Subgenome-aware analyses reveal the genomic consequences of ancient allopolyploid hybridizations throughout the cotton family.

Malvaceae comprise some 4,225 species in 243 genera and nine subfamilies and include economically important species, such as cacao, cotton, durian, and jute, with cotton an important model system for studying the domestication of polyploids. Here, we use chromosome-level genome assemblies from representatives of five or six subfamilies (depending on the placement of Ochroma) to differentiate coexisting subgenomes and their evolution during the family's deep history. The results reveal that the allohexaploid Helicteroideae partially derive from an allotetraploid Sterculioideae and also form a component of the allodecaploid Bombacoideae and Malvoideae. The ancestral Malvaceae karyotype consists of 11 protochromosomes. Four subfamilies share a unique reciprocal chromosome translocation, and two other subfamilies share a chromosome fusion. DNA alignments of single-copy nuclear genes do not yield the same relationships as inferred from chromosome structural traits, probably because of genes originating from different ancestral subgenomes. These results illustrate how chromosome-structural data can unravel the evolutionary history of groups with ancient hybrid genomes.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

IGF-1-mediated FOXC1 overexpression induces stem-like properties through upregulating CBX7 and IGF-1R in esophageal squamous cell carcinoma.

Substantial evidence attests to the pivotal role of cancer stem cells (CSC) in both tumorigenesis and drug resistance. A member of the forkhead box (FOX) family, FOXC1, assumes significance in embryonic development and organogenesis. Furthermore, FOXC1 functions as an overexpressed transcription factor in various tumors, fostering proliferation, enhancing migratory capabilities, and promoting drug resistance, while maintaining stem-cell-like properties. Despite these implications, scant attention has been devoted to its role in esophageal squamous cell carcinoma. Our investigation revealed a pronounced upregulation of FOXC1 expression in ESCC, correlating with a poor prognosis. The downregulation of FOXC1 demonstrated inhibitory effects on ESCC tumorigenesis, proliferation, and tolerance to chemotherapeutic agents, concurrently reducing the levels of stemness-related markers CD133 and CD44. Further studies validated that FOXC1 induces ESCC stemness by transactivating CBX7 and IGF-1R. Additionally, IGF-1 activated the PI3K/AKT/NF-κB and MEK/ERK/NF-κB pathways through its binding to IGF-1R, thereby augmenting FOXC1 expression. Conversely, suppressing FOXC1 impeded ESCC stemness induced by IGF-1. The presence of a positive feedback loop, denoted by IGF-1-FOXC1-IGF-1R, suggests the potential of FOXC1 as a prognostic biomarker for ESCC. Taken together, targeting the IGF-1-FOXC1-IGF-1R axis emerges as a promising approach for anti-CSC therapy in ESCC.

Performance Optimization of Ionic Polymer Sensors through Characteristic Regulation of Chemically Prepared Interfacial Electrodes.

Ionic polymer sensors (IPSs) have broad application prospects in health monitoring, environmental perception, and human-computer interaction. The performance of IPSs with chemically prepared electrodes is generally superior to that with physically prepared electrodes due to the area difference of the electric double layer (EDL), but the effects of the electrode characteristics prepared by chemical methods on the performance of IPSs have not been revealed. Therefore, in this paper, we studied the impact of the characteristics of chemically prepared electrodes on the performance of IPSs and realized the performance optimization of IPSs through electrode characteristic regulation. By controlling the matrix surface roughening, immersion reduction plating (IRP) cycles, and electroplating (EP) time, the sensing performances of IPS samples with different electrode interface roughnesses, electrode penetration depths, and surface resistances were investigated, respectively. The experimental results indicated that the response voltage of the IPS can be improved by increasing the electrode interface roughness and the electrode penetration depth and reducing the surface resistance. In addition, we have proven that the sensing performance of the IPS is determined by its intrinsic capacitance characteristics. Through coupling electrode characteristic regulations such as roughening and increasing IRP cycles and EP time, a high-performance IPS was obtained, and its response amplitude was improved by 237.8%. The obtained high-performance sensor has been applied in human motion detection, which has good potential to develop wearable devices with high stability for physiological activity monitoring.

Deep learning predicts cervical lymph node metastasis in clinically node-negative papillary thyroid carcinoma.

OBJECTIVES: Precise determination of cervical lymph node metastasis (CLNM) involvement in patients with early-stage thyroid cancer is fairly significant for identifying appropriate cervical treatment options. However, it is almost impossible to directly judge lymph node metastasis based on the imaging information of early-stage thyroid cancer patients with clinically negative lymph nodes. METHODS: Preoperative US images (BMUS and CDFI) of 1031 clinically node negative PTC patients definitively diagnosed on pathology from two independent hospitals were divided into training set, validation set, internal test set, and external test set. An ensemble deep learning model based on ResNet-50 was built integrating clinical variables, BMUS, and CDFI images using a bagging classifier to predict metastasis of CLN. The final ensemble model performance was compared with expert interpretation. RESULTS: The ensemble deep convolutional neural network (DCNN) achieved high performance in predicting CLNM in the test sets examined, with area under the curve values of 0.86 (95% CI 0.78-0.94) for the internal test set and 0.77 (95% CI 0.68-0.87) for the external test set. Compared to all radiologists averaged, the ensemble DCNN model also exhibited improved performance in making predictions. For the external validation set, accuracy was 0.72 versus 0.59 (p = 0.074), sensitivity was 0.75 versus 0.58 (p = 0.039), and specificity was 0.69 versus 0.60 (p = 0.078). CONCLUSIONS: Deep learning can non-invasive predict CLNM for clinically node-negative PTC using conventional US imaging of thyroid cancer nodules and clinical variables in a multi-institutional dataset with superior accuracy, sensitivity, and specificity comparable to experts. CRITICAL RELEVANCE STATEMENT: Deep learning efficiently predicts CLNM for clinically node-negative PTC based on US images and clinical variables in an advantageous manner. KEY POINTS: • A deep learning-based ensemble algorithm for predicting CLNM in PTC was developed. • Ultrasound AI analysis combined with clinical data has advantages in predicting CLNM. • Compared to all experts averaged, the DCNN model achieved higher test performance.

High-performance paper-based humidity sensors with Nafion/AgNWs hybrid electrodes.

In the past decade, the development of medical health and human-computer interfaces has put forward requirements for the non-contact application of flexible electronics. Among them, flexible humidity sensors play an important role in the field of non-contact sensing by virtue of their rapid response to humidity changes. In this paper, a flexible paper-based humidity sensor with high performance was fabricated by embedded Au@AgNWs electrodes on filter paper through spraying and electroplating (EP) methods. Benefitting from the moisture-sensitive properties of the paper and the tight integration of the electrodes into the filter paper, the sensor shows the humidity monitoring range of 33-100% RH, large response value of I/I0 = 1958, excellent linearity of R2 = 0.99662 and hysteresis performance under the low excitation voltage of only DC 1 V. In addition, the good biocompatibility of the paper-based humidity sensor endows it with multifunctional applications for breath detection, non-contact applications and food security monitoring. Easy access to raw materials and convenient preparation methods of this work provide new ideas for the development and commercialization of flexible humidity sensors.

Modulating the Luminescence, Photosensitizing Properties, and Mitochondria-Targeting Ability of D-π-A-Structured Dihydrodibenzo[a,c]phenazines.

Herein, pyridinium and 4-vinylpyridinium groups are introduced into the VIE-active N,N'-disubstituted-dihydrodibenzo[a,c]phenazines (DPAC) framework to afford a series of D-π-A-structured dihydrodibenzo[a,c]phenazines in consideration of the aggregation-benefited performance of the DPAC module and the potential mitochondria-targeting capability of the resultant pyridinium-decorated DPACs (DPAC-PyPF6 and DPAC-D-PyPF6). To modulate the properties and elucidate the structure-property relationship, the corresponding pyridinyl/4-vinylpyridinyl-substituted DPACs, i.e., DPAC-Py and DPAC-D-Py, are designed and studied as controls. It is found that the strong intramolecular charge transfer (ICT) effect enables the effective separation of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of DPAC-PyPF6 and DPAC-D-PyPF6, which is conducive to the generation of ROS. By adjusting the electron-accepting group and the π-bridge, the excitation, absorption, luminescence, photosensitizing properties as well as the mitochondria-targeting ability can be finely tuned. Both DPAC-PyPF6 and DPAC-D-PyPF6 display large Stokes shifts (70-222 nm), solvent-dependent absorptions and emissions, aggregation-induced emission (AIE), red fluorescence in the aggregated state (λem = 600-650 nm), aggregation-promoted photosensitizing ability with the relative singlet-oxygen quantum yields higher than 1.10, and a mitochondria-targeting ability with the Pearson coefficients larger than 0.85. DPAC-D-PyPF6 shows absorption maximum at a longer wavelength, slightly redder fluorescence and better photosensitivity as compared to DPAC-PyPF6, which consequently leads to the higher photocytotoxicity under the irradiation of white light as a result of the larger π-conjugation.

Transcription factor 3 promotes migration and invasion potential and maintains cancer stemness by activating ID1 expression in esophageal squamous cell carcinoma.

Transcription factor 3 (TCF3) is a member of the basic Helix - Loop - Helix (bHLH) transcription factor (TF) family and is encoded by the TCF3 gene (also known as E2A). It has been shown that TCF3 functions as a key transcription factor in the pathogenesis of several human cancers and plays an important role in stem cell maintenance and carcinogenesis. However, the effect of TCF3 in the progression of esophageal squamous cell carcinoma (ESCC) is poorly known. In our study, TCF3 was found to express highly and correlated with cancer stage and prognosis. TCF3 was shown to promote ESCC invasion, migration, and drug resistance both from the results of in vivo and in vitro assays. Moreover, further studies suggested that TCF3 played these roles through transcriptionally regulating Inhibitor of DNA binding 1(ID1). Notably, we also found that TCF3 or ID1 was associated with ESCC stemness. Furthermore, TCF3 was correlated with the expression of cancer stemness markers CD44 and CD133. Therefore, maintaining cancer stemness might be the underlying mechanism that TCF3 transcriptionally regulated ID1 and further promoted ESCC progression and drug resistance.

Three new species of Entomobryidae (Collembola, Entomobryoidea) from China.

Three new species of entomobryid springtails (Collembola) from China are described here. Homidiapseudozhangisp. nov. is characterised by a narrow irregular longitudinal stripe on the body, smooth chaetae e and l1 of the labial base, and the relative position of the specialized microchaeta on Abd. I; H.qianensissp. nov. by its colour pattern on the antennae and nine sutural macrochaetae on the head; and Entomobryashaanxiensissp. nov. by its colour pattern, labral papillae and the lateral process of labial papilla E. Specimens of Akabosiamatsudoensis Kinoshita, 1919 from China are redescribed, including description of some characters for the first time.

Near-infrared AIEgens with high singlet-oxygen yields for mitochondria-specific imaging and antitumor photodynamic therapy.

AIE-active photosensitizers (PSs) are promising for antitumor therapy due to their advantages of aggregation-promoted photosensitizing properties and outstanding imaging ability. High singlet-oxygen (1O2) yield, near-infrared (NIR) emission, and organelle specificity are vital parameters to PSs for biomedical applications. Herein, three AIE-active PSs with D-π-A structures are rationally designed to realize efficient 1O2 generation, by reducing the electron-hole distribution overlap, enlarging the difference on the electron-cloud distribution at the HOMO and LUMO, and decreasing the ΔEST. The design principle has been expounded with the aid of time-dependent density functional theory (TD-DFT) calculations and the analysis of electron-hole distributions. The 1O2 quantum yields of AIE-PSs developed here can be up to 6.8 times that of the commercial photosensitizer Rose Bengal under white-light irradiation, thus among the ones with the highest 1O2 quantum yields reported so far. Moreover, the NIR AIE-PSs show mitochondria-targeting capability, low dark cytotoxicity but superb photo-cytotoxicity, and satisfactory biocompatibility. The in vivo experimental results demonstrate good antitumor efficacy for the mouse tumour model. Therefore, the present work will shed light on the development of more high-performance AIE-PSs with high PDT efficiency.

Muscular injury as an independent risk factor for esophageal stenosis after endoscopic submucosal dissection of esophageal squamous cell cancer.

BACKGROUND AND AIMS: Stenosis after esophageal endoscopic submucosal dissection (ESD) has a high incidence, and muscular injury is an important risk factor for esophageal stenosis. Hence, this study aimed to classify muscular injury degrees and investigate their association with postoperative stenosis. METHODS: This retrospective study included 1033 patients with esophageal mucosal lesions treated with ESD between August 2015 and March 2021. Demographic and clinical parameters were analyzed, and stenosis risk factors were identified using multivariate logistic regression. A novel muscular injury classification system was proposed and used to investigate the association between different muscular injury degrees and postoperative stenosis. Finally, a scoring system was established to predict muscular injury. RESULTS: Of 1033 patients, 118 (11.4%) had esophageal stenosis. The multivariate analysis demonstrated that the history of endoscopic esophageal treatment, circumferential range, and muscular injury were significant risk factors for esophageal stenosis. Patients with type II muscular injuries tended to develop complex stenosis (n = 13 [36.1%], P < .05), and type II muscular injuries were more likely to predispose patients to severe stenosis than type I (73.3% and 92.3%, respectively). The scoring system showed that patients with high scores (3-6) were more likely to have muscular injury. The score model presented good discriminatory power in the internal validation (area under the receiver-operating characteristic curve, .706; 95% confidence interval, .645-.767) and goodness-of-fit in the Hosmer-Lemeshow test (P = .865). CONCLUSIONS: Muscular injury was an independent risk factor for esophageal stenosis. The scoring system demonstrated good performance in predicting muscular injury during ESD.

A high-quality chromosome-level Eutrema salsugineum genome, an extremophile plant model.

BACKGROUND: Eutrema salsugineum (2n = 14), a halophyte in the family Brassicaceae, is an attractive model to study abiotic stress tolerance in plants. Two versions of E. salsugineum genomes that previously reported were based on relatively short reads; thus, the repetitive regions were difficult to characterize. RESULTS: We report the sequencing and assembly of the E. salsugineum (Shandong accession) genome using long-read sequencing and chromosome conformation capture data. We generated Oxford Nanopore long reads at high depth (> 60X) of genome coverage with additional short reads for error correction. The new assembly has a total size of 295.5 Mb with 52.8% repetitive sequences, and the karyotype of E. salsugineum is consistent with the ancestral translocation Proto-Calepineae Karyotype structure in both order and orientation. Compared with previous assemblies, this assembly has higher contiguity, especially in the centromere region. Based on this new assembly, we predicted 25,399 protein-coding genes and identified the positively selected genes associated with salt and drought stress responses. CONCLUSION: The new genome assembly will provide a valuable resource for future genomic studies and facilitate comparative genomic analysis with other plants.

Strain and Pressure Sensors Based on MWCNT/PDMS for Human Motion/Perception Detection.

Flexible wearable devices have attracted wide attention in capacious fields because of their real-time and continuous monitoring of human information. The development of flexible sensors and corresponding integration with wearable devices is of great significance to build smart wearable devices. In this work, multi-walled carbon nanotube/polydimethylsiloxane-based (MWCNT/PDMS) resistive strain sensors and pressure sensors were developed to integrate a smart glove for human motion/perception detection. Firstly, MWCNT/PDMS conductive layers with excellent electrical and mechanical properties (resistivity of 2.897 KΩ · cm, elongation at break of 145%) were fabricated via a facile scraping-coating method. Then, a resistive strain sensor with a stable homogeneous structure was developed due to the similar physicochemical properties of the PDMS encapsulation layer and MWCNT/PDMS sensing layer. The resistance changes of the prepared strain sensor exhibited a great linear relationship with the strain. Moreover, it could output obvious repeatable dynamic response signals. It still had good cyclic stability and durability after 180° bending/restoring cycles and 40% stretching/releasing cycles. Secondly, MWCNT/PDMS layers with bioinspired spinous microstructures were formed by a simple sandpaper retransfer process and then assembled face-to-face into a resistive pressure sensor. The pressure sensor presented a linear relationship of relative resistance change and pressure in the range of 0-31.83 KPa with a sensitivity of 0.026 KPa-1, and a sensitivity of 2.769 × 10-4 KPa-1 over 32 KPa. Furthermore, it responded quickly and kept good cycle stability at 25.78 KPa dynamic loop over 2000 s. Finally, as parts of a wearable device, resistive strain sensors and a pressure sensor were then integrated into different areas of the glove. The cost-effective, multi-functional smart glove can recognize finger bending, gestures, and external mechanical stimuli, which holds great potential in the fields of medical healthcare, human-computer cooperation, and so on.

Assessment of Autologous Blood marker localIzation and intraoperative coLonoscopy localIzation in laparoscopic colorecTal cancer surgery (ABILITY): a randomized controlled trial.

BACKGROUND: Laparoscopic colorectal surgery has been proved to have similar oncological outcomes with open surgery. Due to the lack of tactile perception, surgeons may have misjudgments in laparoscopic colorectal surgery. Therefore, the accurate localization of a tumor before surgery is important, especially in the early stages of cancer. Autologous blood was thought a feasible and safe tattooing agent for preoperative endoscopic localization but its benefits remain controversial. We therefore proposed this randomized trial to the accuracy and safety of autogenous blood localization in small, serosa-negative lesion which will be resected by laparoscopic colectomy. METHODS: The current study is a single-center, open-label, non-inferiority, randomized controlled trial. Eligible participants would be aged 18-80 years and diagnosed with large lateral spreading tumors that could not be treated endoscopically, malignant polyps treated endoscopically that required additional colorectal resection, and serosa-negative malignant colorectal tumors (≤ cT3). A total of 220 patients would be randomly assigned (1:1) to autologous blood group or intraoperative colonoscopy group. The primary outcome is the localization accuracy. The secondary endpoint is adverse events related to endoscopic tattooing. DISCUSSION: This trial will investigate whether autologous blood marker achieves similar localization accuracy and safety in laparoscopic colorectal surgery compared to intraoperative colonoscopy. If our research hypothesis is statistically proved, the rational introduction of autologous blood tattooing in preoperative colonoscopy can help improve identification of the location of tumors for laparoscopic colorectal cancer surgery, performing an optimal resection, and minimizing unnecessary resections of normal tissues, thereby improving the patient's quality of life. Our research data will also provide high quality clinical evidence and data support for the conduction of multicenter phase III clinical trials. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, NCT05597384. Registered 28 October 2022.

No-touch endoscopic full-thickness resection technique for gastric gastrointestinal stromal tumors.

BACKGROUND : There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. METHODS : In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS : The median tumor size was 2.5 cm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (> 3.0 cm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. CONCLUSIONS : NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty.

Rapid Preparation of Novel Ionic Polymer-Metal Composite for Improving Humidity Sensing Effect.

Ionic polymer-metal composites (IPMCs) have attracted attention in recent years due to their integration of actuation and sensing functions. As one of the main sensing functions of IPMCs, humidity sensing has been of consistent interest in wearable health monitors and artificial skin. However, there are still some technical challenges in that classical IPMCs have poor humidity sensing performance due to their dense surface electrode, and IPMCs are damaged easily due to an electrode/membrane mismatch. In this work, through the spraying and electrodepositing process, we developed an efficient method to rapidly prepare a Au-shell-Ag-NW (silver nanowire)-based IPMC with high strength, low surface resistance and excellent humidity sensing performance. Meanwhile, we optimized the preparation method by clarifying the influence of solvent type and electrodepositing time on the performance of the Au-shell-Ag-NW-based IPMC, thus effectively improving the humidity sensing effect and strength of the IPMC. Compared with previous research, the humidity electrical response (~9.6 mV) of the Au-shell-Ag-NW-based IPMC is at least two orders of magnitude higher than that of the classical IPMC (~0.41 mV), which is mainly attributed to the sparse gap structure for promoting the exchange of water molecules in the environment and Nafion membrane, a low surface resistance (~3.4 Ohm/sq) for transmitting the signal, and a seamless connection between the electrode and Nafion membrane for fully collecting the ion charges in the Nafion membrane. Additionally, the Au-shell-Ag-NW-based IPMC could effectively monitor the human breathing process, and the humidity sensing performance did not change after being exposed to the air for 4 weeks, which further indicates that the Au-shell-Ag-NW-based IPMC has good application potential due to its efficient preparation technology, high stability and good reproducibility.

Cellular Uptake and Transport Mechanism of 6-Mercaptopurine Nanomedicines for Enhanced Oral Bioavailability.

Background: Nanomedicines have significant advantages in enhancing the oral bioavailability of drugs, but a deeper understanding of the underlying mechanisms remains to be interpreted. Hence, the present study aims to explain the uptake and trafficking mechanism for 6-MP nanomedicines we previously constructed. Methods: 6-MP loaded poly(lactide-co-glycolide) (PLGA) nanomedicines (6-MPNs) were prepared by the multiple emulsion method. The transcytosis mechanism of 6-MPNs was investigated in Caco-2 cells, Caco-2 monolayers, follicle associated epithelium (FAE) monolayers and rats, including transmembrane pathway, intracellular trafficking, paracellular transport and the involvement of transporter. Results: Pharmacokinetics in rats showed that the area under the curve (AUC) of 6-MP in the 6-MPNs group (147.3 ± 42.89 µg/L·h) was significantly higher than that in the 6-MP suspensions (6-MPCs) group (70.31 ± 18.24 µg/L·h). The uptake of 6-MPNs in Caco-2 cells was time-, concentration- and energy-dependent. The endocytosis of intact 6-MPNs was mediated mainly through caveolae/lipid raft, caveolin and micropinocytosis. The intracellular trafficking of 6-MPNs was affected by endoplasmic reticulum (ER)-Golgi complexes, late endosome-lysosome and microtubules. The multidrug resistance associated protein 4 (MRP4) transporter-mediated transport of free 6-MP played a vital role on the transmembrane of 6-MPNs. The trafficking of 6-MPNs from the apical (AP) side to the basolateral (BL) side in Caco-2 monolayers was obviously improved. Besides, 6-MPNs affected the distribution and expression of zona occludens-1 (ZO-1). The transport of 6-MPNs in FAE monolayers was concentration- and energy-dependent, while reaching saturation over time. 6-MPNs improved the absorption of the intestinal Peyer's patches (PPs) in rats. Conclusion: 6-MPNs improve the oral bioavailability through multiple pathways, including active transport, paracellular transport, lymphatic delivery and MRP4 transporter. The findings of current study may shed light on the cellular uptake and transcellular trafficking mechanism of oral nanomedicines.

A prediction model and nomogram for technical difficulty of peroral endoscopic myotomy.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a promising endoscopic technique for achalasia. We aimed to establish a regression model and develop a simple nomogram to predict the technical difficulty of POEM in a single center with large volume cases. METHODS: 3385 achalasia patients treated with POEM were included, and the technical difficulty was systemically evaluated. All of them were randomized into the training cohort (n = 1693) or internal validation cohort (n = 1692). Then, the prediction model and nomogram were proposed based on multivariate logistic regression analysis in the training cohort and assessed in the validation cohort. RESULTS: Of 3385 patients, technical difficulty happened in 417 (12.32%) cases. In the training stage, six factors were weighted based on the ß coefficient from the regression model, including age, disease duration, sigmoid esophagus, mucosal edema, submucosal fibrosis, and tunnel length. The patients were categorized into low-risk (< 0.1), medium-risk (0.1-0.25), and high-risk (> = 0.25) groups. Our score model performed satisfying discrimination with the areas under the receiver-operating characteristic curve (AUC) of 0.743 (95% confidence interval (CI), 0.701-0.785) and calibration with goodness of fit in the Hosmer-Lemeshow test (P = 0.088) in internal validation. CONCLUSIONS: The prediction model and nomogram demonstrated good performance in predicting the technical difficulty of POEM.

Meta-analysis of exercise intervention on health behaviors in middle-aged and older adults.

Objective: To systematically review and analyze the effects of exercise interventions on health behavior among middle-aged and older adults. Methods: A Meta-analysis was performed using NoteExpress software to screen randomized controlled trials (RCTs) published between January 1, 2000, and March 31, 2023, which were identified through databases including CNKI, Web of Science, Pubmed, and 6 more sources, based on predefined literature inclusion criteria. Following the quality assessment, we conducted both the overall and subgroup Meta-analyses of the exercise intervention moderator variables using Review Manager 5.4.1 software, encompassing data among the 18 RCTs. The effect size was measured as the standardized mean difference within its corresponding 95% confidence interval. Heterogeneity was assessed using the I2 metrics. Results: (1) The overall results indicate a significant impact of exercise intervention on health behaviors, characterized by a large effect size [SMD = 1.02 > 0.8, 95% CI (0.73, 1.32), P < 0.001]. (2) The highest degree of heterogeneity in the relationship between exercise interventions and health behaviors was associated with the duration of one exercise session (I2= 71.2%), which was the most influential moderator variable. (3) The aerobic and resistance intervention in group exercise lasting 30-60 min per time a day, 6-7 times per week over a period of 8-12 weeks demonstrated the most substantial effect size. Conclusion: (1) The exercise intervention significantly promotes the health behavior in middle-aged and older adults, emphasizing the importance of carefully considering the duration of individual exercise sessions when designing and implementing exercise intervention. (2) Considering the accessibility for middle-aged and older adults, the optimal exercise intervention should include the means of group practice, the types of aerobic and resistance exercise, with a duration of 30-60 min per time a day, beginning with a lower weekly frequency and gradually increase to 6-7 times per week, and lasting for 8 to 12 weeks. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024506750.

Clinical characteristics and prognosis of anaplastic thyroid carcinoma: a 20-year single-center retrospective study / 中华耳鼻咽喉头颈外科杂志

Objectives: To investigate the clinical characteristics and prognoses of patients with anaplastic thyroid carcinoma(ATC), and to explore the value of multi-modality treatment in improving overall survival(OS) of ATC patients. Methods: Medical records including clinicopathological data of patients diagnosed with ATC at Cancer Hospital, Chinese Academy of Medical Sciences between 2001 and 2020 were retrospectively analyzed. The cohort were divided into surgery-only and multi-modality subgroups, and the latter included patients treated with surgery plus radiotherapy and/or medical therapy(including chemotherapy, target therapy and immunotherapy). Univariate survival analysis was conducted through Kaplan-Meier method, and multivariate survival analysis was performed using Cox proportional hazard model. Results: A total of 47 patients were included in the study, including 24 males and 23 females, with a median age of 63 years. After a median follow-up duration of 3.37 months, 42 patients died due to tumor recurrence or progression. The median OS of the cohort was 4.33 months. Univariate survival analysis demonstrated that symptoms of recurrent laryngeal nerve(RLN) involvement, distant metastasis, leukocyte elevation, and treatment modality were significantly associated with OS (P values all<0.05). Multivariate analysis showed that symptoms of RLN involvement(HR=2.49, 95%CI: 1.16-5.32, P=0.019), distant metastasis(HR=2.33, 95%CI: 1.06-5.16, P=0.036), and leukocyte elevation(HR=2.50, 95%CI: 1.16-5.40, P=0.020) were all independent risk factors for OS, while multi-modality therapy significantly prolonged OS compared with surgery alone(HR=0.22, 95%CI: 0.10-0.47, P<0.001). Conclusions: Among ATC patients, absence of symptoms of RLN invasion, normal leukocyte level and absence of distant metastasis at initial diagnosis are all independent protective factors for OS and multi-modality treatment can help to improve the prognosis.