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Abstract Influenza-related acute lung injury is a life-threatening condition primarily caused by uncontrolled replication of the influenza virus and intense proinflammatory responses. Cereblon (CRBN) is a protein known for its role in the ubiquitin-proteasome system and as a target of the drug thalidomide. However, the function of CRBN in influenza virus infection remains poorly understood. In this study, we investigated the impact of CRBN on A/Puerto Rico/8/34 (PR8) influenza virus-induced lung injury and its potential as a therapeutic target. Knocking down CRBN in vitro significantly reduces PR8-induced cell death. Using Sftpc-Cre; Crbn flox/flox lung-specific Crbn knockout mice, we demonstrated that Crbn deficiency significantly decreased mortality, weight loss, lung pathology, edema, and viral load in PR8-infected mice. PR8-infected Sftpc-Cre; Crbn flox/flox mice exhibited a marked reduction in lung inflammatory cell infiltration and suppression of MAPK pathway activation, highlighted by a significant downregulation of the MKK4-JNK-c-JUN signaling cascade. Collectively, these findings indicate that CRBN plays a pivotal role in the pathogenesis of influenza-induced lung injury by modulating MAPK pathway signaling, underscoring its therapeutic potential as a target for intervention.

Abstract Background Sugar transporters (STs) play a critical role in the transportation of sugar, participating in plant growth and development, stress/defense responses, and signal transduction processes. Dendrobium catenatum (also known as Dendrobium officinale, hereinafter referred to as D. catenatum) is an important traditional Chinese medicinal herb with remarkable medicinal properties and possessing high economic value. Polysaccharides are the primary active components in D. catenatum, exhibiting diverse pharmacological activities. Sugar transporters function as material supplier and may play the essential roles in the polysaccharide biosynthesis, as well as the key reulators in the signaling and responses to abiotic stresses in Dendrobium plants. However, a comprehensive analysis of sugar transporters in D. catenatum remains elusive, thereby hindering our understanding of sugar partitioning within this species. Results In this work, the members belonging to MST, SUT, and SWEET gene families were identified in four Dendrobium plants. A comprehensive study of sugar transporters was conducted in D. catenatum, including phylogenetic relationship, structural arrangement, regulatory networks, expression profiles, and potential functions analysis. Seven sugar transporters were found to be involved in the process of polysaccharide biosynthesis in D. catenatum. Red-blue light is an effective way to enhance the accumulation of polysaccharides, and exerts an influence on the expression of polysaccharide biosynthesis related genes. Conclusions This study provide insight into the evolution and functional annotation of sugar transporters in Dendrobium, and establishing a foundation for future functional research of sugar transporters involved in polysaccharide biosynthesis and stress response.

Abstract Background Hypertension has become a major public health and social problem endangering the health of Chinese residents, and has brought a large economic burden of diseases to families and even the whole society. Promoting the equity of health service utilization for patients with hypertension is of great significance for reducing the occurrence of cardiovascular and cerebrovascular diseases and reducing the economic burden of patients with hypertension. This study aims to analyze the equity and change of outpatient and inpatient service utilization in patients with hypertension, and to explore its influencing factors. Methods Using the data of Household Health Interview Survey from 34 key points of contact for comprehensive healthcare reform in 17 provinces in 2014 and 2016, the equity and change of outpatient and inpatient service utilization of patients with hypertension were analyzed by concentration index, and the contribution degree of each influencing factor to utilization inequality was analyzed by decomposition of concentration index. Results In 2014 and 2016, the standardized concentration index of two-week visits of hypertension patients was 0.0217 and 0.0141, respectively, indicating that the utilization of outpatient services was basically equitable. The standardized concentration index of times of hospitalization was 0.1593 and 0.1364, and the standardized concentration index of hospital length of stay was 0.1517 and 0.1369, respectively. The rich groups utilized more hospitalization services. Compared with 2014, the concentration index of outpatient and inpatient service utilization of patients with hypertension decreased in 2016, indicating that the inequity of outpatient and inpatient service utilization has further improved. The level of family income was the primary factor affecting the inequality of hospitalization utilization. Conclusions The utilization of outpatient services in patients with hypertension was basically equitable; however, wealthier groups had greater utilization of inpatient services. Overall, the degree of inequity has been reduced. Family economic status was the main factor affecting inequality in utilization of medical services. To achieve common prosperity was the most fundamental measure to improve the inequitable utilization of hospitalization services. At this stage, we should improve the medical assistance system and increase the assistance to vulnerable groups, such as the low-income groups.

Abstract The abounding variations in wild rice provided potential reservoirs of beneficial genes for rice breeding. Maintaining stable and high yields under environmental stresses is a long-standing goal of rice breeding but is challenging due to internal trade-off mechanisms. Here, we report wild rice GL12 W improves grain length and salt tolerance in both indica and japonica genetic backgrounds. GL12 W alters cell length by regulating grain size related genes including GS2, and positively regulates the salt tolerance related genes, such as NAC5, NCED3, under salt stresses. We find that a G/T variation in GL12 promoter determined its binding to coactivator GIF1 and transcription factor WRKY53. GIF1 promotes GL12 W expression in young panicle and WRKY53 represses GL12 W expression under salt stresses. The G/T variation also contributes to the divergence of indica and japonica subspecies. Our results provide useful resources for modern rice breeding and shed insights for understanding yield and salt tolerance trade-off mechanism.

Abstract Objective Bone incision leads to interrupted and sluggish blood flow in the process of distraction osteogenesis (DO), creating a hypoxia (0–2% oxygen tension) at the center of the bone callus. This hypoxia is critical in the coupling of osteogenesis and angiogenesis during DO. This study aimed to investigate the effect of Uniaxial Static Strain (USS) on osteogenesis in osteoblasts under hypoxic conditions, with a focus on the expression of osteogenic markers and angiogenic factors. Methods The USS was made by a multi-unit tension compression device.Osteoblasts were subjected to 10% USS made under hypoxic conditions to mimic the process of DO in vitro. The cell proliferation, alkaline phosphatase (ALP) activity, mineralized nodule formation, and expression of osteogenic and angiogenic markers were evaluated by using a CCK-8 assay, alkaline phosphatase (ALP) staining, ALP activity assay, alizarin red S staining, qRT-PCR, Western blotting and ELISA. Results Hypoxia inhibited osteoblast cell proliferation, ALP activity, mineralized nodule formation, and the expression of runt-related transcription factor 2 (Runx- 2), osteopontin(OPN), osteocalcin (OCN), collagen type I (Col1a1). Conversely, hypoxia upregulated the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF), which are associated with angiogenesis. However, the application of USS enhanced osteoblasts’ osteogenic capacity and upregulated angiogenic factors under hypoxic conditions. Conclusion USS can enhance osteogenesis in osteoblasts under hypoxic conditions. Moreover, it may stimulate angiogenesis by promoting the expression of VEGF, which further contributes to bone formation. This finding provides important implications for understanding the mechanisms involved in bone regeneration and may have clinical applications in optimizing the effectiveness of DO techniques.

Abstract Background Patients undergoing dialysis treatment have long been recognized as having an elevated risk of developing coronary artery disease necessitating coronary artery bypass grafting (CABG). However, the prognostic implications of CABG in dialysis-dependent patients remain underexplored. This study aimed to comprehensively assess both short- and long-term outcomes in dialysis-dependent patients undergoing CABG. Methods In this retrospective analysis, we meticulously matched 55 dialysis-dependent patients with 55 non-dialysis patients, controlling for baseline characteristics including age, sex, etiology, and date of surgery. All patients underwent CABG treatment at our institution between January 2014 and June 2022. We conducted a comparative analysis of postoperative complications and survival rates between the two groups. Results Our findings revealed that the dialysis-dependent group exhibited a significantly higher incidence of postoperative complications compared to the non-dialysis group (92.7% vs. 61.8%; p

ABSTRACT Antimicrobial resistance remains a public health threat. Probiotics harboring antimicrobial resistant genes (ARGs) have, in recent years, been considered a potential health risk. Studies conducted on probiotics from increasingly popular health supplements have raised the possibility of transmitting ARGs to commensals in the human gut, concomitantly establishing a reservoir of ARGs and risking acquisition by opportunistic pathogens. Building on our previous study that reported multiple antibiotic resistance in probiotics of health supplements, in this research, we have attempted to detect their ARGs that may account for resistant phenotypes. ARGs responsible for tetracycline, macrolide, aminoglycoside, and glycopeptide resistance were prevalent in probiotics. Through laboratory adaptive evolution studies, we also show that streptomycin-adapted probiotics gained resistance to erythromycin, tetracycline, and doxycycline more effectively than non-adapted ones. When co-incubated with Enterococcus faecalis, Escherichia coli, or Staphylococcus aureus on Caco-2 and/or HCT-116 cells, streptomycin resistance was transferred from the adapted probiotics to generate transconjugants at frequencies comparable to or higher than that of other studies conducted through filter mating. Consistently, ARGs conferring resistance to streptomycin (aadA) and erythromycin [erm(B)−1] were detected in E. coli and S. aureus transconjugants, respectively, after co-incubation with streptomycin-adapted probiotics on Caco-2 cells. aadA and erm(B)−1 were both detected in E. faecalis transconjugant after the same co-incubation on HCT-116 cells. Our data and future comparative genomics and metagenomics studies conducted on animal models and in healthy, immunocompromised, and/or antibiotic-treated human cohorts will contribute to a more comprehensive understanding of probiotic consumption, application, and safety.IMPORTANCEProbiotics are becoming increasingly popular, with promising applications in food and medicine, but the risk of transferring ARGs to disease-causing bacteria has raised concerns. Our study detected ARGs in probiotics of health supplements conferring resistance to tetracycline, macrolide, aminoglycoside, and glycopeptide drugs. Streptomycin-adapted probiotics also gained resistance to other antibiotics more effectively than non-adapted ones. Importantly, we showed that streptomycin resistance could be transferred to other bacteria after co-incubation with probiotics on human intestinal cells. ARGs responsible for erythromycin and streptomycin resistance, which were initially absent in the recipient bacteria, were also detected in the transconjugants. Our data build the foundation for future studies that will be conducted on animal models and in humans and leveraging advanced metagenomics approaches to clarify the long-term health risk of probiotic consumption.

BackgroundHeart rate variability (HRV) is an important marker of autonomic nervous system function and cardiovascular health. Holter monitoring is a crucial method for evaluating HRV, but the procedure and result analysis are relatively complex. This study aims to develop a simplified diagnostic index for predicting HRV decline in newly diagnosed non-small cell lung cancer (NSCLC) patients and evaluate its prognostic value.MethodsThis retrospective cross-sectional study included 131 newly diagnosed NSCLC patients. Baseline characteristics were compared between normal HRV group and declined HRV group. Univariate and multivariate logistic regression analyses identified significant predictors of HRV decline. A diagnostic index was developed based on resting heart rate (RHR), serum sodium, and interleukin-6 (IL-6) and externally validated. Kaplan-Meier survival analysis assessed the prognostic value of the index.ResultsPatients with declined HRV had higher median RHR (84 b.p.m. vs. 70 b.p.m., p < 0.001), lower serum sodium (136.3 mmol/L vs. 138.7 mmol/L, p < 0.001), lower serum albumin (39 g/L vs. 41 g/L, p = 0.031), higher lactate dehydrogenase (LDH) (202 U/L vs. 182 U/L, p = 0.010), and higher IL-6 (11.42 pg/ml vs. 5.67 pg/ml, p < 0.001). Multivariate analysis identified RHR (OR = 3.143, p = 0.034), serum sodium (OR = 6.806, p < 0.001), and IL-6 (OR = 3.203, p = 0.033) as independent predictors of HRV decline. The diagnostic index, with an area under the curve (AUC) of 0.849, effectively predicted HRV decline. ROC analysis of the external validation data demonstrated an AUC of 0.788. Survival analysis showed that patients with a diagnostic index > 2 had significantly worse overall survival (log-rank p < 0.001).ConclusionsThe study identified key clinical parameters that predict HRV decline in newly diagnosed NSCLC patients. The developed diagnostic index, based on RHR, serum sodium, and IL-6, effectively stratifies patients by HRV status and has significant prognostic value, aiding in early identification and management of high-risk patients.

Abies beshanzuensis M. H. Wu is a critically endangered plant with only three wild mother trees in the world, it has a small distribution range limited to Baishanzu National Park, and its natural regeneration has been extremely low, with fewer than three seedlings appearing from 2007 to 2017. Despite the critically endangered status in China, little is known about the obstacles affecting the natural regeneration and reproduction of this species. In our study, we investigated various factors that could influence seed germination, seedling growth, seed quality, and overall production throughout the life cycle of A. beshanzuensis. Our findings highlighted the importance of litter removal in its natural habitat. Over five years following the removal of litter, we observed the emergence of 687 new seedlings, demonstrating a significant enhancement in both germination and seedling survival. Seedling abundance and mortality were greatly influenced by litter thickness, total carbon content, NO3--N, and available phosphorus. Seedlings height growth rate was significantly affected by litter coverage, canopy density at 1.3 m height, total nitrogen, and litter thickness. Additionally, the insufficient energy and lower values of actual photochemical rate, electron transfer rate, and photochemical quenching coefficient support in leaves with cones in the branch and branches with cones in the branch, contributed to abnormal development of female cones, leading to endosperm and embryo abortion. Our findings underscore the significant impact of environmental factors on seedling germination and growth, and highlight that insufficient energy support and reduced photosynthetic capability during female cone reproductive development may pose significant obstacles to the success of A. beshanzuensis.

Abstract Under subarachnoid hemorrhage (SAH) conditions, astrocytes undergo a marked intensification of glycolytic activity, resulting in the generation of substantial amounts of lactate to maintain the energy demand for neurons and other brain cells. Lactate has garnered increasing attention in recent years because of its emerging role in critical biological processes such as inflammation regulation and neuroprotection, particularly through its histone lactylation. Bromodomain-containing protein 4 (BRD4) plays a crucial role in maintaining neural development and promoting memory formation in the central nervous system. Nonetheless, the function and regulatory mechanism of BRD4 and histone lactylation in astrocytes following SAH remain elusive. Our findings indicate that BRD4, a crucial epigenetic regulator, plays a definitive role in histone lactylation. Both in vitro and in vivo, these results demonstrated that targeted silencing of BRD4 in astrocytes can significantly reduce H4K8la lactylation, thereby aggravating the A1 polarization of astrocytes and ultimately affecting the recovery of neural function and prognosis in mice after SAH. In summary, BRD4 plays a pivotal role in modulating astrocyte polarization following SAH via histone lactylation. Targeting this mechanism might offer an efficient therapeutic strategy for SAH.

Abstract Background Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans. Methods Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software. Results RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP). Conclusions The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.

Summary: Under pathological conditions, astrocytes can transfer mitochondria to neurons, where they exert neuroprotective effects. In this context, we present a protocol for capturing astrocytic mitochondria in neurons of adult mice using a two-photon microscope. We describe an approach for constructing a mouse model with combined labeling of astrocytic mitochondria and neurons. We then detail procedures for the preparation of a coverslip with a customized titanium ring and cranial window for two-photon microscopy scanning.For complete details on the use and execution of this protocol, please refer to Zhou et al. 1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Gastrointestinal cancer is a common malignant tumor with a high incidence worldwide. Despite continuous improvements in diagnosis and treatment strategies, the overall prognosis of gastrointestinal tumors remains poor. Carcinoembryonic antigen (CEA) is highly expressed in various types of cancers, especially in gastrointestinal cancers, making it a potential target for therapeutic intervention. Therefore, the expression of CEA can be used as an indication of the existence of tumors, chosen as a target for molecular imaging diagnosis, and effectively utilized in the targeted therapy of gastrointestinal cancers. In this study, we report the selection and characterization of affibody molecules (ZCEA539, ZCEA546, and ZCEA919) specific to the CEA protein. Their ability to bind to recombinant and native CEA protein has been confirmed by surface plasmon resonance (SPR), immunofluorescence, and immunohistochemistry assays. Furthermore, Dylight755-labeled ZCEA affibody showed accumulation within the tumor site 1 h post injection and was continuously enhanced for 4 h. The Dylight755-labeled ZCEA affibody exhibited high tumor-targeting specificity in CEA+ xenograft-bearing mice and possesses promising characteristics for tumor-targeting imaging. Overall, our results suggest the potential use of ZCEA affibodies as fluorescent molecular imaging probes for detecting CEA expression in gastrointestinal cancer.

Abstract The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.

Abstract Background There is currently a lack of functional assessment tools based on the International Classification of Functioning, Disability, and Health (ICF) theoretical framework that are specific for older adults. Objective The aim of the present study was to develop Chinese assessment standards of the ICF Geriatric Core Set for functional evaluation of older adults. Methods A two-stage study process was conducted to develop the assessment standards of the ICF Geriatric Core Set: establishment of candidate assessment standards, and a modified Delphi consensus process including a pilot survey and two-round formal expert survey. Thirty participants in the field of ICF and geriatric rehabilitation were recruited. The suitability of the assessment standards in the questionnaires was rated using a Likert 5-level scoring method. The arithmetic mean, the full mark ratio and the coefficient of variation (CV) were used as screening indicators for the assessment standards, and modification was made for several standards, in line with the Delphi results and the expert panel discussion. Results Thirty-three candidate assessment standards belonging to 17 categories were generated. A total of 26 and 24 experts in the field of ICF and geriatric rehabilitation participated in the two-round survey, respectively. Five standards belonging to four categories entered into the second-round survey directly, five standards belonged to five categories entered with minor modification, and nine standards belonging to seven categories were redesigned based on the literature and discussion of the expert panel. In the second-round survey,15 assessment standards belonging to 15 categories met the screening requirements and four assessment standards belonged to the two remaining categories that needed a criterion and which the expert panel discussed for the final decision. Conclusions Using the modified Delphi method, the assessment standards of the ICF Geriatric Core Set have been developed.Future work should focus on the reliability and validity of the the assessment standards and their application to the health management of older adults.

Perovskites exhibit catalytic properties on the oxygen evolution reaction (OER) in water electrolysis. Elemental doping by specific preparation methods is a good strategy to obtain highly catalytical active perovskite catalysts. In this work, La0.5Sr0.5Co1−xNixO3−δ perovskite materials doped with different ratios of nickel were successfully synthesized by the sol-gel method. The electrochemical measurement results show that for OER in 1 M KOH solution, La0.5Sr0.5Co0.8Ni0.2O3−δ prepared by the sol-gel method requires only a low overpotential of 213 mV to reach 10 mA cm−2, which is significantly lower than that of La0.5Sr0.5Co0.8Ni0.2O3−δ prepared by the hydrothermal method for the increasing about 45.24% (389 mV at 10 mA cm−2). In addition, La0.5Sr0.5Co0.8Ni0.2O3−δ by the sol-gel method can be kept stable in an alkaline medium tested for 30 h without degradation. This indicates that the prepared La0.5Sr0.5Co0.8Ni0.2O3−δ has better OER performance. The X-ray diffraction (XRD) results show that SrCO3 is the main phase formed, which is a disadvantage of this method. The performance improvement may be affected by the carbonate phase. The scanning electron microscopy (SEM) results show that layer structured La0.5Sr0.5Co0.8Ni0.2O3−δ by the sol-gel method has more surface pores with a pore diameter of about 0.362 μm than spherical granular structured La0.5Sr0.5Co0.8Ni0.2O3−δ by the hydrothermal method. X-ray photoelectronic spectroscopy (XPS) results reveal that the crystal lattice of La0.5Sr0.5Co0.8Ni0.2O3−δ by nickel doping is lengthened, and the electronic configuration of Co is also changed by the sol-gel preparation process. The improved electrocatalytic performance of La0.5Sr0.5Co0.8Ni0.2O3−δ may be attributed to the pore structure formed providing more active sites during the sol-gel process and the improved oxygen mobility with Ni doping by the sol-gel method. The doping strategy using the sol-gel method provides valuable insights for optimizing perovskite catalytic properties.

Abstract Functional traits are important in understanding how plants respond and adapt to their immediate environment. Parrotia subaequalis is a highly endangered arbor species found throughout eastern China, primarily inhabiting hillsides and valleys, yet, little is known about the variation in leaf traits across these environments. In the present study, we tested this by comparing leaf surface area, leaf weight, leaf length, leaf symmetry and leaf mass per unit area, as well as the relationship between leaf traits and environmental factors and the scaling relationship between leaf surface area versus leaf dry mass. We observed significant differences in leaf surface area, weight, and length among the population sites, and these variables were strongly affected by environmental factors, especially high mean annual temperatures in hillside habitats and high mean annual precipitation in valley habitats. The scaling exponents remained numerically variant among the 10 populations, with different slopes greater than 1.0, and the scaling exponents increased significantly with hillside habitats. These metrics correlated with soil thickness associated with different habitat types. The areal ratio (AR) values in all populations deviated from 1, indicating that the two lamina sides were asymmetrical. The standardized symmetry index (SI) values displayed significant variation, especially in leaves from hillside habitats with a high degree of asymmetry. Collectively, our findings demonstrated that leaf functional traits exhibit considerable variability in response to different environmental contexts and provide valuable reference data that could be useful for conserving this endangered species.

Abstract Background To report a case of retinitis with multiple intraocular viral infections after second haematopoietic stem cell transplantation. Case presentation A 39-year-old female patient developed retinitis after a second haematopoietic stem cell transplant. Right eye was tested for three viral infections– cytomegalovirus, Epstein‒Barr virus and herpes simplex virus, while left was infected with cytomegalovirus. The patient was subsequently treated with vitreous cavity ganciclovir injections, and 1 week later both eyes tested negative for aqueous humour viruses. Discussion and conclusion CMV, EBV and HSV belong to the herpes virus family. They are all commonly observed in the body and represent opportunity infectious viruses. The retinitis they cause have different characteristics. But simultaneous infection of the eye by multiple viruses is quite rare. In this case, three viruses were detected in the patient’s eye, but whether the retina was caused by all three viruses at the same time could not be determined. A satisfactory outcome was achieved after treatment with vitreous cavity ganciclovir injection.

Abstract Background Acute kidney injury (AKI) is a prevalent complication following acute type A aortic dissection (ATAAD) surgery and is closely associated with unfavorable prognostic outcomes. Hence, the development of a robust and efficient diagnostic approach to identify high-risk patients is of paramount importance. Methods We conducted a prospective study involving 328 patients who underwent ATAAD surgery at our institution, comprising three distinct cohorts. In addition, 52 patients undergoing alternative cardiopulmonary surgeries and 37 healthy individuals were enrolled as control groups. Employing proteomic analysis, we initially identified plasma proteins potentially linked to AKI occurrence within the plasma proteomic cohort. Subsequent validation was performed in an independent cohort. Utilizing predictors derived from multivariate logistic regression analysis, a nomogram was meticulously formulated and its efficacy was validated in the model construction cohort. Results Proteomics revealed significant elevation of plasma levels of S100A8/A9, pentraxin 3 (PTX3), and chitinase 3-like 1 (CHI3L1) immediately post-surgery in patients who developed ATAAD surgery-associated AKI (ASA-AKI). Receiver operating characteristic (ROC) curves demonstrated impressive predictive performance of S100A8/A9, PTX3, and CHI3L1 at 0 h post-surgery, yielding area under the curve (AUC) values of 0.823, 0.786, and 0.803, respectively, for ASA-AKI prediction. Furthermore, our findings exhibited positive correlations between plasma levels of S100A8/A9, PTX3, CHI3L1, and urinary neutrophil gelatinase-associated lipocalin (NGAL) at 0 h post-surgery, along with correlations between plasma S100A8/A9, CHI3L1 levels, and the Cleveland Clinic score. A logistic regression model incorporating plasma S100A8/A9, PTX3, CHI3L1 levels, urinary NGAL levels, and the Cleveland Clinic score facilitated the construction of a predictive nomogram for ASA-AKI. This nomogram demonstrated robust discriminative ability, achieving an AUC of 0.963 in the model construction cohort. Conclusions Our study underscored the augmentation of plasma S100A8/A9, PTX3, and CHI3L1 levels immediately post-surgery in patients developing ASA-AKI. The incorporation of these three biomarkers, in conjunction with the Cleveland Clinic score and NGAL, into a nomogram demonstrated commendable predictive efficacy. This presents a practical tool for identifying patients at an elevated risk of AKI following ATAAD surgery.

Abstract 21st century has witnessed a profound metamorphosis in human civilization, primarily driven by the confluence of advanced network technologies and industrial modernization. This transformative period has expanded our understanding of the world, paving the way for innovative concepts such as the “smart city”. At its essence, a smart city harnesses the power of artificial intelligence (AI) to revolutionize urban living, presenting a paradigm shift towards more efficient service models and an elevated standard of living for its inhabitants. Integrating AI into the fabric of urban infrastructure marks a monumental leap in societal evolution, underscoring the imperative to cultivate and advance AI technologies. This paper endeavors to elucidate the multifaceted applications of AI within the domains of smart cities, illuminating its pivotal role in shaping and advancing our contemporary era. From intelligent transportation systems and energy management to public safety and healthcare, AI permeates various aspects of urban life, ushering in unprecedented efficiencies and novel solutions to age-old challenges. The symbiotic relationship between AI and smart cities is explored in detail, showcasing how AI technologies are instrumental in optimizing resource allocation, improving decision-making processes, and ultimately enhancing the overall quality of life. Furthermore, this paper delves into the imperative of fostering the development and advancement of AI technologies within the context of smart cities. It underscores the interconnectedness of technological progress and urban development, emphasizing how a concerted effort to cultivate AI capabilities can propel cities into a future marked by sustainable growth, resilience, and innovation. The exploration of challenges and opportunities in deploying AI within urban environments adds a critical dimension to the discourse, encouraging a balanced consideration of ethical, regulatory, and societal implications. In conclusion, this paper seeks to contribute to the ongoing dialogue surrounding smart cities and the transformative impact of AI. By shedding light on the diverse applications of AI within urban landscapes and emphasizing its pivotal role in shaping the trajectory of our era, it underscores the critical importance of advancing AI technology development for the continued progress of smart cities and, by extension, the broader global community.

Nasopharyngeal carcinoma (NPC) is a tumor of the head and neck, with a higher incidence in southern China and Southeast Asia. Radiotherapy and chemotherapy are the main treatments; however, metastasis and recurrence remain the main causes of treatment failure. Further, the majority of patients are diagnosed in the late stage due to lack of tumor-specific biomarker for early diagnosis. Therefore, an effective treatment and early detection can improve the outcome of patient with NPC. Axl and EGFR are co-expressed in NPC tissues and play key roles in tumor proliferation, migration, and invasion, which are often correlated with poor prognosis and therapy resistance. In this study, we generated a novel bispecific affibody (Z239-1907) for the dual targeting and inhibition of Axl and EGFR expression in NPC-positive cells both in vitro and in vivo. The in vitro experiments demonstrated that Z239-1907 had more pronounced antitumor effects than either modality alone (ZAXL239 or ZEGFR1907) in NPC-positive cells. Further, mice bearing NPC-positive tumors showed significant inhibition in tumor growth after treatment with Z239-1907 compared to ZAXL239 and ZEGFR1907. The in vivo tumor targeting ability and imaging also showed that Z239-1907 specifically and selectively targeted NPC xenograft mice models and accumulate at tumor site as early as 30 min and disappeared within 24 h post-injection. Collectively, these results suggest that Z239-1907 dual-target affibody is a promising therapeutic agent and a molecular imaging probe for early diagnosis in NPC.

Ascorbic acid (AA) plays an important role in many physiological and biochemical processes. Adequate quantification of AA is required for controlling the intake of AA for health management. In this study, a portable probe was fabricated based on the assembled FePO4@GO nanozyme by homogeneous precipitation. FePO4@GO exhibits excellent peroxidase (POD) activity. As an efficient free radical scavenger, ascorbic acid scavenges 1O2 free radicals produced by hydrogen peroxide catalyzed by peroxidase enzymes and then inhibits the color reaction of 3,3′,5,5′-tetramethylbenzidine (TMB). A good linear relationship between the color of the reaction system and the concentration of AA in the range of 2.5–75 μM was presented, and the detection limit is 1.25 μM. Furthermore, a visual colorimetric detection platform was constructed using a smartphone. The AA content is accurately reflected by intelligent recognition of color changes in the reaction system. It provides an alternative approach for portable and visual rapid detection of Vitamin C (VC) in medicine. Meanwhile, it also provides a reference for the assembly of an intelligent detection platform based on nanozymes.

The excessive reactive oxygen species (ROS) is a hallmark associated with the initiation and progression of inflammatory bowel disease (IBD), which execrably form a vicious cycle of ROS and inflammation to continually promote disease progression. Here, the gold nanoparticles-embedded ceria nanoparticles (Au/CeO2) with enhanced antioxidant activities are designed to block this cycle reaction for treating IBD by scavenging overproduced ROS. The Au/CeO2 with core-shell and porous structure exhibits significantly higher enzymatic catalytic activities compared with commercial ceria nanoparticles, likely due to the effective exposure of catalytic sites, higher content of Ce (III) and oxygen vacancy, and accelerated reduction from Ce (IV) to Ce (III). Being coated with negatively-charged hyaluronic acid, the Au/CeO2@HA facilitates accumulation in inflamed colon tissues via oral administration, reduces pro-inflammatory cytokines, and effectively alleviates colon injury in colitis mice. Overall, the Au/CeO2@HA with good biocompatibility is a promising nano-therapeutic for treating IBD.

Abstract Background Despite that several original researchers have investigated the association between neck circumference (NC) and the risk of diabetes mellitus (DM), their results remain controversial. This review aimed to quantitatively determine the risk of DM in relation to the NC. Methods We conducted a literature search of PubMed, Embase, and the Web of Science from these databases’ inception through September 2022 to identify observational studies that examined the association between NC and the risk of DM. A meta-analysis of the random-effects model was applied to combine the results of the enrolled studies. Results Sixteen observational studies involving 4,764 patients with DM and 26,159 participants were assessed. The pooled results revealed that NC was significantly associated with the risk of type 2 DM (T2DM) (OR = 2.17; 95% CI: 1.30–3.62) and gestational DM (GDM) (OR = 1.31; 95% CI: 1.17–1.48). Subgroup analysis revealed that after controlling for BMI, the relationship between the NC and T2DM remained statistically significant (OR = 1.94; 95% CI: 1.35–2.79). Moreover, the pooled OR of T2DM was found to be 1.16 (95% CI: 1.07–1.27) for an increment per each centimeter in the NC. Conclusions Integrated epidemiological evidence supports the hypothesis that a greater NC is associated with an increased risk of T2DM and GDM.

The natural environment in the high-altitude regions of Northwest China is extremely harsh, characterized by numerous salt lakes. The high concentrations of chloride salts, sulfates, and alkali metal ions in these areas can induce alkali–silica reactions (ASRs) in concrete. These reactions generate harmful gel within the concrete, causing expansion and cracking, which significantly impacts the durability of concrete structures. This study investigates the evolution of the mechanical properties in high-performance concrete (HPC) under long-term ASR by incorporating different admixtures and varying the equivalent alkali content. A three-dimensional random aggregate mesoscopic model was used to simulate static compression tests under various operational conditions. Non-destructive testing methods were utilized to determine the expansion rate, internal, and surface damage variables of the concrete. The experimental results indicate that the 10-year expansion rate differs from the 1-year rate by approximately 1%, and under long-term ASR mitigation measures, the internal damage in the HPC is minimal, though the surface damage is more severe. As the equivalent alkali content increases, the compressive strength of the concrete cubes decreases, initially rising before falling by 5–15% over time. The HPC with only air-entraining agent added exhibited better mechanical performance than the HPC with both air-entraining and corrosion inhibitors added, with the poorest performance observed in the HPC with only a corrosion inhibitor. A relationship was established between the surface and internal damage variables, with the surface damage initially increasing rapidly before stabilizing as the internal damage rose. Numerical simulations effectively describe the damage behavior of HPC under static uniaxial compression. Comparisons with actual failure morphologies revealed that, in the cube compression tests, crack propagation directly penetrated both coarse and fine aggregates rather than circumventing them. The simulations closely matched the experimental outcomes, demonstrating their accuracy in modeling experiments. This study discusses the compressive mechanical properties of concrete under prolonged ASR through a combination of experimental and simulation approaches. It also delves into the impact of surface damage on the overall mechanical performance and failure modes of concrete. The findings provide experimental and simulation support for the concrete structures in regions with high alkali contents.

[This corrects the article DOI: 10.1371/journal.pone.0217185.].

Abstract Background Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder with complex physiopathological mechanisms that have not been fully understood. Early identification is of great prognostic significance, of which the symptoms and radiological abnormalities can be completely reversed. If the diagnosis and treatment are delayed, ischemia and massive infarction may be developed in some patients. Posterior reversible encephalopathy syndrome (PRES) has been reported mainly in association with postpartum eclampsia, which have been rarely reported, while the association with hypothyroidism has not been reported at home or abroad. Case presentation Here we report on a pregnant 29-year-old with multipara and a chief complication of hypothyroidism. She presented in the emergency department with frequent attacks of severe headache symptoms resulting from reversible cerebral vasoconstriction syndrome (RCVS), accompanied with prenatal eclampsia. PRES was determined by radiological examination. Conclusion To the best of our knowledge, this is the first case of PRES complicated by hypothyroidism and prepartum eclampsia.Clinicians should be alert for the co-occurence of eclampsia, PRES, and RCVS when patients have convulsions after a typical throbbing headache. Moreover, regular monitoring of thyroid function during pregnancy should also occupy certain special attention.

Abstract Objective To investigate the effect of large vestibular aqueduct syndrome (LVAS) on middle ear sound transmission using wideband absorbance immittance (WAI). Methods WAI results from young adult LVAS patients and normal adults were compared. Results Averaged energy absorbance (EA) at ambient and peak pressure in the LVAS group showed differences to the normal group. Under ambient pressure, the average EA of the LVAS group was significantly higher than the normal group at frequencies 472–866 Hz and 6169–8000 Hz (p

ABSTRACT: Magnolol, a natural extract from magnolia officinalis, has received growing interest in its bioactive properties such as antioxidant, anti-inflammatory, and antibacterial activities. Nevertheless, there is little research on Magnolol in the treatment of parasitic infections currently. Eimeria tenella (E. tenella) infection causes damage to epithelial cells and cecal mucosa, resulting in increased intestinal permeability, which is pretty detrimental to the balance of the intestinal microenvironment. However, at present, in the treatment of chicken coccidiosis, the abuse of antibiotics is quite serious, which has brought losses and harms to the chicken farming industry that cannot be ignored. In this study, based on the excellent antioxidant and anti-inflammatory properties of Magnolol, we proved that it does have a desirable therapeutic potential on chicks infected with E. tenella. Actually, the results showed that the clinical symptoms of the chicks infected with E. tenella were relieved and their growth performance was restored by Magnolol treatment. Furthermore, Magnolol improved the antioxidant and anti-inflammatory properties of chicks. Meanwhile, the Magnolol reversed the imbalance of the intestinal microbiota of sick chicks, which recovered the diversity, promoted the potential beneficial bacteria, and inhabited the potential pathogenic bacteria. Overall, Magnolol may be an alternative to chemical drugs that are effective in treating E. tenella infections.

Objectives Dimethyl sulfoxide (DMSO), acetone, ethanol, and methanol are organic solvents commonly used for dissolving drugs in antimicrobial susceptibility testing. However, these solvents have certain antimicrobial activity. Currently, standardized criteria for the selection and dosage of drug solvents in drug susceptibility testing research are lacking. The study aims to provide experimental evidence for the selection and addition limit of drug solvents for the in vitro antifungal susceptibility test of Candida glabrata (C. glabrata). Methods According to the recommendation of the Clinical and Laboratory Standards Institute (CLSI) M27-A3, a 0.5 McFarland C. glabrata suspension was prepared and then diluted 1:1,000. Next, a gradient dilution method was used to prepare 20%, 10%, 5%, and 2.5% DMSO/acetone/ethanol/methanol. The mixture was plated onto a 96-well plate and incubated at a constant temperature of 35 °C for 48 h. The inhibitory effects of DMSO, acetone, ethanol, and methanol on C. glabrata growth and proliferation were analyzed by measuring optical density values at 600 nm (OD600 values). Results After 48 h incubation, the OD600 values of C. glabrata decreased to different extents in the presence of the four common organic solvents. The decrease in the OD600 values was greater with increasing concentrations within the experimental concentration range. When DMSO and acetone concentrations were higher than 2.5% (containing 2.5%) and methanol and ethanol concentrations were higher than 5.0% (containing 5.0%), the differences were statistically significant compared with the growth control wells without any organic solvent (P < 0.05). Conclusion All four organic solvents could inhibit C. glabrata growth and proliferation. When used as solvents for drug sensitivity testing in C. glabrata, the concentrations of DMSO, acetone, ethanol, and methanol should be below 2.5%, 2.5%, 5%, and 5%, respectively.

Metal homeostasis has evolved to tightly modulate the availability of metals within the cell, avoiding cytotoxic interactions due to excess and protein inactivity due to deficiency. Even in the presence of homeostatic processes, however, low bioavailability of these essential metal nutrients in soils can negatively impact crop health and yield. While research has largely focused on how plants assimilate metals, acclimation to metal-limited environments requires a suite of strategies that are not necessarily involved in metal transport across membranes. The identification of these mechanisms provides a new opportunity to improve metal-use efficiency and develop plant foodstuffs with increased concentrations of bioavailable metal nutrients. Here, we investigate the function of two distinct subfamilies of the nucleotide-dependent metallochaperones (NMCs), named ZNG1 and ZNG2, that are found in plants, using Arabidopsis thaliana as a reference organism. AtZNG1 (AT1G26520) is an ortholog of human and fungal ZNG1, and like its previously characterized eukaryotic relatives, localizes to the cytosol and physically interacts with methionine aminopeptidase type I (AtMAP1A). Analysis of AtZNG1, AtMAP1A, AtMAP2A, and AtMAP2B transgenic mutants are consistent with the role of Arabidopsis ZNG1 as a Zn transferase for AtMAP1A, as previously described in yeast and zebrafish. Structural modeling reveals a flexible cysteine-rich loop that we hypothesize enables direct transfer of Zn from AtZNG1 to AtMAP1A during GTP hydrolysis. Based on proteomics and transcriptomics, loss of this ancient and conserved mechanism has pleiotropic consequences impacting the expression of hundreds of genes, including those involved in photosynthesis and vesicle transport. Members of the plant-specific family of NMCs, ZNG2A1 (AT1G80480) and ZNG2A2 (AT1G15730), are also required during Zn deficiency, but their target protein(s) remain to be discovered. RNA-seq analyses reveal wide-ranging impacts across the cell when the genes encoding these plastid-localized NMCs are disrupted.

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL.

Intensive economic and human activities present challenges to the carbon storage capacity of terrestrial ecosystems, particularly in arid regions that are sensitive to climate change and ecologically fragile. Therefore, accurately estimating and simulating future changes in carbon stocks on the northern slope economic belt of Tianshan Mountains (NSEBTM) holds great significance for maintaining ecosystem stability, achieving high-quality development of the economic belt, and realizing the goal of “carbon neutrality” by 2050. This study examines the spatiotemporal evolution characteristics of the NSEBTM carbon stocks in arid regions from 1990 to 2050, utilizing a combination of multi-source data and integrating the Patch-generating Land use Simulation (PLUS) and Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) models. Additionally, an attribution analysis of carbon stock changes is conducted by leveraging land use data. The findings demonstrate that (1) the NSEBTM predominantly consists of underutilized land, accounting for more than 60% of the total land area in the NSEBTM. Unused land, grassland, and water bodies exhibit a declining trend over time, while other forms of land use demonstrate an increasing trend. (2) Grassland serves as the primary reservoir for carbon storage in the NSEBTM, with grassland degradation being the leading cause of carbon loss amounting to 102.35 t over the past three decades. (3) Under the ecological conservation scenario for 2050 compared to the natural development scenario, there was a net increase in carbon storage by 12.34 t; however, under the economic development scenario compared to the natural development scenario, there was a decrease in carbon storage by 25.88 t. By quantitatively evaluating the land use change in the NSEBTM and its impact on carbon storage in the past and projected for the next 30 years, this paper provides scientific references and precise data support for the territorial and spatial decision making of the NSEBTM, thereby facilitating the achievement of “carbon neutrality” goals.

Abstract Objective This study aimed to assess the correlation between residual hearing and audiologic outcomes after cochlear implant (CI) surgery in patients with cochlear nerve deficiency (CND). Methods This retrospective study included 57 patients with CND who underwent CI surgery. Patients were divided into four groups according to hearing level (80–95, 95–110, 110–120, and >120 dB) and three groups according to residual hearing (entire spectrum hearing, partial spectrum hearing, and no spectrum hearing) based on the measured response at each frequency. Auditory performance (categorical auditory performance [CAP], Infant–Toddler Meaningful Auditory Integration Scale [IT‐MAIS]) and speech perception (speech intelligibility rating [SIR] and meaningful use of speech scale [MUSS]) were assessed before and 2 years after the surgery. Results Forty‐seven (82.5%) patients had complete or total hearing loss (≥95 dB) and 17 (29.8%) had no spectrum hearing before CI surgery. Twenty‐nine (50.9%) patients did not exhibit residual hearing at 4 kHz. All patients demonstrated an improvement in auditory performance and speech perception: the CAP score in the 80–95 dB group was significantly higher than that in the 110–120 and >120 dB groups, and the entire spectrum hearing group showed significantly higher CAP, SIR, and IT‐MAIS scores than the partial spectrum hearing group and significantly higher CAP, SIR, IT‐MAIS, and MUSS scores than the no spectrum hearing group. Conclusion For patients with CND, residual hearing, especially high‐frequency residual hearing, was poor and postoperative audiologic outcomes were significantly associated with the range of residual hearing. Level of Evidence 4

Abstract Background Avian coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The extensive use of anticoccidial drugs has resulted in an increase in drug resistance. Ethanamizuril (EZL) is a novel triazine with high anticoccidial activity. Methods We compared oocyst production and sporulation between EZL-sensitive (S) and EZL-resistant Eimeria tenella strains (R10 and R200) and used label-free quantitative proteomics to identify differentially expressed proteins (DEPs) between these strains. Results We generated two EZL-resistant E. tenella strains: strain R10, which was induced using a constant dose of 10 mg EZL/kg poultry feed, and strain R200, which was generated by gradually increasing the EZL dosage to 200 mg EZL/kg poultry feed. With an increase in resistance, the total oocyst output decreased, but the percentage of sporulation did not change significantly. We identified a total of 7511 peptides and 1282 proteins, and found 152 DEPs in the R10 strain versus the S strain, 426 DEPs in the R200 strain versus the S strain and 494 DEPs in the R200 strain versus the R10 strain. When compared with the S strain, 86 DEPs were found to have consistent trends in both resistant strains. The DEPs were primarily involved in ATP and GTP binding, invasion, and membrane components. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the DEPs suggested that they are involved in transcription and translation processes. Protein–protein interaction network analysis of the 86 DEPs showed that 10 proteins were hubs in the functional interaction network (≥ 8 edges) and five of them were ribosomal proteins. Conclusions The results of the present study indicate that the resistance mechanisms of E. tenella against EZL might be related to the transcriptional and translational processes, especially in the factors that inhibit the growth of parasites. The DEPs found in this study provide new insights into the resistance mechanisms of E. tenella against EZL. Further research on these potential targets holds promise for new chemotherapeutic approaches for controlling E. tenella infections. Graphical Abstract

Abstract Substantial progress has been made in the understanding of gas‐involving electrochemical reactions recently for the sake of clean, renewable, and efficient energy technologies. However, the specific influence mechanism of the microenvironment at the reaction interface on the electrocatalytic performance (activity, selectivity, and durability) remains unclear. Here, we provide a comprehensive understanding of the interfacial microenvironment of gas‐involving electrocatalysis, including carbon dioxide reduction reaction and nitrogen reduction reaction, and classify the factors affecting the reaction thermodynamics and kinetics into gas diffusion, proton supply, and electron transfer. This categorization allows a systematic survey of the literature focusing on electrolyzer‐level (optimization of the device, control of the experimental condition, and design of the working electrode), electrolyte‐level (increase of gas solubility, regulation of proton supply, and substitution of anodic reaction), and electrocatalyst‐level strategies (promotion of gas affinity, adjustment of hydrophobicity, and enhancement of conductivity), aiming to retrieve the correlations between the microenvironment and electrochemical performance. Finally, priorities for future studies are suggested to support the comprehensive improvement of next‐generation gas‐involving electrochemical reactions.

Abstract Background Diabetic foot (DF) is one of the most common and serious complications of diabetes mellitus (DM), which brings great psychological and economic pressure to patients. This study aimed to evaluate the efficacy of stem cells in the treatment of diabetic foot. Methods All relevant studies in Cochrane, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases were systematically searched for meta-analysis. The outcomes consisted of ulcer or wound healing rate, amputation rate, new vessels, ankle–brachial index (ABI), transcutaneous oxygen pressure (TcPO2), pain-free walking distance, and rest pain score. Dichotomous outcomes were described as risk ratios (RR) with 95% confidence intervals (CIs), while continuous data were presented as standardized mean differences (SMDs) with 95% CIs. Statistical analysis was performed with RevMan 5.3 software. Results A total of 14 studies with 683 participants were included in the meta-analysis. Meta-analysis showed that stem cell therapy was more effective than conventional therapy in terms of ulcer or wound healing rate [OR = 8.20 (5.33, 12.62)], improvement in lower extremity ischemia(new vessels) [OR = 16.48 (2.88, 94.18)], ABI [MD = 0.13 (0.04, 0.08)], TcO2[MD = 4.23 (1.82, 6.65)], pain-free walking distance [MD = 220.79 (82.10, 359.48)], and rest pain score [MD = − 1.94 (− 2.50, − 1.39)], while the amputation rate was significantly decreased [OR = 0.19 (0.10, 0.36)]. Conclusions The meta-analysis of the current studies has shown that stem cells are significantly more effective than traditional methods in the treatment of diabetic foot and can improve the quality of life of patients after treatment. Future studies should conduct large-scale, randomized, double-blind, placebo-controlled, multicenter trials with high-quality long-term follow-up to demonstrate the most effective cell types and therapeutic parameters for the treatment of diabetic foot.

Abstract Women's blood pressure (BP) changes throughout pregnancy. The effect of BP trajectories on preterm delivery is not clear. The authors aim to evaluate the association between maternal BP trajectories during pregnancy and preterm delivery. The authors studied pregnant women included in the Born in Guangzhou Cohort Study in China between February 2012 and June 2016. Maternal BP was measured at antenatal visits between 13 and 40 gestational weeks, and gestational age of delivery data was collected. The authors used linear mixed models to capture the BP trajectories of women with term, and spontaneous and iatrogenic preterm delivery. BP trajectories of women with various gestational lengths (34, 35, 36, 37, 38, 39, 40 weeks) were compared. Of the 17 426 women included in the analysis, 618 (3.55%) had spontaneous preterm delivery; 158 (.91%) had iatrogenic preterm delivery; and 16 650 (95.55%) women delivered at term. The BP trajectories were all J‐shaped curves for different delivery types. Women with iatrogenic preterm delivery had the highest mean BP from 13 weeks till delivery, followed by those with spontaneous preterm delivery and term delivery (p

While the role of platelets in cardiovascular diseases among the general population has been widely reported, evidence is inconsistent regarding the association between platelet indices with hypertension in pregnant women. In this study, we explored the associations between platelet parameters before 20 gestational weeks, an understudied period, with hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PEEC) and gestational hypertension (GH). Based on the Born in Guangzhou Cohort Study, 12053 singleton pregnant women with platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) measured at 14–19 gestational weeks were included. Conventional multivariable adjustment and propensity score analysis were used to control for confounders. The restricted cubic spline showed that the risk of PEEC increased linearly for PC, and non-linearly for PCT. For GH, the risk increased linearly for PC, MPV, and PCT, and non-linearly for PDW. When these indices were categorized into quintiles, women with higher PC and PCT were associated with increased risk of both PEEC and GH. Women with MPV exceeding the second quintile (≥ 8.8 fL) had a greater risk for GH, but not for PEEC. When HDP was classified into two groups (early- vs late-onset) based on the occurrence time, significant associations persisted for early-onset PEEC, early-onset GH, and late-onset GH. In conclusion, increased PC and PCT before 20 weeks of gestation were both associated with higher risk of PEEC and GH, while elevated MPV was only linked to GH.

Abstract Background Acute kidney injury (AKI) is a serious complication that often occurred after acute type A aortic dissection (ATAAD) surgery. Previous studies proved that the Kidney Disease Improving Global Outcomes (KDIGO) defined stage 3 AKI was associated with lower long-term survival rate. However, the risk factors for developing stage 3 AKI had not been identified. The aim of the study was to explore the risk factors for developing KDIGO stage 3 after ATAAD operation. Methods This study included 993 patients who received ATAAD operation from 2014 to 2019 at the Nanjing Drum Tower Hospital. Postoperative AKI was diagnosed according to the KDIGO criteria. Multivariate logistic regression analyses were applied to identify risk factors for stage 3 AKI. Kaplan–Meier survival analyses and Cox proportional hazards regression model were conducted to explore the association between different AKI stages and postoperative survival rate. Results The mean age of all enrolled patients was 53.0 ± 13.1 years. A total of 236 (23.8%) patients suffered postoperative stage 3 AKI including 165 patients who required renal replacement therapy. Advanced age (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.005–1.057; P = 0.018), prolonged cardiopulmonary bypass (CPB) duration (OR 1.010; 95% CI 1.002–1.018; P = 0.013), and higher drainage volume 24 h after surgery (OR 1.000; 95% CI 1.000–1.001; P = 0.033) were identified as independent risk factors for developing stage 3 AKI. In addition, our result showed that the mortality rate was correlated significantly with the severity of AKI defined by KDIGO criteria and the Cox regression analysis showed that only stage 3 AKI, but not stage 1 and 2, was an independent risk factor for mortality (Hazard ratio 10.365, 95% CI 4.208 to 25.528; P

Abstract There is a paucity of data describing the safety and efficacy of acute type A aortic dissection (ATAAD) repair surgeries in dialysis patients. Our study aimed to investigated the influence of dialysis on early and late outcomes in end-stage renal disease (ESRD) patients who received repair surgery for ATAAD. A total of 882 ATAAD patients who received emergency aortic dissection repair at our center from January 2015 to December 2019 were retrospectively screened in this study and divided into the dialysis group (n = 16) and the non-dialysis group (n = 866), depending on whether they required dialysis for preoperative ESRD. No significant difference of age, preoperative hemodynamics, organ ischemia conditions, operative variables as well as the 30-Day mortality and in-hospital complications was discovered between two groups. However, the survival rates and the proportion of late aortic event (sudden death and reoperation) free population at 1 and 3 years after surgery were significantly decreased in dialysis patients compared to non-dialysis patients. Our study indicated that the short-term surgical outcomes of ATAAD in dialysis patients were comparable to non-dialysis patient. However, the dialysis patients were associated with a worse long-term prognosis.

Background:Macleaya cordata extract (MCE) is effective in the treatment of enteritis, but its mechanism has not been fully elucidated. Therefore, this study combined network pharmacology and molecular docking technologies to investigate the potential pharmacological mechanism of MCE in the treatment of enteritis.Methods: The information of active compounds in MCE was accessed through the literature. Furthermore, PubChem, PharmMapper, UniProt, and GeneCards databases were used to analyze the targets of MCE and enteritis. The intersection of drug and disease targets was imported into the STRING database, and the analysis results were imported into Cytoscape 3.7.1 software to construct a protein–protein interaction (PPI) network and to screen core targets. The Metascape database was used for conducting Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. AutoDock Tools software was used for the molecular docking of active compounds with the core targets.Results: MCE has four active compounds, namely, sanguinarine, chelerythrine, protopine, and allocryptopine, and a total of 269 targets after de-duplication. Furthermore, a total of 1,237 targets were associated with enteritis, 70 of which were obtained by aiding the drug–disease intersection with the aforementioned four active compound targets of MCE. Five core targets including mitogen-activated protein kinase 1 (MAPK1) and AKT serine/threonine kinase 1 (AKT1) were obtained using the PPI network, which are considered the potential targets for the four active compounds of MCE in the treatment of enteritis. The GO enrichment analysis involved 749 biological processes, 47 cellular components, and 64 molecular functions. The KEGG pathway enrichment analysis revealed 142 pathways involved in the treatment of enteritis by the four active compounds of MCE, among which PI3K-Akt and MAPK signaling pathways were the most important pathways. The results of molecular docking showed that the four active compounds demonstrated good binding properties at the five core targets.Conclusion: The pharmacological effects of the four active compounds of MCE in the treatment of enteritis involve acting on signaling pathways such as PI3K-Akt and MAPK through key targets such as AKT1 and MAPK1, thus providing new indications for further research to verify its mechanisms.

Developing novel photoresponsive oxidase mimics is highly useful for environmental pollution monitoring and biological sensing. Herein, long-life room-temperature phosphorescent nitrogen-doped carbon quantum dots (P-NCDs) were synthesized from triethylenetetramine hexaacetic acid via a simple one-step hydrothermal method. The P-NCDs showed high photoresponsive oxidase-like activity. On this basis, a P-NCD-based photostimulated colorimetric sensing system was developed and used to detect Hg2+ in environmental and biological samples. P-NCDs under 365 nm UV lamp irradiation converted dissolved oxygen, via triplet excited state (T1) exciton transfer, to singlet oxygen (1O2), which then oxidized 3,3′,5,5′-tetramethylbenzidine (TMB), leading to a color changing reaction. Cysteine can suppress the catalysis of P-NCDs, and its specific complexation with Hg2+ can recover the oxidation activity of P-NCDs. Hence, efficient colorimetric Hg2+ detection with a linear range of 0.01–14 μM and a detection limit of 3.1 nM was achieved by detecting the color change of TMB. The feasibility of this strategy was validated through real sample analysis. Our study broadens the application scope of phosphorescent nanomaterials into colorimetric sensing.

Background: To investigate the sterilizing effect of antimicrobial photodynamic therapy (aPDT) based on PAD™ Plus on mixed biofilms of Candida albicans and Candida tropicalis. Methods: A mature mixed biofilm model of C. albicans and C. tropicalis was constructed in vitro. FITC-concanavalin A staining was conducted to observe the formation of the extracellular matrix. MTT assay was performed to determine biofilm viability. The chromogenic medium was used to examine the Candida composition of the mixed biofilms. For aPDT treatment, based on PAD™ Plus, the biofilms were incubated with 1 mg/mL TBO for 1, 5, or 10 min, followed by 500 or 750 mW LED illumination for 1 or 2 min. The live/dead fungi were detected by SYTO9/propidium iodide staining. A multivariate factorial design was conducted to analyze the correlations of parameters with the inactivation effect of the mixed biofilms. Results: Mature mixed biofilms formed at 24 h after seeding. Compared with untreated biofilms, following 1-min TBO incubation, 500 mW LED illumination for 1 min inactivated more than 90% of the fungi. Extending the incubation time did not significantly improve the inactivation effect. Application of 750 mW output power or 2 min LED illumination inactivated more than 99% of the fungi without increasing other parameters. Conclusions: PAD™ Plus combined with 1 mg/mL TBO can rapidly inactivate the mature mixed biofilms of C. albicans and C. tropicalis, serving as a robust platform for the treatment of mixed infections of C. albicans and C. tropicalis.

To evaluate the prevalence, influencing factors, and behavior rules of self-medication in children. Articles on self-medication in children from various electronic databases (PubMed, Cochrane Library, Web of Science, the WHO website ( https://www.who.int/ ), ABI, CNKI, and Wanfang), were searched to August 2022. The single-group meta-analyses of the prevalence, influencing factors, and behavior rules of self-medication in children were performed using Revman 5.3 and Stata 16.0. The overall pooled prevalence of self-medication in children was 57% (95% CI: 0.39-0.75, I² = 100%, P

Abstract Background Despite the well-studied effects of gestational weight gain (GWG) on offspring health, little is known about the association of trimester-specific GWG with offspring birth weight among underweight pregnant women. This study aimed to explore the association of trimester-specific GWG rate with small for gestational age (SGA) in underweight women. Methods The GWG rate of underweight pregnant women (pre-pregnancy body mass index [BMI] lower than 18.5 kg/m2) of the Born in Guangzhou Cohort Study was calculated as the weight gain during a specific trimester divided by the corresponding duration of week. Total GWG was calculated as the weight difference between pre-pregnancy and delivery, and was categorized into inadequate, adequate, and excessive weight gain based on the 2009 Institute of Medicine (IOM) weight gain recommendation. The INTERGROWTH-21st standards were used to define SGA. Logistic regression models were used to examine the associations of total GWG and trimester-specific GWG rates with SGA. Associations between trimester-specific GWG rates and SGA were also analyzed separately based on different total GWG categories (i.e. inadequate and adequate/excessive GWG). Results Of the 3839 participants, SGA births occurred in 397 (10.3%), and mean GWG was 14.9 kg (SD 3.9). A lower risk of SGA was observed among women with higher GWG rate (per 0.5 kg/week increase) during the first (adjusted OR [aOR] 0.74, 95%CI 0.57, 0.96) and second (adjusted OR [aOR] 0.40, 95%CI 0.30, 0.55) but not third trimester. Similar association between higher GWG rate during the second trimester and a decreased risk of SGA were observed among women with inadequate (

Basal bulb rot is the major factor restricting the production of lily, caused by Fusarium oxysporum f. sp. lilii. To systematically analyze the transcriptomic and proteomic responses of lily clones to F. oxysporum, we constructed six RNA-seq libraries and four iTRAQ proteomic libraries using lily resistant and susceptible clones sampled at 0, 24 and 48 h post-inoculation (hpi) with F. oxysporum respectively. 137,715 unigenes were generated, of which 7,667 were differentially expressed. 1,679 and 4,051 differentially expressed genes (DEGs) between resistant and susceptible clones were isolated from samples collected at 0 and 48 hpi. Four hundred and thirty three and 155 DEGs were identified in resistant clones sampled at 24 and 48 hpi separately while 550 and 799 DEGs were isolated in the susceptible clones sampled at 24 and 48 hpi respectively. The results of iTRAQ analysis revealed 7,482 proteins in resistant and susceptible clones. Data analysis of transcriptome and proteome indicated that 5,735 proteins corresponded to mRNAs. Three hundred and sixteen and 1,052 DEGs had corresponding DEPs. At 48 hpi, the resistant clones showed 155 DEGs and 108 corresponding DEPs, while the susceptible clones showed 799 DEGs and 316 corresponding DEPs. In general, these results enhance comprehension of the defense response of lily resistant clones to F. oxysporum infection and provide valuable sequence data for studying the resistance mechanism.

A public-private-graph (pp-graph) is developed to model social networks with hidden relationships, and it consists of one public graph in which edges are visible to all users, and multiple private graphs in which edges are only visible to its endpoint users. In contrast with conventional graphs where the edges can be visible to all users, it lacks accurate indexes to evaluate the importance of a vertex in a pp-graph. In this paper, we first propose a novel concept, public-private-core (pp-core) number based on the k-core number, which integrally considers both the public graph and private graphs of vertices, to measure how critical a user is. We then give an efficient algorithm for the pp-core number computation, which takes only linear time and space. Considering that the graphs can be always evolving over time, we also present effective algorithms for pp-core maintenance after the graph changes, avoiding redundant re-computation of pp-core number. Extension experiments conducted on real-world social networks show that our algorithms achieve good efficiency and stability. Compared to recalculating the pp-core numbers of all vertices, our maintenance algorithms can reduce the computation time by about 6–8 orders of magnitude.