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Silver nanoparticles (AgNPs) are progressively becoming an in-demand material for both medical and life use due to their effective antimicrobial properties. The high surface area-to-volume ratio endows AgNPs with enhanced antibacterial capacity accompanied by inevitable cytotoxicity. Surface coating technique could precisely regulate the particle shape, aggregation, and Ag+ release pattern of AgNPs, by which the cytotoxicity could be significantly reduced. Various coating methods have been explored to shell AgNPs, but it remains a great challenge to precisely control the aggregation state of AgNPs and their shell thickness. Herein, we proposed a simple method to prepare a tunable polydopamine (pDA) coating shell on AgNPs just by tuning the reaction pH and temperature, yet we obtained high antibacterial property and excellent biocompatibility. SEM and TEM revealed that pDA coated AgNPs can form core-shell structures with different aggregation states and shell thickness. Both in vitro and in vivo antibacterial tests show that acid condition and heat-treatment lead to appropriate AgNPs cores and pDA shell structures, which endow Ti with sustained antibacterial properties and preferable cell compatibility. One month of implantation in an infected animal model demonstrated that the obtained surface could promote osteogenesis and inhibit inflammation due to its strong antibacterial properties. Therefore, this study provides a promising approach to fabricate biocompatible antibacterial surface.

Mice have genetic and physiological similarities with humans and a well-characterized genetic background that is easy to manipulate. Murine models have become the most favored, robust mammalian systems for experimental analyses of biological processes and disease conditions due to their low cost, rapid reproduction, a wealth of mouse strains with defined genetic conditions (both native ones as well as ones established experimentally), and high reproducibility with respect to that which can be done in experimental studies. In this review, we focus on murine models for liver, an organ with renown regenerative capacity and the organ most central to systemic, complex metabolic and physiological functions for mammalian hosts. Establishment of murine models has been achieved for all aspects of studies of normal liver, liver diseases, liver injuries, and regenerative repair mechanisms. We summarize key information on current mouse systems that partially model facets of clinical scenarios, particularly those associated with drug-induced acute or chronic liver injuries, dietary related, non-alcoholic liver disease (NAFLD), hepatitis virus infectious chronic liver diseases, and autoimmune hepatitis (AIH). In addition, we also include mouse models that are suitable for studying liver cancers (e.g., hepatocellular carcinomas), the aging process (senescence, apoptosis), and various types of liver injuries and regenerative processes associated with them.

Titanium and its alloys are dominant material for orthopedic/dental implants due to their stable chemical properties and good biocompatibility. However, aseptic loosening and peri-implant infection remain problems that may lead to implant removal eventually. The ideal orthopedic implant should possess both osteogenic and antibacterial properties and do proper assistance to in situ inflammatory cells for anti-microbe and tissue repair. Recent advances in surface modification have provided various strategies to procure the harmonious relationship between implant and its microenvironment. In this review, we provide an overview of the latest strategies to endow titanium implants with bio-function and anti-infection properties. We state the methods they use to preparing these efficient surfaces and offer further insight into the interaction between these devices and the local biological environment. Finally, we discuss the unmet needs and current challenges in the development of ideal materials for bone implantation.

Accumulating evidence has proved that autophagy serves as a tumor promoter in formed malignancies, and the autophagy-related prognostic signatures have been constructed as clinical tools to predict prognosis in many high-mortality cancers. Autophagy-related genes have participated in the development and metastasis of hepatocellular carcinoma (HCC), but the understanding of their prognostic value is limited. Thereafter, LIMMA and survival analysis were conducted in both ICGC and TCGA databases and a total of 10 hub autophagy-related genes, namely, NPC1, CDKN2A, RPTOR, SPHK1, HGS, BIRC5, SPNS1, BAK1, ATIC, and MAPK3, were collected. Then, GO, KEGG, correlation, consensus, and PCA analyses were utilized to reveal their potential targeted role in HCC treatment. Single-cell RNA-seq of cancer stem cells also indicated that there was a positive correlation between these genes and stemness. In parallel, we applied univariate, LASSO, and multivariate regression analyses to study the autophagy-related genes and finally proposed that ATIC and BIRC5 were the valuable prognostic indicators of HCC. The signature based on ATIC and BIRC5 exhibited moderate power for predicting the survival of HCC in the ICGC cohort, and its efficacy was further validated in the TCGA cohort. Taken together, we suggested that 10 aforementioned hub genes are promising therapeutic targets of HCC and the ATIC/BIRC5 prognostic signature is a practical prognostic indicator for HCC patients.

Cell transplantation has been proposed as a promising therapeutic strategy for curing the diseases requiring tissue repairing and functional restoration. A preclinical method to systematically evaluate the fates of donor cells in recipients, spatially and temporally, is demanded for judging therapeutic potentials for the particularly designed cell transplantation. Yet, the dynamic cell tracking methodology for tracing transplanted cells in vivo is still at its early phase. Here, we created a practical protocol for dynamically tracking cell via a three-dimensional (3D) technique which enabled us to localize, quantify, and overall evaluate the transplanted hepatocytes within a liver failure mouse model. First, the capacity of 3D bioluminescence imaging for quantifying transplanted hepatocytes was defined. Images obtained from the 3D bioluminescence imaging module were then combined with the CT scanner to reconstruct structure images of host mice. With those reconstructed images, precise locations of transplanted hepatocytes in the liver of the recipient were dynamically monitored. Immunohistochemistry staining of transplanted cells, and the serology assay of liver panel of the host mice were applied to verify the successful engraftment of donor cells in the host livers. Our protocol was practical for evaluating the engraftment efficiency of donor cells at their preclinical phases, which is also applicable as a referable standard for studying the fates of other transplanted cells, such as stem cell-derived cell types, during preclinical studies with cell transplantation therapy.

BackgroundCancer becomes the leading cause of premature death in China. Primary objective of this study was to determine the major risk factors especially glucose intolerance for cancer prophylaxis.MethodsA cluster sampling method was applied to enroll 10,657 community-based adults aged 15-92 years in Shanghai, China in 2013. A structured questionnaire and physical examination were applied in baseline survey. Prediabetes was diagnosed using 75-g oral glucose tolerance test. After excluding 1433 subjects including 224 diagnosed with cancer before and 1 year after baseline survey, the remaining 9,224 subjects were followed-up to December 31, 2020.ResultsA total of 502 new cancer cases were diagnosed. The cancer incidence was 10.29, 9.20, and 5.95/1,000 person-years in diabetes patients, those with prediabetes, and healthy participants, respectively (p

BackgroundFunctions of miRNAs involved in tumorigenesis are well reported, yet, their roles in normal cell lineage commitment remain ambiguous. Here, we investigated a specific “transcription factor (TF)-miRNA-Target” regulatory network during the lineage maturation of biliary tree stem cells (BTSCs) into adult hepatocytes (hAHeps).MethodBioinformatic analysis was conducted based on our RNA-seq and microRNA-seq datasets with four human hepatic-lineage cell lines, including hBTSCs, hepatic stem cells (hHpSCs), hepatoblasts (hHBs), and hAHeps. Short time-series expression miner (STEM) analysis was performed to reveal the time-dependent dynamically changed miRNAs and mRNAs. GO and KEGG analyses were applied to reveal the potential function of key miRNAs and mRNAs. Then, the miRDB, miRTarBase, TargetScan, miRWalk, and DIANA-microT-CDS databases were adopted to predict the potential targets of miRNAs while the TransmiR v2.0 database was used to obtain the experimentally supported TFs that regulate miRNAs. The TCGA, Kaplan–Meier Plotter, and human protein atlas (HPA) databases and more than 10 sequencing data, including bulk RNA-seq, microRNA-seq, and scRNA-seq data related to hepatic development or lineage reprogramming, were obtained from both our or other published studies for validation.ResultsSTEM analysis showed that during the maturation from hBTSCs to hAHeps, 52 miRNAs were downwardly expressed and 928 mRNA were upwardly expressed. Enrichment analyses revealed that those 52 miRNAs acted as pluripotency regulators for stem cells and participated in various novel signaling pathways, including PI3K/AKT, MAPK, and etc., while 928 mRNAs played important roles in liver-functional metabolism. With an extensive sorting of those key miRNAs and mRNAs based on the target prediction results, 23 genes were obtained which not only functioned as the targets of 17 miRNAs but were considered critical for the hepatic lineage commitment. A “TF-miRNA-Target” regulatory network for hepatic lineage commitment was therefore established and had been well validated by various datasets. The network revealed that the PI3K/AKT pathway was gradually suppressed during the hepatic commitment.ConclusionA total of 17 miRNAs act as suppressors during hepatic maturation mainly by regulating 23 targets and modulating the PI3K/AKT signaling pathway. The regulatory network uncovers possible signatures and guidelines enabling us to identify or obtain the functional hepatocytes for future study.

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development. [ABSTRACT FROM AUTHOR]

Background: The shaping of an accurate and stable microcatheter plays a vital role in the successful embolization of intracranial aneurysms. Our study aimed to investigate the application and the role of AneuShape™ software inmicrocatheter shaping for intracranial aneurysm embolization. Methods: From January 2021 to June 2022, 105 patients with single unruptured intracranial aneurysms were retrospectively analyzed with or without AneuShape™ software to assist in microcatheter shaping. The rates of microcatheter accessibility, accurate positioning, and stability for shaping were analyzed. During the operation, fluoroscopy duration, radiation dose, immediate postoperative angiography, and procedure-related complications were evaluated. Results: Compared to the manual group, aneurysm-coiling procedures involving the AneuShape™ software exhibited superior results. The use of the software resulted in a lower rate of reshaping microcatheters (21.82 vs. 44.00%, p = 0.015) and higher rates of accessibility (81.82 vs. 58.00%, p = 0.008), better positioning (85.45 vs. 64.00%, p = 0.011), and higher stability (83.64 vs. 62.00%, p = 0.012). The software group also requiredmore coils for both small (<7mm) and large (=7mm) aneurysms compared to the manual group (3.50 ± 0.19 vs. 2.78 ± 0.11, p = 0.008 and 8.22 ± 0.36 vs. 6.00 ± 1.00, p = 0.081, respectively). In addition, the software group achieved better complete or approximately complete aneurysmobliteration (87.27 vs. 66.00%, p = 0.010) and had a lower procedure-related complication rate (3.60 vs. 12.00%, p = 0.107). Without this software, the operation had a longer intervention duration (34.31 ± 6.51 vs. 23.87 ± 6.98min, p < 0.001) and a higher radiation dose (750.50 ± 177.81 vs. 563.53 ± 195.46 mGy, p < 0.001). Conclusions: Software-based microcatheter shaping techniques can assist in the precise shaping of microcatheters, reduce operating time and radiation dose, improve embolization density, and facilitate more stable and efficient intracranial aneurysm embolization. [ABSTRACT FROM AUTHOR]

Objective: To investigate the analgesic mechanism of electroacupuncture (EA) in rats with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: Thirty male SD rats were randomly divided into sham group, model group and EA group, with ten rats in each group. The CP/CPPS model was prepared by injecting 50 mL of complete Freund’s adjuvant (CFA) into the ventral lobes of the prostate tissue, and the sham group was injected with the same dose of saline. After 14 days of modeling, EA was applied to Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) in the EA group. After four courses, H&E staining was performed to observe the prostate tissue morphology, transcriptome sequencing (RNA-Seq) was performed for each group, and the selected signaling pathways were verified by qRT-PCR. Results: The RNA-Seq analysis results suggested that the analgesic effect of EA on CP/CPPS may be achieved by regulating prostate gene expression, which may be related to multiple biological processes and signaling pathways. qRTPCR results showed that the vanillic acid receptor subtype 1 of the transient receptor potential (TRPV1), phospholipase C (PLC), protein kinase C (PKC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were all upregulated in the model group compared to the sham group (p < 0.01). Compared with the model group, TRPV1, PLC, PKC, cAMP, and PKA were all downregulated in the EA group (p < 0.05, p < 0.01). Conclusion: The analgesic mechanism of EA on CP/CPPS may be achieved through modulation of cAMP-PKA-TRPV1/PLC-PKC-TRPV1 signaling pathway. [ABSTRACT FROM AUTHOR]

Post-stroke anxiety (PSA) is serious psychosomatic comorbidity among patients with stroke, but whether obesity could be positively associated with PSA is currently unknown. The purpose of this study was to investigate the potential association between obesity and subsequent anxiety risk in patients with stroke. A total of 441 patients with acute ischemic stroke (AIS) onset were consecutively recruited within 7 days, and PSA and post-stroke depression (PSD) were evaluated by using a 14-item Hamilton anxiety scale (HAMA) and 17-item Hamilton depression scale (HAMD) at the end of 1-month follow-up. The odds ratio (OR) with 95% CI was estimated for the incidental PSA by using logistic regression analysis. The incidence of PSA was 25.85% at the end of 1-month follow-up, with a significant difference between patients with and without abdominal obesity. Relative fat mass (RFM) and abdominal obesity were significantly associated with an elevated risk of PSA, and the crude ORs were 1.04 (95% CI: 1.01–1.08) and 1.93 (95% CI: 1.11–3.34), respectively. Even after adjustment for obesity-related risk factors and PSA-related clinical measurements, the association remained to be pronounced with abdominal obesity. However, RFM (OR = 1.03, 95% CI: 0.99–1.06, P = 0.053) and abdominal obesity (OR = 1.31, 95% CI: 0.80–2.15, P = 0.280) were not significantly associated with an elevated risk of PSD. Abdominal obesity was independently associated with the PSA instead of PSD, which may help predict PSA risk in clinical practice. Further prospective clinical studies with a long follow-up duration are warranted to verify this finding.

Sensorineural hearing loss (SNHL) is a dominant public health issue affecting millions of people around the globe, which is correlated with the irreversible deterioration of the hair cells and spiral ganglion neurons (SGNs) within the cochlea. Strategies using bioactive molecules that regulate neurite regeneration and neuronal survival to reestablish connections between auditory epithelium or implanted electrodes and SGN neurites would become attractive therapeutic candidates for SNHL. As an intracellular second messenger, cyclic guanosine-3’,5’-monophosphate (cGMP) can be synthesized through activation of particulate guanylate cyclase-coupled natriuretic peptide receptors (NPRs) by natriuretic peptides, which in turn modulates multiple aspects of neuronal functions including neuronal development and neuronal survival. As a cardiac-derived hormone, atrial natriuretic peptide (ANP), and its specific receptors (NPR-A and NPR-C) are broadly expressed in the nervous system where they might be involved in the maintenance of diverse neural functions. Despite former literatures and our reports indicating the existence of ANP and its receptors within the inner ear, particularly in the spiral ganglion, their potential regulatory mechanisms underlying functional properties of auditory neurons are still incompletely understood. Our recently published investigation revealed that ANP could promote the neurite outgrowth of SGNs by activating NPR-A/cGMP/PKG cascade in a dose-dependent manner. In the present research, the influence of ANP and its receptor-mediated downstream signaling pathways on neurite outgrowth, neurite attraction, and neuronal survival of SGNs in vitro was evaluated by employing cultures of organotypic explant and dissociated neuron from postnatal rats. Our data indicated that ANP could support and attract neurite outgrowth of SGNs and possess a high capacity to improve neuronal survival of SGNs against glutamate-induced excitotoxicity by triggering the NPR-A/cGMP/PKG pathway. The neuroregenerative and neuroprotective effects of ANP/NPRA/cGMP/PKG-dependent signaling on SGNs would represent an attractive therapeutic candidate for hearing impairment.

ObjectiveThis study aimed to evaluate how leucine are associated with diabetic nephropathy (DN) in type 2 diabetes (T2D) patients and the gender difference of this association.MethodsWe retrieved 1,031 consecutive patients with T2D who meet the inclusion and exclusion criteria from the same tertiary care center and extracted clinical information from electronic medical record. Plasma leucine was measured by liquid chromatography-mass spectrometer. Restricted cubic spline (RCS) was conducted to examine potential non-linear relationship between leucine and the risk of DN. Logistic regression was used to obtain odds ratio (OR) and confidence interval (CI). Additive interaction was used to estimate the interaction effect between leucine and gender for DN.ResultsWe found there was a negative correlation between leucine and the risk of DN. After stratifying all patients by gender, this relationship only remained significant in women (OR:0.57, CI:0.41–0.79).ConclusionsIn conclusion, T2D patients with high levels of leucine have a lower risk of developing DN in female.