显微红外研究巨噬细胞膜电融合后膜蛋白二级结构的变化

首次尝试了将显微傅里叶变换红外光谱术应用于研究电融合后细胞膜蛋白质二级结构的变化,发现脉冲电场作用于细胞具有穿透效应,施加电脉冲后,整个细胞的蛋白质体系能量增加,表明电泳冲对蛋白的二结构影响很大;同时,还发现用唾液酸苷酶和蛋白酶Ｐｒｏｎａｓｅ分析处理巨噬细胞膜表面后,膜上蛋白质二级结构无序化程度增加,用酶适度处理的细胞将更易发生电融合。     

Identification of immune-enhanced molecular subtype associated with BRCA1 mutations,immune checkpoints and clinical outcome in ovarian carcinoma

Ovarian carcinoma has the highest mortality among the malignant tumours in gynaecology, and new treatment strategies are urgently needed to improve the clinical status of ovarian carcinoma patients. The Cancer Genome Atlas (TCGA) cohort were performed to explore the immune function of the internal environment of tumours and its clinical correlation with ovarian carcinoma. Finally, four molecular subtypes were obtained based on the global immune-related genes. The correlation analysis and clinical characteristics showed that four subtypes were all significantly related to clinical stage; the immune scoring results indicated that most immune signatures were upregulated in C3 subtype, and the majority of tumour-infiltrating immune cells were upregulated in both C3 and C4 subtypes. Compared with other subtypes, C3 subtype had a higher BRCA1 mutation, higher expression of immune checkpoints, and optimal survival prognosis. These findings of the immunological microenvironment in tumours may provide new ideas for developing immunotherapeutic strategies for ovarian carcinoma.     

High‐Efficiency Thermoelectric Power Generation Enabled by Homogeneous Incorporation of MXene in (Bi,Sb)2Te3 Matrix

The (Bi,Sb)₂Te₃ (BST) compounds have long been considered as the benchmark of thermoelectric (TE) materials near room temperature especially for refrigeration. However, their unsatisfactory TE performances in wide‐temperature range severely restrict the large‐scale applications for power generation. Here, using a self‐assembly protocol to deliver a homogeneous dispersion of 2D inclusion in matrix, the first evidence is shown that incorporation of MXene (Ti₃C₂T_x) into BST can simultaneously achieve the improved power factor and greatly reduced thermal conductivity. The oxygen‐terminated Ti₃C₂T_x with proper work function leads to highly increased electrical conductivity via hole injection and retained Seebeck coefficient due to the energy barrier scattering. Meanwhile, the alignment of Ti₃C₂T_x with the layered structure significantly suppresses the phonon transport, resulting in higher interfacial thermal resistance. Accordingly, a peak ZT of up to 1.3 and an average ZT value of 1.23 from 300 to 475 K are realized for the 1 vol% Ti₃C₂T_x/BST composite. Combined with the high‐performance composite and rational device design, a record‐high thermoelectric conversion efficiency of up to 7.8% is obtained under a temperature gradient of 237 K. These findings provide a robust and scalable protocol to incorporate MXene as a versatile 2D inclusion for improving the overall performance of TE materials toward high energy‐conversion efficiency.     

HIF‐1α forms regulatory loop with YAP to coordinate hypoxia‐induced adriamycin resistance in acute myeloid leukemia cells

Despite the improvement in acute myeloid leukemia (AML) treatments, most patients had a poor prognosis and suffered from chemoresistance and disease relapse. Therefore, there is an urgent need for elucidation of mechanism(s) underlying drug resistance in AML. In the present study, we found that AML cells showed less susceptibility to adriamycin (ADR) in the presence of hypoxia, while inhibition of hypoxia‐inducible factor 1α (HIF‐1α) by CdCl₂ can make AML cells re‐susceptibile to ADR even under hypoxia. Moreover, HIF‐1α is overexpressed and plays an important role in ADR‐resistance maintenance in resistant AML cells. We further found hypoxia or induction of HIF‐1α can significantly upregulate yes‐associated protein (YAP) expression in AML cells, and resistant cells express a high level of YAP. Finally, we found that YAP may not only enhance HIF‐1α stability but also promote HIF‐1α's activity on the target gene pyruvate kinase M2. In conclusion, our data indicate that HIF‐1α or YAP may represent a therapeutic target for overcoming resistance toward adriamycin‐based chemotherapy in AML.     

Aerial seed bank in a cold desert annual-ephemeral species: Role of anatomical structure of stem and delayed fruit dehiscence in timing of seed dispersal

Why the fruits are retained on dead upright herbaceous plants and how this relates to seed dispersal and timing of germination remain unclear. Stems of the annual Euclidium syriacum (Brassicaceae) with infructescences bearing indehiscent silicles remain upright after plants die in the spring. We investigated the effect of anatomical structures of stem and pedicle and delayed silicle dehiscence on seed dispersal phenology of this species. For comparison, sections were made of the stem of the annual Goldbachia laevigata (Brassicaceae), which has stems that fall over when plants die. Compared to G. laevigata, the stem of E. syriacum has vascular bundles that are closer together, a thicker xylem and phloem, more fibers, a thicker perimedullary zone and a smaller pith diameter:stem diameter ratio. The thickened pedicle did not form an abcission layer. By late October, 5–20% of seeds were dispersed, depending on the position of infructescences on the plant. Snow covered the plants in late autumn and when it melted in mid-April many of the plants had fallen over, with a high number of seeds germinating in attached silicles; seedlings became rooted in soil. After snowmelt, 14–15% of the silicles on the remaining upright plants contained seeds; all seeds were dispersed by early July. The anatomical structures of the stem and pedicle plus the delayed dehiscence of silicles explain the presence of an aerial seed bank in E. syriacum and delay of germination of many of seeds until spring. Further, pieces of upright plants are broken off and dispersed by wind, which helps to explain the wide distribution of E. syriacum in the cold desert.     

Repeated measures random forests (RMRF): Identifying factors associated with nocturnal hypoglycemia

Nocturnal hypoglycemia is a common phenomenon among patients with diabetes and can lead to a broad range of adverse events and complications. Identifying factors associated with hypoglycemia can improve glucose control and patient care. We propose a repeated measures random forest (RMRF) algorithm that can handle nonlinear relationships and interactions and the correlated responses from patients evaluated over several nights. Simulation results show that our proposed algorithm captures the informative variable more often than naïvely assuming independence. RMRF also outperforms standard random forest and extremely randomized trees algorithms. We demonstrate scenarios where RMRF attains greater prediction accuracy than generalized linear models. We apply the RMRF algorithm to analyze a diabetes study with 2524 nights from 127 patients with type 1 diabetes. We find that nocturnal hypoglycemia is associated with HbA1c, bedtime blood glucose (BG), insulin on board, time system activated, exercise intensity, and daytime hypoglycemia. The RMRF can accurately classify nights at high risk of nocturnal hypoglycemia.     

Mitochondrial haplotypes may modulate the phenotypic manifestation of the LHON-associated m.14484T>C (MT-ND6) mutation in Chinese families

Mitochondrial m.14484T>C (MT-ND6) mutation has been associated with Leber's hereditary optic neuropathy. Previous investigations revealed that the m.14484T>C mutation is a primary factor underlying the development of optic neuropathy but is not sufficient to produce a clinical phenotype. However, mitochondrial haplogroups have been proposed to modulate the phenotypic manifestation of the m.14484T>C mutation. Here, we performed the clinical, genetic evaluation and complete mitochondrial genome sequence analysis of 41 Han Chinese pedigrees carrying the m.14484T>C mutation. These families exhibited a wide range of penetrances and expressivities of optic neuropathy. The average ratio between affected male/female matrilineal relatives from 41 families was 2:1. The penetrance of optic neuropathy in these Chinese pedigrees ranged from 5.6% to 100%, with the average of 23.8%. Furthermore, the age-of-onset for optic neuropathy varied from 4 to 44 years, with the average of 19.3 years. Sequence analysis of their mitochondrial genomes identified distinct sets of polymorphisms belonging to ten Eastern Asian haplogroups, indicating that the m.14484T>C mutation occurred through recurrent origins and founder events. We showed that mitochondrial haplogroups M9, M10 and N9 increased the penetrance of optic neuropathy in these Chinese families. In particular, these mitochondrial haplogroup specific variants: m.3394T>C (MT-ND1), m.14502T>C (MT-ND4) and m.14693A>G (MT-TE) enhanced the penetrance of visual loss in these Chinese families. These data provided the direct evidence that mitochondrial modifiers modulate the variable penetrance and expressivity of optic neuropathy among Chinese pedigrees carrying the m.14484T>C mutation.     

SPLUNC1 Regulates Cell Progression and Apoptosis through the miR-141-PTEN/p27 Pathway,but Is Hindered by LMP1

Little is known about the role of the host defensive protein short palate, lung and nasal epithelium clone 1 (SPLUNC1) in the carcinogenesis of nasopharyngeal carcinoma (NPC). Here we report that SPLUNC1 plays a role at a very early stage of NPC carcinogenesis. SPLUNC1 regulates NPC cell proliferation, differentiation and apoptosis through miR-141, which in turn regulates PTEN and p27 expression. This signaling axis is negatively regulated by the EBV-coded gene LMP1. Therefore we propose that SPLUNC1 suppresses NPC tumor formation and its inhibition by LMP1 provides a route for NPC tumorigenesis.