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In order to systematically understand the urban environmental benefit improvement of municipal solid waste ï¼MSWï¼ classification, based on the disposal data of MSW before and after the MSW classification in Suzhou from 2017 to 2021, the environmental impact potential ï¼EIPï¼ of the MSW collection-transportation-disposal process was calculated, and the environmental benefits of the MSW integrated management in Suzhou to 2035 were predicted. After the MSW classification in Suzhou at the end of 2019, the EIP ï¼in terms of PET2000, the same belowï¼ of the per unit weight of MSW was reduced by 18.38% from 2.34×10-13 t-1 in 2017 to 1.91×10-13 t-1 in 2021. The environmental benefits of the MSW integrated management could be improved by classification. Based on the Suzhou MSW removal and transportation situation in 2021, different classification and disposal scenarios were established to calculate. It was found that after the classification effect showed gradient improvement, and the disposal capacity matched accordingly, the environmental benefits of MSW were further improved. Under the planning disposal capacity scenario of "zero waste to landfill", the EIP and the total carbon emissions of per unit weight of MSW should be reduced by 23.96% and 30.73%, respectively, compared with the actual situation in 2021. Based on the linear model of population and economic development level of Suzhou, it is expected that the annual production of MSW in Suzhou will be increased to 6.965 million tons in 2035. Under the background of continuous improvement of MSW classification and continuous optimization of city appearance and environment in Suzhou, based on the status quo of terminal disposal capacity in Suzhou, the EIP of per unit weight of MSW after improving the efficiency of classification by 2035 was predicted to be 1.54×10-13 t-1, the total EIP would be 1.05×10-6, and the total carbon emissions would increase to 3.80 million tons. Under the ideal scenario of expanding the scale of waste disposal, "zero landfill" of raw MSW, and full resource utilization of food waste, the EIP of per unit weight of MSW in 2035 was predicted to be 1.28×10-13 t-1, and the total EIP and the total carbon emissions would be 8.69×10-7 and 3.23 million tons, respectively, which was approximately 5.65% and 1.23% less than the actual scenario in 2021, respectively. The EIP and carbon emissions of MSW integrated management could be controlled better by the coordinated promotion of classified collection and transportation and quality disposal.
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A CRISPR/Cas12a-coupled multiplexed strand displacement amplification (CMSDA) for the detection of miR155 has been developed. Non-specific amplification was avoided by designing a single-stranded DNA template with a hairpin structure. The detection target miR155 was used as a primer to initiate a multiple-strand displacement reaction to produce abundant ssDNA. ssDNA was recognized by the Cas12a/CrRNA binary complex, activating the trans-cleaving activity of Cas12a. The multiple-strand displacement reaction is more efficiently detected compared with a single-strand displacement reaction. The detection range is from 250 pM to 1 nM, and the limit of the detection is 6.5 pM. The proposed method showed a good applicability in complex serum environments, indicating that the method has a broad prospect for disease detection and clinical application. In addition, we designed a dual-cavity PCR tube, which realized one-tube detection of miRNA155 and avoided open-cap contamination.
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Sistemas CRISPR-Cas , MicroARNs , MicroARNs/análisis , MicroARNs/sangre , MicroARNs/genética , Humanos , Sistemas CRISPR-Cas/genética , ADN de Cadena Simple/química , ADN de Cadena Simple/genética , Límite de Detección , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena de la Polimerasa/métodos , Proteínas Bacterianas , Endodesoxirribonucleasas , Proteínas Asociadas a CRISPRRESUMEN
Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the "Fruits-Vegetables-Dairy" pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the "Puffed food-Bakery-Candy" pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the "Grains-Tubers-Legumes". Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.
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Contaminantes Atmosféricos , Dieta , Fertilización In Vitro , Material Particulado , Femenino , Humanos , Material Particulado/análisis , Adulto , Embarazo , Dieta/estadística & datos numéricos , Estudios Prospectivos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Exposición Materna/estadística & datos numéricos , Masculino , Patrones DietéticosRESUMEN
CpxA is a key member of the envelope stress-responsive Cpx two-component system ubiquitous in Gram-negative bacteria. It is responsible for signal sensing and has dual activities of phosphatase and kinase. CpxA has been revealed to participate in the regulation of physiological processes such as virulence and antimicrobial resistance of bacteria. In recent years, the development of novel antimicrobials targeting CpxA has attracted much attention. Drugs developed based on inhibition of the phosphatase activity of CpxA have shown effectiveness in the treatment of urinary tract infections caused by Escherichia coli. This review introduces the structure and functional domains of CpxA and the activation of Cpx pathways by CpxA. Furthermore, it summarizes the roles of CpxA in the development of antimicrobial resistance and the regulation of bacterial virulence and reviews the latest progress in the development of new antimicrobials targeting this protein. It is expected to assist in the exploration of CpxA-targeting anti-infection strategies for severely antimicrobial-resistant bacteria whose clinical infections are of urgent need to be controlled.
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Proteínas Bacterianas , Farmacorresistencia Bacteriana , Virulencia , Farmacorresistencia Bacteriana/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Mutación , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Antibacterianos/farmacología , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Proteínas QuinasasRESUMEN
Group 3 innate lymphoid cells (ILC3s) play key roles in intestinal inflammation. Olfactomedin 4 (OLFM4) is highly expressed in the colon and has a potential role in dextran sodium sulfate-induced colitis. However, the detailed mechanisms underlying the effects of OLFM4 on ILC3-mediated colitis remain unclear. In this study, we identify OLFM4 as a positive regulator of IL-22+ILC3. OLFM4 expression in colonic ILC3s increases substantially during intestinal inflammation in humans and mice. Compared to littermate controls, OLFM4-deficient (OLFM4-/-) mice are more susceptible to bacterial infection and display greater resistance to anti-CD40 induced innate colitis, together with impaired IL-22 production by ILC3, and ILC3s from OLFM4-/-mice are defective in pathogen resistance. Besides, mice with OLFM4 deficiency in the RORγt compartment exhibit the same trend as in OLFM4-/-mice, including colonic inflammation and IL-22 production. Mechanistically, the decrease in IL-22+ILC3 caused by OLFM4 deficiency involves the apoptosis signal-regulating kinase 1 (ASK1)- p38 MAPK signaling-dependent downregulation of RAR-related orphan receptor gamma (RORγt) protein. The OLFM4-metadherin (MTDH) complex upregulates p38/RORγt signaling, which is necessary for IL-22+ILC3 activation. The findings indicate that OLFM4 is a novel regulator of IL-22+ILC3 and essential for modulating intestinal inflammation and tissue homeostasis.
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Colitis , Interleucina-22 , Interleucinas , Ratones Noqueados , Animales , Ratones , Interleucinas/metabolismo , Interleucinas/genética , Colitis/genética , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/inmunología , Colitis/patología , Humanos , Linfocitos/inmunología , Linfocitos/metabolismo , Ratones Endogámicos C57BL , Factor Estimulante de Colonias de Granulocitos/metabolismo , Factor Estimulante de Colonias de Granulocitos/genética , Inmunidad Innata , Inflamación/metabolismo , Inflamación/genética , Masculino , GlicoproteínasRESUMEN
An unprecedented trimethylsilyl trifluoromethanesulfonate (TMSOTf)-promoted selective double insertion of isocyanides into aldehydes was developed, providing an efficient protocol for synthetically challenging ß-carbonyl α-iminoamides. The given approach is applicable for a diverse selection of readily accessible aldehydes, along with isocyanides serving as essential precursors for "amide" and "imine" scaffolds. The versatile transformations of the given products were demonstrated, and the pivotal intermediates for the plausible mechanism were identified.
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Per- and polyfluoroalkyl substances (PFASs) are a family of "forever chemicals" including perfluorooctane sulfonate (PFOS). These toxic chemicals do not break down in the environment or in our bodies. In the human body, PFOS and perfluoroctanoic acid (PFOA) have a half-life (T1/2) of about 4-5 yr so low daily consumption of these chemicals can accumulate in the human body to a harmful level over a long period. Although the use of PFOS in consumer products was banned in the United States in 2022/2023, this forever chemical remains detectable in our tap water and food products. Every American tested has a high level of PFAS in their blood (https://cleanwater.org/pfas-forever-chemicals). In this report, we used a Sertoli cell blood-testis barrier (BTB) model with primary Sertoli cells cultured in vitro with an established functional tight junction (TJ)-permeability barrier that mimicked the BTB in vivo. Treatment of Sertoli cells with PFOS was found to perturb the TJ-barrier, which was the result of cytoskeletal disruption across the cell cytoplasm, disrupting actin and microtubule polymerization. These changes thus affected the proper localization of BTB-associated proteins at the BTB. Using RNA-Seq transcriptome profiling, bioinformatics analysis, and pertinent biochemical and cell biology techniques, it was discovered that PFOS -induced Sertoli cell toxicity through the c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase, SAPK) and its phosphorylated/active form p-JNK signaling pathway. More importantly, KB-R7943 mesylate (KB), a JNK/p-JNK activator, was capable of blocking PFOS-induced Sertoli cell injury, supporting the notion that PFOS-induced cell injury can possibly be therapeutically managed.NEW & NOTEWORTHY PFOS induces Sertoli cell injury, including disruption of the 1) blood-testis barrier function and 2) cytoskeletal organization, which, in turn, impedes male reproductive function. These changes are mediated by JNK/p-JNK signaling pathway. However, the use of KB-R7943, a JNK/p-JNK activator was capable of blocking PFOS-induced Sertoli cell injury, supporting the possibility of therapeutically managing PFOS-induced reproductive dysfunction.
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Ácidos Alcanesulfónicos , Fluorocarburos , Proteínas Quinasas JNK Activadas por Mitógenos , Células de Sertoli , Fluorocarburos/toxicidad , Ácidos Alcanesulfónicos/toxicidad , Masculino , Animales , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Células de Sertoli/patología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/genética , RNA-Seq , Barrera Hematotesticular/efectos de los fármacos , Barrera Hematotesticular/metabolismo , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Uniones Estrechas/patología , Células Cultivadas , Ratones , Ratas , Ratas Sprague-DawleyRESUMEN
Post-stroke depression (PSD) is a psychological disease that can occur following a stroke and is associated with serious consequences. Research on the pathogenesis and treatment of PSD is still in the infancy stage. Patients with PSD often exhibit gastrointestinal symptoms; therefore the role of gut microbiota in the pathophysiology and potential treatment effects of PSD has become a hot topic of research. In this review, describe the research on the pathogenesis and therapy of PSD. We also describe how the gut microbiota influences neurotransmitters, the endocrine system, energy metabolism, and the immune system. It was proposed that the gut microbiota is involved in the pathogenesis and treatment of PSD through the regulation of neurotransmitter levels, vagal signaling, hypothalamic-pituitary-adrenal axis activation and inhibition, hormone secretion and release, in addition to immunity and inflammation.
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Microbioma Gastrointestinal , Accidente Cerebrovascular , Humanos , Microbioma Gastrointestinal/fisiología , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/microbiología , Depresión/microbiología , Sistema Hipotálamo-Hipofisario/metabolismo , Animales , Sistema Hipófiso-Suprarrenal/metabolismoRESUMEN
Anti-inflammatory and angiogenesis are two important factors in wound healing. Wound dressings with anti-inflammation and vascularization are essential to address complex interventions, expensive treatments, and uncontrolled release mechanisms. Based on the above considerations, we designed a near-infrared (NIR)-responsive hydrogel dressing, which is composed of mPDA-DFO@LA nanoparticles (mPDA: dopamine hydrochloride nanoparticles, DFO: deferoxamine, LA: lauric acid), valsartan (abbreviated as Va), and dopamine-hyaluronic acid hydrogel. The hydrogel dressing demonstrated injectability, bioadhesive, and photothermal properties. The results indicated the obtained dressing by releasing Va can appropriately regulate macrophage phenotype transformation from M1 to M2, resulting in an anti-inflammatory environment. In addition, DFO encapsulated by LA can be sustainably released into the wound site by NIR irradiation, which further prevents excessive neovascularization. Notably, the results in vivo indicated the mPDA-DFO@LA/Va hydrogel dressing significantly enhanced wound recovery, achieving a healing rate of up to 96% after 11 days of treatment. Therefore, this NIR-responsive hydrogel dressing with anti-inflammation, vascularization, and on-demand programmed drug release will be a promising wound dressing for wound infection.
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Antiinflamatorios , Vendajes , Hidrogeles , Nanocompuestos , Cicatrización de Heridas , Animales , Ratones , Angiogénesis/efectos de los fármacos , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Deferoxamina/química , Deferoxamina/farmacología , Deferoxamina/uso terapéutico , Dopamina/química , Dopamina/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Rayos Infrarrojos , Ácidos Láuricos/química , Ácidos Láuricos/farmacología , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Células RAW 264.7 , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Sysmex DI-60 enumerates and classifies leukocytes. Limited research has evaluated the performance of Sysmex DI-60 in abnormal samples, and most focused on leukopenic samples. We evaluate the efficacy of DI-60 in determining white blood cell (WBC) differentials in normal and abnormal samples in different WBC count. Peripheral blood smears (n = 166) were categorised into normal control and disease groups, and further divided into moderate and severe leucocytosis, mild leucocytosis, normal, mild leukopenia, and moderate and severe leukopenia groups based on WBC count. DI-60 preclassification and verification and manual counting results were assessed using Bland-Altman and Passing-Bablok regression analyses. The Kappa test compared the concordance in the abnormal cell detection between DI-60 and manual counting. DI-60 exhibited notable overall sensitivity and specificity for all cells, except basophils. The correlation between the DI-60 preclassification and manual counting was high for segmented neutrophils, band neutrophils, lymphocytes, and blasts, and improved for all cell classes after verification. The mean difference between DI-60 and manual counting for all cell classes was significantly high in moderate and severe leucocytosis (WBC > 30.0 × 109/L) and moderate and severe leukopenia (WBC < 1.5 × 109/L) groups. For blast cells, immature granulocytes, and atypical lymphocytes, the DI-60 verification results were similar to the manual counting results. Plasma cells showed poor agreement. In conclusion, DI-60 demonstrates consistent and reliable analysis of WBC differentials within the range of 1.5-30.0 × 109. Manual counting was indispensable in examining moderate and severe leucocytosis samples, moderate and severe leukopenia samples, and in enumerating of monocytes and plasma cells.
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Leucocitos , Leucopenia , Humanos , Recuento de Leucocitos/métodos , Recuento de Leucocitos/instrumentación , Leucocitos/citología , Leucocitos/patología , Leucopenia/diagnóstico , Leucopenia/sangre , Leucopenia/patología , Leucocitosis/sangre , Leucocitosis/diagnóstico , Leucocitosis/patología , Sensibilidad y Especificidad , Femenino , Masculino , Neutrófilos/citología , Neutrófilos/patología , Persona de Mediana EdadRESUMEN
Herein, a universal nucleic acid analysis platform was constructed for sensitive and accurate detection of miRNA-155 and ctDNA using isothermal amplification-assisted CRISPR/Cas12a and a tetrahedral DNA nanostructure (TDN) supported sensing interface. Under the optimal experimental conditions, the prepared sensor achieved specific detection of miRNA-155 and ctDNA at as low as aM levels in 2.6 h. Furthermore, the platform was also successfully applied to human serum sample recovery experiments and cancer cell lysates, demonstrating outstanding reliability and accuracy. We firmly believe that this work provides a universal, sensitive, and practical tool for early clinical diagnosis.
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Técnicas Biosensibles , Sistemas CRISPR-Cas , ADN , Técnicas Electroquímicas , MicroARNs , Humanos , Sistemas CRISPR-Cas/genética , MicroARNs/análisis , MicroARNs/sangre , ADN/química , Técnicas de Amplificación de Ácido Nucleico , ADN Tumoral Circulante/sangre , Nanoestructuras/química , Límite de Detección , Proteínas Bacterianas , Endodesoxirribonucleasas , Proteínas Asociadas a CRISPRRESUMEN
BACKGROUND: Despite the known reproductive toxicity induced by triptolide (TP) exposure, the regulatory mechanism underlying testicular vacuolization injury caused by TP remains largely obscure. METHODS: Male mice were subjected to TP at doses of 15, 30, and 60⯵g/kg for 35 consecutive days. Primary Sertoli cells were isolated from 20-day-old rat testes and exposed to TP at concentrations of 0, 40, 80, 160, 320, and 640â¯nM. A Biotin tracer assay was conducted to assess the integrity of the blood-testis barrier (BTB). Transepithelial electrical resistance (TER) assays were employed to investigate BTB function in primary Sertoli cells. Histological structures of the testes and epididymides were stained with hematoxylin and eosin (H&E). The expression and localization of relevant proteins or pathways were assessed through Western blotting or immunofluorescence staining. RESULTS: TP exposure led to dose-dependent testicular injuries, characterized by a decreased organ coefficient, reduced sperm concentration, and the formation of vacuolization damage. Furthermore, TP exposure disrupted BTB integrity by reducing the expression levels of tight junction (TJ) proteins in the testes without affecting basal ectoplasmic specialization (basal ES) proteins. Through the TER assay, we identified that a TP concentration of 160â¯nM was optimal for elucidating BTB function in primary Sertoli cells, correlating with reductions in TJ protein expression. Moreover, TP exposure induced changes in the distribution of the BTB and cytoskeleton-associated proteins in primary Sertoli cells. By activating the AKT/mTOR signaling pathway, TP exposure disturbed the balance between mTORC1 and mTORC2, ultimately compromising BTB integrity in Sertoli cells. CONCLUSION: This investigation sheds light on the impacts of TP exposure on testes, elucidating the mechanism by which TP exposure leads to testicular vacuolization injury and offering valuable insights into comprehending the toxic effects of TP exposure on testes.
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Barrera Hematotesticular , Citoesqueleto , Diterpenos , Compuestos Epoxi , Fenantrenos , Proteínas Proto-Oncogénicas c-akt , Células de Sertoli , Transducción de Señal , Serina-Treonina Quinasas TOR , Testículo , Masculino , Animales , Células de Sertoli/efectos de los fármacos , Células de Sertoli/patología , Diterpenos/toxicidad , Fenantrenos/toxicidad , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/patología , Compuestos Epoxi/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Barrera Hematotesticular/efectos de los fármacos , Barrera Hematotesticular/patología , Citoesqueleto/efectos de los fármacos , Ratas , Vacuolas/efectos de los fármacos , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The impact of COVID-19 on reproductive health is controversial. The association between female SARS-CoV-2 infection and laboratory and pregnancy outcomes following subsequent in vitro fertilization (IVF) treatment remains unclear. This study aimed to investigate the relationship between IVF treatment at different time intervals after SARS-CoV-2 infection and reproductive outcomes. METHODS: A prospective cohort study of 920 IVF cycles post-SARS-CoV-2 infection was conducted. Modified Poisson regression and logistic regression models were utilized to evaluate oocyte- and embryo-related outcomes as well as clinical outcomes. Stratified analyses were also performed based on the vaccination status of the female participants. RESULTS: SARS-CoV-2 infection within three months was associated with reduced available [Adjusted RR (aRR): 0.96, 95 %CI: 0.91-1.00] and top-quality embryos (aRR: 0.90, 95 %CI: 0.83-0.98) in subsequent IVF treatment. Among patients failing to finish the three-dose vaccination, the interval between SARS-CoV-2 infection and cycle initiation of less than 90 days was associated with a lower number of oocytes retrieval (aRR: 8.81, 95 %CI: 8.24-9.41 vs aRR: 9.64, 95 %CI: 9.06-10.25), available embryos (aRR: 0.93, 95 %CI: 0.88-0.99), and top-quality embryos (aRR: 0.81, 95 %CI: 0.72-0.91) rather than among fully vaccinated women. Moreover, COVID-19 infection was not associated with biochemical pregnancy, clinical pregnancy, embryo implantation, and early abortion either in fresh embryo transfer (ET) or frozen ET. CONCLUSIONS: This study indicated that initiating IVF treatment within 90 days of SARS-CoV-2 infection might reduce the likelihood of obtaining available and top-quality embryos, especially among those who had not completed the three-dose vaccination. Nevertheless, female COVID-19 infection did not affect pregnancy or early abortion. Further rigorously designed studies are required to support these findings.
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Vacunas contra la COVID-19 , COVID-19 , Fertilización In Vitro , SARS-CoV-2 , Vacunación , Humanos , Femenino , COVID-19/prevención & control , COVID-19/terapia , Embarazo , Adulto , Estudios Prospectivos , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/administración & dosificación , Resultado del Embarazo , Estudios de CohortesRESUMEN
This research proposed a novel pulse-shaping design for directly shaping distorted pulses after the amplification. Based on the principle of the design we made a pulse shaper. With this pulse shaper, we successfully manipulate the pulse's leading edge and width to achieve an 'M'-shaped waveform in an amplification system. Comparative experiments were conducted within this system to compare the output with and without the integration of the pulse shaper. The results show a significant suppression of the nonlinear effect upon adding the pulse shaper. This flexible and effective pulse shaper can be easily integrated into a high-power all-fiber system, supplying the capability to realize the desired output waveform and enhance the spectral quality.
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We evaluated the drying characteristics and structure, as well as the physicochemical and flavor properties, of G. elata treated by hot-air drying (HAD), vacuum drying (VD), freeze drying (FD), microwave drying (MD), and microwave vacuum drying (MVD). We found that MD and MVD showed the shortest drying times, while FD and MVD were able to better retain the active ingredients and color of the samples. However, the different drying methods did not change the internal structure of G. elata, and its main components did not fundamentally change. In addition, E-nose and HS-SPME-GC-MS effectively differentiated the volatile components, and 36 compounds were detected by HS-SPME-GC-MS. Of these samples, alcohols and aldehydes were the main substances identified. In particular, MVD samples possessed the most species of organic volatiles, but the FD method effectively eliminated pungent odors from the G. elata. Overall, MVD shows the most obvious advantages, improving drying rate while maintaining the original shape, color, and active components in G. elata. Ultimately, MVD is the preferred method to obtain high-quality dried G. elata, and our drying-method characterizations can be used to investigate similar structural and chemical changes to similar herbs in the future.
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Circulating tumor DNA (ctDNA) holds great promise as a noninvasive biomarker for cancer diagnosis, treatment, and prognosis. However, the accurate and specific quantification of low-abundance ctDNA in serum remains a significant challenge. This study introduced, for the first time, a novel exponential amplification reaction (EXPAR)-assisted CRISPR/Cas12a-mediated ratiometric dual-signal electrochemical biosensor for ultrasensitive and reliable detection of ctDNA. To implement the dual-signal strategy, a signal unit (ssDNA-MB@Fc/UiO-66-NH2) was prepared, consisting of methylene blue-modified ssDNA as the biogate to encapsulate ferrocene signal molecules within UiO-66-NH2 nanocarriers. The presence of target ctDNA KRAS triggered EXPAR amplification, generating numerous activators for Cas12a activation, resulting in the cleavage of ssDNA-P fully complementary to the ssDNA-MB biogate. Due to the inability to form a rigid structure dsDNA (ssDNA-MB/ssDNA-P), the separation of ssDNA-MB biogate from the UiO-66-NH2 surface was hindered by electrostatic interactions. Consequently, the supernatant collected after centrifugation exhibited either no or only a weak presence of Fc and MB signal molecules. Conversely, in the absence of the target ctDNA, the ssDNA-MB biogate was open, leading to the leakage of Fc signal molecules. This clever ratiometric strategy with Cas12a as the "connector", reflecting the concentration of ctDNA KRAS based on the ratio of the current intensities of the two electroactive signal molecules, enhanced detection sensitivity by at least 60-300 times compared to single-signal strategies. Moreover, this strategy demonstrated satisfactory performance in ctDNA detection in complex human serum, highlighting its potential for cancer diagnosis.
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Técnicas Biosensibles , ADN Tumoral Circulante , Técnicas Electroquímicas , Humanos , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Sistemas CRISPR-Cas/genética , ADN de Cadena Simple/química , Límite de Detección , Endodesoxirribonucleasas/química , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Asociadas a CRISPR/química , Proteínas Bacterianas/química , Proteínas Bacterianas/genéticaRESUMEN
The composition and function of the gut microbiota constantly influence health. Disruptions in this delicate balance, termed gut microbiota dysbiosis, have been implicated in various adverse health events. As the largest global epidemic since 1918, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had devastating consequences. While the primary impact of Corona Virus Disease 2019 (COVID-19) has been on the respiratory system, a growing body of research has unveiled the significant involvement of the gastrointestinal tract as well. Emerging evidence underscores notable alterations in the gut microbiome of COVID-19 patients. In addition, the gut microbiome is also characterized by an abundance of opportunistic pathogens, which is related to disease manifestations of COVID-19 patients. The intricate bidirectional interaction between the respiratory mucosa and the gut microbiota, known as the gut-lung axis, emerges as a crucial player in the pathological immune response triggered by SARS-CoV-2. Here, we discuss microbiota-based gut characteristics of COVID-19 patients and the long-term consequences of gut microbiota dysregulation. These insights could potentially transform the development of long-term interventions for COVID-19, offering hope for improved outcomes and enhanced patient recovery.
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Fat (FAT atypical cadherin) and Dchs (Dachsous cadherin-related protein) in adjacent Sertoli:Sertoli, Sertoli:spermatid, and spermatid:spermatid interfaces create an important intercellular bridge whose adhesive function is in turn supported by Fjx1, a nonreceptor Ser/Thr protein kinase. This concept is derived from earlier studies of Drosophila, which has been confirmed in this and earlier reports as well. Herein, we use the approach of knockdown of Fat1 by RNAi using primary cultures of Sertoli cells that mimicked the blood-testis barrier (BTB) in vivo, and a series of coherent experiments including functional assays to monitor the Sertoli cell tight junction (TJ) permeability barrier and a functional in vitro TJ integrity assay to assess the role of Fat1 in the testis. It was shown that planar cell polarity (PCP) protein Fat1 affected Sertoli cell function through its modulation of actin and microtubule cytoskeletal function, altering their polymerization activity through the Fat1/Fjx1 complex. Furthermore, Fat1 is intimately associated with ß-catenin and α-N-catenin, as well as with Prickle 1 of the Vangl1/Prickle 1 complex, another PCP core protein to support intercellular interactions to confer PCP. In summary, these findings support the notion that the Fat:Dchs and the Vangl2:Fzd PCP intercellular bridges are tightly associated with basal ES/TJ structural proteins to stabilize PCP function at the Sertoli:Sertoli, Sertoli:spermatid, and spermatid:spermatid interface to sustain spermatogenesis.
Asunto(s)
Cadherinas , Proteínas del Tejido Nervioso , Células de Sertoli , Animales , Masculino , Ratones , Ratas , beta Catenina/metabolismo , Barrera Hematotesticular/metabolismo , Cadherinas/metabolismo , Polaridad Celular/fisiología , Células Cultivadas , Células de Sertoli/metabolismo , Espermátides/metabolismo , Uniones Estrechas/metabolismoRESUMEN
1,4-BN-doped polycyclic aromatic hydrocarbons (PAHs) have emerged as very promising emitters in organic light-emitting diodes (OLEDs) due to their narrowband emission spectra that may find application in high-definition displays. While considerable research has focused on investigating the properties of these materials, less attention has been placed on their synthetic methodology. Here we developed an efficient synthetic method for 1,4-BN-doped PAHs, which enables sustainable production of narrowband organic emitting materials. By strategically introducing substituents, such as methyl, tert-butyl, phenyl, and chloride, at the C5 position of the 1,3-benzenediamine substrates, we achieved remarkable regioselective borylation in the para-position of the substituted moiety. This approach facilitated the synthesis of a diverse range of 1,4-BN-doped PAHs emitters with good yields and exceptional regioselectivity. The synthetic method demonstrated excellent scalability for large-scale production and enabled late-stage transformation of the borylated products. Mechanistic investigations provided valuable insights into the pivotal roles of electron effect and steric hindrance effect in achieving highly efficient regioselective borylation. Moreover, the outstanding device performance of the synthesized compounds 10 b and 6 z, underscores the practicality and significance of the developed method.