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Abstract Quantum sensing has emerged as a powerful technique to detect and measure physical and chemical parameters with exceptional precision. One of the methods is to use optically active spin defects within solid-state materials. These defects act as sensors and have made significant progress in recent years, particularly in the realm of two-dimensional (2D) spin defects. In this article, we focus on the latest trends in quantum sensing that use spin defects in van der Waals (vdW) materials. We discuss the benefits of combining optically addressable spin defects with 2D vdW materials while highlighting the challenges and opportunities to use these defects. To make quantum sensing practical and applicable, the article identifies some areas worth further exploration. These include identifying spin defects with properties suitable for quantum sensing, generating quantum defects on demand with control of their spatial localization, understanding the impact of layer thickness and interface on quantum sensing, and integrating spin defects with photonic structures for new functionalities and higher emission rates. The article explores the potential applications of quantum sensing in several fields, such as superconductivity, ferromagnetism, 2D nanoelectronics, and biology. For instance, combining nanoscale microfluidic technology with nanopore and quantum sensing may lead to a new platform for DNA sequencing. As materials technology continues to evolve, and with the advancement of defect engineering techniques, 2D spin defects are expected to play a vital role in quantum sensing.

Abstract Atomic force microscope generally works by manipulating the absolute magnitude of the van der Waals force between tip and specimen. This force is, however, less sensitive to atom species than to tip-sample separations, making compositional identification difficult, even under multi-modal strategies or other atomic force microscopy variations. Here, we report the phenomenon of a light-modulated tip-sample van der Waals force whose magnitude is found to be material specific, which can be employed to discriminate heterogeneous compositions of materials. We thus establish a near-field microscopic method, named light-modulated van der Waals force microscopy. Experiments discriminating heterogeneous crystalline phases or compositions in typical materials demonstrate a high compositional resolving capability, represented by a 20 dB signal-to-noise ratio on a MoTe2 film under the excitation of a 633 nm laser of 1.2 mW, alongside a sub-10 nm lateral spatial resolution, smaller than the tip size of 20 nm. The simplicity of the light modulation mechanism, minute excitation light power, broadband excitation wavelength, and diversity of the applicable materials imply broad applications of this method on material characterization, particularly on two-dimensional materials that are promising candidates for next-generation chips.

Abstract Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

Abstract With a large number of film capacitors being deployed in critical locations in electrical and electronic systems, artificial intelligence (AI) technology is also expected to address the problems encountered in this process. According to our findings, AI applications can cover the entire lifecycle of film capacitors. However, the AI safety hazards in these applications have not received the attention they deserve. To meet this, the authors argue, with specific examples, risks that flawed, erratic, and unethical AI can introduce in the design, operation, and evaluation of film capacitors. Human‐AI common impact and more multi‐dimensional evaluation for AI are proposed to better cope with unknown, ambiguity, and known risks brought from AI in film capacitors now and in the future.

Salvia penghuana, a new species from Guizhou Province of southwestern China, is described and illustrated. Morphologically, Salvia penghuana is similar to S. filicifolia, but can be easily distinguished from the latter by ovate-lanceolate bracts, purple corolla, and foot-shaped fused lower arms of connective. In addition, S. penhuana is morphologically similar to S. cavaleriei, but differs by having 3–4-pinnate leave, ovate-lanceolate bracts, puberulent calyx, and longer upper arms of connective. Based on the fibril root, small calyx and corolla, and completely reduced posterior thecae, S. penghuana should be placed in section Sobiso of subg. Glutinaria.

AbstractOsteoarthritis (OA) is a degenerative disease closely associated with Anoikis. The objective of this work was to discover novel transcriptome-based anoikis-related biomarkers and pathways for OA progression.The microarray datasets GSE114007 and GSE89408 were downloaded using the Gene Expression Omnibus (GEO) database. A collection of genes linked to anoikis has been collected from the GeneCards database. The intersection genes of the differential anoikis-related genes (DEARGs) were identified using a Venn diagram. Infiltration analyses were used to identify and study the differentially expressed genes (DEGs). Anoikis clustering was used to identify the DEGs. By using gene clustering, two OA subgroups were formed using the DEGs. GSE152805 was used to analyse OA cartilage on a single cell level. 10 DEARGs were identified by lasso analysis, and two Anoikis subtypes were constructed. MEgreen module was found in disease WGCNA analysis, and MEturquoise module was most significant in gene clusters WGCNA. The XGB, SVM, RF, and GLM models identified five hub genes (CDH2, SHCBP1, SCG2, C10orf10, P FKFB3), and the diagnostic model built using these five genes performed well in the training and validation cohorts. analysing single-cell RNA sequencing data from GSE152805, including 25,852 cells of 6 OA cartilage.

Abstract Bone cancer pain (BCP) represents a prevalent symptom among cancer patients with bone metastases, yet its underlying mechanisms remain elusive. This study investigated the transcriptional regulation mechanism of Kv7(KCNQ)/M potassium channels in DRG neurons and its involvement in the development of BCP in rats. We show that HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes, which encode Kv7(KCNQ)/M potassium channels in dorsal root ganglion (DRG), contributes to the sensitization of DRG neurons and the pathogenesis of BCP in rats. Also, HDAC2 requires the formation of a corepressor complex with MeCP2 and Sin3A to execute transcriptional regulation of kcnq2/kcnq3 genes. Moreover, EREG is identified as an upstream signal molecule for HDAC2-mediated kcnq2/kcnq3 genes transcription repression. Activation of EREG/EGFR-ERK-Runx1 signaling, followed by the induction of HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes in DRG neurons, leads to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. Consequently, the activation of EREG/EGFR-ERK-Runx1 signaling, along with the subsequent transcriptional repression of kcnq2/kcnq3 genes by HDAC2 in DRG neurons, underlies the sensitization of DRG neurons and the pathogenesis of BCP in rats. These findings uncover a potentially targetable mechanism contributing to bone metastasis-associated pain in cancer patients.

Abstract The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K–L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA.

Abstract The emitter-cavity strong coupling manifests crucial significance for exploiting quantum technology, especially in the scale of individual emitters. However, due to the small light-matter interaction cross-section, the single emitter-cavity strong coupling has been limited by its harsh requirement on the quality factor of the cavity and the local density of optical states. Herein, we present a strategy termed waveguide-assisted energy quantum transfer (WEQT) to improve the single emitter-cavity coupling strength by extending the interaction cross-section. Multiple ancillary emitters are optically linked by a waveguide, providing an indirect coupling channel to transfer the energy quantum between target emitter and cavity. An enhancement factor of coupling strength $$\widetilde{g}/g > 10$$ g ̃ / g > 10 can be easily achieved, which dramatically release the rigorous design of cavity. As an extension of concept, we further show that the ancillae can be used as controlling bits for a photon gate, opening up new degrees of freedom in quantum manipulation.

Abstract Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.

Abstract Background Pruning is an important cultivation management option that has important effects on peach yield and quality. However, the effects of pruning on the overall genetic and metabolic changes in peach leaves and fruits are poorly understood. Results The transcriptomic and metabolomic profiles of leaves and fruits from trees subjected to pruning and unpruning treatments were measured. A total of 20,633 genes and 622 metabolites were detected. Compared with those in the control, 1,127 differentially expressed genes (DEGs) and 77 differentially expressed metabolites (DEMs) were identified in leaves from pruned and unpruned trees (pdLvsupdL), whereas 423 DEGs and 29 DEMs were identified in fruits from the pairwise comparison pdFvsupdF. The content of three auxin analogues was upregulated in the leaves of pruned trees, the content of all flavonoids detected in the leaves decreased, and the expression of almost all genes involved in the flavonoid biosynthesis pathway decreased. The phenolic acid and amino acid metabolites detected in fruits from pruned trees were downregulated, and all terpenoids were upregulated. The correlation analysis revealed that DEGs and DEMs in leaves were enriched in tryptophan metabolism, auxin signal transduction, and flavonoid biosynthesis. DEGs and DEMs in fruits were enriched in flavonoid and phenylpropanoid biosynthesis, as well as L-glutamic acid biosynthesis. Conclusions Pruning has different effects on the leaves and fruits of peach trees, affecting mainly the secondary metabolism and hormone signalling pathways in leaves and amino acid biosynthesis in fruits.

Abstract Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan–Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan–Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P

Abstract Background Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage destruction and inflammation. CC chemokine receptor 1 (CCR1), a member of the chemokine family and its receptor family, plays a role in the autoimmune response. The impact of BX471, a specific small molecule inhibitor of CCR1, on CCR1 expression in cartilage and its effects on OA remain underexplored. Methods This study used immunohistochemistry (IHC) to assess CCR1 expression in IL-1β-induced mouse chondrocytes and a medial meniscus mouse model of destabilization of the medial meniscus (DMM). Chondrocytes treated with varying concentrations of BX471 for 24 h were subjected to IL-1β (10 ng/ml) treatment. The levels of the aging-related genes P16INK4a and P21CIP1 were analyzed via western blotting, and senescence-associated β-galactosidase (SA-β-gal) activity was measured. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan (AGG), and the transcription factor SOX9 were determined through western blotting and RT‒qPCR. Collagen II, matrix metalloproteinase 13 (MMP13), and peroxisome proliferator-activated receptor (PPAR)-γ expression was analyzed via western blot, RT‒qPCR, and immunofluorescence. The impact of BX471 on inflammatory metabolism-related proteins under PPAR-γ inhibition conditions (using GW-9662) was examined through western blotting. The expression of MAPK signaling pathway-related molecules was assessed through western blotting. In vivo, various concentrations of BX471 or an equivalent medium were injected into DMM model joints. Cartilage destruction was evaluated through Safranin O/Fast green and hematoxylin–eosin (H&E) staining. Results This study revealed that inhibiting CCR1 mitigates IL-1β-induced aging, downregulates the expression of iNOS, COX-2, and MMP13, and alleviates the IL-1β-induced decrease in anabolic indices. Mechanistically, the MAPK signaling pathway and PPAR-γ may be involved in inhibiting the protective effect of CCR1 on chondrocytes. In vivo, BX471 protected cartilage in a DMM model. Conclusion This study demonstrated the expression of CCR1 in chondrocytes. Inhibiting CCR1 reduced the inflammatory response, alleviated cartilage aging, and retarded degeneration through the MAPK signaling pathway and PPAR-γ, suggesting its potential therapeutic value for OA. Graphical Abstract

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

Reducing the oral bioavailability of metal contaminants including As, Cd, and Pb in foods can protect human health. Studies showed reduced metal bioavailability with elevated Ca and Fe intake; however, the effectiveness of enhancing food Ca and Fe bioavailability remains unknown. Based on a mouse bioassay and using metal accumulation in mouse tissues (kidneys and liver) as the bioavailability endpoint, this study investigated the roles of casein phosphopeptides (CPP, food nutrition fortifier) in lowering the As, Cd, and Pb bioavailability from consuming a metal-contaminated wheat. The CPP amendment at 0.10–0.50% in wheat promoted its Ca bioavailability, causing 33–62% and 59–80% decreases in the gene expression encoding for duodenal Ca and phosphate transporters in mice. This limited transcellular transport of Cd2+ and inorganic arsenate via Ca and phosphate transporters respectively, thus leading to 27% and 34% decreases in Cd and As contents in mouse kidneys fed with wheat at 0.50% CPP amendment. In addition, CPP promoted the colonization of Feacalibaculum and Bifidobacterium in mouse gut, likely promoting As excretion in feces by 81–112%. In contrast to As and Cd, CPP failed to reduce Pb contents in mouse tissue after consuming CPP-amended wheat, probably by elevating wheat-Pb solubility in the intestinal fluid by 48–136%. However, co-amendment of 0.30% CPP and 500 ​μg ​g−1 Ca as Ca gluconate lowered the As, Cd, and Pb contents in mouse kidneys by 38–71%. The data indicate that fortifying Ca together with CPP in wheat can reduce human exposure to multi-metals via dietary intake.

Purpose Develop an albumin nanoparticle-based nanoprobe for targeted glioblastoma (GBM) diagnosis and treatment, utilizing Angopep-2 for low-density lipoprotein receptor-related protein (LRP) targeting. Methods Combined albumin-coated superparamagnetic iron oxide (SPIO), Carmustine (BCNU), and indocyanine green (ICG). Assessed morphology, size, Zeta potential, fluorescence, and drug encapsulation. Conducted in vitro fluorescence/MRI imaging and cell viability assays, and in vivo nanoprobe accumulation evaluation in brain tumors. Results ANG-BSA/BCNU/ICG MNPs exhibited superior targeting and cytotoxicity against GBM cells in vitro. In vivo, enhanced brain tumor accumulation during imaging was observed. Conclusion This targeted imaging and drug delivery system holds promise for efficient GBM therapy and intraoperative localization, addressing Blood-brain barrier (BBB) limitations with precise drug delivery and imaging capabilities.

Total knee arthroplasty (TKA) is an effective treatment for end-stage knee joint diseases. The debate over preserving or sacrificing the posterior cruciate ligament (PCL) in mobile-bearing TKA (MB TKA) still needs to be solved due to the lack of high-quality evidence, particularly meta-analyses comparing these techniques. This study aims to conduct a meta-analysis to compare the outcomes of PCL retention (CR) and PCL sacrifice (PS) in terms of clinical and functional knee scores, range of motion, complication rates, and revision rates and to validate these findings through animal experiments. A comprehensive search was conducted using MEDLINE, Cochrane, and Embase databases. Relevant studies were selected for the meta-analysis using RevMan 5.3. Additionally, an animal experiment using Sprague-Dawley rats simulated MB TKA to compare the effects of PCL retention and sacrifice surgeries. 12 studies were included in the meta-analysis. No significant differences were found between CR and PS techniques regarding HSS, KSS, KSFS, WOMAC, ROM, and medial/lateral instability. However, CR MB showed slight superiority in NKJS, while PS MB had better outcomes in complication and revision rates. In the animal study, CR rats exhibited significant early postoperative inflammation, but both groups’ knee structures gradually normalized. The meta-analysis indicates that PCL retention (CR MB) and sacrifice (PS MB) have similar effects on various clinical and functional knee scores. However, PS MB is significantly better at reducing complications and revision rates. The animal experiment confirms PS MB’s advantages in reducing inflammation and promoting joint recovery. Despite the strong evidence, long-term follow-up and larger-scale randomized controlled trials are necessary to confirm these findings.

Objective: This study aimed to assess the efficacy of a modified exhaust method in pediatric open-heart surgery involving cardiopulmonary bypass. Method: Data from 303 cases conducted at the Department of Cardiac Surgery, Guizhou Hospital, Shanghai Children's Medical Center, between October 2023 and March 2024 were analyzed. Among these cases, 202 utilized the modified exhaust method, divided into group A (101 cases with median thoracotomy) and group C (101 cases with lateral thoracotomy), while 101 cases used the traditional exhaust method in group B (median thoracotomy). Comparative analysis included general patient data, cardiopulmonary bypass duration, aortic cross-clamp time, time for exhaust and reperfusion upon opening, post-reperfusion ST segment abnormalities on electrocardiogram, intracardiac pneumogram observations via esophageal ultrasound, relevant plasma biochemical indexes on postoperative day one, postoperative drainage volume, duration of ventilator use, and length of stay in the intensive care unit (ICU). Results: There was no difference in between-group comparisons regarding age (27.98 ± 3.57 vs. 34.05 ± 3.96 months; P = 0.401) and weight (12.23 ± 0.55vs. 12.59 ± 0.70 Kg; P = 0.563). Longer Cardiopulmonary bypass times were observed in patients undergoing median thoracotomy than those undergoing lateral thoracotomy (group B: 108.47 ± 2.30 min vs. group C: 117.03 ± 2.82 min, P = 0.002; group A: 108.91 ± 2.63 min vs. group C: 117.03 ± 2.82 min, P = 0.035). Exhaust and rebound times after opening were significantly shorter in the modified exhaust-method group compared with the traditional-method group (Group A: 52.62 ± 1.39 s vs. Group B: 65.20 ± 1.49 s, P 0.05). Conclusions: The modified exhaust method demonstrates overall good immediate results in pediatric congenital heart surgery. It was superior to the traditional exhaust method in terms of reducing exhaust times and potentially minimizing the risk of local aortic injuries. Additionally, it appeared to be suitable for lateral thoracotomy surgery.

Deep learning models have made great accomplishments in space weather forecasting. The critical frequency of the ionospheric F2 layer (foF2) is a key ionospheric parameter, which can be understood and predicted by some advanced new deep learning technologies. In this paper, we utilized an Informer architecture model to predict foF2 for several hours up to 48 h and analyzed its variations during periods of quiet, moderate, and intense geomagnetic conditions. The Informer method forecasts the temporal variations of foF2 by processing and training the past and present foF2 data from the Haikou station, China, during 2006–2014. It is evident that the Informer–foF2 model achieves better prediction performance than the widely used long short-term memory model. The Informer–foF2 model captures the correlation features within the foF2 time series and better predicts the variations ranging for hours up to days during different geomagnetic activities.

Abstract Crystallization is a fundamental phenomenon which describes how the atomic building blocks such as atoms and molecules are arranged into ordered or quasi-ordered structure and form solid-state materials. While numerous studies have focused on the nucleation behavior, the precise and spatiotemporal control of growth kinetics, which dictates the defect density, the micromorphology, as well as the properties of the grown materials, remains elusive so far. Herein, we propose an optical strategy, termed optofluidic crystallithography (OCL), to solve this fundamental problem. Taking halide perovskites as an example, we use a laser beam to manipulate the molecular motion in the native precursor environment and create inhomogeneous spatial distribution of the molecular species. Harnessing the coordinated effect of laser-controlled local supersaturation and interfacial energy, we precisely steer the ionic reaction at the growth interface and directly print arbitrary single crystals of halide perovskites of high surface quality, crystallinity, and uniformity at a high printing speed of 102 μm s−1. The OCL technique can be potentially extended to the fabrication of single-crystal structures beyond halide perovskites, once crystallization can be triggered under the laser-directed local supersaturation.

Abstract Pixel‐level labeling of regions of interest in an image is a key step in building a labeled training dataset for supervised deep learning networks of images. However, traditional manual labeling of cancerous regions in digital pathological images by doctors is time‐consuming and inefficient. To address this issue, this paper proposes an automatic labeling method for whole slide images, which combines clustering and edge detection techniques. The proposed method utilizes the multi‐level feature fusion model and the Long‐Short Term Memory network to discriminate the cancerous nature of the whole slide images, thereby improving the classification accuracy of the whole slide images. Subsequently, the automatic labeling of cancerous regions is achieved by integrating a density‐based clustering algorithm and an edge point extraction algorithm, both based on the discriminated results of the cancerous properties of whole slide images. The experimental results demonstrate the effectiveness of the proposed method, which offers an efficient and accurate solution to the challenging task of cancerous region labeling in digital pathological images.

The warm flow characteristics and microstructural evolution features in a solution-treated 7075 aluminum alloy are revealed. An elastic-visco-plastic constitutive model is developed to capture the flow stress behavior of 7075 aluminum alloy under warm deformation. The variations of microstructure features, including grain and subgrain size, are also analyzed under warm deformation, and are further incorporated in the proposed unified constitutive model. The results indicate that the dynamic recovery (DRV), related to dislocation annihilation and formation/growth of sub-grains, is the domain softening mechanism. The DRV behavior is enhanced at higher temperatures or lower strain rates. Warm external temperature field assists the plastic deformation by means of activating and accelerating the dynamic softening, while the reduced strain rate also gives sufficient time for the softening. Through experimental validation, the proposed constitutive model successfully captures the grain/subgrain features and flow behavior of the studied 7075 aluminum alloy during warm deformation. The predicted result is in a great agreement with the experimental stress-strain data, demonstrating the excellent predictive performance of the model. Moreover, the proposed model also successfully predicts the average grain/subgrain size.

Abstract Background Gestational diabetes mellitus (GDM) is a common complication of pregnancy, with significant short-term and long-term implications for both mothers and their offspring. Previous studies have indicated the potential benefits of vitamin D in reducing the risk of GDM, yet little is known about this association in twin pregnancies. This study aimed to investigate maternal vitamin D status in the second trimester and examine its association with the risk of GDM in twin pregnancies. Methods We conducted a prospective cohort study based on data from the Chongqing Longitudinal Twin Study (LoTiS). Peripheral blood serum was collected from the mothers in the second trimester to measure 25(OH)D concentrations. GDM was diagnosed at 23–26 weeks of gestation using a 75-g 2-h oral glucose tolerance test. We used multivariable logistic regression analyses to examine the correlations between vitamin D status and the risk of GDM. Results Of the total participants, 93 (29.9%) women were diagnosed with GDM. The mean serum 25(OH)D concentration in the second trimester was 31.1 ± 11.2 ng/mL, and the rate of vitamin D insufficiency and deficiency were 23.5% and 18.7%, respectively. Compared to women with a 25(OH)D concentration

Abstract Background Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. Methods Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1 −/− ) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. Results In vivo, Itln-1 −/− mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. Conclusion The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.

Abstract Opportunistic spectrum access (OSA), a promising technology to resolve radio spectrum scarcity, is still faced with some challenges, of which one is potentially frequent channel handoff (CH) even handoff blocking (HB) for secondary user (SU) to avoid primary user (PU). Reaccess is a direct way to resolve HB. However, multiple handoff blocking‐then‐reaccess (H‐BTR) are time consuming. Whether it is worthwhile to make multiple H‐BTR, is an interesting but hardly mentioned issue. To this end, the multiple H‐BTR‐based OSA are focused on here. Three key indices, the average transmission probability, handoff delay, and average reaccess times of SU in the H‐BTR‐based OSA, are deduced as close form first. Then, the effects of H‐BTR frequency and service traffic rate of SU on OSA are discussed. Finally, the H‐BTR‐based OSA is compared to two other schemes, the handoff without BTR (HWBTR)‐based OSA and the stop‐and‐waiting (SW)‐based OSA. Theoretical and simulated results show that the H‐BTR‐based OSA performs best among three schemes. Making H‐BTR in moderate frequency according to service traffic rate can increase transmission opportunity while additional delay of SU is tolerable, thus the performance of OSA can be well improved.

Abstract Background The prevalence of macrolide-resistant Mycoplasma pneumoniae has increased considerably. Treatment in children has become challenging. This study aimed to evaluate the efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods. Methods We retrospectively analyzed the data of patients with macrolide-resistant Mycoplasma pneumoniae pneumonia hospitalized between May 2019 to August 2022. According to treatment, patients were divided into three groups: oral doxycycline treatment alone (DOX group), changed from intravenous azithromycin to oral doxycycline (ATD group), and intravenous azithromycin treatment alone (AZI group). ATD group cases were separated into two sub-groups: intravenous azithromycin treatment

AIM: To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty (SLAK) with corneal crosslinking (CXL) on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo. The lenticules were collected from patients undertaking small incision lenticule extraction (SMILE) for the correction of myopia. Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength. RESULTS: All surgeries were conducted successfully with no significant complications. Their best corrected visual acuity (BCVA) ranged from 0.05 to 0.8-2 before surgery. The pre-operational total corneal thickness ranged from 345-404 μm and maximum keratometry (Kmax) ranged from 50.8 to 86.3. After the combination surgery, both the corneal keratometry (range 55.9 to 92.8) and total corneal thickness (range 413-482 μm) significantly increased. Four out of 5 patients had improvement of corneal biomechanical parameters (reflected by stiffness parameter A1 in Corvis ST). However, 3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze. Despite the onset of corneal edema right after SLAK, the corneal topography and thickness generally stabilized after 3mo. CONCLUSION: SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia. Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.

Vehicle Routing Problem with Uncertain Demands (VRPUD) is one of the research hotspots in the field of logistics scheduling. In this paper, a Discrete Jaya (DJaya) algorithm is presented for the VRPUD to minimize the total cost. A novel dividing-point-based coding scheme is designed to represent solutions with higher robustness. In addition, an efficient repair strategy is embedded into the decoding process to avoid the failure of producing feasible solutions. The best and worst solutions are employed to generate offspring solutions in DJaya. Several efficient local search methods are also presented to enhance the exploitation ability and increase the diversity of solutions. Based on the benchmark data sets of the VRPUD, numerical simulations are carried out for the proposed DJaya algorithm with uncertain demands. Computational results and comparisons with the state-of-the-art algorithms demonstrate the superiority of the proposed algorithm in solving VRPUD.

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes severe inflammatory response, respiratory disease and sow reproductive failure. Quercetin is among the widely occurring polypheno found abundantly in nature. Quercetin has anti‐inflammatory, anti‐oxidative and anti‐viral properties. Objectives This study aimed to explore the effect and mechanism of quercetin on PRRSV‐induced inflammation in MARC‐145 cells. Methods Observing the cytopathic effect and measurements of inflammatory markers in MARC‐145 cells collectively demonstrate that quercetin elicits a curative effect on PRRSV‐induced inflammation. Liquid chromatography–mass spectrometry was further used for a non‐targeted metabolic analysis of the role of quercetin in the metabolic regulation of PRRSV inflammation in MARC‐145 cells. Results It was shown that quercetin attenuated PRRSV‐induced cytopathy in MARC‐145 cells. Quercetin treatment inhibited PRRSV replication in MARC‐145 cells in a dose‐dependent manner. We also found that quercetin inhibited PRRSV‐induced mRNA expression and secretion levels of tumour necrosis factor‐α, interleukin 1β and interleukin 6. Metabolomics analysis revealed that quercetin ameliorated PRRSV‐induced inflammation. Pathway analysis results revealed that PRRSV‐induced pathways including arachidonic acid metabolism, linoleic acid, glycerophospholipid and alanine, aspartate and glutamate metabolism were suppressed by quercetin. Moreover, we confirmed that quercetin inhibited the activation of NF‐κB/p65 pathway, probably by attenuating PLA2, ALOX and COX mRNA expression. Conclusions These results provide a crucial insight into the molecular mechanism of quercetin in alleviating PRRSV‐induced inflammation.

BackgroundPathogens can impact host RNA modification machinery to establish a favorable cellular environment for their replication. In the present study, we investigated the effect of Toxoplasma gondii infection on host RNA modification profiles and explored how these modifications may influence the host-parasite interaction.Methodology/principal findingsWe analyzed the modification levels of ∼ 80 nt tRNA and 17-50 nt sncRNAs in mouse liver, spleen, and serum using liquid chromatography and tandem mass spectrometry analysis. The results revealed alterations in RNA modification profiles, particularly during acute infection. The liver exhibited more differentially abundant RNA modifications than the spleen. RNA modification levels in serum were mostly downregulated during acute infection compared to control mice. Correlations were detected between different RNA modifications in the liver and spleen during infection and between several RNA modifications and many cytokines. Alterations in RNA modifications affected tRNA stability and protein translation.Conclusions/significanceThese findings provide new insight into the role of RNA modifications in mediating the murine host response to T. gondii infection.

Abstract Although zinc‒air batteries (ZABs) are regarded as one of the most prospective energy storage devices, their practical application has been restricted by poor air electrode performance. Herein, we developed a free‐standing air electrode that is fabricated on the basis of a multifunctional three‐dimensional interconnected graphene network. Specifically, a three‐dimensional interconnected graphene network with fast mass and electron transport ability, prepared by catalyzing growth of graphene foam on nickel foam and then filling reduced graphene oxide into the pores of graphene foam, is used to anchor iron phthalocyanine molecules with atomic Fe‒N4 sites for boosting the oxygen reduction during discharging and nanosized FeNi hydroxides for accelerating the oxygen evolution during charging. As a result, the obtained air electrode exhibited an ultra‐small electrocatalytic overpotential of 0.603 V for oxygen reactions, a high peak power density of 220.2 mW cm‒2, and a small and stable charge‒discharge voltage gap of 0.70 V at 10 mA cm‒2 after 1136 cycles. Furthermore, in situ Raman spectroscopy together with theoretical calculations confirmed that phase transformation of FeNi hydroxides takes place from α‐Ni(OH)x to β‐Ni(OH)x to γ‐Ni(3+δ)+OOH for the oxygen evolution reaction and Ni is the active center while Fe enhances the activity of Ni active sites.

Pueraria lobata, commonly known as kudzu, is a medicinal and food plant widely used in the food, health food, and pharmaceutical industries. It has clinical pharmacological effects, including hypoglycemic, antiinflammatory, and antioxidant effects. However, its mechanism of hypoglycemic effect on type 2 diabetes mellitus (T2DM) has not yet been elucidated. In this study, we prepared a Pueraria lobata oral liquid (POL) and conducted a comparative study in a T2DM rat model to evaluate the hypoglycemic effect of different doses of Pueraria lobata oral liquid. Our objective was to investigate the hypoglycemic effect of Puerarin on T2DM rats and understand its mechanism from the perspective of metabolomics. In this study, we assessed the hypoglycemic effect of POL through measurements of FBG, fasting glucose tolerance test, plasma lipids, and liver injury levels. Furthermore, we examined the mechanism of action of POL using hepatic metabolomics. The study's findings demonstrated that POL intervention led to improvements in weight loss, blood glucose, insulin, and lipid levels in T2DM rats, while also providing a protective effect on the liver. Finally, POL significantly affected the types and amounts of hepatic metabolites enriched in metabolic pathways, providing an important basis for revealing the molecular mechanism of Pueraria lobata intervention in T2DM rats. These findings indicate that POL may regulate insulin levels, reduce liver damage, and improve metabolic uptake in the liver. This provides direction for new applications and research on Pueraria lobata to prevent or improve T2DM.

Reliable communication and intensive computing power cannot be provided effectively by temporary hot spots in disaster areas and complex terrain ground infrastructure. Mitigating this has greatly developed the application and integration of UAV and Mobile Edge Computing (MEC) to the Internet of Things (IoT). However, problems such as multi-user and huge data flow in large areas, which contradict the reality that a single UAV is constrained by limited computing power, still exist. Due to allowing UAV collaboration to accomplish complex tasks, cooperative task offloading between multiple UAVs must meet the interdependence of tasks and realize parallel processing, which reduces the computing power consumption and endurance pressure of terminals. Considering the computing requirements of the user terminal, delay constraint of a computing task, energy constraint, and safe distance of UAV, we constructed a UAV-Assisted cooperative offloading energy efficiency system for mobile edge computing to minimize user terminal energy consumption. However, the resulting optimization problem is originally nonconvex and thus, difficult to solve optimally. To tackle this problem, we developed an energy efficiency optimization algorithm using Block Coordinate Descent (BCD) that decomposes the problem into three convex subproblems. Furthermore, we jointly optimized the number of local computing tasks, number of computing offloaded tasks, trajectories of UAV, and offloading matching relationship between multi-UAVs and multiuser terminals. Simulation results show that the proposed approach is suitable for different channel conditions and significantly saves the user terminal energy consumption compared with other benchmark schemes.

Abstract Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Abstract We construct rotating hybrid axion-miniboson stars (RHABSs), which are asymptotically flat, stationary, axially symmetric solutions of (3+1)-dimensional Einstein–Klein–Gordon theory. RHABSs consist of an axion field (ground state) and a free complex scalar field (first excited state). The solutions of RHABSs have two types of nodes, including $$^1S^2S$$ 1 S 2 S state and $$^1S^2P$$ 1 S 2 P state. For different axion decay constants $$f_a$$ f a , we present the mass M of RHABSs as a function of the synchronized frequency, as well as the nonsynchronized frequency, and explore the mass M versus the angular momentum J for the synchronized frequency and the nonsynchronized frequency, respectively. Furthermore, we study the effect of axion decay constant $$f_a$$ f a and free scalar field mass $$\mu _f$$ μ f on the existence domain of the synchronized frequency $$\omega $$ ω .

Abstract Background Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk. Methods A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique. Results Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37–0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16–0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35–0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42–0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05–1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P

AIM: To describe the clinical, electrophysiological, and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity, anterior segment and dilated fundus, visual field, spectral-domain optical coherence tomography (OCT) and electroretinogram (ERG). The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result. Then we reviewed the characteristics of the patients reported with the same variant. RESULTS: A 30-year male presented with severe early retinal degeneration who complained night blindness, decreased visual acuity, vitreous floaters and amaurosis fugax. The best corrected vision was 0.04 OD and 0.12 OS, respectively. The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye. Autofluorescence shows bilateral symmetrical hypo-autofluorescence. ERG revealed that the amplitudes of a- and b-wave were severely decreased. Multifocal ERG showed decreased amplitudes in the local macular area. A homozygous missense variant c.146C>T (chr14:68191267) was found. The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied. CONCLUSION: An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported. The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.

Abstract Atomic and close-to-atom scale manufacturing is a promising avenue toward single-photon emitters, single-electron transistors, single-atom memory, and quantum-bit devices for future communication, computation, and sensing applications. Laser manufacturing is outstanding to this end for ease of beam manipulation, batch production, and no requirement for photomasks. It is, however, suffering from optical diffraction limits. Herein, we report a spatial resolution improved to the quantum limit by exploiting a threshold tracing and lock-in method, whereby the two-order gap between atomic point defect complexes and optical diffraction limit is surpassed, and a feature size of

Background & Aims: Hepatic ischemia-reperfusion injury (HIRI) often occurs in liver surgery, such as partial hepatectomy and liver transplantation, in which myeloid macrophage-mediated inflammation plays a critical role. Cell division cycle 42 (Cdc42) regulates cell migration, cytoskeleton rearrangement, and cell polarity. In this study, we explore the role of myeloid Cdc42 in HIRI. Methods: Mouse HIRI models were established with 1-hour ischemia followed by 12-hour reperfusion in myeloid Cdc42 knockout (Cdc42mye) and Cdc42flox mice. Myeloid-derived macrophages were traced with RosamTmG fluorescent reporter under LyzCre-mediated excision. The experiments for serum or hepatic enzymic activities, histologic and immunologic analysis, gene expressions, flow cytometry analysis, and cytokine antibody array were performed. Results: Myeloid deletion of Cdc42 significantly alleviated hepatic damages with the reduction of hepatic necrosis and inflammation, and reserved hepatic functions following HIRI in mice. Myeloid Cdc42 deficiency suppressed the infiltration of myeloid macrophages, reduced the secretion of proinflammatory cytokines, restrained M1 polarization, and promoted M2 polarization of myeloid macrophages in livers. In addition, inactivation of Cdc42 promoted M2 polarization via suppressing the phosphorylation of STAT1 and promoting phosphorylation of STAT3 and STAT6 in myeloid macrophages. Furthermore, pretreatment with Cdc42 inhibitor, ML141, also protected mice from hepatic ischemia-reperfusion injury. Conclusions: Inhibition or deletion of myeloid Cdc42 protects liver from HIRI via restraining the infiltration of myeloid macrophages, suppressing proinflammatory response, and promoting M2 polarization in macrophages.

The liver plays an important role in regulating lipid metabolism in animals. This study investigated the function and mechanism of lncLLM in liver lipid metabolism in hens at the peak of egg production. The effect of lncLLM on intracellular lipid content in LMH cells was evaluated by qPCR, Oil Red O staining, and detection of triglyceride (TG) and cholesterol (TC) content. The interaction between lncLLM and MYH9 was confirmed by RNA purification chromatin fractionation (CHIRP) and RNA immunoprecipitation (RIP) analysis. The results showed that lncLLM increased the intracellular content of TG and TC and promoted the expression of genes related to lipid synthesis. It was further found that lncLLM had a negative regulatory effect on the expression level of MYH9 protein in LMH cells. The intracellular TG and TC content of MYH9 knockdown cells increased, and the expression of genes related to lipid decomposition was significantly reduced. In addition, this study confirmed that the role of lncLLM is at least partly through mediating the ubiquitination of MYH9 protein to accelerate the degradation of MYH9 protein. This discovery provides a new molecular target for improving egg-laying performance in hens and treating fatty liver disease in humans.

Sanghuangprous vaninii is a medicinal macrofungus cultivated extensively in China. Both the mycelia and fruiting bodies of S. vaninii have remarkable therapeutic properties, but it remains unclear whether the mycelia may serve as a substitute for the fruiting bodies. Furthermore, S. vaninii is a perennial fungus with therapeutic components that vary significantly depending on the growing year of the fruiting bodies. Hence, it is critical to select an appropriate harvest stage for S. vaninii fruiting bodies for a specific purpose. With the aid of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), metabolomics based on ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS) was used to preliminarily determine 81 key active metabolites and 157 active pharmaceutical metabolites in S. vaninii responsible for resistance to the six major diseases. To evaluate the substitutability of the mycelia and fruiting bodies of S. vaninii and to select an appropriate harvest stage for the fruiting bodies of S. vaninii, we analyzed the metabolite differences, especially active metabolite differences, among the mycelia and fruiting bodies during three different harvest stages (1-year-old, 2-year-old, and 3-year-old). Moreover, we also determined the most prominent and crucial metabolites in each sample of S. vaninii. These results suggested that the mycelia show promise as a substitute for the fruiting bodies of S. vaninii and that extending the growth year does not necessarily lead to higher accumulation levels of active metabolites in the S. vaninii fruiting bodies. This study provided a theoretical basis for developing and using S. vaninii.

BackgroundHemorrhagic fever with renal syndrome (HFRS) is a natural epidemic disease that can be caused by the Hantaan virus (HTNV). Malaria is caused by plasmodium and can be transmitted by a mosquito bite. The similar manifestations shared by these disorders pose a challenge for clinicians in differential diagnosis, in particular, coupled with a false-positive serological test.Case presentationA 46-year-old man was admitted for fever and chills for over 10 days and was suspected of being co-infected with HFRS and malaria due to a history of travel to malaria-endemic areas and a positive HTNV-immunoglobulin M (IgM) test. Although leukocytosis, thrombocytopenia, renal injury, lymphocytosis, overexpression of interleukin-6, and procalcitonin were observed during the hospitalization, the hypotensive, oliguria, and polyuria phases of the HFRS course were not observed. Instead, typical symptoms of malaria were found, including a progressive decrease in erythrocytes and hemoglobin levels with signs of anemia. Furthermore, because the patient had no history of exposure to HFRS endemic areas, exposure to an HTNV-infected rodent, or a positive HTNV-IgG test, and false serological tests of IgM can be caused by various factors, the HFRS coinfection with malaria was ruled out.ConclusionMisdiagnosis can be easily induced by a false serological test, in particular the IgM test which can be influenced by various factors. A combination of health history, epidemiology, physical examination, precise application of specific examinations involving tests of conventional laboratory parameters as well as well-accepted methods such as the immunochromatographic (ICG) test, real-time reverse transcription-polymerase chain reaction (PCR), and Western blot (WB), and acquaintance with disorders with similar manifestations will contribute to the precise diagnosis in clinical treatment.

Quickly localizing the identified white dwarf (WD) binaries is the basic requirement for the space-based gravitational wave (GW) detection. In fact, the amplitude of GW signals are modulated by the periodic motion of GW detectors on the solar orbit. The intensity of the observed signals is enhanced according to the observation time beyond a year to enhance a high signal to noise ratio (SNR). As data gap exists, the completeness of the data observed for a long time depends on filling gaps in the data. Actually, in a year period, the GW sources have a best observation orbit position of GW detectors, where the intensity of GW is maximum. Thus, the best positions can be searched for the verified GW sources of the sky map to enhance SNR too, which avoids filling data gaps. For the three arms response intensity of the GW signals changing more clearly with the location of the GW sources relative to the detector, the noises and the suppression of noise by time delay interferometer are ignored. As a verification case, the four WD binaries are chosen, whose best observation orbit positions of the GW detectors are related to the direction of WD binaries perpendicular to the detection arms. The two verification binaries: J0806 and V407 Vul are observed at the best orbit positions by TAIJI for the short time of 2 and 3 days respectively. The corresponding intensities of GWs are above the values of the TAIJI sensitivity curve, significantly. Location parameter estimation of the verification WD binaries are performed using the Metropolis–Hastings MCMC method. The confidence level of the parameters obtained in the best position is significantly several times higher than that in the worst position where the direction of WD binaries are almost parallel to the detection arms. Compared with a single detector, the network of two detectors improve slightly the accuracy of location of the verification binaries. These results imply that the searching of GW signals and parameter estimation of GW sources from the experimental data of the space-based mission do not ignore the orbit positions relevant to GW sources.

ABSTRACT: Understanding the characteristics of bacteriophages is crucial for the optimization of phage therapy. In this study, the biological and genomic characteristics of coliphage LHE83 were determined and its synergistic effects with different types of antibiotics against E. coli E82 were investigated. Phage LHE83 displayed a contractile tail morphology and had a titer of 3.02 × 109 pfu/mL at an optimal MOI of 0.01. Meanwhile, phage LHE83 exhibited good physical and chemical factors tolerance. The 1-step growth analysis revealed a latent period of approx. 10 min with a burst size of 87 pfu/infected cell. Phage LHE83 belongs to the genus Dhakavirus. Its genome consists of 170,464 bp with a 40% GC content, and a total of 268 Open Reading Frames (ORF) were predicted with no detected virulent or resistant genes. ORF 213 was predicted to encode the receptor binding protein (RBP) and confirmed by the antibody-blocking assay. Furthermore, a phage-resistant strain E. coli E82R was generated by co-culturing phage LHE83 with E. coli E82. Genomic analysis revealed that OmpA served as the receptor for phage LHE83, which was further confirmed by phage adsorption assay using E. coli BL21ΔOmpA, E. coli BL21ΔOmpA: OmpA and E. coli BL21:OmpA strains. Additionally, a synergistic effect was observed between phage LHE83 and spectinomycin against the drug-resistant strain E. coli E82. These results provide a theoretical basis for understanding the interactions between phages, antibiotics, and host bacteria, which can assist in the clinical application of phages and antibiotics against drug-resistant bacteria.

The widespread use of copper and tetracycline as growth promoters in the breeding industry poses a potential threat to environmental health. Nevertheless, to the best of our knowledge, the potential adverse effects of copper and tetracycline on the gut microbiota remain unknown. Herein, mice were fed different concentrations of copper and/or tetracycline for 6 weeks to simulate real life–like exposure in the breeding industry. Following the exposure, antibiotic resistance genes (ARGs), potential pathogens, and other pathogenic factors were analyzed in mouse feces. The co-exposure of copper with tetracycline significantly increased the abundance of ARGs and enriched more potential pathogens in the gut of the co-treated mice. Copper and/or tetracycline exposure increased the abundance of bacteria carrying either ARGs, metal resistance genes, or virulence factors, contributing to the widespread dissemination of potentially harmful genes posing a severe risk to public health. Our study provides insights into the effects of copper and tetracycline exposure on the gut resistome and potential pathogens, and our findings can help reduce the risks associated with antibiotic resistance under the One Health framework.

Background: Coinfection poses a persistent threat to global public health due to its severe effect on individual-level infection risk and disease outcome. Coinfection of SARS-CoV2 with one or more pathogens has been documented. Nevertheless, this virus co-infected with the Hantaan virus (HTNV) is rarely reported. Case summary: Here, we presented three cases of HTNV complicated with SARS-CoV2 infection. Not only the conditions including general clinical manifestations, immune and inflammation parameters fluctuation presented in the single infection of HTNV or SARS-CoV2 can be found, but also the unexpected manifestations have attracted our attention that presented as more symptoms of HTNV infection including exudative changes in both lungs and an amount of bilateral pleural effusion as well as bilateral kidney enlargement rather than typical viral pneumonia in SARS-CoV2 infection. Fortunately, the conditions of patients gradually return to normal which is beneficial from the antiviral treatment, hemodialysis, and various supportive therapies including anti-inflammation, liver and gastric mucosa protection. Conclusion: Unexpected manifestations of coinfection patients present herein may be associated with multiple factors including virus load, competition or antagonism among antigens, and the susceptibility of target cells to the various pathogens, even though the pathogenesis of HTNV and SARS-CoV2 remains to be elucidated. Given that these two viruses have posed a profound influence on the socioeconomic, healthcare system worldwide, and the threat of coinfection to public health, it is warranted for clinicians, public health authorities, and infectious disease researchers to have a high index of consideration for patients co-infected with HTNV and SARS-CoV2.

Abstract The Myodural Bridge (MDB) is a physiological structure that is highly conserved in mammals and many of other tetrapods. It connects the suboccipital muscles to the cervical spinal dura mater (SDM) and transmits the tensile forces generated by the suboccipital muscles to the SDM. Consequently, the MDB has broader physiological potentials than just fixing the SDM. It has been proposed that MDB significantly contributes to the dynamics of cerebrospinal fluid (CSF) movements. Animal models of suboccipital muscle atrophy and hyperplasia were established utilizing local injection of BTX-A and ACE-031. In contrast, animal models with surgical severance of suboccipital muscles, and without any surgical operation were set as two types of negative control groups. CSF secretion and reabsorption rates were then measured for subsequent analysis. Our findings demonstrated a significant increase in CSF secretion rate in rats with the hyperplasia model, while there was a significant decrease in rats with the atrophy and severance groups. We observed an increase in CSF reabsorption rate in both the atrophy and hyperplasia groups, but no significant change was observed in the severance group. Additionally, our immunohistochemistry results revealed no significant change in the protein level of six selected choroid plexus-CSF-related proteins among all these groups. Therefore, it was indicated that alteration of MDB-transmitted tensile force resulted in changes of CSF secretion and reabsorption rates, suggesting the potential role that MDB may play during CSF circulation. This provides a unique research insight into CSF dynamics.

Abstract Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet β-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes.

Abstract The internet of things accelerates the wireless connections of massive devices to provide all kinds of new services, and thus intensifies the spectrum scarcity and access delay. Cognitive radio (CR) technology brings a solution for the issue. As a typical CR scheme, opportunistic spectrum access (OSA) has been addressed widely in the past decade. However, the tradeoff between two key indexes, the throughput of cognitive radio network (CRN) and the delay of secondary user (SU), is rarely mentioned so far, which ignites the authors’ work in this paper. Taking into account a channel handoff (CH) based multi‐channel OSA scenario, the authors first analyze the opportunistic transmission performance of SU, and model the throughput of CRN as well as the handoff delay of SU. Then, the authors build up a delay‐constraint throughput optimization problem, and thus formulate the throughput‐delay tradeoff for OSA. Finally, the optimal traffic rates of SU for a good throughput‐delay tradeoff are derived according to maximizing the throughput of CRN. Theoretical and simulated results show that to enhance the throughput and to reduce the delay do not conflict always. By well adjusting the traffic rates of SU according to the traffic rates of primary user, the throughput of CRN can be improved while the handoff delay can be kept under a given level.