Napabucasin deactivates STAT3 and promotes mitoxantrone-mediated cGAS-STING activation for hepatocellular carcinoma chemo-immunotherapy.

The immune resistance of tumor microenvironment (TME) causes immune checkpoint blockade therapy inefficient to hepatocellular carcinoma (HCC). Emerging strategies of using chemotherapy regimens to reverse the immune resistance provide the promise for promoting the efficiency of immune checkpoint inhibitors. The induction of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) in tumor cells evokes the adaptive immunity and remodels the immunosuppressive TME. In this study, we report that mitoxantrone (MIT, a chemotherapeutic drug) activates the cGAS-STING signaling pathway of HCC cells. We provide an approach to augment the efficacy of MIT using a signal transducer and activator of transcription 3 (STAT3) inhibitor called napabucasin (NAP). We prepare an aminoethyl anisamide (AEAA)-targeted polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA)-based nanocarrier for co-delivery of MIT and NAP. The resultant co-nanoformulation can elicit the cGAS-STING-based immune responses to reshape the immunoresistant TME in the mice orthotopically grafted with HCC. Consequently, the resultant co-nanoformulation can promote anti-PD-1 antibody for suppressing HCC development, generating long-term survival, and inhibiting tumor recurrence. This study reveals the potential of MIT to activate the cGAS-STING signaling pathway, and confirms the feasibility of nano co-delivery for MIT and NAP on achieving HCC chemo-immunotherapy.

MiR-875-5p suppresses Gli1 to alter the hedgehog signaling pathway, which in turn has hepatocellular cancer-related tumor suppressing properties.

Background: One of the most prevalent cancers worldwide is HCC, which has put patient health at risk. Increasing evidence indicated that messenger RNAs (mRNAs) played significant roles in modulating tumorigenesis. It has been established that Gli1 acts as an oncogene in a number of malignancies. However, more research was necessary to understand the Gli1 regulation mechanism in HCC. Methods: Microarray technology was used to evaluate the expression of mRNAs. RT-qPCR was utilized to evaluate Gli1 and miR-875-5p expression. To investigate the role of Gli1, tests using CCK-8, EdU, transwell, immunofluorescence, and Western blot analysis was performed. RIP, RNA pull down, and luciferase reporter assays were employed to verify the interaction between Gli1 and miR-875-5p. Results: In tissues and cells of HCC, Gli1 expression appeared to be upregulated, especially in metastatic samples and advanced stages of the disease. A worse outcome was predicted by elevated Gli1 expression. Additionally, in HCC, Gli1 inhibition impeded the growth, migration, and development of the EMT. Since miR-875-5p was shown to have a molecular target in Gli1, miR-875-5p mediated the negative regulation of Gli1. In HCC tissues, its expression pattern was less prominent. In HCC tissues, there was an inverse relationship between Gli1 expression and miR-875-5p expression. Overexpressing Gli1 helped to partially counteract the suppression of HCC migration, proliferation, and EMT formation by miR-875-5p overexpression. Conclusions: MiR-875-5p in HCC suppresses tumors by downregulating Gli1, which supplies a novel treatment for HCC patients.

[Clinical study on the effects of cluster needling at scalp points with needle retaining combined with the training of the upper-limb intelligent rehabilitation robot on shoulder function in stroke patients during convalescence]. / å¤´ç©´ä¸›åˆºç•™é’ˆç»“åˆä¸Šè‚¢æ™ºèƒ½åº·å¤æœºå™¨äººå¯¹è„‘å’ä¸­æ¢å¤æœŸæ‚£è€ è‚©å ³èŠ‚åŠŸèƒ½å½±å“çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To explore the effects of cluster needling at scalp points with needle retaining combined with the training of the upper-limb intelligent rehabilitation robot on shoulder function in stroke patients during convalescence. METHODS: Ninety stroke patients during convalescence were collected and randomized into scalp point group, robot training group and combined intervention group, with 30 cases each. In the scalp point group, the cluster needling was delivered at scalp points with the needles retained. In the robot training group, the patients were trained with the upper-limb intelligent rehabilitation robot. In the combined intervention group, the patients received both the cluster needling and the training of the upper-limb intelligent rehabilitation robot. In each group, the treatment was given once daily, 5 treatments a week with 2 days rest, for consecutive 4 weeks. Separately, before and after treatment, the score of Fugl-Meyer assessment upper extremity scale (FMA-UE) and the score of activity of daily living (ADL) were evaluated. Using the in-built assessment system of the upper-limb intelligent rehabilitation robot, the range of motion (ROM) of forward flexion, horizontal abduction and horizontal adduction of the affected shoulder joint were evaluated. With surface electromyogram (sEMG), the sEMG value of the deltoid muscle and the pectoralis major on the affected side were detected. RESULTS: Compared with the values before treatment, ADL score and FMA-UA score increased in patients of the three groups (P<0.05), and ROM of forward flexion, horizontal abduction and horizontal adduction of the affected shoulder joint was larger (P<0.05), the sEMG value of the fasciculi pectoralis major anterior of patients in the combined intervention group was reduced (P<0.05), and the sEMG of anterior deltoid tract was elevated in the three groups (P<0.05). When compared with the scalp point group and the robot group, in the combined intervention group, after treatment, ADL score and FMA-UA score were higher (P<0.05), ROM of forward flexion, horizontal abduction and horizontal adduction of the affected shoulder joint elevated (P<0.05) and sEMG value of the fasciculi pectoralis major anterior reduced (P<0.05), while which of the anterior deltoid tract was elevated (P<0.05). CONCLUSIONS: The cluster needling at scalp points with needle retaining, combined with the training of the upper-limb intelligent rehabilitation robot, improves the upper limb motor function and the range of motion of the shoulder joint in stroke patients during convalescence.

Image-based multi-omics analysis for oral science: recent progress and perspectives.

OBJECTIVES: The diagnosis and treatment of oral and dental diseases rely heavily on various types of medical imaging. Deep learning-mediated multi-omics analysis can extract more representative features than those identified through traditional diagnostic methods. This review aims to discuss the applications and recent advances in image-based multi-omics analysis in oral science and to highlight its potential to enhance traditional diagnostic approaches for oral diseases. STUDY SELECTION, DATA, AND SOURCES: A systematic search was conducted in the PubMed, Web of Science, and Google Scholar databases, covering all available records. This search thoroughly examined and summarized advances in image-based multi-omics analysis in oral and maxillofacial medicine. CONCLUSIONS: This review comprehensively summarizes recent advancements in image-based multi-omics analysis for oral science, including radiomics, pathomics, and photographic-based omics analysis. It also discusses the ongoing challenges and future perspectives that could provide new insights into exploiting the potential of image-based omics analysis in the field of oral science. CLINICAL SIGNIFICANCE: This review article presents the state of image-based multi-omics analysis in stomatology, aiming to help oral clinicians recognize the utility of combining omics analyses with imaging during diagnosis and treatment, which can improve diagnostic accuracy, shorten times to diagnosis, save medical resources, and reduce disparity in professional knowledge among clinicians.

Nano co-delivery of doxorubicin and plumbagin achieves synergistic chemotherapy of hepatocellular carcinoma.

Doxorubicin (DOX) is a chemotherapy drug used for hepatocellular carcinoma (HCC) treatment, but its effectiveness can be dramatically dampened by cancer cell chemoresistance. Signal transducer and activator of transcription 3 (STAT3) is implicated with drug resistance in a range of cancers (e.g., HCC), and the STAT3 inhibition can reverse the resistance of cancer cells to chemotherapeutic drugs. In the present study, a combination regimen to improve the efficiency of DOX was provided via the STAT3 blockade using plumbagin (PLB). A poly(lactic-co-glycolic acid) decorated by polyethylene glycol and aminoethyl anisamide was produced in the present study with the hope of generating the nanoparticles for co-delivery of DOX and PLB. The resulting co-formulation suppressed the STAT3 activity and achieved the synergistic chemotherapy, which led to tumor inhibition in the mice with subcutaneous DOX-resistant HCC, without causing any toxicity. The present study reveals the synergism of DOX and PLB, and demonstrates a promising combinatorial approach for treating HCC.

Modified five times simulated body fluid for efficient biomimetic mineralization.

Simulated body fluid (SBF) is widely utilized in preclinical research for estimating the mineralization efficacy of biomaterials. Therefore, it is of great significance to construct an efficient and stable SBF mineralization system. The conventional SBF solutions cannot maintain a stable pH value and are prone to precipitate homogeneous calcium salts at the early stages of the biomimetic process because of the release of gaseous CO2. In this study, a simple but efficient five times SBF buffered by 5 % CO2 was developed and demonstrated to achieve excellent mineralized microstructure on a type of polymer-aligned nanofibrous scaffolds, which is strikingly similar to the natural human bone tissue. Scanning electron microscopy and energy-dispersive X-ray examinations indicated the growth of heterogeneous apatite with a high-calcium-to-phosphate ratio on the aligned nanofibers under 5 times SBF buffered by 5 % CO2. Moreover, X-ray diffraction spectroscopy and Fourier transform infrared analyses yielded peaks associated with carbonated hydroxyapatite with less prominent crystallization. In addition, the biomineralized aligned polycaprolactone nanofibers demonstrated excellent cell attachment, alignment, and proliferation characteristics in vitro. Overall, the results of this study showed that 5 × SBFs buffered by 5 % CO2 partial pressure are attractive alternatives for the efficient biomineralization of scaffolds in bone tissue engineering, and could be used as a model for the prediction of the bone-bonding bioactivity of biomaterials.

Pengzhenrongella frigida sp. nov., isolated from a glacier.

A Gram-stain-positive, rod-shaped bacterium, designated as HLT2-17T, was isolated from soil sample taken from the Hailuogou glacier in Sichuan province, PR China. Strain HLT2-17T was capable of growing at 4-25°C and in NaCl concentrations ranging from 0 to 2% (w/v). The highest level of 16S rRNA gene sequence similarity was observed with Pengzhenrongella phosphoraccumulans M0-14T (98.3 %) and Pengzhenrongella sicca LRZ-2T (98.2 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain HLT2-17T and its closest relatives, P. phosphoraccumulans M0-14T and P. sicca LRZ-2T, were 80.0-84.0 % and 23.3-27.7 %, respectively. Phylogenomic analysis indicated that strain HLT2-17T clustered together with strains P. phosphoraccumulans M0-14T and P. sicca LRZ-2T. Strain HLT2-17T contained C16 : 0 and anteiso-C15 : 0 as the major fatty acids, and MK-9(H4) as the menaquinone. Therefore, based on a polyphasic approach, we propose that strain HLT2-17T (=CGMCC 1.11116T= NBRC 110443T) represents a novel species of the genus Pengzhenrongella and suggest the name Pengzhenrongella frigida sp. nov.

Complications and adverse events of high-intensity focused ultrasound in its application to gynecological field - a systematic review and meta-analysis.

OBJECTIVE: To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice. METHOD: We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0. RESULTS: This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders. CONCLUSION: The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.

A pyocin-like T6SS effector mediates bacterial competition in Yersinia pseudotuberculosis.

Within the realm of Gram-negative bacteria, bacteriocins are secreted almost everywhere, and the most representative are colicin and pyocin, which are secreted by Escherichia coli and Pseudomonas aeruginosa, respectively. Signal peptides at the amino terminus of bacteriocins or ABC transporters can secrete bacteriocins, which then enter bacteria through cell membrane receptors and exert toxicity. In general, the bactericidal spectrum is usually narrow, killing only the kin or closely related species. Our previous research indicates that YPK_0952 is an effector of the third Type VI secretion system (T6SS-3) in Yersinia pseudotuberculosis. Next, we sought to determine its identity and characterize its toxicity. We found that YPK_0952 (a pyocin-like effector) can achieve intra-species and inter-species competitive advantages through both contact-dependent and contact-independent mechanisms mediated by the T6SS-3 while enhancing the intestinal colonization capacity of Y. pseudotuberculosis. We further identified YPK_0952 as a DNase dependent on Mg2+, Ni2+, Mn2+, and Co2+ bivalent metal ions, and the homologous immune protein YPK_0953 can inhibit its activity. In summary, YPK_0952 exerts toxicity by degrading nucleic acids from competing cells, and YPK_0953 prevents self-attack in Y. pseudotuberculosis.IMPORTANCEBacteriocins secreted by Gram-negative bacteria generally enter cells through specific interactions on the cell surface, resulting in a narrow bactericidal spectrum. First, we identified a new pyocin-like effector protein, YPK_0952, in the third Type VI secretion system (T6SS-3) of Yersinia pseudotuberculosis. YPK_0952 is secreted by T6SS-3 and can exert DNase activity through contact-dependent and contact-independent entry into nearby cells of the same and other species (e.g., Escherichia coli) to help Y. pseudotuberculosis to exert a competitive advantage and promote intestinal colonization. This discovery lays the foundation for an in-depth study of the different effector protein types within the T6SS and their complexity in competing interactions. At the same time, this study provides a new development for the toolbox of toxin/immune pairs for studying Gram-negative bacteriocin translocation.

NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer.

BACKGROUND: Metabolic reprogramming plays a key role in cancer progression and clinical outcomes; however, the patterns and primary regulators of metabolic reprogramming in colorectal cancer (CRC) are not well understood. AIM: To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in promoting progression of CRC. METHODS: We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Consensus clustering was used to cluster CRC based on dysregulated metabolic genes. A prediction model was constructed based on survival-related metabolic genes. Sphere formation, migration, invasion, proliferation, apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC. mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells. In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth. RESULTS: We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes. Among these genes, NOX4 was highly expressed in tumor tissues and correlated with worse survival. In vitro, NOX4 overexpression induced clone formation, migration, invasion, and stemness in CRC cells. Furthermore, RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway. Trametinib, a MEK1/2 inhibitor, abolished the NOX4-mediated tumor progression. In vivo, NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis, whereas trametinib treatment can reversed the metastasis. CONCLUSION: Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis, suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

Accelerating carrier separation to boost the photocatalytic CO2 reduction performance of ternary heterojunction Ag-Ti3C2Tx/ZnO catalysts.

Developing low-cost and efficient photocatalyst/co-catalyst systems that promote CO2 reduction remains a challenge. In this work, Ag-Ti3C2Tx composites were made using a self-reduction technique, and unique Ag-Ti3C2Tx/ZnO ternary heterojunction structure photocatalysts were created using an electrostatic self-assembly process. The photocatalyst's close-contact heterogeneous interface increases photogenerated carrier migration efficiency. The combination of Ti3C2Tx and Ag improves the adsorption active sites and reaction centers for ZnO, making it a key site for CO2 adsorption and activation. The best photocatalysts had CO and CH4 reduction efficiencies of 11.985 and 0.768 µmol g-1 h-1, respectively. The CO2 conversion was 3.35 times better than that of pure ZnO, which demonstrated remarkable stability even after four cycle trials with no sacrificial agent. Furthermore, in situ diffuse reflectance infrared Fourier transform spectroscopy (in situ DRIFTS) and valence band spectroscopy were utilized to propose the photocatalytic reaction mechanism and electron transfer channels of the Ag-Ti3C2Tx/ZnO system, confirming that CHO* and CO* are the important intermediates in the generation of CH4 and CO. This study introduces a novel method for the development of new and efficient photocatalysts and reveals that Ti3C2Tx MXene is a viable co-catalyst for applications.

Association of disease activity with depression and anxiety in systemic lupus erythematosus: A comparison of SLEDAI-2K and SLE-DAS.

OBJECTIVE: To explore the association of disease activity, as evaluated by both the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K), with depression and anxiety in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted among 85 Chinese patients with SLE. Disease activity was measured using SLEDAI-2K and SLE-DAS scoring systems. Depression and anxiety were assessed using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Scale-7 (GAD-7), respectively. Multivariate logistic regression analysis was performed to evaluate the association of disease activity scores, as well as specific clinical and laboratory items, with depression and anxiety. RESULTS: There was a robust correlation between SLEDAI-2K and SLE-DAS scores in overall patients (Spearman's r = 0.764, 95% confidence interval (CI) 0.655-0.842; p< 0.001) and those with moderate-to-high disease activity (Spearman's r = 0.792, 95%CI 0.616-0.892; p< 0.0001). However, the correlation weakened for patients with mild disease activity or remission (Spearman's r = 0.450, 95%CI 0.188-0.652; p= 0.001). Multivariate logistic regression analysis did not show a significant correlation between SLEDAI-2K and SLE-DAS scores and depression/anxiety. The presence of mucosal ulcer/serositis significantly increased the risk of depression (OR = 4.472, 95%CI 1.035-19.328, p= 0.045) and anxiety (OR = 3.978, 95%CI 1.051-15.049, p= 0.042). CONCLUSION: The SLE-DAS scoring system demonstrated a comparable ability to assess disease activity in SLE compared with SLEDAI-2K. Though neither scoring system showed significant associations with depression and anxiety, the presence of mucosal ulcer/serositis markedly heightened the risk of both among SLE patients.

Analysis of related factors influencing postoperative recurrence of adenomyosis treated with HIFU.

OBJECTIVE: To analyze the efficacy of high-intensity focused ultrasound (HIFU) for adenomyosis and postoperative recurrence and its influencing factors. METHODS: Clinical and follow-up data of 308 patients with adenomyosis who were treated with HIFU in Haifu Center, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from September 2017 to January 2022 were retrospectively analyzed. The recurrence of adenomyosis and the efficacy of HIFU at 6 months after surgery were followed up. To explore factors influencing postoperative prognosis and recurrence, the following variables were analyzed: patients' age, course of disease, gravidity and parity, size of the uterus, duration of HIFU, duration of irradiation, treatment intensity, dysmenorrhea score, time of follow-up, combined treatment of traditional Chinese medicine (TCM), western medicine adjuvant treatment, lesion location and type, and menorrhagia. RESULTS: Among the 308 patients, 238 (77%) were followed up from 6 to 36 months, with an average follow-up time of 15.24 ± 9.97 months. The other 70 (23%) were lost to follow-up. At 6-month after surgery, efficacy rates of dysmenorrhea and menorrhagia management were 86.7% and 89.3%, respectively. Postoperative recurrence rates were 4.8% (1-12 months), 9.0% (12-24 months), and 17.0% (24-36 months) for dysmenorrhea; and 6.3% (1-12 months), 2.4% (12-24 months), and 12.2% (24-36 months) for menorrhagia. Multivariate logistic regression analyses showed that parity (P = 0.043, OR = 1.773, 95% CI 1.018-3.087), uterine size (P = 0.019, OR = 1.004, 95% CI 1.001-1.007), combined treatment of TCM (P = 0.047, OR = 1.846, 95% CI 1.008-3.381), diffuse lesion type (P = 0.013, OR = 0.464, 95% CI 0.254-0.848) and ablation rate (P = 0.015, OR = 0.481, 95%CI 0.267-0.868) were prognostic factors (P < 0.05). Age, course of disease, gravidity, duration of HIFU, duration of irradiation, treatment intensity, preoperative dysmenorrhea score, time of follow-up, western medicine adjuvant therapy, lesion location, and preoperative menstrual volume had no effect on prognosis (P > 0.05). CONCLUSION: HIFU can effectively relieve dysmenorrhea and reduce menstrual volume in patients with adenomyosis. Parity, uterine size, lesion type (diffuse), and ablation rate are risk factors for symptom recurrence after HIFU, while the combination of TCM therapy is a protective factor for relapse. We, therefore, recommend TCM in the adjuvant setting after HIFU according to patient condition.

Revitalizing antitumor immunity: Leveraging nucleic acid sensors as therapeutic targets.

Nucleic acid sensors play a critical role in recognizing and responding to pathogenic nucleic acids as danger signals. Upon activation, these sensors initiate downstream signaling cascades that lead to the production and release of pro-inflammatory cytokines, chemokines, and type I interferons. These immune mediators orchestrate diverse effector responses, including the activation of immune cells and the modulation of the tumor microenvironment. However, careful consideration must be given to balancing the activation of nucleic acid sensors to avoid unwanted autoimmune or inflammatory responses. In this review, we provide an overview of nucleic acid sensors and their role in combating cancer through the perception of various aberrant nucleic acids and activation of the immune system. We discuss the connections between different programmed cell death modes and nucleic acid sensors. Finally, we outline the development of nucleic acid sensor agonists, highlighting how their potential as therapeutic targets opens up new avenues for cancer immunotherapy.

Prognostic value of oxidative stress-related genes in colorectal cancer and its correlation with tumor immunity.

Oxidative stress (OS) plays an essential role in chronic diseases such as colorectal cancer (CRC). In this study, we aimed to explore the relation between oxidative stress-related genes and CRC prognosis and their involvement in the immune microenvironment. Totally 101 OS-related genes were selected from the MsigDB database. Then, univariate Cox regression was used to explore the prognostic value of the selected genes correlated with the CRC patient survival in the TCGA database. A total of 9 prognostic OS-related genes in CRC were identified. Based on consensus clustering, CRC patients were then categorized into two molecular subtypes. A prognostic risk model containing 8 genes was established using Lasso regression, and CRC patients were divided into high or low-risk groups based on the median risk scores. The predictive value of the 8 genes in CRC prognosis was validated using ROC curves, which indicate that CTNNB1, STK25, RNF112, SFPQ, MMP3, and NOL3 were promising prognostic biomarkers in CRC. Furthermore, the immune cell infiltration levels in different risk groups or CRC subtypes were analyzed. We found that the high-risk or C1 subtype had immunosuppressive microenvironment, which might explain the unfavorable prognosis in the two groups of CRC patients. Additionally, functional experiments were conducted to investigate the effects of OS-related genes on CRC cell proliferation, stemness, and apoptosis. We found that CTNNB1, HSPB1, MMP3, and NOL3 were upregulated in CRC tissues and cells. Knockdown of CTNNB1, HSPB1, MMP3, and NOL3 significantly suppressed CRC cell proliferation, stemness and facilitated CRC cell apoptosis. In conclusion, we established prognostic CRC subtypes and an eight-gene risk model, which may provide novel prognostic indicators and benefit the design of individualized therapeutic strategies for CRC patients.

Hsa_circ_0092355 Accelerates Papillary Thyroid Cancer Progression by Regulating the miR-543/PDE5A Pathway.

CircRNAs have been found to participate in the progression of various tumors. In the present study, we aimed to clarify the role of hsa_circ_0092355 in papillary thyroid cancer (PTC) cell development. RT-qPCR was used to determine the expression of hsa_circ_0092355, miR-543, and PDE5A. PTC cell proliferation was ascertained via a cell colony formation assay and the CCK-8 test. Western blotting was performed to examine the expression levels of PDE5A and apoptosis-associated proteins (Bcl-2 and Bax) in PTC cells. A scratch wound assay was performed to measure the migration of PTC cells. A mouse xenograft test was performed to assess the effects of hsa_circ_0092355 in vivo. RIP and dual-luciferase reporter assays confirmed the association between miR-543 and hsa_circ_0092355 or PDE5A. Associations between miR-543, hsa_circ_0092355, and PDE5A were evaluated using Pearson's correlation coefficient. Upregulation of hsa_circ_0092355 was observed in PTC tissues. The hsa_circ_0092355 knockdown blocked the proliferation and migration of PTC cells and induced apoptosis. Moreover, hsa_circ_0092355 knockdown blocked PTC xenograft tumor growth in vivo. The miR-543 inhibitor could reverse the changes induced by hsa_circ_0092355 knockdown by hsa_circ_0092355 targeting miR-543. Furthermore, miR-543 suppresses PTC progression by downregulating PDE5A expression. Our findings suggest that the PTC tumor promoter hsa_circ_0092355 may promote carcinogenesis by controlling the miR-543/PDE5A pathway.

Association of anti-Ro52 antibody with depression and anxiety in patients with connective tissue diseases: an observational, single-centre, cross-sectional study.

OBJECTIVES: To explore the risk factors of anxiety and depression, especially their association with serum autoantibodies, in patients with connective tissue diseases (CTDs). METHODS: Three hundred and fifty-two inpatients with CTDs were recruited and their demographic, serological and imaging data were collected through the medical record system. Depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Analysis of variance (ANOVA), rank sum test, chi-square test and logistic regression were performed to investigate risk factors for depression and anxiety. RESULTS: The prevalence of depression (PHQ-9 ≥ 5) and anxiety (GAD-7 ≥5) in CTD patients was significantly higher than that in the Chinese general population (depression: 44.3% vs. 32.2%, anxiety: 39.5% vs. 22.2%). Sleep time was a protective factor for both depression and anxiety (OR=0.734, 95% CI: 0.616~0.874, p<0.001 and OR=0.684, 95% CI: 0.559~0.835, P<0.001, respectively) while anti-Ro52 antibody was a risk factor for them (OR=5.466, 95% CI: 2.978~10.032, p<0.001 and OR=4.075, 95% CI: 2.073~8.010, p<0.001, respectively). Further analysis showed that anti-Ro52 antibody was a risk factor for depression and anxiety in all four subgroups, namely SLE, SS, RA, and other CTDs. CONCLUSIONS: Anti-Ro52 antibody is probably a risk factor for depression and anxiety in patients with connective tissue diseases. CTD patients with the presence of anti-Ro52 antibody are more prone to depression and anxiety than those without it.

Development and evaluation of a monoclonal antibody-based blocking ELISA to detect antibodies against the E2 protein of bovine viral diarrhea virus-1.

With the rapid development of cattle industry, bovine viral diarrhea virus (BVDV) is becoming widespread in China, which causes serious economic losses to the industry. Effective vaccination and viral surveillance are critical for the prevent and control of BVDV infection. In the present study, the immunogenic domain of E2 protein of BVDV-1 was expressed by prokaryotic pET-28a vector. Monoclonal antibodies (mAbs) against E2 protein were prepared and systemically examined by western blot, immunofluorescence assay, blocking ELISA (bELISA) and virus neutralization test (VNT). The mAb 1E2B3, which showed good reactivity and neutralizing activity to BVDV-1 strains, was selected for ELISA establishment. After a series of screening and optimization, a novel bELISA for highly sensitive and specific detection of BVDV-1 antibodies was established, using HRP-labeled 1E2B3 and recombinant E2 protein. ROC analysis of 91 positive and 84 negative reference bovine serum samples yielded the area under the curve (AUC) of 0.9903. A diagnostic specificity of 96.43 % and a sensitivity of 95.6 % were achieved when the cutoff value was set at 24.31 %. There was no cross reaction to the positive sera of classical swine fever virus (CSFV), BVDV-2, border disease virus (BDV), bovine parainfluenza virus type 3 (BPIV3), infectious bovine rhinotracheitis virus (IBRV), foot-and-mouth disease virus (FMDV), Mycoplasma bovis (M.bovis) and Brucella. The total agreement rate of bELISA with VNT was 93.96 % (249/265). In addition, the result of bELISA was positively correlated with neutralizing antibody titer, and the bELISA could well distinguish the serum samples before and after BVDV vaccination. These results indicate that the established bELISA in this study is specific, sensitive, simple and convenient, which provides technical support for the vaccine efficacy evaluation, prevention and control of BVD in the future.

Comparison of the bioactive components and antioxidant activities of wild-type Zanthoxylum nitidum roots from various regions of Southern China.

Zanthoxylum nitidum is a traditional Chinese herb, but limited information is available concerning its antioxidant activity of Z. nitidum. In this study, the bioactive components, content, and antioxidant activity of Z. nitidum roots from various regions in southern China were detected and evaluated. The results revealed that the highest nitidine chloride content found in S13. The S1 contained significantly higher concentrations of hesperidin, total flavonoids, and total phenols than other samples. The samples from S13, S1, and S12 had the strongest comprehensive antioxidant activity. Stoichiometric analysis revealed that samples from various regions were effectively identified and classified. This is the first study to investigate the antioxidant activity of wild-type Z. nitidum in southern China. It lays the groundwork for Z. nitidum harvesting, origin identification, sensible use, as well as the quality evaluation of Z. nitidum resources, particularly in vitro antioxidant activity assessment.

Emerging roles of plasmacytoid dendritic cell crosstalk in tumor immunity.

Plasmacytoid dendritic cells (pDCs) are a pioneer cell type that produces type I interferon (IFN-I) and promotes antiviral immune responses. However, they are tolerogenic and, when recruited to the tumor microenvironment (TME), play complex roles that have long been a research focus. The interactions between pDCs and other components of the TME, whether direct or indirect, can either promote or hinder tumor development; consequently, pDCs are an intriguing target for therapeutic intervention. This review provides a comprehensive overview of pDC crosstalk in the TME, including crosstalk with various cell types, biochemical factors, and microorganisms. An in-depth understanding of pDC crosstalk in TME should facilitate the development of novel pDC-based therapeutic methods.