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Abstract Background Immune checkpoint inhibitors (ICIs) show optimal treatment effects on recurrent or metastatic nasopharyngeal carcinoma(R/M NPC). Nonetheless, whether metastatic sites impact ICIs efficacy remains unclear. Methods We performed a secondary analysis of R/M NPC patients treated with KL-A167, a programmed cell death-ligand 1(PD-L1) inhibitor, based on a multicenter, single-arm, phase II study from China between 2019 and 2021 years, which represents the first and most comprehensive analysis of the effectiveness of a PD-L1 inhibitor in patients who have been previously treated. The Cox proportional hazard model was utilized to evaluate the association between sites and PFS and OS. Sensitivity analysis and subgroup analysis were carried out to confirm the reliability of our findings. Results A total of 153 R/M NPC patients were included. The mean age was 47 years and 81% of patients were males. All patients in our study had distant metastasis, with a majority (n = 69) presenting with more than 2 sites of distant metastasis upon admission. The collected sites of metastasis included liver, lung, lymph and bone. Among the 153 patients, 37.9% (58 patients) received anti-PD-L1 treatment for a minimum of 6 months, and 17.6% (27 patients) were treated for at least 12 months. By conducting multivariate analysis, R/M NPC patients with non-liver metastases presented significantly longer progress-free survival (PFS, HR:1.67, CI:1.09–0.2.55, p = 0.018) and overall survival (OS, HR:2.52, CI:1.49–4.28, p 0.005). Our sensitive analysis showed liver metastases patients with less other site metastases (0 or 1) had shorter OS compared to non-liver metastases patients with more other metastases(≥ 2). Furthermore, subgroup analysis indicated the robustness evidence liver metastasis indeed a valuable prognostic factor for survival. Conclusions Compared to patients with other metastatic sites, R/M NPC patients with liver metastasis have poor survival patterns when receiving anti-PD-L1 therapy. Our study provides rational evidence for the urgent need to explore more efficacy treatment modalities for NPC patients with liver metastasis.

Abstract Background Dexamethasone has been widely used in treating severe COVID-19 patients due to its anti-inflammatory properties. However, its long-term impact on mortality remain unclear. Objective To evaluate the effect of dexamethasone on short-term (28-day) and long-term (1-year) mortality in hospitalized COVID-19 patients and to explore its efficacy across different respiratory support. Methods A retrospective cohort study was conducted using the MIMIC-IV (v3.0) database. A total of 576 confirmed COVID-19 patients were included, with 288 patients receiving dexamethasone and 288 not receiving it, matched by propensity scores. Survival analyses assessed the impact of dexamethasone on mortality, and subgroup analyses were performed based on the type of respiratory support received. Results After propensity score matching, dexamethasone treatment was associated with reduced mortality at both 28 days (adjusted HR 0.67, 95% CI 0.46–0.99, P = 0.045) and 1 year (adjusted HR 0.66, 95% CI 0.47–0.92, P = 0.014). Subgroup analysis revealed differential treatment effects by respiratory support type (P for interaction = 0.001 at 28 days and 0.004 at 1 year). The survival benefit was most pronounced in patients receiving NIV (28-day adjusted HR 0.15, 95% CI 0.05–0.42, P

Abstract The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs’ preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs’ biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials. Graphical Abstract

There is a need to reduce human–wildlife conflicts in the area around Liupanshan Nature Reserve in Ningxia Hui Autonomous Region, China. This study investigated the financial losses caused by wild boar and their causes. A questionnaire investigation (n = 135) and a field test were conducted, which included 108 sample lines and 97 infrared cameras. A principal component analysis and generalised linear model was used to analyse the importance of the effect of the factors on wild boar damage. Based on an estimate of 17,049 wild boars in the study area, we found that in the agricultural land owned by the residents, the boar density of each county and distance from the village to the nature reserve were the most significant factors that affected crop damage. Then, financial losses in spring, summer, and autumn had a moderate effect on financial loss, and the crop type had the lowest effect. We recommend reducing the wild boar population by increasing leisure hunting and the number of leopards. Additionally, a focus on farmland protection is a practical way to prevent wild boar invasions. Meanwhile, it is also necessary to conduct long-term monitoring of wild boar population status and manage the relationship between the government, research teams, and local people to more efficiently and comprehensively reduce conflicts between humans and wild boars.

Fast motion and high adaptability are crucial for the practical applications of miniature robots. However, combining these capabilities into a single robot skillfully is challenging, particularly in the domain of miniature structural design. Inspired by the amphibious motion of crocodiles in nature, a hollow piezoelectric miniature robot (HPMR) is proposed. The key benefit of the HPMR is to concurrently output the oscillating motion of the driving foot (oscillating mode) and the rotating motion of the internal rotor (rotating mode). That is, the mode of single‐energy‐input‐multimotion output allows the robot to balance the requirements of speed and adaptability. In the oscillating mode, HPMR can run at speeds of up to 12.3 BL s−1 and realize a displacement resolution of 0.3 μm. Following the conical rotor assembly, the rotor can operate at a speed of 890 rpm, with a displacement resolution of 7.28 mrad. In the rotating mode, the robot demonstrates its multitasking ability in moving amphibiously, carrying loads, running on surfaces with varying roughness, crossing obstacles, and resisting shocks. The results show that the HPMR is capable of fast, high‐resolution moving combined with high adaptability, opening up the possibility of using it for mobile detection tasks in real‐world settings.

Abstract Objectives Microcephaly is caused by reduced brain volume and most usually associated with a variety of neurodevelopmental disorders (NDDs). To provide an overview of the diagnostic yield of whole exome sequencing (WES) and promote novel candidates in genetically unsolved families, we studied the clinical and genetic landscape of an unselected Chinese cohort of patients with microcephaly. Methods We performed WES in an unselected cohort of 103 NDDs patients with microcephaly as one of the features. Full evaluation of potential novel candidate genes was applied in genetically undiagnosed families. Functional validations of selected variants were conducted in cultured cells. To augment the discovery of novel candidates, we queried our genomic sequencing data repository for additional likely disease-causing variants in the identified candidate genes. Results In 65 families (63.1%), causative sequence variants (SVs) and clinically relevant copy number variants (CNVs) with a pathogenic or likely pathogenic (P/LP) level were identified. By incorporating coverage analysis to WES, a pathogenic or likely pathogenic CNV was detected in 15 families (16/103, 15.5%). In another eight families (8/103, 7.8%), we identified variants in newly reported gene (CCND2) and potential novel neurodevelopmental disorders /microcephaly candidate genes, which involved in cell cycle and division (PWP2, CCND2), CDC42/RAC signaling related actin cytoskeletal organization (DOCK9, RHOF), neurogenesis (ELAVL3, PPP1R9B, KCNH3) and transcription regulation (IRF2BP1). By looking into our data repository of 5066 families with NDDs, we identified additional two cases with variants in DOCK9 and PPP1R9B, respectively. Conclusion Our results expand the morbid genome of monogenic neurodevelopmental disorders and support the adoption of WES as a first-tier test for individuals with microcephaly.

At present, casein can be isolated from skim milk by membrane filtration technology, and micellar casein concentrate could be obtained by concentration, sterilization, drying. In this paper, the factors affecting the composition of micellar casein concentrate and its application in cheese production were reviewed. It was found that pH value, temperature and diafiltrant during membrane filtration all affected the composition of micellar casein concentrate, resulting in different concentrations of casein, whey protein, lactose and calcium. It is also possible to standardize raw milk by micellar casein concentrate to produce cheese with the same composition and quality. It is also possible to obtain different raw milk compositions by micellar casein concentrate having different components to produce cheese with desired quality and function. In conclusion, the addition of micellar casein concentrate could affect the composition, texture and flavor of cheese during cheese production, but these problems could be solved by adjusting the process parameters of membrane filtration and cheesemaking. Further research will be still required to find an economic way to preserve micellar casein concentrate and give it extended shelf life, good rennet properties to ensure cheese quality and yield.

Nanostructured bismuth oxide bromide (BiOBr) has attracted considerable attention as a visible light catalyst. However, its photocatalytic degradation efficiency is limited by its low specific surface area. In this study, a solvothermal approach was employed to synthesize BiOBr, which was subsequently loaded onto cellulose nanofibers (CNFs) to obtain a bismuth halide composite catalyst. The performance of this catalyst in the removal of refractory organic pollutants such as tetracycline (TC) from solutions under visible light excitation was examined. Our results indicate that BiOBr/CNF effectively removes TC from the solution under light conditions. At a catalyst dosage of 100 mg/L, the removal efficiency for TC (with an initial concentration of 100 mg/L) was 94.2%. This study elucidates the relationship between the microstructure of BiOBr/CNF composite catalysts and their improved photocatalytic activity, offering a new method for effectively removing pollutants from water.

Abstract In this phase I study, the safety, pharmacokinetics, and antitumour activity of the HER2-targeted antibody–drug conjugate A166 were evaluated in patients with HER2-expressing advanced solid tumours. Patients with advanced solid tumours refractory to standard therapies received A166 at doses of 0.1, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8 or 6.0 mg/kg Q3W in a standard “3 + 3” design. Dose cohorts were expanded at 4.8 and 6.0 mg/kg Q3W. Primary endpoints were assessment of the safety and tolerability of A166 and identification of the maximum tolerated dose or recommended phase II dose. In total, 81 patients were enroled and received A166 (n = 1 for 0.1 mg/kg; n = 3 for each of 0.3, 0.6, 1.2, 2.4 and 3.6 mg/kg doses; n = 27 for 4.8 mg/kg; n = 38 for 6.0 mg/kg). No dose-limiting toxicity or drug-related deaths occurred. The most common treatment-related adverse events at grade 3 or higher were corneal epitheliopathy (30.9%), blurred vision (18.5%), dry eyes (7.4%), and peripheral sensory neuropathy (6.2%). The Cmax and area under the curve of Duo-5, its free payload, were approximately 0.1% and 0.2% of those of the ADC, respectively. For all assessable HER2-positive breast cancer patients enroled in the 4.8 mg/kg and 6.0 mg/kg cohorts, the corresponding ORRs were 73.9% (17/23) and 68.6% (24/35), respectively, and the median PFS was 12.3 and 9.4 months, respectively. A166 has a recommended phase II dose of 4.8 mg/kg Q3W, manageable toxicity, good stability in the circulation and promising antitumour activities in HER2-positive breast cancer patients.

This case report describes a 47-year-old woman with systemic lupus erythematosus (SLE) complicated by Libman–Sacks endocarditis (LSE) who developed multiple organ dysfunction after mitral valve replacement surgery. The patient presented with a 5-day history of cough, sputum, and fever. Transthoracic echocardiography showed significant vegetations on the mitral valve. Biopsy was performed, and the pathological diagnosis was SLE complicated by LSE. After the mitral valve replacement surgery, the patient developed clinical manifestations of hepatic and renal dysfunction, cardiopulmonary failure, oliguria, and shock. The clinical symptoms significantly improved after administration of mechanical ventilation, continuous renal replacement therapy, plasma exchange, anti-inflammatory and anti-infection treatments, immunomodulatory and immunosuppressive therapies, and low-molecular-weight heparin anticoagulation. Multiple organ dysfunction after mitral valve replacement in patients with SLE complicated by LSE has rarely been reported. This report discusses the clinical manifestations, pathogenesis, and treatment of this severe complication. We hope the sharing of our experience in this case will provide a clinical basis for the treatment of severe multiple organ dysfunction after mitral valve replacement in patients with SLE complicated by LSE.

The construction of networks within natural wood (NW) lumens to produce porous wood aerogels (WAs) with fascinating characteristics of being lightweight, flexible, and porous is significant for the high value-added utilization of wood. Nonetheless, how wood species affect the structure and properties of WAs has not been comprehensively investigated. Herein, typical softwood of fir and hardwoods of poplar and balsa are employed to fabricate WAs with abundant nanofibrillar networks using the method of lignin removal and nanofibril’s in situ regeneration. Benefiting from the avoidance of xylem ray restriction and the exposure of the cellulose framework, hardwood has a stronger tendency to form nanofibrillar networks compared to softwood. Specifically, a larger and more evenly distributed network structure is displayed in the lumens of balsa WAs (WA-3) with a low density (59 kg m−3), a high porosity (96%), and high compressive properties (strain = 40%; maximum stress = 0.42 MPa; height retention = 100%) because of the unique structure and properties of WA-3. Comparatively, the specific surface area (SSA) exhibits 25-, 27-, and 34-fold increments in the cases of fir WAs (WA-1), poplar WAs (WA-2), and WA-3. The formation of nanofibrillar networks depends on the low-density and thin cell walls of hardwood. This work offers a foundation for investigating the formation mechanisms of nanonetworks and for expanding the potential applications of WAs.

The smart grid optimizes traditional power grids and provides more intelligent services for end users and utilities. However, due to the large number of unsafe devices in the smart grid, there are corresponding risks when implementing relevant solutions on these devices. Therefore, in this article, a security demand response management scheme based on blockchain is proposed to safely make energy trading decisions, thereby realizing the management of the overall load of users in the power grid. In this scheme, the miner node is the verifier. These nodes are responsible for verifying energy transactions in the smart grid (SG) and adding corresponding blocks to the blockchain. Successful energy transactions only occur in blocks in the blockchain. Here, the proposed method is validated through experiments on electric vehicles. The experimental results demonstrate the effectiveness of the proposed scheme in demand response management.

The emergence of carbapenem-resistant organisms posed considerable threat to global health while only limited treatment options are available and led to efforts to discover a novel way to treat them. To evaluate in vitro synergistic activity of meropenem plus ertapenem, a total of 203 carbapenem-resistant strains, collected from 12 provinces and municipalities in China, were examined with a dual carbapenem combination therapy. The statistical software R was used for analysis. Two hundred and one (201) of carbapenem-resistant strains mainly produced four types of carbapenemase: KPC-2 (n = 142, 69.95%), OXA-232 (n = 7, 3.45%), NDM (n = 38, 18.72%; 36 NDM-1, 1 NDM-4, 1 NDM-5), and IMP (n = 15, 7.39%; 1 IMP-26, 10 IMP-30, 4 IMP-4). Fifty-one out of two hundred and three (51/203 or 25.12%) of the examined strains showed a synergistic effect for the meropenem plus ertapenem combination throughout the checkerboard method, while only three isolates showed potential clinically relevant synergy (3/203, 1.48%). An additive effect was observed in 55/203 (27.09%) of the examined strains. Ninety-seven of the examined isolates (47.78%) showed fractional inhibitory concentration (FIC) greater or equal to 2 (indicating antagonism). The synergistic activity of meropenem plus ertapenem combination suggests this combination can be a possible way to treat the infection caused by the carbapenem-resistant organisms, especially for IMP or NDM producer with a lesser minimum inhibitory concentration (MIC) and the infected individual who was not recommended to use colistin or tigecycline.

(1) Background: Vaccine safety is an important topic with public health implications on a global scale. The purpose of this study was to systematically review available literature assessing sensorineural hearing loss (SNHL) incidence and severity following both coronavirus disease 2019 (COVID-19) and non-COVID-19 vaccinations, as well as prognosis and outcomes. (2) Methods: This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Relevant publications evaluating post-vaccination SNHL were selected from PubMed and Embase, searching from inception to July 2023. (3) Results: From 11 observational studies, the incidence of post-vaccination SNHL was low for both COVID-19 and non-COVID-19 vaccines, ranging from 0.6 to 60.77 per 100,000 person-years, comparable to all-cause SNHL. (4) Conclusions: The incidence rates of SNHL following COVID-19 and non-COVID-19 vaccinations remained reassuringly low. Most patients experienced improved hearing function in the weeks to months following vaccination. This study underscores the importance and safety of vaccinations and encourages ongoing surveillance and detailed reporting of hearing loss cases post-vaccination.

Inspired by the biomaterial nacre, we report a versatile and facile strategy to rugged, flame retardant superhydrophobic materials by embedding a nacre-like montmorillonite (MMT) based gas barrier layer into hierarchical epoxy-resins. The well-aligned MMT layer imparted excellent oxygen and water barrier properties that rendered the coating surface water repellent yet protected the substrate materials from fire by suppressing heat and oxygen transfer. The hierarchical epoxy not only provided the robust superhydrophobic structure but offered strong adhesion to MMT layer. After application of this coating to a flammable sponge, it demonstrated superhydrophobicity with a contact angle of ∼153°. Furthermore, the material was rugged, resisting 1200 compression cycles and induced marked flame retardancy. The coated sponge delayed ignition (689% delay in ignition time) and promoted significant flame extinguishing property, compared with the uncoated material (demonstrated by LOI, CONE combustion, and fire scenario tests). Owing to its robustness and multifunctionality, the coated sponge was able to efficiently separate oil from multi-environments including strong corrosive, icy, boiling or vibrating mixtures. Additionally, the versatile application to wood, cotton, textile and other lignocellulosic substrates has been verified. This research opens up a new direction for durable waterproof and fireproof materials.

Ensuring that the elderly drink adequate fluids to meet their recommended daily allowance is often a challenge, especially among the elderly in hospitals and long-term care settings. The complex interplay of biological, medical and psychosocial factors that cause the elderly to become dehydrated is difficult to tackle especially in care settings where there is a staff shortage and heavy workload. The team realised that 90% of the elderly inpatients in the general ward of a teaching hospital in Singapore were not drinking enough to meet their needs, despite the hot and humid weather. Reasons which contributed to inadequate fluid intake included human resources, environmental, patient and system factors. Strategies were put in place to improve fluid intake but were not successful, due to staff shortage and time constraints. The team ended up innovating and producing a dysphagia cup to improve fluid intake, promote independence among patients while encouraging them to drink more, improve nursing efficiency, reduce caregiver burden and reduce aspiration risk. The cup was able to meet all the expectations with good feedback from the care team, patients and their families.

In view of two modes of general shear failure and composite failure of reinforced ground, a new solution to the ultimate bearing capacity of strip footings resting on reinforced ground near slope was derived based on the unified strength theory and the application procedures were given. Effects of the intermediate principal stress, the vertical spacing between reinforced material layers, the number of reinforced material layers, and the tensile strength of reinforced materials were comprehensively taken into consideration in the new solution. Compared with other methods, the effectiveness and parameter influence characteristics of the proposed method were discussed. The results showed that the obtained solution to the ultimate bearing capacity of reinforced ground agreed well with the results of model tests reported in the literature, and it had wide applicability. With the increase of the effect of intermediate principal stress, the ultimate bearing capacity of reinforced ground near slope subjected to general shear failure and composite failure increased markedly. As the vertical spacing between reinforced material layers increased, the ultimate bearing capacity of reinforced ground near slope increased first and then decreased under the general shear failure, but it would gradually reduce under the composite failure. The influence of the number of reinforced layers under the general shear failure can be divided into three stages, and that under the composite failure can be divided into two stages. Meanwhile, the effect of the tensile strength of reinforced materials cannot be ignored. The research results can provide useful references for the optimization design of reinforced ground near slope.

OBJECTIVES The Xiuwacu Mo-W deposit is a typical hydrothermal quartz vein deposit in the Yidun island arc Cu-Mo metallogenic belt, northwest Yunnan. Numerous studies have been conducted on rock and ore chronology and petrogenesis, dynamics, but its ore-forming fluid evolution has been rarely studied. OBJECTIVES To reveal the origin and evolution of ore-forming fluids of the Xiuwacu Mo-W deposit. METHODS Scanning electron microscope (SEM) cathodoluminescence method, and in situ trace element (LA-ICP-MS) and in situ Sr (fs-LA-MC-ICP-MS) isotope analyses of scheelite. RESULTS The occurrences of scheelite and the cathodoluminescence images indicated three generations of scheelite, Ⅰ, Ⅱ, and Ⅲ, with the middle stage scheelite being the most developed. The rare earth element pattern of the scheelite in the early stage was similar to that of the porphyritic granite. It showed a right-inclined pattern with light rare earth enrichment and a moderate negative Eu anomaly (δEu=0.42). The average Mo content was 3.0%, and the average 87Sr/86Sr was 0.7098, close to the specular feldspar granite (0.7075-0.7098). Compared with scheelite in the early stage, the content of light rare earth elements in the scheelite from the middle stage was low, and Eu also had a medium negative anomaly (δEu=0.37). Mo content was reduced to an average of 2445μg/g, and 87Sr/86Sr increased to 0.7113. The rare earth distribution pattern of scheelite in the later stage showed an arched pattern with relative enrichment of middle rare earth and no Eu anomaly (δEu=0.93). Mo content of scheelite decreased to 56μg/g, and average 87Sr/86Sr was 0.7083. Conclusion From early to late, the gradual decrease of light rare-earth elements, especially La and Ce, in scheelite indicates the crystallization of bastnaesite. The increase in δEu and the sharp decrease in Mo content indicate the transformation of ore-forming fluids from oxidation to reduction. The change of Sr isotope composition indicates the change in the source of ore-forming materials. The magmatic fluid contributed a lot in the early stage, and the large-scale interaction between the magma-hydrothermal fluids and surrounding rocks is responsible for the formation of scheelite in the middle stage. The strata provide amounts of Ca for scheelite formation, indicating that strong water-rock interaction played an important role in the formation of the deposit.

Abstract Background While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding of the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing E. coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants. Methods We analysed ARGs in the first year of life among 75 infants at risk of eczema who had stool samples collected at multiple timepoints using metagenomics. Results The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively. Conclusion In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.

BACKGROUND The Nanyangtian scheelite deposit is an important skarn scheelite deposit in Yunnan Province, which is located in Laojunshan W-Sn deposit area, Southeast Yunnan. Due to its complex geological background and multi-stage metallogenic characteristics, its mineralization age and genesis remain controversial. OBJECTIVES To explore the metallogenic age, genesis and material origins of two types of scheelite deposits in order to explore formation patterns. METHODS Molybdenum Re-Os isotope dating was used to constrain the age, whereas in situ trace element and in situ Sr isotopes of scheelite were used to determine the composition of trace elements and Sr isotopes in scheelite. RESULTS The Re-Os isochron age of molybdenite associated with scheelite in the feldspar-quartz mineral vein of Nanyantian was 151.0±1.3Ma, younger than the age of skarn mineralization, indicating a later mineralization event. The skarn-type scheelite was enriched in light rare earth elements with negative Eu anomaly (δEu=0.46). The average content of ∑REE, Mo and Sr in skarn scheelite were 65.60, 240.16 and 883.43μg/g, respectively. Feldspar-quartz vein-type scheelite showed a flat rare earth pattern with positive Eu anomaly (δEu=2.8) and average content of ∑REE, Mo and Sr were 194.40, 16.01 and 129.26μg/g, respectively. respectively. The skarn scheelite had a relatively low and uniform 87Sr/86Sr value of 0.71319 to 0.71491, indicating that the ore-forming fluids were mainly magmatic-hydrothermal in origin, whereas feldspar-quartz vein type scheelite had a wide 87Sr/86Sr range of 0.71537 to 0.72803, with an average of 0.72079, characteristic of metamorphic fluids. CONCLUSIONS The differences in trace and rare earth element contents between two types of mineralization indicate that they have different fluid sources. The negative Eu anomaly of the skarn-type scheelite indicates a high oxygen fugacity environment, whereas the feldspar-quartz vein-type scheelite is formed in a reductive environment in terms of positive Eu anomaly. Sr isotopes of two different types of scheelite display a feature of binary mixing, indicating that feldspar-quartz vein-type scheelite has a superimposed transformation effect on skarn-type scheelite, and the strong metasomatism of ore-forming fluids and surrounding rocks is the key to the formation of scheelite.

IntroductionLupus nephritis (LN) is a major risk factor of morbidity and mortality. Glomerular injury is associated with different pathogeneses and clinical presentations in LN patients. However, the molecular mechanisms involved are not well understood. This study aimed to explore the molecular characteristics and mechanisms of this disease using bioinformatics analysis.MethodsTo characterize glomeruli in LN, microarray datasets GSE113342 and GSE32591 were downloaded from the Gene Expression Omnibus database and analyzed to determine the differentially expressed genes (DEGs) between LN glomeruli and normal glomeruli. Functional enrichment analyses and protein–protein interaction network analyses were then performed. Module analysis was performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape software. Immunofluorescence staining was performed to identify the glomerular expression of S100A8 in various International Society of Nephrology/Renal Pathology Society (ISN/RPS) class LN patients. The image of each glomerulus was acquired using a digital imaging system, and the green fluorescence intensity was quantified using Image-Pro Plus software.ResultsA total of 13 DEGs, consisting of 12 downregulated genes and one upregulated gene (S100A8), were identified in the microarray datasets. The functions and pathways associated with the DEGs mainly include inflammatory response, innate immune response, neutrophil chemotaxis, leukocyte migration, cell adhesion, cell–cell signaling, and infection. We also found that monocytes and activated natural killer cells were upregulated in both GSE113342 and GSE32591. Glomerular S100A8 staining was significantly enhanced compared to that in the controls, especially in class IV.ConclusionsThe DEGs identified in the present study help us understand the underlying molecular mechanisms of LN. Our results show that glomerular S100A8 expression varies in different pathological types; however, further research is required to confirm the role of S100A8 in LN.

Developing highly porous and conductive carbon electrodes is crucial for high-performance electrochemical double-layer capacitors. We provide a method for preparing supercapacitor electrode materials using zeolitic imidazolate framework-8 (ZIF-8)-coated wood fibers. The material has high nitrogen (N)-doping content and a specific surface area of 593.52 m2 g−1. When used as a supercapacitor electrode, the composite exhibits a high specific capacitance of 270.74 F g−1, with an excellent capacitance retention rate of 98.4% after 10,000 cycles. The symmetrical supercapacitors (SSCs) with two carbon fiber electrodes (CWFZ2) showed a high power density of 2272.73 W kg−1 (at an energy density of 2.46 W h kg−1) and an energy density of 4.15 Wh kg−1 (at a power density of 113.64 W kg−1). Moreover, the SSCs maintained 81.21% of the initial capacitance after 10,000 cycles at a current density of 10 A g−1, which proves that the SSCs have good cycle stability. The excellent capacitance performance is primarily attributed to the high conductivity and N source provided by the zeolite imidazole framework. Because of this carbon material’s unique structural features and N-doping, our obtained CWFZ2 electrode material could be a candidate for high-performance supercapacitor electrode materials.

As a primary cause of dementia and death in older people, Alzheimer’s disease (AD) has become a common problem and challenge worldwide. Abnormal accumulation of tau proteins in the brain is a hallmark pathology of AD and is closely related to the clinical progression and severity of cognitive deficits. Here, we found that overexpression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) effectively promoted the degradation of tau, thereby rescuing neuron loss, synaptic damage, and cognitive impairments in a mouse model of tauopathy with AAV-full-length human Tau (hTau) injected into the hippocampal CA1 area (hTau mice). Overexpression of PINK1 activated autophagy, and chloroquine but not MG132 reversed the PINK1-induced decrease in human Tau levels and cognitive improvement in hTau mice. Furthermore, PINK1 also ameliorated mitochondrial dysfunction induced by hTau. Taken together, our data revealed that PINK1 overexpression promoted degradation of abnormal accumulated tau via the autophagy–lysosome pathway, indicating that PINK1 may be a potential target for AD treatment.

ABSTRACT Pseudomonas aeruginosa may become multidrug-resistant (MDR) due to multiple inherited and acquired resistance mechanisms. The human gastrointestinal tract is known as a reservoir of P. aeruginosa and its resistance genes. In this study, we collected 76 intestinal carbapenem-resistant P. aeruginosa (CRPA) strains from clinical inpatients admitted to our hospital from 2014 to 2019, together with their medical data. We aim to analyze the clinical risk factors associated with CRPA infection and its molecular features. We found that the prevalence of CRPA in P. aeruginosa strains was 41.3% (95% confidence interval [CI], 34.1 to 48.8%). We also identified four variables associated with intestinal CRPA positivity, prior antibiotic exposure to aminoglycosides or carbapenems, underlying diabetes mellitus, and extraintestinal P. aeruginosa isolation. blaKPC-2 is the only detected carbapenemase gene, accounting for 21.1% of CRPA strains. The genetic environment showed that the blaKPC-2 gene was flanked immediately by ISKpn8 and ISKpn6 and several other mobile elements further upstream or downstream. Four sequence types (STs) were identified, with ST463 as the dominant sequence type. In conclusion, screening for P. aeruginosa colonization upon hospital admission could reduce the risk of P. aeruginosa infection and spread of CRPA in the hospital. IMPORTANCE Pseudomonas aeruginosa may become multidrug-resistant (MDR) due to multiple inherited and acquired resistance mechanisms. The human gastrointestinal tract is known as a reservoir of P. aeruginosa and its resistance genes. Risk factor analysis and molecular epidemiology are critical for preventing their potential dissemination. Here, we identified four risk factors associated with intestinal CRPA—prior antibiotic exposure to aminoglycosides or carbapenems, underlying diabetes mellitus, and extraintestinal P. aeruginosa isolation. Further, we found similar genetic environments with several mobile elements surrounding the blaKPC gene, a carbapenemase gene only detected in intestinal CRPA strains in this study. These findings are of significant public health importance, as the information will facilitate the control of the emergence and spread of CRPA.

A simple imidazo[1,2-a]pyridine-hemicyanine-based near-infrared (NIR) TBET cassette was designed and synthesized. This cassette exhibits ultra large Stokes shifts (400 nm). Furthermore, the cassette has high selectivity and sensitivity toward sulfur dioxide in water. It was practically applied for detecting SO2 derivatives in living cells.

Photocatalytic oxidation is considered one of the most effective ways to remove formaldehyde from indoor air. However, the use of powder photocatalysts is limited by their low adsorption capacity and strong aggregation tendency. Hence, there is a need for a composite material with good cycling stability and high degradation efficiency. In the present study, a unique wood-based composite is produced by arranging Cu–TiO2 nanoparticles on porous structured wood. The porous structure of wood can adsorb formaldehyde, and the abundant functional groups on the surface can act as a reaction platform for anchoring the Cu–TiO2 nanoparticles. Cu doping facilitates electron interaction between TiO2 and Cu, promotes the transfer of charge carriers, lowers the electron–hole recombination rate, and improves the photocatalytic degradation efficiency of formaldehyde. The photocatalytic efficiency of the wood-based composites was highest (85.59%) when the n(Cu)/n(Ti) ratio was 7%. After nine cycles, the wood composites still had a high degradation rate, indicating good recyclability. Overall, this wood composite is an eco-friendly and promising material for indoor air filtration.

To study the deformation behavior of the high rockfill (HRF) embankment during construction and operation, based on more than a 50-m high rockfill embankment of the second-class road reconstruction project from Xunyang to Ankang of the national road 316 in Shaanxi, China, the centrifuge model test was performed to study the deformation laws of HRF embankment. The test results showed the following: (i) the HRF embankment was stable during construction and operation; (ii) during construction, the settlement occurred at the embankment top, and uplift occurred at the slope foot. Moreover, the deformation at the top was greater than that at the slope foot, and the deformations at both the top and the slope toe reached the maximum value at the end of construction; (iii) during operation, the settlement at the embankment top continued, and it changed rapidly at the start of operation. And then, the rate of the settlement slowed down and reached a steady state finally. The deformation of the slope foot was very small. This study can provide basis and reference for the design and construction of a similar project in mountain areas.

Abstract Background Earlier vascular healing after drug-eluting stent (DES) implantation may reduce the incidence of late stent thrombosis and provide theoretical evidence to shorten dual antiplatelet therapy duration in patients with high bleeding risks. The BuMA supreme stent is a newly developed DES-coated with the sirolimus by using the international patent electronic grafted eG™ technology. Previous randomized trials showed that BuMA stents had better stent-strut coverage at 3-month follow-ups, which were evaluated by optical coherence tomography (OCT). However, there have been a limited number of studies that are directly evaluating the extent of neointima formation at the first and second months after stent implantation in high-bleeding-risk patients with coronary artery disease. This clinical trial is designed to demonstrate the non-inferiority of the BuMA supreme stent compared to the XIENCE stent in early neointimal formation. Methods/design This is a prospective, multicenter, randomized trial. Forty patients will be assigned into the first-month OCT group, and another 40 patients into the second-month OCT group. The patients in each cohort will be randomized again into two groups in a 1:1 ratio, either being implanted with the BuMA Supreme stent or the Xience V/Prime/Xpedition stent. The primary endpoint is stent-strut neointimal coverage rate (%) at the first and second months, respectively. Secondary endpoints include neointimal hyperplasia area/volume, neointimal hyperplasia thickness, stent-strut malapposition rate, late lumen loss (LLL), restenosis rate, device/lesion/clinical success rate, device-oriented composite endpoints at the first and second months, stent thrombosis and other serious adverse events and bleeding events at follow-up. Discussion The results will provide the first accurate imaging evidence on neointimal formation of the BuMA Supreme stent and the Xience stent at 1–2 months post PCI. The result should inspire further exploration and adjustment of DAPT treatments. Trial registration ClinicalTrials.gov, ID: NCT02747329. Registered on 21 April 2016. Last updated 17 May 2018.

This research is devoted to the wave propagation characteristics analysis of nanobeams made of nanoporous metal foams. Three nanoporosity distribution models, namely, symmetry, asymmetry and uniform distributions, are taken into account. The nonlocal elasticity theory together with the Euler-Bernoulli and Timoshenko beam theories is used to model the present system. The wave dispersion relations for nanoporous metal foam nanobeams are derived detailedly. In addition, studies are carried out to scrutinize the effects of the nanoporosity coefficient, the nanoporosity distribution, the nonlocal parameter and the beam thickness on wave propagation characteristics in nanoporous metal foam nanobeams. These findings can be applied to the design of nanoporous metal foam nanostructures in engineering fields. Keywords: Nanoporous metal foam nanobeam, Wave propagation, Nonlocal elasticity, Euler-Bernoulli beam theory, Timoshenko beam theory

The sudden outbreak of coronavirus disease 2019 (COVID-19) has caused a huge impact on the Chinese residents' health and economic level. In the pandemic background, the country and its institutions have introduced pandemic-related insurance to stabilize the national situation. At this stage, insurance has played an increasingly important role in social life. With the popularization of insurance, the idea of buying insurance to avoid risk has gradually become popular among people. Among them, the New Rural Cooperative Medical System (NRCMS) has been farmers' common choice. The NRCMS, a mutual aid system created by farmers spontaneously in the country, plays a great role in guaranteeing farmers access to basic health services, alleviating poverty caused by disease and returning to poverty due to disease, and promoting poverty alleviation and rural revitalization. Given this backdrop, we study the efficiency of the NRCMS that can effectively promote poverty alleviation and rural revitalization and ensure the people's happy life. Implementing the Data Envelopment Analysis (DEA), we find that technological progress is one of the main factors influencing the efficiency of the NRCMS. Therefore, it is important to improve the technology for providing the efficiency of the NRCMS and promoting the happiness of the society.

In this paper, wave dispersion analysis of lipid tubules is presented by using the first-order shear deformation (FSD) shell theory. The small-scale effect is revealed explicitly based on the nonlocal strain gradient theory (NSGT). Different types of lipid tubules with size-dependent material properties are taken into account. Hamilton’s principle is utilized to derive the equations of wave motion. The analytical solutions of phase velocity and wave frequency of propagated waves are obtained. In addition, detailed investigations are implemented to highlight the effects of the types of lipid tubules, the longitudinal and circumferential wave numbers, the material length scale parameters and the nonlocal parameters on the wave dispersion characteristics of lipid tubules.

The pretreatment of lignocellulosic biomass is important for efficient bioethanol conversion, but causes undesirable by-products that inhibit microbial growth, conversely affecting the bioconversion efficiency. In this study, the main inhibitors derived from dilute phosphoric acid plus steam-exploded poplar wood were identified as 0.22 g/L furfural, 3.63 g/L acetic acid, 0.08 g/L syringaldehyde, etc., indicating the green nature and low toxicity of the pretreatment process. The effects of the three typical inhibitors (furfural, acetic acid, and syringaldehyde) on Saccharomyces cerevisiae 1517RM growth were analyzed and shown to prolong the lag phase of microbial growth to different degrees. In all the inhibitor groups, the ergosterol secretion was boosted, indicating low cell membrane fluidity and robustness of the strain to an adverse environment. The cell electronegativity and morphology of S. cerevisiae 1517RM also changed under different growth conditions, which was helpful for monitoring the physicochemical properties of cells. Furfural, acetic acid, and syringaldehyde had a synergistic effect on each other, providing an important reference to improving the subsequent ethanol fermentation process.

Metallic oxides are promising electrochemically active materials which can supply large energy density and capacitance, while always suffer from weak electrical conductivity and structural stability. Herein, a green and low-tortuosity wood-derived anisotropic carbon is developed to stabilize CuO and improve its conductivity. The low tortuosity and large surface area of anisotropic carbon is capable to act as an electrolyte storage to supply fast transport channels for the ionic migration, which is verified by the kinetic analysis. As expected, the composite electrode has superior electrochemical performances with a large specific capacitance of 694.8 F g−1 at the current density of 0.5 A g−1 (131.5% and 344.2% higher than that of the individual CuO (300.1 F g−1) and the individual carbon (156.4 F g−1)) and high cycling stability. As the current density dramatically increases 100 times to 50 A g−1, the composite electrode still retains 46.7% of the original capacitance, reflecting its outstanding rate capability. More importantly, the composite acts as an advanced cathode material to assemble hybrid supercapacitors, possessing a high cell voltage of 1.5 V and good cycling stability (91.2% capacitance retention after 5000 cycles) and high energy density (13.6 W h kg−1 at 350.3 W kg−1).

This paper investigates nonlinear free vibration of three-dimensional graphene foam skeleton reinforced rectangular plates. The three-dimensional graphene foam skeleton can distribute in different patterns along the thickness direction of the plate. According to the mixing rule, the effective Poisson’s ratio, mass density and elastic modulus of three-dimensional graphene foam reinforced (3D-GFR) plates are described. In the framework of the von Kármán nonlinear plate theory, Hamilton’s principle is utilized to derive equations of motion. Then, analytical nonlinear frequencies of 3D-GFR plates are solved by using the Galerkin method and the harmonic balance method. Results show that 3D-GFR plates exhibit hardening nonlinearity. The effect of porosity coefficient on nonlinear vibration depends on the foam skeleton distribution. In addition, the nonlinear frequencies of 3D-GFR plates increase as the skeleton weight fraction rises.

BACKGROUND The Kunyang phosphate deposit in central Yunnan is the largest marine sedimentary phosphorite deposit in China. The deposit is hosted in black shale of the Lower Cambrian Meishucun Formation. However, there is still some controversy on the material source of the phosphorite and the deposition age of the black shale. OBJECTIVES To precisely date the black shale and provide direct constraint for the depositional age of the phosphorite and to better understand the successive depositional environment evolution from the phosphorite to black shale in vertical profiles. METHODS Negative Thermal Ionization Mass Spectrometry (NTIMS) Re-Os isotope tracer and dating studies were performed on phosphorite of Zhongyicun Member and black shale of Shiyantou Member in the Kunyang phosphate deposit. RESULTS The Re-Os isochron age of black shale in the Shiyantou Member is 521.9±5.4 Ma, which directly constrains the deposition age of black shale in the Kunyang Phosphate deposit. The phosphorite and black shale samples have initial 187Os/188Os values from 0.6576 to 0.7671 and of 0.887, respectively. The phosphorite and black shale samples have 187Re/188Os values of 2.582-240.5 and 96.24-341.8, respectively. The δEu and δCe values of trace elements in the phosphorite and black shale show changes from low to high in the vertical profile. This evidence indicates that the formation of the Kunyang phosphorus deposit occurred in the period of rapid erosion in the mainland and a large amount of terrigenous debris involvement in diagenesis-mineralization also occurred. CONCLUSIONS Based on previous studies, the atmospheric oxygen content increased rapidly, aggravating the weathering of the continental crust and the input of a large number of highly radioactive terrestrial Os caused the initial 187Os/188Os initial ratio to increase gradually during the Cambrian Period. In addition, due to the rise of the global sea level, the paleo-marine environment of the Lower Cambrian Meishucun gradually changed from shallow water oxidization to deep water reduction. The Kunyang phosphorus deposit formed during the early stages of the sea-inward-cycle sedimentation.

Searching for high-efficient, good long-term stability, and low-cost electrocatalysts toward oxygen reduction reaction (ORR) is highly desirable for the development of sustainable energy conversion devices. Iron–nitrogen doped carbon (Fe–N/C) catalysts have been recognized as the most promising candidates for traditional Pt-based catalysts that benefit from their high activity, excellent anti-poisoning ability, and inexpensiveness. Here, a super-dispersed and high-performance Fe–N/C catalyst was derived from chemically Fe-doped zeolitic imidazolate frameworks (ZIFs) by directly bonding Fe ions to imidazolate ligands within 3D frameworks. It produced a series of catalysts, whose sizes could be tuned in the range from 62 to over 473 nm in diameter. After rationally regulating the component and heating treatment, the best ORR activity was measured for the catalyst with a size of 105 nm, which was obtained when the Fe3+/Zn2+ molar ratio was 0.05 and carbonization temperature was 900 °C. It exhibited a high onset potential (Eonset = 0.99 V) and half-wave potential (E1/2 = 0.885 V) compared with a commercial 20% Pt/C catalyst (Eonset = 0.10 V, E1/2 = 0.861 V) as well as much better durability and methanol resistance in an alkaline electrolyte.

Abstract An environment-friendly fluorescent nano-hybrid hydrogel has been synthesized successfully, from cellulose nanocrystal (CNC), acrylic acid (AA) and phosphorescent Eu2+/Dy3+ doped SrAl2O4 via free radical polymerization. The hydrogel network matrix fixed Eu2+/Dy3+ doped SrAl2O4 nanoparticles by polymer chains with coordinate bonds that prevented particles from aggregating and quenching in water. The fluorescent nano-hybrid hydrogel exhibited extremely high water absorption of which the swelling ratio in distilled water and NaCl salt solution were respectively of 323.35 g/g and 32.65 g/g. Furthermore, the hydrogel displayed excellent water retention property that can keep half of the moisture even exposed to 80 °C for 210 min. Besides, the hydrogel had bright green fluorescence under the sunlight or ultraviolet excitation, and the fluorescence intensity was up to 125477 after swelling 50 times in water. The time-resolved photoluminescence (TRPL) afterglow decay examination showed that the fluorescent emission persisted for 4 h after hydrogels excited at 368 nm wavelength UV-light for 10 min. The fluorescence intensity behaved significant linear relationship with the swelling ratio. As a result, these hydrogels were considered as promising candidates for the preparation of stable and sensitive sensor materials in green water detection.

In this paper, free vibration and buckling of polymeric shells reinforced with three-dimensional graphene foams (3D-GrFs) are investigated for the first time. The 3D-GrFs/polymer composites are prepared by infiltrating liquid epoxy resin into the porous structure. Thereinto, three-dimensional graphene foams can distribute uniformly or non-uniformly in the shell thickness direction. The effective Young’s modulus, mass density and Poisson’s ratio are predicted by the rule of mixture. Based on Love’s thin shell theory, governing equations and corresponding boundary conditions are derived by Hamilton’s principle. Then, free vibration and axial buckling of three-dimensional graphene foam reinforced polymer (3D-GrFRP) shells are analyzed by using the Navier method and the Galerkin method. Results show that the 3D-GrF skeleton type, the 3D-GrF skeleton weight fraction, the foam coefficient, the radius-to-thickness ratio, and the length-to-radius ratio play important role on mechanical characteristics of 3D-GrFRP shells. Keywords: 3D graphene foams, Reinforced polymer shells, Love’s shell theory, Buckling, Vibration

Bending and buckling behaviors of three-dimensional graphene foam (3D-GrF) plates are investigated in the framework of the two-variable refined plate theory (TRPT). The material properties of three-dimensional graphene foams vary continuously along thickness direction of the plate. The TRPT considers the effect of transverse shear strains that vary quadratically along the thickness of the plate. In addition, this theory does not need to consider the shear correction factor. By using Hamilton’s principle, the governing equations are obtained. Analytical solutions for the bending problem of 3D-GrF plates are derived via Navier’s method. Additionally, buckling problem of 3D-GrF plates with various boundary conditions are analyzed by employing the Galerkin method. Results obtained in this study are verified by comparing with the published ones. Finally, the influences of pore distribution, porosity coefficient, transverse distributed load, aspect ratio, length-to-thickness ratio, mode number and axial compression ratio on bending and buckling behaviors of 3D-GrF plates are discussed. Keywords: Three-dimensional graphene foam, Plate, Buckling, Bending, Two-variable refined plate theory