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1.
IUCrdata ; 7(Pt 8): x220775, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36340975

RESUMO

The asymmetric unit of the title three-dimensional metal-organic hybrid compound, [Co2(C6H2O4S)2(C3H7NO)2] n , comprises two cobalt(II) cations, one residing on a twofold axis and the other on a centre of inversion, one thio-phene-2,5-di-carboxyl-ate (tdc2-) ligand and one coordinating di-methyl-formamide (DMF) solvent mol-ecule. Both of the cobalt(II) cations exhibit an octa-hedral coordination environment from the four carboxyl O atoms of the tdc2- anions in a µ 4-κ 1:κ 1:κ 1:κ 1 fashion and two O atoms from DMF. A pair of carboxyl O atoms and one DMF molecule connect the adjacent cobalt(II) cations into an infinite chain, leading to a rod-spacer framework with rhombus-window channels, yet no residual solvent-accessible voids are present because the coordinating DMF molecules are oriented into the potential channels.

2.
Int J Clin Pharm ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36346544

RESUMO

BACKGROUND: Remimazolam and dexmedetomidine are commonly used as sedatives. However, the effects and safety of remimazolam alone or in combination with dexmedetomidine have not been investigated. AIM: We sought to investigate the clinical effects of remimazolam alone or in combination with dexmedetomidine in bronchoscopy, and their influence on cognitive function. METHOD: Ninety eligible patients who underwent bronchoscopy under intravenous anesthesia were randomly divided into three groups: propofol control, remimazolam, and remimazolam plus dexmedetomidine. The primary outcome was the incidence of perioperative hypoxemia. Secondary outcomes included induction and maintenance doses of remimazolam, hemodynamic variables, scores for modified Observer's Assessment of Alertness/Sedation (MOAA/S), coughing, limb movement, incidence of adverse events, patient satisfaction, bronchoscopist satisfaction, incidence of post-operative cognitive dysfunction (POCD), time to loss of consciousness (LoC), and time to awake. RESULTS: The incidence of hypoxemia, hypotension, and bronchoscopist satisfaction score were significantly decreased, and time to LoC and time to awake were markedly longer in the remimazolam and remimazolam plus dexmedetomidine groups than in the propofol control group (p < 0.05). The remimazolam group had significantly decreased induction and maintenance doses of remimazolam and a shorter time to LoC than the remimazolam plus dexmedetomidine group (p < 0.05). Scores for coughing, limb movement, MOAA/S, and post-operative patient satisfaction were comparable among the three groups. POCD was not induced in any of the groups. CONCLUSION: Remimazolam is safe and effective for painless bronchoscopy, with a low incidence of adverse reactions, and exhibits a good synergistic effect with dexmedetomidine. TRIAL REGISTRATION: This trial protocol had been registered on Chinese Clinical Trial Registry (ChiCTR2000041435, date: 2020 12 26.

3.
Nat Commun ; 13(1): 6666, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335107

RESUMO

The idea of spatial confinement has gained widespread interest in myriad applications. Especially, the confined short hydrogen-bond (SHB) network could afford an attractive opportunity to enable proton transfer in a nearly barrierless manner, but its practical implementation has been challenging. Herein, we report a SHB network confined on the surface of ionic covalent organic framework (COF) membranes decorated by densely and uniformly distributed hydrophilic ligands. Combined experimental and theoretical evidences have pointed to the confinement of water molecules allocated to each ligand, achieving the local enrichment of hydronium ions and the concomitant formation of SHBs in water-hydronium domains. These overlapped water-hydronium domains create an interconnected SHB network, which yields an unprecedented ultrahigh proton conductivity of 1389 mS cm-1 at 90 °C, 100% relative humidity.

4.
Sci Total Environ ; : 160290, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36410489

RESUMO

Refractory black carbon (rBC) aerosols emitted from incomplete combustion are important climate forcers. Understanding the chemical characteristics and evolution of rBC-related components is particularly crucial to assess rBC environmental impacts. Here, we explored the chemical components of rBC in Shenzhen, China, using a soot-particle aerosol mass spectrometer (SP-AMS). The observations showed that the rBC coating was mainly composed of secondary aerosols with an average mass contribution of 84.7 %. Among them, secondary organic coating occupied ∼57.7 % of the total coating mass. Exploration of the relationship between secondary organic aerosol (SOA) coating and Ox (=NO2 + O3, an indicator of the extent of photochemical processing) showed that SOA coating was generated mainly through photochemical oxidation during the day. Similarly, sulfate coating, with a small mass fraction of 0.9 %, was also dominated by photochemical oxidation. In contrast, nitrate coating responded positively to ambient relative humidity, especially at night, indicating that it was driven by heterogeneous reactions. In addition, the increased ratio of nitrate on rBC to bulk nitrate at night suggested that black carbon surface could facilitate nocturnal nitrate formation.

5.
Front Genet ; 13: 1000515, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386816

RESUMO

In several tumors, Nicotinamide N-Methyltransferase (NNMT) was identified as a bridge between methylation metabolism and tumorigenesis and was associated with a poor prognosis. This research aims is to study the prognostic value of NNMT in cancer, its relationship with DNA methylation, and the immune microenvironment. On the basis of the Cancer Genome Atlas and the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Cellminer, Gene Expression Profiling Interactive Analysis, Human Protein Atlas and Clinical Proteomic Tumor Analysis Consortium, we used a series of bioinformatics strategies to investigate the potential carcinogenicity of NNMT, including the relationship between NNMT expression and prognosis, tumor mutational burden, microsatellite instability, and sensitivity analysis of anticancer drugs. The GeneMANIA, STRING, and BioGRID databases were examined for protein-protein interactions, and Gene Ontology and the Kyoto Encyclopedia of Genes were used to infer the signal pathway. The results indicated that NNMT was significantly expressed in several tumor tissues compared to the matching non-tumor tissues. Increased NNMT expression was linked to reduced OS, DSS, and DFI. In addition, there was a link between NNMT expression and TMB and MSI in 18 cancer types, and between NNMT expression and DNA methylation in 23 cancer types. Further study of NNMT gene alteration data revealed that deletion was the most prevalent form of NNMT mutation, and that there was a significant negative association between NNMT expression and mismatch repair genes. In addition, there was a strong positive connection between NNMT and immune infiltration in 28 types of tumors, and the immune cells that infiltrated the tumors displayed a characteristic NNMT pattern. According to the enrichment study, cell migration, cell motility, and cell adhesion were highly enriched in biological processes, and NNMT may be associated with the PI3K-Akt signaling pathway. By downregulating gene methylation or impacting the immunological microenvironment widely, NNMT may drive carcinogenesis and cause a poor prognosis. Our research showed that NNMT could be used as a biomarker of tumor immune infiltration and poor prognosis, thus providing a unique strategy for cancer therapy.

6.
J Am Chem Soc ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394830

RESUMO

Several classes of ribosomally synthesized and post-translationally modified peptides (RiPPs) are composed of multiple macrocycles. The enzymes that assemble these macrocycles must surmount the challenge of installing a single specific set of linkages out of dozens of distinct possibilities. One class of RiPPs that includes multiple macrocycles are the graspetides, named after the ATP-grasp enzymes that install ester or amide linkages between pairs of nucleophilic and electrophilic side chains. Here, using heterologous expression and NMR spectroscopy, we characterize the connectivity and structure of amycolimiditide, a 29 aa graspetide with a stem-loop structure. The stem includes four esters and extends over 20 Å. The loop of amycolimiditide is distinguished by the presence of an aspartimide moiety, installed by a dedicated O-methyltransferase enzyme. We further characterize the biosynthesis of amycolimiditide in vitro, showing that the amycolimiditide ATP-grasp enzyme AmdB operates in a strict vectorial manner, installing esters starting at the loop and proceeding down the stem. Surprisingly, the O-methyltransferase AmdM that aspartimidylates amycolimiditide prefers a substrate with all four esters installed, despite the fact that the most distal ester is ∼30 Å away from the site of aspartimidylation. This study provides insights into the structure and diversity of aspartimidylated graspetides and also provides fresh insights into how RiPP biosynthetic enzymes engage their peptide substrates.

7.
Cancer Med ; 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36404592

RESUMO

BACKGROUD: There were limitations existing in programmed cell-death ligand 1 (PD-L1) as predictive biomarkers for breast cancer (BC), hence exploring the correlation between PD-L1 levels and other biomarkers in BC may become a very useful therapeutic clinical tool. METHODS: A total of 301 Chinese patients with different BC subtypes including 47 HR+/HER2+, 185 HR+/HER2-, 38 HR-/HER2+, and 31 triple-negative breast cancer (TNBC) were enrolled in our study. Next-generation sequencing based Yuansu450 gene panel was used for genomic alteration identification and PD-L1 expression was tested using immunohistochemistry. RESULTS: The most prevalent BC-related mutations were TP53 mutations, followed by mutations in PIK3CA, ERBB2, CDK12, and GATA3 in our Chinese cohort. We found that mutations DDR2 and MYCL were only mutated in HR-/HER2+ subtype, whereas H3-3A and NRAS mutations were only occurred in HR-/HER2- subtype. The percentage of patients with PD-L1-positive expression was higher in patients with HR-/HER2- mainly due to the percentage of PD-L1-high level. Mutational frequencies of TP53, MYC, FAT4, PBRM1, PREX2 were observed to have significant differences among patients with different BC subtypes based on PD-L1 levels. Moreover, a positive correlation was observed between TMB and PD-L1 level in HR+/HER2- subtype, and showed that the proportion of patients with high PD-L1 expression was higher than that of patients with low PD-L1 expression in the HR+/HER2- and HR+/HER2+ cohorts with high Ki67 expression. CONCLUSIONS: The genomic alterations based on PD-L1 and other biomarkers of different cohorts may provide more possibilities for the treatment of BC with different subtypes.

8.
Clin Oral Investig ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318336

RESUMO

OBJECTIVES: To investigate the variant of an amelogenesis imperfecta (AI) family and to explore the function of the FAM83H (family with sequence similarity 83 member H) in the enamel formation. MATERIALS AND METHODS: We investigated a five-generation Chinese family diagnosed with AI; clinical data was collected, whole-exome sequencing (WES) was conducted to explore the pathogenic gene and variants and Sanger sequencing was used to verify the variants. The three-dimensional protein structures of wild-type and mutant FAM83H were predicted using alpha fold 2. To study the possible regulatory function of Fam83h on amelogenesis, immunolocalization was performed to observe the expression of Fam83h protein in Sprague-Dawley rat postnatal incisors. The mRNA and protein level of amelogenin, enamelin, kallikrein-related peptidase-4 and ameloblastin were also detected after the Fam83h was knocked down by small interfering RNA (siRNA) in HAT-7 cells. RESULTS: A known nonsense variant (c.973 C > T) in exon 5 of FAM83H gene was found in this family, causing a truncated protein (p.R325X). Immunolocalization of Fam83h in Sprague-Dawley rat postnatal incisors showed that Fam83h protein expression was detected in presecretory and secretory stages. When Fam83h expression was reduced by siRNA, the expression of amelogenin, enamelin, kallikrein-related peptidase-4 decreased. However, the expression of ameloblastin increased. CONCLUSIONS: FAM83H gene variant (c.973 C > T) causes AI. FAM83H regulates the secretion of enamel matrix proteins and affects ameloblast differentiation. CLINICAL RELEVANCE: This study provided that FAM83H variants could influence enamel formation and provided new insights into the pathogenesis of AI.

9.
Biology (Basel) ; 11(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36358270

RESUMO

Tensins are a family of cellular-adhesion constituents that have been extensively studied. They have instrumental roles in the pathogenesis of numerous diseases. The mammalian tensin family comprises four members: tensin1 (TNS1), tensin2, tensin3, and tensin4. Among them, TNS1 has recently received attention from researchers because of its structural properties. TNS1 engages in various biological processes, such as cell adhesion, polarization, migration, invasion, proliferation, apoptosis, and mechano-transduction, by interacting with various partner proteins. Moreover, the abnormal expression of TNS1 in vivo is associated with the development of various diseases, especially tumors. Interestingly, the role of TNS1 in different tumors is still controversial. Here, we systematically summarize three aspects of TNS1: the gene structure, the biological processes underlying its action, and the dual regulatory role of TNS1 in different tumors through different mechanisms, of which we provide the first overview.

10.
EBioMedicine ; 86: 104340, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36356476

RESUMO

BACKGROUND: Early detection of gastric cancer (GC) remains challenging. We aimed to examine urine proteomic signatures and identify protein biomarkers that predict the progression of gastric lesions and risk of GC. METHODS: A case-control study was initially designed, covering subjects with GC and gastric lesions of different stages. Subjects were aged 40-69 years, without prior diagnosis of renal or urological diseases. We enrolled a total of 255 subjects, with 123 in the discovery stage from Linqu, China, a high-risk area for GC and 132 in the validation stage from Linqu and Beijing. A prospective study was further designed for a subset of 60 subjects with gastric lesions, which were followed for 297-857 days. FINDINGS: We identified 43 differentially expressed urine proteins in subjects with GC vs. mild or advanced gastric lesions. Baseline urinary levels of ANXA11, CDC42, NAPA and SLC25A4 were further positively associated with risk of gastric lesion progression. Three of them, except for SLC25A4, also had higher expression in GC than non-GC tissues. Integrating these four proteins showed outstanding performance in predicting the progression of gastric lesions (AUC (95% CI): 0.92 (0.83-1.00)) and risk of GC (AUC (95% CI): 0.81 (0.73-0.89) and 0.84 (0.77-0.92) for GC vs. mild or advanced gastric lesions respectively). INTERPRETATION: This study revealed distinct urine proteomic profiles and a panel of proteins that may predict the progression of gastric lesions and risk of GC. These biomarkers in a non-invasive approach may have translational significance for defining high-risk populations of GC and its early detection. FUNDING: Funders are listed in the Acknowledgement.

11.
Clin Neurol Neurosurg ; 223: 107503, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36368168

RESUMO

BACKGROUND: Spinocerebellar ataxias (SCA) are often caused by expansions of short tandem repeats. Recent methodological advances have made repeat expansion detection with long-read sequencing (LRS) feasible. Our study investigated one family with SCA 36 and further summarized the genetic and clinical characteristics of the total of 161 patients across different ethnic groups reported worldwide. METHODS: We enrolled a pedigree of 4 patients. The proband was a 55-year-old male. And he was screened for dynamic mutations of SCA subtypes by Tri-prime PCR (TP-PCR) and capillary electrophoresis, showing NOP56 as the candidate gene. The cosegregation was conducted by screening the NOP56 gene in his daughter and further confirmed by low-coverage (∼15 ×) LRS on the Oxford Nanopore platform. RESULTS: The SCA36 pedigree included a total of 4 patients. The proband showed the initial manifestation at the age of 45 years old, which was characterized by truncal ataxia. Genetic test results showed the (GGCCTG)n expansion in NOP56 gene (3/>15 and 6/>15 times respectively). To clarify the diagnosis genetically, LRS was performed in his daughter showing a large intronic insertion (chr20: 2633004 INS 7603 bp) containing (GGCCTG)n expansion of 782 units in NOP56 as the causative mutation. CONCLUSIONS: We identified one SCA36 pedigree by combining TP-PCR with LRS. Our study suggested LRS as an effective tool for molecular diagnosis. LRS also worked as a supplementary but necessary diagnostic tool for dynamic mutation-related SCA on the basis of repeat-primed PCR as well as capillary electrophoresis.

12.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(11): 1363-1368, 2022 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-36382453

RESUMO

Objective: To investigate the effectiveness of total elbow arthroplasty (TEA) via olecranon osteotomy approach. Methods: Between January 2011 and December 2021, 22 patients (25 sides) with elbow joint disease were treated with TEA via olecranon osteotomy approach. There were 9 males and 13 females with an average age of 52.0 years (range, 32-80 years). The disease involved unilateral elbow joint in 19 cases, including 12 cases on the left side and 7 cases on the right side, and 3 cases with bilateral elbow joints. There were 3 cases (3 sides) of osteoarthritis, 7 cases (9 sides) of rheumatoid arthritis, 6 cases (7 sides) of traumatic arthritis, 4 cases (4 sides) of distal humeral fracture, and 2 cases (2 sides) of elbow tuberculosis. The operation time, intraoperative blood loss, and postoperative complications were recorded. The Mayo Elbow Performance Score (MEPS) and range of motion (ROM) were used to evaluate the elbow joint function, and imaging was used to review the position of the prosthesis and the healing of the osteotomy. Results: The operation time ranged from 53 to 120 minutes (mean, 90.6 minutes); intraoperative blood loss ranged from 10 to 200 mL (mean, 68.4 mL). All incisions healed by first intention. All patients were followed up 3.9-126.7 months, with a median time of 47.6 months. At last follow-up, the MEPS scores of 22 patients ranged from 72 to 100 (mean, 91.6); the elbow joint function was rated as excellent in 17 sides, good in 7 sides, and fair in 1 side, with an excellent and good rate of 96%. Elbow joint ROM was 98°-140° in flexion (mean, 119.7°), 5°-23° in extension (mean, 13.9°), 70°-90° in anterior rotation (mean, 83.3°), and 63°-90° in posterior rotation (mean, 79.4°). The follow-up time of 17 patients (20 sides) without fracture and joint stiffness before operation was 3.9-126.7 months, with a median time of 53.9 months; at last follow-up, the MEPS score and the elbow joint ROM were significantly better than those before operation ( P<0.05). The follow-up time of 5 patients (5 sides) with fracture and joint stiffness before operation was 12.0-124.2 months, with a median time of 40.1 months. At last follow-up, MEPS scores ranged from 89 to 100 (mean, 91.2), and elbow joint ROM restored. Two cases (2 sides) developed ulnar nerve symptoms after operation, and 1 case (1 side) suffered from periprosthetic fracture and periprosthetic infection after revision, and the elbow prosthesis was removed. The prosthesis survival rate was 96%. During follow-up, no prosthesis loosening occurred. Conclusion: The intraoperative visual field exposure of TEA via the olecranon osteotomy approach is sufficient, which can reduce the incidence of complications such as triceps weakness and ulnar nerve injury, effectively improve the function of the elbow joint, and obtain satisfactory effectiveness.


Assuntos
Artroplastia de Substituição do Cotovelo , Articulação do Cotovelo , Fraturas do Úmero , Olécrano , Osteoartrite , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Articulação do Cotovelo/cirurgia , Olécrano/cirurgia , Cotovelo/lesões , Perda Sanguínea Cirúrgica , Resultado do Tratamento , Amplitude de Movimento Articular , Osteoartrite/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia
13.
Leg Med (Tokyo) ; 60: 102175, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36417774

RESUMO

Alcohol is often found in the blood of the deceased. To cover up the true cause of victim's death, postmortem instillation of alcohol occurs in some criminal cases. Explaining the finding of alcohol is extremely vital in forensic practice. This study aims to evaluate whether ethyl glucuronide (EtG) and ethyl sulfate (EtS) in blood and vitreous humor (VH) can be used to distinguish alcoholic death and postmortem alcohol instillation. Saline or 12.6 g/kg ethanol (antemortem alcohol poisoning group) was introduced into rabbits' stomachs 2 h before sacrificed. Same amount of ethanol was introduced into rabbits' stomachs at 0 h, 0.5 h, 1 h and 2 h after death in four subgroups of postmortem alcohol instillation group, respectively. Cardiac blood and VH were collected at 10 min, 4 h, 10 h and 24 h after death in blank and antemortem alcohol poisoning group, and after instillation of alcohol in postmortem alcohol instillation group. Blood was also collected at 34 h. Ethanol and EtG levels in blood and VH and EtS in VH in antemortem alcohol poisoning group were overlapped with those in postmortem alcohol instillation group. The contents of EtG and EtS in blood in antemortem alcohol poisoning group (mean ≥ 7.833 µg/mL for EtG and ≥ 19.990 µg/mL for EtS) were much higher than those in postmortem alcohol instillation group (mean ≤ 0.118 µg/mL for EtG and ≤ 0.091 µg/mL for EtS), but apparent decomposition was observed in EtG, which might lead to misinterpretation. Blood EtS showed better stability and could be used to distinguish alcoholic death and postmortem alcohol instillation.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36204118

RESUMO

Background: Osteoarthritis (OA) is a multifactorial disease with various risk factors, resulting in the degeneration of articular cartilage and whole joints. However, to date, no effective disease-modifying therapy for OA has been developed. Oxymatrine (OMT) is associated with many pharmacological effects, including anti-inflammatory, antiapoptotic, and antioxidative properties. However, the role of OMT in OA remains unclear. Materials and Methods: An IL-1ß-induced chondrocyte model and anterior cruciate ligament transection (ACLT)-induced murine model of OA were constructed. The effect of OMT on chondrocyte viability was assessed using the CCK-8 assay. The protein level was assessed by Western blot analysis, and the apoptosis rate was assessed by flow cytometry in vitro and TUNEL staining in OA model mice. The effect of OMT on the degradation of articular cartilage in ACLT-induced OA mice was assessed by histological analysis. Results: OMT at 0-2 mg/mL showed no conspicuous cytotoxicity on chondrocytes after 24 hours of incubation. OMT at 0.5, 1, and 2 mg/mL inhibited IL-1ß-triggered apoptosis, upregulated MMP13, MMP9, and Col X, and upregulated Col II in chondrocytes in vitro. OMT represses the NF-κB signaling cascade in IL-1ß-triggered chondrocytes in vitro. In an in vivo study, OMT decreased the apoptosis rate of chondrocytes and exerted a protective effect against the degradation of articular cartilage in ACLT-triggered OA mice. Conclusion: OMT plays a protective role against chondrocyte injury induced by IL-1ß in vitro or ACLT in vivo. OMT may play a role in chondrocytes during OA by inhibiting NF-κB signaling by decreasing the phosphorylation of p65 and IκB. OMT treatment may be a promising chondroprotective approach to delay OA cartilage progression.

15.
Front Genet ; 13: 1008416, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186418

RESUMO

Background: Epithelial-mesenchymal transition (EMT) is a critical process in tumor invasion and metastasis. EMT has been shown to significantly influence the invasion, metastasis, and poor prognosis in lung adenocarcinoma (LUAD). This study aimed to develop a novel EMT-related prognostic model capable of predicting overall survival (OS) in patients with LUAD. Methods: A total of 283 LUAD patients from TCGA RNA-seq dataset were assigned to a training cohort for model building, and 310 LUAD patients from GEO RNA-seq dataset were assigned to a validation cohort. EMT genes were acquired from MsigDB database and then prognosis-related EMT genes were identified by univariate Cox regression. Lasso regression was then performed to determine the genes and the corresponding variables to construct a prognosis risk model from the training cohort. Furthermore, characteristics of the tumor microenvironment (TME), mutation status and chemotherapy responses were analyzed to assess the differences between the two risk groups based on the prognostic model. In addition, RT-qPCR was employed to validate the expression patterns of the 6 genes derived from the risk model. Results: A six-gene EMT signature (PMEPA1, LOXL2, PLOD2, MMP14, SPOCK1 and DCN) was successfully constructed and validated. The signature assigned the LUAD patients into high-risk and low-risk groups. In comparison with the low-risk group, patients in the high-risk group had a significantly lower survival rate. ROC curves and calibration curves for the risk model demonstrated reliable stratification and predictive ability. The risk model was robustly correlated with multiple TME characteristics. Besides, the data showed that patients in the low-risk group had more immune activities, higher stemness scores and cytolytic activity scores and higher TMB. In addition, RT-qPCR results revealed that PMEPA1, LOXL2, PLOD2, MMP14, and SPOCK1 were notably upregulated in LUAD tissues, while DCN was downregulated. Conclusion: Our study successfully developed a novel EMT-related signature to predict prognosis of LUAD patients and guide treatment strategies. The six genes derived from the prediction signature might play a potential role in antitumor immunity and serve as promising therapeutic targets in LUAD.

16.
Front Pharmacol ; 13: 946445, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36278191

RESUMO

Lotus (Nelumbo nucifera) leaves are widely used for both edible and medicinal applications. For its further utilization, we studied the vasodilatory activity of lotus leaf extract for the first time. In this study, we obtained the extracts using different ratios of water and ethanol, which was followed by polarity-dependent extraction. We found that the CH2Cl2 layer exhibited better vasodilatory activity (EC50 = 1.21 ± 0.10 µg/ml). HPLC and ESI-HRMS analysis of the CH2Cl2 layer using the standard product as a control revealed that nuciferine (Emax = 97.95 ± 0.76%, EC50 = 0.36 ± 0.02 µM) was the main component in this layer. Further research revealed that nuciferine exerts a multi-target synergistic effect to promote vasodilation, via the NO signaling pathway, K+ channel, Ca2+ channel, intracellular Ca2+ release, α and ß receptors, etc. Nuciferine exhibits good vasodilatory activity, and it exhibits the potential to be utilized as a lead compound.

17.
Abiotech ; 3(2): 140-145, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36304519

RESUMO

Weeds are a major biotic constraint that can cause dramatic crop production losses. Herbicide technology has been widely used by farmers as the most cost-effective weed control measure, and development of new strategy to improve herbicide tolerance in plants is urgently needed. The CRISPR/Cas9-based genome editing tool has been used in diverse applications related to agricultural technology for crop improvement. Here we identified three polyamine uptake transporter (PUT) genes in rice that are homologous to the Arabidopsis AtRMV1. We successfully demonstrate that CRISPR/Cas9-targeted mutagenesis of OsPUT1/2/3 greatly improves paraquat resistance in rice without obvious yield penalty. Therefore, manipulation of these loci could be valuable for producing transgene-free rice with improved herbicide resistance in future. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-022-00075-4.

18.
BMC Oral Health ; 22(1): 457, 2022 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-36309721

RESUMO

BACKGROUND: The present study aimed to develop a novel protein-repellent and antibacterial polymethyl methacrylate (PMMA) dental resin with 2-methacryloyloxyethyl phosphorylcholine (MPC) and quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM), and to investigate the effects of water-aging for 6 months on the mechanical properties, protein adsorption, and antibacterial activity of the dental resin. METHODS: Four groups were tested: PMMA control; PMMA + 3% MPC; PMMA + 1.5% DMAHDM; and PMMA + 3% MPC + 1.5% DMADDM in acrylic resin powder. Specimens were water-aged for 1 d, 3 months, and 6 months at 37 ℃. Their mechanical properties were then measured using a three-point flexure test. Protein adsorption was measured using a micro bicinchoninic acid (BCA) method. A human saliva microcosm model was used to inoculate bacteria on water-aged specimens and to investigate the live/dead staining, metabolic activity of biofilms, and colony-forming units (CFUs). RESULTS: The flexural strength and elastic modulus showed a significant loss after 6 months of water-ageing for the PMMA control (mean ± SD; n = 10); in contrast, the new protein repellent and antibacterial PMMA resin showed no strength loss. The PMMA-MPC-DMAHDM-containing resin imparted a strong antibacterial effect by greatly reducing biofilm viability and metabolic activity. The biofilm CFU count was reduced by about two orders of magnitude (p < 0.05) compared with that of the PMMA resin control. The protein adsorption was 20% that of a commercial composite (p < 0.05). Furthermore, the PMMA-MPC-DMAHDM-containing resin exhibited a long-term antibacterial performance, with no significant difference between 1 d, 3 months and 6 months (p > 0.05). CONCLUSIONS: The flexural strength and elastic modulus of the PMMA-MPC-DMAHDM-containing resin were superior to those of the PMMA control after 6 months of water-ageing. The novel PMMA resin incorporating MPC and DMAHDM exhibited potent and lasting protein-repellent and antibacterial properties.


Assuntos
Polimetil Metacrilato , Água , Humanos , Antibacterianos/farmacologia , Biofilmes , Metacrilatos/farmacologia , Metilaminas/farmacologia , Polimetil Metacrilato/farmacologia , Proteínas , Água/farmacologia , Fatores de Tempo
19.
Pest Manag Sci ; 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36205305

RESUMO

BACKGROUND: The diamondback moth (DBM) Plutella xylostella has developed resistance to almost all insecticides used to control it. Populations of DBM in temperate regions mainly migrate from annual breeding areas. However, the distribution pattern of insecticide resistance of DBM within the context of long-distance migration remains unclear. RESULTS: In this study, we examined the frequency of 14 resistance mutations for 52 populations of DBM collected in 2010, 2011, 2017 and 2018 across China using a high-throughput KASP genotyping method. Mutations L1041F and T929I conferring pyrethroid resistance, and mutations G4946E and E1338D conferring chlorantraniliprole resistance were near fixation in most populations, whereas resistant alleles of F1020S, M918I, A309V and F1845Y were uncommon or absent in most populations. Resistance allele frequencies were relatively stable among different years, although the frequency of two mutations decreased. Principal component analysis based on resistant allele frequencies separated a southern population as an outlier, whereas the immigrants clustered with other populations, congruent with the migration pattern of northern immigrants coming from the Sichuan area of southwestern China. Most resistant mutations deviated from Hardy-Weinberg equilibrium due to a lower than expected frequency of heterozygotes. The deviation index of heterozygosity for resistant alleles was significantly higher than the index obtained from single nucleotide polymorphisms across the genome. These findings suggest heterogeneous selection pressures on resistant mutations. CONCLUSION: Our results provide a picture of resistant mutation patterns in DBM shaped by insecticide usage and migration of this pest, and highlight the widespread distribution of resistance alleles in DBM. © 2022 Society of Chemical Industry.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36293901

RESUMO

In this study, the concentrations of potentially toxic elements in 283 topsoil samples were determined. Håkanson toxicity response coefficient modified matter element extension model was introduced to evaluate the soil elements contamination, and the results were compared with the pollution index method. The sources and spatial distribution of soil elements were analyzed by the combination of the PMF model and IDW interpolation. The results are as follows, 1: The concentration distribution of potentially toxic elements is different in space. Higher concentrations were found in the vicinity of the mining area and farmland. 2: The weight of all elements has changed significantly. The evaluation result of the matter-element extension model shows that 68.55% of the topsoil in the study area is clean soil, and Hg is the main contamination element. The evaluation result is roughly the same as that of the pollution index method, indicating that the evaluation result of the matter-element extension model with modified is accurate and reasonable. 3: Potentially toxic elements mainly come from the mixed sources of atmospheric sedimentation and agricultural activities (22.59%), the mixed sources of agricultural activities and mining (20.26%), the mixed sources of traffic activities, nature and mining (36.30%), the mixed sources of pesticide use and soil parent material (20.85%).


Assuntos
Mercúrio , Metais Pesados , Praguicidas , Poluentes do Solo , Solo , Metais Pesados/análise , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Monitoramento Ambiental/métodos , Medição de Risco , Mercúrio/análise , Praguicidas/análise , China
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