1ASD families had heavier childcare burden and poorer quality of life than TD families.2Mothers had heavier childcare burden than fathers both in ASD and TD children.3Childcare burden mediated the ...effect of child social impairment of ASD children on maternal quality of life, fathers not.
This study evaluated the life quality of Chinese parents of preschool children with autism spectrum disorder (ASD) and their association with child social impairment and childcare burden. The participants included 406 families of children with ASD and 513 families with typically developing (TD) children. The findings indicated that parents in the ASD group had a lower quality of life than parents in the TD group, whereas only mother of children with ASD experienced a greater childcare burden than mother with TD children. Lower parental quality of life were associated with higher social impairment of children. To further clarify the correlativity of child social impairment, parental quality of life and childcare burden, the mediation analyses were conducted. The results showed that childcare burden mediated the influence of child social impairment on maternal quality of life, while it has no mediating effect on fathers. It implies that social impairment of children affects parental quality of life in different ways.
Blueberry is an important agricultural crop with high nutritional, health, and economic value. Despite the well‐studied blueberry cultivation methods and soil requirements, little is known about how ...beneficial bacteria function in organic blueberry cultivation systems and their effects on acidic soils. In this study, a single bacteria Bacillus amyloliquefaciens JC65 and three biocontrol bacteria consortiums containing JC65 were applied to organic system. The effect of bacteria to blueberry growth, yield, fruit quality, and soil quality was investigated. A consortium of three mixed Bacillus (B. amyloliquefaciens JC65, B. licheniforims HS10 and B. subtilis 7ze3) showed the highest growth improvement efficiency. The bacterial inoculation increased blueberry leaf chlorophyll content, net photosynthetic rate by 21.50%, 13.21% at 30 days, and increased average plant height by 2.72% at 69 days. Compared with the control, the inoculated plants showed an increased yield of 14.56%. Interestingly, blueberry fruit quality was also improved with supplement of the bacterial consortium. Fruit anthocyanin, soluble sugar, vitamin C, soluble solids, and soluble protein content were increased by 5.99%, 4.21%, 17.31%, 2.41%, and 21.65%, respectively. Besides, beneficial bacterial consortium also enables sustainable agriculture by improving soil ammonium nitrogen and organic matter by 3.77% and 2.96% after blueberry planting. In conclusion, the combination of beneficial bacteria showed a synergistic activity in organic system to promote the blueberry yield, fruit quality, and soil nutrient preservation.
We conclude that addition of beneficial microbe in organic blueberry production significantly promotes plant growth and improves blueberry fruit quality. Interestingly, by combination of different beneficial microorganism, the promotion effect on blueberry production was enhanced significantly, indicating synergistic activity among specific mixture of bacteria. The soil retention ability of the beneficial microbe is also shown, especially for increase of soil organic matter.
Epstein-Barr virus (EBV) is implicated as an aetiological factor in B lymphomas and nasopharyngeal carcinoma. The mechanisms of cell-free EBV infection of nasopharyngeal epithelial cells remain ...elusive. EBV glycoprotein B (gB) is the critical fusion protein for infection of both B and epithelial cells, and determines EBV susceptibility of non-B cells. Here we show that neuropilin 1 (NRP1) directly interacts with EBV gB(23-431). Either knockdown of NRP1 or pretreatment of EBV with soluble NRP1 suppresses EBV infection. Upregulation of NRP1 by overexpression or EGF treatment enhances EBV infection. However, NRP2, the homologue of NRP1, impairs EBV infection. EBV enters nasopharyngeal epithelial cells through NRP1-facilitated internalization and fusion, and through macropinocytosis and lipid raft-dependent endocytosis. NRP1 partially mediates EBV-activated EGFR/RAS/ERK signalling, and NRP1-dependent receptor tyrosine kinase (RTK) signalling promotes EBV infection. Taken together, NRP1 is identified as an EBV entry factor that cooperatively activates RTK signalling, which subsequently promotes EBV infection in nasopharyngeal epithelial cells.
A simple and sensitive liquid chromatography with tandem mass spectrometry method was developed for simultaneous quantification of paeoniflorin, albiflorin, oxypaeoniflorin, liquiritin, ...liquiritigenin, glycyrrhetinic acid, and glycyrrhizin in rat plasma after oral administration of Shaoyao‐Gancao decoction, which is traditionally used in the treatment of polycystic ovary syndrome. The plasma samples were pretreated with methanol as precipitant. The method exhibited good linearity (correlation coefficient (R2) > 0.99) with lower quantification limits of 0.595–4.69 ng/mL for all analytes. Intra‐ and interbatch precision, accuracy, recovery, and stability of the method were all within accepted criteria. The results showed that the pharmacokinetic behaviors of the seven compounds were altered in the pathological status of polycystic ovary syndrome. Furthermore, a total of 36 metabolites were structurally identified based on their accurate masses and fragment ions. The major metabolic pathway involves phase I metabolic reactions (such as hydroxylation), phase II metabolic reactions (such as sulfation and glucuronidation conjugation) as well as the combined multiple‐step metabolism. This study is the first report on the pharmacokinetic and metabolic information of Shaoyao‐Gancao decoction in both normal and model rats, which would provide scientific evidences for the bioactive chemical basis of herbal medicines and also promote the clinical application of Shaoyao‐Gancao decoction for treating polycystic ovary syndrome.
Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits unique histological characteristics within the immune-cell-rich microenvironment, but the role of tertiary lymphoid structure (TLS) in ...EBVaGC is not yet fully understood.
We retrospectively identified EBVaGC from 8517 consecutive GC cases from the two top cancer centers in China. Furthermore, we evaluated the prognostic value of TLS in 148 EBVaGC patients from our institute and then validated it in an external cohort (76 patients). TLS was quantified and its relationships with overall survival (OS) and therapeutic response were further analyzed. Multiplex immunofluorescence staining and targeted sequencing were used to characterize the composition of TLS and the genomic landscape, respectively.
In our study, EBVaGC was observed in 4.3% (190/4436) and 2.6% (109/4081) of GCs in the training and validation cohorts, respectively. TLS was identified in the intratumor (94.6%) and peritumor (77.0%) tissues with lymphoid aggregates, primary and secondary (i.e., mature TLSs) follicles in EBVaGC. Kaplan-Meier analysis showed that mature TLS in intratumoral tissues was associated with a favorable OS in the training and validation cohorts (p < 0.0001; p = 0.0108). Multivariate analyses demonstrated that intratumoral TLS maturation, pTNM, and PD-L1 expression were independent prognostic factors for OS (p < 0.05). Furthermore, the mature TLS was significantly associated with a good response to treatment in EBVaGC patients. Interestingly, the mutation frequency of SMARCA4 was significantly lower in the mature TLS groups.
Intratumoral mature TLS was associated with a favorable prognosis and good therapeutic response, suggesting that it is a potential prognostic biomarker and predicts a good therapeutic response in EBVaGC patients.
Novel dual inhibitors of histone deacetylase (HDAC) and heat-shock protein 90 (HSP90) are synthesized and evaluated. These compounds are endowed with potent HDAC and HSP90 inhibitory activities with ...IC50 values in nanomolar range with Compound 20 (HDAC IC50 = 194 nM; HSP90α IC50 = 153 nM) and compound 26 (HDAC IC50 = 360 nM; HSP90α IC50 = 77 nM) displaying most potent HDAC and HSP90α inhibitory activities. Both of these compounds induce HSP70 expression and down regulate HSP90 client proteins which play important roles in the regulation of survival and invasiveness in cancer cells. In addition, compounds 20 and 26 induce acetylation of α-tubulin and histone H3. Significantly, compounds 20 and 26 could effectively reduce programmed death-ligand 1 (PD-L1) expression in IFN-γ treated lung H1975 cells in a dose dependent manner. These findings suggest that dual inhibition of HDAC and HSP90 that can modulate immunosuppressive ability of tumor area may provide a better therapeutic strategy for cancer treatment in the future.
Display omitted
•N-alkyl-hydroxybenzoyl anilide hydroxamates show potent dual inhibition of HDAC and HSP90a.•Lead compounds 20 and 26 induce HSP70 expression and down regulate HSP90 client proteins.•Compounds 20 and 26 displayed their HDAC inhibitory effects due to increased acetylated α-tubulin and histone H3 levels.•Compounds 20 and 26 could effectively reduce programmed death-ligand 1 (PD-L1) expression in IFN-γ treated lung H1975 cells.
All-weather operation is considered an ultimate pursuit of the practical development of sodium-ion batteries (SIBs), however, blocked by a lack of suitable electrolytes at present. Herein, by ...introducing synergistic manipulation mechanisms driven by phosphorus/silicon involvement, the compact electrode/electrolyte interphases are endowed with improved interfacial Na-ion transport kinetics and desirable structural/thermal stability. Therefore, the modified carbonate-based electrolyte successfully enables all-weather adaptability for long-term operation over a wide temperature range. As a verification, the half-cells using the designed electrolyte operate stably over a temperature range of −25 to 75 °C, accompanied by a capacity retention rate exceeding 70% even after 1700 cycles at 60 °C. More importantly, the full cells assembled with Na3V2(PO4)2O2F cathode and hard carbon anode also have excellent cycling stability, exceeding 500 and 1000 cycles at −25 to 50 °C and superb temperature adaptability during all-weather dynamic testing with continuous temperature change. In short, this work proposes an advanced interfacial regulation strategy targeted at the all-climate SIB operation, which is of good practicability and reference significance.
Abstract
Background
Glioblastoma is associated with poor prognosis and high mortality. Although the use of first-line temozolomide can reduce tumor growth, therapy-induced stress drives stem cells ...out of quiescence, leading to chemoresistance and glioblastoma recurrence. The specificity protein 1 (Sp1) transcription factor is known to protect glioblastoma cells against temozolomide; however, how tumor cells hijack this factor to gain resistance to therapy is not known.
Methods
Sp1 acetylation in temozolomide-resistant cells and stemlike tumorspheres was analyzed by immunoprecipitation and immunoblotting experiments. Effects of the histone deacetylase (HDAC)/Sp1 axis on malignant growth were examined using cell proliferation–related assays and in vivo experiments. Furthermore, integrative analysis of gene expression with chromatin immunoprecipitation sequencing and the recurrent glioblastoma omics data were also used to further determine the target genes of the HDAC/Sp1 axis.
Results
We identified Sp1 as a novel substrate of HDAC6, and observed that the HDAC1/2/6/Sp1 pathway promotes self-renewal of malignancy by upregulating B cell-specific Mo-MLV integration site 1 (BMI1) and human telomerase reverse transcriptase (hTERT), as well as by regulating G2/M progression and DNA repair via alteration of the transcription of various genes. Importantly, HDAC1/2/6/Sp1 activation is associated with poor clinical outcome in both glioblastoma and low-grade gliomas. However, treatment with azaindolyl sulfonamide, a potent HDAC6 inhibitor with partial efficacy against HDAC1/2, induced G2/M arrest and senescence in both temozolomide-resistant cells and stemlike tumorspheres.
Conclusion
Our study uncovers a previously unknown regulatory mechanism in which the HDAC6/Sp1 axis induces cell division and maintains the stem cell population to fuel tumor growth and therapeutic resistance.
Developing a high-performance, low-cost, and safer rechargeable battery is a primary challenge in next-generation electrochemical energy storage. In this work, a quasi-solid-state (QSS) sodium-ion ...full battery (SIFB) is designed and fabricated. Hard carbon cloth derived from cotton cloth and Na3V2(PO4)2O2F (NVPOF) are employed as the anode and the cathode, respectively, and a sodium ion-conducting gel-polymer membrane is used as both the QSS electrolyte and separator, accomplishing the high energy and power densities in the QSS sodium-ion batteries. The energy density can reach 460 W h kg–1 according to the mass of the cathode materials. Moreover, the fabricated QSS SIFB also exhibits an excellent rate performance (e.g., about 78.1 mA h g–1 specific capacity at 10 C) and a superior cycle performance (e.g., ∼90% capacity retention after 500 cycles at 10 C). These results show that the developed QSS SIFB is a hopeful candidate for large-scale energy storage.
Background
Small extracellular vesicles (sEVs) mediate intercellular communication that contributes to hepatocellular carcinoma (HCC) progression via multifaceted pathways. The success of cell entry ...determines the effect of sEV on recipient cells. Here, we aimed to delineate the mechanisms underlying the uptake of sEV in HCC.
Methods
Macropinocytosis was examined by the ability of cells to internalize dextran and sEV. Macropinocytosis was analyzed in Na(+)/H(+) exchanger 7 (NHE7)‐knockdown and ‐overexpressing cells. The properties of cells were studied using functional assays. pH biosensor was used to evaluate the intracellular and endosomal pH. The expression of NHE7 in patients’ liver tissues was examined by immunofluorescent staining. Inducible silencing of NHE7 in established tumors was performed to reveal the therapeutic potential of targeting NHE7.
Results
The data revealed that macropinocytosis controlled the internalization of sEVs and their oncogenic effect on recipient cells. It was found that metastatic HCC cells exhibited the highest efficiency of sEV uptake relative to normal liver cells and non‐metastatic HCC cells. Attenuation of macropinocytic activity by 5‐(N‐ethyl‐N‐isopropyl)‐amiloride (EIPA) limited the entry of sEVs and compromised cell aggressiveness. Mechanistically, we delineated that high level of NHE7, a sodium‐hydrogen exchanger, alkalized intracellular pH and acidized endosomal pH, leading to the maturation of macropinosomes. Inducible inhibition of NHE7 in established tumors developed in mice delayed tumor development and suppressed lung metastasis. Clinically, NHE7 expression was upregulated and linked to dismal prognosis of HCC.
Conclusions
This study advances the understanding that NHE7 enhances sEV uptake by macropinocytosis to promote the malignant properties of HCC cells. Inhibition of sEV uptake via macropinocytosis can be exploited as a treatment alone or in combination with conventional therapeutic approaches for HCC.
PDF
