Multiplicity of Nontrivial Solutions for a Class of Nonlocal Elliptic Operators Systems of Kirchhoff Type

We investigate the existence and multiplicity of nontrivial solutions for a Kirchhoff type problem involving the nonlocal integrodifferential operators with homogeneous Dirichlet boundary conditions. The main tool used for obtaining our result is Morse theory

Finite-Time Stability of Fractional-Order BAM Neural Networks with Distributed Delay

Based on the theory of fractional calculus, the generalized Gronwall inequality and estimates of mittag-Leffer functions, the finite-time stability of Caputo fractional-order BAM neural networks with distributed delay is investigated in this paper. An illustrative example is also given to demonstrate the effectiveness of the obtained result

Effects of 4A Zeolite Additions on the Structure and Performance of LDPE Blend Microfiltration Membrane through Thermally Induced Phase Separation Method

Microfiltration membranes, 4A zeolite/LDPE, were prepared by blending low density polyethylene (LDPE) and4A zeolite through thermally induced phase separation (TIPS) process with diphenyl ether (DPE) as diluent. The effects of 4A zeolite loading on the pore structure and water permeation performance of the 4A zeolite/LDPE blend membranes were investigated. The incorporation of 4A zeolite particles greatly enhanced the connectivity of membrane pores, the pore size, and thus the water flux of 4A zeolite/LDPE blend membranes due to the gradually stronger DPE-zeolite affinity with the increase of the 4A zeolite loading. The water flux increased from 0 of LDPE control membrane to 87 L/m2h of 4A zeolite/LDPE blend membrane with 4A zeolite loading of 10 wt%. In addition, increasing the DPE content and cooling bath temperature is in favor of the water flux of 4A zeolite/LDPE blend membranes

The FOXO Transcription Factor Controls Insect Growth and Development by Regulating Juvenile Hormone Degradation in the Silkworm, \u3cem\u3eBombyx mori\u3c/em\u3e

Forkhead box O (FOXO) functions as the terminal transcription factor of the insulin signaling pathway and regulates multiple physiological processes in many organisms, including lifespan in insects. However, how FOXO interacts with hormone signaling to modulate insect growth and development is largely unknown. Here, using the transgene-based CRISPR/Cas9 system, we generated and characterized mutants of the silkworm Bombyx mori FOXO (BmFOXO) to elucidate its physiological functions during development of this lepidopteran insect. The BmFOXO mutant (FOXO-M) exhibited growth delays from the first larval stage and showed precocious metamorphosis, pupating at the end of the fourth instar (trimolter) rather than at the end of the fifth instar as in the wild-type (WT) animals. However, different from previous reports on precocious metamorphosis caused by juvenile hormone (JH) deficiency in silkworm mutants, the total developmental time of the larval period in the FOXO-M was comparable with that of the WT. Exogenous application of 20-hydroxyecdysone (20E) or of the JH analog rescued the trimolter phenotype. RNA-seq and gene expression analyses indicated that genes involved in JH degradation but not in JH biosynthesis were up-regulated in the FOXO-M compared with the WT animals. Moreover, we identified several FOXO-binding sites in the promoter of genes coding for JH-degradation enzymes. These results suggest that FOXO regulates JH degradation rather than its biosynthesis, which further modulates hormone homeostasis to control growth and development in B. mori. In conclusion, we have uncovered a pivotal role for FOXO in regulating JH signaling to control insect development

Photodynamic therapy in combination with immune checkpoint inhibitors plus chemotherapy for first-line treatment in advanced or metastatic gastric or gastroesophageal junction cancer: A phase 2–3 clinical trial protocol

Introduction: The immune checkpoint inhibitor (ICI) has been approved as the first-line therapy for metastatic gastric cancer in China. The treatment response of immune checkpoint inhibitor is highly dependent on the immune condition within the tumor microenvironment. Photodynamic therapy (PDT) has a long history in cancer treatment, and recent studies showed it had an immunomodulatory effect on the tumor. Here we will conduct a trial to assess whether or not a combination with Photodynamic therapy will improve the outcomes of immune checkpoint inhibitor-based treatment in patients with advanced or metastatic gastric cancer.Methods: This study is a single-center, open-label, randomized controlled, phase 2–3 trial. Patients (18–65 years old) with untreated gastric or gastroesophageal junction adenocarcinoma will be eligible for this trial. Sixty participants will be enrolled and randomly divided into the test group (n = 30) and control group (n = 30) to receive photodynamic therapy in combination with immune checkpoint inhibitor plus chemotherapy and immune checkpoint inhibitor plus chemotherapy, respectively. The primary is progression-free survival (PFS). The secondary outcomes include objective response rates (ORRs) and the occurrence of adverse events. In addition, we will also assess the changes in peripheral blood mononuclear cells (PBMCs) and tumor microenvironment after photodynamic therapy treatment in the test group. Evaluation of the tumor response will be performed every two cycles for a maximum of eight cycles.Discussion: Photodynamic therapy has an immunomodulatory effect on the tumor microenvironment; however, this has not been demonstrated for gastric cancer in a clinical trial. Based on our experience of photodynamic therapy treatment in digestive tract tumors, we plan to conduct a randomized controlled trial on this topic. This will be the first study to evaluate the synergistic effect of photodynamic therapy with immunochemotherapy for patients with advanced gastric cancer.Ethics and dissemination: It was approved by the Institutional Research Ethics Committee of Lanzhou University Second Hospital (No. 2022A-491). When this trial is completed, it will be shared at conferences and submitted for a potential publication in a peer-reviewed journal.Clinical Trial Registration:http://www.chictr.org.cn/, identifier ChiCTR2200064280

ZSM-5 Filled Polyether Block Amide Membranes for Separating EA from Aqueous Solution by Pervaporation

ZSM-5 filled polyether block amide membranes (PEBA), PEBA/ZSM-5, were prepared and used to recover aroma, ethyl acetate (EA), from aqueous solution by pervaporation (PV). The membranes demonstrated high EA permselectivity, and with the increase of ZSM-5 loading, the separation factor increased initially and then decreased, while the total flux demonstrated the similar variation until the ZSM-5 loading was 10 wt%, at which it reached the lowest value. After that, it began to increase again. On the other hand, the separation factor, and total flux of the PEBA/ZSM-5 membrane containing 10 wt% ZSM-5, PEBA/ZSM-5-10, increased with the increase of feed concentration and temperature. The best PV performance, separation factor and total flux of PEBA/ZSM-5-10 membrane were 185.5 and 199.5 gm−2h−1, respectively, with feed concentration of 5 wt% EA at 50°C

Experimental and computational study on anti-gastric cancer activity and mechanism of evodiamine derivatives

Introduction: Human topoisomerase 1 (TOP1) is an important target of various anticancer compounds. The design and discovery of inhibitors targeting TOP1 are of great significance for the development of anticancer drugs. Evodiamine and thieno [2,3-d] pyridine hybrids show potential antitumor activity. Herein, the anti-gastric cancer activities of these hybrids were investigated.Methods: The inhibitory effects of different concentrations of ten evodiamine derivatives on the gastric cancer cell line SGC-7901 were assessed using a methyl thiazolyl tetrazolium assay. Compounds EVO-1 and EVO-6 strongly inhibited gastric cancer cell proliferation, with inhibition rates of 81.17% ± 5.08% and 80.92% ± 2.75%, respectively. To discover the relationship between the structure and activity of these two derivatives, density functional theory was used to investigate their optimized geometries, natural population charges, frontier molecular orbitals, and molecular electrostatic potentials. To clarify their anti-gastric cancer mechanisms, molecular docking, molecular dynamics simulations, and binding free energy calculations were performed against TOP1.Results: The results demonstrated that these compounds could intercalate into the cleaved DNA-binding site to form a TOP1–DNA–ligand ternary complex, and the ligand remained secure at the cleaved DNA-binding site to form a stable ternary complex. As the binding free energy of compound EVO-1 with TOP1 (−38.33 kcal·mol−1) was lower than that of compound EVO-6 (−33.25 kcal·mol−1), compound EVO-1 could be a more potent anti-gastric cancer agent than compound EVO-6.Discussion: Thus, compound EVO-1 could be a promising anti-gastric cancer drug candidate. This study may facilitate the design and development of novel TOP1 inhibitors

Single longitudinal mode narrow linewidth thulium-doped fiber laser based on an eye-shaped dual-ring filter

A single-longitudinal-mode (SLM) thulium-doped fiber laser, based on an eye-shaped passive dual-ring filter, is designed and constructed. The eye-shaped passive compound cavity consisting of four couplers is used to increase the longitudinal mode spacing, and its performance is numerically analyzed in detail. A homemade uniform fiber Bragg grating serves as a wavelength selection device and a saturable absorber is used to further suppress the intense longitudinal mode competition in the laser cavity, ensuring the single-longitudinal-mode output. The experimental results demonstrate a laser output with a center wavelength of 2,049.85 nm and an optical signal-to-noise ratio of 63 dB. Moreover, the power fluctuation is less than 0.6 dB, and the center wavelength fluctuation is less than 0.03 nm over a continuous measurement period of 60 min, demonstrating an excellent stability. The laser linewidth is measured using an unbalanced Michelson interferometer and β-separation line method, resulting in a linewidth of 11.22 kHz

Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys

Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT