Crown ether decorated silicon photonics for safeguarding against lead poisoning.

Lead (Pb2+) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb2+ poisoning.

CH-VAD left ventricular assist implantation combined with the Bentall procedure and coronary artery bypass grafting.

Left ventricular assist device (LVAD) implantation is an effective alternative treatment to heart transplantation, especially for end-stage heart failure patients who are ineligible for or unable to await a heart transplant. This report describes a complex and innovative surgery where LVAD implantation was performed alongside multiple concomitant cardiac and aortic procedures. A 62-year-old male patient with complicated comorbidities developed acute myocardial infarction and subsequent refractory advanced heart failure. Given his critically ill condition and intractable anatomical malformations, the CH-VAD left ventricular assist system implantation was performed concomitantly with the Bentall procedure, coronary artery bypass grafting, tricuspid valvuloplasty, and foramen ovale closure. The patient was successfully discharged. This case details the medical decision-making process and surgical strategy and demonstrates the feasibility of LVAD implantation combined with multiple additional cardiac and aortic procedures in expert cardiac centres. Success relies on experienced cardiac surgeons and a multidisciplinary LVAD Heart Team, ensuring excellence in surgical techniques, preoperative evaluation, post-operative care, and rehabilitation.

Heparanase interacting BCLAF1 to promote the development and drug resistance of ICC through the PERK/eIF2α pathway.

Intrahepatic cholangiocarcinoma (ICC) is a primary epithelial carcinoma known for its aggressive nature, high metastatic potential, frequent recurrence, and poor prognosis. Heparanase (HPSE) is the only known endogenous ß-glucuronidase in mammals. In addition to its well-established enzymatic roles, HPSE critically exerts non-catalytic function in tumor biology. This study herein aimed to investigate the non-enzymatic roles of HPSE as well as relevant regulatory mechanisms in ICC. Our results demonstrated that HPSE was highly expressed in ICC and promoted the proliferation of ICC cells, with elevated HPSE levels implicating a poor overall survival of ICC patients. Notably, HPSE interacted with Bcl-2-associated factor 1 (BCLAF1) to upregulate the expression of Bcl-2, which subsequently activated the PERK/eIF2α-mediated endoplasmic reticulum (ER) stress pathway to promote anti-apoptotic effect of ICC. Moreover, our in vivo experiments revealed that concomitant administration of gemcitabine and the Bcl-2 inhibitor navitoclax enhanced the sensitivity of ICC cells with highly expressed HPSE to chemotherapy. In summary, our findings revealed that HPSE promoted the development and drug resistance of ICC via its non-enzymatic function. Bcl-2 may be considered as an effective target with therapeutic potential to overcome ICC chemotherapy resistance induced by HPSE, presenting valuable insights into the development of novel therapeutic strategies against ICC.

Potential roles of heparanase in cancer therapy: Current trends and future direction.

Heparanase (HPSE; heparanase-1) is an endo-ß-glucuronidase capable of degrading the carbohydrate moiety of heparan sulfate proteoglycans, thus modulating and facilitating the remodeling of the extracellular matrix and basement membrane. HPSE activity is strongly associated with major human pathological complications, including but not limited to tumor progress and angiogenesis. Several lines of literature have shown that overexpression of HPSE leads to enhanced tumor growth and metastatic transmission, as well as poor prognosis. Gene silencing of HPSE or treatment of tumor with compounds that block HPSE activity are shown to remarkably attenuate tumor progression. Therefore, targeting HPSE is considered as a potential therapeutical strategy for the treatment of cancer. Intriguingly, recent findings disclose that heparanase-2 (HPSE-2), a close homolog of HPSE but lacking enzymatic activity, can also regulate antitumor mechanisms. Given the pleiotropic roles of HPSE, further investigation is in demand to determine the precise mechanism of regulating action of HPSE in different cancer settings. In this review, we first summarize the current understanding of HPSE, such as its structure, subcellular localization, and tissue distribution. Furthermore, we systematically review the pro- and antitumorigenic roles and mechanisms of HPSE in cancer progress. In addition, we delineate HPSE inhibitors that have entered clinical trials and their therapeutic potential.

Heparanase in cancer progression: Structure, substrate recognition and therapeutic potential.

Heparanase, a member of the carbohydrate-active enzyme (CAZy) GH79 family, is an endo-ß-glucuronidase capable of degrading the carbohydrate moiety of heparan sulphate proteoglycans, thus modulating and facilitating remodeling of the extracellular matrix. Heparanase activity is strongly associated with major human pathological complications, including but not limited to tumour progress, angiogenesis and inflammation, which make heparanase a valuable therapeutic target. Long-due crystallographic structures of human and bacterial heparanases have been recently determined. Though the overall architecture of human heparanase is generally comparable to that of bacterial glucuronidases, remarkable differences exist in their substrate recognition mode. Better understanding of regulatory mechanisms of heparanase in substrate recognition would provide novel insight into the anti-heparanase inhibitor development as well as potential clinical applications.

Sub-kHz linewidth, hybrid III-V/silicon wavelength-tunable laser diode operating at the application-rich 1647-1690†nm.

The wavelength region about of 1650 nm enables pervasive applications. Some instances include methane spectroscopy, free-space/fiber communications, LIDAR, gas sensing (i.e. C2H2, C2H4, C3H8), surgery and medical diagnostics. In this work, through the hybrid integration between an III-V optical amplifier and an extended, low-loss wavelength tunable silicon Vernier cavity, we report for the first time, a III-V/silicon hybrid wavelength-tunable laser covering the application-rich wavelength region of 1647-1690 nm. Room-temperature continuous wave operation is achieved with an output power of up to 31.1 mW, corresponding to a maximum side-mode suppression ratio of 46.01 dB. The laser is ultra-coherent, with an estimated linewidth of 0.7 kHz, characterized by integrating a 35 km-long recirculating fiber loop into the delayed self-heterodyne interferometer setup. The laser linewidth is amongst the lowest in hybrid/heterogeneous III-V/silicon lasers.

Facile Preparation of Homogeneous Copper Nanoclusters Exhibiting Excellent Tetraenzyme Mimetic Activities for Colorimetric Glutathione Sensing and Fluorimetric Ascorbic Acid Sensing.

Nanozymes are artificial enzymes, which can substitute traditional biological enzymes for multifield applications. However, to date, it remains challenging to search novel mimic enzymes or multienzyme mimics. Herein, a facile and green method for preparing monodisperse, homogeneous copper nanoclusters (Cu NCs) with smaller size was developed, which used cysteamine as a template and hydrazine hydrate as a reductant to reduce Cu2+. The as-prepared Cu NCs exhibited excellent tetraenzyme-like activities, including peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-, and ascorbic acid oxidase (AAO)-mimic activities. The mechanisms, kinetics, and catalytic performances of Cu NCs were systematically studied. Moreover, based on the POD-like activity of Cu NCs, sensitive and simple colorimetric sensing glutathione (GSH) was explored, with the low limit of detection of 0.89 µM GSH (S/N = 3). Additionally, a novel fluorimetric ascorbic acid (AA) sensor was developed with the linear range of 0.5-30 µM and limit of detection (LOD) of 0.144 µM, on the basis of the principle that AA is oxidized to dehydroascorbic acid (DHAA) specifically catalyzed by the AAO-like activity of Cu NCs, while DHAA can further react with o-phenylenediamine (OPDA) to generate a highly fluorescent quinoxaline (DFQ) derivative. The as-proposed colorimetric GSH sensor and the fluorimetric AA sensor were capable of detecting GSH and AA, respectively, in real samples accurately and reproducibly. Thus, the Cu NCs-based multienzyme mimic is a promising candidate for biocatalysis and biosensing.

Smartphone-based application to improve medication adherence in patients after surgical coronary revascularization.

BACKGROUND: Secondary preventive therapies play a key role in the prevention of adverse events after coronary artery bypass grafting (CABG). However, adherence to secondary preventive drugs after CABG is often poor. With the increasing penetration of smartphones, health-related smartphone applications might provide an opportunity to improve medication adherence. We aimed to evaluate the effectiveness and feasibility of using a smartphone-based application to improve medication adherence in patients after CABG. METHODS: The Measurement and Improvement Studies of Surgical coronary revascularizatION: medication adherence (MISSION-2) study is a multicenter randomized controlled trial that planned to enroll over 1000 patients who underwent isolated CABG at one of four large teaching hospitals in China; all enrolled participants had access to a smartphone and were able to operate at least three smartphone applications. The investigators randomly assigned the participants to one of two groups: (1) the intervention group with an advanced smartphone application for 6 months which was designed specifically for this trial and did not exist before. Participants could receive medication reminders and cardiac health education by the smartphone application or (2) the control group with usual care. The primary outcome was CABG secondary preventive medication adherence as measured by the translated Chinese version of the 8-item Morisky Medication Adherence Scale (MMAS-8) at 6 months after randomization. The secondary outcomes were mortality, major adverse cardiovascular and cerebrovascular events (MACCE), cardiovascular rehospitalization, self-reported secondary preventive medication use after 6 months of follow-up, blood pressure (BP), body mass index (BMI), and self-reported smoking status. All analyses were conducted using the intention-to-treat principle. RESULTS: A total of 1000 patients (mean age, 57.28 [SD, 9.09] years; 85.5% male) with coronary heart disease after CABG were enrolled between September 2015 and September 2016 and were randomly assigned to the intervention (n = 501) or control group (n = 499). At 6 months, the proportion of low-adherence participants, categorized by MMAS-8 scores, was 11.8% in the intervention group and 11.7% in the control group (RR = 1.005, 95% CI 0.682 to 1.480, P = 1.000). Similar results were found in sensitivity analyses that considered participants who withdrew from the study, or were lost to follow-up as nonadherent. There were no significant differences in the secondary clinical outcome measures, and there were no significant differences in the primary outcome across the subgroups tested. In the intervention group, the proportion of participants who used and operated the application during the first month after CABG was 88.1%; however, the use rate decreased sharply from 42.5% in the second month to 9.2% by the end of the study (6 months). CONCLUSIONS: A smartphone-based application supporting secondary prevention among patients after CABG did not lead to a greater adherence to secondary preventive medications. The limited room for improvement in medication adherence and the low participants' engagement with the smartphone applications might account for these non-significant outcomes.

Facile synthesis of magnetic hierarchical flower-like Co3O4 spheres: Mechanism, excellent tetra-enzyme mimics and their colorimetric biosensing applications.

Magnetic hierarchical flower-like Co3O4 spheres (Co3O4 nanoflowers) were facilely prepared via one-step surfactant-free and template-free wet chemical route at room temperature. The formation mechanism of Co3O4 nanoflowers was explored. The as-prepared Co3O4 nanoflowers exhibited excellent tetra-enzyme mimetic activities, including oxidase-like, peroxidase-like, catalase-like and superoxide dismutase (SOD)-like activity. The catalytic mechanism of the Co3O4 nanoflowers was studied in detail. The oxidase-like catalytic activity of Co3O4 nanoflowers was derived from the inherent oxygen vacancies of Co3O4, while the peroxidase-like catalytic activity originated from the •OH radical generated by hydrogen peroxide (H2O2). Only one specific enzyme mimics reaction with Co3O4 nanoflowers can be obtained by inhibiting specifically other nanozymes via varying pH, adding appropriate scavengers or selecting its specific substrate. Further, the steady-state kinetic and catalytic performance of the oxidase-, peroxidase- and catalase mimics of Co3O4 nanoflowers were studied. Based on the oxidase-like and peroxidase-like activities of Co3O4 nanoflowers, bifunctional colorimetric sensing platforms were constructed for the sensitive detection of acid phosphatase (ACP) with the linear range of 0.1-25 U L-1 and H2O2 with the linear range of 4-400 µM. Further, it is capable of detecting ACP in serum samples and H2O2 in water samples, respectively. Thus, the tetra-enzyme mimetic Co3O4 nanoflowers show broad prospects in the fields of biosensors, tumor therapy, environmental monitoring and biocatalysis.

Establishment of a New Platform for the Management of Patients After Cardiac Surgery: Descriptive Study.

BACKGROUND: Medical care for the Chinese population has been focused on first-line treatment, but with little follow-up on treated patients. As an important part of clinical work, follow-up evaluations are of great significance for the long-term survival of patients and for clinical and scientific research. However, the overall follow-up rate of discharged patients after surgery has been low for many years because of the limitations of certain follow-up methods and the presence of objective, practical problems. OBJECTIVE: This study aimed to construct a new two-way interactive telemedicine follow-up platform to improve the collection of clinical data after cardiac surgery and provide reliable and high-quality follow-up services. METHODS: Computer and network technologies were employed in the context of "Internet +" to develop follow-up databases and software compatible with a mobile network. Postoperative follow-up quality data including the follow-up rate and important postoperative indices were used as standards to evaluate the new follow-up management model after cardiac surgery. RESULTS: This system has been officially operated for more than 5 years. A total of 5347 patients undergoing cardiac surgery have been enrolled, and the total follow-up rate was 90.22%. In addition, 6349 echocardiographic images, 4717 electrocardiographic images, and 3504 chest radiographic images have been uploaded during follow-up assessments. The international standardized ratio was 20,696 person-times. CONCLUSIONS: This new management follow-up platform can be used to effectively collect clinical data, provide technical support for academic research, extend medical services, and provide more help to patients. It is of great significance for managing patients after cardiac surgery.

Serum IFN-γ levels predict the therapeutic effect of mesenchymal stem cell transplantation in active rheumatoid arthritis.

BACKGROUND: To explore the mechanism of the different clinical efficacies of mesenchymal stem cell transplantation (MSCT) and identify a possible serum biomarker for predicting the therapeutic effect of MSCT in rheumatoid arthritis (RA) patients. METHODS: A total of 105 patients with persistently active RA and poor responses to traditional medication were randomly divided into MSCT and control groups. Outcomes were evaluated according to the 28-joint Disease Activity Score and Health Assessment Questionnaire, serological indicators, regulatory T cell (Treg) to T helper 17 (Th17) cell ratio, and inflammatory cytokine levels. Twelve weeks after MSCT, the outcomes of the MSCT group were evaluated according to the European League against Rheumatism response criteria. Patients with a good or moderate response were added to the response group, and those with no response were added to the no-response group. RESULTS: No serious adverse events were reported for either MSCT subgroup (28 in the response group and 24 in the no-response group). The therapeutic effects lasted for 48 weeks without continuous administration. Notably, a transient increase in serum IFN-γ (>2 pg/ml) levels was observed in the response group, but not in the no-response group. Furthermore, an increase in IL-10 levels and the Treg/Th17 ratio and a reduction in IL-6 levels appeared 2-3 weeks after the transient IFN-γ increase. CONCLUSIONS: Allogeneic MSCT is safe and feasible, and we propose high serum IFN-γ levels as a potent biomarker for predicting MSCT response. Trial registration chictr.org, ChiCTR-ONC-16008770. Registered 3 July 2016, http://www.chictr.org.cn/showproj.aspx?proj=14820.

Quality Measurement and Improvement Study of Surgical Coronary Revascularization: Medication Adherence (MISSION-2).

BACKGROUND: Secondary preventive therapies play a key role in the prevention of adverse outcomes after coronary artery bypass grafting (CABG). However, medication adherence after CABG is often poor, and conventional interventions for improving adherence have limited success. With increasing penetration of smartphones, health-related smartphone applications might provide an opportunity to improve adherence. Carefully designed trials are needed to provide reliable evidence for the use of these applications in patients after CABG. METHODS: The Measurement and Improvement Studies of Surgical Coronary Revascularization: Medication Adherence (MISSION-2) study is a multicenter randomized controlled trial, aiming to randomize 1000 CABG patients to the intervention or control groups in a 1:1 ratio. We developed the multifaceted, patient-centered, smartphone-based Heart Health Application to encourage medication adherence in the intervention group through a health self-management program initiated during hospital admission for CABG. The application integrated daily scheduled reminders to take the discharge medications, cardiac educational materials, a dynamic dashboard to review cardiovascular risk factors and secondary prevention targets, and weekly questionnaires with interactive feedback. The primary outcome was secondary preventive medication adherence measured by the Chinese version of the 8-item Morisky Medication Adherence Scale at 6 months after randomization. Secondary outcomes included all-cause death, cardiovascular rehospitalization, and a composite of death, myocardial infarction, stroke, and repeat revascularization. DISCUSSION: Findings will not only provide evidence regarding the feasibility and effectiveness of the described intervention for improving adherence to CABG secondary preventive therapies but also explore a model for outpatient health self-management that could be translated to various chronic diseases and widely disseminated across resource-limited settings. TRIAL REGISTRATION: https://clinicaltrials.gov (NCT02432469).

Use of etanercept to treat rheumatoid arthritis in an HIV-positive patient: a case-based review.

Rheumatoid arthritis (RA) is a relatively common autoimmune disease that is associated with progressive disability and systemic complications, with a relatively high socioeconomic burden. The treatment of RA has been revolutionized by the use of biological drugs, such as anti-tumor necrosis factor (TNF) agents. A wide spectrum of RA disease severity has been reported among patients with human immunodeficiency virus (HIV) infection. Yet, only a few cases using anti-TNF therapy have been described in this clinical population. Therefore, the aim of our case-based review was to describe the successful use of etanercept in a 38-year-old female patient with RA concomitant with HIV infection, who had been resistant to the first-line anti-rheumatic therapies. As per routine care guidelines, the patient was screened for hepatitis virus infection, latent tuberculosis, and other infectious conditions, prior to the initiation of etanercept treatment. CD4 cell count, HIV viral load, and adverse effects were closely monitored during the treatment. The HIV infection remained stable with etanercept treatment, without the need for anti-retrovirus agents. No adverse effects and serious infections were identified during the treatment. Therefore, anti-TNF therapy is a viable alternative for the treatment of RA in patients with HIV, who do not respond to conventional anti-rheumatic therapies. The relationship between TNF-α and HIV infection, as well as cautionary guidelines regarding the utilization of anti-TNF therapy in this clinical population, is discussed.

Synthesis and antiproliferative activity of pterostilbene and 3'-methoxy pterostilbene Mannich base derivatives against Hela cells.

Fourteen novel pterostilbene (1) and [Formula: see text]-methoxy pterostilbene (2) Mannich base derivatives (3-16) were synthesized via the microwave-assisted Mannich reaction of 1 or 2 with various secondary amines and formaldehyde. The regioselectivity of the reaction occurred preferentially at [Formula: see text] position of the B-ring of stilbene. The biological testing results showed that all the target compounds exhibit antiproliferative activity against Hela cells from [Formula: see text]-[Formula: see text]. Compounds 1-3, 7, 11-13, and 16 displayed higher (lower [Formula: see text] values) activity than the positive control cisplatin [Formula: see text].

In vivo self-bio-imaging of tumors through in situ biosynthesized fluorescent gold nanoclusters.

Fluorescence imaging in vivo allows non-invasive tumor diagnostic thus permitting a direct monitoring of cancer therapies progresses. It is established herein that fluorescent gold nanoclusters are spontaneously biosynthesized by cancerous cell (i.e., HepG2, human hepatocarcinoma cell line; K562, leukemia cell line) incubated with micromolar chloroauric acid solutions, a biocompatible molecular Au(III) species. Gold nanoparticles form by Au(III) reduction inside cells cytoplasms and ultimately concentrate around their nucleoli, thus affording precise cell imaging. Importantly, this does not occur in non-cancerous cells, as evidenced with human embryo liver cells (L02) used as controls. This dichotomy is exploited for a new strategy for in vivo self-bio-imaging of tumors. Subcutaneous injections of millimolar chloroauric acid solution near xenograft tumors of the nude mouse model of hepatocellular carcinoma or chronic myeloid leukemia led to efficient biosynthesis of fluorescent gold nanoclusters without significant dissemination to the surrounding normal tissues, hence allowing specific fluorescent self-bio-marking of the tumors.

[Coexpression of hepatitis B virus X gene and hepatitis C virus C gene in HepG2 cells and its effect on the expression of VEGF].

OBJECTIVE: To establish an experimental model of HCV C-HBV X co-expression protein and explore its effect on the expression of VEGF. METHODS: The HBV X gene was recovered by enzyme excision and inserted into PBK-CMV and PBK-HCVC, and recombinant plasmids PBK-X and PBK-X-C were constructed. The plasmids PBK-CMV, PBK-X, PBK-HCVC and PBK-X-C were transfected into HepG2 cells with liposomes. After being selected by G418, resistant colonies were obtained. Reverse transcription PCR and Western blot were used to show HBV X and HCV core protein expression. VEGF was analyzed using immunohistochemical methods and Western blot. RESULTS: The recombinant plasmid PBK-X-C expressed HBV X and HCV core protein efficiently under the control of the vectors promoter. VEGF and VEGF mRNA of the cells co-expressing HCV C-HBV X proteins were higher than those cells expressing HBV X, HCV C and vector alone. CONCLUSION: HBV X-HCV C co-expression protein can increase the expression of VEGF of HepG2 cells. It suggests that HBV and HCV have a synergic action in the carcinogenesis.

[The role of mitochondrial damages in Helicobacter pylori-induced apoptosis of gastric cancer cells].

OBJECTIVE: To explain the role of mitochondrial pathway in the apoptosis of SGC-7901 cell line induced by concentrated Helicobacter pylori culture supernatant (CHCS). METHODS: Cytochrome oxidase (COX) I expression was detected by Western blotting. Cell apoptosis and mitochondrial membrane potential were measured by flow cytometry. RESULTS: CHCS could induce the apoptosis of SGC-7901 in a dose- and time-dependent manner. Apoptotic rates gradually enhanced followed by the concentrations increasing. The mitochondrial membrane potential (MMP) began to descend after treating CHCS for 4 h, and MMP descended most distinctly in 8 h. It descended the lowest point in 12 h, and it had no special changes in 24 h. The expression of COX I was notably lower than that of control group after CHCS treating (632.8 +/- 40.6 vs 895.1 +/- 44.2, P < 0.05). CONCLUSION: Mitochondrial pathway may play an important role in the apoptosis of SGC-7901 cells induced by CHCS.