CD133 ligand-enhanced etoposide-liposome complex for targeted killing of lung cancer cells.

Lung cancer has a high incidence rate and a low cure rate, hence the urgent need for effective treatment methods. Current lung cancer drugs have several drawbacks, including low specificity, poor targeting, drug resistance, and irreversible damage to normal tissues. Therefore, there is a need to develop a safe and effective new drug that can target and kill tumor cells. In this study, we combined nanotechnology and biotechnology to develop a CD133 ligand-modified etoposide-liposome complex (Lipo@ETP-CD133) for targeted therapy of lung cancer. The CD133 ligand targeted lung cancer stem cells, causing the composite material to aggregate at the tumor site, where high levels of ETP liposomes could exert a strong tumor-killing effect. Our research results demonstrated that this nano-drug had efficient targeting and tumor-killing effects, indicating its potential for clinical application.

NIMO: A Natural Product-Inspired Molecular Generative Model Based on Conditional Transformer.

Natural products (NPs) have diverse biological activity and significant medicinal value. The structural diversity of NPs is the mainstay of drug discovery. Expanding the chemical space of NPs is an urgent need. Inspired by the concept of fragment-assembled pseudo-natural products, we developed a computational tool called NIMO, which is based on the transformer neural network model. NIMO employs two tailor-made motif extraction methods to map a molecular graph into a semantic motif sequence. All these generated motif sequences are used to train our molecular generative models. Various NIMO models were trained under different task scenarios by recognizing syntactic patterns and structure-property relationships. We further explored the performance of NIMO in structure-guided, activity-oriented, and pocket-based molecule generation tasks. Our results show that NIMO had excellent performance for molecule generation from scratch and structure optimization from a scaffold.

Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer: study protocol for a randomised controlled trial.

BACKGROUND: A single injection of local anaesthetic (LA) in the erector spinae plane block (ESPB) can reduce pain after modified radical mastectomy (MRM) surgery, but the duration of analgesia is affected by the duration of the LA. The aim of this study is to investigate the effect of continuous ESPB on acute and chronic pain and inflammatory response after MRM surgery. METHODS: In this prospective, randomised, controlled trial, we will recruit 160 patients, aged 18-80 years, scheduled for elective MRM surgery under general anaesthesia. They will be randomly assigned to two groups: a continuous ESPB group (group E) and a sham block group (group C). Both groups of patients will have a nerve block (group C pretended to puncture) and an indwelling catheter fixed prior to surgery. Electronic pumps containing LA are shielded. The primary outcome is the total consumption of analgesic agents. The secondary outcomes include the levels of inflammation-related cytokines; the occurrence of chronic pain (post-mastectomy pain syndrome, PMPS); static and dynamic pain scores at 2, 6, 12, 24 and 48 h postoperatively; and post-operative and post-puncture adverse reactions. DISCUSSION: Analgesia after MRM surgery is important and chronic pain can develop when acute pain is prolonged, but the analgesic effect of a nerve block with a single injection of LA is limited by the duration of drug action. The aim of this trial is to investigate whether continuous ESPB can reduce acute pain after MRM surgery and reduce the incidence of chronic pain (PMPS), with fewer postoperative analgesic drug-related complications and less inflammatory response. Continuous ESPB and up to 12 months of follow-up are two innovations of this trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ) ChiCTR2200061935. Registered on 11 July 2022. This trial is a prospective registry with the following registry names: Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer.

Pretreatment of Luzhou distiller's grains for feed protein production using crude enzymes produced by a synthetic microbial consortium.

Chinese distillers' grains (CDGs) have low fermentation efficiency due to the presence of lignocellulosic components, such as rice husk. In this study, a microbial consortium synthesized was used based on the "functional complementarity" principle to produce lignocellulolytic crude enzyme. The crude enzyme was used to hydrolyze CDGs. After enzymatic hydrolysis, lignocellulose was damaged to varying degrees and the crystallinity decreased. Subsequently, the feed protein was produced using yeast through two pathways. The results showed that the crude enzyme produced by the microbial consortium (comprising Trichoderma reesei, Aspergillus niger, and Penicillium) exhibited excellent enzymatic efficiency, yielding 27.88%, 19.64%, and 10.88% of reducing sugar, cellulose, and hemicellulose. The true protein content of CDGs increased by 53.49% and 48.35% through the first and second pathways, respectively. Notably, the second pathway demonstrated higher economic benefits to produce feed protein. This study provides a pathway for high-quality utilization of CDGs.

The efficacy of pericapsular nerve group block for postoperative analgesia in patients undergoing hip surgery: A systematic review and meta-analysis of randomized controlled trials.

Background: As an optional regional anesthesia approach, pericapsular nerve group (PENG) block has been successfully utilized to manage pain for hip surgeries without affecting motor function. The present meta-analysis aimed to verify the efficacy of PENG block for postoperative analgesia in patients undergoing hip surgery. Methods: A total of 497 academic articles were identified after a systematic search in the databases of PubMed, Embase, Web of Science, and Cochrane Library up to 25 August 2022. The primary outcome was postoperative 24-h morphine consumption. Secondary outcomes included the time of the first request for rescue analgesia, static and dynamic pain scores 6 and 24 h after surgery, and incidence of postoperative nausea and vomiting (PONV). We calculated mean differences (MDs) with 95% confidence intervals (CIs) for postoperative 24-h morphine consumption, time of the first request for rescue analgesia, static and dynamic pain scores 6 and 24 h after surgery, and odds ratios (ORs) with 95% CIs for incidence of PONV. The chi-square test was used for heterogeneity analysis, and heterogeneity was assessed by I 2. Statistical analysis was performed using Review Manager 5.4. Results: Numerous electronic databases were searched, and finally, nine studies were identified. There was no significant difference in morphine consumption during the postoperative 24 h [MD: -2.57, 95% CI: (-5.42, 0.27), P = 0.08] and the time of the first request for rescue analgesia [MD: 1.79, 95% CI: (-1.06, 4.64), P = 0.22] between the PENG block and control groups. PENG block did not reveal a significant difference in 6 h [MD: -0.17, 95% CI: (-0.92, 0.57), P = 0.65] [MD: -0.69, 95% CI: (-1.58, 0.21), P = 0.13] and 24 h [MD: -0.25, 95% CI: (-1.54, 1.05), P = 0.71], [MD: 0.05, 95% CI: (-0.84, 0.93), P = 0.91] static and dynamic pain scores compared with other nerve block methods. Moreover, the two groups have a similar risk of PONV (OR: 1.29, 95% CI = 0.53-3.10, P = 0.57). Conclusion: This review shows that PENG block can act as an alternative multimodal analgesia for hip surgery, and compared with the other kinds of nerve block, there was no significant difference in the postoperative analgesic effect of PENG block. Systematic review registration: Supplementary Datasheet 1, identifier: CRD 42022356496.

The effect and safety of dexmedetomidine as an adjuvant to local anesthetics in erector spinae plane block: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dexmedetomidine (DEX) has been thought to be an effective adjuvant to local anesthetics (LAs) in erector spinae plane block (ESPB), however, this method of use is not recorded in the drug instructions. Hence, our meta-analysis will evaluate its efficacy and safety for the first time. METHODS: A systematic search of published articles was conducted in the PubMed, Embase, Web of science, and Cochrane Library databases up to July 17, 2022, using specific keywords related to our aims. The time first to request rescue analgesia, number of patient controlled intravenous analgesia (PCIA) presses, rate of rescue analgesia use, postoperative nausea and vomiting (PONV), arrhythmia, and hypotension were calculated by using random-effect models. This systematic review and meta-analysis was registered with PROSPERO (registration number: CRD42022345488). RESULTS: Numerous electronic databases were searched and finally 8 studies with a total of 570 patients, 303 in the DEX arm, 267 in the control arm were included. As an adjuvant to LAs, DEX significantly increased the time to first request of rescue analgesia (mean difference [MD] = 8.40, 95% confidence interval [CI] = 4.70-12.10, P < 0.00001), reduced the number of PCIA presses (MD = -4.12, 95% CI = -7.79 to -0.45, P = 0.03) and the rate of rescue analgesia (odds ratio [OR] = 0.33, 95% CI = 0.17-0.65, P = 0.002). Moreover, the combination reduced the risk of PONV (OR = 0.57, 95% CI = 0.36-0.91, P = 0.02). In addition, there was no difference in the incidence of hypotension (OR = 1.01, 95% CI = 0.37-2.74, P = 0.99) and arrhythmia (OR = 0.76, 95% CI = 0.19-3.07, P = 0.70). CONCLUSION: DEX can reduce analgesic requirements after various surgical procedures when used as an adjuvant to LAs for ESPB. Moreover, there was no significant difference between the two groups in terms of safety indicators (arrhythmia, hypotension).

In Situ Synthesis of Hierarchical Porous Zr-MOFs on Columnar Activated Carbon and Application in Toxic Gas Adsorption.

Metal organic frameworks (MOFs) have been explored as adsorption materials owing to their diversity, controllable structure, high specific surface area, and abundant active sites. However, the shaping of MOFs has become a critical issue hindering their commercial application. A binder or high pressure is commonly used in traditional powder shaping, causing pores to be blocked or collapsed and porosity to be decreased, eventually leading to the degradation of adsorption performance. In this paper, Zr-MOFs were in situ grown on a columnar activated carbon (CAC) matrix, and a series of Zr-MOFs/CAC composites were prepared. The adsorption properties for SO2 and NO2 were measured by dynamic adsorption tests, and the Wheel-Jonas model was used to calculate the saturated adsorption capacity. Abundant mesopores can be formed between MOF crystals and activated carbon particles, and the mesoporosity of Zr-MOFs/CAC composites reached over 50%. Owing to the abundant mesoporous, increased activated sites as well as the synergistic effect between MOFs and activated carbon, the as-obtained HP-Zr-MOFs/CAC exhibited the best adsorption performance both for SO2 and NO2, which are 34.2 and 17.4 mg g-1, respectively, while the adsorption capacities of CAC for SO2 and NO2 are 20.9 and 6.6 mg g-1, respectively. The outstanding performance and facile synthesis process of HP-Zr-MOFs/CAC composites could provide ideas to develop other hierarchical porous MOFs/activated carbon composites.

Circ_0003221 Downregulation Restrains Cervical Cancer Cell Growth, Metastasis and Angiogenesis by Governing the miR-139-3p/S100A14 Pathway.

Circular RNA (circRNA) has considerable potency in carcinogenesis, which has aroused much attention. The objective of our study was to disclose the role of circ_0003221 in cervical cancer. Circ_0003221, miR-139-3p, and S100 calcium-binding protein A14 (S100A14) mRNA were quantified by quantitative real-time PCR (qPCR). The proliferation of cancer cells was checked by CCK-8 assay and EdU assay. The migration and invasion of cancer cells were checked by transwell assay. Angiogenesis was determined by tube formation assay. The protein levels of epithelial-mesenchymal transition (EMT)-related markers, angiogenesis-related markers, and S100A14 protein were measured by western blot. The interplays between miR-139-3p and circ_0003221 or S100A14 were ensured by RIP assay and dual-luciferase reporter assay. Further animal study was conducted to verify the role of circ_0003221 in vivo. Circ_0003221 was highly expressed in cancer tissues and cells, and its downregulation suppressed cancer cell proliferation, migration, invasion, and angiogenesis and also delayed tumor growth in vivo. Circ_0003221 bound to miR-139-3p and sequestered miR-139-3p expression. The inhibitory cancer cell biological behaviors by circ_0003221 downregulation were recovered by miR-139-3p suppression. S100A14 was a target gene of miR-139-3p. MiR-139-3p upregulation repressed cancer cell malignant phenotypes by depleting S100A14. Importantly, circ_0003221 positively regulated S100A14 expression by targeting miR-139-3p. Circ_0003221 downregulation restrains cervical cancer cell growth, metastasis, and angiogenesis by governing the miR-139-3p/S100A14 pathway.

Trichosanthin inhibits cervical cancer by regulating oxidative stress-induced apoptosis.

Based on many studies, trichosanthin (TCS) has an antiviral effect that regulates immune response, and targets cancer cells to exert broad-spectrum anti-tumor pharmacological activities. It is speculated that TCS may be a potential natural active drug for preventing as well as treating cervical cancer. But the clearer impact along with underlying TCS mechanism on cervical cancer are still unclear. The purpose of this study is to investigate the function and potential mechanism of TCS in cervical cancer. We measured the viability of cervical cancer cell lines (HeLa & caski cells) using CCK-8 analysis, detected cell proliferation efficiency through Ki-67 staining, analyzed cell apoptosis rate via flow cytometry as well as annexin V-FITC/PI double staining, performed apoptosis-related protein expression through western blotting, evaluated cell migration along with invasion by wound as well as transwell assays, carried out MMP via JC-1 and Rh123 fluorescent probes, as well as detected intracellular ATP and ROS levels by flow cytometry, respectively, to evaluate the effects of TCS. We found that TCS inhibited viability along with proliferation, induced apoptosis, as well as inhibited HeLa & caski cell migration along with invasion in a time- and dose-dependent manner. Additionally, TCS also reduced MMP, and the production of adenosine triphosphate, as well as induced the increase of intracellular reactive oxygen species in cancer cell lines. In accordance with the present studies, TCS inhibits HeLa & caski cell proliferation along with migration but promotes their apoptosis, which may be mediated by regulating oxidative stress.

Comparison of Viromes in Ticks from Different Domestic Animals in China.

Ticks are involved in the transmission of various arboviruses and some tick-borne viruses pose significant threats to the health of humans or livestock. This study aimed to investigate the geographical distribution of tick species and tick-associated viruses in central and eastern China. Total 573 ticks from domestic animals including dogs, sheep and cattle were collected in 2017. Two genera of ticks were identified including Rhipicephalus and Haemaphysalis. Sequencing was performed on Miseq Illumina platform to characterize the tick viromes from the four different sampling locations. Following trimming, 13,640 reads were obtained and annotated to 19 virus families. From these sequences, above 37.74% of the viral reads were related to the RNA viruses. Virome comparison study revealed that the tick viral diversity was considerably different in the two identified tick genera. The viral diversity of R. microplus was significantly different from that of other Rhipicephalus species. On the other hand, substantial overlap in viral species was observed between the same genera. In addition, we found no evidence that the natural host played a major role in shaping virus diversity based on the comparison of their viromes. Rather, the geographic location seems to significantly influence the viral families. Phylogenetic study indicated that the novel negative-sense RNA viruses identified in this study was closely related to Bole tick virus 1 and 3 viruses. In conclusion, the present study provides a baseline for comparing viruses detected in ticks, according to species, natural hosts, and geographic locations.

Adult Human Glioblastomas Harbor Radial Glia-like Cells.

Radial glia (RG) cells are the first neural stem cells to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like cells with typical RG morphology and markers. The cells exhibit the classic and unique mitotic behavior of normal RG in a cell-autonomous manner. Single-cell RNA sequencing analyses of glioblastoma cells reveal transcriptionally dynamic clusters of RG-like cells that share the profiles of normal human fetal radial glia and that reside in quiescent and cycling states. Functional assays show a role for interleukin in triggering exit from dormancy into active cycling, suggesting a role for inflammation in tumor progression. These data are consistent with the possibility of persistence of RG into adulthood and their involvement in tumor initiation or maintenance. They also provide a putative cellular basis for the persistence of normal developmental programs in adult tumors.

Entry of sapelovirus into IPEC-J2 cells is dependent on caveolae-mediated endocytosis.

BACKGROUND: Porcine sapelovirus (PSV), a species of the genus Sapelovirus within the family Picornaviridae, are a significant cause of enteritis, pneumonia, polioencephalomyelitis and reproductive disorders in pigs. However, the life cycle of PSV on the molecular level is largely unknown. METHODS: Here, we used chemical inhibitors, RNA interference, and overexpression of dominant negative (DN) mutant plasmids to verify the roles of distinct endocytic pathways involved in PSV entry into porcine small intestinal epithelial cell line (IPEC-J2). RESULTS: Our experiments indicated that PSV infection was inhibited when cells were pre-treated with NH4Cl or chloroquine. Inhibitors nystatin, methyl-ß-cyclodextrin, dynasore and wortmannin dramatically reduced PSV entry efficiency, whereas the inhibitors chlorpromazine and EIPA had no effect. Furthermore, overexpression caveolin DN mutant and siRNA against caveolin also decreased virus titers and VP1 protein synthesis, whereas overexpression EPS15 DN mutant and siRNA against EPS15 did not reduce virus infection. CONCLUSIONS: Our findings suggest that PSV entry into IPEC-J2 cells depends on caveolae/lipid raft mediated-endocytosis, that is pH-dependent and requires dynamin and PI3K but is independent of clathrin and macropinocytosis.

Porcine sapelovirus enters PK-15 cells via caveolae-dependent endocytosis and requires Rab7 and Rab11.

To comprehensively understand the endocytosis of Sapelovirus A (PSV) entry into PK-15 cells, we studied PSV infection in the context of cell perturbations through drug inhibition, siRNA silencing and overexpression of dominant negative (DN) mutants. We showed here that PSV infection of PK-15 cells was unaffected by pretreated with chlorpromazine, EIPA, knockdown of the clathrin heavy chain or overexpression of Eps15 DN mutant. Conversely, PSV infection was sensitive to NH4Cl, chloroquine, dynasore, nystatin, MßCD and wortmannin with reduced PSV VP1 expression levels and virus titer. Additionally, PSV invasion leaded to rapid actin rearrangement and disruption of the cellular actin network enhanced PSV infection. After internalization the virus was transported to late endosomes and/or cycling endosomes that requires the participation of Rab7 and Rab11. Our findings demonstrate that PSV uses caveolae-dependent endocytosis as the predominant entry portal into PK-15 cells which requires low pH, dynamin, Rab7 and Rab11.

Epidemiological and molecular analysis of avian influenza A(H7N9) virus in Shanghai, China, 2013-2017.

BACKGROUND: Human infections with a novel avian influenza A virus (H7N9) were reported in Shanghai municipality, China, at the beginning of 2013. High-pathogenic avian influenza (HPAI) H7N9 virus emerged in late February 2017 along with existing low-pathogenic avian influenza (LPAI) H7N9 virus, and this has the potential to develop into a pandemic that could be harmful to humans. METHODS: To elucidate the epidemiological characteristics of H7N9-infected cases from 2013 to 2017 in Shanghai, data on the 59 laboratory-confirmed human cases and 26 bird and environmental contamination cases were collected from the WHO website and Food and Agriculture Organization Emergency Prevention System for Animal Health (FAO EMPRES-AH). Full-length sequences of H7N9 viruses that emerged in Shanghai were collected from the Global Initiative on Sharing Avian Influenza Data to analyze the evolutionary and genetic features. RESULTS: We found that genetically different strains emerged in every epidemic in Shanghai, and most of the circulating H7N9 strains had affinity to human-type receptors, with the characteristics of high-virulence and low-pathogenic influenza viruses. Furthermore, our findings suggest that the Shanghai chicken strains are closely related to the HPAI H7N9 virus A/Guangdong/17SF003/2016, indicating that this viral strain is of avian origin and generated from the LPAI H7N9 viruses in Shanghai. The gradual decrease in H7N9 human infection in Shanghai was probably due to the control measures taken by the Shanghai government and the enhanced public awareness leading to a reduced risk of H7N9 virus infection. However, LPAI H7N9 viruses from poultry and environmental samples were continually detected in Shanghai across the epidemics, increasing the risk of new emerging H7N9 outbreaks. CONCLUSION: It is important to consistently obtain sufficient surveillance data and implement prevention measures against H7N9 viruses in Shanghai municipality.

Benefits of procyanidins on gut microbiota in Bama minipigs and implications in replacing antibiotics.

Several studies have reported the effect of absorption of procyanidins and their contribution to the small intestine. However, differences between dietary interventions of procyanidins and interventions via antibiotic feeding in pigs are rarely reported. Following 16S rRNA gene Illumina MiSeq sequencing, we observed that both procyanidin administration for 2 months (procyanidin-1 group) and continuous antibiotic feeding for 1 month followed by procyanidin for 1 month (procyanidin-2 group) increased the number of operational taxonomic units, as well as the Chao 1 and ACE indices, compared to those in pigs undergoing antibiotic administration for 2 months (antibiotic group). The genera Fibrobacter and Spirochaete were more abundant in the antibiotic group than in the procyanidin-1 and procyanidin-2 groups. Principal component analysis revealed clear separations among the three groups. Additionally, using the online Molecular Ecological Network Analyses pipeline, three co-occurrence networks were constructed; Lactobacillus was in a co-occurrence relationship with Trichococcus and Desulfovibrio and a co-exclusion relationship with Bacillus and Spharerochaeta. Furthermore, metabolic function analysis by phylogenetic investigation of communities by reconstruction of unobserved states demonstrated modulation of pathways involved in the metabolism of carbohydrates, amino acids, energy, and nucleotides. These data suggest that procyanidin influences the gut microbiota and the intestinal metabolic function to produce beneficial effects on metabolic homeostasis.

Antimicrobial and antioxidant capacity of glucosamine-zinc(II) complex via non-enzymatic browning reaction.

Coordination compounds play an important role in the life process, and have been widely used in food, cosmetics and pharmaceutical industry. Herein, we have developed a novel kind of glucosamine-zinc(II) complex (GlcN-ZC) for food additive using non-enzymatic browning reaction. The GlcN-ZC was characterized by FTIR and XRD. Moreover, UV absorbance changes, browning intensity, fluorescence changes, antioxidant activity and antimicrobial assessment of GlcN-ZC were also evaluated. Results showed the GlcN-ZC intermediate compounds were accumulated in non-enzymatic browning while prolonging heating time and melanoidins were produced in the final stage. The fluorescence changes confirmed that fluorophores were formed during the non-enzymatic reaction and fluorescence intensity reached a maximun at 60 min. The highest radical scavenging activity of GlcN-ZC formed after 180 min of heating was 79.2%. Furthermore, GlcN-ZC exhibited excellent antibacterial activity against E. coli and S. aureus. Therefore, GlcN-ZC can be used as a novel promising additive in the food industry.

An enzyme-like imprinted-polymer reactor with segregated quantum confinements for a tandem catalyst.

This study was aimed at addressing the present challenge in tandem catalysts, as to how to furnish catalysts with tandem catalytic-ability without involving the precise control and man-made isolation of different types of catalytic sites. This objective was realized by constructing an enzyme-like imprinted-polymer reactor made of a unique polymer composite inspired from the compartmentalization of cells, a composite of a reactive imprinted polymer (containing acidic catalytic sites), and encapsulated metal nanoparticles (acting as catalytic reduction sites). The compilation of two types of catalytic sites with admissible access allowed this reactor to behave like compartments of cells for enzymatic reactions and hence catalytically constituted two quantum interaction-segregated domains, which led to the occurrence of catalytic tandem processes. Unlike the reported functional reactors that run tandem catalysis by largely depending on the precise control and man-made isolation of different types of catalytic sites, tandem catalysis in this reactor run naturally with segregated quantum confinements, which does not involve the precise control and isolation of different types of catalytic sites. This protocol presents new opportunities for the development of functional catalysts for complicated chemical processes.

Integrated signal probe based aptasensor for dual-analyte detection.

For the multi-analyte detection, although the sensitivity has commonly met the practical requirements, the reliability, reproducibility and stability need to be further improved. In this work, two different aptamer probes labeled with redox tags were used as signal probe1 (sP1) and signal probe2 (sP2), which were integrated into one unity DNA architecture to develop the integrated signal probe (ISP). Comparing with the conventional independent signal probes for the simultaneous multi-analyte detection, the proposed ISP was more reproducible and accurate. This can be due to that ISP in one DNA structure can ensure the completely same modification condition and an equal stoichiometric ratio between sP1 and sP2, and furthermore the cross interference between sP1 and sP2 can be successfully prevented by regulating the complementary position of sP1 and sP2. The ISP-based assay system would be a great progress for the dual-analyte detection. Combining with gold nanoparticles (AuNPs) signal amplification, the ISP/AuNPs-based aptasensor for the sensitive dual-analyte detection was explored. Based on DNA structural switching induced by targets binding to aptamer, the simultaneous dual-analyte detection was simply achieved by monitoring the electrochemical responses of methylene blue (MB) and ferrocene (Fc) This proposed detection system possesses such advantages as simplicity in design, easy operation, good reproducibility and accuracy, high sensitivity and selectivity, which indicates the excellent application of this aptasensor in the field of clinical diagnosis or other molecular sensors.