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Abstract The NOD2 signaling pathway, which plays an important role in the mechanisms of inflammatory bowel disease (IBD) development, has been closely associated with ubiquitination. It was revealed in this study that NOD2 receptor activation could obviously affect the expression of 19 ubiquitination-related genes, with N4BP3 being the most prominently expressed and upregulated. In addition, N4BP3 knockdown was found to reduce the mRNA levels of MDP-induced inflammatory factors, while N4BP3 overexpression elevated their mRNA levels as well as the levels of phospho-ERK1/2, phospho-JNK, phospho-P38 and phospho-NF-κB P65 proteins. Immunoprecipitation tests showed that N4BP3 could pull down RIPK2 and promote its K63-linked ubiquitination. In human tissue specimen assays and mouse experiments, we found that the expression of N4BP3 was significantly elevated in Crohn’s disease (CD) patients and IBD mice, and N4BP3 knockdown reduced the dextran sulfate sodium-induced pathological score and the expression of inflammatory factors in the mouse colon tissue. In conclusion, N4BP3 is able to interact with RIPK2 and promote its K63-linked ubiquitination, to further promote the NOD2-MAPK/NF-κB pathway, thereby increasing promoting the release of inflammation factors and the degree of IBD inflammation.

Abstract Purpose To investigate whether the body composition parameters can be employed as potential biomarkers for predicting the progression risk of chronic kidney disease (CKD). Materials and methods Four hundred sixteen patients diagnosed with CKD were included in this retrospective study. Patients with a greater than 50% decline in estimated glomerular filtration rate or progression to end-stage kidney disease were in the high-risk group, otherwise, they were in a low-risk group. Body composition area, the index, and radiodensities in the Hounsfield unit (HU), which reflect the degree of X-ray absorption, were measured on abdominal CT images. Risk factors in body composition and clinical parameters of CKD were identified by Cox regression and utilized to construct the nomogram. The performance of the nomogram was assessed using time receiver operating characteristics curves, calibration curves, and decision curve analysis. Results There were 254 patients in low-risk group and 162 in high-risk group (268 males, 148 females, mean age: 55.89 years). Urea, diabetes, 24 h-urinary protein, mean arterial pressure, and subcutaneous adipose tissue radiodensity (SATd) were valuable indicators for predicting the high-risk group. The area under curve values for the nomogram of training/validation set at 1 year, 2 years, and 3 years were 0.805/0.753, 0.784/0.783, and 0.846/0.754, respectively. For diabetic CKD patients, extra attention needs to be paid to visceral to subcutaneous fat ratio and renal sinus fat radiodensity. Conclusion SATd was the most valuable noninvasive indicator of all body composition parameters for predicting high-risk populations with CKD. The nomogram we constructed has generalization with easily obtainable indicators, good performance, differentiation, and clinical practicability. Critical relevance statement Radiodensity rather than an area of adipose tissue can be used as a new biomarker of prognosis for CKD patients, providing new insights into risk assessment, stratified management, and treatment for CKD patients. Key Points Obesity is an independent risk factor for the development and prognosis of CKD. Adipose tissue radiodensity is more valuable than fat area in prognosticating for kidney disease. Parameters that prognosticate in diabetic CKD patients are different from those in other CKD patients. Graphical Abstract

ObjectiveTo analyze the host factors affecting the drug resistance of Helicobacter pylori (Hp).MethodsPatients with Hp infection were consecutively recruited in the Affiliated Suzhou Hospital of Nanjing Medical University from November 2021 to October 2023. Endoscopic biopsy specimens were collected for pathological diagnosis, Hp strain culture and antimicrobial susceptibility test. Nineteen factors involving the basic information, lifestyle, dietary habits, and health status of the patients were collected through electronic medical records and questionnaires. Logistic regression was used to evaluate the association between the patients' factors and drug resistance to clarithromycin, levofloxacin, amoxicillin, furazolidone, tetracycline and metronidazole.ResultsA total of 115 patients (Hp strain 115) with Hp infection who met the inclusion and exclusion criteria were enrolled. There were 53 males (46.09%) and 62 females (53.91%), with an average age of (45.16±13.39) years. Gastroscopic pathology showed 86 cases (74.78%) of superficial gastritis, 6 cases (5.22%) of atrophic gastritis, 14 cases (12.17%) of intestinal metaplasia, 6 cases (5.22%) of low-grade intraepithelial neoplasia, and 3 cases (2.61%) of high-grade intraepithelial neoplasia/gastric cancer. The drug resistance rates of Hp strains to metronidazole, levofloxacin and clarithromycin were 91.30% (105/115), 53.04% (61/115) and 51.30% (59/115), respectively. Resistance to amoxicillin, furazolidone and tetracycline was not found. Dual drug resistance: levofloxacin + metronidazole dual resistance rate was 50.43% (58/115), clarithromycin + metronidazole dual resistance rate was 47.83% (55/115), clarithromycin + levofloxacin dual resistance rate was 36.52% (42/115). Multidrug resistance: clarithromycin + levofloxacin + metronidazole triple resistance rate was 34.78% (40/115). Multivariate Logistic regression analysis showed that (metronidazole was not included in the multivariate analysis due to the absence of sensitive strains), previous Hp eradication history (OR=74.782, 95% CI: 10.377-538.886, P < 0.001) and tap water (OR=4.919, 95% CI: 1.160-20.859, P=0.031) increased the risk of clarithromycin resistance, and age ≥50 years increased the risk of levofloxacin resistance (OR=4.261, 95% CI: 1.420-12.785, P=0.010), previous Hp eradication history (OR=5.855, 95% CI: 2.209-15.517, P < 0.001), 40-59 years old (OR= 3.269, 95% CI: 1.254-8.520, P=0.015) increased the risk of dual resistance to clarithromycin and levofloxacin.ConclusionsThe drug resistance rate of Hp strains isolated from patients in the Affiliated Suzhou Hospital of Nanjing Medical University to metronidazole, levofloxacin and clarithromycin were high, and dual drug resistance and multidrug resistance were prominent. Age, previous Hp eradication history and drinking water source may be associated with single or dual drug resistance to clarithromycin and levofloxacin. Comprehensive consideration, reasonable selection of antibiotics and individualized treatment should be taken into account during Hp eradication.

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on the targeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how to implement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections; 2) How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drug delivery microrobots have shown great application prospect in oral drug delivery due to their characteristics of flexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobots developed in recent years and divides them into four categories according to different driving modes: magnetic-controlled drug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobots and biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such as materials science, mechanical engineering, medicine, and control systems, this paper begins by introducing the gastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typical materials involved in the design process of oral drug delivery microrobots. To enhance readers' understanding of the working principles and design process of oral drug delivery microrobots, we present a guideline for designing such microrobots. Furthermore, the current development status of various types of oral drug delivery microrobots is reviewed, summarizing their respective advantages and limitations. Finally, considering the significant concerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translation for various oral drug delivery microrobots presented in this paper, providing corresponding suggestions for addressing some existing challenges.

Laser cladding is an advanced surface engineering technology capable of producing Ni-based coatings with high wear resistance. Incorporating graphene (Gr) into Ni-based coatings has great potential for improving the tribological properties of component surface. To date, the effects of Ni-decorated Gr (Ni@Gr) content on the tribological properties of Ni@Gr/Ni-based composite coatings and their surface wear mechanism have yet to be fully understood. In this study, Ni@Gr/Ni-based composite coatings with varying Ni@Gr contents (0, 2, 4, and 6 wt%) were prepared by laser cladding, and the effects of different Ni@Gr contents on the microstructure and tribological properties were investigated in detail. The results showed that the incorporation of Ni@Gr resulted in significant grain refinement and enhanced dislocations, along with an increase in carbide content. The smallest grain size (2.88 μm) and highest hardness (1039.3 HV0.2) were observed in the Ni@Gr/Ni-based composite coating with 4 wt% Ni@Gr. Simultaneously, the coefficient of the friction (COF) and the wear volume of the coating reach the minimum values of 0.3221 and 2.0123 × 10−2 mm−3, representing a 15.44% and 36.29% reduction compared to the pure Ni-based alloy coating, respectively. Based on the observed results, the wear mechanism of Ni@Gr/Ni-based composite coatings was analyzed and revealed. The high wear resistance of the coating is attributed to the optimal mechanical properties resulting from grain refinement and dislocation strengthening, as well as the uniformly distributed Ni@Gr with easily sheared layered structures that generate a lubricating film, effectively reducing the contact area between the coating and the grinding ball while resisting friction loads. This study could provide a deep understanding of the wear mechanism of Gr-doped surface coatings, contributing to the advancement of this field.

ABSTRACT Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). CP-COV03 is a novel antiviral candidate that significantly enhanced the bioavailability of niclosamide through inorganic-based drug delivery technology. The active pharmaceutical ingredient of CP-COV03, niclosamide, has been previously shown to possess broad-spectrum antiviral activity against over 30 different viruses in the in vitro tests. The aim of this study is to confirm the antiviral activity of CP-COV03 against the SFTSV in an in vitro model. Vero cells and SFTS viral stock NCCP43270, a 2015 Gangwon Province isolate, were used to obtain the 50% tissue culture infective dose of the virus. Vero cells seeded in 96-well plates were infected with SFTSV for 1 h. SFTSV-infected cells were treated with CP-COV03 at various concentrations of 0.1–100 μM and incubated for 7 days. On the seventh day of the culture, the cytopathic effect (CPE) of SFTSV was checked by microscopy and the cell viability was checked by using Cell Counting Kit-8 assay. The CPE reduced as the CP-COV03 concentration increased. The 50% inhibitory concentration (IC50) range of CP-COV03 was below 0.125 µM, as determined from the viral titers of culture supernatants collected on the third day posttreatment of CP-COV03. The plaque reduction assay showed that the IC50 of CP-COV03 was 1.893 µM, as determined from the percentage reduction of plaque counts for each drug concentration on the second day posttreatment with CP-COV03. This study suggests that CP-COV03 could be used as a potential antiviral agent for SFTS.IMPORTANCEWe demonstrated a concentration-dependent response and identified low a IC50 of CP-COV03. This result is comparable to other antiviral drugs used against viruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that our study makes a significant contribution to the literature as our findings suggest that CP-COV03 may serve as a potential treatment for SFTS, highlighting its importance in the field of antiviral research.

Scrub root systems play a crucial role in preventing soil erosion and nutrient loss. However, the effects of the root system configuration on soil nutrient dynamics and microbial changes at various evolutionary stages remain poorly understood. In this study, we investigated the relationship between soil physical and chemical properties and the diversity of bacteria and fungi throughout the evolutionary stages of the scrub root systems. This was achieved through a combination of whole-root excavation and root tracing techniques. The results indicated that root diameter was the main factor contributing to the continuous increase in carbon (C): phosphorus (P) and nitrogen (N): P ratios as the scrub sand pile developed. The soil organic carbon (SOC), total soil nitrogen (TN), and total soil phosphorus (TP) contents in the soil in the four evolutionary stages were the highest during the developmental stage, but the change in TP content was not statistically significant (P > 0.05). Partial least squares path modeling and redundancy analysis (RDA) indicated that root system stoichiometric C and N contents were positively correlated with microbial diversity (R2 = 0.85). There was no correlation between the evolutionary stage and soil nutrient TN, whereas soil nutrient TN was negatively correlated with microbial diversity (R2 = −0.92). These findings elucidate the relationship between the evolutionary stage of root chemical measurement characteristics, soil elements and microorganisms, and their subsequent effects on root elemental composition and microbial diversity. This study enhances the current understanding of plant–soil interactions in desert steppe ecosystems.

Diabetic liver injury (DLI) is a complication that impairs the quality of life of diabetic patients. Ginsenoside Rg1 is hepatoprotective, but its role and mechanism in diabetic liver injury need further investigation. Therefore, using in vivo experiments, we investigated the implication of ginsenoside Rg1 on hepatic lipid deposition, hepatic injury, hepatic fibrosis, and associated inflammation using a type 2 diabetes mellitus (T2DM) mouse model. We observed that Rg1 significantly ameliorated hepatic lipid deposition and hepatic fibrosis in T2DM mice. Meanwhile, Rg1 significantly reduced the expression of CD36, p-PLC, CaN, and NFAT2 and inhibited the activation of the NLRP3 inflammasome. Molecular docking results indicated that Rg1 binds well to PLC. In vitro experiments also demonstrated that Rg1 can inhibit calcium overload by regulating PA + HG-induced PLC activation in HepG2 cells. These results suggest that Rg1 treatment prevents T2DM-induced liver injury by inhibiting hepatic lipid deposition and the PLC-NFAT2-NLRP3 signaling pathway.

Automatically and accurately identifying the deformation zone of coastal slope landslides is crucial for exploring the mechanism of landslides and predicting landslide disasters. To this end, this study proposes an integrated automatic recognition method combining Image Clipping (IC), Image Information Enhancement (IE), Adaptive K-means Clustering Segmentation (AKS), and Optimization (O): IC-IE-AKS-O, which achieves precise extraction of the deformation area in coastal slope landslide images. Firstly, due to the more complex natural environment of field slopes, to extend the monitoring duration, we introduce a hierarchical operation algorithm based on the HSV color model, which effectively mitigates the impact of sunlight, rain, and foggy weather on image recognition accuracy. Secondly, this study proposes a 2D landslide image segmentation technique that combines K-means clustering with global threshold segmentation for landslide images, enabling the segmentation of small image regions with precision. Finally, we combine image information enhancement technology with image segmentation technology. To verify its effectiveness, we identify a landslide image of a coastal slope in Pingtan. The method displays an average relative error of 5.20% and 5.14% in the X and Y directions, respectively. Its advantages are threefold: (1) The combination of image information enhancement and segmentation techniques can more accurately identify landslide areas that appear blurred in the image; (2) expanding the temporal dimension of coastal slope monitoring; (3) providing excellent boundary conditions and segmentation results. The practical application of this method ensures the stable and accurate operation of the coastal slope monitoring system, providing a safeguard for the sustainable development of marine safety.

Abstract Right-sided infective endocarditis (RSIE) is less common than left-sided infective endocarditis (LSIE) and exhibits distinct epidemiological, clinical, and microbiological characteristics. Previous studies have focused primarily on RSIE in patients with intravenous drug use. We investigated the characteristics and risk factors for RSIE in an area where intravenous drug use is uncommon. A retrospective cohort study was conducted at a tertiary hospital in South Korea. Patients diagnosed with infective endocarditis between November 2005 and August 2017 were categorized into LSIE and RSIE groups. Of the 406 patients, 365 (89.9%) had LSIE and 41 (10.1%) had RSIE. The mortality rates were 31.7% in the RSIE group and 31.5% in the LSIE group (P = 0.860). Patients with RSIE had a higher prevalence of infection with Staphylococcus aureus (29.3% vs. 13.7%, P = 0.016), coagulase-negative staphylococci (17.1% vs. 6.0%, P = 0.022), and gram-negative bacilli other than HACEK (12.2% vs. 2.2%, P = 0.003). Younger age (adjusted odds ratio [aOR] 0.97, 95% confidence interval [CI] 0.95–0.99, P = 0.006), implanted cardiac devices (aOR 37.75, 95% CI 11.63–141.64, P ≤ 0.001), and central venous catheterization (aOR 4.25, 95% CI 1.14–15.55, P = 0.029) were independent risk factors for RSIE. Treatment strategies that consider the epidemiologic and microbiologic characteristics of RSIE are warranted.

Twins play a crucial role in elucidating the structure and deformation characteristics of materials. However, in materials with low-symmetry crystal structures, solving the twin relationships remains a challenging task. In this study, we propose a general method for determining twin elements K1, η1, K2, and η2, which are essential for twin analysis. The proposed method involves three main steps: (1) representing misorientation data measured by electron back-scattered diffraction (EBSD) and transmission electron microscopy (TEM) in matrix form, (2) identifying additional 180° rotation elements related to twin elements K1 or η1 by traversing all symmetrically equivalent misorientations, and (3) using a minimum and crystal structure-dependent uniform shear as the constraint to determine the other twin elements (K2andη2). By combining the experimental data and the proposed method, we systematically analyze the complex twin relationships of Cu–Zn–Al shape memory alloys (SMAs) with monoclinic martensite (M18R). This methodology has been demonstrated to be effective and possesses broad applicability.

Abstract Background Hospice care professionals often experience trauma patient deaths and multiple patient deaths in a short period of time (more so than other nurses). This repeated exposure to the death process and the death of patients leads to greater psychological pressure on hospice care professionals. But at present, people pay more attention to the feelings and care burden of the family members of dying patients but pay less attention to medical staff. Thus, this study aimed to develop a scale on the burden of care for hospice care providers and assess the coping capacity of hospice professionals. Raising awareness of the psychological burden of hospice professionals. Methods Through a literature review, research group discussion, Delphi method and a pre-survey of professional coping skills among nurses, 200 hospice professionals who had received training in hospice care from pilot institutions engaged in or providing hospice care were selected for investigation. Cronbach’s α coefficient and split-half reliability were used to test the internal consistency of the scale, and content validity and explore factor analysis (EFA) were used to test the construct validity of the scale. Results Two rounds of Delphi methods were carried out, and the effective recovery rate was 100%. The expert authority coefficients of the two rounds were 0.838 and 0.833, respectively. The Kendall’s W coefficient of experts in the first round was 0.121 ~ 0.200 (P 0.4, and the factor loading of each item was also > 0.4. Conclusion The scale is an open-access, short, easy-to-administer scale. And which for assessing hospice care burden among hospice professionals developed in this study demonstrated strong reliability and validity. This tool can serve as a dependable instrument for evaluating the burden of hospice care for terminally ill patients by professionals in the hospice setting.

In nature, co-evolution shaped balanced entities of host plants and their associated microorganism. Plants maintain this balance by detecting their associated microorganism and coordinating responses to them. Quorum sensing (QS) is a widespread bacterial cell-to-cell communication mechanism to modulate the collective behavior of bacteria. As a well-characterized QS signal, N-acyl homoserine lactones (AHL) also influence plant fitness. Plants need to coordinate their responses to diverse AHL molecules since they might host bacteria producing various AHL. This opinion paper discusses plants response to a mixture of multiple AHL molecules. The function of various phytohormones and WRKY transcription factors seems to be characteristic for plants’ response to multiple AHL. Additionally, the perspectives and possible approaches to facilitate further research and the application of AHL-producing bacteria are discussed.

ABSTRACTTo fully develop the medicinal and edible value of myrtle and improve the market visibility, myrtle berries and glutinous rice were used as raw materials and co-fermented using rice leaven. Uniform design method was used to determine the optimal fermentation conditions. The co-fermentation product was then underwent post-processing, including blending, grinding and homogenization, to produce a novel myrtle rice beverage, which was analyzed for product characteristics. Results showed that the optimal fermentation conditions were a myrtle berries of 24%, a rice leaven of 1%, a water addition amount of 100%, a fermentation temperature of 22°C, a fermentation time of 96 h. The co-fermented product was diluted 1:3 with water, ground, and homogenized with 0.1% agar and 0.2% xanthan gum to produce the final myrtle rice beverage. The beverage boasts a low sugar and alcohol content, along with a moderate level of acidity, making it a healthy beverage with antioxidant properties.

Abstract All‐solid‐state batteries equipped with solid‐state electrolytes (SSEs) have gained significant interest due to their enhanced safety, energy density, and longevity in comparison to traditional liquid organic electrolyte‐based batteries. However, many SSEs, such as sulfides and hydrides, are highly sensitive to water, limiting their practical use. As one class of important perovskites, the Ruddlesden–Popper perovskite oxides (RPPOs), show great promise as SSEs due to their exceptional stability, particularly in terms of water resistance. In this review, the crystal structure and synthesis methods of RPPOs SSEs are first introduced in brief. Subsequently, the mechanisms of ion transportation, including oxygen anions and lithium‐ions, and the relevant strategies for enhancing their ionic conductivity are described in detail. Additionally, the progress made in developing flexible RPPOs SSEs, which are critical for flexible and wearable electronic devices, has also been summarized. Furthermore, the key challenges and prospects for exploring and developing RPPOs SSEs in all‐solid‐state batteries are suggested. This review presents in detail the synthesis methods, the ion transportation mechanism, and strategies to enhance the room temperature ionic conductivity of RPPOs SSEs, providing valuable insights on enhancing their ionic conductivity and thus for their practical application in solid‐state batteries.

Abstract Although stem cell therapy holds promise for the treatment of spinal cord injury (SCI), its practical applications are limited by the low degree of neural differentiation. Electrical stimulation is one of the most effective ways to promote the differentiation of stem cells into neurons, but conventional wired electrical stimulation may cause secondary injuries, inflammation, pain, and infection. Here, based on the high conductivity of graphite and the electromagnetic induction effect, graphite nanosheets with neural stem cells (NSCs) are proposed as an electromagnetic cellularized patch to generate in situ wirelessly pulsed electric signals under a rotating magnetic field for regulating neuronal differentiation of NSCs to treat SCI. The strength and frequency of the induced voltage can be controlled by adjusting the rotation speed of the magnetic field. The generated pulsed electrical signals promote the differentiation of NSCs into functional mature neurons and increase the proportion of neurons from 12.5% to 33.7%. When implanted in the subarachnoid region of the injured spinal cord, the electromagnetic cellularized patch improves the behavioral performance of the hind limbs and the repair of spinal cord tissue in SCI mice. This work opens a new avenue for remote treatment of SCI and other nervous system diseases.

Capturing finer and discriminative difference features (DFs) is key to obtaining a high-quality change detection (CD) map. However, there is still significant scope for further study on fine-grained detection, especially concerning terms of improving structural integrity and reducing internal holes or sticking in DF. To this end, we propose a progressive difference amplification network (PDANet) with edge sensitivity to detect changed areas in optical remote sensing images (RSIs), where the key point is to amplify DF and reinforce edge detail to improve CD accuracy. The edge sensitivity (ES) encoder is designed to capture the long-distance dependency, which compensates for the limited receptive fields of the convolutional neural network with fixed kernels. Meanwhile, we introduce the prior edge in the network training stage, which collaborates with the ESE to improve the structural integrity of the changed areas. On the other hand, the difference amplification decoder is proposed to enhance the representation of the changed areas, and it is achieved by integrating multiscale DF and reconstructing the original single RSI using DF as full-stage guidance. Finally, the CD map and edge map are predicted based on the reconstructed feature and the maximum scale DF. Extensive experiments on one instance dataset and three CD benchmark datasets demonstrate that PDANet outperforms the state-of-the-art CD competitors both qualitatively and quantitatively.

This study aims to augment the impact of dialect-related cultural elements among adolescents, thereby facilitating a more effective inheritance and progression of Chinese dialect culture within the contemporary socio-cultural milieu.Firstly, based on the LSTM architecture, the bidirectional long short-term memory-conditional random field (BLSTM-CRF) model framework for dialect recognition was optimized and established. Subsequently, employing the BLSTM-CRF model for dialect recognition and the acquisition of dialectal voice samples, the natural language sequence input underwent conversion into word vectors or character vectors. The word vectors or character vectors were input into the BLSTM layer to obtain the hidden state vector corresponding to each position, representing the context information of that position. The hidden state vector was input into a fully connected layer, and the CRF layer was adopted to calculate and find the highest scoring label sequence as the final prediction result. Secondly, the FBM theoretical model was utilized to analyze the target user needs through user research methods. Finally, a design framework oriented by dialect recognition and user needs was constructed, and interactive product design was carried out. On the basis of BLSTM-CRF, the product design framework is improved to complete the interactive application design. Integrating user needs and Long Short-Term Memory (LSTM) algorithms into the design of dialect products, we explore ways to preserve and disseminate dialect culture among the younger generation. This provides new insights for the digital inheritance and development of dialects, and also serves as a reference for the design process of related cultural apps.

Abstract Background Plants can perceive bacterial molecules such as the quorum sensing signals N-acyl homoserine lactones (AHL), thus modifying their fitness in response to environmental factors. Even though the benefits conferred by AHL depend on various hormone signaling pathways, the understanding of AHL signaling, especially the response to AHL presence, remains largely unknown. Methods Weighted gene co-expression network analysis (WGCNA), multi-omics network analysis, and reverse transcription quantitative PCR (RT-qPCR) assays were used to identify key genes in AHL signaling. Results To obtain comprehensive insights on AHL signaling, we integrated available transcriptome data from Arabidopsis thaliana exposed to different single or multiple AHL molecules and performed a weighted gene co-expression network analysis. We identified several key genes regulated in plants exposed to multiple AHL molecules. Multi-omics network analysis and RT-qPCR assay revealed a potential role of WRKY transcription factors. Conclusions Results presented here offer good indications for exploring the mechanism of plants' response to bacterial signaling molecules, which could further support the application of AHL-producing bacteria in sustainable agriculture.

We synthesized a boron-doped reduced graphene oxide (BrGO) material characterized by various electrical properties, through simultaneous thermal reduction and doping procedures, using a metal–organic chemical vapor deposition technique. X-ray photoelectron spectroscopy (XPS) was used to study the impact of the doping level on the B bonding in the reduced graphene oxide (rGO) layer that is influenced by the annealing temperature. The synthesized BrGO layer demonstrated a high B concentration with a considerable number of O-B bonds, that were altered by annealing temperatures. This resulted in a decreased work function and the formation of a Schottky contact between the BrGO and n-type Si substrate. Due to the higher proportion of B-C and B-C3 bonding in the BrGO/Si device than that in the rGO/Si, the decreased Schottky barrier height of the BrGO/n-Si vertical junction photodetector resulted in a higher responsivity. This study showcases a promise of a simple B-doping method in use to alter the electrical characteristics of graphene materials.

In the in-situ leaching method of ionic rare earth, ion exchange reaction between rare earth ions and leaching agent ions is carried out, which allows the rare earth ions to be leached from the ore body as the leaching solution flows through the pores. This indicates that the leaching process of rare earth ions is closely related to the seepage field, ion exchange field, and ion migration process of the leaching solution. In this study, an ionic rare earth mine located in Longnan of Jiangxi Province was taken as the research object. By conducting nuclear magnetic resonance scanning on the ore samples of this mine and vectorizing the nuclear magnetic resonance images, a two-dimensional geometric model of pores was obtained. Then, COMSOL Multiphysics software was used to establish a coupled numerical model of seepage–exchange–migration of the ionic rare earth mine during the leaching process at the pore scale to study the seepage situation of leaching solution with different injection strengths and concentrations, as well as the exchange and migration process. The results show that increasing the concentration of magnesium ions can increase the difference of ion diffusion concentration, accelerate the forward exchange rate of ions, promote the forward exchange reaction, and improve the concentration gradient of rare earth ions in the leaching solution. The more significant the diffusion effect, the higher the ion migration rate, while at the same time inhibiting the reverse adsorption of rare earth ions, and accelerating the leaching efficiency of rare earth ions. In addition, increasing the strength of the injection solution allows rare earth ions to leach out of the ore body earlier, shortens the leaching cycle, and thus reduces the peak concentration of leached rare earth ions. By analyzing the effects of the strength of the injection solution and leaching concentration on ionic rare earth leaching, the influence of those two factors on engineering economy can be briefly evaluated, which can be provided as a reference for the optimization of ionic rare earth mining technology.

Summary: Mitochondrial dysfunction critically contributes to many major human diseases. The impact of specific gut microbial metabolites on mitochondrial functions of animals and the underlying mechanisms remain to be uncovered. Here, we report a profound role of bacterial peptidoglycan muropeptides in promoting mitochondrial functions in multiple mammalian models. Muropeptide addition to human intestinal epithelial cells (IECs) leads to increased oxidative respiration and ATP production and decreased oxidative stress. Strikingly, muropeptide treatment recovers mitochondrial structure and functions and inhibits several pathological phenotypes of fibroblast cells derived from patients with mitochondrial disease. In mice, muropeptides accumulate in mitochondria of IECs and promote small intestinal homeostasis and nutrient absorption by modulating energy metabolism. Muropeptides directly bind to ATP synthase, stabilize the complex, and promote its enzymatic activity in vitro, supporting the hypothesis that muropeptides promote mitochondria homeostasis at least in part by acting as ATP synthase agonists. This study reveals a potential treatment for human mitochondrial diseases.

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

Abstract Background Small renal mass (SRM) biopsy remains under-utilized due to stigma. Meanwhile, the alarmingly high benign findings in resected kidney masses highlight the need for improved preoperative diagnosis and patient selection. Methods The purpose of this study is to review the success rate of SRM biopsy and to evaluate its impact on patient management. A total of 168 percutaneous image-guided core needle biopsies (CNBs) of SRMs were retrieved at a tertiary academic center between 2015 and 2019. Subsequent treatment choices, side effects and outcomes were retrospectively reviewed. Results The diagnostic rate of CNB was 86.9%. Benign neoplasms accounted for a significant portion (14.3%) of SRM. Renal cell carcinomas (RCCs) were the most common diagnoses (69.6%) as expected. In biopsy-resection correlation, the positive predictive value of CNB was 100%. Tumor typing and subtyping by CNB were highly accurate, 100% and 98.3% respectively. Nuclear grading for clear cell RCC was accurate in 83.8% cases. The CNB results had significant impact on treatment. Most patients with RCCs underwent either resection (54.1%) or ablation (33.9%), in contrast to observation in benign neoplasms (90.5%). Most importantly, the benign resection rate (3.2%) in this series was much lower than the national average. Conclusion CNB provided accurate diagnoses for the majority of SRMs and revealed benign diagnoses in a subset of clinically suspicious lesions. Employment of CNB in suspicious SRM may help avoid overtreatment for benign lesions.

Abstract Background In nature, beneficial bacteria triggering induced systemic resistance (ISR) may protect plants from potential diseases, reducing yield losses caused by diverse pathogens. However, little is known about how the host plant initially responds to different beneficial bacteria. To reveal the impact of different bacteria on barley (Hordeum vulgare), bacterial colonization patterns, gene expression, and composition of seed endophytes were explored. Results This study used the soil-borne Ensifer meliloti, as well as Pantoea sp. and Pseudomonas sp. isolated from barley seeds, individually. The results demonstrated that those bacteria persisted in the rhizosphere but with different colonization patterns. Although root-leaf translocation was not observed, all three bacteria induced systemic resistance (ISR) against foliar fungal pathogens. Transcriptome analysis revealed that ion- and stress-related genes were regulated in plants that first encountered bacteria. Iron homeostasis and heat stress responses were involved in the response to E. meliloti and Pantoea sp., even if the iron content was not altered. Heat shock protein-encoding genes responded to inoculation with Pantoea sp. and Pseudomonas sp. Furthermore, bacterial inoculation affected the composition of seed endophytes. Investigation of the following generation indicated that the enhanced resistance was not heritable. Conclusions Here, using barley as a model, we highlighted different responses to three different beneficial bacteria as well as the influence of soil-borne Ensifer meliloti on the seed microbiome. In total, these results can help to understand the interaction between ISR-triggering bacteria and a crop plant, which is essential for the application of biological agents in sustainable agriculture.

Solid organ transplant (SOT) recipients are at significant risk of hepatitis B (HB) virus (HBV) reactivation (HBVr). Despite the clinical significance of HBVr after solid organ transplantation, data on the risk factors for HBVr and vaccine effectiveness in SOT recipients with resolved HBV infection are limited. This study evaluated the risk factors for HBVr and the seroconversion rates after HBV vaccination in SOT recipients. Patients who had undergone solid organ transplantation and those with a resolved HBV infection were identified. We matched patients who experienced post-transplantation HBVr with those who did not. We also explored the characteristics and seroconversion rates of HBV-vaccinated patients following transplantation. In total, 1299 SOT recipients were identified as having a resolved HBV infection at the time of transplantation. Thirty-nine patients experienced HBVr. Pre-transplant HB surface antibodies (anti-HBs) positivity and allograft rejection within 3 months after transplantation were independently associated with HBVr. Among the 17 HBV-vaccinated patients, 14 (82.4%) received three or fewer vaccine doses, and 13 (76.5%) had seroconversion with positive anti-HBs results. Pre-transplant anti-HBs(−) status and allograft rejection were risk factors for HBVr in SOT recipients with a resolved HBV infection, and HBV vaccination after transplantation resulted in a high rate of anti-HBs seroconversion. HBV vaccination after transplantation should be considered to reduce the HBVr risk.

The population of Caragana tibetica, situated on the edge of the typical grassland-to-desert transition in the Mu Us Sandy Land, plays a vital ecological role in maintaining stability within the regional fragile ecosystem. Despite the consistent growth of C. tibetica following animal grazing, the biological mechanisms underlying its compensatory growth in response to livestock consumption remain unclear. Analyzing 48 metabolomic profiles from C. tibetica, our study reveals that the grazing process induces significant changes in the metabolic pathways of C. tibetica branches. Differential metabolites show correlations with soluble protein content, catalase, peroxidase, superoxide dismutase, malondialdehyde, and proline levels. Moreover, machine learning models built on these differential metabolites accurately predict the intensity of C. tibetica grazing (with an accuracy of 83.3%). The content of various metabolites, indicative of plant stress responses, including Enterolactone, Narceine, and Folcepri, exhibits significant variations in response to varying grazing intensities (P

Background Type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) poses a serious health threat and becomes a new challenge. T2DM patients with CKD fall into three categories, diabetic nephropathy (DN), non-diabetic kidney disease (NDKD), and diabetic nephropathy plus non-diabetic kidney disease (DN + NDKD), according to kidney biopsy. The purpose of our study was to compare the clinical characteristics and kidney outcomes of DN, NDKD, and DN + NDKD patients. Methods Data on clinical characteristics, pathological findings, and prognosis were collected from June 2016 to July 2022 in patients with previously diagnosed T2DM and confirmed DN and or NDKD by kidney biopsy at Tongji Hospital in Wuhan, China. The endpoint was defined as kidney transplantation, dialysis, or a twofold increase in serum creatinine. Results In our 6-year retrospective cohort research, a total of 268 diabetic patients were admitted and categorized into three groups by kidney biopsy. The 268 patients were assigned to DN (n = 74), NDKD (n = 109), and DN + NDKD (n = 85) groups. The most frequent NDKD was membranous nephropathy (MN) (n = 45,41.28%). Hypertensive nephropathy was the most common subtype in the DN+NDKD group (n = 34,40%). A total of 34 patients (12.7%) reached the endpoint. The difference between the Kaplan-Meier survival curves of the DN, NDKD, and DN + NDKD groups was significant (p

Summary: Various synthetic substances were utilized in large quantities during the recent coronavirus pandemic, COVID-19. Some of these chemicals could potentially enter drinking water sources. Persistent, mobile, and toxic (PMT) substances have been recognized as a threat to drinking water resources. It has not yet been assessed how many COVID-19 related substances could be considered PMT substances. One reason is the lack of high-quality experimental data for the identification of PMT substances. To solve this problem, we applied a machine learning model to identify the PMT substances among COVID-19 related chemicals. The optimal model achieved an accuracy of 90.6% based on external test data. The model interpretation and causal inference indicated that our approach understood causation between PMT properties and molecular descriptors. Notably, the screening results showed that over 60% of the COVID-19 chemicals considered are candidate PMT substances, which should be prioritized to prevent undue pollution of water resources.

Far-infrared radiation is known as the ''light of life''. To investigate if it has positive effects on tomatoes and the proper location and time period of the far-infrared treatment. This study adopted tomato 'Taiji No.1′ as the plant material with 8 μm-14 μm far-infrared treatments. The results found that far-infrared radiation can significantly increase antioxidant capacity of senescent leaves. The proper location of the far-infrared lines was placed at the root and growth layer of the plant, which enhanced the net photosynthetic rate of plants by 44.01 % compared with the CK (no far-infrared treatment). It also promoted fruit ripening and increased the yield by 20.25 % compared with the CK. For the time period, far-infrared treatment during the periods of 6:00–9:00 am (gradual increase in photosynthesis) and 15:00–18:00 pm (gradual decrease in photosynthesis) (DT6) showed the optimum effect, which even surpassed 24 h and 16 h far-infrared treatments. The net photosynthetic rate of DT6 increased by 31.05 % compared with the CK (no far-infrared treatment). Among all the treatments, DT6 had the highest soluble sugar, fructose, and glucose contents. Among the common aroma compounds of tomato, sweet-related compounds were higher in the far-infrared treatment group than in the CK. DT6 treatment also had the highest yield and profit margin.

AbstractDiabetic kidney disease (DKD) is a severe complication of type 2 diabetes mellitus (T2DM). However, the pathogenesis of DKD remains unclear, and effective treatment strategies are still lacking. Ginsenoside Rg1 (Rg1) has been reported to improve DKD, but the mechanism is unclear. NADPH oxidase 4 (NOX4) is an essential reactive oxygen species (ROS) source in the kidney. The mitogen-activated protein kinase (MAPK) signaling may exacerbate renal fibrosis. Therefore, we hypothesized that Rg1 might alleviate renal injury and fibrosis by inhibiting NOX4 and MAPK signaling in T2DM-induced DKD. We found that Rg1 significantly improves lipid deposition, fibrosis, and ROS production and reduces NOX4, p22phox, p47phox, p-ERK, p-JNK, and p-P38 MAPK expressions in the T2DM mice kidneys. We also found that the high-fat diet treatment in mice and the palmitate (PA) and PA + HG (high glucose) exposure in human mesangial cells could significantly induce lipid deposition, ROS production, fibrosis, and the activation of NOX4–MAPK signaling. The results suggest that high lipid and glucose may play a significant role in DKD progression, while Rg1 may attenuate renal fibrosis by inhibiting NOX4–MAPK signaling.

Abstract Based on the author’s fieldwork in China and Japan, literature research and the study of specimen materials and video data on weddings of ROK, Japan and China, which are collected by the Japan National Museum of Ethnology (or Minpaku), this paper attempts to explore the cultural symbolic significance that humans bestow on food, and to further reveal the cultural diversity in East Asia and the common structure of human mind by comparing the flow of food and the ways and scopes in which the wedding foods are consumed in East Asia. In East Asia wedding customs, expectations through food for the bride’s fertility and her belonging to her husband’s patrilineal family are very common. However, the food and eating behaviors that express expectations for the groom are rare, only slightly visible in the dry bonito at the time of engagement in Japan and the 12 bowls of rice that the groom will eat on the day of the Yao wedding in China. Dried bonito signifies virility and victory of men, reflecting the features of Japanese maritime culture and the influence of samurai culture in history. East Asian wedding rituals are diverse in form, but the commonality among them can also be seen, that is, human beings find cultural meanings in different natural environments that correspond to human society, and then internalize the natural attributes through homophonic pun, imitation and other ways. Food is used in weddings to express people’s best wishes for the happiness of the newlyweds’ families, to have descendants and longevity of their marriage.

Irritable bowel syndrome (IBS) is a common digestive psychosomatic diseases, mainly manifested as recurrent abdominal pain and abnormal bowel movements. The intestinal dysfunction is often comorbidized with anxiety, depression and other emotional problems, resulting in increased intestinal burden and even a decrease in the quality of life. The etiology and pathogenesis of IBS are unclear, but it is currently believed that IBS involves abnormal gut-brain interaction caused by a combination of various factors, including visceral hypersensitivity, intestinal immune activation, intestinal infection, intestinal dysbacteriosis, and psychosocial stress. Recent studies have observed the disorders of gut microbiota-regulated kynurinaine metabolism in IBS patients, and found that the metabolite kynurenic acid (KA) has important correlations with inflammatory responses, pain stimuli and mood changes. KA may play a protective role in IBS such as anti-inflammatory and pain relief and thus has the potential to become a new approach for the diagnosis and treatment of IBS. In this work, studies related to KA and IBS are reviewed.

Visceral adiposity index (VAI) is a new metric for evaluating visceral adiposity dysfunction. The aim of the present study was to explore the association between VAI and incident chronic kidney disease (CKD) in the American elderly population. We included 6085 participants aged 60 years or older with available data on renal function and VAI from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 and divided them into four groups according to the VAI quartiles. VAI values were ln-transformed to reduce skewness. We conducted multivariable logistic regression analyses and spline smoothing plot analyses to evaluate the association between VAI and CKD. After fully adjusting for confounding factors, higher lnVAI was associated with a higher risk of CKD (OR, 1.23; 95 %CI, 1.02, 1.48). Compared to the Q1 group (VAI 3.0). The adjusted ORs (95% CI) in Q3 and Q4 were 1.74 (1.24, 2.42) and 1.59 (1.08, 2.33). Adjusted smoothed plots suggested a nonlinear relationship between lnVAI and CKD. The development of CKD increased with increasing VAI among participants with a lnVAI between −0.6 and 1.6 (VAI: 0.5–5.0). In conclusion, VAI is significantly associated with the risk of CKD in the US elderly population aged 60 years or older.

Salmonella enterica, a foodborne and human pathogen, is a constant threat to human health. Agricultural environments, for example, soil and plants, can be ecological niches and vectors for Salmonella transmission. Salmonella persistence in such environments increases the risk for consumers. Therefore, it is necessary to investigate the mechanisms used by Salmonella to adapt to agricultural environments. We assessed the adaptation strategy of S. enterica serovar Typhimurium strain 14028s to agricultural-relevant situations by analyzing the abundance of intermediates in glycolysis and the tricarboxylic acid pathway in tested environments (diluvial sand soil suspension and leaf-based media from tomato and lettuce), as well as in bacterial cells grown in such conditions. By reanalyzing the transcriptome data of Salmonella grown in those environments and using an independent RT-qPCR approach for verification, several genes were identified as important for persistence in root or leaf tissues, including the pyruvate dehydrogenase subunit E1 encoding gene aceE. In vivo persistence assay in tomato leaves confirmed the crucial role of aceE. A mutant in another tomato leaf persistence-related gene, aceB, encoding malate synthase A, displayed opposite persistence features. By comparing the metabolites and gene expression of the wild-type strain and its aceB mutant, fumarate accumulation was discovered as a potential way to replenish the effects of the aceB mutation. Our research interprets the mechanism of S. enterica adaptation to agriculture by adapting its carbon metabolism to the carbon sources available in the environment. These insights may assist in the development of strategies aimed at diminishing Salmonella persistence in food production systems.

Abstract Background Renal anemia is caused by end-stage renal disease (ESRD) but has a complex etiology. The application of dietary fiber (DF) to regulate the gut microbiota has shown effective therapeutic effects in some diseases, but its role in renal anemia is not clear. The aim of this study was to explore the effect of DF on renal anemia by regulating the gut microbiota and its metabolite, short-chain fatty acids (SCFAs). Methods A total of 162 ESRD patients were enrolled and randomly distributed into a DF or a control group (received oral DF or potato starch, 10 g/day for 8 weeks). Hemoglobin (Hb), serum iron (Fe2+), serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin and the dosage of recombinant human erythropoietin (rhEPO) before and after intervention in patients were analyzed. The gut microbiota and SCFAs in both groups were analyzed by 16S rDNA sequencing and gas chromatography–mass spectrometry, respectively. Spearman’s correlation test was used to analyze the correlation between the gut microbiota, SCFAs and the hematological indicators. Results Compared with the control group, (1) the patients in the DF group had higher Hb [117.0 (12.5) g/L vs. 94.0 (14.5) g/L, p

Abstract A broadband circularly polarized (CP) dipole antenna with a backed cavity is presented in this letter. The proposed antenna consists of a pair of rotational symmetric short‐circuited branches and a Γ‐shaped feed structure. Each branch is designed to be axe‐shaped so that the antenna can achieve a broad 3‐dB axial ratio (AR) bandwidth. The coupled feeding method assures the antenna is wideband, and the shorting‐to‐the‐ground technique miniaturizes the lateral dimensions of the antenna. The profile of the proposed antenna is around 0.16λL (λL denotes the wavelength of the lower bound frequency). The introduction of a back cavity effectively enhances the boresight gain and improves the isolation level if the antenna is used to form an array. Finally, the design is prototyped, and the measurement results agree well with the simulation. The fractal voltage standing wave ratio (VSWR)

ObjectiveTo characterize the cardiac phenotype associated with the novel pathogenic variant (c.1526del) of LMNA gene, which we identified in a large, six-generation family.Methods and ResultsA family tree was constructed. The clinical data of living and deceased family members were collected. DNA samples from 7 family members were analyzed for LMNA mutations using whole-exome high-throughput sequencing technology. The clinical presentation of pathogenic variant carriers was evaluated. In this six-generation family (n = 67), one member experienced sudden death at the age of 40-years-old. Three pathogenic variant carriers were identified to possess a novel heterozygous deletion mutation in LMNA gene (HGVS: NM_170707.4, c.1526del) located at exon 9 of LMNA chr1:156137145, which creates a premature translational stop signal (p.Pro509Leufs*39) in the LMNA gene and results in an mutant lamin A protein product. The main symptoms of the pathogenic variant carriers were palpitation, fatigue, and syncope, which typically occurred around 20-years-old. AV-conduction block and non-sustained ventricular tachycardia were the first signs of disease and would rapidly progress to atrial standstill around 30-years-old. Significant right atrial enlargement and bicuspid aortic valve malformation was also commonly seen in patients who carried this pathogenic variant.ConclusionThe pathogenic variant of c.1526del p.P509Lfs*39 was a frameshift deletion located at exon 9 of LMNA chr1:156137145 and causes severe right atrial enlargement, sick sinus syndrome, atrial standstill, ventricular tachycardia, and bicuspid aortic valve malformation. Our findings expand the phenotypic spectrum of novel LMNA gene mutations.

Plants may harbor the human pathogen Salmonella enterica. Interactions between S. enterica and different plant species have been studied in individual reports. However, disparities arising from the distinct experimental conditions may render a meaningful comparison very difficult. This study explored interaction patterns between different S. enterica strains including serovars Typhimurium 14028s and LT2 and serovar Senftenberg, and different plants (Arabidopsis, lettuce, and tomato) in one approach. Better persistence of S. enterica serovar Typhimurium strains was observed in all tested plants, whereas the resulting symptoms varied depending on plant species. Genes encoding pathogenesis-related proteins were upregulated in plants inoculated with Salmonella. Furthermore, transcriptome of tomato indicated dynamic responses to Salmonella, with strong and specific responses already 24 h after inoculation. By comparing with publicly accessible Arabidopsis and lettuce transcriptome results generated in a similar manner, constants and variables were displayed. Plants responded to Salmonella with metabolic and physiological adjustments, albeit with variability in reprogrammed orthologues. At the same time, Salmonella adapted to plant leaf-mimicking media with changes in biosynthesis of cellular components and adjusted metabolism. This study provides insights into the Salmonella-plant interaction, allowing for a direct comparison of responses and adaptations in both organisms.

The development of cathode materials with high specific capacity is the key to obtaining high-performance lithium-ion batteries, which are crucial for the efficient utilization of clean energy and the realization of carbon neutralization goals. Li-rich Mn-based cathode materials (LRM) exhibit high specific capacity because of both cationic and anionic redox activity and are expected to be developed and applied as cathode materials for a new generation of high-energy density lithium-ion batteries. Nevertheless, the difficulty of regulating anionic redox reactions poses significant challenges to LRM, such as low initial Coulombic efficiency, poor rate capability, and fast cycling capacity and voltage decay. To address the existing challenges of LRM, this review introduces their basic physicochemical characteristics in detail, analyzes the original causes of these challenges, focuses on the recent progress of the modification strategies, and then especially discusses the development prospects of LRM from different aspects.

Abstract Background Green-fleshed radish (Raphanus sativus L.) is an economically important root vegetable of the Brassicaceae family, and chlorophyll accumulates in its root tissues. It was reported that the basic helix-loop-helix (bHLH) transcription factors play vital roles in the process of chlorophyll metabolism. Nevertheless, a comprehensive study on the bHLH gene family has not been performed in Raphanus sativus L. Results In this study, a total of 213 Raphanus sativus L. bHLH (RsbHLH) genes were screened in the radish genome, which were grouped into 22 subfamilies. 204 RsbHLH genes were unevenly distributed on nine chromosomes, and nine RsbHLH genes were located on the scaffolds. Gene structure analysis showed that 25 RsbHLH genes were intron-less. Collineation analysis revealed the syntenic orthologous bHLH gene pairs between radish and Arabidopsis thaliana/Brassica rapa/Brassica oleracea. 162 RsbHLH genes were duplicated and retained from the whole genome duplication event, indicating that the whole genome duplication contributed to the expansion of the RsbHLH gene family. RNA-seq results revealed that RsbHLH genes had a variety of expression patterns at five development stages of green-fleshed radish and white-fleshed radish. In addition, the weighted gene co-expression network analysis confirmed four RsbHLH genes closely related to chlorophyll content. Conclusions A total of 213 RsbHLH genes were identified, and we systematically analyzed their gene structure, evolutionary and collineation relationships, conserved motifs, gene duplication, cis-regulatory elements and expression patterns. Finally, four bHLH genes closely involved in chlorophyll content were identified, which may be associated with the photosynthesis of the green-fleshed radish. The current study would provide valuable information for further functional exploration of RsbHLH genes, and facilitate clarifying the molecular mechanism underlying photosynthesis process in green-fleshed radish.

A series of stringent non-pharmacological and pharmacological interventions were implemented to contain the pandemic but the pandemic continues. Moreover, vaccination breakthrough infection and reinfection in convalescent coronavirus disease 2019 (COVID-19) cases have been reported. Further, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants emerged with mutations in spike (S) gene, the target of most current vaccines. Importantly, the mutations exhibit a trend of immune escape from the vaccination. Herein the scientific question that if the vaccination drives genetic or antigenic drifts of SARS-CoV-2 remains elusive. We performed correlation analyses to uncover the impacts of wide vaccination on epidemiological characteristics of COVID-19. In addition, we investigated the evolutionary dynamics and genetic diversity of SARS-CoV-2 under immune pressure by utilizing the Bayesian phylodynamic inferences and the lineage entropy calculation respectively. We found that vaccination coverage was negatively related to the infections, severe cases, and deaths of COVID-19 respectively. With the increasing vaccination coverage, the lineage diversity of SARS-CoV-2 dampened, but the rapid mutation rates of the S gene were identified, and the vaccination could be one of the explanations for driving mutations in S gene. Moreover, new epidemics resurged in several countries with high vaccination coverage, questioning their current pandemic control strategies. Hence, integrated vaccination and non-pharmacological interventions are critical to control the pandemic. Furthermore, novel vaccine preparation should enhance its capabilities to curb both disease severity and infection possibility.

Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults. However, the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment. Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer. The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma. In this study, a combination of hydrogel-liposome nanoplatform encapsulated with Temozolomide and ferroptosis inducer Erastin was constructed. The αvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy. As biocompatible drug reservoirs, cross-linked GelMA (gelatin methacrylamide) hydrogel and cRGD-coated liposome realized the sustained release of internal contents. In the modified intracranial tumor resection model, GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d. The results indicated that nanoplatform (T+E@LPs-cRGD+GelMA) improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects. It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance. Furthermore, transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform (T+E@LPs-cRGD+GelMA) implicated in. It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway. Collectively, this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.

Forage quality is a key property of grassland ecosystems. In this study, grassland forage qualities were measured at 373 sampling sites throughout Guizhou Province in the karst mountain region of Southwest China, and the factors affecting it were explored. The forage quality level of most plant species was categorized into four levels: (1) preferred forage species; (2) desirable forage species; (3) consumed but undesirable forage species; and (4) non-consumable or toxic forage species. High temperature and precipitation appeared to facilitate the growth of preferred forage species, but limited the growth of other plants. Increasing soil pH had a positive impact on the number and biomass of preferred forage plants, but a negative influence on other plants, especially non-consumable or toxic plants. Both GDP and population density had a positive correlation with the number and biomass of preferred forage species, while such correlations for other levels of forage species tended to be negative. Grazing could lead to a decrease in the preferred forage species. Therefore, it is suggested that by focusing on soil improvement in grassland and maintaining an appropriate grazing intensity, global warming and rapid economic growth in Guizhou Province will likely contribute to increase the forage quality of karst grasslands in Southwest China.

Puberty is a complex biological process of sexual development, influenced by genetic, metabolic-nutritional, environmental and socioeconomic factors, characterized by the development of secondary sexual characteristics, maturation of the gonads, leading to the acquisition of reproductive capacity. The onset of central precocious puberty (CPP) is mainly associated with the early activation of the hypothalamic–pituitary–gonadal (HPG) axis and increased secretion of gonadotropin-releasing hormone (GnRH), leading to increased pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and activation of gonadal function. Due to the expense and invasiveness of current diagnostic testing and drug therapies for CPP, it would be helpful to find serum and genetic markers to facilitate diagnosis. In this paper, we summarized the related factors that may affect the expression of GnRH1 gene and the secretion and action pathway of GnRH and related sex hormones, and found several potential targets, such as MKRN3, DLK1 and KISS1. Although, the specific mechanism still needs to be further studied, we would be encouraged if the insights from this review could provide new insights for future research and clinical diagnosis and treatment of CPP.

Coronary artery spasm (CAS) is characterized by reversible diffuse or focal vasoconstriction, a phenomenon that plays an important role in the pathogenesis of ischemic heart disease. Fatal arrhythmias, such as ventricular tachycardia/fibrillation and complete atrioventricular block (AV-B), are very common in patients with CAS. Nondihydropyridine calcium channel blockers (CCBs) such as diltiazem were recommended as first-line medications for treating and preventing CAS episodes. However, its use remains controversial in CAS patients with AV-B as this type of CCB can also cause AV-B itself. Here, we present the use of diltiazem in a patient with complete AV-B caused by CAS. The patient's chest pain was rapidly relieved, and complete AV-B was promptly restored to sinus rhythm following the administration of intravenous diltiazem without any adverse effects. In this report, we highlight the useful and effective application of diltiazem for treating and preventing complete AV-B caused by CAS.

Abstract Highly sensitive and reliable hydrogen detection is prerequisite for the large‐scale implementation of green energy hydrogen. It remains a tough challenge to get a highly selective H2 sensor to low concentration H2 gas with low working temperature. In this work, high performance flexible hydrogen sensor using ultrathin SnO2 film decorated by Pd nanoparticles (NPs) on polyimide (PI) was developed based on versatile atomic layer deposition (ALD) and cluster beam deposition (CBD). The influence of Pd NPs loading amount and operating temperature on the performance of hydrogen sensors was studied. The sensors obtain an extremely high response over 20000 to 30 ppm H2 at the relatively low operating temperature of 75–125 °C. The Pd NPs@SnO2/PI sensor achieves a wide detection range of 0.1‐5000 ppm with the limit of detection (LOD) of 100 ppb at 125 °C. A low LOD of 250 ppb can still be achieved at room temperature. The sensors also exhibit outstanding sensing selectivity for hydrogen over interfering gases and excellent mechanical resistance after 2000 bending cycles. The mechanism for improved sensing performance of ALD ultrathin film with CBD‐derived noble metal NPs decoration may be a feasible strategy for the construction of highly sensitive, selective, and flexible hydrogen sensors.

Summary: mRNA vaccines are effective in preventing severe COVID-19, but breakthrough infections, emerging variants, and waning immunity warrant the use of boosters. Although mRNA boosters are being implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of individuals primed with the mRNA-1273 or BNT162b2 vaccines, we report that lower antibody levels before boost are associated with higher fold-increase in antibody levels after boost, suggesting that pre-existing antibody modulates the immunogenicity of mRNA vaccines. Our studies in mice show that pre-existing antibodies accelerate the clearance of vaccine antigen via Fc-dependent mechanisms, limiting the amount of antigen available to prime B cell responses after mRNA boosters. These data demonstrate a “tug of war” between pre-existing antibody responses and de novo B cell responses following mRNA vaccination, and they suggest that transient downmodulation of antibody effector function may improve the efficacy of mRNA boosters.

Primary tumors “spread the spark” by establishing a pre-metastatic niche. Here the authors develop an in-situ assembled peptide FR17 to serve as a “flame-retarding blanket” to extinguish the “fire” of the pre-metastatic microenvironment.