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Abstract The α-tubulin subtype, Tubulin α-1b chain (TUBA1B), has been shown to influence immune cell infiltration, cancer growth, and survival across various malignancies. However, a comprehensive study has not yet been undertaken examining the immunological and predictive effects of TUBA1B in a pan-carcinoma context. Using data from TCGA, GEO, and other databases, we analyzed TUBA1B expression across various carcinoma types using transcriptional profiling, prognostic implications, genetic and epigenetic alterations, methylation patterns, and immunological significance. To validate our findings, we conducted Western blot analysis to assess TUBA1B protein levels in matched breast cancer tissue samples and performed CCK-8 proliferation assay, flow cytometry, transwell invasion, and migration assays to comprehensively examine the functional impact of TUBA1B on breast cancer cells. Our pan-cancer analysis found TUBA1B upregulation across most tumor types, with varying expression patterns in distinct immune and molecular subtypes. High TUBA1B expression was an independent risk factor and associated with poor prognoses in several cancers, including BRCA, KICH, LGG, LUAD, and MESO. TUBA1B also demonstrates moderate to high diagnostic accuracy in most tumor types. Increased m6A methylation levels were observed in the TUBA1B gene, while its promoter region displayed low methylation levels. TUBA1B's expression impacted some cancers by elevating tumor mutation burden, microsatellite instability, neoantigen formation, immune cell infiltration, and the modulation of immune checkpoints. Functional enrichment analysis highlights TUBA1B’s involvement in important cellular processes such as the cell cycle, p53 signaling, cell senescence, programmed cell death, and the regulation of immune-related pathways. Moreover, our study reveals higher TUBA1B protein expression in breast cancer tissues compared to adjacent tissues. In vitro experiments confirm that TUBA1B deletion reduces breast cancer cell proliferation, invasion, and migration while increasing apoptosis. In conclusion, our study suggests that TUBA1B could potentially serve as a diagnostic marker for predicting cancer immunological profiles and survival outcomes and shed light on the expression and role of TUBA1B in breast cancer, providing a solid foundation for considering it as a promising therapeutic target for breast cancer patient treatment.

Abstract Background The present study aimed to investigate the expression level, biological function, and underlying mechanism of transmembrane protein 176B (TMEM176B) in gastric cancer (GC). Methods TMEM176B expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). The function of TMEM176B was determined by various in vitro assays including colony formation, 5-ethynyl-2ʹ-deoxyuridine (EdU), Transwell, and flow cytometry. Bioinformatics techniques were then used to elucidate the signaling pathways associated with TMEM176B activity. Tumor formation experiments were conducted on nude mice for in vivo validation of the preceding findings. TMEM176B expression was cross-referenced to clinicopathological parameters and survival outcomes. Results It was observed that TMEM176B was overexpressed in GC cells and tissues. Targeted TMEM176B abrogation inhibited colony formation, proliferation, migration, and invasion but promoted apoptosis in GC cell lines while TMEM176B overexpression had the opposite effects. Subsequent experimental validation disclosed an association between TMEM176B and the phosphatidylinositol 3-carboxykinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling axis. Moreover, TMEM176B affects GC cancer progression by regulating asparagine synthetase (ASNS). The in vivo assays confirmed that TMEM176B is oncogenic and the clinical data revealed a connection between TMEM176B expression and the clinicopathological determinants of GC. Conclusion The foregoing results suggest that TMEM176B significantly promotes the development of gastric cancer and is an independent prognostic factor of it.

Abstract Objective The research intended to probe the connection between the risk of stroke and serum vitamin D levels. Methods Three electronic databases (Cochrane Library, EMBASE, PubMed) were searched according to the subject terms from inception until July 29, 2022, and retrieved researches were screened on the basis of inclusion and exclusion criteria. Two investigators conducted the quality assessment and data extraction. Using Stata 16.0 software, a meta‐analysis was conducted on the extracted data. Findings In total, 27 studies with 45,302 participants were included. Among these studies, 20 focused on stroke risk, while 7 examined stroke prognosis. According to the meta‐analysis findings, it was observed that a higher stroke risk is connected to reduced levels of serum vitamin D. This association was reflected in a combined relative risk (RR) of 1 .28 (95% confidence interval (CI): 1.15–1.42) and a worse prognosis after stroke (RR = 2.95, 95% CI: 1.90–4.60). Additional analysis indicated that no apparent relationship between a decrease in vitamin D and the probability of experiencing a hemorrhagic stroke was found. The RR found was 1.93 (95% CI: 0.95–3.95). On the other hand, it was observed that a reduction in serum vitamin D levels was linked to an elevated likelihood of developing an ischemic stroke. The RR identified was 1.72 (95% CI: 1.78–2.03). Moreover, a lower level of vitamin D in the bloodstream was associated with a more unfavorable prognosis for individuals who suffered from a stroke. The RR for this correlation was 2.95 (95% CI: 1.90–4.60). However, further research is required to confirm the above‐mentioned findings. Conclusion In conclusion, lower concentration vitamin D was found to be related to an increased risk of stroke, which could mainly be reflected in ischemic stroke patients but not in patients with hemorrhagic stroke. A lower serum vitamin D level was correlative with the poor prognosis of stroke.

Abstract This paper studies the existence of radial solutions of the boundary value problem of p-Laplace equation with gradient term { − Δ p u = K ( | x | ) f ( | x | , u , | ∇ u | ) , x ∈ Ω , ∂ u ∂ n = 0 , x ∈ ∂ Ω , lim | x | → ∞ u ( x ) = 0 , $$ \textstyle\begin{cases} -\Delta_{p} u= K( \vert x \vert ) f( \vert x \vert , u, \vert \nabla u \vert ) ,\quad x\in\Omega , \\ \frac{\partial u}{\partial n}=0 ,\quad x\in\partial\Omega, \\ \lim_{ \vert x \vert \to\infty}u(x)=0 , \end{cases} $$ where Ω = { x ∈ R N : | x | > r 0 } $\Omega=\{x\in\mathbb{R}^{N}: |x|>r_{0}\}$ , N ≥ 3 $N\ge3$ , 1 < p ≤ 2 $1< p\le2$ , K : [ r 0 , ∞ ) → R + $K: [r_{0}, \infty)\to\mathbb{R}^{+}$ , and f : [ r 0 , ∞ ) × R × R + → R $f: [r_{0}, \infty)\times\mathbb{R}\times\mathbb{R}^{+}\to \mathbb{R}$ are continuous. Under certain inequality conditions of f, the existence results of radial solutions are obtained.

Objective Red beds are widely used in palaeomagnetic studies as they can carry stable natural remanence. Most previous studies on red beds have mainly focused on lacustrine-fluvial facies, with limited targeting the aeolian red beds. Consequently, the influence of aeolian deposition processes and sedimentary environments on remanence records remains poorly understood. Methods In this study, we conducted a palaeomagnetic investigation of the red beds from the Upper Cretaceous Daijiaping Formation in the Chaling Basin, Hunan Province, China, to compare the stability and reliability of remanence in aeolian and lacustrine-fluvial red beds. Results Rock magnetic results indicate that magnetite, maghemite and hematite are the dominant magnetic remanence carriers. Specimens were subjected to stepwise thermal demagnetization, and only 1/6 of the specimens yielded characteristic remanent magnetisations (ChRMs). Although the mean directions of ChRM in both aeolian(Ds=222.7°, Is=-43.3°, κ=5.9, α95=20.6°, n=11) and lacustrine-fluvial (Ds=204.6°, Is=-47.8°, κ=2.4, α95=23.1°, n=28) samples are statistically indistinguishable, the distribution of individual ChRM directions is scattered, as evidenced by the large α95 values. Thin section observation reveals that the aeolian samples are predominantly composed of fine grains, with some coarser grains and almost no interstitial fillings compared with the lacustrine-fluvial red beds. This makes them susceptible to physical disturbance and subsequent chemical alteration, which compromises the stability of their remanence records. Analysis of palaeomagnetic data of specimens from different positions of an aeolian foreset bed reveals that the reliability of remanence is significantly influenced by aeolian depositional processes in case the angle between the foreset bed and the bedding plane is larger than 20°. Statistical analysis of palaeomagnetic data previously published from the Cretaceous red beds in South China and these in this study suggests that the remanence records in the Cretaceous aeolian red beds in South China tend to be less stable and less reliable, compared with that of the coeval lacustrine-fluvial red beds. It is probably because of their loose structure and low hematite content, which hinders the acquisition of primary remanence and makes them susceptible to diagenetic alteration. Conclusion These findings provide valuable insights for studying the stability and reliability of remanence in aeolian red beds and their application in palaeomagnetic study.

Abstract Background Microbiota alterations are linked with gastric cancer (GC). However, the relationship between the oral microbiota (especially oral fungi) and GC is not known. In this study, we aimed to apply 2b-RAD sequencing for Microbiome (2b-RAD-M) to characterize the oral microbiota in patients with GC. Methods We performed 2b-RAD-M analysis on the saliva and tongue coating of GC patients and healthy controls. We carried out diversity, relative abundance, and composition analyses of saliva and tongue coating bacteria and fungi in the two groups. In addition, indicator analysis, the Gini index, and the mean decrease accuracy were used to identify oral fungal indicators of GC. Results In this study, fungal imbalance in the saliva and tongue coating was observed in the GC group. At the species level, enriched Malassezia globosa (M. globosa) and decreased Saccharomyces cerevisiae (S. cerevisiae) were observed in saliva and tongue coating samples of the GC group. Random forest analysis indicated that M. globosa in saliva and tongue coating samples could serve as biomarkers to diagnose GC. The Gini index and mean decreases in accuracy for M. globosa in saliva and tongue coating samples were the largest. In addition, M. globosa in saliva and tongue coating samples classified GC from the control with areas under the receiver operating curve (AUCs) of 0.976 and 0.846, respectively. Further ecological analysis revealed correlations between oral bacteria and fungi. Conclusion For the first time, our data suggested that changes in oral fungi between GC patients and controls may help deepen our understanding of the complex spectrum of the different microbiotas involved in GC development. Although the cohort size was small, this study is the first to use 2b-RAD-M to reveal that oral M. globosa can be a fungal biomarker for detecting GC.

Abstract The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquire early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogram and reverse the immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells of healthy donors or metastatic female breast cancer patients, induce robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a promising therapy for solid tumors.

The experiment for measuring the solar spectrum at different latitudes and altitudes was conducted to obtain a suitable Air Mass Zero (AM0) standard solar cell calibration strategy with high altitude balloon flight calibration method. This is the world’s first acquisition of solar spectrum data at an altitude of 35 km using high-altitude balloon platform. The solar spectrum at the upper boundary of the atmosphere was measured and the spectral distribution was obtained from 20 to 35 km during the ascent. The results show that spectral distribution at 35 km is almost equivalent to that of AM0, the peak irradiance at 35 km is close to that of AM0, and the highest peak of this spectrum is at 450.2 nm. Comparing the results taken at different altitude, the effect of ozone, oxygen and water vapor is clearly seen. The measurement methods and results discussed in this paper can assist in verifying the accuracy of space solar cell calibration using high-altitude balloons. It could also provide a reference for the design of photovoltaic energy systems for near space aircrafts. Finally, the results taken from the launch site may be of use for the air quality monitoring and the design of photovoltaic system used in ground-based solar power generation in the Qinghai-Tibet Plateau.

This paper discusses the existence of positive radial symmetric solutions of the nonlinear biharmonic equation ▵2u=f(u,▵u) on an annular domain Ω in RN with the Navier boundary conditions u|∂Ω=0 and ▵u|∂Ω=0, where f:R+×R−→R+ is a continuous function. We present some some inequality conditions of f to obtain the existence results of positive radial symmetric solutions. These inequality conditions allow f(ξ,η) to have superlinear or sublinear growth on ξ,η as |(ξ,η)|→0 and ∞. Our discussion is mainly based on the fixed-point index theory in cones.

The conflict between industrial solid waste treatment and environmental protection in Inner Mongolia is becoming increasingly prominent. Using industrial solid waste such as mineral powder, fly ash and wet calcium carbide slag as raw materials, using the alkali excitation method to prepare geopolymer, and replacing part of the cement for pavement base can effectively absorb industrial solid waste and realize the dual goals of waste utilization and environmental protection. Through mechanical properties tests before and after a freeze–thaw cycle and micro tests such as scanning electron microscopy (SEM) and mercury intrusion porosimetry (MIP), the strength variation rule and mechanism of geopolymer-cement stabilized aggregate under freeze–thaw cycles were deeply investigated. The relationship between different porosity indexes and mechanical properties in mercury intrusion porosimetry (MIP) was established by grey relation analysis. The results prove that a mixture with impaired properties after freeze–thaw cycles and the anti-freezing performance of the mixture with 20% geopolymer content are better than that of the mixture with no geopolymer content and 40% geopolymer content. The loss rates of unconfined compressive strength (UCS) after 5, 10 and 20 freeze–thaw cycles were 9.5%, 27.6% and 36.4%, respectively. The appropriate addition of geopolymer can enhance the anti-freezing performance of a stable aggregate. Following freezing and thawing cycles, the unconfined compressive strength (UCS) damage of the mixture is mainly influenced by a rise in total porosity, and the grey correlation degree is 0.75. The increase in more harmful pores and total porosity mainly results in an indirect tensile strength (ITS) loss. The grey correlation degree is 0.91. The compressive rebound modulus (CRM) is not affected by the change in pores but decreases with a rise in the geopolymer dosage.

This paper concerns with the existence of radial solutions of the biharmonic elliptic equation ▵2u=f(|x|,u,|∇u|,▵u) in an annular domain Ω={x∈RN:r1<|x|

The economic friction and political conflicts between some countries and regions have made multinational corporations increasingly focus on the reliability and credibility of manufacturing supply chains. In view of the impact of poor manufacturing entity reliability and service reputation on the new-era manufacturing industry, the time-varying reliability and time-varying credibility of cloud manufacturing (CMfg) services were studied from the perspective of combining nature and society. Taking time-varying reliability, time-varying credibility, composition complexity, composition synergy, execution time, and execution cost as objective functions, a new six-dimension comprehensive evaluation model of service quality was constructed. To solve the optimization problem, this study proposes an improved chaos sparrow search algorithm (ICSSA), where the Bernoulli chaotic mapping formula was introduced to improve the basic sparrow search algorithm (BSSA), and the position calculation formulas of the explorer sparrow and the scouter sparrow were enhanced. The Bernoulli chaotic operator changed the symmetry of the BSSA, increased the uncertainty and randomness of the explorer sparrow position in the new algorithm, and affected the position update and movement strategies of the follower and scouter sparrows. The asymmetric chaotic characteristic brought better global search ability and optimization performance to the ICSSA. The comprehensive performance of the service composition (SvcComp) scheme was evaluated by calculating weighted relative deviation based on six evaluation elements. The WFG and DTLZ series test functions were selected, and the inverse generation distance (IGD) index and hyper volume (HV) index were used to compare and evaluate the convergence and diversity of the ICSSA, BSSA, PSO, SGA, and NSGA-III algorithms through simulation analysis experiments. The test results indicated that the ICSSA outperforms the BSSA, PSO, SGA, and NSGA-III in the vast majority of testing issues. Finally, taking disinfection robot manufacturing tasks as an example, the effectiveness of the proposed CMfg SvcComp optimization model and the ICSSA were verified. The case study results showed that the proposed ICSSA had faster convergence speed and better comprehensive performance for the CMfg SvcComp optimization problem compared with the BSSA, PSO, SGA, and NSGA-III.

AbstractThe swirling transport characteristics of grain particles in bulk grain pipeline after fluidization were studied. A spinning device was designed for the lateral filling pipe. The filling pipe was distributed uniformly along the circumference of the same section of the main pipe, the number was set to 3–7, and the included angles with the main pipe were 20°, 30°, and 40°, respectively. CFD-DEM was used to simulate the swirl transport of grain particles in a horizontal pipeline. The main multiphase inlet velocity was 20 m/s, and the gas velocity was 30 m/s in the side supplementary pipe. By comparing grain conveying speed, flow field pressure drop, and other indicators, it is concluded that when the number of filling pipes is 5, the spiral conveying distance is the longest, the conveying effect is good. By comparing the multiphase flow trajectory, it is concluded that the optimal spiral conveying effect is achieved when the angle between the side filling pipe and the main pipe is 30°. The experimental results show that the number of filling pipes is 5, and the conveying effect is the best when the angle between them and the main pipe is 30°, which is consistent with the simulation results

Abstract Permittivity at microwave frequencies determines the practical applications of microwave dielectric ceramics. The accuracy and universality of the permittivity prediction by Clausius–Mossotti equation depends on the dielectric polarizability (αD) database. The most influential αD database put forward by Shannon is facing three challenges in the 5 G era: (1) Few data, (2) Simplistic relation and (3) Low frequency (kHz–MHz) oriented. Here, we optimized and extended the Shannon’s database for microwave frequencies by the four-stage multiple linear regression and support vector machine model. In comparison with the conventional database, the optimized and extended databases achieved higher accuracy and expanded the amount of data from 60 to more than 900. Besides, we analyzed the relationships between αD and ion characteristics, including ionic radius (IR), atomic number (N), valence state (V) and coordination number (CN). We found that the positive cubic law of “αD ~ IR3” discussed in Shannon’s work was valid for the IR changed by the N, but invalid for the change caused by the CN.

This article discusses the existence and uniqueness of radial solution for the elliptic equation system $ \left \{ \begin{array}{ll} -\triangle u = f(|x|, \ u, \ v, \ |\nabla u|), \; \; x\in \Omega, \\[10pt] -\triangle v = g(|x|, \ u, \ v, \ |\nabla v|), \; \; x\in \Omega, \\[10pt] u|_{\partial \Omega} = 0, \; v|_{\partial \Omega} = 0, \end{array} \right. $ where $ \Omega = \{x\in \mathbb{R}^{N}:\; r_1 < |x| < r_2\}, \; N\ge 3, \; f, \; g:[r_1, \; r_2]\times \mathbb{R}\times \mathbb{R}\times \mathbb{R}^+\to \mathbb{R} $ are continuous. Due to the appearance of the gradient term in the nonlinearity, the equation system has no variational structure and the variational method cannot be applied to it directly. We will give the correlation conditions of $ f $ and $ g $, that is, $ f $ and $ g $ are superlinear or sublinear, and prove the existence and uniqueness of radial solutions by using Leray-Schauder fixed point theorem.

Abstract Objectives Reporting the clinicopathological information of thyroid cancer (TC) patients from a central medical center of east China, and constructing the nomogram predicting lymph node metastasis (LNM). Methods We collected the patients who underwent thyroid cancer surgery in our institute from July 1, 2019 to July 31, 2021, a total of 253 subjects were enrolled. We used HiPure FFPE DNA Kit to extract DNA and RNApure FFPE Kit to extract RNA from the paraffin sections of tumor tissue, the extracted DNA samples and RNA samples were used for NGS sequencing. The clinical and pathological information of TCGA‐THCA cohort was obtained as the validation cohort. Multivariate logistic regression analysis was performed to identify the independent prognostic factor, and the nomogram was subsequently constructed by “rms” R package. Results Secondary cases contained more mutation of BRAF (90.48% vs. 62.07%) and TERT (33.0% vs. 3.0%), as compared with primary cases. Primary patients with positive lymph node were younger (40.9 ± 10.8 vs. 45.3 ± 11.8, p = 0.0031) and contained advanced TI‐RADS levels (4c: 22.8% vs. 8.3%, 5: 6.5% vs. 0/0%, p = 1.878e‐03), as well as more RET genetic alteration (16.3% vs. 2.7%, p = 2.566e‐03). We chose age, tumor diameter, RET fusion, and gender to construct the LNM predicting nomogram. Calibration plot, DCA curve, and the clinical impact plot verified the preferable prognostic value of the nomogram, with an AUC value of 0.724 (0.656–0.792). We successfully validated the prognostic value of the nomogram in TCGA‐THCA cohort. RET fusion might impact the process of protein digestion and absorption, cytokine‐cytokine receptor interaction, ECM‐receptor interaction, focal adhesion. Conclusion We provide a novel nomogram to predict the LNM for TC patients, including the features of patient's age, gender, tumor diameter, and RET alteration. Further studies from multiple medical centers are essential to validate the nomogram.

The pointing accuracy of large radio telescopes is affected by antenna structure errors, installation errors, servo errors, gravity, and varying environmental factors. Although an on-line pointing model had been developed in the past for several large radio telescopes to correct these effects, it is also valuable to explore new ways to correct these effects. Therefore, in order to estimate the dynamic pointing error of large radio telescopes under solar radiation, a new way based on digital twin (DT) is used in this paper. Digital models of the Wuqing 70-m radio telescope (WRT70) are created based on the DT operational framework. Finally, the reliability of the WRT70’s DT system is verified, and the dynamic pointing error of WRT70 (staying at the position of the elevation angle of 90° and the azimuth angle of 180°) on two sunny days in different seasons is estimated by the created DT system. The research results show that the pointing error of large radio telescopes under solar radiation fluctuates greatly and the seasonal differences are very striking. The maximum elevation pointing error of WRT70 under solar radiation around the winter solstice is over 40 arcsec, which is equal to 4/11 of the beam width for WRT70 operating at 8 GHz. In this paper, it is feasible to estimate the time-varying pointing errors of large radio telescopes at rest under solar radiation by constructing a DT system, but it is not effective to estimate the dynamic pointing errors of large radio telescopes in operation. It is expected to establish a dynamic pointing error model and calibrate the dynamic pointing errors of large radio telescopes in operation by DT technology in the future.

PolSAR image classification has attracted extensive significant research in recent decades. Aiming at improving PolSAR classification performance with speckle noise, this paper proposes an active complex-valued convolutional-wavelet neural network by incorporating dual-tree complex wavelet transform (DT-CWT) and Markov random field (MRF). In this approach, DT-CWT is introduced into the complex-valued convolutional neural network to suppress the speckle noise of PolSAR images and maintain the structures of learned feature maps. In addition, by applying active learning (AL), we iteratively select the most informative unlabeled training samples of PolSAR datasets. Moreover, MRF is utilized to obtain spatial local correlation information, which has been proven to be effective in improving classification performance. The experimental results on three benchmark PolSAR datasets demonstrate that the proposed method can achieve a significant classification performance gain in terms of its effectiveness and robustness beyond some state-of-the-art deep learning methods.

Abstract Autonomous long‐duration aerostats (LDA) are one of the most popular research directions of high‐altitude platforms (HAPS) in recent years. Solar photovoltaic (PV) array is the energy source of autonomous long‐duration aerostat, whose power generation predicting accuracy and speed affect the subsequent flight control strategy. Limited by incompleteness cognition of near space, current predicting results cannot meet the requirements of autonomous LDA. In this paper, a novel rapid prediction model of the PV array is proposed. Based on spatial position relation of PV cells, this model can predict the power of single PV cell in any state. The four influence factors including time difference, angle, efficiency loss and temperature are analyzed and optimized comprehensively and innovatively. The new model can be applied in both static state aerostat and dynamic state aerostat. Compared with the traditional model, the efficiency can be improved by 50% and the prediction accuracy can be improved by 10%.

Local electric-field around multitype pores (dielectric pore, interface pore, electrode pore) in multilayer ceramic capacitors (MLCCs) was investigated using Kelvin probe force microscopy combined with the finite element simulation to understand the effect of pores on the electric reliability of MLCCs. Electric-field is found to be concentrated significantly in the vicinity of these pores and the strength of the local electric-field is 1.5–5.0 times of the nominal strength. Unexpectedly, the concentration degree of the pores in the inner electrode is much higher than that in the dielectrics and dielectric-electrode interfaces. Meanwhile, geometry orientations are found to have a remarkable influence on the local electric field strength. The pores act as an insulation degradation precursor via local electric, thermal center, and oxygen vacancies accumulation center. Such unusual local electric field concentration of multitype pores can provide new insights into the understanding of insulation degradation evolution, processing tailoring and design optimization for MLCCs.

The identification of marine alkenones and anomalously high carbonate carbon isotopic values in sediments suggest the Qaidam Basin in the northern Tibetan Plateau was uplifted from sea level to its present altitude since the Mid-Miocene.

Lithium-ion (Li-ion) batteries are widely used in such devices as today’s electrical vehicles, consumer electronics, and unmanned aerial vehicles, and will play a key role in the future. Unexpected Li-ion battery abnormities may result in serious inconvenience and enormous replacement costs. Thus, the diagnostic and prognostic methods play important roles in battery replacement scheduling, maintenance strategy development, and battery failure precaution, However, many published methods are unsuitable for both battery capacity and end-of-discharge. In this paper, a hybrid ensemble approach, integrating k-fold cross validation (k-CV) and genetic algorithm with back-propagation neural network (GA-BPNN), is proposed for capacity and end-of-discharge of Li-ion battery prognostics combined with geometrical features. Geometrical features extracted from charge-discharge cycles of Li-ion batteries are set as the inputs of the neural network. K-fold cross validation is introduced to determine the number of BPNN hidden layer neurons, genetic algorithm is used to initialize and optimize the connection weights and thresholds of BPNN. By the critical geometrical feature extraction and the ensemble BPNN model with k-fold cross validation and genetic algorithm, accurate battery capacity and end-of discharge are accomplished, making the proposed model can potentially be used for real-time estimate for the conditions given in this article. The performance of the proposed approach is demonstrated by using actual Li-ion battery data, which is supplied by the NASA Ames Research Center database.

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons — namely, glucose-inhibited (GI) neurons — paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.

A detailed morphological description and comparative study were conducted on numerous large-sized hamster remains collected from the late Middle Pleistocene Locality 2 of Shanyangzhai (Syz 2), Hebei Province, China. The comparisons reveal that these fossils are highly similar to the extant Tscherskia triton in size and morphology, including the small degree of alternating between the main opposite cusps on M1-3, the presence of axioloph on M3, and mesolophids on m1-2 that are present but seldom reach the lingual margin of the teeth, among other features. However, minor differences between the two still exist. Consequently, all these fossils are designated as a chronosubspecies of the extant species, T. triton varians comb. nov. The skull and molar morphologies of Cricetinus varians and T. triton were meticulously compared to resolve the long-standing debate regarding the validity of Cricetinus Zdansky, 1928 and C. varians Zdansky, 1928. The findings indicate that the differences between the two are slight; as a result, C. varians can only be considered a chronosubspecies of T. triton, i.e., T. triton varians comb. nov., and Cricetinus should be recognized as a junior synonym of Tscherskia. We tentatively propose that, among the seven species once referred to Cricetinus, C. europaeus, C. gritzai, C. janossyi, and C. koufosi should be reassigned to Tscherskia, while C. beremendensis should be transferred to Allocricetus, and C. mesolophidos to Neocricetodon. Excluding Tscherskia sp. from the Late Pliocene Youhe fauna, there are no reliable Tscherskia fossils in China earlier than the Middle Pleistocene. Based on the current evidence, Tscherskia may have originated from Neocricetodon during the Early Pliocene in Europe and subsequently spread to Asia. T. triton is its sole surviving representative, which now exclusively inhabits East Asia.

Abstract Background Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood. Results We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either male or female mice. Interestingly, male mutant mice showed not only decreased food intake but also decreased physical activity, resulting in unchanged body weight. Further, POMC-specific SK3 deficiency impaired glucose balance specifically in female mice but not in male mice. Finally, no sex differences were detected in the expression of SK3 and SK current in total POMC neurons. However, we found higher SK current but lower SK3 positive neuron population in male POMC neurons co-expressing estrogen receptor α (ERα) compared to that in females. Conclusion These results revealed a sexually dimorphic role of SK3 in POMC neurons in both energy and glucose homeostasis independent of body weight control, which was associated with the sex difference of SK current in a subpopulation of POMC + ERα + neurons.

Abstract Cellular senescence is characterized by a tumor-suppressive program as well as a pro-inflammatory secretome. Neutrophils constitute significant compositions of malignancies and play key roles in tumor development. However, the role of senescent neutrophils in cancer progression is presently unexplored. Here, we demonstrate that neutrophils display enhanced senescence in breast cancer patients receiving chemotherapy. The senescent neutrophils produce increased number of exosomes, which confer drug resistance to tumor cells in vitro and in vivo. Mechanistically, senescent neutrophils-derived exosomal piRNA-17560 enhances the expression of fat mass and obesity-associated protein (FTO) in breast cancer cells. The upregulation of FTO further strengthens ZEB1 transcripts stability and expression by decreasing N6-methyladenosine (m6A) RNA methylation, leading to chemoresistance and epithelial-mesenchymal transition (EMT) of tumor cells. Clinically, the level of exosomal piR-17560 correlates with poor chemotherapy response in patients with breast cancer. In addition, YTHDF2 is essential for the posttranscriptional regulation of ZEB1 by piRNA-17560/FTO signaling. Senescent neutrophils secret exosomal piR-17560 in a STAT3-dependent manner. Altogether, this study suggests that senescent neutrophils-derived exosomal piR-17560 confers chemoresistance to tumor cells and senescent neutrophils may serve as a potential therapeutic target in breast cancer.

The rising prevalence of obesity has become a worldwide health concern. Obesity usually occurs when there is an imbalance between energy intake and energy expenditure. However, energy expenditure consists of several components, including metabolism, physical activity, and thermogenesis. Toll-like receptor 4 (TLR4) is a transmembrane pattern recognition receptor, and it is abundantly expressed in the brain. Here, we showed that pro-opiomelanocortin (POMC)-specific deficiency of TLR4 directly modulates brown adipose tissue thermogenesis and lipid homeostasis in a sex-dependent manner. Deleting TLR4 in POMC neurons is sufficient to increase energy expenditure and thermogenesis resulting in reduced body weight in male mice. POMC neuron is a subpopulation of tyrosine hydroxylase neurons and projects into brown adipose tissue, which regulates the activity of sympathetic nervous system and contributes to thermogenesis in POMC-TLR4-KO male mice. By contrast, deleting TLR4 in POMC neurons decreases energy expenditure and increases body weight in female mice, which affects lipolysis of white adipose tissue (WAT). Mechanistically, TLR4 KO decreases the expression of the adipose triglyceride lipase and lipolytic enzyme hormone-sensitive lipase in WAT in female mice. Furthermore, the function of immune-related signaling pathway in WAT is inhibited because of obesity, which exacerbates the development of obesity reversely. Together, these results demonstrate that TLR4 in POMC neurons regulates thermogenesis and lipid balance in a sex-dependent manner.

The immune function of the intestinal mucosa plays a crucial role in the intestinal health of hosts. As signaling molecules and precursors of metabolic reactions, intestinal chyme metabolites are instrumental in maintaining host immune homeostasis. Saba (SB) pigs, a unique local pig species in central Yunnan Province, China. However, research on jejunal metabolites in this species is limited. Here, we used immunohistochemistry and untargeted metabolomics by liquid chromatography mass spectrometry (LC-MS/MS) to study differences in jejunal immunophenotypes and metabolites between six Landrace (LA) and six SB piglets (35 days old). The results showed that the levels of the anti-inflammatory factor interleukin 10 (IL-10) were markedly higher in SB piglets than in LA piglets (P < 0.01), while the levels of the proinflammatory factors IL-6, IL-1β, and Toll-like receptor 2 (TLR-2) were markedly lower (P < 0.01). Furthermore, the levels of mucin 2 (MUC2) and zona occludens (ZO-1), which are related to mucosal barrier function, were significantly higher in SB piglets than in LA piglets (P < 0.01), as were villus height, villus height/crypt depth ratio, and goblet cell number (P < 0.05). Differences in jejunal chyme metabolic patterns were observed between the two piglets. In the negative ion mode, cholic acid metabolites ranked in the top 20 and represented 25% of the total. Taurodeoxycholic acid (TDCA) content was significantly higher in SB piglets than in LA piglets (P < 0.01). TDCA positively correlated with ZO-1, villus height, villus height/crypt depth ratio, and goblet cell number. These results suggest that SB pigs have a strong jejunal immune function and that TDCA was positively regulates jejunal immunity and mucosal barrier function. Our findings provide a reference for understanding intestinal immune function in different pig breeds and for the discovery of potential biomarkers to help solve health issues related to pig production.

In view of the prominent problem that nonlinear vibration of a belt conveyor can easily occur during the vertical grain-conveyance process due to the coupling effect of airflow clamping and traction of the conveyor belt, which seriously affects the efficiency and stability of conveying materials by the belt conveyor, a method of solving the vibration analysis of the vertical lifting section of the bulk grain belt unloader by using nonlinear vibration is proposed. Firstly, based on the laminated plate theory, the vertical lifting belt and the grain material clamped by the belt are laminated. The nonlinear vibration differential equation of the vertical lifting section of the bulk grain-carrying ship unloader is established by elastic–plastic mechanics, and solved by perturbation theory and Galerkin discrete analysis. The vibration response curve and structural natural frequency of the vertical lifting section of the bulk grain-carrying machine are obtained by numerical solution, and the influence of the volume content of the clamped material on the vibration response and structural natural frequency of the lifting section is analyzed. This study provides theoretical support for the design of pressure-supply parameters, overall structure and operation parameters of the subsequent entrainment ship unloader, promotes the rapid development of the entrainment ship unloader, provides theoretical support for the design, manufacture, later operation, and maintenance of the entrainment ship unloader, and thus provides equipment and technical support for building an efficient and intelligent port.

Understanding how drought is impacted by both natural and human influences is crucial to the sustainable utilization and protection of water resources. We established a drought severity index (DSI) based on the terrestrial water storage anomaly (TWSA) derived from the GRACE satellite to detect drought characteristics and trends over ten major river basins in China from 2002 to 2017. The influence of natural factors (terrestrial water storage components, precipitation, evapotranspiration, runoff, NDVI, and teleconnection factors (ENSO, PDO, NAO, and AO)) and a human factor (LULC) on drought were investigated and quantified from the perspective of water storage components based on the Theil–Sen trend and Mann–Kendall test method, the perspective of climate change based on cross wavelet transforms, and the perspective of water balance based on Random Forest. The results indicated that (1) almost all humid and arid basins experienced major drought periods during 2002–2006 and 2014–2017, respectively. The southern IRB and central YZRB regions exhibited notable declines in DSI trends, while the majority of the HLRB, IRB, LRB, YRB, HRB, and SWRB experienced significant increases in DSI trends; (2) abnormal groundwater decreases were the main cause of drought triggered by insufficient terrestrial water storage in most basins; (3) ENSO was the strongest teleconnection factor in most humid basins, and NAO, PDO, and AO were the strongest teleconnection factors in the arid basins and PRB. Most significant resonance cycles lasted 12–64 months in 2005–2014; and (4) the influence of an anthropogenic driver (LULC) has become as important as, or more important than, natural factors (runoff and teleconnection factors) on hydrological drought.

Abstract Objective The present study comparatively analyzed short-term clinical effectiveness and long-term follow-up endpoints associated with robotic-assisted sphincter-preserving surgery (RAS) and laparoscopic-assisted sphincter-preserving surgery (LAS) when used to treat low rectal cancer. Method Within such a single-center retrospective cohort analysis, low rectal cancer patients that underwent RAS (n=200) or LAS (n=486) between January 2015 and beginning of July 2018 were enrolled. Results The mean operative durations in the RAS and LAS cohorts were 249±64 min and 203±47 min, respectively (P 6 months post-surgery (P

Abstract Emerging evidence indicated that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) exert critical effects on tumorigenesis of multiple malignancies, including gastric cancer (GC). We aim to explore the effects of long intergenic non-protein coding RNA 467 (LINC00467) and miR-27b-3p on GC. GC cells were initially cultured. LINC00467, miR-27b-3p, and signal transducer and activator of transcription 3 (STAT3) expression in GC were detected. The altered LINC00467 and/or miR-27b-3p were transfected into screened cells. Then, the biological activities of GC cells and the tumor growth in vivo were examined. The binding relationships among LINC00467, miR-27b-3p, and STAT3 were confirmed. It was indicated that LINC00467 was increased while miR-27b-3p was decreased in GC tissues and cells. Inhibition of LINC00467 hindered GC cell malignancy and blocked tumor development by upregulating miR-27b-3p. LINC00467 sponged miR-27b-3p and STAT3 was targeted by miR-27b-3p. It was discovered that LINC00467 reduction upregulates miR-27b-3p to repress malignant GC cell growth via inhibiting STAT3. This research may deepen the insight of molecular mechanisms on GC.

Abstract Common hepatic artery pseudoaneurysm is a rare and potentially life‐threatening complication after pancreaticoduodenectomy, and the possible cause is unclear. We report a case of intraperitoneal hemorrhage after pancreaticoduodenectomy who was discharged after embolization under digital subtraction angiography. We conside that this complication may be related to iatrogenic injury.

With the improvement of consumers' requirements for pork quality, the method of crossbreeding with excellent local pig breeds to improve meat quality is popular. Saba pig has high reproduction rate, good meat quality and high utilization rate of roughage, but its excellent characteristics have not been fully developed and utilized. To promote the development and utilization of Saba pigs and production of high-quality pork, the meat quality traits and glycolysis potential of Duroc × (Landrace × Yorkshire) (DLY), Berkshire × (Duroc × Saba) (BDS), and Duroc × (Berkshire × Saba) (DBS) three-way crossbred pigs were compared. The results showed that DLY had the highest live weight, carcass weight, lean meat percentage, drip loss, glycolysis potential, muscle diameter, and relative mRNA expression levels of type IIb muscle fibers as well as the lowest ultimate pH (p < 0.05). The lightness value of DBS was the highest (p < 0.05). Among the three crossbred pigs, myristic, arachidic, palmitoleic, and eicosenoic acids were the highest in BDS. These results indicated that the carcass traits of local crossbred pigs were worse than those of DLY pigs, but meat quality was markedly higher, with BDS showing the best meat quality.

Seminal roots play an important role in acquisition of water and nutrients by maize seedlings. Compared with its teosinte ancestor, maize underwent a change in seminal root number (SRN). Although several key genes controlling SRN have been cloned, identification and utilization of new genes from teosinte would be useful for improving maize root architecture. In this study, a maize-teosinte BC2F6 population containing 206 individuals genotyped by resequencing was used to conduct high-resolution quantitative trait locus (QTL) mapping of SRN. A new major QTL on chromosome 7 (qSRN7) was identified. Differentially expressed genes (DEGs) based on RNA-Seq were identified between two inbred lines with no SRN and multiple SRN at two periods of seminal roots primordia formation. A total of 116 DEGs detected in at least one period were identified within the qSRN7 interval. Three DEGs (Zm00001d021572, Zm00001d021579 and Zm00001d021861) associated with SRN were identified through regional association mapping. When compared with reported domestication-related selective sweeps, Zm00001d021572 was selected during maize domestication. Our findings provide important insights into the genetic basis of SRN and identify a promising candidate gene for further studies on SRN.

Sorafenib, a tyrosine kinase inhibitor, has an important antitumor effect as a ferroptosis inducer in multiple cancers, including gastric cancer (GC). However, the status of sorafenib as a ferroptosis inducer has recently been questioned. There is very limited information about the relationship between ferroptosis and ATF2, and the role of ATF2 in sorafenib-induced ferroptosis has not been studied. In this study, we investigated the role and underlying molecular mechanisms of ATF2 in sorafenib-induced ferroptosis in GC. We found that ATF2 was significantly upregulated in GC tissues and predicted a poor clinical prognosis. Silencing ATF2 significantly inhibited the malignant phenotype of GC cells. In addition, we observed that ATF2 was activated during sorafenib-induced ferroptosis in GC cells. ATF2 knockdown promoted sorafenib-induced ferroptosis, while ATF2 overexpression showed the opposite results in GC cells. Using ChIP-Seq and RNA-Seq, we identified HSPH1 as a target of ATF2 and further validated it by ChIP‒qPCR analysis. HSPH1 can interact with SLC7A11 (cystine/glutamate transporter) and increase its protein stability. Importantly, knockdown of HSPH1 partly reversed the effects caused by ATF2 overexpression on sorafenib-induced ferroptosis in GC cells. In addition, the results from the tumor xenograft model showed that ATF2 knockdown can effectively enhance sorafenib sensitivity in vivo. Collectively, our study reveals a novel mechanism by which sorafenib induces ferroptosis in GC.

Compared with other energy sources in the near-space, solar energy is more renewable, stable, and accessible, which makes solar cells the main source of energy for long-endurance near-space vehicles. However, due to the limited solar cells laying area and complex flight conditions, near-space vehicles are facing tense energy supply situation during flight. Therefore, fast and accurately online power prediction of the solar array, which has important significance for power management, efficient use, and reliable operation of the energy system, is the key point to solving the situation at present. In this paper, a hybrid online power prediction method combined particle filter and power calculation model is proposed. Firstly, a comprehensive solar cell array power calculation model for the near-space vehicle is established. Then, the particle filter algorithm is used to estimate optimally the important parameters in the power calculation model with the flight data, to realize the dynamic, rapid, and accurate prediction of the power generation of the vehicle during flight. Finally, the data obtained from flight tests of the stratospheric aerostat and high-altitude scientific balloon are verified and compared with the other four models. The results demonstrate that the generation power prediction method proposed in this paper has higher prediction accuracy, which will be a good guiding significance for the actual flight of different types of near-space vehicles.

Three-port converter (TPC) with non-regulated bus cannot meet the voltage stability demands of high-altitude platforms (HAPs) during daytime operations. In contrast, full-regulated bus TPC is complex in topology and inferior in power density, although it can maintain voltage stability across whole day operations. Therefore, semi-regulated bus TPCs are more suitable for this scenario, which can not only maintain voltage stability during daytime operations, but also have simple topology. However, conventional semi-regulated bus structure converts the power twice, leading to lower efficiency and power density. In order to overcome this problem, the paper proposes a novel semi-regulated bus TPC that can be used on high-altitude platforms. The topology only has one conversion between the ports. It regulates the bus voltage during the day and prevents the loss of diode during the night by directly discharging through the MOSFET and achieving high efficiency. The paper adopts GaN devices to elevate the working frequency to further improve the power density, and conduct a theoretical analysis for all working modes and provide key equations. The closed-loop transfer function of the system is deduced for stability analysis. The results show that the proposed topology has high efficiency and power density.

Low permittivity microwave dielectric ceramics (MWDCs) are attracting great interest because of their promising applications in the new era of 5G and IoT. Although theoretical rules and computational methods are of practical use for permittivity prediction, unsatisfactory predictability and universality impede rational design of new high-performance materials. In this work, based on a dataset of 254 single-phase microwave dielectric ceramics (MWDCs), machine learning (ML) methods established a high accuracy model for permittivity prediction and gave insights of quantitative chemistry/structure-property relationships. We employed five commonly-used algorithms, and introduced 32 intrinsic chemical, structural and thermodynamic features which have correlations with permittivity for modeling. Machine learning results help identify the permittivity decisive factors, including polarizability per unit volume, average bond length, and average cell volume per atom. The feature-property relationships were discussed. The optimal model constructed by support vector regression with radial basis function kernel was validated its superior predictability and generalization by verification dataset. Low permittivity material systems were screened from a dataset of ∼3300 materials without reported microwave permittivity by high-throughput prediction using optimal model. Several predicted low permittivity ceramics were synthesized, and the experimental results agree well with ML prediction, which confirmed the reliability of the prediction model.

Abstract Energy savings and environmental protection are the only way for the sustainable development of the automotive industry. The poor shifting performance of automobile transmission may reduce the driver's driving pleasure and make the driver feel tired. In addition, improper shifting would also increase fuel consumption. Therefore, in view of the importance of improving the shift performance of vehicle transmission, GSA testing technology was employed for the existing shift quality problems of commercial vehicles to continuously realize high shifting efficiency and low fuel consumption. Through the establishment of subjective and objective evaluation criteria of the experimentally determined shift performance of commercial vehicles, a reliable theoretical basis is provided for product optimization design and shift performance evaluation. As a result, the shift control strategy and optimization matching measures are formulated to ensure that the power, smoothness and transmission of the whole vehicle system meet the technical requirements and finally achieve a rapid and stable gearshift. Thus, this work unveils the high potential of improving the shift performance and quality of the whole vehicle and is expected to have an impact on reducing fuel consumption and emissions in the relevant automotive industry, contributing to the establishment of a more sustainable society.

Background: Peripheral arterial occlusive disease (PAOD) is a peripheral artery disorder that increases with age and often leads to an elevated risk of cardiovascular events. The purposes of this study were to explore the underlying competing endogenous RNA (ceRNA)-related mechanism of PAOD and identify the corresponding immune cell infiltration patterns.Methods: An available gene expression profile (GSE57691 datasets) was downloaded from the GEO database. Differentially expressed (DE) mRNAs and lncRNAs were screened between 9 PAOD and 10 control samples. Then, the lncRNA-miRNA-mRNA ceRNA network was constructed on the basis of the interactions generated from the miRcode, TargetScan, miRDB, and miRTarBase databases. The functional enrichment and protein–protein interaction analyses of mRNAs in the ceRNA network were performed. Immune-related core mRNAs were screened out through the Venn method. The compositional patterns of the 22 types of immune cell fraction in PAOD were estimated through the CIBERSORT algorithm. The final ceRNA network and immune infiltration were validated using clinical tissue samples. Finally, the correlation between immune cells and mRNAs in the final ceRNA network was analyzed.Results: Totally, 67 DE_lncRNAs and 1197 DE_mRNAs were identified, of which 130 DE_mRNAs (91 downregulated and 39 upregulated) were lncRNA-related. The gene ontology enrichment analysis showed that those down- and upregulated genes were involved in dephosphorylation and regulation of translation, respectively. The final immune-related core ceRNA network included one lncRNA (LINC00221), two miRNAs (miR-17-5p and miR-20b-5p), and one mRNA (CREB1). Meanwhile, we found that monocytes and M1 macrophages were the main immune cell subpopulations in PAOD. After verification, these predictions were consistent with experimental results. Moreover, CREB1 was positively correlated with naive B cells (R = 0.55, p = 0.035) and monocytes (R = 0.52, p = 0.049) and negatively correlated with M1 macrophages (R = −0.72, p = 0.004), resting mast cells (R = −0.66, p = 0.009), memory B cells (R = −0.55, p = 0.035), and plasma cells (R = −0.52, p = 0.047).Conclusion: In general, we proposed that the immune-related core ceRNA network (LINC00221, miR-17-5p, miR-20b-5p, and CREB1) and infiltrating immune cells (monocytes and M1 macrophages) could help further explore the molecular mechanisms of PAOD.

This paper deals with the existence of positive radial solutions of the $ p $-Laplace equation $ \left\{\begin{array}{ll} -\Delta_p\,u= K(|x|)\,f(u)\,,\quad x\in\Omega\,,\qquad\qquad\\[6pt] \frac{\partial u}{\partial n}=0\,,\qquad x\in\partial\Omega,\\[6pt] \lim_{|x|\to\infty}u(x)=0\,, \end{array}\right. $ where $ \Omega = \{x\in {\mathbb{R}}^N:\, |x| > r_0\} $, $ N\ge 2 $, $ 1 < p < N $, $ K: [r_0, \, \infty)\to {\mathbb{R}}^+ $ is continuous and $ 0 < \int_{r_0}^{\infty}r^{N-1}K(r)\, dr < \infty $, $ f\in C({\mathbb{R}}^+, \, {\mathbb{R}}^+) $. Under the inequality conditions related to the asymptotic behaviour of $ f(u)/u^{p-1} $ at $ 0 $ and infinity, the existence results of positive radial solutions are obtained. The discussion is based on the fixed point index theory in cones.

Abstract The aim of this paper is to consider a fully cantilever beam equation with one end fixed and the other connected to a resilient supporting device, that is, { u ( 4 ) ( t ) = f ( t , u ( t ) , u ′ ( t ) , u ″ ( t ) , u ‴ ( t ) ) , t ∈ [ 0 , 1 ] , u ( 0 ) = u ′ ( 0 ) = 0 , u ″ ( 1 ) = 0 , u ‴ ( 1 ) = g ( u ( 1 ) ) , $$ \textstyle\begin{cases} u^{(4)}(t)=f(t,u(t),u'(t),u''(t),u'''(t)), \quad t\in [0,1], \\ u(0)=u'(0)=0, \\ u''(1)=0,\qquad u'''(1)=g(u(1)), \end{cases} $$ where f : [ 0 , 1 ] × R 4 → R $f:[0,1]\times \mathbb{R}^{4}\rightarrow \mathbb{R}$ , g : R → R $g: \mathbb{R}\rightarrow \mathbb{R}$ are continuous functions. Under the assumption of monotonicity, two existence results for solutions are acquired with the monotone iterative technique and the auxiliary truncated function method.

Pro-opiomelanocortin (POMC) neurons are important for the regulation of body weight and glucose balance. The inhibitory tone to POMC neurons is mediated primarily by the GABA receptors. However, the detailed mechanisms and functions of GABA receptors are not well understood. The α5 subunit of GABAA receptor, Gabra5, is reported to regulate feeding, and we found that Gabra5 is highly expressed in POMC neurons. To explore the function of Gabra5 in POMC neurons, we knocked down Gabra5 specifically from mature hypothalamic POMC neurons using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 strategy. This POMC-specific knock-down of Gabra5 did not affect body weight or food intake in either male or female mice. Interestingly, the loss of Gabra5 caused significant increases in the firing frequency and resting membrane potential, and a decrease in the amplitude of the miniature inhibitory postsynaptic current (mIPSC) in male POMC neurons. However, the loss of Gabra5 only modestly decreased the frequency of mIPSC in female POMC neurons. Consistently, POMC-specific knock-down of Gabra5 significantly improved glucose tolerance in male mice but not in female mice. These results revealed a sexually dimorphic role of Gabra5 in POMC neuron activity and glucose balance, independent of body weight control.

Due to the more demanding quality requirements for the vehicle manipulating comfort imposed by the market in recent years, the driver's feeling during gear shifting has become very important in the design stage of the shifting systems. This paper combines the ergonomics theory with the vehicle shifting device, and expounds the application and practice of the ergonomics in the innovative design of the vehicle shifting device. Firstly, GSA analysis system is used to pre-evaluate the static and dynamic shifting performance of the whole vehicle, and analyzes the shifting device of the vehicle transmission according to ergonomics theory. And then the corresponding improvement measures are put forward for the existing defects in the shifting device. Finally, the post-test analysis is carried out to verify the effectiveness in improving the driving experience of the whole vehicle, and ultimately enhance the competitiveness of the studied shifting device in the vehicle industry.

Abstract Background Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines. Methods The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro. Results INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein. Conclusions These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells.

Antibiotic resistance genes (ARGs) are emerging environmental contaminants that threaten human and animal health. Intestinal microbiota may be an important ARGs repository, and intensive animal farming is a likely contributor to the environmental burden of ARGs. Using metagenomic sequencing, we investigated the structure, function, and drug resistance of the jejunal microbial community in Landrace (LA, Kunming), Saba (SB, Kunming), Dahe (DH, Qujing), and Diannan small-ear piglets (DS, Xishuangbanna) from different areas in Yunnan Province, China. Remarkable differences in jejunal microbial diversity among the different pig breeds, while the microbial composition of pig breeds in close areas tends to be similar. Functional analysis showed that there were abundant metabolic pathways and carbohydrate enzymes in all samples. In total, 32,487 ARGs were detected in all samples, which showed resistance to 38 categories of drugs. The abundance of ARGs in jejunum was not significantly different between LA and SB from the same area, but significantly different between DS, DH and LA or SB from different areas. Therefore, the abundance of ARGs was little affected by pig breeds and microorganism community structure, but it was closely related to geographical location. In addition, as a probiotic, Lactobacillus amylovorus is also an important ARGs producing bacterium. Our results revealed the antibiotic exposure and intestinal microbial resistance of farms in the study areas, which could provide basic knowledge and potential strategies for rational use of antibiotics and reducing the risk of ARGs transmission in animal husbandry.