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Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.
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Asma , Óxido Nítrico , Obesidad , Sobrepeso , Anciano , Femenino , Humanos , Masculino , Pueblo Asiatico , Asma/fisiopatología , Asma/metabolismo , Asma/diagnóstico , Índice de Masa Corporal , Pruebas Respiratorias , Pruebas de Provocación Bronquial , China/epidemiología , Prueba de Óxido Nítrico Exhalado Fraccionado , Óxido Nítrico/metabolismo , Óxido Nítrico/análisis , Obesidad/fisiopatología , Obesidad/metabolismo , Sobrepeso/fisiopatología , Sobrepeso/metabolismo , Pruebas de Función Respiratoria , Hipersensibilidad Respiratoria/fisiopatología , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/diagnóstico , Estudios RetrospectivosRESUMEN
Background: Osteoarthritis (OA) is the most common joint disease worldwide, but its cause remains unclear. Oestrogen protects against OA, but its clinical use is limited. G protein-coupled receptor 30 (GPR30) is a receptor that binds oestrogen, and GPR30 treatment has benefitted patients with some degenerative diseases. However, its effects on OA prevention and treatment remain unclear. Moreover, several studies have found that activation of estrogen receptors exerting anti-ferroptosis effects, which plays an important role in chondrocyte survival. Therefore, this study explored the general and ferroptosis-related effects and mechanisms of GPR30 in OA. Methods: Genome-wide RNA sequencing, western blotting, and immunohistochemistry were used to evaluate GPR30 expression and ferroptosis-related indicators in cartilage tissues from clinical patients. Next, we investigated the effects of G1 (a GPR30 receptor agonist) on the function and pathology of OA in an animal model. We also treated chondrocytes with erastin (ferroptosis agonist) plus G1, G15 (GPR30 receptor antagonist), GPR30 short hairpin RNA, or ferrostatin-1 (ferroptosis inhibitor), then measured cell viability and ferroptosis-related indices and performed proteomics analyses. Finally, western blotting and reverse transcription-polymerase chain reaction were used to assess the effects of G1 on yes-associated protein 1 (YAP1) and ferritin heavy chain 1 (FTH1) expression. Results: GPR30 expression was lower in the OA cartilage tissues than in the normal tissues, and G1 treatment significantly improved the locomotor ability of mice. Moreover, chondrocyte cell viability significantly decreased after erastin treatment, but G1 treatment concentration-dependently mitigated this effect. Furthermore, G1 treatment decreased phosphorylated YAP1 expression, increased activated YAP1 expression, and increased FTH1 transcription and protein expression, protecting against ferroptosis. Conclusion: GPR30 activation inhibited ferroptosis in chondrocytes by suppressing YAP1 phosphorylation, which regulates FTH1 expression.The Translational Potential of this Article: These results provide a novel potential target for therapeutic OA interventions.
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To explore the safe utilization technology of farmland polluted by the heavy metals cadmium (Cd) and lead (Pb) and to realize the safe production of agricultural products, a pot experiment was conducted to investigate the effects of two soil passivators and five foliar inhibitors on Cd and Cd-accumulation and quality of lettuce with low Pb and Cd accumulation (KCW). The results showed that different control measures had different effects on the soil pH value of lettuce, and the application of 45 g·m-2biochar-based passivator had the most significant difference in improving the soil pH value, which was increased by 0.8 units compared with that in CK. By using 72 g·m-2 of humic acid passivator yielded notable difference in reducing the soil pH value of lettuce. A reduction of 0.25 units was achieved compared with that in CK. Among all the control measures, the application of 45 g·m-2 biocharcoal-based passivation agent had the best effect on reducing soil available Cd content, which was significantly reduced by 53% compared with that in CK, and the application of 135 g·m-2biocharcoal-based passivation agent had the best effect on reducing soil available Pb content, which was significantly reduced by 64% compared with that in CK. Spraying 0.8% FAK-Zn foliar inhibitor not only had the best control effect on reducing Cd and Pb contents in the edible parts of lettuce, which were significantly reduced by 77% and 60%, respectively, compared with that in CK, but it also significantly reduced Cd and Pb enrichment coefficients and transport coefficients from the root to the edible parts of the lettuce. Different control measures had different effects on the nutritional quality of lettuce, and 0.4% FAK-Zn foliar inhibitor had the best effect on soluble protein. The 0.6% FAK-Zn had the best effect on soluble sugar, and the 0.4% FAK-Zn inhibitor had the best effect on vitamin C content. The application of biocarbon-based passivator could effectively repair lettuce soil polluted by Cd and Pb, whereas the application of FAK-Zn leaf surface inhibitor could effectively inhibit the accumulation, absorption, and transfer of Cd and Pb in lettuce; improve the nutritional quality of lettuce; provide a theoretical basis for safe production of vegetables polluted by heavy metals; and promote the recycling of resources and environment.
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Cadmio , Lactuca , Plomo , Verduras , SueloRESUMEN
BACKGROUND AND PURPOSE: To determine the effects of resistance training (RT) on symptoms, function, and lower limb muscle strength in patients with knee osteoarthritis (KOA), and to determine the optimal dose-response relationships. DATA SOURCES: We searched the PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and ClinicalTrials.gov databases from inception to January 23, 2022. ELIGIBILITY CRITERIA: Randomized controlled trials that examined the effects of RT in KOA patients (mean age ≥50 years) were included. DATA SYNTHESIS: We applied Hedges' g of the random-effects model to calculate the between-subject standardized mean difference (SMDbs). A random-effects metaregression was calculated to explain the influence of key training variables on the effectiveness of RT. We used the Grading of Recommendations Assessments, Development and Evaluation (GRADE) method to appraise the certainty of evidence. RESULTS: A total of 46 studies with 4289 participants were included. The analysis revealed moderate effects of RT on symptoms and function (SMDbs =-0.52; 95% CI: -0.64 to -0.40), and lower limb muscle strength (SMDbs = 0.53; 95% CI: 0.42 to 0.64) in the intervention group compared with the control group. The results of the metaregression revealed that only the variable "training period" (P< .001) had significant effects on symptoms, function, and lower limb muscle strength, and the 4 to 8 weeks of training subgroup showed greater effects than other subgroups (SMDbs =-0.70, -0.91 to -0.48; SMDbs = 0.76, 0.56 to 0.96). CONCLUSIONS: Compared with inactive treatments, RT is strongly recommended to improve symptoms, function, and muscle strength in individuals with KOA. Dose-response relationship analysis showed that 4 to 8 weeks of RT had more benefits.
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BACKGROUND: The ascomycetous heterothallic yeast Wickerhamomyces anomalus (WA) has received considerable attention and has been widely reported in the winemaking industry for its distinctive physiological traits and metabolic attributes. An increased concentration of ethanol during ethanol fermentation, however, causes ethanol stress (ES) on the yeast cells. Trehalose has been implicated in improving survival under various stress conditions in microorganisms. Herein, we determined the effects of trehalose supplementation on the survival, differentially expressed genes (DEGs), cellular morphology, and oxidative stress tolerance of WA in response to ES. RESULTS: The results indicated that trehalose improved the survival and anomalous surface and ultrastructural morphology of WA. Additionally, trehalose improved redox homeostasis by reducing the levels of reactive oxygen species (ROS) and inducing the activities of antioxidant enzymes. In addition, DEGs affected by the application of trehalose were enriched in these categories including in gene expression, protein synthesis, energy metabolism, and cell cycle pathways. Additionally, trehalose increased the content of intracellular malondialdehyde (MDA) and adenosine triphosphate. CONCLUSIONS: These results reveal the protective role of trehalose in ES mitigation and strengthen the possible uses of WA in the wine fermentation sector.
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Saccharomycetales , Trehalosa , Adenosina Trifosfato , EtanolRESUMEN
Loss of function of progranulin (PGRN), encoded by the granulin (GRN) gene, is implicated in several neurodegenerative diseases. Several therapeutics to boost PGRN levels are currently in clinical trials. However, it is difficult to test the efficacy of PGRN-enhancing drugs in mouse models due to the mild phenotypes of Grn-/- mice. Recently, mice deficient in both PGRN and TMEM106B were shown to develop severe motor deficits and pathology. Here, we show that intracerebral ventricle injection of PGRN-expressing AAV1/9 viruses partially rescues motor deficits, neuronal loss, glial activation, and lysosomal abnormalities in Tmem106b-/-Grn-/- mice. Widespread expression of PGRN is detected in both the brain and spinal cord for both AAV subtypes. However, AAV9 but not AAV1-mediated expression of PGRN results in high levels of PGRN in the serum. Together, these data support using the Tmem106b-/-Grn-/- mouse strain as a robust mouse model to determine the efficacy of PGRN-elevating therapeutics.
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In this work, we reported a systemic study on the enhanced efficiency of launching hyperbolic phonon polaritons (PhPs) in stacked α-phase molybdenum trioxide (α-MoO3) flakes. By using the infrared photo-induced force microscopy (PiFM), real-space near-field images (PiFM images) of mechanically exfoliated α-MoO3 thin flakes were recorded within three different Reststrahlen bands (RBs). As referred with PiFM fringes of the single flake, PiFM fringes of the stacked α-MoO3 sample within the RB 2 and RB 3 are greatly improved with the enhancement factor (EF) up to 170%. By performing numerical simulations, it reveals that the general improvement in near-field PiFM fringes arises from the existence of a nanoscale thin dielectric spacer in the middle part between two stacked α-MoO3 flakes. The nanogap acts as a nanoresonator for prompting the near-field coupling of hyperbolic PhPs supported by each flake in the stacked sample, contributing to the increase of polaritonic fields, and verifying the experimental observations Our findings could offer fundamental physical investigations into the effective excitation of PhPs and will be helpful for developing functional nanophotonic devices and circuits.
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BACKGROUND: Heterozygous loss-of-function mutations in the progranulin (PGRN) gene (GRN) cause a reduction in PGRN and lead to the development of frontotemporal dementia (FTD-GRN). PGRN is a secreted lysosomal chaperone, immune regulator, and neuronal survival factor that is shuttled to the lysosome through multiple receptors, including sortilin. Here, we report the characterization of latozinemab, a human monoclonal antibody that decreases the levels of sortilin, which is expressed on myeloid and neuronal cells and shuttles PGRN to the lysosome for degradation, and blocks its interaction with PGRN. METHODS: In vitro characterization studies were first performed to assess the mechanism of action of latozinemab. After the in vitro studies, a series of in vivo studies were performed to assess the efficacy of a mouse-cross reactive anti-sortilin antibody and the pharmacokinetics, pharmacodynamics, and safety of latozinemab in nonhuman primates and humans. RESULTS: In a mouse model of FTD-GRN, the rodent cross-reactive anti-sortilin antibody, S15JG, decreased total sortilin levels in white blood cell (WBC) lysates, restored PGRN to normal levels in plasma, and rescued a behavioral deficit. In cynomolgus monkeys, latozinemab decreased sortilin levels in WBCs and concomitantly increased plasma and cerebrospinal fluid (CSF) PGRN by 2- to threefold. Finally, in a first-in-human phase 1 clinical trial, a single infusion of latozinemab caused a reduction in WBC sortilin, tripled plasma PGRN and doubled CSF PGRN in healthy volunteers, and restored PGRN to physiological levels in asymptomatic GRN mutation carriers. CONCLUSIONS: These findings support the development of latozinemab for the treatment of FTD-GRN and other neurodegenerative diseases where elevation of PGRN may be beneficial. Trial registration ClinicalTrials.gov, NCT03636204. Registered on 17 August 2018, https://clinicaltrials.gov/ct2/show/NCT03636204 .
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Demencia Frontotemporal , Humanos , Ratones , Animales , Progranulinas/genética , Demencia Frontotemporal/tratamiento farmacológico , Demencia Frontotemporal/genética , Demencia Frontotemporal/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Mutación/genéticaRESUMEN
Purpose: The present study aimed to identify clinicopathological characteristics of breast cancer liver metastasis (BCLM) as well as to characterize the risk and prognostic factors for the liver metastasis (LM) of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population. Materials and methods: Patients with metastatic breast cancer (MBC) who were hospitalized in the Breast Cancer Center at Chongqing University between January 2011 and December 2019 were included in the present study. Logistic regression analyses were conducted to identify risk factors for the presence of BCLM. Cox proportional hazard regression models were performed to determine the prognostic factors for the survival of BCLM patients. The correlation between LM and overall survival was assessed by the Kaplan-Meier method. Results: In total, 1,228 eligible MBC patients, including 325 cases (26.5%) with de novo metastasis (cohort A) and 903 cases (73.5%) with relapsed metastasis (cohort B), were enrolled in the present study. In cohort A and cohort B, 81 (24.9%) and 226 (25.0%) patients had BCLM, respectively. Patients in these two cohorts had different clinicopathological features. Logistic regression analysis identified that the human epidermal growth factor receptor 2 (HER2) status in cohort A as well as the HER2 status and invasive ductal carcinoma histology in cohort B were risk factors for BCLM. The median OS of patients with LM was inferior to that of non-LM patients (17.1 vs. 37.7 months, P = 0.0004 and 47.6 vs. 84.0 months, P < 0.0001, respectively). Cox analysis identified that the primary T stage, Ki67 level, and breast surgery history were independent prognostic factors for cohorts A and B, respectively. Conclusions: De novo and relapsed MBC patients have different risk and prognostic factors for LM. Patients with BCLM have an unfavorable prognosis.
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Histone lysine specific demethylase 1 (LSD1) has been recognized as an important epigenetic target for cancer treatment. Although several LSD1 inhibitors have entered clinical trials, the discovery of novel potent LSD1 inhibitors remains a challenge. In this study, the antipsychotic drug chlorpromazine was characterized as an LSD1 inhibitor (IC50 = 5.135 µM), and a series of chlorpromazine derivatives were synthesized. Among them, compound 3s (IC50 = 0.247 µM) was the most potent one. More importantly, compound 3s inhibited LSD1 in the cellular level and downregulated the expression of programmed cell death-ligand 1 (PD-L1) in BGC-823 and MFC cells to enhance T-cell killing response. An in vivo study confirmed that compound 3s can inhibit MFC cell proliferation without significant toxicity in immunocompetent mice. Taken together, our findings indicated that the novel LSD1 inhibitor 3s tethering a phenothiazine scaffold may serve as a lead compound for further development to activate T-cell immunity in gastric cancer.
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Inhibidores Enzimáticos , Neoplasias Gástricas , Animales , Ratones , Inhibidores Enzimáticos/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Línea Celular Tumoral , Clorpromazina/uso terapéutico , Linfocitos T/metabolismo , Proliferación Celular , Histona Demetilasas/metabolismo , Muerte Celular , Relación Estructura-ActividadRESUMEN
Chlorogenic acid (CA) has a wide range of biological activities but the chemical structure is extremely unstable. In this study, CA was grafted onto a soluble oat ß-glucan (OßGH) to improve the stability. Although the crystallinity and thermal stability of CA-OßGH conjugates reduced, the storage stability of CA significantly improved. The DPPH and ABTS scavenging ability of CA-OßGH IV (graft ratio 285.3 mg CA/g) were higher than 90 %, which is closed to activities of equivalent concentration of Vc (93.42 %) and CA (90.81 %). The antibacterial abilities of CA-OßGH conjugates are improved compared to the equivalent content of CA and potassium sorbate. Particularly, the inhibition rate of CA-OßGH for gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) are significantly higher than that of gram-negative bacteria (Escherichia coli). The results demonstrated that covalent grafted CA with soluble polysaccharide is an effective strategy to enhance its stability and biological activities.
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Antagonizing the CD47-signal regulatory protein (SIRP)α pathway, a critical myeloid checkpoint, promotes antitumor immunity. In this study, we describe the development of AL008, a pan-allelic, SIRPα-specific Ab that triggers the degradation of SIRPα and, concurrently, stimulates FcγR activation of myeloid cells through an engineered Fc domain. AL008 showed superior enhancement of phagocytosis of tumor cells opsonized with antitumor Ag Abs compared with another SIRPα Ab tested. Unlike ligand-blocking SIRPα Abs, AL008 demonstrated single-agent activity by increasing tumor cell engulfment by human monocyte-derived macrophages even in the absence of opsonizing agents. This effect was due to enhanced Fc function, as blocking FcγR2A abrogated AL008-mediated phagocytic activity. AL008 also promoted human monocyte-derived dendritic cell-mediated T cell proliferation. In humanized mouse models, AL008 induced internalization of SIRPα and increased expression of CD86 and HLA-DR on human tumor-associated macrophages, confirming that the mechanism of action is retained in vivo. Monotherapy treatment with AL008 significantly reduced tumor growth in humanized mice implanted with human MDA-MB-231 tumor cells. AL008 also significantly potentiated the effects of T cell checkpoint blockade with anti-programmed death ligand-1 in syngeneic tumor models. This dual and specific mechanism of AL008, to our knowledge, provides a novel therapeutic strategy for targeting myeloid cells for immune activation.
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Neoplasias , Receptores Fc , Humanos , Ratones , Animales , Receptores Fc/metabolismo , Inmunoterapia , Fagocitosis , Macrófagos , Neoplasias/patología , Antígenos de Diferenciación , Antígeno CD47/metabolismoRESUMEN
Wickerhamomyces anomalus (W. anomalus) is widely reported in the brewing industry and has positive effects on the aromatic profiles of wines because of its unique physiological characteristics and metabolic features. However, the accumulation of ethanol during fermentation inhibits the growth of W. anomalus. Thiamine is involved in the response against various abiotic stresses in microorganisms. Therefore, we used transcriptomic and metabolomic analyses to study the effect of thiamine on ethanol-stressed W. anomalus. The results indicate that thiamine could alleviate the inhibitory effect of ethanol stress on the survival of W. anomalus. Differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) caused by the thiamine intervention were identified as oxidative phosphorylation through integrated transcriptomic and metabolomic analyses. In addition, ethanol treatment decreased the content of intracellular adenosine triphosphate (ATP), while thiamine partially alleviated this phenomenon. The present comprehensive transcriptional overview and metabolomic analysis provide insights about the mechanisms of thiamine protection on W. anomalus under ethanol stress and promote the potential applications of W. anomalus in the fermentation industry.
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BACKGROUND: Primary testicular neuroendocrine tumors (TNETs) are sporadic, accounting for only 0.23% of all testicular tumors. Few cases have been reported in the literature, and no uniform treatment protocol exists. We report a case of a primary TNET with liver lymph node metastasis diagnosed at the age of 24 years and discuss its clinicopathological features, diagnosis, differential diagnosis, treatment, and prognosis. CASE SUMMARY: We report the case of a 24-year-old patient with a primary TNET with liver lymph node metastasis. The patient was found to have a right testicular swelling of about 3 cm × 4 cm in size with unclear borders and no testicular pressure pain seven years ago without any examination or treatment. One month ago, an ultrasound examination was performed for persistent enlargement of the right testis, which showed an occupying lesion of the right testis approximately 110 mm × 102 mm × 82 mm in size. Magnetic resonance imaging scan of the testis (plain scan) showed that the right testis was an occupying lesion with inhomogeneous density and mixed signal, the boundary was still clear, and the possibility of seminoma was considered; chest X-ray and computed tomography did not show any apparent abnormalities. The patient underwent radical orchiectomy, and the pathological examination suggested a right TNET with a typical carcinoid tumor histological type. One month after the surgery, the patient received nine cycles of lanreotide chemotherapy at a dose of 90 mg/mo without adverse effects. No distant lymph node or other organ metastases were detected at follow-up. He is in good physical condition and attends regular follow-up visits. CONCLUSION: Neuroendocrine tumors are rare in clinical practice, and the diagnosis mainly relies on the characteristics of microscopic tumor cells and immunohistochemical features. Treatment involves radical orchiectomy. If it is accompanied by distant lymph node metastasis and the metastatic lesion can be resected, it should be surgically removed; if it cannot be resected, growth inhibitor analog octreotide or lanreotide chemotherapy can be administered to obtain good results, with close postoperative follow-up to prevent recurrence and metastasis.
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BACKGROUND: Wickerhamomyces anomalus (W. anomalus) is a kind of non-Saccharomyces yeast that has a variety of unique physiological characteristics and metabolic features and is widely used in many fields, such as food preservation, biomass energy, and aquaculture feed protein production. However, the mechanism of W. anomalus response to ethanol stress is still unclear, which greatly limits its application in the production of ethanol beverages and ethanol fuels. Therefore, we checked the effects of ethanol stress on the morphology, the growth, and differentially expressed genes (DEGs) and metabolites (DEMs) of W. anomalus. RESULTS: High concentrations of ethanol (9% ethanol and 12% ethanol) remarkably inhibited the growth of W. anomalus. Energy metabolism, amino acid metabolism, fatty acids metabolism, and nucleic acid metabolism were significantly influenced when exposing to 9% ethanol and 12% ethanolstress, which maybe universal for W. anomalus to response to different concentrations of ethanol stressl Furthermore, extracellular addition of aspartate, glutamate, and arginine significantly abated ethanol damage and improved the survival rate of W. anomalus. CONCLUSIONS: The results obtained in this study provide insights into the mechanisms involved in W. anomalus response to ethanol stress. Therefore, new strategies can be realized to improve the ethanol tolerance of W. anomalus through metabolic engineering.
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Etanol , Saccharomycetales , Etanol/farmacología , Etanol/metabolismo , Transcriptoma , Saccharomycetales/genética , Saccharomycetales/metabolismo , LevadurasRESUMEN
Natural products (NPs) and their structural analogs represent a major source of novel drug development for disease prevention and treatment. The development of new drugs from NPs includes two crucial aspects. One is the discovery of NPs from medicinal plants/microorganisms, and the other is the evaluation of the NPs in vivo at various physiological and pathological states. The heterogeneous spatial distribution of NPs in medicinal plants/microorganisms or in vivo can provide valuable information for drug development. However, few molecular imaging technologies can detect thousands of compounds simultaneously on a label-free basis. Over the last two decades, mass spectrometry imaging (MSI) methods have progressively improved and diversified, thereby allowing for the development of various applications of NPs in plants/microorganisms and in vivo NP research. Because MSI allows for the spatial mapping of the production and distribution of numerous molecules in situ without labeling, it provides a visualization tool for NP research. Therefore, we have focused this mini-review on summarizing the applications of MSI technology in discovering NPs from medicinal plants and evaluating NPs in preclinical studies from the perspective of new drug research and development (R&D). Additionally, we briefly reviewed the factors that should be carefully considered to obtain the desired MSI results. Finally, the future development of MSI in new drug R&D is proposed.
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Productos Biológicos , Espectrometría de Masas/métodos , Plantas , Investigación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
Herein, we report the two-photon pumped amplified spontaneous emission (ASE) in the 2D RPPs flakes at room temperature. We prepared high-quality (BA)2(MA)n-1PbnI3n+1 (n = 1, 2, 3, 4, 5) flakes by mechanical exfoliating from the fabricated crystals. We show that the (BA)2(MA)n-1PbnI3n+1 flakes display a tunable two-photon pumped emission from 527â nm to 680â nm, as n increases from 1 to 5. Furthermore, we demonstrated two-photon pumped ASE from the (BA)2(MA)n-1PbnI3n+1 (n = 3, 4, 5) flakes. The two-photon pumped ASE thresholds of the RPPs are lower than lots of the other semiconductor nanostructures, indicating an excellent performance of the RPPs for two-photon pumped emission. In addition, we investigated the pump-wavelength-dependent two-photon pumped ASE behaviors of the RPPs flakes, which suggest that the near-infrared laser in a wide wavelength range can be converted into visible light by the frequency upconversion process in RPPs. This work has opened new avenues for realizing nonlinearly pumped ASE based on the RPPs, which shows great potential for the applications in wavelength-tunable frequency upconversion.
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BACKGROUND: This meta-analysis aimed to evaluate the efficacy and safety of dexamethasone in the treatment of acute respiratory distress syndrome (ARDS). METHODS: A systematic search of electronic databases was carried out from inception to May 1, 2022, including PUBMED, EMBASE, Cochrane Library, Wangfang, VIP, and CNKI. Other searches were also checked for dissertations/theses and the reference lists of the included studies. Two team members examined all citations and selected eligible articles. Randomized controlled trials (RCTs) reporting the efficacy and safety of dexamethasone for the treatment of ARDS were included, and the quality of eligible RCTs was assessed using the Cochrane Risk of Bias Tool. If necessary, we conducted data synthesis and meta-analysis. The primary outcome was all-cause mortality. Secondary outcomes were mechanical ventilation duration (day), ventilator-free status at 28 days; intensive care unit (ICU) free (day), ICU mortality, hospital mortality, sequential organ failure assessment (SOFA) as mean and range, SOFA as No. of patients, peak airway pressure (cmH2O), arterial oxygen pressure (mm Hg), days with PaO2 > 10kPa, PaO2, and the occurrence rate of adverse events. RESULTS: Four studies involving 702 patients were included in this analysis. This study showed that dexamethasone could significantly reduce all-cause mortality (odds ratio (OR) = 0.62, 95% confidence interval (CI) [0.44, 0.88], I2 = 30%, P < .001), and decrease ventilator-free status at 28 days (MD = 3.65, 95% CI [1.49, 5.80], I2 = 51%, P < .001). No significant differences in occurrence rates of adverse events were found between dexamethasone and routine or standard care. CONCLUSIONS: Evidence from the meta-analysis suggests that dexamethasone is an effective and relatively safe treatment for all-cause mortality and ventilator-free status at 28 days in patients with ARDS. Owning to the small number of eligible RCTs, the conclusions of present study are warranted in the future study.