Natural marmatite photocatalyst for treatment of mineral processing wastewater to help zero wastewater discharge.

Mineral processing wastewater (MPW) with large discharge and high toxicity affects environmental safety, and the realizing zero discharge of MPW is of great significance for reducing environmental pollution, saving water resources, and promoting the sustainable development of the mining industry. In this study, we reported natural marmatite (NM) as a low-cost and efficient photocatalyst for the treatment of MPW to help zero wastewater discharge. The photocatalytic activity of NM was evaluated by the removal of total organic carbon (TOC) from MPW under visible-light illumination, and the optimal degradation conditions were discussed. Results showed that superoxide free radicals (·O2-) were the dominant active species responsible for organic pollutants degradation, and 74.25% TOC removal was obtained after 120 min reaction under the optimum treatment conditions. Meanwhile, the wastewater treated by NM photocatalysis can be reused in the flotation system without adverse impact on the product index. Based on these findings, a model of zero wastewater discharge for flotation with the help of photocatalytic treatment was established, it indicated that the water of the whole system can be balanced without affecting the ore dressing index, which showed that visible light-driven photocatalyst has a promising application prospect in the treatment and recycling of industrial wastewater.

Culture and expansion of murine proximal airway basal stem cells.

BACKGROUND: The stem cell characteristic makes basal cells desirable for ex vivo modeling of airway diseases. However, to date, approaches allowing them extensively in vitro serial expansion and maintaining bona fide stem cell property are still awaiting to be established. This study aims to develop a feeder-free culture system of mouse airway basal stem cells (ABSCs) that sustain their stem cell potential in vitro, providing an experimental basis for further in-depth research and mechanism exploration. METHODS: We used ROCK inhibitor Y-27632-containing 3T3-CM, MEF-CM, and RbEF-CM to determine the proper feeder-free culture system that could maintain in vitro stem cell morphology of mouse ABSCs. Immunocytofluorescence was used to identify the basal cell markers of obtained cells. Serial propagation was carried out to observe whether the stem cell morphology and basal cell markers could be preserved in this cultivation system. Next, we examined the in vitro expansion and self-renewal ability by evaluating population doubling time and colony-forming efficiency. Moreover, the differentiation potential was detected by an in vitro differentiation culture and a 3D tracheosphere assay. RESULTS: When the mouse ABSCs were cultured using 3T3-CM containing ROCK inhibitor Y-27632 in combination with Matrigel-coated culture dishes, they could stably expand and maintain stem cell-like clones. We confirmed that the obtained clones comprised p63/Krt5 double-positive ABSCs. In continuous passage and maintenance culture, we found that it could be subculture to at least 15 passages in vitro, stably maintaining its stem cell morphology, basal cell markers, and in vitro expansion and self-renewal capabilities. Meanwhile, through in vitro differentiation culture and 3D tracheosphere culture, we found that in addition to maintaining self-renewal, mouse ABSCs could differentiate into other airway epithelial cells such as acetylated tubulin (Act-Tub) + ciliated and MUC5AC + mucus-secreting cells. However, they failed to differentiate into alveoli epithelial cells, including alveolar type I and alveolar type II. CONCLUSION: We established an in vitro feeder-free culture system that allows mouse ABSCs to maintain their stem cell characteristics, including self-renewal and airway epithelium differentiation potential, while keeping up in vitro expansion stability.

Therapeutic Potential of Chinese Medicine for Endogenous Neurogenesis: A Promising Candidate for Stroke Treatment.

Strokes are a leading cause of morbidity and mortality in adults worldwide. Extensive preclinical studies have shown that neural-stem-cell-based treatments have great therapeutic potential for stroke. Several studies have confirmed that the effective components of traditional Chinese medicine can protect and maintain the survival, proliferation, and differentiation of endogenous neural stem cells through different targets and mechanisms. Therefore, the use of Chinese medicines to activate and promote endogenous nerve regeneration and repair is a potential treatment option for stroke patients. Here, we summarize the current knowledge regarding neural stem cell strategies for ischemic strokes and the potential effects of these Chinese medicines on neuronal regeneration.

Regulation of glucolipid metabolism and gut microbiota by green and black teas in hyperglycemic mice.

A high-sugar and -fat diet (HSFD) has become a primary risk factor for diabetes, and dietary intervention shows a substantial effect on the prevention and management of hyperglycemia. In this study, the chemical compositions of the aqueous extracts of stir-fried green tea (GT) and congou black tea (BT) were compared. Moreover, their potential mechanisms and regulatory effects on hepatic glycolipid metabolism and gut microbiota disorders in hyperglycemic mice were further explored. Our results show that GT or BT intervention had a prominent regulatory effect on glycolipid metabolism. Moreover, they could significantly regulate the levels of serum metabolic signatures, the activities of key enzymes in liver glucose metabolism, and the expression of genes or proteins related to glycolipid metabolism via activating the IRS-1-PI3K/AKT-GLUT2 signaling pathway. Significantly, GT or BT administration adjusted the composition and diversity of the gut microbiota, mainly reflecting a significant increase in the abundance of beneficial bacteria (including Allobaculum, Lactobacillus, and Turicibacter) and reducing the abundance of harmful or conditionally pathogenic bacteria (mainly including Clostridiales and Bacteroides). Our results suggest that dietary supplementation with GT or BT could exert a practical anti-diabetic effect. Meanwhile, BT intervention showed a better regulation effect on glycolipid metabolism. This study reveals that GT and BT have excellent potential for developing anti-diabetic food.

Removal of chemical oxygen demand and ammonia nitrogen from high salinity tungsten smelting wastewater by one-step electrochemical oxidation: From bench-scale test, pilot-scale test, to industrial test.

In recent years, electrochemical oxidation (EO) shows the characteristics of green and high efficiency in removing chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) from wastewater, which has been favored by researchers. However, at present, most of current studies on EO remain in laboratory stage, reports about pilot-scale or even industrial tests with large treatment capacity are few, which slowing down the use of the advanced technology to practical application. In this study, bench-scale tests, pilot-scale tests (treatment capacity 200-500 L/h), and industrial tests (treatment capacity 100 m3/h) were carried out by EO technology in view of the characteristics of tungsten smelting wastewater (TSW) with high salinity (NaCl), COD, and NH3-N. Results showed that the removal of COD and NH3-N was a competitive reaction in the EO process, and COD could be removed more preferentially than NH3-N. When NH3-N content was low, the influent pH had a minimal effect on its removal, and when NH3-N content was high, increasing the influent pH was beneficial to its removal. Industrial tests showed that the one-step removal of COD and NH3-N in TSW met the standard, and the power consumption per cubic meter of wastewater was only 4.2 kW h, and the treatment cost was much lower than the two-step process of "breaking point chlorination to remove NH3-N and adding oxidant to remove COD". This study has successfully realized industrial application of EO technology in TSW treatment for the first time and provided a successful case, which is helpful to accelerate the popularization and application of this technology in the field of high salinity organic ammonia nitrogen wastewater treatment.

Hysteroscopic dilation techniques in hysteroscopic adhesiolysis. / é•œä¸‹æ‰©å®«æ³•åœ¨å®«è ”é•œå®«è ”ç²˜è¿žåˆ†ç¦»æœ¯ä¸­çš„åº”ç”¨.

OBJECTIVES: Intrauterine adhesion (IUA) is mainly caused by intrauterine operations such as pregnancy-related curettage and hysteroscopic surgery, resulting in the trauma to the basal layer of the endometrium. Hysteroscopic adhesiolysis is a crucial step in the comprehensive treatment of IUA, and the most common complication is uterine perforation. More than half of all uterine perforations occur during the hysteroscopy or probe/dilator pass through the internal os. Furthermore, inappropriate surgical procedures may lead to endometrial injury, recurrence or even aggravation of adhesions, and complications such as cervix laceration and false passage formation. This study aims to explore the usage of the hysteroscopic dilatation techniques to dilate the internal os and lower uterine segment, which is via hysteroscopy entering the internal os laterally and swinging, or by directly opening the forceps or scissors and bluntly spreading dissection under direct hysteroscopic vision. By using the hysteroscopic dilatation techniques, we intend to improve the effectiveness and safety of cervical dilation in patients with IUA in the internal os and/or lower uterine segment. METHODS: A total of 282 patients with adhesions in the internal os or lower uterine segment underwent HA in the Third Xiangya Hospital of Central South University from January 2020 to June 2021 were included, ranging from 21 to 46 (33.0±4.8) years old in age and 5 to 12 in the American Fertility Society score. Among them, there were 2 cases of false passage formation caused by traditional dilatation in other hospitals. All patients underwent hysteroscopy with integrated hysteroscopy with 5Fr instrument channel and 4.9 mm outer sheath diameter. The internal orifice of cervix and the lower segment of uterine cavity were dilated under the microscope. After the hysteroscopy entered the uterine cavity, the separation of uterine cavity adhesion and the placement of uterine contraceptive ring or uterine stent into the uterine cavity were performed routinely. Age, surgical records, and surgical videos of all included cases were collected. The success rate of dilation and the incidence of surgical complications were assessed. RESULTS: In all cases, the hysteroscopys successfully entered into the uterine cavity by using the hysteroscopic dilatation techniques without failure and switching to cervical dilators. In the 2 cases of false passage due to previous cervical dilation, the uterine cavity was identified and found successfully under direct hysteroscopic vision. During the whole surgery, the vision was clear, and no complications (such as cervix laceration, false passage formation, uterine perforation or water intoxication) occurred. One to 3 months postoperative hysteroscopy revealed no significant fibrotic stenosis in the internal os and lower uterine segment. CONCLUSIONS: The hysteroscopic dilation techniques are a strategy for separation methods that is following structural hierarchy anatomy in the mode of "see and treat" for the adhesion in the internal os and uterine cavity under direct hysteroscopic vision. This method not only has ultrasound guidance, but also has the judgment of structural hierarchy anatomy under direct hysteroscopic vision, so there is less chance of anatomical level judgment error. This method makes full use of the hysteroscopic judgement of the experienced hysteroscopic surgeons, so that surgeons can timely find and avoid re-entering the old false passage caused by previous surgery. The adhesions in the internal os and lower uterine segment were separated by the hysteroscopic dilation techniques. In this way, the damage to the endometrium caused by forced insertion of the hysteroscopy can be avoided. Meticulous separation of adhesions and cervical dilation under direct hysteroscopic vision can effectively reduce the occurrence of surgical complications such as false passage formation, cervical laceration, and uterine perforation. The use of mini-hysteroscopy eliminates the need for preoperative cervical preparation, avoiding associated risks and side effects. Moreover, for patients with adhesions in the internal os and lower uterine segment, preoperative cervical preparation is not effective in cervical dilation, while the hysteroscopic dilation techniques are effective, with higher patient acceptance due to the absence of preoperative cervical preparation. For the skilled hysteroscopic surgeons, the hysteroscopic dilation technique is easy to operate and worthy of clinical application.

Green and Oolong Tea Extracts With Different Phytochemical Compositions Prevent Hypertension and Modulate the Intestinal Flora in a High-Salt Diet Fed Wistar Rats.

Green tea (GT) and oolong tea (OLT) are widely consumed beverages, and their preventive and regulatory effects on hypertension have been reported. However, the interventional effects of GT and OLT on hypertension induced by a high-salt diet and its mechanism have not been fully explored. This study evaluated the anti-hypertensive effects of GT and OLT and their underlying mechanisms. The in vivo anti-hypertensive effects of GT and OLT and their capability to prevent hypertension and regulate the intestinal microbiota in Wistar rats fed with a high-salt diet were evaluated. Our results show that GT and OLT supplementations could regulate oxidative stress, inflammation, gene expression, and parameter levels related to blood pressure (BP) and prevent the increase in BP induced by a high-salt diet. Furthermore, both GT and OLT boosted the richness and diversity of intestinal microbiota, increased the abundance of beneficial bacteria and reduced the abundance of harmful bacteria and conditionally pathogenic bacteria, and regulated the intestinal microbial metabolism pathway related to BP. Among them, OLT presented better effects than GT. These findings indicate that GT and OLT can prevent hypertension caused by high-salt diets, which may be due to the regulation of intestinal flora by GT and OLT.

Roles of airway basal stem cells in lung homeostasis and regenerative medicine.

Airway basal stem cells (BSCs) in the proximal airways are recognized as resident stem cells capable of self-renewing and differentiating to virtually every pseudostratified epithelium cell type under steady-state and after acute injury. In homeostasis, BSCs typically maintain a quiescent state. However, when exposed to acute injuries by either physical insults, chemical damage, or pathogen infection, the remaining BSCs increase their proliferation rate apace within the first 24 h and differentiate to restore lung homeostasis. Given the progenitor property of airway BSCs, it is attractive to research their biological characteristics and how they maintain homeostatic airway structure and respond to injury. In this review, we focus on the roles of BSCs in lung homeostasis and regeneration, detail the research progress in the characteristics of airway BSCs, the cellular and molecular signaling communications involved in BSCs-related airway repair and regeneration, and further discuss the in vitro models for airway BSC propagation and their applications in lung regenerative medicine therapy.

The Whitening, Moisturizing, Anti-aging Activities, and Skincare Evaluation of Selenium-Enriched Mung Bean Fermentation Broth.

Selenium-enriched mung bean (Se-MB) is a combination of mung bean (MB) and selenium (Se), which have a variety of potential biological activities. However, little is known about the skincare activity of Se-MB. The chemical composition of Se-MB fermentation broth (Se-MBFB) was analyzed to investigate the whitening, moisturizing, and anti-aging activities of Se-MBFB. The tyrosinase inhibition, anti-melanogenic in melanocytes (B16F10 cells), and moisturizing effect in human dermal fibroblasts (HDFs) were analyzed. Besides, the free radical scavenging activity of Se-MBFB was assessed in vitro. To verify the in vivo effects and the potential of practical applications of Se-MBFB, a clinical trial was conducted on the participants: 31 Chinese women aged 25-60 years, with no pigmentation disorder, no illness, no history of hypersensitivity reaction, and no use of skincare product on the face. The participants used an Se-MBFB masque for 15-20 min after cleaning the face. The measurement points were Week 0, 2, and 4 (W0, W2, and W4) after using the masque, and target sites were cheek and canthus. The following parameters were recorded on the target sites at each visit: melanin index, skin color, cuticle moisture content, transepidermal water loss, and crow's feet. The results demonstrated that Se-MBFB was rich in polyphenols, peptides, and γ-aminobutyric acid (GABA), displayed significant free radical scavenging and tyrosinase inhibiting activities, decreased the synthesis of melanin, and upregulated the aquaporin-3 (AQP3) expression. The test of the Se-MBFB mask showed that after 4 weeks of using the Se-MBFB facemask, the faces of the participants became whiter with reduced wrinkles and increased moisture content. Se-MB possessed the excellent whitening, moisturizing, and antioxidant efficacy, which could lay a scientific foundation for utilization and development of skincare products of Se-MB and its related industrial cosmetics products.

G protein nucleolar 3 promotes Non-Hodgkin lymphoma progression by activating the Wnt/ß-catenin signaling pathway.

G protein nucleolar 3 (GNL3), which acts as an oncoprotein in various carcinomas, is associated with tumor progression; however, little is known regarding GNL3 function in non-Hodgkin lymphoma (NHL). In this study, we first used in silico analysis to determine associations between GNL3 and diffuse large B-cell lymphoma (DLBCL). We then examined the effect of GNL3 on NHL progression, including cell proliferation, apoptosis, and cell cycle progression, and determined its underlying molecular mechanism using in vitro lymphoma cell lines and in vivo mouse xenograft models. We found that GNL3 mRNA levels were markedly higher in DLBCL tissues than in normal tissues, with these higher levels associated with poor prognosis. Additionally, GNL3 overexpression promoted NHL cell proliferation and cell cycle progression and reduced apoptosis in vitro, and enhanced tumorigenesis in an in vivo xenograft model. Moreover, we found that GNL3 upregulated the levels of Wnt/ß-catenin signaling pathway-related factors and downstream target genes, whereas the opposite result was observed in GNL3-silenced cells. Furthermore, a rescue experiment using a Wnt/ß-catenin inhibitor (XAV939) confirmed that GNL3 promotes NHL progression by activating the Wnt/ß-catenin signaling pathway. These findings demonstrated that GNL3 functions as an oncogenic driver in NHL via the Wnt/ß-catenin pathway.

Liubao brick tea activates the PI3K-Akt signaling pathway to lower blood glucose, metabolic disorders and insulin resistance via altering the intestinal flora.

Diabetes and its related metabolic disorders are worldwide public health issues. Many studies have shown that changes in the structure and composition of the intestinal flora are closely related to the host's physiological and pathological processes. In this study, we aim to explore the effect of Liubao tea (LBT) extract on hyperglycemic mice with metabolic disorders and intestinal flora dysbiosis and to further study its regulatory effect on insulin resistance and its potential regulatory mechanism. Our results show that LBT had a good hypoglycemic effect and could significantly alleviate the metabolic disorder evoked by hyperglycemia. The gut microbial sequencing showed that LBT treatment increased the diversity of intestinal flora, increased the abundance of beneficial bacteria, and reduced the abundance of harmful or conditional pathogenic bacteria, as well as significantly altered 39 of the top 50 OTUs with abundance. Besides, LBT could activate the PI3K-Akt-PPARs-GLUT2 cascade signaling pathway to improve metabolic disorders, thereby alleviating insulin resistance. These results suggest that LBT has excellent potential to become a natural functional food for the prevention of hyperglycemia and insulin resistance.

Simultaneously Detecting Monoamine Oxidase A and B in Disease Cell/Tissue Samples Using Paper-Based Devices.

As enzymes in the outer membrane of the mitochondrion, monoamine oxidases (MAOs) can catalyze the oxidative deamination of monoamines in the human body. According to different substrates, MAOs can be divided into MAO-A and MAO-B. The imbalance of the MAO-A is associated with neurological degeneration, while excess MAO-B activity is closely connected with Parkinson's disease (PD) and Alzheimer's disease (AD); therefore, detection of MAOs is of great significance for the diagnosis and treatment of these diseases. This work reports the multiplexed detection of MAO-A and MAO-B using paper-based devices based on chemiluminescence (CL). The detection limits were 5.01 pg/mL for MAO-A and 8.50 pg/mL for MAO-B in human serum. In addition, we used paper-based devices to detect MAOs in human cells and tissue samples and found that the results of paper-based detection and Western blotting (WB) showed the same trend. While only one antibody can be incubated on the same membrane by WB, multiple antibodies incubated on the same paper enabled simultaneous detection of MAO-A and MAO-B by paper-based devices. The paper-based assay could be used for preliminary early screening of clinical samples for MAOs and can be extended as an alternative to WB for multiplexed detection of various proteins in disease cell or tissue samples.

Bronchoscopic Treatment of Tracheobronchial Fistula With Autologous Platelet-Rich Plasma.

Tracheobronchial fistula (TBF) is a challenging management condition. Several bronchoscopic procedures have been tried for fistula closure. However, none has been found to be superior to the others. We herein describe a novel technique involving the submucosal injection of autologous platelet-rich plasma (auto-PRP) around the fistula to close the TBF. After auto-PRP treatment, all 3 TBF patients have successfully healed. No treatment-related complications and fistula-related symptoms were detected. Thus, this application of auto-PRP for fistula closure is a feasible and cost-effective strategy and could be recommended as a valuable therapeutic alternative for repairing postoperative TBF.

Chimeric antigen receptor therapy in hematological malignancies: antigenic targets and their clinical research progress.

Chimeric antigen receptor (CAR)-based immunotherapy has achieved dramatic success in the treatment of B cell malignancies, based on the summary of current research data, and has shown good potential in early phase cancer clinical trials. Modified constructs are being optimized to recognize and destroy tumor cells more effectively. By targeting the proper B-lineage-specific antigens such as CD19 and CD20, adoptive immunotherapy has demonstrated promising clinical results and already plays a role in the treatment of several lymphoid malignancies, which highlights the importance of target selection for other CAR therapies. The high efficacy of CAR-T cells has resulted in the approval of anti-CD19-directed CAR-T cells for the treatment of B cell malignancies. In this review, we focus on the basic structure and current clinical application of CAR-T cells, detail the research progress of CAR-T for different antigenic targets in hematological malignancies, and further discuss the current barriers and proposed solutions, investigating the possible mechanisms of recurrence of CAR-T cell therapy. A summary of the paper is also given to overview as the prospects for this therapy.

Impact of dehydroepianrosterone (DHEA) supplementation on serum levels of insulin-like growth factor 1 (IGF-1): A dose-response meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Inconsistencies exist with regard to the influence of dehydroepiandrosterone (DHEA) supplementation on insulin-like growth factor 1 (IGF-1) levels. The inconsistencies could be attributed to several factors, such as dosage, gender, and duration of intervention, among others. To address these inconsistencies, we conducted a systematic review and meta-analysis to combine findings from randomized controlled trials (RCTs) on this topic. METHODS: Electronic databases (Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar) were searched for relevant literature published up to February 2020. RESULTS: Twenty-four qualified trials were included in this meta-analysis. It was found that serum IGF-1 levels were significantly increased in the DHEA group compared to the control (weighted mean differences (WMD): 16.36 ng/ml, 95% CI: 8.99, 23.74; p = .000). Subgroup analysis revealed that a statistically significant increase in serum IGF-1 levels was found only in women (WMD: 23.30 ng/ml, 95% CI: 13.75, 32.87); in participants who supplemented 50 mg/d DHEA (WMD: 15.75 ng/ml, 95% CI: 7.61, 23.89); in participants undergoing DHEA intervention for >12 weeks (WMD: 17.2 ng/ml, 95% CI: 8.02, 26.22); in participants without an underlying comorbidity (WMD: 19.11 ng/ml, 95% CI: 10.69, 27.53); and in participants over the age of 60 years (WMD: 19.79 ng/ml, 95% CI: 9.86, 29.72). CONCLUSION: DHEA supplementation may increase serum IGF-I levels especially in women and older subjects. However, further studies are warranted before DHEA can be recommended for clinical use.

EPS8-mediated regulation of multiple myeloma cell growth and survival.

Epidermal growth factor receptor pathway substrate 8 (EPS8), which acts as an oncoprotein in various carcinomas, is associated with tumor progression. However, its impact on multiple myeloma (MM) has not been determined. Here, we investigate the role of EPS8 in MM and consider the potential of EPS8 as an anti-MM target. We confirmed overexpression of EPS8 in MM cells compared with plasma cells derived from healthy volunteers. Knockdown of EPS8 significantly abrogated MM cell survival, migration and invasion. Moreover, depletion of EPS8 overcomes drug resistance. TNFα or bone marrow stromal cell culture supernatants induce EPS8, which is blocked by the IKKß inhibitor MLN120B, suggesting that EPS8 is regulated by NF-κB signaling in MM cells. Mithramycin (MTM), a selective EPS8 inhibitor, suppressed MM cell proliferation and exerted potent anti-MM activity in xenograft tumor models. A synergistic effect of MTM and bortezomib (BTZ) was also observed in vitro and in vivo. Mechanistically, treatment of MM cells with MTM reduced the expression of EPS8 and related pathways. Additionally, the EPS8-knockdown phenotype can be rescued by shRNA-resistant EPS8. Taken together, we describe overexpression of EPS8 in MM by highlighting its role as a potential target and reveal therapeutic targeting of EPS8 by MTM as a novel therapy for MM.

Two-component ratiometric sensor for Cu2+ detection on paper-based device.

The copper(II) ion (Cu2+) has played an indispensable role in diverse kinds of functional physiological processes of organisms, which has become of growing interest. Despite the fact that numerous Cu2+ test papers using fluorescent probes have been fabricated, sensors featuring the ratiometric property that integrates quenched probes and an inner standard dye are rarely reported. Herein, a two-component ratiometric sensor in a paper-based device is proposed to realize highly selective Cu2+ detection. To overcome shortcomings such as low signal-to-noise ratio and incorrect response of the quenching probe, a novel BODIPY-based turn-off probe (P2017) is designed and introduced into the paper-based device with better water solubility and selectivity for Cu2+ detection. Furthermore, a reference dye (B001), exhibiting an emission at 690 nm when the excitation wavelength is 480 nm, is also introduced into the paper-based device. These two components can enhance the quality of the signal as P2017 is sensitively quenched by Cu2+, while B001 with a photostable property, serving as an internal benchmark, is unable to react with Cu2+. The results indicated that the two components provided a new concept for optimizing paper-based device fabrication and developing accurate, simple, and inexpensive Cu2+ detection methods, which could be potentially applied to monitor human health and the environment in remote areas. Graphical abstract.

CD19 chimeric antigen receptor-redirected T cells combined with epidermal growth factor receptor pathway substrate 8 peptide-derived dendritic cell vaccine in leukemia.

BACKGROUND: Chimeric antigen receptor (CAR)-T cell therapy opens a new era for cancer treatment. However, in prolonged follow-up, relapse has emerged as one of the major obstacles. Dendritic cell (DC) vaccination is a promising treatment to eradicate tumor cells and prevent relapse. The epidermal growth factor receptor (EGFR) pathway substrate 8 (Eps8) gene is involved in regulating cancer progression and is considered an attractive target for specific cancer immunotherapy. The purpose of this study was to explore a combinatorial therapy using CAR-T cells and a DC vaccine such as Eps8-DCs to increase leukemia treatment efficacy. METHODS: We pulsed DCs with Eps8-derived peptides to generate Eps8-DCs, engineered T cells to express a second-generation CAR specific for CD19, and analyzed the effects of the Eps8-DCs on the in vitro expansion, phenotype and effector functions of the CD19 CAR-T cells. RESULTS: The Eps8-DCs significantly reduced the activation-induced cell death and enhanced the proliferative potential of CAR-T cells during in vitro expansion. In addition, the expanded T cells co-cultured with the Eps8-DCs exhibited an increased percentage of central memory T cells (Tcms) and a decreased percentage of effector memory T cells (Tems). The Eps8-DCs enhanced CD19 CAR-T cell immune functions, including cytokine production, CD107a degranulation activity and cytotoxicity. DISCUSSION: This study demonstrates that Eps8-DCs exert synergistic effect on CD19 targeting CAR-T cells and paves the way for clinical trials using the combination of DC vaccination and engineered T cells in relapsed leukemia.

A paper-based chemiluminescence immunoassay device for rapid and high-throughput detection of allergen-specific IgE.

The fast and precise detection of potential allergen-specific immunoglobulin E (sIgE) is imperative for the diagnosis and appropriate treatment of allergic diseases. In this study, we have successfully fabricated a novel paper-based immunoassay device for the detection of sIgE in allergic diseases. We used Can f 1, one of the main dog allergens, as a model allergen to detect sIgE in human sera. To achieve excellent performance, the experimental parameters were optimized. Further, we extended this device for potential applications in the clinical diagnosis of allergic diseases: worthwhile clinical performance in the detection of allergens was achieved as compared to that achieved by commercial enzyme-linked immunosorbent assay (ELISA) kit. Therefore, it was proven that this strategy has the advantages of high-throughput, rapid, sensitive, and highly accurate detection of trace amounts of sIgEs. Furthermore, by simply changing the antigen and antibody, this device could be used for the high-throughput detection of other allergens, so as to achieve multiallergen detection and appropriate desensitization therapy, thereby making it promising in the determination of allergic diseases in clinics.

Fast response two-photon fluorogenic probe based on Schiff base derivatives for monitoring nitric oxide levels in living cells and zebrafish.

Numerous excellent fluorogenic probes for NO detection based on NO-mediated reactions have been developed. However, some of them still suffer from limitations such as low selectivity, slow response, and a short excitation wavelength (<500 nm). Herein, a novel two-photon fluorogenic probe (XNO1) based on a Schiff base derivative has been reported for the first time. This new mechanism with a Schiff base structure as the specific response moiety towards NO endows the probe with fast responsibility, high selectivity and pH-independent properties. Furthermore, XNO1 has been demonstrated to be lysosome-targeted and to successfully monitor exogenous/endogenous NO in living cells and zebrafishes with one- and two-photon fluorescence imaging.