The brassinosteroid receptor StBRI1 promotes tuber development by enhancing plasma membrane H+-ATPase activity in potato.

The brassinosteroid (BR) receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1) plays a critical role in plant growth and development. Although much is known about how BR signaling regulates growth and development in many crop species, the role of StBRI1 in regulating potato (Solanum tuberosum) tuber development is not well understood. To address this question, a series of comprehensive genetic and biochemical methods were applied in this investigation. It was determined that StBRI1 and Solanum tuberosum PLASMA MEMBRANE (PM) PROTON ATPASE2 (PHA2), a PM-localized proton ATPase, play important roles in potato tuber development. The individual overexpression of StBRI1 and PHA2 led to a 22% and 25% increase in tuber yield per plant, respectively. Consistent with the genetic evidence, in vivo interaction analysis using double transgenic lines and PM H+-ATPase activity assays indicated that StBRI1 interacts with the C-terminus of PHA2, which restrains the intramolecular interaction of the PHA2 C-terminus with the PHA2 central loop to attenuate autoinhibition of PM H+-ATPase activity, resulting in increased PHA2 activity. Furthermore, the extent of PM H+-ATPase autoinhibition involving phosphorylation-dependent mechanisms corresponds to phosphorylation of the penultimate Thr residue (Thr-951) in PHA2. These results suggest that StBRI1 phosphorylates PHA2 and enhances its activity, which subsequently promotes tuber development. Altogether, our results uncover a BR-StBRI1-PHA2 module that regulates tuber development and suggest a prospective strategy for improving tuberous crop growth and increasing yield via the cell surface-based BR signaling pathway.

Facile Synthesis of MXene-Ti3C2/Co Nanosheet Hydrogel Sensor with the Assistance of a Smartphone for On-Site Monitoring of Glucose in Beverages.

A one-step cobaltous chloride (CoCl2) molten salt method was employed to prepare multilayer MXene-Ti3C2/Co materials with further ultrasonic treatment to acquire single-layer MXene-Ti3C2/Co nanosheets (NSs). MXene-Ti3C2/Co NSs were characterized, and their enzyme-like activities were investigated. Under the catalysis of MXene-Ti3C2/Co NSs, 3,3',5,5'-tetramethylbenzidine (TMB) could be oxidized by H2O2, with the color changing from colorless to blue. The affinity of MXene-Ti3C2/Co NSs to H2O2 and TMB was better than that of nanozymes reported in previous studies. The MXene-Ti3C2/Co NSs were used for the colorimetric determination of H2O2/glucose, with limits of detection (LODs) of 0.033 mM and 1.7 µM, respectively. MXene-Ti3C2/Co NSs embedded in sodium alginate (SA) hydrogel were used to construct a sensor platform. The digital pictures combined with a smartphone-installed app (color recognizer) could be used to analyze RGB values for colorimetric detection of glucose in beverages. This point-of-care testing platform has the advantages of cost-effectiveness and good transferability, with the potential to realize quick, intelligent and on-site detection.

Long-term outcomes of refractory esophageal strictures after endoscopic submucosal dissection of superficial esophageal neoplasms.

BACKGROUND: Many studies have focused on prophylactic therapy for post-endoscopic submucosal dissection (ESD) of esophageal strictures. However, various strategies cannot prevent the occurrence of postoperative strictures after extensive ESD. Postoperative strictures often inevitably occur, and endoscopic dilation is still a temporarily effective therapy. METHODS: This study included patients with post-ESD refractory esophageal strictures (RESs) from January 2014 to November 2019. Clinical effectiveness was assessed using univariate analysis and multivariate logistic regression. Hierarchical linear models were used to identify factors that predicted the dysphagia-free period. RESULTS: A total of 50 patients fulfilled the inclusion criteria and entered the study. Twenty-seven (54%) patients had a history of prophylactic oral steroid therapy. Forty-six patients (92%) underwent ≥ 75% circumferential resection, including 32 (64%) cases involving entire circumferential ESD. The mean dysphagia-free period of 50 patients was 2.9 months (95% CI 2.3-3.5). The dysphagia-free period had a linear growth trend over time, increasing by 6.9 days per endoscopic therapy, and the estimated last dysphagia-free period was 85.9 days. Old and female patients had shorter dysphagia-free periods compared with young and male patients. Endoscopic therapy success was achieved in 30 (60%) patients. Multivariate analysis revealed that circumferential lesions (OR 6.106, 95% CI 1.013-36.785, P = 0.048) were significant predictive factors for poor clinical outcome. CONCLUSION: Endoscopic dilation seemed effective in patients with post-ESD RESs by increasing the dysphagia-free period. After approximately 10 continuous dilations, 60% of patients achieved endoscopic success, and the remission rate of obstruction was increased. Prophylactic oral steroid therapy could reduce the occurrence of RESs. However, once a RES had occurred, prophylactic steroid therapy could not reduce the frequency of dilations or change the long-term outcomes. TRIAL REGISTRATION: This study was prospectively registered and approved by the Ethics Committee of West China Hospital of Sichuan University (IRB number: ChiCTR-ONN-17012382) on 2015.

Co(OH)2/MXene-Ti3C2 nanocomposites with triple-enzyme mimic activities as hydrogel sensing platform for on-site detection of hypoxanthine.

Novel Co(OH)2/MXene-Ti3C2 nanocomposites with oxidase (OXD)-mimic, peroxidase (POD)-mimic, and catalase (CAT)-mimic activities were prepared by a simple two-step method. The Co(OH)2/MXene-Ti3C2 nanocomposites with triple-enzyme mimic activities were embedded into sodium alginate (SA) gels for the first time to fabricate a target-responsive hydrogel-assisted assay. The catalytic mechanism and steady-state kinetics of Co(OH)2/MXene-Ti3C2 nanocomposites were investigated. Subsequently, hypoxanthine (Hx) was catalyzed by xanthine oxidase (XOD) to form H2O2, which reacts with 3,3',5,5'-tetramethyl-benzidine (TMB) in the presence of Co(OH)2/MXene-Ti3C2 nanocomposites to form a blue oxide (ox-TMB) in the hydrogel. The visible color change of the hydrogel with the increase of Hx concentration can be recognized through a smartphone App to transfer the red (R), green (G), and blue (B) values for the quantitative determination of  Hx, with a detection range from 5 to 250 µM, and detection limit of 0.2 µM. The method was applied to the determination of Hx content in different aquatic products. The spiked recoveries of the aquatic products were from 94.1 to 106.4%, and the relative standard deviations (RSD) were less than 5.4%. Our results show that the Co(OH)2/MXene-Ti3C2 nanocomposites hydrogel-assisted colorimetric biosensor is cost-effective, sensitive, and selective and has excellent application prospects for in-the-field determination of Hx.

Regulatory changes in China on xenotransplantation and related products.

BACKGROUND: Given the persistence and the worldwide shortage of organs from both the deceased and living donors for clinical transplantation, pig organs or tissues hold immense promises for the patients on the waiting list, and xenotransplantation is deemed as one of the solutions to the organ shortage crisis. Indeed, the emerging gene editing technologies, such as CRISPR/Cas9, have led to tremendous progress in the generation of genetically modified pigs to overcome many barriers associated. METHOD: We presented a description of the xenotransplantation regulations in China and the related products. RESULT: Several groups in China have successfully generated transgenic pigs with the elimination of immune rejection or coagulation-related genes, and both pre-clinical and clinical studies have been reported. However, the pre-clinical evaluation and clinical application of porcine xenotransplantation raises ethical and regulatory considerations. Herein, in this review, we will summarize and discuss the progress in xenotransplantation in China and xenotransplantation-related products from the regulatory perspective. CONCLUSION: There has been remarkable progress in both the genetically modified pigs and pre-clinical studies in China, and China will be the first country to successfully fulfill the xenotransplantation from pig organ to human in the near future.

Effects of oxycodone applied for patient-controlled analgesia on postoperative cognitive function in elderly patients undergoing total hip arthroplasty: a randomized controlled clinical trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after orthopedic surgery, which is not conducive to the prognosis of the elderly. AIMS: We performed this study to investigate the effects of oxycodone applied for patient-controlled intravenous analgesia (PCIA) on postoperative cognitive function in elderly patients after total hip arthroplasty (THA). METHODS: Ninety-nine participants were enrolled and allocated into two groups: oxycodone group (group O) and sufentanil group (group S). The primary outcome was the incidence of POCD, diagnosed according to the changes in the Mini-mental status examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. The secondary outcomes included the plasma levels of S-100B protein and neuron-specific enolase (NSE), the amount of postoperative analgesic consumption and the incidence of adverse reactions. RESULTS: The incidence of POCD was significantly lower in patients receiving oxycodone up to the 3rd postoperative day (POD, 1st POD 27.3% vs. 51.1%, P = 0.021; 3rd POD 20.5% vs. 40.0%, P = 0.045), as compared to patients receiving sufentanil. The MMSE and MoCA scores of both groups decreased to varying degrees. However, compared with group S, the MMSE scores at 1st POD, 3rd POD, 5th POD and 7st POD in group O were higher than that in group S, while MoCA scores at 1st POD, 3rd POD and 5th POD in group O were higher. Compared with group S, the plasma levels of S-100B protein in group O at 4 h, 8 h, 12 h post-surgery were lower. While the plasma levels of NSE in group O at 4 h, 8 h, 12 h, 24 h post-surgery were lower. Number of PCIA boluses and consumption of analgesic drug during the first two POD were similar between two groups. However, postoperative incidence of nausea, vomiting and pruritus was significantly lower in patients receiving oxycodone. CONCLUSION: Oxycodone applied for PCIA in elderly patients after THA could reduce the incidence of POCD, improve postoperative cognitive function and decrease the adverse reactions.

Low-dose combined exposure of carboxylated black carbon and heavy metal lead induced potentiation of oxidative stress, DNA damage, inflammation, and apoptosis in BEAS-2B cells.

Black carbon (BC) and heavy metal lead (Pb), as typical components of atmospheric PM2.5, have been shown to cause a variety of adverse health effects. However, co-exposure to BC and Pb may induce pulmonary damage by aggravating toxicity via an unknown mechanism. This study aimed to investigate the combined toxicity of carboxylated black carbon (c-BC) and lead acetate (Pb) on human bronchial epithelial cells (BEAS-2B) at the no-observed-adverse-effect level (NOAEL). Cells were exposed to c-BC (6.25 µg/mL) and Pb (4 µg/mL) alone or their combination, and their combined toxicity was investigated by focusing on cell viability, oxidative stress, DNA damage, mitochondrial membrane potential (MMP), apoptosis, and cellular inflammation. Factorial analyses were also used to determine the potential interactions between c-BC and Pb. The results suggested that the combination of c-BC and Pb could significantly increase the production of reactive oxygen species (ROS), malondialdehyde (MDA), and lactate dehydrogenase leakage (LDH) and decrease the activities of glutathione (GSH) and superoxide dismutase (SOD). The excessive oxidative stress could increase the levels of inflammatory cytokine IL-6 and TNF-α, and induce oxidative DNA damage and dissipation of MMP. Moreover, the results also suggested that the combined group could enhance the cellular apoptotic rate and the activation of apoptotic markers like caspase-3, caspase-8, and caspase-9. The factorial analysis further demonstrated that synergistic interaction was responsible for the combined toxicity of c-BC and Pb co-exposure. Most noticeably, the co-exposure of c-BC and Pb could induce some unexpected toxicity, even beyond the known toxicities of the individual compounds in BEAS-2B cells at the NOAEL.

Novel compound heterozygous DNAAF2 mutations cause primary ciliary dyskinesia in a Han Chinese family.

PURPOSE: Primary ciliary dyskinesia (PCD), which commonly causes male infertility, is an inherited autosomal recessive disorder. This study aimed to investigate the clinical manifestations and screen mutations associated with the dynein axonemal assembly factor 2 (DNAAF2) gene in a Han Chinese family with PCD. METHODS: A three-generation family with PCD was recruited in this study. Eight family members underwent comprehensive medical examinations. Genomic DNA was extracted from the participants' peripheral blood, and targeted next-generation sequencing technology was used to perform the mutation screening. The DNAAF2 expression was analyzed by immunostaining and Western blot. RESULTS: The proband exhibited the typical clinical features of PCD. Spermatozoa from the proband showed complete immotility but relatively high viability. Two novel compound heterozygous mutations in the DNAAF2 gene, c.C156A [p.Y52X] and c.C26A [p.S9X], were identified. Both nonsense mutations were detected in the proband, whereas the other unaffected family members carried either none or only one of the two mutations. The two nonsense heterozygous mutations were not detected in the 600 ethnically matched normal controls or in the Genome Aggregation Database. The defect of the DNAAF2 and the outer dynein arms and inner dynein arms were notably observed in the spermatozoa from the proband by immunostaining. CONCLUSION: This study identified two novel compound heterozygous mutations of DNAAF2 leading to male infertility as a result of PCD in a Han Chinese family. The findings may enhance the understanding of the pathogenesis of PCD and improve reproductive genetic counseling in China.

Progress in multiple genetically modified minipigs for xenotransplantation in China.

Pig-to-human organ transplantation provides an alternative for critical shortage of human organs worldwide. Genetically modified pigs are promising donors for xenotransplantation as they show many anatomical and physiological similarities to humans. However, immunological rejection including hyperacute rejection (HAR), acute humoral xenograft rejection (AHXR), immune cell-mediated rejection, and other barriers associated with xenotransplantation must be overcome with various strategies for the genetic modification of pigs. In this review, we summarize the outcomes of genetically modified and cloned pigs achieved by Chinese scientists to resolve the above-mentioned problems in xenotransplantation. It is now possible to knockout several porcine genes associated with the expression of sugar residues, antigens for (naturally) existing antibodies in humans, including GGTA1, CMAH, and ß4GalNT2, and thereby preventing the antigen-antibody response. Moreover, insertion of human complement- and coagulation-regulatory transgenes, such as CD46, CD55, CD59, and hTBM, can further overcome effects of the humoral immune response and coagulation dysfunction, while expression of regulatory factors of immune responses can inhibit the adaptive immune rejection. Furthermore, transgenic strategies have been developed by Chinese scientists to reduce the potential risk of infections by endogenous porcine retroviruses (PERVs). Breeding of multi-gene low-immunogenicity pigs in China is also presented in this review. Lastly, we will briefly mention the preclinical studies on pig-to-non-human primate xenotransplantation conducted in several centers in China.

Xenotransplantation in China: Present status.

The main obstacle to organ transplantation is the shortage of organs from deceased individuals. Especially in China, the ratio of patients on the waiting list versus the transplant recipients is 30:1. Therefore, there is an urgent need for organ donors. Genetically modified pig organs have proved to be a new source for xenotransplantation, and Chinese scientists have made considerable progress in this area during recent years. In this paper, we review four important aspects of the xenotransplantation field in China. First, a large variety of genetically modified pigs have been generated by Chinese scientists: all these genetically modified pigs and the purpose of these modifications will be summarized. Second, the preclinical research in pig-to-nonhuman primate xenotransplantation is outlined. The survival time and major biochemical parameters for the xenografts are summarized. Third, regarding the bench-to-bed approach, more suitable organs have been developed for xenotransplantation in humans, and in particular, pig islet transplantation into diabetic patients as well as pig-to-human cornea and skin transplantation. Fourth, we briefly address the regulations and prospects for recruiting xenotransplantation experts in China. Based on recent progress, we anticipate that genetically modified pigs will offer suitable organs for the treatment of end-stage organ diseases in humans in the near future. Given the recent influx of world-renowned scientists in xenotransplantation to China, our country will definitely become one of the major centers of xenotransplantation research and development in the world.

Promising potentials of Tibetan macaques in xenotransplantation.

Organ transplantation is a crucial medical procedure, as it is often the only treatment for patients suffering from end-stage organ failure. Unfortunately, the shortage of donor organs limits the number of patients whose lives can be saved. Carrying out research on xenotransplantation with the aim of eventually replacing human organ transplants with those of animals is very promising, as it could effectively bridge the shortfall in donor organs. Thanks to the success of cloned pigs and to the emergence of gene-editing techniques, genetically modified pigs have come to be considered ideal animal donors for human xenotransplantation and have been widely used in basic research. Such research focuses on pig-to-nonhuman primates transplantation, as the recipients are suitable for preclinical studies because both their genes and organ sizes are similar to those of humans. Chinese transplantation scientists have carried out several experiments on Tibetan macaques, including successful preclinical transplants of material from genetically modified pigs, as well as research on such topics as intraocular pressure, Parkinson's disease, advanced cancer, islet transplantation, and liver transplantation. This article reviews basic and applied research on Tibetan macaques in xenotransplantation, as well as the issues of immune rejection and ethical concerns. We aim to demonstrate the various advantages of Tibetan macaques as transplant recipients compared to other nonhuman primate species and to provide a perspective for the future establishment of Tibetan macaques as principal recipients in preclinical studies of xenotransplantation.

Xenotransplantation in Asia.

The organ shortage crisis affects most of the world today. In Asia, rates of deceased organ donation are extremely low due to sociocultural factors. In this context, implementing new organ donation policies is not enough; xenotransplantation remains the most promising way to solve the organ crisis. Most of the early research on xenotransplantation was conducted in the US and Europe. Today, however, Asia has caught up on its Western counterparts partly due to the increasing demand for organ transplants. Given the growing influence of countries such as China, South Korea, and Japan in xenotransplantation, this article provides the reader with an essential global understanding of the scientific and ethical issues currently at stake. Furthermore, it sheds light on the beliefs and values that shape the response of the Asian public to both organ donation and xenotransplantation.

The role of endoscopic dilation and stents in refractory benign esophageal strictures: a retrospective analysis.

BACKGROUND: The outcomes of patients with refractory benign esophageal strictures (RBES) are unclear, and the clinical efficacy of dilation versus stent placement is lacking. Our objective was to explore the role of endoscopic dilation and stents placement in the management of RBES. METHODS: RBES patients treated with dilation and stents in our hospital between January 2009 and December 2017 were included in this study. The primary outcomes were to assess clinical effectiveness and adverse events. The secondary outcome was to identify factors that predicted the dysphagia-free period. RESULTS: Among 75 RBES patients (54 male; median age 59 years), 39 (52%), 20 (26.7%), 3 (4%), 10 (13.3%), and 3 (4%), were postsurgical, post-ESD, achalasia of cardia, caustic and mixed etiology, respectively. The median number of endoscopic therapy was 5 times (range 3, 21). Endoscopic therapy was successful in 46 patients (61.3%). Patients treated with dilation showed a higher success rate (70.9%, 39/55) than that treated with stents (35%, 7/20). Fifteen patients died during follow-up. Nineteen patients had adverse events after endoscopic therapy. In total, the mean dysphagia-free period was 3.4 months (95% CI, 2.5-4.3). The patients treated with dilation demonstrated a dysphagia-free period of 3.7 months (95% CI, 2.7-5), while patients treated with stents displayed a dysphagia-free period of 2.3 months (95% CI, 1.5-3). The dysphagia-free period had a linear growth trend over time, with an increase of 12 days per endoscopic therapy. CONCLUSION: The dysphagia-free period increased by 12 days per endoscopic therapy, so the endoscopic therapy tended to be effective in patients with RBES by increasing the dysphagia-free period. However, compared to dilation therapy, stent therapy was not effective in increasing the dysphasia-free period and reducing the times and frequency of dilation. In addition, univariate and multivariate analyses also indicated that etiology may predict the endoscopic therapy outcome. TRIAL REGISTRATION: This study was retrospectively registered and approved by the Ethics Committee of West China Hospital of Sichuan University (IRB number: ChiCTR1800016321 ).

The neo-potential therapeutic strategy in preeclampsia: Downregulated miR-26a-2-3p motivates endothelial cell injury by targeting 15-LOX-1.

Preeclampsia (PE) poses a life-threatening risk for both mothers and babies, and its onset and progression are linked to endothelial injury. The enzyme 15-lipoxygenase-1 (15-LOX-1), critical in arachidonic acid metabolism, is implicated in various diseases, yet its specific role and precise mechanisms in PE remain largely unknown. In this study, we found that 15-LOX-1 and its main metabolite, 15-HETE, were significantly increased in both the placenta and serum of PE patients. This increase was accompanied by elevated levels of endothelial injury markers, including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). A positive correlation between 15-LOX-1 and those markers in the placenta. In Alox15-/- mice, Alox15 deficiency reduced endothelial cell injury in PE-like mice induced by L-NAME. In vitro studies showed that hypoxia-induced upregulation of 15-LOX-1 reduced the cell viability, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs), while increasing apoptosis and inflammatory cell adhesion. Mechanistically, the p38 MAPK pathway was identified as a downstream target of 15-LOX-1. Knocking down 15-LOX-1 or inhibiting p38 MAPK activation improved endothelial cell injury in hypoxia-treated HUVECs. Furthermore, downregulation of miR-26a-2-3p was found to correlate negatively and colocalize with 15-LOX-1 upregulation in the placenta of PE patients. Luciferase reporter assays further confirmed that miR-26a-2-3p directly bind to the 3'UTR of 15-LOX-1, targeting its expression. Moreover, miR-26a-2-3p agomir ameliorated the PE-like phenotype in mice through the 15-LOX-1/p38 MAPK axis, improving endothelial dysfunction. Therefore, our study provides novel insights into the pathogenesis of PE and highlight modulating the miR-26a-2-3p/15-LOX-1/p38 MAPK axis as a potential therapeutic target for PE.

Multifaceted regulation and functions of 53BP1 in NHEJ­mediated DSB repair (Review).

The repair of DNA double­strand breaks (DSBs) is crucial for the preservation of genomic integrity and the maintenance of cellular homeostasis. Non­homologous DNA end joining (NHEJ) is the predominant repair mechanism for any type of DNA DSB during the majority of the cell cycle. NHEJ defects regulate tumor sensitivity to ionizing radiation and anti­neoplastic agents, resulting in immunodeficiencies and developmental abnormalities in malignant cells. p53­binding protein 1 (53BP1) is a key mediator involved in DSB repair, which functions to maintain a balance in the repair pathway choices and in preserving genomic stability. 53BP1 promotes DSB repair via NHEJ and antagonizes DNA end overhang resection. At present, novel lines of evidence have revealed the molecular mechanisms underlying the recruitment of 53BP1 and DNA break­responsive effectors to DSB sites, and the promotion of NHEJ­mediated DSB repair via 53BP1, while preventing homologous recombination. In the present review article, recent advances made in the elucidation of the structural and functional characteristics of 53BP1, the mechanisms of 53BP1 recruitment and interaction with the reshaping of the chromatin architecture around DSB sites, the post­transcriptional modifications of 53BP1, and the up­ and downstream pathways of 53BP1 are discussed. The present review article also focuses on the application perspectives, current challenges and future directions of 53BP1 research.

Background-free room temperature phosphorescence and digital image colorimetry detection of melamine by carbon nitride quantum dots in cellulose matrix with smartphone-based portable device.

Carbon nitride quantum dots (CNQDs) were embedded in the sodium carboxymethyl cellulose (CMC) matrix to form CNQDs-CMC film to explore the room temperature phosphorescence (RTP) of CNQDs, which suppress the non-radiative relaxation process due to the internal hydrogen bonding interactions between CMC and CNQDs. Then, a simple, inexpensive, background-free miniature device integrating with CNQDs-CMC film and smartphone was fabricated for rapid and quantitative detection of melamine (MEL). In the present of MEL, the yellow RTP color of the CNQDs-CMC film was quenched and photographed by the smartphone. The Color Recognizer APP in the smartphone recognized the red (R) value for quantitative detection of MEL. Thus, digital image colorimetry (DIC) determination of MEL was achieved due to the visible RTP color change of CNQDs-CMC film. The smartphone-based miniature device provided a promising platform for the on-site monitoring analytes in the complex matrix including food safety, environmental screening, health monitoring, and disease prevention.

Smartphone-assisted miniature device based on nitrogen and sulfur co-doped carbon dots for point-of-care testing of tetracycline.

A miniature device was design for the point-of-care testing (POCT) of tetracycline (TC) including a ratio fluorescence test strip, a sample slot, a UV lamp and a smartphone. The nitrogen and sulfur co-doped carbon dots (N, S-CDs) and Eu3+ were dropped onto the filter paper to construct the ratio fluorescence test strips for the specific detection of TC. Under the excitation at 390 nm, the fluorescence emission of N, S-CDs at 530 nm decreases through inner filter effect (IEF) after addition of Eu3+. When the further addition of TC, the emission of N, S-CDs at 530 nm kept unchanged while the emission of Eu3+ at 616 nm was obviously enhanced for the antenna effect (AE) between Eu3+ and TC. The ratio changes of the two-fluorescence emission realized the quantitative detection of TC. In addition, the test strips with different concentrations of TC showed different fluorescence color from green to red under a 365 nm UV lamp. The miniature device was designed as a fluorescence photo reader with the merits of the powerful functions of smartphones and the portability of test strips. The smartphone camera takes a fluorescent color image of the test strips and the photos are recognized by a color recognizer on the smartphone to obtain RGB (red-greenblue) values which reflect the concentrations of the analytes. Therefore, we established a fast, sensitive and efficient POCT of TC. In particular, the proposed nanomaterial-based POCT platform will open a new route towards the development of ratio fluorescence probe for TC analysis for environment samples.

Cu nanoclusters decorated Ti3C2 nanosheets composite with tetraenzyme mimic activities and the application for smartphone-assisted detection of hypoxanthine.

MXene-based nanozymes have increased research enthusiasm in the field of food safety and environment monitoring. Herein, the Cu NCs/Ti3C2 NSs nanocomposites were prepared by modifying copper nanoclusters (Cu NCs) on the surface of Ti3C2 nanosheets (NSs) with a simple two-step method. The Cu NCs/Ti3C2 NSs nanocomposites had outstanding tetraenzyme mimic activities, i.e. peroxidase (POD)-mimics, catalase (CAT)-mimics, ascorbic acid oxidase (AAO)-mimics and superoxide dismutase (SOD)-mimics. Modification of Cu NCs on Ti3C2 NSs can enhance tetraenzyme mimic activities because of the synergistic catalytic effect between Cu NCs and Ti3C2 NSs. The catalytic mechanism and steady-state kinetics of Cu NCs/Ti3C2 NSs were also investigated. Based on the POD-mimic activity of Cu NCs/Ti3C2 NSs, a simple and rapid colorimetric method was established for the on-site detection of hypoxanthine (Hx), with the linear range of 5-200 µM and limit of detection (LOD) was 0.25 µM. The visible color change with the increase of Hx concentration can be recognized by a smartphone APP to transfer the red (R), green (G) and blue (B) value for the quantitative analysis of Hx, with the linear range of 10-200 µM, which provided a convenient method for the real-time detection of Hx. This work not only provides a significant route to fabricate nanocomposite with outstanding tetraenzyme mimic activities but also offers a low-cost and rapid method for monitoring the freshness of aquatic products.

Genetic engineering of pigs for xenotransplantation to overcome immune rejection and physiological incompatibilities: The first clinical steps.

Xenotransplantation has the potential to solve the shortfall of human organ donors. Genetically modified pigs have been considered as potential animal donors for human xenotransplantation and have been widely used in preclinical research. The genetic modifications aim to prevent the major species-specific barriers, which include humoral and cellular immune responses, and physiological incompatibilities such as complement and coagulation dysfunctions. Genetically modified pigs can be created by deleting several pig genes related to the synthesis of various pig specific antigens or by inserting human complement- and coagulation-regulatory transgenes. Finally, in order to reduce the risk of infection, genes related to porcine endogenous retroviruses can be knocked down. In this review, we focus on genetically modified pigs and comprehensively summarize the immunological mechanism of xenograft rejection and recent progress in preclinical and clinical studies. Overall, both genetically engineered pig-based xenografts and technological breakthroughs in the biomedical field provide a promising foundation for pig-to-human xenotransplantation in the future.

Discovery of Potent and Isoform-selective Histone Deacetylase Inhibitors Using Structure-based Virtual Screening and Biological Evaluation.

Histone deacetylases (HDACs) are key enzymes in epigenetics and promising targets for anticancer therapy. Although several drugs targeting HDAC have been approved for the treatment of tumors, their clinical use has been limited by their deleterious side effects and poor efficacy. Herein, we discover four potent HDAC inhibitors through pharmacophore model screening and molecular docking. These compounds are able to bind HDACs 1, 3, and 6 with nanomolar affinity. Among them, compound 3 shows greater inhibitory effect on HDACs 1, 3, and 6 than that of vorinostat (SAHA). Evaluation of anticancer activity indicates that compound 3 significantly inhibits the growth of solid cancer cells including HGC-27, AGS, MDA-MB-231, A549, MCF-7, and H460 cells. In vivo anticancer study suggests that compound 3 can also markedly inhibit the growth of HGC-27 cells-derived xenograft, with no observable toxicity. These findings suggest that compound 3 may be as a potential HDAC-targeting inhibitor for solid tumor therapy.