Global marine microbial diversity and its potential in bioprospecting.

The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems1,2. However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications3,4. Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine.

Upregulation of proBDNF/p75NTR signaling in immune cells and its correlation with inflammatory markers in patients with major depression.

ProBDNF is the precursor protein of brain-derived neurotrophic factor (BDNF) expressed in the central nervous system and peripheral tissues. Previous studies showed that the blood levels of both proBDNF and p75 neurotrophic receptors (p75NTR) in major depressive disorder (MDD) were increased, but which blood cell types express proBDNF and its receptors is not known. Furthermore, the relationship between proBDNF/p75NTR and inflammatory cytokines in peripheral blood of MDD is unclear. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from depressive patients (n = 32) and normal donors (n = 20). We examined the expression of proBDNF and inflammatory markers and their correlative relationship in patients with major depression. Using flow cytometry analysis, we examined which blood cells express proBDNF and its receptors. Finally, the role of proBDNF/p75NTR signal in inflammatory immune activity of PBMCs was verified in vitro experiments. Inflammatory cytokines in PBMC from MDD patients were increased and correlated with the major depression scores. The levels of IL-1ß and IL-10 were also positively correlated with the major depression scores, while the levels of TNF-α and IL-6 were negatively correlated with the major depression scores. Intriguingly, the levels of sortilin were positively correlated with IL-1ß. Q-PCR and Western blots showed proBDNF, p75NTR, and sortilin levels were significantly increased in PBMCs from MDD patients compared with that from the normal donors. Flow cytometry studies showed that proBDNF and p75NTR were present mainly in CD4+ and CD8+ T cells. The number of proBDNF and p75NTR positive CD4+ and CD8+ T cells from MDD patients was increased and subsequently reversed after therapeutic management. Exogenous proBDNF protein or p75ECD-Fc treatment of cultured PBMC affected the release of inflammatory cytokines in vitro. ProBDNF promoted the expression of inflammatory cytokines, while p75ECD-Fc inhibited the expression of inflammatory cytokines. Given there was an inflammatory response of lymphocytes to proBDNF, it is suggested that proBDNF/p75NTR signaling may upstream inflammatory cytokines in MDD. Our data suggest that proBDNF/p75NTR signaling may not only serve as biomarkers but also may be a potential therapeutic target for MDD.

Flexible and Robust Core-Shell PANI/PVDF@PANI Nanofiber Membrane for High-Performance Electromagnetic Interference Shielding.

Developing high-performance electromagnetic interference (EMI) shielding materials that are lightweight and flexible and have excellent mechanical properties is an ideal choice for modern integrated electronic devices and microwave protection. Herein, we report the preparation of core-shell polyaniline (PANI)-based nanofiber membranes for EMI shielding through seed polymerization. Electrospinning a PANI solution leads to homogeneously dispersed PANI on the nanofiber surface, with abundant attachment sites for aniline through electrostatic adsorption and hydrogen bonding interaction, allowing PANI to grow on the nanofiber surfaces. This stable core-shell heterostructure provides more interfaces for reflecting and absorbing microwaves. The PANI/PVDF@PANI membranes achieved a shielding efficiency (SE) of 44.7 dB at a thickness of only 1.2 mm, exhibiting an exceptionally high specific EMI shielding effectiveness (SE/t) of 372.5 dB cm-1. Furthermore, the composite membrane exhibits outstanding mechanical stability, durability, air permeability, and moisture permeability, also making it suitable for applications such as EM shielding clothing.

Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases.

Nearly one-fifth of patients with non-small cell Lung Cancer (NSCLC) will develop liver metastases (LMs), and the overall treatment strategy of LMs will directly affect the survival of patients. However, some retrospective studies have found that patients receiving chemotherapy or targeted therapy have a poorer prognosis once LMs develop. In recent years, multiple randomised controlled trials (RCTS) have shown significant improvements in outcomes for patients with advanced lung cancer following the introduction of immune checkpoint inhibitors (ICIs) compared to conventional chemotherapy. ICIs is safe and effective in patients with LMs, although patients with LMs are mostly underrepresented in randomised clinical trials. However, NSCLC patients with LMs have a significantly worse prognosis than those without LMs when treated with ICIs, and the mechanism by which LMs induce systemic anti-tumour immunity reduction is unknown, so the management of LMs in patients with NSCLC is a clinical challenge that requires more optimised therapies to achieve effective disease control. In this review, we summarised the mechanism of ICIs in the treatment of LMs, the clinical research and treatment progress of ICIs and their combination with other therapies in patients with LMs from NSCLC.

Formation of Bridged Disulfide in Epidithiodioxopiperazines.

Epidithiodioxopiperazine (ETP) alkaloids, featuring a 2,5-diketopiperazine core and transannular disulfide bridge, exhibit a broad spectrum of biological activities. However, the structural complexity has prevented efficient chemical synthesis and further clinical research. In the past few decades, many achievements have been made in the biosynthesis of ETPs. Here, we discuss the biosynthetic progress and summarize them as two comprehensible metabolic principles for better understanding the complex pathways of α, α'- and α, ß'-disulfide bridged ETPs. Specifically, we systematically outline the catalytic machineries to install α, α'- and α, ß'-disulfide by flavin-containing oxygenases. This concept would contribute to the medical and industrial applications of ETPs.

Lack of ceramide synthase 5 protects retinal ganglion cells from ocular hypertensive injury.

Ceramides with varying acyl-chain lengths can have unique biological actions and hence, cellular responses to ceramides may depend not on their overall concentration but on that of individual ceramide species. The purpose of this study was to determine individual ceramide species impacting retinal ganglion cell (RGC) loss under the ocular hypertensive condition. Induced pluripotent stem cell (iPSC)-derived RGCs and primary cultures of human astrocytes were used to determine the effect of individual ceramide species on both RGC viability and astrocyte secretion of inflammatory cytokines in vitro. In in vivo experiments with wild-type (WT) and ceramide synthase 5 (CerS5) knockout mice, intraocular pressure was unilaterally elevated with microbead injection. Retinal function and morphology were evaluated using pattern electroretinography (pERG) and immunofluorescence, respectively. Ceramide levels were determined by LC-MS/MS analysis. Exposure to C16:0-, C18:0-, C18:1-, C20:0- and C24:0-ceramides significantly reduces RGC viability in vitro, with the very long chain C24:0-ceramide being the most neurotoxic; treatment with C18:0-, C18:1- and C24:0-ceramides stimulates an increase of TNF-α secretion by astrocytes. The retinas of CerS5 KO mice have significantly reduced levels of C16:0- and C18:1-ceramides compared to WT; ocular hypertensive eyes of these mice maintain higher pERG amplitudes and RGC numbers compared to WT. Individual ceramides with different chain lengths have different effects on RGCs and astrocytes. Our results demonstrate that suppressing C16:0- and C18:1-ceramide species effectively protects RGCs against ocular hypertensive injury. These results provide a basis for targeting specific ceramide species in the treatment of glaucoma.

Structural and resting-state connection abnormalities of habenula in obsessive-compulsive disorder.

BACKGROUND: Previous studies have suggested that the habenula (Hb) may be involved in the mechanism of obsessive-compulsive disorder (OCD). However, the specific role of Hb in OCD remains unclear. This study aimed to explore the structural and functional abnormalities of Hb in OCD and their relationship with the clinical symptoms. METHODS: Eighty patients with OCD and 85 healthy controls (HCs) were recruited as the primary dataset. The grey matter volume, resting-state functional connectivity (FC), and effective connectivity (EC) of the Hb were calculated and compared between OCD group and HCs. An independent replication dataset was used to verify the stability and robustness of the results. RESULTS: Patients with OCD exhibited smaller Hb volume and increased FC of right Hb-left hippocampus than HCs. Dynamic causal model revealed an increased EC from left hippocampus to right Hb and a less inhibitory causal influence from the right Hb to left hippocampus in the OCD group compared to HCs. Similar results were found in the replication dataset. CONCLUSIONS: This study suggested that abnormal structure of Hb and hippocampus-Hb connectivity may contribute to the pathological basis of OCD.

Elderly patients with advanced HER2-positive breast cancer with liver metastases benefit from low dose disitamab vedotin (RC48): case series and literature review.

Currently, although some antibody-drug conjugates have been shown to be safe and effective in the treatment of drug-resistant relapsed human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+ or IHC 2+/fluorescence in situ hybridization+) breast cancer, they are already approved for clinical use in China. But the clinical needs of advanced HER2-positive patients cannot be met due to adverse reactions, drug resistance, drug accessibility and other problems, thus affecting the prognosis of patients. In particular, the representation of elderly and frail patients in randomized clinical trials is significantly under-represented. We report on two elderly women with breast cancer who developed recurrent metastatic lesions after breast cancer surgery and were again confirmed HER2-positive by histopathology and immunohistochemistry. They all developed multiple metastases in the liver after second- or third-line anti-HER2 therapy. Subsequent treatment with RC48 produced good responses and tolerable adverse reactions. One patient obtained progression-free survival for more than 7 months. Based on preliminary evidence, this study shows that RC48 in HER2-positive breast cancer with liver metastases can achieve rapid remission, thereby reducing tumor load and improving patients' quality of life. In particular, RC48 has low side effects and can be well tolerated by elderly patients after dose adjustment, providing them with treatment opportunities. It needs to be further discussed in the future research.

Personality and cognition: shoal size discrimination performance is related to boldness and sociability among ten freshwater fish species.

Several studies have reported that animals' personalities are often correlated with individual differences in cognition. Here, we tested whether personality is related to cognition across species, focusing on 10 freshwater fishes and a task relevant for fitness, the ability to discriminate shoal size. Bolder species exhibited more 'shuttle' behavior for information sampling during shoal selection and showed high performance (HP) in the numerical discrimination than shyer species, i.e., low performance (LP) species. Species at both the high and low ends of sociability showed LP, possibly due to loosened selection pressure because of either no need to perform shoal size discrimination tasks frequently in nature for very high sociability species or decreased willingness and motivation to join and stay within shoals for very low sociability species. Notably, the numerical discrimination was sensitive to the numerical contrast ratio in LP species but not in HP species, suggesting that the numerical system used for size discrimination also varied between species. Overall, we demonstrated the interspecies relationship between personality and shoal size discrimination across fish species, suggesting an evolutionary link between numerical abilities and behavior.

Synthesis of P-Rich Carbon Quantum Dots for Sensitive Fluorescent Detection of 2-Methylimidazole.

Using o-phenylenediamine as carbon source and phytic acid as phosphorus source, two P-rich carbon quantum dots RCDs and BCDs were synthesized successfully by changing the reaction temperature and time of hydrothermal method. It was found that RCDs with red emission could realize sensitive detection of 2-methylimidazole, and 2-methylimidazole had no obvious quenching effect on BCDs with blue emission, which made RCDs a sensitive, quick and selective fluorescence sensor for 2-methylimidazole detection. Under the optimal experimental conditions, the fluorescence intensity of RCDs decreased with the increasing of 2-methylimidazole concentration. The detection of 2-methylimidazole concentration by the carbon quantum dots sensor showed a good linear relationship in the range of 5 ~ 110 µM, and the low detection limit was 0.61 µM (S/N = 3). The sensor is able to detect 2-methylimidazole in lake water, enabling the application of real samples. The results show that this work provides a simple fluorescence method to detect 2-methylimidazole in water.

Application Value of Conventional Ultrasound Combined with Shear Wave Elastography in Diagnosing Renal Fibrosis in Diabetic Nephropathy.

Background: Diabetic nephropathy is a common acute complication of diabetes mellitus and is the leading cause of chronic kidney disease (CKD) worldwide. Renal fibrosis is a major pathological change in diabetic nephropathy. Objective: To explore the diagnostic value of shear wave elastography (SWE) for renal fibrosis in patients with advanced diabetic nephropathy. Design: This was a retrospective study. Setting: This study was conducted in Heilongjiang Provincial Hospital. Participants: Sixty patients with diabetic nephropathy renal fibrosis who accepted therapy in our hospital from January 2021 to December 2022 (observation group, OG) and 60 healthy physical examination patients (control group, CG) in the same period were selected for the study. Interventions: All subjects were examined by conventional ultrasound and SWE. Primary Outcome Measures: (1) conventional ultrasonic parameters and SWE parameters and (2) clinical biochemical indicators. Results: Compared to CG, SCr and BUN in OG were higher, while eGFR in OG was lower (P < .05). Compared to CG, the cortical thickness of OG was less, and the cortical hardness of OG was more (P < .05). Compared to CKD4 patients, eGFR in CKD3 patients was higher, while SCr and BUN in CKD3 patients were lower (P < .05). Compared to CKD4 patients, the cortical thickness in CKD3 patients was higher, and cortical hardness in CKD3 patients was lower (P < .05). Conclusion: The cortical thickness and cortical hardness parameters in SWE imaging of patients with advanced diabetic nephropathy renal fibrosis are different from those of healthy people. The parameters are also significantly different in patients with different CKD stages and are significantly correlated with SCr, BUN, and eGFR, which can be used for the diagnosis of diabetic nephropathy renal fibrosis.

A new three-dimensional (3D) molecularly imprinted polymer fluoroprobe based on green-red dual-emission signals of carbon quantum dots and self-polymerization of dopamine (CDs@PDA-MIPs) for sensitive detection of nifedipine.

Nifedipine (NIF), as one of the dihydropyridine calcium channel blockers, is widely used in the treatment of hypertension. However, misuse or ingestion of NIF can result in serious health issues such as myocardial infarction, arrhythmia, stroke, and even death. It is essential to design a reliable and sensitive detection method to monitor NIF. In this work, an innovative molecularly imprinted polymer dual-emission fluorescent sensor (CDs@PDA-MIPs) strategy was successfully designed for sensitive detection of NIF. The fluorescent intensity of the probe decreased with increasing NIF concentration, showing a satisfactory linear relationship within the range 1.0 × 10-6 M ~ 5.0 × 10-3 M. The LOD of NIF was 9.38 × 10-7 M (S/N = 3) in fluorescence detection. The application of the CDs@PDA-MIPs in actual samples such as urine and Qiangli Dingxuan tablets has been verified, with recovery ranging from 97.8 to 102.8% for NIF. Therefore, the fluorescent probe demonstrates great potential as a sensing system for detecting NIF.

Elevating Detection Performance in Optical Remote Sensing Image Object Detection: A Dual Strategy with Spatially Adaptive Angle-Aware Networks and Edge-Aware Skewed Bounding Box Loss Function.

In optical remote sensing image object detection, discontinuous boundaries often limit detection accuracy, particularly at high Intersection over Union (IoU) thresholds. This paper addresses this issue by proposing the Spatial Adaptive Angle-Aware (SA3) Network. The SA3 Network employs a hierarchical refinement approach, consisting of coarse regression, fine regression, and precise tuning, to optimize the angle parameters of rotated bounding boxes. It adapts to specific task scenarios using either class-aware or class-agnostic strategies. Experimental results demonstrate its effectiveness in significantly improving detection accuracy at high IoU thresholds. Additionally, we introduce a Gaussian transform-based IoU factor during angle regression loss calculation, leading to the development of Edge-aware Skewed Bounding Box Loss (EAS Loss). The EAS loss enhances the loss gradient at the final stage of angle regression for bounding boxes, addressing the challenge of further learning when the predicted box angle closely aligns with the real target box angle. This results in increased training efficiency and better alignment between training and evaluation metrics. Experimental results show that the proposed method substantially enhances the detection accuracy of ReDet and ReBiDet models. The SA3 Network and EAS loss not only elevate the mAP of the ReBiDet model on DOTA-v1.5 to 78.85% but also effectively improve the model's mAP under high IoU threshold conditions.

Genome-Wide Identification and Characterization of the Sweet Orange (Citrus sinensis) GATA Family Reveals a Role for CsGATA12 as a Regulator of Citrus Bacterial Canker Resistance.

Citrus bacterial canker (CBC) is a severe bacterial infection caused by Xanthomonas citri subsp. citri (Xcc), which continues to adversely impact citrus production worldwide. Members of the GATA family are important regulators of plant development and regulate plant responses to particular stressors. This report aimed to systematically elucidate the Citrus sinensis genome to identify and annotate genes that encode GATAs and evaluate the functional importance of these CsGATAs as regulators of CBC resistance. In total, 24 CsGATAs were identified and classified into four subfamilies. Furthermore, the phylogenetic relationships, chromosomal locations, collinear relationships, gene structures, and conserved domains for each of these GATA family members were also evaluated. It was observed that Xcc infection induced some CsGATAs, among which CsGATA12 was chosen for further functional validation. CsGATA12 was found to be localized in the nucleus and was differentially upregulated in the CBC-resistant and CBC-sensitive Kumquat and Wanjincheng citrus varieties. When transiently overexpressed, CsGATA12 significantly reduced CBC resistance with a corresponding increase in abscisic acid, jasmonic acid, and antioxidant enzyme levels. These alterations were consistent with lower levels of salicylic acid, ethylene, and reactive oxygen species. Moreover, the bacteria-induced CsGATA12 gene silencing yielded the opposite phenotypic outcomes. This investigation highlights the important role of CsGATA12 in regulating CBC resistance, underscoring its potential utility as a target for breeding citrus varieties with superior phytopathogen resistance.

Diagnostic accuracy of artificial intelligence-assisted caries detection: a clinical evaluation.

OBJECTIVE: This clinical study aimed to evaluate the practical value of integrating an AI diagnostic model into clinical practice for caries detection using intraoral images. METHODS: In this prospective study, 4,361 teeth from 191 consecutive patients visiting an endodontics clinic were examined using an intraoral camera. The AI model, combining MobileNet-v3 and U-net architectures, was used for caries detection. The diagnostic performance of the AI model was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, with the clinical diagnosis by endodontic specialists as the reference standard. RESULTS: The overall accuracy of the AI-assisted caries detection was 93.40%. The sensitivity and specificity were 81.31% (95% CI 78.22%-84.06%) and 95.65% (95% CI 94.94%-96.26%), respectively. The NPV and PPV were 96.49% (95% CI 95.84%-97.04%) and 77.68% (95% CI 74.49%-80.58%), respectively. The diagnostic accuracy varied depending on tooth position and caries type, with the highest accuracy in anterior teeth (96.04%) and the lowest sensitivity for interproximal caries in anterior teeth and buccal caries in premolars (approximately 10%). CONCLUSION: The AI-assisted caries detection tool demonstrated potential for clinical application, with high overall accuracy and specificity. However, the sensitivity varied considerably depending on tooth position and caries type, suggesting the need for further improvement. Integration of multimodal data and development of more advanced AI models may enhance the performance of AI-assisted caries detection in clinical practice.

Identification of the shared gene signatures and molecular pathways in systemic lupus erythematosus and diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) incidence is higher in systemic lupus erythematosus (SLE) patients than the general population, but the molecular mechanisms behind this link remain ambiguous. The aim of this study was to investigate shared gene signatures and molecular pathways between SLE and DLBCL. METHODS: We procured expression profiles of SLE and DLBCL from public databases and identified common differentially expressed genes (DEGs). Functional pathway enrichment and protein-protein interaction (PPI) analyses were performed on these shared genes. The molecular complex detection technology (MCODE) and eXtreme Gradient Boosting (XGBoost) machine learning algorithm were used to select core shared genes, followed by Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis. RESULTS: We identified 54 DEGs as shared genes, among which CD177, CEACAM1, GPR84 and IFIT3 were identified as core shared genes. These genes showed strong associations with inflammatory and immune response pathways. We found a significant positive correlation between GPR84 and IFIT3 expression levels and the immune microenvironment. Decreased expression levels of GPR84 and IFIT3 were linked to enhanced immune therapy sensitivity, potentially due to lower dysregulation scores during low expression. We also discovered that TP53 mutations might elevate CD177 and GPR84 expression and that reduced expression levels of GPR84 and IFIT3 were linked with better overall survival and progression-free survival in DLBCL patients. CONCLUSIONS: Our study provides valuable insights into the shared molecular mechanisms underpinning the pathogenesis of SLE and DLBCL. These findings could potentially offer new biomarkers and therapeutic targets for SLE and DLBCL.

MnF2 Surface Modulated Hollow Carbon Nanorods on Porous Carbon Nanofibers as Efficient Bi-Functional Oxygen Catalysis for Rechargeable Zinc-Air Batteries.

Developing highly efficient bi-functional noble-metal-free oxygen electrocatalysts with low-cost and scalable synthesis approach is challenging for zinc-air batteries (ZABs). Due to the flexible valence state of manganese, MnF2 is expected to provide efficient OER. However, its insulating properties may inhibit its OER process to a certain degree. Herein, during the process of converting the manganese source in the precursor of porous carbon nanofibers (PCNFs) to manganese fluoride, the manganese source is changed to manganese acetate, which allows PCNFs to grow a large number of hollow carbon nanorods (HCNRs). Meanwhile, manganese fluoride will transform from the aggregation state into uniformly dispersed MnF2 nanodots, thereby achieving highly efficient OER catalytic activity. Furthermore, the intrinsic ORR catalytic activity of the HCNRs/MnF2 @PCNFs can be enhanced due to the charge modulation effect of MnF2 nanodots inside HCNR. In addition, the HCNRs stretched toward the liquid electrolyte can increase the capture capacity of dissolved oxygen and protect the inner MnF2 , thereby enhancing the stability of HCNRs/MnF2 @PCNFs for the oxygen electrocatalytic process. MnF2 surface-modulated HCNRs can strongly enhance ORR activity, and the uniformly dispersed MnF2 can also provide higher OER activity. Thus, the prepared HCNRs/MnF2 @PCNFs obtain efficient bifunctional oxygen catalytic ability and high-performance rechargeable ZABs.

Early Circulating Tumor DNA Dynamics Predict Neoadjuvant Therapy Response and Recurrence in Colorectal Liver Metastases: A Prospective Study.

BACKGROUND: For patients with colorectal liver metastases (CRLM) who receive neoadjuvant therapy (NAT), reliable indicators that can early and accurately predict treatment response are lacking. This study was conducted to prospectively investigate the potential of early circulating tumor DNA (ctDNA) dynamics as a precise predictor of NAT response and recurrence in CRLM. METHODS: This study prospectively enrolled 34 patients with CRLM who received NAT, with blood samples collected and subjected to deep targeted panel sequencing at two time points: 1 day before the first and the second cycles of NAT. Correlations of ctDNA mean variant allele frequency (mVAF) dynamics and treatment response were assessed. The performance of early ctDNA dynamics in predicting treatment response was assessed and compared with those of carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9). RESULTS: The baseline ctDNA mVAF was significantly associated with pre-NAT tumor diameter (r = 0.65; P < 0.0001). After one cycle of NAT, the ctDNA mVAF declined remarkably (P < 0.0001). The dynamic change in ctDNA mVAF of 50% or more was significantly correlated with better NAT responses. The discriminatory capacity of ctDNA mVAF changes was superior to that of CEA or CA19-9 in predicting radiologic response (area under the curve [AUC], 0.90 vs 0.71 vs 0.61) and pathologic tumor regression grade (AUC, 0.83 vs 0.64 vs 0.67). The early changes in ctDNA mVAF but not CEA or CA19-9 were an independent indicator of recurrence-free survival (RFS) (hazard ratio, 4.0; P = 0.023). CONCLUSIONS: For CRLM patients receiving NAT, an early ctDNA change is a superior predictor of treatment response and recurrence compared with conventional tumor markers.

Regulatory role of Chitinase 3-like 1 gene in papillary thyroid carcinoma proved by integration analyses of single-cell sequencing with cohort and experimental validations.

Papillary thyroid carcinoma (PTC) is one of the most common thyroid carcinomas. The gross extrathyroidal extension and extensive metastases of PTC lead to high rates of recurrence and poor clinical outcomes. However, the mechanisms underlying PTC development are poorly understood. In this study, using single-cell RNA sequencing, the transcriptome profiles of two PTC patients were addressed, including PTC1 with low malignancy and good prognosis and PTC2 with high malignancy and poor prognosis. We found that epithelial subcluster Epi02 was the most associated with the malignant development of PTC cells, with which the fold change of Chitinase 3-like 1 (CHI3L1) is on the top of the differentially expressed genes between PTC1 and PTC2 (P < 0.001). However CHI3L1 is rarely investigated in PTC as far. We then studied its role in PTC with a series of experiments. Firstly, qRT-PCR analysis of 14 PTC patients showed that the expression of CHI3L1 was positively correlated with malignancy. In addition, overexpression or silencing of CHI3L1 in TPC-1 cells, a PTC cell line, cultured in vitro showed that the proliferation, invasion, and metastasis of the cells were promoted or alleviated by CHI3L1. Further, immunohistochemistry analysis of 110 PTC cases revealed a significant relationship between CHI3L1 protein expression and PTC progression, especially the T (P < 0.001), N (P < 0.001), M stages (P = 0.007) and gross ETE (P < 0.001). Together, our results prove that CHI3L1 is a positive regulator of malignant development of PTC, and it promotes proliferation, invasion, and metastasis of PTC cells. Our study improves understanding of the molecular mechanisms underlying the progression of PTC and provides new insights for the clinical diagnosis and treatment of PTC.

Cognitive function and neuroimaging characteristics in patients with childhood-onset type 1 diabetes mellitus.

AIMS: In this study, we used neuropsychological tests and neuroimaging to examine the cognitive functions and neuroimaging characteristics to explore the brain mechanism of cognitive deficits in patients with childhood-onset type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: A total of 30 patients with childhood-onset T1DM and 28 healthy controls (HC) participated in the study. Neuropsychological tests were used to assess intelligence quotient, memory, and executive function. Voxel-based morphometry-diffeomorphic anatomical registration through exponential lie algebra analysis and amplitude of low-frequent fluctuation (ALFF) were performed to evaluate the brain grey matter volume and neural spontaneous activity for each participant. RESULTS: Compared with HC, patients with childhood-onset T1DM showed a significant decline in verbal memory (p = 0.001) and visual memory (p = 0.002). Patients with T1DM had smaller grey matter volumes at the midbrain, thalamus, and cerebellar culmen. They demonstrated an increased ALFF value in the left precentral gyrus, left postcentral gyrus, left insula, and left supramarginal gyrus and a decreased ALFF value in the basal ganglia (putamen nucleus), right insula, right superior temporal gyrus, and cerebellar posterior lobe than the healthy control group. In the T1DM group, the ALFF value in the right insula was positively related to the verbal memory scores (r = 0.423, p = 0.025). CONCLUSIONS: Childhood-onset T1DM was associated with cognitive deficits and changes in brain structure and function. These findings suggest that the brain structural and functional alterations in these regions may be the neuropathology of cognitive deficits in patients with T1DM.