Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis.

BACKGROUND: We previously reported results of a pooled analysis of two zanubrutinib studies in relapsed or refractory (R/R) MCL showing better survival outcomes when zanubrutinib is used in second-line versus later-line. Here, we present an updated pooled analysis with a longer follow-up of 35.2 months. METHODS: Data were pooled from two studies-BGB-3111-AU-003 (NCT02343120) and BGB-3111-206 (NCT03206970) of zanubrutinib in R/R MCL. The patients were divided into two groups based on the treatment line of zanubrutinib: the second-line and the later-line group. The inverse propensity score weighting method was used to balance the baseline covariates between the groups. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), PFS, and OS rates, objective response rate (ORR), duration of response (DOR), and safety. RESULTS: Among 112 pooled patients, 41 (36.6%) patients received zanubrutinib as second-line and 71 (63.4%) patients as later-line therapy. After weighting, OS was significantly improved in the second-line versus later-line group (HR, 0.459 [95% CI: 0.215, 0.98]; p = 0.044) with median OS not estimable in both groups. The PFS was similar between the two groups (HR, 0.78 [95% CI: 0.443, 1.373]; p = 0.389) but with numerically longer median PFS in the second-line versus later-line group (27.8 vs. 22.1 months). ORR was numerically higher in the second-line versus later-line (88.6% vs. 85.7%), and DOR was similar between the two groups (25.2 vs. 25.1 months). Zanubrutinib showed a similar safety profile in both groups. CONCLUSION: Zanubrutinib in second-line treatment was associated with significantly improved OS compared with later-line treatment of R/R MCL.

Evaluating anti-viral effect of Tylvalosin tartrate on porcine reproductive and respiratory syndrome virus and analyzing the related gene regulation by transcriptomics.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen, characterized by its genetic and antigenic variation. The PRRSV vaccine is widely used, however, the unsatisfied heterologic protection and the risk of reverse virulence raise the requirement to find some new anti-PRRSV strategies for disease control. Tylvalosin tartrate is used to inhibit PRRSV in the field non-specifically, however, the mechanism is still less known. METHODS: The antiviral effects of Tylvalosin tartrates from three producers were evaluated in a cell inoculation model. Their safety and efficacy concentrations, and effecting stage during PRRSV infection were analyzed. And, the Tylvalosin tartrates regulated genes and pathways which are potentially related to the anti-viral effect were further explored by using transcriptomics analysis. Last, the transcription level of six anti-virus-related DEGs was selected to confirm by qPCR, and the expression level of HMOX1, a reported anti-PRRSV gene, was proved by western blot. RESULTS: The safety concentrations of Tylvalosin tartrates from three different producers were 40 µg/mL (Tyl A, Tyl B, and Tyl C) in MARC-145 cells and 20 µg/mL (Tyl A) or 40 µg/mL (Tyl B and Tyl C) in primary pulmonary alveolar macrophages (PAMs) respectively. Tylvalosin tartrate can inhibit PRRSV proliferation in a dose-dependent manner, causing more than 90% proliferation reduction at 40 µg/mL. But it shows no virucidal effect, and only achieves the antiviral effect via long-term action on the cells during the PRRSV proliferation. Furthermore, GO terms and KEGG pathway analysis was carried out based on the RNA sequencing and transcriptomic data. It was found that the Tylvalosin tartrates can regulate the signal transduction, proteolysis, and oxidation-reduction process, as well as some pathways such as protein digestion and absorption, PI3K-Akt signaling, FoxO signaling, and Ferroptosis pathways, which might relate to PRRSV proliferation or host innate immune response, but further studies still need to confirm it. Among them, six antivirus-related genes HMOX1, ATF3, FTH1, FTL, NR4A1, and CDKN1A were identified to be regulated by Tylvalosin tartrate, and the increased expression level of HMOX1 was further confirmed by western blot. CONCLUSIONS: Tylvalosin tartrate can inhibit PRRSV proliferation in vitro in a dose-dependent manner. The identified DEGs and pathways in transcriptomic data will provide valuable clues for further exploring the host cell restriction factors or anti-PRRSV target.

Costs and Healthcare Resource Utilization Associated with Posterior Capsule Opacification After Cataract Surgery with Five Different Intraocular Lenses: An Economic Analysis for Spain.

Purpose: To estimate the economic impact of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy and its related complications for five different intraocular lenses (IOLs) from the payer and hospital perspectives in Spain. Materials and Methods: The three-year incidence rates of Nd:YAG laser capsulotomy after cataract surgery with five different single-piece acrylic monofocal IOLs (AcrySof IOLs, AJL LLASY60, IOL Tech Stabibag, Medicontur Bi-flex, Zeiss Asphina) for 8293 patients were derived from odds ratios of multivariate analysis adjusted for age, gender, and diabetic retinopathy. A cost-consequence model for a hypothetical cohort of 2000 eyes was then developed to quantify the potential impact of Nd:YAG capsulotomy in terms of costs and time for each of the included IOLs, from the payer and hospital perspectives. Results: The adjusted three-year Nd:YAG laser capsulotomy incidence was 5.0% (95% CI 3.9 to 6.1) for AcrySof and ranged from 26.0% to 44.0% for the other four IOLs. The average costs of Nd:YAG treatment and related complications were €261.90 for payers and €19.99 for hospitals. The average time needed for Nd:YAG treatment and related complications was 32.82 minutes. Model estimates based on 2000 hypothetical cataract surgeries showed that AcrySof IOLs could lead to cost savings between €110,259.90 and €205,591.50 for payers. For hospitals, time, and cost savings with AcrySof ranged from 230.29 hours and €8415.79 compared to Zeiss Asphina to 429.40 hours and €15,692.15 compared to AJL LLASY60 IOLs. Conclusion: Post cataract surgery, AcrySof IOLs were associated with a significantly lower incidence of Nd:YAG treatment and its subsequent complications compared to other IOLs. Our analysis shows that IOL choice is an important factor that can reduce the burden for patients, payers, and hospitals.

Nd:YAG capsulotomy incidence associated with five different single-piece monofocal intraocular lenses: a 3-year Spanish real-world evidence study of 8293 eyes.

OBJECTIVES: To investigate the associations between different single-piece monofocal intraocular lenses (IOLs) and neodymium-doped yttrium aluminum garnet laser (Nd:YAG) capsulotomy incidence 3 years after cataract surgery in a Spanish cohort. METHODS: This is a longitudinal retrospective cohort study. Data were extracted from the electronic medical records of two large regional hospitals in Spain. Patients aged ≥65 years receiving cataract surgery with placement of five different IOLs and with ≥6 months of baseline data were included. We report the Nd:YAG capsulotomy incidence 3 years post cataract surgery, and the survival plot over the 3 years of follow-up time. The associated adjusted (age, gender, and diabetic retinopathy) multivariate analysis with odds ratios (ORs) and 95% CIs is also presented. RESULTS: The cohort (53% female, mean age 75 ± 5.9 years) included 14,519 eyes (Alcon AcrySof = 2968, AJL LLASY60 = 1776, Medicontur Bi-flex = 5176, Zeiss Asphina = 4478, and IOL Tech Stabibag = 121). Of these, 8293 were retained until 3-year follow-up. At 3 years after cataract surgery, the Nd:YAG capsulotomy incidence was 5% for Alcon AcrySof, while it ranged from 21.2% to 31.1% for the other IOLs (p < 0.0001 for each comparison). The odds for Nd:YAG capsulotomy were significantly higher (p < 0.0001) for other IOLs compared with those of Alcon AcrySof (ORs = 8.85, 5.86, 5.74, 5.21 for AJL LLASY60, Medicontur Bi-flex, IOL Tech Stabibag, and Zeiss Asphina, respectively). CONCLUSIONS: The lower Nd:YAG capsulotomy rates for Alcon AcrySof IOLs compared to the other IOLs support the importance of lens choice in reducing patient burden and treatment costs.

The study of Cu/Fe-doped Al-MCM-41 to degrade Rhodamine B.

Textile wastewater has been recognized as one of the most difficult to treat environmental problems. Aiming to acquire an excellent treatment effect that could meet the stringent discharge regulations, a series of Cu- and Fe-doped Al-MCM-41 heterogeneous Fenton catalysts with different metal contents (1.21-3.45 wt%) were successfully synthesized by co-precipitation method to degrade Rhodamine B. Their physicochemical properties were analysed by X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, nitrogen physisorption and scanning electron microscopy. The incorporation of metal did not alter MCM-41's mesostructure, but increasing the contents of metal would decrease the order of MCM-41s' structure. The effects of temperature, pH, H2O2 dosage, dye concentration and the dosage of catalysts on Rhodamine B degradation were also investigated. It was found that M2 with 2.71 wt% of active metals performed best on Rhodamine B degradation. For the high concentration of Rhodamine B (400 mg/L), the decolorization efficiency could reach 96.0% using only 40 mM H2O2 within 50 min at 60 °C. Further adding 40 mM of H2O2, the chemical oxygen demand removal reached 75.1% after 100 min. M2 showed excellent stability and could be reused at least three times without any obvious deterioration in catalytic activity. M2 fitted well with the Freundlich isotherms and the first-order rate model.

Phytophthora infestans RXLR effectors act in concert at diverse subcellular locations to enhance host colonization.

Oomycetes such as the potato blight pathogen Phytophthora infestans deliver RXLR effectors into plant cells to manipulate host processes and promote disease. Knowledge of where they localize inside host cells is important in understanding their function. Fifty-two P. infestans RXLR effectors (PiRXLRs) up-regulated during early stages of infection were expressed as fluorescent protein (FP) fusions inside cells of the model host Nicotiana benthamiana. FP-PiRXLR fusions were predominantly nucleo-cytoplasmic, nuclear, or plasma membrane-associated. Some also localized to the endoplasmic reticulum, mitochondria, peroxisomes, or microtubules, suggesting diverse sites of subcellular activity. Seven of the 25 PiRXLRs examined during infection accumulated at sites of haustorium penetration, probably due to co-localization with host target processes; Pi16663 (Avr1), for example, localized to Sec5-associated mobile bodies which showed perihaustorial accumulation. Forty-five FP-RXLR fusions enhanced pathogen leaf colonization when expressed in Nicotiana benthamiana, revealing that their presence was beneficial to infection. Co-expression of PiRXLRs that target and suppress different immune pathways resulted in an additive enhancement of colonization, indicating the potential to study effector combinations using transient expression assays. We provide a broad platform of high confidence P. infestans effector candidates from which to investigate the mechanisms, singly and in combination, by which this pathogen causes disease.

Hydrogenation and hydrodeoxygenation of biomass-derived oxygenates to liquid alkanes for transportation fuels.

An attractive approach for the production of transportation fuels from renewable biomass resources is to convert oxygenates into alkanes. In this paper, C5-C20 alkanes formed via the hydrogenation and hydrodeoxygenation of the oligomers of furfuryl alcohol(FA) can be used as gasoline, diesel and jet fuel fraction. The first step of the process is the oligomers of FA convert into hydrogenated products over Raney Ni catalyst in a batch reactor. The second step of the process converts hydrogenated products to alkanes via hydrodeoxygenation over different bi-functional catalysts include hydrogenation and acidic deoxidization active sites. After this process, the oxygen content decreased from 22.1 wt% in the oligomers of FA to 0.58 wt% in the hydrodeoxygenation products.