Review on the application of upconversion nanomaterials in heavy metal detection

As a widespread element,heavy metals have a significant impact on human health and threaten human health.It is of great significance to develop analytical technologies that can detect heavy metal ions quickly and accurately.In comparison to conventional fluorescent materials such as organic dyes,quantum dot(QD)labels,and carbon quantum dots(CD),fluorescence detection technology utilizing lanthanide(Ln)ion-doped upconversion nanoparticles(UCNPs)stands out due to its distinctive attributes.These include a notably reduced autofluorescence background,enhanced tissue penetration capabilities,biocompatibility with cellular tissues,and minimal photodamage inflicted on biological samples.The utilization of this technology has garnered considerable attention across multiple fields.In the domain of heavy metal detection,traditional laboratory methods necessitate costly instrumentation and a fully equipped laboratory,involving intricate sample processing procedures and protracted detection periods,as well as a demand for skilled personnel.In contrast,the implementation of this material offers rapid and cost-effective detection,significantly mitigating the technical barriers for operators.Consequently,this represents an exceptional avenue to curtail expenses and broaden the scope of detection within the analytical process.This paper reviews the research progress of UCNPs in the detection of heavy metal ions,encompassing a brief elucidation of the luminescence principle of upconversion nanomaterials and commonly used detection principles.Additionally,it provides a detailed overview of the research status of several common non-metal ions and essential heavy metals.Furthermore,it summarizes the current focal points in UCNP detection and discusses the challenges and prospects associated with it.

TREATMENT OF 119 CASES OF VERRUCAVULGARIS AND VERRUCA PLANA BY EXTERNALAPPLICATION OF PULVIS PEPPER ALBA

Both verruca vulgaris and verrucaplana are commonly encountered in clinic.We treated 119 cases of the disease by exter-nal application of Pulvis Pepper Alba withsatisfactory results. A brief summary of thetreatment is given as follows.

Intelligent diagnosis of atrial septal defect in children using echocardiography with deep learning

Background Atrial septal defect(ASD)is one of the most common congenital heart diseases.The diagnosis of ASD via transthoracic echocardiography is subjective and time-consuming.Methods The objective of this study was to evaluate the feasibility and accuracy of automatic detection of ASD in children based on color Doppler echocardiographic static images using end-to-end convolutional neural networks.The proposed depthwise separable convolution model identifies ASDs with static color Doppler images in a standard view.Among the standard views,we selected two echocardiographic views,i.e.,the subcostal sagittal view of the atrium septum and the low parasternal four-chamber view.The developed ASD detection system was validated using a training set consisting of 396 echocardiographic images corresponding to 198 cases.Additionally,an independent test dataset of 112 images corresponding to 56 cases was used,including 101 cases with ASDs and 153 cases with normal hearts.Results The average area under the receiver operating characteristic curve,recall,precision,specificity,F1-score,and accuracy of the proposed ASD detection model were 91.99,80.00,82.22,87.50,79.57,and 83.04,respectively.Conclusions The proposed model can accurately and automatically identify ASD,providing a strong foundation for the intelligent diagnosis of congenital heart diseases.

Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency

Objective Melittin and its derivatives have been characterized to establish effective gene delivery systems.Their capability of facilitating endosomal release enhances the nanoparticles-based gene delivery.Nevertheless,little investigation has been conducted to explore its potential application in the context of viral vectors.Methods Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus vectors.These vectors carrying either gfp or fluc genes were subjected to qPCR assays and transduction assays of HEK293T cells to investigate the efficiency of vector production and gene delivery.In addition,the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice.Finally,the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle.Results A total of 76 melittin-related peptides were compiled from existing literature.Among them,cMA2,Melt13,p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2 vectors.The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV.Mechanistically,bafilomycin A1,a vacuolar endosome acidification inhibitor,completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors.Most importantly,p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 mice.Conclusion The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression.While further modifications remain an area of interest,our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery.

Differential Expression of MicroRNA in Endothelial Cells Incubated with Serum of Hypertension Patients with Blood-Stasis Syndrome

Objective： To screen out blood-stasis syndrome （BSS）-associated microRNA and therefore determine the possible target for treating hypertension. Methods： A high-energy sequencing method and digital gene expression sequencing theory were adopted to sequence microRNA （miRNA） and messenger RNA （mRNA）, and to determine differential expression in human umbilical vein endothelial cells incubated with serum samples from hypertension patients with or without BSS, and healthy controls. The results were confirmed using gene prediction software. Results： A total of 13 miRNAs and 11 mRNAs showed statistical difference both in the BSS/normal groups and BSS/non-BSS groups, respectively. Four pairs of target mRNNmiRNA were identified： FRMD4Nhsa-miR-34a, MAP3K14/hsa-miR-34a, PER1/hsa-miR-34a, and FGF2/hsa-miR-132. Conclusion： Four mRNNmiRNA pairs mentioned above seem to be involved in pathogenesis and maintenance of hypertension with BSS.

Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway

Objective:Physical exercise,a common non-drug intervention,is an important strategy in cancer treatment,including hepatocellular carcinoma(HCC).However,the mechanism remains largely unknown.Due to the importance of hypoxia and cancer stemness in the development of HCC,the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness.Methods:A physical exercise intervention of swimming(30 min/d,5 d/week,for 4 weeks)was administered to BALB/c nude mice bearing subcutaneous human HCC tumor.The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring,hematoxylin and eosin(HE)staining,and immunohistochemistry(IHC)detection of proliferating cell nuclear antigen(PCNA)and Ki67.The expression of stemness transcription factors,including Nanog homeobox(NANOG),octamer-binding transcription factor 4(OCT-4),v-Myc avian myelocytomatosis viral oncogene homolog(C-MYC)and hypoxia-inducible factor-1a(HIF-1a),was detected using real-time reverse transcription polymerase chain reaction.A hypoxia probe was used to explore the intratumoral hypoxia status.Western blot was used to detect the expression of HIF-1a and proteins related to protein kinase B(Akt)/glycogen synthase kinase-3β(GSK-3β)/β-catenin signaling pathway.The IHC analysis of platelet endothelial cell adhesion molecule-1(CD31),and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion.SMMC-7721 cells were treated with nude mice serum.The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors.The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1a.Further,the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected.Results:Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor.HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention.Swimming potently alleviated the intratumoral hypoxia,attenuated the cancer stemness,and inhibited the Akt/GSK-3β/β-catenin signaling pathway.Additionally,the desmin+/CD31+ratio,rather than the number of CD31+vessels,was significantly increased in swimming-treated mice.In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere,as well as the m RNA expression level of stemness transcription factors.Consistent with the in vivo results,HIF-1a and Akt/GSK-3β/β-catenin signaling pathway were also inhibited in cells treated with serum from swimming group.Conclusion:Swimming alleviated hypoxia and attenuated cancer stemness in HCC,through suppression of the Akt/GSK-3β/β-catenin signaling pathway.The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor.