Evidence Supporting a Role of Alternative Splicing Participates in Melon (Cucumis melo L.) Fruit Ripening.

One key post-transcriptional modification mechanism that dynamically controls a number of physiological processes in plants is alternative splicing (AS). However, the functional impacts of AS on fruit ripening remain unclear. In this research, we used RNA-seq data from climacteric (VED, Harukei 3) and non-climacteric (PI, PS) melon cultivars to explore alternative splicing (AS) in immature and mature fruit. The results revealed dramatic changes in differential AS genes (DAG) between the young and mature fruit stages, particularly in genes involved in fruit development/ripening, carotenoid and capsaicinoid biosynthesis, and starch and sucrose metabolism. Serine/arginine-rich (SR) family proteins are known as important splicing factors in AS events. From the melon genome, a total of 17 SR members were discovered in this study. These genes could be classified into eight distinct subfamilies based on gene structure and conserved motifs. Promoter analysis detected various cis-acting regulatory elements involved in hormone pathways and fruit development. Interestingly, these SR genes exhibited specific expression patterns in reproductive organs such as flowers and ovaries. Additionally, concurrent with the increase in AS levels in ripening fruit, the transcripts of these SR genes were activated during fruit maturation in both climacteric and non-climacteric melon varieties. We also found that most SR genes were under selection during domestication. These results represent a novel finding of increased AS levels and SR gene expression during fruit ripening, indicating that alternative splicing may play a role in fruit maturation.

Mechanical-Enhanced and Durable Zwitterionic Hydrogel Coating for Inhibiting Coagulation and Reducing Bacterial Infection.

Blood-contact medical devices are indispensable for clinical interventions, yet their susceptibility to thrombosis and bacterial infections poses substantial risks to treatment efficacy and patient well-being. This study introduces a polysulfobetaine/alginate-CuII (SAC) zwitterionic hydrogel coating on polyurethane (PU) surfaces. This approach retains the superhydrophilic and antifouling nature of pSBMA while conferring the antibacterial effects of copper ions. Meanwhile, the copper alginate network intertwines with the polysulfobetaine (pSBMA) network, enhancing its mechanical properties and overcoming inherent weaknesses, thereby improving coating durability. Compared to the substrate, the SAC hydrogel coating significantly reduces thrombus adhesion mass by approximately 81.5% during extracorporeal blood circulation and effectively prevents bacterial biofilm formation even in a high-concentration bacterial milieu over 30 days. Moreover, the results from an isolated blood circulation model in New Zealand white rabbits affirm the impressive anticoagulant efficacy of the SAC hydrogel coating. The findings suggest that this hydrogel coating and its application method hold promise as a solution for blood-contact material surface modification to address thrombosis and bacterial biofilm formation simultaneously.

Tough, conductive hydrogels based on gelatin and oxidized sodium carboxymethyl cellulose as flexible sensors.

Natural polymer-based hydrogels have been wildly used in electronic skin, health monitoring and human motion sensing. However, the construction of hydrogel with excellent mechanical strength and electrical conductivity totally using natural polymers still faces many challenges. In this paper, gelatin and oxidized sodium carboxymethylcellulose were used to synthesize a double-network hydrogel through the dynamic Schiff base bonds. Then, the mechanical strength of the hydrogel was further enhanced by immersing it in an ammonium sulfate solution based on the Hofmeister effect between gelatin and salt. Finally, the gelatin/oxidized sodium carboxymethylcellulose hydrogel exhibited high tensile properties (614 %), tensile fracture strength (2.6 MPa), excellent compressive fracture strength (64 MPa), and compressive toughness (4.28 MJ/m3). Also, the electrical conductivity reached 3.94 S/m. The hydrogel after salt soaked was fabricated as strain sensors, which could accurately monitor the movement of many joints in the human body, such as fingers, wrists, elbows, neck, and throat. Therefore, the designed hydrogel fully originated from natural polymers and has great application potential in motion detection and information recording.

Strong cathode electroluminescence biosensor based on CeO2 functionalized PCN-222@Ag NPs for sensitive detection of p-Tau-181 protein.

Electrochemiluminescence (ECL) biosensors provide a convenient and high sensitivity method for early disease diagnosis. However, creating luminophore arrays relying on powerful ECL signals remains a daunting task. Porphyrin-centered metal organic frameworks (MOFs) exhibit remarkable potential in ECL sensing applications. In this paper, based on a simple one-pot synthesis method, PCN-222@Ag NPs doped with CeO2 was synthesized to enhance the ECL performance. Due to the strong catalytic ability of CeO2, the ECL signal strength of the new material PCN-222@CeO2@Ag NPs is much higher than that of the PCN-222@Ag NPs and PCN-222. The luminous properties of PCN-222@CeO2@Ag NPs become more intense and stable due to the excellent electronic conductivity of Ag NPs. Based on the fact that CuS@PDA composite can quench the ECL signal of PCN-222@CeO2@Ag NPs, we constructed a novel sandwich ECL immune sensor for the detection of phosphorylated Tau 181 (p-Tau-181) protein. The ECL sensor has a great linear relationship with p-Tau-181 protein concentration, ranging from 1 pg/mL to 100 ng/mL. The detection limit is as low as 0.147 pg/mL. This work provides new ideas for developing sensitive ECL sensors for the p-Tau-181 protein, the marker of Alzheimer's disease.

Psychological symptoms and quality of life in patients with inflammatory bowel disease in China: A multicenter study.

AIMS: To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors. METHODS: A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model. RESULTS: A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits. CONCLUSION: IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL.

Dietary long-chain fatty acids promote colitis by regulating palmitoylation of STAT3 through CD36-mediated endocytosis.

The Western diet, characterized by its high content of long-chain fatty acids (LCFAs), is widely recognized as a significant triggering factor for inflammatory bowel disease (IBD). While the link between a high-fat diet and colitis has been observed, the specific effects and mechanisms remain incompletely understood. Our study provides evidence that the diet rich in LCFAs can disrupt the integrity of the intestinal barrier and exacerbate experimental colitis in mice. Mechanistically, LCFAs upregulate the signal transducer and activator of transcription-3 (STAT3) pathway in the inflammatory model, and STAT3 knockout effectively counters the pro-inflammatory effects of LCFAs on colitis. Specifically, palmitic acid (PA), a representative LCFA, enters intestinal epithelial cells via the cluster of differentiation 36 (CD36) pathway and participates in the palmitoylation cycle of STAT3. Inhibiting this cycle using pharmacological inhibitors like 2-Bromopalmitate (2-BP) and ML349, as well as DHHC7 knockdown, has the ability to alleviate inflammation induced by PA. These findings highlight the significant role of dietary LCFAs, especially PA, in the development and progression of IBD. Diet adjustments and targeted modulation offer potential therapeutic strategies for managing this condition. Model of LCFAs involvement in the palmitoylation cycle of STAT3 upon internalization into cells. Following cellular uptake through CD36, LCFAs are converted to palmitoyl-CoA. In the presence of DHHC7, palmitoyl-CoA binds to STAT3 at the C108 site, forming palmitoylated STAT3. Palmitoylation further promotes phosphorylation at the Y705 site of STAT3. Subsequently, palmitoylated STAT3 undergoes depalmitoylation by APT2 and translocates to the nucleus to exert its biological functions.

All-Natural Injectable Antibacterial Hydrogel Enabled by Chitosan and Borneol.

Hydrogels with intrinsic antimicrobial capabilities based on natural strategies have been studied as a hot topic in biomedicine. Nevertheless, it is highly challenging to thoroughly develop a bacteriostatic natural hydrogel. Borneol as a traditional Chinese medicine possesses a unique broad-spectrum antibacterial activity under a membrane-breaking mechanism. In this study, a range of fully natural antibacterial hydrogels are designed and synthesized via the Schiff base cross-linking of carboxymethyl chitosan and dialdehyde dextran grafted natural borneol. The borneol with three configurations is hydrophilically modified onto dextran to boost its antibacterial activity. Also, the synergism of hydrophilic-modified borneol groups and positively charged ammonium ions of carboxymethyl chitosan make the hydrogels totally constrict the E. coli and S. aureus growth during 24 h. Furthermore, the hydrogels exhibit good in vitro cytocompatibility through cytotoxicity, protein adhesion, and hemolytic tests. In view of the injectability, the hydrogels can be delivered to the target site through a minimally invasive route. In short, this work offers a potential tactic to develop antibacterial hydrogels for the treatment of topical wound infections.

2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation.

BACKGROUND & AIMS: 2'-Fucosyllactose (2'-FL), the primary constituent of human milk oligosaccharides, has been identified as a potential regulator of inflammation in inflammatory bowel disease. Despite this recognition, the specific mechanisms through which 2'-FL alleviates ulcerative colitis (UC) remain ambiguous. This study seeks to investigate the potential anti-inflammatory properties of 2'-FL concerning intestinal inflammation and uncover the associated mechanisms. METHODS: C57BL/6J mice were orally administered a daily dose of 500 mg/kg 2'-FL for 11 consecutive days, followed by the induction of colitis using 3 % (wt/vol) dextran sulfate sodium (DSS) for the final 6 days. Subsequently, a comprehensive range of techniques, including an Acyl-biotin exchange assay, fluorescein-isothiocyanate-labeled dextran assay, histopathology, ELISA, quantitative real-time PCR, Western blot, immunofluorescence staining, immunohistochemistry staining, Alcian blue-periodic acid schiff staining, TdT-mediated dUTP nick end labeling, transmission electron microscopy, iTRAQ quantitative proteomics, bioinformatics analysis, and the generation of signal transducer and activator of transcription 3 (STAT3) knockout mice, were employed to explore the relevant molecular mechanisms. RESULTS: Administration of 2'-FL significantly ameliorated DSS-induced colitis in mice and enhanced the integrity of the intestinal mucosal barrier. 2'-FL downregulated the phosphorylation of STAT3 and inhibited STAT3-related signaling pathways in colon tissues, which, in turn, reduced inflammatory responses. Interestingly, knockdown of STAT3 attenuated the protective effects of 2'-FL, highlighting that 2'-FL-mediated inflammatory attenuation is dependent on STAT3 expression. Additionally, 2'-FL could influence STAT3 activation by modulating the palmitoylation and depalmitoylation of STAT3. CONCLUSIONS: 2'-FL promotes the recovery of the intestinal mucosal barrier and suppresses inflammation in ulcerative colitis by inhibiting the palmitoylation and phosphorylation of STAT3.

Cyclodextrin regulated natural polysaccharide hydrogels for biomedical applications-a review.

Cyclodextrin and its derivative (CDs) are natural building blocks for linking with other components to afford functional biomaterials. Hydrogels are polymer network systems that can form hydrophilic three-dimensional network structures through different cross-linking methods and are developing as potential materials in biomedical applications. Natural polysaccharide hydrogels (NPHs) are widely adopted in biomedical field with good biocompatibility, biodegradability, low cytotoxicity, and versatility in emulating natural tissue properties. Compared with conventional NPHs, CD regulated natural polysaccharide hydrogels (CD-NPHs) maintain good biocompatibility, while improving poor mechanical qualities and unpredictable gelation times. Recently, there has been increasing and considerable usage of CD-NPHs while there is still no review comprehensively introducing their construction, classification, and application of these hydrogels from the material point of view regarding biomedical fields. To draw a complete picture of the current and future development of CD-NPHs, we systematically overview the classification of CD-NPHs, and provide a holistic view on the role of CD-NPHs in different biomedical fields, especially in drug delivery, wound dressing, cell encapsulation, and tissue engineering. Moreover, the current challenges and prospects of CD-NPHs are discussed rationally, providing an insight into developing vibrant fields of CD-NPHs-based biomedicine, and facilitating their translation from bench to clinical medicine.

Evaluation on the inclusion behavior of ß-cyclodextrins with lycorine and its hydrochloride.

Lycorine (Lyc) and its hydrochloride (Lyc∙HCl) as effective drugs can fight against many diseases including novel coronavirus (COVID-19) based on their antiviral and antitumor mechanism. Beta-cyclodextrin (ß-CD) is considered a promising carrier in improving its efficacy while minimizing cytotoxicity due to the good spatial compatibility with Lyc. However, the detailed mechanism of inclusion interaction still remains to be further evaluated. In this paper, six inclusion complexes based on ß-CDs, Lyc and Lyc∙HCl were processed through ultrasound in the mixed solvent of ethanol and water, and their inclusion behavior was characterized after lyophilization. It was found that the inclusion complexes based on sulfobutyl-beta-cyclodextrin (SBE-ß-CD) and Lyc∙HCl had the best encapsulation effect among prepared inclusion complexes, which may be attributed to the electrostatic interaction between sulfonic group of SBE-ß-CD and quaternary amino group of Lyc∙HCl. Moreover, the complexes based on SBE-ß-CD displayed pH-sensitive drug release property, good solubilization, stability and blood compatibility, indicating their potential as suitable drug carriers for Lyc and Lyc∙HCl.

A self-gelling powder based on polyacrylic acid/polyacrylamide/quaternate chitosan for rapid hemostasis.

In order to improve the hemostatic effect of the hemostatic dressing for non-compressible wounds, unknown bleeding points and irregularly shaped wounds, a self-gelling hemostasis powder based on polyacrylic acid/polyacrylamide/quaternate chitosan (PAA/PAM/QCS) is prepared in this study. When in contact with water, the PAA/PAM/QCS can fuse and rapidly form a stable hydrogel in a short time (< 0.25 min). The PAA/PAM ratio is the main parameter that modulates the formation of the self-gel. The PAA/PAM self-gel can be formed only when the PAA/PAM ratio is 5:5, and the introduction of QCS does not influence the self-gelling behaviors and hydrogel stability. Moreover, the PAA/PAM/QCS self-gel shows good adhesive properties on wet tissue surfaces. In addition, the introduction of QCS improves the antibacterial activity of the self-gelling hemostasis powder. Furthermore, the prepared PAA/PAM/QCS powder can rapidly adsorb lots of blood, aggregate blood cells and platelets. The hemostatic results in vivo show that PAA/PAM/QCS powder is superior to the control group and commercial product groups (chitosan powder) with performance similar to hemostatic zeolite in terms of the amount of bleeding and hemostatic time. Therefore, the PAA/PAM/QCS self-gelling powder shows great application prospects for rapid hemostasis.

Intracellular calprotectin (S100A8/A9) facilitates DNA damage responses and promotes apoptosis in head and neck squamous cell carcinoma.

OBJECTIVES: In head and neck squamous cell carcinoma (HNSCC), poor prognosis and low survival rates are associated with downregulated calprotectin. Calprotectin (S100A8/A9) inhibits cancer cell migration and invasion and facilitates G2/M cell cycle arrest. We investigated whether S100A8/A9 regulates DNA damage responses (DDR) and apoptosis in HNSCC after chemoradiation. MATERIALS AND METHODS: Human HNSCC cases in TCGA were analyzed for relationships between S100A8/A9 and expression of apoptosis-related genes. Next, S100A8/A9-expressing and non-expressing carcinoma lines (two different lineages) were exposed to genotoxic agents and assessed for 53BP1 and γH2AX expression and percent of viable/dead cells. Finally, S100A8/A9-wild-type and S100A8/A9null C57BL/6j mice were treated with 4-NQO to induce oral dysplastic and carcinomatous lesions, which were compared for levels of 53BP1. RESULTS: In S100A8/A9-high HNSCC tumors, apoptosis-related caspase family member genes were upregulated, whereas genes limiting apoptosis were significantly downregulated based on TCGA analyses. After X-irradiation or camptothecin treatment, S100A8/A9-expressing carcinoma cells (i.e., TR146 and KB-S100A8/A9) showed significantly higher 53BP1 and γH2AX expression, DNA fragmentation, proportions of dead cells, and greater sensitivity to cisplatin than wild-type KB or TR146-S100A8/A9-KD cells. Interestingly, KB-S100A8/A9Δ113-114 cells showed similar 53BP1 and γH2AX levels to S100A8/A9-negative KB and KB-EGFP cells. After 4-NQO treatment, 53BP1 expression in oral lesions was significantly greater in calprotectin+/+ than S100A8/A9null mice. CONCLUSIONS: In HNSCC cells, intracellular calprotectin is strongly suggested to potentiate DDR and promote apoptosis in response to genotoxic agents. Hence, patients with S100A8/A9-high HNSCC may encounter more favorable outcomes because more tumor cells enter apoptosis with increased sensitivity to chemoradiation therapy.

The diagnostic value of multiparameter cardiovascular magnetic resonance for early detection of light-chain amyloidosis from hypertrophic cardiomyopathy patients.

Background: Early-stage amyloidosis of the heart is prone to be underdiagnosed or misdiagnosed, increasing the risk of early heart failure and even death of the patient. To ensure timely intervention for cardiac light-chain amyloidosis (AL CA), it is vital to develop an effective tool for early identification of the disease. Recently, multiparameter cardiovascular magnetic resonance (CMR) has been used as a comprehensive tool to assess myocardial tissue characterization. We aimed to investigate the difference in left ventricular (LV) strain, native T1, extracellular volume (ECV), and late gadolinium enhancement (LGE) between AL CA patients, hypertrophic cardiomyopathy patients (HCM), and healthy control subjects (HA). Moreover, we explored the value of multiparameter CMR for differential diagnosis of the early-stage AL CA patients from HCM patients, who shared similar imaging characteristics under LGE imaging. Methods: A total of 38 AL CA patients, 16 HCM patients, and 17 HA people were prospectively recruited. All subjects underwent LGE imaging, Cine images, and T1 mapping on a 3T scanner. The LV LGE pattern was recorded as none, patchy or global. LV strain, native T1, and ECV were measured semi-automatically using dedicated CMR software. According to clinical and biochemical markers, all patients were classified as Mayo stage I/II and Mayo stage IIIa/IIIb. Univariable and multivariable logistic regression models were utilized to identify independent predictors of early-stage AL CA from HCM patients. Receiver operator characteristic (ROC) curve analysis and Youden's test were done to determine the accuracy of multiparameter CMR in diagnosing Mayo stage I/II AL CA and establish a cut-off value. Results: For Mayo stage I/II AL CA patients, the global longitudinal strain (GLS) absolute value (11.9 ± 3.0 vs. 9.5 ± 1.8, P < 0.001) and the global circumferential strain (GCS) absolute value (19.0 ± 3.6 vs. 9.5 ± 1.8, P < 0.001) were significantly higher than in HCM patients. The native T1 (1334.9 ± 49.9 vs. 1318.2 ± 32.4 ms, P < 0.0001) and ECV values (37.8 ± 5.7 vs. 31.3 ± 2.5%, P < 0.0001) were higher than that of HCM patients. In multiparameter CMR models, GCS (2.097, 95% CI: 1.292-3.403, P = 0.003), GLS (1.468, 95% CI: 1.078-1.998, P = 0.015), and ECV (0.727, 95% CI: 0.569-0.929, P = 0.011) were the significant variables for the discrimination of the early-stage AL CA patients from HCM patients. ROC curve analysis and Youden's test were used on GCS, GLS, ECV, and pairwise parameters for differentiating between Mayo stage I/II AL CA and HCM patients, respectively. The combination of GLS, GCS, and ECV mapping could distinguish Mayo stage I/II AL amyloidosis patients from hypertrophic cardiomyopathy with excellent performance (AUC = 0.969, Youden index = 0.813). Conclusion: In early-stage AL CA patients with atypical LGE, who had similar imaging features as HCM patients, ECV mapping, GCS, and GLS were correlated with the clinical classification of the patients. The combination of GCS, GLS, and ECV could differentiate early-stage AL CA from HCM patients. Multiparameter CMR has the potential to provide an effective and quantitative tool for the early diagnosis of myocardial amyloidosis.

Simulation of Adsorption Process of l-Tryptophan on Mixed-Mode Resin HD-1 with Combined Physical Adsorption and Ion Exchange.

The mass-transfer process of l-tryptophan (l-Trp) in the hydrophobic interaction/ion-exchange mixed-mode resin HD-1 particles and fixed bed was studied experimentally and theoretically. The adsorption kinetics of l-Trp in single-component and multicomponent adsorption systems was investigated under different pH conditions. The co-adsorption of sodium ions (Na+) and l-Trp anions was found to be negligible. A modified liquid-film linear driving force model considering the physical adsorption of l-Trp zwitterions and anions as well as ion exchange of l-Trp cations was proposed. The dissociation equilibria of l-Trp molecules and functional groups on the resin were introduced in the model. The model could well fit the kinetic adsorption curves of l-Trp at different pH values. The presence of Na+ and the impurity amino acid l-glutamic acid (l-Glu) did not significantly affect the mass-transfer rate of l-Trp. The dynamic adsorption processes of l-Trp under different pH and concentration conditions were studied. A modified transport-dispersive model considering axial diffusion, liquid-film mass transfer, and a combined physical adsorption and ion-exchange equilibrium was established, which could predict the adsorption breakthrough curves of l-Trp well. During the dynamic adsorption process, the pH of mobile phase in the fixed bed changed with changing the l-Trp concentration in the mobile phase. l-Trp was well separated from Na+ and l-Glu with the purity of l-Trp higher than 99%, the recovery rate higher than 95%, and a concentration of 4.69 × 10-3 mol/L. The elution chromatographic peaks of l-Trp, l-Glu, and Na+ and the pH of the outlet solution were predicted satisfactorily.

Molecular Imprinted ZnS Quantum Dots-Based Sensor for Selective Sulfanilamide Detection.

Combining molecular imprinted polymers and water-soluble manganese-doped zinc sulfide quantum dots (Mn2+: ZnS QDs), a new molecule imprinted polymers-based fluorescence sensor was designed. The molecule imprinted quantum dots (MIP@QDs) were constructed by coating molecular imprinted polymers layer on the surface of ZnS: Mn2+ QDs using the surface molecular imprinting technology. The developed MIP@QDs-based sensor was used for rapid and selective fluorescence sensing of sulfanilamide in water samples. The binding experiments showed that the MIP@QDs has rapid fluorescent responses, which are highly selective of and sensitive to the detection of sulfanilamide. The respond time of the MIP@QDs was 5 min, and the imprinting factor was 14.8. Under optimal conditions, the developed MIP@QDs-based sensor shows a good linearity (R2 = 0.9916) over a sulfanilamide concentration range from 2.90 × 10-8 to 2.90 × 10-6 mol L-1, with a detection limit of 3.23 × 10-9 mol L-1. Furthermore, the proposed MIP@QDs-based sensor was applied to the determination of sulfanilamide in real samples, with recoveries of 96.80%-104.33%, exhibiting good recyclability and stability. Experimental results showed that the prepared MIP@QDs has the potential to serve as a selective and sensitive sensor for the fluorescence sensing of sulfonamides in water samples.

P2RY13 Exacerbates Intestinal Inflammation by Damaging the Intestinal Mucosal Barrier via Activating IL-6/STAT3 Pathway.

The pathogenesis of ulcerative colitis (UC) is unclear, while genetic factors have been confirmed to play an important role in its development. P2RY13 is a G protein-coupled receptor (GPCRs), which are involved in the pathogenesis of inflammation and immune disorders. According to GEO database analysis, we first observed that the expression of P2Y13 was increased in UC patients. Therefore, we sought to determine the role of P2Y13 in the development of colitis. Our data showed that P2RY13 was highly expressed in the inflamed intestinal tissues of UC patients. In mice, pharmacological antagonism of P2Y13 can significantly attenuate the intestinal mucosal barrier disruption. In LPS-induced NCM460 cell, knockdown or pharmacological inhibition of P2RY13 increased the expression of intestinal tight junction protein and reduced apoptosis. In addition, we found that the effect of P2Y13 on colitis is related to the activation of the IL-6/STAT3 pathway. Activation of P2Y13 increases IL-6 expression and promotes STAT3 phosphorylation and nuclear transport. Deletion of the STAT3 gene in the intestinal epithelial cells of mice significantly mitigated the exacerbation of colitis due to P2Y13 activation. Thus, P2Y13 can aggravate intestinal mucosal barrier destruction by activating the IL-6/STAT3 pathway. P2Y13 might be a potential drug target for UC.

ORAOV 1 Detection Made with Metal Organic Frameworks Based on Ti3C2Tx MXene.

In this work, a two-dimensional (2D) MOF sheet with electrochemiluminescence (ECL) activity is prepared with Ti3C2Tx MXene as the metal precursor and the meso-tetra(4-carboxyl-phenyl) porphyrin (H2TCPP) as the organic ligand. The atomically thin 2D Ti3C2Tx MXene is utilized as the metal precursor and soft template to produce the MOF with a 2D nanosheet morphology (Ti3C2Tx-PMOF). Ti3C2Tx MXene is a kind of strong electron acceptor, which can deprotonate H2TCPP due to the high electronegativity and low work function of its terminal atoms. The deprotonated H2TCPP continues to bind with Ti atoms to form the 2D MOF sheet. The ECL activity is inherited from H2TCPP and stabilized by introducing Ag NPs. Then, we construct an ECL biosensor based on the Ag NPs/Ti3C2Tx-PMOF to detect the oral cancer overexpressed 1 (ORAOV 1). A bipedal three-dimensional DNA walker strategy is adopted to further improve the biosensor sensitivity. As expected, the biosensor exhibits sterling sensitivity and selectivity. The ECL biosensor responds linearly to ORAOV 1 concentrations in the range of 10 fM-1 nM, and the detection limit is as low as 3.3 fM (S/N = 3). It means that Ag NPs/Ti3C2Tx-PMOF is a potential material to design and construct the high-performance ECL biosensors.

Chitosan-enhanced nonswelling hydrogel with stable mechanical properties for long-lasting underwater sensing.

Existing anti-swelling hydrogels with poor mechanical strength restrict their underwater human monitoring as wearable electronic sensing equipment. Herein, a nonswelling double network (DN) hydrogel with strong self-recoverability (97.22%) was developed by adding chitosan (CS) to poly(acrylic acid-2-methoxyethyl acrylate)-Fe3+ [P(AA-MEA)-Fe] network. Owing to the introduction of CS, the hydrogel displayed excellent nonswelling properties under aqueous solutions (pH = 1, 4 and 7), physiological saline, seawater, dodecane, n-hexane and chloroform. Besides, CS improved mechanical properties of hydrogel through non-covalent network (large stretchability of 1199%, tensile strength of 0.462 MPa and toughness of 2.01 MJ/m3). Surprisingly, the hydrogel still reached the extensibility (1072%) and tensile stress (0.467 MPa) even after immersing in water for 7 days. Fabricating hydrogel as flexible strain sensor, periodic real-time signals of human movements (e.g., joint actions and electronic skin touching) were accurately monitored under the water and seawater. The nonswelling P(AA-MEA)-CS-Fe hydrogel shows huge potential in underwater sensing.

Chirality-Induced Bionic Scaffolds in Bone Defects Repair-A Review.

Due to lack of amino sugar with aging, people will suffer from various epidemic bone diseases called "undead cancer" by the World Health Organization. The key problem in bone tissue engineering that is not completely resolved is the repair of critical large-scale bone and cartilage defects. The chirality of the extracellular matrix plays a decisive role in the physiological activity of bone cells and the occurrence of bone tissue, but the mechanism of chirality in regulating cell adhesion and growth is still in the early stage of exploration. The application progress of chirality-induced bionic scaffolds is reviewed here in bone defects repair based on "soft" and "hard" scaffolds. The aim is to summarize the effects of different chiral structures (l-shaped and d-shaped) in the process of inducing bionic scaffolds in bone defects repair. In addition, many technologies and methods as well as issues worthy of special consideration for preparing chirality-induced bionic scaffolds are also introduced. It is expected that this work can provide inspiring ideas for designing new chirality-induced bionic scaffolds and promote the development of chirality in bone tissue engineering.