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1.
Chem Commun (Camb) ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522979

RESUMO

We here found that while Meldrum's acid as the reactive warhead allows for the attachment of a single chemical modification on aldehyde-containing proteins, pyrazolone derivatives in combination with a phosphine nucleophile enable protein dual site-specific conjugation with the same or distinct moieties. These reactions are efficient and convergent under biocompatible conditions and allow access to protein bioconjugates with superior stability, homogeneity and flexibility. Our work expands the repertoire of bioconjugation chemistries and offers opportunities to construct bioconjugates with defined structure that have potential for medical and biomaterial applications.

2.
Reg Anesth Pain Med ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523480

RESUMO

INTRODUCTION: Understanding postoperative opioid use patterns among different populations is key to developing opioid stewardship programs. METHODS: We performed a retrospective cohort study on opioid prescribing, use, and pain after general surgery procedures for patients cared for by a transitional pain service at a veterans administration hospital. Discharge opioid prescription quantity, 90-day opioid prescription, and patient reported outcome pain measures were compared between chronic opioid users and non-opioid users (NOU). Additionally, 90-day total opioid use was evaluated for NOU. RESULTS: Of 257 patients, 34 (13%) were on chronic opioid therapy, over 50% had a mental health disorder, and 29% had a history and/or presence of a substance use disorder. NOU were prescribed a median (IQR) of 10 (7, 12) tablets at discharge, while chronic opioid users were prescribed 6 (0, 12) tablets (p<0.001). 90-day opioid prescription (not including baseline opioid prescription for chronic users) was 10 (7, 15) and 6 (0, 12) tablets, respectively (p=0.001). There were no differences in changes in pain intensity or pain interference scores during recovery between groups. Median 90-day opioid use post discharge for NOU was 4 (0, 10) pills. DISCUSSION: Non-opioid and chronic opioid users required very few opioid pills following surgery, and patients on chronic opioid therapy quickly returned to their baseline opioid use after a small opioid prescription at discharge. There was no difference in pain recovery between groups. Opioid prescribing guidelines should include patients on chronic opioid therapy and could consider recommending a more conservative prescribing approach.

3.
Anim Sci J ; 93(1): e13733, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35537808

RESUMO

This study aimed to investigate the performance of least-squares support vector machines to predict carcass characteristics in Tan sheep using noninvasive in vivo measurements. A total of 80 six-month-old Tan sheep (37 rams and 43 ewes) were examined. Back fat thickness and eye muscle area between the 12th and 13th ribs were measured using real-time ultrasound in live Tan sheep. All carcasses were dissected to hind leg, longissimus dorsi muscle, lean meat, fat, and bone to determine carcass composition. Multiple linear regression (MLR), partial least squares regression (PLSR), and least-squares support vector machines (LSSVM) were applied to correlate the live Tan sheep characteristics with carcass composition. The results showed that the LSSVM model had a better efficacy for estimating carcass weight, longissimus dorsi muscle weight, lean meat weight, fat weight, lean meat, and fat percentage in live lambs (R = 0.94, RMSE = 0.62; R = 0.73, RMSE = 0.02; R = 0.86, RMSE = 0.47; R = 0.78, RMSE = 0.63; R = 0.73, RMSE = 0.02; R = 0.65, RMSE = 0.03, respectively). LSSVM algorithm was a potential alternative to the conventional MLR method. The results demonstrated that LSSVM model might have great potential to be applied to the evaluation of sheep with superior carcass traits by combining with real-time ultrasound technology.

4.
Sci Rep ; 12(1): 7118, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35504960

RESUMO

Natural killer/T-cell lymphoma (NKTCL) in children and adolescents is a rare type of T/NK cell neoplasms. The aim of the present study was to analyze the clinicopathological and genetic features of this rare entity of lymphoma. We evaluated the clinical, histopathological and molecular features of 22 young people with NKTCL, including 15 males and 7 females, with a median age of 15 years. The results revealed that the nasal site was the most involved region while non-nasal sites were observed in 27.3% out of all cases. The tumor cells were composed of small­sized to large cells and 19 (86.4%) cases exhibited coagulative necrosis. The neoplastic cells in all patients were positive for CD3 and the cytotoxic markers. Nineteen (86.4%) cases were positive for CD56. Reduced expression of CD5 was observed in all available cases. CD30 was heterogeneously expressed in 15 (75.0%) cases. All 22 patients were EBV positive. Seven (36.8%) out of all the 19 patients during the follow-up died of the disease, and the median follow­up period was 44 months. Moreover, patients treated with radiotherapy/chemotherapy showed significantly inferior OS compared with the untreated patients. High mutation frequencies were detected including KMT2C (5/5), MST1 (5/5), HLA-A (3/5) and BCL11A (3/5), which involved in modifications, tumor suppression and immune surveillance. These results suggest that NKTCL in children and adolescents exhibits histopathological and immunohistochemical features similar to the cases in adults. Active treatment is necessary after the diagnosis of NKTCL is confirmed. Furthermore, genetic analyse may provide a deep understanding of this rare disease.


Assuntos
Linfoma Extranodal de Células T-NK , Células T Matadoras Naturais , Adolescente , Adulto , Criança , Feminino , Humanos , Antígeno Ki-1 , Células Matadoras Naturais/patologia , Linfoma Extranodal de Células T-NK/diagnóstico , Masculino , Células T Matadoras Naturais/patologia , Estudos Retrospectivos
5.
J Bone Joint Surg Am ; 104(9): 774-779, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506951

RESUMO

BACKGROUND: The purpose of the present study was to analyze the association between sex hormone deficiency and rotator cuff repair (RCR) with use of data from a large United States insurance database. METHODS: A retrospective analysis of insured subjects from the Truven Health MarketScan database was conducted, collecting data for RCR cases as well as controls matched for age, sex, and years in the database. Multivariable logistic regression models adjusted for matching variables were utilized to compare RCR status with estrogen deficiency status and testosterone deficiency status. These associations were confirmed with use of data from the Veterans Genealogy Project database, with which the relative risk of RCR was estimated for patients with and without sex hormone deficiency. RESULTS: The odds of RCR for female patients with estrogen deficiency were 48% higher (odds ratio, 1.48; 95% confidence interval, 1.44 to 1.51; p < 0.001) than for those without estrogen deficiency. The odds of RCR for males with testosterone deficiency were 89% higher (odds ratio, 1.89; 95% confidence interval, 1.82 to 1.96; p < 0.001) than for those without testosterone deficiency. Within the Veterans Genealogy Project database, the relative risk of estrogen deficiency among RCR patients was 2.58 (95% confidence interval, 2.15 to 3.06; p < 0.001) and the relative risk of testosterone deficiency was 3.05 (95% confidence interval, 2.67 to 3.47; p < 0.001). CONCLUSIONS: Sex hormone deficiency was significantly associated with RCR. Future prospective studies will be necessary to understand the pathophysiology of rotator cuff disease as it relates to sex hormones. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Seguro , Lesões do Manguito Rotador , Artroscopia/efeitos adversos , Estrogênios , Feminino , Hormônios Esteroides Gonadais , Humanos , Incidência , Masculino , Estudos Prospectivos , Reoperação , Estudos Retrospectivos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/epidemiologia , Lesões do Manguito Rotador/etiologia , Lesões do Manguito Rotador/cirurgia , Testosterona , Estados Unidos/epidemiologia
6.
Clin Cosmet Investig Dermatol ; 15: 763-781, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35510223

RESUMO

Purpose: To study the efficacy of Ba Zhen Tang in delaying skin photoaging and its potential mechanism based on network pharmacology and molecular docking. Methods: First, we screened the active components and targets of Ba Zhen Tang by Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and The Universal Protein Resource (UniProt). The target genes of skin photoaging were obtained from GeneCards and GeneMap database. Then, we analyzed the protein-protein interaction (PPI) by STRING database. The network map was constructed by Cytoscape. Finally, we performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis by Metascape database. The molecular docking via Autodock Vina and Pymol. Furthermore, skin photoaging cellular models were established, and the effects of Ba Zhen Tang on ameliorating skin photoaging were investigated. Results: A total of 160 active ingredients in Ba Zhen Tang and 60 targets of Ba Zhen Tang for delaying skin photoaging were identified. By GO enrichment analysis, 1153 biological process entries, 45 cellular component entries and 89 molecular functional entries were obtained. A total of 155 signal pathways were obtained by KEGG analysis. Ba Zhen Tang is related to MAPK signaling pathway, TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications, etc., which directly affect the key nodes of photoaging. The molecular docking results showed that there was a certain affinity between the main compounds (kaempferol, quercetin, ß-sitosterol, naringenin) and core target genes (PTGS2, CASP3, MAPK1, MAPK3, TP53). Ba Zhen Tang-treated mouse serum inhibited the senescence and p16INK4a expression of human immortalized keratinocyte (HaCaT) cells irradiated by ultraviolet-B (UVB). Conclusion: Our study elucidated the potential pharmacological mechanism of Ba Zhen Tang in the treatment of photoaging through multiple targets and pathways. The therapeutic effects of Ba Zhen Tang on skin photoaging were validated in cellular models.

7.
Arthrosc Sports Med Rehabil ; 4(2): e471-e478, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35494278

RESUMO

Purpose: To compare magnetic resonance imaging (MRI) with magnetic resonance arthrogram (MRA) in the identification of hip capsular defects in patients who previously underwent hip arthroscopy. Methods: Patients who underwent revision hip arthroscopy for capsular insufficiency by a single surgeon between March 2014 and December 2019 were identified by Current Procedural Terminology code. Patients with arthroscopically confirmed capsular defects treated surgically who underwent both MRI and MRA between their primary and revision surgeries were identified. Imaging studies were blinded, randomized, and distributed to two fellowship-trained musculoskeletal radiologists. Radiologists evaluated 14 components of different anatomic structures, including the presence of capsular defect and defect grading, over 2 months, with a 2-week washout period between 4 sets of reads to obtain 2 complete reads from each radiologist. Data were analyzed in R version 4.0.2. Results: Two hundred thirty patients underwent revision hip arthroscopy between March 2014 and December 2019. Twelve patients had both an MRI and an MRA of the operated hip performed between their primary and revision surgeries. Time between primary and revision hip arthroscopy was 2.0 ± 1.5 years (R: .3-6.3). Time between MRI and MRA was .6 ± .6 years (R: .0-1.6). Sensitivity for detecting hip capsular defects was significantly higher for MRA than for MRI (87.5%, 95% CI: [68,96] vs 50%, 95% CI: [31,69], respectively; P = .008). Conclusions: This retrospective review demonstrates that MRA has higher sensitivity than MRI in detecting surgically confirmed capsular defects. MRA may be more helpful in identifying capsular defects in patients presenting with hip instability symptoms who have had a previous hip arthroscopy. Level of Evidence: Level IV, diagnostic case series.

8.
Front Microbiol ; 13: 855059, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495696

RESUMO

Increasing demand for recombinant proteins necessitates efficient protein production processes. In this study, a continuous process for human epidermal growth factor (hEGF) secretion by Escherichia coli was developed by taking advantage of biofilm formation. Genes bcsB, fimH, and csgAcsgB that have proved to facilitate biofilm formation and some genes moaE, yceA, ychJ, and gshB potentially involved in biofilm formation were examined for their effects on hEGF secretion as well as biofilm formation. Finally, biofilm-based fermentation processes were established, which demonstrated the feasibility of continuous production of hEGF with improved efficiency. The best result was obtained from ychJ-disruption that showed a 28% increase in hEGF secretion over the BL21(DE3) wild strain, from 24 to 32 mg/L. Overexpression of bcsB also showed great potential in continuous immobilized fermentation. Overall, the biofilm engineering here represents an effective strategy to improve hEGF production and can be adapted to produce more recombinant proteins in future.

9.
Cell Death Discov ; 8(1): 221, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459209

RESUMO

Lorlatinib is a promising third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that has been approved for treating ALK-positive non-small-cell lung cancer (NSCLC) patients with previous ALK-TKI treatment failures. However, the inevitable emergence of acquired resistance limits its long-term efficacy. A more comprehensive understanding of the acquired resistance mechanisms to lorlatinib will enable the development of more efficacious therapeutic strategies. The efficacy of chloroquine (CQ) in combination with lorlatinib in ALK-positive NSCLC cells in vitro and in vivo was assessed using CCK-8, colony formation, immunofluorescence staining, flow cytometry analysis, western blot analysis, and xenograft implantation. Here, we show that lorlatinib induced apoptosis and protective autophagy in ALK-positive NSCLC cells. However, the protective autophagy can gradually lead to decreased cytotoxicity of loratinib in ALK-positive NSCLC cells. Meanwhile, we found that the combination of lorlatinib and CQ, an inhibitor of autophagy, inhibited autophagy and promoted apoptosis both in vitro and in vivo, which sensitized cells to lorlatinib through the dephosphorylation of Foxo3a and promoted nuclear translocation, then activation of Foxo3a/Bim axis. Taken together, our results suggest that inhibition of protective autophagy might be a therapeutic target for delaying the occurrence of acquired resistance to lorlatinib in ALK-positive NSCLC patients.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35484308

RESUMO

MicroRNA-365 (miR-365) has been revealed to be a vital regulator in tumorigenesis of multiple cancers, while there is a large gap in the knowledge about miR-365 expression and gastric cancer (GC). This research focused on the effects of miR-365 and paired box 6 (PAX6) on GC development. Levels of miR-365 and PAX6 in GC tissues and cell lines were determined, followed by the screening of the AGS and NCI-N87 cells. Gain- or loss-of-function assays were used to analyze the effect of miR-365, PAX6 on AGS and NCI-N87 cell behaviors. The effects of altered miR-365 and PAX6 on animal models were observed. Moreover, to assess the interaction between miR-365 and PAX6, we implemented the bioinformatic method and dual luciferase reporter gene assay. MiR-365 was decreased while PAX6 was increased in GC tissues and cell lines. There existed a negative association between miR-365 and PAX6. The promoted miR-365 could repress oncogenicity in vivo and malignant transformation in vitro of GC. PAX6 was the target gene of miR-365. Overexpression of PAX6 reversed the inhibitory effect of up-regulated miR-365 on malignant behavior of gastric cancer cells. Our research displays that the amplification of miR-365 could suppress the malignant behaviors of GC cells via inhibiting PAX6, which may be helpful for GC treatment.

11.
Angew Chem Int Ed Engl ; : e202203878, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35438229

RESUMO

Despite recent interests in developing lysine-targeting covalent inhibitors, no general approach is available to create such compounds. We report herein a general approach to develop cell-active covalent inhibitors of protein kinases by targeting the conserved catalytic lysine residue using key SuFEx and salicylaldehyde-based imine chemistries. We validated the strategy by successfully developing (irreversible and reversible) covalent inhibitors against BCR-ABL kinase. Our lead compounds showed high levels of selectivity in biochemical assays, exhibited nanomolar potency against endogenous ABL kinase in cellular assays, and were active against most drug-resistant ABL mutations. Among them, the salicylaldehyde-containing A5 is the first-ever reversible covalent ABL inhibitor that possessed time-dependent ABL inhibition with prolonged residence time and few cellular off-targets in K562 cells. Bioinformatics further suggested the generality of our strategy against the human kinome.

12.
Int J Mol Sci ; 23(7)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35408924

RESUMO

Tapetal programmed cell death (PCD) is a complex biological process that plays an important role in pollen formation and reproduction. Here, we identified the MYB2 transcription factor expressed in the tapetum from stage 5 to stage 11 that was essential for tapetal PCD and pollen development in Arabidopsis&nbsp;thaliana. Downregulation of MYB2 retarded tapetal degeneration, produced defective pollen, and decreased pollen vitality. EMSA and transcriptional activation analysis revealed that MYB2 acted as an upstream activator and directly regulated expression of the proteases CEP1 and ßVPE. The expression of these proteases was lower in the buds of the myb2 mutant. Overexpression of either/both CEP1 or/and ßVPE proteases partially recover pollen vitality in the myb2 background. Taken together, our results revealed that MYB2 regulates tapetal PCD and pollen development by directly activating expression of the proteases CEP1 and ßVPE. Thus, a transcription factor/proteases regulatory and activated cascade was established for tapetal PCD during another development in Arabidopsis&nbsp;thaliana. Highlight: MYB2 is involved in tapetal PCD and pollen development by directly regulating expression of the protease CEP1 and ßVPE and establishes a transcription factor/proteases regulatory and activated cascade.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fenômenos Biológicos , Apoptose , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Pólen , Transativadores , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Glob Chang Biol ; 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35429205

RESUMO

Ammonia (NH3 ) and nitrous oxide (N2 O) are two important air pollutants that have major impacts on climate change and biodiversity losses. Agriculture represents their largest source and effective mitigation measures of individual gases have been well studied. However, the interactions and trade-offs between NH3 and N2 O emissions remain uncertain. Here, we report the results of a two-year field experiment in a wheat-maize rotation in the North China Plain (NCP), a global hotspot of reactive N emissions. Our analysis is supported by a literature synthesis of global croplands, to understand the interactions between NH3 and N2 O emissions and to develop the most effective approaches to jointly mitigate NH3 and N2 O emissions. Field results indicated that deep placement of urea with nitrification inhibitors (NIs) reduced both emissions of NH3 by 67% to 90% and N2 O by 73% to 100%, respectively, in comparison with surface broadcast urea which is the common farmers' practice. But, deep placement of urea, surface broadcast urea with NIs, and application of urea with urease inhibitors probably led to trade-offs between the two gases, with a mitigation potential of -201% to 101% for NH3 and -112% to 89% for N2 O. The literature synthesis showed that deep placement of urea with NIs had an emission factor of 1.53%-4.02% for NH3 and 0.22%-0.36% for N2 O, which were much lower than other fertilization regimes and the default values recommended by IPCC guidelines. This would translate to a reduction of 3.86-5.47 Tg N yr-1 of NH3 and 0.41-0.50 Tg N yr-1 of N2 O emissions, respectively, when adopting deep placement of urea with NIs (relative to current practice) in global croplands. We conclude that the combination of NIs and deep placement of urea can successfully tackle the trade-offs between NH3 and N2 O emissions, therefore avoiding N pollution swapping in global croplands.

14.
Sensors (Basel) ; 22(8)2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35459059

RESUMO

The last decade has seen significant advances in power optimization for IoT sensors. The conventional wisdom considers that if we reduce the power consumption of each component (e.g., processor, radio) into µW-level of power, the IoT sensors could achieve overall ultra-low power consumption. However, we show that this conventional wisdom is overturned, as bus communication can take significant power for exchanging data between each component. In this paper, we analyze the power efficiency of bus communication and ask whether it is possible to reduce the power consumption for bus communication. We observe that existing bus architectures in mainstream IoT devices can be classified into either push-pull or open-drain architecture. push-pull only adapts to unidirectional communication, whereas open-drain inherently fits for bidirectional communication which benefits simplifying bus topology and reducing hardware costs. However, open-drain consumes more power than push-pull due to the high leakage current consumption while communicating on the bus. We present Turbo, a novel approach introducing low power to the open-drain based buses by reducing the leakage current created on the bus. We instantiate Turbo on I2C bus and evaluate it with commercial off-the-shelf (COTS) sensors. The results show a 76.9% improvement in power efficiency in I2C communication.

15.
Sensors (Basel) ; 22(8)2022 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35459067

RESUMO

The rapid development of Internet of Things (IoT) applications calls for light-weight IoT sensor nodes with both low-power consumption and excellent task execution efficiency. However, in the existing system framework, designers must make trade-offs between these two. In this paper, we propose an "edge-to-end integration" design paradigm, Butterfly, which assists sensor nodes to perform sensing tasks more efficiently with lower power consumption through their (high-performance) network infrastructures (i.e., a gateway). On the one hand, to optimize the power consumption, Butterfly offloads the energy-intensive computational tasks from the nodes to the gateway with only microwatt-level power budget, thereby eliminating the power-consuming Microcontroller (MCU) from the node. On the other hand, we address three issues facing the optimization of task execution efficiency. To start with, we buffer the frequently used instructions and data to minimize the volume of data transmitted on the downlink. Furthermore, based on our investigation on typical sensing data structures, we present a novel last-bit transmission and packaging mechanism to reduce the data amount on the uplink. Finally, we design a task prediction mechanism on the gateway to support efficient scheduling of concurrent tasks on multiple MCU-free Butterfly nodes. The experiment results show that Butterfly can speed up the task rate by 4.91 times and reduce the power consumption of each node by 94.3%, compared to the benchmarks. In addition, Butterfly nodes have natural security advantages (e.g., anti-capture) as they offload the control function with all application information up to the gateway.


Assuntos
Tecnologia sem Fio
16.
Protein Cell ; 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35384603

RESUMO

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.

17.
Front Plant Sci ; 13: 814015, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386666

RESUMO

Peanut embryo development is easily affected by a variety of nutrient elements in the soil, especially the calcium level. Peanut produces abortive embryos in calcium-deficient soil, but underlying mechanism remains unclear. Thus, identifying key transcriptional regulators and their associated regulatory networks promises to contribute to a better understanding of this process. In this study, cellular biology and gene expression analyses were performed to investigate peanut embryo development with the aim to discern the global architecture of gene regulatory networks underlying peanut embryo abortion under calcium deficiency conditions. The endomembrane systems tended to disintegrate, impairing cell growth and starch, protein and lipid body accumulation, resulting in aborted seeds. RNA-seq analysis showed that the gene expression profile in peanut embryos was significantly changed under calcium deficiency. Further analysis indicated that multiple signal pathways were involved in the peanut embryo abortion. Differential expressed genes (DEGs) related to cytoplasmic free Ca2+ were significantly altered. DEGs in plant hormone signaling pathways tended to be associated with increased IAA and ethylene but with decreased ABA, gibberellin, cytokinin, and brassinosteroid levels. Certain vital genes, including apoptosis-inducing factor, WRKYs and ethylene-responsive transcription factors, were up-regulated, while key regulators of embryo development, such as TCP4, WRI1, FUS3, ABI3, and GLK1 were down-regulated. Weighted gene co-expression network analysis (WGCNA) identified 16 significant modules associated with the plant hormone signaling, MAPK signaling, ubiquitin mediated proteolysis, reserve substance biosynthesis and metabolism pathways to decipher regulatory network. The most significant module was darkolivegreen2 and FUS3 (AH06G23930) had the highest connectivity among this module. Importantly, key transcription factors involved in embryogenesis or ovule development including TCP4, GLK1, ABI3, bHLH115, MYC2, etc., were also present in this module and down regulated under calcium deficiency. This study presents the first global view of the gene regulatory network involved in peanut embryo abortion under calcium deficiency conditions and lays foundation for improving peanut tolerances to calcium deficiency by a targeted manipulation of molecular breeding.

18.
Synth Syst Biotechnol ; 7(2): 765-774, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35387228

RESUMO

Corynebacterium glutamicum represents an emerging recombinant protein expression factory due to its ideal features for protein secretion, but its applicability is harmed by the lack of an autoinduction system with tight regulation and high yield. Here, we propose a new recombinant protein manufacturing platform that leverages ethanol as both a delayed carbon source and an inducer. First, we reanalysed the native inducible promoter PICL from the acetate uptake operon and found that its limited capacity is the result of the inadequate translation initial architecture. The two strategies of bicistronic design and ribozyme-based insulator can ensure the high activity of this promoter. Next, through transcriptional engineering that alters transcription factor binding sites (TFBSs) and the first transcribed sequence, the truncated promoter PA256 with a dramatically higher transcription level was generated. When producing the superfolder green fluorescent protein (sfGFP) under 1% ethanol conditions, PA256 exhibited substantially lower protein accumulation in prophase but an approximately 2.5-fold greater final yield than the strong promoter PH36. This superior expression mode was further validated using two secreted proteins, camelid antibody fragment (VHH) and endoxylanase (XynA). Furthermore, utilizing CRISPRi technology, ethanol utilization blocking strains were created, and PA256 was shown to be impaired in the phosphotransacetylase (PTA) knockdown strains, indicating that ethanol metabolism into the tricarboxylic acid cycle is required for PA256 upregulation. Finally, this platform was applied to produce the "de novo design" protein NEO-2/15, and by introducing the N-propeptide of CspB, NEO-2/15 was effectively secreted with the accumulation 281 mg/L obtained after 24 h of shake-flask fermentation. To the best of our knowledge, this is the first report of NEO-2/15 secretory overexpression.

19.
Neuromodulation ; 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35393238

RESUMO

OBJECTIVES: In the practice of intrathecal drug delivery, consensus exists regarding the cephalad to caudad location of the catheter tip relative to dermatomal distribution of pain. However, data are lacking on the importance of dorsal vs ventral tip location relative to the spinal cord. We hypothesize that a dorsally placed catheter tip improves efficacy because of closer proximity to nociceptive pathways. MATERIALS AND METHODS: A retrospective review of 298 patients with cancer with intrathecal drug delivery systems implanted at the Huntsman Cancer Institute from May 2014 to June 2020 was performed. Patients were stratified by catheter tip location zones based on available radiographic studies. Patient-controlled intrathecal medication dose requirements and rate of change were compared with catheter zone and other variables, including the presence of adjuncts such as bupivacaine and ziconotide. RESULTS: A total of 158 patients were suitable for analysis demonstrating a dorsal tip in 63.9% (n = 101) and ventral tip in 36.1% (n = 57), with a median follow-up of 17 days (interquartile range [IQR], 10-24). There was no difference in daily dose change from implant to discharge between the dorsal group 8.2% (IQR, 0.0-41.5) and ventral group 20.8% (IQR, 0.0-66.7; p = 0.12). Daily dose change from discharge to follow-up was 2.6% (IQR, 0.0-7.1) in the dorsal group and 1.8% (IQR, 0.0-5.7) in the ventral group (p = 0.92). Catheter tip location had no impact on systemic opioid use. CONCLUSIONS: We did not find significant associations between dorsal vs ventral catheter tip location and measures of pain relief, including change in intrathecal dose or systemic opioid use.

20.
Biomed Opt Express ; 13(3): 1243-1260, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35414996

RESUMO

An adaptive brightness fusion method (ABFM) for near-infrared fluorescence imaging is proposed to adapt to different lighting conditions and make the equipment operation more convenient in clinical applications. The ABFM is designed based on the network structure of Attention Unet, which is an image segmentation technique. Experimental results show that ABFM has the function of adaptive brightness adjustment and has better fusion performance in terms of both perception and quantification. Generally, the proposed method can realize an adaptive brightness fusion of fluorescence and visible images to enhance the usability of fluorescence imaging technology during surgery.

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