Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress.

Running exercise has been shown to alleviate depressive symptoms. However, the mechanism underlying the antidepressant effects of running exercise is not fully understood. The imbalance of M1/M2 microglia phenotype/polarization and concomitant dysregulation of neuroinflammation play crucial roles in the pathogenesis of depression. Running exercise increases circulating levels of adiponectin which is known to cross the blood‒brain barrier and suppress inflammatory responses. AdipoR1 is an adiponectin receptor that is involved in regulating microglial phenotypes and activation states. However, whether running exercise regulates hippocampal microglial phenotypes and neuroinflammation through adiponectin/AdipoR1 to exert its antidepressant effects remains unclear. In the current study, 4 weeks of running exercise significantly alleviated the depressive-like behaviors of chronic unpredictable stress (CUS)-exposed mice. Moreover, running exercise decreased the microglial numbers and altered microglial morphology in three subregions of the hippocampus to restore the M1/M2 balance; these effects were accompanied by regulation of pro-/anti-inflammatory cytokine production and secretion in CUS-exposed mice. These effects may involve elevation of peripheral tissue (adipose tissue and muscle) and plasma adiponectin levels, and hippocampal AdipoR1 levels as well as activation of the AMPK-NF-κB/STAT3 signaling pathway by running exercise. When an adeno-associated virus was used to knock down hippocampal AdipoR1, mice showed depressive-like behaviors and alterations in microglia and inflammatory factor expression in the hippocampus that were similar to those observed in CUS-exposed mice. Together, these results suggest that running exercise maintains the M1/M2 balance and inhibits neuroinflammation in the hippocampus of CUS-exposed mice. These effects might occur via adiponectin/AdipoR1-mediated activation of the AMPK-NF-κB/STAT3 signaling pathway.

Targeting VPS72 inhibits ACTL6A/MYC axis activity in HCC progression.

BACKGROUND AND AIMS: HCC is a highly heterogeneous disease that is caused largely by genomic copy number variations. Herein, the mechanistic and therapeutically targeted role of vacuolar protein sorting 72 homologue (VPS72), a novel copy number variation cis-driven gained gene identified by genome-wide copy number variation and transcriptome analyses in HCC, is not well understood. APPROACH AND RESULTS: First, overexpression of VPS72 enhanced the initiation and progression of HCC in vitro and in vivo . Mechanistically, VPS72 interacted with the oncoproteins MYC and actin-like 6A (ACTL6A) and promoted the formation of the ACTL6A/MYC complex. Furthermore, ACTL6A regulated VPS72 protein stability by weakening the interaction between tripartite motif containing 21 (TRIM21) and VPS72. Thus, the interaction between VPS72 and ACTL6A enhanced the affinity of MYC for its target gene promoters and promoted their transcription, thereby contributing to HCC progression, which was inhibited by adeno-associated virus serotype 8 (AAV8)-mediated short hairpin RNA (shRNA) against VPS72. CONCLUSIONS: This study reveals the molecular mechanism of ACTL6A/VPS72/MYC in HCC, providing a theoretical basis and therapeutic target for this malignancy.

Bright solitons in a spin-orbit-coupled dipolar Bose-Einstein condensate trapped within a double-lattice.

By effectively controlling the dipole-dipole interaction, we investigate the characteristics of the ground state of bright solitons in a spin-orbit coupled dipolar Bose-Einstein condensate. The dipolar atoms are trapped within a double-lattice which consists of a linear and a nonlinear lattice. We derive the motion equations of the different spin components, taking the controlling mechanisms of the dipole-dipole interaction into account. An analytical expression of dipole-dipole interaction is derived. By adjusting the dipole polarization angle, the dipole interaction can be adjusted from attraction to repulsion. On this basis, we study the generation and manipulation of the bright solitons using both the analytical variational method and numerical imaginary time evolution. The stability of the bright solitons is also analyzed and we map out the stability phase diagram. By adjusting the long-range dipole-dipole interaction, one can achieve manipulation of bright solitons in all aspects, including the existence, width, nodes, and stability. Considering the complexity of our system, our results will have enormous potential applications in quantum simulation of complex systems.

Real-imaginary spectrum decomposition of the transparency spectra in microwave dressed Rydberg systems.

To distinguish the contributions of electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) in their applications in precision laser spectroscopy, we propose a real-imaginary spectrum decomposition method to investigate the transparency spectra in a four-level microwave (MW) dressed Rydberg system. We show that the opening transparency windows in the absorption spectra of probe field is a prominent character by EIT, EIT-ATS crossover, and ATS when the MW field is turned off and the intensity of the control field is adjusted. When the MW field is turned on and gradually increased, the EIT is destroyed and disappears. In addition, the most prominent characters that open a transparency window are the EIT-ATS crossover and the ATS. Then, if we further increase the intensity of the MW field, we find that the transparency windows open mainly due to the ATS. Compared to the previous considerations of this issue, which were limited to three-level systems, our four-level scheme reported here is useful for understanding the features of quantum interference in multilevel atomic systems, and has potential applications to study enhanced sensitivity, measurement spectroscopic, quantum processing, quantum communication, and transmission.

Upregulation of CENPM promotes breast carcinogenesis by altering immune infiltration.

BACKGROUND: The involvement of centromere protein M (CENPM) in various types of cancer has been established, however, its impact on breast cancer and immune infiltration remains unknown. METHODS: We examined the expression of CENPM in different cancer types by utilizing the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression Pan-Cancer (GEO) databases. Using data from the TCGA, we examined the correlation between the expression of CENPM, the prognosis, and the clinicopathological features of individuals diagnosed with breast cancer. We conducted an enrichment analysis of CENPM using the clusterProfiler R software tool, utilizing data obtained from breast cancer patients and specimens at our institution. In addition to examining the correlation between CENPM expression and genes associated with immune checkpoints, the TIDE algorithm was employed to explore the potential of CENPM as a biomarker for immunotherapy in breast cancer. The impact of CENPM on the growth of breast cancer cells was evaluated through the utilization of the CCK8 test and the colony formation assay. The effect of CENPM on the migration of breast cancer cells was assessed using scratch and transwell assays. RESULTS: Research findings indicate that elevated levels of CENPM are linked to patient outcomes in breast cancer and various clinicopathological features. Furthermore, elevated levels of CENPM expression correlated with decreased levels of CD8 + T cells and mast cells, increased levels of Tregs and Th2, and reduced levels of CD8 + T cells. Additionally, the coexpression of CENPM with the majority of genes related to immune checkpoints indicates its potential to forecast the effectiveness of treatment in breast cancer. Suppression of CENPM hampers the growth and movement of breast tumor cells. CONCLUSIONS: In summary, our study findings indicate that CENPM may serve as a cancer-causing gene in breast cancer and also as a biomarker for predicting the efficacy of immunotherapy. The oncogene CENPM is associated with breast cancer and is involved in cell proliferation and immune infiltration.

Amplified P2X3 pathway activity in muscle afferent dorsal root ganglion neurons and exercise pressor reflex regulation in hindlimb ischaemia-reperfusion.

Hindlimb ischaemia-reperfusion (IR) is among the most prominent pathophysiological conditions observed in peripheral artery disease (PAD). An exaggerated arterial blood pressure (BP) response during exercise is associated with an elevated risk of cardiovascular events in individuals with PAD. However, the precise mechanisms leading to this exaggerated BP response are poorly elucidated. The P2X3 signalling pathway, which plays a key role in modifying the exercise pressor reflex (EPR), is the focus of the present study. We determined the regulatory role of P2X3 on the EPR in a rat model of hindlimb IR. In vivo and in vitro approaches were used to determine the expression and functions of P2X3 in muscle afferent nerves and EPR in IR rats. We found that in IR rats there was (1) upregulation of P2X3 protein expression in the L4-6 dorsal root ganglia (DRG); (2) amplified P2X currents in isolated isolectin B4 (IB4)-positive muscle DRG neurons; and (3) amplification of the P2X-mediated BP response. We further verified that both A-317491 and siRNA knockdown of P2X3 significantly decreased the activity of P2X currents in isolated muscle DRG neurons. Moreover, inhibition of muscle afferents' P2X3 receptor using A-317491 was observed to alleviate the exaggerated BP response induced by static muscle contraction and P2X-induced BP response by α,ß-methylene ATP injection. P2X3 signalling pathway activity is amplified in muscle afferent DRG neurons in regulating the EPR following hindlimb IR.

Gut neuroendocrine signaling regulates synaptic assembly in C. elegans.

Synaptic connections are essential to build a functional brain. How synapses are formed during development is a fundamental question in neuroscience. Recent studies provided evidence that the gut plays an important role in neuronal development through processing signals derived from gut microbes or nutrients. Defects in gut-brain communication can lead to various neurological disorders. Although the roles of the gut in communicating signals from its internal environment to the brain are well known, it remains unclear whether the gut plays a genetically encoded role in neuronal development. Using C. elegans as a model, we uncover that a Wnt-endocrine signaling pathway in the gut regulates synaptic development in the brain. A canonical Wnt signaling pathway promotes synapse formation through regulating the expression of the neuropeptides encoding gene nlp-40 in the gut, which functions through the neuronally expressed GPCR/AEX-2 receptor during development. Wnt-NLP-40-AEX-2 signaling likely acts to modulate neuronal activity. Our study reveals a genetic role of the gut in synaptic development and identifies a novel contribution of the gut-brain axis.

PvMR1, a novel C-type lectin plays a crucial role in the antibacterial immune response of Pacific white shrimp, Penaeus vannamei.

C-type lectins (CTLs) are important immune molecules in innate immune, which participate in non-self recognition and clearance of pathogens. Here, a new CTL with two distinct C-type lectin domains (CTLDs) from Pacific white shrimp Penaeus vannamei, designated as PvMR1 was identified. The obtained PvMR1 coding sequence (CDS) was 1044 bp long encoding a protein with 347 amino acids. PvMR1 had two CTLD, a conserved mannose-specific EPN motif and a galactose-specific QPD motif, clustering into the same branch as the crustacean CTLs. PvMR1 was widely distributed in shrimp tissues with the highest transcription level in the hepatopancreas, with significantly induced mRNA expression on the hepatopancreas and intestines after immune challenge with Vibrio anguillarum. In vitro assays with recombinant PvMR1 (rPvMR1) protein revealed that it exhibited a wide range of antimicrobial activity, bacterial binding ability, and bacterial agglutination activity in a Ca2+-independent manner. Moreover, PvMR1 promoted bacterial phagocytosis in hemocytes. Furthermore, rPvMR1 treatment could significantly enhance the bacterial clearance in hemolymph and greatly improved the survival of shrimp under V. anguillarum infection in vivo. These results collectively suggest that PvMR1 plays an important role in antibacterial immune response of P. vannamei.

Damage of polyethylene microplastics on the intestine multilayer barrier, blood cell immune function and the repair effect of Leuconostoc mesenteroides DH in the large-scale loach (Paramisgurnus dabryanus).

Polyethylene microplastics (PE-MPs) has become a global concern due to their widespread distribution and hazardous properties in aquatic habitats. In this study, the accumulation effect of PE-MPs in the intestine of large-scale loach (Paramisgurnus dabryanus) was explored by adding different concentrations of PE-MPs to the water, the destination of PE-MPs after breaking the intestinal barrier and the effects caused. The collected data showed that PE-MPs accumulation for 21d altered the histomorphology and antioxidant enzyme activity of the intestine, induced dysbiosis of the intestinal flora. 10 mg/L of PE-MPs induced a significant increase in the transcript levels of intestinal immunity factors in loach after 21d of exposure. Moreover, the levels of diamine oxidase (DAO) and d-lactic acid (D-Lac) in the gut and serum of loach were significantly increased after exposure to PE-MPs at all concentrations (1, 5, 10 mg/L). Subsequently, the presence of PE-MPs was detected in the blood, suggesting that the disruption of the intestinal multilayer barrier allowed PE-MPs to spill into the circulation. The accumulation of PE-MPs (1,5,10 mg/L) in the blood led to massive apoptosis and necrosis of blood cells and activated phagocytosis in response to PE-MPs invasion. To alleviate the damage, this study further exposure the effect of probiotics on PE-MPs treated loach by adding Leuconostoc mesenteroides DH (109 CFU/g) to the feed. The results showed that DH significantly increased the intestinal index and reduced the levels of DAO and D-Lac. To investigate the reason, we followed the PE-MPs in the intestine and blood of the loach and found that the number of PE-MPs particles was significantly reduced in the probiotic group, while the PE-MPs content in the feces was elevated. Thus, we concluded that DH reducing the accumulation of PE-MPs in the intestinal by increases fecal PE-MPs, which in turn mitigates the damage to the intestinal barrier caused by PE-MPs, and reduces the amount of PE-MPs in the blood. This work offers a robust analysis to understand the mechanisms of damage to the intestinal barrier by MPs and the fate of MPs after escaping the intestinal barrier and provide a new perspective on the application of probiotics in mitigating PE-MPs toxicity.

Carbon-coated silicon/graphite oxide composites as anode materials for highly stable lithium-ion batteries.

Silicon (Si) has been widely investigated as an anode material for lithium-ion batteries (LIBs) due to its high theoretical capacity. However, the huge volume expansion and low electrical conductivity limit its practical application to some extent. Here, we prepared silicon/reduced graphene oxide/amorphous carbon (Si/G/C) anode materials for lithium-ion batteries using a facile synergistic cladding layer. The protective effect of different carbon layers was explored and it was found that ternary composites have excellent electrochemical properties. In this work, the surface of Si was first modified using ammonia, and the positively charged Si was tightly anchored to the graphene sheet layer. In contrast, amorphous carbon was used as a reinforcing coating for further coating to synergistically build up the cladding layer of Si NPs with graphene oxide. The ternary composite (Si/G/C) material greatly ensures the structural integrity of the composites and shows excellent cycling as well as rate performance compared to Si/reduced graphene oxide and Si/carbon composites. For the Si/G/C composite, at a current density of 1 A g-1, it can be stably cycled over 267 times with 70% capacity retention (only 0.0711% capacity reduction per cycle).

Revisiting Structure-activity Relationships: Unleashing the potential of selective Janus kinase 1 inhibitors.

Janus kinases (JAKs), a kind of non-receptor tyrosine kinases, the function has been implicated in the regulation of cell proliferation, differentiation and apoptosis, immune, inflammatory response and malignancies. Among them, JAK1 represents an essential target for modulating cytokines involved in inflammation and immune function. Rheumatoid arthritis, atopic dermatitis, ulcerative colitis and psoriatic arthritis are areas where approved JAK1 drugs have been applied for the treatment. In the review, we provided a brief introduction to JAK1 inhibitors in market and clinical trials. The structures of high active JAK1 compounds (IC50 ≤ 0.1 nM) were highlighted, with primary focus on structure-activity relationship and selectivity. Moreover, the druggability processes of approved drugs and high active compounds were analyzed. In addition, the issues involved in JAK1 compounds clinical application as well as strategies to surmount these challenges, were discussed.

The Effect of Distance Education on Self-care in Patients With Heart Failure in the Chronic or Stable Phase: A Systematic Review and Meta-analysis.

BACKGROUND: Health education is important for self-care in patients with heart failure. However, the evidence for the effect of distance education as an intervention to deliver instruction for patients after discharge through digital devices on self-care is limited. OBJECTIVES: In this study, our aim was to explore the effect of distance education on self-care in patients with heart failure. METHODS: We searched 11 electronic databases and 3 trial registries for randomized controlled trials with low risk of bias and high-quality evidence to compare the effect of usual and distance education on self-care. Quality appraisal was performed using the Cochrane Risk of Bias Tool. Using the Review Manager 5.4 tool, a meta-analysis was conducted. Certainty of the evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Fifteen articles were eligible for this study. Compared with usual education, distance education improved self-care maintenance (mean difference [MD], 6.62; 95% confidence interval [CI], 3.93-9.31; GRADE, moderate quality), self-care management (MD, 5.10; 95% CI, 3.25-6.95; GRADE, high quality), self-care confidence (MD, 6.66; 95% CI, 4.82-8.49; GRADE, high quality), heart failure knowledge (MD, 0.78; 95% CI, 0.01-1.56; GRADE, moderate quality), and quality of life (MD, -5.35; 95% CI, -8.73 to -1.97; GRADE, moderate quality). Subgroup analysis revealed distance education was more effective than usual education in self-care when the intervention was conducted for 1 to 6 months, more than 3 times per month, and a single intervention lasting more than 30 minutes. CONCLUSIONS: This review shows the benefits of distance education on self-care, heart failure knowledge, and quality of life of patients with heart failure. The intervention duration, frequency, and duration of a single intervention could have affected the intervention effect.

Using Sandwiched Silicon/Reduced Graphene Oxide Composites with Dual Hybridization for Their Stable Lithium Storage Properties.

Using silicon/reduced graphene oxide (Si/rGO) composites as lithium-ion battery (LIB) anodes can effectively buffer the volumetric expansion and shrinkage of Si. Herein, we designed and prepared Si/rGO-b with a sandwiched structure, formed by a duple combination of ammonia-modified silicon (m-Si) nanoparticles (NP) with graphene oxide (GO). In the first composite process of m-Si and GO, a core-shell structure of primal Si/rGO-b (p-Si/rGO-b) was formed. The amino groups on the m-Si surface can not only hybridize with the GO surface to fix the Si particles, but also form covalent chemical bonds with the remaining carboxyl groups of rGO to enhance the stability of the composite. During the electrochemical reaction, the oxygen on the m-Si surface reacts with lithium ions (Li+) to form Li2O, which is a component of the solid-electrolyte interphase (SEI) and is beneficial to buffering the volume expansion of Si. Then, the p-Si/rGO-b recombines with GO again to finally form a sandwiched structure of Si/rGO-b. Covalent chemical bonds are formed between the rGO layers to tightly fix the p-Si/rGO-b, and the conductive network formed by the reintroduced rGO improves the conductivity of the Si/rGO-b composite. When used as an electrode, the Si/rGO-b composite exhibits excellent cycling performance (operated stably for more than 800 cycles at a high-capacity retention rate of 82.4%) and a superior rate capability (300 mA h/g at 5 A/g). After cycling, tiny cracks formed in some areas of the electrode surface, with an expansion rate of only 27.4%. The duple combination of rGO and the unique sandwiched structure presented here demonstrate great effectiveness in improving the electrochemical performance of alloy-type anodes.

Research progress on the regulatory mechanisms of Irisin on cognitive dysfunction in patients with Alzheimer's disease and the interventional role of Irisin in associated diseases.

Irisin, a peptide produced during exercise, is believed to play a role in regulating energy levels within the body. Moreover, Irisin has the ability to traverse the blood-brain barrier and engage in various pathophysiological processes within the central nervous system. An increasing body of research identifies Irisin as a significant therapeutic target for neurodegenerative diseases, indicating a strong link between Irisin and the development of cognitive impairments. In this paper, we present a concise review of effects of different types of exercise on Irisin production, and the mechanisms underlying the Irisin's intervention in various diseases including metabolic diseases, kidney injury and depression. Following this, we delve into an in-depth exploration of its role in modulating cognitive dysfunction among patients with Alzheimer's disease (AD), focusing on recent advancements in three critical areas: neuroinflammation, mitochondrial dysfunction, and protein misfolding. Finally, we put forth 3 hypotheses: (1) exercise-induced fibronectin type III domain containing protein 5 (FNDC5) stimulation and subsequent Irisin cleavage may be associated with the stress response in energy metabolism; (2) Irisin, as a myokine, likely plays a role in mitochondrial repair mechanisms to ameliorate cognitive impairment in AD patients; (3) Irisin is a homeostatic factor that maintains energy homeostasis and is closely related to the dynamic stability of the body's internal environment.

[UPLC-Q-TOF-MS-based metabolomics reveals mechanism of Morinda officinalis iridoid glycosides in treating rheumatoid arthritis and bone loss].

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.

Systematic Proteomics Study on the Embryonic Development of Danio rerio.

The early development of zebrafish (Danio rerio) is a complex and dynamic physiological process involving cell division, differentiation, and movement. Currently, the genome and transcriptome techniques have been widely used to study the embryonic development of zebrafish. However, the research of proteomics based on proteins that directly execute functions is relatively vacant. In this work, we apply label-free quantitative proteomics to explore protein profiling during zebrafish's embryogenesis, and a total of 5961 proteins were identified at 10 stages of zebrafish's early development. The identified proteins were divided into 11 modules according to weighted gene coexpression network analysis (WGCNA), and the characteristics between modules were significantly different. For example, mitochondria-related functions enriched the early development of zebrafish. Primordial germ cell-related proteins were identified at the 4-cell stage, while the eye development event is dominated at 5 days post fertilization (dpf). By combining with published transcriptomics data, we discovered some proteins that may be involved in activating zygotic genes. Meanwhile, 137 novel proteins were identified. This study comprehensively analyzed the dynamic processes in the embryonic development of zebrafish from the perspective of proteomics. It provided solid data support for further understanding of the molecular mechanism of its development.

Phylogeography of cultivated and wild ophiopogon japonicus based on chloroplast DNA: exploration of the origin and sustainable cultivation.

BACKGROUND: Ophiopogon japonicus, mainly planted in Sichuan (CMD) and Zhejiang (ZMD) province in China, has a lengthy cultivation history. During the long period of domestication, the genetic diversity of cultivated O. japonicus has substantially declined, which will affect the population continuity and evolutionary potential of this species. Therefore, it is necessary to clarify the phylogeography of cultivated O. japonicus to establish a theoretical basis for the utilization and conservation of the genetic resources of O. japonicus. RESULT: The genetic diversity and population structure of 266 O. japonicus individual plants from 23 sampling sites were analyzed based on 4 chloroplast DNA sequences (atpB-rbcL, rpl16, psbA-trnH and rpl20-5'rps12) to identify the effects of domestication on genetic diversity of cultivars and determine their geographic origins. The results showed that cultivated O. japonicus and wild O. japonicus had 4 and 15 haplotypes respectively. The genetic diversity of two cultivars (Hd = 0.35700, π = 0.06667) was much lower than that of the wild populations (Hd = 0.76200, π = 0.20378), and the level of genetic diversity in CMD (Hd = 0.01900, π = 0.00125) was lower than that in ZMD (Hd = 0.06900, π = 0.01096). There was significant difference in genetic differentiation between the cultivated and the wild (FST = 0.82044), especially between the two cultivars (FST = 0.98254). This species showed a pronounced phylogeographical structure (NST > GST, P < 0.05). The phylogenetic tree showed that the genetic difference between CMD and ZMD was not enough to distinguish the cultivars between the two producing areas by using O. amblyphyllus Wang et Dai as an outgroup. In addition, both CMD and ZMD have a closer relationship with wild populations in Sichuan than that in Zhejiang. The results of the TCS network and species distribution model suggested that the wild population TQ located in Sichuan province could serve as the ancestor of cultivated O. japonicus, which was supported by RASP analysis. CONCLUSION: These results suggest that cultivated O. japonicus has experienced dramatic loss of genetic diversity under anthropogenic influence. The genetic differentiation between CMD and ZMD is likely to be influenced by founder effect and strong artificial selection for plant traits. It appears that wild populations in Sichuan area are involved in the origin of not only CMD but also ZMD. In addition, we also raise some suggestions for planning scientific strategies for resource conservation of O. japonicus based on its genetic diversity and population structure.

A New Structure with Localized sp2 Bonding for Fivefold Twinning in Diamond.

Changes in atomic bonding configuration in carbon from sp3 to sp2 are known to exist in certain structural defects in diamond, such as twin boundaries, grain boundaries, and dislocations, which have a significant impact on many properties of diamond. In this work, the atomic structure of fivefold twinning in detonation synthesized ultra-dispersed diamonds is investigated using a combination of techniques, including spherical aberration-corrected high-resolution electron microscopy (HREM), HREM image simulations, and molecular mechanics (MM) calculations. The experimental HREM images reveal clearly that the fivefold twinning in diamond has two distinct structures. In addition to the concentric fivefold twins, where the core structure is the intersection of five {111} twinning boundaries, a new extended core structure with co-hybridization of bonding is identified and analyzed in fivefold twinning. The atomic structure forming these fivefold twinning boundaries and their respective core structures is proposed to involve both the tetrahedral sp3 and planar graphitic sp2 bonding configurations, in which a co-hybridized planar hexagon of carbon serves as a fundamental structural unit. The presence of this sp2 -bonded planar unit of hexagonal carbon rings in general grain boundaries is also discussed.

Asymmetric Hairpins DNA Encapsulated Silver Nanoclusters for In Situ Fluorescence Imaging of Fusion Gene Isoforms in Bone Marrow.

Rapid and accurate imaging of the BCR/ABL fusion gene isoforms (e.g., e13a2, e14a2 and co-expression type) of chronic myeloid leukemia (CML) is of vital importance to first-line drug selection, but there is no assay that meets clinical needs (e.g., clinical kits > 18 h without isoforms information). Herein, an in situ imaging platform is developed for the rapid and accurate detection of CML fusion gene isoforms using asymmetric sequence-enhanced hairpins DNA encapsulated silver nanoclusters (ADHA) and catalyzed hairpin assembly (CHA). The specific detection of e13a2 and e14a2 fusion gene isoforms with detection limits of 19.2 am (11.558 copies µL-1 ) and 32.56 am (19.601 copies µL-1 ) in one-pot is achieved. The feasibility of the developed assay for real-world applications are demonstrated by one-step fluorescence imaging (40 min) of e13a2, e14a2 and co-expression type in bone marrow quantitatively (International Standard: 15.66%-168.878%) and further validated by cDNA-sequencing. This work suggests that the developed imaging platform holds great potential for rapid identification of the fusion gene isoforms and isoform related treatment monitoring.

BORIS variant SF2(C2/A4) promotes the malignant development of liver cancer by activating epithelial-mesenchymal transition and hepatic stellate cells.

The underlying mechanisms of metastasis and recurrence of liver cancer remain largely unknown. Here, we found that Brother of the Regulator of Imprinted Sites (BORIS) variant SF2(C2/A4) was highly expressed in high metastatic potential hepatocellular carcinoma (HCC) cells and clinical tumor samples, related to the formation of satellite nodules. Its over expression promoted self-renewal, the expression of tumor stem cell markers, chemoresistance, wound healing rate, invasion and metastasis of HepG2 and Hep3B cells; reinforced epithelial-mesenchymal transition (EMT), decreased the expression of E-cadherin and increased N-cadherin and Vimentin. Subcellular localization experiment showed that BORIS SF2(C2/A4) was localized in nucleus and cytoplasm. Further double luciferase reporter gene experiment confirmed that it bound to TWIST1 gene promoter and significantly increased latter expression. BORIS SF2(C2/A4) knock down induced apoptosis of HCCLM3 and PLC/PRF/5 cells, and increased the protein content of cleaved caspase 3. Additionally, BORIS SF2(C2/A4) over expression increased the expression of fibroblast growth factor 2 (FGF2) in HepG2 and Hep3B cells. FGF2 expressed higher in HCC tumor tissues than in paired peri-tumor tissues, and its expression was positively correlated with BORIS SF2(C2/A4). Interestingly, high expression of FGF2 is also associated with the formation of satellite nodules. Moreover, using the medium from BORIS SF2(C2/A4) overexpressed cell lines to coculture hepatic stellate cell (HSCs) line LX-2, the latter could be activated and increased the expression of CD90 and PIGF, which is consistent with the effect of adding bFGF alone. These results indicate that BORIS SF2(C2/A4) plays a role in deterioration of liver cancer by regulating TWIST1 to induce EMT, and by FGF2 to activate HSCs.