PD-1 inhibitors-based second-line therapy for metastatic gastric cancer

BackgroundMetastatic gastric cancer (MGC) patients with progression on first-line treatment still have poor outcomes on chemotherapy. The KEYNOTE-061 study demonstrated that pembrolizumab, a PD-1inhibitor, was not better than paclitaxel as second-line therapy for MGC. Herein, we explored the efficacy and safety of PD-1inhibitor based treatment for MGC patients in the second line.MethodsIn this observational, retrospective study, we enrolled MGC patients treated with anti-PD-1 based therapy as second-line in our hospital. We primarily assessed the treatment’s efficacy and safety. We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses.ResultsWe enrolled 129 patients with an objective response rate (ORR) of 16.3% and a disease control rate (DCR) of 79.1%. Patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents had ORR of 19.6% and higher DCR of 94.1%. The median progression-free survival (PFS) was 4.10 months, and the median overall survival (OS) was 7.60 months. In univariate analysis, patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents and with prior anti-PD-1 history were significantly associated with favorable PFS and OS. In the multivariate analysis, different combination therapy and prior anti-PD-1 history were independent prognosis biomarkers for PFS and OS. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 28 (21.7%) patients. Common adverse events (AEs) included fatigue, hyper/hypothyroidism, neutrophil decrease, anemia, skin reactions, proteinuria, and hypertension. We did not observe treatment-related deaths.ConclusionOur current results indicated that PD-1-inhibitor and chemo-anti-angiogenic agents combination therapy and prior PD-1 treatment history might improve clinical activity for GC immunotherapy as second-line treatment with acceptable safety profiles. Further studies are needed to verify those outcomes for MGC in other centers

Daily time-use patterns and obesity and mental health among primary school students in shanghai: a population-based cross-sectional study

Physical activity, screen viewing, sleep, and homework among children have been independently linked to health outcomes. However, few studies have assessed the independent associations between time spent in daily activities and children’s physical and mental health. This study describes time spent in four activities among primary school students in Shanghai, and examines the relationship between daily time-use patterns and obesity and mental health. The representative sample consists of 17,318 children aged 6–11 years in Shanghai. Time spent in moderate to vigorous physical activities (MVPA), screen viewing, sleep, and homework was measured by validated questionnaires. Logistic regressions were performed. We also fitted generalized additive models (GAM) and performed two-objective optimization to minimize the probability of poor mental health and obesity. In 2014, 33.7% of children spent ˂1 hour/day on MVPA, 15.6% spent ≥ 2 hours/day on screen viewing, 12.4% spent ˂ 9 hours/day on sleep, and 27.2% spent ≥ 2 hours/day on homework. The optimization results suggest that considering the 24-hour time limit, children face trade-offs when allocating time. A priority should be given to the duration of sleep and MVPA. Screen exposure should be minimized to save more time for sleep and other beneficial activities

The Unified Equation of State for Dark Matter and Dark Energy

We assume that dark matter and dark energy satisfy the unified equation of state: $p=B(z)\rho$, with $p=p_{dE}$, $\rho=\rho_{dm}+\rho_{dE}$, where the pressure of dark matter $p_{dm}=0$ has been taken into account. A special function $B=-\frac{A}{(1+z)^{\alpha}}$ is presented, which can well describe the evolution of the universe. In this model, the universe will end up with a Big Rip. By further simple analysis, we know other choices of the function $B$ can also describe the universe but lead to a different doomsday.Comment: 7 pages, 3 figures, ws-mpla.cls, accepted by MPL

The Real Scalar Field in Schwarzschild-de Sitter Spacetime

In this paper, the real scalar field equation in Schwarzschild-de Sitter spacetime is solved numerically with high precision. A method called polynomial approximation is introduced to derive the relation between the tortoise coordinate x and the radius r. This method is different from the tangent approximation [1] and leads to more accurate result. The Nariai black hole is then discussed in details. We find that the wave function is harmonic only near the horizons as I. Brevik and B. Simonsen [1] found. Howerver the wave function is not harmonic in the region of the potential peak, with amplitude increasing instead. Furthermore, we also find that, when cosmological constant decreases, the potential peak increases, and the maximum wave amplitude increases.Comment: 11 pages, 5 figures. To be published in volume 35(2003), G.R.

Influences of beta-alanine and l-histidine supplementation on growth performance, meat quality, carnosine content, and mRNA expression of carnosine-related enzymes in broilers

The current study investigated the effect of dietary L-histidine and beta-alanine sup-plementation on growth performance, meat quality, carnosine content, and gene expression of carnosine-related enzymes in broilers. A two-factor design was adopted in this study. A total of 640 1-day-old male broilers were assigned to eight treatments with factorial arrangement containing four levels of L-histidine (0, 650, 1300, or 1950 mg/kg) and two levels of beta-alanine (0 or 1200 mg/kg) supplementation; 0 mg/kg histidine and/or 0 mg/kg were treated as control groups. Each treatment including eight replicates with 10 birds each and the feeding trial lasted for 42 days. Dietary supple-mentation with L-histidine and beta-alanine did not affect average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) of broilers during the grower (22–42 days) and the entire phase (1–42 days), compared with the control group (p > 0.05). The only exception was a significantly reduced ADG in the 1950 mg/kg L-histidine group in the starter period (1–21 days, p < 0.05). L-Histidine at 1950 mg/kg significantly decreased redness (a*) and yellowness (b*) values of the meat at 45 min postmortem (p < 0.05), whereas it increased b* value and pH in breast muscle at 24 h postmortem. Moreover, dietary supplementation with beta-alanine alone or combination with L-histidine significantly increased ∆pH in breast muscle (p < 0.01). Dietary L-histidine markedly increased total superoxide dismutase activity and total antioxidant capacity (T-AOC) both in breast muscle (p < 0.01) and in plasma (p < 0.01), and it decreased malondialdehyde (MDA) concentration in breast muscle (p < 0.01). Dietary addition of beta-alanine, alone or combination, significantly increased T-AOC in breast muscle (p < 0.01) and markedly decreased MDA content both in breast muscle and in plasma (p < 0.01). Addition of L-histidine and beta-alanine significantly increased muscle peptide (carnosine and anserine) content (p < 0.05) and upregulated the expression of carno-sine synthase, transporter of carnosine/ L-histidine, and L-histidine decarboxylase genes (p < 0.05), with greater change occurring in the combination group of 1300 mg/kg L-histidine and 1200 mg/kg beta-alanine. Overall, dietary L-histidine and beta-alanine could improve meat quality and antioxi-dant capacity, enhance the carnosine and anserine content, and upregulate the gene expression of carnosine synthesis-related enzymes in broilers

Whole-genome sequencing and comparative genome analysis of Xanthomonas fragariae YM2 causing angular leaf spot disease in strawberry

BackgroundAngular leaf spot disease caused by plant pathogenic bacterium Xanthomonas fragariae seriously threatens strawberry crop production globally.MethodsIn this study, we sequenced the whole genome of X. fragariae YM2, isolated from Yunnan Province, China. In addition, we performed a comparative genome analysis of X. fragariae YM2 with two existing strains of X. fragariae YL19 and SHQP01 isolated from Liaoning and Shanghai, respectively.ResultsThe results of Nanopore sequencing showed that X. fragariae YM2 comprises one single chromosome with a contig size of 4,263,697 bp, one plasmid contig size of 0.39 Mb, a GC content ratio of 62.27%, and 3,958 predicted coding genes. The genome of YM2 comprises gum, hrp, rpf, and xps gene clusters and lipopolysaccharide (LPS), which are typical virulence factors in Xanthomonas species. By performing a comparative genomic analysis between X. fragariae strains YM2, YL19, and SHQP01, we found that strain YM2 is similar to YL19 and SHQP01 regarding genome size and GC contents. However, there are minor differences in the composition of major virulence factors and homologous gene clusters. Furthermore, the results of collinearity analysis demonstrated that YM2 has lower similarity and longer evolutionary distance with YL19 and SHQP01, but YL19 is more closely related to SHQP01.ConclusionsThe availability of this high-quality genetic resource will serve as a basic tool for investigating the biology, molecular pathogenesis, and virulence of X. fragariae YM2. In addition, unraveling the potential vulnerabilities in its genetic makeup will aid in developing more effective disease suppression control measures

Forward modeling of P- and S-waves response of fractures intersected with horizontal wells in tight reservoirs

Horizontal wells play an important role in expanding the drilling volume of reservoirs and oil production area, and are widely used in unconventional reservoirs. Fractures have a positive effect on reservoir permeability, but fractures can also cause accidents such as casing deformation and inter-well frac-hit. It is of great significance to identify and evaluate fractures intersected with horizontal wells in tight reservoirs. In this paper, a three-dimensional numerical model of horizontal wells and fractures in tight reservoirs is designed. The responses of monopole P-wave and dipole S-wave to fractures with different width, dip angle and filling medium are systematically studied, by using three-dimensional finite difference algorithm. The results show that when the fracture is filled with calcite, the amplitude attenuation of monopole P-wave and dipole S-wave has a monotonic exponential increase with the increase of fracture width and the decrease of fracture dip angle. In the real data processing, the amplitude attenuation of P- and S-waves can be used to jointly evaluate the fracture filled with calcite. When the fracture is filled with water, both P- and S-waves have prominent amplitude attenuation. P wave amplitude attenuation does not have a monotonic variation with the increase of fracture width but it has a monotonic increase with the decrease of fracture dip angle. S wave amplitude attenuation has a monotonic increase with the increase of fracture width and the decrease of fracture dip angle. The amplitude attenuation of P- and S- waves rises significantly when the fracture is filled with natural gas. This study is crucial for better understanding the response of P- and S-waves to fractures intersected with borehole in tight reservoirs, and it provides useful information for the inversion of fracture parameters by using P- and S-waves

Isolation, characterization, and genomic analysis of a novel bacteriophage MA9V-1 infecting Chryseobacterium indologenes: a pathogen of Panax notoginseng root rot

Chryseobacterium indologenes is one of the primary causative agents of root rot of Panax notoginseng, which significantly affected plant growth and caused economic losses. With the increasing incidence of antibiotic-resistant bacterial phytopathogens, phage therapy has been garnered renewed attention in treating pathogenic bacteria. However, the therapeutic potential of phage therapy on root rot of P. notoginseng has not been evaluated. In this study, we isolated a novel lytic phage MA9V-1 infecting C. indologenes MA9 from sewage and monitored the formation of clear and round plaques with a diameter of approximately 0.5–1.5 mm. Phage MA9V-1 exhibited rapid absorption (&gt;75% in 8 min), a latency period of 20 min, and a burst size of 10 particles per cell. Transmission electron microscopy indicated that the phage MA9V-1 is a new myovirus hosting C. indologenes MA9. Sequencing of phage genomes revealed that phage MA9V-1 contained a linear double-stranded DNA genome of 213,507 bp with 263 predicted open reading frames, including phage structure, host lysing, and DNA polymerase/helicase but no genes of tRNA, virulence, and antibiotic resistance. Our proteomic tree and genomic analysis revealed that phage MA9V-1 shares identity with Sphingomonas phage PAU and Tenacibaculum phage PTm1; however, they also showed apparent differences. Further systemic evaluation using phage therapy experiments on P. notoginseng suggested that phage MA9V-1 can be a potential candidate for effectively controlling C. indologenes MA9 infection. Thus, we have presented a novel approach to solving root rot in P. notoginseng

Surfactant-Assisted in situ Chemical Etching for the General Synthesis of ZnO Nanotubes Array

In this paper, a general low-cost and substrate-independent chemical etching strategy is demonstrated for the synthesis of ZnO nanotubes array. During the chemical etching, the nanotubes array inherits many features from the preformed nanorods array, such as the diameter, size distribution, and alignment. The preferential etching along c axis and the surfactant protection to the lateral surfaces are considered responsible for the formation of ZnO nanotubes. This surfactant-assisted chemical etching strategy is highly expected to advance the research in the ZnO nanotube-based technology