Abstract The heterogeneity of microelement strength of rock particle materials is one of the main factors that cause the size effect of the rock particle crushing behavior. In this paper, a numerical model of rock particles that considering the characteristic of microscopic heterogeneous bond strength was established by using Weibull distribution theory through discrete element method. Single particle crushing experiments were carried out on five groups of rock particles and numerical particles with different particle sizes (6-21 mm), the crushing strength and failure modes of rock particles and numerical particles with different sizes were obtained. The results shows that the proposed numerical model can effectively reproduce the size effect of rock particle crushing behavior. The particle crushing strength data are satisfied the Weibull statistical model and have obvious size effect. The particle failure modes can be divided into three different failure types: “brittle” failure, “quasi brittle” failure, and “ductile” failure. As the particle size increase, the particle failure mode changes from “ductile” failure to “brittle” failure. Finally, a microscopic damage function model of particle crushing was established based on the numerical simulation results, which explained the microscopic mechanism of the size effect of particle crushing behavior. This study not only helps to improve the stability of engineering materials, but also optimizes engineering design and construction, and promotes related technological innovation.

Liver cancer is a malignant tumor found worldwide. mRNA turnover 4 homolog (MRTO4) is highly expressed in hepatocellular carcinoma (HCC) tissues, and we explored its relationship with HCC. All cancer data were downloaded from the Cancer Genome Atlas (TCGA), the Cancer Immune Atlas (TCIA), and the Human Protein Atlas (THPA). Stromal scores, immune scores, and ESTIMATE scores were calculated by “ESTIMATE” R package. Single sample gene set enrichment analysis and CIBERSORT were used to evaluate the immune status and infiltration of cancer tissues. pRRophetic R package was used to predict the half-maximal inhibitory concentration (IC50) of different drugs in each sample. MRTO4 overexpression was associated with poor prognosis in HCC, and positively correlated with the stage and grade of HCC patients. The average immunophenoscore (IPS) of the low MRTO4 group was significantly higher than that of the high MRTO4 group. Tumor microenvironment (TME) scores were significantly higher in the low MRTO4 group than in the high MRTO4 group in HCC. MRTO4 expression was positively correlated with tumor mutation burden (TMB) and was positively correlated with most immune checkpoint gene expressions in HCC. Drug sensitivity analysis showed significantly higher IC50 values for 5-fluorouracil, gemcitabine, and sorafenib in patients with low MRTO4 expression than in those with high MRTO4 expression. MRTO4 acts as an independent prognostic and immunological biomarker and is correlated with clinical stage, tumor grade, and drug sensitivity in HCC. It may serve as a putative therapeutic target and potential biomarker for prognosis of HCC.

Abstract Excessive heavy metal cadmium in tomatoes is harmful to human health. The detection of heavy metals in tomato leaves can determine whether the heavy metals in tomatoes exceed the standard. In order to quickly, non-destructively and efficiently detect whether heavy metals on the surface of tomato leaves exceed the standard, a new wavelength interval selection method called Synergy interval PLS couple with Monte Carlo method (MC-siPLS) was proposed. From the seedling stage, concentration of 0, 0.05, 0.1, 0.2, 0.5, 1, 2, 5, 10 mg/L cadmium chloride (CdCl2) was used for irrigation under normal nutrient elements respectively. A total of 405 leaf samples were collected. Using the VIS-NIR hyperspectral instrument, the tomato leaves were set as the region of interest to obtain hyperspectral data, then used Atomic Absorption Spectrometry (AAS) method to detect heavy metals in tomato leaves. In addition, 5 different PLS algorithm were used to compare with MC-siPLS. Furthermore, the best model was given by MC-siPLS with RMSEP = 0.5378, R2 = 0.9870. The results show that MC-siPLS was better than similar wavelength interval selection methods, which had great application potential in the nondestructive detection of heavy metals in tomato leaves. This method maybe determines whether tomatoes contain excess cadmium early. health standard quickly nondestructively non destructively MCsiPLS MC siPLS (MC-siPLS proposed stage 0 005 05 0.05 01 1 0.1 02 2 0.2 0.5 mgL mg L CdCl2 CdCl (CdCl2 respectively 40 collected VISNIR VIS NIR instrument data AAS (AAS addition MCsiPLS. siPLS. Furthermore 05378 5378 0.5378 R 09870 9870 0.9870 methods early 00 0.0 0. (CdCl 4 0537 537 0.537 0987 987 0.987 053 53 0.53 098 98 0.98 09 9 0.9

Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.

SUMMARY: This study aimed to accurately localize the location and depth of the centre of the highest region of muscle spindle abundance (CHRMSA) of the triceps brachii muscle. Twenty-four adult cadavers were placed in the prone position. The curve connecting the acromion and lateral epicondyle of the humerus close to the skin was designed as the longitudinal reference line (L), and the curve connecting the lateral and the medial epicondyle of the humerus was designed as the horizontal reference line (H). Sihler's staining was used to visualize the dense intramuscular nerve region of the triceps brachii muscle. The abundance of muscle spindle was calculated after hematoxylin and eosin stain. CHRMSA was labelled by barium sulphate, and spiral computed tomography scanning and three- dimensional reconstruction were performed. Using the Syngo system, the projection points of CHRMSA on the posterior and anterior arm surface (P and P' points), the position of P points projected to the L and H lines (PL and PH points), and the depth of CHRMSA were determined. The PL of the CHRMSA of the long, medial, and lateral heads of the triceps brachii muscle were located at 34.83 %, 75.63 %, and 63.93 % of the L line, respectively, and the PH was located at 63.46 %, 69.62 %, and 56.07 % of the H line, respectively. In addition, the depth was located at 34.73 %, 35.48 %, and 35.85 % of the PP' line, respectively. These percentage values are all the means. These body surface locations and depths are suggested to be the optimal blocking targets for botulinum toxin A in the treatment of triceps brachii muscle spasticity.

RESUMEN: Este estudio tuvo como objetivo localizar con precisión la ubicación y la profundidad del centro de la región más alta del huso muscular (CHRMSA) del músculo tríceps braquial. Se colocaron veinticuatro cadáveres adultos en posición prona y se designó la curva que conecta el acromion y el epicóndilo lateral del húmero cerca de la piel como la línea de referencia longitudinal (L), y la curva que conecta los epicóndilos lateral y medial del húmero fue designada como la línea de referencia horizontal (H). Se usó la tinción de Sihler para visualizar la región nerviosa intramuscular densa del músculo tríceps braquial. La abundancia de huso muscular se calculó después de la tinción con hematoxilina y eosina. CHRMSA se marcó con sulfato de bario y se realizó una tomografía computarizada espiral y una reconstrucción tridimensional. Usando el sistema Syngo, fueron determinados los puntos de proyección de CHRMSA en la superficie posterior y anterior del brazo (puntos P y P'), la posición de los puntos P pro- yectados en las líneas L y H (puntos PL y PH) y la profundidad de CHRMSA. Los PL de la CHRMSA de las cabezas larga, medial y lateral del músculo tríceps braquial se ubicaron en el 34,83 %, 75,63 % y 63,93 % de la línea L, respectivamente, y el PH se ubicó en el 63,46 %, 69,62 %, y 56,07 % de la línea H, respectivamente. La profundidad se ubicó en el 34,73 %, 35,48 % y 35,85 % de la línea PP', respectivamente. Estos valores porcentuales son todas las medias. Se sugiere que estas ubicaciones y profundidades de la superficie corporal son los objetivos de bloqueo óptimos para la toxina botulínica A en el tratamiento de la espasticidad del músculo tríceps braquial.

Resumo Objetivo: O objetivo desta pesquisa é investigar quais fatores influenciam na lealdade dos usuários de sistemas inteligentes de compartilhamento de bicicletas sem estações. Metodologia: Um total de 374 indivíduos que tiveram experiência anterior com o uso de sistemas inteligentes de compartilhamento de bicicletas sem estações foi reunido e o método parcial de mínimos quadrados (PLS) foi utilizado para analisar os modelos de medição e estrutural. Resultados: Os resultados indicaram que a lealdade do cliente era o construto final produzido pelo valor ecológico percebido, pela satisfação do cliente e pelo prazer percebido, que são avaliados como mediadores parciais entre a qualidade do serviço e a lealdade do cliente. Contribuições: Este estudo: 1) oferece uma nova perspectiva para se examinar o comportamento de lealdade do consumidor em um contexto de sistemas inteligentes de compartilhamento de bicicletas sem estações inteligentes; 2) identifica o papel da qualidade do serviço como um estímulo importante; 3) confirma o prazer percebido não apenas como um efeito sobre a lealdade do cliente, mas também como atuando como um excelente mediador; e 4) oferece evidência empírica para os prestadores do sistema inteligente de compartilhamento de bicicletas sem estações aprimorarem a adoção do transporte ecológico e fortalecerem a lealdade do cliente ao sistema inteligente.

Abstract Purpose: The purpose of this research is to investigate which factors influence users’ loyalty to smart dockless bike-sharing systems (DBSS). Design/methodology/approach: A sample of 374 subjects who had previously experienced smart DBSS was obtained and the partial least squares (PLS) method was performed to analyze the measurement and structural models. Findings: The results indicated that customer loyalty was the final construct produced by perceived green value, customer satisfaction, and perceived pleasure, which were found to be partial mediators between service quality and customer loyalty. Originality/value: This study (1) provides a new perspective from which to examine consumer loyalty behavior in a smart DBSS context, (2) it identifies the role of service quality as an important stimulus, (3) it confirms that perceived pleasure not only has an effect on customer loyalty, but also acts as an excellent mediator, and (4) it provides empirical evidence for smart DBSS providers to enhance the adoption of green transport and to strengthen customer loyalty to smart DBSS.

Abstract The perforation tests of 45 # steel target plate and 2A12 aluminium alloy target plate by PELE (the Penetrator with Lateral Efficiency) were carried out in this paper to study the perforation failure characteristics of metal target plate. The macroscopic morphology of perforation on the target plate and the plug was observed, and the perforation wall was cut and polished to observe the distribution and trend of the cracks in the perforation wall by scanning electron microscopy (SEM) and metallographic microscopy. The magnitude and direction of the force produced by PELE on the target during penetration were calculated by numerical simulation. The experimental and numerical results show that, the perforation failure of metal target plate by PELE is different from the ductile perforation by conical-nosed projectile and the punching failure by flat-nosed projectile. The longitudinal cross section of the perforation is funnel-shaped and the shape of the plug is like a circular truncated cone. In the process of penetrating the target plate, the expansion of the filling causes the jacket to exert a force with a certain angle to the direction of projectile movement, which is the main reason for the funnel-shaped perforation and the circular truncated cone shaped plug.

Abstract: The great potential of crowdsourcing contest is bringing the issue of how to sustain solvers’ participation intention to be a hot topic in research and practice. This study uses the framework of Expectation-confirmation model to explain solvers’ continuance intention. Due to the uncertainties inherent in crowdsourcing contest, trust, a salient psychological belief, should be taken into account with the Expectation-confirmation model framework to predict solvers’ continuance intention. In addition, the intensive demand of intelligence and competition indicate interaction and fairness as two crucial factors for solvers to achieve expectation, thus suggesting that they may have influence on the confirmation level. Corresponding to these challenges, this study integrates platform trust, interaction, and perceived fairness into an extended Expectation-confirmation model to examine solvers’ continuance intention. Using a sample of 306 solvers, empirical results show that satisfaction, perceived benefits, and platform trust, which are positively associated with confirmation, are three significant antecedents of solvers’ continuance intention. Confirmation is further found to be significantly determined by interaction and perceived fairness. These findings provide some implications in both theory and practice for understanding the process of triggering sustained intention with an Expectation-confirmation model framework in crowdsourcing contest.

Abstract Spider venoms are known to contain proteins and polypeptides that perform various functions including antimicrobial, neurotoxic, analgesic, cytotoxic, necrotic, and hemagglutinic activities. Currently, several classes of natural molecules from spider venoms are potential sources of chemotherapeutics against tumor cells. Some of the spider peptide toxins produce lethal effects on tumor cells by regulating the cell cycle, activating caspase pathway or inactivating mitochondria. Some of them also target the various types of ion channels (including voltage-gated calcium channels, voltage-gated sodium channels, and acid-sensing ion channels) among other pain-related targets. Herein we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against the pathophysiological conditions including cancer and pain.

SUMMARY: The nerve entry points (NEPs) cannot yet be accurately localized for the treatment of thigh adductor muscles spasticity in chemical neurolysis. The aim of this study was to identify the location and depth of the NEPs of thigh adductor muscles by spiral computed tomography (CT) and bony landmarks. Forty lower limbs of twenty adult cadavers were dissected in supine position. A curved line on skin surface from the tip of greater trochanter of femur to the center of pubic tubercle was designated as the horizontal reference line (H). Another curved line from the tip of great trochanter to the lateral epicondyle of femur was designated as the longitudinal reference line (L). Following dissection, the NEPs were labeled with barium sulfate, and their body surface projection points (P) were determined by spiral CT. Projection of NEP in the opposite direction was designated as P'. The percentage location of the intersections (PH and PL) of P with the H and L and the percentage depth of NEPs were determined with the Syngo system. The PH for the NEP of pectineus, gracilis, adductor longus, adductor brevis and adductor magnus muscles branch were located at 76.41±0.71 %, 93.85±2.07 %, 92.05±2.15 %, 80.75±1.20 % and 88.08±1.09 % of the H, respectively. The PLwere at 1.64±0.04 %, 29.89±1.90 %, 16.06±1.32 %, 11.66±0.11 % and 22.94±0.90 % of the L, respectively. The depth of NEP from P points were at 17.52±0.52 %, 38.38±2.75 %, 20.88±0.79 %, 20.35±0.82 % and 39.52±0.67 % of PP', respectively. These results help to carry out more precise localization of the NEPs. It should provide a novel anatomical guide for improving the efficacy and efficiency of chemical neurolysis in treating thigh adductor muscle spasticity.

RESUMEN: Aún no se pueden localizar con precisión los puntos de entrada del nervio (PEN) para el tratamiento de la espasticidad de los músculos aductores del muslo a través de la neurólisis química. El objetivo de este estudio fue identificar la ubicación y la profundidad de los PEN de los músculos aductores del muslo mediante tomografía computarizada espiral (TC) y puntos de referencia óseos. Se disecaron loa miembros inferiores de 20 cadáveres adultos en posición supina. Se trazó una línea curva en la superficie de la piel desdeel ápice del trocánter mayor del fémur hasta el centro del tubérculo púbico y se designó como línea de referencia horizontal (H). Otra línea curva desde el ápice del trocánter mayor hasta el epicóndilo lateral del fémur se designó como línea de referencia longitudinal (L). Después de la disección, los PEN se marcaron con sulfato de bario y sus puntos de proyección de la superficie del cuerpo (P) se determinaron mediante TC helicoidal. La proyección de PEN en la dirección opuesta se designó como P '. El porcentaje de ubicación de las intersecciones (PH y PL) de P con H y L y la profundidad porcentual de los PEN se determinaron con el sistema Syngo. Los PH para los PEN de los músculos pectineus, gracilis, adductor longus, aductor brevis y rama aductora del músculo aductor magnus se localizaron en 76,41±0,71 %, 93,85±2,07 %, 92,05±2,15 %, 80,75±1,20 % y 88,08±1,09 % de H, respectivamente. Los PL estuvieron en 1,64±0,04 %, 29,89±1,90 %, 16,06±1,32 %, 11,66±0,11 % y 22,94±0,90 % de la L, respectivamente. La profundidad de PEN de P puntos fue de 17,52±0,52 %, 38,38±2,75 %, 20,88±0,79 %, 20,35±0,82 % y 39,52±0,67 % de PP ', respectivamente. Estos resultados ayudan a realizar una localización más precisa de los PEN. Se debe proponer una nueva guía anatómica para mejorar la eficacia y la eficiencia de la neurólisis química en el tratamiento de la espasticidad del músculo aductor del muslo.

ABSTRACT Repirinast is a new, synthetic, disodium cromoglycate-like antiallergic agent for oral administration in humans. This study evaluated the safety, tolerability and pharmacokinetics of repirinast tablets in healthy Chinese volunteers. This was a phase I, open-label, randomized, single- and multiple-dose study. Subjects were assigned to receive a single dose of repirinast tablet at either 150, 300, or 450 mg, or multiple doses of 150 mg twice daily for 5 days. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of active metabolite MY-1250 (deesterified repirinast) were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 0.75 hour, and the mean t1/2 was approximately 16.21 hours. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 150 to 450 mg. In the multiple-dose study, the steady-state was reached within 3 days with no accumulation. Repirinast tablet was well tolerated in healthy Chinese subjects.

L-3-n-butilftalida (L-NMP) é um antioxidante natural, que pode ser utilizado para o tratamento do acidente isquêmico agudo e demência vascular. Este estudo avaliou segurança, tolerância e farmacocinética de comprimidos de L-NBP em chineses voluntários sadios. Este foi um estudo monocêntrico, randomizado, duplo cego, com controle por placebo e doses única e múltipla. Os indivíduos receberam dose única de comprimido de L-NBP de 80, 160, 320 ou 480 mg (n=40) e doses múltiplas de 160 mg duas vezes ao dia, por sete dias (n=12). Amostras de plasma foram analisadas com LC-MS/MS. Os parâmetros farmacocinéticos do L-NBP foram calculados utilizando análise não compartimental, com o programa WinNonlin. A análise estatística foi realizada utilizando-se o programa SPSS. Todos os eventos adversos (EAs) foram moderados e de duração limitada. EAs nesse estudo ocorreram menos frequentemente e mais moderadamente do que os EAs relacionados para cápsulas moles de DL-NBP. Não se observaram eventos adversos graves (EAG), morte ou abandono do estudo. Com dose única, atingiu-se o Cmax em cerca de 1 hora e o t1/2 médio foi de, aproximadamente, 13,76 h. A área sob a curva (ASC) e o Cmax aumentaram com o aumento da dose, mas não se observou proporcionalidade na faixa acima de 160 a 480 mg. No estudo de dose múltipla, o equilíbrio foi alcançado em três dias, com pequeno acúmulo. Em resumo, o comprimido de L-NMP foi bem tolerado em indivíduos chineses saudáveis. O acúmulo pequeno apareceu após doses repetidas.

L-3-n-butylphthalide (L-NBP) is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40), or multiple doses of 160 mg twice daily for 7 days (n=12). Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses.

Powdery mildew (Oidium heveae Steinm.) is one of the most important leaf diseases in rubber tree (Hevea brasiliensis). However, physiological and molecular processes associated with the Hevea-powdery mildew interaction are still unclear. In this study, effects of powdery mildew infection on the mitochondrial and chloroplast functions in rubber tree were comprehensively investigated. Powdery mildew damaged the structure and function of mitochondria prior to chloroplasts, causing inner and outer membranes disruption. The intact rate of mitochondria membrane was reduced from 70% in control leaves to 23.1% in the leaves at 5 days after inoculation (dai). Significant decreases in the activities of cytochrome c oxidase, NADH oxidation and malate dehydrogenase (MDH) were observed in the powdery mildew-infected leaves. Tricarboxylic acid cycle (TCA) and electron transfer capacity were seriously impaired after powdery mildew invasion. Chlorophyll (Chl) contents, maximal photochemical efficiency (Fv/Fm), actual photochemical efficiency of photosystem II (ΦPSII), and electron transport rate (ETR) were dramatically decreased in the infected leaves from 10 dai. Our results provided new insights into understanding the mechanism of Hevea-powdery mildew interaction in rubber tree.