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Abstract Background Multiple studies have shown that tumor-associated macrophages (TAMs) promote cancer initiation and progression. However, the reprogramming of macrophages in the tumor microenvironment (TME) and the cross-talk between TAMs and malignant subclones in intrahepatic cholangiocarcinoma (iCCA) has not been fully characterized, especially in a spatially resolved manner. Deciphering the spatial architecture of variable tissue cellular components in iCCA could contribute to the positional context of gene expression containing information pathological changes and cellular variability. Methods Here, we applied spatial transcriptomics (ST) and digital spatial profiler (DSP) technologies with tumor sections from patients with iCCA. Results The results reveal that spatial inter- and intra-tumor heterogeneities feature iCCA malignancy, and tumor subclones are mainly driven by physical proximity. Tumor cells with TME components shaped the intra-sectional heterogenetic spatial architecture. Macrophages are the most infiltrated TME component in iCCA. The protein trefoil factor 3 (TFF3) secreted by the malignant subclone can induce macrophages to reprogram to a tumor-promoting state, which in turn contributes to an immune-suppressive environment and boosts tumor progression. Conclusions In conclusion, our description of the iCCA ecosystem in a spatially resolved manner provides novel insights into the spatial features and the immune suppressive landscapes of TME for iCCA.

Background The disorder of serum uric acid metabolism during pregnancy is associated with adverse pregnancy outcomes, while few studies have analyzed and compared the correlation of serum uric acid and serum uric acid/creatinine ratio levels with adverse pregnancy outcomes. Objective To explore the correlation of serum uric acid and serum uric acid/creatinine ratio levels with adverse pregnancy outcomes in late pregnancy. Methods A total of 743 pregnant women with singleton live births who were routinely examined and delivered at Nanjing Drum Tower Hospital from 2015 to 2022 were selected . Based on the occurrence of adverse pregnancy outcomes, pregnant women were divided into normal group (344 cases) and adverse outcome group (399 cases) . Serum uric acid and serum uric acid/creatinine ratio were divided into three levels by quartiles, respectively, including Q1 (serum uric acid359 μmol/L) and q1 (serum uric acid/creatinine ratio7.94) . According to the median age of pregnant women, they were divided into the age subgroup

Background: Atypical speech prosody has been commonly found among autistic children. Yet it remains unknown whether prosody impairment originates from poor pitch ability in general or whether it is the result of the difficulty in understanding and using prosody for communicative purposes. Aims: To investigate whether native Mandarin Chinese-speaking autistic children with intellectual impairment were able to accurately produce native lexical tones, which are pitch patterns that distinguish word meaning lexically and serve little social purpose. Methods & Procedures: Using a picture-naming task, thirteen 8-13-year-old Mandarin Chinese-speaking autistic children with intellectual impairment were tested on their production of Chinese lexical tones. Chronical age-matched typically developing (TD) children were included as the control group. Perceptual assessment and phonetic analyses were conducted with the produced lexical tones. Outcomes & Results: The majority of the lexical tones produced by the autistic children were perceived as accurate by adult judges. Phonetic analysis of the pitch contours found no significant difference between the two groups, and the autistic children and TD children used the phonetic features in comparable ways when differentiating the lexical tones. However, the lexical tone accuracy rate was lower among the autistic children than among the TDs, and the larger individual difference was observed among the autistic children than the TD children. Conclusions & Implications: These results indicate that autistic children are able to produce the global contours of the lexical tones, and pitch deficits do not seem to qualify as a core feature of autism.

Abstract Background and aim The presence of microvascular invasion (MVI) will impair the surgical outcome of hepatocellular carcinoma (HCC). Adipose and muscle tissues have been confirmed to be associated with the prognosis of HCC. We aimed to develop and validate a nomogram based on adipose and muscle related-variables for preoperative prediction of MVI in HCC. Methods One hundred fifty-eight HCC patients from institution A (training cohort) and 53 HCC patients from institution B (validation cohort) were included, all of whom underwent preoperative CT scan and curative resection with confirmed pathological diagnoses. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied to data dimensionality reduction and screening. Nomogram was constructed based on the independent variables, and evaluated by external validation, calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results Histopathologically identified MVI was found in 101 of 211 patients (47.9%). The preoperative imaging and clinical variables associated with MVI were visceral adipose tissue (VAT) density, intramuscular adipose tissue index (IMATI), skeletal muscle (SM) area, age, tumor size and cirrhosis. Incorporating these 6 factors, the nomogram achieved good concordance index of 0.79 (95%CI: 0.72–0.86) and 0.75 (95%CI: 0.62–0.89) in training and validation cohorts, respectively. In addition, calibration curve exhibited good consistency between predicted and actual MVI probabilities. ROC curve and DCA of the nomogram showed superior performance than that of models only depended on clinical or imaging variables. Based on the nomogram score, patients were divided into high (> 273.8) and low (

The use of electrospinning technology to construct edible nano-delivery carriers has been one of the most important way to improve the utilize efficiency of novel localized drugs or food active components. However, it is still challenging to develop nanofibers with natural polymers due to many problems such as the toxicity of organic reagent and difficulty in forming the nanostructure. In this study, natural plant polysaccharide guar gum （guar gum，GG） were selected as the fiber forming substrate to co-load corn starch（starch，ST）, and successfully developed a edible GG/ST composite nanofiber delivery carrier. The results showed that the minimum molecular entanglement concentration of GG as a fiber forming matrix was 1.1 wt%. A series of GG/ST composite solution were prepared (4∶1, 2∶1, 1∶1, and 1∶4). Through static and dynamic rheological testing of GG/ST solution and characterization of fiber microstructure, it was found that the ratio of GG/ST at 2∶1 was the optimal concentration to obtain the uniform and smooth fiber nanostructure. When the ST content is 5w%~10w%, beaded fiber morphology in the structure and unnormal distribution of diameter was observed, and electrospinning process had little effect on the improvement of the fiber structure. This study provide a support for developing edible nano carriers and offered a basis for developing targeted drugs or functional foods in the future.

Abstract Background The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in the occurrence and development of various tumors. However, the underlying mechanism of MALAT1 in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. Methods The expression levels of MALAT1 in HCC tissues and different cell lines were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 in HCC cells by cell counting kit 8 (CCK-8), colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure AMPK and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. Results We found that MALAT1 was upregulated in HCC, and MALAT1 knockdown in HCC cells inhibited cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B‑related factor 2 (BRF2), which was associated with tumor recurrence, large tumor size, and poor prognosis in HCC. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge has-miR-1-3p, which upregulated BRF2 expression. Knockdown of BRF2 inhibited the progression of HCC by activating the LKB1/AMPK signaling pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown on HCC cell viability. Moreover, ASO targeting MALAT1 inhibited the growth of xenograft tumors. Conclusions Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future.

Abstract As an important hydrolytic enzyme that yields 2-AG and free fatty acids, diacylglycerol lipase alpha (DAGLA) is involved in exacerbating malignant phenotypes and cancer progression, but the role of the DAGLA/2-AG axis in HCC progression remains unclear. Here, we found that the upregulation of components of the DAGLA/2-AG axis in HCC samples is correlated with tumour stage and patient prognosis. In vitro and in vivo experiments demonstrated that the DAGLA/2-AG axis promoted HCC progression by regulating cell proliferation, invasion and metastasis. Mechanistically, the DAGLA/2AG axis significantly inhibited LATS1 and YAP phosphorylation, promoted YAP nuclear translocation and activity, and ultimately led to TEAD2 upregulation and increased PHLDA2 expression, which could be enhanced by DAGLA/2AG-induced activation of the PI3K/AKT pathway. More importantly, DAGLA induced resistance to lenvatinib therapy during HCC treatment. Our study demonstrates that inhibiting the DAGLA/2-AG axis could be a novel therapeutic strategy to inhibit HCC progression and enhance the therapeutic effects of TKIs, which warrant further clinical studies.