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1.
CRISPR J ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35506993

RESUMO

DNA repair after Cas9 cutting can result in deletions/insertions, genomic rearrangements, and rare nucleotide substitutions. However, most work has only focused on deletions/insertions resulting from repair after CRISPR-Cas9 action. Here, we comprehensively analyzed the editing outcomes induced by CRISPR-Cas9 treatment in yeast Xanthophyllomyces dendrorhous by Sanger and Illumina sequencing and identified diverse DNA repair patterns, including DNA deletions, interchromosomal translocations, and on-target nucleotide substitutions (point mutations). Some deletions were observed repeatedly, and others, especially large deletions, varied in size. Genome sequencing and structural variation analysis showed that the interchromosomal translocations happened between Cas9 target sites and the endogenous ADH4 promoter. In contrast to previous studies, analysis revealed that the on-target point mutations were not random. Importantly, these point mutations showed strong sequence dependence that is not consistent with previous work in Hela cells, where CRISPR-mediated substitutions were found to lack sequence dependence and conversion preferences. Finally, we found that the non-homologous end joining components Ku70, Ku80, Mre11, or RAD50, and the overlapping roles of non-essential DNA polymerases were necessary for the production of both point mutations and deletions. This work expands our knowledge of CRISPR-Cas9 mediated DNA repair.

2.
Front Microbiol ; 13: 855399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495715

RESUMO

Fusarium oxysporum KB-3 had been reported as a mycorrhizal fungus of Bletilla striata, which can promote the seed germination and vegetative growth. Endohyphal bacteria were demonstrated in the hyphae of the KB-3 by 16S rDNA PCR amplification and SYTO-9 fluorescent nucleic acid staining. A strain Klebsiella aerogenes KE-1 was isolated and identified based on the multilocus sequence analysis. The endohyphal bacterium was successfully removed from the wild strain KB-3 (KB-3-), and GFP-labeled KE-1 was also transferred to the cured strain KB-3- (KB-3+). The production of indole-3-acetic acid (IAA) in the culturing broths of strains of KE-1, KB-3, KB-3-, and KB-3+ was examined by HPLC. Their IAA productions were estimated using Salkowski colorimetric technique. The highest concentrations of IAA were 76.9 (at 48 h after inoculation), 31.4, 9.6, and 19.4 µg/ml (at 60 h after inoculation), respectively. Similarly, the three fungal cultural broths exhibited plant promoting abilities on the tomato root and stem growth. The results indicated that the ability of mycorrhizal Fusarium strain KB-3 to promote plant growth was enhanced because its endohyphal bacterium, Klebsiella aerogenes KE-1, produced a certain amount of IAA.

3.
EMBO Rep ; : e53932, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35403787

RESUMO

Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases.

4.
Acta Biochim Pol ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35452205

RESUMO

In this study, the function and regulation of long non-coding RNA (lncRNA) LINC00342 in lung adenocarcinoma were investigated. From The Cancer Genome Atlas (TCGA) datasets and Gene Expression Omnibus (GEO) datasets, LINC00342 was found to be up-regulated in lung adenocarcinoma. The high expression of LINC00342 was also validated in lung cancer cell lines. LINC00342 induced invasion and epithelial-mesenchymal transition (EMT) process of A549 cells. By analyzing GEO datasets, TPBG was confirmed positively correlated to LINC00342 and highly expressed in lung adenocarcinoma. In addition, TPBG induced invasion and EMT process of A549 cells. Through bioinformatics analysis and luciferase assay, miR-15b was validated as a direct target of both LINC00342 and TPBG. Ectopic miR-15 expression repressed LINC00342 and TPBG. Interestingly, LINC00342 overexpression inhibited miR-15b and induced TPBG, whereas ectopic TPBG unchanged LINC00342 and miR-15b levels. In conclusion, LINC00342 promotes metastasis of lung adenocarcinoma through inducing TPBG targeted by miR-15b.

5.
J Environ Sci (China) ; 114: 98-114, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35459518

RESUMO

The characteristics of wintertime volatile organic compounds (VOCs) in the North China Plain (NCP) region are complicated and remain obscure. VOC measurements were conducted by a proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS) at a rural site in the NCP from November to December 2018. Uncalibrated ions measured by PTR-ToF-MS were quantified and the overall VOC compositions were investigated by combining the measurements of PTR-ToF-MS and gas chromatography-mass spectrometer/flame ionization detector (GC-MS/FID). The measurement showed that although atmospheric VOCs concentrations are often dominated by primary emissions, the secondary formation of oxygenated VOCs (OVOCs) is non-negligible in the wintertime, i.e., OVOCs accounts for 42% ± 7% in the total VOCs (151.3 ± 75.6 ppbV). We demonstrated that PTR-MS measurements for isoprene are substantially overestimated due to the interferences of cycloalkanes. The chemical changes of organic carbon in a pollution accumulation period were investigated, which suggests an essential role of fragmentation reactions for large, chemically reduced compounds during the heavy-polluted stage in wintertime pollution. The changes of emission ratios of VOCs between winter 2011 and winter 2018 in the NCP support the positive effect of "coal to gas" strategies in curbing air pollutants. The high abundances of some key species (e.g. oxygenated aromatics) indicate the strong emissions of coal combustion in wintertime of NCP. The ratio of naphthalene to C8 aromatics was proposed as a potential indicator of the influence of coal combustion on VOCs.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Carvão Mineral , Monitoramento Ambiental , Prótons , Tempo de Reação , Compostos Orgânicos Voláteis/análise
6.
Histopathology ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35486499

RESUMO

INTRODUCTION: The presence of micropapillary (MIP) in early-stage lung adenocarcinoma was associated with a poorer prognosis, especially in patients undergoing sublobectomy. However, data on the sensitivity of frozen section (FS) evaluation of MIP was still limited. We included the concept of filigree pattern on FS to assess its effect on the diagnostic sensitivity and specificity of MIP, and verify its prognostic value in stage T1 lung adenocarcinoma. METHODS: A panel of five pathologists evaluated 125 patients with T1 lung adenocarcinoma from January to February 2014 as a study cohort, and 151 patients from January to February 2020 as a validation cohort. The diagnostic accuracy of filigree and classical micropapillary (cMIP) pattern on FS was investigated. RESULTS: Diagnostic sensitivity of MIP pattern on FS increased from 43.2% to 65.3% and 56.8% to 81.1% in the study cohort and validation cohort, and both with good specificity. Filigree not only increased the sensitivity of identifying MIP when absence of cMIP, but also increased the sensitivity when presence of minor amount of cMIP. The almost perfect agreement among five pathologists was reached on cMIP and substantial agreement was reached on the filigree in the two cohorts. Moreover, the cMIP and filigree were both correlated with poorer recurrence-free survival (pcMIP = 0.003; pfiligree = 0.032) and overall survival (pcMIP = 0.004; pfiligree = 0.005). CONCLUSION: Identification of filigree may improve the diagnostic sensitivity of MIP pattern on FS. FS was feasible for the detection of filigree and cMIP patterns in stage T1 lung adenocarcinomas.

7.
Biomed Pharmacother ; 150: 112959, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35430392

RESUMO

The metabolism, tissue distribution and excretion of taxifolin in rat after oral administration of taxifolin encapsulated zein-caseinate Nanoparticles (TZP) were studied. The isomerization of taxifolin in rat small intestine and colon was found. Besides isomers, 16 metabolites of taxifolin were identified in rat feces, plasma and urine by UPLC-QTOF-MS. In colon, taxifolin underwent the metabolism of hydration, dehydration and ring-fission through the gut microflora. The main metabolites of taxifolin found in plasma and urine were its sulfated, glucuronidated, and/or methylated products. The dynamic variation of taxifolin and its metabolites in tissues and urine were quantified by UPLC-QqQ-MS/MS. Taxifolin and its metabolites could be quickly absorbed and distributed in the tissues, and relatively low concentrations were found in the heart and brain. The feces excretion of taxifolin was determined by HPLC. The total excretion during 24 h was 2.83 ± 0.80% to its given does, and the maximum excretion was found during 8-10 h post administration. Compared with feces, the excretion of taxifolin and its metabolites in urine was much faster, and the total excretion was 1.96 ± 0.23% during 12 h.

8.
Clin Interv Aging ; 17: 211-221, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35256845

RESUMO

Purpose: To investigate the association of sarcopenia index (SI) [(serum creatinine/serum cystatin C) × 100] with mortality, nutritional risk/malnutrition and sarcopenia among hospitalized older adults. Subjects and Methods: A prospective analysis was performed in 758 hospitalized older adults. Anthropometric measures and biochemical parameters were carried out for each patient. Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) 2019 algorithm. Nutritional risk/malnutrition was defined according to the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria. The logistic regression analysis was employed for the analysis of correlation between the SI and other variables. Cox regression analysis was employed to analyze correlation between the SI and mortality. Results: A total of 758 participants agreed to participate in this study (589 men and 169 women; mean age: 85.6±6.1 years). The median of the follow-up period was 212 days. A total of 112 patients died. A high SI (per 1-SD was 22.1) was independently associated with all-cause mortality (HR per 1-SD = 0.61, 95% CI: 0.47-0.79), nutritional risk/malnutrition (OR per 1-SD = 0.38, 95% CI: 0.29-0.49) and sarcopenia (OR per 1-SD = 0.58, 95% CI: 0.45-0.74). High SI was positively correlated with albumin (r = 0.32, P < 0.001), hemoglobin (r = 0.24, P < 0.001), body mass index (BMI) (r = 0.12, P = 0.001), waist circumference (WC) (r = 0.08, P = 0.046), calf circumference (CC) (r = 0.45, P < 0.001), hand grip strength (HGS) (r = 0.52, P < 0.001) and negatively correlated with triglyceride glucose (TyG) (r = -0.11, P = 0.007). Conclusion: The SI based on serum cystatin C and creatinine is associated with long-term mortality, nutritional risk/malnutrition and sarcopenia in hospitalized older Chinese patients.


Assuntos
Creatinina , Cistatina C , Desnutrição , Sarcopenia , Idoso , Idoso de 80 Anos ou mais , Feminino , Força da Mão , Humanos , Masculino , Desnutrição/complicações , Sarcopenia/mortalidade
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 274: 121096, 2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35272124

RESUMO

As a highly toxic reagent, hydrazine (N2H4) is notorious to human beings and the environment. To simply and conveniently detect N2H4 in environmental and biological systems, a ratiometric fluorescent probe MA-N2H4 was developed with excellent sensitivity and selectivity. Probe MA-N2H4 was readily prepared based on a naphthalene as the fluorescent scaffold and an indanedione group as the responsive moiety for N2H4. This probe displayed a red-emitting fluorescence at 670 nm with a large Stokes shift (200 nm). After treatment with N2H4, a significant blue-shifted emission at 440 nm could be observerd, which led to an extremely large emission wavelength shift (230 nm). The fluorescent intensity ratio (I440/I670) of probe MA-N2H4 was rapidly and significantly increased (273-fold) within 18 min. The detection limit for N2H4 was 0.5 µM. In addition, the probe was successfully employed for tracking N2H4 in living cells and zebrafish through a ratiometric manner.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Animais , Hidrazinas , Espectrometria de Fluorescência
10.
J Integr Plant Biol ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35355415

RESUMO

The important antimalarial drug artemisinin is biosynthesized and stored in Artemisia annua glandular trichomes and the artemisinin content correlates with trichome density; however, the factors affecting trichome development are largely unknown. Here, we demonstrate that the A. annua R2R3 MYB transcription factor TrichomeLess Regulator 1 (TLR1) negatively regulates trichome development. In A. annua, TLR1 overexpression lines had 44.7%-64.0% lower trichome density and 11.5%-49.4% lower artemisinin contents and TLR1-RNAi lines had 33%-93.3% higher trichome density and 32.2%-84.0% higher artemisinin contents compared with non-transgenic controls. TLR1 also negatively regulates the expression of anthocyanin biosynthetic pathway genes in A. annua. When heterologously expressed in Arabidopsis thaliana, TLR1 interacts with GLABROUS3a, positive regulator of trichome development, and represses trichome development. Yeast two-hybrid and pull-down assays indicated that TLR1 interacts with the WUSCHEL homeobox (WOX) protein AaWOX1, which interacts with the LEAFY-like transcription factor TLR2. TLR2 overexpression in Arabidopsis and A. annua showed that TLR2 reduces trichome development by reducing gibberellin levels. Furthermore, artemisinin contents were 19%-43% lower in TLR2-overexpressing A. annua plants compared to controls. These data indicate that TLR1 and TLR2 negatively regulate trichome density by lowering gibberellin levels and may enable approaches to enhance artemisinin yields.

11.
Cell Mol Life Sci ; 79(3): 180, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35254515

RESUMO

Abnormal mossy fiber connections in the hippocampus have been implicated in schizophrenia. However, it remains unclear whether this abnormality in the patients is genetically determined and whether it contributes to the onset of schizophrenia. Here, we showed that iPSC-derived hippocampal NPCs from schizophrenia patients with the A/A allele at SNP rs16864067 exhibited abnormal NPC polarity, resulting from the downregulation of SOX11 by this high-risk allele. In the SOX11-deficient mouse brain, abnormal NPC polarity was also observed in the hippocampal dentate gyrus, and this abnormal NPC polarity led to defective hippocampal neurogenesis-specifically, irregular neuroblast distribution and disrupted granule cell morphology. As granule cell synapses, the mossy fiber pathway was disrupted, and this disruption was resistant to activity-induced mossy fiber remodeling in SOX11 mutant mice. Moreover, these mutant mice exhibited diminished PPI and schizophrenia-like behaviors. Activation of hippocampal neurogenesis in the embryonic brain, but not in the adult brain, partially alleviated disrupted mossy fiber connections and improved schizophrenia-related behaviors in mutant mice. We conclude that disrupted mossy fiber connections are genetically determined and strongly correlated with schizophrenia-like behaviors in SOX11-deficient mice. This disruption may reflect the pathological substrate of SOX11-associated schizophrenia.


Assuntos
Fibras Musgosas Hipocampais/metabolismo , Neurogênese , Fatores de Transcrição SOXC/fisiologia , Esquizofrenia/metabolismo , Animais , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Camundongos , Camundongos Transgênicos , Fibras Musgosas Hipocampais/fisiopatologia , Fatores de Transcrição SOXC/genética , Esquizofrenia/fisiopatologia , Sinapses
12.
Neurol Sci ; 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35332438

RESUMO

OBJECTIVES: Glucocerebrosidase (GBA) gene may be a risk factor for dementia with Lewy bodies (DLB). However, due to the small number of existing studies and the small sample size of previous investigations, it is necessary to conduct objective and quantitative analyses of the association between GBA variants and DLB. There is no consensus regarding the relationship between GBA and the clinical characteristics of DLB. Therefore, we conducted multiple systematic reviews and meta-analyses with a particular focus on the age of onset, sex, and cognitive impairment. METHODS: PubMed, Cochrane, and EMBASE databases were searched to retrieve related studies. The odds ratios and 95% confidence interval were calculated to determine the association between GBA and DLB and between GBA and the clinical characteristics of DLB. RESULTS: Our meta-analysis confirmed that the GBA variant rate was significantly higher in the DLB group than in the control group, as were the variant rates of L444P, N370S, and E326K, whereas the variant rate of T369M showed no significant difference between the groups. Furthermore, the relevant literature was summarised again for meta-analyses. The GBA variant group had a younger age of onset and lower Montreal Cognitive Assessment score than the GBA non-variant group in DLB patients. GBA variants do not differ between sexes in DLB patients. CONCLUSIONS: GBA variants increased the risk of DLB, especially N370S, E326K, and L444P which are strongly associated with DLB, but T369M was not. Patients harbouring GBA variants have an earlier age of onset, more severe cognitive impairment, and rapid symptom progression; however, sex is irrelevant in DLB.

13.
Sci Adv ; 8(10): eabm2546, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35275718

RESUMO

Human cytomegalovirus (HCMV) encodes multiple surface glycoprotein complexes to infect a variety of cell types. The HCMV Pentamer, composed of gH, gL, UL128, UL130, and UL131A, enhances entry into epithelial, endothelial, and myeloid cells by interacting with the cell surface receptor neuropilin 2 (NRP2). Despite the critical nature of this interaction, the molecular determinants that govern NRP2 recognition remain unclear. Here, we describe the cryo-EM structure of NRP2 bound to Pentamer. The high-affinity interaction between these proteins is calcium dependent and differs from the canonical carboxyl-terminal arginine (CendR) binding that NRP2 typically uses. We also determine the structures of four neutralizing human antibodies bound to the HCMV Pentamer to define susceptible epitopes. Two of these antibodies compete with NRP2 binding, but the two most potent antibodies recognize a previously unidentified epitope that does not overlap the NRP2-binding site. Collectively, these findings provide a structural basis for HCMV tropism and antibody-mediated neutralization.

15.
Environ Sci Technol ; 56(4): 2204-2212, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35104400

RESUMO

Nitrous acid (HONO) is an important component of the global nitrogen cycle and can regulate the atmospheric oxidative capacity. Soil is an important source of HONO. [HONO]*, the equilibrium gas-phase concentration over the aqueous solution of nitrous acid in the soil, has been suggested as a key parameter for quantifying soil fluxes of HONO. However, [HONO]* has not yet been well-validated and quantified. Here, we present a method to retrieve [HONO]* by conducting controlled dynamic chamber experiments with soil samples applied with different HONO concentrations at the chamber inlet. We show a bi-directional soil-atmosphere exchange of HONO and confirm the existence of [HONO]* over soil: when [HONO]* is higher than the atmospheric HONO concentration, HONO will be released from soil; otherwise, HONO will be deposited. We demonstrate that [HONO]* is a soil characteristic, which is independent of HONO concentrations in the chamber but varies with different soil water contents. We illustrate the robustness of using [HONO]* for quantifying soil fluxes of HONO, whereas the laboratory-determined chamber HONO fluxes can largely deviate from those in the real world for the same soil sample. This work advances the understanding of the soil-atmosphere exchange of HONO and the evaluation of its impact on the atmospheric oxidizing capacity.


Assuntos
Ácido Nitroso , Solo , Atmosfera , Ciclo do Nitrogênio , Microbiologia do Solo , Água
16.
Cells ; 11(3)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35159125

RESUMO

Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is an economically important disease in most citrus production regions worldwide. Xcc secretes a transcriptional activator like effector (TALE) PthA4 to bind to the effector binding elements (EBEs) in the promoter region of canker susceptibility gene LOB1 to activate its expression, which in turn causes canker symptoms. Editing the EBE region with Cas9/gRNA has been used to generate canker resistant citrus plants. However, most of the EBE-edited lines generated contain indels of 1-2 bp, which has higher possibility to be overcome by PthA4 adaptation. The adaptation capacity of TALEs inversely correlates with the number of mismatches with the EBE. LbCas12a/crRNA is known to generate longer deletion than Cas9. In this study, we used a temperature-tolerant and more efficient LbCas12a variant (ttLbCas12a), harboring the single substitution D156R, to modify the EBE region of LOB1. We first constructed GFP-p1380N-ttLbCas12a:LOBP, which was shown to be functional via Xcc-facilitated agroinfiltration in Pummelo (Citrus maxima) leaves. Subsequently, we stably expressed ttLbCas12a:LOBP in Pummelo. Eight transgenic lines were generated, with seven lines showing 100% mutations of the EBE, among which one line is homozygous. The EBE-edited lines had the ttLbCas12a-mediated deletions of up to 10 bp. Importantly, the seven lines were canker resistant and no off-targets were detected. In summary, ttLbCas12a can be used to efficiently generate biallelic/homozygous citrus mutant lines with short deletions, thus providing a useful tool for the functional study and breeding of citrus.


Assuntos
Citrus , Xanthomonas , Citrus/genética , Doenças das Plantas/genética , Regiões Promotoras Genéticas , Xanthomonas/genética
17.
Artigo em Inglês | MEDLINE | ID: mdl-35206638

RESUMO

This paper aims to examine the influence of Economic Policy Uncertainty (EPU) on environmental performance, as well as the moderating effect of social development and the political regimes in EPU's influence on environmental performance. To investigate such essential issues, we conducted Generalized Method of Moments (GMM) estimations by utilizing cross-country data covering 137 countries during the period of 2001-2018, according to the Stochastic Impacts by Regression on Population, Affluence and Technology (STIRPAT) model. Our empirical estimations support that EPU negatively affects environmental performance; this idea was still supported when we conducted an empirical analysis by changing the measurements, employing alternative estimations and constructing new samples. Furthermore, not only would the absolute level of EPU bring worse environmental performance, but so would an increase in EPU. Moreover, higher economic performance, globalization and a high quality of governance can help countries to alleviate the adverse environmental effect of EPU. Additionally, EPU's negative effect on environmental performance is stronger in right-wing countries, autocracies and non-OECD countries, compared to their counterparts. Our study provides substantial policy implications for governments participating in the international treaties of environmental protection, to mitigate environmental degradation.


Assuntos
Desenvolvimento Econômico , Mudança Social , Dióxido de Carbono/análise , Internacionalidade , Incerteza
18.
bioRxiv ; 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35132410

RESUMO

One major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce antibody resistance. We engineered two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv) 2 design (14-H-06) but not the CrossMAb design (14-crs-06) increases antigen-binding and virus-neutralizing activities and spectrum against multiple SARS-CoV-2 variants including the Omicron, than the cocktail. X-ray crystallography and computational simulations reveal distinct neutralizing mechanisms for individual cocktail antibodies and suggest higher inter-spike crosslinking potentials by 14-H-06 than 14-crs-06. In mouse models of infections by SARS-CoV-2 and the Beta, Gamma, and Delta variants, 14-H-06 exhibits higher or equivalent therapeutic efficacy than the cocktail. Rationally engineered bsAbs represent a cost-effective alternative to antibody cocktails and a promising strategy to improve potency and breadth.

19.
Sleep Breath ; 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35132533

RESUMO

STUDY OBJECTIVES: This study aimed to develop a deep learning-based model to detect obstructive sleep apnea (OSA) using craniofacial photographs. METHODS: Participants referred for polysomnography (PSG) were recruited consecutively and randomly divided into the training, validation, and test groups for model development and evaluation. Craniofacial photographs were taken from five different angles (front, right 90° profile, left 90° profile, right 45° profile, and left 45° profile) and inputted to the convolutional neural networks. The neural networks extracted features from photographs and outputted the probabilities of the presence of the disease. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated using PSG diagnosis as the reference standard. These analyses were repeated using two apnea-hypopnea index thresholds (≥ 5 and ≥ 15events/h). RESULTS: A total of 393 participants were enrolled. Using the operating point with maximum sum of sensitivity and specificity, the model of the photographs exhibited an AUC of 0.916 (95% confidence interval [CI], 0.847-0.960) with a sensitivity of 0.95 and a specificity of 0.80 at an AHI threshold of 5 events/h; an AUC of 0.812 (95% CI, 0.729-0.878) with a sensitivity of 0.91 and a specificity of 0.73 at an AHI threshold of 15 events/h. CONCLUSIONS: The results suggest that combining craniofacial photographs and deep learning techniques can help detect OSA automatically. The model may have potential utility as a tool to assess OSA probability in clinics or screen for OSA in the community.

20.
Small ; 18(12): e2105906, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35098651

RESUMO

Intrinsic hydrogen evolution reaction (HER) activity and the mechanism of antiperovskite Ni3 In1-x Cux N bulk cubic particles and multi-crystalline nanoplates are thoroughly investigated. Stoichiometric Ni3 In0.6 Cu0.4 N reaches the best HER performance, with an overpotential of 102 mV in its multi-crystalline nanoplates obtained from the LDH-derived method, and 143 mV in its bulk cubic particles from the citric method. DFT calculation reveals that Ni-In or Ni-Cu paired on the (100) plane serve as primary active sites. The Ni-Cu pair exhibits stronger OH* and H* affinity that correspondingly reduce OH* and H* adsorption free energy. Introducing specific amounts of the Ni-Cu pair, that is In:Cu = 0.6:0.4 in Ni3 In0.6 Cu0.4 N, can optimize OH* and H* adsorption free energy to facilitate water dissociation in the HER process, while avoiding OH* adsorption getting too strong to block active sites. Besides, Ni3 In0.6 Cu0.4 N turns the water adsorption step spontaneous, which may be attributed to the shifted d-band center and polarizing effect from surface In-Cu charge distribution. This work expands the scope for material design in an antiperovskite system by tailoring the chemical components and morphology for optimal reaction free energy and performance.

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