Development and validation of a novel colonoscopy withdrawal time indicator based on YOLOv5.

BACKGROUND AND AIM: The study aims to introduce a novel indicator, effective withdrawal time (WTS), which measures the time spent actively searching for suspicious lesions during colonoscopy and to compare WTS and the conventional withdrawal time (WT). METHODS: Colonoscopy video data from 472 patients across two hospitals were retrospectively analyzed. WTS was computed through a combination of artificial intelligence (AI) and manual verification. The results obtained through WTS were compared with those generated by the AI system. Patients were categorized into four groups based on the presence of polyps and whether resections or biopsies were performed. Bland Altman plots were utilized to compare AI-computed WTS with manually verified WTS. Scatterplots were used to illustrate WTS within the four groups, among different hospitals, and across various physicians. A parallel box plot was employed to depict the proportions of WTS relative to WT within each of the four groups. RESULTS: The study included 472 patients, with a median age of 55 years, and 57.8% were male. A significant correlation with manually verified WTS (r = 0.918) was observed in AI-computed WTS. Significant differences in WTS/WT among the four groups were revealed by the parallel box plot (P < 0.001). The group with no detected polyps had the highest WTS/WT, with a median of 0.69 (interquartile range: 0.40, 0.97). WTS patterns were found to be varied between the two hospitals and among senior and junior physicians. CONCLUSIONS: A promising alternative to traditional WT for quality control and training assessment in colonoscopy is offered by AI-assisted computation of WTS.

Trypsin Encapsulation in the Zeolitic Imidazolate Framework for Low-Molecular Weight Protein Analysis with High Selectivity and Efficiency.

Low-molecular weight proteins (LWPs) are important sources of biological information in biomarkers, signaling molecules, and pathology. However, the separation and analysis of LWPs in complex biological samples are challenging, mainly due to their low abundance and the complex sample pretreatment procedure. Herein, trypsin modified by poly(acrylic acid) (PAA) was encapsulated by a zeolitic imidazolate framework (ZIF-L). Mesopores were formed on the ZIF-L with the introduction of PAA. An alternative strategy for separation and pretreatment of LWPs was developed based on the prepared ZIF-L-encapsulated trypsin with adjustable pore size. The mesoporous structure of the prepared materials selectively excluded high-molecular weight proteins from the reaction system, allowing LWPs to enter the pores and react with the internal trypsin, resulting in an improved separation efficiency. The hydrophobicity of the ZIF-L simplified the digestion process by inducing significant structural changes in substrate proteins. In addition, the enzymatic activity was significantly enhanced by the developed encapsulation method that maintained the enzyme conformation, allowed low mass transfer resistance, and possessed a high enzyme-to-substrate ratio. As a result, the ZIF-L-encapsulated trypsin can achieve highly selective separation, valid denaturation, and efficient digestion of LWPs in a short time by simply mixing with substrate proteins, greatly simplifying the separation and pretreatment process of the traditional hydrolysis method. The prepared materials and the developed strategy demonstrated an excellent size-selective assay performance in model protein mixtures, showing great potential in the application of proteomics analysis.

Enhancing Chymotrypsin Activity and Stability of Capillary Immobilized Enzyme Microreactors Using Zeolitic Imidazolate Frameworks as Encapsulation Materials.

Open-tubular immobilized enzyme microreactors (OT-IMERs) are some of the most widely used enzyme reaction devices due to the advantages of simple preparation and fast sample processing. However, the traditional approaches for OT-IMERs preparation had some defects such as limited enzyme loading amount, susceptibility to complex sample interference, and less stability. Here, we report a strategy for the preparation of highly active and stable OT-IMERs, in which the single-stranded DNA-enzyme composites were immobilized in capillaries and then encapsulated in situ in the capillaries via zeolitic imidazolate frameworks (ZIF-L). The phosphate groups of the DNA adjusted the surface potential of the enzyme to negative values, which could attract cations, such as Zn2+, to promote the formation of ZIF-L for enzyme encapsulation. Using chymotrypsin (ChT) as a model enzyme, the prepared ChT@ZIF-L-IMER has higher activity and better affinity than the free enzyme and ChT-IMER. Moreover, the thermal stability, pH stability, and organic solvent stability of ChT@ZIF-L-IMER were much higher than those of free enzyme and ChT-IMER. Furthermore, the activity of ChT@ZIF-L-IMER was much higher than that of ChT-IMER after ten consecutive reactions. To demonstrate the versatility of this preparation method, we replaced ChT with glucose oxidase (GOx). The stability of GOx@ZIF-L-IMER was also experimentally demonstrated to be superior to that of GOx and GOx-IMER. Finally, ChT@ZIF-L-IMER was used for proteolytic digestion analysis. The results showed that ChT@ZIF-L-IMER had a short digestion time and high digestive efficiency compared with the free enzyme. The present study broadened the synthesis method of OT-IMERs, effectively integrating the advantages of metal-organic frameworks and IMER, and the prepared OT-IMERs significantly improved enzyme stability. All of the results indicated that the IMER prepared by this method had a broad application prospect in capillary electrophoresis-based high-performance enzyme analysis.

Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts.

Background: This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Methods: Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. Results: A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Conclusion: Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.

Retinol and retinol binding protein 4 levels and COVID-19: a Mendelian randomization study.

BACKGROUND: The Corona Virus Disease 2019 (COVID-19) pandemic has struck globally. Whether the related proteins of retinoic acid (RA) signaling pathway are causally associated with the risk of COVID-19 remains unestablished. We conducted a two-sample Mendelian randomization (MR) study to assess the associations of retinol, retinol binding protein 4 (RBP4), retinol dehydrogenase 16 (RDH16) and cellular retinoic acid binding protein 1 (CRABP1) with COVID-19 in European population. METHODS: The outcome utilized the summary statistics of COVID-19 from the COVID-19 Host Genetics Initiative. The exposure data were obtained from public genome wide association study (GWAS) database. We extracted SNPs from exposure data and outcome data. The inverse variance weighted (IVW), MR-Egger and Wald ratio methods were employed to assess the causal relationship between exposure and outcome. Sensitivity analyses were performed to ensure the validity of the results. RESULTS: The MR estimates showed that retinol was associated with lower COVID-19 susceptibility using IVW (OR: 0.69, 95% CI: 0.53-0.90, P: 0.0065), whereas the associations between retinol and COVID-19 hospitalization or severity were not significant. RBP4 was associated with lower COVID-19 susceptibility using the Wald ratio (OR: 0.83, 95% CI: 0.72-0.95, P: 0.0072). IVW analysis showed RDH16 was associated with increased COVID-19 hospitalization (OR: 1.10, 95% CI: 1.01-1.18, P: 0.0199). CRABP1 was association with lower COVID-19 susceptibility (OR: 0.95, 95% CI: 0.91-0.99, P: 0.0290) using the IVW. CONCLUSIONS: We found evidence of possible causal association of retinol, RBP4, RDH16 and CRABP1 with the susceptibility, hospitalization and severity of COVID-19. Our study defines that retinol is significantly associated with lower COVID-19 susceptibility, which provides a reference for the prevention of COVID-19 with vitamin A supplementation.

Research Note: SOCS2 contributes to reduction of the third digit during development of the chicken forelimb.

The development of the avian wing pattern has been the subject of heated debate due to its special shape. The Suppressor of cytokine signaling 2 (SOCS2) gene encodes a negative regulator of growth hormone (GH) signaling and bone growth and is known to be strongly expressed in the third digit of chicken forelimbs. These observations suggest that SOCS2 might regulate the morphology of the avian wing, however, the function of SOCS2 in avian limb development remains unknown. Here, we reexamined SOCS2 expression in successive developmental stages of chicken limb development by in situ hybridization (ISH) and describe extended expression from the posterior of the stypolod to the third digit of the forelimbs. We used the RCAS avian retrovirus to overexpress SOCS2 in the developing chicken limb buds, which resulted in reduced or malformed chicken wings while hindlimbs developed normally. Transcriptome sequencing (mRNA-Seq) revealed changes in expression of genes known to be associated with growth and development in forelimbs with overexpressed SOCS2. This study highlights a pivotal role for SOCS2 during the development of the wing in the chicken and provides new insight into molecular mechanisms regulating avian limb development.

Small extracellular vesicles purification and scale-up.

Exosomes are small extracellular vesicles (sEVs) secreted by cells. With advances in the study of sEVs, they have shown great potential in the diagnosis and treatment of disease. However, sEV therapy usually requires a certain dose and purity of sEVs to achieve the therapeutic effect, but the existing sEV purification technology exists in the form of low yield, low purity, time-consuming, complex operation and many other problems, which greatly limits the application of sEVs. Therefore, how to obtain high-purity and high-quality sEVs quickly and efficiently, and make them realize large-scale production is a major problem in current sEV research. This paper discusses how to improve the purity and yield of sEVs from the whole production process of sEVs, including the upstream cell line selection and cell culture process, to the downstream isolation and purification, quality testing and the final storage technology.

EvoAI enables extreme compression and reconstruction of the protein sequence space.

Designing proteins with improved functions requires a deep understanding of how sequence and function are related, a vast space that is hard to explore. The ability to efficiently compress this space by identifying functionally important features is extremely valuable. Here, we first establish a method called EvoScan to comprehensively segment and scan the high-fitness sequence space to obtain anchor points that capture its essential features, especially in high dimensions. Our approach is compatible with any biomolecular function that can be coupled to a transcriptional output. We then develop deep learning and large language models to accurately reconstruct the space from these anchors, allowing computational prediction of novel, highly fit sequences without prior homology-derived or structural information. We apply this hybrid experimental-computational method, which we call EvoAI, to a repressor protein and find that only 82 anchors are sufficient to compress the high-fitness sequence space with a compression ratio of 1048. The extreme compressibility of the space informs both applied biomolecular design and understanding of natural evolution.

Robotic Actuation-Mediated Quantitative Mechanogenetics for Noninvasive and On-Demand Cancer Therapy.

Cell mechanotransduction signals are important targets for physical therapy. However, current physiotherapy heavily relies on ultrasound, which is generated by high-power equipment or amplified by auxiliary drugs, potentially causing undesired side effects. To address current limitations, a robotic actuation-mediated therapy is developed that utilizes gentle mechanical loads to activate mechanosensitive ion channels. The resulting calcium influx precisely regulated the expression of recombinant tumor suppressor protein and death-associated protein kinase, leading to programmed apoptosis of cancer cell line through caspase-dependent pathway. In stark contrast to traditional gene therapy, the complete elimination of early- and middle-stage tumors (volume ≤ 100 mm3) and significant growth inhibition of late-stage tumor (500 mm3) are realized in tumor-bearing mice by transfecting mechanogenetic circuits and treating daily with quantitative robotic actuation in a form of 5 min treatment over the course of 14 days. Thus, this massage-derived therapy represents a quantitative strategy for cancer treatment.

Association between exposure to chemical mixtures and epigenetic ageing biomarkers: Modifying effects of thyroid hormones and physical activity.

Evidence on the effects of internal chemical mixture exposures on biological age is limited. It also remains unclear whether hormone homeostasis and lifestyle factors can modify such a relationship. Based on the Biomarkers for Air Pollutants Exposure (BAPE) study, which involved healthy older adults aged 60-69 years in China, we found that chemical mixture exposures, including metals, polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFASs), phthalates (PAEs), and organophosphate esters (OPEs), were significantly associated with shortened DNAmTL and accelerated SkinBloodClock, in which PFASs and OPEs in blood were the primary contributors to DNAmTL, while metals and PAEs had relatively higher contributions in urine. Furthermore, lower levels of thyroxin appeared to exacerbate the adverse effects of environmental chemicals on epigenetic ageing but relatively higher levels of physical activity had the beneficial impact. These findings may have important implications for the development of healthy ageing strategy and aged care policy, particularly in light of the global acceleration of population ageing.

Do wearing masks and preservatives have a combined effect on skin health?

Chemical exposure and local hypoxia caused by mask-wearing may result in skin physiology changes. The effects of methylparaben (MeP), a commonly used preservative in personal care products, and hypoxia on skin health were investigated by HaCaT cell and ICR mouse experiments. MeP exposure resulted in lipid peroxidation and interfered with cellular glutathione metabolism, while hypoxia treatment disturbed phenylalanine, tyrosine, and tryptophan biosynthesis pathways and energy metabolism to respond to oxidative stress. A hypoxic environment increased the perturbation of MeP on the purine metabolism in HaCaT cells, resulting in increased expression of proinflammatory cytokines. The synergistic effects were further validated in a mouse model with MeP dermal exposure and "mask-wearing" treatment. CAT, PPARG, and MMP2 were identified as possible key gene targets associated with skin health risks posed by MeP and hypoxia. Network toxicity analysis suggested a synergistic effect, indicating the risk of skin inflammation and skin barrier aging.

Cdc42-driven endosomal cholesterol transport promotes collateral resistance in HER2-positive gastric cancer.

Resistance to trastuzumab and the poor efficacy of subsequent chemotherapy have become major challenges for HER2-positive gastric cancer (GC). As resistance evolves, tumor cells may acquire a new drug susceptibility profile, profoundly impacting the subsequent treatment selection and patient survival. However, the interplay between trastuzumab and other types of drugs in HER2-positive GC remains elusive. In our study, we utilized resistant cell lines and tissue specimens to map the drug susceptibility profile of trastuzumab-resistant GC, discovering that resistance to trastuzumab induces collateral resistance to commonly used chemotherapeutic agents. Additionally, patients with collateral resistance distinguished by a 13-gene scoring model in HER2-positive GC cohorts are predicted to have a poor prognosis and may be sensitive to cholesterol-lowering drugs. Mechanistically, endosomal cholesterol transport is further confirmed to enrich cholesterol in the plasma membrane, contributing to collateral resistance through the Hedgehog-ABCB1 axis. As a driver for cholesterol, Cdc42 is activated by the formation of the NPC1-TßRI-Cdc42 complex to facilitate endosomal cholesterol transport. We demonstrated that inhibiting Cdc42 activation with ZCL278 reduces cholesterol levels in the plasma membrane and reverses collateral resistance between trastuzumab and chemotherapy in vitro and in vivo. Collectively, our findings verify the phenomena and mechanism of collateral resistance between trastuzumab and chemotherapy, and propose a potential therapeutic target and strategy in the second-line treatment for trastuzumab-resistant HER2-positive GC.

Bedside electrical impedance tomography to assist the management of pulmonary embolism: A case report.

Background: Pulmonary embolism (PE) is a common worldwide disease with high mortality. Timely diagnosis and management of PE could significantly improve clinical outcomes. Electrical impedance tomography (EIT) is a novel noninvasive technique to monitor lung perfusion and help detect PE at the bedside. Here we present a case of clinical management of subsegmental PE with the help of the bilateral ventilation and perfusion(V/Q) asymmetry EIT image. Case presentation: A 72-year-old cancer patient with respiratory failure and acute kidney injury in the intensive care unit was suspected of PE based on his clinical manifestation. The contraindication of computed tomography pulmonary angiography (CTPA) for PE diagnosis prevented escalating anticoagulation therapy. Besides EIT ventilation and perfusion monitoring showed an abnormal asymmetry V/Q match between the bilateral lungs which promoted our decision to start systemic continuous anticoagulation therapy and improved the patient clinically. The following CTPA which clarified the diagnosis of PE suggests that the patient has benefited from our decision. Conclusion: For critically ill patients with suspected PE, the asymmetry of the EIT V/Q image may provide crucial objective information for clinical management.

Performance of Artificial Intelligence in Detecting Diabetic Macular Edema From Fundus Photography and Optical Coherence Tomography Images: A Systematic Review and Meta-analysis.

BACKGROUND: Diabetic macular edema (DME) is the leading cause of vision loss in people with diabetes. Application of artificial intelligence (AI) in interpreting fundus photography (FP) and optical coherence tomography (OCT) images allows prompt detection and intervention. PURPOSE: To evaluate the performance of AI in detecting DME from FP or OCT images and identify potential factors affecting model performances. DATA SOURCES: We searched seven electronic libraries up to 12 February 2023. STUDY SELECTION: We included studies using AI to detect DME from FP or OCT images. DATA EXTRACTION: We extracted study characteristics and performance parameters. DATA SYNTHESIS: Fifty-three studies were included in the meta-analysis. FP-based algorithms of 25 studies yielded pooled area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of 0.964, 92.6%, and 91.1%, respectively. OCT-based algorithms of 28 studies yielded pooled AUROC, sensitivity, and specificity of 0.985, 95.9%, and 97.9%, respectively. Potential factors improving model performance included deep learning techniques, larger size, and more diversity in training data sets. Models demonstrated better performance when validated internally than externally, and those trained with multiple data sets showed better results upon external validation. LIMITATIONS: Analyses were limited by unstandardized algorithm outcomes and insufficient data in patient demographics, OCT volumetric scans, and external validation. CONCLUSIONS: This meta-analysis demonstrates satisfactory performance of AI in detecting DME from FP or OCT images. External validation is warranted for future studies to evaluate model generalizability. Further investigations may estimate optimal sample size, effect of class balance, patient demographics, and additional benefits of OCT volumetric scans.

Worldwide productivity and research trend of publications concerning extracellular vesicles role in fibrosis: A bibliometric study from 2013 to 2022.

Background: Fibrosis is a heavy burden on the global healthcare system. Recently, an increasing number of studies have demonstrated that Extracellular vesicles play an important role in intercellular communication under both physiological and pathological conditions. This study aimed to explore the role of extracellular vesicles' in fibrosis using bibliometric methods. Methods: Original articles and reviews related to extracellular vesicles and fibrosis were obtained from the Web of Science Core Collection database on November 9, 2022. VOSviewer was used to obtain general information, including co-institution, co-authorship, and co-occurrence visualization maps. The CiteSpace software was used to analyze citation bursts of keywords and references, a timeline view of the top clusters of keywords and cited articles, and the dual map. R package "bibliometrix" was used to analyze annual production, citation per year, collaboration network between countries/regions, thematic evolution map, and historiography network. Results: In total, 3376 articles related to extracellular vesicles and fibrosis published from 2013 to 2022 were included in this study, with China and the United States being the top contributors. Shanghai Jiao Tong University has the highest number of publications. The main collaborators were Giovanni Camussi, Stefania Bruno, Marta Tepparo, and Cristina Grange. Journals related to molecular, biology, genetics, health, immunology, and medicine tended to publish literature on extracellular vesicles and fibrosis. "Recovery," "heterogeneity," "degradation," "inflammation," and "mesenchymal stem cells" are the keywords in this research field. Literature on extracellular vesicles and fibrosis associated with several diseases, including "kidney disease," "rheumatoid arthritis," and "skin regeneration" may be the latest hot research field. Conclusions: This study provides a comprehensive perspective on extracellular vesicles and fibrosis through a bibliometric analysis of articles published between 2013 and 2022. We identified the most influential countries, institutions, authors, and journals. We provide information on recent research frontiers and trends for scholars interested in the field of extracellular vesicles and fibrosis. Their role in biological processes has great potential to initiate a new upsurge in future research.

Development and characterization of a novel neutralizing scFv vectored immunoprophylaxis against botulinum toxin type A.

Botulinum toxin is a protein toxin secreted by Clostridium botulinum that is strongly neurotoxic. Due to its characteristics of being super toxic, quick acting, and difficult to prevent, the currently reported antiviral studies focusing on monoclonal antibodies have limited effectiveness. Therefore, for the sake of effectively prevention and treatment of botulism and to maintain country biosecurity as well as the health of the population, in this study, we intend to establish a single chain antibody (scFv) targeting the carboxyl terminal binding functional domain of the botulinum neurotoxin heavy chain (BONT/AHc) of botulinum neurotoxin type A, and explore the value of a new passive immune method in antiviral research which based on adeno-associated virus (AAV) mediated vector immunoprophylaxis (VIP) strategy. The scFv small-molecular single-chain antibody sequenced, designed, constructed, expressed and purified by hybridoma has high neutralising activity and affinity level, which can lay a good foundation for the modification and development of antibody engineering drugs. In vivo experiments, AAV-mediated scFv engineering drug has good anti-BONT/A toxin neutralisation ability, has advantages of simple operation, stable expression and good efficacy, and may be one of the effective treatment strategies for long-term prevention and protection of BONT/A botulinum neurotoxin.

A study on the Si1-xGex gradual buffer layer of III-V/Si multi-junction solar cells based on first-principles calculations.

III-V/Si multi-junction solar cells have been widely studied in recent years due to their excellent theoretical efficiency (∼42%). In order to solve the problem of lattice mismatch between Si and III-V compounds of III-V/Si solar cells, different hexagonal Si1-xGex buffer layer models on the surface of hexagonal diamond Si(001) were built, and the structural, electronic and optical properties of the proposed models were calculated based on first principles calculations. The results showed that all models of the designed buffer layer could effectively reduce the lattice mismatch, and the buffer layer hex-Si1-xGex (x = 0, 0.75, and 1) is the ideal model and has achieved the best lattice-matching improvement with high defect formation energy, as well as direct band gap properties and a larger light adsorption coefficient. These theoretical models, with their analyzed properties, could offer a promising pathway toward realizing high efficiency and low cost III-V/Si multi-junction solar cells.

Succinylation proteomic analysis identified differentially expressed succinylation sites affecting porcine muscle fiber type function.

Muscle fiber type is a major factor in pork meat quality, however, the role of post-translational protein modifications, especially succinylation, in the regulation of muscle fiber type is not fully understood. Here we performed protein succinylation profiles of fast-type biceps femoris (BF) and slow-type soleus (SOL) muscles. A total of 4,221 succinylation sites were identified from these samples, of which 294 sites were differentially expressed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that these succinylated proteins were mainly involved in glycolysis, tricarboxylic acid cycle, and fatty acid metabolism. Succinylation modification of the CRAT and RAB10 proteins was verified by co-immunoprecipitation. Protein-protein interaction (PPI) network analysis unveiled the interactions of these succinylated proteins that regulate pig myofiber type conversion. This investigation offers fresh perspectives into the molecular roles of protein succinylation in the regulation of pig myofiber type transformation and meat quality.

[Circadian rhythm and health: dialogue between traditional Chinese medicine and modern medicine].

Circadian rhythm refers to the daily rhythmic variations in an organism. The irregular lifestyles of modern humans have led to a high incidence of chronic diseases, highlighting an inseparable relationship between disrupted circadian rhythm and disease development. TCM has long discussed rhythmic variations, with records dating back to the Yellow Emperor's Inner Canon(Huang Di Nei Jing), which laid a rich theoretical foundation for the research on circadian rhythm. Modern medical research has provided a more comprehensive explanation of its molecular mechanisms. This article integrated the current understanding of circadian rhythm in both Chinese and western medicine, emphasizing the crucial relationship between rhythm regulation and disease treatment. By highlighting the interdisciplinary nature of the two fields, it offers new directions for exploring the field of chronomedicine.