Boron Quantum Dots Pillared Ti3 C2 Tx Membrane Electrode with High Rate Performance for Supercapacitor.

A sonication-assisted liquid-phase preparation technique is developed to prepare boron quantum dots (BQDs) with a lateral size of 3 nm in a solution of NMP and NBA; it shows a direct bandgap semiconductor with a bandgap of 3 eV and a specific capacitance of 41 F g-1 . A BQDs(10)-Ti3 C2 Tx membrane electrode with excellent capacitance and high flexibility is prepared by using Ti3 C2 Tx nanosheets (NSs) as assembled units and BQDs as pillar; it gives a specific capacitance of 524 F g-1 at 1 A g-1 in 6 m H2 SO4 electrolyte, a high capacity retention of 75%, and a minimum relaxation time of 0.51 s. An all-solid-state BQDs(10)-Ti3 C2 Tx flexibility supercapacitor is assembled by using a BQDs(10)-Ti3 C2 Tx membrane as electrodes and PVA/H2 SO4 hydrogel as electrolyte; it not only shows an area specific capacitance of 552 mF cm-2 at 1.25 mA cm-2 , a retention rate of 75%, a capacity retention of 93% after 5000 cycles, and an energy density of 40.4 Wh cm-3 at a volume power density of 416 W cm-3 , but also provides superior flexibility and can be bent to different degrees, showing that the assembled BQDs(10)-Ti3 C2 Tx membrane electrode and BQDs(10)-Ti3 C2 Tx flexible supercapacitor display broad application prospects in field of portable/wearable electronic devices.

TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.

BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

DSPose: Dual-Space-Driven Keypoint Topology Modeling for Human Pose Estimation.

Human pose estimation is the basis of many downstream tasks, such as motor intervention, behavior understanding, and human-computer interaction. The existing human pose estimation methods rely too much on the similarity of keypoints at the image feature level, which is vulnerable to three problems: object occlusion, keypoints ghost, and neighbor pose interference. We propose a dual-space-driven topology model for the human pose estimation task. Firstly, the model extracts relatively accurate keypoints features through a Transformer-based feature extraction method. Then, the correlation of keypoints in the physical space is introduced to alleviate the error localization problem caused by excessive dependence on the feature-level representation of the model. Finally, through the graph convolutional neural network, the spatial correlation of keypoints and the feature correlation are effectively fused to obtain more accurate human pose estimation results. The experimental results on real datasets also further verify the effectiveness of our proposed model.

[Effect of Danzhi Xiaoyao Powder on behavior and mitochondrial morphology and function of anxiety model rats].

Danzhi Xiaoyao Powder is a classical prescription for anxiety. This study aims to analyze the effect of this medicine on mitochondrial morphology and function of anxiety rats and explore the mechanism of it against anxiety. Specifically, uncertain empty bottle drinking water stimulation(21 days) was employed to induce anxiety in rats. The elevated plus-maze test and open field test were respectively performed on the 7 th, the 14 th, and the 21 st days of the stimulation, so as to detect the anxiety-related protein index brain-derived neurotrophic factor(BDNF) and evaluate the anxiety level of animals. On this basis, the effect of this prescription on anxiety rats was preliminarily evaluated. After the behavioral test on the 21 st day, rats were killed and the brain tissues were separated for the observation of the mitochondrial morphology and the determination of mitochondrial function-related indicators and the adenosine 5'-monophosphate-activated protein kinase(AMPK) level. The results showed that Danzhi Xiaoxiao Powder could alleviate the anxiety-like behavior of rats, significantly increase the percentage of time in open arm in elevated plus-maze test and the ration of activity time in the central area of the field, dose-dependently raise the activity levels of respiratory chain complex Ⅰ,Ⅱ,Ⅲ and Ⅳ and the adenosine triphosphate(ATP) content, and elevate the levels of BDNF and phosphorylated AMPK(p-AMPK). Clear structure and intact morphology of mitochondrial cristae in medial prefrontal cortex cells and amygdala were observed in the Danzhi Xiaoyao Powder group. In summary, Danzhi Xiaoyao Powder exerts therapeutic effect on anxiety, and the mechanism is the likelihood that p-AMPK protects the structure and maintains the function of mitochondria.

HUWE1 promotes EGFR ubiquitination and degradation to protect against renal tubulointerstitial fibrosis.

Injury of renal tubular epithelial cells is a key feature of the pathogenicity associated with tubulointerstitial fibrosis and other kidney diseases. HUWE1, an E3 ubiquitin ligase, acts by participating in ubiquitination and degradation of its target proteins. However, the detailed mechanisms by which HUWE1 might regulate fibrosis in renal tubular epithelial cells have not been established. Here, the possible regulation of renal tubulointerstitial fibrosis by HUWE1 was investigated by examining the expression of HUWE1 and EGFR in unilateral ureteral obstruction (UUO) mice. Markedly consistent reciprocal changes in HUWE1 and EGFR expression were observed at the protein and mRNA levels in the kidney after UUO injury. Expression of HUWE1 inhibited TGF-ß-induced injury to HK-2 cells, while HUWE1 overexpression decreased the expression of EGFR. Further analysis indicated that HUWE1 physically interacted with EGFR and promoted its ubiquitination and degradation. HUWE1 expression also showed clinical relevance in renal disease, as it notably decreased in multiple types of clinical nephropathy, while EGFR expression significantly increased when compared to the normal kidney. Therefore, this study demonstrated that HUWE1, which serves as an E3 ubiquitin ligase specific for EGFR, promotes EGFR ubiquitination and degradation, thereby regulating EGFR expression and providing protection against kidney injury.

Lead optimization of selective tubulin inhibitors as anti-trypanosomal agents.

Previously synthesized tubulin inhibitors showed promising in vitro selectivity and activity against Human African Trypanosomiasis. Current aim is to improve the ligand efficiency and reduce overall hydrophobicity of the compounds, by lead optimization. Via combinatorial chemistry, 60 new analogs were synthesized. For biological assay Trypanosoma brucei brucei Lister 427 cell line were used as the parasite model and for the host model human embryonic kidney cell line HEK-293 and mouse macrophage cell line RAW 264.7 were used to test efficacy. Of the newly synthesized compounds 5, 39, 40, and 57 exhibited IC50s below 5 µM inhibiting the growth of trypanosome cells and not harming the mammalian cells at equipotent concentration. Comparably, the newly synthesized compounds have a reduced amount of aromatic moieties resulting in a decrease in molecular weight. Due to importance of tubulin polymerization during protozoan life cycle its activity was assessed by western blot analyses. Our results indicated that compound 5 had a profound effect on tubulin function. A detailed structure activity relationship (SAR) was summarized that will be used to guide future lead optimization.

Synthesis and biological evaluation of anti-cancer agents that selectively inhibit Her2 over-expressed breast cancer cell growth via down-regulation of Her2 protein.

Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast cancer cells. A structure activity relationship (SAR) was summarized. Compounds 16 and 17 were also examined by western blot assay to check their effect on Her2 protein. The results reveal that the compounds could decrease the Her2 protein, which explains their selectivity to Her2 over-expressed breast cancer cells. Furthermore, the compounds inhibited the chaperone activity of small chaperone protein that could stabilize Her2 protein.

Synthesis and biological evaluation of a new series of cinnamic acid amide derivatives as potent haemostatic agents containing a 2-aminothiazole substructure.

Ten new cinnamic acid derivatives containing a 2-aminothiazole substructure were designed and synthesized. This series of compounds exhibited good thermostabilities as demonstrated by thermogravimetric analysis. In coagulation assays (prothrombin time, activated partial thromboplastin time and thrombin time) in vitro, most compounds demonstrated excellent activities to promote blood coagulation. Among the studied series, compounds N1, N4, N5 and W5 exhibited a significant coagulation activity. Further studies indicated that compound N5 (IC50=1.87µmol/L) displayed the most suitable efficacy of promoting platelet aggregation than the clinically used haemostatic drug etamsylate (IC50=46.22µmol/L). Furthermore, the relationship between the functional groups of the compounds and the corresponding blood coagulant activity was explored in this study.

Synthesis and biological evaluation of selective tubulin inhibitors as anti-trypanosomal agents.

African trypanosomiasis is still a threat to human health due to the severe side-effects of current drugs. We identified selective tubulin inhibitors that showed the promise to the treatment of this disease, which was based on the tubulin protein structural difference between mammalian and trypanosome cells. Further lead optimization was performed in the current study to improve the efficiency of the drug candidates. We used Trypanosoma brucei brucei cells as the parasite model, and human normal kidney cells and mouse macrophage cells as the host model to evaluate the compounds. One new analog showed great potency with an IC50 of 70nM to inhibit the growth of trypanosome cells and did not affect the viability of mammalian cells. Western blot analyses reveal that the compound decreased tubulin polymerization in T. brucei cells. A detailed structure activity relationship (SAR) was summarized that will be used to guide future lead optimization.

Mechanobiological insight into brain diseases based on mechanosensitive channels: Common mechanisms and clinical potential.

BACKGROUND: As physical signals, mechanical cues regulate the neural cells in the brain. The mechanosensitive channels (MSCs) perceive the mechanical cues and transduce them by permeating specific ions or molecules across the plasma membrane, and finally trigger a series of intracellular bioelectrical and biochemical signals. Emerging evidence supports that wide-distributed, high-expressed MSCs like Piezo1 play important roles in several neurophysiological processes and neurological disorders. AIMS: To systematically conclude the functions of MSCs in the brain and provide a novel mechanobiological perspective for brain diseases. METHOD: We summarized the mechanical cues and MSCs detected in the brain and the research progress on the functional roles of MSCs in physiological conditions. We then concluded the pathological activation and downstream pathways triggered by MSCs in two categories of brain diseases, neurodegenerative diseases and place-occupying damages. Finally, we outlined the methods for manipulating MSCs and discussed their medical potential with some crucial outstanding issues. RESULTS: The MSCs present underlying common mechanisms in different brain diseases by acting as the "transportation hubs" to transduce the distinct signal patterns: the upstream mechanical cues and the downstream intracellular pathways. Manipulating the MSCs is feasible to alter the complicated downstream processes, providing them promising targets for clinical treatment. CONCLUSIONS: Recent research on MSCs provides a novel insight into brain diseases. The common mechanisms mediated by MSCs inspire a wide range of therapeutic potentials targeted on MSCs in different brain diseases.

Progress of Mitochondrial Function Regulation in Cardiac Regeneration.

Heart failure and myocardial infarction, global health concerns, stem from limited cardiac regeneration post-injury. Myocardial infarction, typically caused by coronary artery blockage, leads to cardiac muscle cell damage, progressing to heart failure. Addressing the adult heart's minimal self-repair capability is crucial, highlighting cardiac regeneration research's importance. Studies reveal a metabolic shift from anaerobic glycolysis to oxidative phosphorylation in neonates as a key factor in impaired cardiac regeneration, with mitochondria being central. The heart's high energy demands rely on a robust mitochondrial network, essential for cellular energy, cardiac health, and regenerative capacity. Mitochondria's influence extends to redox balance regulation, signaling molecule interactions, and apoptosis. Changes in mitochondrial morphology and quantity also impact cardiac cell regeneration. This article reviews mitochondria's multifaceted role in cardiac regeneration, particularly in myocardial infarction and heart failure models. Understanding mitochondrial function in cardiac regeneration aims to enhance myocardial infarction and heart failure treatment methods and insights.

Benthic foraminiferal community structure and its response to environmental factors revealed using high-throughput sequencing in the Zhoushan Fishing Ground, East China Sea.

Benthic foraminifera are excellent tools for monitoring marine environments and reconstructing paleoenvironments. This study investigated the structure and diversity of benthic foraminiferal communities in 20 superficial sediment samples obtained from the Zhoushan Fishing Ground (ZFG) using high-throughput sequencing based on small subunit ribosomal DNA and RNA amplification. The results revealed Rotaliida as the most dominant group, with spatial heterogeneity in foraminiferal distribution. Total benthic foraminiferal communities exhibited higher species richness and diversity compared to active communities. While heavy metal pollution in the ZFG was moderate, areas with elevated concentrations of heavy metals exhibited low diversity and richness in foraminiferal communities. Total foraminiferal community structure was primarily influenced by factors such as water depth and Hg, Pb, Cd, and Zn levels. Notably, Hg levels emerged as a critical factor impacting the structure and diversity of the active foraminiferal community. The dominant species, Operculina, exhibited tolerance toward heavy metal pollution.

An ACC-VTA-ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences.

The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic pain. ACC glutamatergic neurons (ACCGlu) projecting to the VTA indirectly inhibit dopaminergic neurons (VTADA) by activating local GABAergic interneurons (VTAGABA), and this effect is reinforced after nerve injury. VTADA neurons in turn project to the ACC and synapse to the initial ACCGlu neurons to convey feedback information from emotional changes. Thus, an ACCGlu-VTAGABA-VTADA-ACCGlu positive-feedback loop mediates the progression to and maintenance of persistent pain and comorbid anxiodepressive-like behavior. Disruption of this feedback loop relieves hyperalgesia and anxiodepressive-like behavior in a mouse model of neuropathic pain, both acutely and in the long term.

Comparison and quantification of estrogen receptor-mediated responsiveness to endocrine disruptors in bivalves by using complementary model and a novel yeast assay approach.

Endocrine disrupting chemicals (EDCs) in estuaries and coastal habitats have been widely detected over the world and caused global concern. Bivalves have been shown to be vulnerable to endocrine disruption. However, estrogen receptors (ERs) sensitivity to steroids and EDCs has long been considered to be restricted to vertebrates. In the present study, a computational simulation docking model was applied to qualitatively predict the binding behavior of two bivalve ERs to estradiol and compared the docking activity with zebra fish ERa. A novel reconstituted yeast system was constructed by using transcriptional activator GAL-4 consists of ER-expressing plasmid and ERE (estrogen responsive element)-containing plasmid. The assays showed that bivalve ER specifically activate transcription in response to tested steroids and EDCs, but the activation ability is weaker compared to zebra fish ERa. The results corroborate the presence of an active ER in bivalve molluscs and provide a promising tool for screening of marine environmental pollutants active in disturbing ERs of bivalves, as well as understanding the underlying mechanism across taxonomic groups and phyla.

Stress can affect mitochondrial energy metabolism and AMPK/SIRT1 signaling pathway in rats.

OBJECTION: To investigate the potential link between aberrant mitochondrial energy metabolism mediated by the AMPK/SIRT1 pathway and the etiology of anxiety disorders. METHODS: The anxiety rat model was established by uncertain empty water bottle（UEWB）stress. Rats were submitted behavioral tests on the seventh, fourteenth, and twenty-first days and had the prefrontal cortex and amygdala removed for biochemical tests. The morphological alterations of the mitochondria in the medial prefrontal cortex and amygdala were examined by using a transmission electron microscope. Expression levels of AMPK, SIRT1, PGC-1, NRF-1 and NRF-2 were tested by western-blot analysis. ATP, respiratory chain complex and caspase enzyme expressions were tested by neurochemical and biochemical assays. RESULTS: Rats showed anxiety-like behavior after being exposed to the uncertain empty water bottle (UEWB) stress model. In model rats, mitochondrial structure is damaged, mitochondrial energy metabolism is decreased, and the expression of proteins associated with AMPK/SIRT1 pathway is significantly reduced in the brain. CONCLUSION: The level of mitochondrial energy metabolism correlates with anxiety-like behavior. The main mechanism of anxiety disorder is a disturbance of mitochondrial energy metabolism, which might be related to AMPK/SIRT1 pathway.

Potencies of organotin compounds in scallop RXRa responsive activity with a GAL4-based reconstituted yeast assay in vitro.

Retinoid X receptor (RXR) has been found to be a major target in various processes of endocrine disruption from the exposure to organotin compounds (OTCs), including imposex in gastropod mollusks. It was also reported in bivalves that OTCs caused intersex and skewed sex ratio. In order to evaluate the effect of these ligand-like OTCs, we constructed a reconstituted yeast system (CfRE system) based on GAL4 yeast two-hybrid principle using scallop Chlamys farreri retinoid X receptor (CfRXRa) and retinoid X response element (RXRE) to investigate the ligand-induced transactivation of CfRXRa. Responses of CfRXRa to 9-cis retinoic acid (9cRA) and tested four OTCs showed concentration-dependent response which is comparable with reported RXRa in vitro assay of human and gastropods. The detective limits of the CfRE system were found to be 100 nM for 9cRA and 10-1000 nM for the tested OTCs. While the tested non-Sn endocrine disrupting chemicals, including Benzo[a]pyrene, 2,4-Dichlorophenol, Nonylphenol, and Tetrabromobisphenol A, showed no effect on CfRXRa response. The present assay system may provide a valuable tool for screening assessments of unidentified environmental ligand chemicals on bivalve mollusks. It is also useful for comparison of sensitivity differences among species exposed to EDCs.

Use of GAL4 factor-based yeast assay to quantify the effects of xenobiotics on RXR homodimer and RXR/PPAR heterodimer in scallop Chlamys farreri.

Retinoid X receptor (RXR) and peroxisome proliferators-activated receptors (PPAR) have been shown as important targets of endocrine disrupting effects caused by organotin compounds (OTCs). In vitro methods for non-model species are instrumental in revealing not only mechanism of toxicity but also basic biology. In the present study, we constructed the GAL4 factor-based recombinant yeast systems of RXRα/RXRα (RR), RXRα/PPARα (RPα) and RXRα/PPARγ (RPγ) of the scallop Chlamys farreri to investigate their transcriptional activity under the induction of OTCs (tributyltin chloride, triphenyltin chloride, tripropyltin chloride and bis(tributyltin)oxide), their spiked sediments and five other non­tin compounds (Wy14643, rosiglitazone, benzyl butyl phthalate, dicyclohexyl phthalate and bis(2-ethylhexyl) phthalate). The results showed that the natural ligand of RXR, 9-cis-retinoic acid (9cRA), induces transcriptional activity in all three systems, while four OTCs induced the transcriptional activity of the RR and RPα systems. None of the five potential non­tin endocrine disruptors induced effects on the RPα and RPγ systems. The spiked sediment experiment demonstrated the feasibility of the recombinant yeast systems constructed in this study for environmental sample detection. These results suggest that OTCs pose a threat to affect function of RXRα and PPARα of bivalve mollusks. The newly developed GAL4 factor-based yeast two-hybrid system can be used as a valuable tool for identification and quantification of compounds active in disturbing RXR and PPAR of bivalves.

Total and active benthic foraminiferal community and their response to heavy metals revealed by high throughput DNA and RNA sequencing in the Zhejiang coastal waters, East China Sea.

Benthic foraminifera, large protists abundant in marine environments, have been widely used as bioindicators of environmental conditions. In this study, high-throughput sequencing based on small subunit rDNA and rRNA amplifications was used to investigate total and active benthic foraminifera community composition and diversity from nineteen and twelve superficial marine sediment samples in the Zhejiang coastal waters, respectively. The results showed that the dominant taxa of total foraminifera changed from Buliminellidae (hyaline) to Saccamminidae (agglutinated) from north to south along the coastal waters of Zhejiang Province. According to our survey, heavy metal contamination was moderate in Zhejiang coastal waters, and the potential ecological risks posed by Cd and Hg were higher. The contamination level of heavy metals at Yueqing Bay was the highest, followed by those at Sanmen Bay and Hangzhou Bay. Cd, Cu and grain size may be key factors affecting the distribution and composition of active foraminiferal communities.

Effects of BαP and TBBPA on multixenobiotic resistance (MXR) related efflux transporter activity and gene expressions in gill cells of scallop Chlamys farreri.

The multixenobiotic resistance mechanism (MXR) provides aquatic organisms with the capacity to adapt to polluted environments, which can be inhibited by chemosensitizers. In the present study, the effect of two typical marine persistent organic pollutants, benzo(a)pyrene (BaP) and tetrabromobisphenol A (TBBPA), on the most relevant ABC transporters, ABCB1, ABCC1, and ABCG2 of scallop Chlamys farreri was tested. MXR transporter efflux activity of cultured gill cells of the scallops was evaluated by measuring the intracellular fluorescent intensity of Calcein-AM and rhodamine 123 with flow cytometry. The results showed that ABCB1 and ABCC1 transporters demonstrated increased activity compared with ABCG2 in mediating MXR efflux activity. BaP and TBBPA were able to suppress the efflux transporter activity of ABC transporters significantly, of which BaP revealed block effects by acting on the ABCB1 transporter. Additionally, exposure of BaP and TBBPA only significantly upregulated the expression level of ABCC1 gene. This study demonstrated the promising utility of efflux transporter activity in conjunction with biomarkers such as mRNA levels in identification of chemosensitizer.

The interaction of S100A16 and GRP78 actives endoplasmic reticulum stress-mediated through the IRE1α/XBP1 pathway in renal tubulointerstitial fibrosis.

Recent studies have indicated that the development of acute and chronic kidney disease including renal fibrosis is associated with endoplasmic reticulum (ER) stress. S100 calcium-binding protein 16 (S100A16) as a novel member of the S100 family is involved in kidney disease; however, few studies have examined fibrotic kidneys for a relationship between S100A16 and ER stress. In our previous study, we identified GRP78 as a protein partner of S100A16 in HK-2 cells. Here, we confirmed a physical interaction between GRP78 and S100A16 in HK-2 cells and a markedly increased expression of GRP78 in the kidneys of unilateral ureteral occlusion mice. S100A16 overexpression in HK-2 cells by infection with Lenti-S100A16 also induced upregulation of ER stress markers, including GRP78, p-IRE1α, and XBP1s. Immunofluorescence staining demonstrated that the interaction between S100A16 and GRP78 predominantly occurred in the ER of control HK-2 cells. By contrast, HK-2 cells overexpressing S100A16 showed colocalization of S100A16 and GRP78 mainly in the cytoplasm. Pretreatment with BAPTA-AM, a calcium chelator, blunted the upregulation of renal fibrosis genes and ER stress markers induced by S100A16 overexpression in HK-2 cells and suppressed the cytoplasmic colocalization of GRP78 and S100A16. Co-immunoprecipitation studies suggested a competitive binding between S100A16 and IRE1α with GRP78 in HK-2 cells. Taken together, our findings demonstrate a significant increase in S100A16 expression in the cytoplasm following renal injury. GRP78 then moves into the cytoplasm and binds with S100A16 to promote the release of IRE1α. The subsequent phosphorylation of IRE1α then leads to XBP1 splicing that activates ER stress.