Biocompatibility of synthetic nanomaterials and their applications in gene delivery

Nanomedicine is the use of nanoscale or nanostructured materials in medicine that due to their structure have unique medical effects. Prominent applications of nanomedicine are the use of nanomaterials for the delivery of drugs and nucleic acids (to correct gene defects). Nanomaterials offer several attractive features as delivery vehicles: First, their size in the nano-regime endows them with more desirable pharmacokinetic and biodistribution profiles in vivo. Second, they are amenable to diverse chemical engineering that enables loading of a wide range of substances. Third, they can protect therapeutic agents from premature degradation or from inducing undesired side effects. In this thesis, two types of synthetic nanomaterials, namely silica and polythiophene, were investigated for their biocompatibility and applications in gene delivery. In Paper I, human red blood cell hemolysis and premyelocytic leukemia HL-60 cell cytotoxicity induced by silica nanoparticles with distinct physicochemical properties were studied, suggesting that silica nanoparticles potentially induce membrane permeability through a universal mechanism of action. Moreover, plasma protected against silica nanoparticle-induced membrane damage primarily by shielding the surface of silica particles. In Paper II, the cytotoxicity and oxidative stress induced by amorphous silica nanoparticles were compared to nanoparticles with similar size but different chemical compositions. Overexpression of the liver phase II enzyme microsomal glutathione transferase 1 (MGST1) in human breast carcinoma MCF-7 cells reversed the cytotoxicity and oxidative stress induced by some silica nanoparticles but did not protect against the cytotoxic effects induced by zinc oxide nanoparticles. In Paper III, amino-functionalized silica nanoparticles were used to deliver plasmid DNA (pDNA) into human breast carcinoma MCF-7 cells, with the nonporous particles delivering pDNA at higher efficiency than their mesoporous counterparts (with 2.4 nm pore diameter). In Paper IV, polythiophene nanoparticles were used as vectors to deliver small interference RNA (siRNA) into human osteosarcoma U2-OS cells and human cervical carcinoma HeLa cells. The cationic polythiophenes were considerably more efficient delivery vectors than their zwitteronic counterparts. In conclusion, studies to improve the understanding of the biocompatibility and delivery efficiency of nanomaterials, are crucial to assist the rationale design of nanomaterials for delivery applications

Experimental Study on Chinese Athletes’ Physical Distribution in Sanda Competition

Reasonable distribution of physical strength plays a very important role in adversary Sanda competition. According to the physical characteristics of Sanda athletes, this paper studied the physical distribution during Sanda competition. The results are as follows: a) If an athlete’s opponent is physically stronger, then he is not supposed to be recklessly but to take defense-oriented strategies. The athlete has to avoid the opponent’s heavy blow and seize the opportunity to accurately counterattack. b) If his physical strength is equal with the opponent’s, the athlete is supposed to maintain self-physical strength, and try to consume opponent physically. c) If the athlete is physically stronger, then he should actively attack, but not rampage. Two specific tactics are proposed: i) try to consume the opponent’s strength if the opponent is very easily excited or impetuous; ii) try to use defensive strategies if the opponent less attack

Self-Presentation on the Web: Agencies Serving Abused and Assaulted Women

Objectives. We examined the content and usability of the Web sites of agencies serving women victims of violence. Methods. We entered the names of a systematic 10% sample of 3774 agencies listed in 2 national directories into a search engine. We took (in April 2012) and analyzed screenshots of the 261 resulting home pages and the readability of 193 home and first-level pages. Results. Victims (94%) and donors (68%) were the primary intended audiences. About one half used social media and one third provided cues to action. Almost all (96.4%) of the Web pages were rated “fairly difficult” to “very confusing” to read, and 81.4% required more than a ninth-grade education to understand. Conclusions. The service and marketing functions were met fairly well by the agency home pages, but usability (particularly readability and offer of a mobile version) and efforts to increase user safety could be improved. Internet technologies are an essential platform for public health. They are particularly useful for reaching people with stigmatized health conditions because of the anonymity allowed. The one third of agencies that lack a Web site will not reach the substantial portion of the population that uses the Internet to find health information and other resources

Preparation, structural and magnetic characterization of trinuclear and one-dimensional cyanide-bridged Co(III)-Cu(II) complexes

341-345By employing two trans-dicyanocobolt(III) building blocks K[Co(bpb)(CN)2] (bpb2- = 1,2-bis(pyridine-2-carboxamido)benzenate), K[Co(bpmb)(CN)2] (bpmb2- = 1,2-bis(pyridine-2-carboxamido)-4-methyl-benzenate) and one 14-membered macrocycle Cu(II) compound as assembling segment, two cyanide-bridged CoIII-CuII complexes {{[Cu(cyclam)][Co(bpb)(CN)2]}ClO4}n·nCH3OH·nH2O (1) and {[Cu(cyclam)][Co(bpmb)(CN)2]2}·4H2O (2) (cyclam = 1,4,8,11-tetraazacyclotetradecane) have been successfully prepared and characterized by elemental analysis, IR spectroscopy and X-ray structure determination. Single X-ray diffraction analysis shows that complex 1 can be structurally characterized as one-dimensional cationic single chain consisting of alternating units of [Cu(cyclam)]2+ and [Co(bpb)(CN)2]- with free ClO4- as balanced anion, while complex 2 presents cyanide-bridged neutral trinuclear bimetallic structure containing Co2Cu core, giving clear information that the substitute group on the cyanide precursor has obvious influence on the structure type of the target compound. Investigation over magnetic properties of complex 1 reveals the weak antiferromagnetic coupling between the neighboring Cu(II) ions through the diamagnetic cyanide building block

DFlow: Efficient Dataflow-based Invocation Workflow Execution for Function-as-a-Service

The Serverless Computing is becoming increasingly popular due to its ease of use and fine-grained billing. These features make it appealing for stateful application or serverless workflow. However, current serverless workflow systems utilize a controlflow-based invocation pattern to invoke functions. In this execution pattern, the function invocation depends on the state of the function. A function can only begin executing once all its precursor functions have completed. As a result, this pattern may potentially lead to longer end-to-end execution time. We design and implement the DFlow, a novel dataflow-based serverless workflow system that achieves high performance for serverless workflow. DFlow introduces a distributed scheduler (DScheduler) by using the dataflow-based invocation pattern to invoke functions. In this pattern, the function invocation depends on the data dependency between functions. The function can start to execute even its precursor functions are still running. DFlow further features a distributed store (DStore) that utilizes effective fine-grained optimization techniques to eliminate function interaction, thereby enabling efficient data exchange. With the support of DScheduler and DStore, DFlow can achieving an average improvement of 60% over CFlow, 40% over FaaSFlow, 25% over FaasFlowRedis, and 40% over KNIX on 99%-ile latency respectively. Further, it can improve network bandwidth utilization by 2x-4x over CFlow and 1.5x-3x over FaaSFlow, FaaSFlowRedis and KNIX, respectively. DFlow effectively reduces the cold startup latency, achieving an average improvement of 5.6x over CFlow and 1.1x over FaaSFlowComment: 22 pages, 13 figure

The impact of farm household tourism operations on poverty reduction and conservation under the control policies of China’s protected areas

Against the global trend of increasing multiple participants involvement in protected areas management, the Chinese government has implemented a series of stricter policies since 2015. Tourism is an important alternative livelihood for farmers near protected areas. Based on survey data from 1,028 households in six protected areas, this study uses the propensity score matching (PSM) method to empirically examine the change effects of poverty reduction and conservation of farmers engaged in tourism under the influence of protected areas tourism management policies. The PSM method reduces sample self-selection bias and improves the accuracy of research conclusions. The findings reveal that irrespective of whether the areas are subjected to regulatory policies or not, tourism operations are significantly and inversely correlated with households’ multidimensional poverty index, and are notably positively correlated with their comprehensive conservation index. Consequently, tourism operations exhibit substantial poverty alleviation and protective effects. However, the current suite of protected areas control policies has curtailed the sustainable growth of tourism within these areas, resulting in 9.64% decrease in poverty alleviation effects and 10.33% decrease in protective effects derived from tourism operations. Despite their restrictive impacts on tourism, these policies have yielded some positive outcomes, fostering social equity within protected areas and catalyzing the transition from traditional livelihoods. Drawing upon these empirical findings, this study proposes recommendations and directions for fine-tuning China’s existing regulatory policies pertaining to tourism in protected areas

Case report: Mononeuropathy multiplex of extranodal natural killer/T-cell lymphoma misdiagnosed as systemic vasculitis

BackgroundExtranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract.Case presentationWe encountered an ENKTL patient who presented with purpura-like rashes and foot drops as initial symptoms and later developed other peripheral nerve involvement. The nerve conduction study of both the motor nerve and the sensory nerve showed axonal damage resembling mononeuropathy multiplex. Although the initial response to steroids was encouraging, the patient's symptoms reappeared and aggravated. A biopsy of the abdominal subcutaneous fat tissue with additional immunohistochemistry revealed neoplastic NK/T lymphocytes.ConclusionWe reported the first case presented as mononeuropathy multiplex as the initial clinical manifestation in ENKTL patients. Lymphoma should be considered in the diagnosis of atypical mononeuropathy in multiplex patients

BAM15 as a mitochondrial uncoupler: a promising therapeutic agent for diverse diseases

Subcellular organelles dysfunction is implicated in various diseases, including metabolic diseases, neurodegenerative diseases, cancer, and cardiovascular diseases. BAM15, a selective mitochondrial uncoupler, has emerged as a promising therapeutic agent due to its ability to enhance mitochondrial respiration and metabolic flexibility. By disrupting the coupling between electron transport and ATP synthesis, BAM15 dissipates the proton gradient, leading to increased mitochondrial respiration and energy expenditure. This review provides a comprehensive overview of BAM15, including its mechanism of action and potential therapeutic applications in diverse disease contexts. BAM15 has shown promise in obesity by increasing energy expenditure and reducing fat accumulation. In diabetes, it improves glycemic control and reverses insulin resistance. Additionally, BAM15 has potential in non-alcoholic fatty liver disease, sepsis, and cardiovascular diseases by mitigating oxidative stress, modulating inflammatory responses, and promoting cardioprotection. The safety profile of BAM15 is encouraging, with minimal adverse effects and remarkable tolerability. However, challenges such as its high lipophilicity and the need for alternative delivery methods need to be addressed. Further research is necessary to fully understand the therapeutic potential of BAM15 and optimize its application in clinical settings