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Abstract A high efficiency simulation method for propagation-based phase-contrast imaging, called directional macro-wavefront (DMWF), is developed with the aim of simulating high-energy phase-contrast imaging. This method takes both Monte Carlo and wave optical propagation into consideration. Traditional wave-optics-based simulation methods for phase-contrast imaging encounter unacceptable computational complexity when high-energy radiation is used. In contrast, this method effectively addresses this issue by using macro-wavefront integration. Several simulation examples using typical parameters of inverse Compton scattering sources are presented to illustrate the excellent energy adaptability and efficiency of the DMWF method. This method provides a more efficient approach for phase-contrast imaging simulations, which will drive the advancement of high-energy phase-contrast imaging.

Abstract Sign language is an important way to provide expression information to people with hearing and speaking disabilities. Therefore, sign language recognition has always been a very important research topic. However, many sign language recognition systems currently require complex deep models and rely on expensive sensors, which limits the application scenarios of sign language recognition. To address this issue, based on computer vision, this study proposed a lightweight, dual-path background erasing deep convolutional neural network (DPCNN) model for sign language recognition. The DPCNN consists of two paths. One path is used to learn the overall features, while the other path learns the background features. The background features are gradually subtracted from the overall features to obtain an effective representation of hand features. Then, these features are flatten into a one-dimensional layer, and pass through a fully connected layer with an output unit of 128. Finally, use a fully connected layer with an output unit of 24 as the output layer. Based on the ASL Finger Spelling dataset, the total accuracy and Macro-F1 scores of the proposed method is 99.52% and 0.997, respectively. More importantly, the proposed method can be applied to small terminals, thereby improving the application scenarios of sign language recognition. Through experimental comparison, the dual path background erasure network model proposed in this paper has better generalization ability.

Abstract CUL4B, a crucial scaffolding protein in the largest E3 ubiquitin ligase complex CRL4B, is involved in a broad range of physiological and pathological processes. While previous research has shown that CUL4B participates in maintaining intestinal homeostasis and function, its involvement in facilitating intestinal recovery following ionizing radiation (IR) damage has not been fully elucidated. Here, we utilized in vivo and in vitro models to decipher the role of CUL4B in intestinal repair after IR-injury. Our findings demonstrated that prior to radiation exposure, CUL4B inhibited the ubiquitination modification of PSME3, which led to the accumulation of PSME3 and subsequent negative regulation of p53-mediated apoptosis. In contrast, after radiation, CUL4B dissociated from PSME3 and translocated into the nucleus at phosphorylated histones H2A (γH2AX) foci, thereby impeding DNA damage repair and augmenting p53-mediated apoptosis through inhibition of BRCA1 phosphorylation and RAD51. Our study elucidated the dynamic role of CUL4B in the repair of radiation-induced intestinal damage and uncovered novel molecular mechanisms underlying the repair process, suggesting a potential therapeutic strategy of intestinal damage after radiation therapy for cancers.

Abstract The significance means of the seismic reinforcement effect of a pile-anchor system for slope reinforcement has been widely recognized. However, cases of deformation failure and instability sliding of the pile-anchor system itself and the reinforced slope under seismic action continue to be recorded. Therefore, it is crucial to evaluate the seismic performance of slopes reinforced by a pile-anchor system to prevent the system’s failure. Current evaluation models of a slope reinforced by a pile-anchor system mainly focus on slope stability; however, the safety of the pile-anchor system itself is not sufficiently considered in these models. Consequently, in this study, we propose a multi-objective optimization evaluation (MOE) model for evaluating the seismic performance of slopes reinforced by a pile-anchor system that considers slope stability, safety of the pile-anchor system, and dynamic response of the slope. This model considers slope displacement, acceleration amplification factor of a slope, pile displacement, and anchor displacement as negative indexes, and anti-slide pile bending moment, shear force, and anchor axial force as intermediate indexes. The comprehensive weight of relevant indexes is obtained by combining subjective and objective weights, and the seismic reinforcement effect of the pile-anchor system is evaluated subsequently. In conclusion, the MOE model proposed in this study provides a novel solution for the optimization evaluation of a slope reinforced by a pile-anchor system in forthcoming projects.

Abstract Rescues from building collapse accidents present a significant challenge for China’s emergency rescue system. However, there are also many risk factors in a training scenario, which have been summarized in this study. A hierarchical indicator system for personnel safety was established, including 12 first-level indicators and 23s-level indicators. Then, an improved Grey-DEMATEL-ISM-MICMAC evaluation model was constructed to evaluate the level of risk. Influencing factor scores were determined according to the responses from the questionnaire survey. The influencing degree, influenced degree, centrality, and causality were identified, and the importance, relevance, and clustering of the various factors were obtained after making quantitative calculations. The results showed that the order of priority for solving the essential issues was safety education (A2), operating standards and proficiency (A10), equipment inspection (A4), equipment warehousing maintenance and records (A21). The solving of safety education was identified to be the most essential priority. The priority control order of direct causes was Scientific design and construction (A5), Potential fixed hazards in the facility (A12), Physical fitness of personnel (A1), Weather influences (A18), and Initiation efficiency of emergency plans (A20), and direct control measures for these five factors could achieve a relatively significant effect.

Abstract UQCRFS1 has been reported to be highly expressed in gastric and breast cancer, but the mechanism remains unclear. The prognosis and biological functions of UQCRFS1 in ovarian cancer (OC) have not been evaluated. The expression of UQCRFS1 in EOC was detected by GEPIA and HPA websites, and the prognosis value was investigated by Kaplan–Meier analysis. Then the correlation between the UQCRFS1 gene and tumor-related signature were analyzed by Spearman correlation analysis and rank sum test. Subsequently, the expression of the UQCRFS1 gene in four ovarian cancer cell lines was detected. A2780 and OVCAR8 with the highest expression of UQCRFS1 were selected in the following biological experiments. Cell proliferation was detected by CCK8 assay, cell cycle and apoptosis were determined by flow cytometry, reactive oxygen species (ROS) production was detected by DCFH-DA, DNA damage gene mRNA expression was analyzed by RT-PCR, and AKT/mTOR pathway protein expression were also examined by western blot after siRNA transfection. We found that UQCRFS1 was high-expression in EOC and associated with poor prognosis. Spearman correlation analysis revealed that the high expression of UQCRFS1 is associated with the cell cycle, apoptosis, oxidative phosphorylation, and DNA damage. Further studies found that knockdown of UQCRFS1 cells reduced cell proliferation, cell cycle arrest at the G1 phase, increased proportion of apoptosis, ROS production, and expression of DNA damage genes, inhibited ATK/mTOR pathway. The study suggested that UQCRFS1 may be a candidated target for diagnosis and treatments in OC.

Abstract The scattering of guided waves propagating through pipe bends is studied by means of normal mode expansion. First, the bi-orthogonality relationship for normal modes in pipe bends is derived, based on which the displacement and stress fields at the interfaces between the straight and curved parts are expanded with the normal modes in both parts. Then, based on the displacement and stress field continuity principle, the scattering problem is regarded as an eigenproblem of a transfer matrix, the solution of which gives the mode conversions at the interfaces. A case study is presented of the low-frequency longitudinal mode incident on a pipe bend, and it is found that the dominant mode conversions are L(0,1) reflection and mode conversion from L(0,1) to F(1,1). Finite element simulations and experiments are also conducted. L(0,1) bend reflection and mode-converted F(1,1) are clearly observed, which agrees well with the theoretical predictions.

Abstract 7-Met, a derivative of soybean isoflavone, is a natural flavonoid compound that has been reported to have multiple signaling pathways regulation effects. This study investigated the therapeutic effects of 7-Met on mice with atopic dermatitis induced by fluorescein isothiocyanate (FITC), or oxazolone (OXZ). 7-Met ameliorated FITC or OXZ-induced atopic dermatitis symptoms by decreasing ear thickness, spleen index, mast cell activation, neutrophil infiltration and serum IgE levels in female BALB/c mice. In FITC-induced atopic dermatitis mice, 7-Met reduced Th1 cytokines production and regulated Th1/Th2 balance by downregulating the secretion of thymic stromal lymphopoietin (TSLP) via inactivation of the NF-κB pathway. In OXZ-induced atopic dermatitis, 7-Met functioned through the reduction of Th17 cytokine production. Our study showed that 7-Methoxyisoflavone alleviated atopic dermatitis by regulating multiple signaling pathways and downregulating chemokine production.

Abstract Feelings of inferiority are complex emotions that usually indicate perceived weakness and helplessness. A lack of timely and effective interventions may bring serious consequences to individuals with inferiority feelings. Due to privacy concerns, those people often hesitate to seek face-to-face help, but they usually spontaneously share their feelings on social media, which makes social media a good resource for ample inferiority-related data. We randomly selected a sample of posts indicating inferiority feelings to explore the causes of inferiority. Through language analysis and natural language processing, we constructed a Word2Vec model of inferiority based on social media data and applied it to the cause analysis of inferiority feelings. The main causes of inferiority feelings are personal experience, social interaction, love relationship, etc. People feeling inferior about their personal experiences usually are largely influenced by their ways of thinking and life attitudes. Social and emotional factors overlap somewhat in the development of inferiority. In love relationships, males are more prone to inferiority feeling than females. These findings will help relevant institutions and organizations better understand people with inferiority feelings and facilitate the development of targeted treatment for those with potential self-esteem problems.

Abstract Huntington’s disease (HD) is a neurodegenerative disease. MicroRNAs (miRNAs) are small non-coding RNAs that mediate post-transcriptional regulation of target genes. Although miRNAs are extensively edited in human brains, the editome of miRNAs in brains of HD patients is largely unknown. By analyzing the small RNA sequencing profiles of brain tissues of 28 HD patients and 83 normal controls, 1182 miRNA editing sites with significant editing levels were identified. In addition to 27 A-to-I editing sites, we identified 3 conserved C-to-U editing sites in miRNAs of HD patients. 30 SNPs in the miRNAs of HD patients were also identified. Furthermore, 129 miRNA editing events demonstrated significantly different editing levels in prefrontal cortex samples of HD patients (HD-PC) when compared to those of healthy controls. We found that hsa-mir-10b-5p was edited to have an additional cytosine at 5’-end in HD-PC, and the edited hsa-mir-10b repressed GTPBP10 that was often downregulated in HD. The down-regulation of GTPBP10 might contribute to the progression of HD by causing gradual loss of function of mitochondrial. These results provide the first endeavor to characterize the miRNA editing events in HD and their potential functions.

Abstract Both aquatic and terrestrial biodiversity information can be detected in riverine water environmental DNA (eDNA). However, the effectiveness of using riverine water eDNA to simultaneously monitor the riverine and terrestrial biodiversity information remains unidentified. Here, we proposed that the monitoring effectiveness could be approximated by the transportation effectiveness of land-to-river and upstream-to-downstream biodiversity information flows and described by three new indicators. Subsequently, we conducted a case study in a watershed on the Qinghai–Tibet Plateau. The results demonstrated that there was higher monitoring effectiveness on summer or autumn rainy days than in other seasons and weather conditions. The monitoring of the bacterial biodiversity information was more efficient than the monitoring of the eukaryotic biodiversity information. On summer rainy days, 43–76% of species information in riparian sites could be detected in adjacent riverine water eDNA samples, 92–99% of species information in riverine sites could be detected in a 1-km downstream eDNA sample, and half of dead bioinformation (the bioinformation labeling the biological material that lacked life activity and fertility) could be monitored 4–6 km downstream for eukaryotes and 13–19 km downstream for bacteria. The current study provided reference method and data for future monitoring projects design and for future monitoring results evaluation.

Abstract There is currently a high level of demand for rapid COVID-19 tests, that can detect the onset of the disease at point of care settings. We have developed an ultra-portable, self-contained, point-of-care nucleic acid amplification test for diagnosis of active COVID-19 infection, based on the principle of loop mediated isothermal amplification (LAMP). The LAMP assay is 100% sensitive and specific to detect a minimum of 300 RNA copies/reaction of SARS-CoV-2. All of the required sample transportation, lysing and amplification steps are performed in a standalone disposable cartridge, which is controlled by a battery operated, pocket size (6x9x4cm3) unit. The test is easy to operate and does not require skilled personnel. The total time from sample to answer is approximately 35 min; a colorimetric readout indicates positive or negative results. This portable diagnostic platform has significant potential for rapid and effective testing in community settings. This will accelerate clinical decision making, in terms of effective triage and timely therapeutic and infection control interventions.

Abstract The shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens’ principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. This novel method, which we refer to as Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a refinement of the ionoacoustic approach. With its capability of completely monitoring a single, focused proton bunch with prompt readout and high repetition rate, I-BEAT is a promising approach to meet future requirements of experiments and applications in the field of laser-based ion acceleration. We demonstrate its functionality at two laser-driven ion sources for quantitative online determination of the kinetic energy distribution in the focus of single proton bunches.

Abstract The function of the NAD(P)H oxidases (NOXs) family member NOX4 is to generate reactive oxygen species (ROS), however, the molecular function of NOX4 has not been fully studied and waiting to be clarified. To elucidate the function of endogenous Nox4 in human thyroid carcinomas, papillomatosis thyroid cancer cells were used to study the cell growth by knocking down the expression of NOX4 and knocking out its functional partner p22phox/CYBA. As a result, the increasement of mitochondrial ROS(mROS) was abolished due to both knockdown of NOX4 and p22phox knockout in hypoxia, which destabilized HIF1α decreasing glycolysis and retarded cell growth. These data suggests that Nox4 is potent oncotarget due to its role in regulating glycolysis through mROS-HIF1α pathway, thereby mediating proliferation in thyroid carcinomas.

Abstract More than 100 counties, mainly in southwest China, report incidence rates of leprosy >1/100,000. The current study analysed the epidemiology of leprosy in southwest China to improve our understanding of the transmission pattern and improve control programs. 207 counties were selected in southwest China. Leprosy patients and their household contacts were recruited. The data from the medical interview and the serological antileprosy antibody of the leprosy patients were analysed. A total of 2,353 new cases of leprosy were interviewed. The distribution of leprosy patients was partly associated with local natural and economic conditions, especially several pocket areas. A total of 53 from 6643 household contacts developed leprosy, and the incidence rate of leprosy in the household contacts was 364/100,000 person-years. We found that NDO-BSA attained higher positive rates than MMP-II and LID-1 regardless of clinical types, disability and infection time in leprosy patients. By means of combination of antigens, 88.4% patients of multibacillary leprosy were detected, in contrast to 59.9% in paucibacillary leprosy. Household contacts should be given close attention for the early diagnosis, disruption of disease transmission and precise control. Applications of serology for multi-antigens were recommended for effective coverage and monitoring in leprosy control.

Abstract Tumor protein p53 acts as a trans-activator that negatively regulates cell division by controlling a set of genes required for cell cycle regulation, making it a tumor suppressor in different types of tumors. Because the transcriptional activity of p53 plays an important role in the occurrence and development of tumors, reactivation of p53 transcriptional activity has been sought as a novel cancer therapeutic strategy. There is great interest in developing high-throughput assays to identify inhibitors of molecules that bind the transcription-activation domain of p53, especially for wt p53-containing tumors. In the present study, taking MDM2 as an example, a novel amplified luminescent proximity homogeneous assay (AlphaLISA) was modified from a binding competition assay to detect the interactions between the transcription-activation domain of p53 and its ligands. This assay can be adapted as a high-throughput assay for screening new inhibitors. A panel of well-known p53-MDM2 binding inhibitors was used to validate this method, and demonstrated its utility, sensitivity and robustness. In summary, we have developed a novel protein-protein interaction detection immunoassay that can be used in a high-throughput format to screen new drug candidates for reactivation of p53. This assay has been successfully validated through a series of p53-MDM2 binding inhibitors.

Abstract Localized surface plasmon polaritons (SPPs), which can decay non-radiatively into hot carriers, have been widely employed to extend the responses of traditional semiconductor-based photocatalytic and photovoltaic devices to sub-bandgap photons. However, radiative decay is unavoidable and adverse to device performances. Here, we propose to take advantage of propagating SPPs, another form of SPPs, which possess non-radiative decay only. A special gold-titanium dioxide nanowire array with each nanowire capped with a nanocone is proposed. The adjacent nanocones forming top gradual openings attribute to efficient sunlight harvesting, while the neighbouring nanowires forming bottom nanoslots allow sufficient absorption due to the propagating SPPs. With the combined advantages, almost 100% of light is absorbed by a very thin gold film in the visible range, and 73% in the whole considered range of 400–1170 nm, superior to the nanocone cell based on localized SPPs, let alone the nanowire-based and planar counterparts. Therefore, much better photovoltaic conversion performance is achieved with short-circuit current density of 0.74 mA/cm2 and open-circuit voltage of 0.41 V. This work confirms the superiority of non-radiative decay of propagating SPPs to the localized SPPs in terms of generation of hot carriers, providing a promising way of extracting electrons in metal into photocurrent.

Based on the characteristics of Kummell's disease (KD) and related anatomical structures of the thoracolumbar spine, a novel bone cement screw system has been designed to effectively avoid the cement loosening and displacement. This experiment aimed to assess the biological effects of the novel bone cement screw system in KD on fresh cadaveric thoracolumbar spine specimens, thereby discussing its potential application value and providing a foundation for clinical implementation. This study employed a total of 50 fresh female adult cadaver specimens. Each specimen underwent extraction of the T12 to L2 segment followed by the creation of an artificial KD model at the L1 segment and subsequent establishment of five distinct types of bone cement repair models. Model A represents the percutaneous vertebroplasty (PVP) model, Model B combines PVP with unilateral percutaneous pediculoplasty (PPP), Model C combines PVP with bilateral PPP, Model D introduces the novel bone cement screw combined with unilateral PVP, and Model E combines the novel screw with bilateral PVP, each group consists of 10 specimens. Subsequently, the six-axis spine robot was employed to execute cement three-dimensional biomechanical strength tests in six directions, including anterior flexion and posterior extension, left and right lateral bending, as well as left and right rotation. The novel bone cement screw, whether used unilaterally or bilaterally in combination with the PVP model, exhibits significantly reduced bone cement mobility and superior biomechanical stability during anterior flexion, posterior extension, left lateral bending, and right lateral bending (P<0.05).No significant differences were observed among the five models under both left and right rotation (P > 0.05).When comparing the novel bone cement screw combined with PVP unilaterally and bilaterally, no statistically significant difference was observed in the stability of bone cement across all six directions of motion (P>0.05). To conclude, this novel bone cement bridging screw system exhibits superior biomechanical stability compared to commonly used treatments. Furthermore, both unilateral and bilateral implementations of the novel bone cement screw system yield without significant differences observed. These findings present a reliable and innovative approach for clinical management of KD., (© 2024. The Author(s).)

The characteristics of dopamine self-polymerization were used to cover the nano-titanium dioxide (TiO 2 ) surface and produce nano-titanium dioxide-polydopamine (TiO 2 -PDA). The reducing nature of dopamine was then used to reduce silver nitrate to silver elemental particles on the modified nano-titanium dioxide: The resulting TiO 2 -PDA-Ag nanoparticles were used as antimicrobial agents. Finally, the antibacterial agent was mixed with silicone to obtain an antibacterial silicone composite material. The composition and structure of antibacterial agents were analyzed by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron energy spectroscopy, and X-ray diffraction. Microscopy and the antibacterial properties of the silicone antibacterial composites were studied as well. The TiO 2 -PDA-Ag antimicrobial agent had good dispersion versus nano-TiO 2 . The three were strongly combined with obvious characteristic peaks. The antibacterial agents were evenly dispersed in silicone, and the silicone composite has excellent antibacterial properties. Bacillus subtilis (B. subtilis) adhesion was reduced from 246 × 10 4  cfu/cm 2 to 2 × 10 4  cfu/cm 2 , and colibacillus (E. coli) reduced from 228 × 10 4  cfu/cm 2 leading to bacteria-free adhesion., (© 2024. The Author(s).)

Freeze-thaw cycles are frequently overlooked as a pivotal factor contributing to leakage and structural failures in clayey soil-impermeable barriers used in landfills or tailings repositories in regions subject to seasonal freezing. This investigation explores the recovery and residual strength properties of Jilin ball clay undergoing six freeze-thaw cycles, and assesses the pore structure characteristics through a series of nuclear magnetic resonance (NMR) tests. The results indicate that normal stress has a greater impact on peak recovery strength than dry density and rest periods. Cohesion increases earlier and more significantly during rest periods compared to internal friction angle. Although the pore diameter remains consistent within the micropores during the freeze-thaw cycles, the soil's structural integrity undergoes notable changes. The concluding analysis provides valuable insights for the construction and management of impermeable barriers in landfills or tailings repositories within seasonally frozen areas., (© 2024. The Author(s).)

Previous studies suggested odor stimulation may influence feeding of premature neonates. Therefore, this systematic review and meta-analysis of randomized controlled trials was conducted to assess the effect of human milk odor stimulation on feeding of premature infants. All randomized controlled trials related to human milk odor stimulation on feeding in premature infants published in PubMed, Cochrane, Library, Medline, Embase, Web of science databases and Chinese biomedical literature databases, China National Knowledge Infrastructure, China Science and Technology Journal Database (VIP) and Wanfang Chinese databases were searched, and The Cochrane Handbook 5.1.0 was used to evaluate the quality and authenticity of the literature. Relevant information of the included studies was extracted and summarized, and the evaluation indexes were analyzed using ReviewManager5.3. The retrieval time was from the establishment of the database to July 28, 2022.12 articles were assessed for eligibility, and six randomized controlled studies were eventually included in the meta-analysis (PRISMA). A total of 6 randomized controlled studies with 763 patients were finally included in the study, and the quality evaluation of literatures were all grade B. Human milk odor stimulation reduced the transition time to oral feeding in premature infants [SMD = - 0.48, 95% CI (- 0.69, - 0.27), Z = 4.54, P < 0.00001] and shortened the duration of parenteral nutrition [MD = - 1.01, 95% CI (- 1.70, - 0.32), Z = 2.88, P = 0.004]. However, it did not change the length of hospitalization for premature infants [MD = - 0.03, 95% CI (- 0.41, 0.35), Z = 0.17, P = 0.86]. The implementation of human milk odor stimulation can reduce the transition time to oral feeding and the duration of parenteral nutrition in premature infants, but further studies are needed to determine whether it can reduce the length of hospital stay in premature infants. More high-quality, large-sample studies are needed to investigate the effect of human milk odor stimulation on the feeding process and other outcomes in premature infants., (© 2024. The Author(s).)

Durability is one of the technical bottlenecks restricting fuel cell electric vehicle development. As a result, significant time and resources have been invested in research related to this area worldwide. Current durability research mainly focuses on the single cell and stack levels, which is quite different from the usage scenarios of actual vehicles. There is almost no research on developing durability test cycles on the fuel cell system level. This paper proposes a universal model for developing a durability test cycle for fuel cell system based on the China automotive test cycle. Large-scale comparison tests of the fuel cell systems are conducted. After 1000 h test, the output performance degradation of three mass-produced fuel cell system is 14.49%, 9.59%, and 4.21%, respectively. The test results show that the durability test cycle proposed in this paper can effectively accelerate the durability test of the fuel cell system and evaluate the durability performance of the fuel cell system. Moreover, the methodology proposed in this paper could be used in any other test cycles such as NEDC (New European Driving Cycle), WLTC (Worldwide Harmonized Light Vehicles Test Procedure), etc. And it has comprehensive application value and are significant for reducing the cost of durability testing of fuel cell systems and promoting the industrialization of fuel cell electric vehicles., (© 2024. The Author(s).)

Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination of network pharmacology and molecular experiments. Kaempferol and OP-related targets were retrieved from the public database. A protein-protein interaction (PPI) network of common targets was constructed using the STRING database and visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO and KEGG of potential therapeutic targets were conducted using the Hiplot platform. Molecular docking was performed using Molecular operating environment (MOE) software, and cell experiments were conducted to validate the mechanism of kaempferol in treating OP. Network pharmacology analysis identified 54 overlapping targets between kaempferol and OP, with 10 core targets identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, the AGE/RAGE signaling pathway, and the TNF signaling pathway. Molecular docking results indicated stable binding of kaempferol and two target proteins, AKT1 and MMP9. In vitro cell experiments demonstrated significant upregulation of AKT1 expression in MC3T3-E1 cells (p < 0.001) with kaempferol treatment, along with downregulation of MMP9 expression (p < 0.05) compared to the control group. This study predicted the core targets and pathways of kaempferol in OP treatment using network pharmacology, and validated these findings through in vitro experiments, suggesting a promising avenue for future clinical treatment of OP., (© 2024. The Author(s).)

The objective is to compare the clinical efficacy and safety of the S8 navigation system and the Tinavi orthopaedic surgery robot in the treatment of upper cervical instability. The research methods adopted are as follows. The clinical data of patients with upper cervical instability who underwent surgery from May 2021 to December 2021 were analysed retrospectively. Patients were divided into a navigation group (assisted by the S8 navigation system) and a tinavi group (assisted by the Tinavi robot) according to the auxiliary system used. Computed tomography and digital radiography were performed after the operation. The accuracy of pedicle screw placement was evaluated using the criteria put forward by Rampersaud. Degree of facet joint violation, visual analogue scale score, neck disability index and Japanese orthopaedic association score were recorded and assessed during follow-up examinations in both groups. Record two groups of surgery-related indicators. Record the complications of the two groups. A total of 50 patients were included. 21 patients in the navigation group and 29 in the tinavi group. The results of the study are as follows. The average follow-up time was 12.1 months. There was no significant difference in nail placement accuracy between the navigation and tinavi groups (P > 0.05); however, the navigation group had a significantly higher rate of facet joint violation than that of tinavi group (P < 0.05), and the screws were placed closer to the anterior cortex (P < 0.05). Significantly more intraoperative fluoroscopies were performed in the tinavi group than in the navigation group, and the operation time was significantly longer in the tinavi group than in the navigation group (P < 0.05). The time of single nail implantation, intraoperative blood loss and incision length in navigation group were significantly longer than those in tinavi group. There were no statistically significant differences in other indicators between the two groups (P > 0.05). We come to the following conclusion. The Stealth Station S8 navigation system (Medtronic, USA), which also uses an optical tracking system, and the Tinavi Orthopedic robot have shown the same high accuracy and satisfactory clinical results in the treatment of upper cervical instability. Although the S8 navigation system still has many limitations, it still has good application prospects and is a new tool for spine surgery., (© 2024. The Author(s).)

Osteoporosis is a common bone disease characterized by loss of bone mass, reduced bone strength, and deterioration of bone microstructure. ROS-induced oxidative stress plays an important role in osteoporosis. However, the biomarkers and molecular mechanisms of oxidative stress are still unclear. We obtained the datasets from the Gene Expression Omnibus (GEO) database, and performed differential analysis, Venn analysis, and weighted correlation network analysis (WGCNA) analysis out the hub genes. Then, the correlation between inflammatory factors and hub genes was analyzed, and a Mendelian randomization (MR) analysis was performed on cytokines and osteoporosis outcomes. In addition, "CIBERSORT" was used to analyze the infiltration of immune cells and single-cell RNA-seq data was used to analyze the expression distribution of hub genes and cell-cell communications. Finally, we collected human blood samples for RT-qPCR and Elisa experiments, the miRNA-mRNA network was constructed using the miRBase database, the 3D structure was predicted using the RNAfold, Vfold3D database, and the drug sensitivity analysis was performed using the RNAactDrug database. We obtained three differentially expressed genes associated with oxidative stress: DBH, TAF15, and STAT4 by differential, WGCNA clustering, and Venn screening analyses, and further analyzed the correlation of these 3 genes with inflammatory factors and immune cell infiltration and found that STAT4 was significantly and positively correlated with IL-2. Single-cell data analysis showed that the STAT4 gene was highly expressed mainly in dendritic cells and monocytes. In addition, the results of RT-qPCR and Elisa experiments verified that the expression of STAT4 was consistent with the previous analysis, and a significant causal relationship between IL-2 and STAT4 SNPs and osteoporosis was found by Mendelian randomization. Finally, through miRNA-mRNA network and drug sensitivity analysis, we analyzed to get Palbociclib/miR-141-3p/STAT4 axis, which can be used for the prevention and treatment of osteoporosis. In this study, we proposed the Palbociclib/miR-141-3p/STAT4 axis for the first time and provided new insights into the mechanism of oxidative stress in osteoporosis., (© 2023. The Author(s).)

The objective was to compare the clinical efficacy of percutaneous pedicle screw internal fixation with the aid of the TINAVI orthopaedic surgery robot with that of traditional open surgery for Levine-Edward type IIA (postreduction) hangman fractures and to evaluate the safety and efficacy of the TINAVI robot-assisted orthopaedic surgery procedure. The clinical data of 60 patients with Levine-Edward type IIA (postreduction) hangman fractures treated surgically from June 2015 to February 2022 were analysed retrospectively. Among these patients, 25 were treated with percutaneous pedicle screw fixation under TINAVI (the robot group), and 35 were treated with pedicle screw implantation assisted by a conventional C-arm X-ray machine (the traditional operation group). The pedicle screw placement grade was evaluated according to the Rampersaud scale. The correct rate of pedicle screw placement was calculated. The invasion of adjacent facet joints, VAS score (Visual Analogue Scale), NDI score (Neck Disability Index), SF-36 score (36-Item Short-Form Health Survey questionnaire), EQ-5D score (EuroQol-5 dimensions questionnaire) and operation-related data were recorded, and patients were followed up. All patients were followed up for an average of 15.0 ± 3.4 months. The accuracy of screw placement in the robot group was higher than that in the traditional operation group, while the rates of intraoperative blood loss and invasion of the facet joint were lower and the incision length and length of hospital stay were shorter. On the 3rd day after the operation, the VAS score in the robot group was significantly higher than that in the traditional operation group, but there was no significant difference in the NDI score. On the 3rd day after the operation, the SF-36 and EQ-5 questionnaire scores of the robot group were better than those of the traditional operation group. No complications occurred in any of the patients. Postoperative cervical X-ray showed that the cervical vertebra was stable, and there was no fracture, angle or displacement. Postoperative CT showed that all fractures healed, and the average healing time was 3.4 months. The treatment of Levine-Edward IIA (postrepositioning) hangman fractures with percutaneous pedicle fixation assisted by the TINAVI orthopaedic surgery robot can significantly improve screw placement accuracy with a low rate of invasion of the adjacent facet joint, a short operation time, a low bleeding rate, and high patient satisfaction. Although there are still many disadvantages, it still has good prospects for application., (© 2023. Springer Nature Limited.)

The insecticidal crystalline proteins (Crys) are a family of insect endotoxin functioning in crop protection. As insects keep evolving into tolerance to the existing Crys, it is necessary to discover new Cry proteins to overcome potential threatens. Crys possess three functional domains at their N-termini, and the most active region throughout evolution was found at the domain-III. We swapped domain-IIIs from various Cry proteins and generated seven chimeric proteins. All recombinants were expressed in Escherichia coli and their toxicity was assessed by dietary exposure assays. Three of the seven Crys exhibited a high toxicity to Asian corn borer over the controls. One of them, Cry1Ab-Gc, a chimeric Cry1Ab being replaced with the domain-III of Cry1Gc, showed the highest toxicity to rice stem borer when it was over-expressed in Oryza sativa. Furthermore, it was also transformed into maize, backcrossed into commercial maize inbred lines and then produced hybrid to evaluate their commercial value. Transgenic maize performed significant resistance to the Asian corn borer without affecting the yield. We further showed that this new protein did not have adverse effects on the environment. Our results indicated that domain III swapped of Crys could be used as an efficient method for developing new engineered insecticidal protein., (© 2022. The Author(s).)

In recent years, with the in-depth research on spinal tuberculosis, posterior surgery alone has been praised highly by more and more surgeons due to the better correction of kyphosis, better maintenance of spinal physiological curvature, smaller surgical trauma and fewer surgical complications. However, there is currently lack of relevant reports about the efficacy of posterior surgery alone in the treatment of tuberculosis in the T4-6 segments. This study aimed to evaluate the clinical study efficacy and feasibility of one-stage posterior-only surgical treatment for thoracic spinal tuberculosis in the T4-6 segments. 67 patients with tuberculosis in T4-6 segments who underwent one-stage posterior-only surgery were included in this study. The clinical efficacy was evaluated using statistical analysis based on the data about erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Oswestry Dability Index (ODI) score, Visual Analogue Scale (VAS) score and Cobb angle before surgery, after surgery and at the last follow-up. All patients completed fusion during the follow-up period of 6-9 months. ESR and CRP were returned to normal for all patients at 6 months follow-up. In the meanwhile, among the 27 patients combined with neurological impairment, neurological functions of 22 cases (81.48%) recovered completely at the last follow-up (P < 0.05). Cobb angle of the kyphosis was improved from preoperative 34.8 ± 10.9° to postoperative 9.6 ± 2.8°, maintaining at 11.3 ± 3.2° at the last follow-up, The ODI and VAS scores were improved by 77.10% and 81.70%, respectively. This 5-year follow-up study shows that better clinical efficacy can be achieved for tuberculosis in T4-6 segments using one-stage posterior-only approach by costotransverse debridement in combination with bone graft and internal fixation. The posterior surgical method cannot only effectively accomplish debridement, obtain satisfactory clinical results, but also well correct kyphotic deformity and maintain it., (© 2022. The Author(s).)

Influenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan-Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1)., (© 2022. The Author(s).)

Fusion with a titanium mesh cage (TMC) has become popular as a conventional method after cervical anterior corpectomy, but postoperative TMC subsidence has often been reported in the literature. We designed a novel anatomic cervical TMC to reduce the postoperative subsidence rate. According to the test process specified in the American Society of Testing Materials (ASTM) F2267 standard, three-dimensional finite element analysis was used to compare the anti-subsidence characteristics of a traditional TMC (TTMC) and novel TMC (NTMC). Through analysis, the relative propensity values of a device to subside (Kp) of the TTMC and NTMC were 665.5 N/mm and 1007.2 N/mm, respectively. A higher Kp measurement is generally expected to indicate that the device is more resistant to subsidence into a vertebral body. The results showed that the novel anatomic titanium mesh cage (NTMC) significantly improved the anti-subsidence performance after anterior cervical corpectomy and fusion (ACCF), which was approximately 51.3% higher than that of the traditional titanium mesh cage., (© 2021. The Author(s).)

Local and general anesthesia are the main techniques used during percutaneous kyphoplasty (PKP); however, both are associated with adverse reactions. Monitored anesthesia with dexmedetomidine may be the appropriate sedative and analgesic technique. Few studies have compared monitored anesthesia with other anesthesia modalities during PKP. Our aim was to determine whether monitored anesthesia is an effective alternative anesthetic approach for PKP. One hundred sixty-five patients undergoing PKP for osteoporotic vertebral compression fractures (OVCFs) were recruited from a single center in this prospective, non-randomized controlled study. PKP was performed under local anesthesia with ropivacaine (n = 55), monitored anesthesia with dexmedetomidine (n = 55), and general anesthesia with sufentanil/propofol/sevoflurane (n = 55). Perioperative pain was assessed using a visual analogue score (VAS). Hemodynamic variables, operative time, adverse effects, and perioperative satisfaction were recorded. The mean arterial pressure (MAP), heart rate, VAS, and operative time during monitored anesthesia were significantly lower than local anesthesia. Compared with general anesthesia, monitored anesthesia led to less adverse anesthetic effects. Monitored anesthesia had the highest perioperative satisfaction and the lowest VAS 2 h postoperatively; however, the monitored anesthesia group had the lowest MAP and heart rate 2 h postoperatively. Based on better sedation and analgesia, monitored anesthesia with dexmedetomidine achieved better patient cooperation, a shorter operative time, and lower adverse events during PKP; however, the MAP and heart rate in the monitored anesthesia group should be closely observed after surgery.

16S rRNA sequencing of human fecal samples has been tremendously successful in identifying microbiome changes associated with both aging and disease. A number of studies have described microbial alterations corresponding to physical frailty and nursing home residence among aging individuals. A gut-muscle axis through which the microbiome influences skeletal muscle growth/function has been hypothesized. However, the microbiome has yet to be examined in sarcopenia. Here, we collected fecal samples of 60 healthy controls (CON) and 27 sarcopenic (Case)/possibly sarcopenic (preCase) individuals and analyzed the intestinal microbiota using 16S rRNA sequencing. We observed an overall reduction in microbial diversity in Case and preCase samples. The genera Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, and Lachnoclostridium-known butyrate producers-were significantly less abundant in Case and preCase subjects while Lactobacillus was more abundant. Functional pathways underrepresented in Case subjects included numerous transporters and phenylalanine, tyrosine, and tryptophan biosynthesis suggesting that protein processing and nutrient transport may be impaired. In contrast, lipopolysaccharide biosynthesis was overrepresented in Case and PreCase subjects suggesting that sarcopenia is associated with a pro-inflammatory metagenome. These analyses demonstrate structural and functional alterations in the intestinal microbiota that may contribute to loss of skeletal muscle mass and function in sarcopenia.

Uterine contraction (UC) is an essential clinical indicator in the progress of labour and delivery. Electrohysterogram (EHG) signals recorded on the abdomen of pregnant women reflect the uterine electrical activity. This study proposes a novel algorithm for automatic recognition of UCs with EHG signals to improve the accuracy of detecting UCs. EHG signals by electrodes, the tension of the abdominal wall by tocodynamometry (TOCO) and maternal perception were recorded simultaneously in 54 pregnant women. The zero-crossing rate (ZCR) of the EHG signal and its power were calculated to modulate the raw EHG signal and highlight the EHG bursts. Then the envelope was extracted from the modulated EHG for UC recognition. Besides, UC was also detected by the conventional TOCO signal. Taking maternal perception as a reference, the UCs recognized by EHG and TOCO were evaluated with the sensitivity, positive predictive value (PPV), and UC parameters. The results show that the sensitivity and PPV are 87.8% and 93.18% for EHG, and 84.04% and 90.89% for TOCO. EHG detected a larger number of UCs than TOCO, which is closer to maternal perception. The duration and frequency of UC obtained from EHG and TOCO were not significantly different (p > 0.05). In conclusion, the proposed UC recognition algorithm has high accuracy and simple calculation which could be used for real-time analysis of EHG signals and long-term monitoring of UCs.

Arterial pulse waveform analysis has been widely used to reflect physiological changes in the cardiovascular system. This study aimed to comprehensively investigate the changes of waveform characteristics of both photoplethysmographic (PPG) and radial pulses with gestational age during normal pregnancy. PPG and radial pulses were simultaneously recorded from 130 healthy pregnant women at seven gestational time points. After normalizing the arterial pulse waveforms, the abscissa of notch point, the total pulse area and the reflection index were extracted and compared between different measurement points and between the PPG and radial pulses using post-hoc multiple comparisons with Bonferrioni correction. The results showed that the effect of gestational age on all the three waveform characteristics was significant (all p < 0.001) after adjusting for maternal age, heart rate and blood pressures. All the three waveform characteristics demonstrated similar changing trends with gestational age, and they were all significantly different between the measurements from gestational week 12-15 and the others (all p < 0.05, except for the PPG total pulse area between the first and second measurement points). In conclusion, this study has comprehensively quantified similar changes of both PPG and radial pulse waveform characteristics with gestational age.

Aldehyde dehydrogenase (ALDH) is a key enzyme for the catalytic oxidation of acetaldehyde to acetic acid. Genetic polymorphisms of ALDH2 have been associated with a wide range of diseases and cancers. However, little information is found about the association between ALDH2 polymorphisms and lumbar disc herniation (LDH) in Chinese Han population. We investigated the association between single nucleotide polymorphisms (SNPs) in ALDH2 and LDH risk in a case-control study that included 380 LDH cases and 692 healthy controls. Eight SNPs were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for gender and age. In the allele model analysis, we found the frequency of the "A" allele of rs671 was significantly higher in LDH cases than in controls (OR = 1.414, 95%CI: 1.109-1.803, P = 0.005). In the genetic model analysis, we found the minor allele "A" of rs671 was associated with increased risk of LDH under log-additive model (OR = 1.42, 95%CI: 1.11-1.82, P = 0.0062); and the minor allele "C" of rs7296651 was associated with decreased risk of LDH under over-dominant model (OR = 0.72, 95%CI: 0.53-0.97, P = 0.031). Additionally, the haplotype "GGCTCACG" constructed by rs886205, rs2238152, rs4648328, rs441, rs4646778, rs671, rs11066028, and rs7296651 was associated with increased risk of LDH (OR = 1.45; 95% CI = 1.11-1.90; P = 0.0071). Our data shed new light on the association between genetic polymorphisms of ALDH2 and LDH susceptibility in a Chinese Han population.

The aim of this study was to evaluate the efficacy and feasibility of a life-size 3-dimensional printing assisted posterior internal fixation. We performed a retrospective review of 138 patients who received posterior atlantoaxial internal fixation from October 2009 to March 2015 with a minimum follow-up period of 12 months. Group A included 76 patients who received the conventional free-hand technique. Group B included 62 patients who were treated with internal fixation assisted by 3D printing. The placement accuracy of the screw was evaluated in the computed tomography images according to the methods of Hojo and clinical outcomes were evaluated using the visual analogue scale, the Japanese Orthopedic Association Score, and the Neck Disability Index score. There were no significant differences in the clinical results at any of the follow-up time points regarding the JOA, VAS, or NDI scores between two group. However, compared to Group A, Group B had better results for screw installation (P = 0.003), shorter surgery time (P = 0.001), and less blood loss (P = 0.037). Compared to the conventional free-hand technique, 3D printed model-assisted is helpful to screw placement in atlantoaxial internal fixation, which can be used as a common tool to provides important guidance for upper cervical surgery.

Recurrent complex spinal tuberculosis accompanied by sinus tract formation is one of the most common and complex types of recurrent tuberculosis. To date, only very few studies have reported the strategies and effectiveness of surgical treatments on postoperative recurrent spinal tuberculosis accompanied by sinus tract formation. In this study, 21 recurrent patients out of 87 patients with complex spinal tuberculosis were reviewed. The data of the patients, including age, gender, existence of drug-resistant mycobacterium tuberculosis, postoperative standard chemotherapy, completeness of lesion debridement, reconstruction of the spinal stability, nutritional status, accompaniment by tuberculosis in other regions, timing of the operations, and areas of the lesions, were collected for single- and multiple-factor analyses. The clinical outcomes were evaluated by long-term follow-ups. The results showed that 7 factors were significantly associated with postoperative recurrence of complex spinal tuberculosis accompanied by sinus tract formation. This suggested that when we treat complex spinal tuberculosis, we should pay more attention to these seven indicators to avoid postoperative recurrence, and our clinical outcomes suggested that it is difficult to treat recurrent complicated spinal tuberculosis combined with sinus tract formation. The key for successful surgical treatment includes effective chemotherapy, radical debridement and proper reconstruction of spinal stability.

Non-invasive measurement of uterine activity using electrohysterogram (EHG) surface electrodes has been attempted to monitor uterine contraction. This study aimed to computationally compare the performance of acquiring EHG signals using monopolar electrode and three types of Laplacian concentric ring electrodes (bipolar, quasi-bipolar and tri-polar). With the implementation of dipole band model and abdomen model, the performances of four electrodes in terms of the local sensitivity were quantified by potential attenuation. Furthermore, the effects of fat and muscle thickness on potential attenuation were evaluated using the bipolar and tri-polar electrodes with different radius. The results showed that all the four types of electrodes detected the simulated EHG signals with consistency. That the bipolar and tri-polar electrodes had greater attenuations than the others, and the shorter distance between the origin and location of dipole band at 20 dB attenuation, indicating that they had relatively better local sensitivity. In addition, ANOVA analysis showed that, for all the electrodes with different outer ring radius, the effects of fat and muscle on potential attenuation were significant (all p < 0.01). It is therefore concluded that the bipolar and tri-polar electrodes had higher local sensitivity than the others, indicating that they can be applied to detect EHG effectively.

miRNAs, a class of short but stable noncoding RNA molecules, have been revealed to play important roles in the DNA damage response (DDR). However, their functions in cancer genome instability and the consequent clinical effect as the response to chemotherapy have not been fully elucidated. In this study, we utilized multidimensional TCGA data and the known miRNAs involved in DDR to identify a miRNA-regulatory network that responds to DNA damage. Additionally, based on the expression of ten miRNAs in this network, we developed a 10-miRNA-score that predicts defects in the homologous recombination (HR) pathway and genome instability in ovarian cancer. Importantly, consistent with the association between HR defects and improved response to chemotherapeutic agents, the 10-miRNA-score predicts the outcome of ovarian cancer patients treated with platinum agents, with a surprisingly better performance than the indexes of DNA damage. Therefore, our study demonstrates the implication of miRNA expression on cancer genome instability and provides an alternative method to identify DDR defects in patients who show the best effect with platinum drug treatment.

The longhorned beetle Aromia bungii (Coleoptera: Cerambycidae) is a major pest of stone fruit trees in the genus Prunus, including cherries, apricots, and peaches. Its native range includes China, Korea, Mongolia, and eastern Russia, but it has recently invaded and become established in several countries in Europe, and Japan, and it has been intercepted in shipments coming into North America and Australia. Here, we report the identification of its male-produced aggregation pheromone as the novel compound (E)-2-cis-6,7-epoxynonenal. In field trials in its native range in China, and in recently invaded areas of Japan, the pheromone attracted both sexes of the beetle. Thus, the pheromone should find immediate use in worldwide quarantine surveillance efforts to detect the beetle in incoming shipments. The pheromone will also be a crucial tool in ongoing efforts to eradicate the beetle from regions of the world that it has already invaded.

Epigenetic therapy is a novel tumor therapeutic method and refers to the targeting of the aberrant epigenetic modifications presumably at cancer-related genes by chemicals which are epigenetic targeting drugs (ETDs). Not like in treating hematopoietic cancer, the clinical trials investigating the potential use of ETDs in the solid tumor is not encouraging. Instead, the curative effects of ETD delivered together with DNA targeting chemo drugs (DTDs) are quite promising according to our meta-analysis. To investigate the synergistic mechanism of ETD and DTD drug combination, the therapeutic effect was studied using both cell lines and mouse engrafted tumors. Mechanically we show that HDAC inhibitors and DNMT inhibitors are capable of increasing the chromatin accessibility to cisplatin (CP) and doxorubicin (Dox) through chromatin decompaction globally. Consequently, the combination of ETD and DTD enhances the DTD induced DNA damage and cell death. Engrafted tumors in SCID mice also show increased sensitivity to irradiation (IR) or CP when the tumors were pretreated by ETDs. Given the limited therapeutic effect of ETD alone, these results strongly suggest that the combination of DTD, including irradiation, and ETD treatment is a very promising choice in clinical solid tumor therapy.

High-confidence detection of point mutations is important for disease diagnosis and clinical practice. Hybridization probes are extensively used, but are hindered by their poor single-nucleotide selectivity. Shortening the length of DNA hybridization probes weakens the stability of the probe-target duplex, leading to transient binding between complementary sequences. The kinetics of probe-target binding events are highly dependent on the number of complementary base pairs. Here, we present a single-molecule assay for point mutation detection based on transient DNA binding and use of total internal reflection fluorescence microscopy. Statistical analysis of single-molecule kinetics enabled us to effectively discriminate between wild type DNA sequences and single-nucleotide variants at the single-molecule level. A higher single-nucleotide discrimination is achieved than in our previous work by optimizing the assay conditions, which is guided by statistical modeling of kinetics with a gamma distribution. The KRAS c.34 A mutation can be clearly differentiated from the wild type sequence (KRAS c.34 G) at a relative abundance as low as 0.01% mutant to WT. To demonstrate the feasibility of this method for analysis of clinically relevant biological samples, we used this technology to detect mutations in single-stranded DNA generated from asymmetric RT-PCR of mRNA from two cancer cell lines.

Cancer is believed to be a result of accumulated mutations. However, this concept has not been fully confirmed owing to the impossibility of tracking down the ancestral somatic cell. We sought to verify the concept by exploring the correlation between cancer risk and mutation accumulation among different tissues. We hypothesized that the detected mutations through bulk tumor sequencing are commonly shared in majority, if not all, of tumor cells and are therefore largely a reflection of the mutations accumulated in the ancestral cell that gives rise to tumor. We collected a comprehensive list of mutation frequencies revealed by bulk tumor sequencing, and investigated its correlation with cancer risk to mirror the correlation between mutation accumulation and cancer risk. This revealed an approximate 1:1 relationship between mutation frequency and cancer risk in 41 different cancer types based on the sequencing data of 5,542 patients. The correlation strongly suggests that variation in cancer risk among tissues is mainly attributable to distinct mutation accumulation rates. Moreover, the correlation establishes a baseline to evaluate the effect of non-mutagenic carcinogens on cancer risk. Finally, our mathematic modeling provides a reasonable explanation to reinforce that cancer risk is predominantly determined by the first rate-limiting mutation.

Recently, Press and Dyson have proposed a new class of probabilistic and conditional strategies for the two-player iterated Prisoner's Dilemma, so-called zero-determinant strategies. A player adopting zero-determinant strategies is able to pin the expected payoff of the opponents or to enforce a linear relationship between his own payoff and the opponents' payoff, in a unilateral way. This paper considers zero-determinant strategies in the iterated public goods game, a representative multi-player game where in each round each player will choose whether or not to put his tokens into a public pot, and the tokens in this pot are multiplied by a factor larger than one and then evenly divided among all players. The analytical and numerical results exhibit a similar yet different scenario to the case of two-player games: (i) with small number of players or a small multiplication factor, a player is able to unilaterally pin the expected total payoff of all other players; (ii) a player is able to set the ratio between his payoff and the total payoff of all other players, but this ratio is limited by an upper bound if the multiplication factor exceeds a threshold that depends on the number of players.

There is no effective strategy for the treatment of spinal cord injury (SCI). An appropriate combination of hydrogel materials and neurotrophic factor therapy is currently thought to be a promising approach. In this study, we performed experiments to evaluate the synergic effect of implanting hydroxyl ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL) hydrogel incorporated with basic fibroblast growth factor (bFGF) into the site of surgically induced SCI. Prior to implantation, the combined hydrogel was surrounded by an acellular vascular matrix. Sprague-Dawley rats underwent complete spinal cord transection at the T-9 level, followed by implantation of bFGF/HEMA-MOETACL 5 days after transection surgery. Our results showed that the bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating tissue eight weeks after implantation. Furthermore, this newly designed implant promoted both nerve tissue regeneration and functional recovery following SCI. These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for intrathecal, localized and sustained delivery of bFGF to the injured spinal cord and provide evidence for the possibility that this approach may have clinical applications in the treatment of SCI.