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Objective: Malnutrition, accompanied by an inflammatory profile, is a risk factor for poor prognosis in hemodialysis patients. The purpose of this study was to investigate the predictive value of NLR combined with GNRI for all-cause and cardiovascular mortality in hemodialysis patients. Methods: A total of 240 maintenance hemodialysis (MHD) patients in hemodialysis centers were enrolled in this retrospective study. The influencing factors of all-cause death in hemodialysis patients were analyzed by COX regression. The cut-off values of GNRI and NLR for predicting mortality in enrolled MHD patients were 89.01 and 4, respectively. Based on these cut-off values, the patients were divided into four groups: G1: high GNRI (≥ 89.01) + high NLR (≥ 4) group; G2: high GNRI (≥ 89.01) + low NLR (<4) group, G3: low GNRI (< 89.01) + high NLR (≥4) group; G4: low GNRI (< 89.01) + low NLR (<4). Results: During the follow-up period (average: 58 months), the all-cause mortality was 20.83%(50/240) and the cardiovascular mortality was 12.08%(29/240). Both NLR and GNRI were independent risk factors for the prognosis of MHD patients (P<0.05). Survival analysis showed that patients with low GNRI had a lower survival rate than those with high GNRI, whereas patients with high NLR had a lower survival rate than those with low NLR. Kaplan-Meier curve for all-cause mortality revealed that compared to G1, G2, and G4, G3 had the lowest survival rate, while G2 had the highest survival rate among all groups (P < 0.05). Kaplan-Meier curve for cardiovascular mortality showed that G3 had lower survival than G1, G2, and G4 (P < 0.001). Conclusions: Our study demonstrates that bothGNRI and NLR are associated with all-cause mortality and cardiovascular mortality in MHD patients. Combining these two factorsmay contribute to a prognostic evaluation for MHD patients. [ABSTRACT FROM AUTHOR]

Background: The serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte (P/MII) ratio might be a more predictable indicator of pregnancy and neonatal outcomes as compare to P/estradiol (E2) or P alone. Hence, we conducted a larger population study to compare the pregnancy and neonatal outcomes in the low and high P/MII ratio. Methods: A retrospective, single-center, larger population cohort study between January 2015 and August 2021. Calculate the threshold effect of P/MII ratio on clinical pregnancy rate according to the construct smooth curve fitting. Divide data into two groups by threshold for comparison. Results: 3566 fresh ICSI-ET cycles were included, in which 929 singleton delivery and 676 twin deliveries. Compare to P/MII ≤ 0.367 group, it indicated that the P/MII > 0.367 group had a lower clinical pregnancy rate and live birth rate, furthermore, a significantly higher rate of LBW and SGA were observed in the singleton and twin deliveries. No deleterious impact of high P/MII ratio on embryo quality and undesirable pregnancy outcomes was shown. Conclusions: When P/MII is higher than 0.367, may have adverse impacts on pregnancy and neonatal outcomes for ICSI cycle. [ABSTRACT FROM AUTHOR]

Temperature has been studied in relation to many health outcomes. However, few studies have explored its effect on the risk of hospital admission for rheumatoid arthritis (RA). A distributed lag non-linear model (DLNM) was used to analyze associations between mean temperature, diurnal temperature range (DTR), temperature change between neighboring days (TCN), and daily admissions for RA from 2015 to 2019 in Anqing, China. Subgroup analyses based on age, gender, rheumatoid factors, and admission route were performed. In total, 1456 patients with RA were hospitalized. Regarding the cumulative-lag effects of extreme cold temperature (5th percentile = 3℃), the risks of admissions for RA were increased and highest at lag 0–11 (RR = 2.68, 95% CI: 1.23–5.86). Exposing to low (5th percentile = 1.9℃) and high (95th percentile = 14.2℃) DTRs both had increased risks of RA admission, with highest RRs of 1.40 (95% CI: 1.03–1.91) and 1.24 (95% CI: 1.0–1.53) at lag 0 day, respectively. As for TCN, the marginal risk of admission in RA patients was found when exposed to high TCN (95th percentile = 2.9℃) with the largest single-day effect at lag 10 (RR = 1.11, 95% CI: 1.01–1.23). In subgroup analyses, females were more susceptible to extreme cold temperature, low and high DTRs, and high TCN. In regard to extreme cold temperature, significant risk of hospital admission in females only appeared at lag 2 (RR = 1.48, 95% CI: 1.02–2.15) and lag 0–2 (RR = 2.35, 95% CI: 1.11–4.95). It is clear that RA patients exposed to changing temperature may increase risks of admission. [ABSTRACT FROM AUTHOR]

The site selectivity for lysine conjugation on a native protein is difficult to control and characterize. Here, we applied mass spectrometry to examine the conjugation kinetics of Trastuzumab-IgG (Her-IgG) and α-lactalbumin under excess linker concentration ([L]0) based on the modified Michaelis–Menten equation, in which the initial rate constant per amine (kNH2 = Vmax/NH2/KM) was determined by the maximum reaction rate (Vmax/NH2) under saturated accessible sites and initial amine–linker affinity (1/KM). Reductive amination (RA) displayed 3–4 times greater Vmax/NH2 and a different panel of conjugation sites than that observed for N-hydroxysuccinimide ester (NHS) chemistry using the same length of polyethylene glycol (PEG) linkers. Moreover, faster conversion power rendered RA site selectivity among accessible amine groups and a greater tunable range of linker/protein ratio for aldehyde-linkers compared to those of the same length of NHS-linkers. Single conjugation with high yield or poly-conjugations with site homogeneity was demonstrated by controlling [L]0 or gradual addition to minimize the [L]0/KM ratio. Formaldehyde, the shortest aldehyde-linker with the greatest 1/KM, exhibited the highest selectivity and was shown to be a suitable probe to predict conjugation profile of aldehyde-linkers. Four linkers on the few probe-predicted hot spots were elucidated by kinetically controlled RA with conserved drug efficacy when conjugated with the payload. This study provides insights into controlling factors for homogenous and predictable amine bioconjugation. [ABSTRACT FROM AUTHOR]

An etanercept biosimilar, TuNEX ® , was compared to the innovator drug, Enbrel ® , for its reaction to stress-induced oxidation and deamidation, which may affect drug efficacy. A tryptic peptide map of both etanercept products was generated by liquid chromatography (LC) using mass spectrometry (MS) and ultraviolet (UV) spectrophotometry detection methods. The sequence of each modified or non-modified peptide peak was assigned based on accurate measurement of the mass of the protein and analysis utilizing tandem MS. Similar profiles of intrinsic oxidation on methionine (M) and deamidation on asparagine (N) were obtained for the two products, regardless of a two-amino acid (AA) residue variance in the heavy chain (Fc) between them. The level of oxidative stress exerted by tert -butyl hydroperoxide (tBHP), and alkaline stress exerted by a pH 10.4 solution, was examined using an LC-UV method. The results indicated that TuNEX ® demonstrated a similar stress-induced modification profile compared to that of Enbrel ® . For both products, oxidative stress increased the oxidation from an intrinsically low (0–6.9%) to moderate or high (42–100%) level for almost all M residues (M30, M174, M187, M223, M272, and M448); alkaline stress increased the deamidation level of N404 from a low (0.0 or 1.7%) to moderate (19–26%) level. Based the results of a cell-based bioactivity assay, TuNEX ® also exhibited a similar level of bioactivity as Enbrel ® in unstressed, oxidative-stressed, or alkaline-stressed conditions. The bioactivity of both products remained unaltered by oxidative stress but was reduced by alkali stress. In conclusion, our data indicated that TuNEX ® exhibits a similar chemical stress profile as that of Enbrel ® in terms of oxidation and deamidation as well as bioactivity. [ABSTRACT FROM AUTHOR]

We reported an improved combinatorial approach for identifying site-specific O-glycosylation using both glycan cleaved and non-cleaved methods. In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (Δ R t ). Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. This considerably reduced to 0% FDR by Δ R t filtering. This approach was then applied to a protein mixture composed of therapeutic Factor IX and Enbrel ® mixed with fetuin and kappa-casein. A total of 26 glycosylation sites each of which corresponds to 1–4 glycans were positively mapped and confirmed. The FDR decreased from 33% to 3.3% by Δ R t filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. Thus, our approach is useful for in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics. [ABSTRACT FROM AUTHOR]

Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of death worldwide, and desperately needs effective treatments, such as cell therapy. Cardiopulmonary progenitors (CPPs) are stem cells for both heart and lung, but their repairing role in damaged heart is still unknown. Here, we obtained CPPs from E9.5 mouse embryos, maintained their stemness while expanding, and identified their characteristics by scRNA‐seq, flow cytometry, quantitative reverse transcription‐polymerase chain reaction, and differentiation assays. Moreover, we employed mouse MI model to investigate whether CPPs could repair the injured heart. Our data identified that CPPs exhibit hybrid fibroblastic, endothelial, and mesenchymal state, and they could differentiate into cell lineages within the cardiopulmonary system. Moreover, intramyocardial injection of CPPs improves cardiac function through CPPs exosomes (CPPs‐Exo) by promotion of cardiomyocytic proliferation and vascularization. To uncover the underlying mechanism, we used miRNA‐seq, bulk RNA‐seq, and bioinformatic approaches, and found the highly expressed miR‐27b‐3p in CPPs‐Exo and its target gene Sik1, which can influence the transcriptional activity of CREB1. Therefore, we postulate that CPPs facilitate cardiac repair partially through the SIK1‐CREB1 axis via exosomal miR‐27b‐3p. Our study offers a novel insight into the role of CPPs‐Exo in heart repair and highlights the potential of CPPs‐Exo as a promising therapeutic strategy for MI. [ABSTRACT FROM AUTHOR]

Purpose: To compare hepatobiliary phase (HBP) images obtained 10 and 20 min after Gd-EOB-DTPA-enhanced MRI for liver function assessment in clinic on 3.0 T MR imaging. Methods: 103 patients were separated into four groups: 38 patients for the normal liver function (NLF) group, 33 patients for the liver cirrhosis with Child-Pugh A (LCA) group, 21 patients for the liver cirrhosis with Child-Pugh B group, and 11 patients for a liver cirrhosis with Child-Pugh C group. T1 relaxation times (T1rt) were measured on T1 mapping and reduction rates of T1rt (rrT1rt) were calculated. HBP images were obtained at the 10- and 20-min mark after Gd-EOB-DTPA enhancement. Results: T1rt on pre-enhancement imaging showed no significant difference ( p > 0.05) among all four groups. T1rt for both the 10-min HBP and the 20-min HBP showed a significant difference ( p < 0.05) among all groups, but showed no significant difference ( p > 0.05) between the NLF group and the LCA group. T1rt and rrT1rt showed no significant difference ( p > 0.05) between 10-min HBP and 20-min HBP among all groups. The ROC analysis on 10-min HBP and 20-min HBP showed a lower diagnostic performance between NLF group and LCA group (AUC from 0.532 to 0.582), but high diagnostic performance (AUC from 0.788 to 1.000) among others group. Conclusions: In comparing 10-min HBP and 20-min HBP T1 mapping after Gd-EOB-DTPA enhancement, our results suggest that 10-min HBP T1 mapping is a feasible option for quantitatively assessing liver function. [ABSTRACT FROM AUTHOR]

Sophora davidii is an important plant resource in the karst region of Southwest China, but S. davidii plant-height mutants are rarely reported. Therefore, we performed phenotypic, anatomic structural, transcriptomic and metabolomic analyses to study the mechanisms responsible for S. davidii plant-height mutants. Phenotypic and anatomical observations showed that compared to the wild type, the dwarf mutant displayed a significant decrease in plant height, while the tall mutant displayed a significant increase in plant height. The dwarf mutant cells were smaller and more densely arranged, while those of the wild type and the tall mutant were larger and loosely arranged. Transcriptomic analysis revealed that differentially expressed genes (DEGs) involved in cell wall biosynthesis, expansion, phytohormone biosynthesis, signal transduction pathways, flavonoid biosynthesis and phenylpropanoid biosynthesis were significantly enriched in the S. davidii plant-height mutants. Metabolomic analysis revealed 57 significantly differential metabolites screened from both the dwarf and tall mutants. A total of 8 significantly different flavonoid compounds were annotated to LIPID MAPS, and three metabolites (chlorogenic acid, kaempferol and scopoletin) were involved in phenylpropanoid biosynthesis and flavonoid biosynthesis. These results shed light on the molecular mechanisms of plant height in S. davidii mutants and provide insight for further molecular breeding programs. [ABSTRACT FROM AUTHOR]

Highlights: [•] A 3-step comparison strategy is demonstrated for biosimilars. [•] Comparisons include sequencing, targeted modifications and non-targeted tryptic map. [•] Anti-Her2 trastuzumab is compared with the correct and mutated biosimilars. [•] Non-targeted intensity comparisons are shown to correctly identify the variants. [•] The method provides extra-dimensional view to assess the complexity for biosimilars. [Copyright &y& Elsevier]

Abstract: Recent evidence indicates that during copper (Cu) stress, the roots of metallicolous plants manifest a higher activity of acid invertase enzymes, which are rate-limiting in sucrose catabolism, than non-metallicolous plants. To test whether the higher activity of acid invertases is the result of higher expression of acid invertase genes, we isolated partial cDNAs for acid invertases from two populations of Rumex japonicus (from metalliferous and non-metalliferous soils), determined their nucleotide sequences, and designed primers to measure changes in transcript levels during Cu stress. We also determined the growth of the plants’ roots, Cu accumulation, and acid invertase activities. The seedlings of R. japonicus were exposed to control or 20μM Cu2+ for 6d under hydroponic conditions. The transcript level and enzyme activity of acid invertases in metallicolous plants were both significantly higher than those in non-metallicolous plants when treated with 20μM. Under Cu stress, the root length and root biomass of metallicolous plants were also significantly higher than those of non-metallicolous plants. The results suggested that under Cu stress, the expression of acid invertase genes in metallicolous plants of R. japonicus differed from those in non-metallicolous plants. Furthermore, the higher acid invertase activities of metallicolous plants under Cu stress could be due in part to elevated expression of acid invertase genes. [Copyright &y& Elsevier]

Abstract Cr3+-doped near-infrared (NIR) long-lasting phosphorescence (LLP) phosphors have drawn great attention for the promising application in unique bio-labels. Most of the studies are focused on gallate materials. Here we report a novel non-gallates NIR LLP phosphor Sr 2 MgWO 6 :Cr3+ that exhibit broadband emission at 700–1000 nm. X-ray powder diffraction, photoluminescence spectra, photoluminescence excitation spectra, LLP decay curves and thermoluminescence glow curves were determined to study the NIR LLP property and mechanism of Sr 2 MgWO 6 :Cr3+. Although Sr 2 MgWO 6 :0.4%Cr3+ gives the strongest NIR emission, the optimum content of Cr3+ in Sr 2 MgWO 6 phosphor for LLP was 0.1%. Trap type and depth in Sr 2 MgWO 6 :Cr3+ were also discussed according to the thermoluminescence glow curves. Sr 2 MgWO 6 :Cr3+ phosphor is promising in optical information storage, night-vision surveillance, and in vivo bio-imaging. Highlights • A novel double perovskite phosphor of Sr 2 MgWO 6 :Cr3+ has been synthesized by solid-state reaction in air. • The Sr 2 MgWO 6 :Cr3+ phosphor exhibit both intense near infrared (NIR) and long-lasting phosphorescence (LLP) phenomenon. • The LLP afterglow of Sr 2 MgWO 6 :0.1%Cr3+ remains observable for more than 11,000 s. • The trap type and depth were also discussed according to thermoluminescence glow curves. • The possible fluorescence and LLP mechanism in Sr 2 MgWO 6 :Cr3+ phosphors are analyzed. [ABSTRACT FROM AUTHOR]

Abstract Pichia pastoris expression is a mature and efficient eukaryotic expression system. In this work, Aspergillus oryzae lipase (AOL, with the molecular mass of 28 kDa), which can perform highly stereoselective hydrolysis of (R, S)-methyl 2-(4-hydroxyphenoxy) propanoate, was expressed in P. pastoris X-33. The specific activity of AOL was 432 U/mg, which was obtained by fed-batch cultivation in a 5 L bioreactor using a methanol feeding strategy. After fermentation, the supernatant was concentrated by ultrafiltration with a 10 kDa cut-off membrane and purified with DEAE-Sepharose™ FF ion-exchange chromatography and phenyl Seflnose™ 6 FF hydrophobic interaction chromatography. The purified lipase activity reached 5509 U/mg. AOL showed high activity toward short-chain triacylglyceride (C 4), and the optimum temperature and pH were 40 °C and 8.0, respectively. The purified enzyme activity was inhibited by Zn2+ and Cu2+. Moreover, the K m and V max values were 1 mM and 32.89 mmol/min, respectively. Highlights • The recombinant strain P. pastoris X-33/pPICZɑA-aol was constructed. • The recombinant A. oryzae lipase was obtained in fed-batch cultivation. • The enzymatic properties of recombinant A. oryzae lipase were studied. [ABSTRACT FROM AUTHOR]

The exploration of low-cost, long-term stable, and highly electrochemically active cathode catalysts is important for the practical application of microbial fuel cell (MFC). In this work, a series of the 3D hierarchical porous Co–N–C (3DHP Co–N–C) materials are designed and synthesized by a metal-organic framework ZIF-67 as a precursor and SiO 2 sphere of different sizes as the hard template. The 3DHP Co–N–C-2 with 129 nm macropore exhibits excellent ORR performance in 0.1 M KOH solution with a half-wave potential of 0.80 V vs. RHE and superior durability than Pt/C (20%) due to the specific macropore-mesopore-micropore structure that exposes a large number of active sites and accelerates the electrolyte transport and oxygen diffusion. The MFC with 3DHP Co–N–C-2 as the cathode catalysts shows excellent performance with a maximum power density of 426.9 ± 7.87 mW m−2 and favorable durability after 50 d of operation. In addition, 16s rDNA results reveal the presence of different dominant electrogenic bacteria and different abundance of important non-electrogenic bacteria in the anode biofilm in MFCs using cathode catalysts with different ORR activity. And 3DHP Co–N–C-2 was found to be beneficial to the synergistic effect of electrogenic and non-electrogenic bacteria. This study explores electrocatalysts in terms of both electrocatalytic activity and anode microorganisms, providing new and comprehensive insights into the power generation of MFC. [Display omitted] • The 3DHP Co–N–C was synthesized by a hard template method. • The hierarchical porous structure of 3DHP Co–N–C facilitated electrocatalysis. • The microbial community in MFC with 3DHP Co–N–C favored electricity production. [ABSTRACT FROM AUTHOR]