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.

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.

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.].

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.

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).

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.

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.

[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.

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.

The impact of adjuvant EGFR-TKIs and 14-gene molecular assay on stage I non-small cell lung cancer with sensitive EGFR mutations.

Background: Currently, the role of EGFR-TKIs as adjuvant therapy for stage I, especially IA NSCLC, after surgical resection remains unclear. We aimed to compare the effect of adjuvant EGFR-TKIs with observation in such patients by incorporating an established 14-gene molecular assay for risk stratification. Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Guangzhou Medical University (Study ID: ChNCRCRD-2022-GZ01). From March 2013 to February 2019, completely resected stage I NSCLC (8th TNM staging) patients with sensitive EGFR mutation were included. Patients with eligible samples for molecular risk stratification were subjected to the 14-gene prognostic assay. Inverse probability of treatment weighting (IPTW) was employed to minimize imbalances in baseline characteristics. Findings: A total of 227 stage I NSCLC patients were enrolled, with 55 in EGFR-TKI group and 172 in the observation group. The median duration of follow-up was 78.4 months. After IPTW, the 5-year DFS (HR = 0.30, 95% CI, 0.14-0.67; P = 0.003) and OS (HR = 0.26, 95% CI, 0.07-0.96; P = 0.044) of the EGFR-TKI group were significantly better than the observation group. For subgroup analyses, adjuvant EGFR-TKIs were associated with favorable 5-year DFS rates in both IA (100.0% vs. 84.5%; P = 0.007), and IB group (98.8% vs. 75.3%; P = 0.008). The 14-gene assay was performed in 180 patients. Among intermediate-high-risk patients, EGFR-TKIs were associated with a significant improvement in 5-year DFS rates compared to observation (96.0% vs. 70.5%; P = 0.012), while no difference was found in low-risk patients (100.0% vs. 94.9%; P = 0.360). Interpretation: Our study suggested that adjuvant EGFR-TKI might improve DFS and OS of stage IA and IB EGFR-mutated NSCLC, and the 14-gene molecular assay could help patients that would benefit the most from treatment. Funding: This work was supported by China National Science Foundation (82022048, 82373121).

Association between polymorphisms of anti-inflammatory gene alleles and periodontitis risk in a Chinese Han population.

OBJECTIVE: Cytokines that mediate the immune responses are important in the pathogenesis of periodontitis. The genetic polymorphisms of IL-10, TNFAIP3 (A20), and NF-κB1 (p105/p50) and their association with the risk of periodontitis were investigated. METHOD: Venous blood from 102 clinical periodontal healthy participants and 100 patients with periodontitis was collected to genotype the IL-10 (rs1800872), A20 (rs2230926, rs5029937, rs6927127), and NF-κB1 (rs28362491) SNP loci by Sanger technology. Univariable and multivariable logic regression and path analysis model was used to analyze the genotypes and alleles. RESULT: Single-gene mutations in the A20 (rs2230926, rs5029937, rs6927127) and IL-10 (rs1800872) genes were not associated with the risk of periodontitis. NF-κΒ1 (rs28362491) gene influenced periodontitis susceptibility by affecting CAL. The combined effect of A20 and IL-10 was related to the risk of periodontitis (ORa = 0.123-0.151). One site mutated in the A20 (rs2230926, rs5029937, rs6927127) gene or IL-10 (rs1800872) gene reduced the risk of periodontitis. CONCLUSION: Single gene polymorphisms in A20 and IL-10 genes were not associated with the risk of periodontitis. NF-κB1 gene polymorphism indirectly affects susceptibility to periodontitis. The combined effect of anti-inflammatory gene polymorphisms (A20 and IL-10) correlated with the decreased risk of periodontitis. CLINICAL RELEVANCE: This study helps to explore the potential mechanisms underlying the role of anti-inflammatory genes in the progression of periodontal disease and provides a basis for the selection and development of appropriate periodontal treatment strategies based on the genetic profile of the patient.

On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine.

IMPORTANCE: This study highlights the crucial role RNA processing plays in regulating viral gene expression and replication. By targeting SR kinases, we identified harmine as a potent inhibitor of HIV-1 as well as coronavirus (HCoV-229E and multiple SARS-CoV-2 variants) replication. Harmine inhibits HIV-1 protein expression and reduces accumulation of HIV-1 RNAs in both cell lines and primary CD4+ T cells. Harmine also suppresses coronavirus replication post-viral entry by preferentially reducing coronavirus sub-genomic RNA accumulation. By focusing on host factors rather than viral targets, our study offers a novel approach to combating viral infections that is effective against a range of unrelated viruses. Moreover, at doses required to inhibit virus replication, harmine had limited toxicity and minimal effect on the host transcriptome. These findings support the viability of targeting host cellular processes as a means of developing broad-spectrum anti-virals.

Gap-enhanced gold nanodumbbells with single-particle surface-enhanced Raman scattering sensitivity.

Gap-enhanced Raman tags (GERTs) have been widely used for surface-enhanced Raman scattering (SERS) imaging due to their excellent SERS performances. Here, we reported a synthetic strategy for novel gap-enhanced dumbbell-like nanoparticles with anisotropic shell coatings. Controlled shell growth at the tips of gold nanorods was achieved by using cetyltrimethylammonium bromide (CTAB) as a capping agent. A mechanism related to the shape-directing effects of CTAB was proposed to explain the findings. Optimized gap-enhanced gold dumbbells exhibited highly enhanced SERS responses compared to rod cores, with an enhancement ratio of 101.5. We further demonstrated that gap-enhanced AuNDs exhibited single-particle SERS sensitivity with an acquisition time as fast as 0.1 s per spectrum, showing great potential for high-speed SERS imaging.

A depth-of-interaction rebinning method based on both geometric and activity weights.

BACKGROUND AND OBJECTIVE: For positron emission tomography (PET) scanners with depth-of-interaction (DOI) measurement, the DOI rebinning method that utilizes DOI information to process the projection data is critical to image quality. Current DOI rebinning methods map coincidence events onto the rebinned sinogram based on the correlation of lines of response (LOR). This study aims to incorporate prior radioactivity distribution of the imaging object into DOI rebinning to obtain better image quality. METHODS: A DOI rebinning method based on both geometric and activity weights was proposed to assign coincidence events to the rebinned sinogram defined by a virtual ring. The geometric weights, representing the correlation between LORs, were calculated based on the areas of intersection. The activity weights, reflecting the activity distribution of the imaging object, were derived from the previous reconstructed image. RESULTS: Monte Carlo simulation data from four phantoms, including the image quality phantom, Derenzo phantom, and two rat-like ROBY phantoms, was used to evaluate the proposed method. The recovery coefficient (RC), contrast recovery coefficient (CRC), structural similarity index measure (SSIM), and peak signal-to-noise ratio (PSNR) were used as image quality metrics. Compared to other DOI rebinning methods, the proposed method achieved the highest RC (maximum improvement of 32%) and CRC at the same noise level and was also optimal in terms of the SSIM and PSNR. Meanwhile, incorporating the prior activity distribution into DOI rebinning also improved the image reconstruction speed. CONCLUSIONS: This work developed a new DOI rebinning method combining the correlation of LORs with the prior activity distribution, achieving relatively optimal image quality and reconstruction speed. Furthermore, it still needs to be evaluated on the actual equipment.