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Abstract Myocardial infarction (MI) has a 5-year mortality rate of more than 50% due to the lack of effective treatments. Interactions between cardiomyocytes and the MI microenvironment (MIM) can determine the progression and fate of infarcted myocardial tissue. Here, a specially designed Melanin-based composite nanomedicines (MCN) is developed to effectively treat MI by reprogramming the MIM. MCN is a nanocomposite composed of polydopamine (P), Prussian blue (PB) and cerium oxide (CexOy) with a Mayuan-like structure, which reprogramming the MIM by the efficient conversion of detrimental substances (H+, reactive oxygen species, and hypoxia) into beneficial status (O2 and H2O). In coronary artery ligation and ischemia reperfusion models of male mice, intravenously injecting MCN specifically targets the damaged area, resulting in restoration of cardiac function. With its promising therapeutic effects, MCN constitutes a new agent for MI treatment and demonstrates potential for clinical application.

Abstract Background An increasing number of clinical studies have begun to explore combination strategies with immune checkpoint inhibitors, aiming to present new opportunities for overcoming anti-PD-1 treatment resistance in gastric cancer. Unfortunately, the exploration of certain immune checkpoint inhibitor combination strategies has yielded suboptimal results. Therefore, it is necessary to comprehensively analyze the expression patterns of immune checkpoints and identify optimal combination regimens of anti-PD-1 inhibitors with other immune checkpoint inhibitors. Methods Leveraging single-cell RNA sequencing (scRNA-seq) and multivariate linear regression interaction models, we dissected the immune checkpoint expression characteristics of CD8+ T cells in gastric cancer and the immune checkpoint expression pattern (ICEP) mediating anti-PD-1 treatment resistance. Furthermore, we employed transcription factor analysis and CellOracle to explore the transcriptional regulatory mechanisms governing CD8+ T cell differentiation fates. Finally, we utilized Nichenet and spatial transcriptomic analysis to investigate the spatial expression patterns of immune checkpoints. Results Interaction analysis indicated that, among the known immune checkpoints, co-expression of NKG2A and PD-1 might exert a more profound inhibitory effect on the proliferative capacity of CD8+ T cells. The co-expression analysis revealed differential co-expression pattern of PD-1 and NKG2A, defined as ICEP1 (CD8+ T cells co-expressing PD-1, CTLA-4, TIGIT, LAG-3 or CD38) and ICEP2 (CD8+ T cells solely expressing NKG2A or co-expressing with other immune checkpoints), reflecting the co-occurrence pattern of PD-1 and the mutual exclusivity of NKG2A. Further, these two ICEP CD8+ T cell subsets represented distinct CD8+ T cell differentiation fates governed by MSC and RUNX3. Notably, ICEP2 CD8+ T cells were associated with anti-PD-1 therapy resistance in gastric cancer. This phenomenon may be attributed to the recruitment of LGMN+ macrophages mediated by the CXCL16-CXCR6 signaling pathway. Conclusion This study unveiled two distinct ICEPs and the mutually exclusivity and co-occurrence characteristics of CD8+ T cells in gastric cancer. The ICEP2 CD8+ T cell subset, highly expressed in gastric cancer patients resistant to anti-PD-1 therapy, may be recruited by LGMN+ macrophages through CXCL16-CXCR6 axis. These findings provide evidence for NKG2A as a novel immunotherapeutic target in gastric cancer and offer new insights into combination strategies for immune checkpoint inhibitors in gastric cancer. Graphical Abstract

Abstract Objective To explore the potential association between dietary live microbes and the prevalence of Chronic Obstructive Pulmonary Diseases (COPD). Methods In this cross-sectional study, data of 9791 participants aged 20 years or older in this study were collected from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018. Participants in this study were classified into three groups according to the Sanders’ dietary live microbe classification system: low, medium, and high dietary live microbe groups. COPD was defined by a combination of self-reported physician diagnoses and standardized medical status questionnaires. Logistic regression and subgroup analysis were used to assess whether dietary live microbes were associated with the risk of COPD. Results Through full adjustment for confounders, participants in the high dietary live microbe group had a low prevalence of COPD in contrast to those in low dietary live microbe group (OR: 0.614, 95% CI: 0.474–0.795, and p

Abstract Objectives This study aims to compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) to traditional diagnostic methods in patients with lower respiratory tract infections (LRTIs), elucidate the etiological spectrum of these infections, and explore the impact of mNGS on guiding antimicrobial therapy. Methods We retrospectively analyzed data from 128 patients admitted to the Respiratory Department of Anqing 116 Hospital between July 2022 and July 2023. All patients had undergone both mNGS and conventional microbiological techniques (CMT) for LRTI diagnosis. We assessed the diagnostic performance of these methods and examined the influence of mNGS on antimicrobial decision-making. Results Overall, mNGS demonstrated superior sensitivity (96.8%) and accuracy (96.8%) compared to CMT. For Mycobacterium tuberculosis detection, the accuracy and sensitivity of mNGS was 88.8% and 77.6%, which was lower than the 94.7% sensitivity of the T-spot test and the 79.6% sensitivity of CMT. In fungal pathogen detection, mNGS showed excellent sensitivity (90.5%), specificity (86.7%), and accuracy (88.0%). Bacteria were the predominant pathogens detected (75.34%), with Mycobacterium tuberculosis (41.74%), Streptococcus pneumoniae (21.74%), and Haemophilus influenzae (16.52%) being most prevalent. Bacterial infections were most common (62.10%), followed by fungal and mixed infections (17.74%). Of the 118 patients whose treatment regimens were adjusted based on mNGS results, 102 (86.5%) improved, 7 (5.9%) did not respond favorably, and follow-up was lost for 9 patients (7.6%). Conclusions mNGS offers rapid and precise pathogen detection for patients with suspected LRTIs and shows considerable promise in diagnosing Mycobacterium tuberculosis and fungal infections. By broadening the pathogen spectrum and identifying polymicrobial infections, mNGS can significantly inform and refine antibiotic therapy.

Abstract Sepsis is a leading cause of death worldwide. This syndrome is commonly accompanied by overactivation of coagulation, excessive reactive oxygen species (ROS), and inflammatory cytokine storm. Notably, disseminated intravascular coagulation (DIC) accounts for around 40% of sepsis‐associated deaths. However, anticoagulant therapy is still difficult for sepsis treatment because of the lethal bleeding side effects. Although the relationship between ROS and inflammatory cytokine storm has been described clearly, the pathogenic role of ROS in DIC, however, is still unclear, which renders novel therapeutic approaches hard to achieve bedside for inhibiting DIC. Herein, our new finding reveals that ROS greatly facilitates the entry of lipopolysaccharide (LPS) into the macrophage cytoplasm, which subsequently activates the caspase‐11/gasdermin D pathway, and finally induces DIC through phosphatidylserine exposure. Based on this finding, novel gallic acid‐modified Mo‐based polyoxometalate dots (M‐dots) with outstanding antioxidant activity are developed to provide ideal and efficient inhibition of DIC. As expected, M‐dots are capable of markedly inhibiting sepsis‐caused coagulation, organ injury, and death in sepsis. This therapeutic strategy, blocking the upstream pathway of coagulation rather than coagulation itself, can avoid the side effects of extensive bleeding caused by conventional anticoagulation therapy, and will provide a new avenue for the efficient treatment of sepsis.

Abstract The encryption of user data is crucial when employing electronic health record services to guarantee the security of the data stored on cloud servers. Attribute-based encryption (ABE) scheme is considered a powerful encryption technique that offers flexible and fine-grained access control capabilities. Further, the multi-user collaborative access ABE scheme additionally supports users to acquire access authorization through collaborative works. However, the existing multi-user collaborative access ABE schemes do not consider the different weights of collaboration users. Therefore, using these schemes for weighted multi-user collaborative access results in redundant attributes, which inevitably reduces the efficiency of the ABE scheme. This paper proposes a revocable and verifiable weighted attribute-based encryption with collaborative access scheme (RVWABE-CA), which can provide efficient weighted multi-user collaborative access, user revocation, and data integrity verification, as the fundamental cornerstone for establishing a robust framework to facilitate secure sharing of electronic health records in a public cloud environment. In detail, this scheme employs a novel weighted access tree to eliminate redundant attributes, utilizes encryption version information to control user revocation, and establishes Merkle Hash Tree for data integrity verification. We prove that our scheme is resistant against chosen plaintext attack. The experimental results demonstrate that our scheme has significant computational efficiency advantages compared to related works, without increasing storage or communication overhead. Therefore, the RVWABE-CA scheme can provide an efficient and flexible weighted collaborative access control and user revocation mechanism as well as data integrity verification for electronic health record systems.

Background Numerous studies have linked the inflammatory pathway in psoriasis and metabolic disease, while no specific marker defined it. It is worth exploring the association of β2-microglobulin (β2M) in psoriasis severity and comorbidities.Objectives To investigate the correlation between blood β2M level and psoriasis severity, to explore the inflammatory factors influencing the occurrence of psoriasis comorbidities such as arthritis, diabetes, and hypertension.Methods Ninety-seven psoriasis patients were analyzed in the cohort retrospective study during 12 weeks.Results Significantly higher levels of blood β2M and ESR were observed in the group that patients’ PASI ≥10 than in the group that PASI

Hypoxic-ischemic encephalopathy (HIE) poses a significant challenge in neonatal medicine, often resulting in profound and lasting neurological deficits. Current therapeutic strategies for hypoxia-ischemia brain damage (HIBD) remain limited. Ferroptosis has been reported to play a crucial role in HIE and serves as a potential therapeutic target. However, the mechanisms underlying ferroptosis in HIBD remain largely unclear. In this study, we found that elevated lysyl oxidase (LOX) expression correlates closely with the severity of HIE, suggesting LOX as a potential biomarker for HIE. LOX expression levels and enzymatic activity were significantly increased in HI-induced neuronal models both in vitro and in vivo. Notably, we discovered that HI-induced brain tissue injury results in increased stiffness and observed a selective upregulation of the mechanosensitive ion channel Piezo1 in both brain tissue of HIBD and primary cortex neurons. Mechanistically, LOX increases its catalytic substrates, the Collagen I/III components, promoting extracellular matrix (ECM) remodeling and possibly mediating ECM cross-linking, which leads to increased stiffness at the site of injury and subsequent activation of the Piezo1 channel. Piezo1 senses these stiffness stimuli and then induces neuronal ferroptosis in a GPX4-dependent manner. Pharmacological inhibition of LOX or Piezo1 ameliorated brain neuronal ferroptosis and improved learning and memory impairments. Furthermore, we identified traumatic acid (TA) as a novel LOX inhibitor that effectively suppresses LOX enzymatic activity, mitigating neuronal ferroptosis and promoting synaptic plasticity. In conclusion, our findings elucidate a critical role for LOX-mediated ECM mechanical stress-induced Piezo1 activation in regulating ferroptotic cell death in HIBD. This mechanistic insight provides a basis for developing targeted therapies aimed at ameliorating neurological outcomes in neonates affected by HIBD.

Collisions between ions and neutral particles are often ignored in plasma numerical simulations. However, when studying plasma jets, the collision between neutral particles and ions is significant for ion transport, so calculations cannot ignore this. Therefore, this study adopted a two-fluid model and numerically simulated the process of ion emission from the sheath edge in atmospheric pressure plasma. In this study, particle collisions are treated as Maxwellian particle collisions. We analyze the influence of several parameters, such as sheath thickness and potential drop within the sheath. We also discuss the relaxation phenomenon of relative motion between ions and neutral particles. The research results show a transition from a non-equilibrium state to an equilibrium state in the ion migration region. Based on this change process, the ion migration region can be divided into relaxation and equilibrium zones. The relaxation zone is very thin, where the velocity and temperature of ions vary greatly. In the equilibrium zone, ions and neutral particles can be regarded as a single fluid. This study explores the interaction theory between neutral particles and ions in numerical simulations of plasmas.

Abstract Introduction Many asthmatic patients are exposed to cigarette smoke actively or passively, which contributes to asthma exacerbation and poor control. This study is to explore the effects of cigarette smoke on pathological changes in murine surrogate of asthma. Methods C57BL/6 mice were sensitised and challenged with ovalbumin (OVA) to establish a surrogate of asthma and then administered with cigarette smoke extract (CSE). Airways hyperresponsiveness (AHR) was measured using the Flexivent system. Histological staining (haematoxylin‐eosin [HE], periodic acid Schiff [PAS], Congo red and Masson's trichrome) was employed to measure pathological changes in sections of lung tissue of experimental mice. Enzyme‐linked immunosorbent assay (ELISA) was used to measure the concentrations of total and OVA‐specific IgE, cytokines and chemokines (eotaxin‐1, IL‐13, IL‐1β, TNF‐α, IL‐17A, IL‐33) in the lung tissue homogenates. Immunoreactivity for vWF and α‐SMA in lung tissue sections was detected by immunohistochemistry. Results Exposure of the animals to CSE significantly reduced OVA‐induced AHR, the number of eosinophils in bronchoalveolar lavage fluid (BALF) and eosinophils infiltrating into the lung tissue, as well as concentrations of some cytokines in lung homogenate. In contrast, it significantly enhanced the number of macrophages and M2 in BALF, as well as collagen deposition, smooth muscle thickness and alveolar destruction in lung tissue. Conclusion CSE inhibits OVA‐induced AHR, changes inflammation ‘phenotypes’, while accelerates some aspects of airways remodelling, which might contribute to worse symptoms and be refractory to anti‐inflammation therapies for asthmatics.

Abstract This study aimed to investigate the relationship between serum phosphate levels, changes in serum phosphate levels, and 28-day mortality in patients with septic shock. In this retrospective study, data were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database between 2008 and 2019. Patients were divided into three groups according to the tertiles of serum phosphate levels. Kaplan–Meier curves and log-rank test analyses were used for survival analysis. Multivariate logistic regression, and restricted cubic spline (RCS) curve were used to explore the association between serum phosphate, delta serum phosphate levels and 28-day mortality. In total, 3296 patients with septic shock were included in the study, and the 28-day mortality was 30.0%. Serum phosphate levels were significantly higher in the non-survivor group than in the survivor group. The Kaplan–Meier curves showed significant differences among the three groups. Multivariate logistic regression analysis and the RCS curve showed that serum phosphate levels were independently and positively associated with the 28-day mortality of septic shock. Non-survivors had higher delta serum phosphate levels than survivors. Survival analysis showed that patients with higher delta serum phosphate levels had higher 28-day mortality. A non-linear relationship was detected between delta serum phosphate and 28-day mortality with a point of inflection at − 0.3 mg/dL. Serum phosphate levels were positively and independently associated with 28-day mortality in septic shock. Delta serum phosphate level was a high-risk factor for patients with septic shock.

ObjectiveThis study aimed to assess the diagnostic value of prenatal echocardiography for identifying transposition of the great arteries (TGA) during pregnancy and evaluating the associated outcomes.MethodsWe conducted a retrospective analysis of 121 prenatally diagnosed patients with TGA at our hospital between January 2012 and September 2022. This analysis included prenatal ultrasound, prenatal screening, clinical management and follow-up procedures.ResultsAmong the 103 fetuses considered in the study, 90 (87.4%) were diagnosed with complete transposition of the great arteries (D-TGA), while 13 (12.6%) exhibited corrected transposition of the great arteries (CC-TGA). Diagnoses were distributed across the trimester, with 8 D-TGA and 2 CC-TGA patients identified in the first trimester, 68 D-TGA patients and 9 CC-TGA patients in the second trimester, and 14 D-TGA and 2 CC-TGA patients referred for diagnosis in the third trimester. Induction of labour was pursued for 76 D-TGA patients (84.4%) and 11 CC-TGA patients (84.6%), and 14 D-TGA patients (15.6%) and 2 CC-TGA patients (15.4%) continued pregnancy until delivery. Among the D-TGA patients, 9 fetuses (10.0%) underwent surgery, two of which were inadvertent fatality, while the remaining seven experienced positive outcomes. Additionally, seven TGA patients received palliative care, leading to four fatalities among D-TGA patients (5.2%), whereas 1 D-TGA patients and 2 CC-TGA patients survived.ConclusionThis study underscores the feasibility of achieving an accurate prenatal diagnosis of TGA during early pregnancy. The utility of prenatal ultrasound in the development of personalized perinatal plans and the application of multidisciplinary treatment during delivery are conducive.

Rapid advances in nanomedicine have enabled potential applications in cancer therapy. The enhanced permeability and retention (EPR) effect is the primary rationale for the passive targeting of nanoparticles in oncology. However, growing evidence indicates that the accumulation of nanomaterials via the EPR effect could be more efficient. Inspired by our clinical observation of the Gap Junction connecpion between folliculostellate cells and pituitary adenoma cells, we designed a novel drug delivery system that targets tumours by coating folliculostellate cell (FS) membranes onto PLGA nanoparticles (NPs). The resulting FSNPs, inheriting membrane proteins from the folliculostellate cell membrane, significantly enhanced the EPR effect compared to nanoparticles without cancer cell membranes. We further demonstrated that mitotane encapsulation improved the therapeutic efficacy of mitotane in both heterotopic and orthotopic pituitary adenoma models. Owing to its significant efficacy, our FS cell membrane-coated nanoplatforms has the potential to be translated into clinical applications for the treatment of invasive pituitary adenoma.

Abstract Background Psoriasis is an inflammatory disease mediated by helper T (Th)17 and Th1 cells. MicroRNA-125a (miR-125a) is reduced in the lesional skin of psoriatic patients. However, the mechanism by which miR-125a participates in psoriasis remains unclear. Methods The levels of miR-125a-5p and its downstream targets (ETS-1, IFN-γ, and STAT3) were detected in CD4+ T cells of healthy controls and psoriatic patients by quantitative real-time PCR (qRT-PCR). In vitro, transfection of miR-125a-5p mimics was used to analyze the effect of miR-125a-5p on the differentiation of Th17 cells by flow cytometry. Imiquimod (IMQ)-induced mouse model was used to evaluate the role of upregulating miR-125a-5p by intradermal injection of agomir-125a-5p in vivo. Results miR-125a-5p was downregulated in peripheral blood CD4+ T cells of psoriatic patients, which was positively associated with the proportion of regulatory T cells (Tregs) and negatively correlated with the Psoriasis Area and Severity Index (PASI) score. Moreover, the miR-125a-5p mimics promoted the differentiation of Tregs and downregulated the messenger RNA (mRNA) levels of ETS-1, IFN-γ, and STAT3 in murine CD4+ T cells. Furthermore, agomir-125a-5p alleviated psoriasis-like inflammation in an IMQ-induced mouse model by downregulating the proportion of Th17 cells. Conclusions miR-125a-5p may have therapeutic potential in psoriasis by restoring the suppressive function of Tregs on Th17 cells through targeting STAT3, and on Th1 cells indirectly through targeting ETS-1 and IFN-γ.

Abstract Background Trastuzumab is a first‐line targeted therapy for human epidermal growth factor receptor‐2 (HER2)‐positive gastric cancer. However, the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit, and there is currently no effective reversal measure. Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves, while the understanding of the mechanisms of environment‐mediated drug resistance is relatively lacking. This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients. Methods Trastuzumab‐sensitive and trastuzumab‐resistant HER2‐positive tumor tissues and cells were collected for transcriptome sequencing. Bioinformatics were used to analyze cell subtypes, metabolic pathways, and molecular signaling pathways. Changes in microenvironmental indicators (such as macrophage, angiogenesis, and metabolism) were verified by immunofluorescence (IF) and immunohistochemical (IHC) analyses. Finally, a multi‐scale agent‐based model (ABM) was constructed. The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM. Results Based on transcriptome sequencing, molecular biology, and in vivo experiments, we found that the level of glutamine metabolism in trastuzumab‐resistant HER2‐positive cells was increased, and glutaminase 1 (GLS1) was significantly overexpressed. Meanwhile, tumor‐derived GLS1 microvesicles drove M2 macrophage polarization. Furthermore, angiogenesis promoted trastuzumab resistance. IHC showed high glutamine metabolism, M2 macrophage polarization, and angiogenesis in trastuzumab‐resistant HER2‐positive tumor tissues from patients and nude mice. Mechanistically, the cell division cycle 42 (CDC42) promoted GLS1 expression in tumor cells by activating nuclear factor kappa‐B (NF‐κB) p65 and drove GLS1 microvesicle secretion through IQ motif‐containing GTPase‐activating protein 1 (IQGAP1). Based on the ABM and in vivo experiments, we confirmed that the combination of anti‐glutamine metabolism, anti‐angiogenesis, and pro‐M1 polarization therapy had the best effect in reversing trastuzumab resistance in HER2‐positive gastric cancer. Conclusions This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism, M2 macrophage polarization, and pro‐angiogenic function of macrophages, leading to acquired trastuzumab resistance in HER2‐positive gastric cancer. A combination of anti‐glutamine metabolism, anti‐angiogenesis, and pro‐M1 polarization therapy may provide a new insight into reversing trastuzumab resistance.

Abstract. Background:. Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis. Methods:. Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists. Results:. A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%–11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%–12.5%) for males and 9.6% (95% CI, 7.7%–11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%–59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%–6.2%). Conclusion:. The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.

Abstract Background The true incidence of acute gastrointestinal illness in China is underrecognized by surveillance systems. The aims of this study were to estimate the incidence and prevalence of self-reported AGI in the community of China, and to investigate sociodemographic and epidemiological determinants of AGI. Methods We conducted a 12-months cross-sectional population-based survey in eight provinces of China during 2014–2015. The survey determined the prevalence and incidence of acute gastrointestinal illness (AGI) in the total permanent resident population in China according to the census of the population in 2010. The random multilevel population sample was stratified by geographic, population, and socioeconomic status. We used a recommended case definition of AGI, with diarrhea (three loose or watery stools) and/or any vomiting in a four-week recall. A face-to-face survey was conducted by selecting the member in the household with the most recent birthday. Results Among 56,704 sampled individuals, 948 (1,134 person-time) fulfilled the case definition; 98.5% reported diarrhea. This corresponds to 2.3% (95% CI:1.9%-2.8%) of an overall standardized four-week prevalence and 0.3 (95% CI: 0.23–0.34) episodes per person-year of annual adjusted incidence rate. There was no significant difference between males and females. The incidence rates were higher among urban residents, and in the spring and summer. In the whole study period, 50% of the cases sought medical care, of which 3.9% were hospitalized and 14.3% provided a biological sample for laboratory identification of the causative agent. Children aged 0–4 and young adults aged 15–24, people living in rural areas and people who traveled frequently had higher prevalence of AGI. Conclusion Results showed that AGI represents a substantial burden in China, and will contribute to the estimation of the global burden of AGI. Complemented with data on the etiologies of AGI, these estimates will form the basis to estimate the burden of foodborne diseases in China.

Currently, there are no clinical drugs available to treat acute kidney injury (AKI). Given the high prevalence and high mortality rate of AKI, the development of drugs to effectively treat AKI is a huge unmet medical need and a research hotspot. Although existing evidence fully demonstrates that reactive oxygen and nitrogen species (RONS) burst at the AKI site is a major contributor to AKI progression, the heterogeneity, complexity, and unique physiological structure of the kidney make most antioxidant and anti-inflammatory small molecule drugs ineffective because of the lack of kidney targeting and side effects. Recently, nanodrugs with intrinsic kidney targeting through the control of size, shape, and surface properties have opened exciting prospects for the treatment of AKI. Many antioxidant nanodrugs have emerged to address the limitations of current AKI treatments. In this review, we systematically summarized for the first time about the emerging nanodrugs that exploit the pathological and physiological features of the kidney to overcome the limitations of traditional small-molecule drugs to achieve high AKI efficacy. First, we analyzed the pathological structural characteristics of AKI and the main pathological mechanism of AKI: hypoxia, harmful substance accumulation-induced RONS burst at the renal site despite the multifactorial initiation and heterogeneity of AKI. Subsequently, we introduced the strategies used to improve renal targeting and reviewed advances of nanodrugs for AKI: nano-RONS-sacrificial agents, antioxidant nanozymes, and nanocarriers for antioxidants and anti-inflammatory drugs. These nanodrugs have demonstrated excellent therapeutic effects, such as greatly reducing oxidative stress damage, restoring renal function, and low side effects. Finally, we discussed the challenges and future directions for translating nanodrugs into clinical AKI treatment.

Acute kidney injury (AKI) can lead to loss of kidney function and a substantial increase in mortality. The burst of reactive oxygen species (ROS) plays a key role in the pathological progression of AKI. Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI. Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases. However, most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules, the main damage site of AKI. Here, an ultra-small Tungsten-based nanodots (TWNDs) with strong ROS scavenging can be very effective for treatment of AKI. TWNDs can reach the tubular site after crossing the glomerular barrier, and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies. To our knowledge, this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI. Through in-depth study of the therapeutic mechanism, such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing mitophagy. In addition, TWNDs can also reduce the infiltration of inflammatory cells. This work provides a new way to passively target mitochondria for AKI, and give inspiration for the treatment of many major diseases closely related to mitochondria, such as myocardial infarction and cerebral infarction.

Abstract The knowledge of body size/weight is necessary for the general growth enhancement of swine as well as for making informed decisions that concern their health, productivity, and yield. Therefore, this work aims to automate the collection of pigs’ body parameters using images from Kinect V2 cameras, and the development of Multilayer Perceptron Neural Network (MLP NN) models to predict their weight. The dataset obtained using 3D light depth cameras contains 9980 pigs across the S21 and S23 breeds, and then grouped into 70:15:15 training, testing, and validation sets, respectively. Initially, two MLP models were built and evaluations revealed that model 1 outperformed model 2 in predicting pig weights, with root mean squared error (RMSE) values of 5.5 and 6.0 respectively. Moreover, employing a normalized dataset, two new models (3 and 4) were developed and trained. Subsequently, models 2, 3, and 4 performed significantly better with a RMSE value of 5.29 compared to model 1, which has a RMSE value of 6.95. Model 3 produced an intriguing discovery i.e. accurate forecasting of pig weights using just two characteristics, age and abdominal circumference, and other error values show corresponding results

The severity of rice blast and its impacts on rice yield are closely related to the inoculum quantity of Magnaporthe oryzae, and automatic detection of the pathogen spores in microscopic images can provide a rapid and effective way to quantify pathogen inoculum. Traditional spore detection methods mostly rely on manual feature extraction and shallow machine learning models, and are mostly designed for the indoor counting of a single spore class, which cannot handle the interference of impurity particles in the field. This study achieved automatic detection of rice blast fungus spores in the mixture with other fungal spores and rice pollens commonly encountered under field conditions by using deep learning based object detection techniques. First, 8959 microscopic images of a single spore class and 1450 microscopic images of mixed spore classes, including the rice blast fungus spores and four common impurity particles, were collected and labelled to form the benchmark dataset. Then, Faster R-CNN, Cascade R-CNN and YOLOv3 were used as the main detection frameworks, and multiple convolutional neural networks were used as the backbone networks in training of nine object detection algorithms. The results showed that the detection performance of YOLOv3_DarkNet53 is superior to the other eight algorithms, and achieved 98.0% mean average precision (intersection over union > 0.5) and an average speed of 36.4 frames per second. This study demonstrated the enormous application potential of deep object detection algorithms in automatic detection and quantification of rice blast fungus spores.

Sensory neuron membrane proteins (SNMPs) play important roles in insect chemoreception and SNMP1s have been reported to be essential in detecting sex pheromones in Drosophila and some lepidopteran species. However, SNMPs for Cyrtotrachelus buqueti (Coleoptera: Curculionidae), a major insect pest of bamboo plantations, remain uncharacterized. In this study, a novel SNMP gene, CbuqSNMP1b, from C. buqueti was functionally characterized. The expression of CbuqSNMP1b was significantly higher in antennae than in other tissues of both sexes and the expression level was significantly male-biased. Additionally, CbuqSNMP1b showed significantly higher transcription levels in the adult stage and very low transcription levels in other stages, suggesting that CbuqSNMP1b is involved in the process of olfaction. Fluorescence binding assays indicated that CbuqSNMP1b displayed the strongest binding affinity to dibutyl phthalate (Ki = 9.03 μM) followed by benzothiazole (Ki = 11.59 μM) and phenol (Ki = 20.95 μM) among fourteen C. buqueti volatiles. Furthermore, molecular docking revealed key residues in CbuqSNMP1b that interact with dibutyl phthalate, benzothiazole, and phenol. In conclusion, these findings will lay a foundation to further understand the olfactory mechanisms of C. buqueti and promote the development of novel methods for controlling this pest.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important adverse event in the development of chronic obstructive pulmonary disease (COPD). Hyperphosphatemia is associated with higher mortality in patients with multiple diseases. In this study, we aimed to determine the relationship between serum phosphate and the risk of in-hospital mortality in patients with AECOPD. Methods: In the present study, patients with AECOPD were enrolled in the electronic Intensive Care Unit Collaborative Research Database (eICU-CRD), and divided into three groups according to the tertiles of serum phosphate level. The primary outcome measure was all-cause in-hospital mortality. The association between serum phosphate level and in-hospital mortality was investigated using multivariate logistic regression analysis. Moreover, subgroup analysis was performed to explore whether the relationship was consistent among different subgroups. Results: A total of 1199 AECOPD patients were included in this study. Non-survivors had higher serum phosphate levels than survivors. All patients were classified into lowest tertile, median tertile, and highest tertile, respectively. Multivariate logistic regression analysis indicated that serum phosphate was positively associated with in-hospital mortality after adjusting for confounders. Moreover, there was a significant trend across tertiles when serum phosphate level was diverted as a categorical variable. In addition, subgroup analysis demonstrated that serum phosphate was consistently associated with a higher risk of in-hospital mortality in different subgroups. Conclusion: Higher serum phosphate was positively associated with the increased in-hospital mortality in patients with AECOPD. Hyperphosphatemia may be an underlying high-risk factor for in-hospital mortality owing to AECOPD.

Salicylic acid (SA) has been recognized as a promising molecule for improving abiotic stress tolerance in plants due to its ability to enhance antioxidant defense system, and promote root architecture system. Recent research has focused on uncovering the mechanisms by which SA confers abiotic stress tolerance in horticultural crops. SA has been shown to act as a signaling molecule that triggers various physiological and morphological responses in plants. SA regulates the production of reactive oxygen species (ROS). Moreover, it can also act as signaling molecule that regulate the expression of stress-responsive genes. SA can directly interact with various hormones, proteins and enzymes involved in abiotic stress tolerance. SA regulates the antioxidant enzymes activities that scavenge toxic ROS, thereby reducing oxidative damage in plants. SA can also activate protein kinases that phosphorylate and activate transcription factors involved in stress responses. Understanding these mechanisms is essential for developing effective strategies to improve crop resilience in the face of changing environmental conditions. Current information provides valuable insights for farmers and plant researchers, offering new strategies to enhance crop resilience and productivity in the face of environmental challenges. By harnessing the power of SA and its signaling pathways, farmers can develop more effective stress management techniques and optimize crop performance. Plant researchers can also explore innovative approaches to breed or engineer crops with enhanced stress tolerance, thereby contributing to sustainable agriculture and food security.

Abstract The fast conversion of hydrogen peroxide (H2O2) into reactive oxygen species (ROS) at tumor sites is a promising anticancer strategy by manipulating nanomedicines with near‐infrared light in the second region (NIR‐II). However, this strategy is greatly compromised by the powerful antioxidant capacity of tumors and the limited ROS generation rate of nanomedicines. This dilemma mainly stems from the lack of an effective synthesis method to support high‐density copper‐based nanocatalysts on the surface of photothermal nanomaterials. Herein, a multifunctional nanoplatform (MCPQZ) with high–density cuprous (Cu2O) supported molybdenum disulfide (MoS2) nanoflowers (MC NFs) is developed for the efficient killing of tumors via a potent ROS storm by an innovative method. Under NIR‐II light irradiation, the ROS intensity and maximum reaction velocity (Vmax) produced by MC NFs are 21.6 and 33.8 times that of the non–irradiation group in vitro, which is much higher than most current nanomedicines. Moreover, the strong ROS storm in cancer cells is efficiently formed by MCPQZ (increased by 27.8 times compared to the control), thanks to the fact that MCPQZ effectively pre–weakens the multiple antioxidant systems of cancer cells. This work provides a novel insight to solve the bottleneck of ROS‐based cancer therapy.

Background: The comparative benefits and acceptability of HIF-PHIs for treating anemia have not been well researched to date. We sought to compare the effectiveness of 6 HIF-PHIs and 3 ESAs for the treatment of renal anemia patients undergoing dialysis.Data sources: Cochrane Central Register of Controlled Trials, PubMed, Embase, Cochrane Library, MEDLINE, Web of Science, and clinicaltrials.gov databases.Results: Twenty-five RCTs (involving 17,204 participants) were included, all of which were designed to achieve target Hb levels by adjusting thee dose of HIF-PHIs. Regarding the efficacy in achieving target Hb levels, no significant differences were found between HIF-PHIs and ESAs in Hb response at the dose-adjusted designed RCTs selected for comparison. Intervention with roxadustat showed a significantly lower risk of RBC transfusion than rhEPO, with an OR and 95% CI of 0.76 (0.56–0.93). Roxadustat and vadadustat had higher risks of increasing the discontinuation rate than ESAs; the former had ORs and 95% CIs of 1.58 (95% CI: 1.21–2.06) for rhEPO, 1.66 (1.16–2.38) for DPO (darbepoetin alfa), and 1.76 (1.70–4.49) for MPG-EPO, and the latter had ORs and 95% CIs of 1.71 (1.09–2.67) for rhEPO, 1.79 (1.29–2.49) for DPO, and 2.97 (1.62–5.46) for MPG-EPO. No differences were observed in the AEs and SAEs among patients who received the studied drugs. Results of a meta-analysis of gastrointestinal disorders among AEs revealed that vadadustat was less effect on causing diarrea than DPO, with an OR of 0.97 (95% CI, 0.9–0.99). Included HIF-PHIs, were proven to be more effective than ESAs in reducing hepcidin levels and increasing TIBC and serum iron level with OR of −0.17 (95% CI, −0.21 to −0.12), OR of 0.79 (95% CI, 0.63–0.95), and OR of 0.39 (95% CI, 0.33–0.45), respectively.Conclusion: HIF-PHIs and ESAs have their characteristics and advantages in treating anemia undergoing dialysis. With the selected dose-adjusted mode, some HIF-PHIs appeared to be a potential treatment for DD-CKD patients when ompared with rhEPO, due to its effectiveness in decreasing the risk of RBC transfusion rate or regulating iron or lipid metabolism while achieving target Hb levels.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=306511; Identifier: CRD42022306511

Abstract Preventing islet β‐cells death is crucial for treating type 2 diabetes mellitus (T2DM). Currently, clinical drugs are being developed to improve the quality of T2DM care and self‐care, but drugs focused on reducing islets β‐cell death are lacking. Given that β‐cell death in T2DM is dominated ultimately by excessive reactive oxygen species (ROS), eliminating excessive ROS in β‐cells is a highly promising therapeutic strategy. Nevertheless, no antioxidants have been approved for T2DM therapy because most of them cannot meet the long‐term and stable elimination of ROS in β‐cells without eliciting toxic side‐effects. Here, it is proposed to restore the endogenous antioxidant capacity of β‐cells to efficiently prevent β‐cell death using selenium nanodots (SENDs), a prodrug of the antioxidant enzyme glutathione peroxidase 1 (GPX1). SENDs not only scavenge ROS effectively, but also “send” selenium precisely to β‐cells with ROS response to greatly enhance the antioxidant capacity of β‐cells by increasing GPX1 expression. Therefore, SENDs greatly rescue β‐cells by restoring mitophagy and alleviating endoplasmic reticulum stress (ERS), and demonstrate much stronger efficacy than the first‐line drug metformin for T2DM treatment. Overall, this strategy highlights the great clinical application prospects of SENDs, offering a paradigm for an antioxidant enzyme prodrug for T2DM treatment.

Abstract A forward-secure group signature (FSGS) ensures the unforgeability of signatures in the past time period despite signing secret key is leaked in the current time period. As we know, traditional FSGS schemes are mostly relying on number-theoretic assumptions unable to resist quantum attacks. Therefore, we present an efficient lattice-based fully dynamic (i.e. users can flexibly join or quit the group) forward-secure group signature (DFSGS) by combining an improved version of FSGS scheme proposed by Ling. Based on an efficient zero-knowledge argument, we construct argument of knowledge of the committed value and the plaintext that help with privacy protection. Our DFSGS scheme is proved to be anonymous and forward-secure traceable relying on short integer solution and learning with errors assumptions in random oracle model. Moreover, the lengths of group public key and signature of our DFSGS scheme have been improved, and the length of user secret key has no connection with the quantity of group members.

ObjectivesThis study aims to investigate the efficacy of prenatal ultrasonography in diagnosing the anomalous origin of the fetal pulmonary artery (AOFPA).MethodsA total of 26 AOFPA cases were retrospectively analyzed from January 2014 to January 2023. The features of the AOFPA were characterized by comparing the prenatal ultrasonic data with the results of anatomical casting after pregnancy termination or postnatal imaging and surgical intervention. Missed diagnoses and misdiagnoses were expounded.ResultsOf the 26 AOFPA cases, there were 13 cases of pulmonary artery sling, 8 cases of anomalous origin of the unilateral pulmonary artery, and five cases of unilateral absence of the pulmonary artery; 17 cases received pathological anatomy and casting after pregnancy termination, and nine cases were confirmed by postnatal imaging and surgery. Nineteen cases were accurately prenatally diagnosed (19/26, 73.1%), and seven cases were missed or misdiagnosed (7/26, 26.9%).ConclusionsPrenatal ultrasonography has a favorable diagnostic efficacy for anomalous origin of the fetal pulmonary artery. The absence of either the left or right pulmonary artery from the image of pulmonary artery bifurcation may indicate origin abnormalities of the pulmonary artery in fetuses, which signifies the necessity to detect the abnormal origin of the pulmonary artery on the affected side and other potential intracardiac malformation complications.

With the development of artificial intelligence, automatically and accurately counting chickens has become a reality. However, insufficient lighting, irregular sizes, and dense flocks make this a challenging task. The existing methods cannot perform accurate and stable counting. In this article, a dense flock of chickens counting network (DFCCNet) is proposed based on density map regression, where features from different levels are merged using feature fusion to obtain more information for distinguishing chickens from the background, resulting in more stable counting results. Multi-scaling is used to detect and count chickens at various scales, which can improve the counting accuracy and ensure stable performance for chickens of different sizes. Feature convolution kernels are adopted to convolve feature maps, which can extract more accurate target information, reduce the impact of occlusion, and achieve more reliable and precise results. A dataset of dense flocks of chickens (namely Dense-Chicken) has been collected and constructed, which contains 600 images of 99,916 chickens, with labeled points and boxes. It can be accessed by researchers as benchmark data. The proposed method was compared with some state-of-the-art algorithms, to validate its effectiveness. With its robustness being verified by counting in three kinds of density situations, with the mean absolute error being 4.26, 9.85, and 19.17, respectively, and a speed of 16.15 FPS. DFCCNet provides an automatic and fast approach to counting chickens in a dense farming environment. It can be easily embedded into handheld devices for application in agricultural engineering.

Pheromone-binding proteins (PBPs) play important roles in binding and transporting sex pheromones. However, the PBP genes identified in coleopteran insects and their information sensing mechanism are largely unknown. Cyrtotrachelus buqueti (Coleoptera: Curculionidae) is a major insect pest of bamboo plantations. In this study, a novel PBP gene, CbuqPBP2, from C. buqueti was functionally characterized. CbuqPBP2 was more abundantly expressed in the antennae of both sexes than other body parts, and its expression level was significantly male-biased. Fluorescence competitive binding assays showed that CbuqPBP2 exhibited the strongest binding affinity to dibutyl phthalate (Ki = 6.32 μM), followed by styrene (Ki = 11.37 μM), among twelve C. buqueti volatiles. CbuqPBP2, on the other hand, showed high binding affinity to linalool (Ki = 10.55), the main volatile of host plant Neosinocalamus affinis. Furthermore, molecular docking also demonstrated the strong binding ability of CbuqPBP2 to dibutyl phthalate, styrene, and linalool, with binding energy values of −5.7, −6.6, and −6.0 kcal/mol, respectively, and hydrophobic interactions were the prevailing forces. The knockdown of CbuqPBP2 expression via RNA interference significantly reduced the electroantennography (EAG) responses of male adults to dibutyl phthalate and styrene. In conclusion, these results will be conducive to understanding the olfactory mechanisms of C. buqueti and promoting the development of novel strategies for controlling this insect pest.

From 2018, several foodborne diseases caused by the consumption of wet rice noodles contaminated with microorganisms have attracted the attention of consumers and surveillance departments. We explored the crucial risk factors for the contamination of Bacillus cereus during the various steps of the wet rice noodles production chain (from raw material to marketing phase). A total of 273 samples were collected in each corresponding production phase. The contamination level was quantitatively detected in the samples, and the corresponding temperature and time were recorded and analyzed using @Risk software. The quantitative detection results of raw material were determined as the initial contamination level in the model to predict the final contamination level and assess the key risk factors for B. cereus contamination in wet rice noodles. The model predicted that the final contamination level of B. cereus was in the range of −3.55 to 4.34 log CFU/g in 95% wet rice noodles at the marketing phase. The highest predicted contamination level was 6.28 log CFU/g, and the risk of exceeding the threshold was 0.80%. The model was verified to be valid for R2 > 0.96, and the predicted results could be used for reference. Moreover, the sensitivity analysis revealed that in addition to raw material, the key control factors were buffering temperature in the packaging delivery phase, transporting temperature and time from factory to marketing phase; their correlation coefficients (r) were 0.18, 0.16, and 0.15, respectively. Therefore, manufacturers need to adjust the current predelivery buffering and transporting mode. It is recommended to reduce the predelivery buffering temperature, and refrigerated trucks are preferred to control the proliferation of B. cereus in transported food, thus reducing the occurrence of foodborne diseases and improving the safety of food.

Primary extraskeletal Ewing sarcoma (EES) is a rare small round cell malignancy that accounts for less than 1% of all sarcomas. It is found most commonly in the trunk and lower limbs and very rarely in the pleura and can be easily misdiagnosed in clinical practice. This study presents the case of an 11-year-old boy who presented to our hospital with no apparent cause of left shoulder pain for 6 months. On physical examination, tenderness was noted in the left chest wall and shoulder joint, which had a limited range of motion. Computed tomography (CT) and magnetic resonance imaging (MRI) of the chest revealed an irregular soft tissue mass in the upper left thorax, with a wide base attached to the adjacent pleura and bone destruction of the adjacent left first rib. The patient’s bone scan showed a dense focus of increased radiotracer accumulation in the left first rib. A subsequent CT-guided aspiration biopsy of the left pleural mass with histomorphology and immunohistochemical phenotyping led to a diagnosis of extraskeletal Ewing sarcoma. To inhibit tumor growth, alternating systemic chemotherapy cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) and isocyclophosphamide and etoposide (IE) were administered at 3-week intervals. After completing three VDC and two IE cycles, the child’s condition was well and the pain in the left shoulder joint was relieved. However, a repeat MRI of the chest showed that the mass did not shrink.

Acute kidney injury has always been considered a sword of Damocles over hospitalized patients and has received increasing attention due to its high morbidity, elevated mortality, and poor prognosis. Hence, AKI has a serious detrimental impact not only on the patients, but also on the whole society and the associated health insurance systems. Redox imbalance caused by bursts of reactive oxygen species at the renal tubules is the key cause of the structural and functional impairment of the kidney during AKI. Unfortunately, the failure of conventional antioxidant drugs complicates the clinical management of AKI, which is limited to mild supportive therapies. Nanotechnology-mediated antioxidant therapies represent a promising strategy for AKI management. In recent years, two-dimensional (2D) nanomaterials, a new subtype of nanomaterials with ultrathin layer structure, have shown significant advantages in AKI therapy owing to their ultrathin structure, large specific surface area, and unique kidney targeting. Herein, we review recent progress in the development of various 2D nanomaterials for AKI therapy, including DNA origami, germanene, and MXene; moreover, we discuss current opportunities and future challenges in the field, aiming to provide new insights and theoretical support for the development of novel 2D nanomaterials for AKI treatment.

ABSTRACT Infection by fungal pathogens is the main factor leading to postharvest rot and quality deterioration of fruit and vegetables. Rotting caused by Alternaria alternata is a concerning disease for numerous crops in both production and postharvest stages, especially tomato black spots. In this study, the double Petri dish assay showed that the VOCs of Ceratocystis fimbriata WJSK-1 and Mby inhibited the mycelial growth of fungal pathogen A. alternata, with a percentage inhibition of 52.2% and 42.9%. Then, HS-SPME-GC-MS technology was used to analyze the volatiles produced by two strains of C. fimbriata (WJSK-1, Mby), a total of 42 volatile single components were obtained, the main volatiles compounds identified include nine esters, 10 ketones, five alcohols, four aldehydes, three aromatic hydrocarbons, three heterocycles, four alkenes, three alkanes, and one acid. After that, the antifungal activity of a single volatile component was evaluated both in vitro and in vivo, four single components with antifungal effects were screened out, namely, benzaldehyde, nonanal, 2-Phenylethanol and isoamyl acetate, with IC50 values show the smallest values for benzaldehyde and nonanal at 0.11 μL mL−1, 0.04 μL mL−1. A. alternata exposed to VOCs had abnormal morphology for hyphae, delayed sporulation, and inhibited spore germination. In vivo experiment shows that the four volatile components can effectively suppress disease incidence on fungal-inoculated fruit; the two aldehydes (benzaldehyde and nonanal) have more prominent effect on delaying fruit onset of disease. The results showed that VOCs produced by C. fimbriata have potential as a fumigant for controlling black rot in cherry tomatoes. IMPORTANCE In this research, the volatile organic compounds (VOCs) produced based on C. fimbriata exhibited strong antifungal activity against the fungal pathogen A. alternata. Our aim is to explore their bacteriostatic components. HS-SPME-GC-MS technology was used to analyze the volatiles produced by the C. fimbriata strain (WJSK-1, Mby). Postharvest cherry tomato fruit black rot caused by A. alternata was treated both in vitro and in vivo, with pure individual components produced by C. fimbriata. The benzaldehyde, nonanal, 2-Phenylethanol, and isoamyl acetate from C. fimbriata can effectively inhibit growth of A. alternata, and delay disease. It has the potential to be developed as a new type of fumigant, a potential replacement for fungicides in the future.

Abstract With the rapid development of cloud computing technology and communication technology, cloud storage has become a tool used by people in daily life. Cloud storage service enables users to outsource data to cloud servers and retrieve desired document efficiently. Individual privacy in outsource data are very sensitive and should be prevented from any leakage. Public-key encryption with keyword search (PEKS) scheme resolves this tension, while public-key authentication encryption with keyword search (PAEKS) scheme improve its keyword guessing attacks problem potentially. Whereas, the loss of keyword privacy, the limitation of single user interaction and low efficiency make PEKS/PAEKS schemes far from enough in practical applications.In this paper, we develop a multi-recipient public key encryption scheme with keyword search without pairing (MREKS) for cloud storage under public key infrastructure. The proposed scheme has the merits of supporting multi-recipient keyword search way as well as requiring no expensively bilinear pairing operations under standard model. We present a concrete and efficient construction of MREKS, and prove its security based on discrete logarithm assumptions. Furthermore, we embed the algorithm of data plaintext encryption and decryption into the scheme, which makes the scheme more practical. We show that our scheme enjoys much more efficiency than previous PEKS/PAEKS scheme in the simulation experiment, especially the keyword encryption is optimized by 79.5%.

Interventional coronary reperfusion strategies are widely adopted to treat acute myocardial infarction, but morbidity and mortality of acute myocardial infarction are still high. Reperfusion injuries are inevitable due to the generation of reactive oxygen species (ROS) and apoptosis of cardiac muscle cells. However, many antioxidant and anti-inflammatory drugs are largely limited by pharmacokinetics and route of administration, such as short half-life, low stability, low bioavailability, and side effects for treatment myocardial ischemia reperfusion injury. Therefore, it is necessary to develop effective drugs and technologies to address this issue. Fortunately, nanotherapies have demonstrated great opportunities for treating myocardial ischemia reperfusion injury. Compared with traditional drugs, nanodrugs can effectively increase the therapeutic effect and reduces side effects by improving pharmacokinetic and pharmacodynamic properties due to nanodrugs’ size, shape, and material characteristics. In this review, the biology of ROS and molecular mechanisms of myocardial ischemia reperfusion injury are discussed. Furthermore, we summarized the applications of ROS-based nanoparticles, highlighting the latest achievements of nanotechnology researches for the treatment of myocardial ischemia reperfusion injury.

Abstract Background Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear. Objective To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA). Methods In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured. Results Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients. Conclusion PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex. Trial registration ChiCTR2000036192

Molybdenum is a trace dietary element necessary for the survival of humans. Some molybdenum-bearing enzymes are involved in key metabolic activities in the human body (such as xanthine oxidase, aldehyde oxidase and sulfite oxidase). Many molybdenum-based compounds have been widely used in biomedical research. Especially, MoS2-nanomaterials have attracted more attention in cancer diagnosis and treatment recently because of their unique physical and chemical properties. MoS2 can adsorb various biomolecules and drug molecules via covalent or non-covalent interactions because it is easy to modify and possess a high specific surface area, improving its tumor targeting and colloidal stability, as well as accuracy and sensitivity for detecting specific biomarkers. At the same time, in the near-infrared (NIR) window, MoS2 has excellent optical absorption and prominent photothermal conversion efficiency, which can achieve NIR-based phototherapy and NIR-responsive controlled drug-release. Significantly, the modified MoS2-nanocomposite can specifically respond to the tumor microenvironment, leading to drug accumulation in the tumor site increased, reducing its side effects on non-cancerous tissues, and improved therapeutic effect. In this review, we introduced the latest developments of MoS2-nanocomposites in cancer diagnosis and therapy, mainly focusing on biosensors, bioimaging, chemotherapy, phototherapy, microwave hyperthermia, and combination therapy. Furthermore, we also discuss the current challenges and prospects of MoS2-nanocomposites in cancer treatment.

Microorganism-produced volatile organic compounds (VOCs) are considered promising environmental-safety fumigants in food preservation. In this study, the VOCs from fungal Ceratocystis fimbriata strains (WSJK-1, Mby) were tested against postharvest fungi Monilinia laxa, Fusarium oxysporum, Monilinia fructicola, Botrytis cinerea, Alternaria solani, and Aspergillus flavus in vitro. The mycelial growth was significantly inhibited, in particular M. fructicola and B. cinerea (76.95, 76.00%), respectively. VOCs were identified by headspace solid-phase microextraction coupled with Gas Chromatography–Mass Spectrometry (HS-SPME-GC–MS); 40 compounds were identified. The antifungal activity of 21 compounds was tested by the minimum inhibitory concentrations (MIC) value. Benzaldehyde, 2-Phenylethanol, and 1-Octen-3-ol showed strong antifungal activity with the MIC in vitro ranging from 0.094 to 0.284 ml L−1 depending on the pathogen tested. The optical microscope showed serious morphological damage, including cell deformation, curling, collapse, and deficiency in mycelial or conidia cell structures treated with C. fimbriata VOCs and pure compounds. In vivo tests, C. fimbriata VOCs decreased brown rot severity in peaches, and compounds Benzaldehyde and 2-Phenylethanol could reduce peach brown rot in peaches at 60 μl L−1. The VOCs produced by C. fimbriata strain have good antifungal effects; low concentration fumigation could control peach brown rot. Its fragrance is fresh, safe, and harmless, and it is possible to replace chemical fumigants. It could be used as a potential biofumigant to control fruit postharvest transportation, storage, and food preservation. To the best of our knowledge, this is the first report on the antifungal activity and biocontrol mechanism of VOCs produced by C. fimbriata.

Periodontal disease (PD) is a local inflammatory disease with high morbidity, manifesting tissue destruction results from inflammation of the host immune response to bacterial antigens and irritants. The supportive function of connective tissue and skeletal tissue can be jeopardized without prompt and effective intervention, representing the major cause of tooth loss. However, traditional treatments exhibited great limitations, such as low efficacies, causing serious side effects and recurrent inflammatory episodes. As a major defense mechanism, reactive oxygen species (ROS) play important roles in the pathological progression of PD. Antioxidant therapy is widely believed to be an effective strategy for ROS-triggered diseases, including oxidative stress-induced PD. Most antioxidants can only scavenge one or a few limited kinds of ROS and cannot handle all kinds. In addition, current antioxidant nanomaterials present limitations associated with toxicity, low stability, and poor biocompatibility. To this end, we develop ultra-small molybdenum-based nanodots (MoNDs) with strong ROS in oxidative stress-induced PD. To the best of our knowledge, this is the first time that MoNDs have been used for PD. In the present study, MoNDs have shown extremely good therapeutic effects as ROS scavengers. Spectroscopic and in vitro experiments provided strong evidence for the roles of MoNDs in eliminating multiple ROS and inhibiting ROS-induced inflammatory responses. In addition, the mouse model of PD was established and demonstrated the feasibility of MoNDs as powerful antioxidants. It can alleviate periodontal inflammation by scavenging multiple ROS without obvious side effects and exhibit good biocompatibility. Thus, this newly developed nanomedicine is effective in scavenging ROS and inhibiting M1 phenotypic polarization, which provides promising candidates for the treatment of PD.

Drug-induced liver injury (DILI) is a serious clinical disease associated with reactive oxygen species (ROS) burst and subsequent inflammatory responses. However, traditional treatments were limited by low efficacy and serious side effects due to the special liver structure. Here, we developed a molybdenum (Mo)-based nanoparticles, EGM NPs, after overall consideration of the pathophysiology of DILI and the advantages of nanodrugs. It demonstrated that EGM NPs treated acetaminophen (APAP)-induced DILI by scavenging ROS and inhibiting inflammation. EGM NPs effectively scavenged various ROS and reduced cell apoptosis at the cellular level. More importantly, EGM NPs can treat APAP-induced DILI in vivo, reducing the levels of liver function indicators in mice with liver injury, scaling down the area of hepatocyte necrosis and successfully inhibiting endoplasmic reticulum (ER) stress in the liver. EGM NPs also showed a certain anti-inflammatory effect by reducing infiltration of macrophages, decreasing pro-inflammatory factors and inhibiting the expression levels of inducible nitric oxide synthase (NOS2) and myeloperoxidase (MPO). Collectively, our findings suggest that EGM NPs-based nanotherapeutic is a novel strategy for the treatment of DILI.

Abstract Immunotherapy has revolutionized cancer treatment, dramatically improving survival rates of melanoma and lung cancer patients. Nevertheless, immunotherapy is almost ineffective against ovarian cancer (OC) due to its cold tumor immune microenvironment (TIM). Many traditional medications aimed at remodeling TIM are often associated with severe systemic toxicity, require frequent dosing, and show only modest clinical efficacy. In recent years, emerging nanomedicines have demonstrated extraordinary immunotherapeutic effects for OC by reversing the TIM because the physical and biochemical features of nanomedicines can all be harnessed to obtain optimal and expected tissue distribution and cellular uptake. However, nanomedicines are far from being widely explored in the field of OC immunotherapy due to the lack of appreciation for the professional barriers of nanomedicine and pathology, limiting the horizons of biomedical researchers and materials scientists. Herein, a typical cold tumor‐OC is adopted as a paradigm to introduce the classification of TIM, the TIM characteristics of OC, and the advantages of nanomedicines for immunotherapy. Subsequently, current nanomedicines are comprehensively summarized through five general strategies to substantially enhance the efficacy of immunotherapy by heating the cold OC. Finally, the challenges and perspectives of this expanding field for improved development of clinical applications are also discussed.

Abstract Background Biomarkers for distinguishing psoriatic arthritis (PsA) from psoriasis without arthritis (PsO) are still lacking. Methods We applied isobaric tags for relative and absolute quantification (iTRAQ) and LC–MS/MS to analyze the proteome profile of peripheral blood mononuclear cells (PBMCs) collected from patients with PsO, patients with PsA, and healthy controls. Bioinformatics analysis and western blotting were performed to identify and validate differentially expressed proteins. Results We identified 389, 199, 291, and 60 significantly differentially expressed proteins (adj.p

Sepsis-associated encephalopathy (SAE) is an intricated complication of sepsis that brings abnormal emotional and memory dysfunction and increases patients’ mortality. Patients’ alterations and abnormal function seen in SAE occur in the hippocampus, the primary brain region responsible for memory and emotional control, but the underlying pathophysiological mechanisms remain unclear. In the current study, we employed an integrative analysis combining the RNA-seq-based transcriptomics and liquid chromatography/mass spectrometry (LC-MS)-based metabolomics to comprehensively obtain the enriched genes and metabolites and their core network pathways in the endotoxin (LPS)-injected SAE mice model. As a result, SAE mice exhibited behavioral changes, and their hippocampus showed upregulated inflammatory cytokines and morphological alterations. The omics analysis identified 81 differentially expressed metabolites (variable importance in projection [VIP] > 1 and p < 0.05) and 1747 differentially expressed genes (Foldchange >2 and p < 0.05) were detected in SAE-grouped hippocampus. Moreover, 31 compounds and 100 potential target genes were employed for the Kyoto Encyclopedia of Genes and Genomes (KEGG) Markup Language (KGML) network analysis to explore the core signaling pathways for the progression of SAE. The integrative pathway analysis showed that various dysregulated metabolism pathways, including lipids metabolism, amino acids, glucose and nucleotides, inflammation-related pathways, and deregulated synapses, were tightly associated with hippocampus dysfunction at early SAE. These findings provide a landscape for understanding the pathophysiological mechanisms of the hippocampus in the progression of SAE and pave the way to identify therapeutic targets in future studies.

This study explored the effects of combined urea and 3,4-dimethylpyrazole phosphate (DMPP) on several components critical to the soil system: net nitrification rates; communities of targeted ammonia oxidizers [ammonia-oxidizing archaea (AOA) and bacteria (AOB) and complete ammonia-oxidizing bacteria (comammox)]; non-targeted nitrite-oxidizing bacteria (NOB) and bacteria. We conducted the study in two contrasting soils (acidic and neutral) over the course of 28 days. Our results indicated that DMPP had higher inhibitory efficacy in the acidic soil (30.7%) compared to the neutral soil (12.1%). The abundance of AOB and Nitrospira-like NOB were positively associated with nitrate content in acidic soil. In neutral soil, these communities were joined by the abundance of AOA and Nitrobacter-like NOB in being positively associated with nitrate content. By blocking the growth of AOB in acidic soil—and the growth of both AOB and comammox in neutral soil—DMPP supported higher rates of AOA growth. Amplicon sequencing of the 16S rRNA gene revealed that urea and urea + DMPP treatments significantly increased the diversity indices of bacteria, including Chao 1, ACE, Shannon, and Simpson in the acidic soil but did not do so in the neutral soil. However, both urea and urea + DMPP treatments obviously altered the community structure of bacteria in both soils relative to the control treatment. This experiment comprehensively analyzed the effects of urea and nitrification inhibitor on functional guilds involved in the nitrification process and non-targeted bacteria, not just focus on targeted ammonia oxidizers.