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Haohua Yuan,1 Huan Gui,1 Shuanghui Chen,1 Lan Zhu,1 Chenglv Wang,1 Qianyu Jing,2 Hang Lv,1 Quan Wan,2 Shuyi Wang,1 Shengwen Zhou,1 Xiaodong Ren,1 Yingjie Nie,1,3 Linzhao Li1 1Medical College, Guizhou University, Guizhou Province, 550025, People’s Republic of China; 2School of Preclinical Medicine of Zunyi Medical University, Zunyi, Guizhou Province, 563000, People’s Republic of China; 3NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, 550002, People’s Republic of ChinaCorrespondence: Yingjie Nie; Linzhao Li, Medical College of Guizhou University, Guiyang, Guizhou Province, 550025, People’s Republic of China, Tel +86-085188274013; +86-085188274016, Email nienyj@hotmail.com; lzli@gzu.edu.cnPurpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD).Methods: R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo.Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival.Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.Keywords: R848, 2-HP-β-CD, anti-TNFR2, TIME, immunotherapy

Huiting Zhou,1,* Xiaying Lu,2,3,* Jie Huang,1,* Patrick Jordan,2 Shurong Ma,1 Lingqi Xu,1 Fangjie Hu,1 Huan Gui,1 He Zhao,1 Zhenjiang Bai,1 H Paul Redmond,2 Jiang Huai Wang,2 Jian Wang1 1Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland; 3Department of Physiology, Gannan Medical University, Ganzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Wang, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China, Email wj196312@vip.163.com Jiang Huai Wang, Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland, Email jh.wang@ucc.ieBackground: Neonates are susceptible to a wide range of microbial infection and at a high risk to develop severe sepsis and septic shock. Emerged evidence has shown that induction of trained immunity triggers a much stronger inflammatory response in adult monocytes/macrophages, thereby conferring protection against microbial infection.Methods: This study was carried out to examine whether trained immunity is inducible and exerts its protection against microbial sepsis in neonates.Results: Induction of trained immunity by Bacillus Calmette-Guerin (BCG) plus bacterial lipoprotein (BLP) protected neonatal mice against cecal slurry peritonitis-induced polymicrobial sepsis, and this protection is associated with elevated circulating inflammatory cytokines, increased neutrophil recruitment, and accelerated bacterial clearance. In vitro stimulation of neonatal murine macrophages with BCG+BLP augmented both inflammatory response and antimicrobial activity. Notably, BCG+BLP stimulation resulted in epigenetic remodeling characterized by histone modifications with enhanced H3K4me3, H3K27Ac, and suppressed H3K9me3 at the promoters of the targeted inflammatory and antimicrobial genes. Critically, BCG+BLP stimulation led to a shift in cellular metabolism with increased glycolysis, which is the prerequisite for subsequent BCG+BLP-triggered epigenetic reprogramming and augmented inflammatory response and antimicrobial capacity.Conclusion: These results illustrate that BCG+BLP induces trained immunity in neonates, thereby protecting against microbial infection by boosting both inflammatory and antimicrobial responses.Keywords: trained immunity, inflammatory response, antimicrobial activity, epigenetic reprogramming, intracellular metabolic rewiring, neonatal sepsis

ObjectiveThe aim of this study was to evaluate six vaginal douching agents (Iodine, Saline, Iodine followed by saline, chlorhexidine acetate followed by saline, Ozone, Potassium permanganate) on oocytes pick-up related pelvic infection (OPU-PI) and IVF outcome in patients underwent assisted reproduction technology (ART).DesignThrough searching PubMed, Embase, Cochrane Library, Web of Science, Ovid, CINAHL CNKI, only human clinical trials were collected to study the effects of the six vaginal douching agents on OPU-PI and IVF outcomes. The included studies were evaluated for methodological quality by the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly.ResultsThe clinical trials were collected between the earliest available date and June 2022. Eight studies were included, the total sample size used in the study was 12,567. The results of the network meta-analysis showed that Ozone can significantly decrease OPU-PI; Iodine followed by saline can be a antiseptic protocol ranked first without affecting the quality of oocytes and Chlorhexidine acetate followed by saline can improve patients' clinical pregnancy rate.ConclusionBased on Ranking Plot of the Network, this review reports the best evidence available regarding different vaginal douching agents used before OPU.

Jianhua Wang,1,2,&ast; Juan Xu,1– 3,&ast; Shuling Liu,1,2 Fei Han,1,4 Qiaojun Wang,1,4 Hao Gui,1,4 Rui Chen1,2 1Sleep Center, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215004, People’s Republic of China; 2Department of Respiratory Medicine, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, People’s Republic of China; 3Department of Respiratory Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng City, Yancheng, People’s Republic of China; 4Department of Neurology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Chen Email chenruigood@126.comPurpose: To investigate the effect of continuous positive airway pressure (CPAP) on sleep electroencephalogram (EEG) activity in patients with obstructive sleep apnea (OSA) and to examine the correlation between quantitative EEG changes and cognitive function.Patients and Methods: A total of 69 men and 11 women were collected with an average age of 39.61 ± 7.67 years old from among middle-aged patients who had first visits with snoring as their main complaint. All of them completed sleep questionnaires, neurocognitive tests and night polysomnography (PSG). The patients in the OSA group also completed the second night of PSG monitoring under CPAP after pressure titration. A power spectrum analysis of EEG was used, and the correlation between the frequency powers of EEG and the scores of the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA) were further analyzed.Results: Compared with the control group, the delta/alpha power ratio (DAR) and the (delta + theta)/(alpha + beta) power ratio (the slowing ratio, TSR) of the OSA group before CPAP were higher (P < 0.05). The DAR and TSR of the OSA patients decreased significantly after CPAP. ESS scores were correlated with parameters such as respiratory-related microarousal index (RRMAI), apnea hypopnea index (AHI), and the average absolute power of delta, DAR and TSR (P < 0.05). The PSQI, MMSE and MoCA scores were not correlated with the average absolute power of each frequency band, DAR or TSR (P > 0.05).Conclusion: Patients with OSA have greater slow frequency EEG activity during sleep than the control group. CPAP treatment reversed the slow frequency EEG activity in patients with OSA.Keywords: obstructive sleep apnea, quantitative electroencephalogram, cognitive function, continuous positive airway pressure

Qi Gong,1,* Liping Ye,2,* Huiwen Gui,1 Jing Liu,1 Huanyin Li,1 Qian Sun1 1Department of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People’s Republic of China; 2Nursing Department, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huanyin LiDepartment of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, 170 Shenlong Road, Minhang District, Shanghai 201199, People’s Republic of ChinaTel/Fax +86 216 492 3400Email li_huanyin@sina.comBackground: Stroke ranks as the third-leading cause of years of life lost worldwide. ANGPTL3 plays important roles in lipid metabolism, atherosclerosis, and occurrence of stroke. The purpose of this study was to evaluate associations of genetic variants in the ANGPTL3 gene with ischemic stroke (IS) risk.Methods: A case–control study was conducted to evaluate the associations of tag single-nucleotide polymorphisms (SNPs) of the ANGPTL3 gene and risk of IS, as well as serum lipid levels. Dual-luciferase reporter assays in the HEK293T cell line was conducted to evaluate the promoter activity of ANGPTL3 rs6690733.Results: We found rs6690733 (C vs A: OR 1.34, 95% CI 1.13–1.59; P=0.001) and rs12563308 (C vs T: OR 0.77, 95% CI 0.64–0.93, P=0.007) were significantly associated with susceptibility to IS. Even corrected for Bonferroni adjustment, the two variants were still significant (0.007×4=0.028). Carriers of the minor allele of SNP rs6690733 had significantly higher levels of TC and LDL-C, while carriers of the minor allele of SNP rs12563308 had significantly lower levels of TC and LDL-C (all P

Xiang-Jun Tang,1,* Kuan-Ming Huang,1,* Hui Gui,1,* Jun-Jie Wang,2 Jun-Ti Lu,1 Long-Jun Dai,1,3 Li Zhang,1 Gang Wang2 1Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan, 2Department of Pharmaceutics, Shanghai Eighth People’s Hospital, Jiangsu University, Shanghai, People’s Republic of China; 3Department of Surgery, University of British Columbia, Vancouver, BC, Canada *These authors contributed equally to this work Abstract: As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viability was assessed using a methylthiazol tetrazolium assay and a real-time cell analyzer. Immunoblotting and quantitative reverse transcriptase polymerase chain reaction techniques were used for determining the expression levels of related molecules in protein and mRNA. The results indicated that myricetin-induced cytotoxicity was highly potentiated by the encapsulation of myricetin. Mitochondrial apoptotic pathway was demonstrated to be involved in myricetin-induced glioblastoma cell death. The epidermal growth factor receptor (EGFR)/PI3K/Akt pathway located in the plasma membrane and cytosol and the RAS-ERK pathway located in mitochondria served as upstream and downstream targets, respectively, in myricetin-induced apoptosis. MiR-21 inhibitors interrupted the expression of EGFR, p-Akt, and K-Ras in the same fashion as myricetin-loaded mixed micelles (MYR-MCs) and miR-21 expression were dose-dependently inhibited by MYR-MCs, indicating the interaction of miR-21 with MYR-MCs. This study provided evidence supportive of further development of MYR-MC formulation for preferentially targeting mitochondria of glioblastoma cells. Keywords: myricetin, glioblastoma, EGFR, miR-21, mitochondrial apoptosis, mixed micelles, anticancer, drug delivery

Background: Finding out the effective ways of teaching and assessing communication skills remain a challenging part of medication education. This study aims at exploring the usefulness and effectiveness of having additional feedback using qualitative analysis in assessment of communication skills in undergraduate medical training. We also determined the possibilities of using qualitative analysis in developing tailored strategies for improvement in communication skills training. Methods: This study was carried out on medical students (n=87) undergoing their final year clinical performance examination on communication skills using standardized patient by video-recording and transcribing their performances. Video-recordings of 26 students were randomly selected for qualitative analysis, and additional feedback was provided. We assessed the level of acceptance of communication skills scores between the study and nonstudy group and within the study group, before and after receiving feedback based on qualitative analysis. Results: There was a statistically significant increase in the level of acceptance of feedback after delivering additional feedback using qualitative analysis, where the percentage of agreement with feedback increased from 15.4 to 80.8% (p

Background & Aims: Most knowledge about gastrointestinal (GI)-tract dendritic cells (DC) relies on murine studies where CD103+ DC specialize in generating immune tolerance with the functionality of CD11b+/â subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon. Methods: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing. Results: Colonic DC identified were myeloid (mDC, CD11c+CD123â) and further divided based on CD103 and SIRPα (human analog of murine CD11b) expression. CD103-SIRPα+ DC were the major population and with CD103+SIRPα+ DC were CD1c+ILT3+CCR2+ (although CCR2 was not expressed on all CD103+SIRPα+ DC). CD103+SIRPα- DC constituted a minor subset that were CD141+ILT3âCCR2â. Proximal colon samples had higher total DC counts and fewer CD103+SIRPα+ cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4+CD45RA+ T-cells. However, DC and DC-invoked T-cell expression of mucosal homing markers (β7, CCR9) was lower for proximal DC. CCR2 was expressed on circulating CD1c+, but not CD141+ mDC, and mediated DC recruitment by colonic culture supernatants in transwell assays. Proximal colon DC produced higher levels of cytokines. Mucosal microbiota profiling showed a lower microbiota load in the proximal colon, but with no differences in microbiota composition between compartments. Conclusions: Proximal colonic DC subsets differ from those in distal colon and are more mature. Targeted immunotherapy using DC in T-cell mediated GI tract inflammation may therefore need to reflect this immune compartmentalization. Keywords: CCR2, Dendritic Cells, Distal Colon, Human Gastrointestinal Tract, Proximal Colon, Microbiota

The flight of the owl is silent owing to non-smooth leading edges of the owl's wings and the curved serration of the feathers. This study applied this concept of bionics to blade design for horizontal axis wind turbines to reduce aerodynamic noise. The flow and sound field distribution around a rotating wind turbine with three blades were investigated. A numerical simulation method that combines large eddy simulation (LES) and FW-H acoustic equation was adopted to compare aerodynamic noise between the blade prototype and the bionic blade. The comparison revealed that the sound pressure level of the bionic blade was reduced over middle and high frequencies, thereby achieving a noise reduction of 6.9 dB. The intensity of the wake vortex shedding of the bionic blade was lower, and the interaction between the shedding vortices in the bionic blade was smaller compared with that in the prototype blade, indicating that the aerodynamic noise induced by the shedding vortex was effectively reduced. [ABSTRACT FROM AUTHOR]

Peritoneal adhesions commonly occur following abdominal or pelvic surgery and can cause serious complications. Currently, physical barriers are the primary approach used in clinical practice to prevent adhesion, although their effectiveness is frequently inadequate. In this study, we developed an injectable peptide-loaded hydrogel with multiple functions, including self-fusion, tissue-adhesiveness, anti-inflammation, anti-cell adhesion and anti-angiogenesis. To assess the effectiveness of these hydrogels, which are stabilized by dynamic imine bonds and acetal connections, in preventing postoperative abdominal adhesions, we utilized both a rat abdominal adhesion model and a rat model simulating repeated-injury adhesions. In comparison to the commercially available HA hydrogel, as-prepared hydrogels exhibited significant reductions in inflammation, fibrosis, and angiogenesis, leading to an obvious decrease in peritoneal adhesions. Moreover, this peptide-loaded hydrogel demonstrated an ideal degradation time, maintaining an in vivo viability for about 10 days. We believe this peptide-loaded hydrogel presents a promising solution for the challenging clinical issue of postoperative abdominal adhesions.

Abstract Cervical cancer is a significant global health issue, its prevalence and prognosis highlighting the importance of early screening for effective prevention. This research aimed to create and validate an artificial intelligence cervical cancer screening (AICCS) system for grading cervical cytology. The AICCS system was trained and validated using various datasets, including retrospective, prospective, and randomized observational trial data, involving a total of 16,056 participants. It utilized two artificial intelligence (AI) models: one for detecting cells at the patch-level and another for classifying whole-slide image (WSIs). The AICCS consistently showed high accuracy in predicting cytology grades across different datasets. In the prospective assessment, it achieved an area under curve (AUC) of 0.947, a sensitivity of 0.946, a specificity of 0.890, and an accuracy of 0.892. Remarkably, the randomized observational trial revealed that the AICCS-assisted cytopathologists had a significantly higher AUC, specificity, and accuracy than cytopathologists alone, with a notable 13.3% enhancement in sensitivity. Thus, AICCS holds promise as an additional tool for accurate and efficient cervical cancer screening.

Electroencephalography (EEG) has demonstrated significant value in diagnosing brain diseases. In particular, brain networks have gained prominence as they offer additional valuable insights by establishing connections between EEG signal channels. While brain connections are typically delineated by channel signal similarity, there lacks a consistent and reliable strategy for ascertaining node characteristics. Conventional node features such as temporal and frequency domain properties of EEG signals prove inadequate for capturing the extensive EEG information. In our investigation, we introduce a novel adaptive method for extracting node features from EEG signals utilizing a distinctive task-induced self-supervised learning technique. By amalgamating these extracted node features with fundamental edge features constructed using Pearson correlation coefficients, we showed that the proposed approach can function as a plug-in module that can be integrated to many common GNN networks (e.g., GCN, GraphSAGE, GAT) as a replacement of node feature selections module. Comprehensive experiments are then conducted to demonstrate the consistently superior performance and high generality of the proposed method over other feature selection methods in various of brain disorder prediction tasks, such as depression, schizophrenia, and Parkinson’s disease. Furthermore, compared to other node features, our approach unveils profound spatial patterns through graph pooling and structural learning, shedding light on pivotal brain regions influencing various brain disorder prediction based on derived features.

Objective To observe the effect of auricular acupoint scraping therapy on postoperative pain and sleep quality of patients with lower extremity fracture. Methods Totally 70 cases of patients undergoing surgery for lower limb fracture were randomly divided into control group and observation group, with 35 cases in each group. The control group received routine treatment and nursing measures, while the observation group was given auricular acupoint scraping therapy based on the routine treatment and nursing measures. Visual analog pain scale (VAS), Pittsburgh Sleep Quality Index (PSQI) score and patient satisfaction before and after treatment were compared between the two groups. Results There was no significant difference in VAS and PSQI scores between two groups before surgery (P＜0. 05). The VAS scores of observation group was significantly decreased compared with those in the control group at 6h, 12h, 24h, 48h and 72h after surgery(P＜0. 05). The PSQI scores of the observation group were significantly decreased compared with those in the control group at 48 h and 72h after surgery (P＜0. 01). The satisfaction degree of the observation group was higher than that of the control group (P＜0. 01). No treatment-related adverse reactions were observed in two groups. Conclusion The auricular acupoint scraping therapy is effective to reduce the postoperative pain and improve the sleep quality of patients undergoing surgery for lower extremity fracture. (目的 观察耳穴推刮术对下肢骨折术后患者疼痛和睡眠质量的影响。方法 选取下肢骨折术后患者70例, 按照随机数字表法分为对照组和观察组, 每组35例。对照组采取常规治疗和护理措施, 观察组在对照组基础上开展耳穴推刮疗法。比较2组患者治疗前后不同时间段内视觉模拟疼痛评分(VAS)、匹兹堡睡眠质量指数量表(PSQI)评分及患者满意度。结果 术前两组患者的VAS、PSQI评分比较, 差异无统计学意义(P＞0. 05)。观察组患者术后6 h、12h、24h、48h、72 h VAS评分低于对照组, 差异有统计学意义(P＜0. 05)。观察组术后48 h、72 h PSQI评分低于对照组, 差异有统计学意义(P＜0. 01)。观察组患者满意度评分高于对照组, 差异有统计学意义(P＜0. 01)。两组均未见治疗相关不良反应。结论 耳穴推刮疗法可以有效缓解下肢骨折术后患者疼痛程度, 提高睡眠质量。)

Abstract Background Colorectal cancer (CRC) is the third frequently diagnosed cancer with high incidence and mortality rate worldwide. Our previous report has demonstrated that circCOL1A1 (hsa_circ_0044556) functions as an oncogene in CRC, and Gene Ontology (GO) analysis has also revealed the strong association between circCOL1A1 and angiogenesis. However, the mechanism of circCOL1A1 or exosomal circCOL1A1 in CRC angiogenesis remains elusive. Methods Purified exosomes from CRC cells were characterized by nanoparticle tracking analyzing, electron microscopy and western blot. qRT-PCR, immunohistochemistry or western blot were employed to test the expression of circCOL1A1, EIF4A3, Smad pathway and angiogenic markers. Cell proliferation of HUVECs was monitored by CCK-8 assay. The migratory and angiogenic capabilities of HUVECs were detected by wound healing and tube formation assay, respectively. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down and FISH assays were used to detect the interactions among circCOL1A1, EIF4A3 and Smad2/3 mRNA. The in vitro findings were verified in xenograft model. Results CRC cell-derived exosomal circCOL1A1 promoted angiogenesis of HUVECs via recruiting EIF4A3. EIF4A3 was elevated in CRC tissues, and it stimulated angiogenesis of HUVECs through directly binding and stabilizing Smad2/3 mRNA. Moreover, exosomal circCOL1A1 promoted angiogenesis via inducing Smad2/3 signaling pathway in vitro, and it also accelerated tumor growth and angiogenesis in vivo. Conclusion CRC cell-derived exosomal circCOL1A1 promoted angiogenesis via recruiting EIF4A3 and activating Smad2/3 signaling.

This study aimed to explore the value of color Doppler ultrasonography combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in differential diagnosis of gastric stromal tumor (GST) and gastric cancer (GC). An analysis of the clinical data of 180 patients with clinically suspected gastric space occupying lesions. According to the postoperative pathological results, 180 suspected gastric space-occupying lesion patients were divided into GST group (n = 83) and GC group (n = 97). Color Doppler ultrasonography, serum tumor markers CEA and CA19-9 were compared. The research results showed that serum CEA and CA19-9 levels were lower in patients with GST group than those with GC group (both P < 0.001). With postoperative pathology as the gold standard, detection rates of GST and GC by combination of color Doppler ultrasound (CDUS), serum CEA, and CA19-9 were higher than those of each index alone (both P < 0.001). There was no difference between detection rates of GST and GC by combination of CDUS, serum CEA, and CA19-9 (P = 0.058). Color Doppler ultrasonography combined with serum tumor markers CEA and CA19-9 tests has a certain differential diagnostic value for GST and GC, which may provide a reliable reference basis for clinical diagnosis and treatment.

Abstract Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P

Abstract Chronic infection with the bacterial pathogen Pseudomonas aeruginosa often leads to coexistence of heterogeneous populations carrying diverse mutations. In particular, loss-of-function mutations affecting the quorum-sensing regulator LasR are often found in bacteria isolated from patients with lung chronic infection and cystic fibrosis. Here, we study the evolutionary dynamics of polymorphic P. aeruginosa populations using isolates longitudinally collected from patients with chronic obstructive pulmonary disease (COPD). We find that isolates deficient in production of different sharable extracellular products are sequentially selected in COPD airways, and lasR mutants appear to be selected first due to their quorum-sensing defects. Polymorphic populations including lasR mutants display survival advantages in animal models of infection and modulate immune responses. Our study sheds light on the multistage evolution of P. aeruginosa populations during their adaptation to host lungs.

Remote sensing technology can be used to monitor changes in crop planting areas to guide agricultural production management and help achieve regional carbon neutrality. Agricultural UAV remote sensing technology is efficient, accurate, and flexible, which can quickly collect and transmit high-resolution data in real time to help precision agriculture management. It is widely used in crop monitoring, yield prediction, and irrigation management. However, the application of remote sensing technology faces challenges such as a high imbalance of land cover types, scarcity of labeled samples, and complex and changeable coverage types of long-term remote sensing images, which have brought great limitations to the monitoring of cultivated land cover changes. In order to solve the abovementioned problems, this paper proposed a multi-scale fusion network (MSFNet) model based on multi-scale input and feature fusion based on cultivated land time series images, and further combined MSFNet and Model Diagnostic Meta Learning (MAML) methods, using particle swarm optimization (PSO) to optimize the parameters of the neural network. The proposed method is applied to remote sensing of crops and tomatoes. The experimental results showed that the average accuracy, F1-score, and average IoU of the MSFNet model optimized by PSO + MAML (PSML) were 94.902%, 91.901%, and 90.557%, respectively. Compared with other schemes such as U-Net, PSPNet, and DeepLabv3+, this method has a better effect in solving the problem of complex ground objects and the scarcity of remote sensing image samples and provides technical support for the application of subsequent agricultural UAV remote sensing technology. The study found that the change in different crop planting areas was closely related to different climatic conditions and regional policies, which helps to guide the management of cultivated land use and provides technical support for the realization of regional carbon neutrality.

Summary: CircRNAs are implicated in colorectal cancer (CRC) development and progression. Protein O-fucosyltransferase 1 (POFUT1) plays an oncogenic role via activating Notch1 signaling in CRC. However, the roles of circPOFUT1, which is originated from POFUT1, have not been investigated. Our study showed circPOFUT1 was highly expressed in CRC tissues and cells. CircPOFUT1 enhanced the proliferation, migration and invasion of CRC cells, and promoted tumor growth and liver metastasis in vivo. It also reinforced stemness and chemoresistance of CRC cells. Mechanistically, circPOFUT1 regulated the function of E2F7 via sponging miR-653-5p, thereby transcriptionally inducing WDR66 expression and further promoting metastasis in CRC. On the other hand, circPOFUT1 promoted stemness and chemoresistance of CRC cells via stabilizing BMI1 in an IGF2BP1-dependent manner. In conclusion, circPOFUT1 fosters CRC metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1.

Atmospheric fine particle pollution has an important impact on regional environment, global climate and human health, so it has been one of the key and difficult points of air pollution prevention and control. In recent years, due to the continuous promotion of China's air pollution prevention and control plan, the problem of atmospheric fine particle pollution has been significantly improved, and the relevant measurement technology has also made considerable progress. In this paper, the development and application of atmospheric fine particle measurement technology in recent years are reviewed based on the information of physical and chemical parameters such as atmospheric fine particle number concentration, particle size distribution and chemical composition. For the measurement of fine particle number concentration, it mainly includes diffusion charge counting and condensation particle counting. The former is mainly applicable to the combustion emission scenario, and the latter is applicable to the urban air low concentration scenario. For the measurement of fine particle size, it mainly involves single particle size and overall particle size spectrum analysis. The single particle size is mostly determined by electron microscopy and optical microscopy, and the particle size spectrum analysis is mainly determined by electro migration classification. For the component measurement of fine particles, aerosol mass spectrometry and spectral analysis are mainly used. Finally, in view of the new requirements of research on the evolution mechanism of atmospheric particulates and intelligent monitoring and supervision, this paper discusses the future development of atmospheric fine particulates in multi-parameter comprehensive characterization, rapid measurement of dynamic processes, high-performance micro-nano sensors and other directions.

In order to study, the distribution characteristics and internal links of soil enzyme activities, nutrient content and woody plant diversity in negative topographic habitats of tiankeng, the tiankeng forests of the Dashiwei tiankeng group in Guangxi were selected as the object, and the relationship between species diversity and soil factors of woody plants was explored by correlation analysis and redundancy analysis methods, based on the community diversity survey and soil habitat survey along the inner area-top area-outer area of tiankeng. The results were as follows: (1) There were 21 species, 31 genera and 20 families of woody plants in the inside area of tiankeng, 91 species, 58 genera and 58 families of woody plants in the top area of tiankeng, and 47 species, 30 genera and 30 families of woody plants in the outside area of tiankeng. The Margalef index and Patrick index in the inside areas of tiankeng were significantly lower than those in the top and outside areas of tiankeng, indicating that the individuals of species increased, but the species distribution was steady. (2) The total soil nitrogen content in the outside areas of tiankeng was significantly higher than those in the top and outside areas of tiankeng. The soil total magnesium content, soil phosphorus content and soil available phosphorus content in the inside area of tiankeng were significantly higher than those in the top and outside area of tiankeng. The soil alkaline phosphatase content and soil urease activities in the outside area of tiankeng were significantly higher than those in the top and inside area of tiankeng. The soil phosphorus content in the tiankeng was higher, but the soil enzyme activities were lower. (3) The species diversity was strongly correlated with soil nutrients and soil enzyme activities. In conclusion, it can be seen that the habitats of the tiankeng have a great influence on the species diversity, soil enzyme activity and soil nutrient content distribution characteristics, and the soil available phosphorus content, soil alkaline phosphatase activity, soil moisture content, soil urease activity, soil total magnesium content and soil total phosphorus content are the key factors affecting the species diversity of woody plants in the tiankeng forest. The results provide a theoretical basis for the protection and reconstruction of plant resources in karst areas.