Effective targeted therapy for non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) mutations remains an unmet need. This study investigated the antitumor ...effect of an irreversible pan-HER receptor tyrosine kinase inhibitor, pyrotinib.
Using patient-derived organoids and xenografts established from an HER2-A775_G776YVMA-inserted advanced lung adenocarcinoma patient sample, we investigated the antitumor activity of pyrotinib. Preliminary safety and efficacy of pyrotinib in 15 HER2-mutant NSCLC patients in a phase II clinical trial are also presented.
Pyrotinib showed significant growth inhibition of organoids relative to afatinib in vitro (P = 0.0038). In the PDX model, pyrotinib showed a superior antitumor effect than afatinib (P = 0.0471) and T-DM1 (P = 0.0138). Mice treated with pyrotinib displayed significant tumor burden reduction (mean tumor volume, −52.2%). In contrast, afatinib (25.4%) and T-DM1 (10.9%) showed no obvious reduction. Moreover, pyrotinib showed a robust ability to inhibit pHER2, pERK and pAkt. In the phase II cohort of 15 patients with HER2-mutant NSCLC, pyrotinib 400 mg resulted in a objective response rate of 53.3% and a median progression-free survival of 6.4 months.
Pyrotinib showed activity against NSCLC with HER2 exon 20 mutations in both patient-derived organoids and a PDX model. In the clinical trial, pyrotinib showed promising efficacy.
NCT02535507.
This systematic review and meta-analysis was performed to compare the clinical effect of surgical treatment of peri-implantitis alone or in combination with graft material. Literature searches were ...conducted up to June 20, 2020. Randomized controlled trials (RCTs) comparing the clinical effects of open flap debridement (OFD) alone and OFD with adjunctive graft materials for the treatment of peri-implantitis were included. Probing depth (PD) changes and marginal bone level (MBL) changes were assessed and expressed as the standardized mean difference (SMD) with 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were conducted. The search yielded 7419 articles, five of which were analysed quantitatively. The adjunctive use of graft materials in OFD did not provide additional PD improvements (SMD 0.46, 95% CI −0.13 to 1.05; P = 0.13), but did yield additional MBL improvements (SMD 1.04, 95% CI 0.71–1.37; P < 0.01). The degradability of the material, number of implants included per patient, and risk of bias did not have significant effects on the results, but the origin of the material may affect the PD improvements. Based on the available evidence, the adjunctive use of graft materials in the surgical treatment of peri-implantitis can significantly improve MBL changes but not PD changes.
Aims
The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama transmits the bacterium ‘Candidatus Liberibacter asiaticus’ (Las), which causes citrus huanglongbing (HLB) disease. Although many ...studies have been conducted on the biology of ACP on different host plants, few have taken the plant, Las bacteria and the vector insect within one context to evaluate the effects of Las on the fitness of ACP under field conditions. Understanding the relationship between Las and ACP is critical for both ACP and HLB disease management.
Methods and Results
We estimated the development and survival of ACP immatures, the longevity and fecundity of ACP female adults in four treatments (Las‐positive or ‐negative ACP on Las‐infected and ‐free citrus plants). Las‐positive ACP immatures developed significantly faster on Las‐infected citrus than those on Las‐free plants. The fecundity and longevity of Las‐positive female adults were also greater, or longer on Las‐infected citrus shoots, whereas the survival of Las‐positive immatures was significantly lower on Las‐infected citrus shoots, compared to those that developed on Las‐free plants. Similarly, the intrinsic rate of population increase (rm) was highest (0·1404) when Las‐positive ACP fed on Las‐infected citrus shoots and the lowest (0·1328) when the Las‐negative ACP fed on Las‐free citrus shoots.
Conclusions
Both the Las infection in ACP and citrus plants had obvious effects on the biology of ACP. When compared to the Las infection in ACP insects, the Las infection in citrus shoots had a more significant effect on the fitness of ACP.
Significance and Impact of the Study
To efficiently prevent the occurrence and spread of HLB disease, it is critical to understand the ecological basis of vector outbreaks and disease incidence, especially under field conditions. Thus, this study has increased our understanding of the epidemiology of HLB transmitted by psyllids in nature.
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•Demonstrated conversion of switchgrass-derived bio-oil aqueous phase to hydrogen.•Enriched anode community capable of simultaneously converting inhibitory compounds.•Achieved ...hydrogen production rate of 4.3LH2/L-day using biomass-derived liquids.•Long-term operation with high Coulombic, conversion and overall energy efficiencies.
A new approach to hydrogen production using an integrated pyrolysis–microbial electrolysis process is described. The aqueous stream generated during pyrolysis of switchgrass was used as a substrate for hydrogen production in a microbial electrolysis cell, achieving a maximum hydrogen production rate of 4.3LH2/L anode-day at a loading of 10g COD/L-anode-day. Hydrogen yields ranged from 50±3.2% to 76±0.5% while anode Coulombic efficiency ranged from 54±6.5% to 96±0.21%, respectively. Significant conversion of furfural, organic acids and phenolic molecules was observed under both batch and continuous conditions. The electrical and overall energy efficiency ranged from 149–175% and 48–63%, respectively. The results demonstrate the potential of the pyrolysis–microbial electrolysis process as a sustainable and efficient route for production of renewable hydrogen with significant implications for hydrocarbon production from biomass.
The aim of this observational retrospective cohort study was to identify management procedures that are associated with herd-level eradication of Streptococcus agalactiae in dairy herds. The ...objective was to compare herds that recovered from Strep. agalactiae with herds that remained infected with Strep. agalactiae on the basis of specific management procedures. Data from the Danish surveillance program for Strep. agalactiae, where all milk delivering dairy herds are tested yearly, were used to identify study herds. One hundred ninety-six herds that were classified in the program as infected with Strep. agalactiae, in both January 2013 and January 2014, were identified as study herds. These were followed until January 2017. One hundred forty-four herds remained infected every year until January 2017. Forty-six herds recovered from Strep. agalactiae after January 2014 (were tested negative continuously after January 2015, January 2016, or January 2017 and remained noninfected in the program from recovery until January 2017). Herd characteristics and management procedures were obtained through the Danish Cattle Database. Herd characteristics included herd size, yield, milking system, and bulk milk somatic cell count (SCC). Management procedures included the proportion of cows culled within 100 d after calving due to mastitis, the extent of diagnoses relative to the extent of mastitis treatments, the proportion of cows treated for mastitis during lactation, the proportion of cows treated for mastitis early in lactation, the proportion of cows treated at dry-off, and the median length of the dry period for cows receiving dry cow treatment. All variables were calculated on herd level. Multivariable logistic regression was used to analyze the association between herd infection status and management procedures. A higher proportion of culling due to mastitis within 100 d from calving was associated with a higher probability of herd-level recovery from Strep. agalactiae in herds with conventional milking system. For example, herds with conventional milking, a bulk milk SCC of 260,000 cells/mL, and 10% early culling due to mastitis had a recovery probability of 0.13, whereas similar herds with 20% early culling due to mastitis had a recovery probability of 0.15. A higher proportion of mastitis treatments within 250 d postcalving was associated with a higher probability of herd-level recovery for herds with a relatively high bulk milk SCC. For example, herds with conventional milking, a bulk milk SCC of 260,000 cells/mL, and 10% lactational mastitis treatments had a recovery probability of 0.12, whereas similar herds with 20% lactational mastitis treatments had a recovery probability of 0.15. Herds with a low bulk milk SCC (<220,000 cells/mL) combined with a low proportion of lactational treatments (<0.2) had a relatively high probability of herd-level recovery (>0.2). Additional variables, including the proportion of dry cow treatments, were not associated with herd-level recovery from Strep. agalactiae.
Summary
Body conformation at birth and teat number are economically important traits in the pig industry, as these traits are usually explored to evaluate the growth and reproductive potential of ...piglets. To detect genetic loci and candidate genes for these traits, we performed a GWAS on 269 pigs from a recently developed Chinese breed (Sushan) using 38 128 informative SNPs on the Affymetrix Porcine SNP 55K Array. In total, we detected one genome‐wide significant (P = 1.31e‐6) SNP for teat number on chromosome X and 15 chromosome‐wide significant SNPs for teat number, body weight, body length, chest circumference and cannon circumference at birth on chromosomes 1, 3, 4, 6, 7, 9, 10, 13, 14, 15, 17 and 18. The most significant SNP had an additive effect of 0.74 × total teat number, explaining 20% of phenotypic variance. Five significant SNPs resided in the previously reported quantitative trait loci for these traits and seven significant SNPs had a pleiotropic effect on multiple traits. Intriguingly, 12 of the genes nearest to the significant SNPs are functionally related to body conformation and teat number traits, including SPRED2, MKX, TMSB4X and ESR1. GO analysis revealed that candidate genes proximal to the significant SNPs were enriched in the G‐protein coupled receptor and steroid hormone‐mediated signaling pathway. Our findings shed light on the genetic basis of the measured traits and provide molecular markers especially for the genetic improvement of teat number in Sushan and related pigs.
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