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Terahertz spectroscopy has unique advantages in the study of biological molecules in aqueous solutions. However, water has a strong absorption capability in the terahertz region. Reducing the amount of liquid could decrease interference with the terahertz wave, which may, however, affect the measurement accuracy. Therefore, it is particularly important to balance the amount and water content of liquid samples. In this work, a terahertz metamaterial sensor based on metallic strips is designed, fabricated, and used to detect reverse micelles. An aqueous confinement environment in reverse micelles can improve the signal-to-noise ratio of the terahertz response. Due to "water pool" trapped in reverse micelles, the DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) solution and DOPC emulsion can successfully be identified in intensity by terahertz spectroscopy. Combined with the metamaterial sensor, an obvious frequency shift of 30 GHz can be achieved to distinguish the DOPC emulsion (5%) from the DOPC solution. This approach may provide a potential way for improving the sensitivity of detecting trace elements in a buffer solution, thus offering a valuable toolkit toward bioanalytical applications.
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Micelas , Espectroscopía de Terahertz , Técnicas Biosensibles , Metales/química , Fosfatidilcolinas/química , Agua/químicaRESUMEN
Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.
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Factor de Transcripción CDX2 , Proliferación Celular , Autorrenovación de las Células , Histona Acetiltransferasas , Trofoblastos , Trofoblastos/metabolismo , Factor de Transcripción CDX2/metabolismo , Factor de Transcripción CDX2/genética , Animales , Femenino , Humanos , Ratones , Embarazo , Autorrenovación de las Células/genética , Histona Acetiltransferasas/metabolismo , Histona Acetiltransferasas/genética , Aborto Habitual/metabolismo , Aborto Habitual/genética , Ratones Noqueados , Histonas/metabolismo , Diferenciación Celular , Placentación/genéticaRESUMEN
Aquaporin 5 (AQP5) has been shown to have a pro-carcinogenic effect in numerous types of malignancies. This research intends to investigate the role and the molecular mechanism of AQP5 on enriched gastric cancer stem cells (GCSCs). Methods: Immunohistochemistry, western blot (WB), and RT-qPCR techniques were employed to identify the presence of AQP5 in gastric cancer (GC) and the neighboring paracancerous tissues. Additionally, a statistical analysis was conducted to determine the correlation between AQP5 expression and the pathological and histological parameters. Furthermore, the study aimed to assess the predictive value of AQP5 expression in long-term survival after GC surgery. GCSCs were enriched using the serum-free culture method. The expression of AQP5 in enriched GCSCs was explored using RT-qPCR and WB. Plate cloning, transwell, WB, RT-qPCR, and the sphere-forming assay were utilized to monitor the proliferation, migration, and self-renewal capability of GCSCs after AQP5 knockdown. WB and Immunofluorescence for Detecting the Effect of AQP5 on Autophagy. WB, RT-qPCR, and other experiments were used for in-depth investigation of the potential molecular regulatory mechanism of AQP5 in GC. Results: AQP5 was highly expressed in GC tissues and GC cells, and overexpression of AQP5 was associated with lymph node metastasis, increased tumor size, and low 5-year postoperative survival in GC patients; other studies have shown that the AQP5 was highly expressed in GCSCs. Knockdown of AQP5 suppressed tumorigenesis in vivo and inhibited the proliferative, migratory, and self-renewal capability of GCSCs. It was also found that AQP5 could activate the autophagy phenomenon of GCSCs, and mechanistically, we found that AQP5 could regulate TRPV4 to affect the self-renewal ability of GCSCs. Conclusion: AQP5 can be further explored for GC therapy, as it has shown a significant impact on the self-renewal capability of GCSCs, which prevents GC progression.
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Lead-free halide double perovskite Cs2AgInCl6 has been extensively studied in recent years due to the lead toxicity and poor stability of common lead halide perovskites. In this study, sodium (Na+) and bismuth (Bi3+) doped into Cs2AgInCl6 double perovskite, then Cs2Ag1-xNaxIn1 - yBiyCl6 films with broadband warm-yellow emissions were achieved by the blade coating method. Herein, Na and Bi content were changed as variables at a series of parameter optimization experiments, respectively. In the Cs2Ag1-xNaxIn1 - yBiyCl6 systems, Na+ broke the parity-forbidden transition of Cs2AgInCl6, and Bi3+ suppressed non-radiative recombination. The partial replacement of Ag+ with Na+ ions and doping with Bi3+ cations were crucial for increasing the intensity of the PL emission. The experimental results showed that the photoluminescence quantum yield of the Cs2Ag0.4Na0.6In0.8Bi0.2Cl6 film was 66.38%, which was the highest data among all samples. It demonstrated remarkable stability under heat and ultraviolet conditions. After five thermal cycles, the PL intensity of the Cs2Ag0.4Na0.6In0.8Bi0.2Cl6 film is only reduced to approximately 5.7% of the initial value. After 720 h continuous ultraviolet irradiation, there occurred 31.9% emission decay of the film.
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In females, the pathophysiological mechanism of poor ovarian response (POR) is not fully understood. Considering the expression level of p62 was significantly reduced in the granulosa cells (GCs) of POR patients, this study focused on identifying the role of the selective autophagy receptor p62 in conducting the effect of follicle-stimulating hormone (FSH) on antral follicles (AFs) formation in female mice. The results showed that p62 in GCs was FSH responsive and that its level increased to a peak and then decreased time-dependently either in ovaries or in GCs after gonadotropin induction in vivo. GC-specific deletion of p62 resulted in subfertility, a significantly reduced number of AFs and irregular estrous cycles, which were same as pathophysiological symptom of POR. By conducting mass spectrum analysis, we found the ubiquitination of proteins was decreased, and autophagic flux was blocked in GCs. Specifically, the level of nonubiquitinated Wilms tumor 1 homolog (WT1), a transcription factor and negative controller of GC differentiation, increased steadily. Co-IP results showed that p62 deletion increased the level of ubiquitin-specific peptidase 5 (USP5), which blocked the ubiquitination of WT1. Furthermore, a joint analysis of RNA-seq and the spatial transcriptome sequencing data showed the expression of steroid metabolic genes and FSH receptors pivotal for GCs differentiation decreased unanimously. Accordingly, the accumulation of WT1 in GCs deficient of p62 decreased steroid hormone levels and reduced FSH responsiveness, while the availability of p62 in GCs simultaneously ensured the degradation of WT1 through the ubiquitinâproteasome system and autophagolysosomal system. Therefore, p62 in GCs participates in GC differentiation and AF formation in FSH induction by dynamically controlling the degradation of WT1. The findings of the study contributes to further study the pathology of POR.
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Hormona Folículo Estimulante , Células de la Granulosa , Folículo Ovárico , Proteína Sequestosoma-1 , Ubiquitinación , Proteínas WT1 , Animales , Hormona Folículo Estimulante/metabolismo , Hormona Folículo Estimulante/farmacología , Femenino , Proteínas WT1/metabolismo , Proteínas WT1/genética , Ratones , Folículo Ovárico/metabolismo , Folículo Ovárico/efectos de los fármacos , Células de la Granulosa/metabolismo , Células de la Granulosa/efectos de los fármacos , Proteína Sequestosoma-1/metabolismo , Proteína Sequestosoma-1/genética , Ratones Endogámicos C57BL , Autofagia/efectos de los fármacos , Proteolisis/efectos de los fármacos , Humanos , Ratones NoqueadosRESUMEN
Studies have shown that the prostaglandin (PG) family acts as allergic inflammatory mediator in malignant diseases. Furthermore, prostaglandin E2 (PGE2) and its related receptors, as well as the prostaglandin D2 (PGD2)/PGD2 receptor (PTGDR2), play irreplaceable roles in tumorigenesis and anti-tumor therapy. Several experiments have demonstrated that PGD2 signaling through PTGDR2 not only directly inhibits cancer cell survival, proliferation, and migration but also reduces resistance towards conventional chemotherapeutic agents. Recent studies from our and other laboratories have shown that PGD2, its ligands, and related metabolites can significantly alter the tumor microenvironment (TME) by promoting the secretion of chemokines and cytokines, thereby inhibiting tumor progression. Additionally, reduced PGD2 expression has been associated with poor prognosis in patients with gastric, breast, lung, and pancreatic cancers, validating the preclinical findings and their clinical relevance. This review focuses on the current understanding of PGD2/PTGDR2 expression patterns and biological activity in cancer, proposing questions to guide the assessment of PGD2 and its receptors as potential targets for effective cancer therapies.
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BACKGROUND: Many studies have documented the protective effects of regulating macrophage M1/M2 polarization in inflammatory diseases characterized by their imbalance state. In pathological diseases associated with inflammation, mesenchymal stem cells (MSCs) regulate macrophages, thereby having anti-inflammatory and tissue regenerative effects. Exosomes have been suggested as an alternative mechanism that underlies the paracrine function of MSCs. Thus, this study explored the anti-inflammatory impact of human umbilical cord MSCssecreted exosomes (hucMSCs-EX) by influencing macrophage polarization in normal and inflammatory environments in vitro. METHODS: In this study, hucMSCs-conditioned medium (hucMSCs-CM) and hucMSCs- EX were used to treat RAW264.7 macrophages with or without LPS. The expressions of TNF- α, IL-10, IL-6, IL-1ß, and Arg-1 were quantified by qPCR. The expressions of IL-6 and IL-10 were evaluated by ELISAs. Western blots (WB) were performed to observe the expressions of CD206, NF-κB P65, NF-κB p-p65, p-STAT3, STAT3, and NF-κB phosphorylation. The number of cells expressing CD206 and the fluorescence intensity were measured via flow cytometry (FC) and immunofluorescence staining. Cell propagation and migration were examined via MTT and transwell assays, respectively. RESULTS: The inhibition of LPS-induced inflammatory polarization by hucMSCs-EX or hucMSCs- CM led to increases in IL-10 and arginase (Arg) levels and decreases in those of IL-6 and TNF-α. Moreover, hucMSCs-EX enhanced the CD206 expression in RAW264.7 cells and accelerated the propagation and migration of LPS-induced cells. The suppressive impact of hucMSCs-EX on the LPS-induced phenotypic polarization of M1 macrophages was linked with the reduction of NF-κB signaling. They stimulated the transition of M2 macrophages by enhancing the activity of STAT3 in RAW264.7 cells. CONCLUSION: This study indicated that hucMSCs-EX enhances the macrophage transition into the M2 phenotype by inhibiting the NF-κB p65 axis and stimulating that of STAT3.
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Aim: To evaluate a novel antisense oligonucleotide drug targeting human IGF-1R in preclinical and phase I studies of liver cancer. Materials & methods: The tolerability and safety of an investigational new drug were evaluated in a dose-escalation trial involving 17 patients with advanced liver cancer after preclinical assessment of pharmacokinetics and pharmacodynamics. Results: The drug exposure levels in the phase I trial were determined by the in vivo efficacy with pharmacokinetics evaluation in rats and rhesus monkeys. This clinical study showed that the maximum tolerated dose was 3.96 mg/kg, and the dose-limiting toxicity dose was 4.4 mg/kg. Conclusion: The drug was safe and tolerable in patients with advanced liver cancer.Clinical Trial Registration: ChiCTR2100044235 (www.chictr.org.cn).
CT102 is a potential new drug for liver cancer treatment. It belongs to a new form of medicine using gene therapy technology called antisense oligonucleotides. There are some antisense oligonucleotides approved for treating rare diseases. This study evaluated the antitumor effect, metabolism and safety of CT102 in preclinical and clinical trials. The results showed that CT102 could inhibit tumor growth in mice with liver cancer and maintain high levels in the liver. It was found that CT102 was safe and tolerable in patients with advanced liver cancer. This suggests that CT102 has therapeutic potential for liver cancer treatment. The good tolerability and safety of CT102 in patients supports further studies on liver cancer treatment.
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AIMS: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections poses a significant threat to human health, necessitating urgent development of new antimicrobial agents. Silver nanoparticles (AgNPs), which are among the most widely used engineered nanomaterials, have been extensively studied. However, the impact of AgNPs on CRKP and the potential for drug resistance development remain inadequately explored. METHODS AND RESULTS: In this study, broth dilution method was used to determine the minimum inhibitory concentration (MIC) was determined using the broth dilution method. Results indicated MIC values of 93.1 ± 193.3 µg ml-1 for AgNPs, 2.3 ± 5.1 µg ml-1 for AgNO3, and 25.1 ± 48.3 µg ml-1 for imipenem (IMI). The combined inhibitory effect of AgNPs and IMI on CRKP was assessed using the checkerboard method. Moreover, after 6-20 generations of continuous culture, the MIC value of AgNPs increased 2-fold. Compared to IMI, resistance of Kl. pneumoniae to AgNPs developed more slowly, with a higher fold increase in MIC observed after 20 generations. Whole-genome sequencing revealed four nonsynonymous single nucleotide polymorphism mutations in CRKP after 20 generations of AgNP treatment. CONCLUSION: We have demonstrated that AgNPs significantly inhibit CRKP isolates and enhance the antibacterial activity of imipenem against Kl. pneumoniae. Although the development of AgNP resistance is gradual, continued efforts are necessary for monitoring and studying the mechanisms of AgNP resistance.
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Antibacterianos , Carbapenémicos , Imipenem , Klebsiella pneumoniae , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Plata , Imipenem/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Plata/farmacología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , Humanos , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Farmacorresistencia Bacteriana/genéticaRESUMEN
The conventional fabrication of bulk van der Waals (vdW) materials requires a temperature above 1,000 °C to sinter from the corresponding particulates. Here we report the near-room-temperature densification (for example, â¼45 °C for 10 min) of two-dimensional nanosheets to form strong bulk materials with a porosity of <0.1%, which are mechanically stronger than the conventionally made ones. The mechanistic study shows that the water-mediated activation of van der Waals interactions accounts for the strong and dense bulk materials. Initially, water adsorbed on two-dimensional nanosheets lubricates and promotes alignment. The subsequent extrusion closes the gaps between the aligned nanosheets and densifies them into strong bulk materials. Water extrusion also generates stresses that increase with moulding temperature, and too high a temperature causes intersheet misalignment; therefore, a near-room-temperature moulding process is favoured. This technique provides an energy-efficient alternative to design a wide range of dense bulk van der Waals materials with tailored compositions and properties.
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Mycotoxin contamination is widespread in plants and herbs, posing serious threats to the consumer and human health. Of them, alternariol (AOH) has attracted great attention as an "emerging" mycotoxin in medicinal herbs. However, a specific and high-throughput extraction method for AOH is currently lacking. Thus, developing an efficient pre-treatment technique for AOH detection is extremely vital. Here, a novel automated magnetic solid-phase extraction method was proposed for the highly efficient extraction of AOH. Combining the aptamer-functionalized magnetic nanoparticles (AMNPs) and the automatic purification instrument, AOH could be extracted in medicinal herbs in high throughput (20 samples) and a short time (30 min). The main parameters affecting extraction were optimized, and the method was finally carried out by incubation AMNPs with 3 mL of sample solution for 10 min, and then desorption in 75% methanol for liquid-phase detection. Under optimal conditions, good reproducibility, stability, and selectivity were realized with an adsorption capacity of 550.84 ng/mg. AOH extraction in three edible herbs showed good resistance to matrix interference with recovery rates from 86% to 111%. In combination with AMNPs and the automatic purification instrument, high-throughput and labor-free extraction of AOH in different complex matrices was achieved, which could be extended in other complex matrices.
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Lactonas , Nanopartículas de Magnetita , Micotoxinas , Plantas Medicinales , Humanos , Cromatografía Líquida de Alta Presión/métodos , Reproducibilidad de los Resultados , Micotoxinas/análisis , Oligonucleótidos , Extracción en Fase Sólida/métodosRESUMEN
In a growing follicle, the survival and maturation of the oocyte largely depend on support from somatic cells to facilitate FSH-induced mutual signaling and chemical communication. Although apoptosis and autophagy in somatic cells are involved in the process of FSH-induced follicular development, the underlying mechanisms require substantial study. According to our study, along with FSH-induced antral follicles (AFs) formation, both lysine-specific demethylase 1 (LSD1) protein levels and autophagy increased simultaneously in granulosa cells (GCs) in a time-dependent manner, we therefore evaluated the importance of LSD1 upon facilitating the formation of AFs correlated to autophagy in GCs. Conditional knockout of Lsd1 in GCs resulted in significantly decreased AF number and subfertility in females, accompanied by marked suppression of the autophagy in GCs. On the one hand, depletion of Lsd1 resulted in accumulation of Wilms tumor 1 homolog (WT1), at both the protein and mRNA levels. WT1 prevented the expression of FSH receptor (Fshr) in GCs and thus reduced the responsiveness of the secondary follicles to FSH induction. On the other hand, depletion of LSD1 resulted in suppressed level of autophagy by upregulation of ATG16L2 in GCs. We finally approved that LSD1 contributed to these sequential activities in GCs through its H3K4me2 demethylase activity. Therefore, the importance of LSD1 in GCs is attributable to its roles in both accelerating autophagy and suppressing WT1 expression to ensure the responsiveness of GCs to FSH during AFs formation.
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Células de la Granulosa , Folículo Ovárico , Femenino , Autofagia/genética , Hormona Folículo Estimulante/farmacología , Células de la Granulosa/metabolismo , Folículo Ovárico/metabolismo , Transducción de Señal , Animales , RatonesRESUMEN
Rationale: Premature ovarian insufficiency (POI) is an accelerated reduction in ovarian function inducing infertility. Folliculogenesis defects have been reported to trigger POI as a consequence of ovulation failure. However, the underlying mechanisms remain unclear due to the genetic complexity and heterogeneity of POI. Methods: We used whole genome sequencing (WGS), conditional knockout mouse models combined with laser capture microdissection (LCM), and RNA/ChIP sequencing to analyze the crucial roles of polycomb repressive complex 1 (PRC1) in clinical POI and mammalian folliculogenesis. Results: A deletion mutation of MEL18, the key component of PRC1, was identified in a 17-year-old patient. However, deleting Mel18 in granulosa cells (GCs) did not induce infertility until its homolog, Bmi1, was deleted simultaneously. Double deficiency of BMI1/MEL18 eliminated PRC1 catalytic activity, upregulating cyclin-dependent kinase inhibitors (CDKIs) and thus blocking GC proliferation during primary-to-secondary follicle transition. This defect led to damaged intercellular crosstalk, eventually resulting in gonadotropin response failure and infertility. Conclusions: Our findings highlighted the pivotal role of PRC1 as an epigenetic regulator of gene transcription networks in GC proliferation during early folliculogenesis. In the future, a better understanding of molecular details of PRC1 structural and functional abnormalities may contribute to POI diagnosis and therapeutic options.
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Infertilidad , Insuficiencia Ovárica Primaria , Adolescente , Animales , Femenino , Humanos , Ratones , Núcleo Celular , Proliferación Celular/genética , Mamíferos , Complejo Represivo Polycomb 1/genética , Insuficiencia Ovárica Primaria/genética , Reproducción , Modelos Animales de Enfermedad , Ratones NoqueadosRESUMEN
Silver nanoparticles (AgNPs) have wide clinical applications because of their excellent antibacterial properties; however, they can cause liver inflammation in animals. Macrophages are among the main cells mediating inflammation and are also responsible for the phagocytosis of nanomaterials. The NLRP3 inflammasome is a major mechanism of inflammation, and its activation both induces cytokine release and triggers inflammatory cell death (i.e., pyroptosis). In previous studies, we demonstrated that mitophagy activation plays a protective role against AgNP-induced hepatotoxicity. However, the exact molecular mechanisms underlying these processes are not fully understood. In this study, we demonstrate that AgNP exposure induces NLRP3 inflammasome activation, mitochondrial damage and pyroptosis in vivo and in vitro. NLRP3 silencing or inhibiting mitochondrial reactive oxygen species (ROS) overproduction reduces PINK1-Parkin-mediated mitophagy. Meanwhile, the inhibition of mitophagy ROS production, mitochondrial, NLRP3-mediated inflammation, and pyroptosis in RAW264.7 cells were more pronounced than in the control group. These results suggest that PINK1-Parkin-mediated mitophagy plays a protective role by reducing AgNP-induced mitochondrial ROS and subsequent NLRP3 inflammasome activation.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Nanopartículas del Metal , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Nanopartículas del Metal/toxicidad , Plata/toxicidad , Mitofagia , Inflamación , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas QuinasasRESUMEN
Zero-dimensional pores spanning only a few angstroms in size in two-dimensional materials such as graphene are some of the most promising systems for designing ion-ion selective membranes. However, the key challenge in the field is that so far a crack-free macroscopic graphene membrane for ion-ion separation has not been realized. Further, methods to tune the pores in the Å-regime to achieve a large ion-ion selectivity from the graphene pore have not been realized. Herein, we report an Å-scale pore size tuning tool for single layer graphene, which incorporates a high density of ion-ion selective pores between 3.5 and 8.5 Å while minimizing the nonselective pores above 10 Å. These pores impose a strong confinement for ions, which results in extremely high selectivity from centimeter-scale porous graphene between monovalent and bivalent ions and near complete blockage of ions with the hydration diameter, DH, greater than 9.0 Å. The ion diffusion study reveals the presence of an energy barrier corresponding to partial dehydration of ions with the barrier increasing with DH. We observe a reversal of K+/Li+ selectivity at elevated temperature and attribute this to the relative size of the dehydrated ions. These results underscore the promise of porous two-dimensional materials for solute-solute separation when Å-scale pores can be incorporated in a precise manner.
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OBJECTIVE: To study the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow of patients with fever of unknown origin. METHODS: A total of 465 patients with fever of unknown origin in our hospital from January 2019 to December 2021 were selected as the research objects, which was to reviewed retrospectively the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow. RESULTS: The positive rates of hemophagocytes detected in the three lines decreased group, the two lines decreased group, the one line decreased group, normal group of the three lines and at least one of the three lines increased group were 86.4%, 62.1%, 38.3%, 34.6% and 33.3%, respectively. The number of hemophagocytes per unit area in the three lines decreased group was significantly higher than that in the other four groups ( P < 0.001). The number of hemophagocytes per unit area in the two lines decreased group was higher than that in the one line decreased group, normal group of three lines and at least one of the three lines increased group ( P < 0.01). There was no significant difference in the number of hemophagocytes per unit area between the group with a decreased number of one line and the other two groups with a normal number of three lines and the group with at least one increased number of three lines (P >0.05). The missed rates of hemophagocytes in the five groups were 15.78%, 22.03%, 62.22%, 77.78% and 53.84%, respectively. CONCLUSION: For patients with fever of unknown origin, especially those with obvious decrease in the number of three lines and two lines in peripheral blood cells, which should pay attention to the detection of hemophagocytes in bone marrow. Meanwhile, if the number of three lines was normal even at least one of the three lines increased, the presence of hemophagocytes in the bone marrow slice should be also carefully observed.
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Médula Ósea , Fiebre de Origen Desconocido , Humanos , Estudios Retrospectivos , Células Sanguíneas , Células de la Médula ÓseaRESUMEN
Improving the nitrogen and phosphorus removal rates and efficiently controlling membrane fouling are the keys to fully exploiting the applicability of anaerobic membrane bioreactor (AnMBR) process in high-concentration wastewater treatment. To that purpose, an integrated reactor composed of an anaerobic ceramic membrane bioreactor and N anaerobic fluidized bed (AnCMBR-AFB) was built and pollutant removal efficiency, nitrogen and phosphorus recovery characteristics, and membrane pollution features of this integrated reactor were investigated. The results revealed that the integrated reactor had good pollutant removal efficiency, with turbidity, chromaticity, and UV254 average values of the effluent being 0.470 NTU, 0.011 A, and 0.057 cm-1, respectively, and the average CODCr removal rate was 80%. The nitrogen and phosphorus recoveries were significantly higher than the nitrogen and phosphorus removal rates of conventional AnMBR at 23.20 ± 1.17% and 43.34 ± 1.54%, respectively. Microscopic analysis revealed the formation of magnesium ammonium phosphate (MAP) crystals on the carrier's surface, and friction between the carrier and the membrane surface could delay membrane fouling while allowing the contaminated membrane surface to retain significant roughness. Membrane fouling was mostly brought on by amides and saturated hydrocarbons, and inorganic metal ions also played a role to some extent.
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Contaminantes Ambientales , Aguas Residuales , Eliminación de Residuos Líquidos/métodos , Nitrógeno , Fósforo , Anaerobiosis , Reactores Biológicos , Membranas Artificiales , Aguas del AlcantarilladoRESUMEN
Nonobstructive azoospermia is the leading cause of male infertility. Abnormal levels of transmembrane protein 225 (TMEM225), a testis-specific protein, have been found in patients with nonobstructive azoospermia, suggesting that TMEM225 plays an essential role in male fertility. Here, we generated a Tmem225 KO mouse model to explore the function and mechanism of TMEM225 in male reproduction. Male Tmem225 KO mice were infertile. Surprisingly, Tmem225 deletion did not affect spermatogenesis, but TMEM225-null sperm exhibited abnormalities during epididymal maturation, resulting in reduced sperm motility and an abnormal hairpin-loop configuration. Furthermore, proteomics analyses of cauda sperm revealed that signaling pathways related to mitochondrial function, the glycolytic pathway, and sperm flagellar morphology were abnormal in Tmem225 KO sperm, and spermatozoa lacking TMEM225 exhibited high reactive oxygen species levels, reduced motility, and flagellar folding, leading to typical asthenospermia. These findings suggest that testicular TMEM225 may control the sperm maturation process by regulating the expression of proteins related to mitochondrial function, glycolysis, and sperm flagellar morphology in epididymal spermatozoa.
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Azoospermia , Humanos , Masculino , Ratones , Animales , Azoospermia/metabolismo , Maduración del Esperma , Motilidad Espermática , Semen , Espermatozoides/metabolismo , Testículo/metabolismo , Espermatogénesis , Fertilidad , Ratones NoqueadosRESUMEN
To investigate the effects and underlying molecular mechanisms of the interaction between the non-structural protein 1 (NS1) and nucleolar and coiled-body phosphoprotein 1 (NOLC1) on rRNA synthesis through nucleolar telomeric repeat-binding factor 2 (TRF2) under nucleolar stress in avian influenza A virus infection. The analysis of TRF2 ties into the exploration of ribosomal protein L11 (RPL11) and mouse double minute 2 (MDM2) because TRF2 has been found to interact with NOLC1, and the RPL11-MDM2 pathway plays an important role in nucleolar regulation and cellular processes. Both human embryonic kidney 293T cells and human lung adenocarcinoma A549 cells were transfected with the plasmids pCAGGS-HA and pCAGGS-HA-NS1, respectively. In addition, A549 cells were transfected with the plasmids pEGFP-N1, pEGFP-N1-NS1, and pDsRed2-N1-TRF2. The cell cycle was detected by flow cytometry, and coimmunoprecipitation was applied to examine the interactions between different proteins. The effect of NS1 on TRF2 was detected by immunoprecipitation, and the colocalization of NOLC1 and TRF2 or NS1 and TRF2 was visualized by immunofluorescence. Quantitative real-time PCR was conducted to detect the expression of the TRF2 and p21. There is a strong interaction between NOLC1 and TRF2, and the colocalization of NOLC1 and TRF2 in the nucleus. The protein expression of NOLC1 in A549-HA-NS1 cells was lower than that in A549-HA cells, which was accompanied by the upregulated protein expression of p53 in A549-HA-NS1 cells (all p < .05). TRF2 was scattered throughout the nucleus without clear nucleolar aggregation. RPL11 specifically interacted with MDM2 in the NS1 group, and expression of the p21 gene was significantly increased in the HA-NS1 group compared with the HA group (p < .01). NS1 protein can lead to the reduced aggregation of TRF2 in the nucleolus, inhibition of rRNA expression, and cell cycle blockade by interfering with the NOLC1 protein and generating nucleolar stress.
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Abrasive suspension jet (ASJ), an accurate cold-cutting technology, can address traditional processing issues relating to carbon-fiber-reinforced plastics (CFRPs) like tool wear, interlayer delamination, large heat-affected zone, and low surface roughness. This study employed the use of an ASJ to cut CFRPs and an ultra-depth optical microscope to scan the cut surface to analyze interlayer delamination, surface roughness, kerf taper, and shoulder damage. Regression analysis was conducted to establish a prediction model for cutting quality based on surface roughness, kerf taper, and shoulder damage. Various types of CFRP cutting quality were analyzed using jet parameters. It was found that the use of ASJ to process CFRP results in the following defects: The range of surface roughness variation is from 0.112 µm to 0.144 µm. Surface roughness is most influenced by stand-off distance, followed by traverse speed and jet pressure. The range of kerf taper variation is from 4.737° to 10.1°. Kerf taper is most influenced by stand-off distance, followed by jet pressure and traverse speed. The range of shoulder damage variation is from 3.384 µm2 to 10 µm2. Shoulder damage is most influenced by jet pressure, followed by traverse speed and stand-off distance. A prediction model for cutting quality was developed based on surface roughness, kerf taper, and shoulder damage, providing data support for ASJ cutting of CFRPs. The optimal parameter combination is a stand-off distance of 1 mm, a jet pressure of 30 MPa, and a traverse speed of 30 mm/min.