A portable and user-friendly method using personal glucose meters for on-site quantitative detection of organophosphorus pesticide (OP) was developed. The inhibition of organophosphorus compounds on ...acetylcholinesterase (AChE) leads to reduced yields of thiocholine formed by the enzymatic hydrolysis of acetylthiocholine chloride. Ferricyanide (Fe(CN)63-), the mediator used in glucose test strips for electron transfer to the electrode, can be rapidly reduced to ferrocyanide (Fe(CN)64-) by thiocholine. This reaction enables direct measurement of thiocholine by personal glucose meters in the same way as measuring the glucose in blood, offering an interesting choice to quantify OP. After incubation of AChE for 30 min and enzymatic reaction of 10 min, the yield of thiocholine was measured by a personal glucose meter, achieving detection limit of 5 μg L−1 for paraoxon. The proposed method was successfully applied to the detection in apples and cucumbers, presenting promising potential for on-site OP detection in food samples.
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•.Reduction of Fe(CN)63- in glucose meter strip to Fe(CN)64- through thiocholine.•.Detection of thiocholine in the same way as detection of glucose in blood.•.Converting chemical signals into readable results by widely available glucose meters.•.On-site determinations of organophosphorus pesticide by a pocket-size device.•.Low-cost and user-friendly method for detection in food samples.
Immunotherapy, a burgeoning field differs from traditional cancer treatments, is revolutionizing oncologic therapeutics. It aims to stimulate the innate and adaptive immune system of a patient to ...fight against tumor cells. However, low response rate and immune-related adverse effects (irAEs) remain problems during its management. A novel technology using nanomaterials may bring a solution. Various nanoparticles have been investigated as delivery systems to augment cancer therapeutic efficacy in the lab and clinic. In this review, we briefly summarize the connotation of immunotherapy, the application of nanotechnology in cancer, especially focusing on the synergistic effect of nanoplatform-based technology combined with cancer immunotherapy, hoping to make readers a deep insight into this interdisciplinary field.
The therapeutic potential of adult neural stem cells (NSCs)-derived from bone marrow (BM) has been recently described in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple ...sclerosis; however, the beneficial effects are modest due to their marginal anti-inflammatory capacity. To overcome this weakness and endow BM-NSC therapy with profound anti-inflammatory capacity, in this study we pretreated EAE mice with osthole, a natural coumarin with a broad spectrum of pharmacological activities, including anti-inflammation, immunomodulation, and neuroprotection, before NSC-application and continued throughout the study. We found that osthole conferred a potent anti-inflammatory capacity to this BM-NSC therapy, thus more profoundly suppressing ongoing EA and exhibiting significant advantages over conventional NSC-therapy as follows: 1) Enhanced anti-inflammatory effect, thus improving survival environment for engrafted BM-NSCs and protecting myelin sheaths from further demyelination; 2) Drove transplanted (exogenous) BM-NSCs to differentiate into more oligodendrocytes and neurons but inhibited differentiation into astrocytes, thus promoting remyelination and axonal growth, and reducing astrogliosis; and 3) augmented CNS neurotrophic support thus promoted resident (endogenous) repair of myelin/axonal damage. These effects make the BM-NSCs–based therapy a more promising approach to enhance remyelination and neuronal repopulation, thus more effectively promoting anatomic and functional recovery from neurological deficits.
Integrating chemodynamic therapy (CDT) and photodynamic therapy (PDT) into one nanoplatform can produce much more reactive oxygen species (ROS) for tumor therapy. Nevertheless, it is still a great ...challenge to selectively generate sufficient ROS in tumor regions. Meanwhile, CDT and PDT are restricted by insufficient H2O2 content in the tumor as well as by the limited tumor tissue penetration of the light source. In this study, a smart pH/ROS-responsive nanoplatform, Fe2+@UCM-BBD, is rationally designed for tumor combination therapy. The acidic microenvironment can induce the pH-responsive release of doxorubicin (DOX), which can induce tumor apoptosis through DNA damage. Beyond that, DOX can promote the production of H2O2, providing sufficient materials for CDT. Of note, upconversion nanoparticles at the core can convert the 980 nm light to red and green light, which are used to activate Ce6 to produce singlet oxygen (1O2) and achieve upconversion luminescence imaging, respectively. Then, the ROS-responsive linker bis-(alkylthio)alkene is cleaved by 1O2, resulting in the release of Fenton reagent (Fe2+) to realize CDT. Taken together, Fe2+@UCM-BBD exhibits on-demand therapeutic reagent release capability, excellent biocompatibility, and remarkable tumor inhibition ability via synergistic chemo/photodynamic/chemodynamic combination therapy.
It is believed that neuronal death caused by abnormal deposition of amyloid-beta peptide is the major cause of the cognitive decline in Alzheimer’s disease. Adult neurogenesis plays a key role in the ...rescue of impaired neurons and amelioration of cognitive impairment. In the present study, we demonstrated that osthole, a natural coumarin derivative, was capable of promoting neuronal stem cell (NSC) survival and inducing NSC proliferation in vitro. In osthole-treated APP/PS1 transgenic mice, a significant improvement in learning and memory function was seen, which was associated with a significant increase in the number of new neurons (Ki67+/NF-M+) and a decrease in apoptotic cells in the hippocampal region of the brain. These observations suggested that osthole promoted NSC proliferation, supported neurogenesis, and thus efficiently rescued impaired neurons in the hippocampus and ameliorated cognitive impairment. We also found that osthole treatment activated the Notch pathway and upregulated the expression of self-renewal genes Notch 1 and Hes 1 mRNA in NSCs. However, when Notch activity was blocked by the γ-secretase inhibitor DAPT, the augmentation of Notch 1 and Hes 1 protein was ameliorated, and the proliferation-inducing effect of osthole was abolished, suggesting that the effects of osthole are at least in part mediated by activation of the Notch pathway.
Alzheimer's disease (AD), a neurodegenerative disease, is characterized by memory loss and synaptic damage. Up to now, there are limited drugs to cure or delay the state of this illness. Recently, ...the Fyn tyrosine kinase is implicated in AD pathology triggered by synaptic damage. Thus, Fyn inhibition may prevent or delay the AD progression. Therefore, in this paper, we investigated whether Panaxadiol could decrease synaptic damage in AD and the underlying mechanism.
The ability of learning and memory of mice has detected by Morris Water Maze. The pathological changes detected by H&E staining and Nissl staining. The percentage of cell apoptosis and the calcium concentration were detected by Flow Cytometry in vitro. The amount of synaptic protein and related proteins in the Fyn/GluN2B/CaMKIIα signaling pathway were detected by Western Blot.
In the present article, Panaxadiol could significantly improve the ability of learning and memory of mice and reduce its synaptic dysfunction. Panaxadiol could down-regulate GluN2B's phosphorylation level by inhibition Fyn kinase activity, Subsequently, decrease Ca2+-mediated synaptic damage, reducing LDH leakage, inhibiting apoptosis in AD, resulting in facilitating the cells survival. For the underlying molecular mechanism, we used PP2 to block the Fyn/GluN2B/CaMKIIα signaling pathway. The results from WB showed that the expression of related proteins in the Fyn signaling pathway decreased with PP2 treated.
Our results indicate that Panaxadiol could decrease synaptic damage, which will cause AD via inhibition of the Fyn/GluN2B/CaMKIIα signaling pathway. Thus, the Panaxadiol is a best promising candidate to test as a potential therapy for AD.
As DC motor servo systems are more and more widely applied in the manufacturing industry and aerospace domain, the requirements on control performance are increased by the complicated various working ...environments. With regard to the uncertainties including modeling error, parameter variations and external disturbances in DC motor servo system, one Nonlinear Extended Disturbance Observer (NESO) is constructed, and its output will be used as the design reference of disturbance compensation term in control system. Based on the as-built NESO in inner loop, one outer-loop compound controller by means of state-space design method is proposed in order to realize the high-precision position tracking ability of the servo system. Computer simulation results show that compared with conventional control schemes, the proposed control scheme can guarantee fewer tracking errors of DC motor servo system. Moreover, it possesses stronger robustness against system uncertainties including modeling error, parameter variations and friction moment disturbance.
In this study, we aimed to improve understanding of the clinical manifestations, laboratory findings, and risk factors of
Clostridium perfringens
sepsis in patients with acute leukemia and to analyze ...treatment strategies for improving prognosis. We analyzed clinical manifestations, laboratory data, diagnosis, and treatment strategies in three cases of
C. perfringens
sepsis in patients with acute leukemia. We also reviewed and analyzed the relevant literature, incorporating our findings into the discussion. All three patients developed septic shock with neutropenia following chemotherapy. Analysis of blood samples confirmed the presence of
C. perfringens
, and two patients had fulminant intravascular hemolysis and developed multiple organ dysfunction syndrome. Two patients survived and one died despite timely and full-dose antibacterial treatments, blood purification, and noninvasive positive pressure ventilation. Overall, our findings showed that
C. perfringens
sepsis is rare in patients with acute leukemia but progresses rapidly. A high mortality rate was observed, and patients often experienced refractory shock and intravascular hemolysis. This demonstrates the importance of early detection and diagnosis. Multimodal treatments, including fluid resuscitation, antibiotics, organ support, and blood purification, are essential for success.
Natural biologically active substances have received continuous attention for the potentially beneficial health properties against chronic diseases. In this study, bacteriostatic active substance ...from
Camellia oleifera
meal, which is a major by-product of the
Camellia
oil processing industry, were extracted with continuous phase change extraction (CPCE) method and separated by HSCCC. Compared with traditional extraction methods, CPCE possessed higher extraction efficiency. Two main substances were separated and purified (above 90.0%). The structure of them were further identified by UV, LC–ESI–MS–MS, 1H-NMR, and 13C-NMR as flavonoids F2 kaempferol 3-
O
-β-
d
-glucopyranosyl-(1 → 2)-α-
l
-rhamnopyranosyl-(1 → 6)-β-
d
-glucopyranoside and J2 kaempferol 3-
O
-β-
d
-xylopyranosyl-(1 → 2)-α-
l
-rhamnopyranosyl-(1 → 6)-β-
d
-glucopyranoside for the first time in
C. Oleifera
meal. The results of antibacterial activity measurement showed that both compounds have excellent antibacterial activity. And the antibacterial stability of F2 were finally confirmed: F2 showed broad spectrum antibacterial activity against
Escherichia coli
,
Staphylococcus aureus
,
Salmonella enteriditis
,
Bacillus thuringiensis
,
Aspergillus niger
and
Rhizopus nigricans
. Besides, F2 exhibited relatively high stable property even at high temperature, acid and metal ion solutions. The findings of this work suggest the possibility of employing
C. oleifera
meal as an attractive source of health-promoting compounds, and at the same time facilitate its high-value reuse and reduction of environmental burden.
With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies, cancer immunotherapy has undergone a profound transformation over the past decades. Recently, ...therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens, including tumor-associated antigens and tumor-specific antigens. The objective was to amplify and diversify the intrinsic repertoire of tumor-specific T cells. However, the complete realization of these capabilities remains an ongoing pursuit. Therefore, we provide an overview of the current landscape of cancer vaccines in this review. The range of antigen selection, antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine design. Furthermore, this review addresses the current status of clinical trials and discusses their strategies, focusing on tumor-specific immunogenicity and anti-tumor efficacy assessment. However, current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges, including tumor immune microenvironment suppression, optimal candidate identification, immune response evaluation, and vaccine manufacturing acceleration. Therefore, the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.
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