The Composite Immune Risk Score predicts overall survival after allogeneic hematopoietic stem cell transplantation: A retrospective analysis of 1838 cases.

There has been little consensus on how to quantitatively assess immune reconstitution after hematopoietic stem cell transplantation (HSCT) as part of the standard of care. We retrospectively analyzed 11 150 post-transplant immune profiles of 1945 patients who underwent HSCT between 2012 and 2020. 1838 (94.5%) of the cases were allogeneic HSCT. Using the training set of patients (n = 729), we identified a composite immune signature (integrating neutrophil, total lymphocyte, natural killer, total T, CD4+ T, and B cell counts in the peripheral blood) during days 91-180 after allogeneic HSCT that was predictive of early mortality and moreover simplified it into a formula for a Composite Immune Risk Score. When we verified the Composite Immune Risk Score in the validation (n = 284) and test (n = 391) sets of patients, a high score value was found to be associated with hazard ratios (HR) of 3.64 (95% C.I. 1.55-8.51; p = .0014) and 2.44 (95% C.I., 1.22-4.87; p = .0087), respectively, for early mortality. In multivariate analysis, a high Composite Immune Risk Score during days 91-180 remained an independent risk factor for early mortality after allogeneic HSCT (HR, 1.80; 95% C.I., 1.28-2.55; p = .00085). In conclusion, the Composite Immune Risk Score is easy to compute and could identify the high-risk patients of allogeneic HSCT who require targeted effort for prevention and control of infection.

Crystal Structure and Ferroelectric Evidence of BaZnSi3 O8 , a Low-Permittivity Microwave Dielectric Ceramic.

BaZnSi3 O8 ceramic was prepared by the conventional solid-state method and sintered at 1100 °C. XRD and synchrotron Rietveld refinement analyses revealed the BaZnSi3 O8 ceramic presented a monoclinic structure with a space group of P21 /a (No.14), which is reported for the first time. The BaZnSi3 O8 ceramic presented a weak ferroelectricity, which was confirmed by the P-E loop and the 90° nanoscale ferroelectric domain. Although ϵr -T displayed two ϵr abnormal peaks at 400 °C and 460 °C, the Curie temperature (Tc ) was located at 460 °C according to the dielectric loss and Curie-Weiss law. Moreover, the BaZnSi3 O8 ceramic exhibited optimized microwave dielectric properties with ϵr =6.55, Q×f=52400 GHz, and τf =-24.5 ppm/°C. Hence, the BaZnSi3 O8 ceramic in the ternary BaO-ZnO-SiO2 system possessed both weak ferroelectricity and microwave dielectric properties. These results are expected to break the technical barrier of ferroelectric phase shifter applications in microwave and even millimeter-wave frequency bands.

Scale-up cultivation enhanced arachidonic acid accumulation by red microalgae Porphyridium purpureum.

The present study attempts to cultivate Porphyridium purpureum under different scale-up conditions for further development and commercialization of microalgae-derived PUFAs such as ARA and EPA. Different temperatures (25, 30, and 35 °C) and light intensities (70, 165, and 280 µmol/m2s) were applied to the 50 L pilot-scale cultivation of P. purpureum in ASW. The cultivation under the light intensity of 280 µmol/m2s at 35 °C obtained biomass concentration up to 9.52 g/L, total fatty acid content to 56.82 mg/g, and ARA content to 22.29 mg/g. While the maximum EPA content of 7.00 mg/g was achieved under the light intensity of 280 µmol/m2s at 25 °C and the highest ratio of UFAs to TFAs of 74.66% was also obtained in this trial. Both biomass concentration and TFAs content were improved by increasing light intensity and temperature. Moreover, the ratio of ARA to EPA was enhanced by increasing cultivation temperature under the light intensity of 280 µmol/m2s. In contrast with flask culture, the conversion of linoleic acid (C18:2) to ARA was enhanced in scale-up culture, leading to more ARA content. Phosphate limitation enhanced the synthesis of lipid and LPUFAs. Moreover, the biomass concentration and biosynthesis of palmitic acid were preferred by sufficient C (NaHCO3).

Pangenome analysis reveals genomic variations associated with domestication traits in broomcorn millet.

Broomcorn millet (Panicum miliaceum L.) is an orphan crop with the potential to improve cereal production and quality, and ensure food security. Here we present the genetic variations, population structure and diversity of a diverse worldwide collection of 516 broomcorn millet genomes. Population analysis indicated that the domesticated broomcorn millet originated from its wild progenitor in China. We then constructed a graph-based pangenome of broomcorn millet based on long-read de novo genome assemblies of 32 representative accessions. Our analysis revealed that the structural variations were highly associated with transposable elements, which influenced gene expression when located in the coding or regulatory regions. We also identified 139 loci associated with 31 key domestication and agronomic traits, including candidate genes and superior haplotypes, such as LG1, for panicle architecture. Thus, the study's findings provide foundational resources for developing genomics-assisted breeding programs in broomcorn millet.

K-Space Data Reconstruction Algorithm-Based MRI Diagnosis and Influencing Factors of Knee Anterior Cruciate Ligament Injury.

This study was aimed at investigating the diagnostic value of MRI based on K-space data reconstruction algorithm for anterior cruciate ligament (ACL) injury of knee joint and the influencing factors of ligament injury. 96 patients with ACL injury of knee joint were selected, and they were randomly divided into two groups: group A (arthroscopy) and group B (MRI examination), and another 96 healthy volunteers in the same period were selected as the control group. The test results of each indicator were compared. The results showed that the signal-to-noise ratio (SNR) of SMASH algorithm was higher than that of sum of squares (SOS) algorithm. In group A, there were 66 positive and 30 negative tests, and in group B, there were 56 positive and 40 negative tests (P < 0.05). The intercondylar fossa width, the intercondylar fossa width index, and the ratio of tibial intercondylar eminence width to intercondylar fossa width in group B were lower than those in the control group (P < 0.05). Compared with the traditional SOS algorithm, SMASH algorithm can improve the image quality, reduce the impact of damage data on the final synthesis image, and improve the image SNR. In clinical work, the ratio of the width of tibial intercondylar eminence to the width of femoral intercondylar fossa can be measured by imaging data to evaluate the matching between tibial intercondylar eminence and femoral intercondylar fossa, so as to evaluate the risk of ACL rupture.

Hemostatic Performance of ɑ-Chitin/Gelatin Composite Sponges with Directional Pore Structure.

Biomedical materials with effective hemostatic properties are in great demand in clinical and battlefield application for severe hemorrhage control. In this study, nearly amorphous chitin is obtained by treating α-chitin with superfine grinding, and the solubility of chitin in hexafluoro-2-propanol (HFIP) is significantly increased. Chitin and gelatin mixtures are prepared by adding different amount of gelatin to the 8 mg mL-1 chitin solution. In the presence water (nonsolvent), the mixtures are gelled as HFIP is replaced by water, and chitin/gelatin composite sponges with directional pore structure are prepared by directional freeze drying of the hydrogel. The structure, porosity, liquid absorbing capacity, biodegradability, and hemostatic properties of the sponges with different ratios of gelatin are investigated. The results show that the sponge with the mass ratio of chitin/gelatin of 1:1 is potential hemostatic material with high absorbing capacity, hemocompatibility, and the best hemostatic performance. The in vivo study demonstrates that hemostatic time of the composite sponge (73 s) is much shorter than of that of gauze (193 s), chitin sponge (132 s) as well as gelatin sponge (116 s) in rat femoral artery injury model.

Chitosan/Gelatin Composite Nonwoven Fabric Scaffold Seeding Minimal Function Unit of Skin for Functional Skin Regeneration.

The construction of intact functional skin is a challenging field in tissue engineering. Traditional skin tissue engineering, using "seed cells" as a bioactive source for scaffolding materials maybe not efficient enough. Here a new strategy is shown for constructing functional tissue-engineered skin with Minimal Functional Unit of Skin (MFUS) as the source of bioactivity. Chitosan/gelatin non-woven fabric is used as the scaffold. MFUS is derived from autologous skin with full-thickness skin microstructure and complete functional skin unit harvesting. A mathematical model is used to calculate the MFUS Minimal Harvest Diameter and Angle (MHDA). Chitosan/gelatin non-woven fabric (CS+GEL) is porous and absorbable, with an elastic modulus meeting the requirement of skin engineering. It supports layered and 3D growth of MFUS. The degradation rate of chitosan, including filament diameter and density is evaluated in vivo. MFUS-engineered skin could reduce the density of local nerve fibers in the early stage, potentially reducing pain during wound healing, as well as could limit excessive fibroblast cell migration in the later stage, potentially reducing scar formation. This study proposes a new strategy for the clinical treatment of large full-thickness skin defects by constructing intact functional at minimal cost.

Dynamic forecasting of severe acute graft-versus-host disease after transplantation.

Forecasting of severe acute graft-versus-host disease (aGVHD) after transplantation is a challenging 'large p, small n' problem that suffers from nonuniform data sampling. We propose a dynamic probabilistic algorithm, daGOAT, that accommodates sampling heterogeneity, integrates multidimensional clinical data and continuously updates the daily risk score for severe aGVHD onset within a two-week moving window. In the studied cohorts, the cross-validated area under the receiver operator characteristic curve (AUROC) of daGOAT rose steadily after transplantation and peaked at ≥0.78 in both the adult and pediatric cohorts, outperforming the two-biomarker MAGIC score, three-biomarker Ann Arbor score, peri-transplantation features-based models and XGBoost. Simulation experiments indicated that the daGOAT algorithm is well suited for short time-series scenarios where the underlying process for event generation is smooth, multidimensional and where there are frequent and irregular data missing. daGOAT's broader utility was demonstrated by performance testing on a remotely different task, that is, prediction of imminent human postural change based on smartphone inertial sensor time-series data.

A Phenogenetic Axis that Modulates Clinical Manifestation and Predicts Treatment Outcome in Primary Myeloid Neoplasms.

Although the concept of "myeloid neoplasm continuum" has long been proposed, few comparative genomics studies directly tested this hypothesis. Here we report a multi-modal data analysis of 730 consecutive newly diagnosed patients with primary myeloid neoplasm, along with 462 lymphoid neoplasm cases serving as the outgroup. Our study identified a "Pan-Myeloid Axis" along which patients, genes, and phenotypic features were all aligned in sequential order. Utilizing relational information of gene mutations along the Pan-Myeloid Axis improved prognostic accuracy for complete remission and overall survival in adult patients of de novo acute myeloid leukemia and for complete remission in adult patients of myelodysplastic syndromes with excess blasts. We submit that better understanding of the myeloid neoplasm continuum might shed light on how treatment should be tailored to individual diseases. Significance: The current criteria for disease diagnosis treat myeloid neoplasms as a group of distinct, separate diseases. This work provides genomics evidence for a "myeloid neoplasm continuum" and suggests that boundaries between myeloid neoplastic diseases are much more blurred than previously thought.

Effects of degree of deacetylation on hemostatic performance of partially deacetylated chitin sponges.

Chitin/chitosan hemostatic materials have long been studied for uncontrolled hemorrhage, an urgent clinical problem due to severe blood-vessel damage or hemophilia. As one of the basic structural parameters of chitin, the degree of deacetylation (DD) significantly affects the material's physical, chemical, as well as biological properties. In this study, partially deacetylated chitins with a wide range of DD (23-81%) were prepared by homogeneous deacetylation, and sponges with these various chitins were fabricated by freeze-drying to study the effects of DD on their hemostatic properties. Among all sponge samples, the chitosan sponge with a DD of 48% showed the highest water absorption, whole blood adsorption, RBC adsorption rate, and the best hemostatic performance in an uncontrolled bleeding model of the rat femoral artery, demonstrating that a certain proportion of acetyl amino and amino groups could also activate the coagulation system and promote the adhesion of platelet and erythrocyte.

Value of combination of 25-(OH)-D3, IL-6, and cyclic peptide containing citrulline antibodies in different stages of rheumatoid arthritis.

OBJECTIVE: To determine the value of a combination of 25-hydroxyvitamin D3 (25-(OH)-D3), interleukin-6 (IL-6), and cyclic peptide containing citrulline (CCP) antibodies in the acute stage and remission stage of patients with rheumatoid arthritis (RA). METHODS: A retrospective analysis was made on 80 RA patients who received treatment in Wenjiang District People's Hospital of Chengdu from February 2017 to February 2020. According to their condition, they were identified as acute-stage patients (n=48) or remission-stage patients (n=32). In addition, 40 healthy individuals who received physical examination in our hospital during the same period were enrolled in a control group. Serum 25-(OH)-D3, IL-6, and CCP antibodies in all enrolled participants were quantified, and their levels were compared between RA patients at the acute stage and those at the remission stage before therapy, and also between patients with different efficacy after 3 months of therapy. The correlations of serum 25-(OH)-D3, IL-6, and CCP antibodies with disease activity score in 28 joints (DAS-28) were analyzed. A corresponding joint receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of the combination of 25-(OH)-D3, IL-6, and CCP antibodies in the staging of RA patients, and logistic regression was used to establish an efficacy risk model. RESULTS: The highest serum 25-(OH)-D3 level was found in the control group, followed by the remission-stage patients and then acute-stage patients from high to low (all P<0.05), and the lowest levels of serum IL-6 and CCP antibodies were also found in the control group, followed by the remission-stage patients and then the acute-stage patients from low to high (all P<0.05). The Pearson's test revealed a negative correlation of 25-(OH)-D3 with DAS-28 and a positive correlation of IL-6 and CCP antibodies with DAS-28. According to ROC curve-based analysis, the area under the joint curve of 25-(OH)-D3, IL-6, and CCP antibodies was >0.9. After therapy, patients showed an increase in 25-(OH)-D3 and decreases in IL-6 and CCP antibodies (all P<0.05). The logistic model confirmed that the area under the ROC curve of RA affecting the efficacy on patients was >0.8. CONCLUSION: A combination of 25-(OH)-D3, IL-6, and CCP antibodies can be adopted as a diagnostic indicator in acute and remission stages of RA. A risk factor model of clinical efficacy in RA patients can help us effectively identify high-risk patients before therapy and take intervention measures early.

Superfine grinding induced amorphization and increased solubility of α-chitin.

As the most common structure of chitin, α-chitin is insoluble in common aquatic and organic solvents, and is very difficult to be processed due to its highly ordered crystalline structure and the large number of intermolecular and intramolecular hydrogen bonds. Amorphization of α-chitin has been proved to be a valid measure for improving its subsequent functionalization efficiency and depolymerization yield. In this study, superfine grinding (SFG) was introduced to make α-chitin amorphous, and it was found that SFG effectively reduced the particle size, changed the microstructure, and significantly reduced the crystallinity of α-chitin. Chitin with crystallinity as low as 8.39 % was obtained after 60 min of SFG treatment, and the amorphous chitin became readily dissolved in 10 % NaOH solution after one round of freezing-thawing process. As continuous manner could be employed, SFG might be a powerful and efficient method for preparing amorphous chitin to help its processing and modification of various applications.

Study of injectable Blueberry anthocyanins-loaded hydrogel for promoting full-thickness wound healing.

Injectable hydrogels with high anti-inflammatory and wound-healing properties are highly desirable for clinical application. In the present study, injectable hydrogels were prepared based on carboxymethyl chitosan and oxidized hyaluronic acid. Blueberry anthocyanins (BA), which are known for their antioxidant and antiinflammatory properties, were successfully loaded into the hydrogels. The gelation kinetics and mechanical properties of the hydrogels were investigated. Oxidized hyaluronic acid with an oxidation degree of 38.1% conferred a suitable gelation time (~70 s) and mechanical properties (76.0 kPa compression stress at strain of 80%) of the hydrogel. The injectable BA-loaded hydrogel significantly accelerated the wound healing process in a full-thickness skin wound model in rats, promoted epithelial and tissue regeneration, exerted antiinflammatory effects, and promoted collagen deposition and angiogenesis. Besides, the hydrogel could upregulate the expression of VEGF and IL-10 proteins, downregulate the NF-κB level, and promote macrophage transformation from M1 phenotype to M2. The promotion of the BA-loaded hydrogel on wound healing were mainly realized by its biological effects, including antioxidant and anti-inflammatory effects, and regulation of various wound healing related factors. The results suggested that BA and the hydrogels exert synergistic effects in promoting wound healing. Injectable BA-loaded hydrogels appear to be promising candidates for wound healing application.

Cation and Anion Co-doped Perovskite Nanofibers for Highly Efficient Electrocatalytic Oxygen Evolution.

Perovskite oxides have been recognized as one of the most attractive oxygen evolution reaction (OER) catalysts because of their low cost, earth abundance, and robust nature. Herein, one-dimensional porous LaFe1-xNixO3 (LFNO) perovskite oxide nanofibers (LFNO NFs) are fabricated with a feasible electrospinning route and its further post-calcination treatment. By tailoring the atomic percent of Fe and Ni in the perovskite oxide, we determined that LaFe0.25Ni0.75O3 (LFNO-III) NFs afford the best OER activity among all the prepared perovskite oxides. Especially remarkable is that the further selenide-doped LaFe0.25Ni0.75O3 (LFNOSe-III) NFs exhibit outstanding OER activity with a low overpotential of 287 mV at 10 mA cm-2 and a small Tafel slope of 87 mV dec-1 in 1 M KOH solution, markedly exceeding that of the parent perovskite oxide and the commercial RuO2. It also delivers decent durability with no significant degradation after 22 h of stability test. In the meanwhile, density functional theory calculations are also conducted to justify the optimized adsorption features of *OH, *O, and *OOH intermediates and unveil that the electrocatalytic active sites are the Ni atoms adjacent to Fe in the Ni- and Se codoped perovskite. This work provides an effective method for the development of highly efficient perovskite oxide catalysts.

Crystal structures, dielectric properties and ferroelectricity in stuffed tridymite-type BaAl(2-2x)(Zn0.5Si0.5)2xO4 solid solutions.

BaAl(2-2x)(Zn0.5Si0.5)2xO4 (x = 0, 0.2, 0.4, 0.6, 0.8, 1.0) solid solutions with weak ferroelectricity were prepared using a conventional solid-state reaction method. Zn atoms preferentially occupied the 6c-Wyckoff site of Al1 and the 2b-Wyckoff site of Al4, whereas Si atoms filled the 6c-Wyckoff site of Al2 and the 2b-Wyckoff site of Al3. As such, the cell volume shrank abnormally as the number of larger [Zn0.5Si0.5]3+ compared to Al3+ increased. There were two anomalous peaks in the dielectric constant. One peak at low temperature represented a second-order ferroelectric transition. Relaxor-like behaviour and a stable dielectric constant against temperature from -50 °C to 400 °C were observed at x = 0.4. This result was attributed to disorder in the 2b-Wyckoff site Al/(Zn0.5Si0.5) and distortion in the tetrahedron.

Alismol, a Sesquiterpenoid Isolated from Vladimiria souliei, Suppresses Proinflammatory Mediators in Lipopolysaccharide-Stimulated Microglia.

Microglia activation plays an important role in the pathogenesis of various neurodegenerative diseases by producing neurotoxic factors, such as proinflammatory cytokines and nitric oxide (NO); therefore, suppression of microglia activation is a potential therapeutic approach against these diseases. Previous study showed that alismol, a sesquiterpenoid isolated from the roots of Vladimiria souliei inhibits interferon-γ-induced NO production in murine macrophage RAW264.7 cells. In the present study, we found that alismol reduced NO and prostaglandin E2 (PGE2) levels and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated primary and cultured microglia. Alismol also inhibited the mRNA and protein expression of proinflammatory cytokines including interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. Further mechanistic studies revealed that alismol inhibited LPS-induced nuclear factor-κB (NF-κB) activation but not mitogen-activated protein kinase (MAPK) pathway. Finally, we demonstrated the neuroprotective effects of alismol in microglia-neuron coculture systems. Collectively, these results suggest that the inhibition of microglia activation by alismol may provide potential therapeutic strategy for various neuroinflammatory diseases.

Enhancement of the solubility and stability of D-amino acid oxidase by fusion to an elastin like polypeptide.

An elastin-like polypeptide (ELP) was fused to D-amino acid oxidases (DAAO). ELP-DAAO exhibited a better solubility in aqueous solutions than DAAO, and its enzymatic activity is about 1.6 times that of DAAO. The stability of the proteins was investigated by interacting with urea at various concentrations. The circular dichroism and fluorescence spectra were measured. The results demonstrated that that ELP-DAAO exhibited a much better stability than DAAO, and ELP-DAAO has retained the α-helix content with a high percentage even at a high urea concentration. The results of this work have demonstrated that the ELP tag can be utilized to purify DAAO, in the meantime the solubility and stability of the enzyme are improved.

Sesquiterpenes inhibiting NO production from Celastrus orbiculatus.

Two new (1 and 2) and one known (3) ß-dihydroagarofuran sesquiterpenes were isolated from the fruits of Celastrus orbicultus Thunb. Their structures were elucidated as 1ß,13-diacetoxy-8ß,9ß-dibenzoyloxy-ß-dihydroagarofuran (1), 1ß,13-diacetoxy-8α-hydroxy-9ß-benzoyloxy-ß-dihydroagarofuran (2), and 1ß,6α,13-triacetoxy-9α-benzoyloxy-ß-dihydroagarofuran (3), on the basis of spectroscopic data analyses. All the compounds exhibited inhibitory effects on LPS-induced nitric oxide production in murine microglial BV-2 cells.

Neuroprotective labdane diterpenes from Fritillaria ebeiensis.

By bioactivity-guided isolation, two labdane diterpenes (1 and 2) have been isolated from the bulbs of Fritillaria ebeiensis. Their structures were elucidated as 6α,7ß-dihydroxy-labda-8(17),12(E),14-triene (1) and 6-oxo-2α-hydroxy-labda-7,12(E), 14-triene (2), on the basis of spectroscopic data analysis (IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR). Both of the isolates showed neuroprotective effects against MPP(+)-induced neuronal cell death in human dopaminergic neuroblastoma SH-SY5Y cells.