Prediction of treatment response in lupus nephritis using density of tubulointerstitial macrophage infiltration

BackgroundLupus nephritis (LN) is a common disease with diverse clinical and pathological manifestations. A major challenge in the management of LN is the inability to predict its treatment response at an early stage. The objective of this study was to determine whether the density of tubulointerstitial macrophage infiltration can be used to predict treatment response in LN and whether its addition to clinicopathological data at the time of biopsy would improve risk prediction.MethodsIn this retrospective cohort study, 430 patients with LN in our hospital from January 2010 to December 2017 were included. We used immunohistochemistry to show macrophage and lymphocyte infiltration in their biopsy specimens, followed by quantification of the infiltration density. The outcome was the treatment response, defined as complete or partial remission at 12 months of immunosuppression.ResultsThe infiltration of CD68+ macrophages in the interstitium increased in patients with LN. High levels of CD68+ macrophage infiltration in the interstitium were associated with a low probability of treatment response in the adjusted analysis, and verse vice. The density of CD68+ macrophage infiltration in the interstitium alone predicted the response to immunosuppression (area under the curve [AUC], 0.70; 95% CI, 0.63 to 0.76). The addition of CD68+cells/interstitial field to the pathological and clinical data at biopsy in the prediction model resulted in an increased AUC of 0.78 (95% CI, 0.73 to 0.84).ConclusionThe density of tubulointerstitial macrophage infiltration is an independent predictor for treatment response in LN. Adding tubulointerstitial macrophage infiltration density to clinicopathological data at the time of biopsy significantly improves risk prediction of treatment response in LN patients

Analysis of patent application attention: a network analysis method

Patent is an important embodiment of innovation. Before patent application, many people will check a patent application process on the Internet to understand the steps of a patent application. In fact, these people’s search is also a means to understand whether innovative enterprises or individuals imply the importance of innovation. It has become a new crucial problem to obtain more information about time-series data. Research has found that the concept of VG can provide deeper information in time-series data so that it can understand the information of patent applications more comprehensively. After analyzing the data from 1 January 2011 to 31 December 2018, we find: i) there are very few peaks and valleys, and 80% of searches are in the normal range. ii) according to the central value of the ranking, it can be found that the peaks of the annual patent application search times time series occurred in December last year, after January, February of this year or after August-October, and iii) after clustering the time series data, we find that the attention of people shows noticeable segmentation effect.Published versionThis paper is supported in part by the National Natural Science Foundation of China under Grant 71871159, in part by the Fujian innovation strategy research plan project under Grant 2020R0021, in part by the Fujian Social Science Planning Project under Grant FJ2020B024, in part by the 2nd Fujian Young Eagle Program Youth Top Talent Program, and in part by the Fujian science and technology economic integration service platform. The Academy-Locality Cooperation Project of the Chinese Academy of Engineering under Grant 2021-FJZD-4

Holocene Paleoclimate Records in Equatorial West Africa: Insights Based on the Characterization of Glycerol Dialkyl Glycerol Tetraethers

One gravity core retrieved from the Niger Delta was used to explore the origin of deposited organic matter (OM) and the paleo-climatic and environmental conditions over the Holocene in equatorial West Africa. The geochemical properties of sediments including glycerol dialkyl glycerol tetraethers (GDGTs) and elemental (%OC, %N, C/N) and isotopic (δ13Corg, δ15N) signatures were determined. The determination constrained the age of the column and revealed that the sediment OM was mainly derived from a marine source. The isoprenoid (iso)GDGTs were the dominant GDGTs, with a small amount of branched (br)GDGTs, which led to a low-branched and isoprenoid tetraether index (BIT, 0.02–0.21) and represented a low terrestrial input. Most isoGDGTs and OH-GDGTs were produced in situ by Marine Group I (MG-I) Thaumarchaeota, while the brGDGTs were mainly transported from land. A two-endmember model quantified the contribution of terrestrial OM, as 0.9–19.9% by BIT and 1.1–32.6% by δ13C. Accordingly, the millennium-scale sea surface temperatures (SSTs) were reconstructed based on the cyclopentane ring distribution (TEX86H) and the ring index of OH-GDGTs (RI-OH). The top core SSTs were lower than the modern mean annual SST due to the growth season and habitat depth of Thaumarchaeota. The reconstructed SSTs clearly revealed the four stages of paleoclimate change, in particular, the drought episode of 8.2 kyr and the following humid period. The above research has enhanced our understanding of the paleoclimate change in river outflow during the Holocene at the millennium scale

Progress and perspective on lignocellulosic hydrolysate inhibitor tolerance improvement in Zymomonas mobilis

Abstract Pretreatment is the key step to overcome the recalcitrance of lignocellulosic biomass making sugars available for subsequent enzymatic hydrolysis and microbial fermentation. During the process of pretreatment and enzymatic hydrolysis as well as fermentation, various toxic compounds may be generated with strong inhibition on cell growth and the metabolic capacity of fermenting strains. Zymomonas mobilis is a natural ethanologenic bacterium with many desirable industrial characteristics, but it can also be severely affected by lignocellulosic hydrolysate inhibitors. In this review, analytical methods to identify and quantify potential inhibitory compounds generated during lignocellulose pretreatment and enzymatic hydrolysis were discussed. The effect of hydrolysate inhibitors on Z. mobilis was also summarized as well as corresponding approaches especially the high-throughput ones for the evaluation. Then the strategies to enhance inhibitor tolerance of Z. mobilis were presented, which include both forward and reverse genetics approaches such as classical and novel mutagenesis approaches, adaptive laboratory evolution, as well as genetic and metabolic engineering. Moreover, this review provided perspectives and guidelines for future developments of robust strains for efficient bioethanol or biochemical production from lignocellulosic materials

Multi-omics analysis reveals promiscuous O-glycosyltransferases involved in the diversity of flavonoid glycosides in Periploca forrestii (Apocynaceae)

Flavonoid glycosides are widespread in plants, and are of great interest owing to their diverse biological activities and effectiveness in preventing chronic diseases. Periploca forrestii, a renowned medicinal plant of the Apocynaceae family, contains diverse flavonoid glycosides and is clinically used to treat rheumatoid arthritis and traumatic injuries. However, the mechanisms underlying the biosynthesis of these flavonoid glycosides have not yet been elucidated. In this study, we used widely targeted metabolomics and full-length transcriptome sequencing to identify flavonoid diversity and biosynthetic genes in P. forrestii. A total of 120 flavonoid glycosides, including 21 C-, 96 O-, and 3 C/O-glycosides, were identified and annotated. Based on 24,123 full-length coding sequences, 99 uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) were identified and classified into 14 groups. Biochemical assays revealed that four UGTs exhibited O-glycosyltransferase activity toward apigenin and luteolin. Among them, PfUGT74B4 and PfUGT92A8 were highly promiscuous and exhibited multisite O-glycosylation or consecutive glycosylation activities toward various flavonoid aglycones. These four glycosyltransferases may significantly contribute to the diversity of flavonoid glycosides in P. forrestii. Our findings provide a valuable genetic resource for further studies on P. forrestii and insights into the metabolic engineering of bioactive flavonoid glycosides

A First-in-Human Study of the Bioheart Sirolimus-Eluting Bioresorbable Vascular Scaffold in Patients with Coronary Artery Disease:Two-Year Clinical and Imaging Outcomes

Introduction: Newer generation bioresorbable scaffolds (BRSs) with thinner struts and improved deliverability are expected to enhance safety and efficacy profiles. Bioheart (Bio-Heart, Shanghai, China) BRS is constructed from a PLLA (poly-l-lactic acid) backbone coated with a PDLLA (poly d-l-lactic acid) layer eluting sirolimus. We report 2-year serial intracoronary imaging findings. Methods: In this first-in-human study, 46 patients with single de novo lesions in native coronary vessels (vessel size 3.0–3.75 mm, lesion length ≤ 25 mm) were enrolled at a single institution. Baseline intravascular ultrasound (IVUS) and post-implantation IVUS and optical coherence tomography (OCT) examinations were mandatory. After successful implantations of BRS, the 46 patients were randomized to two different follow-up cohorts in a 2:1 ratio. Thirty patients in cohort 1 had to undergo angiography, IVUS, and OCT follow-ups at 6 and 24 months, respectively. The 16 patients in cohort 2 underwent the same types of imaging follow-ups at 12 and 36 months, respectively. Clinical follow-ups were scheduled uniformly in both cohorts at 1, 6, and 12 months and annually up to 5 years for all patients. Results: Between August and November 2016, a total of 54 patients were assessed. However, 8 patients could not meet all the inclusion criteria; thus, the remaining 46 patients (age 57.5 ± 8.7 years, 34.8% female, 50.0% with unstable angina, 26.1% diabetics) with 46 target lesions were enrolled in this study. All patients in both cohorts were required to complete clinical follow-up uniformly and regularly. In cohort 1, one patient had definite scaffold thrombosis within 6 months of follow-up; thus, after 6 months, cohort 1 had 96.7% patients. Imaging follow-up was available in 24 patients, and in-scaffold late loss was 0.44 ± 0.47 mm; intracoronary imaging confirmed the late loss was mainly due to to neointimal hyperplasia, but not scaffold recoil. Conclusions: Serial 2-year clinical and imaging follow-up results confirmed the preliminary safety and efficacy of Bioheart BRS for treatment of simple coronary lesions.</p