Research progress of the netrins and their receptors in cancer.

Netrins, a family of secreted and membrane-associated proteins, can regulate axonal guidance, morphogenesis, angiogenesis, cell migration, cell survival, and tumorigenesis. Four secreted netrins (netrin 1, 3, 4 and 5) and two glycosylphosphatidylinositols-anchored membrane proteins, netrin-G1 and G2, have been identified in mammals. Netrins and their receptors can serve as a biomarker and molecular therapeutic target for pathological differentiation, diagnosis and prognosis of malignant cancers. We review here the potential roles of the netrins family and their receptors in cancer.

Targeted metabolomics combined with machine learning to identify and validate new biomarkers for early SLE diagnosis and disease activity.

BACKGROUND: The early diagnosis of systemic lupus erythematosus (SLE) and the assessment of disease activity progression remain a great challenge. Targeted metabolomics has great potential to identify new biomarkers of SLE. METHODS: Serum from 44 healthy participants and 89 SLE patients were analyzed using HM400 high-throughput targeted metabolomics. Machine learning (ML) with seven learning models and trained the model several times iteratively selected the two best prediction model in a competitive way, which were independent validated by enzyme-linked immunosorbent (ELISA) with 90 SLE patients. RESULTS: In this study, 146 differential metabolites, most of them organic acids, amino acids, and bile acids, were detected between patients with initial SLE and healthy participants, and 8 potential biomarkers were found by intersection of ML and statistics (area under the curve [AUC] > 0.95) showing a significant positive correlation with clinical indicators. In addition, we identified and validated 2 potential biomarkers for SLE classification (P < 0.05, AUC > 0.775; N-Methyl-L-glutamic acid, L-2-aminobutyric acid) showing a significant correlation with the SLE Disease Activity Index. These differential metabolites were mainly involved in metabolic pathways, amino acid biosynthesis, 2-oxocarboxylic acid metabolism and other pathways. CONCLUSION: This study indicated that the tricarboxylic acid cycle might be associated with SLE drug therapy. We identified 8 diagnostic models biomarkers and 2 biomarkers that could be used to identify initial SLE and distinguish different activity degree, which will promote the development of new tools for the diagnosis and evaluation of SLE.

Identifying clinical risk factors correlated with addictive features of non-suicidal self-injury among a consecutive psychiatric outpatient sample of adolescents and young adults.

Non-suicidal self-injury (NSSI) is an issue primarily of concern in adolescents and young adults. Recent literature suggests that persistent, repetitive, and uncontrollable NSSI can be conceptualized as a behavioral addiction. The study aimed to examine the prevalence of NSSI with addictive features and the association of this prevalence with demographic and clinical variables using a cross-sectional and case-control design. A total of 548 outpatients (12 to 22 years old) meeting the criteria for NSSI disorder of DSM-5 were enrolled and completed clinical interviews by 4 psychiatrists. NSSI with addictive features were determined by using a single-factor structure of addictive features items in the Ottawa self-injury inventory (OSI). Current suicidality, psychiatric diagnosis, the OSI, the revised Chinese Internet Addiction Scale, the Childhood Trauma Questionnaire, and the 20-item Toronto Alexithymia Scale were collected. Binary logistic regression analyses were used to explore associations between risk factors and NSSI with addictive features. This study was conducted from April 2021 to May 2022. The mean age of participants was 15.93 (SD = 2.56) years with 418 females (76.3%), and the prevalence of addictive NSSI was 57.5% (n = 315). Subjects with addictive NSSI had a higher lifetime prevalence of nicotine and alcohol use, a higher prevalence of current internet addiction, suicidality, and alexithymia, and were more likely to have physical abuse/neglect, emotional abuse, and sexual abuse than NSSI subjects without addictive features. Among participants with NSSI, the strongest predictors of addictive features of NSSI were female (OR = 2.405, 95% CI 1.512-3.824, p < 0.0001), alcohol use (OR = 2.179, 95% CI 1.378-3.446, p = 0.001), current suicidality (OR = 3.790, 95% CI 2.351-6.109, p < 0.0001), and psysical abuse in childhood (OR = 2.470, 95% CI 1.653-3.690, p < 0.0001). Nearly 3 out of 5 patients (12-22 years old) with NSSI met the criteria of NSSI with addictive features in this psychiatric outpatients sample. Our study demonstrated the importance of the necessity to regularly assess suicide risk, and alcohol use, as well as focus more on females and subjects who had physical abuse in childhood to prevent addictive NSSI.

A novel approach to deriving the fine-scale daily NO2 dataset during 2005-2020 in China: Improving spatial resolution and temporal coverage to advance exposure assessment.

Surface NO2 pollution can result in serious health consequences such as cardiovascular disease, asthma, and premature mortality. Due to the extensive spatial variation in surface NO2, the spatial resolution of a NO2 dataset has a significant impact on the exposure and health impact assessment. There is currently no long-term, high-resolution, and publicly available NO2 dataset for China. To fill this gap, this study generated a NO2 dataset named RBE-DS-NO2 for China during 2005-2020 at 1 km and daily resolution. We employed the robust back-extrapolation via a data augmentation approach (RBE-DA) to ensure the predictive accuracy in back-extrapolation before 2013, and utilized an improved spatial downscaling technique (DS) to refine the spatial resolution from 10 km to 1 km. Back-extrapolation validation based on 2005-2012 observations from sites in Taiwan province yielded an R2 of 0.72 and RMSE of 10.7 µg/m3, while cross-validation across China during 2013-2020 showed an R2 of 0.73 and RMSE of 9.6 µg/m3. RBE-DS-NO2 better captured spatiotemporal variation of surface NO2 in China compared to the existing publicly available datasets. Exposure assessment using RBE-DS-NO2 show that the population living in non-attainment areas (NO2 ≥ 30 µg/m3) grew from 376 million in 2005 to 612 million in 2012, then declined to 404 million by 2020. Unlike this national trend, exposure levels in several major cities (e.g., Shanghai and Chengdu) continued to increase during 2012-2020, driven by population growth and urban migration. Furthermore, this study revealed that low-resolution dataset (i.e., the 10 km intermediate dataset before the downscaling) overestimated NO2 levels, due to the limited specificity of the low-resolution model in simulating the relationship between NO2 and the predictor variables. Such limited specificity likely biased previous long-term NO2 exposure and health impact studies employing low-resolution datasets. The RBE-DS-NO2 dataset enables robust long-term assessments of NO2 exposure and health impacts in China.

Integration of molecular docking, molecular dynamics and network pharmacology to explore the multi-target pharmacology of fenugreek against diabetes.

Fenugreek is an ancient herb that has been used for centuries to treat diabetes. However, how the fenugreek-derived chemical compounds work in treating diabetes remains unclarified. Herein, we integrate molecular docking and network pharmacology to elucidate the active constituents and potential mechanisms of fenugreek against diabetes. First, 19 active compounds from fenugreek and 71 key diabetes-related targets were identified through network pharmacology analysis. Then, molecular docking and simulations results suggest diosgenin, luteolin and quercetin against diabetes via regulation of the genes ESR1, CAV1, VEGFA, TP53, CAT, AKT1, IL6 and IL1. These compounds and genes may be key factors of fenugreek in treating diabetes. Cells results demonstrate that fenugreek has good biological safety and can effectively improve the glucose consumption of IR-HepG2 cells. Pathway enrichment analysis revealed that the anti-diabetic effect of fenugreek was regulated by the AGE-RAGE and NF-κB signalling pathways. It is mainly associated with anti-oxidative stress, anti-inflammatory response and ß-cell protection. Our study identified the active constituents and potential signalling pathways involved in the anti-diabetic effect of fenugreek. These findings provide a theoretical basis for understanding the mechanism of the anti-diabetic effect of fenugreek. Finally, this study may help for developing anti-diabetic dietary supplements or drugs based on fenugreek.

Multifunctional tunable visible light metalens based on double-layer barium titanate.

A tunable metalens plays an indispensable role in the development of integrated optics, multi-imaging systems, etc. We propose a multifunctional tunable metalens that combines a double-layer barium titanate (BTO) structure and geometric phase in the visible light band. The refractive indices of the upper and lower layer BTO nanorods can be tuned continuously and independently by applying external voltage (0-60 V), and the lower layer can be converted between a full-wave plate and normal scattering unit, while the scatterers of the upper layer can be switched between a half-wave plate and full-wave plate. The voltages of the upper and lower layers can be adjusted to achieve different functions such as optical switches, conversion between monofocal and bifocal metalenses, adjustment of bifocal intensity, and broadband focusing (585-690 nm). Simulation results show that the multifunctional tunable metalens has a good focusing effect. A metalens with high focusing efficiency, dynamic reconfigurability, and a switching function has tremendous application potential in the fields of multifunctional devices, biomedicine, optical communication, imaging, and so on.

Design of a vortex metalens with high focusing efficiency using propagation phase.

Three vortex-focused beams are produced with linearly polarized light along the x or y axis at a wavelength of 1550 nm. First, a polarization-independent vortex metalens with a topological charge of three and focal length of 3000 nm is designed by selecting cylindrical-shaped elements. This design has a focusing efficiency of 83%. Second, vortex beams with different focal lengths and topological charges are achieved by combining various shapes of structures. Both designs have a focusing efficiency of greater than 92%. The designed metasurface is of great significance to optical communication and radar detection.

SnSe2 realizes soliton rain and harmonic soliton molecules in erbium-doped fiber lasers.

Two-dimensional layered metal chalcogenides (LMCs) are widely used in battery anode materials, energy conversion, and semiconductor devices, because of their high energy storage characteristics, high thermoelectric characteristics, and large electron mobility. SnSe2 as a kind of LMC has strong nonlinear optical characteristics. However, its research on dissipative system dynamics as a saturable absorber has not been studied. In this work, we obtained SnSe2 nanosheets using lithium ion intercalation and we reported a passively mode-locked fiber laser with SnSe2 as a saturable absorber to achieve the dissipative soliton in a dissipative system. Due to the high third-order nonlinearity of SnSe2, the evolution of square wave pulses from 2 to 16 ns was obtained in a fiber ring cavity. Through adjusting the polarization state, the evolution phenomenon of soliton rain, the soliton rain phenomenon with a spectrum of dual-wavelengths, and a bound state harmonic phenomenon with a frequency of 313 MHz were obtained. Therefore, the strong nonlinear fiber laser based on SnSe2 provides a good platform for study the pulsation, explosion, rainfall and other phenomena.

Three-dimensional Ag2S cubes for switchable multi-wavelength ultrashort pulse application.

Three-dimensional (3D) materials are widely used in optoelectronics, thermodynamics and ultrafast fiber lasers because of their excellent nonlinear optical properties. Silver sulfide (Ag2S) is a kind of 3D material with a unique cubic structure and large absorption coefficient. In this paper, a double-balance detection system is used to measure the saturation absorption intensity of Ag2S as 226.6 MW cm-2and the modulation depth as 13.9%. In the ring fiber laser, Ag2S is used as a saturable absorber (SA) to obtain a stable dual-wavelength mode locking. The center wavelengths of the mode locking are 1536.9 and 1544.5 nm, and the corresponding 3 dB bandwidths are 1.3 and 1.5. nm. By adjusting the polarization controller, a tuning process from two wavelengths to multiple wavelengths is realized, and the tunable width is 13.1 nm. This phenomenon is due to the combined effect of birefringence and nonlinear effects in the cavity. To our knowledge, this is the first report of a multiplexed fiber laser with Ag2S as a SA. The emergence of this result provides a valuable reference information for the multifunctional compact fiber laser, and the formed system can be applied in the fields of fiber sensing, telecommunications and optical communication.

In2Se3 nanosheets for harmonic mode-locked fiber laser.

Two-dimensional materials with a sheet structure have excellent optical, electrical and mechanical properties, and have attracted much attention in recent years, especially In2Se3 (the N-type semiconductor compound), which has a rapid development in the fields of materials science and optical communication. In this paper, the nonlinear saturation absorption characteristics of In2Se3 are studied. The In2Se3 nanosheet dispersion can be used in ultrafast photonics applications. The nonlinear absorption is measured by power dependent method, and the modulation depth and saturation intensity are 3.8% and 246.6 MW cm-2, respectively. More importantly, In2Se3 is used as a saturable absorber (SA) in a passively mode-locked erbium-doped fiber laser. The proposed mode-locked fiber laser is demenstrated with a center wavelength of 1529.4 nm, a fundamental frequency of 5.9 MHz, a spectral width of 3.96 nm, a pulse width of 1.38 ps, and a signal-to-noise ratio of 55 dB. For the first time, harmonic mode-locking with a high-repetition rate of 431 MHz is achieved when the pump power is 360 mW corresponding to 73rd-order harmonic mode locking. It can be seen that In2Se3 is indeed a new excellent photonic material, which can be used in fiber optic communication, SAs photonics, laser material processing and light modulators.

Few-layer bismuthene for femtosecond soliton molecules generation in Er-doped fiber laser.

Bismuthene, a mono-elemental two-dimensional material with a novel kind of few-layer structure purely consisting of bismuth, has been predicted to have a prominent optical response and enhanced stability in theory. In this paper, few-layer bismuthene is employed as the saturable absorber. The mode-locker is fabricated by dropping bismuthene on a microfiber in a passively mode-locked, Er-doped fiber laser. The single pulse can be obtained at 122.1 mW, with 621.5 fs pulse duration at 1557.5 nm central wavelength, 10.35 nm spectral width and fundamental repetition of 22.74 MHz. Thanks to the outstanding nonlinear effect and semimetal of the bismuthene, dual-pulses, octonary-pulses and fourteen-pulses soliton molecules with tightly and loosely temporal separation can be achieved for the first time, to the best of our knowledge. The preceding indicates that bismuthene will have wide potential in many applications, such as optical fiber communications, optical logical gate, and laser materials processing, etc.

Donor-Derived Regulatory T Cells Attenuate the Severity of Acute Graft-Versus-Host Disease after Cord Blood Transplantation.

Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a curative therapy for some types of hematological disorders. However, allo-PBSCT is commonly complicated with acute graft-versus-host disease (aGVHD), characterized by host tissues being attacked by the grafted donor lymphocytes due to disparities of human leukocyte antigen (HLA) between the donor and host. By contrast, cord blood transplantation (CBT) is typically associated with low-grade severity of aGVHD, but the underlying mechanisms remain unclear. Donor-derived CD4(+) alloreactive T cells (ATs) are of a specific lymphocyte subset, which can be activated by the recipient's HLA, and play a crucial role in the onset of aGVHD. In the present study, we aimed to explore the difference in the property of CD4(+) ATs between cord blood (CB) and adult peripheral blood (APB). We thus found that CB and APB CD4(+) ATs contained not only effector T cells (Teffs) that execute aGVHD, but also a distinct subset of FoxP3(+) regulatory T cells (Tregs) that may alleviate aGVHD. Importantly, CB CD4(+) ATs contained higher percentage of FoxP3(+) Tregs, compared to APB CD4(+) ATs (P < 0.001), while lower percentage of Teffs (Th1, Th2 and Th17 cells) was detected in CB CD4(+) ATs (P < 0.05, P < 0.001 and P < 0.05, respectively). Our findings suggest that FoxP3(+) Tregs in CB CD4(+) ATs may contribute to attenuating the severity of aGVHD observed after CBT.

Identification and validation of a novel glycolysis-related ceRNA network for sepsis-induced cardiomyopathy.

Purpose: Sepsis-induced cardiomyopathy (SIC) is a major life-threatening condition in critically infected patients. Early diagnosis and intervention are important to improve patient prognosis. Recognizing the pivotal involvement of the glycolytic pathway in SIC, this study aims to establish a glycolysis-related ceRNA network and explore novel diagnostic avenues. Materials and methods: SIC-related datasets were carefully filtered from the GEO database. CytoHubba was used to identify differentially expressed genes (DEGs) associated with glycolysis. A predictive method was then used to construct an lncRNA-miRNA-mRNA network. Dual-luciferase reporter assays validated gene interactions, and the specificity of this ceRNA network was confirmed in peripheral blood mononuclear cells (PBMCs) from SIC patients. Logistic analysis was used to examine the correlation between the ceRNA network and SIC. Diagnostic potential was assessed using receiver operating characteristic (ROC) curves, and correlation analysis investigated any associations between gene expression and clinical indicators. Results: IER3 was identified as glycolysis-related DEG in SIC, and a ceRNA network (SNHG17/miR-214-3p/IER3) was established by prediction. Dual luciferase reporter gene assay confirmed the presence of mutual binding between IER3, miR-214-3p and SNHG17. RT-qPCR verified the specific expression of this ceRNA network in SIC patients. Multivariate logistic analysis established the correlation between the ceRNA network and SIC. ROC analysis demonstrated its high diagnostic specificity (AUC > 0.8). Correlation analysis revealed a negative association between IER3 expression and oxygenation index in SIC patients (p < 0.05). Furthermore, miR-214-3p expression showed a negative correlation with NT-proBNP (p < 0.05). Conclusion: In this study, we identified and validated a ceRNA network associated with glycolysis in SIC: SNHG17/miR-214-3p/IER3. This ceRNA network may play a critical role in the onset and development of SIC. This finding is important to further our understanding of the pathophysiological mechanisms underlying SIC and to explore potential diagnostic and therapeutic targets for SIC.

Comprehensive analysis and prognostic assessment of senescence-associated genes in bladder cancer.

BACKGROUND: The prevalence and mortality of bladder cancer (BLCA) present a significant medical challenge. While the function of senescence-related genes in tumor development is recognized, their prognostic significance in BLCA has not been thoroughly explored. METHODS: BLCA transcriptome datasets were sourced from the TCGA and GEO repositories. Gene groupings were determined through differential gene expression and non-negative matrix factorization (NMF) methodologies. Key senescence-linked genes were isolated using singular and multivariate Cox regression analyses, combined with lasso regression. Validation was undertaken with GEO database information. Predictive models, or nomograms, were developed by merging risk metrics with clinical records, and their efficacy was gauged using ROC curve methodologies. The immune response's dependency on the risk metric was assessed through the immune phenomenon score (IPS). Additionally, we estimated IC50 metrics for potential chemotherapeutic agents. RESULTS: Reviewing 406 neoplastic and 19 standard tissue specimens from the TCGA repository facilitated the bifurcation of subjects into two unique clusters (C1 and C2) according to senescence-related gene expression. After a stringent statistical evaluation, a set of ten pivotal genes was discerned and applied for risk stratification. Validity tests for the devised nomograms in forecasting 1, 3, and 5-year survival probabilities for BLCA patients were executed via ROC and calibration plots. IC50 estimations highlighted a heightened responsiveness in the low-risk category to agents like cisplatin, cyclopamine, and sorafenib. CONCLUSIONS: In summation, our research emphasizes the prospective utility of risk assessments rooted in senescence-related gene signatures for enhancing BLCA clinical oversight.

Non-coding RNAs are involved in tumor cell death and affect tumorigenesis, progression, and treatment: a systematic review.

Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and non-programmed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors.

Comprehensive analysis of the role of Netrin G1 (NTNG1) in hepatocellular carcinoma cells.

Netrin G1 (NTNG1) is a member of the Netrin family and plays a crucial role in various human cancers. However, the molecular functions of NTNG1 in HCC and the underlying mechanisms remain unclear. HCC expression data was obtained from the GEO database and analyzed using various bioinformatics tools. The expression of NTNG1 in HCC tissues and liver cancer cells was evaluated through RT-qPCR and western blotting. Cells with stable NTNG1 overexpression and knockdown were established, and CCK-8, colony formation, and flow cytometry assays were conducted in vitro. The xenograft model was utilized to verify the tumorigenesis capacity of NTNG1 in vivo. IHC was employed to analyze the expression of NTNG1 and CD163 proteins. HCC-specific genes were screened, followed by functional enrichment and immune cell infiltration analysis. Finally, the Co-IP was used to detect the interaction between NTNG1 and N-cadherin. NTNG1 was highly expressed in HCC tissues and liver cancer cells, and associated with significantly poorer OS rates. In addition, NTNG1 overexpression in liver cancer cells significantly increased their proliferation, colony growth, invasion, migration, and EMT, while inhibiting apoptosis. Bioinformatics analyses indicated that NTNG1 was closely related to EMT and tumor infiltration. IHC staining revealed a positive correlation between NTNG1 expression and CD163 in HCC tissues. Additionally, an EMT inhibitor attenuated the expression levels of EMT-related markers and counteracted the effects of NTNG1 overexpression in liver cancer cells. This study is the first to identify NTNG1 as a potential therapeutic target in HCC, promoting tumor development and progression by regulating EMT.

PLA inhibits TNF-α-induced PANoptosis of prostate cancer cells through metabolic reprogramming.

Previous studies have shown that phenyllactic acid (alpha-Hydroxyhydrocinnamic acid, 2-Hydroxy-3-phenylpropionic acid, PLA), a type of organic acid metabolite, has excellent diagnostic efficacy when used to differentiate between prostate cancer, benign prostatic hyperplasia, and prostatitis. This research aims to explore the molecular mechanism by which PLA influences the PANoptosis of prostate cancer (PCa) cell lines. First, we found that PLA was detected in all prostate cancer cell lines (PC-3, PC-3 M, DU145, LNCAP). Further experiments showed that the addition of PLA to prostate cancer cells could promote ATP generation, enhance cysteine desulfurase (NFS1) expression, and reduce tumor necrosis factor alpha (TNF-α) levels, thereby inhibiting apoptosis in prostate cancer cells. Notably, overexpression of NFS1 can inhibit the binding of TNF-α to serpin mRNA binding protein 1 (SERBP1), suggesting that NFS1 competes with TNF-α for binding to SERBP1. Knockdown of SERBP1 significantly reduced the level of small ubiquity-related modifier (SUMO) modification of TNF-α. This suggests that NFS1 reduces the SUMO modification of TNF-α by competing with SERBP1, thereby reducing the expression and stability of TNF-α and ultimately inhibiting apoptosis in prostate cancer cell lines. In conclusion, PLA inhibits TNF-α induced panapoptosis of prostate cancer cells through metabolic reprogramming, providing a new idea for targeted treatment of prostate cancer.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Integrating Single-Cell and Spatial Transcriptomics to Uncover and Elucidate GP73-Mediated Pro-Angiogenic Regulatory Networks in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.

circSPECC1 Promotes Proliferation and Migration of LNCaP Prostate Cancer Cells by Affecting Their Epithelial-Mesenchymal Transition.

Objective: To determine the effects of circSPECC1 (hsa_circ_0000745) on the proliferation and migration of LNCaP prostate cancer cells and to explore the potential molecular mechanism. Methods: Stable circSPECC1 shRNA-expressing and circSPECC1-overexpressing LNCaP cell lines were constructed, and relative gene expression levels were determined by RT-PCR. MTT and clonogenic assays were used to assess proliferative ability while a scratch test was used to analyze cell migration. Western blotting was used to determine protein expression levels. The effects of circSPECC1 on the proliferation of LNCaP prostate cancer cells were observed in vivo. Results: circSPECC1 was found to be derived from the SPECC1 (sperm antigen with calponin homology and coiled-coil domains 1) parent gene and to form a loop. Overexpression of circSPECC1 promoted the proliferation and migration of the LNCaP cells, whereas decreased expression of circSPECC1 inhibited these properties. Overexpression of circSPECC1 promoted the expression of MMP-2, MMP-9, VEGF, vimentin, and N-cad but downregulated the expression of E-cad. Decreased expression of circSPECC1 inhibited the expression of MMP-2, MMP-9, VEGF, vimentin, and N-cad but increased the expression of E-cad. Conclusion: circSPECC1 promotes cell proliferation and migration by affecting the epithelial-mesenchymal transition of LNCaP prostate cancer cells.