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1.
Chemosphere ; 311(Pt 1): 136858, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36252903

RESUMO

Enshi City, in the Hubei Province of China, is known as the world capital of selenium with the most abundant selenium resource. An important selenium hyperaccumulator plant, Cardamine violifolia, was found to naturally grow in this high-selenium ecosystem. However, relatively little is known about the impact of the selenium levels on microbial community and functional shifts in C. violifolia rhizosphere. Here, we tested the hypothesis that underground microbial diversity and function vary along a selenium gradient, including antibiotic resistance genes (ARGs). Comprehensive metagenomic analyses, such as taxonomic investigation, functional detection, and ARG annotation, showed that selenium, mercury, cadmium, lead, arsenic, and available phosphorus and potassium were correlated with microbial diversity and function. Thaumarchaeota was exclusively dominant in the highest selenium concentration of mine outcrop, and Rhodanobacter and Nitrospira were predominant in the high-selenium ecosystem. The plant C. violifolia enriched a high concentration of selenium in the rhizosphere compared to those in the bulk soil, and it recruited Variovorax and Polaromonas in its rhizosphere. Microbial abundance showed a trend of increasing first and then decreasing from low to high selenium concentrations. Annotation of ARGs showed that the multidrug resistance genes adeF, mtrA, and poxtA, the aminoglycoside resistance gene rpsL, and the sulfonamide resistant gene sul2 were enriched in the high-selenium system. It was discovered that putative antibiotic resistant bacteria displayed obvious differences in the farmland and the soils with various selenium concentrations, indicating that a high-selenium ecosystem harbors the specific microbes with a higher capacity to enrich or resist selenium, toxic metals, or antibiotics. Taken together, these results reveal the effects of selenium concentration and the selenium hyperaccumulator plant C. violifolia on shaping the microbial functional community and ARGs. Metalloid selenium-inducible antibiotic resistance is worth paying attention to in future.


Assuntos
Microbiota , Selênio , Selênio/farmacologia , Selênio/análise , Antibacterianos/farmacologia , Ecossistema , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Solo , Microbiologia do Solo , Genes Bacterianos
2.
Clin Imaging ; 93: 115-116, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35989110

RESUMO

We read with great interest the recent study conducted by Xu et al1. In this study, the authors investigated the correlation of programmed death ligand-1 (PD-L1) expression with metabolic parameters measured by 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT) and its prognostic value in patients with surgically resected non-small-cell lung cancer (NSCLC). The results of this study1 found that in NSCLC patients, the maximum standardized uptake value (SUVmax) measured by 18F-FDG PET/CT was a predictor of PD-L1 expression, and both PD-L1 and TLG were prognostic factors for the prognosis of NSCLC patient. Undoubtedly, the novel findings of this study help to further refine the risk stratification of NSCLC patients. However, after reading this article carefully, we would like to share the following points.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Antígeno B7-H1/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Neoplasias Pulmonares/diagnóstico por imagem , Estudos Retrospectivos
3.
Adv Sci (Weinh) ; : e2204849, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36354175

RESUMO

Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians' offspring (CO), and nine offspring spouses or neighbors (Control, age-matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic-phenotype-clusters (CPC) and the naïve-phenotype-clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T-cell-receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.

4.
Cell Prolif ; : e13359, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36354207

RESUMO

The anaphase promoting complex/cyclosome (APC/C) and its cofactors CDH1 and CDC20 regulate the accumulation/degradation of CCNB1 during mouse oocyte meiotic maturation. Generally, the CCNB1 degradation mediated by APC/CCDC20 activity is essential for the transition from metaphase to anaphase. Here, by using siRNA and mRNA microinjection, as well as time-lapse live imaging, we showed that Septin 9, which mediates the binding of septins to microtubules, is critical for oocyte meiotic cell cycle progression. The oocytes were arrested at the MI stage and the connection between chromosome kinetochores and spindle microtubules was disrupted after Septin 9 depletion. As it is well known that spindle assembly checkpoint (SAC) is an important regulator of the MI-AI transition, we thus detected the SAC activity and the expression of CDC20 and CCNB1 which were the downstream proteins of SAC during this critical period. The signals of Mad1 and BubR1 still remained on the kinetochores of chromosomes in Septin 9 siRNA oocytes at 9.5 h of in vitro culture when most control oocytes entered anaphase I. The expression of CCNB1 did not decrease and the expression of CDC20 did not increase at 9.5 h in Septin 9 siRNA oocytes. Microinjection of mRNA encoding Septin 9 or CDC20 could partially rescue MI arrest caused by Septin 9 siRNA. These results suggest that Septin 9 is required for meiotic MI-AI transition by regulating the kinetochore-microtubule connection and SAC protein localization on kinetochores, whose effects are transmitted to APC/CCDC20 activity and CCNB1 degradation in mouse oocytes.

5.
Cell Rep ; 41(8): 111644, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36417852

RESUMO

Oct4 is exclusively expressed in rodent inner cell mass (ICM) but silenced in its trophectoderm (TE). However, for many non-rodent animals, including pig, cattle, rabbit, goat, and human, OCT4 has a remarkable expression in early TE. This study, applying pig as the main research model, proves that OCT4 expression in TE is supported by a unique GATA motif in the OCT4 upstream conserved regulatory region, and GATA4 is responsible for its activation. Moreover, OCT4 acts as a specific regulator of a narrow range of genes (including BCL2A1 and HNRNP2AB1) that are essential for the first wave of rapid proliferation in early TE. This study describes the regulatory mechanism to direct the OCT4 expression and its significance in TE of porcine preimplantation embryo.


Assuntos
Blastocisto , Roedores , Humanos , Suínos , Animais , Bovinos , Coelhos
7.
Plant Physiol ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36417279

RESUMO

Excess light causes severe photodamage to photosystem II (PSII) where the primary charge separation for electron transfer takes place. Dissection of mechanisms underlying the PSII maintenance and repair cycle in green algae promotes the usage of genetic engineering and synthetic biology to improve photosynthesis and biomass production. In this study, we systematically analyzed the high light (HL) responsive immunophilin genes in Chlamydomonas (Chlamydomonas reinhardtii) and identified one chloroplast lumen-localized immunophilin, CYN28, as an essential player in HL tolerance. Lack of CYN28 caused HL hypersensitivity, severely reduced accumulation of PSII supercomplexes, and compromised PSII repair in cyn28. The thylakoid FtsH (filamentation temperature-sensitive H) is an essential AAA family metalloprotease involved in the degradation of photodamaged D1 during the PSII repair cycle and was identified as one potential target of CYN28. In the cyn28 mutant, the thylakoid FtsH undergoes inefficient turnover under HL condition. The CYN28-FtsH1/2 interaction relies on the FtsH N-terminal proline residues and is strengthened particularly under HL. Further analyses demonstrated CYN28 displays peptidyl-prolyl isomerase (PPIase) activity, which is necessary for its physiological function. Taken together, we propose that immunophilin CYN28 participates in PSII maintenance and regulates the homeostasis of FtsH under HL stress via its PPIase activity.

8.
J Ethnopharmacol ; : 115893, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36368565

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Panax japonicus C. A. Meye (PJ) has unique effects on diseases by "qi" stagnation and blood stasis in ancient. Modern studies have shown that PJ can treat diabetic kidney disease (DKD) caused by deficiency and blood stasis. AIM OF THE STUDY: This study evaluated the potential effects of PJ on DKD, a microvascular complication, and investigated its possible mechanisms. MATERIALS AND METHODS: In this study, the chemical constituents of PJ were analyzed by HPLC. In vivo studies, we constructed a diabetic mice model by HDF combined with STZ, then administered PJ to diabetic mice for 6 weeks. Blood lipid, BUN, 24h urine protein, and renal tissue HE staining were detected to comprehensively evaluate the protective effect of PJ on DKD. Metabolomics investigated the metabolic pathways influenced by PJ in the treatment of DKD. Moreover, the potential targets and signal pathways were investigated using network pharmacology. Finally, molecular docking predicts affinity of active compounds and core targets, and western blotting was used to detect core target expression levels. RESULTS: In vivo study, PJ can reduce hyperlipidemia, serum BUN, and 24-hour urinary protein in diabetic mice, and protect the pathological changes in renal tissue. Metabolomics results showed that PJ had significant regulatory effect on unsaturated fatty acids, glycerophospholipid metabolism, and purine metabolism. Network pharmacology showed that MAPK1, MAPK8, Bcl-2, and Caspase 3 were the core targets in PJ against DKD. Molecular docking revealed that Bcl-2 and Caspase 3 have a strong affinity for Chikusetsusaponin Iva, Ginsenoside Rb1, and Ginsenoside Rg1. Moreover, when compared to the model group, the PJ group had higher levels of anti-apoptosis protein Bcl-2 and lower levels of pro-apoptosis protein Caspase 3. CONCLUSION: PJ can reduce blood lipids, regulate the biosynthesis of unsaturated fatty acids and purine metabolism, thereby alleviating the renal injury of diabetic mice. Moreover, it can regulate the Bcl-2/caspase 3 apoptosis signaling pathway to prevent the apoptosis of renal cells and protect the renal function of diabetic mice.

9.
Trials ; 23(1): 933, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348365

RESUMO

BACKGROUND: Acute pancreatitis (AP) is a common digestive disease with increased incidence globally but without internationally licenced pharmacological therapy. Moderately severe and severe acute pancreatitis (MSAP/SAP) contributes predominately for its morbidities and mortality and has been managed in West China Hospital for decades using the traditional Chinese medicinal formula chaiqin chengqi decoction (CQCQD). The current study tests whether the early administration of CQCQD will result in improved clinical outcomes in predicted MSAP/SAP patients. METHODS: This is a single-centre, randomised, controlled, double-blind pragmatic clinical trial. AP patients aged 18-75 admitted within 72 h of onset will be assessed at admission for enrolment. We excluded the predicted mild acute pancreatitis (Harmless Acute Pancreatitis Score > 2 at admission) and severe organ failure (Sequential Organ Failure Assessment [SOFA] score of respiratory, cardiovascular, or renal systems > 3) at admission. Eligible patients will be randomly allocated on a 1:1 basis to CQCQD or placebo control administration based on conventional therapy. The administration of CQCQD and placebo is guided by the Acute Gastrointestinal Injury grade-based algorithm. The primary outcome measure will be the duration of respiratory failure (SOFA score of respiratory system ≥ 2) within 28 days after onset. Secondary outcome measures include occurrence of new-onset any organ failure (SOFA score of respiratory, cardiovascular, or renal system ≥ 2) and new-onset persistent organ failure (organ failure lasts > 48 h), dynamic surrogate biochemical markers and clinical severity scores, gut-centred treatment modalities, local complications status, intensive care need and duration, surgical interventions, mortality, and length of hospital stay. Follow-up will be scheduled on 6, 12, and 26 weeks after enrolment to assess AP recurrence, local complications, the requirement for surgical interventions, all-cause mortality, and patient-reported outcomes. DISCUSSION: The results of this study will provide high-quality evidence to appraise the efficacy of CQCQD for the early management of AP patients. TRIAL REGISTRATION: Chictr.org.cn Registry ( ChiCTR2000034325 ). Registered on 2 July, 2020.


Assuntos
Medicamentos de Ervas Chinesas , Pancreatite , Humanos , Doença Aguda , Medicamentos de Ervas Chinesas/efeitos adversos , Pulmão , Pancreatite/diagnóstico , Pancreatite/tratamento farmacológico , Pancreatite/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Pragmáticos como Assunto
10.
BMC Musculoskelet Disord ; 23(1): 964, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348396

RESUMO

BACKGROUND: Medial epicondyle fractures are one of the more common humerus fractures, but humeral medial condyle fracture (HMCF) is rare. Nonunion of medial humeral condyle fractures due to functional exercise is less common. CASE PRESENTATION: We report a 5-year-old patient with a nonunion HMCF due to excessive functional exercise, who bruised the elbow 1 year ago and had no positive findings on all imaging studies. On this physical examination, there was a snapping and palpable lump in the elbow joint during movement, but the patient did not feel any discomfort and the range of motion of the joint was normal. X rays and computed tomography (CT) showed that the left HMCF was discontinuous, the broken ends were dislocated, and the joint alignment was poor. Open reduction (OR) and screw fixation was used during the operation, and the patient recovered well at 3-month follow-up. CONCLUSIONS: The rarity and low radiographic appearance of displaced HMCF are easily overlooked and can eventually lead to nonunion HMCF, especially when radiographically difficult to visualize before age 5 years. Therefore, regardless of whether there are signs or imaging abnormalities in the growth process of adolescents, they should be vigilant, shorten the time interval for re-examination, and early detection and timely treatment can avoid some complications caused by this.


Assuntos
Articulação do Cotovelo , Fraturas não Consolidadas , Fraturas do Úmero , Adolescente , Humanos , Pré-Escolar , Articulação do Cotovelo/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/etiologia , Fraturas do Úmero/cirurgia , Úmero/cirurgia , Fraturas não Consolidadas/diagnóstico por imagem , Fraturas não Consolidadas/etiologia , Fraturas não Consolidadas/cirurgia , Amplitude de Movimento Articular , Resultado do Tratamento
11.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362072

RESUMO

A kind of hydroxylated polymethoxyflavone (PMFs) existing in the citrus genus, 5-Demethyltangeretin (5-DTAN), has been reported to possess several bioactivities in vitro and in vivo. The aim of this study was to investigate whether acetylation could enhance the anticancer activity and oral bioavailability of 5-DTAN. PC-3 human prostate cancer cells were treated with tangeretin (TAN), 5-DTAN, and 5-acetylated TAN (5-ATAN), and the results showed that the cytotoxic effect 5-ATAN (IC50 value of 5.1 µM) on the cell viability of PC-3 cells was stronger than that of TAN (IC50 value of 17.2 µM) and 5-DTAN (IC50 value of 11.8 µM). Compared to 5-DTAN, 5-ATAN treatment caused a more pronounced DNA ladder, increased the sub-G1 phase population, and induced G2/M phase arrest in the cell cycle of PC-3 cells. We also found that 5-ATAN triggered the activation of caspase-3 and the progression of the intrinsic mitochondrial pathway in PC-3 cells, suggesting the induction of apoptosis. In a cell wound healing test, 5-ATAN dose-dependently reduced the cell migration, and the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was decreased after 48 h of 5-ATAN treatment. Moreover, oral administration of 5-ATAN showed a significantly stronger inhibitory effect on tumor size and tumor weight in tumor-bearing nude mice than those of vehicle or the 5-DTAN group (p < 0.05). Furthermore, pharmacokinetic results showed that single-dose oral administration of 5-ATAN exhibited a higher maximum concentration (Cmax) and area under the curve (AUC) of 5-DTAN in plasma than that of 5-DTAN. More extensive distribution of 5-DTAN to most tissues of mice was also observed in mice treated with 5-ATAN for 7 days. In conclusion, acetylation strongly enhances the anticancer activity and oral bioavailability of 5-DTAN and could be a promising strategy to promote the potential bioactivities of natural products.


Assuntos
Metaloproteinase 2 da Matriz , Triacetonamina-N-Oxil , Masculino , Humanos , Camundongos , Animais , Acetilação , Disponibilidade Biológica , Camundongos Nus , Triacetonamina-N-Oxil/farmacologia , Apoptose , Linhagem Celular Tumoral
12.
Front Mol Neurosci ; 15: 986710, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36385754

RESUMO

Ras-related protein Rab-20 (Rab20) is induced in hypoxia and contributes to hypoxia-induced apoptosis. However, the role and mechanism of Rab20 in cerebral ischemia/reperfusion (I/R) injury need to be elucidated. We established a cerebral I/R injury model in the mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells to determine the effects of Rab20 in cerebral I/R injury. Rab20 expression was upregulated in mice after I/R and in HT22 cells after OGD/R. Upregulated Rab20 was mainly located in neurons. Rab20 inhibition significantly alleviated brain infarct volume, neurological deficits, and neuronal apoptosis in mice after I/R. Moreover, Rab20 knockdown significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Rab20 knockdown significantly alleviated OGD/R-induced mitochondrial fission by repressing mitochondrial dynamin-related protein 1 (Drp-1) recruitment and increasing Drp-1 (Ser637) phosphorylation and ameliorated mitochondrial dysfunction by reducing the mitochondrial reactive oxygen species (ROS) and cellular calcium accumulation and increasing the mitochondrial membrane potential. In addition, Rab20 knockdown significantly alleviated cytochrome c release from the mitochondria into the cytosol in HT22 cells after OGD/R. Rab20 contributes to cerebral I/R injury by regulating mitochondria-associated apoptosis pathways. Targeting Rab20 may be an attractive strategy for the treatment of cerebral I/R injury.

13.
Life (Basel) ; 12(11)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36430982

RESUMO

Accurate and reliable outcome predictions can help evaluate the functional recovery of ischemic stroke patients and assist in making treatment plans. Given that recovery factors may be hidden in the whole-brain features, this study aims to validate the role of dynamic radiomics features (DRFs) in the whole brain, DRFs in local ischemic lesions, and their combination in predicting functional outcomes of ischemic stroke patients. First, the DRFs in the whole brain and the DRFs in local lesions of dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) images are calculated. Second, the least absolute shrinkage and selection operator (Lasso) is used to generate four groups of DRFs, including the outstanding DRFs in the whole brain (Lasso (WB)), the outstanding DRFs in local lesions (Lasso (LL)), the combination of them (combined DRFs), and the outstanding DRFs in the combined DRFs (Lasso (combined)). Then, the performance of the four groups of DRFs is evaluated to predict the functional recovery in three months. As a result, Lasso (combined) in the four groups achieves the best AUC score of 0.971, which improves the score by 8.9% compared with Lasso (WB), and by 3.5% compared with Lasso (WB) and combined DRFs. In conclusion, the outstanding combined DRFs generated from the outstanding DRFs in the whole brain and local lesions can predict functional outcomes in ischemic stroke patients better than the single DRFs in the whole brain or local lesions.

14.
Exp Gerontol ; : 112037, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36436758

RESUMO

BACKGROUND: The excessive activation of the microglia leads to the release of inflammatory factors that contribute to neuronal cell loss and neurodegeneration in Parkinson's Disease (PD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) that belongs to a newly found neurotrophic factors (NTFs) family has been reported to promote neuronal survival in the PD models. However, the effects of the MANF on neuroinflammation in PD remain unclear. METHODS: AAV8-MANF virus was constructed to determine whether the high expression of MANF can protect the neuroinflammation-induced dopaminergic neurodegeneration in rats with 6-OHDA-induced PD. Rotarod performance test, immunofluorescent staining and western bolt were employed to evaluate the behavioral dysfunction, dopaminergic neurodegeneration, microglia activation, and signal activation. 6-OHDA treated SH-SY5Y cells and LPS treated BV-2 cells were used as the in vitro model for MANF neuroprotective and neuroinflammation mechanisms. Cell vitality and apoptosis were evaluated with MTT, CCK-8 and flow cytometric analysis. The AKT/GSK3ß-Nrf2 signaling and the TNF-α/IL6 expression were measured by Western Blot. RESULTS: Our findings indicated that the elevated MANF expression by the AAV8-MANF administration ameliorated the motor dysfunction and protected the dopaminergic neurons in the 6-OHDA treated rats. The upregulated CD11b in the rat SN caused by the 6-OHDA administration was significantly attenuated by the pretreatment of the AAV8-MANF. Furthermore, the levels of p-AKT, p-GSK3ß, BCL-2, and Nrf-2 were upregulated by the high expression of the MANF. Under the oxidative stress of the 6-OHDA, the MANF significantly reduced the apoptotic effect of the TNF-α on the SH-SY5Y cells. In the LPS treated BV-2 cells, the MANF reduced the production of the TNF-α and IL-6, via enhancing the Nrf-2, p-Akt, p-GSK, and p-NF-κß level. CONCLUSIONS: These results suggested that the MANF prevented the dopaminergic neurodegeneration caused by the microglia activation in PD via activation of the AKT/GSK-Nrf-2 signaling axis.

15.
Plant Biotechnol J ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36326663

RESUMO

Wheat stripe rust caused by the fungus Puccinia striiformis f. sp. tritici (Pst) is one of the most destructive wheat diseases resulting in significant losses to wheat production worldwide. The development of disease-resistant varieties is the most economical and effective measure to control diseases. Altering the susceptibility genes that promote pathogen compatibility via CRISPR/Cas9-mediated gene editing technology has become a new strategy for developing disease-resistant wheat varieties. Calcineurin B-like protein (CBL)-interacting protein kinases (CIPKs) has been demonstrated to be involved in defence responses during plant-pathogen interactions. However, whether wheat CIPK functions as susceptibility factor is still unclear. Here, we isolated a CIPK homoeologue gene TaCIPK14 from wheat. Knockdown of TaCIPK14 significantly increased wheat resistance to Pst, whereas overexpression of TaCIPK14 resulted in enhanced wheat susceptibility to Pst by decreasing different aspects of the defence response, including accumulation of ROS and expression of pathogenesis-relative genes. We generated wheat Tacipk14 mutant plants by simultaneous modification of the three homoeologues of wheat TaCIPK14 via CRISPR/Cas9 technology. The Tacipk14 mutant lines expressed race-nonspecific (RNS) broad-spectrum resistance (BSR) to Pst. Moreover, no significant difference was found in agronomic yield traits between Tacipk14 mutant plants and Fielder control plants under greenhouse and field conditions. These results demonstrate that TaCIPK14 acts as an important susceptibility factor in wheat response to Pst, and knockout of TaCIPK14 represents a powerful strategy for generating new disease-resistant wheat varieties with BSR to Pst.

16.
J Affect Disord ; 323: 131-139, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36442653

RESUMO

BACKGROUND: Soluble epoxide hydrolase (sEH, encoded by EPHX2) and P2X2 (a subtype of ATP receptors) may mediate the antidepressant-like effects of ATP. We sought to determine whether polymorphisms and mRNA expression of EPHX2 and P2X2 are associated with depression and suicidal behavior and how cognition may mediate such associations. METHOD: We examined 83 single nucleotide polymorphisms (SNPs) of EPHX2 and P2X2. Subjects were MDD suicide attempters (N = 143), MDD non-suicide attempters (N = 248), and healthy volunteers (HV, N = 110). Data on demographics, depression severity, and suicide attempts were collected. Participants completed a set of cognitive tasks. Polymorphisms were genotyped using MALDI-TOF MS within the MassARRAY system. The expression of mRNA was measured using real-time polymerase chain reaction (RT-PCR). RESULTS: Cognitive function was a significant mediator (p = 0.006) of the genetic effect on depression. Allele C of rs202059124 was associated with depression risk (OR = 11.57, 95%CI: 2.33-209.87, p = 0.0181). A significant relationship was found between P2X2 mRNA expression and depression (OR = 0.68, 95%CI: 0.49-0.94, p = 0.0199). One haploblock (rs9331942 and rs2279590) was associated with suicide attempts: subjects with haplotype GC (frequency = 19.8 %, p = 0.017) and AT (frequency = 35.2 %, p < 0.001) had a lower rate of suicide attempts. CONCLUSIONS: Our results confirmed that cognitive impairment plays a role in the effect of rs9331949 on depression. Moreover, we confirmed a relationship between P2X2, EPHX2, and MDD in humans and presented preliminary haplotype-based evidence that implicates EPHX2 in suicide. LIMITATIONS: The main limitation of this study is the limited sample size. More comprehensive and multi-domain cognition tasks and different assessment measures are required in further study.

18.
Magn Reson Med ; 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36336852

RESUMO

PURPOSE: Compared to conventional arterial spin labeling (ASL) methods, velocity-selective ASL (VSASL) is more sensitive to artifacts from eddy currents, diffusion attenuation, and motion. Background suppression is typically suboptimal in VSASL, especially of CSF. As a result, the temporal SNR and quantification accuracy of VSASL are compromised, hindering its application despite its advantage of being delay-insensitive. METHODS: A novel dual-module VSASL (dm-VSASL) strategy is developed to improve the SNR efficiency and the temporal SNR with a more balanced gradient configuration in the label/control image acquisition. This strategy applies for both VS saturation (VSS) and VS inversion (VSI) labeling. The dm-VSASL schemes were compared with single-module labeling and a previously developed multi-module schemes for the SNR performance, background suppression efficacy, and sensitivity to artifacts in simulation and in vivo experiments, using pulsed ASL as the reference. RESULTS: Dm-VSASL enabled more robust labeling and efficient backgroud suppre across brain tissues, especially of CSF, resulting in significantly reduced artifacts and improved temporal SNR. Compared to single-module labeling, dm-VSASL significantly improved the temporal SNR in gray (by 90.8% and 94.9% for dm-VSS and dm-VSI, respectively; P < 0.001) and white (by 41.5% and 55.1% for dm-VSS and dm-VSI, respectively; P < 0.002) matter. Dm-VSI also improved the SNR of VSI by 5.4% (P = 0.018). CONCLUSION: Dm-VSASL can significantly improve the robustness of VS labeling, reduce artifacts, and allow efficient background suppression. When implemented with VSI, it provides the highest SNR efficiency among VSASL methods. Dm-VSASL is a powerful ASL method for robust, accurate, and delay-insensitive perfusion mapping.

19.
Health Syst (Basingstoke) ; 11(4): 251-275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325420

RESUMO

It has been established that high no-show rates of publicly supported health systems in economically depressed areas are largely due to a lack of inexpensive, reliable transportation. The purpose of this paper is to determine the financial feasibility of offering transportation and investigate the net cost savings by reducing no-show rates. The approach starts with a data analysis on 636 patients at the Family Health Center (FHC) in San Antonio, Texas, followed by logistic regression to determine the impact of various transportation factors on cancellations/no-shows and late arrivals. We then investigate the costs savings that could be realised by reducing the no-show rate from 24.3% by up to 60%. Finally, we analyse the expenses that would be incurred should the FHC provide transportation. The full analysis indicates a cost reduction of more than $15,000 per month can be achieved when the no-show rate is reduced by 25% down to 18.2%.

20.
J Cell Physiol ; 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36183380

RESUMO

Miro1, a mitochondrial Rho GTPase1, is a kind of mitochondrial outer membrane protein involved in the regulation of mitochondrial anterograde transport and its subcellular distribution. Mitochondria influence reproductive processes of mammals in some aspects. Mitochondria are important for oocyte maturation, fertilization and embryonic development. The purpose of this study was to evaluate whether Miro1 regulates mouse oocyte maturation by altering mitochondrial homeostasis. We showed that Miro1 was expressed in mouse oocyte at different maturation stages. Miro1 mainly distributed in the cytoplasm and around the spindle during oocyte maturation. Small interference RNA-mediated Miro1 depletion caused significantly abnormal distribution of mitochondria and endoplasmic reticulum as well as mitochondrial dysfunction, resulting in severely impaired germinal vesicle breakdown (GVBD) of mouse oocytes. For those oocytes which went through GVBD in the Miro1-depleted group, part of them were inhibited in meiotic prophase I stage with abnormal chromosome arrangement and scattered spindle length. Our results suggest that Miro1 is essential for maintaining the maturation potential of mouse oocyte.

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