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1.
Am J Physiol Cell Physiol ; 327(2): C291-C309, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38826136

RESUMO

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.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Proteínas Quinases JNK Ativadas por Mitógeno , Células de Sertoli , Fluorocarbonos/toxicidade , Ácidos Alcanossulfônicos/toxicidade , Masculino , Animais , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , RNA-Seq , Barreira Hematotesticular/efeitos dos fármacos , Barreira Hematotesticular/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Células Cultivadas , Camundongos , Ratos , Ratos Sprague-Dawley
2.
Anal Chem ; 96(18): 6930-6939, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38652001

RESUMO

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.


Assuntos
Técnicas Biossensoriais , DNA Tumoral Circulante , Técnicas Eletroquímicas , Humanos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Sistemas CRISPR-Cas/genética , DNA de Cadeia Simples/química , Limite de Detecção , Endodesoxirribonucleases/química , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Associadas a CRISPR/química , Proteínas de Bactérias/química , Proteínas de Bactérias/genética
3.
Opt Express ; 32(6): 9397-9404, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571175

RESUMO

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.

4.
Opt Express ; 32(2): 2124-2131, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297749

RESUMO

This paper provides a method to effectively suppress the severe ASE self-saturation when achieving high repetition frequency tunability with high output power and narrow pulse width in active Q-switched all-fiber lasers. By studying the regularity of the system's multi-stable state, we first ensured that the laser system operated in a steady state. Then output avoids uneven distribution of pulse energy or missing pulses due to period bifurcation state or chaos state. By adding multiple gain sub-rings within the cavity, the sub-ring structure itself indirectly mitigates the ASE self-saturation while smoothing the pulse. The method will avoid the severe power loss caused by traditional smoothing methods by adjusting the AOM rising edge time. It will also avoid lowering the ASE lasing threshold at high repetition frequency. Meanwhile, the intra-cavity backward ASE can be effectively absorbed by inserting the gain fiber in the sub-rings to directly mitigate the ASE self-saturation. The system's continuously adjustable repetition frequency can be as high as over 300 kHz. It ensures that output power above the watt level and a < 0.2 nm narrow bandwidth can be maintained while tuning the repetition frequency. The narrowest smoothing pulse width of 28 ns has been reached.

5.
Cytokine ; 173: 156415, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37952311

RESUMO

BACKGROUND: Endothelial nitric oxide (NO) produced by endothelial Nitric Oxide Synthase (eNOS) can promote the expression of pro-angiogenic cytokines and is favorable for angiogenesis. However, the relationship between NOS3 gene polymorphisms and genetic susceptibility to congenital heart disease (CHD) was still unclear. METHODS: We searched five databases including Pubmed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang, to find all studies on NOS3 gene polymorphisms and CHD. Rstudio was used to merge the data included in the study to obtain OR, 95%CI, and forest plots. RESULTS: Five relevant literatures were included, including three sites of NOS3 gene, rs1799983 (G894T), rs2070744 (T-786C), and rs7830 (G10T). Several models including the homozygous model of rs1799983 (G894T) gene polymorphism (TT VS GG: OR = 1.602, 95%CI: 1.098 âˆ¼ 2.337, P = 0.027), rs7830 (G10T) gene polymorphism allele model (A VS C: OR = 1.171, 95%CI: 1.029 âˆ¼ 1.333, P = 0.017), homozygous model (AA VS CC: OR = 1.474, 95%CI: 1.122 âˆ¼ 1.936, P = 0.005) and implicit model (AA VS CC + AC: OR = 1.451, 95%CI: 1.133 âˆ¼ 1.859, P = 0.003) indicated that there was a correlation. The results of the combined analysis of each gene model of rs2070744 (T-786C) gene polymorphism sites were not statistically significant, and their P values were all>0.05. CONCLUSION: rs1799983 (G894T) and rs7830 (G10T) polymorphic sites might play a role in the susceptibility of sporadic congenital heart disease and increase the risk of CHD. Yet, it is still necessary to expand the sample size and conduct more prospective/retrospective studies to confirm whether the rs2070744 (T-786C) polymorphism tended to increase the incidence of CHD.


Assuntos
Cardiopatias Congênitas , Óxido Nítrico Sintase Tipo III , Humanos , Óxido Nítrico Sintase Tipo III/genética , Estudos Retrospectivos , Estudos Prospectivos , Polimorfismo Genético , Predisposição Genética para Doença , Estudos de Casos e Controles , Cardiopatias Congênitas/genética , Polimorfismo de Nucleotídeo Único/genética , Genótipo
6.
Org Biomol Chem ; 22(8): 1654-1661, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38295370

RESUMO

A detailed theoretical mechanistic investigation on chiral phosphoric acid (CPA)-catalyzed Paal-Knorr reactions, in the presence and absence of a Lewis acid, for the synthesis of N-N axially chiral atropisomers is described herein. Density functional theory (DFT) studies elucidate that in the absence of a Lewis acid, CPA catalyzes both the initial cyclization and the subsequent dehydroxylation processes, ambiguously identified as the rate-determining step in the reactions. Conversely, when a Lewis acid participates in the reaction, it facilitates the second dehydroxylation process with a significantly lower energy barrier, thereby reversing the rate-determining step to the initial cyclization step. It is noteworthy that in the case of N-aminoindoles, both the S-configurational transition state TS1 in the cyclization step and TS2 in the dehydroxylation process are favourable. In contrast, for the synthesis of a bispyrrole, the R-configurational TS1 and the S-configurational TS2 are dominant. Therefore, the enantiodivergence observed is essentially induced by the reversed rate-determining steps in the absence or presence of a Lewis acid in the case of a bispyrrole. Furthermore, the non-covalent interaction (NCI) and atoms-in-molecules (AIM) analysis of the TS structures reveal that the non-covalent interactions play a pivotal role in determining the enantiodivergence observed in these reactions.

7.
Ecotoxicol Environ Saf ; 282: 116685, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38971096

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Dieta , Fertilização in vitro , Material Particulado , Feminino , Humanos , Material Particulado/análise , Adulto , Gravidez , Dieta/estatística & dados numéricos , Estudos Prospectivos , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Exposição Materna/estatística & dados numéricos , Masculino , Padrões Dietéticos
8.
Ecotoxicol Environ Saf ; 279: 116502, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38788563

RESUMO

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 µg/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 640 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 160 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.


Assuntos
Barreira Hematotesticular , Citoesqueleto , Diterpenos , Compostos de Epóxi , Fenantrenos , Proteínas Proto-Oncogênicas c-akt , Células de Sertoli , Transdução de Sinais , Serina-Treonina Quinases TOR , Testículo , Masculino , Animais , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/patologia , Diterpenos/toxicidade , Fenantrenos/toxicidade , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Compostos de Epóxi/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Barreira Hematotesticular/efeitos dos fármacos , Barreira Hematotesticular/patologia , Citoesqueleto/efeitos dos fármacos , Ratos , Vacúolos/efeitos dos fármacos , Ratos Sprague-Dawley
9.
Mikrochim Acta ; 191(8): 470, 2024 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023769

RESUMO

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.


Assuntos
Sistemas CRISPR-Cas , MicroRNAs , MicroRNAs/análise , MicroRNAs/sangue , MicroRNAs/genética , Humanos , Sistemas CRISPR-Cas/genética , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase/métodos , Proteínas de Bactérias , Endodesoxirribonucleases , Proteínas Associadas a CRISPR
10.
Int J Mol Sci ; 25(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38338707

RESUMO

Acute colitis is a complex disease that can lead to dysregulation of the gut flora, inducing more complex parenteral diseases. Dandelion polysaccharides (DPSs) may have potential preventive and therapeutic effects on enteritis. In this study, LPS was used to induce enteritis and VC was used as a positive drug control to explore the preventive and therapeutic effects of DPS on enteritis. The results showed that DPS could repair the intestinal barrier, down-regulate the expression of TNF-α, IL-6, IL-1ß, and other pro-inflammatory factors, up-regulate the expression of IL-22 anti-inflammatory factor, improve the antioxidant capacity of the body, and improve the structure of intestinal flora. It is proved that DPS can effectively prevent and treat LPS-induced acute enteritis and play a positive role in promoting intestinal health.


Assuntos
Enterite , Microbioma Gastrointestinal , Taraxacum , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Lipopolissacarídeos , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Inflamação
11.
Angew Chem Int Ed Engl ; 63(18): e202402020, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38385590

RESUMO

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.

12.
Opt Express ; 31(26): 43125-43134, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38178414

RESUMO

We demonstrate a single-stage all-fiber nanosecond amplifier with a total average power of greater than 1.4 kW by employing what we believe to be a novel multi-cavity passively Q-switched fiber laser as the seed laser. The multi-cavity seed laser adopts a piece of Yb-doped fiber (YDF) as saturable absorber (SA), and it includes two external cavities resonating at 1030 nm and an internal cavity working at 1064 nm, respectively. Using such a scheme, a stable dual-channel laser output with a total average power of >35 W, a pulse width of 45 ns, and an optical conversion efficiency of 72% operating at 1064 nm is achieved. By power scaling the multi-cavity seed laser, a dual-channel single-stage nanosecond amplifier is obtained with a single-port average power of exceeding 700 W and a pulse energy of about 7.3 mJ. To the best of our knowledge, this work is the highest average power and optical conversion efficiency for passively Q-switched all-fiber laser employing SA fiber, and the highest average power for a single-stage all-fiber nanosecond amplifier.

13.
Microbiome Res Rep ; 3(1): 7, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455085

RESUMO

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.

14.
Foods ; 13(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38672883

RESUMO

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.

15.
Reprod Biol ; 24(1): 100846, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160586

RESUMO

Perfluorooctanesulfonate or perfluorooctane sulfonic acid (PFOS), a type of perfluorinated compound, is mainly found in consumer products. Exposure to PFOS could cause male reproductive toxicity by causing injury to the blood-testis barrier (BTB). However, the specific mechanisms through which PFOS affects male reproduction remain unclear. The mammalian target of rapamycin (mTOR) is a vital protein kinase that is believed to be a central regulator of autophagy. In this study, we established in vivo and in vitro models to explore the effects of PFOS on the BTB, autophagy, and the regulatory role of the mTOR signaling pathway. Adult mice were developmentally exposed to 0, 0.5, 5, and 10 mg/kg/day PFOS for five weeks. Thereafter, their testicular morphology, sperm counts, serum testosterone, expression of BTB-related proteins, and autophagy-related proteins were evaluated. Additionally, TM4 cells (a mouse Sertoli cell line) were used to delineate the molecular mechanisms that mediate the effects of PFOS on BTB. Our results demonstrated that exposure to PFOS induced BTB injury and autophagy, as evidenced by increased expression of autophagy-related proteins, accumulation of autophagosomes, observed through representative electron micrographs, and decreased activity of the PI3K/AKT/mTOR pathway. Moreover, treatment with chloroquine, an autophagy inhibitor, alleviated the effects of PFOS on the integrity of TM4 cells in the BTB and the PI3K/AKT/mTOR pathway. Overall, this study highlights that exposure to PFOS destroys the integrity of the BTB through PI3K/AKT/mTOR-mediated autophagy.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Proteínas Proto-Oncogênicas c-akt , Células de Sertoli , Animais , Masculino , Camundongos , Autofagia , Proteínas Relacionadas à Autofagia/metabolismo , Barreira Hematotesticular , Mamíferos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sêmen/metabolismo , Células de Sertoli/metabolismo , Serina-Treonina Quinases TOR/metabolismo
16.
Sci Rep ; 14(1): 14344, 2024 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906933

RESUMO

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.


Assuntos
Leucócitos , Leucopenia , Humanos , Contagem de Leucócitos/métodos , Contagem de Leucócitos/instrumentação , Leucócitos/citologia , Leucócitos/patologia , Leucopenia/diagnóstico , Leucopenia/sangue , Leucopenia/patologia , Leucocitose/sangue , Leucocitose/diagnóstico , Leucocitose/patologia , Sensibilidade e Especificidade , Feminino , Masculino , Neutrófilos/citologia , Neutrófilos/patologia , Pessoa de Meia-Idade
17.
Front Psychol ; 15: 1284277, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38283203

RESUMO

Introduction: In recent years, the pursuit of a master's degree has become a social phenomenon of wide concern. It is essential to understand why large number of students choose to pursue master's degree. This study aims to empirically analyze the factors that influence the intent to pursue a master's degree. Method: Based on the extended theory of planned behavior, this study conducts a questionnaire survey of university students in Shandong Province, which has had the highest number of people taking the postgraduate entrance examination in China for several years. A total of 440 questionnaires were finally collected, including 417 valid questionnaires. And then ordinary least squares (OLS) regression was used to analyze the factors that influence the intent to pursue a master's degree. Results: In general, the intent to pursue a master's degree is positively influenced by attitude (ß = 0.161, p < 0.01) and subjective norms (ß = 0.208, p < 0.01), and negatively influenced by risk perception (ß = -0.084, p < 0.05). Compared with male students, female students' intent is more likely to be influenced by risk perception (ß = -0.144, p < 0.05) and social factors (ß = 0.140, p < 0.05). The intent of upperclass students tends to be positively influenced by perceived behavioral control (ß = 0.125, p < 0.05), whereas the negative impact of risk perception (ß = -0.219, p < 0.05) on the intent is significant for underclass students. The intent of students in rural areas are more sensitive to risk perception (ß = -0.194, p < 0.01) than those of students in cities. In private universities, social factors (ß = 0.445, p < 0.05) significantly affect the intent to pursue a master's degree. In ordinary public universities, the intent of students is more likely to be influenced by risk perception (ß = -0.082, p < 0.05). Conclusion: The study is helpful to strengthen the understanding of the influencing factors of the intent to pursue a master's degree. In general, the intent to pursue a master's degree is mainly influenced by attitude, subjective norms and risk perception. Moreover, the influencing factors vary among different groups (e.g., female vs. male, rural areas vs. cities). Furthermore, attitude, subjective norms, perceived behavioral control, risk perception, and social factors have greater impacts on the intent of students from low-income households than those from high-income households. This study can provide policy implications for universities to take targeted educational measures to encourage students to make a choice that suits their own development after graduation.

18.
Org Lett ; 26(30): 6335-6340, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39046225

RESUMO

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.

19.
Huan Jing Ke Xue ; 45(7): 4361-4374, 2024 Jul 08.
Artigo em Zh | MEDLINE | ID: mdl-39022980

RESUMO

In order to systematically understand the urban environmental benefit improvement of municipal solid waste (MSW) classification, based on the disposal data of MSW before and after the MSW classification in Suzhou from 2017 to 2021, the environmental impact potential (EIP) 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 (in terms of PET2000, the same below) 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.

20.
Chem Commun (Camb) ; 60(52): 6667-6670, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38860504

RESUMO

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.


Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , DNA , Técnicas Eletroquímicas , MicroRNAs , Humanos , Sistemas CRISPR-Cas/genética , MicroRNAs/análise , MicroRNAs/sangue , DNA/química , Técnicas de Amplificação de Ácido Nucleico , DNA Tumoral Circulante/sangue , Nanoestruturas/química , Limite de Detecção , Proteínas de Bactérias , Endodesoxirribonucleases , Proteínas Associadas a CRISPR
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