensitivity analysis and subgroup analysis were performed. Publication bias was assessed Egger’s and Begg’s tests. This study was registered on PROSPERO (ID: CRD42022297014).ResultsThis cumulative analysis included 672 participants from seven clinical trials. The study group contained 354 CRPC patients, while the other group contained 318 HSPC patients. Pooled results from the seven eligible studies showed that the expression of positive AR-V7 was significantly higher in men with CRPC compared to those with HSPC (RR = 7.55, 95% CI: 4.61–12.35, p < 0.001). In the sensitivity analysis, the combined RRs did not change substantially, ranging from 6.85 (95% CI: 4.16–11.27, p < 0.001) to 9.84 (95% CI: 5.13–18.87, p < 0.001). In the subgroup analysis, a stronger association was detected in RNA in situ hybridization (RISH) measurement in American patients, and those studies were published before 2011 (all p < 0.001). There was no significant publication bias identified in our study.ConclusionEvidence from the seven eligible studies demonstrated that patients with CRPC had a significantly elevated positive expression of AR-V7. More investigations are still warranted to clarify the association between CRPC and AR-V7 testing.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022297014.

BackgroundTransforming growth factor (TGF)-β signaling is strongly related to the development and progression of tumor. We aimed to construct a prognostic gene signature based on TGF-β signaling-related genes for predicting clinical prognosis and immunotherapy responses of patients with clear cell renal cell carcinoma (ccRCC).MethodsThe gene expression profiles and corresponding clinical information of ccRCC were collected from the TCGA and the ArrayExpress (E-MTAB-1980) databases. LASSO, univariate and multivariate Cox regression analyses were conducted to construct a prognostic signature in the TCGA cohort. The E-MTAB-1980 cohort were used for validation. Kaplan-Meier (K-M) survival and time-dependent receiver operating characteristic (ROC) were conducted to assess effectiveness and reliability of the signature. The differences in gene enrichments, immune cell infiltration, and expression of immune checkpoints in ccRCC patients showing different risks were investigated.ResultsWe constructed a seven gene (PML, CDKN2B, COL1A2, CHRDL1, HPGD, CGN and TGFBR3) signature, which divided the ccRCC patients into high risk group and low risk group. The K-M analysis indicated that patients in the high risk group had a significantly shorter overall survival (OS) time than that in the low risk group in the TCGA (p < 0.001) and E-MTAB-1980 (p = 0.012). The AUC of the signature reached 0.77 at 1 year, 0.7 at 3 years, and 0.71 at 5 years in the TCGA, respectively, and reached 0.69 at 1 year, 0.72 at 3 years, and 0.75 at 5 years in the E-MTAB-1980, respectively. Further analyses confirmed the risk score as an independent prognostic factor for ccRCC (p < 0.001). The results of ssGSEA that immune cell infiltration degree and the scores of immune-related functions were significantly increased in the high risk group. The CIBERSORT analysis indicated that the abundance of immune cell were significantly different between two risk groups. Furthermore, The risk score was positively related to the expression of PD-1, CTLA4 and LAG3.These results indicated that patients in the high risk group benefit more from immunotherapy.ConclusionWe constructed a novel TGF-β signaling-related genes signature that could serve as an promising independent factor for predicting clinical prognosis and immunotherapy responses in ccRCC patients.

Micro Raman tomographic imaging (mRTI) is an excellent measurement technique that can nondestructively measure and image the fracture state of the crystal lattice inside materials with a high spatial resolution. mRTI has been successfully used for translucent materials such as wide bandgap semiconductor wafers. The applicability of this measurement method was evaluated by observing the wear damage in polycrystalline industrial ceramics materials. The influence of optical diffusion on the surface and inside of polycrystalline materials is a concern for the internal measurements by the optical beam. The quality degradation of spectral signals due to disturbances in the optical beam was confirmed by mRTI measurements on a commercial alumina plate. The application of surface polishing treatment was attempted to reduce the influence of surface optical diffusion. Three kinds of the surfaces were observed by mRTI, as the initial surface of the alumina plate, polished with #400 and #800 diamond abrasive lapping film, respectively. It was confirmed that the effective measurement depth range can be extended by reducing the surface roughness. However, we confirmed that excessive surface polishing may overwrite the damage on the measurement surface, making it difficult to observe the original damage.

Near β-Ti alloys, a perfect candidate material for numerous applications in the aerospace, are expected to exhibit high temperature endurability. Here, in order to evaluate the high temperature oxidation mechanism of the near β-Ti alloy, detailed microstructural characterization was performed on a near β-Ti alloy, Ti-55511 alloy after isothermal heat treatment at 600 °C in a tube furnace. Parabolic oxidation kinetics was observed. The oxide layer consisted of Al2O3, TiO2, VO2, and Magnéli phases. Polymorphic phase transformations and Magnéli phases played critical roles in the oxide layer thickening. The formation of defects was highly correlated with the incorporation of oxygen into Al2O3 and VO2, which resulted in lattice distortion of the oxides. Continuous oxidation led to the formation of the higher-valence oxide V2O5 in VO2 particles.

Purpose: The aim of this study was to conduct a comprehensive transcriptomic analysis to explore the potential biological functions of noncoding RNA (ncRNAs) in temporomandibular joint osteoarthritis (TMJOA).Methods: Whole transcriptome sequencing was performed to identify differentially expressed genes (DEGs) profiles between the TMJOA and normal groups. The functions and pathways of the DEGs were analyzed using Metascape, and a competitive endogenous RNA (ceRNA) network was constructed using Cytoscape software.Results: A total of 137 DEmRNAs, 65 DEmiRNAs, 132 DElncRNAs, and 29 DEcircRNAs were identified between the TMJOA and normal groups. Functional annotation of the DEmRNAs revealed that immune response and apoptosis are closely related to TMJOA and also suggested key signaling pathways related to TMJOA, including chronic depression and PPAR signaling pathways. We identified vital mRNAs, including Klrk1, Adipoq, Cryab, and Hspa1b. Notably, Adipoq expression in cartilage was significantly upregulated in TMJOA compared with normal groups (10-fold, p < 0.001). According to the functional analysis of DEmRNAs regulated by the ceRNA network, we found that ncRNAs are involved in the regulation of autophagy and apoptosis. In addition, significantly DEncRNAs (lncRNA-COX7A1, lncRNA-CHTOP, lncRNA-UFM1, ciRNA166 and circRNA1531) were verified, and among these, circRNA1531 (14.5-fold, p < 0.001) and lncRNA-CHTOP (14.8-fold, p < 0.001) were the most significantly downregulated ncRNAs.Conclusion: This study showed the potential of lncRNAs, circRNAs, miRNAs, and mRNAs may as clinical biomarkers and provides transcriptomic insights into their functional roles in TMJOA. This study identified the transcriptomic signatures of mRNAs associated with immunity and apoptosis and the signatures of ncRNAs associated with autophagy and apoptosis and provides insight into ncRNAs in TMJOA.

Ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, have had a profound impact on millions of patients. In the past couple of decades, these diseases have been treated using conventional techniques but have also presented certain challenges and limitations that affect patient experience and outcomes. To address this, biomaterials have been used for ocular drug delivery, and a wide range of systems have been developed. This review will discuss some of the major classes and examples of biomaterials used for the treatment of prominent ocular diseases, including ocular implants (biodegradable and non-biodegradable), nanocarriers (hydrogels, liposomes, nanomicelles, DNA-inspired nanoparticles, and dendrimers), microneedles, and drug-loaded contact lenses. We will also discuss the advantages of these biomaterials over conventional approaches with support from the results of clinical trials that demonstrate their efficacy.

The functional and mechanical properties of steel slag (SS)–red mud (RM)–electrolytic manganese residue (EMR)-based composite mortar under different matching ratio conditions were investigated in this paper to examine the synergistic cementing effect among multiple solid wastes. The hydration characteristics of the composite mortar and its microstructure were characterized by the heat of hydration assessment, X-ray diffraction, thermogravimetric analysis, and other tests. The results of the study showed that compared with the pure cement group, 30% SS alone will inhibit the hydration reaction of the slurry, thus reducing the mechanical properties of the mortar, while compounding the appropriate amount of RM, and EMR can effectively reduce the negative impact of SS on the mechanical properties of the mortar. The flexural and compressive strengths of the composite mortar at 28 d were the highest when 15% of SS, 12% of RM, and 3% of EMR were mixed, which were 7.2 MPa and 41.4 MPa at 28 d, respectively. Compared with the test group with 30% SS alone, the flexural and compressive strengths increased by 18.0% and 25.5%. This is mainly because the incorporation of RM and EMR not only plays the role of physical filling, but the free alkali in RM and sulfate material in EMR can also compoundly stimulate the hydration activity of SS to produce more calcium alumina (AFt) and hydrated calcium silicate (C–S–H gel), thus improving the microstructure of mortar, which makes the overall decrease of 26.35% of multiharmful and harmful pores and the overall increase of harmless and less harmful pores of composite mortar specimens of 43.57%.

Temporomandibular joint osteoarthritis (TMJOA) is a common degenerative joint disease that can cause severe pain and dysfunction. It has a serious impact on the quality of lives of patients. Since mechanism underlying the pathogenesis of TMJOA is not fully understood, the development of effective tools for early diagnosis and disease-modifying therapies has been hindered. Animal models play a key role in understanding the pathological process of diseases and evaluating new therapeutic interventions. Although some similarities in disease processes between animals and humans are known, no one animal model is sufficient for studying all characteristics of TMJOA, as each model has different translatability to human clinical conditions. For the past 4 decades, TMJOA animal models have been studied by numerous researchers and can be broadly divided into induced, naturally occurring, and genetically modified models. The induced models can be divided into invasive models (intra-articular injection and surgical induction) or non-invasive models (mechanical loading, high-fat diet, and sleep deprivation). Different types of animal models simulate different pathological expressions of TMJOA and have their unique characteristics. Currently, mice, rats, and rabbits are commonly used in the study of TMJOA. This review sought to provide a general description of current experimental models of TMJOA and assist researchers in selecting the most appropriate models for different kinds of research.

To promote Tibetan meteorological research, the third Tibetan Plateau (TP) Experiment for atmospheric sciences (TIPEX III) has been carried out over the plateau region since 2014, with near-surface heat fluxes measured at different sites. Using the observational data of near-surface heat fluxes measured at 8 plateau stations in TIPEX III, as well as the ECMWF ERA Interim reanalysis data, the land-atmosphere heat transfers over different regions of TP and their responses to the South Asian summer monsoon (SASM) during active/break periods were investigated. Inhomogeneity was found in the land-atmosphere heat transfers over the plateau, with large differences among plateau stations. During the observation period, the daily averaged total heat transfer (the sum of sensible and latent heat flux) varied from 70.2 to 101.2 Wm−2 among the 8 plateau stations, with the sensible heat flux from 18.8 to 60.1 Wm−2 and the latent heat flux from 10.1 to 74.7 Wm−2. These heat transfers were strongly affected by the SASM evolution, but with strong inhomogeneities over the plateau stations. Overall, the more southern station locations exhibited more SASM impacts. The land-atmosphere heat transfers (the total, sensible and latent heat fluxes) were greatly weakened/strengthened during the SASM active/break period at Namco (southeast plateau), Baingoin (central plateau), Lhari (central plateau), and Nagqu (central plateau), which were closely related to the weakened/strengthened radiation conditions. However, the SASM impacts were quite small or even negligible for the other plateau stations, which complicated our conclusions, and further investigations are still needed.

The rotary in-feed grinding is the most promising process to ensure the controllability of wafer geometry including the thickness and flatness. This makes it be widely applied into manufacturing of mono-crystal wafers, such as silicon, silicon carbide, sapphire, lithium tantalate, and etc. Unlike the conventional surface grinding, however, the rotary in-feed grinding is a complex material removal operation in which the extent of interaction between the abrasives and wafer keeps varying during the wheel/wafer contact zone. Such characteristic property significantly influences the chip formation, the homogeneousness of surface topography, the variations in grinding forces and the power consumption in the radial direction of the wafer. In this paper, the grinding mechanisms including the geometry, statics and surface topography were theoretically analyzed on a proposed grinding model and organized as follows. Described in Section 2 is the geometric analysis which mathematically expresses the wafer profile and a variety of information regarding to the dimensions of chip formed. The results suggest that the chip cross section increases proportionally as increasing in the wafer radial distance. Based on the results of chip formation, the grinding forces respectively exerted on an individual abrasive, a single wheel segment and whole wafer are calculated in the Section 3. Also, the necessary grinding power and generated grinding heat are estimated by statics analysis. In the Section 4, the surface roughness and its variation in a radial direction of the wafer are then derived by taking into consideration of the distribution of abrasive protrusion in height-wise.

Paramyxoviruses are a group of RNA viruses, such as mumps virus, measles virus, Nipah virus, Hendra virus, Newcastle disease virus, and parainfluenza virus, usually transmitted by airborne droplets that are predominantly responsible for acute respiratory diseases. In this paper, we identified a novel paramyxovirus belonging to genus Jeilongvirus infecting 4/112 (3.6%) bats from two trapping sites of Hainan Province of China. In these animals, the viral RNA was detected exclusively in kidney tissues. This is the first full-length Jeilongvirus genome (18,095 nucleotides) from bats of genus Hipposideros, which exhibits a canonical genome organization and encodes SH and TM proteins. Results, based on phylogenic analysis and genetic distances, indicate that the novel paramyxovirus formed an independent lineage belonging to genus Jeilongvirus, representing, thus, a novel species. In addition, the virus-host macro-evolutionary analysis revealed that host-switching was not only a common co-phylogenetic event, but also a potential mechanism by which rats are infected by bat-origin Jeilongvirus through cross-species virus transmission, indicating a bat origin of the genus Jeilongvirus. Overall, our study broadens the viral diversity, geographical distribution, host range, and evolution of genus Jeilongvirus.

In this study, single groove nanoscratch experiments using a friction force microscope (FFM) with a monocrystalline diamond tip were conducted on a c-plane sapphire wafer to analyze the ductile-regime removal and deformation mechanism including the anisotropy. Various characteristics, such as scratch force, depth, and specific energy for each representative scratch direction on the c-plane of sapphire, were manifested by the FFM, and the results of the specific scratch energy showed a trend of six-fold symmetry on taking lower values than those of the other scratch directions when the scratch directions correspond to the basal slip directions as 0001⟨112¯0⟩. Since this can be due to the effect of most probably basal slip or less probably basal twinning on the c-plane, a molecular dynamics (MD) simulation of zinc, which is one of the hexagonal close-packed (hcp) crystals with similar slip/twining systems, was attempted to clarify the phenomena. The comparison results between the nanoscratch experiment and the MD simulation revealed that both the specific scratch energy and the burr height were minimized when scratched in the direction of the basal slip. Therefore, it was found that both the machining efficiency and the accuracy could be improved by scratching in the direction of the basal slip in the single groove nanoscratch of c-plane sapphire.

Abstract The change in ambient temperature is one of the risk factors for the aggravation of bronchial asthma (BA). Yet, whether the ambient temperature influences the immune functions associated with allergic asthma remains unknown. In this study, we treated asthmatic mice with standard temperature (ST, 20 °C) or thermoneutral temperature (TT, 30 °C). The results showed that the airway inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR) were significantly reduced in the mice treated with TT as compared with the mice treated with ST. The imbalance of Th1/Th2 response in the lung was improved following housing the mice at TT. In addition, the pulmonary Treg cells were increased in asthmatic mice after TT treatment. The temperature stress (29 °C and 41 °C) drove naïve CD4T cells towards Th2 cells. Our data demonstrate that the change of ambient temperature was a risk factor to aggravate experimental asthma.

Surface heating is important in terms of the thermal effect of the Tibetan Plateau on atmospheric systems in Asia. The complex mountain terrain across the Tibetan Plateau introduces small-scale heterogeneity in the local atmosphere and land–air heat exchange that biases our understanding of the Tibetan thermal effect and misleads boundary-layer parameterization for numerical studies and predictions. It is therefore essentially important to evaluate heterogeneity in the Tibetan mountains. An observational experiment was conducted in a small region with a complex landscape in the eastern Himalayas from June 9 to July 9, 2013. This study analyzes the observations of three major land covers and discusses the observed heterogeneity of the local atmosphere and land–air heat exchange. A heterogeneity rate is defined to approximately quantify the heterogeneity observed in the atmospheric properties and land–air heat exchange. Obvious heterogeneity is found in the local atmosphere across the complex terrain of the Eastern Himalayas, which could introduce uncertainties up to 33.3 percent in our knowledge related to the local weather and climate. A large heterogeneity is revealed in the land–air heat exchange, which would bias our understanding of total surface heating in this region up to 16 percent and of heating properties up to 62 percent. Therefore, attention should be given to the uncertainties introduced by small-scale heterogeneity in any weather and climate studies across a complex terrain, such as the eastern Himalayas. In addition, the heterogeneity rate provided could be a useful measure to generally identify the uncertainties in our understanding of the local atmosphere and land–air heat exchange across a complex terrain.

The Dalmatian Pelican (Pelecanus crispus), in the order Pelecaniformes, its habitat is distributed in Europe, Asia, and Africa. It is a large waterfowl that is of international concern. In this study, we first sequenced and described the complete mitochondrial genome and phylogeny of P. crispus. The results showed that the whole genome of P. crispus was 16,131 bp in length, and contained 13 protein-coding genes, 22 transfer RNA genes, two ribosome RNA genes, and one non-coding control region. The overall base composition of the mitochondrial DNA was 30.48% for A, 23.15% for T, 31.68% for C, and 14.69% for G, with a GC content of 46.37%. A phylogenetic tree of P. crispus in Pelecaniformes confirmed that P. crispus was sister to C. occidentalis. This information will be useful in the current understanding of the phylogeny and evolution of Pelecaniformes.

The Collared Crow (Corvus pectoralis), in the order Passeriformes, it widely distributed in large areas encompassing China and northern Vietnam. It is a vulnerable bird that is of international concern. In this study, we first sequenced and described the complete mitochondrial genome and phylogeny of C. pectoralis. The results showed that the whole genome of C. pectoralis was 16,857 bp long and contains 13 PCGs, 2 ribosomal RNA genes, 23 transfer RNA genes, and 1 loop region. The overall base composition of the mitochondrial DNA was 31.13% for A, 29.52% for C, 24.46% for T, and 14.89% for G, with a GC content of 44.41%. The phylogenetic tree showed that C. pectoralis was clustered with C. brachyrhynchos and then together with other two crows in family Passeriformes. This information will be useful in the current understanding of the phylogeny and evolution of Passeriformes.

As the most prominent feature of the polar stratosphere, polar vortex results in widespread changes in the climate system, especially in the ozone variation. In this study, the linkage between polar vortex and ozone depletion in Antarctic stratosphere during the period 1979–2016 is investigated; we calculated the averaged total column ozone within the polar vortex based on the vortex edge (−28.8 PVU PV contour) instead of the geographical region defined by latitude and longitude. Results from the spatial patterns of ozone and polar vortex suggest that the morphological changes of polar vortex can impact the horizontal distribution of ozone and the ozone within the polar vortex experiences a severe depletion in spring. The negative relationship between ozone and polar vortex in terms of vortex area, strength, and breakup time is significant with the correlation coefficients of −0.57, −0.68, and −0.76, respectively. The breakup time of polar vortex plays an important role in the relation between polar vortex and ozone depletion with the highest-value correlation coefficient among three polar vortex parameters. Furthermore, the possible mechanism for this relationship is also discussed in this article.

A molecular dynamics simulation is performed to clarify the energy dissipation process in the atomic-scale friction, particularly with the two-dimensional atomic-scale stick-slip phenomenon as observed in the friction experiment by AFM/FFM. In the present simulation, a well defined Cu{1 0 0} surface is scanned in the direction of with different scan position by a carbon atom probe using a simple model where the effect of cantilever stiffness of the atomic force microscope is taken into consideration. From the simulation results, it is clarified that the dissipated mechanical energy thorough the one or two-dimensional atomic-scale stick-slip phenomenon can be calculated more precisely from the stored elastic energy using the amplitude of stick-slip force signal in each direction than the work calculated using the average friction force.

A high-performance liquid chromatography coupled with an evaporative light scattering detector (HPLC–ELSD) has been developed to evaluate the quality of Asparagus filicinus through a simultaneous determination of six steroidal saponins and one ecdysone, including aspafiliosides A, B, C, E, G, filiasparoside A and 20-hydroxyecdysone. With a C18 analytical column, the seven analytes were separated efficiently using acetonitrile–water as the mobile phase in a gradient program. The method limits of detection ranged 0.125–0.225 μg, and the method limits of quantitation ranged 0.408–0.720 μg, respectively. The intra- and inter-day precisions of the method were evaluated and were all less than 3%. All the recoveries for the spiked analytes ranged 95.16%–100.61%. The proposed method was successfully applied to quantify the seven components in thirteen samples from different localities in China.

This study aims to clarify the interaction between a silicon wafer and individual diamond abrasives in grinding to support the estimation of optimal grinding conditions for minimizing the subsurface damages and maximizing the removal rate. In this paper, the effects of adhesion (or lubrication) between a Si wafer and a diamond abrasive on the material removal and tool wear were analyzed by means of the molecular dynamics simulation. A few simulations were performed with changing the dissociation (cohesion) energy of a Morse potential function between a pair of Si and C atoms to evaluate the influence of adhesion on the material removal process. As a result, a trend similar to the actual diamond grinding process of silicon wafer was confirmed, which suggested that the reduction in adhesion (or proper lubrication) is effective for the reduction in subsurface damages, grinding forces, grinding temperature and tool wear, but may lead to reduction in the material removal rate as well.

Silicon (Si) is a fundamental material in the semiconductor industry. The advancement of semiconductor devices have offered convenience and comfort to our life. In order to raise productivity and economic efficiency, the semiconductor industry keeps looking for use of larger size Si wafers. The next generation wafer is expected to be sized as large as 450 mm in diameter. Many wafering processes including lapping, grinding and polishing have been studied and grinding technology stands out as the most promising process for large-size Si wafer manufacturing. In the current in-feed grinding scheme adopted for Si wafers, the wheel diameter used is generally equal to or larger than the wafer diameter. In turn, larger diameter wheels require larger size machine tools and production lines, which lead to increase in manufacturing costs. In this paper, both experiment and kinematical analysis have been carried out to investigate the feasibility of using small diameter grinding wheels to grind large size Si wafers, mainly focusing on the effects of wheel diameter on wafer geometry and surface roughness. The results show that both wheels generated a central convex profile on the wafer and the small wheel achieved a slightly better flatness than the large wheel. The surface roughness were similar one to another for most area of the wafer except the fringe around its edge. All these experimental results were predicable by the kinematic model established in this paper. Particularly, the kinematic analysis found that the cutting path made by small wheel with diameter equaling to the wafer radius was parallel each other at the fringe around wafer edge, which directly worsened the surface roughness.

The aim of this study is to enhance the value and utilization of red mud generated in the Bayer process by preparing composite cement mortars. The effects of two different types of Bayer red mud with varying physical and chemical characteristics on the fluidity, mechanical strength, mineral composition, and microstructure of the composite cement mortar were systematically evaluated. The results showed that the optimal addition of red mud A was 10 wt%, while it was 20 wt% for red mud B. The mechanical properties of the composite cement mortar met the standards for P·O42.5 cement. Furthermore, the composite mortar with the addition of red mud B showed higher flexural and compressive strengths compared to the composite mortar with red mud A. This improvement is attributed to the smaller particle size of red mud B, which filled the micro-pores and increased the compactness of the cement stone, as well as its higher content of Na2O, K2O, and other free alkalis, which resulted in more obvious alkali activation, accelerating the hydration of the active minerals in the slurry. [ABSTRACT FROM AUTHOR]