Molecular Force Sensors for Biological Application.

The mechanical forces exerted by cells on their surrounding microenvironment are known as cellular traction forces. These forces play crucial roles in various biological processes, such as tissue development, wound healing and cell functions. However, it is hard for traditional techniques to measure cellular traction forces accurately because their magnitude (from pN to nN) and the length scales over which they occur (from nm to µm) are extremely small. In order to fully understand mechanotransduction, highly sensitive tools for measuring cellular forces are needed. Current powerful techniques for measuring traction forces include traction force microscopy (TFM) and fluorescent molecular force sensors (FMFS). In this review, we elucidate the force imaging principles of TFM and FMFS. Then we highlight the application of FMFS in a variety of biological processes and offer our perspectives and insights into the potential applications of FMFS.

Quality of life and its related-influencing factors in patients with cervical cancer based on the scale QLICP-CE(V2.0).

BACKGROUND: Quality of life research can guide clinical workers to adopt more targeted treatment and intervention measures, so as to achieve the purpose of improving patients' quality of life. The objective of this study was to evaluate health-related quality of life in Chinese patients with cervical cancer and to explore its influencing factors. METHODS: A total of 186 patients with cervical cancer were investigated by using the QLICP-CE (V2.0) scale (Quality of Life Instruments for Cancer Patients-Cervical Cancer) developed by our group in China. The data were analyzed by t-test, one-way ANOVA, univariate analysis, and multivariate linear regression. RESULTS: The total score of quality of life scale for cervical cancer patients was (62.58 ± 12.69), Univariate analysis of objective clinical indexes showed that creatinine concentration was a negative influence factor in the psychological domain, potassium ion concentration was a negative influence factor in the common symptoms and side effect domain, erythrocyte content was a positive influence factor physical domain and common general domain. Multiple linear regression results suggested that clinical staging was the influencing factor of common symptom and side effect domain, common general module and total score of scale. Marital status has different degrees of influence on the psychological, social, and common general domains. The level of education also influenced scores in the social domain. CONCLUSION: The total score of quality of life in patients with cervical cancer who received active treatment was acceptable. Marital status, clinical staging, and educational level are the factors that affect the quality of life of patients with cervical cancer. At the same time, potassium ion concentration, red blood cell count and creatinine concentration also have important effects on quality of life in patients with cervical cancer. Therefore, it is very important to give personalized treatment and nursing to patients based on various factors.

Under-5, infant, and neonatal mortality trends and causes of death, 1991-2022: Findings from death surveillance in Xicheng district of Beijing, China.

Overall, China has made substantial progress in improving child survival over the past few decades, but a detailed understanding of child mortality trend at local level is limited. This study aimed to present a comprehensive analysis of under-5, infant, and neonatal mortality rates and its trend in Xicheng district of Beijing, China. We used the surveillance data of under-5 children reported by Preventive Health Department of Xicheng District Community Health Service Center from 1991 to 2022. The data was collected based on the Child Death Reporting Card of the Beijing Under-5 Mortality Rate Surveillance Network. Data check was performed by each community health service center and related medical institutions. We extracted data included maternal age, date of death, date of birth, gender, census register, classification of any causes of death, and utilization of healthcare services before death and doubly input it in the Excel 2016 program. Categorization of the causes of death was adapted by the International Categorization of Diseases (ICD-10). Mortality rates and distribution of the leading causes of death were analyzed with descriptive statistics and the Pearson's Chi-square test using SAS 14.0 software. The Chi-square trend test was used to explore the trends in mortality. Interrupted time series analysis (ITSA) was conducted to assess the impact of the two-child policy on mortality using STATA statistical packages. From 1991 to 2022, totally, there were 166,061 live births and 793 (4.78 ‰) under-5 deaths. The mortality rates of under-5 children, infants and neonates in Xicheng district decreased from 14.75 ‰, 11.25 ‰ and 8.00 ‰ to 1.03 ‰, 0.83 ‰ and 0.41 ‰ respectively. All mortality rates showed an overall significant decline trend (χ2 trend for neonatal = -15.8136, P trend for neonatal < 0.001; χ2 trend for infant = -17.6652, P trend for infant < 0.001; χ2 trend for under-5 = -18.9103, P trend for under-5 < 0.001). The leading causes of death among under-5 children were congenital heart disease (1.65 ‰), birth asphyxia (1.44 ‰), and other congenital abnormalities (except congenital heart disease and down's syndrome) (1.36 ‰). ITSA results showed that the two-child policy did not change the overall decreased trend of child mortality rates. Future preventive measures for child healthcare should give a priority for congenital heart disease, birth asphyxia, and other congenital abnormalities.

Association of osteoporosis risk and polymorphisms of osteoprotegerin gene T950C in postmenopausal Chinese women: A PRISMA-compliant meta-analysis.

BACKGROUND: This study aimed to assess the association between the T950C polymorphism and osteoporosis in postmenopausal Chinese women to further reduce the influence of different genetic backgrounds by meta-analysis and subgroup analysis. METHODS: Through November 2022, a systematic online investigation was performed with the aid of the Cochrane Library, EMBASE, PubMed, Web of Science and the Chinese National Knowledge Infrastructure to find case-control studies looking into the correlation between the osteoprotegerin gene (OPG) T950C polymorphism and postmenopausal osteoporosis susceptibility. RESULTS: This study included 6 studies with a total of 1669 postmenopausal osteoporosis cases and 2992 controls. In the recessive model, postmenopausal women with the CC genotype (mutant homozygote at the T950C locus) had a lower risk of osteoporosis, indicating that the CC genotype of OPG T950C might show a preventive effect on osteoporosis after menopause. In a stratified analysis by geographic area, the population from South China had a significantly higher risk under the dominant model [CC + TC (heterozygote at the T950C locus) vs TT (wild-type homozygotes at the T950C locus): odds ratio = 1.34, 95% confidence interval = 1.17-1.54, P < .01], while the population from South China had a significantly lower risk under the recessive model (CC vs TC + TT: odds ratio = 0.79, 95% confidence interval = 0.69-0.95, P = .02). CONCLUSIONS: Together, the OPG T950C polymorphism may be associated with osteoporosis risk in postmenopausal Chinese women, according to this meta-analysis. Because of the study's limitations, more large-scale research is needed to corroborate these findings.

ICOS/ICOSLG and PD-1 Co-Expression is Associated with the Progression of Colorectal Precancerous- Carcinoma Immune Microenvironment.

Purpose: This study aimed to investigate the expression of inducible T-cell co-stimulator (ICOS) and its ligand (ICOSLG), along with their association with clinicopathological features and influence on the immune profile in colorectal cancer (CRC). Patients and Methods: The Cancer Genome Atlas Colorectal Adenocarcinoma cohorts were used. We also analyzed 131 clinical samples of colon lesions, including precancerous lesions (hyperplastic polyps, low-grade dysplasia, and high-grade dysplasia) and CRC tissues. We conducted immunohistochemical (IHC) assays and multiple IHC (mIHC) of CD4+, Foxp3+ tumor-infiltrating lymphocytes (TILs), and PD-1/PD-L1 immune checkpoints in precancerous lesions and CRC samples from our patient subsets to determine changes and correlations in ICOS and ICOSLG expression during progression through the adenoma-carcinoma pathway. Results: High expression of ICOS and ICOSLG was a significant factor in CRC in multiple analyses and was positively correlated with CD4+/Foxp3+ TIL density and PD-1/PD-L1 expression, which increased with the sequential progression of lesions from precancerous tissues to carcinoma. Multivariable logistic regression analysis suggested that the location and expression level of ICOS/ICOSLG may be involved in precancerous-carcinoma progression. The co-expression status of PD-1 and ICOS/ ICOSLG could stratify patients with colorectal lesions into three groups of low, moderate, and high risk of progression. According to this classification and mIHC assays, we found a strong correlation between increased PD-1+ICOS+ or PD-1+ICOSLG+ co-expression and CRC, which might be deemed an independent factor in carcinogenesis. Conclusion: Increased ICOS/ICOSLG expression may be associated with the progressive formation of Foxp3+ TILs in the immune microenvironment and may further promote the development of the abnormal cytology of colorectal lesions from precancerous neoplasia to CRC. Our findings support the interpretation that enhanced co-expression of PD-1+ICOS+ or PD-1+ICOSLG+ contributes to the immune-active microenvironment of the colorectal adenoma-carcinoma sequence.

Incidence of colorectal cancer at different screening intervals after index colonoscopy and post-polypectomy: a meta-analysis of 811,181 participants.

OBJECTIVES: To examine the evidence on the incidence of colorectal cancers (CRCs) at a follow-up screening colonoscopy (after index colonoscopy and post-polypectomy) in individuals with no adenoma, low-risk adenomas, and high-risk adenomas. METHODS: We included studies reporting the incidence of CRCs at different screening intervals after index colonoscopy and post-polypectomy. The main outcome was pooled cumulative incidence rate of CRCs stratified by intervals of 3, 5, 10, and >10 years. RESULTS: Fourteen studies with 811,181 participants were analyzed, including 10 multicenter studies and 3 national CRC screening programs. The cumulative incidence of CRCs was 0.63% (95% confidence interval [CI]: 0.30, 0.97) in the high-risk-adenoma group at 3 years, 0.37% (95% CI: 0.13, 0.61) and 0.67% (95% CI: 0.36, 0.99) in the low-risk-adenoma group at 5 and 10 years, respectively, and 0.32% (95% CI: 0.20, 0.45) and 0.50% (95% CI: 0.30, 0.69) in the no-adenoma-group at 10 and >10 years, respectively. CONCLUSION: This meta-analysis summarizes the results of colonoscopy surveillance programs with detailed data support for different screening intervals. The data on date suggest that reasonable surveillance intervals are within 3 years for the high-risk-adenoma group, 5-10 years for the low-risk-adenoma group, and ≥10 years for the no-adenoma group.

Gradual Stress-Relaxation of Hydrogel Regulates Cell Spreading.

There is growing evidence that the mechanical properties of extracellular matrices (ECMs), including elasticity and stress-relaxation, greatly influence the function and form of the residing cells. However, the effects of elasticity and stress-relaxation are often correlated, making the study of the effect of stress-relaxation on cellular behaviors difficult. Here, we designed a hybrid network hydrogel with a controllable stress-relaxation gradient and a constant elasticity. The hydrogel is crosslinked by covalent bonds and dynamic peptide-metal ion coordination interactions. The stress-relaxation gradient is controlled by spatially controlling the coordination and covalent crosslinker ratios. The different parts of the hydrogel exhibit distinct stress-relaxation amplitudes but the have same stress-relaxation timescale. Based on this hydrogel, we investigate the influence of hydrogel stress-relaxation on cell spreading. Our results show that the spreading of cells is suppressed at an increasing stress-relaxation amplitude with a fixed elasticity and stress-relaxation timescale. Our study provides a universal route to tune the stress-relaxation of hydrogels without changing their components and elasticity, which may be valuable for systematic investigations of the stress-relaxation gradient in cell cultures and organoid constructions.

Strong and Reversible Covalent Double Network Hydrogel Based on Force-Coupled Enzymatic Reactions.

Biological load-bearing tissues are strong, tough, and recoverable under periodic mechanical loads. However, such features have rarely been achieved simultaneously in the same synthetic hydrogels. Here, we use a force-coupled enzymatic reaction to tune a strong covalent peptide linkage to a reversible bond. Based on this concept we engineered double network hydrogels that combine high mechanical strength and reversible mechanical recovery in the same hydrogels. Specifically, we found that a peptide ligase, sortase A, can promote the proteolysis of peptides under force. The peptide bond can be re-ligated by the same enzyme in the absence of force. This allows the sacrificial network in the double-network hydrogels to be ruptured and rebuilt reversibly. Our results demonstrate a general approach for precisely controlling the mechanical and dynamic properties of hydrogels at the molecular level.

The influence of hypertensive disorders during pregnancy on the perinatal outcome of different chorionic twins.

OBJECTIVE: To investigate the influence of hypertensive disorders of pregnancy (HDP) on the perinatal outcomes in twin pregnancies. METHODS: This was a retrospective single-center study in which, 2160 twin pregnancies delivered between January 2016 and December 2019 were analyzed, 1661 of which were dichorionic (DC) and 499 monochorionic (MC). The perinatal outcomes were compared in 404 twin pregnancies with HDP, including 157 gestational hypertension (GH), 107 mild pre-eclampsia (MPE), 140 severe pre-eclampsia (SPE), and 1756 twins without hypertensive disorders of pregnancy (no-HDP). Multiple linear regression was performed to analyze the association between perinatal outcome and HDP. Stratified sampling by twin chorionicity (DC and MC) was also conducted. RESULTS: There were 330 (19.9%) DC cases complicated with HDP and 74 (14.8%) MC with HDP, and the difference between the two groups was statistically significant (p=.011). After stratification by chorionicity, in the DC twin, there were significantly more deliveries in the GH group, MPE group, and SPE group before 37 weeks than in the no-HDP group (p=.000). Statistically significant differences were found among the four groups in the average small fetus birthweight, the intertwin weight difference, the relative weight discordance, the growth discordance, the incidence of very low birth weight (VLBW), low birth weight (LBW), and the Apgar scores of the small fetus (p<.05). In MC twins, By comparison only on the average gestational age at delivery, the average small fetus birthweight, Apgar scores of large and small fetuses among the four groups, the difference was statistically significant (p<.05). According to multiple linear regression analysis, after controlling for multiple confounding factors, it was found when the degree of HDP in DC twins increased by one grade, the small fetus birthweight decreased by an average of 19.044 g (p=.007), the intertwin weight difference increased by an average of 14.311 g (p=.034), the relative weight discordance increased by an average of 0.6% (p=.013), and the gestational age at delivery decreased by an average of 0.160 weeks (p=.001). CONCLUSIONS: The perinatal outcomes of different chorionic twins with HDP are different. HDP has a greater impact on the perinatal outcomes of DC twins. The risk of adverse perinatal outcomes in DC twin pregnancy will increase accordingly with each increase in the grade of HDP, but HDP has little or no relevance on the perinatal outcomes of MC twins.

Clinical Impact of X-Ray Repair Cross-Complementary 1 (XRCC1) and the Immune Environment in Colorectal Adenoma-Carcinoma Pathway Progression.

PURPOSE: Colorectal cancer (CRC) can develop via a hypermutagenic pathway characterized by frequent somatic DNA base-pair mutations. Alternatively, the immunogenicity of tumor cells themselves may influence the anticancer activity of the immune effector cells. Impaired DNA repair mechanisms drive mutagenicity, which then increase the neoantigen load and immunogenicity. However, no studies have analyzed immune checkpoint protein expression, particularly programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), in adenoma-carcinoma progression and its relationship with the emergence of other DNA repair gene mutation. MATERIALS AND METHODS: We investigated mutations of 10 genes involved in DNA repair function: XRCC1, TP53, MLH1, MSH, KRAS, GSTP, UMP, MTHF, DPYD, and ABCC2. We performed sequencing to determine mutations and immunohistochemistry of immune checkpoints in clinical samples and determined changes in XRCC1 expression during progression through the adenoma-carcinoma pathway. We further investigated the prognostic associations of gene XRCC1 according to the expression, mutational profile, and immune profile using The Cancer Genome Atlas-colon adenocarcinoma (TCGA-COAD) dataset. RESULTS: From clinical samples, XRCC1 mutation demonstrated the strongest association with adenomas with a mutation frequency of 56.2% in adenomas and 34% in CRCs (p =0.016). XRCC1 was abnormally expressed and altered by mutations contributing to adenoma carcinogenesis. High expression of XRCC1, CD4, FOXP3, and PD-1/PD-L1 showed an overall upward trend with increased lesion severity (all p < 0.01). PD-1/PD-L1 expression and CD4+ intraepithelial lymphocytes (IELs) correlated with cytological dysplasia progression, specifically in patients with wild-type XRCC1 (all p < 0.01), whereas FOXP3 expression was independently associated with adenoma-carcinoma progression. From TCGA-COAD analysis, XRCC1 expression was associated with patients survival, tumor-infiltrating lymphocytes and immune marker expression. CONCLUSION: Increased IEL density and PD-1/PD-L1 expression correlate with cytological dysplasia progression and specifically with the XRCC1 mutation status in CRC. Our findings support a stepwise dysplasia-carcinoma sequence of adenoma carcinogenesis and an XRCC1 hypermutated phenotypic mechanism of lesions.

Multicolor fluorescence encoding of different microRNAs in lung cancer tissues at the single-molecule level.

The simultaneous detection of multiple microRNAs (miRNAs) will facilitate early clinical diagnosis. Herein, we demonstrate the integration of multicolor fluorophore-encoded cascade signal amplification with single-molecule detection for simultaneous measurement of different miRNAs in lung cancer tissues. This assay involves two linear templates and two circular templates without the requirement of any fluorescent-labeled probes. The binding of target miRNAs to their corresponding linear templates initiates the cyclic strand displacement amplification, generating many triggers which can specifically hybridize with the corresponding biotin-labeled AP probes to initiate the apurinic/apyrimidic endonuclease 1-assisted cyclic cleavage reaction for the production of more biotin-labeled primers for each miRNA. The resultant two primers can react with their corresponding circular templates to initiate rolling circle amplification which enables the incorporation of Cy5-dCTP/Cy3-dGTP nucleotides, resulting in the simultaneous production of abundant biotin-/multiple Cy5/Cy3-labeled DNA products. After magnetic separation and exonuclease cleavage, the amplified products release abundant Cy5 and Cy3 fluorescent molecules which can be simply monitored by single-molecule detection, with Cy3 indicating miR-21 and Cy5 indicating miR-155. This assay involves three consecutive amplification reactions, enabling the conversion of extremely low abundant target miRNAs into large numbers of Cy5/Cy3 fluorophore-encoded DNA products which can release abundant fluorescent molecules for the generation of amplified signals. This assay exhibits high sensitivity, good selectivity, and the capability of multiplexed assay. This method can simultaneously quantify miR-155 and miR-21 in living cells and in lung cancer tissues, and it can distinguish the expression of miRNAs between non-small cell lung cancer patients and healthy persons. The accuracy and reliability of the proposed method are further validated by quantitative reverse transcription polymerase chain reaction.

The effect of integrated rice-frog ecosystem on rice morphological traits and methane emission from paddy fields.

Integrated Rice-frog Ecosystem (IRFE) has the potential to reduce methane (CH4) emission and maintain yields from paddy fields. However, the quantitative relationship between rice morphological traits and CH4 emission remains to be explored. In this study, a 2-year field experiment was conducted to evaluate the effect of IRFE on rice morphological traits and CH4 emission from paddy fields and the ecological mechanisms. This study was conducted to analyze twelve aboveground and eight underground rice morphological traits, rice yields, and CH4 flux and emission from the paddy fields with six frog densities (0, 3750, 7500, 15,000, 30,000, and 60,000 frogs ha-1). The results showed that IRFE reduced CH4 emission by 24.70%-41.75% and 21.68%-51.21% in the 2018 and 2019 rice growth seasons, respectively. Moreover, CH4 emission decreased with the increase of frogs. Frogs also increased the diameter, biomass, and volume of rice roots, thus promoting rice growth. Root biomass, thousand-grain weight, and harvest index were also closely related to the yield. Root porosity and oxygen secretion capacity were negatively correlated with CH4 flux. Frogs increased root porosity and oxygen secretion, thereby reducing CH4 emission. The present study demonstrated that reducing CH4 emission and improving rice yields could be simultaneously achieved by altering rice morphological traits in IRFE.

Guidance Point Generation-Based Cooperative UGV Teleoperation in Unstructured Environment.

Teleoperation is widely used for unmanned ground vehicle (UGV) navigation in military and civilian fields. However, the human operator has to limit speed to ensure the handling stability because of the low resolution of video, limited field of view and time delay in the control loop. In this paper, we propose a novel guidance point generation method that is well suited for human-machine cooperative UGV teleoperation in unstructured environments without a predefined goal position. The key novelty of this method is that the guidance points used for navigation can be generated with only the local perception information of the UGV. Firstly, the locally occupied grid map (OGM) was generated utilizing a probabilistic grid state description method, and converted into binary image to constructed the convex hull of obstacle area. Secondly, we proposed an improved thinning algorithm to extract skeletons of navigable regions from binary images, and find out the target skeleton related to the position of the UGV utilizing the k-nearest neighbor (kNN) algorithm. The target skeleton was reconstructed at the midline position of the navigable region using the decreasing gradient algorithm in order to obtain the appropriate skeleton end points for use as candidate guidance points. For visually presenting the driving trend of the UGV and convenient touch screen operation, we transformed guidance point selection into trajectory selection by generating the predicted trajectory correlative to candidate guidance points based on the differential equation of motion. Experimental results show that the proposed method significantly increases the speed of teleoperated UGV.

Calcium Dobesilate (CaD) Attenuates High Glucose and High Lipid-Induced Impairment of Sarcoplasmic Reticulum Calcium Handling in Cardiomyocytes.

Calcium dobesilate (CaD) is used effectively in patients with diabetic microvascular disorder, retinopathy, and nephropathy. Here we sought to determine whether it has an effect on cardiomyocytes calcium mishandling that is characteristic of diabetic cardiomyopathy. Cardiomyocytes were sterile isolated and cultured from 1 to 3 days neonatal rats and treated with vehicle (Control), 25 mM glucose+300 µM Palmitic acid (HG+PA), 100 µM CaD (CaD), or HG+PA+CaD to test the effects on calcium signaling (Ca2+ sparks, transients, and SR loads) and reactive oxygen species (ROS) production by confocal imaging. Compared to Control, HG+PA treatment significantly reduced field stimulation-induced calcium transient amplitudes (2.22 ± 0.19 vs. 3.56 ± 0.21, p < 0.01) and the levels of caffeine-induced calcium transients (3.19 ± 0.14 vs. 3.72 ± 0.15, p < 0.01), however significantly increased spontaneous Ca2+ sparks firing levels in single cardiomyocytes (spontaneous frequency 2.65 ± 0.23 vs. 1.72 ± 0.12, p < 0.01) and ROS production (67.12 ± 4.4 vs. 47.65 ± 2.12, p < 0.05), which suggest that HG+PA treatment increases the Spontaneity Ca2+ spark frequency, and then induced partial reduction of SR Ca2+ content and subsequently weaken systolic Ca2+ transient in cardiomyocyte. Remarkably, these impairments in calcium signaling and ROS production were largely prevented by pre-treatment of the cells with CaD. Therefore, CaD may contribute to a good protective effect on patients with calcium mishandling and contractile dysfunction in cardiomyocytes associated with diabetic cardiomyopathy.

Interaction of Humic Acid with Graphene Oxide: Relation to Antibacterial Activities Against Escherichia coli.

Graphene oxide (GO) sheets attracted great attention as effectively antibacterial agents in water treatment and environmental remediation applications. In the study, the interaction of humic acid (HA) as the model of natural organic matter (NOM) with GO and their antibacterial activities against Escherichia coli (E. coli) was investigated. The interaction between GO and HA molecules was analyzed by isothermal titration calorimetry (ITC) and fluorescence spectroscopy analysis. The study demonstrated that GO reaction with HA was a spontaneously exothermic process, which enabled formation of stable and well dispersed GO-HA complex in aqueous solution. Both GO and GO-HA could significantly inhibit the growth of E. coli and present dose-dependent bactericidal property. GO and GO-HA showed more obvious antibacterial activity in saline solution than in LB broth. We suggest the surface wrinkles of GO and GO-HA could contribute to the firm wrapping of E. coli, which is the principle factor for the antibacterial activity of GO and GO-HA. Especially, GO-HA exhibit less surface wrinkles in comparison with GO, corresponding to its reduced antibacterial activity in saline solution.

Evaluation of functional training specifically on physical and cognitive functions intervention among children aged 4-5 / 中国学校卫生

Objective@#To investigate effects of functional training on physical and cognitive function in 4-5 years old children, so as to provide a reference for the research on development of children s physical and cognitive functions.@*Methods@#The 173 participants aged 4-5 were enrolled from 6 kindergartens in Xicheng District, Beijing and were divided into experimental (n=94) and control groups (n=79) by randomized digital tables. The experimental group were asked to receive a 18 week special designed functional movement training, which were not performed to the control group. The two groups were tested with physical and cognitive assessments before and after the intervention, and the results were compared pre/post in individual group and between groups with t tests.@*Results@#Compared with control group, the score of standing long jump among children in the experimental group was improved by 5.72%, and that of feet jump was improved by 23.79%, that of 10-meter-shuttle run was improved by 13.95%, that of simple reaction was by 20.34%, and that of attention was by 18.96%, and all the improvement was of statistical significance(t=-2.75, 6.68, 10.79, 5.07, 4.32, P<0.01).@*Conclusion@#Both physical and cognitive functions were enhanced by the functional physical training in 4-5 year-old children.

Diagnostic efficacy of the Japan Narrow-band-imaging Expert Team and Pit pattern classifications for colorectal lesions: A meta-analysis.

BACKGROUND: Pit pattern classification using magnifying chromoendoscopy is the established method for diagnosing colorectal lesions. The Japan Narrow-band-imaging (NBI) Expert Team (JNET) classification is a novel NBI magnifying endoscopic classification that focuses on the vessel, and surface patterns. AIM: To determine the diagnostic efficacy of each category of the JNET and Pit pattern classifications for colorectal lesions. METHODS: A systematic literature search was performed using PubMed, Embase, the Cochrane Library, and Web of Science databases. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic curve of each category of the JNET and Pit pattern classifications were calculated. RESULTS: A total of 19227 colorectal lesions in 31 studies were included. The diagnostic performance of the JNET classification was equivalent to the Pit pattern classification in each corresponding category. The pooled sensitivity, specificity, and area under the curve (AUC) for each category of the JNET classification were as follows: 0.73 (95%CI: 0.55-0.85), 0.99 (95%CI: 0.97-1.00), and 0.97 (95%CI: 0.95-0.98), respectively, for Type 1; 0.88 (95%CI: 0.78-0.94), 0.72 (95%CI: 0.64-0.79), and 0.84 (95%CI: 0.81-0.87), respectively, for Type 2A; 0.56 (95%CI: 0.47-0.64), 0.91 (95%CI: 0.79-0.96), and 0.72 (95%CI: 0.68-0.76), respectively, for Type 2B; 0.51 (95%CI: 0.42-0.61), 1.00 (95%CI: 1.00-1.00), and 0.90 (95%CI: 0.87-0.93), respectively, for Type 3. CONCLUSION: This meta-analysis suggests that the diagnostic efficacy of the JNET classification may be equivalent to that of the Pit pattern classification. However, due to its simpler and clearer clinical application, the JNET classification should be promoted for the classification of colorectal lesions, and to guide the treatment strategy.

Rolling circle amplification-driven encoding of different fluorescent molecules for simultaneous detection of multiple DNA repair enzymes at the single-molecule level.

DNA repair enzymes (e.g., DNA glycosylases) play a critical role in the repair of DNA lesions, and their aberrant levels are associated with various diseases. Herein, we develop a sensitive method for simultaneous detection of multiple DNA repair enzymes based on the integration of single-molecule detection with rolling circle amplification (RCA)-driven encoding of different fluorescent molecules. We use human alkyladenine DNA glycosylase (hAAG) and uracil DNA glycosylase (UDG) as the target analytes. We design a bifunctional double-stranded DNA (dsDNA) substrate with a hypoxanthine base (I) in one strand for hAAG recognition and an uracil (U) base in the other strand for UDG recognition, whose cleavage by APE1 generates two corresponding primers. The resultant two primers can hybridize with their respective circular templates to initiate RCA, resulting in the incorporation of multiple Cy3-dCTP and Cy5-dGTP nucleotides into the amplified products. After magnetic separation and exonuclease cleavage, the Cy3 and Cy5 fluorescent molecules in the amplified products are released into the solution and subsequently quantified by total internal reflection fluorescence (TIRF)-based single-molecule detection, with Cy3 indicating the presence of hAAG and Cy5 indicating the presence of UDG. This strategy greatly increases the number of fluorescent molecules per concatemer through the introduction of RCA-driven encoding of different fluorescent molecules, without the requirement of any specially labeled detection probes for simultaneous detection. Due to the high amplification efficiency of RCA and the high signal-to-ratio of single-molecule detection, this method can achieve a detection limit of 6.10 × 10-9 U mL-1 for hAAG and 1.54 × 10-9 U mL-1 for UDG. It can be further applied for simultaneous detection of multiple DNA glycosylases in cancer cells at the single-cell level and the screening of DNA glycosylase inhibitors, holding great potential in early clinical diagnosis and drug discovery.

Stretchable hydrogels with low hysteresis and anti-fatigue fracture based on polyprotein cross-linkers.

Hydrogel-based devices are widely used as flexible electronics, biosensors, soft robots, and intelligent human-machine interfaces. In these applications, high stretchability, low hysteresis, and anti-fatigue fracture are essential but can be rarely met in the same hydrogels simultaneously. Here, we demonstrate a hydrogel design using tandem-repeat proteins as the cross-linkers and random coiled polymers as the percolating network. Such a design allows the polyprotein cross-linkers only to experience considerable forces at the fracture zone and unfold to prevent crack propagation. Thus, we are able to decouple the hysteresis-toughness correlation and create hydrogels of high stretchability (~1100%), low hysteresis (< 5%), and high fracture toughness (~900 J m-2). Moreover, the hydrogels show a high fatigue threshold of ~126 J m-2 and can undergo 5000 load-unload cycles up to 500% strain without noticeable mechanical changes. Our study provides a general route to decouple network elasticity and local mechanical response in synthetic hydrogels.

Diagnostic value of liquid-based cytology and smear cytology in pancreatic endoscopic ultrasound-guided fine needle aspiration: A meta-analysis.

BACKGROUND: Smear cytology (SC) using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the established and traditional choice for diagnosing pancreatic lesions. Liquid-based cytology (LBC) is a novel alternative cytological method, however, the comparative diagnostic efficacy of LBC remains inconclusive. AIM: To examine the diagnostic efficacy of LBC and SC for pancreatic specimens obtained through EUS-FNA via a systematic review and meta-analysis. METHODS: A systematic literature search was performed using PubMed, EMBASE, the Cochrane Library, and Web of Science. The numbers of true positives, false positives, true negatives, and false negatives for each cytological test (LBC and CS) were extracted from the included studies. The pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated, and the AUC was compared by Tukey's multiple comparisons test. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies II tool. RESULTS: A total of 1656 patients in eight studies were included. The pooled sensitivity and specificity and the AUC for LBC were 0.76 (95%CI: 0.72-0.79), 1.00 (95%CI: 0.98-1.00), and 0.9174, respectively, for diagnosing pancreatic lesions. The pooled estimates for SC were as follows: Sensitivity, 0.68 (95%CI: 0.64-0.71); specificity, 0.99 (95%CI: 0.96-100.00); and AUC, 0.9714. Similarly, the corresponding values for LBC combined with SC were 0.87 (95%CI: 0.84-0.90), 0.99 (95%CI: 0.96-1.00), and 0.9894. Tukey's multiple comparisons test was used to compare the sensitivities and AUCs of the three diagnostic methods; statistically significant differences were found between the three methods, and LBC combined with SC was superior to both LBC (P < 0.05) and SC (P < 0.05). The pooled sensitivity and AUC did not change significantly in the sensitivity analysis. CONCLUSION: LBC may be sensitive than SC in the cytological diagnosis of pancreatic lesions, however, the superior diagnostic performance of their combination emphasizes their integrated usage in the clinical evaluation of pancreatic lesions.