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Background and purpose: For patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients. However, the reference original research trastuzumab (Herceptin®) is more expensive. Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment. This clinical trial aimed to evaluate the efficacy, pharmacokinetics, safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab (Herceptin®) in patients with HER2-positive metastatic breast cancer. Methods: This multi-center, randomised, double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China. This study complied with the research protocol, the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials. It was approved by the hospital's medical ethics committee. The clinical trial registration agency is the State Food and Drug Administration (clinical trial approval number: 2015L04224; clinical trial registration number: CTR20170516). Written informed consent was obtained from subjects before enrollment. Enrolled patients were randomly assigned to the AK-HER2 group and the control group, respectively receiving AK-HER2 or trastuzumab (initial loading dose 8 mg/kg, maintenance dose 6 mg/kg, every 3 weeks as a treatment cycle, total treatment time is 16 cycles) in combination with docetaxel (75 mg/m2, treatment duration is at least 9 cycles). The primary endpoint of this clinical trial was the objective response rate (ORR9) between the AK-HER2 group and the control group in the 9th cycle. Secondary efficacy endpoints included ORR16, disease control rate (DCR), clinical benefit rate (CBR), progression-free survival (PFS) and 1-year survival rate. In this study, 100 subjects (AK-HER2 group to control group=1:1) were randomly selected for blood sample collection after the 6th cycle of medication, The collection time points were 45 minutes after infusion (the end of administration), 4, 8, 24, 72, 120, 168, 336, and 504 hours after the end of administration. After collection, blood samples were analyzed by PK parameter set (PKPS). Other evaluation parameters included safety and immunogenicity assessment. Results: A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep. 2017 and Mar. 2021. In the AK-HER2 group (n=237), 129 subjects in the experimental group achieved complete response (CR) or partial response (PR), and the ORR9 was 54.4%. There were 134 subjects in the control group (n=241) who achieved CR or PR, and the ORR9 was 55.6%. The ORR9 ratio between the AK-HER2 group and the control group was 97.9% [90% confidence interval (CI): 85.4%-112.2%, P=0.784], which was not statistically significant. In all secondary efficacy endpoints, no statistically significant differences were observed between the two groups. We conducted a mean ratio analysis of pharmacokinetics (PK) parameters between the AK-HER2 group and the control group, and the results suggested that the pharmacokinetic characteristics of the two drugs are similar. The incidence of treatment emergent adverse event (TEAE) leading to drug reduction or suspension during trastuzumab treatment was 3.6% (10 cases) in the AK-HER2 group and 8.1% (22 cases) in the control group. There was statistically significant difference between the two groups (P=0.027). The incidence rate was significantly lower in the AK-HER2 group than in the control group, and there was no statistically significant difference among the other groups. The differences in the positive rates of anti-drug antibodies (ADA) and neutralizing antibodies (NAB) between groups were of no statistical significance (P=0.385 and P=0.752). Conclusion: In patients with HER2-positive metastatic breast cancer, AK-HER2 was comparable to the trastuzumab (Herceptin®) in terms of drug efficacy, pharmacokinetics, safety and immunogenicity.

Mast cells are a type of innate immune cells, and have long been considered to be related to the pathogenesis of allergic and autoimmune diseases. However, in recent years, a number of studies have found that mast cells play an indispensable role in tumor development, metastasis, infiltration and angiogenesis, providing new ideas for tumor diagnosis and immunotherapy. Once mast cells have infiltrated solid tumors, they are known as tumor-associated mast cells (TAMCs) and are one of the most controversial immune cells in tumor tissues with remarkable heterogeneity. In view of the important role of mast cells in inflammation and the immune system, this paper reviews the mechanisms of mast cells in solid tumor development and their relationship with angiogenesis and lymphangiogenesis, aiming to deepen the understanding of the relationship between mast cells and tumors.

The Urho Formation in the Lower Permian System at the Junggar Basin in China commonly develops zeolite cements. The presence of zeolite minerals in various states of occurrence and uneven distribution in glutenite reservoirs makes it indeterminate to interpret the well logging response characteristics such as acoustic, resistivity, radioactivity, and nuclear magnetic resonance (NMR). This poses significant challenges for the evaluation of well loggings in glutenite reservoirs containing laumontite and the determination of oil and gas reserves. In this study, through petrophysics experiments such as whole-rock X-ray diffraction, conventional petrophysical properties, mercury injection, and electron microprobe analysis, the characteristics of glutenite reservoirs containing laumontite and the well logging response mechanisms were analyzed from the perspectives of mineral composition of rocks, geochemical characteristics, and principle of loggings. A multimineral optimization method was used to calculate the laumontite content. The results indicate that in the study area, the cementation of zeolite minerals dominated by laumontite suppresses the pore development in the reservoir, which is a crucial factor in the formation of complex pore structures and low-porosity low-permeability reservoirs. Since laumontite exhibits a water-bearing framework structure with numerous micropores and crystal water, the laumontite-bearing glutenite reservoirs are characterized by low natural gamma radiation, low density, high neutron porosity, and high electrical resistivity. The acoustic interval transit time shows no significant differences, while the NMR T2 spectrum exhibits a short relaxation time.

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and high mortality rates. It remains a prevailing clinical need to distinguish whether the patient can benefit from therapy, such as chemotherapy. By integrating single-cell and global transcriptome data, we have for the first time identified TCL1A+ B cell functions that are prognostically relevant in TNBC. This finding broadens the perspective of traditional tumor-infiltrating lymphocytes in predicting survival, especially the potential value of B cells in TNBC. Single-cell RNA-seq data from five TNBC patients were collected to identify the association between immune cell populations and clinical outcomes. Functional analysis was according to gene set enrichment analysis using pathways from MsigDB. Subsequently, the gene signature of TCL1A+ B cells based on differential expression genes of TCL1A+ B cells versus other immune cells was used to explore the correlation with tumor microenvironment (TME) and construct a prognostic signature using a non-parametric and unsupervised method. We identified TCL1A+ B cells as a cluster of B cells associated with clinical outcomes in TNBC. Functional analysis demonstrated its function in B cell activation and regulation of immune response. The highly enriched TCL1A+ B cell population was found to be associated with a thermal TME with anti-tumor effects. A high abundance of TCL1A+ B cell population is positively correlated with a favorable therapeutic outcome, as indicated by longer overall survival. The present study suggests that TCL1A+ B cells play a key role in the treatment and prognostic prediction of TNBC, although further studies are needed to validate our findings. Moreover, the integration of transcriptome data at various resolutions provides a viable approach for the discovery of novel prognostic markers.

(1) Background: Immune-related adverse events (irAEs) are a series of unique organ-specific inflammatory toxicities observed in patients with hepatocellular carcinoma (HCC) undergoing PD-1 inhibition combination therapy. The specific underlying mechanisms remain unclear. (2) Methods: We recruited 71 patients with HCC undergoing PD-1 inhibition combination therapy. These patients were then divided into two groups based on irAE occurrence: 34 had irAEs and 37 did not. Using Olink proteomics, we analyzed the aberrant inflammation-related proteins (IRPs) in these patient groups. For single-cell RNA sequencing (scRNA-seq) analysis, we collected peripheral blood mononuclear cells (PBMCs) from two representative patients at the pretreatment, irAE occurrence, and resolution stages. (3) Results: Our study revealed distinct plasma protein signatures in HCC patients experiencing irAEs after PD-1 inhibition combination therapy. We clarified the relationship between monocyte activation and irAEs, identified a strongly associated CD14-MC-CCL3 monocyte subset, and explored the role of the IFN-γ signaling pathway in monocyte activation during irAEs. (4) Conclusions: The activation of monocytes induced by the IFN-γ signaling pathway is an important mechanism underlying the occurrence of irAEs in HCC patients receiving PD-1 inhibition combination therapy.

Objective To investigate the effect of indocyanine green(ICG) fluorescence imaging to indicate blood supply of sigmoid-rectal anastomosis in laparoscopic anterior resection of rectal cancer. Methods Here a retrospective cohort study including 175 consecutive patients with rectal cancer scheduled for laparoscopic surgery in Department of Gastrointestinal Surgery of Renji Hospital between January 2019 and December 2022 was analysed. These patients were classified into two groups, according to using ICG or not within surgery: the ICG group (n=65) and the control group (n=110). Operation situations and complications were compared between the two groups. Results The operation time of ICG group was longer than that of control group [(151.6±4.8) min vs (139.5±3.7) min, P=0.04], and the preventive ileostomy rate was lower than that of control group (12.3% vs 34.6%, P=0.01), while the other operation data (intraoperative blood loss, number of lymph node dissection), were similar between the two groups (P>0.05). The rate of anastomotic leakage in ICG group were lower than that in control group (4.6% vs 14.6%, P=0.04), and there was no significant differences in wound infection, urinary retention and intestinal obstruction between the two groups (P>0.05). Conclusions The ICG displays that the blood supply in laparoscopic anterior resection of rectal cancer can reduce the incidence of anastomotic leakage, which improves the surgical safety and the quality of postoperative life.

Anastomotic leakage (AL) is one of the inevitable and severe complications after laparoscopic-assisted anterior resection of low rectal cancer. With the improvement of surgical technology and cognitive concept, the position of sigmoid-rectal anastomosis is becoming lower and lower, and the problem of AL is more challenging. Preventive stoma is currently a common method to deal with AL, but over-reliance on stoma and the stoma-related complications have also troubled surgeons. Based on years of practical experience, we summarized how to avoid unnecessary stoma through the risk assessment scale, and how to detect and deal with AL in the early stage of laparoscopic-assisted anterior resection of low rectal cancer.

Objective: This study aimed to improve the application range and bioavailability of ursolic acid. Methods: The W/O/W pickering emulsion was prepared by a two-step process with ursolic acid as emulsifier and pectin as external aqueous phase. The preparation conditions of W/O emulsion were optimized by a single factor experiment, and the effects of pectin mass concentration on physicochemical properties, microstructure, rheological properties and long-term stability of W/O/W pickering emulsion were studied. Results: The optimal preparation technology of W/O emulsion was ursolic acid mass concentration of 4 g/100 mL, water-oil mass ratio of 2∶3, homogenization speed of 9 000 r/min, homogenization time of 5 min. The particle size of the double emulsion prepared with pectin as the external aqueous phase was between 30～40 μm. The absolute value of zeta potential, rheological property and storage stability of the emulsion at 4 ℃ were significantly improved with the increase of pectin mass concentration. Conclusion: The stable pickering double emulsion could be prepared when the mass concentration of pectin was 0.3, 0.4, 0.5 g/100 mL.

Flight load analysis is a complex and arduous task, and developing a fast analysis method during the conceptual design stage is of great importance to improve the efficiency of flight load calculation. Based on the small disturbance linear analysis theory, the theoretical calculation methods of wing-body aerodynamic load, horizontal tail aerodynamic load, vertical tail aerodynamic load, control surface hinge moment, and the engineering calculation methods of aerodynamic load distribution, inertial load distribution, shear and bending moment of lift surface are summarized. This is a simplified calculation method of flight load. A mathematical model of a certain single seat competitive aircraft is established in the Matlab environment, taking the configuration dimension, mass characteristics and aerodynamic derivative as inputs, the response process of aerodynamic load, inertial load, control surface hinge moment, shear and bending moment are obtained. The results show that the simplified method can quickly get the dynamic parameters with less input data, and the calculation results can be used to satisfy the load requirements of structural design in the conceptual design stage.

In this article, the influence of trapezoidal magnetization method on cogging torque of permanent magnet motor is studied. First, the structure is analyzed by analytical method to explain its mechanism of reducing cogging torque. Then, in order to verify the effectiveness of the formula, a six-slot four-pole motor is introduced for finite element analysis. Through comparison of the original structure motor, the magnet skew structure motor, and the trapezoidal magnetic pole structure motor, it demonstrates that the trapezoidal magnetic pole structure motor can effectively reduce the Cogging torque and does not produce additional axial electromagnetic force. Finally, a magnetizing fixture with a trapezoidal magnetic pole structure is made to magnetize the magnetic ring. The magnetized magnetic ring is installed on the motor, and the Cogging torque, Back EMF, etc., are tested. The test results are in good agreement with the simulation results. This method can be used to optimize the cogging torque of the permanent magnet motor.

BackgroundDuchenne muscular dystrophy (DMD, ORPHA:98896) is a lethal X-linked recessive disease that manifests as progressive muscular weakness and wasting. Mutations in the dystrophy gene (DMD) are the main cause of Duchenne muscular dystrophy.Case presentationThis study aims to determine novel mutations of DMD and help preimplantation genetic diagnosis (PGD) for family planning. Here present a 4-year-old Chinses boy with DMD, whole-exome sequencing (WES) was performed to identify the molecular basis of the disease. It was confirmed that the boy carried a novel hemizygous mutation of NC_000023.11(NM_004006.3): c.5912_5922 + 19delinsATGTATG in DMD which inherited from his mother. This led to the aberrant splicing of DMD which demonstrated by a minigene splicing assay and further resulted in the impairment of the dystrophy protein.ConclusionsOur study discovered a novel splicing mutation of DMD in a DMD patient, which expands the variant spectrum of this gene and provide precise genetic diagnosis of DMD for timely therapy. Meanwhile, this finding will supply valuable information for preimplantation genetic diagnosis.

The gastrointestinal microbiota develop alongside the host and play a vital role in the health of cecal fermenters such as chinchillas. However, little is known about the microbiota architecture in healthy chinchillas. Illumine-based 16S rRNA gene amplicon sequencing was used to investigate the microbiota present in six different gastrointestinal tract regions of three healthy adult chinchillas. The findings revealed significantly more abundant microbiota in the large intestine compared with the proximal segments. In addition, the cecum exhibited better evenness compared to the colon. The core microbiota are Firmicutes, Bacteroidota, Actinobacteriota, and Proteobacteria at the phylum level. The signature microbiota of each segment were identified. The cecum had 10 signature microbiota, which had the widest coverage and overlapped with that of the cecum. The stomach had five signature microbiota, exhibiting the second widest coverage and overlapping with the duodenum. No signature microbiota were detected in the jejunum and ileum. While similarities exist with the microbiota of other cecal fermenters, chinchillas exhibit distinct microbiota closely related to their unique digestive mechanisms. This study is a preliminary study of the gastrointestinal microbiota architecture and distribution in healthy chinchillas. Further study is needed in order to better understand the effect of gastrointestinal microbiota on the health of the chinchilla.

Over the past decade, two-dimensional (2D) Ti3C2Tx MXenes demonstrated attractive characteristics such as high electrical conductivity, tunable layered structure, controllable interfacial chemical composition, high optical transparency, and excellent electromagnetic wave absorption, enabling Ti3C2Tx MXenes as promising electrode materials in energy storage devices. Among these devices, flexible energy storage devices have attracted wide attention and developed rapidly due to the synchronously excellent electrochemical and mechanical properties. This review summarizes the recent progress of Ti3C2Tx MXenes pertaining to novel material preparation and promising applications in energy storage and conversion including batteries, supercapacitors, solar cells, and solar steam generation. This work aims to provide an in-depth and reasonable understanding of the relationship between the unique nanostructure/chemical composition of Ti3C2Tx MXenes and competitive electrochemical properties, which will facilitate the development of 2D Ti3C2Tx MXenes for practical energy storage and solar energy conversion devices.

We concern with the extinction behavior of the solution for a parabolic p-Laplacian equation with gradient source and singular potential. By energy estimate approach, Hardy-Littlewood-Sobolev inequality, a series of ordinary differential inequalities, and super-solution and sub-solution methods, we obtain the conditions on the occurrence of the extinction phenomenon of the weak solution.

Acute-on-chronic liver failure (ACLF) is a major cause of liver-related death worldwide, but its key pathological features remain incompletely defined. This study aimed to reveal the molecular basis of hepatitis B virus-related ACLF (HBV-ACLF) by transcriptome sequencing of human liver tissue. A total of 18 human liver tissues from patients with different stages of HBV-related disease were collected for RNA sequencing, and liver tissues from patients and mouse models with ACLF were used for subsequent validation. Specifically, 6,853 differentially expressed genes (DEGs) and 5,038 differentially expressed transcripts were identified in patients with ACLF compared to patients with chronic hepatitis B (CHB) and normal controls (NCs). Investigation of functional by KEGG pathway enrichment analysis revealed prominent immune and metabolic dysregulation at the ACLF stage. We found that the key genes FGF19, ADCY8 and KRT17, which are related to immunometabolic disturbances, were significantly upregulated in the progression of ACLF. The three key genes were validated in human and mouse samples, indicating their prognostic and therapeutic potential in ACLF. In summary, our work reveals that immunometabolic disorder is involved in HBV-ACLF pathogenesis and indicates that FGF19, ADCY8 and KRT17 may be sensitive biomarkers for HBV-related ACLF.

BackgroundThe family with sequence similarity 72 member A (FAM72A) protein has been identified as an effector of multiple pathological processes in many cancers. The value of FAM72A in HCC remains largely unknown.MethodsData from TCGA-LIHC, ICGC-LIRI-JP, IMvigor210, cBioPortal, GeneMANIA, and TIMER were processed and visualized to explore the association between FAM72A and the prognosis, stemness phenotype, mutational burden, immune cell infiltration, and drug sensitivity in HCC patients. Potential pathways were also revealed. Furthermore, we experimentally verified the results in vivo and in vitro using immunohistochemistry, western blotting, and CCK-8 assays.ResultsFirst, FAM72A mRNA expression was significantly upregulated in HCC. High FAM72A expression was independently associated with a poor prognosis. Experimental validation confirmed that FAM72A was remarkably overexpressed in HCC patients and mice. Moreover, FAM72A knockdown suppressed HCC cell proliferation. In addition, the frequency of TP53 mutations was significantly higher in the high FAM72A expression group. Subsequently, the enrichment analysis revealed that FAM72A was closely related to immune processes and mTOR pathways. Silencing FAM72A increased the expression levels of mTOR in HCC cell lines. The FAM72A-mTOR pathway was strongly associated with a poor prognosis for patients with HCC. Patients with high FAM72A expression levels might be more resistant to sorafenib. Furthermore, the expression of FAM72A and mTOR was significantly associated with the abundance of some tumor-infiltrating immune cells, especially CD4+ T cells. Finally, patients with high levels of FAM72A and mTOR were more sensitive to immunotherapy.ConclusionsFAM72A, a member of the FAM72 family, might be a prognostic and immunotherapeutic target for HCC patients.

Aim: Bladder outlet obstruction (BOO) leads to bladder wall remodeling accompanying the progression from inflammation to fibrosis where pathological hydrostatic pressure (HP)-induced alteration of bladder smooth muscle cells (BSMCs) hypertrophic and excessive extracellular matrix (ECM) deposition play a pivotal role. Recently, we have predicted survivin (BIRC5) as a potential hub gene that might be critical during bladder fibrosis by bioinformatics analyses from rat BOO bladder, but its function during BOO progression remains unknown. Here, we investigated the role of survivin protein on bladder dysfunction of BOO both in vitro and in vivo.Methods: Sprague-Dawley female rats were divided into three groups: control group, BOO group, and BOO followed by the treatment with YM155 group. Bladder morphology and function were evaluated by Masson staining and urodynamic testing. To elucidate the underlying mechanism, hBSMCs were subjected to pathological HP of 200 cm H2O and co-cultured with the presence or absence of survivin siRNA and/or autophagy inhibitor 3-MA. Autophagy was evaluated by the detection of Beclin1 and LC3B-II expression, proliferation was conducted by the EdU analysis and PCNA expression, and fibrosis was assessed by the examination of Col 1 and Fn expression.Results: BOO led to a gradual alteration of hypertrophy and fibrosis of the bladder, and subsequently induced bladder dysfunction accompanied by increased survivin expression, while these histological and function changes were attenuated by the treatment with YM155. HP significantly increased survivin expression, upregulated Col1 and Fn expression, enhanced proliferation, and downregulated autophagy markers, but these changes were partially abolished by survivin siRNA treatment, which was consistent with the results of the BOO rat experiment. In addition, the anti-fibrotic and anti-proliferative effects of the survivin siRNA treatment on hBSMCs were diminished after the inhibition of autophagy by the treatment with 3-MA.Conclusion: In summary, the upregulation of survivin increased cell proliferation and fibrotic protein expression of hBSMC and drove the onset of bladder remodeling through autophagy during BOO. Targeting survivin in pathological hBSMCs could be a promising way to anti-fibrotic therapeutic approach in bladder remodeling secondary to BOO.

BackgroundThe p.Ser267Phe mutation in the SLC10A1 gene can cause NTCP deficiency. However, the full clinical presentation of p.Ser267Phe homozygous individuals and its long-term consequences remain unclear. Hence, in the present study, we characterized the phenotypic characteristics of NTCP deficiency and evaluated its long-term prognosis.MethodsTen NTCP p.Ser267Phe homozygous individuals were recruited and a comprehensive medical evaluation with a 5-year follow-up observation was performed. The phenotypic characteristics of NTCP deficiency were also demonstrated using an NTCP-global knockout mouse model.ResultsDuring the 5-year follow-up observation of 10 NTCP p.Ser267Phe homozygous adults, we found that the most common phenotypic features of NTCP deficiency in adults were hypercholanemia, vitamin D deficiency, bone loss, and gallbladder abnormalities. The profile of bile acids (BAs) in the serum was significantly altered in these individuals and marked by both elevated proportion and concentration of primary and conjugated BAs. Moreover, the NTCP deficiency led to increased levels of serum BAs, decreased levels of vitamin D, and aggravated the osteoporotic phenotype induced by estrogen withdrawal in mice.ConclusionsBoth mice and humans with NTCP deficiency presented hypercholanemia and were more prone to vitamin D deficiency and aggravated osteoporotic phenotype. Therefore, we recommend monitoring the levels of BAs and vitamin D, bone density, and abdominal ultrasounds in individuals with NTCP deficiency.

One of the biggest challenges hindering a table tennis robot to play as well as a professional player is the ball’s accurate motion control, which depends on various factors such as the incoming ball’s position, linear, spin velocity and so forth. Unfortunately, some factors are almost impossible to be directly measured in real practice, such as the ball’s spin velocity, which is difficult to be estimated from vision due to the little texture on the ball’s surface. To perform accurate motion control in table tennis, this study proposes to learn a ball stroke strategy to guarantee desirable “target landing location” and the “over-net height” which are two key indicators to evaluate the quality of a stroke. To overcome the spin velocity challenge, a deep reinforcement learning (DRL) based stroke approach is developed with the spin velocity estimation capability, through which the system can predict the relative spin velocity of the ball and stroke it back accurately by iteratively learning from the robot-environment interactions. To pre-train the DRL-based strategy effectively, this paper develops a virtual table tennis playing environment, through which various simulated data can be collected. For the real table tennis robot implementation, experimental results demonstrate the superior performance of the proposed control strategy compared to that of the traditional aerodynamics-based method with an average landing error around 80mm and the landing-within-table probability higher than 70%.

The gastrointestinal microbiota plays an important role in health of the host animals and the detrimental influence of pharmaceutical treatment on the fecal microbiota receives an increasing concern. The clinical use of ivermectin on chinchillas has not yet been evaluated. The purpose of our study was to assess the influence of ivermectin injection on the fecal bacterial microbiota of chinchillas. A with-in subject, before and after study was performed on 10 clinically healthy chinchillas during a 14-day period, all chinchillas received the same ivermectin treatment, and the microbiota from their fecal samples before and after administration were compared as two experimental groups. Fecal samples were collected on day 0 (before ivermectin administration) and day 14 (post ivermectin administration). Fecal bacterial microbiota was analyzed by bacterial 16S rRNA gene sequencing. No clinical abnormalities were observed post subcutaneous administration of ivermectin. No significant alteration was found in the abundance and diversity of fecal bacterial microbiota after treatment, but the dominant position of some bacterial species changed. In conclusion, ivermectin administration was associated with minimal alternations of the fecal bacterial microbiota in healthy chinchillas, and these changes had no observed negative effect on general health of chinchillas in short term.

In the flexible manufacturing system, a reasonable production scheduling is crucial in shortening the processing completion time and improving the equipment utilization. Traditional manual scheduling cannot effectively solve the complex workshop scheduling problems and cannot provide a scheduling solution that meets the requirements in a short period of time, which can lead to a decrease in processing efficiency. Aiming at the complex job shop scheduling problem, the genetic algorithm is used to find the optimal scheduling solution in this study, taking the number of overdue jobs, the total overdue time, the job completion time, the comprehensive load rate and the maximum load rate of the machine tool as the performance indicators of the scheduling algorithm. The chromosomes are designed as process gene chain and equipment gene chain to improve the diversity and the robustness to scheduling problems of chromosome through crossover, variation, selection and other processes. The impact of different parameter settings on the performance indicators of each scheduling algorithm is researched by adjusting the four algorithm-related parameters, and there has been a certain improvement in the results of the scheduling problems. This study provides a reference for the design and optimization of production scheduling algorithm based on genetic algorithm.

The medium altitude long endurance (MALE) UAV has many advantages, which can be used to carry out a variety of military and civil missions, and has become the research and development hotspot of various countries. In order to make the MALE UAV have good dynamic and economic performance in all flight stages, a method of matching constant speed propeller for piston engine is proposed. According to the speed and fuel consumption characteristic curve of piston engine, the economic working points of the engine are selected and then efficiencies of each propeller on the economic working points above are compared and analyzed. Wind tunnel tests of full scale engine and propeller are conducted. Results show that the proposed method could be used to select optimal constant propeller for preliminarily selected piston engine.

Intracranial hemorrhage (ICH) causes high mortality and disability without effective treatment in the clinical setting. (−)-Epigallocatechin-3-gallate (EGCG) exerts an essential role in the central nervous system and offers a promising therapeutic agent for the treatment of oxidative damage-related diseases. MiR-137 can inhibit the oxidative stress and apoptosis to attenuate neuronal injury. However, the role of EGCG in regulating miR-137-3p and neuronal Parthanatos remains to be unclear. In the present study, we build the ICH mice model to investigate the antioxidant effects of EGCG via upregulating miR-137-3p and inhibiting neuronal Parthanatos. We revealed that EGCG upregulated miR-137-3p and inhibited neuronal Parthanatos, and promoted the functional recovery, alleviated ICH-induced brain injury, and reduced oxidative stress in mice following ICH. However, following the inhibition of miR-137-3p and activation of Parthanatos, EGCG was unable to exert neuroprotective roles. These combined results suggest that EGCG may upregulate miR-137-3p and inhibit neuronal Parthanatos to accelerate functional recovery in mice after ICH, laying the foundation for EGCG to be a novel strategy for the treatment of neuronal injuries related to Parthanatos.

This study proposes a time-space compression (TSC) model and evaluates the TSC effect of high-speed rail (HSR) on a sample of 2662 classified tourist destinations from 2008 to 2019 in China with the help of GIS technology. Based on panel models, this study finds that, within five hours: (1) the TSC effect of HSR on tourist destinations in eastern and central China is three times stronger than that in western and north-eastern China; (2) the negative impact coefficient of TSC of HSR on tourist destination development in China within temporal distances (3 h, 4 h, 5 h) are −0.193, −0.117, and −0.091 respectively; and (3) the farther the temporal distance, the weaker the inhibitory effect. Results from this study contribute to the literature by providing empirical evidence of the potentially negative TSC effect on regional and tourism development. Findings provide managerial implications suggesting that tourist destinations should implement marketing policies to retain tourists and prevent the loss of tourists brought by the opening of HSR.

Tissue engineering is an emerging field to create functional tissue components and whole organs. The structural and functional defects caused by congenital malformation, trauma, inflammation or tumor are still the major clinical challenges facing modern urology, and the current treatment has not achieved the expected results. Recently, 3D bioprinting has gained attention for its ability to create highly specialized tissue models using biological materials, bridging the gap between artificially engineered and natural tissue structures. This paper reviews the research progress, application prospects and current challenges of 3D bioprinting in urology tissue engineering.

Objective: To identify the effect of music on outpatient-based cystoscopy.Methods: We systematically reviewed the effect of music on all reported outpatient for cystoscopy and extracted data from randomized trials from inception to February 3, 2021, with no language restrictions. The analysis was completed via STATA version 14.2.Results: A total of 27 studies were initially identified, and 6 articles containing 639 patients were included in the final analysis. In terms of post-procedural pain perception, a pooled analysis of 6 articles containing 639 patients showed that music seems to improve discomfort in patients who undergo cystoscopy (WMD: −1.72; 95%CI: −2.37 to −1.07). This improvement remained consistent in patients undergoing flexible cystoscopy (FC) (WMD: −1.18; 95% CI: −1.39 to −0.98) and rigid cystoscopy (RC) (WMD: −2.56; 95% CI: −3.64 to −1.48). The music group also had less post-procedural anxiety than those in no music group during cystoscopy (WMD: −13.33; 95% CI: −21.61 to −5.06), which was in accordance with the result of FC (WMD: −4.82; 95% CI: −6.38 to −3.26) than RC (WMD: −26.05; 95% CI: −56.13 to 4.04). Besides, we detected a significantly lower post-procedural heart rate (HR) in the music group than no music group during cystoscopy (WMD: −4.04; 95% CI: −5.38 to −2.71), which is similar to the results of subgroup analysis for FC (WMD: −3.77; 95% CI: −5.84 to −1.70) and RC (WMD: −4.24; 95% CI: −5.98 to −2.50). A pooled analysis of three trials indicated that patients in the music group had significantly higher post-operative satisfaction visual analog scale (VAS) scores than those in the no-music group during RC. However, there was no significant difference between the music group and no music group regarding post-procedural systolic pressures (SPs) during cystoscopy (WMD: −3.08; 95% CI: −8.64 to 2.49). For male patients undergoing cystoscopy, the music seemed to exert a similar effect on decreasing anxiety and pain, and it might serve as a useful adjunct to increase procedural satisfaction.Conclusions: These findings indicate that listening to music contributes to the improvement of pain perception, HR, and anxiety feeling during cystoscopy, especially for male patients undergoing RC. Music might serve as a simple, inexpensive, and effective adjunct to sedation during cystoscopy.

Migration and embedding of an intrauterine contraceptive device (IUCD) in the urinary bladder wall is rare. We present such a case of a 30-year-old woman with complaints of persistent lower urinary tract symptoms and a history of IUCD placement 8 years earlier. The IUCD was successfully removed with cystoscopy alone. The patient recovered well and had her second baby after the surgery without complaints of new urinary symptoms.

A quarter of humanity is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) with a 5-10% risk of developing tuberculosis (TB) disease. Variability in responses to Mtb infection could be due to host or pathogen heterogeneity. Here, we focused on host genetic variation in a Peruvian population and its associations with gene regulation in monocyte-derived macrophages and dendritic cells (DCs). We recruited former household contacts of TB patients who previously progressed to TB (cases, n = 63) or did not progress to TB (controls, n = 63). Transcriptomic profiling of monocyte-derived DCs and macrophages measured the impact of genetic variants on gene expression by identifying expression quantitative trait loci (eQTL). We identified 330 and 257 eQTL genes in DCs and macrophages (False Discovery Rate (FDR) < 0.05), respectively. Four genes in DCs showed interaction between eQTL variants and TB progression status. The top eQTL interaction for a protein-coding gene was with FAH, the gene encoding fumarylacetoacetate hydrolase, which mediates the last step in mammalian tyrosine catabolism. FAH expression was associated with genetic regulatory variation in cases but not controls. Using public transcriptomic and epigenomic data of Mtb-infected monocyte-derived dendritic cells, we found that Mtb infection results in FAH downregulation and DNA methylation changes in the locus. Overall, this study demonstrates effects of genetic variation on gene expression levels that are dependent on history of infectious disease and highlights a candidate pathogenic mechanism through pathogen-response genes. Furthermore, our results point to tyrosine metabolism and related candidate TB progression pathways for further investigation.

By energy estimate approach and the method of upper and lower solutions, we give the conditions on the occurrence of the extinction and nonextinction behaviors of the solutions for a quasilinear parabolic equation with nonlinear source. Moreover, the decay estimates of the solutions are studied.