Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo.

Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies.

Efficacy of aerobic training and resistance training combined with external diaphragm pacing in patients with chronic obstructive pulmonary disease: A randomized controlled study.

OBJECTIVE: To evaluate the efficacy of aerobic training, resistance training combined with external diaphragm pacing in patients with chronic obstructive pulmonary disease. DESIGN: Randomized controlled trial. SETTING: The Fourth Rehabilitation Hospital of Shanghai, China. PARTICIPANTS: 82 (67.0 ± 6.5 years, 59.8% male) patients with stable chronic obstructive pulmonary disease were randomized to intervention group 1 (n = 27), intervention group 2 (n = 28), and control group (n = 27). INTERVENTION: Intervention group 1 received aerobic and resistance training, while intervention group 2 received additional external diaphragm pacing. Control group received aerobic training only. MAIN MEASURES: 1-year follow-up of physical activity, body composition, respiratory function and diaphragm function. RESULTS: Intervention groups 1 and 2 showed statistically improvements in the difference value compared with control group in terms of 6-min walk distance (-95.28 ± 20.09 and -101.92 ± 34.91 vs -63.58 ± 23.38), forced expiratory volume in 1 s (-0.042 ± 0.027 and -0.130 ± 0.050 vs -0.005 ± 0.068), fat-free mass (-2.11 ± 3.74 and -3.82 ± 3.74vs 0.28 ± 1.49) and chronic obstructive pulmonary disease assessment test value (2.16 ± 0.85 and 2.38 ± 1.02 vs 1.50 ± 0.93). Intervention group 2 showed significant difference in arterial oxygen pressure (-4.46 ± 3.22 vs -1.92 ± 3.45), diaphragm excursion during deep breaths (-0.82 ± 0.74 vs -0.38 ± 0.29), and diaphragm thickness fraction (-8.77 ± 3.22 vs -4.88 ± 2.69) compared with control group. CONCLUSION: The combination of aerobic training, resistance training, and external diaphragm pacing obtained significant improvements in physical activity, respiratory function, body composition, arterial oxygen pressure, and diaphragm function in patients with chronic obstructive pulmonary disease. TRIAL REGISTRATION: ChiCTR1800020257, www.chictr.org.cn/index.aspx.

Microbiota-mediated shaping of mouse spleen structure and immune function characterized by scRNA-seq and Stereo-seq.

Gut microbes exhibit complex interactions with their hosts and shape an organism's immune system throughout its lifespan. As the largest secondary lymphoid organ, the spleen has a wide range of immunological functions. To explore the role of microbiota in regulating and shaping the spleen, we employ scRNA-seq and Stereo-seq technologies based on germ-free (GF) mice to detect differences in tissue size, anatomical structure, cell types, functions, and spatial molecular characteristics. We identify 18 cell types, 9 subtypes of T cells, and 7 subtypes of B cells. Gene differential expression analysis reveals that the absence of microorganisms results in alterations in erythropoiesis within the red pulp region and congenital immune deficiency in the white pulp region. Stereo-seq results demonstrate a clear hierarchy of immune cells in the spleen, including marginal zone (MZ) macrophages, MZ B cells, follicular B cells and T cells, distributed in a well-defined pattern from outside to inside. However, this hierarchical structure is disturbed in GF mice. Ccr7 and Cxcl13 chemokines are specifically expressed in the spatial locations of T cells and B cells, respectively. We speculate that the microbiota may mediate the structural composition or partitioning of spleen immune cells by modulating the expression levels of chemokines.

Growth restriction and congenital heart disease caused by a novel TAB2 mutation: A case report.

Congenital heart disease (CHD) is a malformation present from birth caused by the abnormal development of the heart and large blood vessels during the prenatal development. The TGF-ß activated kinase 1 (MAP3K7) binding protein 2 (TAB2) gene plays an important role in the embryonic development of heart tissue. When haploid dosage is insufficient, it can lead to CHD or cardiomyopathy. The present study reported a case study of a Chinese child with growth restriction and CHD. The results of whole exome sequencing suggested that a novel frameshift mutation (c.1056delC/p.Ser353fsTer8) occurred in TAB2. The parents of this patient are wild-type at this locus; therefore, it may be a de novo mutation. The mutant plasmid was constructed in vitro, and the western blotting results showed that the mutation may cease protein expression. This indicated the pathogenic harmfulness of this mutation. In conclusion, the present study emphasizes that TAB2 defects should be investigated in patients with unexplained short stature and CHD, irrespective of family history regarding CHD or cardiomyopathy. The current study provided new data on the mutation spectrum and provided information for second pregnancies and genetic counseling of the parents of patients.

Screening of a High-Affinity Aptamer for Aflatoxin M1 and Development of Its Colorimetric Aptasensor.

Aflatoxin M1 (AFM1), a secondary metabolite of Aspergillus spp., is highly toxic and widely present in food matrices. Therefore, the detection of AFM1 is of great importance for the protection of food safety. In this study, a five-segment sequence was designed as the initial library. Graphene oxide-SELEX (GO-SELEX) was applied to screen AFM1. After seven rounds of repeated screening, affinity and specificity assays showed that aptamer 9 was the best candidate for AFM1. The dissociation constant (Kd) of aptamer 9 was 109.10 ± 6.02 nM. To verify the efficiency and sensitivity aptamer for the detection of AFM1, a colorimetric sensor based on the aptamer was constructed. The biosensor showed good linearity in the range of AFM1 concentration of 0.5-500.0 ng/mL with a detection limit of 0.50 ng/mL. This colorimetric method was successfully used for the detection of AFM1 in milk powder samples. Its detection recovery was 92.8-105.2%. This study was conducted to provide a reference for the detection of AFM1 in food.

A review of the occurrence, metabolites and health risks of butylated hydroxyanisole (BHA).

Butylated hydroxyanisole (BHA) is mainly used as a food additive due to its antioxidant properties, which prevent or delay oxidation reactions and extend the storage life of products. The widespread use of BHA has led to its extensive presence in various environmental matrices and human tissues. Food intake is the main route of human exposure to BHA. Under different conditions, BHA can produce different metabolites, with tert-butyl hydroquinone (TBHQ) being one of the major products. Several studies have shown that BHA could cause thyroid system damage, metabolic and growth disorders, neurotoxicity, and carcinogenesis. Mechanisms such as endocrine disruption, genotoxicity, disturbances of energy metabolism, reactive oxygen species (ROS) production, signaling pathways, and imbalances in calcium homeostasis appear to be associated with the toxic effects of BHA. Avoiding the toxic effects of BHA to the maximum extent possible is a top priority. Finding safe, non-toxic and environmentally friendly alternatives to BHA should be the focus of subsequent research. In all, this review summarized the current situation related to BHA and might make recommendations for future research directions. © 2023 Society of Chemical Industry.

Clinical application of spinal robot in cervical spine surgery: safety and accuracy of posterior pedicle screw placement in comparison with conventional freehand methods.

The novel robot-assisted (RA) technique has been utilized increasingly to improve the accuracy of cervical pedicle screw placement. Although the clinical application of the RA technique has been investigated in several case series and comparative studies, the superiority and safety of RA over conventional freehand (FH) methods remain controversial. Meanwhile, the intra-pedicular accuracy of the two methods has not been compared for patients with cervical traumatic conditions. This study aimed to compare the rate and risk factors of intra-pedicular accuracy of RA versus the conventional FH approach for posterior pedicle screw placement in cervical traumatic diseases. A total of 52 patients with cervical traumatic diseases who received cervical screw placement using RA (26 patients) and FH (26 patients) techniques were retrospectively included. The primary outcome was the intra-pedicular accuracy of cervical pedicle screw placement according to the Gertzbin-Robbins scale. Secondary outcome parameters included surgical time, intraoperative blood loss, postoperative drainage, postoperative hospital stay, and complications. Moreover, the risk factors that possibly affected intra-pedicular accuracy were assessed using univariate analyses. Out of 52 screws inserted using the RA method, 43 screws (82.7%) were classified as grade A, with the remaining 7 (13.5%) and 2 (3.8%) screws classified as grades B and C. In the FH cohort, 60.8% of the 79 screws were graded A, with the remaining screws graded B (21, 26.6%), C (8, 10.1%), and D (2, 2.5%). The RA technique showed a significantly higher rate of optimal intra-pedicular accuracy than the FH method (P = 0.008), but there was no significant difference between the two groups in terms of clinically acceptable accuracy (P = 0.161). Besides, the RA technique showed remarkably longer surgery time, less postoperative drainage, shorter postoperative hospital stay, and equivalent intraoperative blood loss and complications than the FH technique. Furthermore, the univariate analyses showed that severe obliquity of the lateral atlantoaxial joint in the coronal plane (P = 0.003) and shorter width of the lateral mass at the inferior margin of the posterior arch (P = 0.014) were risk factors related to the inaccuracy of C1 screw placement. The diagnosis of HRVA (P < 0.001), severe obliquity of the lateral atlantoaxial joint in the coronal plane (P < 0.001), short pedicle width (P < 0.001), and short pedicle height (P < 0.001) were risk factors related to the inaccuracy of C2 screw placement. RA cervical pedicle screw placement was associated with a higher rate of optimal intra-pedicular accuracy to the FH technique for patients with cervical traumatic conditions. The severe obliquity of the lateral atlantoaxial joint in the coronal plane independently contributed to high rates of the inaccuracy of C1 and C2 screw placements. RA pedicle screw placement is safe and useful for cervical traumatic surgery.

Plasma 25-hydroxyvitamin D levels and survival in stage III colon cancer: Findings from CALGB/SWOG 80702 (Alliance).

PURPOSE: To assess whether higher plasma 25-hydroxyvitamin D (25[OH]D) are associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association. PATIENTS AND METHODS: Plasma samples were collected from 1437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). Mediation analysis was performed for circulating inflammatory biomarkers of CRP, IL-6, and sTNF-R2. RESULTS: Vitamin D deficiency (25(OH)D<12 ng/ml) was present in 13% of total patients at baseline and in 32% of Black patients. Compared with deficiency, non-deficient vitamin D status (≥12 ng/ml) was significantly associated with improved DFS, OS and TTR (all Plog-rank<0.05), with multivariable-adjusted hazard ratios of 0.68 (95% confidence interval [CI], 0.51-0.92) for DFS, 0.57 (0.40-0.80) for OS, and 0.71 (0.52-0.98) for TTR. A U-shaped dose-response pattern was observed for DFS and OS (both Pnon-linearity<0.05). The proportion of the association with survival that was mediated by sTNF-R2 was 10.6% (P mediation=0.04) for DFS and 11.8% (P mediation=0.05) for OS, whereas CRP and IL-6 were not shown to be mediators. Plasma 25(OH)D was not associated with the occurrence of ≥ grade 2 adverse events. CONCLUSIONS: Non-deficient vitamin D is associated with improved outcomes in patients with stage III colon cancer, largely independent of circulation inflammations. A randomized trial is warranted to elucidate if adjuvant vitamin D supplementation improves patient outcomes.

Protein Function Prediction with Functional and Topological Knowledge of Gene Ontology.

Gene Ontology (GO) is a widely used bioinformatics resource for describing biological processes, molecular functions, and cellular components of proteins. It covers more than 5000 terms hierarchically organized into a directed acyclic graph and known functional annotations. Automatically annotating protein functions by using GO-based computational models has been an area of active research for a long time. However, due to the limited functional annotation information and complex topological structures of GO, existing models cannot effectively capture the knowledge representation of GO. To solve this issue, we present a method that fuses the functional and topological knowledge of GO to guide protein function prediction. This method employs a multi-view GCN model to extract a variety of GO representations from functional information, topological structure, and their combinations. To dynamically learn the significance weights of these representations, it adopts an attention mechanism to learn the final knowledge representation of GO. Furthermore, it uses a pre-trained language model (i.e., ESM-1b) to efficiently learn biological features for each protein sequence. Finally, it obtains all predicted scores by calculating the dot product of sequence features and GO representation. Our method outperforms other state-of-the-art methods, as demonstrated by the experimental results on datasets from three different species, namely Yeast, Human and Arabidopsis. Our proposed method's code can be accessed at: https://github.com/Candyperfect/Master.

Association between Urine Albumin-to-creatinine Ratio and Intracranial Atherosclerotic Plaque in Chinese Adults - Results from the PRECISE Study.

AIMS: Intracranial plaque may cause stroke in the absence of luminal stenosis. Although urine albumin-to-creatinine ratio (ACR) has been proved an established risk factor for cardiovascular disease, stroke and carotid atherosclerosis, little is known on the relationship between urine ACR and intracranial plaque. METHODS: Subjects with history of stroke or coronary heart disease (CHD) were excluded in the PRECISE study. The intracranial plaque was assessed by vessel wall magnetic resonance imaging (MRI). Subjects were stratified according to ACR tertiles. Logistic regression and ordinal regression were performed to analyze the association between ACR and the presence of intracranial plaque or sum of the stenosis score for each artery. RESULTS: 2962 individuals were included with the mean age of 61.0±6.6 years. The median ACR was 11.7mg/g (interquartile range 7.0-22.0 mg/g), and the mean estimated glomerular filtration rate (eGFR) based on combination of creatinine and cystatin C was 88.5 ±14.8 ml/min·1.73m 2. 495 (16.7%) participants had intracranial plaque. The highest ACR tertile with ACR ＞16.00mg/g was independently associated with the presence of intracranial plaque (OR 1.38, 95% CI: 1.05-1.82, p=0.02) and the odds of higher intracranial plaque burden (common OR 1.39, 95% CI: 1.05-1.83, p=0.02) after adjustment of confounding factors. No significant association was observed between eGFR and intracranial plaque presence or intracranial plaque burden. CONCLUSIONS: Among a low-risk community-dwelling population without prior stroke or CHD in China, ACR was independently associated with intracranial plaque presence and plaque burden measured by vessel wall MRI.

Effects of forage type on the rumen microbiota, growth performance, carcass traits, and meat quality in fattening goats.

Forages fed to goats influence ruminal microbiota, and further contribute to affect growth performance, meat quality and its nutritional composition. Our objective for current study was to investigate the effects of different forages on growth performance, carcass traits, meat nutritional composition, rumen microflora, and the relationships between key bacteria and amino acids and fatty acids in the longissimus dorsi and semimembranosus muscles of goats. Boer crossbred goats were separately fed commercial concentrate diet supplemented with Hemarthria altissima (HA), Pennisetum sinese (PS), or forage maize (FG), and then slaughtered 90 days after the beginning of the experiment. Growth performances did not vary but carcass traits of dressing percentage, semi-eviscerated slaughter percentage, and eviscerated slaughter percentage displayed significant difference with the treatment studied. Meats from goats fed forage maize, especially semimembranosus muscles are rich in essential amino acids, as well as an increase in the amount of beneficial fatty acids. Our 16S rRNA gene sequencing results showed that the Firmicutes, Bacteroidetes, and Proteobacteria were the most dominant phyla in all groups but different in relative abundance. Further, the taxonomic analysis and linear discriminant analysis effect size (LEfSe) identified the specific taxa that were differentially represented among three forage treatments. The spearman's correlation analysis showed that rumen microbiota was significantly associated with the goat meat nutritional composition, and more significant positive correlations were identified in semimembranosus muscles when compared with longissimus dorsi muscles. More specifically, the lipid metabolism-related bacteria Rikenellaceae_RC9_gut_group showed positively correlated with meat amino acid profile, while genera Oscillospiraceae_UCG-005 were positively correlated with fatty acid composition. These bacteria genera might have the potential to improve nutritional value and meat quality. Collectively, our results showed that different forages alter the carcass traits, meat nutritional composition, and rumen microflora in fattening goats, and forage maize induced an improvement in its nutritional value.

Preparation and characterization of curcumin/chitosan conjugate as an efficient photodynamic antibacterial agent.

Curcumin (Cur) is a natural pigment with excellent biological activity. The poor stability and insolubility of Cur in water severely limit its application. Therefore, to overcome these dilemmas which are big hindrances in their application, a novel derivative (COCS-Cur) was prepared by the esterification reaction of carboxylated chitosan (COCS) and Cur. The structure and properties of conjugate were determined through a series of characterizations. The derivatives had excellent solubility as well as stability. In addition, antioxidant and photodynamic antibacterial experiments proved that COCS-Cur had the excellent free radical scavenging ability and photodynamic antibacterial activity. The derivatives presented a better antibacterial effect on Staphylococcus aureus (S. aureus) than Escherichia coli (E. coli). Noteworthy, the COCS-Cur derivatives showed no obvious toxicity which makes them a stronger contender and potential antimicrobial agent or functional nutrient for application in the food industry.

Broad-Spectrum Detection of Tetracyclines by Riboswitch-Based Cell-Free Expression Biosensing.

We describe a sensitive and selective method for the determination of tetracycline content in foods using a riboswitch sensor. The sensor is based on a cell-free expression system that can be lyophilized to produce paper-based sensors or tube-based sensors for long-term storage. The riboswitch constructed using artificially screened tetracycline RNA aptamers was cloned into the pET-28a(+) vector of Escherichia coli TOP 10. The expression of the green fluorescent protein was positively correlated with the concentration of tetracyclines. The binding of tetracyclines to the aptamer domain results in a conformational change in the riboswitch secondary structure, resulting in the exposure of the ribosome binding site thereby promoting expression. The detection limits of the prepared sensor for the detection of tetracycline, oxytetracycline, chlortetracycline, and doxycycline were 0.47, 0.079, 0.084, and 0.43 µM, respectively. Moreover, the 1 µM tetracyclines allow for qualitative detection in milk samples by the naked eye. The work provides a proof-of-principle for riboswitch design to address global health and food safety.

Data Science Curriculum in the iField.

Many disciplines, including the broad Field of Information (iField), have been offering Data Science (DS) programs. There have been significant efforts exploring an individual discipline's identity and unique contributions to the broader DS education landscape. To advance DS education in the iField, the iSchool Data Science Curriculum Committee (iDSCC) was formed and charged with building and recommending a DS education framework for iSchools. This paper reports on the research process and findings of a series of studies to address important questions: What is the iField identity in the multidisciplinary DS education landscape? What is the status of DS education in iField schools? What knowledge and skills should be included in the core curriculum for iField DS education? What are the jobs available for DS graduates from the iField? What are the differences between graduate-level and undergraduate-level DS education? Answers to these questions will not only distinguish an iField approach to DS education but also define critical components of DS curriculum. The results will inform individual DS programs in the iField to develop curriculum to support undergraduate and graduate DS education in their local context.

Bimetallic bionic taste sensor for perception of the synergistic effect of umami substances.

Synergistic effect is one of the main properties of umami substances, elucidating the synergistic effect of umami is of great significance in the food industry. In this study, a bimetallic bionic taste sensor was developed to evaluate the synergistic effect of umami substances based on the perceptual mechanism of the human taste system. The Venus flytrap domain of T1R1 which is in charge of recognizing umami ligands was employed as the sensing element and self-assembled on the bimetallic nanomaterial (MoS2-PtPd) by Au-S bonding, the binding of receptors and ligands is characterized by changes of electrical signals. The sensor had good linearity (R2 > 0.99) and wide detection range in the detection of different kinds of umami substances (amino acids, nucleotides, organic acids, umami peptides) with detection limits as low as 0.03 pM. Comparing with electronic tongues, the sensor owned multiple characteristics of human taste system and could recognize the presence of synergistic effect of umami substances in a variety of real samples. Moreover, the differences in synergistic effect at different concentrations and ratios were also explored, the findings showed that the synergistic effect was more obvious at lower concentrations and balanced ratios of multiple umami substances added. The strategy would afford a promising platform for in-depth research on the mechanism of synergistic effect and multifunctional industrial applications.

Pancreatic cancer is associated with medication changes prior to clinical diagnosis.

Patients with pancreatic ductal adenocarcinoma (PDAC) commonly develop symptoms and signs in the 1-2 years before diagnosis that can result in changes to medications. We investigate recent medication changes and PDAC diagnosis in Nurses' Health Study (NHS; females) and Health Professionals Follow-up Study (HPFS; males), including up to 148,973 U.S. participants followed for 2,994,057 person-years and 991 incident PDAC cases. Here we show recent initiation of antidiabetic (NHS) or anticoagulant (NHS, HFS) medications and cessation of antihypertensive medications (NHS, HPFS) are associated with pancreatic cancer diagnosis in the next 2 years. Two-year PDAC risk increases as number of relevant medication changes increases (P-trend <1 × 10-5), with participants who recently start antidiabetic and stop antihypertensive medications having multivariable-adjusted hazard ratio of 4.86 (95%CI, 1.74-13.6). These changes are not associated with diagnosis of other digestive system cancers. Recent medication changes should be considered as candidate features in multi-factor risk models for PDAC, though they are not causally implicated in development of PDAC.

Aurantio-obtusin ameliorates obesity by activating PPARα-dependent mitochondrial thermogenesis in brown adipose tissues.

Obesity contributes to the progression of various chronic diseases, and shortens life expectancy. With abundant mitochondria, brown adipose tissue (BAT) dissipates energy through heat to limit weight gain and metabolic dysfunction in obesity. Our previous studies have shown that aurantio-obtusin (AO), a bioactive ingredient in Chinese traditional medicine Cassiae semen significantly improves hepatic lipid metabolism in a steatotic mouse model. In the current study we investigated the effects of AO on lipid metabolism in the BAT of diet-induced obesity mice and in oleic acid and palmitic acid (OAPA)-stimulated primary mature BAT adipocytes. Obese mice were established by feeding a HFHS diet for 4 weeks, and then administered AO (10 mg/kg, i.g.) for another 4 weeks. We showed that AO administration significantly increased the weight of BAT and accelerated energy expenditure to protect the weight increase in the obese mice. Using RNA sequencing and molecular biology analysis we found that AO significantly enhanced mitochondrial metabolism and UCP1 expression by activating PPARα both in vivo and in vitro in the primary BAT adipocytes. Interestingly, AO administration did not improve metabolic dysfunction in the liver and white adipose tissue of obese mice after interscapular BAT excision. We demonstrated that low temperature, a trigger of BAT thermogenesis, was not a decisive factor for AO to stimulate the growth and activation of BATs. This study uncovers a regulatory network of AO in activating BAT-dependent lipid consumption and brings up a new avenue for the pharmaceutical intervention in obesity and related comorbidities.

Improving Protein Function Prediction by Adaptively Fusing Information From Protein Sequences and Biomedical Literature.

Proteins are the main undertakers of life activities, and accurately predicting their biological functions can help human better understand life mechanism and promote the development of themselves. With the rapid development of high-throughput technologies, an abundance of proteins are discovered. However, the gap between proteins and function annotations is still huge. To accelerate the process of protein function prediction, some computational methods taking advantage of multiple data have been proposed. Among these methods, the deep-learning-based methods are currently the most popular for their capability of learning information automatically from raw data. However, due to the diversity and scale difference between data, it is challenging for existing deep learning methods to capture related information from different data effectively. In this paper, we introduce a deep learning method that can adaptively learn information from protein sequences and biomedical literature, namely DeepAF. DeepAF first extracts the two kinds of information by using different extractors, which are built based on pre-trained language models and can capture rudimentary biological knowledge. Then, to integrate those information, it performs an adaptive fusion layer based on a Cross-attention mechanism that considers the knowledge of mutual interactions between two information. Finally, based on the mixed information, DeepAF utilizes logistic regression to obtain prediction scores. The experimental results on the datasets of two species (i.e., Human and Yeast) show that DeepAF outperforms other state-of-the-art approaches.

Influence of the initial recurrence site on prognosis after radical surgery for colorectal cancer: a retrospective cohort study.

BACKGROUND & AIMS: In this retrospective study, we aimed to elucidate how the initial recurrence site influences the post-recurrence survival (PRS) after the curative resection of colorectal cancer. PATIENTS AND METHODS: We collected samples from patients with stage I-III colorectal adenocarcinoma who were admitted to Yunnan Cancer Hospital from January 2008 to December 2019. Four hundred and six patients who developed recurrence after radical resection were included. The cases were classified according to the original site of recurrence as follows: liver metastases (n = 98), lung metastases (n = 127), peritoneum (n = 32), other individual organ (n = 69), two or more organs or sites (n = 49), and local recurrence (n = 31). Kaplan-Meier survival curves were used to compare the PRS of patients with different initial sites of recurrence. The influence of the initial recurrence site on PRS was analyzed using the Cox proportional hazards model. RESULTS: The 3-year PRS of simple liver metastasis was 54.04% (95% CI, 45.46%-64.24%), and the 3-year PRS of simple lung metastasis was 50.05% (95% CI, 42.50%-58.95%). No significant difference was observed between simple liver metastasis or simple lung metastasis and local recurrence with a 3-year PRS of 66.99% (95% CI, 53.23%-84.32%). The 3-year PRS for peritoneal metastases was 25.43% (95% CI, 14.76%-43.82%), and the 3-year PRS for two or more organ sites was 34.84% (95% CI, 24.16%-50.24%). The peritoneal (hazard ratio [HR], 1.75; 95% CI, 1.10-2.79; P = 0.0189) and metastasis to two or more organs or sites (HR, 1.59; 95% CI, 1.05-2.43; P = 0.0304) were PRS-independent adverse prognostic factors. CONCLUSION: The prognosis of patients with peritoneum and multiple organs or sites recurred was poor. This study suggests early monitoring of peritoneal and multiple organ or site recurrence after surgery. This part of patients should receive comprehensive treatment as early as possible to improve their prognosis.

Study of binding mechanism of aptamer to kanamycin and the development of fluorescent aptasensor in milk detection.

Aptasensors being versatile sensing platforms presented higher sensitivity toward target detection. However, lacking theoretical basis of recognition between most targets and their corresponding aptamers has impeded their applications. Herein, we conducted a study to explore the binding mechanism of aptamer to kanamycin (Kana) and developed rapid fluorescent aptasensing methods. Based on the fluorescence polarization results, base mutations were performed at different sites of the aptamer. The key binding nucleotides of Kana was identified as T7, T8, C13 and A15 by using isothermal titration calorimetry (ITC). The Kmut3 (2.18 µM) with lower dissociation constants (Kd), one-third of the native aptamer (6.91 µM), was also obtained. In addition, the lower K+ concentration and temperature were found to be conducive to Kana binding. Circular dichroism (CD) results revealed that the binding of Kana can trigger the change of base stacking force and helix force. On the aforementioned basis, a fluorescent sensor was designed with the native aptamer and Kmut3 as recognition elements. The comparison results proved that the Kmut3 presented a 3 times lower limit of detection of 59 nM compared to the native aptamer (148 nM). Notably, this developed aptasensor can be finished in 45 min and was convenient to operate.