Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. RESULTS: OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. CONCLUSIONS: We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.

Investigation of the peptides with calcium chelating capacity in hydrolysate derived from spent hen meat.

Calcium peptide chelates are developed as efficient supplements for preventing calcium deficiency. Spent hen meat (SHM) contains a high percentage of proteins but is generally wasted due to the disadvantages such as hard texture. We chose the underutilized SHM to produce peptides to bind calcium by proteolysis and aimed to investigate chelation between calcium and peptides in hydrolysate for a sustainable purpose. The optimized proteolysis conditions calculated from the result of response surface methodology for two-step hydrolysis were 0.30% (wenzyme/wmeat) for papain with a hydrolysis time of 3.5 h and 0.18% (wenzyme/wmeat) for flavourzyme with a hydrolysis time of 2.8 h. The enzymatic hydrolysate (EH) showed a binding capacity of 63.8 ± 1.8 mg calcium/g protein. Ethanol separation for EH improved the capacity up to a higher value of 68.6 ± 0.6 mg calcium/g protein with a high association constant of 420 M-1 (25°C) indicating high stability. The separated fraction with a higher amount of Glu, Asp, Lys, and Arg had higher calcium-binding capacity, which was related to the number of ─COOH and ─NH2 groups in peptide side chains according to the result from amino acid analysis and Fourier transform infrared spectroscopy. Two-step enzymatic hydrolysis and ethanol separation were an efficient combination to produce peptide mixtures derived from SHM with high calcium-binding capacity. The high percentage of hydrophilic amino acids in the separated fraction was concluded to increase calcium-binding capacity. This work provides foundations for increasing spent hen utilization and developing calcium peptide chelates based on underutilized meat.

An integrated approach to prioritizing ecological restoration of abandoned mine lands based on cost-benefit analysis.

How to increase the usable land area by adhering to environmentally friendly ecological restoration of mines with limited funds is a challenge that many cities are currently facing. Cost-benefit analysis (CBA) can provide efficient and effective restoration decisions for abandoned mine land (AML) ecological restoration with limited financial resources. Thus, this study proposes an integrated approach for coupling ecological benefits and restoration costs, including hotspots/coldspots analysis based on five ecosystem services (ESs), landscape connectivity analysis based on graph theory model, hidden costs, and project implementation costs to prioritize AML restoration. The study was conducted on 54 abandoned mine lands (AMLs) in Chaoyang city, the ecological security barrier of China's northern sand prevention belt (NSPB). The comprehensive analysis prioritized the restoration of AMLs into four levels, of which 9 mines were in priority I, where restoration was recommended as a priority, and 22 mines were in priority II, where restoration could be carried out within the affordability of funds. In addition, our model indicates areas with high ecological benefits, in which the ecological source area (7423.66 km2) and the ecosystem service hotspots area (2028.44 km2) are mostly distributed in the southwestern part of Chaoyang city, the two mountain ranges of Songling mountain and Nuruerhu mountain. This study provides scientific spatial guidance to ensure that the AMLs realizes effective restoration and management.

Bioactive atropisomers: Unraveling design strategies and synthetic routes for drug discovery.

Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.

One-Step Purification and Immobilization of Glycosyltransferase with Zn-Ni MOF for the Synthesis of Rare Ginsenoside Rh2.

Uridine diphosphate (UDP)-glucosyltransferases (UGTs) have received increasing attention in the field of ginsenoside Rh2 conversion. By harnessing the metal chelation between transition metal ions and imidazole groups present on His-tagged enzymes, a specific immobilization of the enzyme within metal-organic frameworks (MOFs) is achieved. This innovative approach not only enhances the stability and reusability of the enzyme but also enables one-step purification and immobilization. Consequently, the need for purifying crude enzyme solutions is effectively circumvented, resulting in significant cost savings during experimentation. The use of immobilized enzymes in catalytic reactions has shown great potential for achieving higher conversion rates of ginsenoside Rh2. In this study, highly stable mesoporous Zn-Ni MOF materials were synthesized at 150 °C by a solvothermal method. The UGT immobilized on the Zn-Ni MOF (referred to as UGT@Zn-Ni MOF) exhibited superior pH adaptability and thermal stability, retaining approximately 76% of its initial activity even after undergoing 7 cycles. Furthermore, the relative activity of the immobilized enzyme remained at an impressive 80.22% even after 45 days of storage. The strong specific adsorption property of Zn-Ni MOF on His-tagged UGT was confirmed through analysis using polyacrylamide gel electrophoresis. UGT@Zn-Ni MOF was used to catalyze the conversion reaction, and the concentration of rare ginsenoside Rh2 was generated at 3.15 µg/mL. The results showed that Zn-Ni MOF is a material that can efficiently purify and immobilize His-tagged enzyme in one step and has great potential for industrial applications in enzyme purification and ginsenoside synthesis.

Disruption of gonadotropin hormone biosynthesis by parabens: A potential development and reproduction-associated adverse outcome pathway.

Parabens are widely used as antibacterial preservatives in foods and personal care products. The knowledge about the modes of toxic action of parabens on development and reproduction remain very limited. The present study attempted to establish a development and reproduction-associated adverse outcome pathway (AOP) by evaluating the effects of methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) on the biosynthesis of gonadotropins, which are key hormones for development and reproduction. MP and BP significantly upregulated the mRNA and protein levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in pituitary gonadotropic cells in a concentration-dependent manner. Activation of gonadotropin-releasing hormone receptor (GnRHR) was required for gonadotropin biosynthesis induced by BP, but not MP. Molecular docking data further demonstrated the higher binding efficiency of BP to human GnRHR than that of MP, suggesting GnRHR as a potential molecular initiative event (MIE) for BP-induced gonadotropin production. L-type voltage-gated calcium channels (VGCCs) were found to be another candidate for MIE in gonadotropic cells response to both MP and BP exposure. The calcium-dependent activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2 was subsequently required for MP- and BP-induced activation of GnRHR and L-type VGCCs pathways. In summary, MP and BP promoted gonadotropin biosynthesis through their interactions with cellular macromolecules GnRHR, L-type VGCCs, and subsequent key event ERK1/2. This is the first study to report the direct interference of parabens with gonadotropin biosynthesis and establish a potential AOP based on pathway-specific mechanism, which contributes to the effective screening of environmental chemicals with developmental and reproductive health risks.

A Highly-Fluorinated Lithium Borate Main Salt Empowering Stable Lithium Metal Batteries.

Traditional lithium salts are difficult to meet practical application demand of lithium metal batteries (LMBs) under high voltages and temperatures. LiPF6, as the most commonly used lithium salt, still suffers from notorious moisture sensitivity and inferior thermal stability under those conditions. Here, we synthesize a lithium salt of lithium perfluoropinacolatoborate (LiFPB) comprising highly-fluorinated and borate functional groups to address the above issues. It is demonstrated that the LiFPB shows superior thermal and electrochemical stability without any HF generation under high temperatures and voltages. In addition, the LiFPB can form a protective outer-organic and inner-inorganic rich cathode electrolyte interphase on LiCoO2 (LCO) surface. Simultaneously, the FPB- anions tend to integrate into lithium ion solvation structure to form a favorable fast-ion conductive LiBxOy based solid electrolyte interphase on lithium (Li) anode. All these fantastic features of LiFPB endow LCO (1.9 mAh cm-2)/Li metal cells excellent cycling under both high voltages and temperatures (e.g., 80 % capacity retention after 260 cycles at 60 °C and 4.45 V), and even at an extremely elevated temperature of 100 °C. This work emphasizes the important role of salt anions in determining the electrochemical performance of LMBs at both high temperature and voltage conditions.

Chiral nanomaterials in tissue engineering.

Addressing significant medical challenges arising from tissue damage and organ failure, the field of tissue engineering has evolved to provide revolutionary approaches for regenerating functional tissues and organs. This involves employing various techniques, including the development and application of novel nanomaterials. Among them, chiral nanomaterials comprising non-superimposable nanostructures with their mirror images have recently emerged as innovative biomaterial candidates to guide tissue regeneration due to their unique characteristics. Chiral nanomaterials including chiral fibre supramolecular hydrogels, polymer-based chiral materials, self-assembling peptides, chiral-patterned surfaces, and the recently developed intrinsically chiroptical nanoparticles have demonstrated remarkable ability to regulate biological processes through routes such as enantioselective catalysis and enhanced antibacterial activity. Despite several recent reviews on chiral nanomaterials, limited attention has been given to the specific potential of these materials in facilitating tissue regeneration processes. Thus, this timely review aims to fill this gap by exploring the fundamental characteristics of chiral nanomaterials, including their chiroptical activities and analytical techniques. Also, the recent advancements in incorporating these materials in tissue engineering applications are highlighted. The review concludes by critically discussing the outlook of utilizing chiral nanomaterials in guiding future strategies for tissue engineering design.

Characteristics and fractionations of sediment oxygen demand in a complex tidal river network area.

Tidal river networks are affected by the tide and influenced by complex factors related to sediment oxygen demand (SOD). In this study, we used chemical inhibition to measure the oxygen consumption of different types of SOD to explore the specific oxygen consumption mechanism of sediments. Then, we evaluated the diffusion fluxes of the sediment-water interface and factors affecting SOD using diffusive gradients in thin films. Total SOD in the tidal river network area of the Pearl River basin was ∼0.5928 g/m2/day, which was 8.47% higher than that in the non-tidal river network area but lower than that in black and odorous water reported previously. In the tidal river network area, biological SOD was 15.6% higher in summer than in winter, and the difference in total SOD was greatly influenced by human activity. We observed a significant effect of sediment on SOD in winter, whereas there were no significant correlations between sediment and SOD in summer. Different particle-size distributions lead to different organic matter contents, resulting in different biological SOD ratios between seasons. Our study found that seasonal tidal changes can affect ion exchange at the sediment water interface, leading to changes in SOD.These findings will be of great significance for the study of phenomena associated with low dissolved oxygen in tidal river networks and provide directions for future sediment pollution control.

The Role of Sensory Nerves in Dental Pulp Homeostasis: Histological Changes and Cellular Consequences after Sensory Denervation.

Homeostatic maintenance is essential for pulp function. Disrupting pulp homeostasis may lead to pulp degeneration, such as fibrosis and calcifications. Sensory nerves constitute a crucial component of the dental pulp. However, the precise involvement of sensory nerves in pulp homeostasis remains uncertain. In this study, we observed the short-term and long-term histological changes in the dental pulp after inferior alveolar nerve transection. Additionally, we cultured primary dental pulp cells (DPCs) from the innervated and denervated groups and compared indicators of cellular senescence and cellular function. The results revealed that pulp fibrosis occurred at 2 w after the operation. Furthermore, the pulp area, as well as the height and width of the pulp cavity, showed accelerated reductions after sensory denervation. Notably, the pulp area at 16 w after the operation was comparable to that of 56 w old rats. Sensory denervation induced excessive extracellular matrix (ECM) deposition and increased predisposition to mineralization. Furthermore, sensory denervation promoted the senescence of DPCs. Denervated DPCs exhibited decelerated cell proliferation, arrest in the G2/M phase of the cell cycle, imbalance in the synthesis and degradation of ECM, and enhanced mineralization. These findings indicate that sensory nerves play an essential role in pulp homeostasis maintenance and dental pulp cell fate decisions, which may provide novel insights into the prevention of pulp degeneration.

Single-cell transcriptomics of peripheral blood mononuclear cells indicates impaired immune and inflammatory responses in alcohol-associated hepatitis.

Alcohol-associated hepatitis (AH) is often diagnosed at advanced stages, and severe AH usually carries poor prognosis and high short-term mortality. In addition, it is challenging to understand the molecular mechanisms of immune dysregulation and inflammation in AH due to the cellular complexity and heterogeneity. Using single-cell RNA sequencing, previous studies found that AH causes dysfunctional innate immune response in monocytes, involving activation of pattern recognition receptors (PRRs) and cytokine signaling pathways. To better understand the coordinated systemic immune response in AH patients, we performed combined single-cell transcriptome, cell-surface protein, and lymphocyte antigen receptor analysis of peripheral blood mononuclear cell (PBMC) samples. Our results showed inflammatory cytokines and chemokines were highly expressed in AH, including IL-2, IL-32, CXC3R1 and CXCL16 in monocytes and NK cells, whereas HLA-DR genes were reduced in monocytes. In addition, we also found altered differentiation of T-helper cells (TH1 and TH17), which could further lead to neutrophil recruitment and macrophage activation. Lastly, our results also suggest impaired NK-cell activation and differentiation in AH with reduced gene expression of KLRC2 and increased gene expression of KLRG1. Our findings indicate different mechanisms may be involved in impaired immune and inflammatory responses for the cellular subtypes of the PBMCs in AH.

Joint estimation of pose, depth, and optical flow with a competition-cooperation transformer network.

Estimating depth, ego-motion, and optical flow from consecutive frames is a critical task in robot navigation and has received significant attention in recent years. In this study, we propose PDF-Former, an unsupervised joint estimation network comprising a full transformer-based framework, as well as a competition and cooperation mechanism. The transformer framework captures global feature dependencies and is customized for different task types, thereby improving the performance of sequential tasks. The competition and cooperation mechanisms enable the network to obtain additional supervisory information at different training stages. Specifically, the competition mechanism is implemented early in training to achieve iterative optimization of 6 DOF poses (rotation and translation information from the target image to the two reference images), the depth of target image, and optical flow (from the target image to the two reference images) estimation in a competitive manner. In contrast, the cooperation mechanism is implemented later in training to facilitate the transmission of results among the three networks and mutually optimize the estimation results. We conducted experiments on the KITTI dataset, and the results indicate that PDF-Former has significant potential to enhance the accuracy and robustness of sequential tasks in robot navigation.

The association of lipoprotein (a) with coronary artery calcification: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Coronary artery calcification (CAC) is a crucial pathophysiological characteristic of atherosclerosis. The association between lipoprotein (a) [Lp(a)] and CAC is inconsistent. We aimed to assess the relationship between Lp(a) and CAC by exploring the association between elevated Lp(a) and CAC prevalence, the relationship between Lp(a) level and CAC prevalence, and the correlation between elevated Lp(a) and CAC progression. METHODS: We searched the PubMed, Web of Science, and EMBASE databases up to November 01, 2023. Studies exploring the association between serum Lp(a) and CAC (quantified using the Agatston score) were included. Association between Lp(a) level or elevated Lp(a) (higher than the cutoff values of 30 mg/dL, 50 mg/dL, or the highest quartile ranging from 33 to 38.64 mg/dL) and prevalence [CAC score >0 or >100, log (CAC score+1) >0] or progression (an increase in CAC score >0 or ≥100) of CAC were analysed. Odds ratios and 95% confidence intervals were calculated using a random-effects model. RESULTS: 40,073 individuals from 17 studies were included. Elevated Lp(a) was associated with a higher prevalence of CAC (OR, 1.31; 95% CI, 1.06 to 1.61; p = 0.01). As a continuous variable, Lp(a) level was positively correlated with the prevalence of CAC (OR, 1.05; 95% CI, 1.02 to 1.08; p = 0.003). Furthermore, elevated Lp(a) was associated with greater CAC progression (OR, 1.54; 95% CI, 1.23 to 1.92; p = 0.0002). CONCLUSIONS: This meta-analysis suggested that Lp(a) is associated with prevalence and progression of CAC. Further studies are required to explore whether Lp(a)-lowering therapy could prevent or inhibit CAC, ultimately reducing coronary artery disease risk.

Surface-Water Nitrate Exposure to World Populations Has Expanded and Intensified during 1970-2010.

Excessive nitrate in surface waters deteriorates the water quality and threatens human health. Human activities have caused increased nitrate concentrations in global surface waters over the past 50 years. An assessment of the long-term trajectory of surface-water nitrate exposure to world populations and the associated potential health risks is imperative but lacking. Here, we used global spatially explicit data on surface-water nitrate concentrations and population density, in combination with thresholds for health risks from epidemiological studies, to quantify the long-term changes in surface-water nitrate exposure to world populations at multiple spatial scales. During 1970-2010, global populations potentially affected by acute health risks associated with surface-water nitrate exposure increased from 6 to 60 million persons per year, while populations at potential chronic health risks increased from 169 to 1361 million persons per year. Potential acute risks have increasingly affected Asian countries. Populations potentially affected by chronic risks shifted from dominance by high-income countries (in Europe and North America) to middle-income countries (in Asia and Africa). To mitigate adverse health effects associated with surface-water nitrate exposure, anthropogenic nitrogen inputs to natural environments should be drastically reduced. International and national standards of maximum nitrate contamination may need to be lowered.

High-resolution awake mouse fMRI at 14 Tesla.

High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radiofrequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Using a 14T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100×100×200µm resolution with a 2s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust BOLD responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 seconds prior to the air-puff in awake mice with repetitive stimulation, which was not detectable with the randomized stimulation paradigm. This early BC activation indicated learned anticipation through the vibrissa system and association cortices in awake mice under continuous training of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas.

Sensor Scheduling for Remote State Estimation with Limited Communication Resources: A Time- and Event-Triggered Hybrid Approach.

This paper proposes a time- and event-triggered hybrid scheduling for remote state estimation with limited communication resources. A smart sensor observes a physical process and decides whether to send the local state estimate to a remote estimator via a wireless communication channel; the estimator computes the state estimate of the process according to the received data packets and the known scheduling mechanism. Based on the existing optimal time-triggered scheduling, we employ a stochastic event trigger to save precious communication chances and further improve the estimation performance. The minimum mean-squared error (MMSE) state estimate is derived since the Gaussian property is preserved. The estimation performance upper bound and communication rate are analyzed. The main results are illustrated by numerical examples.

Fractional flow reserve versus intravascular imaging to guide decision-making for percutaneous coronary intervention in intermediate lesions: A meta-analysis.

BACKGROUND: Both fractional flow reserve (FFR) and intravascular imaging (IVI) have been used to guide the decision-making for percutaneous coronary intervention (PCI) in intermediate coronary stenosis. Nevertheless, studies that directly compared the prognostic significance of these two strategies are scarce. AIMS: The aim of this meta-analyses was to evaluate the impact of FFR versus IVI to guide the decision-making in PCI for intermediate stenosis on clinical outcomes. METHODS: We systematically searched PubMed, Embase, Cochrane, and relevant database from inception date to September 2022 for observational studies and randomized clinical trials (RCTs) which compared FFR and IVI-based decision-making in PCI for intermediate stenosis. The primary outcome was a composite of major adverse cardiac event (MACE). Pooled risk ratios (RR) were calculated using random effects models and heterogeneity were evaluated with the I2 statistic. RESULTS: We identified 5 studies (3 RCTs and 2 observational studies) with 3208 patients. The follow-up duration ranged from 12 to 24 months. Among five studies, four compared FFR with intravascular ultrasound while one compared FFR with optical coherence tomography. There was no statistically difference between FFR and IVI in the incidence of MACE (RR: 1.19; 95% confidence interval: 0.85-1.68; p = 0.31) and its individual components. These results were consistent regardless of various cut-off value of PCI across the studies. Compared with IVI, FFR was associated with a lower PCI rate (37.0% vs. 60.3%; p < 0.001). CONCLUSIONS: The decision to perform PCI for intermediate stenosis guided by FFR or IVI showed a similar clinical outcome. The use of FFR significantly reduced the need for PCI.

Three anthocyanin-rich berry extracts regulate the in vitro digestibility of corn starch: Physicochemical properties, structure and α-amylase.

This study aimed to compare the regulatory effects of blue honeysuckle anthocyanins (BHA), blueberry anthocyanins (BBA), and blackcurrant anthocyanins (BCA) on the in vitro digestibility of corn starch in terms of starch physicochemical properties and structure, as well as α-amylase inhibition. The results revealed that adding all three anthocyanins lowered digestibility in the following order: BHA > BCA > BBA. The terminal digestibility (C∞) decreased from 73.84 % to 57.3 % with the addition of 10 % BHA, while the resistant starch (RS) content increased from 4.39 % to 48.82 %. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis indicated that anthocyanins and starch interacted through noncovalent bonds. Differential scanning calorimetry (DSC) analysis showed that the gelatinization enthalpy was dramatically lowered in all three anthocyanin groups, with 10 % BHA producing a 38.58 % drop. Rheological property analysis showed that anthocyanins increased the apparent viscosity and modulus with starch. The interaction between anthocyanin and α-amylase was mainly through the formation of hydrogen bonds and hydrophobic forces. This research provides theoretical guidance for developing low glycemic index (GI) anthocyanin starch-based foods.

Activation of the 5-hydroxytryptamine 4 receptor ameliorates tight junction barrier dysfunction in the colon of type 1 diabetic mice.

Hyperglycemia drives dysfunction of the intestinal barrier. 5-Hydroxytryptaine 4 receptor (5-HT 4R) agonists have been considered therapeutics for constipation in clnic. However, the roles of 5-HT 4R activation in mucosa should be fully realized. Here, we investigate the effects of 5-HT 4R activation on diabetes-induced disruption of the tight junction (TJ) barrier in the colon. Not surprisingly, the TJ barrier in diabetic mice with or without 5-HT 4R is tremendously destroyed, as indicated by increased serum fluorescein isothiocyanate (FITC)-dextran and decreased transepithelial electrical resistance (TER). Simultaneously, decreased expressions of TJ proteins are shown in both wild-type (WT) and 5-HT 4R knockout (KO) mice with diabetes. Notably, chronic treatment with intraperitoneal injection of a 5-HT 4R agonist in WT mice with diabetes repairs the TJ barrier and promotes TJ protein expressions, including occludin, claudin-1 and ZO-1, in the colon, whereas a 5-HT 4R agonist does not improve TJ barrier function or TJ protein expressions in 5-HT 4R KO mice with diabetes. Furthermore, stimulation of 5-HT 4R inhibits diabetes-induced upregulation of myosin light chain kinase (MLCK), Rho-associated coiled coil protein kinase 1 (ROCK1), and phosphorylated myosin light chain (p-MLC), which are key molecules that regulate TJ integrity, in the colonic mucosa of WT mice. However, such action induced by a 5-HT 4R agonist is not observed in 5-HT 4R KO mice with diabetes. These findings indicate that 5-HT 4R activation may restore TJ integrity by inhibiting the expressions of MLCK, ROCK1 and p-MLC, improving epithelial barrier function in diabetes.

Brain-like position measurement method based on improved optical flow algorithm.

In this paper, a brain-like navigation scheme based on fuzzy kernel C-means (FKCM) clustering assisted pyramid Lucas Kanade (LK) optical flow algorithm is developed to measure the position of vehicle. The Speed Cell and Place Cell in animals' brain are introduced to construct the brain-like navigation mechanism which involves the optical flow method and image template matching to imitate the cells above-mentioned separately. To eliminate the singular values during optical flow calculation, the output of pyramid LK algorithm is clustered by FKCM algorithm firstly. Then, the velocity is calculated and integrated to get the position of the vehicle, and the brain-like navigation scheme is introduced to correct the position measurement errors by eliminating the accumulated errors resulting from velocity integration. The prominent advantages of the presented method are: (i) a pure visual brain-like position measurement method based on the concept of speed cells and place cells is proposed, making visual navigation more accurate and intelligent; (ii) the FKCM algorithm is used to eliminate the singular value of the pyramid LK algorithm, which improves the calculated velocity accuracy. Also, experimental comparison with classical pyramid LK algorithm is given to illustrate the superiority of the proposed method in position measurement.