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1.
Curr Biol ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34216556

RESUMO

The establishment of the symbiotic interaction between rhizobia and legumes involves the Nod factor signaling pathway. Nod factor recognition occurs through two plant receptors, NFR1 and NFR5. However, the signal transduction mechanisms downstream of NFR1-NFR5-mediated Nod factor perception remain largely unknown. Here, we report that a small guanosine triphosphatase (GTPase), GmROP9, and a guanine nucleotide exchange factor, GmGEF2, are involved in the soybean-rhizobium symbiosis. We show that GmNFR1α phosphorylates GmGEF2a at its N-terminal S86, which stimulates guanosine diphosphate (GDP)-to-GTP exchange to activate GmROP9 and that the active form of GmROP9 can associate with both GmNFR1α and GmNFR5α. We further show that a scaffold protein, GmRACK1, interacts with active GmROP9 and contributes to root nodule symbiosis. Collectively, our results highlight the symbiotic role of GmROP9-GmRACK1 and support the hypothesis that rhizobial signals promote the formation of a protein complex comprising GmNFR1, GmNFR5, GmROP9, and GmRACK1 for symbiotic signal transduction in soybean.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34240232

RESUMO

OBJECTIVES: Based on an artificial intelligence approach, this study attempted to establish prognostic models to predict 3-month overt hepatic encephalopathy (OHE) occurrence, 1-year mortality, and liver dysfunction for cirrhotic patients with acute variceal bleeding (AVB) treated with early transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: This retrospective study included patients treated with early TIPS between January 2016 and November 2019. Independent risk factors associated with occurrence of OHE within 3 months, 1-year mortality, and liver dysfunction after early TIPS were identified using univariate and multivariate logistic analyses. Artificial neural network (ANN) models and prognostic nomograms based on the independent risk factors were established and validated internally. RESULTS: A total of 207 patients were included, with 33 (15.9%) experienced OHE within 3 months after TIPS creation. The albumin-bilirubin grade (P = 0.015), age (≤ 65, > 65 years) (P < 0.001), gender (P = 0.002), and alcoholic cirrhosis (P = 0.013) was identified as independent risk factors associated with 3-month OHE. Presence of portal vein thrombosis (P = 0.034) and model for end-stage liver disease score (P = 0.063) were identified as independent risk factors associated with 1-year mortality. The platelet-albumin-bilirubin grade (P = 0.041) and a history of hepatic encephalopathy (P = 0.018) were identified as independent risk factors associated with liver dysfunction after TIPS creation. Three ANN models and three nomograms were then established and validated with high accuracy. CONCLUSIONS: The ANN and nomogram models have potential to accurately predict early occurrence of OHE, mortality, and liver dysfunction after early TIPS creation for cirrhotic patients with AVB.

3.
Adv Mater ; : e2101026, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240482

RESUMO

A full-spectrum (300-850 nm) responsive donor-acceptor (D-A) supramolecular photocatalyst tetraphenylporphinesulfonate/fullerene (TPPS/C60 ) is successfully constructed. The theoretical spectral efficiency of TPPS/C60 is as high as 70%, offering the possibility of full-solar-spectrum light harvesting. The TPPS/C60 performs a highly efficient photocatalytic H2 evolution rate of 276.55 µmol h-1 (34.57 mmol g-1 h-1 ), surpassing many reported organic photocatalysts. The D-A structure effectively promotes electron transfer from TPPS to C60 , which is beneficial to the photocatalytic reaction. Specifically, a giant internal electric field in the D-A structure is built via the enhanced molecular dipole, which dramatically promotes the charge separation (CS) efficiency by 2.35 times. Transient absorption spectra results show a long-lived CS state TPPS•+ -C60 •- in the D-A structure, which effectively promotes participation of photogenerated electrons in the reduction reaction. Briefly, this work provides a novel approach for designing high-performance photocatalytic materials via enhancing the interfacial electric field.

4.
J Acoust Soc Am ; 149(5): 3517, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34241112

RESUMO

This paper proposes a multiple signal classification (MUSIC) framework for direction-of-arrival estimation by combining multiple circular arrays in the circular-harmonics domain. We jointly transform the received signals of all sub-arrays into the circular harmonics domain to generate a set of sound field coefficients containing the direction information of the sound sources. These coefficients are then formulated in a form in which MUSIC algorithm can be applied. Compared with the conventional circular-harmonics-domain localization methods, which are based on a single circular array, the proposed method can provide sufficient spatial resolution over different frequency ranges by adjusting the distribution of sub-arrays. Furthermore, the mean square error of the estimated sound field coefficients is derived for guiding this adjustment. Numerical simulation results indicate that a reasonable distribution of sub-arrays can effectively avoid the performance degradation caused by the zeros of Bessel functions, which is an inherent problem of the modal array signal processing. Simulation and experimental results with different configuration parameters demonstrate that the proposed method provides a better localization performance compared to the state-of-the-art methods.

5.
Opt Lett ; 46(13): 3017-3020, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197368

RESUMO

We propose and demonstrate an optical trap on the basis of a normal single-mode fiber (SMF), which is used to trap two particles in the axial direction at the same time without contact based on mode division multiplexing technology. We design and manufacture a tapered fiber probe. The LP11 mode beam is excited by docking a normal SMF to a 980 nm SMF with a 2 µm offset. Then the beams of LP01 and LP11 are both transmitted in the fiber. To converge the LP11 mode beam, a SMF with a tapered end is used to produce a cage for trapping the first microparticle. This particle acts as a lens to converge the LP01 mode beam to trap the second microparticle. We verify the feasibility of trapping two particles simultaneously through simulation. With this function, the proposed optical trap is easier to manipulate different individual particles for comparison and testing, which can promote the development of the biological, biophysical, colloidal, and soft matter fields.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34212188

RESUMO

CONTEXT: Adrenal glands imaging is recommended by the current guidelines for the work-up of primary aldosteronism (PA). However, its diagnostic performance has not been established in large multi-ethnic cohorts of patients submitted to adrenal vein sampling (AVS) and adrenalectomy. OBJECTIVE: To assess the diagnostic accuracy of cross-sectional adrenal imaging. DESIGN: International multi-center study. SETTING: Tertiary referral centers. PATIENTS OR OTHER PARTICIPANTS: 1625 PA patients seeking surgical cure enrolled in an international study involving 19 centers in North America, Europe, Asia, and Australia. 1311 (81%) had imaging data available and 369 (23%), who received a final diagnosis of surgically cured unilateral PA, were examined. INTERVENTION(S): Patients underwent AVS and imaging by computed tomography (CT) and/or magnetic resonance (MR). MAIN OUTCOME MEASURE(S): The accuracy of detection of unilateral PA at imaging was estimated by the area under the receiver operator characteristics (ROC) curve using cure (biochemical and/or full clinical success) as the reference at follow-up after unilateral adrenalectomy. RESULTS: In the cohort of 1311 patients with imaging data available, 34% and 7% of cases showed no detectable or bilateral nodules, respectively. Imaging did not detect the culprit adrenal in 28% of the surgically cured unilateral PA patients. Moreover, the clinical outcome did not differ significantly between the imaging-positive and imaging-negative patients. CONCLUSIONS: Cross-sectional imaging did not identify a lateralized cause of disease in around 40% of PA patients and failed in identifying the culprit adrenal in more than one fourth of patients with unilateral PA.

7.
Huan Jing Ke Xue ; 42(7): 3442-3450, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212671

RESUMO

Based on Landsat satellite remote sensing images, this study interprets land use changes in the Yangtze River Delta (YRD) region from 2000 to 2018. Combined with changes in nitrogen fertilizer application, the changes in ammonia emissions from farmland ecosystem due changes in land use and nitrogen fertilizer application were further investigated. The results show that along with the rapid urbanization process, the area of cultivated land in the YRD region has gradually decreased from 276269 km2 (49% of total land area) in 2000 to 244001 km2 (44%) in 2018. The effects of changes in land use and nitrogen fertilizer application on ammonia emissions from farmland ecosystems mainly include emissions from soil background and nitrogen fertilizer application. From 2000 to 2018, ammonia emissions due to the application of nitrogen fertilizer decreased from 690 kt·a-1 to 541 kt·a-1 (relative decrease by 22%), while the ammonia emissions from the soil background reduced from 32 kt·a-1 to 29 kt·a-1 (decrease by 9%). During the past 20 years, urbanization in the YRD region has accelerated, and the area of cultivated land and the total amount of nitrogen fertilizer application have significantly reduced, thus resulting in reductions in ammonia emissions from the farmland ecosystem.


Assuntos
Amônia , Ecossistema , Agricultura , Amônia/análise , China , Fertilizantes/análise , Nitrogênio/análise , Rios , Solo
8.
Planta ; 254(2): 25, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226949

RESUMO

MAIN CONCLUSION: Some salt-stress responsive DEGs, mainly involved in ion transmembrane transport, hormone regulation, antioxidant system, osmotic regulation, and some miRNA jointly regulated the salt response process in allotriploid Populus cathayana. The molecular mechanism of plant polyploid stress resistance has been a hot topic in biological research. In this study, Populus diploids and first division restitution (FDR) and second division restitution (SDR) triploids were selected as research materials. All materials were treated with 70 mM NaCl solutions for 30 days in the same pot environment. We observed the growth state of triploids and diploids and determined the ratio of potassium and sodium ions, peroxidase (POD) activity, proline content, and ABA and jasmonic acid (JA) hormone content in leaves in the same culture environment with the same concentration of NaCl solution treatment. In addition, RNA-seq technology was used to study the differential expression of mRNA and miRNA. The results showed that triploid Populus grew well and the K+ content and the K+/Na+ ratio in the salt treatment were significantly lower than those in the control. The contents of ABA, JA, POD, and proline were increased compared with contents in diploid under salt stress. The salt-stress responsive DEGs were mainly involved in ion transport, cell homeostasis, the MAPK signaling pathway, peroxisome, citric acid cycle, and other salt response and growth pathways. The transcription factors mainly included NAC, MYB, MYB_related and AP2/ERF. Moreover, the differentially expressed miRNAs involved 32 families, including 743 miRNAs related to predicted target genes, among which 22 miRNAs were significantly correlated with salt-stress response genes and related to the regulation of hormones, ion transport, reactive oxygen species (ROS) and other biological processes. Our results provided insights into the physiological and molecular aspects for further research into the response mechanisms of allotriploid Populus cathayana to salt stress. This study provided valuable information for the salt tolerance mechanism of allopolyploids.


Assuntos
MicroRNAs , Populus , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Populus/genética , Tolerância ao Sal/genética , Transcriptoma
9.
J Integr Plant Biol ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236765

RESUMO

The formation of nitrogen-fixing nodules on legume roots requires the coordination of infection by rhizobia at the root epidermis with the initiation of cell divisions in the root cortex. During infection, rhizobia attach to the tip of elongating root hairs which then curl to entrap the rhizobia. However, the mechanism of root hair deformation and curling in response to symbiotic signals is still elusive. Here, we found that small GTPases (MtRac1/MtROP9 and its homologs) are required for root hair development and rhizobial infection in Medicago truncatula. Our results show that the Nod factor receptor LYK3 phosphorylates the guanine nucleotide exchange factor MtRopGEF2 at S73 which is critical for the polar growth of root hairs. In turn, phosphorylated MtRopGEF2 can activate MtRac1. Activated MtRac1 was found to localize at the tips of root hairs and to strongly interact with LYK3 and NFP. Taken together, our results support the hypothesis that MtRac1, LYK3, and NFP form a polarly localized receptor complex that regulates root hair deformation during rhizobial infection. This article is protected by copyright. All rights reserved.

10.
Cell Death Dis ; 12(7): 707, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267186

RESUMO

Both bench and bedside investigations have challenged the supportive role of Hedgehog (Hh) activity in the progression of colorectal cancers, thus raising a critical need to further deeply determine the contribution of Hh to the growth of colorectal cancer. Combining multiple complementary means, including in vitro and in vivo inflammatory colorectal cancer models, and pathological analysis of clinical colorectal cancer patients samples. We report that colorectal cancer cells hijack prostaglandin E2 (PGE2) to non-canonically promote Hh transcriptional factor Gli activity and Gli-dependent proliferation of colorectal cancer cells in a Smo-independent manner. Mechanistically, PGE2 activates c-Jun N-terminal kinase (JNK), which in turn enables Gli2 to evade ubiquitin-proteasomal degradation by phosphorylating Gli2 at Thr1546. This study not only presents evidence for understanding the contribution of Hh to colorectal cancers, but also provides a novel molecular portrait underlying how PGE2-activated JNK fine-tunes the evasion of Gli2 from ubiquitin-proteasomal degradation. Therefore, it proposes a rationale for the future evaluation of chemopreventive and selective therapeutic strategies for colorectal cancers by targeting PGE2-JNK-Gli signaling route.

11.
Immunopharmacol Immunotoxicol ; 43(4): 478-486, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34196265

RESUMO

OBJECTIVE: To investigate effects of dexmedetomidine (DEX) on miR-205-5p/HMGB1 axis in cerebral ischemic/reperfusion (I/R) injury. METHODS: Both in vivo I/R rat model and in vitro hypoxia/reoxygenation (H/R) cell model using rat hippocampal neurons cells were established. miR-205-5p was overexpressed or inhibited by transfection of miR-205-5p mimics or inhibitor. HMGB1 was overexpressed by transfection overexpression plasmids (OE-HMGB1). TTC staining was used for measurement of infraction volume. Oxidative stress was evaluated by measurement of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) and inflammation was evaluated by measurement of IL-1ß, IL-6 and TNF-α. Dual luciferase reporter assay was performed to confirm binding between miR-205-5p and HMGB1. The expression levels of miR-205-5p, and HMGB1 were measured using RT-qPCR. Western blotting was used to test the protein expression levels of HMGB1, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase (GPx), glutathione reductase (GR), heme oxygenase 1 (HO-1) and catalase (CAT). RESULTS: Treatment of DEX significantly reduced brain infraction volume, decreased Longa's neurological function score and inhibited oxidative stress and inflammation in brain tissues of I/R rats, which were all reversed by inhibition of miR-205-5p. Both treatment of DEX or overexpression of miR-205-5p restricted oxidative stress and inflammation in H/R rat hippocampal neurons cells. The inhibition of miR-205-5p reversed the effects of DEX, while the overexpression of HMGB1 reversed the effects of miR-205-5p overexpression in H/R rat hippocampal neurons cells. Dual luciferase reporter assay showed miR-205-5p directly targeted HMGB1. CONCLUSION: DEX improved I/R injury by suppressing brain oxidative stress and inflammation DEX improved I/R injury by suppressing brain oxidative stress and inflammation through activating miR-205-5p/HMGB1 axis through activating miR-205-5p/HMGB1 axis.

12.
Mol Ecol Resour ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34310851

RESUMO

Standard plant DNA barcodes based on 2-3 plastid regions, and nrDNA ITS show variable levels of resolution, and fail to discriminate among species in many plant groups. Genome skimming to recover complete plastid genome sequences and nrDNA arrays has been proposed as a solution to address these resolution limitations. However, few studies have empirically tested what gains are achieved in practice. Of particular interest is whether adding substantially more plastid and nrDNA characters will lead to an increase in discriminatory power, or whether the resolution limitations of standard plants barcodes are fundamentally due to plastid genomes and nrDNA not tracking species boundaries. To address this, we used genome skimming to recover near-complete plastid genomes and nuclear ribosomal DNA from Rhododendron species and compared discrimination success with standard plant barcodes. We sampled 218 individuals representing 145 species of this species-rich and taxonomically difficult genus, focusing on the global biodiversity hotspots of the Himalaya-Hengduan Mountains. Only 33% of species were distinguished using ITS+matK+rbcL+trnH-psbA. In contrast, 55% of species were distinguished using plastid genome and nrDNA sequences. The vast majority of this increase is due to the additional plastid characters. Thus, despite previous studies showing an asymptote in discrimination success beyond 3-4 plastid regions, these results show that a demonstrable increase in discriminatory power is possible with extensive plastid genome data. However, despite these gains, many species remain unresolved, and these results also reinforce the need to access multiple unlinked nuclear loci to obtain transformative gains in species discrimination in plants.

13.
Colloids Surf B Biointerfaces ; 206: 111951, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34243032

RESUMO

Giant lipid vesicles (GLVs) are usually adopted as models of cell membranes and electroformation is the most commonly used method for GLV formation. However, GLV electroformation are known to be suppressed by the presence of salt and the mechanism is not clear so far. In this paper, the lipid hydration and GLV electroformation were investigated as a function of the concentration of sodium chloride by depositing the lipids on the bottom substrates and top substrates. In addition, the electrohydrodynamic force generated by the electroosmotic flow (EOF) on the lipid phase was calculated with COMSOL Multiphysics. It was found that the mechanisms for the failure of GLV electroformation in salt solutions are: 1) the presence of sodium chloride decreases the membrane permeability to aqueous solution by accelerating the formation of well-packed membranes, suppressing the swelling and detachment of the lipid membranes; 2) the presence of sodium chloride decreased the electrohydrodynamic force by increasing the medium conductivity.

14.
Life Sci ; 282: 119820, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34273377

RESUMO

AIMS: It has been demonstrated that miR-145 is expressed in primordial follicles and modulates the initiation of primordial follicle development. We aimed to explore the function of miR-145 in mouse granulosa cells (mGCs). MATERIALS AND METHODS: The proliferation and differentiation of GCs were examined via MTT, EDU assay, QRT-PCR, ELISA and electron microscope analysis. The target of miR-145 was determined by bioinformatics analysis and luciferase reporter assay and the molecular mechanisms were examined via western blot and quantitative Real-Time RT-PCR. KEY FINDINGS: We proved that down-regulation of miR-145 could inhibit GCs proliferation and differentiation. In addition, we provided evidence that Crkl was the target gene of miR-145. The miR-145 antagomir caused an increase in Crkl expression and activation of the JNK/p38 MAPK pathway. Overexpression of Crkl with pEGFP-N1-Crkl vector inhibited GCs differentiation and progesterone synthesis as well as activation of the JNK/p38 MAPK pathway. SIGNIFICANCE: Our study shows that miR-145 targets Crkl and through the JNK/p38 MAPK signaling pathway promotes the GCs proliferation, differentiation, and steroidogenesis. MiR-145 may play an important role in the ovarian physiology and pathology.

15.
J Ethnobiol Ethnomed ; 17(1): 46, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301287

RESUMO

BACKGROUND: Douyu Village, inhabited by the Lhoba people, is situated within the Eastern Himalayas, in southeastern Tibet, China. The village is located among high mountains and valleys, which feature complex terrain with cold and dry climates and distinctive vegetation types and species. The Lhoba people in this village are isolated from other groups in China. The Lhoba people have lived in this village since the 15th century and mainly depended on gathering, hunting, and swidden agriculture before the 1960s. Because they have a long history and live under extreme climatic, geographical, and ecological conditions, the Lhoba people in Douyu Village may have unique traditional knowledge about wild plants. Thus, this research aims to record the traditional botanical knowledge of the Lhoba people in Douyu. METHODS: An ethnobotanical study was conducted on the Lhoba people in Douyu Village in Longzi County, Tibet, China. Semi-structured interviews and group discussions with informed consent were used in the study. We interviewed 41 informants (14 key informants) between 18 and 75 years of age. All information was collected, organized, and compiled into "use reports" for quantitative analysis. The informant consensus factor (ICF) was used to determine the homogeneity of the informants' knowledge of medicinal plants, while the cultural importance index (CI) was used to estimate the cultural importance of shared species. RESULTS: A total of 91 wild species (90 vascular plants and 1 fungus) belonging to 71 genera and 39 families utilized by the Lhoba people in Douyu were documented. Of these species, Pimpinella xizangense and Wikstroemia lungtzeensis are endemic to Longzi County, while Sinopodophyllum hexandrum and Paeonia ludlowii are endangered species in China. All habitats, from the field vegetation at the valley bottoms to the alpine shrubland and meadows, were used for plant collection, and the numbers of species of plants collected from the various vegetation types (except for fields) decreased with increasing altitude. Our study found that 55 species are edible plants and fungi, 29 species are medicinal plants, and 38 species are used for other purposes. Medicinal plants are used for 11 categories of diseases, among which diseases of blood-forming organs (ICF = 0.96) and gastrointestinal diseases (ICF = 0.95) exhibited the highest ICF values. Based on the CI values, the most important plants in this study area are Berberis xanthophloea, B. kongboensis, Sinopodophyllum hexandrum, Vicatia thibetica, and Hippophae rhamnoides subsp. gyantsensis. Moreover, a comparison of the wild plants used by Lhoba ethnic groups in three counties in China showed significant differences among these regions. CONCLUSIONS: Our study demonstrates that the wild plants utilized by the Lhoba people in Douyu Village are highly diverse, at 90 plant and one fungal species, which reflects not only the number of species but also their diversified functions. The extreme climatic, geographical, and ecological conditions of Douyu within the high mountains and valleys of the Eastern Himalayas potentially affect the Lhoba people's culture, including plant utilization practices, and contribute to the rich diversity of the wild plants used by the local people.

16.
Biotechnol Lett ; 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34275026

RESUMO

The major challenge in utilizing pesticides lies in identifying the precise application that would improve the efficiency of these pesticides and decline their environmental and health hazards at the same time. Such application requires the development of specific formulations that enable controlled, stimuli-responsive release of the pesticides. Gelatin is a relatively cheap material characterized by temperature-sensitivity and abundant amino acid groups, which makes it suitable for the storage and controlled release of pesticides. In this study, gelatin microspheres were prepared by emulsion and cross-linking, then they were loaded with 2,4-dichlorophenoxyacetic acid sodium (2,4-D Na) as a model herbicide. To achieve temperature-tunable release of 2,4-D Na from the microspheres, NH4HCO3 was added to the formulations at different concentrations. The prepared formulations were characterized by SEM, FTIR, and size distribution analyzes, and their drug loading capacities were determined. Based on bioassay experiments, the 2,4-D Na-NH4HCO3-loaded gelatin microspheres can effectively control the spread of dicotyledonous weeds. Therefore, the strategy proposed herein can be used to develop novel, effective herbicide formulations.

17.
J Am Chem Soc ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34279083

RESUMO

Chiral chromophores and their ordered assemblies are intriguing for yielding circularly polarized luminescence (CPL) and exploring intrinsic structure-light emission relationships. With the extensively studied chiral organic molecules and inorganic nanoparticle assemblies for the amplified CPL, the assemblies of copper halide hybrid clusters have attracted intensive attention due to their potential efficient CPL. Here, we report robust chiral phosphine-copper iodide hybrid clusters and their layered assemblies in crystalline states for amplified CPL. We reveal that the intermolecular interactions endow the clusters with the capability of assembling into chiral crystalline CPL materials, including hexagonal platelet-shaped microcrystals (glum ≈ 9.5 × 10-3) and highly oriented crystalline films (glum ≈ 5 × 10-3). Owing to the high crystalline feature of the thin film, we demonstrate an electroluminescent device with bright electroluminescence (1200 cd m-2).

18.
Cell Transplant ; 30: 9636897211033778, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34269100

RESUMO

Acute graft-versus-host disease (aGVHD) is one of the most common complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Janus kinase (JAK) inhibitors are considered as reliable and promising agents for patients with aGVHD. The prophylactic and therapeutic effects of SHR0302, a novel JAK inhibitor, were evaluated in aGVHD mouse models. The overall survival (OS), progression-free survival (PFS), bodyweight of mice, GVHD scores were observed and recorded. The bone marrow and spleen samples of diseased model mice or peripheral blood of patients were analyzed. SHR0302 could prevent and reverse aGVHD in mouse models with preserving graft-versus-tumor effect. Functionally, SHR0302 improved the OS and PFS, restored bodyweight, reduced GVHD scores, and reduced immune cells infiltrated in target tissues. SHR0302 treatment also enhanced the hematopoietic reconstruction compared to the control group. Mechanistically, our results suggested that SHR0302 could inhibit the activation of T cells and modulate the differentiation of helper T (Th) cells by reducing Th1 and increasing regulatory T (Treg) cells. In addition, SHR0302 decreased the expression of chemokine receptor CXCR3 on donor T cells and the secretion of cytokines or chemokines including interleukin (IL)-6, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), CXCL10, etc. thereby destroying the IFN-γ/CXCR3/CXCL10 axis which promotes the progression of GVHD. Besides, SHR0302 decreased the phosphorylation of JAK and its downstream STATs, AKT and ERK1/2, which ultimately regulated the activation, proliferation, and differentiation of lymphocytes. Experiments on primary cells from aGVHD patients also confirmed the results. In summary, our results indicated that JAK inhibitor SHR0302 might be used as a novel agent for patients with aGVHD.

19.
Aesthetic Plast Surg ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269845

RESUMO

BACKGROUND: Various operative methods exist for nipple reconstruction. Selection of an appropriate skin flap and core strut material is imperative in achieving a satisfactory outcome in nipple reconstruction. Long-term maintenance of nipple projection requires further investigation by surgeons. We propose a new technique that uses a semilunar flap and omega-shaped acellular dermal matrix (ADM). METHODS: Total 53 nipples were reconstructed by this method. An omega-shaped ADM strut was inserted into the barrel made by a semilunar flap. The footplates of omega-shaped ADM struts were spread out under the subcutaneous tissue of the donor site of the semilunar flap to support the dome of the omega strut. RESULTS: The mean maintenance rate of nipple projection was 95.12 ± 6.30% at 3 weeks, 80.60 ± 8.93% at 3 months, and 71.70 ± 8.67% at 6 months postoperatively when compared to the projection observed in the immediate postoperative period. Thirty-five patients (66.0%) showed a maintenance rate over 70% at 6 months post operation, with most patients (94.3%) demonstrating a maintenance rate greater than 60%. CONCLUSIONS: Our study with the omega-shaped ADM strut showed superior maintenance rates of projection when compared to other studies on that used AlloDerm® as a core strut for nipple reconstruction. Omega-shaped struts, when made with cross-linked thick ADM, supported the skin flap quite well. We propose that our method combining the semilunar flap with an omega-shaped ADM may be a good option for nipple reconstruction. LEVEL OF EVIDENCE IV: "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 ."

20.
Haematologica ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196166

RESUMO

Chemotherapy dosages are often compromised, but most reports lack data on dosages that are actually delivered. In two consecutive acute lymphoblastic leukemia (ALL) trials that differed in their asparaginase formulation, native E. coli L-asparaginase in St. Jude Total 15 (T15, n=365) and pegaspargase in Total 16 (T16, n=524), we tallied the dose intensities (DIs) for all medications on the low-risk (LR) or standard-risk (SR) arms, analyzing 504,039 dosing records. The median DI for each drug ranged from 61-100%; DIs for several drugs were over 10% higher on T15 than on T16: cyclophosphamide (p < 0.0001 for SR), cytarabine (p < 0.0001 for SR), and mercaptopurine (p < 0.0001 for LR and < 0.0001 for SR). We attributed the lower dosages on T16 to the higher asparaginase dosages on T16 than T15 (p.

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