ACTH-dependent Cushing Syndrome with No Peripheral Response But a Marked Petrosal Sinus ACTH Response to Desmopressin.

Desmopressin is increasingly used for the diagnosis of Cushing disease (CD) since corticotropin-releasing hormone became unavailable. We report the case a 32-year-old man who presented with overt Cushing syndrome. Morning blood cortisol, ACTH, 1 mg dexamethasone suppression test, 24-hour urinary free cortisol, and bedtime salivary cortisol were highly variable, reaching markedly elevated values. Intravenous desmopressin administration produced no ACTH or cortisol increase. Pituitary magnetic resonance imaging, thoracic computed tomography, and DOTATATE positron emission tomography scan identified no lesion. Inferior petrosal sinus sampling (IPSS) with desmopressin stimulation resulted in elevated central-to-peripheral ACTH ratio and prolactin co-secretion, while peripheral ACTH remained stable. No corticotroph tumor was identified on pituitary surgery pathology. Hypercortisolism persisted postoperatively. Cabergoline was initiated, after which the patient rapidly developed transient severe adrenal insufficiency (AI). Bilateral adrenalectomy was performed in view of persistent hypercortisolism. This is an unusual case of petrosal sinus ACTH response to desmopressin without any peripheral response, suggesting a central source of ACTH. Thus, desmopressin should still be used during IPSS in patients with no peripheral response. It is unclear whether the AI episode resulted from a combination of nadir of cyclic hypercortisolism, partial apoplexy, and response to cabergoline of an occult corticotroph tumor.

Lysineless HiBiT and NanoLuc Tagging Systems as Alternative Tools Monitoring Targeted Protein Degradation.

Target protein degradation (TPD) has emerged as a revolutionary approach in drug discovery, leveraging the cell's intrinsic machinery to selectively degrade disease-associated proteins. Proteolysis-Targeting Chimeras (PROTACs) exemplify this strategy, exploiting heterobifunctional molecules to induce ubiquitination and subsequent degradation of target proteins. The clinical advancement of PROTACs underscores their potential in therapeutic intervention, with numerous projects progressing through clinical stages. However, monitoring subtle changes in protein abundance induced by TPD molecules demands highly sensitive assays. Nano-luciferase (nLuc) fusion proteins, or the NanoBiT technology derived from it, offer a robust screening platform due to their high sensitivity and stability. Despite these advantages, concerns have arisen regarding potential degradation artifacts introduced by tagging systems due to the presence of lysine residues on them, prompting the development of alternative tools. In this study, we introduce HiBiT-RR and nLuc K0 , variants devoid of lysine residues, to mitigate such artifacts. Our findings demonstrate that HiBiT-RR maintains similar sensitivity and binding affinity with the original HiBiT. Moreover, the comparison between nLuc WT and nLuc K0 constructs reveals variations in degradation patterns induced by certain PROTAC molecules, emphasizing the importance of choosing appropriate tagging systems to ensure the reliability of experimental outcomes in studying protein degradation processes.

Application of personalized templates in minimally invasive management of coronal dens invaginatus: a report of two cases.

BACKGROUND: Treating the coronal dens invaginatus (CDI) with pulp infection commonly involves the removal of invagination, which increases the risk of perforation and fracture, and compromises the tooth structure. Minimally invasive endodontic management of CDI is highly recommended. This report describes two cases of type II CDI with the application of personalized templates. CASE PRESENTATION: Two cases of type II CDI, affecting the main root canal in a maxillary canine and a lateral incisor, were diagnosed. A guided endodontics (GE) approach was applied. Cone-beam computed tomography and intraoral scans were imported and aligned in a virtual planning software to design debridement routes and templates. The MICRO principle (which involves the aspects of Mechanical (M) debridement, Irrigation (I), Access cavities (C), Rectilinear routes (R), and Obstruction (O)) was proposed for designing optimal debridement routes for future applications. The templates were innovatively personalized and designed to preserve the tooth structure maximally while effectively debriding the root canal. Root canal treatment with supplementary disinfection was then performed. The follow-up of the two patients revealed favorable clinical and radiographic outcomes. CONCLUSIONS: The GE approach could be a feasible method for preserving healthy dental structure while effectively debriding the root canal, thereby achieving successful and minimally invasive endodontic treatment for CDI.

Development of natural perfume as potential fungicide candidates: construction and biological evaluation of vanillin analogs bearing the 1,3,4-oxadiazole/1,3-thiazolidin-4-one fragments.

Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds 6j (29.73 µg/ml) and 7a (38.15 µg/ml) displayed excellent inhibitory activity against the spore of Fusarium solani. The inhibitory activity of compound 7d (10.53 µg/ml) against the spore of Alternaria solani was more than 42-fold that of vanillin. Compound 7a (37.54 µg/ml) showed better antifungal activity against the spore of B. cinerea than positive controls. The cytotoxicity assay confirmed that compounds 6k, 7a, and 7d showed good selectivity and less toxicity to normal mammalian cells.

Efficient Deep Spiking Multilayer Perceptrons With Multiplication-Free Inference.

Advancements in adapting deep convolution architectures for spiking neural networks (SNNs) have significantly enhanced image classification performance and reduced computational burdens. However, the inability of multiplication-free inference (MFI) to align with attention and transformer mechanisms, which are critical to superior performance on high-resolution vision tasks, imposes limitations on these gains. To address this, our research explores a new pathway, drawing inspiration from the progress made in multilayer perceptrons (MLPs). We propose an innovative spiking MLP architecture that uses batch normalization (BN) to retain MFI compatibility and introduce a spiking patch encoding (SPE) layer to enhance local feature extraction capabilities. As a result, we establish an efficient multistage spiking MLP network that blends effectively global receptive fields with local feature extraction for comprehensive spike-based computation. Without relying on pretraining or sophisticated SNN training techniques, our network secures a top-one accuracy of 66.39% on the ImageNet-1K dataset, surpassing the directly trained spiking ResNet-34 by 2.67%. Furthermore, we curtail computational costs, model parameters, and simulation steps. An expanded version of our network compares with the performance of the spiking VGG-16 network with a 71.64% top-one accuracy, all while operating with a model capacity 2.1 times smaller. Our findings highlight the potential of our deep SNN architecture in effectively integrating global and local learning abilities. Interestingly, the trained receptive field in our network mirrors the activity patterns of cortical cells.

Novel insights into the protective effects of leonurine against acute kidney injury: Inhibition of ER stress-associated ferroptosis via regulating ATF4/CHOP/ACSL4 pathway.

Acute kidney injury (AKI) is a common and serious global health problem with high risks of mortality and the development of chronic kidney diseases. Leonurine is a unique bioactive component from Leonurus japonicus Houtt. and exerts antioxidant, antiapoptotic or anti-inflammatory properties. This study aimed to explore the benefits of leonurine on AKI and the possible mechanisms involved, with a particular foc on the regulation of ferroptosis and endoplasmic reticulum (ER) stress. Our results showed that leonurine exhibited prominent protective effects against AKI, as evidenced by the amelioration of histopathological alterations and reduction of renal dysfunction. In addition, leonurine significantly suppressed ferroptosis in AKI both in vivo and in vitro by effectively restoring ultrastructural abnormalities in mitochondria, decreasing ASCL4 and 4-HNE levels, scavenging reactive oxygen species (ROS), as well as increasing GPX4 and GSH levels. In parallel, leonurine also markedly mitigated ER stress via down-regulating PERK, eIF-2α, ATF4, CHOP and CHAC1. Further studies suggested that ER stress was closely involved in erastin-induced ferroptosis, and leonurine protected tubular epithelial cells in vitro by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway. Mechanistically, ATF4 silencing in vitro regulated CHOP and ACSL4 expressions, ultimately weakening both ER stress and ferroptosis. Notably, analyses of single-cell RNA sequencing data revealed that ATF4, CHOP and ASCL4 in renal tubular cells were all abnormally upregulated in patients with AKI compared to healthy controls, suggesting their contributions to the pathogenesis of AKI. Altogether, these findings suggest that leonurine alleviates AKI by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway, thus providing novel mechanisms for AKI treatment.

Correction: An activator of G protein-coupled receptor and MEK1/2-ERK1/2 signaling inhibits HIV-1 replication by altering viral RNA processing.

[This corrects the article DOI: 10.1371/journal.ppat.1008307.].

Lossless Spin-Orbit Torque in Antiferromagnetic Topological Insulator MnBi_{2}Te_{4}.

We formulate and quantify the spin-orbit torque (SOT) in intrinsic antiferromagnetic topological insulator MnBi_{2}Te_{4} of a few septuple-layer thick in charge-neutral condition, which exhibits pronounced layer-resolved characteristics and even-odd contrast. Contrary to traditional current-induced torques, our SOT is not accompanied by Ohm's currents, thus being devoid of Joule heating. We study the SOT-induced magnetic resonances, where in the tri-septuple-layer case we identify a peculiar exchange mode that is blind to microwaves but can be exclusively driven by the predicted SOT. As an inverse effect, the dynamical magnetic moments generate a pure adiabatic current, which occurs concomitantly with the SOT and gives rise to an overall reactance for the MnBi_{2}Te_{4}, enabling a lossless conversion of electric power into magnetic dynamics.

Manipulating chiral spin transport with ferroelectric polarization.

A magnon is a collective excitation of the spin structure in a magnetic insulator and can transmit spin angular momentum with negligible dissipation. This quantum of a spin wave has always been manipulated through magnetic dipoles (that is, by breaking time-reversal symmetry). Here we report the experimental observation of chiral spin transport in multiferroic BiFeO3 and its control by reversing the ferroelectric polarization (that is, by breaking spatial inversion symmetry). The ferroelectrically controlled magnons show up to 18% modulation at room temperature. The spin torque that the magnons in BiFeO3 carry can be used to efficiently switch the magnetization of adjacent magnets, with a spin-torque efficiency comparable to the spin Hall effect in heavy metals. Utilizing such controllable magnon generation and transmission in BiFeO3, an all-oxide, energy-scalable logic is demonstrated composed of spin-orbit injection, detection and magnetoelectric control. Our observations open a new chapter of multiferroic magnons and pave another path towards low-dissipation nanoelectronics.

Exploring the molecular and immune-landscape of lung cancer associated with cystic airspaces.

To explore the molecular biological characteristics of lung cancer associated with cystic airspaces (LCCA) and its potential roles on prognosis. A total of 165 LCCAs and 201 non-LCCAs were enrolled in this study. Bulk RNA sequencing was implemented in eight LCCAs and nine non-LCCAs to explore the differentially expressed genes. TCGA data were used to analyze LCCA-specific genes that associated with overall survival (OS). The median age was 60 (IQR 53 to 65) years in LCCA cohort. We found LCCA were predominant in men and had less visceral pleura invasion (VPI) or lympho-vascular invasion (LVI). Moreover, LCCA presented with higher histological heterogeneity. Kaplan-Meier analysis showed that patients of age more than 60 and positive VPI had significantly less PFS in LCCA. Cox regression suggested that LCCA, micropapillary subtype proportion and VPI were the independent risk factors for PFS. LCCA had up-regulated pathways associated with EMT, angiogenesis and cell migration. In addition, LCCA displayed higher levels of immunosuppressor infiltration (M2 macrophages, CAFs and MDSCs) and distinct cell death and metabolic patterns. BCR/TCR repertoire analysis revealed less BCR richness, clonality and high-abundance shared clonotypes in LCCA. Finally, Cox regression analysis identified that four cystic-specific genes, KCNK3, NRN1, PARVB and TRHDE-AS1, were associated with OS of lung adenocarcinoma (LUAD). And cystic-specific risk scores (CSRSs) were calculated to construct a nomogram, which performance well. Our study for the first time indicated significantly distinct molecular biological and immune characteristics between LCCA and non-LCCA, which provide complementary prognostic values in early-stage non-small cell lung cancer (NSCLC).

[Effect and mechanism of Jiedu Huoxue Decoction in regulating YAP/ACSL4 pathway to inhibit ferroptosis in treatment of acute kidney injury].

Jiedu Huoxue Decoction(JDHX), first recorded in the Correction on Errors in Medical Works by WANG Qing-ren, is an effective formula screened out from ancient formulas by the traditional Chinese medicine(TCM) master ZHANG Qi to treat acute kidney injury(AKI) caused by heat, toxicity, stasis, and stagnation. This paper elucidated the therapeutic effect of JDHX on AKI and probed into the potential mechanism from ferroptosis. Thirty-two male C57BL/6 mice were randomized into four groups(n=8): normal, model, and low-and high-dose JDHX. Since the clinical treatment of AKI depends on supportive or alternative therapies and there is no specific drug, this study did not include a positive drug group. The low dose of JDHX corresponded to half of clinically equivalent dose, while the high dose corresponded to the clinically equivalent dose. Mice were administrated with JDHX by gavage daily for 7 consecutive days, while those in the normal group and the model group were administered with the corresponding volume of distilled water. On day 5 of drug administration, mice in other groups except the normal group were injected intraperitoneally with cisplatin solution at a dose of 20 mg·kg~(-1) to induce AKI, and the normal group was injected with saline. All of the mice were sacrificed 72 h after modeling, blood and kidney samples were collected for subsequent analysis. The levels of serum creatine(Scr) and blood urea nitrogen(BUN) were measured by the commercial kits. The expression level of kidney injury molecule 1(KIM-1) in the serum was measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Prussian blue staining were employed to observe the pathological changes, glycogen deposition, and iron deposition, respectively, in the renal tissue. In addition, the levels of glutathione(GSH), superoxide dismutase(SOD), and catalase(CAT) in the renal tissue were examined by biochemical colorimetry. Western blot was performed to determine the protein levels of acyl-CoA synthetase long chain family member 4(ACSL4), lysophosphatidylcholine acyltransferase 3(LPCAT3), and Yes-associated protein(YAP, a key molecule in the Hippo pathway) in the renal tissue. Immunohistochemistry was then employed to detect the location and expression of YAP in the renal tissue. Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was performed to measure the mRNA levels of ACSL4 and glutathione peroxidase 4(GPX4). Compared with the normal group, the model group showed elevated serum levels of Scr, BUN, and KIM-1. In the AKI model group, the tubular epithelial cells underwent atrophy and necrotic detachment, disappearance of brush border, and some tubules became protein tubules or experienced vacuole-like degeneration. In addition, this group presented widening of the interstitium or even edema, increased renal tubule injury score, and obvious glycogen and iron deposition in parts of the renal tissue. Moreover, the model group had lower GSH, SOD, and CAT levels, higher ASCL4 and LPCAT3 levels, and lower GPX4 expression and higher YAP expression than the normal group. Compared with the model group, high dose of JDHX effectively protected renal function, lowered the levels of Scr, BUN and KIM-1, alleviated renal pathological injury, reduced glycogen and iron deposition, and elevated the GSH, SOD, and CAT levels in the renal tissue. Furthermore, JDHX down-regulated the protein levels of ACSL4, LPCAT3, and YAP and up-regulated the level of GPX4, compared with the model group. In conclusion, JDHX can protect mice from cisplatin-induced AKI by inhibiting ferroptosis via regulating the YAP/ACSL4 signaling pathway.

Noninvasive Diagnosis of Kidney Dysfunction Using a Small-Molecule Manganese-Based Magnetic Resonance Imaging Probe.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a promising approach for the diagnosis of kidney diseases. However, safety concerns, including nephrogenic systemic fibrosis, limit the administration of gadolinium (Gd)-based contrast agents (GBCAs) in patients who suffer from renal impairment. Meanwhile, nanomaterials meet biosafety concerns because of their long-term retention in the body. Herein, we propose a small-molecule manganese-based imaging probe Mn-PhDTA as an alternative to GBCAs to assess renal insufficiency for the first time. Mn-PhDTA was synthesized via a simple three-step reaction with a total yield of up to 33.6%, and a gram-scale synthesis can be realized. Mn-PhDTA has an r1 relaxivity of 2.72 mM-1 s-1 at 3.0 T and superior kinetic inertness over Gd-DTPA and Mn-EDTA with a dissociation time of 60 min in the presence of excess Zn2+. In vivo and in vitro experiments demonstrate their good stability and biocompatibility. In the unilateral ureteral obstruction rats, Mn-PhDTA provided significant MR signal enhancement, enabled distinguishing structure changes between the normal and damaged kidneys, and evaluated the renal function at different injured stages. Mn-PhDTA could act as a potential MRI contrast agent candidate for the replacement of GBCAs in the early detection of kidney dysfunction and analysis of kidney disease progression.

Prevalence and progression of pneumonia in immunocompetent adults with varicella.

Pneumonia is the most common complication of varicella infections. Although previous studies have tended to focus mainly on immunocompromised patients, varicella pneumonia can also occur in healthy adults. Therefore, in this study, we aimed to assess the progression of varicella pneumonia in immunocompetent hosts. This retrospective study involved immunocompetent adult outpatients with varicella who attended the adult Fever Emergency facility of Peking University Third Hospital from April 1, 2020, to October 31, 2022. Varicella pneumonia was defined as a classic chickenpox-type rash in patients with infiltrates on chest computed tomography. The study included 186 patients, 57 of whom had a contact history of chickenpox exposure. Antiviral pneumonia therapy was administered to 175 patients by treating physicians. Computed tomography identified pneumonia in 132 patients, although no deaths from respiratory failure occurred. Seventy of the discharged patients were subsequently contacted, all of whom reported being well. Follow-up information, including computed tomography findings, was available for 37 patients with pneumonia, among whom 24 reported complete resolution whereas the remaining 13 developed persistent calcifications. Notably, we established that the true incidence of varicella pneumonia is higher than that previously reported, although the prognosis for immunocompetent hosts is generally good.

Few-shot concealed object detection in sub-THz security images using improved pseudo-annotations.

In this research, we explore the few-shot object detection application for identifying concealed objects in sub-terahertz security images, using fine-tuning based frameworks. To adapt these machine learning frameworks for the (sub-)terahertz domain, we propose an innovative pseudo-annotation method to augment the object detector by sourcing high-quality training samples from unlabeled images. This approach employs multiple one-class detectors coupled with a fine-grained classifier, trained on supporting thermal-infrared images, to prevent overfitting. Consequently, our approach enhances the model's ability to detect challenging objects (e.g., 3D-printed guns and ceramic knives) when few-shot training examples are available, especially in the real-world scenario where images of concealed dangerous items are scarce.

Managing Impending Nonsevere Hypoglycemia With Oral Carbohydrates in Type 1 Diabetes: The REVERSIBLE Trial.

OBJECTIVE: Current guidelines recommend initiating treatment for nonsevere (NS) hypoglycemia with 15 g carbohydrates (CHO) at 15-min intervals when blood glucose (BG) reaches <70 mg/dL (3.9 mmol/L). Despite this recommendation, NS hypoglycemia management remains challenging for individuals living with type 1 diabetes (T1D). We aimed to assess the efficacy of 15 g CHO at higher BG levels. RESEARCH DESIGN AND METHODS: A total of 29 individuals with T1D participated in an open-label crossover study. After an inpatient subcutaneous insulin-induced decrease in BG in the fasting state, 16 g CHO was administered orally at a plasma glucose (PG) of <70 (3.9), ≤80 (4.5), or ≤90 mg/dL (5.0 mmol/L). The primary outcome was time spent in hypoglycemia (<70 mg/dL) after initial CHO intake. RESULTS: When comparing the <70 (control) with the ≤80 and ≤90 mg/dL treatment groups, 100 vs. 86 (P = 0.1201) vs. 34% (P < 0.0001) of participants reached hypoglycemia, respectively. These hypoglycemic events lasted 26.0 ± 12.6 vs. 17.9 ± 14.7 (P = 0.026) vs. 7.1 ± 11.8 min (P = 0.002), with a PG nadir of 56.57 ± 9.91 vs. 63.60 ± 7.93 (P = 0.008) vs. 73.51 ± 9.37 mg/dL (P = 0.002), respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥70 mg/dL), compared with 52% in the ≤80 mg/dL group and 31% in the ≤90 mg/dL group, with no significant rebound hyperglycemia (>180 mg/dL) within the first hour. CONCLUSIONS: For some impending NS hypoglycemia episodes, individuals with TID could benefit from CHO intake at a higher BG level.

Highly Sensitive Early Diagnosis of Kidney Damage Using Renal Clearable Zwitterion-Coated Ferrite Nanoprobe via Magnetic Resonance Imaging In Vivo.

Iron oxide nanoprobes exhibit substantial potential in magnetic resonance imaging (MRI) of kidney diseases and can eliminate the nephrotoxicity of gadolinium-based contrast agents (GBCAs). Nevertheless, there is an extreme shortage of highly sensitive and renal clearable iron oxide nanoprobes suitable for early kidney damage detection through MRI. Herein, a renal clearable ultra-small ferrite nanoprobe (UMFNPs@ZDS) is proposed for highly sensitive early diagnosis of kidney damage via structural and functional MRI in vivo for the first time. The nanoprobe comprises a ferrite core coated with a zwitterionic layer, and possesses a high T1 relaxivity (12.52 mm-1s-1), a small hydrodynamic size (6.43 nm), remarkable water solubility, excellent biocompatibility, and impressive renal clearable ability. In a rat model of unilateral ureteral obstruction (UUO), the nanoprobe-based MRI can not only accurately visualize the locations of renal injury, but also provide comprehensive functional data including peak value, peak time, relative renal function (RRF), and clearance percentage via MRI. The findings prove the immense potential of ferrite nanoprobes as a superior alternative to GBCAs for the early diagnosis of kidney damage.

A method for Porphyromonas gingivalis based on recombinase polymerase amplification and lateral flow strip technology.

OBJECTIVE: A practical visual detection method was established to detect Porphyromonas gingivalis (P. gingivalis) by employing a combination of recombinase polymerase amplification and lateral flow strips (RPA-LF) assay, designed for conducting point-of-care testing in clinical settings. METHODS: Primers and probes targeting the P. gingivalis pepO gene were designed. The RPA-LF assay was established by optimising reaction temperature and time, determining the limit of detection (LOD). The specificity of the method was determined by assessing its cross-reactivity with deoxyribonucleic acid from 23 pathogenic bacteria. Finally, the clinical samples from healthy controls (n = 30) and individuals with periodontitis (n = 31) were analysed. The results were compared with those obtained using real-time polymerase chain reaction (PCR). RESULTS: The optimal reaction temperature and time were 39 °C and 12 min. The method exhibited a LOD at 6.40 × 10-4 µg/mL and demonstrated high specificity and sensitivity during cross-reactivity assessment. The RPA-LF assay achieved a P. gingivalis detection rate of 84 % in individuals with periodontitis and 3 % in healthy controls. The results were consistent with those obtained through real-time PCR. CONCLUSION: An RPA-LF assay was developed for detecting P. gingivalis, characterised by its high sensitivity, high specificity, simple operational procedure, and rapid reaction time.

A Comparative Visual Analytics Framework for Evaluating Evolutionary Processes in Multi-Objective Optimization.

Evolutionary multi-objective optimization (EMO) algorithms have been demonstrated to be effective in solving multi-criteria decision-making problems. In real-world applications, analysts often employ several algorithms concurrently and compare their solution sets to gain insight into the characteristics of different algorithms and explore a broader range of feasible solutions. However, EMO algorithms are typically treated as black boxes, leading to difficulties in performing detailed analysis and comparisons between the internal evolutionary processes. Inspired by the successful application of visual analytics tools in explainable AI, we argue that interactive visualization can significantly enhance the comparative analysis between multiple EMO algorithms. In this paper, we present a visual analytics framework that enables the exploration and comparison of evolutionary processes in EMO algorithms. Guided by a literature review and expert interviews, the proposed framework addresses various analytical tasks and establishes a multi-faceted visualization design to support the comparative analysis of intermediate generations in the evolution as well as solution sets. We demonstrate the effectiveness of our framework through case studies on benchmarking and real-world multi-objective optimization problems to elucidate how analysts can leverage our framework to inspect and compare diverse algorithms.

Tumor-Promoting Effects of Microrna-421/4-Aminobutyrate Aminotransferase Axis in Hepatocellular Carcinoma.

Background: MicroRNA-421 (miR-421) has been implicated in hepatocellular carcinoma (HCC), but its potential mechanism in HCC remains unclear. Objectives: The study aimed to study the potential mechanism of miR-421 in HCC which is necessary. Methods: The downstream target genes of miR-421 were screened in HCC tissues and cells using miDIP, Targetscan, and starBase databases. Differential analysis, survival analysis, and Pearson correlation analysis were performed between miR-421 and its downstream target genes. Quantitative reverse transcription polymerase chain reaction and western blot were used to assay RNA and protein levels of 4-aminobutyrate aminotransferase (ABAT) and epithelial-mesenchymal transition (EMT)-related proteins. Cell-based assays, including CCK-8, wound healing, transwell, flow cytometry, and metabolic measurements, were implemented to assess proliferation, migration, invasion, cell cycle, and apoptosis of HCC cells with different treatments. Dual-luciferase assay was utilized to detect the targeting relationship between miR-421 and ABAT. Results: miR-421 level was elevated in HCC tissues and cells, and low miR-421 expression hindered phenotype progression of HCC cells. ABAT was identified as a direct target of miR-421 in HCC cells, and miR-421 could inhibit ABAT expression. Rescue assay revealed that miR-421 promoted HCC cell tumorigenesis progress and affected cell metabolic remodeling through down-regulating ABAT. Conclusion: The miR-421/ABAT regulatory axis promoted HCC cell tumorigenesis progress, highlighting its potential as a therapeutic target for HCC.

Noninvasive Methods for Detecting Advanced Liver Fibrosis and Cirrhosis in Patients with Chronic Hepatitis B: A Single-Center Retrospective Study.

Background and Aims: The performance of noninvasive assessments to rule-in or rule-out fibrosis may improve when combined. We aimed to evaluate the efficiencies of sequential algorithms based on the aspartate aminotransferase-to-platelet ratio index (APRI), the fibrosis index based on four factors (FIB-4), and transient elastography (TE) for the assessment of advanced fibrosis (AF) and cirrhosis. Methods: This study enrolled 179 CHB subjects who underwent liver biopsy (LB) before antiviral treatment. Results: AF and cirrhosis were identified in 71 (39.7%) and 28 (15.7%) patients, respectively. Compared with TE alone, sequential FIB-4-TE and APRI-TE algorithms saved a slightly higher number of liver biopsies for the identification of advanced fibrosis (69.3% or 68.2% vs 63.7%, P=0.263 or P=0.372, respectively). For the identification of cirrhosis, sequential FIB-4-TE and APRI-TE algorithms saved a significantly higher number of liver biopsies than TE alone (83.2% or 88.3% vs 69.8%, P=0.003 or P=0.000, respectively). No significant difference was found between the sequential algorithms and TE alone in the diagnostic accuracy for the detection of AF and cirrhosis. Conclusion: The sequential algorithms could significantly reduce the need for liver biopsy with high accuracy for diagnosis of AF and cirrhosis in CHB patients, which would be optimal especially in resource-limited areas.