Search

As the basic unit of residents’ activities and social management, communities are the disaster bearers of various public security emergencies. To improve the ability and level of community governance, as well as to strengthen the construction of resilient communities, a tripartite evolutionary game model of local government, developers, and home buyers is built, and numerical simulation is carried out using Matlab to analyze the impact mechanism of main parameters on the evolutionary stability strategy. The results show that: (1) The three parties’ different initial intentions will lead to different evolutionary stability strategies of the system, and the system’s final evolution result will reach the ideal state only when the initial willingness of developers and buyers is high. (2) The greater the government’s subsidy coefficient and the greater the regulatory intensity, the more likely it is that developers will choose to build resilient communities. (3) Public awareness of disaster prevention and mitigation is an important determinant of the purchase of resilient community housing strategies. To achieve rapid development of resilient communities, the intensity of regulation must be continuously improved, the public’s awareness of disaster prevention and mitigation must be strengthened, and the government’s regulatory costs must be reduced.

Chemical reactions of single molecules, caused by rapid formation or breaking of chemical bonds, are difficult to observe even with state-of-the-art instruments. A biological nanopore can be engineered into a single molecule reactor, capable of detecting the binding of a monatomic ion or the transient appearance of chemical intermediates. Pore engineering of this type is however technically challenging, which has significantly restricted further development of this technique. We propose a versatile strategy, “programmable nano-reactors for stochastic sensing” (PNRSS), by which a variety of single molecule reactions of hydrogen peroxide, metal ions, ethylene glycol, glycerol, lactic acid, vitamins, catecholamines or nucleoside analogues can be observed directly. PNRSS presents a refined sensing resolution which can be further enhanced by an artificial intelligence algorithm. Remdesivir, a nucleoside analogue and an investigational anti-viral drug used to treat COVID-19, can be distinguished from its active triphosphate form by PNRSS, suggesting applications in pharmacokinetics or drug screening., Monitoring single molecule chemical reactions can be difficult and nanopore based strategies which have shown promise are technically challenging. Here, the authors report on a technique which allows for the direct observation of different reactions and demonstrate the ability to distinguish clinically relevant analogues.

Folding of RNA can produce elaborate tertiary structures, corresponding to their diverse roles in the regulation of biological activities. Direct observation of RNA structures at high resolution in their native form however remains a challenge. The large vestibule and the narrow constriction of a Mycobacterium smegmatis porin A (MspA) suggests a sensing mode called nanopore trapping/translocation, which clearly distinguishes between microRNA, small interfering RNA (siRNA), transfer RNA (tRNA) and 5 S ribosomal RNA (rRNA). To further profit from the acquired event characteristics, a custom machine learning algorithm is developed. Events from measurements with a mixture of RNA analytes can be automatically classified, reporting a general accuracy of ~93.4%. tRNAs, which possess a unique tertiary structure, report a highly distinguishable sensing feature, different from all other RNA types tested in this study. With this strategy, tRNAs from different sources are measured and a high structural conservation across different species is observed in single molecule., Nanopores have been used for direct observation of RNA structure in native environments but have limited RNA differentiation capabilities. Here, the authors report on the use of Mycobacterium smegmatis porin A nanopores for the trapping and translocation identification of microRNA, siRNA, tRNA and ribosomal RNA.

The transcription factor p300 is reportedly involved in age-associated human diseases, including intervertebral disc degeneration (IDD). In this study, we investigate the potential role and pathophysiological mechanism of p300 in IDD. Clinical tissue samples were collected from patients with lumbar disc herniation (LDH), in which the expression of p300, forkhead box O3 (FOXO3), and sirtuin 1 (Sirt1) was determined. Nucleus pulposus cells (NPCs) isolated from clinical degenerative intervertebral disc (IVD) tissues were introduced with oe-p300, oe-FOXO3, Wnt/β-catenin agonist 1, C646 (p300/CBP inhibitor), or si-p300 to explore the functional role of p300 in IDD and to characterize the relationship between p300 and the FOXO3/Sirt1/Wnt/β-catenin pathway. Also, we established a rat IDD model by inducing needle puncture injuries in the caudal IVDs for further verification of p300 functional role. We found that p300 was downregulated in the clinical tissues and NPCs of IDD. Overexpression of p300 promoted the proliferation and autophagy of NPCs while inhibiting cell apoptosis, which was associated with FOXO3 upregulation. p300 could increase the expression of FOXO3 by binding to the Sirt1 promoter, and thus, contributed to inactivation of the Wnt/β-catenin pathway. In vivo results further displayed that p300 slowed down the progression of IDD by disrupting the Wnt/β-catenin pathway through the FOXO3/Sirt1 axis. Taken together, we suggest that p300 can act to suppress IDD via a FOXO3-dependent mechanism, highlighting a potential novel target for treatment of IDD.

Acknowledging its unique conical lumen structure, Mycobacterium smegmatis porin A (MspA) was the first type of nanopore that has successfully sequenced DNA. Recent developments of nanopore single molecule chemistry have also suggested MspA to be an optimum single molecule reactor. However, further investigations with this approach require heavy mutagenesis which is labor intensive and requires high end instruments for purifications. We here demonstrate an efficient and economic protocol which performs rapid and multiplex preparation of a variety of MspA mutants. The prepared MspA mutants were demonstrated in operations such as nanopore insertion, sequencing, optical single channel recording (oSCR), nanopore single molecule chemistry and nanopore rectification. The performance is no different from that of pores however prepared by other means. The time of all human operations and the cost for a single batch of preparation have been minimized to 40 min and 0.4$, respectively. This method is extremely useful in the screening of new MspA mutants, which has an urgent requirement in further investigations of new MspA nanoreactors. Its low cost and simplicity also enable efficient preparations of MspA nanopores for both industrial manufacturing and academic research.

OBJECTIVE: To compare the effectiveness of percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) and Wiltse-approach TLIF (W-TLIF) in the treatment of lumbar spondylolisthesis. METHODS: The clinical data of 47 patients with lumbar spondylolisthesis who met the selection criteria between July 2018 and June 2019 were retrospectively analyzed, in which 21 patients were treated with PE-TLIF (PE-TLIF group) and 26 patients were treated with W-TLIF (W-TLIF group). There was no significant difference between the two groups in age, gender, disease duration, level of spondylolisthesis vertebrae, spondylolisthesis degree, spondylolisthesis type, and preoperative visual analogue scale (VAS) score of low back pain and leg pain, lumbar Japanese Orthopaedic Association (JOA) score, and the disc height (DH), segmental lordosis (SL), and Taillard index (TI) of the operated vertebrae (P>0.05). The operation time, intraoperative blood loss, postoperative drainage, postoperative bedridden time, and complications were compared between the two groups. The VAS score and JOA score were used to evaluate the improvement of pain and function. At last follow-up, DH, SL, and TI of operated vertebrae were measured by X-ray films, and lumbar CT was performed to evaluate the interbody fusion. RESULTS: Compared with W-TLIF group, the operation time in PE-TLIF group was significantly longer, but the intraoperative blood loss and postoperative drainage were significantly less, and the postoperative bedridden time was significantly shorter (P0.05). At last follow-up, the DH, SL, and TI of operated vertebrae of the two groups significantly improved when compared with those before operation (P0.05). According to Suk’s standard, the fusion rates of PE-TLIF group and W-TLIF group were 90.5% (19/21) and 92.3% (24/26), respectively, with no significant difference (χ(2)=0.000, P=1.000). At last follow-up, there was no case of Cage sunk into the adjacent vertebral body, or dislodgement of Cage anteriorly or posteriorly in both groups. CONCLUSION: PE-TLIF and W-TLIF are both effective in the treatment of grade Ⅰ and Ⅱ lumbar spondylolisthesis. Although the operation time is prolonged, PE-TLIF has less intraoperative blood loss and postoperative drainage, shorter postoperative bedridden time, and can get more obvious short-term improvement of low back pain and function.

Objective. To probe into the efficacy of Yishen Huashi granules combined with linagliptin tablets in the treatment of type 2 diabetic nephropathy (DN) and its effect on blood glucose and renal function in patients. Methods. 70 patients with type 2 DN at our hospital between May 2020 and May 2022 were chosen as the research objects and separated into the control group and the research group based on their treatments. With 35 cases in each group, the patients treated with initial therapy and linagliptin tablets were enrolled in the control group, and those who received the above treatments and also Yishen Huashi granules were included in the research group. Their clinical indexes such as blood glucose and renal function were compared with both groups after treatment. Results. After treatment, the research group had remarkably lower fasting blood glucose (FPG), 2 h-postprandial blood glucose (2 h-PBG), and glycosylated hemoglobin A1c (HbA1c) levels than those in the control group ( P < 0.05 ). After treatment, the research group had remarkably lower levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) ( P < 0.05 ) and higher high-density lipoprotein (HDL) levels ( P < 0.05 ) than those in the control group. After treatment, the urinary microalbumin (u-mALB) level was remarkably lower in both groups ( P < 0.05 ) and was distinctly lower in the research group than in the control group ( P < 0.05 ). After treatment, the research group had remarkably lower renal function indexes such as serum creatinine (SCr), blood urea nitrogen (BUN), urinary protein (UPro), and urinary albumin excretion rate (UAER) ( P < 0.05 ) and a higher estimated glomerular filtration rate (eGFR) level ( P < 0.05 ) than those in the control group. The efficacy was evaluated by the traditional Chinese medicine (TCM) syndrome score after treatment. There were no patients in complete remission between both the groups, where slight differences were found in the proportion of significant remission ( P > 0.05 ), with the total effective rate of the research group remarkably higher than that of the control group ( P < 0.05 ). Conclusion. The combination of Yishen Huashi granules and linagliptin tablets can reduce the blood glucose and blood lipid levels in patients with type 2 DN and lower UPro and protect renal function at the same time, which provides a new idea and a method for clinical treatment of type 2 DN with integrated traditional Chinese and Western medicine.

Smart community is an important constituent part of a smart city and an extension and deepening of the concept of the latter. When it comes to smart community, the digitalization upgrading of traditional community service is conducted via information technology, in an effort to improve the service experience of community residents and elevate their happiness index. From social functions, smart community also has the advantages in facilitating the smart transformation of cities, promoting the harmonious society construction, and improving governmental efficiency and image, among others. However, various problems persist in the construction and development process of a smart community, such as mismatching service contents and low service quality. To explore the influencing factors of smart community service quality, a total of 16 influencing factors were extracted from 5 dimensions: service object, service subject, government role, management system, and service content. The relationships among the influencing factors were analyzed via the decision-making trial and evaluation laboratory (DEMATEL)-interpretative structural modeling (ISM) composite model, and a multi-order explanation model was constructed for these influencing factors. Result shows that the legal guarantee is the root cause influencing the smart community service quality. Development standard, basic service, and expected service are deep influencing factors that play mediating roles. Middle-layer factors such as service and operating systems have a direct bearing on quality perception. The surface-layer factors directly decide residential assessment on the smart community service quality. This study has also manifested the feasibility of the integrated DEMATEL-ISM method in analyzing the action mechanism of influencing factors for smart community service quality, providing a new analytical idea and modeling method for the smart community service quality.

In the formation of coordination interactions between metal ions and amino acids in natural metalloproteins, the bound metal ion is critical either for the stabilization of the protein structure or as an enzyme co-factor. Though extremely small in size, metal ions, when bound to the restricted environment of an engineered biological nanopore, result in detectable perturbations during single channel recordings. All reported work of this kind was performed with engineered α-hemolysin nanopores and the observed events appear to be extremely small in amplitude (∼1–3 pA). We speculate that the cylindrical pore restriction of α-hemolysin may not be optimal for probing extremely small analytes. Mycobacterium smegmatis porin A (MspA), a conical shaped nanopore, was engineered to interact with Ca2+, Mn2+, Co2+, Ni2+, Zn2+, Pb2+ and Cd2+ and a systematically larger event amplitude (up to 10 pA) was observed. The measured rate constant suggests that the coordination of a single ion with an amino acid follows hard–soft-acid–base theory, which has never been systematically validated in the case of a single molecule. By adjusting the measurement pH from 6.8 to 8.0, the duration of a single ion binding event could be modified with a ∼46-fold time extension. The phenomena reported suggest MspA to be a superior engineering template for probing a variety of extremely small analytes, such as monatomic and polyatomic ions, small molecules or chemical intermediates, and the principle of hard–soft-acid–base interaction may be instructive in the pore design.

This Letter reports a novel synthetic methodology for the fabrication of three-dimensional (3D) nanostructured CdS@carbon fiber (CF) networks and the validation of its feasibility for applications as a general platform for photoelectrochemical (PEC) bioanalysis. Specifically, 3D architectures are currently attracting increasing attention in various fields due to their intriguing properties, while CdS has been most widely utilized for PEC bioanalysis applications because of its narrow band gap, proper conduction band, and stable photocurrent generation. Using CdS as a representative material, this work realized the innovative synthesis of 3D CdS@CF networks via a simple solvothermal process. Exemplified by the sandwich immunoassay of fatty-acid-binding protein (FABP), the as-fabricated 3D CdS@CF networks exhibited superior properties, and the assay demonstrated good performance in terms of sensitivity and selectivity. This work features a novel fabrication of 3D CdS@CF networks that can serve as a general platform for PEC bioanalysis. The methodology reported here is expected to inspire new interest for the fabrication of other 3D nanostructured Cd-chalcogenide (S, Se, Te)@CF networks for wide applications in biomolecular detection and beyond.

In the formation of coordination interactions between metal ions and amino acids in natural metalloproteins, the bound metal ion is critical either for the stabilization of the protein structure or as an enzyme co-factor. Though extremely small in size, metal ions, when bound to the restricted environment of an engineered biological nanopore, result in detectable perturbations during single channel recordings. All reported work of this kind was performed with engineered α-hemolysin nanopores and the observed events appear to be extremely small in amplitude (∼1–3 pA). We speculate that the cylindrical pore restriction of α-hemolysin may not be optimal for probing extremely small analytes. Mycobacterium smegmatis porin A (MspA), a conical shaped nanopore, was engineered to interact with Ca2+, Mn2+, Co2+, Ni2+, Zn2+, Pb2+ and Cd2+ and a systematically larger event amplitude (up to 10 pA) was observed. The measured rate constant suggests that the coordination of a single ion with an amino acid follows hard–soft-acid–base theory, which has never been systematically validated in the case of a single molecule. By adjusting the measurement pH from 6.8 to 8.0, the duration of a single ion binding event could be modified with a ∼46-fold time extension. The phenomena reported suggest MspA to be a superior engineering template for probing a variety of extremely small analytes, such as monatomic and polyatomic ions, small molecules or chemical intermediates, and the principle of hard–soft-acid–base interaction may be instructive in the pore design., The principle of hard–soft-acid–base (HSAB) theory was first validated in single molecule by measurements with engineered Mycobacterium smegmatis porin A (MspA) nanopore reactors.

Acknowledging its unique conical lumen structure, Mycobacterium smegmatis porin A (MspA) was the first type of nanopore that has successfully sequenced DNA. Recent developments of nanopore single molecule chemistry have also suggested MspA to be an optimum single molecule reactor. However, further investigations with this approach require heavy mutagenesis which is labor intensive and requires high end instruments for purifications. We here demonstrate an efficient and economic protocol which performs rapid and multiplex preparation of a variety of MspA mutants. The prepared MspA mutants were demonstrated in operations such as nanopore insertion, sequencing, optical single channel recording (oSCR), nanopore single molecule chemistry and nanopore rectification. The performance is no different from that of pores however prepared by other means. The time of all human operations and the cost for a single batch of preparation have been minimized to 40 min and 0.4$, respectively. This method is extremely useful in the screening of new MspA mutants, which has an urgent requirement in further investigations of new MspA nanoreactors. Its low cost and simplicity also enable efficient preparations of MspA nanopores for both industrial manufacturing and academic research., A rapid and multiplex approach to prepare engineered Mycobacterium smegmatis porin A (MspA) nanopores for single molecule sensing and sequencing.

OBJECTIVE: To compare the clinical and radiological effectiveness of oblique lumbar interbody fusion (OLIF) and posterior lumbar interbody fusion (PLIF) in the treatment of Cage dislodgement after lumbar surgery. METHODS: The clinical data of 40 patients who underwent revision surgery due to Cage dislodgement after lumbar surgery betweem April 2013 and March 2017 were retrospectively analyzed. Among them, 18 patients underwent OLIF (OLIF group) and 22 patients underwent PLIF (PLIF group) for revision. There was no significant difference between the two groups in age, gender, body mass index, intervals between primary surgery and revision surgery, number of primary fused levels, disc spaces of Cage dislodgement, and visual analogue scale (VAS) scores of low back pain and leg pain, Oswestry disability index (ODI), the segmental lordosis (SL) and disc height (DH) of the disc space of Cage dislodgement, and the lumbar lordosis (LL) before revision (P>0.05). The operation time, intraoperative blood loss, hospital stay, and complications of the two groups were recorded and compared. The VAS scores of low back pain and leg pain were evaluated at 3 days, 3, 6, and 12 months after operation, and the ODI scores were evaluated at 3, 6, and 12 months after operation. The SL and DH of the disc space of Cage dislodgement and LL were measured at 12 months after operation and compared with those before operation. CT examination was performed at 12 months after operation, and the fusion of the disc space implanted with new Cage was judged by Bridwell grading standard. RESULTS: The intraoperative blood loss in the OLIF group was significantly less than that in the PLIF group (t=−12.425,P=0.000); there was no significant difference between the two groups in the operation time and hospital stay (P>0.05). Both groups were followed up 12-30 months, with an average of 18 months. In the OLIF group, 2 patients (11.1%) had thigh numbness and 1 patient (5.6%) had hip flexor weakness after operation; 2 patients (9.1%) in the PLIF group had intraoperative dural sac tear. The other patients’ incisions healed by first intention without early postoperative complications. There was no significant difference in the incidence of complications between the two groups (χ(2)=0.519, P=0.642). The VAS scores of low back pain and leg pain, and the ODI score of the two groups at each time point after operation were significantly improved when compared with those before operation (P0.05). At 12 months after operation, SL, LL, and DH in the two groups were significantly increased when compared with preoperative ones (P0.05). CT examination at 12 months after operation showed that all the operated disc spaces achieved bony fusion. According to the Bridwell grading standard, 12 cases were grade Ⅰ and 6 cases were grade Ⅱ in the OLIF group, and 13 cases were grade Ⅰ and 9 cases were grade Ⅱ in the PLIF group; there was no significant difference between the two groups (Z=–0.486,P=0.627). During follow-up, neither re-displacement or sinking of Cage, nor loosening or fracture of internal fixation occurred. CONCLUSION: OLIF and PLIF can achieve similar effectiveness in the treatment of Cage dislodgement after lumbar surgery. OLIF can further reduce intraoperative blood loss and restore the SL and DH of the disc space of Cage dislodgement better.

The first demonstration of direct sequencing of 2′-deoxy-2′-fluoroarabinonucleic acid (FANA) using Nanopore-Induced Phase-Shift Sequencing (NIPSS)., 2′-deoxy-2′-fluoroarabinonucleic acid (FANA), which is one type of xeno-nucleic acid (XNA), has been intensively studied in molecular medicine and synthetic biology because of its superior gene-silencing and catalytic activities. Although urgently required, FANA cannot be directly sequenced by any existing platform. Nanopore sequencing, which identifies a single molecule analyte directly from its physical and chemical properties, shows promise for direct XNA sequencing. As a proof of concept, different FANA homopolymers show well-distinguished pore blockage signals in a Mycobacterium smegmatis porin A (MspA) nanopore. By ligating FANA with a DNA drive-strand, direct FANA sequencing has been demonstrated using phi29 DNA polymerase by Nanopore-Induced Phase Shift Sequencing (NIPSS). When bound with an FANA template, the phi29 DNA polymerase shows unexpected reverse transcriptase activity when monitored in a single molecule assay. Following further investigations into the ensemble, phi29 DNA polymerase is shown to be a previously unknown reverse transcriptase for FANA that operates at room temperature, and is potentially ideal for nanopore sequencing. These results represent the first direct sequencing of a sugar-modified XNA and suggest that phi29 DNA polymerase could act as a promising enzyme for sustained sequencing of a wide variety of XNAs.

Functionality of polymers is crucially fundamental to polymers. However, the application of polymers faces great challenges due to the insufficient function of hydrophobic chain, especially in drug delivery. One novel approach to solve this dilemma involves the use of medicated hydrophobic chains. Herein, the polymer-doxorubicin conjugates are synthesized from hydrophilic copolymer and hydrophobic chain composed of doxorubicin (DOX). DOX, a common hydrophobic anticancer drug, is used to serve as a hydrophobic pendant for inducing self-assembly of polymer-doxorubicin conjugates. The self-assembly of polymer-drug conjugates is employed to encapsulate the unreacted drug for the first time and form drug-loaded polyprodrug micelles that possess a low critical micelle concentration (CMC), which improves the use efficiency of expensive drug. The detachment of DOX moieties from polymer-doxorubicin conjugates caused by amidase facilitates the disintegration of DOX-loaded polyprodrug micelles to trigger the enhanced release of DOX in a slightly acidic medium. It is demonstrated that the DOX-loaded polyprodrug micelles have a higher suppression against cancer cells in in vitro investigations. This work thus proposes a strategy to modify the poor functionality of polymer-based nanostructures, through designing the medicated hydrophobic chains. This strategy facilitates the potential application of polymer-drug conjugates and provides profound insights into the effect of medicated polymer on drug delivery system.

Backgroud Few studies compared radiographic and clinical outcomes between oblique lumbar interbody fusion and posterior lumbar interbody fusion in degenerative lumbar scoliosis. Methods This study retrospectively analyzed the case data of 40 patients with degenerative lumbar scoliosis in our hospital from July 2016 to October 2018. Among which,19 cases underwent oblique lumbar Interbody fusion(OLIF group) and 21 cases underwent posterior lumbar interbody fusion(PLIF group). The duration of the operation, volume of intraoperative hemorrhage, incision length, bed rest time, length of hospital stay, and complications were recorded for all patients. The clinical effects of 40 patients were evaluated by VAS for back pain and Oswestry Disability Index (ODI) and The radiographic parameters were evaluated using the lumbar scoliosis Cobb angle, sagittal vertical axis(SVA), coronal vertical axis(CVA), lumbar lordosis(LL), pelvic tilt(PT), sacral slope(SS), and Disc height(DH). Results The duration of the operation, the volume of intraoperative hemorrhage, incision length, bed rest time, length of hospital stay of the OLIF group were shorter than the PLIF group( P ＜ 0.05 ). The VAS scores for back pain, the ODI of the two groups were significantly decreased, which compared with the preoperative( P ＜ 0.05 )，which in OLIF group was significantly more decreased than in PLIF( P ＜ 0.05 ) at 7 days and 3 months postoperatively, but at the last follow-up there were no significant difference between the two groups( P ＞ 0.05 ); The lumbar scoliosis Cobb angle, SVA, CVA, PT, LL, SS were significantly improved postoperatively( P ＜ 0.05 ). The OLIF group showed higher DH, smaller Cobb angle, and greater LL than the PLIF group at any time point( P ＜ 0.05 ). but there were no significant difference in SVA, CVA, PT and SS between the two groups at any follow-up points( P ＞ 0.05 ). The overall complication rate was slightly higher in the PLIF group（47.62%）than in the OLIF group（26.32%）without significant difference(x 2 =1.931, P =0.165). But the incidence of major complications in the PLIF group was significantly higher than that in the OLIF group (Fisher, P =0.026). Conclusion OLIF provides an alternative minimally invasive treatment for DLS, which compared with PLIF. It has the characteristics of a small incision, rapid recovery, fewer complications related to the surgical approach, and satisfactory orthopedics. Keywords : Minimally invasive, Oblique lumbar interbody fusion, Degenerative adult lumbar scoliosis , Posterior lumbar interbody fusion

Objective To explore the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in vivo and in vitro and its mechanism. Methods 60 rats were underwent surgery to construct rat models of IVDD and divided in the sham group, model group and gradient G-Rg1 groups (10 mg/kg/d, 20 mg/kg/d and 40 mg/kg/d).The change of histology was observed by HE staining, the water content and the expression of β-catenin in IVD were detected. Rat nucleus pulposus cells(NPCs) were isolated from IVDD rats and divided in D-NPCs group, and gradient G-Rg1 groups(20 μg/ml, 50 μg/ml and 100 μg/ml).The cell proliferation activity, cell apoptosis rate,the expression of proteins related to ECM and Wnt/β-catenin were detected respectively, Finally the agonist of Wnt/β-catenin pathway LiCl was used for reversed experiments. Results In vivo, G-Rg1 treatment could improve the structural disorganization, low water content, NPCs number and aggrecan and collagenⅡ expression in IVD and down-regulate the expression of β-catenin. In vitro NPCs, G-Rg1 treatment could improve the low cell proliferation, high apoptosis rate and low expression of aggrecan and collagenⅡ in degenerative NPCs in a dose-dependent manner.G-Rg1 treatment could down-regulate the expression of proteins related to β-catenin signal and LiCl could reverse the increase of cell proliferation and ECM synthesis, decrease of apoptosis of degenerative NPCs induced by G-Rg1. Conclusion G-Rg1 could promote ECM synthesis of degenerative NPCs and inhibiting its apoptosis, improve the IVDD via inhibiting the Wnt/β-catenin pathway.

This work reports a customized methodology for the fabrication of 3D CdS nanosheet (NS)-enwrapped carbon fiber framework (CFF) and its utilization for sensitive split-type CuO-mediated PEC immunoassay. Specifically, the 3D CdS NS-CFF was fabricated via a solvothermal process, while the sandwich immunocomplexing was allowed in a 96 well plate with CuO nanoparticles (NPs) as the signaling labels. The subsequent release of the Cu2+ ions was directed to interact with the CdS NS, generating trapping sites and thus inhibiting its photocurrent generation. In such a protocol, the 3D CdS NS-CFF photoelectrode could not only guarantee its sufficient contact with the Cu2+-containing solution but also supply plenty CdS surface for the Cu2+ ions. Because of the target-dependent release of the Cu2+ ions and its proper coupling with the 3D CdS NS-CFF photoelectrode, a sensitive split-type PEC immunoassay was achieved for the detection of brain natriuretic peptide (BNP). This proposed system exhibited good stability and selectivity, and its applicability for real sample analysis was also demonstrated via comparison with the commercial BNP enzyme-linked immunosorbent assay (ELISA) kit. We expect this work could stimulate more interest in the design and utilization of 3D photoelectrodes for novel PEC bioanalysis.

MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in RNA silencing and post-transcriptional gene regulation. Besides their participation in regulating normal physiological activities, specific miRNA types could act as oncogenes, tumor suppressors or metastasis regulators, which are critical biomarkers for cancer. However, direct characterization of miRNA is challenging due to its unique properties such as its low abundance, sequence similarities and short length. Nanopore Induced Phase Shift Sequencing (NIPSS), which is a variant form of nanopore sequencing, could directly sequence any short analytes including miRNA. In practice, NIPSS clearly discriminates between different identities, isoforms and epigenetic variants of model miRNA sequences. This work demonstrates the first report of direct miRNA sequencing, which serves as a complement to existing miRNA sensing routines by the introduction of single molecule resolution. Future engineering of this technique may assist miRNA based early stage diagnosis or inspire novel cancer therapeutics.nnnnO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/747113v1_ufig1.gif" ALT="Figure 1">nView larger version (33K):norg.highwire.dtl.DTLVardef@216b4borg.highwire.dtl.DTLVardef@b1e88org.highwire.dtl.DTLVardef@1b04aorg.highwire.dtl.DTLVardef@dcdbb7_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background Osteosarcoma is one of the most common primary bone tumour in children and young patients, and the third most common among adults. Its main treatment option is currently based on neoadjuvant or adjuvant chemoradiotherapy along with the lesion's surgical resection. The current study's primary aim is to examine the clinical therapeutic impacts of combined methotrexate, along with other chemotherapeutic agents to treat children and young adults suffering from osteosarcoma. Methods We will perform a comprehensive literature search in English database (PubMed, EMBASE, Cochran Library CINAHL, and PsycINFO) and Chinese database (Chinese National Knowledge Infrastructure, VIP information database, Chinese Biomedical Database, and WanFang Database) with no language restriction from their inception to the search date. Additionally, two independent authors will screen the works of literature obtained from these databases, obtain information, and examine the risks of data included for the studies' bias. Furthermore, we intend to employ the Q statistics as well as I2 statistics to calculate heterogeneity among each study's analysis. Accordingly, we will utilize the funnel plots and Egger test to assess the possibility of publication bias where relevant. Results The current study aims to provide significant information regarding the clinical therapeutic impacts of combines methotrexate along with other chemotherapeutic agents to treat children and young adults suffering from osteosarcoma. Conclusions The present study will generate compelling evidence of combined methotrexate as well as other chemotherapeutic agents for osteosarcoma among children and young adults. Also, it will provide clinical practice suggestions. Ethics and dissemination The study is founded upon published data. Therefore, there is no requirement for ethics approval. Osf registration number March 26, 2021.osf.io/a23rc. (https://osf.io/a23rc/).

O; 6; -carboxymethylguanine (O; 6; -CMG) is a highly mutagenic alkylation product of DNA, triggering transition mutations relevant to gastrointestinal cancer. However, precise localization of a single O; 6; -CMG with conventional sequencing platforms is challenging. Here nanopore sequencing (NPS), which directly senses single DNA bases according to their physiochemical properties, was employed to detect O; 6; -CMG. A unique O; 6; -CMG signal was observed during NPS and a single-event call accuracy of >95 % was achieved. Moreover, O; 6; -CMG was found to be a replication obstacle for Phi29 DNA polymerase (Phi29 DNAP), suggesting this lesion could cause DNA sequencing biases in next generation sequencing (NGS) approaches.

A spiro bisphosphine oxide (SpinPO) was found to be an efficient chiral Lewis base catalyst in asymmetric reductive aldol reaction of enones and aldehydes in the presence of trichlorosilane as the reductant, affording a variety of β-hydroxyketones in good yields with moderate to high levels of diastereo- and enantioselectivities.