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OBJECTIVE: To investigate the effect of flow cytometric minimal residual disease (MRD) detection at different time points during AML chemotherapy on prognosis. METHODS: 130 adult primary AML patients diagnosed and standardized with chemotherapy from March 2018 to March 2022 were retrospectively analyzed, MRD was detected by flow cytometry, Kaplan-Meier curves was used for survival analysis and log-rank test was used for variance analysis, and univariate and multifactor influencing patient survival with COX proportional risk regression model analysis. Cumulative incidence rate (CIR) analysis with competing risk model and variance analysis using Fine-Gray. RESULTS: There were 81 CR1, 26 CR2, 14 PR, and 9 NR patients in 130 patients. OS of the CR1 group was higher than that in the CR2, PR,and NR groups. OS of the CR2 group was higher than that in the PR group, but there was no statistically difference compared to the NR group. There was no statistically difference in OS between the PR and NR groups. 107 patients in CR1 and CR2 were grouped according to MRD detected by flow cytometry, and after the first induction chemotherapy, for patients in the MRD- and MRD+ groups, the 4-year expected RFS rates were 65.3% and 27.9% respectively, the 4-year expected OS rates were 58.7% and 41.4% respectively, and the 4-year expected CIR were 34.7% and 69.7% respectively, with statistically significant differences between 2 groups (χ2=6.639, P =0.010; χ2=6.131, P =0.013 and χ2=6.637ï¼ P =0.010). After the second chemotherapy, for patients in the MRD- and MRD+ groups, the 4-year expected RFS rates were 50.8% and 37.9% respectively, the 4-year expected OS rates were 49.2% and 44.5% respectively, and the 4-year expected CIR were 49.2% and 59.5% respectively, with no statistically significant differences between 2 groups (χ2=1.475, P =0.225; χ2=2.432, P =0.119 and χ2=1.416ï¼ P =0.234). During consolidation therapy, for patients in the MRD - and MRD+ groups, the 4-year expected RFS rates were 51.9% and 29.6% respectively, the 4-year expected OS rates were 67.5% and 24.6% respectively, and the 4-year expected CIR were 48.1% and 70.4% respectively, with statistically significant differences between 2 groups (χ2=20.982, P < 0.001; χ2=17.794, P < 0.001 and χ2=19.879ï¼ P < 0.001). For patients with MRD- at all three time points and positive at either time point, the 4-year expected RFS rates were 69.9% and 33.3% respectively, the 4-year expected OS rates were 59.1% and 44.7% respectively, and the 4-year expected CIR were 30.1% and 65.1% respectively, with statistically significant differences between 2 groups (χ2=7.367, P =0.007; χ2=6.042, P =0.014 and χ2=7.662ï¼ P =0.006). Univariate analysis showed that karyotype at high risk of chromosome was an unfavorable factor affecting patients' RFS and OS, while 2 cycles of induction chemotherapy achieved CR, MRD- after the first induction chemotherapy and MRD- after the second induction chemotherapy was a protective factor affecting patients' RFS and OS. MRD- during consolidation therapy and MRD- at all three time points were all protective factors affecting patients' RFS, OS and CIR. Multivariate analysis showed that induction chemotherapy for 2 cycles achieved CR was a protective factor affecting patients' RFS and CIR, and MRD- during consolidation therapy was a protective factor affecting patients' RFS, OS and CIR. CONCLUSION: Early achievement of CR and MRD- in adult AML patients, especially MRD- during consolidation therapy, is a marker of good prognosis, and flow cytometry is the most commonly used method for MRD detection in AML patients.
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Citometría de Flujo , Leucemia Mieloide Aguda , Neoplasia Residual , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Femenino , Masculino , Modelos de Riesgos ProporcionalesRESUMEN
Cis-13, 16-docosadienoic acid (DDA) is an omega-6 polyunsaturated fatty acid with great potential for application in medicine and health. Using microbial cell factories for DDA production is considered a viable alternative to extracting DDA from plant seeds. In this study, using Yarrowia lipolytica Po1f (Δku70) as a chassis, firstly, the adaptation of three elongases in Po1f (Δku70) were explored. Secondly, the DDA biosynthetic pathway was redesigned, resulting in a DDA content of 0.046 % of total fatty acids (TFAs). Thirdly, through the "push-pull" strategy, the DDA content increased to 0.078 % of TFAs. By enhancing the supply of acetyl-CoA, the DDA production in the engineered strain YL-7 reached 0.391 % of the TFAs (3.19 mg/L). Through optimizing the fermentation conditions, the DDA titer of YL-7 reached 29.34 mg/L. This research achieves the sustainable biological production of DDA in Y. lipolytica.
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Ácidos Grasos Insaturados , Yarrowia , Yarrowia/metabolismo , Yarrowia/genética , Ácidos Grasos Insaturados/metabolismo , Ácidos Grasos Insaturados/biosíntesis , Ingeniería Metabólica/métodos , FermentaciónRESUMEN
A formal [3 + 2] annulation of cyclohexadienone-tethered ynals is enabled by an N-heterocyclic carbene (NHC) catalyst, affording a tricyclo[6.2.1.04,11]undecane framework. This study represents the first demonstration of using CâC double bonds as the reaction partner in the NHC-catalyzed annulation of ynals. This strategy is characterized by mild reaction conditions and 100% atom economy as well as high catalytic performance and efficiency.
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The corn planthopper, Peregrinus maidis, is an economically important pest of corn and sorghum. Here we report the initial steps towards developing a CRISPR-based control method, precision guided sterile insect technique (pgSIT), for this hemipteran pest. Specifically, we evaluated the potential of transformer-2 (tra-2) as a target for sterilizing insects. First, we identified tra-2 transcripts within our P. maidis transcriptome database and performed RNA interference (RNAi) to confirm functional conservation. RNAi-mediated knockdown of Pmtra-2 in nymphs transformed females into pseudomales with deformed ovipositors resembling male claspers. While males showed no overt difference in appearance, they were indeed sterile. Importantly, the results were similar to those observed in another planthopper, Nilaparvata lugens. We also used CRISPR/Cas9 genome editing to assess the impact of tra-2 knockout in injectees. CRISPR-mediated knockout of Pmtra-2 had lethal effects on embryos, and hence not many injectees reached adulthood. However, mosaic knockout of Pmtra-2 did impact female and male fertility, which supports the use of tra-2 as a target for pgSIT in this hemipteran species.
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Hemípteros , Femenino , Masculino , Animales , Interferencia de ARN , Hemípteros/genética , Edición Génica , NinfaRESUMEN
The co-evolution between symbionts and their insect hosts has led to intricate functional interdependencies. Advances in DNA-sequencing technologies have not only reduced the cost of sequencing but, with the advent of highly accurate long-read methods, have also enabled facile genome assembly even using mixed genomic input, thereby allowing us to more easily assess the contribution of symbionts to their insect hosts. In this study, genomic data recently generated from Peregrinus maidis was used to assemble the genome of a bacterial symbiont, Pm Arsenophonus sp. This ~4.9-Mb assembly is one of the largest Arsenophonus genomes reported to date. The Benchmarking Universal Single-Copy Orthologs (BUSCO) result indicates that this Pm Arsenophonus assembly has a high degree of completeness, with 96% of the single-copy Enterobacterales orthologs found. The identity of the Pm Arsenophonus sp. was further confirmed by phylogenetic analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicates a major contribution by Pm Arsenophonus sp. to the biosynthesis of B vitamins and essential amino acids in P. maidis, where threonine and lysine production is carried out solely by Pm Arsenophonus sp. This study not only provides deeper insights into the evolutionary relationships between symbionts and their insect hosts, but also adds to our understanding of insect biology, potentially guiding the development of novel pest control methods.
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Known for its species abundance and evolutionary status complexity, family Roseobacteraceae is an important subject of many studies on the discovery, identification, taxonomic status, and ecological properties of marine bacteria. This study compared and analyzed the phylogenetic, genomic, biochemical, and chemo taxonomical properties of seven species from three genera (Psychromarinibacter, Lutimaribacter, and Maritimibacter) of the family Roseobacteraceae. Moreover, a novel strain, named C21-152T was isolated from solar saltern sediment in Weihai, China. The values of 16S rRNA gene sequence similarity, the average nucleotide identity (ANI), the average amino acid identity (AAI), and the digital DNA-DNA hybridization (dDDH) between genomes of the novel strain and Psychromarinibacter halotolerans MCCC 1K03203T were 97.19, 78.49, 73.45, and 21.90%, respectively. Genome sequencing of strain C21-152T revealed a complete Sox enzyme system related to thiosulfate oxidization as well as a complete pathway for the final conversion of hydroxyproline to α-ketoglutarate. In addition, strain C21-152T was resistant to many antibiotics and had the ability to survive below 13% salinity. This strain had versatile survival strategies in saline environments including salt-in, compatible solute production and compatible solute transport. Some of its physiological features enriched and complemented the knowledge of the characteristics of the genus Psychromarinibacter. Optimum growth of strain C21-152T occurred at 37 â, with 5-6% (w/v) NaCl and at pH 7.5. According to the results of the phenotypic, chemotaxonomic characterization, phylogenetic properties and genome analysis, strain C21-152T should represent a novel specie of the genus Psychromarinibacter, for which the name Psychromarinibacter sediminicola sp. nov. is proposed. The type strain is C21-152T (= MCCC 1H00808T = KCTC 92746T = SDUM1063002T).
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ADN , Rhodobacteraceae , Mapeo Cromosómico , Filogenia , ARN Ribosómico 16S/genética , Rhodobacteraceae/clasificaciónRESUMEN
In nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse natural substances. However, mimicking this natural process with artificial organic catalysts remains a daunting challenge in synthetic chemistry. We report a small molecule-catalyzed asymmetric rearrangement of cyclopropylcarbinyl cations, leading to a series of chiral homoallylic sulfide products with good to excellent yields and enantioselectivities (up to 99% enantiomeric excess). In the presence of a chiral SPINOL-derived N-triflyl phosphoramide catalyst, the dehydration of prochiral cyclopropylcarbinols occurs rapidly to generate symmetrical cyclopropylcarbinyl cations, which are subsequently trapped by thione-containing nucleophiles. A subgram-scale experiment and multiple downstream transformations of the sulfide products are further pursued to demonstrate the synthetic utility. Notably, a few heteroaromatic sulfone derivatives could serve as "covalent warhead" in the enzymatic inhibition of severe acute respiratory syndrome coronavirus 2 main protease.
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The corn planthopper, Peregrinus maidis, is an economically important pest of maize and sorghum. Its feeding behaviour and the viruses it transmits can significantly reduce crop yield. The control of P. maidis and its associated viruses relies heavily on insecticides. However, control has proven difficult due to limited direct exposure of P. maidis to insecticides and rapid development of resistance. As such, alternative control methods are needed. In the absence of a genome assembly for this species, we first developed transcriptomic resources. Then, with the goal of finding targets for RNAi-based control, we identified members of the ATP-binding cassette transporter family and targeted specific members via RNAi. PmABCB_160306_3, PmABCE_118332_5 and PmABCF_24241_1, whose orthologs in other insects have proven important in development, were selected for knockdown. We found that RNAi-mediated silencing of PmABCB_160306_3 impeded ovary development; disruption of PmABCE_118332_5 resulted in localized melanization; and knockdown of PmABCE_118332_5 or PmABCF_24241_1 each led to high mortality within five days. Each phenotype is similar to that found when targeting the orthologous gene in other species and it demonstrates their potential for use in RNAi-based P. maidis control. The transcriptomic data and RNAi results presented here will no doubt assist with the development of new control methods for this pest.
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Hemípteros , Insecticidas , Femenino , Animales , Zea mays/genética , Transportadoras de Casetes de Unión a ATP/genética , Hemípteros/genética , Perfilación de la Expresión GénicaRESUMEN
Reported here is a highly enantioselective homoenolate Michael addition/esterification sequence of cyclohexadienone-tethered enals via N-heterocyclic carbene (NHC) catalysis, affording the enantiopure cis-hydrobenzofurans, cis-hydroindoles, and cis-hydroindenes. The NHC catalyst bearing a nitro group greatly enhances the stereocontrol, and a bulky N-aryl substituent of the triazolium salt in the catalyst is helpful for inhibiting the further aldol condensation after homoenolate Michael addition. The utility of this protocol is highlighted by a gram-scale experiment and versatile downstream transformations.
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BACKGROUND: Adaptations by arthropod pests to host plant defenses of crops determine their impacts on agricultural production. The larval host range of western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is restricted to maize and a few grasses. Resistance of D. v. virgifera to crop rotation practices and multiple insecticides contributes to its status as the most damaging pest of cultivated maize in North America and Europe. The extent to which adaptations by this pest contributes to host plant specialization remains unknown. RESULTS: A 2.42 Gb draft D. v. virgifera genome, Dvir_v2.0, was assembled from short shotgun reads and scaffolded using long-insert mate-pair, transcriptome and linked read data. K-mer analysis predicted a repeat content of ≥ 61.5%. Ortholog assignments for Dvir_2.0 RefSeq models predict a greater number of species-specific gene duplications, including expansions in ATP binding cassette transporter and chemosensory gene families, than in other Coleoptera. A majority of annotated D. v. virgifera cytochrome P450s belong to CYP4, 6, and 9 clades. A total of 5,404 transcripts were differentially-expressed between D. v. virgifera larvae fed maize roots compared to alternative host (Miscanthus), a marginal host (Panicum virgatum), a poor host (Sorghum bicolor) and starvation treatments; Among differentially-expressed transcripts, 1,908 were shared across treatments and the least number were between Miscanthus compared to maize. Differentially-expressed transcripts were enriched for putative spliceosome, proteosome, and intracellular transport functions. General stress pathway functions were unique and enriched among up-regulated transcripts in marginal host, poor host, and starvation responses compared to responses on primary (maize) and alternate hosts. CONCLUSIONS: Manual annotation of D. v. virgifera Dvir_2.0 RefSeq models predicted expansion of paralogs with gene families putatively involved in insecticide resistance and chemosensory perception. Our study also suggests that adaptations of D. v. virgifera larvae to feeding on an alternate host plant invoke fewer transcriptional changes compared to marginal or poor hosts. The shared up-regulation of stress response pathways between marginal host and poor host, and starvation treatments may reflect nutrient deprivation. This study provides insight into transcriptomic responses of larval feeding on different host plants and resources for genomic research on this economically significant pest of maize.
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Escarabajos , Insecticidas , Animales , Zea mays/fisiología , Escarabajos/genética , Larva/metabolismo , Poaceae/genética , Insecticidas/metabolismo , Control Biológico de Vectores , Plantas Modificadas Genéticamente/genética , EndotoxinasRESUMEN
The present study aimed to evaluate the effects of hypercholesterolemia on cardioprotection of ischemic preconditioning and α7 nicotinic acetylcholine receptor (α7nAChR) agonist postconditioning and explore the potential mechanisms that hypercholesterolemia affected their cardioprotection. Hypercholesterolemic and normal rats were divided into the four groups that received the following treatments: i) Hypercholesterolemic control and normal control groups; ii) hypercholesterolemic ischemia/reperfusion (HI) and normal ischemia/reperfusion (NI) groups; iii) hypercholesterolemic ischemic preconditioning (HIPC) and normal ischemic preconditioning (NIPC) groups; and iv) hypercholesterolemic PNU282987 postconditioning (HPNU) and normal PNU282987 postconditioning (NPNU) groups. Serum lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels after ischemia/reperfusion were assayed. Furthermore, infarct size and expression levels of Akt, phosphorylated (p)-Akt and endothelial nitric oxide synthase (eNOS) in ischemic myocardium were assessed. Compared with the NI group, serum LDH, CK-MB, cTnI, TNF-α and IL-6 levels and infarct size were significantly decreased, and myocardial p-Akt/Akt and eNOS/GAPDH ratios were significantly increased in the NIPC and NPNU groups. Compared with the HI group, serum CK-MB, cTnI, TNF-α and IL-6 levels and infarct size were significantly decreased in the HIPC group; however, myocardial p-Akt/Akt and eNOS/GAPDH ratios did not significantly change in the HIPC group. Furthermore, there were no significant difference between the HI and HPNU groups in serum LDH, CK-MB, cTnI, TNF-α and IL-6 levels, infarct size, myocardial p-Akt/Akt and eNOS/GAPDH ratios. In conclusion, hypercholesterolemia could aggravate myocardial ischemia/reperfusion injury, attenuate cardioprotection of ischemic preconditioning and eliminate cardioprotection from α7nAChR agonist postconditioning by enhancing inflammation and inhibiting PI3K/Akt/eNOS pathway.
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BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) is an infective microorganism of worldwide concern because of its varied manifestations and life-threatening potential. Genetic analyses have revealed that subspecies of K. pneumoniae exhibit higher virulence and mortality. However, infections with Klebsiella subspecies are often misdiagnosed and underestimated in the clinic because of difficulties in distinguishing K. pneumoniae from its subspecies using routine tests. This case study reports the rapid and fatal effects of K. pneumoniae subspecies. CASE SUMMARY: A 52-year-old male patient was febrile and admitted to hospital. Examinations excluded viral and fungal causes along with mycoplasma/chlamydia and parasitic infections. Bacterial cultures revealed blood-borne K. pneumoniae sensitive to carbapenem antibiotics, although corresponding treatment failed to improve the patient's symptoms. His condition worsened and death occurred within 72 h of symptom onset from sepsis shock. Application of the PMseq-DNA Pro high throughput gene detection assay was implemented with results obtained after death showing a mixed infection of K. pneumoniae and Klebsiella variicola (K. variicola). Clinical evidence suggested that K. variicola rather than K. pneumoniae contributed to the patient's poor prognosis. CONCLUSION: This is the first case report to show patient death from Klebsiella subspecies infection within a short period of time. This case provides a timely reminder of the clinical hazards posed by Klebsiella subspecies and highlights the limitations of classical laboratory methods in guiding anti-infective therapies for complex cases. Moreover, this report serves as reference for physicians diagnosing similar diseases and provides a recommendation to employ early genetic detection to aid patient diagnosis and management.
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Purpose: It is well known that inflammation plays a key role in complex pathological progressions of alcohol-associated liver disease (ALD). To date, effective therapy for ALD is lacking. P2Y2 receptor (P2Y2R), a G protein-coupled P2Y purinergic receptor, represents a novel pharmacological target in many inflammations. Methods: The alcohol-associated liver injury and inflammation mouse model was established. The effect of P2Y2R on alcohol-induced liver injury and inflammation was evaluated using quantitative real-time PCR, Western blot and immunohistochemical assay. An alcohol-stimulated (100 mmol/L, for 24 h) AML-12 cell model was established. Different agonists, antagonists and P2Y2R siRNA were used to explore the possible mechanisms of P2Y2R. Results: In vivo, results showed that the hepatoprotective effect of P2Y2R blockade by significantly suppressed liver structural abnormalities and lipid infiltration, and decreased levels of ALT/AST and TNF-α/IL-1ß in the high dosage group of suramin (20 mg/kg) compared to control diet (CD)-fed mice. At the same time, we found that alcohol feeding promoted the phosphorylation of EGFR and ERK1/2, both of which were effectively inhibited by suramin (20 mg/kg). In vitro, suramin or P2Y2R silencing effectively inhibited the phosphorylation of EGFR and ERK1/2, similar to the down-regulated effects of their corresponding inhibitors (EGFR inhibitor AG1478 and ERK1/2 inhibitor U0126) accompanied by reduced levels of TNF-α and IL-1ß compared to alcohol-induced AML-12 cell. In addition, we found that silencing P2Y2R attenuated the apoptosis of hepatocyte. Conclusion: Our findings suggest that P2Y2R regulates alcoholic liver inflammation by targeting the EGFR-ERK1/2 signaling pathway and plays an important role in hepatocyte apoptosis, which may provide new ideas for the development of methods to treat ALD.
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Leucemia Mieloide Aguda , Sistema de Señalización de MAP Quinasas , Animales , Receptores ErbB , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Leucemia Mieloide Aguda/metabolismo , Hígado/metabolismo , Ratones , Receptores Purinérgicos P2Y2/metabolismo , Transducción de Señal , Suramina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae), is a major global pest of cereal grains. Infestations are difficult to control as larvae feed inside grain kernels, and many populations are resistant to both contact insecticides and fumigants. We sequenced the genome of R. dominica to identify genes responsible for important biological functions and develop more targeted and efficacious management strategies. The genome was assembled from long read sequencing and long-range scaffolding technologies. The genome assembly is 479.1 Mb, close to the predicted genome size of 480.4 Mb by flow cytometry. This assembly is among the most contiguous beetle assemblies published to date, with 139 scaffolds, an N50 of 53.6 Mb, and L50 of 4, indicating chromosome-scale scaffolds. Predicted genes from biologically relevant groups were manually annotated using transcriptome data from adults and different larval tissues to guide annotation. The expansion of carbohydrase and serine peptidase genes suggest that they combine to enable efficient digestion of cereal proteins. A reduction in the copy number of several detoxification gene families relative to other coleopterans may reflect the low selective pressure on these genes in an insect that spends most of its life feeding internally. Chemoreceptor genes contain elevated numbers of pseudogenes for odorant receptors that also may be related to the recent ontogenetic shift of R. dominica to a diet consisting primarily of stored grains. Analysis of repetitive sequences will further define the evolution of bostrichid beetles compared to other species. The data overall contribute significantly to coleopteran genetic research.
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Escarabajos , Insecticidas , Aclimatación , Animales , Escarabajos/genética , Dominica , Larva/genéticaRESUMEN
Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγhi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγhi and SIRPγlo/- tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγhi cells serve as CSLCs and tumor immune checkpoint-initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/metabolismo , Antígeno CD47/genética , Antígeno CD47/metabolismo , Línea Celular Tumoral , Vía de Señalización Hippo , Humanos , Neoplasias Pulmonares/genética , Transducción de SeñalRESUMEN
Source-apportioned particle concentrations are necessary to properly evaluate the health impacts of air pollution. In this study, a measurement station was established at an urban roadside in northern Taiwan to the investigate lung deposited surface area (LDSA) concentration, a relevant metric for the adverse health effects of aerosol exposure, along with PM1 and equivalent black carbon (eBC) concentrations, particle number concentration (PNC), and particle size distribution (PSD). Through positive matrix factorization and multi-linear regression analysis, we attributed 57% of LDSA to traffic emissions over the entire study. During rush hour, the motorcycle fraction increased to 0.83 and LDSA (77.6 ± 9.9 µm2/cm3) and PNC (14,000 ± 2400 particles/cm3) values peaked, while 74% of LDSA was attributed to traffic. The LDSA ratio, defined as the ratio of measured LDSA to that estimated from the particle size distribution with a spherical assumption, also increased, highlighting the greater degree of fractal morphology during rush hour. The relationship between LDSA emitted by traffic and PNC yielded a higher r2 (0.92) than the r2 between traffic LDSA and eBC (0.82). Finally, the excess lifetime cancer risk linked with traffic emission was 1.56 × 10-4 (i.e. 15.6 excess cancer cases for a population of 100,000 people) based on the LDSA apportionment results.
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Contaminantes Atmosféricos , Contaminación del Aire , Neoplasias , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Monitoreo del Ambiente , Humanos , Pulmón , Motocicletas , Tamaño de la Partícula , Material Particulado/análisis , Emisiones de Vehículos/análisis , Emisiones de Vehículos/toxicidadRESUMEN
PURPOSE: This study investigated the effectiveness of orofacial myofunctional therapy(OMT) in improving facial morphology of children with obstructive sleep apnea (OSA) after adenotonsillectomy (AT). METHODS: Ten children aged from 4-7 years with persistent oral breathing for more than 1 month after adenotonsillectomy were chosen to receive orofacial myofunctional therapy. The patients were required to take photos before and after orofacial myofunctional therapy. In order to compare the soft changes before and after OMT treatment, twelve representative mark points were selected and used for proportion and angle measurements. Graphpad Prism 8 statistical software was used for statistical analysis, to compare the differences in facial morphology of patients before and after treatment. RESULTS: Compared with before OMT, a significant difference was found in the proportion of Sn-Ls/Sn-Stms(P=0.0002), Sn-Stms/Sn-Me'(P<0.05), as well as in the angle of Gs-Sn-Pos (P<0.05), nasolabial angle(P=0.0005), mentolabial angle (P=0.0026) after OMT treatment. CONCLUSIONS: Orofacial myofunctional therapy can be considered as an effective complementary treatment for OSA patients with oral breathing after adenotonsillectomy.
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Apnea Obstructiva del Sueño , Tonsilectomía , Adenoidectomía , Niño , Cara , Humanos , Terapia Miofuncional , Apnea Obstructiva del Sueño/terapiaRESUMEN
Exploration of the diastereodivergent synthesis of spirocyclic oxindoles has been challenging. Herein we report asymmetric [3 + 2] annulations of isatin-derived Morita-Baylis-Hillman (MBH) carbonates and 5-alkenylthiazol-4(5H)-ones. Interestingly, two different chiral catalysts, amide-phosphine and 4-dimethylaminopyridine (DMAP)-thiourea, could lead to two kinds of diastereomeric dispiro oxindoles with three contiguous stereogenic centers. The hexafluoroisopropanol (HFIP) additive plays a vital role in accelerating the reaction and tuning the diastereoselectivity. Moreover, both annulation adducts could be further converted to structurally diverse spirooxindoles.
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Periodontitis is initiated by serious and sustained bacterial infection and ultimately results in chronic immune-mediated inflammation, tissue destruction, and bone loss. The pathogenesis of periodontitis remains unclear. Host immunological responses to periodontal bacteria ultimately determine the severity and mechanisms governing periodontitis progression. This study aimed to clarify the effect of the hypoxia-inducible factor-1α (HIF-1α) activator dimethyloxalylglycine (DMOG) on a mouse periodontitis model and its underlying role in macrophage polarization. qRT-PCR analysis showed that DMOG inhibited the M1-like polarization of both RAW264.7 macrophages and murine bone marrow macrophages (BMMs) and downregulated TNF-α, IL-6, CD86, and MCP-1 expression in vitro. Immunofluorescence staining and flow cytometry also confirmed the less percentage of F4/80 + CD86 + cells after DMOG treatment. The phosphorylation of NF-κB pathway was also inhibited by DMOG with higher level of HIF-1α expression. Furthermore, mice treated with DMOG showed decreased alveolar bone resorption in the experimental periodontitis model, with significant increases in alveolar bone volume/tissue volume (BV/TV) and bone mineral density (BMD). DMOG treatment of mice decreased the ratio of M1/M2 (CD86+/CD206+) macrophages in periodontal tissues, resulting in the downregulation of proinflammatory cytokines such as TNF-α and IL-6 and increased levels of anti-inflammatory factors such as IL-4 and IL-10. DMOG treatment promoted the number of HIF-1α-positive cells in periodontal tissues. This study demonstrated the cell-specific roles of DMOG in macrophage polarization in vitro and provided insight into the mechanism underlying the protective effect of DMOG in a model of periodontitis.
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Pérdida de Hueso Alveolar/tratamiento farmacológico , Aminoácidos Dicarboxílicos/uso terapéutico , Macrófagos/efectos de los fármacos , Periodontitis/tratamiento farmacológico , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/inmunología , Pérdida de Hueso Alveolar/patología , Aminoácidos Dicarboxílicos/farmacología , Animales , Citocinas/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia , Macrófagos/inmunología , Masculino , Maxilar/diagnóstico por imagen , Maxilar/patología , Ratones , Ratones Endogámicos C57BL , FN-kappa B/inmunología , Periodontitis/diagnóstico por imagen , Periodontitis/inmunología , Periodontitis/patología , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Microtomografía por Rayos XRESUMEN
A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00686-x.