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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification.

BACKGROUND: Vascular calcification, which is characterized by calcium deposition in arterial walls and the osteochondrogenic differentiation of vascular smooth muscle cells, is an actively regulated process that involves complex mechanisms. Vascular calcification is associated with increased cardiovascular adverse events. The role of 4-hydroxynonenal (4-HNE), which is the most abundant stable product of lipid peroxidation, in vascular calcification has been poorly investigated. METHODS: Serum was collected from patients with chronic kidney disease and controls, and the levels of 4-HNE and 8-iso-prostaglandin F2α were measured. Sections of coronary atherosclerotic plaques from donors were immunostained to analyze calcium deposition and 4-HNE. A total of 658 patients with coronary artery disease who received coronary computed tomography angiography were recruited to analyze the relationship between coronary calcification and the rs671 mutation in aldehyde dehydrogenase 2 (ALDH2). ALDH2 knockout (ALDH2-/-) mice, smooth muscle cell-specific ALDH2 knockout mice, ALDH2 transgenic mice, and their controls were used to establish vascular calcification models. Primary mouse aortic smooth muscle cells and human aortic smooth muscle cells were exposed to medium containing ß-glycerophosphate and CaCl2 to investigate cell calcification and the underlying molecular mechanisms. RESULTS: Elevated 4-HNE levels were observed in the serum of patients with chronic kidney disease and model mice and were detected in calcified artery sections by immunostaining. ALDH2 knockout or smooth muscle cell-specific ALDH2 knockout accelerated the development of vascular calcification in model mice, whereas overexpression or activation prevented mouse vascular calcification and the osteochondrogenic differentiation of vascular smooth muscle cells. In patients with coronary artery disease, patients with ALDH2 rs671 gene mutation developed more severe coronary calcification. 4-HNE promoted calcification of both mouse aortic smooth muscle cells and human aortic smooth muscle cells and their osteochondrogenic differentiation in vitro. 4-HNE increased the level of Runx2 (runt-related transcription factor-2), and the effect of 4-HNE on promoting vascular smooth muscle cell calcification was ablated when Runx2 was knocked down. Mutation of Runx2 at lysine 176 reduced its carbonylation and eliminated the 4-HNE-induced upregulation of Runx2. CONCLUSIONS: Our results suggest that 4-HNE increases Runx2 stabilization by directly carbonylating its K176 site and promotes vascular calcification. ALDH2 might be a potential target for the treatment of vascular calcification.

Effects of Neolamarckia cadamba leaves extract on microbial community and antibiotic resistance genes in cecal contents and feces of broilers challenged with lipopolysaccharides.

The effects of Neolamarckia cadamba leaves extract (NCLE), with effective ingredients of flavonoids, on antibiotic resistance genes (ARGs) and relevant microorganisms in cecal contents and feces of broilers treated with or without lipopolysaccharide stimulation (LPS) were investigated. LPS stimulation increased (P < 0.05) the relative abundance of ARGs and mobile genetic elements (MGEs), such as tet(W/N/W), APH(3')-IIIa, ErmB, tet (44), ANT (6)-Ia, tet(O), tet (32), Vang_ACT_CHL, myrA, ANT (6)-Ib, IncQ1, tniB, and rep2 in cecal contents. However, the difference disappeared (P > 0.05) when NCLE was added at the same time. These differential ARGs and MGEs were mainly correlated (P < 0.01) with Clostridiales bacterium, Lachnospiraceae bacterium, and Candidatus Woodwardibium gallinarum. These species increased in LPS-stimulated broilers and decreased when NCLE was applied at the same time. In feces, LPS stimulation decreased (P < 0.05) the relative abundance of tet(Q), adeF, ErmF, Mef(En2), OXA-347, tet (40), npmA, tmrB, CfxA3, and ISCrsp1, while the LPS + NCLE treated group showed no significant effect (P > 0.05) on these ARGs. These differential ARGs and MGEs in feces were mainly correlated (P < 0.01) with Clostridiales bacterium, Pseudoflavonifractor sp. An184, Flavonifractor sp. An10, Ruminococcaceae bacterium, etc. These species increased in LPS-stimulated broilers and increased when NCLE was applied at the same time. In conclusion, LPS stimulation and NCLE influenced microbial communities and associated ARGs in both cecal contents and feces of broilers. NCLE alleviated the change of ARGs and MGEs in LPS-induced broilers by maintaining the microbial balance.IMPORTANCEAntibiotics showed a positive effect on gut health regulation and growth performance improvement in livestock breeding, but the antimicrobial resistance threat and environment pollution problem are increasingly severe with antibiotics abuse. As alternatives, plant extract containing bioactive substances are increasingly used to improve immunity and promote productivity. However, little is known about their effects on diversity and abundance of ARGs. Here, we investigated the effects of NCLE, with effective ingredients of flavonoids, on ARGs and relevant microorganisms in cecal contents and feces of broilers treated with or without lipopolysaccharide stimulation. We found that NCLE reduced the abundance of ARGs in cecal contents of lipopolysaccharide-induced broilers by maintaining the microbial balance. This study provides a comprehensive view of cecal and fecal microbial community, ARGs, and MGEs of broiler following LPS stimulation and NCLE treatment. It might be used to understand and control ARGs dissemination in livestock production.

Suggested blood donor deferral strategy regarding hepatitis B infections in China.

BACKGROUND: Hepatitis B virus (HBV) reactivity in individual immunologic and nucleic acid tests (NAT) tests does not represent the true infectious status of the blood donor. This study discusses the use of confirmatory tests to determine when deferral of blood donors is appropriate. METHODS: HBsAg or HBV NAT reactive samples were confirmed via a neutralisation test. All the HBsAg reactive but neutralisation test negative samples were subjected to further anti-HBc testing. The receiver operating characteristic curve was used to obtain the best threshold value using signal-to-cut-off ratios of two HBsAg enzyme-linked immunosorbent assay reagents. RESULTS: Of the 780 HBV reactive samples collected, there were 467 HBsAg reactive but HBV DNA negative samples, of which 65 (13.92%) and 402 (86.08%) were neutralisation test positive and negative, respectively. Of the 402, 91 samples (30% of tested samples) were anti-HBc reactive. HBV DNA positive specimens negative by virus neutralisation were >80% HBcAg positive. A screening strategy was proposed for Chinese blood collection agencies. CONCLUSION: These findings suggest that adopting a screening algorithm for deferring HBV reactive blood donors based on HBsAg and NAT testing followed with HBsAg S/CO consideration and HBcAg testing can be both safe and feasible in China.

Perspectives for the Role of Single-Atom Nanozymes in Assisting Food Safety Inspection and Food Nutrition Evaluation.

Single-atom nanozymes (SAzymes) have been greatly developed for rapid detection, owing to their rich active sites and excellent catalytic activity. Although several excellent reviews concentrating on SAzymes have been reported, they mainly focused on advanced synthesis, sensing mechanisms, and biomedical applications. To date, few reviews elaborate on the promising applications of SAzymes in food safety inspection and food nutrition evaluation. In this paper, we systematically reviewed the enzyme-like activity of SAzymes and the catalytic mechanism, in addition to recent research advances of SAzymes in the domain of food safety inspection and food nutrition evaluation in the past few years. Furthermore, current challenges hampering practical applications of SAzymes in food assay are summarized and analyzed, and possible research areas focusing on SAzyme-based sensors in rapid food testing are also proposed.

Difunctional Microelectrode Arrays for Single-Cell Electrical Stimulation and pH Detection.

Due to its direct effect on biomolecules and cells, electrical stimulation (ES) is now widely used to regulate cell proliferation, differentiation, and neurostimulation and is even used in the clinic for pain relief, treatment of nerve damage, and muscle rehabilitation. Conventional ES is mostly studied on cell populations, but the heterogeneity of cancer cells results in the inability to access the response of individual cells to ES. Therefore, detecting the extracellular pH change (ΔpHe) after ES at the single-cell level is important for the application of ES in tumor therapy. In this study, cellular ΔpHe after periodic impulse electrostimulation (IES) was monitored in situ by using a polyaniline (PANI)-modified gold microelectrode array. The PANI sensor had excellent sensitivity (53.68 mV/pH) and linear correlation coefficient (R2 = 0.999) over the pH range of 5.55-7.41. The cells showed different degrees of ΔpHe after the IES with different intervals and stimulation potential. A shorter pulse interval and a higher stimulation potential could effectively enhance stimulation and increase cellular ΔpHe. At 0.5 V potential stimulation, the cellular ΔpHe increased with decreasing pulse interval. However, if the pulse interval was long enough, even at a higher potential of 0.7 V, there was no significant additional ΔpHe due to the insufficient stimulus strength. Based on the above conclusions, the prepared PANI microelectrode arrays (MEAs) were capable of stimulating and detecting single cells, which contributed to the deeper application of ES in tumor therapy.

Tribbles pseudokinase 3 promotes enterovirus A71 infection via dual mechanisms.

Enterovirus A71 (EV-A71) is the main pathogen causing hand, foot and mouth disease (HFMD) in children and occasionally associated with neurological diseases such as aseptic meningitis, brainstem encephalitis (BE) and acute flaccid paralysis. We report here that cellular pseudokinase tribbles 3 (TRIB3) facilitates the infection of EV-A71 via dual mechanisms. In one hand, TRIB3 maintains the metabolic stability of scavenger receptor class B member 2 (SCARB2), the bona fide receptor of EV-A71, to enhance the infectious entry and spreading of the virus. On the other hand, TRIB3 facilitates the replication of EV-A71 RNA in a SCARB2-independent manner. The critical role of TRIB3 in EV-A71 infection and pathogenesis was further demonstrated in vivo in mice. In comparison to wild-type C57BL/6 mice, EV-A71 infection in TRIB3 knockdown mice (Trib3+/-) resulted in significantly lower viral loads in muscular tissues and reduced lethality and severity of clinical scores and tissue pathology. In addition, TRIB3 also promoted the replication of coxsackievirus B3 (CVB3) and coxsackievirus A16 (CVA16) in vitro. In conclusion, our results suggest that TRIB3 is one of key host cellular proteins required for the infection and pathogenesis of EV-A71 and some other human enteroviruses and may thus be a potential therapeutic target for combating the infection of those viruses.