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Jing Yu,1,* Xi Zhang,1,2,* Qiyue Huang,1 Sirui Tan,1 Xianze Xiong,3 Hongfeng Gou1 1Department of Abdominal Cancer, West China Medical School, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Radiotherapy, The Affiliated Hospital of Hebei University, Baoding, 07100, People’s Republic of China; 3Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongfeng GouDepartment of Abdominal Cancer, West China Medical School, Cancer Center, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaTel +86-28-85422589Fax +86-28-85423609Email gouhongfeng1977@wchscu.cnXianze XiongDepartment of Bile Duct Surgery, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaEmail xianzexiong123@163.comPurpose: The patients with advanced mismatch repair deficiency (dMMR) cancers can benefit from programmed cell death 1 (PD-1) pathway blockade, regardless of the tumor type. Little is known about the prevalence of dMMR in intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (cHCC-CC). This study aimed to assess the mismatch repair (MMR)-related protein expression in patients with ICC and cHCC-CC.Patients and Methods: Formalin-fixed, paraffin-embedded tumor specimens were obtained from patients undergoing surgery at the West china Hospital between 2009 and 2017. The immunoreactions for MLH1, MSH2, MSH6, and PMS2 were investigated to determine the MMR status.Results: A total of 97 patients were evaluated, including 73 ICC patients and 24 cHCC-CC patients. The prevalence of dMMR was only found in two cases of 97 patients (2.06%). Both patients are ICC. In 24 cHCC-CC patients, no dMMR was observed. They did not receive an adjuvant chemotherapy after surgery. At the end of the follow-up, one patient was in a tumor-free state, and the other patient had local recurrence and metastasis. After receiving sintilimumab (an immune checkpoint inhibitor [ICI] for PD- 1), the patient had a partial response.Conclusion: DMMR was detected in few patients with ICC and cHCC-CC. Thus, it is not recommended to routinely evaluate the MMR status of patients with ICC or cHCC-CC after surgery, but that of patients with advanced ICC or cHCC-CC should be assessed.Keywords: mismatch-repair deficiency, intrahepatic cholangiocarcinoma, combined hepatocellular-cholangiocarcinoma, immune checkpoint inhibitors, prognosis

A new technique with carburization followed by magnetic separation is presented for the preparation of high-grade iron carbide from pyrite cinder to promote the high value-added utilization of pyrite cinder. The effects of carburizing temperature, carburizing time and Na2SO4 dosage on carburized pellets were investigated, and the effects of Na2SO4 dosage and grinding fineness on magnetic concentrate were carried out. The optimized process parameters were proposed as follows: carburizing at 650°C for 180 minutes in CO-CO2-H2 gas mixtures, Na2SO4 dosage of 9%, magnetic field intensity of 130 mT, and grinding fineness of 92.25% powder passing 0.025mm. The iron content, total carbon content, total iron and carbon content of magnetic concentrate were 82.62%, 5.60%, and 88.22%, respectively. The recovery rate of iron reached 88.67%. The behaviors and mechanisms of carburization, separation, and Na2SO4, were ascertained with optical microscopy, X-ray powder diffraction (XRD), and scanning electron microscope (SEM).

Determining the shear‐velocity dependence of dry granular friction can provide insight into the controlling variables in a dry granular friction law. Some laboratories believe that the quality of this study is at the forefront of the discipline for the following reasons. Results suggest that granular friction is greatly affected by shear‐velocity (v), but shear experiments over the large range of naturally occurring shear‐velocities are lacking. Herein we examined the shear velocity dependence of dry friction for three granular materials, quartz sand, glass beads and fluorspar, across nine orders of magnitude of shear velocity (10−8–2 m/s). Within this range, granular friction exhibited four regimes, following a broad approximate "m" shape including two velocity‐strengthening and two velocity‐weakening regimes. We discuss the possible physical mechanisms of each regime. This shear velocity dependence appeared to be universal for all particle types, shapes, sizes, and for all normal stresses over the tested range. We also found that ultra‐high frequency vibration as grain surfaces were scoured by micro‐chips were formed by spalling at high shear velocities, creating ∼20 μm diameter impact pits on particle surfaces. This study provides laboratory laws of a friction‐velocity (μ‐v) model for granular materials. Plain Language Summary: Numerous phenomena of earth science can be simplified to shearing granular systems, such as landslide gouge and rock avalanches. It is believed that friction varies with shear velocity, and this is no exception for dry granular materials. Studying the law of friction variation over as large a range of velocity changes as possible aids in establishing a full life‐cycle hypothesis for landslides from initiation, through movement to cessation. We sheared granular materials across nine orders of magnitude, from 10−8 to 2 m/s and obtained an "M" shape law for the variation of friction with velocity. By analyzing the acoustic frequency of shear experiments at different velocities, we discovered that the acoustic frequency increased with shear velocity. By comparing the microscopic morphology of the particle surface before and after high‐velocity shearing, we hypothesized that the impact pits may be left by particle collisions during high‐velocity shearing. We proposed that the role of ultra‐high frequency vibration on high‐velocity shear weakening should be considered, which provides a basis for accurately revealing the physical mechanism of granular friction variation with velocity. Key Points: This paper examines the shear velocity dependence of friction for dry granular materials, across nine orders of magnitude in shear velocity (10−8–2 m/s)An "M‐shaped" law for the variation of friction with velocity is obtained including two velocity‐strengthening and two velocity‐weakening lawsThere is microscopic evidence that ultra‐high frequency vibration may cause high velocity shear weakening [ABSTRACT FROM AUTHOR]

Stress accumulation and release reflected by acoustic emissions (AEs) during shearing of granular materials provide important information on failure mechanisms in seismic faults and landslides controlled by stick‐slip. Among many characteristics (amplitude, energy, counts, and frequency) of AE signals generated by stick‐slip, stress changes corresponding to various frequency AEs in different stages of the stick‐slip process are not clear, which limits our knowledge of the characteristics of precursory signals before stick‐slip failure. To better understand the physical mechanisms of granular stick‐slip, we monitored the mechanical and AE signals using high‐frequency (2 MHz) synchronous acquisition during constant‐speed shear of packs of uniform glass beads with different sizes at different normal stresses. The release rate of AE energy was found to accelerate with the dilatation of the sample volume, and the stress drop of stick‐slip was augmented with the increase of normal stress and particle size. Three characteristic events of single cycle stick‐slip were observed in this study: main slip, minor slip, and microslip. We analyzed the AE frequency spectra of these three event types. Both main slip and minor slip corresponded to stress drop and generated high‐frequency AEs (about several hundred kHz), while the AE frequencies generated by microslip were lower (about tens of kHz) and exhibited stress strengthening, which were not apparent in previous studies due to the low frequency of acquisition. We propose that the microslip is mainly due to sliding on grain contacts, while the main slip and minor slip resulted from breakage and reforming of force chains. Low‐frequency AEs from microslip may suggest a crucial precursor of seismic faults and landslides. Plain Language Summary: The occurrence of earthquakes of similar magnitude (quasi‐periodic earthquakes) in a fault zone every few decades is thought to be controlled by stick‐slip of fault gouges. The mechanical evolution of fault gouges prior to earthquake occurrence is extremely complex and difficult to predict. However, many studies have observed the presence of significant microslip prior to stick‐slip failure of seismic faults, which may provide precursor information for an impending earthquake. Laboratory study of stick‐slip nucleation and failure mechanisms in granular materials provides important understanding of the physical mechanisms of quasi‐periodic earthquakes. Our experimental results of high‐frequency acoustic emission (AE) and ring‐shear simultaneous acquisition showed that stick‐slip failure (corresponding to the occurrence of an earthquake) leads to a decrease in the shear resistance of a granular system, generating high‐frequency acoustic signals. Increments of microslip increased the shear resistance of the granular system, and were recorded as low‐frequency acoustic signals before failure occurred. We suggest that the stick‐slip nucleation and failure were controlled by grain friction and collision, respectively. The different AE frequencies of the two may shed light on the precursor monitoring of quasi‐periodic earthquakes. Key Points: Stick‐slip failure was associated with high‐frequency (∼105 Hz) acoustic emissions (AEs) and micro‐slip during stick‐slip nucleation was associated with low‐frequency (∼104 Hz) AEsHigh‐frequency AEs may be caused by particle collisions after force‐chain breakageLow‐frequency AEs may be caused by particle friction during force‐chain adjustment and may suggest important precursors of laboratory earthquakes [ABSTRACT FROM AUTHOR]

Objective Multiple types of oil reservoirs, including conventional oil, tight oil, and shale oil, have been discovered from the slope area to the depression area in the Jimusaer Depression, demonstrating the characteristics of conventional–unconventional ordered coexistence and complete oil and gas system accumulation. Methods Source rocks, sedimentary reservoirs, and reservoir formation were examined to explore the rules of oil and gas accumulation in hydrocarbon-rich depressions in the Eastern Junggar. Results High-quality, saline, lacustrine facies source rocks are believed to be developed in the Middle Permian of the Eastern Junggar. The source rocks in the Jinan, Jimusaer, and Shishugou Depressions have large scale and best quality and have reached the mature stage of evolution. The inherited ancient uplifts around the Permian hydrocarbon-rich depression provided long-term material sources, with the development of fan deltas, braided river deltas, and saline lake sediments, forming sandy conglomerates, cloudy sandstones, cloudy mudstones, etc., in an orderly manner and demonstrating the characteristics of grain sequence reservoir formation. Conventional oil and gas, tight oil and gas, and shale oil and gas accumulations, demonstrating a complete type of reservoir formation and complete oil and gas system development pattern, are developed from the edge of the basin to the depression area. Conclusions The depressions in the Eastern Junggar Basin show a whole oil and gas system pattern. Significance Under the guidance of the entire oil and gas system reservoir formation model, the southern slope of the Shishugou Sag and the Lucaogou Formation of the Jinan Sag were selected as important exploration zones for future exploration in the Eastern Junggar.

【Objective】 Irrigation water use efficiency is an important parameter in irrigation design. It depends on various factors. In this paper, we compared irrigation water use efficiency calculated using the whole-process method and the head-tail method, from which we further studied the factors that influence water loss in irrigation districts. 【Method】 The study area was Zhongjiang County in Sichuan province. We divided the county into four regions (represented by TW, TH, ON and FO), each region having its typical canal systems and field conditions. The whole-process method calculated the irrigation water use efficiency in each region using a combination of hydrodynamic method, empirical formula and irrigation experiments. The head-tail method calculated the total irrigation amount in each region first by measuring the water flowing into and out of the region at the heads and tails, respectively, as well as other water sources flowing into and out of the region; these, along with the irrigation water consumed by crops, were used to calculate the irrigation water use efficiency. 【Result】 The canal water use efficiency in the largest TW regions was 0.596 and the smallest TH regions was 0.564, with a weight-average of 0.580. The water use coefficient in ON and TW regions in the north of the county was 0.90, thanks to their good hydraulic engineering projects. Affected by their topography, the water use coefficient in the TH and FO regions was 0.85. When the required irrigation guarantee was 75%, the irrigation water use efficiency calculated by the whole-process method was 0.503, compared to 0.492 calculated by the head-tail method. 【Conclusion】 The irrigation water use efficiency calculated by the two methods is comparable and their results are reasonable. The proposed method and the results can help to improve irrigation water use efficiency in regions where the irrigation water use efficiency is currently lower than the national average.

Using a gradient descent algorithm, a study on the linkage between strategic human resource management and organizational effectiveness. A logarithmic function with a base of 10 is used to represent the useful value of the fused elements of the association and simplify the expression formula for the usefulness of management. The usefulness of the management approach in achieving organizational effectiveness is measured using the information gain approach. The square of the difference between the predicted and true values is used as the loss function value, and the gradient descent algorithm is combined with the gradient descent algorithm to divide the effective joint data and calculate the solution gradient for all samples. Evaluation indexes such as accuracy and recall test the joint degree effective prediction model. The results show that the usefulness of the joint degree effective prediction model is classified into three degree levels: average [0,0.2), useful [0.2,0.4), and 40% or more as very useful. The team’s organizational commitment results in 50% of employees working hard, and only 5% are unmotivated to work.

Experimental animals have made important contributions to human medical research and life and health. It is known that the development of laboratory animal science in Japan has been relatively rapid in the past few decades, providing important support for the development of the world's experimental animal field. Therefore, it is of great significance to understand the management mode and resource storage situation of Japanese experimental animals, analyze the advantages of Japanese experimental animal development, and propose suggestions to strengthen the high-quality development of experimental animals in China. Through literature research, the authors first analyzed the management system of experimental animals in Japan, including regulations and policies, research funding management, experimental animal management, talent cultivation, and standard and normative systems. Then, the current status of experimental animal research in Japan was summarized, including experimental animal resources, major research institutions, and production enterprises. On this basis, it was found that the field of experimental animal research in Japan currently exhibits characteristics such as a complete policy system, flexible management methods, rich resource reserves, and large-scale industrial development. Finally, by comparing the existing problems in China, suggestions for the development of experimental animal technology in China are proposed: (1) drawing on the legal management method of experimental animals in Japan, strengthening and improving the legislation and management model of experimental animals in China; (2) increaseing investment in scientific research funds, playing the role of research institutions, societies and industries, and promoting the incremental construction and industrial development of experimental animal resources.

Listeria monocytogenes is a widespread foodborne pathogen contaminating foods during their production or processing stages. Fresh meat is susceptible to such contamination if it is not properly preserved. Our study was conducted to reveal the level of contamination and prevalence of Listeria spp. present in livestock and poultry meat from Gansu province. A total of 1,387 samples were collected from five cities in Gansu Province according to standard sampling procedures, of which 174 samples (12.5%) were positive for Listeria species. Among them, 14 isolates of L. monocytogenes (1.0%), 150 isolates of Listeria innocua (10.8%), and ten isolates of Listeria welshimeri (0.7%) were identified by conventional bacteriological and molecular identification methods. All isolates were subjected to serological assays, antimicrobial susceptibility tests, growth curve assays, determination of biofilm-forming capacity, and cluster analysis of the 16S rRNA gene sequences. Four predominant serotypes of L. monocytogenes were identified, including 1/2a (35.7%, 5/14), 1/2b (14.3%, 2/14), 1/2c (42.9%, 6/14), and 4b (7.1%, 1/14). All L. monocytogenes isolates were resistant to tetracycline and cefoxitin. Most L. innocua isolates (63.6%, 14/22) and L. welshimeri (40%, 4/10) were resistant to tetracycline. The high biofilm-forming ability was observed among 1/2c and 1/2a serotype isolates. The cluster analysis of the 16S rRNA gene sequences revealed a close genetic relationship between the three Listeria species. This study fills the gap in the knowledge of livestock and poultry meat that carry Listeria in slaughterhouses and markets in Gansu Province.

In order to clarified characteristics and function of internalin G (inlG) in Listeria monocytogenes ATCC®19111 (1/2a) (LM), the immune protection of the inlG was evaluated in mice, the homologous recombination was used to construct inlG deletion strains, and their biological characteristics were studied by the transcriptomics analysis. As a result, the immunization of mice with the purified protein achieved a protective effect against bacterial infection. The deletion strain LM-AinlG was successfully constructed with genetic stability. The mouse infection test showed that the virulence of LM was decreased after the deletion of the inlG gene. The deletion strain showed enhanced adhesion to and invasion of Caco-2 cells. Compared to the wild strain, 18 genes were up-regulated, and 24 genes were down-regulated in the LM-AinlG. This study has laid a foundation for further research on the function of inlG and the pathogenesis of LM.

We use the definition of a fractional integral operators, recently introduced by Katugampola, to establish a parameterized identity associated with differentiable mappings. The identity is then used to derive the estimates of upper bound for mappings whose first derivatives absolute values are p-convex mappings. Four examples are also provided to illustrate the obtained results.

We use the definition of a fractional integral operators, proposed by Katugampola, to establish a fractional Hermite-Hadamard’s inequality for p-convex mappings and an identity with two parameters. We derive several parameterized integral inequalities associated with this identity, and provide three examples to illustrate the obtained results.

C14H16N6O7Cd, monoclinic, P21/c (no. 14), a = 12.7095(3) Å, b = 17.4705(4) Å, c = 8.5763(3) Å, β = 93.292(10)°, Z = 4, V = 1901.15(9) Å3, Rgt(F) = 0.0263, wRref(F2) = 0.1047, T = 296(2) K.

Danshen injection, a pharmaceutical dosage form of Danshen, has been widely used in the treatment of coronary heart diseases, myocardial infarction, and hypertension. With more and more adverse drug reactions linked with Danshen injection, its safety comes under suspicion. To evaluate its safety, mice were divided into four groups: vehicle, low-, middle-, and high-Danshen group, and each group was intravenously administered with Danshen injection at a dose of 0, 0.64, 1.55, and 5.76 g/kg/day for 5 days, respectively (the low dosage was the recommended clinical dosage, the middle dosage was the most commonly used higher dosage, and the high dosage was the highest dosage used in clinic). Peripheral vascular toxicity wasn’t observed in the low-dosage group, elevated serum endothelin-1 (ET-1) was observed in the middle-dosage group; and more peripheral vascular toxicities like increased vascular leakage, elevated serum nitrate and ET-1, and vascular endothelial cells apoptosis were detected in the high-dosage group. In vitro study, low-concentration Danshen injection showed protective effect to human umbilical vein endothelial cells (HUVECs), while high concentration displayed strong cytotoxic effects, including increase in nitric oxide and ET-1 production, inhibition of cell viability, and apoptosis induction. Further, the HUVECs’ apoptosis induced by high-concentration Danshen injection was found along with the induction of reactive oxygen species. In conclusion, these results suggest that Danshen injection is nontoxic in its recommended clinical dosage, and the 2.4-fold as the recommended clinical dosage might be the highest safety dosage in clinic treatment. In addition, Danshen injection is a potential vascular toxic drug in its high dosage and shouldn’t be used far beyond its recommended dosage in clinic treatment. [ABSTRACT FROM AUTHOR]