Low dose triptolide reverses chemoresistance in adult acute lymphoblastic leukemia cells via reactive oxygen species generation and DNA damage response disruption

Chemoresistance represents a major challenge for treatment of acute lymphoblastic leukemia (ALL). Thus, new drugs to overcome chemoresistance in ALL are urgently needed. To this end, we established a cytarabine (araC)-resistant ALL cell line (NALM-6/R), which interestingly displayed cross-resistance towards doxorubicin (ADM). Here we report that low dose of triptolide (TPL), a natural product used for treating inflammatory diseases such as arthritis, could reverse araC and ADM resistance and in NALM-6/R cells as well as primary cells from patients with relapsed or refractory (R/R) ALL, reflected by inhibition of cell proliferation and induction of apoptosis in vitro, and repression of tumor growth in vivo in a mouse xenograft model. Mechanistically, these events were associated with impaired mitochondrial membrane potential and increased reactive oxygen species (ROS) production. Co-treatment with TPL and araC or ADM upregulated pro-apoptotic caspase-9 protein, inhibited checkpoint kinase 1 (Chk1) and 2 (Chk2) phosphorylation, and induced γH2A.X (a DNA damage marker). Notably, the combination regimen of TPL and conventional chemotherapeutics also rapidly diminished tumor burden in a patient with R/R ALL. Together, these findings provide preclinical evidence for repurposing use of TPL in combination with chemotherapeutic agents to treat R/R ALL as an alternative salvage regimen

A Reliability-Based Network Equilibrium Model with Electric Vehicles and Gasoline Vehicles

With the popularity of electric vehicles, they have become an indispensable part of traffic flow on the road network. This paper presents a reliability-based network equilibrium model to realise the traffic flow pattern prediction on the road network with electric vehicles and gasoline vehicles, which incorporates travel time reliability, electric vehicles’ driving range and recharge requirement. The mathematical expression of reliable path travel time is derived, and the reliability-based network equilibrium model is formulated as a variational inequality problem. Then a multi-criterion labelling algorithm is proposed to solve the reliable shortest path problem, and a column-generation-based method of the successive average algorithm is proposed to solve the reliability-based network equilibrium model. The applicability and efficiency of the proposed model and algorithm are verified on the Nguyen-Dupuis network and the real road network of Sioux Falls City. The proposed model and algorithm can be extended to other road networks and help traffic managers analyse traffic conditions and make sustainable traffic policies

N′-(4-Hy­droxy­benzyl­idene)ferrocene-1-carbohydrazide

In the title compound, [Fe(C5H5)2(C13H11N2O2)], the dihedral angle between the benzene ring and the cyclo­penta­diene ring bonded to the carbonyl group is 26.1 (2)°. In the crystal, bifurcated O—H⋯(O,N) and N—H⋯O hydrogen bonds link the mol­ecules into a three-dimensional network

The effects of three different grinding methods in DNA extraction of cowpea (Vigna unguiculata L. Walp)

Rapid DNA extraction is a prerequisite for molecular studies. Generally, plant tissue is ground in liquid nitrogen to isolate DNA; but, liquid nitrogen is dangerous and volatile. Besides, liquid nitrogen is not always available in many developing countries. To investigate if high quality DNA could be obtained for downstream PCR analysis without liquid nitrogen, the cowpea DNA was extracted by Hexadecyl trimethyl ammonium bromide cetyl trimethylammonium bromide (CTAB) method and sodium dodecyl sulphate (SDS) method, respectively, each with three different grinding methods, including ground in liquid nitrogen, in preheated mortar and in non-preheated mortar. The DNA was compared according to their yield, purity, integrity and functionality. The results showed that high quality DNA could be obtained by three grinding methods both in CTAB method and SDS method. Without liquid nitrogen, grinding plant tissue in preheated or non-preheated mortar with extraction buffer to extract DNA is feasible.Keywords: Cowpea (Vigna unguiculata), grinding method, liquid nitrogen, DNA extractionAfrican Journal of Biotechnology Vol. 12(16), pp. 1946-195

5-(4-Methyl­phen­yl)-1,3,4-oxadiazol-2-amine

In the crystal structure of the title compound, C9H9N3O, adjacent mol­ecules are linked through N—H⋯N hydrogen bonds into a three-dimensional network

Improved meet-in-the-middle attack on reduced-round Kiasu-BC algorithm

Kiasu-BC algorithm is an internal tweakable block cipher of authenticated encryption algorithm Kiasu as one of first-round candidates in the CAESAR competition.The precomputation complexity is reduced by utilizing the freedom of the tweak and the internal key restriction through the research on structural characteristics of Kiasu-BC algorithm based on AES-128 round function.Combined with the differential enumeration technique, a new 5-round meet-in-the-middle distinguisher was constructed to improve the meet-in-the-middle attack on 8-round Kiasu-BC algorithm.The improved attack requires the time complexity of 2114, the memory complexity of 263 and the data complexity of 2108

Interference between distinguishable photons

Two-photon interference (TPI) lies at the heart of photonic quantum technologies. TPI is generally regarded as quantum interference stemming from the indistinguishability of identical photons, hence a common intuition prevails that TPI would disappear if photons are distinguishable. Here we disprove this perspective and uncover the essence of TPI. We report the first demonstration of TPI between distinguishable photons with their frequency separation up to $10^4$ times larger than their linewidths. We perform time-resolved TPI between an independent laser and single photons with ultralong coherence time ($>10\ \mu$s). We observe a maximum TPI visibility of $72\%\pm 2\%$ well above the $50\%$ classical limit indicating the quantum feature, and simultaneously a broad visibility background and a classical beat visibility of less than $50\%$ reflecting the classical feature. These visibilities are independent of the photon frequency separation and show no difference between distinguishable and indistinguishable photons. Based on a general wave superposition model, we derive the cross-correlation functions which fully reproduce and explain the experiments. Our results reveal that TPI as the fourth-order interference arises from the second-order interference of two photons within the mutual coherence time and TPI is not linked to the photon indistinguishability. This work provides new insights into the nature of TPI with great implications in both quantum optics and photonic quantum technologies.Comment: 7 pages, 5 figures. Comments are welcome. arXiv admin note: substantial text overlap with arXiv:2404.0515

Verification of functional and non-functional requirements of web service composition

Abstract. Web services have emerged as an important technology nowadays. There are two kinds of requirements that are crucial to web service composition, which are functional and non-functional requirements. Functional requirements focus on functionality of the composed service, e.g., given a booking service, an example of functional requirements is that a flight ticket with price higher than $2000 will never be purchased. Non-functional requirements are concerned with the quality of service (QoS), e.g., an example of the booking service’s non-functional requirements is that the service will respond to the user within 5 sec-onds. Non-functional requirements are important to web service composition, and are often an important clause in service-level agreements (SLAs). Even though the functional requirements are satisfied, a slow or unreliable service may still not be adopted. In our paper, we propose an automated approach to verify combined functional and non-functional requirements directly based on the semantics of web service composition. Our approach has been implemented and evaluated on the real-world case studies, which demonstrate the effectiveness of our method.

Fluoxetine improves behavioural deficits induced by chronic alcohol treatment by alleviating RNA editing of 5-HT2C receptors

The alcoholism and major depressive disorder are common comorbidity, with alcohol-induced depressive symptoms being eased by selective serotonin re-uptake inhibitors (SSRIs), although the mechanisms underlying pathology and therapy are poorly understood. Chronic alcohol consumption affects the activity of serotonin 2C receptors (5-HT2CR) by regulating adenosine deaminases acting on RNA (ADARs) in neurons. Astrogliopathic changes contribute to alcohol addiction, while decreased release of ATP from astrocytes can trigger depressive-like behaviours in mice. In this study, we discovered that chronic alcohol treatment increased editing of RNA of 5-HT2CR via up-regulating the expression of ADAR2, consequently reducing the release of ATP from astrocytes induced by 5-HT2CR agonist, MK212. Moreover, SSRI antidepressant fluoxetine decreased the expression of ADAR2 through the transactivation of EGFR/PI3K/AKT/cFos signalling pathway. The increased release of astroglial ATP by MK212 which was suppressed by chronic alcohol consumption, and reduction in ADAR2 activity eliminated the RNA editing of 5-HT2CR increased by alcohol in vitro and recovered the release of ATP from astrocytes induced by MK212. Meanwhile, fluoxetine improved the behavioural and motor symptoms induced by alcohol addiction and decreased the alcohol intake. Our study suggests that the astrocytic 5-HT2CR contribute to alcohol addiction; fluoxetine thus can be used to alleviate depression, treat alcohol addiction and improve motor coordination