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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 compact storage system is a new storage technology in the field of intelligent logistics technology, and its most typical feature is that it can realize multi-depth storage of unit loads. In this paper, the path optimization problem of the co-existence of both single command (SC) and dual command (DC) operations of the stacker in the dual-port layout is studied, and the mathematical model of the problem is established with the shortest travel time of the stacker as the objective. A genetic algorithm (GA)-beam search (BS) hybrid optimization algorithm is designed to solve the model, and the optimal individual obtained by the GA is used as the initial path choice of the BS to avoid local optimum. The effectiveness of the model and algorithm is verified by numerical simulation, and the results show that the operation path optimization model of the stacker and the designed solution method can better adapt to the I/O tasks scheduling requirements in the compact three-dimensional warehouse with dual-port layout, get a more reasonable stacker scheduling scheme, and improve the storage efficiency.

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.

Ti3SiC2 ceramic bulk with a relative density greater than 99% was prepared by hot pressing sintering (HP) using Ti3SiC2 powder as raw material, and the hardness, flexural strength and fracture toughness of HP Ti3SiC2 bulk were 775HV, 520.46 MPa and 7.62 MPa·m1/2, respectively. To evaluate its oxidation-resistance and thermal shock resistance, ultra-high temperature ablation tests were conducted under oxyacetylene flame without cooling. The results show that the Ti3SiC2 ceramics remain flat within 10 s of the ablation, no macrocracks within 25 s.SEM and XRD analysis reveal that Ti3SiC2 samples are decomposed and oxidized during the ultra-high temperature ablation, elements Si and C are oxidized into gaseous Si-O and C-O compounds, TiO2 (rutile) with a loose structure remains on the surface of the sample. To analyze the internal oxide layer, a dense layer composed of rutile TiO2 and Al2TiO5 is observed, under which an Al2O3 particle-enriched layer is found covering the substrate. The dense internal oxide layer can effectively prevent O2 from diffusing inward, thereby reducing the oxidation rate of Ti3SiC2. The high melting point and high viscosity Al2O3 particle layer can absorb a large amount of heat and then reduce the transfer of heat flow to the Ti3SiC2 substrate, thus improving the anti-ablation of the Ti3SiC2 material.

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.

In order to solve the problem that alumina based ceramic core is not easy to remove core, a certain amount of PA66 fiber was added as pore forming material to prepare porous aluminum based ceramic core by hot pressing. The influence of PA66 fiber content on the porosity, room temperature bending strength and sintering shrinkage of aluminum based ceramic core was investigated, and the mechanism of PA66 fiber content on the porosity of aluminum based ceramic core was analyzed. The results show that the porosity of alumina based ceramic core is significantly increased by adding PA66 fiber, and the sintering shrinkage of the core is effectively blocked. With the increase of PA66 fiber, the porosity of alumina based ceramic core is increased, and the bending strength and line shrinkage rate at room temperature are decreased. When the PA66 fiber content is 0.9%(mass fraction), the porosity of the aluminum based ceramic core is 41.14%, the bending strength is 15.33 MPa, and the linear shrinkage rate is 0.418%.

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