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Abstract Imetelstat is a novel, first‐in‐class, oligonucleotide telomerase inhibitor in development for the treatment of hematologic malignancies including lower‐risk myelodysplastic syndromes and myelofibrosis. A nonlinear mixed‐effects model was developed to characterize the population pharmacokinetics of imetelstat and identify and quantify covariates that contribute to its pharmacokinetic variability. The model was developed using plasma concentrations from 7 clinical studies including 424 patients with solid tumors or hematologic malignancies who received single‐agent imetelstat via intravenous infusion at various dose levels (0.4–11.7 mg/kg) and schedules (every week to every 4 weeks). Covariate analysis included factors related to demographics, disease, laboratory results, renal and hepatic function, and antidrug antibodies. Imetelstat was described by a two‐compartment, nonlinear disposition model with saturable binding/distribution and dose‐ and time‐dependent elimination from the central compartment. Theory‐based allometric scaling for body weight was included in disposition parameters. The final covariates included sex, time, malignancy, and dose on clearance; malignancy and sex on volume of the central compartment; and malignancy and spleen volume on concentration of target. Clearance in females was modestly lower, resulting in nonclinically relevant increases in predicted exposure relative to males. No effects on imetelstat pharmacokinetics were identified for mild‐to‐moderate hepatic or renal impairment, age, race, and antidrug antibody status. All model parameters were estimated with adequate precision (relative standard error

Abstract Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)‐negative and early‐stage RA are still to be improved. We aimed to screen autoantibodies in ACPA‐negative patients and evaluated their diagnostic performance. The human genome‐wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti‐ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA‐negative RA, including anti‐ANAPC15, anti‐LSP1, anti‐APBB1, anti‐parathymosin, and anti‐UBL7. Anti‐parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA‐negative early stage (

Abstract Background Paroxysmal kinesigenic dyskinesia (PKD) is the most prevalent kind type of paroxysmal Dyskinesia, characterized by recurrent and transient episodes of involuntary movements. Most PKD cases were attributed to the proline‐rich transmembrane protein 2 (PRRT2) gene, in which the c.649 region is a hotspot for known mutations. Even though some patients with PKD have been genetically diagnosed using whole‐exome sequencing (WES) and Sanger sequencing, there are still cases of missed diagnoses due to the limitations of sequencing technology and analytic methods on throughput. Methods Patients meeting the diagnosis criteria of PKD with negative results of PRRT2‐Sanger sequencing and WES were included in this study. Mutation screening and targeted high‐throughput sequencing were performed to analyze and verify the sequencing results of the potential mutations. Results Six patients with PKD with high mutation ratios of c.649dupC were screened using our targeted high‐throughput sequencing from 26 PKD patients with negative results of PRRT2‐Sanger sequencing and WES (frequency = 23.1%), which compensated for the comparatively shallow sequencing depth and statistical flaws in this region. Compared with the local normal population and other patients with PKD, the mutation ratios of c.649dupC of these six patients with PKD were much higher and also had truncated protein structures and differentially altered mRNA expression. Conclusion Based on the above studies, we emphasize the routine targeted high‐throughput sequencing of the c.649 site in the PRRT2 gene in so‐called genetic‐testing‐negative patients with PKD, and manually calculate the deletion and duplication mutations depth and ratios to lower the rate of clinical misdiagnosis.

Abstract Nonfused ring electron acceptors (NFREAs) are promising candidates for future commercialization of organic solar cells (OSCs) due to their simple synthesis. Still, the power conversion efficiencies (PCEs) of NFREA‐based OSCs have large room for improvement. In this work, by merging end group halogenation and side chain engineering, we developed four A–D–A'–D–A type NFREAs, which we refer to as EH‐4F, C4‐4F, EH‐4Cl, and C4‐4Cl. Single crystal X‐ray diffraction revealed that multiple intermolecular S···F interactions between cyclopentadithiophene and 5,6‐difluoro‐3‐(dicyanomethylene)indanone could cause an unfavorable dimer formation, leading to ineffective π–π stackings in EH‐4F and C4‐4F, whereas no such dimer was found in EH‐4Cl and C4‐4Cl after replacing with 5,6‐dichloro‐3‐(dicyanomethylene)indanone. Moreover, although the shorter n‐butyl side chain resulted in a closer molecular packing in C4‐4Cl, EH‐4Cl (2‐ethylhexyl substitution) with proper crystallinity exhibited enhanced face‐on orientation in thin film, which is favorable for vertical charge transport and further reducing charge recombination. As a result, a PCE of 13.0% is obtained for EH‐4Cl‐based OSC with a fill factor of 0.70. This work highlights the importance of molecular packing and orientation control toward future high‐performance A–D–A'–D–A type NFREAs.

Abstract Antineutrophil cytoplasmic autoantibody (ANCA)‐associated vasculitis (AAV) is a rare and severe systemic autoimmune disease characterized by pauci‐immune necrotizing inflammation of small blood vessels. AAV involves multiple organ systems throughout the body. Our knowledge of the pathogenesis of AAV has increased considerably in recent years, involving cellular, molecular and genetic factors. Because of the controlled environment with no other confounding factors, animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects. However, the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients. The aim of this review is to overview the current status of animal models for AAV, outline the pros and cons of methods, and propose potential directions for future research.

Abstract The improved hybrid discretisation of volume integral equation (VIE) combined with the characteristic basis function method is proposed to analyse the scattering from complex dielectric objects in this study. To mitigate the excessive number of discrete elements which arise from the conformal discretisation on the complex dielectric objects, the hybrid discretisation is developed. For the conventional hybrid discretisation, the conformal Schaubert–Wilton–Glisson (SWG) basis functions are used to discretise the homogeneous regions, meanwhile, the non‐conformal half‐SWG basis functions are employed to discretise the boundary regions which separate different materials or multiscale structures. The hybrid discretisation takes advantage of the merits of both conformal and non‐conformal basis functions and improves the computational efficiency for solving the VIE. In our study, a kind of edge basis function defined within boundary tetrahedral elements substitutes for the SWG basis functions to model the boundary regions, leading to the further reduction on the number of basis functions. Moreover, the characteristic basis functions extracted from the low‐level basis functions are employed to construct the reduced matrix of which the size is considerably smaller than that of the system matrix derived from the VIE. Several numerical results are presented to demonstrate the accuracy and efficiency of the proposed method.

Abstract Siglec‐15, a novel immune suppressor, is upregulated in many human cancers. The aim of this study was to explore the expression of Siglec‐15 in colorectal cancer (CRC), and investigate whether Siglec‐15 could be a potential target for cancer immunotherapy in patients with CRC. We performed immunohistochemical analyses of Siglec‐15 on a cohort of 805 patients with CRC and made comparisons between clinicopathological characteristics, PD‐L1 expression, CD3, CD8, CD45RO tumor‐infiltrating lymphocytes (TILs), and prognosis. We found that Siglec‐15 expression was commonly detected in tumor cells (48.3%) and tumor‐associated stromal cells (33.4%), and was more frequently observed than PD‐L1 expression in tumor cells. In contrast, Siglec‐15 expression was weakly and scarcely found in normal mucosa (13%). Siglec‐15 overexpression in tumor cells was associated with advanced TNM stage (p = 0.020). Co‐expression of Siglec‐15 and PD‐L1 in tumor cells was found in 14.4% of patients, and Siglec‐15 expression was detected in almost half of PD‐L1 negative cases. Elevated Siglec‐15 expression in tumor and stromal cells was associated with sparser CD45RO and CD8 TILs (p = 0.035 and p = 0.004, respectively). The expression of Siglec‐15 did not have prognostic significance. In summary, compared to PD‐L1, Siglec‐15 protein expression is more prevalent in CRC and is associated with advanced disease stage and fewer TILs. These findings support Siglec‐15 as a potential cancer immunotherapy target, in addition to PD‐1/PD‐L1 inhibitors, in patients with CRC.

Abstract Background Genetic testing for pancreatic ductal adenocarcinoma (PDAC) patients is in constant development. However, the status of homologous recombination repair (HRR) genes in unselected Chinese PDAC has not been fully explored. This study aims to characterize the profile of germline mutations in HRR genes in Chinese PDAC patients. Methods A cohort of 256 PDAC patients were enrolled at Zhongshan Hospital Fudan University between 2019 and 2021. Germline DNA was analyzed by next‐generation sequencing using a multigene panel of the 21 HRR genes. Results The germline pathogenic (P)/likely pathogenic (LP) variant rates were 7.0% (18/256) in unselected patients with pancreatic cancer. Among them, 1.6% (4/256) were identified as harboring BRCA2 variants, and 5.5% (14/256) patients carried non‐BRCA variants. Variants were detected in eight non‐BRCA genes, including ATM (4, 1.6%), PALB2 (4, 1.6%), ATR (1, 0.4%), BRIP1 (1, 0.4%), CHEK2 (1, 0.4%), MRE11 (1, 0.4%), PTEN (1, 0.4%), and STK11 (1, 0.4%). ATM, BRCA2, and PALB2 were the most prevalent variant genes. If only BRCA1/2 was tested, 5.5% of P/LP variants would have been lost. Further, we found that the landscape of P/LP HRR variants in various population cohorts was quite different. However, no significant difference was found in clinical characteristics between germline HRR P/LP carriers and non‐carriers. In our study, one case carrying a germline PALB2 variant showed a long‐time response to platinum‐based chemotherapy and PARP inhibitor. Conclusion This study comprehensively depicts the prevalence and characteristics of germline HRR mutations in unselected Chinese PDAC patients. Our findings show the clinical utility of a multigene panel may increase the detection of P/LP HRR carriers.

Abstract Emerging evidence emphasizes the functional impacts of host microbiome on the etiopathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). However, there are limited mechanistic insights into the contribution of microbial biomolecules especially microbial peptides toward modulating immune homeostasis. Here, by mining the metagenomics data of tonsillar microbiome, a deficiency of the encoding genes of lantibiotic peptides salivaricins in RA patients is identified, which shows strong correlation with circulating immune cells. Evidence is provided that the salivaricins exert immunomodulatory effects in inhibiting T follicular helper (Tfh) cell differentiation and interleukin‐21 (IL‐21) production. Mechanically, salivaricins directly bind to and induce conformational changes of IL‐6 and IL‐21 receptors, thereby inhibiting the bindings of IL‐6 and IL‐21 to their receptors and suppressing the downstream signaling pathway. Finally, salivaricin administration exerts both prophylactic and therapeutic effects against experimental arthritis in a murine model of RA. Together, these results provide a mechanism link of microbial peptides‐mediated immunomodulation.

Abstract The tendency of zinc (Zn) anodes to form uncontrolled Zn electrodeposits and the occurrence of side‐reactions at Zn‐electrolyte interfaces are a fundamental barrier hampering broad applications of aqueous rechargeable Zn‐based batteries. Herein, a ferroelectric domain‐mediated strategy is proposed to manipulate the Zn plating behavior and achieve controllable Zn growth orientation by coating Zn foil with a ferroelectric tetragonal KTN (t‐KTN) layer. The ferroelectric domain of t‐KTN single crystals exhibits periodic distribution of upward and downward polarizations, corresponding to alternating positively and negatively charged surfaces. The charged ferroelectric surfaces can manipulate the transfer kinetics of Zn ions and the concentration distribution of anions via the interplay between ferroelectric dipoles and adsorbed ions. With the synergistic effect of the ferroelectric polarization and domain configurations, the well‐aligned interlamellar arrays composed of electrodeposited Zn are formed in the initial deposition process, which enable selective deposition within interlamellar arrays and eliminate the dendrite growth during the following plating process. As a result, the t‐KTN layer‐modified Zn anode enables reversible Zn plating/stripping with low voltage hysteresis for over 1200 h at 1 mA cm−2 in symmetric cells, and the assembled full cell exhibits a significantly enhanced cycling stability of over 5500 cycles at 5 A g−1.

Abstract A successful transfer of organic photovoltaic technologies from lab to fab has to overcome a range of critical challenges such as developing high‐mobility light‐harvesting materials, minimizing the upscaling losses, designing advanced solar modules, controlling film quality, decreasing overall cost, and extending long‐operation lifetime. To realize large‐area devices toward practical applications, much effort has been devoted to understanding the fundamental mechanism of how molecular structures, device architectures, interfacial engineering, and light management and carrier dynamics affect photovoltaic performance. Such studies addressed various fundamental issues of charge carrier behavior in organic heterojunctions primarily in terms of exciton generation dependence upon light incidence, charge transportation dependence on built‐in electric field, and charge extraction versus recombination. In consideration of high‐throughput roll‐to‐roll process for large‐scale fabrication of organic photovoltaic devices, it is highly appreciable to realize high power conversion efficiencies that are highly tolerable to the film thickness. Herein we summarize the recent progress in developing thick‐film organic photovoltaic devices from the perspective of efficiency‐loss mechanisms, material design, and device optimization strategies, proposing guidelines for designing high‐efficiency thickness‐insensitive devices toward mass production.

Abstract The inherent advantages of organic optoelectronic materials endow light‐harvesting systems, including organic photovoltaics (OPVs) and organic photodiodes (OPDs), with multiple advantages, such as low‐cost manufacturing, light weight, flexibility, and applicability to large‐area fabrication, make them promising competitors with their inorganic counterparts. Among them, near‐infrared (NIR) organic optoelectronic materials occupy a special position and have become the subject of extensive research in both academia and industry. The introduction of NIR materials into OPVs extends the absorption spectrum range, thereby enhancing the photon‐harvesting ability of the devices, due to which they have been widely used for the construction of semitransparent solar cells with single‐junction or tandem architectures. NIR photodiodes have tremendous potential in industrial, military, and scientific applications, such as remote control of smart electronic devices, chemical/biological sensing, environmental monitoring, optical communication, and so forth. These practical and potential applications have stimulated the development of NIR photoelectric materials, which in turn has given impetus to innovation in light‐harvesting systems. In this review, we summarize the common molecular design strategies of NIR photoelectric materials and enumerate their applications in OPVs and OPDs.

Abstract Single‐molecule electrical and spin switches have been one of the main research focuses in molecular electronics and spintronics because they may form the most important elements for the future information technology, thus attracting great attention in the scientific community and witnessing significant progresses benefiting from the combination of physics, chemistry, materials, and engineering. The key issue of constructing single‐molecule switches is the development of stimulus‐responsive systems that provide bistable or multiple states. In this review, we summarize the recent advances of this field in terms of the external stimulus that induces the switching. A variety of external stimuli, such as light, electric field, magnetic field, mechanical force, and chemical stimulus, have been successfully employed to activate the reversible switching in single‐molecule junctions by manipulating molecular structures, conformations, electronic states, and spin states. As a burgeoning field, we finally put forward the challenges in molecular electronics and spintronics that need to be solved, which will initiate intense research.

Paste should be kept in homogeneous state without segregation or weak segregation during pipeline transportation, which can reduce the occurrence of pipe blockage accidents in engineering application. Only when the paste is homogeneous can the paste have good stope fluidity, and the stope fluidity is also restricted by the geometric size of the stope and other factors. Therefore, it is very important to study the homogeneity of paste and analyze the influence of paste rheological characteristics on stope fluidity. In this paper, it is pointed out that the vertical settling velocity of solid phase materials in paste in the liquid-phase dense medium is the main factor affecting the homogeneity of paste. Increasing the plastic viscosity and yield stress of the liquid-phase dense medium is beneficial to increase the drag force of aggregate and then reduce the settling speed of aggregate in the liquid-phase dense medium. On this basis, the homogeneity of paste can be judged. In the simplified paste flow field, using Cauchy stress equation and flow boundary conditions, the relationship between paste stope flow performance and paste rheological properties was analyzed, and the relationship model between the slope angle of paste flow formation and paste rheological properties was established. Compared with the experimental results, the error of the model results is small, and the slope angle of paste flow can be well predicted.

As the key connecting components between tower and conductors, electric power fittings play an important role in the provision of the safe operation of transmission lines. Taking 500 kV transmission lines as the research object, electric power fittings failure in heavy icing areas is studied. The following three questions are considered: first, the influence of different ice-shedding methods on the tension of quad bundle conductors; second, the influence of the spans number, span length, height difference, and ice thickness on the conductor tension under the most dangerous ice-shedding mode; lastly, the mechanical characteristics of tension string and suspension string under ice-shedding condition in the stable wind. The results show that the von Mises stress of the parts that connect with the iced conductor in the tension string model is greater than those of the parts connected with the ice-shedding conductor. What is more, the shackle is the most vulnerable part of the whole model, which is prone to wear and damage, and the failure is most likely to occur at the upper shackle. The middle part in the rectangular hanging plate which is connected with the iced conductor is prone to damage, for its maximum stress has already exceeded the yield stress, with a danger degree inferior only to the shackle. In the suspension string model, the von Mises stress of each part is relatively small and does not reach the yield stress. Similarly, the shackle is most likely to be damaged in the overall model, while other parts maintain larger safety margins. The structure of the parts with smaller stress can be optimized according to the simulation results where design margins may be reduced and additional cost benefits realized.

To safely and economically eliminate the threat of high geostress in the coal mining process, based on the engineering case study of pressure relief by slotting residual coal pillars at a mine in the Kailuan mining area, a method of pressure relief by slotting coal seams with a wire saw was explored, and numerical simulation was carried out. The results show that the wire saw can cut coal seams in a large area, with a cutting efficiency and slotting depth greater than those of hydraulic slotting; a stress concentration zone forms in front of the wire saw coal cutting working face and a stress reduction zone and a stress recovery zone form behind. The pressure relief range varies, increasing at first and then decreasing. The exploration and practice of pressure relief by slotting coal seams with a diamond wire provides theoretical guidance and practical reference for pressure relief by slotting coal seams.

Abstract Background Gut microbiome plays a crucial role in modulating human and animal immune responses. Rabies is a fatal zoonosis causing encephalitis in mammals and vaccination is the most effective method to control and eliminate rabies. The relationship between the gut microbiome and humoral immunity post rabies vaccination has not been investigated yet. Methods Mice orally administrated with a cocktail of broad‐spectrum antibiotics were inoculated with rabies vaccines, and humoral immune response was analyzed at indicated time points. The 16S ribosomal RNA (16S rRNA) gene sequencing was performed on fecal samples from groups in vancomycin‐treated and untreated mice. Mice were immunized with rabies vaccines and virus‐neutralizing antibody (VNA) levels were measured, resulting in VNA high (H) and low (L) groups. Then 16S rRNA gene sequencing was performed on fecal samples from H and L group mice. Results After antibiotic (Abx) treatment, mice had decreased levels of rabies virus (RABV)‐specific IgM, IgG, and virus‐neutralizing antibody compared with untreated mice. Abx‐treated mice had fewer T follicular helper cells, germinal center B cells, and antibody secreting cells (ASCs) in lymph nodes than did untreated mice. Gut microbiome facilitated secondary immune responses by increasing the generation of ASCs. Treatment with vancomycin alone had a similarly impaired effect on the humoral immune responses compared with Abx‐treated mice. From the natural population group of mice received rabies vaccines, VNA titers vary significantly and the abundance of Clostridiales and Lachnospiraceae was positively associated with the antibody titers in mice. Conclusions Our results provide the evidence that the gut microbiome impacts humoral immunity post rabies vaccination, and further investigation of the mechanism will help the development of novel adjuvants and vaccines.

Abstract Objective The present study was designed to explore the long‐term differences between three mouse models for depression. Method In the present study, the unpredictable chronic mild stress (UCMS) model, the glucocorticoid/corticosterone model, and the olfactory bulbectomy model were compared at two, three, and five weeks after model induction. Behavioral testing performed included forced‐swimming, tail suspension, open‐field and elevated plus‐maze tests. In addition, 5‐hydroxytryptamine (5‐HT) and dopamine levels, and mRNA and protein expressions related to 5‐HT synthesis, transport, and signaling were analyzed in the hippocampus of tested animals. Results Our results revealed that each model demonstrated a specific profile of markers, whereas the stability of them differed over testing time. Conclusions Each model provided a unique set of advantages that can be considered depending on the context and aims of each study. Among the three models, the UCMS model was mostly stable and appeared to the best model for testing long‐term depression‐like state.

In response to the recent rise in numbers of diabetes patients, many treatments have been developed; but currently, oral antihyperglycemic agents and insulin are still the main clinical treatments. Since current drugs have limitations and harmful side effects, research in alternative treatments has been sought. This article reviews recent research updates of Saskatoon berries (SB), covering its background information, its main active ingredients, its structure, and its function. Flavonoid compounds in Saskatoon berries, in particular flavanol, anthocyanin, and proanthocyanin, possess anti-inflammatory, antitumor, and antidiabetes impacts. The current review synthesizes the latest research on the health benefits of Saskatoon berry in a variety of domains. With further research, SB has the potential to help treat and prevent diabetes in the future.

Objective. The soluble urokinase plasminogen activator receptor (suPAR) is associated with kidney diseases and is used as a prognostic factor of renal function progression. The aim of this study was to explore whether circulating suPAR was associated with antineutrophil cytoplasmic autoantibody- (ANCA-) associated vasculitis (AAV) disease activity. Methods. We evaluated 90 AAV patients with follow-up data and 35 normal controls; their plasma suPAR and C-reactive protein (CRP) levels were measured by ELISA. Associations between these levels, clinical parameters, and prognosis were analyzed. Results. Plasma suPAR levels in AAV patients were significantly higher than in healthy controls (5,920.08±3,447.17 vs. 1,441.97±835.04 pg/mL, P5683.3 pg/mL showed poorer survival than patients with lower levels (log-rank, P=0.001). Besides, multivariate analyses confirmed that plasma suPAR levels were an independent adverse prognostic factor for a composite outcome of end-stage renal disease (ESRD) or death, after adjusting for age and gender (HR 1.05, 95% CI=1.01−1.11, P=0.043). Receiver operating characteristic curves showed a suPAR cutoff value >6662.2 pg/mL for composite outcome with 68% sensitivity and 88% specificity, with an AUC=0.82, (95% CI=0.68−0.96, P

The impinging pressure of a water jet is a key factor in engineering applications, and the jet shape has a great influence on this pressure. In this paper, five different nozzle shapes were designed, and impacting tests were conducted based on a self-designed experimental platform using a PVDF piezoelectric film sensor and a high-speed camera to record the impacting data. Additionally, the computational fluid dynamics (CFD) method was also applied to study the velocity distribution. The results show that the pressure profiles of different water jet shapes impacting onto a solid surface present a consistent pattern, namely, an initial transient and enormous peak pressure and then a longer and smaller stagnation pressure. Although the stagnation pressure in this paper is not sufficiently obvious, the peak pressures of the five water jet shapes are much different from one another. Under the same inlet pressure, the peak pressure of the circular water jet is the largest, and those of the square, triangular, cross-shaped, and elliptical water jets decrease in turn. The flowing regimes captured by the high-speed camera together with the CFD simulation results indicate that the discrepancy in the peak pressure may be a combined action of the liquid velocities and jet head shapes.

In order to investigate the feasibility and reliability of the three-dimensional particle flow method in simulating the type I fracture toughness test, four types of numerical samples were established by particle flow code PFC3D: straight crack three-point bending (SC3PB), edge cracked flattened semicircular disc (ECFSD), cracked chevron notched Brazilian disc (CCNBD), and edge cracked flattened ring (ECFR). Three models with different strength parameters (group A, group B, and group C) were established for each type, in which group A parameters are obtained from the concrete model, group B parameters are applied for simulating marble, and group C parameters are for granite. The type I fracture toughness and the failure form of each model are obtained by conducting the numerical test, and the curves of load versus displacement of loading point are recorded. The numerical test results show that, with the same strength parameter, the maximum difference in test results of each specimen type is 0.39 MPa·m1/2. The KIC of ECFR specimen is 0.13–0.28 MPa·m1/2 smaller than that of CCNBD specimen, and the KIC of ECFSD specimen is slightly higher than that of CCNBD sample. The KIC of SC3PB specimen is 0.06–0.21 MPa·m1/2 smaller than that of the CCNBD sample. When the loading rate is less than 0.01 m/s, the effect of loading rate on fracture toughness can be reduced to less than 0.1 MPa·m1/2.

The premixed abrasive jet possesses a strong strike ability and is widely used in oil and gas exploitation, machining, rust removal, and other fields. The superstrong, forceful impact of the premixed abrasive jet is mainly provided by high-speed abrasive groups. Hence, the abrasive velocity is the basis of this research, by applying the distribution law of abrasive impact force. In this paper, the particle velocity of the premixed abrasive jet is analyzed theoretically, and the corresponding particle velocity model is established. The real-time contrast interpolation method is employed to solve the problem of the variable drag coefficient. Factors such as the nozzle structure, average abrasive diameter, abrasive density, and jet flow are utilized to determine the abrasive velocity of the nozzle outlet. The numerical solution for the abrasive velocity is obtained by dividing the high-pressure pipe and nozzle into several sections, along the axis. Finally, the calculated particle velocity is compared with the particle image velocity measurement (PIV), to verify the correctness of the established model. These results demonstrate that the model calculation is in effective agreement with the experimental results. The deviation between the theoretical value and the experimental mean is 0.18 m/s. The standard deviation of the experimental results is 3.81-4.22 m/s, while the average error is less than 4%.

3-Deoxyglucosone (3DG) is derived from D-glucose during food processing and storage and under physiological conditions. We reported that glucagon-like peptide-1 (GLP-1) secretion in response to an oral glucose load in vivo and high-glucose stimulation in vitro was decreased by acute 3DG administration. In this study, we determined the acute effect of 3DG on GLP-1 secretion under basal conditions and investigated the possible mechanisms. Normal fasting rats were given a single acute intragastric administration of 50 mg/kg 3DG. Plasma basal GLP-1 levels and duodenum 3DG content and sweet taste receptor expression were measured. STC-1 cells were acutely exposed to 3DG (80, 300, and 1000 ng/ml) for 1 h under basal conditions (5.6 mM glucose), and GLP-1 secretion, intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and molecular expression of STR signaling pathway were measured. Under the fasted state, plasma GLP-1 levels, duodenum 3DG content, and duodenum STR expression were elevated in 3DG-treated rats. GLP-1 secretion was increased in 3DG-treated cells under either 5.6 mM glucose or glucose-free conditions. 3DG-induced acute GLP-1 secretion from STC-1 cells under 5.6 mM glucose was inhibited in the presence of the STR inhibitor lactisole, which was consistent with the observation under glucose-free conditions. Moreover, acute exposure to 3DG increased the protein expression of TAS1R2 and TAS1R3 under either 5.6 mM glucose or glucose-free conditions, with affecting other components of STR signaling pathway, including the upregulation of transient receptor potential channel type M5 TRPM5 and the increment of intracellular Ca2+ concentration. In summary, the glucose-free condition was used to first demonstrate the involvement of STR in 3DG-induced acute GLP-1 secretion. These results first showed that acute 3DG administration induces basal GLP-1 secretion in part through upregulation of STR expression.

Sepsis is a common complication of solid organ transplant procedures and, in particular, can affect the prognosis of orthotopic liver transplantation (OLT). This retrospective study determined the pre-, peri-, and postoperative risk factors for sepsis after OLT, using as reference the 2016 Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Pre-, peri-, and postoperative clinical data of the sepsis-positive (n=85) and sepsis-negative (n=41) groups were analyzed for potential risk factors of OLT-related sepsis. The sepsis-positive patients had a significantly higher rate of dialysis (49.4%), longer time under mechanical ventilation (1.5 d), higher hospitalization costs (0.41 million RMB), and worse survival rate (68.5%), compared with the sepsis-negative patients (4.8%, 1 d, 0.30 million RMB, and 73.1%, resp.). The multivariate logistic analysis identified the following as risk factors for OLT-related sepsis: preoperative Child-Pugh grade C (OR 10.43; 95% CI 2.081–52.292; P=0.004), preoperative hypercalcemia (OR 6.372; 95% CI 1.693–23.98; P=0.006), and perioperative acidosis (OR 6.364; 95% CI 1.196–33.869; P=0.030). Patients with preoperative Child-Pugh grade C, preoperative hypercalcemia, or perioperative acidosis are at higher risk for developing sepsis after OLT. When any of these problems occur, timely sepsis management should be planned.