Non-immune functions of B7-H3: bridging tumor cells and the tumor vasculature.

B7-H3 (CD276), an immune checkpoint molecule, is overexpressed in various types of cancer and their tumor vasculature, demonstrating significant associations with adverse clinical outcomes. In addition to its well-known immune functions, B7-H3 exhibits dual co-stimulatory/co-inhibitory roles in normal physiology and the tumor microenvironment. The non-immune functions of B7-H3 in tumor cells and the tumor vasculature, including promoting tumor cell anti-apoptosis, proliferation, invasion, migration, drug resistance, radioresistance, as well as affecting cellular metabolism and angiogenesis, have increasingly gained attention from researchers. Particularly, the co-expression of B7-H3 in both tumor cells and tumor endothelial cells highlights the higher potential and clinical utility of therapeutic strategies targeting B7-H3. This review aims to summarize the recent advances in understanding the non-immune functions of B7-H3 in tumors and provide insights into therapeutic approaches targeting B7-H3, focusing on its co-expression in tumor cells and endothelial cells. The aim is to establish a theoretical foundation and practical reference for the development and optimization of B7-H3-targeted therapies.

ATG10S promotes IFNL1 expression and autophagic degradation of multiple viral proteins mediated by IFNL1.

ATG10S is a newly discovered subtype of the autophagy protein ATG10. It promotes complete macroautophagy/autophagy, degrades multiple viral proteins, and increases the expression of type III interferons. Here, we aimed to investigate the mechanism of ATG10S cooperation with IFNL1 to degrade viral proteins from different viruses. Using western blot, immunoprecipitation (IP), tandem sensor RFP-GFP-LC3B and in situ proximity ligation assays, we showed that exogenous recombinant ATG10S protein (rHsATG10S) could enter into cells through clathrin, and ATG10S combined with ATG7 with IFNL1 assistance to facilitate ATG12-ATG5 conjugation, thereby contributing to the autophagosome formation in multiple cell lines containing different virions or viral proteins. The results of DNA IP and luciferase assays also showed that ATG10S was able to directly bind to a core motif (CAAGGG) within a binding site of transcription factor ZNF460 on the IFNL1 promoter, by which IFNL1 transcription was activated. These results clarified that ATG10S promoted autophagosome formation with the assistance of IFNL1 to ensure autophagy flux and autophagic degradation of multiple viral proteins and that ATG10S could also act as a novel transcription factor to promote IFNL1 gene expression. Importantly, this study further explored the antiviral mechanism of ATG10S interaction with type III interferon and provided a theoretical basis for the development of ATG10S into a new broad-spectrum antiviral protein drug.Abbreviation: ATG: autophagy related; ATG10S: the shorter isoform of autophagy-related 10; CC50: half cytotoxicity concentration; CCV: clathrin-coated transport vesicle; CLTC: clathrin heavy chain; CM: core motif; co-IP: co-immunoprecipitation; CPZ: chlorpromazine; ER: endoplasmic reticulum; HCV: hepatitis C virus; HBV: hepatitis B virus; HsCoV-OC43: Human coronavirus OC43; IFN: interferon; PLA: proximity ligation assay; rHsATG10S: recombinant human ATG10S protein; RLU: relative light unit; SQSTM1: sequestosome 1; ZNF: zinc finger protein.

[Based on CT imaging, surgical approach selection for frontal and ethmoid sinus osteoma].

Objective:To investigate the criteria for selecting surgical approaches for frontal and ethmoid sinus osteomas of different locations and sizes on CT imaging. Methods:Using sagittal and coronal CT images, the following lines were delineated: the F-line（a horizontal line passing nasofrontal beak）, the M-line（a vertical line passing paries medialis orbitae）, and the P-line（a vertical line passing the center of the pupil）. Classification of frontal and ethmoid sinus osteomas was based on their relationship with these lines. Appropriate surgical approaches were selected, including pure endoscopic approaches, endoscopic combined with eyebrow incision approach, and endoscopic combined with coronal incision approach. This method was applied to a single center at the Third Affiliated Hospital of Sun Yat-sen University for endoscopic resection of frontal and ethmoid sinus osteoma. Case Data: Sixteen cases of ethmoid sinus osteomas were treated from January 2020 to September 2023. Among these cases, there were 9 males and 7 females, with ages ranging from 18 to 69 years, and a median age of 48 years. Results:Thirteen cases underwent pure endoscopic resection of the osteoma, while in three cases, a combined approach was utilized. Among the combined approach cases, two exceeded both the M-line and the F-line but did not cross the P-line; therefore, they underwent endoscopic combined with eyebrow incision approach. One case exceeded all three lines and thus underwent endoscopic combined with coronal incision. In all cases, complete resection of the osteoma was achieved as per preoperative planning, and none of the patients experienced significant postoperative complications. Conclusion:For frontal and ethmoid sinus osteomas, it is advisable to perform a thorough preoperative radiological assessment. Based on the size of the osteoma and its relationship to the three lines, an appropriate surgical approach should be chosen to optimize the diagnostic and treatment plan.

Photochemical Synthesis of Thioesters from Aryl Halides and Carboxylic Acids.

Thioesters are important in synthesis, materials science, and biology, and their preparation traditionally relies on the use of disagreeable thiols. Here, we report a thiol-free protocol that stitches together widespread carboxylic acids and aryl halides, producing a diverse array of thioesters. Crucial to this strategy is the discovery that tetramethylthiourea can serve as both a sulfur source and, upon direct excitation by purple light, as a strong reductant, suitable for activating aryl halides via single-electron transfer. Coupling of the resulting aryl radicals provides an isothiouronium ion intermediate, which can be attacked by carboxylic acids via a polar pathway, affording the thioester products under mild conditions.

Elevated hepatitis B virus RNA levels in HBeAg-positive patients with low-level viraemia or previous low-level viraemia.

The understanding of viral transcription and replication activity in HBeAg-positive chronic hepatitis B (CHB) patients with low-level viraemia (LLV) or previous low-level viraemia (pre-LLV) remains unclear. Our aim was to evaluate and compare circulating hepatitis B virus (HBV) RNA levels in these patient groups with those achieving maintained virological response (MVR). This cross-sectional study included 147 patients: 43 in the LLV group, 25 in the pre-LLV group and 79 in the MVR group. Serum HBV RNA levels were assessed using specific RNA target capture combined with simultaneous amplification and testing method. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Median HBV RNA levels were 6.9 copies/mL in the LLV group, 6.1 copies/mL in the pre-LLV group and 3.8 copies/mL in the MVR group. After PSM, significantly higher HBV RNA levels were observed in the LLV group compared to the MVR group (p < .001), and the pre-LLV group also showed higher HBV RNA levels than the MVR group (p < .001). Both LLV and pre-LLV HBeAg-positive CHB patients exhibited elevated circulating HBV RNA levels compared to those achieving MVR.

Electric field control of spin-orbit torque in annealed Ta/CoFeB/HfOxheterostructures via interfacial oxidation modulation.

Electric field control of spin-orbit torque (SOT) exhibits promising potential in advanced spintronic devices through interfacial modulation. In this work, we investigate the influence of electric field and interfacial oxidation on SOT efficiency in annealed Ta/CoFeB/HfOxheterostructures. By varying annealing temperatures, the damping-like SOT efficiency reaches its peak at the annealing temperature of 320 °C, with an 80% field-free magnetization switching ratio induced by SOT having been demonstrated. This enhancement is ascribed to the annealing-induced modulation of oxygen ion migration at the CoFeB/HfOxinterface. By applying voltages across the Ta/CoFeB/HfOxheterostructures, which drives the O2‒migration across the interface, a reversible, bipolar, and non-volatile modulation of SOT efficiency was observed. The collective influence of annealing temperature and electric field effects on SOT carried out in this work provides an effective approach into facilitating the optimization and control of SOT in spintronic devices.

NIR and magnetism dual-response multi-core magnetic vortex nanoflowers for boosting magneto-photothermal cancer therapy.

Due to the relatively low efficiency of magnetic hyperthermia and photothermal conversion, it is rather challenging for magneto-photothermal nanoagents to be used as an effective treatment during tumor hyperthermal therapy. The advancement of magnetic nanoparticles exhibiting a vortex-domain structure holds great promise as a viable strategy to enhance the application performance of conventional magnetic nanoparticles while retaining their inherent biocompatibility. Here, we report the development of Mn0.5Zn0.5Fe2O4 nanoflowers with ellipsoidal magnetic cores, and show them as effective nanoagents for magneto-photothermal synergistic therapy. Comparative studies were conducted on the heating performance of anisometric Mn0.5Zn0.5Fe2O4 (MZF) nanoparticles, including nanocubes (MZF-C), hollow spheres (MZF-HS), nanoflowers consisting of ellipsoidal magnetic cores (MZF-NFE), and nanoflowers consisting of needle-like magnetic cores (MZF-NFN). MZF-NFE exhibits an intrinsic loss parameter (ILP) of up to 15.3 N h m2 kg-1, which is better than that of commercial equivalents. Micromagnetic simulations reveal the magnetization configurations and reversal characteristics of the various MZF shapes. Additionally, all nanostructures displayed a considerable photothermal conversion efficiency rate of more than 18%. Our results demonstrated that by combining the dual exposure of MHT and PTT for hyperthermia treatments induced by MZF-NFE, BT549, MCF-7, and 4T1 cell viability can be significantly decreased by ∼95.7% in vitro.

LARP7 overexpression alleviates aortic senescence and atherosclerosis.

Atherosclerosis, characterized by the accumulation of lipid plaques on the inner walls of arteries, is the leading cause of heart attack, stroke and severe ischemic injuries. Senescent cells have been found to accumulate within atherosclerotic lesions and contribute to the progression of atherosclerosis. In our previous study, we discovered that suppressing Larp7 accelerates senescence by inhibiting Sirt1 activity, resulting in increased atherosclerosis in high-fat diet (HFD) fed and ApoE deficient (ApoEKO) mice. However, there has been no direct evidence demonstrating Larp7 per se could attenuate atherosclerosis. To this end, we generated a tetO-controlled and Cre-activated Larp7 gain-of-function mouse. Through RT-PCR and western blotting, we confirmed Larp7 overexpression in the aortas of HFD-fed ApoEKO; Larp7tetO mice. Larp7 overexpression led to increased Sirt1 activity and decreased cellular senescence signals mediated by p53/p65 in the aortas. Additionally, Larp7 overexpression reduced the presence of p16-positive senescent cells in the aortic lesions. Furthermore, Larp7 overexpression resulted in a decrease in pro-inflammatory macrophages and SASP factors. Consequently, Larp7 overexpression led to a reduction in the area of atherosclerotic lesions in HFD-fed ApoEKO; Larp7tetO mice. In summary, our study provides evidence that Larp7 overexpression holds promise as an approach to inhibit cellular senescence and prevent atherosclerosis.

Dual Stimulus Responsive GO-Modified Tb-MOF toward a Smart Coating for Corrosion Detection.

Smart-sensing coatings that exhibit multistimulus response, rapid indication, and reusability are in urgent need to effectively enhance the practicability of coatings while accurately detecting metal corrosion. In this work, a reusable corrosion self-reporting coating with multiple pH and Fe3+ stimulus responses was first constructed by the integration of a composite fluorescent probe into the resin matrix. This composite sensor was constructed by combining a lanthanide metal-organic framework (Ln-MOF) based on terbium and trimeric acid (H3BTC) with graphene oxide (GO) nanosheets (GO@Tb-BTC). The incorporation of GO formed a sea-urchin-like structure, thereby increasing the specific surface area and active sites of the probe. The coatings were characterized by using electrochemical impedance spectroscopy (EIS), visual observation, and fluorescence spectrophotometry. The surface morphology, wettability, and adhesion of the coating samples were analyzed using SEM, XPS, hydrostatic contact angle test, and an adhesion test. EIS measurements in 3.5 wt % NaCl solution for 72 h demonstrated the superior corrosion protection performance of the 0.3 wt %/GO@Tb-BTC/WEP coating compared to blank coating, with the charge-transfer resistance reaching 4.33 × 107 Ω·cm2, which was 9.5 times higher than that of the pure coating. The bright green fluorescence of GO@Tb-BTC/WEP coating exhibited a turn-off response when there was an excess of OH-/H+, but it demonstrated a reversible turn-on fluorescence when the ambient pH returned to neutral. Furthermore, such Fe3+-triggered fluorescence quenching responded to concentrations as low as 1 × 10-6 M. The fluorescence quenching rate of both intact and damaged coatings surpassed that of visual and EIS detection methods. Significantly, the fluorescence in scratches was effectively quenched within 25 min using 0.3 wt %/GO@Tb-BTC/WPU coating for visual observation. GO@Tb-BTC demonstrated exceptional corrosion self-reporting capabilities in both epoxy and polyurethane systems, making it a versatile option beyond single-coating applications.

Predictors of Nucleos(t)ide Analogues Discontinuation Relapse: Hepatitis B Virus RNA versus Hepatitis B Surface Antigen.

OBJECTIVE: To compare the predictive value of hepatitis B virus (HBV) RNA and HBsAg quantification upon discontinuation of nucleos(t)ide analogues (NAs) therapy for clinical and virological relapse in chronic hepatitis B (CHB). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China, from July 2014 to December 2020. METHODOLOGY: CHB patients received single NAs and discontinued treatment following appropriate standards. HBsAg quantification was conducted using the i2000 Chemiluminescent Immunoassay (CLIA) Analyser, while serum HBV RNA quantification was performed using specific RNA target capture and simultaneous amplification and testing. The main observational endpoints included virological relapse and clinical relapse. RESULTS: Eighty-one patients were recruited, with 15 patients achieving HBsAg loss at cessation. Twenty-nine individuals encountered virological relapse, while 13 patients experienced clinical relapse. Thirty-one patients achieved HBsAg <100 IU/ml at NAs cessation, among whom 26 achieved undetectable HBV RNA, while four patients suffered virological relapse (15.4%). Serum HBV RNA emerged as an independent determinant of virological relapse (HR 1.850), clinical relapse (HR 2.020), and HBsAg loss after NAs cessation (HR 0.138). The presence of HBsAg <100 IU/ml at cessation did not serve as a predictor for virological relapse and clinical relapse. CONCLUSION: Lower HBV RNA levels predict a better off-treatment response. Discontinuation of prolonged NAs therapy appears as a viable and safe choice for patients with undetectable HBV RNA. In comparison to HBV RNA, HBsAg <100 IU/ml at cessation did not show sufficient predictive value for virological relapse and clinical relapse. KEY WORDS: HBV RNA, Hepatitis B surface antigen, Chronic hepatitis B, Relapse.

Comparison of the Diagnosis and Treatment of Nasal Bone Fracture by Physicians in China With Different Levels of Experience.

OBJECTIVE: This study aimed to investigate the conflicts in the diagnosis and treatment of nasal bone fracture by Chinese otolaryngologists to improve the diagnosis and treatment accuracy of junior otolaryngologists and emergency physicians. METHODS: A questionnaire was designed and filled out by otolaryngologists in large general hospitals. The questions included how to choose an auxiliary examination to diagnose nasal bone fracture, whether tamponade is required after closed reduction, the selection of packing materials, the timing of an operation, and the evaluation of postoperative effect. The questionnaire results were divided into 3 groups according to the experience levels of experienced of physicians. RESULTS: A total of 151 otolaryngologists with different levels of experience from 26 provinces in China completed the questionnaire. 90.73% of physicians thought that nasal bone computed tomography was the most important auxiliary examination to diagnose a nasal bone fracture. 52.32% of them compared photos before and after the operation to evaluate postoperative effects. About 53% of physicians thought that 7 to 10 days after reducing local swelling is the optimal time for closed reduction. CONCLUSIONS: There is no obvious difference in the diagnosis and treatment of nasal bone fracture among otolaryngologists with different levels of experience in Chinese otolaryngologists with different levels. Most physicians choose nasal bone computed tomography for diagnosis, perform surgery at 7 to 10 days after injury, and compare photos from before and after the operation to evaluate the postoperative effect.

A urethral leiomyoma presenting with dysuria: A rare case report.

RATIONALE: Leiomyoma is a benign smooth muscle tumor which is rarely found in urethra. We hereby report a case of a 44-year-old female who presented with complaints of dysuria. PATIENT CONCERNS: A 44-year-old female patient presented to the urology outpatient clinic with symptoms of dysuria. The patient described the presence of a protrusion from the urethra during urination. DIAGNOSIS: Urethral leiomyoma. INTERVENTIONS: Physical examination confirmed a solid urethral mass. CT scan and USG reports indicated that the mass originated from the mid-urethra with vascularity at the base. We performed a complete resection of the urethral mass. The patient was discharged after 3 days of observation. OUTCOME: During a follow-up after 1 month, the patient reported improved urinary flow and no occurrence of hematuria. The patient recovered well after discharge. LESSON: Urethral leiomyoma is a rare benign tumor that is often misdiagnosed in clinical practice. Diagnosis requires careful clinical examination. Surgical removal usually works well. It is important to remember that in some cases of acute urinary retention, it can be caused by a complete obstruction of a mass in the urethra. Urologists should be more cautious and experienced in handling such cases.

Allele-Specific Suppression of Variant MHC With High-Precision RNA Nuclease CRISPR-Cas13d Prevents Hypertrophic Cardiomyopathy.

BACKGROUND: Familial hypertrophic cardiomyopathy has severe clinical complications of heart failure, arrhythmia, and sudden cardiac death. Heterozygous single nucleotide variants (SNVs) of sarcomere genes such as MYH7 are the leading cause of this type of disease. CRISPR-Cas13 (clustered regularly interspaced short palindromic repeats and their associated protein 13) is an emerging gene therapy approach for treating genetic disorders, but its therapeutic potential in genetic cardiomyopathy remains unexplored. METHODS: We developed a sensitive allelic point mutation reporter system to screen the mutagenic variants of Cas13d. On the basis of Cas13d homology structure, we rationally designed a series of Cas13d variants and obtained a high-precision Cas13d variant (hpCas13d) that specifically cleaves the MYH7 variant RNAs containing 1 allelic SNV. We validated the high precision and low collateral cleavage activity of hpCas13d through various in vitro assays. We generated 2 HCM mouse models bearing distinct MYH7 SNVs and used adenovirus-associated virus serotype 9 to deliver hpCas13d specifically to the cardiomyocytes. We performed a large-scale library screening to assess the potency of hpCas13d in resolving 45 human MYH7 allelic pathogenic SNVs. RESULTS: Wild-type Cas13d cannot distinguish and specifically cleave the heterozygous MYH7 allele with SNV. hpCas13d, with 3 amino acid substitutions, had minimized collateral RNase activity and was able to resolve various human MYH7 pathological sequence variations that cause hypertrophic cardiomyopathy. In vivo application of hpCas13d to 2 hypertrophic cardiomyopathy models caused by distinct human MYH7 analogous sequence variations specifically suppressed the altered allele and prevented cardiac hypertrophy. CONCLUSIONS: Our study unveils the great potential of CRISPR-Cas nucleases with high precision in treating inheritable cardiomyopathy and opens a new avenue for therapeutic management of inherited cardiac diseases.

A multi-omics study to monitor senescence-associated secretory phenotypes of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is characterized by the progressive degeneration and damage of neurons in the brain. However, developing an accurate diagnostic assay using blood samples remains a challenge in clinic practice. The aim of this study was to explore senescence-associated secretory phenotypes (SASPs) in peripheral blood using mass spectrometry based multi-omics approach and to establish diagnostic assays for AD. METHODS: This retrospective study included 88 participants, consisting of 29 AD patients and 59 cognitively normal (CN) individuals. Plasma and serum samples were examined using high-resolution mass spectrometry to identify proteomic and metabolomic profiles. Receiver operating characteristic (ROC) analysis was employed to screen biomarkers with diagnostic potential. K-nearest neighbors (KNN) algorithm was utilized to construct a multi-dimensional model for distinguishing AD from CN. RESULTS: Proteomics analysis revealed upregulation of five plasma proteins in AD, including RNA helicase aquarius (AQR), zinc finger protein 587B (ZNF587B), C-reactive protein (CRP), fibronectin (FN1), and serum amyloid A-1 protein (SAA1), indicating their potential for AD classification. Interestingly, KNN-based three-dimensional model, comprising AQR, ZNF587B, and CRP, demonstrated its high accuracy in AD recognition, with evaluation possibilities of 0.941, 1.000, and 1.000 for the training, testing, and validation datasets, respectively. Besides, metabolomics analysis suggested elevated levels of serum phenylacetylglutamine (PAGIn) in AD. INTERPRETATION: The multi-omics outcomes highlighted the significance of the SASPs, specifically AQR, ZNF587B, CRP, and PAGIn, in terms of their potential for diagnosing AD and suggested neuronal aging-associated pathophysiology.

Analysis of the Construction of a Predictive Model for Eosinophilic Chronic Rhinosinusitis.

Purpose: This study aimed to determine indices to diagnose and predict eosinophilic chronic rhinosinusitis (ECRS) during the initial clinic visit. Patients and Methods: We retrospectively analyzed 116 patients with chronic rhinosinusitis who underwent endoscopic sinus surgery and were classified according to the postoperative pathological diagnosis. General data and various clinical indicators were analyzed, and indicators with statistically significant differences between groups were further incorporated into a multivariate logistic regression to establish a comprehensive prediction model. The receiver operating characteristic (ROC) curve was used to compare the two significant valuable single factors from previous studies, the difference in CT scores between the ethmoid sinus and the sum difference of the maxillary sinus (EM difference) and the absolute value of peripheral blood eosinophil (bEOS), with a comprehensive prediction model. Results: There were significant differences in history of allergic asthma (p < 0.001), visual analog scale (VAS) score (p=0.005), sino-nasal outcome test-22(SNOT-22) scale score (p=0.004), Lund-Mackay scale score (p=0.017), EM difference (p=0.002), percentage of bEOS (%)(p=0.001), and absolute value of bEOS (×109/L) (p=0.000) between the two groups (p< 0.05). The history of allergic disease, VAS and bEOS were screened out and included in the comprehensive prediction model. The area under the curve (AUC) of the comprehensive prediction model (0.804)> the AUC of the absolute value of the bEOS (0.764)>the AUC of the EM difference (0.655). The AUC of the EM difference and the comprehensive prediction model were statistically different (P=0.025). There was no statistical difference between the absolute value of bEOS and the AUC of the comprehensive prediction model. Conclusion: The comprehensive prediction model covering the three aspects of allergic asthma history, VAS score, and bEOS count had the highest AUC compared to the other predictors and had good predictive power for the diagnosis of ECRS.

Theoretical prediction on the insertion reactions of stannylenoid H2SnLiF with CH3X and SiH3X (X = F, Cl, Br).

Density functional theory was used to study the insertion reaction of stannylenoid H2SnLiF with CH3X, SiH3X (X = F, Cl, Br). Comparing the reaction barrier of H2SnLiF with CH3X, SiH3X, it can be found that the order of the difficulty of insertion reaction is F > Cl > Br. The insertion reaction potential barrier of SiH3X is lower than that of CH3X, which means that SiH3X is easier to react. According to the calculation results, the reaction law in THF solvent is consistent with that in vacuum, while in THF solvent, the barrier is lower and therefore more prone to reactions. This work provides theoretical support for the reaction properties of stannylenoids.

Passivation strategies for enhancing sensitivity and repeatability of microelectrode electrochemical sensors.

The sensitivity and repeatability are crucial for the practical application of electrochemical sensors. Many studies have focused on sensing materials and electrode structure to enhance sensitivity and repeatability rather than insulating layers. In this paper, polyaniline (PANI) microelectrode arrays were prepared to explore the influence of the insulating layer on sensitivity and repeatability of electrochemical sensors. The effects of different types of insulating layers, the sizes of the electrodes, and the thicknesses of the insulating layers were studied by experiment and simulation. The research findings indicated that the kind of organic insulating layers (Polyimide (PI) and SU-8) did not have a significant effect on the performance of the sensors. However, as the electrode area increased, the PANI film deposited on the electrode exhibited improved uniformity and density, leading to significant improvements in sensitivity and repeatability of the sensors. Additionally, the thickness of the insulating layer also had a significant impact on the performance of the device. The microelectrode with thinner insulating layers exhibited improved performance in sensitivity, repeatability and signal-to-noise ratio. The research findings indicated that increasing the electrode size and reducing the thickness of the insulating layer led to a more uniform and dense PANI film, resulting in an array electrode that exhibits excellent performance and remarkable repeatability.

Identification of dihydroquinolizinone derivatives with nitrogen heterocycle moieties as new anti-HBV agents.

The sustained loss of HBsAg is considered a pivotal indicator for achieving functional cure of HBV. Dihydroquinolizinone derivatives (DHQs) have demonstrated remarkable inhibitory activity against HBsAg both in vitro and in vivo. However, the reported neurotoxicity associated with RG7834 has raised concerns regarding the development of DHQs. In this study, we designed and synthesized a series of DHQs incorporating nitrogen heterocycle moieties. Almost all of these compounds exhibited potent inhibition activity against HBsAg, with IC50 values at the nanomolar level. Impressively, the compound (S)-2a (10 µM) demonstrated a comparatively reduced impact on the neurite outgrowth of HT22 cells and isolated mouse DRG neurons in comparison to RG7834, thereby indicating a decrease in neurotoxicity. Furthermore, (S)-2a exhibited higher drug exposures than RG7834. The potent anti-HBV activity, reduced neurotoxicity, and favorable pharmacokinetic profiles underscore its promising potential as a lead compound for future anti-HBV drug discovery.

Multimodal evaluation of the effects of low-intensity ultrasound on cerebral blood flow after traumatic brain injury in mice.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and destruction of the cerebrovascular system is a major factor in the cascade of secondary injuries caused by TBI. Laser speckle imaging (LSCI)has high sensitivity in detecting cerebral blood flow. LSCI can visually show that transcranial focused ultrasound stimulation (tFUS) treatment stimulates angiogenesis and increases blood flow. To study the effect of tFUS on promoting angiogenesis in Controlled Cortical impact (CCI) model. tFUS was administered daily for 10 min and for 14 consecutive days after TBI. Cerebral blood flow was measured by LSCI at 1, 3, 7 and 14 days after trauma. Functional outcomes were assessed using LSCI and neurological severity score (NSS). After the last test, Nissl staining and vascular endothelial growth factor (VEGF) were used to assess neuropathology. TBI can cause the destruction of cerebrovascular system. Blood flow was significantly increased in TBI treated with tFUS. LSCI, behavioral and histological findings suggest that tFUS treatment can promote angiogenesis after TBI.

Long noncoding RNA lnc-SNAPC5-3:4 inhibits malignancy by directly upregulating miR-224-3p in non-small cell lung cancer.

The mounting body of evidence demonstrates the growing importance of long noncoding RNAs in the advancement of tumors. This study aimed to investigate the molecular mechanism of lnc-SNAPC5-3:4 in non-small cell lung cancer (NSCLC). We investigated the expression of miR-224-3p and lnc-SNAPC5-3:4 in clinical NSCLC samples and NSCLC cell lines using reverse transcription polymerase chain reaction (RT-PCR). In vitro studies, A549 cell growth was estimated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EDU), and flow cytometry assays. In vivo studies, NSCLC tumorigenesis was determined using xenograft tumor mouse models, tumor growth was evaluated using antigen Kiel 67 (Ki67) staining, and tumor apoptosis was detected through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The relationship between lnc-SNAPC5-3:4 and miR-224-3p was determined by luciferase reporter gene assay. Results indicated that the expression of lnc-SNAPC5-3:4 was observed to be downregulated in NSCLC tissues and cell lines. After overexpression of lnc-SNAPC5-3:4 in cultured A549 cells, proliferation decreased and apoptosis increased. Furthermore, the expression of miR-224-3p was targeted and negatively regulated by lnc-SNAPC5-3:4. The lnc-SNAPC5-3:4 upregulation inhibited cell proliferation and promoted apoptosis, which was partially blocked by miR-224-3p overexpression in A549 cells. In addition, we constructed a subcutaneous inoculation model using BALB/c nude mice, and the results indicated that lnc-SNAPC5-3:4 overexpression restrained the growth of subcutaneous tumors, decreased Ki67 expression levels, and increased apoptosis, as indicated by TUNEL staining in nude mice. However, miR-224-3p transfection resulted in the reversal of the inhibitory effect of lnc-SNAPC5-3:4 on tumor growth. In conclusion, our study revealed that lnc-SNAPC5-3:4 inhibits tumor progression in NSCLC by targeting miR-224-3p. This study provides a potential therapeutic target for inhibiting NSCLC progression.