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Abstract Objective This study aims to evaluate the impact of virtual simulation experiment teaching model and Massive Open Online Course (MOOC) teaching model on the teaching effect in debridement teaching. Methods The study adopted a quasi-experimental design and used virtual simulation technology to construct a virtual simulation experimental teaching platform for debridement. This study was conducted at the Second Clinical College of Wuhan University. The experimental group was composed of 135 third-year clinical medicine students in the 2020 grade, who received the virtual simulation experimental teaching model; the control group was 122 third-year students in the same major in the 2019 grade, who used the MOOC teaching model. The performance of the two groups of students was evaluated through theoretical tests and animal experiment operation. In addition, the effectiveness of the experimental teaching model and student satisfaction were evaluated through questionnaire surveys. Results The theoretical test scores and animal experiment report scores of the experimental group were significantly higher than those of the control group, and the debridement animal experiment operation time of the experimental group was shorter than that of the control group, and the difference was statistically significant (P

Abstract Bacillus cereus is a bacterium capable of causing late-onset neonatal sepsis. By analyzing 11 cases, this study investigates the diagnosis, treatment, and prognosis of Bacillus cereus infections, aiming to provide insights into clinical diagnosis and therapy. The study scrutinized 11 instances of late-onset neonatal sepsis, including two fatalities attributable to Bacillus cereus, one accompanied by cerebral hemorrhage. An examination and analysis of these cases’ symptoms, signs, laboratory tests, and treatment processes, along with a review of related literature from 2010 to 2020, revealed a high mortality rate of 41.38% in non-gastrointestinal infections caused by Bacillus cereus. Our findings underscore the critical importance of rapid diagnosis and effective antimicrobial therapy in reducing mortality rates. Once the source of infection is identified, implementing effective infection control measures is essential.

Abstract Objective In this study, we added laboratory animal ethics education into both didactic sessions and practical sessions the general surgery laboratory course, with the didactic sessions focus on teaching the fundamental principles of laboratory animal ethics, while the practical sessions emphasize the application of these principles in laboratory classes and have assessed the changes in medical students' perception of laboratory animal ethics following medical students exposure to such education. Methods One hundred and eighty-nine third-year medical students from Wuhan University's Second Clinical College completed a laboratory animal ethics awareness questionnaire and a laboratory animal ethics written examination before and after laboratory animal ethics education. Results After receiving laboratory animal ethics education, the percentage of students who supported euthanasia for the execution of animals and humane treatment of laboratory animals were 95.2% and 98.8%, respectively, which did not differ from the 94.9% and 96.4% observed before the education. Moreover, there was a notable increase in the proportion of students who knew about regulations related to laboratory animals (from 39.9% to 57.1%), welfare issues (from 31.9% to 50.0%), and the 3R principle (from 30.4% to 58.9%) post-education, all statistically significant at P

Abstract Lateral momentum conservation is typically kept in a non-absorptive rotationally symmetric system through mirror symmetry via Noether’s theorem when illuminated by a homogeneous light wave. Therefore, it is still very challenging to break the mirror symmetry and generate a lateral optical force (LOF) in the rotationally symmetric system. Here, we report a general dynamic action in the SO(2) rotationally symmetric system, originating from the polarization-tuned mirror symmetry breaking (MSB) of the light scattering. We demonstrate theoretically and experimentally that MSB can be generally applied to the SO(2) rotationally symmetric system and tuned sinusoidally by polarization orientation, leading to a highly tunable and highly efficient LOF (9.22 pN/mW/μm−2) perpendicular to the propagation direction. The proposed MSB mechanism and LOF not only complete the sets of MSB of light-matter interaction and non-conservative force only using a plane wave but also provide extra polarization manipulation freedom.

Abstract Photoluminescence (PL) colour-changing materials in response to photostimulus play an increasingly significant role in intelligent applications for their programmability. Nevertheless, current research mainly focuses on photochemical processes, with less attention to PL transformation through uniform aggregation mode adjustment. Here we show photochromic luminescence in organic crystals (e.g. dimethyl terephthalate) with PL varying from dark blue to purple, then to bright orange-red, and finally to red. This change is attributed to the emergence of clusters with red emission, which is barely achieved in single-benzene-based structures, thanks to the subtle molecular rearrangements prompted by light. Crucial to this process are the through-space electron interactions among molecules and moderate short contacts between ester groups. The irradiated crystals exhibit reversible PL transformation upon sufficient relaxation, showing promising applications in information storage and smart optoelectronic devices. This research contributes to the development of smart photochromic luminescent materials with significant PL colour transformations through molecular rearrangement.

Background and aims: In all age, FoShou as a Chinese medicinal herb has been active in various kinds of Traditional Chinese medicine formula to treating diabetes. Hesperidin (HES), the main monomeric component of FoShou, has been extensively investigated for interventions with pathogenic mechanism of diabetes as well as subsequent treatment of associated complications. Islet β-cells have an essential effect on dynamically regulating blood sugar. Functional abnormalities in these cells and their death are strongly associated with the onset of diabetes. Therefore, induction of islet endocrine cell lineage re-editing for damaged βcell replenishment would be a promising therapeutic tool. Previously, it has been found that HES can protect islet β-cells in vivo, But, the regenerative function of HES in islet β cells and its role in promoting differential non-β cells transdifferentiation into β cells and cell fate rewriting associated mechanisms remain unclear.This work focused on investigating whether HES can induce islet α cells transdifferentiation into β cells for achieving damaged β cell regeneration and the causes and possible mechanisms involved in the process. Materials and methods: In brief, 60 mg/kg/d streptozotocin (STZ) was administered intraperitoneally in each male C57bL/6J mouse raised by the high-sugar and high-fat diet (HFD) to create a diabetic mouse model with severe β-cell damage. After 28 consecutive days of HES treatment (160 mg/kg; 320 mg/kg; once daily, as appropriate). Tracing the dynamics of α as well as β cell transformation, together with β cells growth and apoptosis levels during treatment by cell lineage tracing. The self-enforcing transcriptional network on which the cell lineage is based is used as a clue to explore the underlying mechanisms. Guangdong Pharmaceutical University's Animal Experiment Ethics Committee (GDPulac2019180) approved all animal experiments. Results: Localization by cell lineage we find that transdifferentiated newborn β-cells derived from α cells appeared in the islet endocrine cell mass of DM mice under HES'action. Compared to the model group, expressed by Tunel staining and CXCL10 levels the overall apoptosis rate of β-cells of the pancreas were reduced,the inflammatory infiltration feedback from HE staining were lower.Ki-67 positive cells showed enhanced β-cell proliferation. Decreased HbA1c and blood glucose contents, elevated C-Peptide and insulin contents which respond to ability of nascent beta cells. Also upregulated the mRNA levels of MafA, Ngn3, PDX-1, Pax4 and Arx. Moreover, increased the expression of TGR5/cAMP-CREB/GLP-1 in mouse intestinal tissues and GLP-1/GLP-1R and cAMP-CREB/IRS2/PDX-1 in pancreatic tissues. Conclusions: HES directly affects β-cells, apart from being anti-apoptotic and reducing inflammatory infiltration. HES promotes GLP-1 release by intestinal L cells by activating the TGR5 receptor in DM mouse and regulating its response element CREB signaling. GLP-1 then uses the GLP-1/GLP-1R system to act on IRS2, IRS2 as a port to influence α precursor cells to express PDX-1, with the mobilization of Pax4 strong expression than Arx so that α cell lineage is finally reversed for achieving β cell endogenous proliferation.

Mitochondria-associated endoplasmic reticulum membranes (MAMs) act as physical membrane contact sites facilitating material exchange and signal transmission between mitochondria and endoplasmic reticulum (ER), thereby regulating processes such as Ca2+/lipid transport, mitochondrial dynamics, autophagy, ER stress, inflammation, and apoptosis, among other pathological mechanisms. Emerging evidence underscores the pivotal role of MAMs in cardiovascular diseases (CVDs), particularly in aging-related pathologies. Aging significantly influences the structure and function of the heart and the arterial system, possibly due to the accumulation of reactive oxygen species (ROS) resulting from reduced antioxidant capacity and the age-related decline in organelle function, including mitochondria. Therefore, this paper begins by describing the composition, structure, and function of MAMs, followed by an exploration of the degenerative changes in MAMs and the cardiovascular system during aging. Subsequently, it discusses the regulatory pathways and approaches targeting MAMs in aging-related CVDs, to provide novel treatment strategies for managing CVDs in aging populations.

The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.

Abstract Untethered capsules hold clinical potential for the diagnosis and treatment of gastrointestinal diseases. Although considerable progress has been achieved recently in this field, the constraints imposed by the narrow spatial structure of the capsule and complex gastrointestinal tract environment cause many open-ended problems, such as poor active motion and limited medical functions. In this work, we describe the development of small-scale magnetically driven capsules with a distinct magnetic soft valve made of dual-layer ferromagnetic soft composite films. A core technological advancement achieved is the flexible opening and closing of the magnetic soft valve by using the competitive interactions between magnetic gradient force and magnetic torque, laying the foundation for the functional integration of both drug release and sampling. Meanwhile, we propose a magnetic actuation strategy based on multi-frequency response control and demonstrate that it can achieve effective decoupled regulation of the capsule’s global motion and local responses. Finally, through a comprehensive approach encompassing ideal models, animal ex vivo models, and in vivo assessment, we demonstrate the versatility of the developed magnetic capsules and their multiple potential applications in the biomedical field, such as targeted drug delivery and sampling, selective dual-drug release, and light/thermal-assisted therapy.

Wearable and stretchable strain sensors have potential values in the fields of human motion and health monitoring, flexible electronics, and soft robotic skin. The wearable and stretchable strain sensors can be directly attached to human skin, providing visualized detection for human motions and personal healthcare. Conductive polymer composites (CPC) composed of conductive fillers and flexible polymers have the advantages of high stretchability, good flexibility, superior durability, which can be used to prepare flexible strain sensors with large working strain and outstanding sensitivity. This review has put forward a comprehensive summary on the fabrication methods, advanced mechanisms and strain sensing abilities of CPC strain sensors reported in recent years, especially the sensors with superior performance. Finally, the structural design, bionic function, integration technology and further application of CPC strain sensors are prospected.

Severe burns are one of the most devastating injuries, in which sustained inflammation and ischemia often delay the healing process. Pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) have been widely studied for promoting wound healing. However, the short half-life and instability of VEGF limit its clinical applications. In this study, we develop a photo-crosslinked hydrogel wound dressing from methacrylate hyaluronic acid (MeHA) bonded with a pro-angiogenic prominin-1-binding peptide (PR1P). The materials were extruded in wound bed and in situ formed a wound dressing via exposure to short-time ultraviolet radiation. The study shows that the PR1P-bonded hydrogel significantly improves VEGF recruitment, tubular formation, and cell migration in vitro. Swelling, Scanning Electron Microscope, and mechanical tests indicate the peptide does not affect the overall mechanical and physical properties of the hydrogels. For in vivo studies, the PR1P-bonded hydrogel dressing enhances neovascularization and accelerates wound closure in both deep second-degree burn and full-thickness excisional wound models. The Western blot assay shows such benefits can be related to the activation of the VEGF–Akt signaling pathway. These results suggest this photo-crosslinked hydrogel dressing efficiently promotes VEGF recruitment and angiogenesis in skin regeneration, indicating its potential for clinical applications in wound healing.

Abstract A 3D nanostructured scaffold as the host for zinc enables effective inhibition of anodic dendrite growth. However, the increased electrode/electrolyte interface area provided by using 3D matrices exacerbates the passivation and localized corrosion of the Zn anode, ultimately bringing about the degradation of the electrochemical performance. Herein, a nanoscale coating of inorganic–organic hybrid (α‐In2Se3‐Nafion) onto a flexible carbon nanotubes (CNTs) framework (ISNF@CNTs) is designed as a Zn plating/stripping scaffold to ensure uniform Zn nucleation, thus achieving a dendrite‐free and durable Zn anode. The introduced inorganic–organic interfacial layer is dense and sturdy, which hinders the direct exposure of deposited Zn to electrolytes and mitigates the side reactions. Meanwhile, the zincophilic nature of ISNF can largely reduce the nucleation energy barrier and promote the ion‐diffusion transportation. Consequently, the ISNF@CNTs@Zn electrode exhibits a low‐voltage hysteresis and a superior cycling life (over 1500 h), with dendrite‐free Zn‐plating behaviors in a typical symmetrical cell test. Additionally, the superior feature of ISNF@CNTs@Zn anode is further demonstrated by Zn‐MnO2 cells in both coin and flexible quasi‐solid‐state configurations. This work puts forward an inspired remedy for advanced Zn‐ion batteries.

BackgroundIt has been shown that inflammation may be associated with cognitive impairment (CI). Diet modulates inflammation. However, there is currently a scarcity of epidemiological studies exploring the connection between the inflammatory potential of diet and CI. The objective was to investigate the correlation between the dietary inflammatory index (DII) and cognitive impairment in older adults in the United States.MethodsThe present investigation utilized a cross-sectional dataset obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dietary intake data was used to calculate DII scores, which were then used to categorize participants into quartiles. Participants’ cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Individuals who scored in the lowest quartile on any of these tests were classified as exhibiting low cognitive performance. The association between DII and cognitive impairment was investigated by multivariate logistic regression, smooth curve fitting, and subgroup analysis.ResultsA total of 947 older adults were enrolled in the study. Following the adjustment of confounding variables, DII scores exhibited a significant and positive correlation with low cognitive performance, as measured by AFT (OR 1.15, 95% CI 1.02–1.28, p = 0.02) and the DSST (OR 1.38, 95% CI 1.13–1.68, p = 0.004). Compared with the lowest quartile of DII, the highest weighted odds ratio of cognitive impairment based on AFT was observed in the fourth quartile group (OR 1.89, 95% CI 1.05–3.38, p = 0.03). Similarly, a comparable pattern was evident in DSST (OR 4.30, 95% CI 1.85–9.98, p = 0.003). Additionally, the smooth curve fitting results showed a nonlinear relationship between DII and cognitive decline evaluated by DSST (p for nonlinearity = 0.016). No interaction effects between cognitive impairment and age or gender were observed in relation to all cognitive test scores.ConclusionThis research reveals a positive link between diet with higher inflammatory potential and cognitive decline among elderly individuals in America. However, additional studies on dietary interventions are necessary to explore the cause-and-effect relationship.

Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that can interfere with the endocrine system and cause liver damage. However, the molecular mechanism of DEHP-induced liver injury is unclear. This study aimed to investigate the effects of DEHP on liver function and its relationship with thioredoxin-interacting protein (TXNIP) and mitochondrial oxidative stress pathway. We used C57BL/6 J mice and THLE-2 liver cells as in vivo and in vitro models, respectively, and treated them with different doses of DEHP, and measured the relevant biochemical indicators and molecular markers. We found that DEHP significantly increased the expression of TXNIP and NLRP3, while decreasing the expression of mitochondrial functional proteins, such as PGC-1α, TFAM, NRF1, NDUHA9, SDHA, MFN1. This resulted in mitochondrial dysfunction, manifested by reduced ATP generation, increased inflammatory factor release, elevated liver enzyme indicators, decreased mitochondrial membrane potential and increased oxidative stress. We further demonstrated that TXNIP upregulation activated NF-κB and MAPK signaling pathways, such as NF-κB, IκB, TAB2, TRAF6, ERK1, JNK, p38 MAPK, MEK1, which exacerbated oxidative stress and inflammation, leading to liver damage. Additionally, we found that treatment with the antioxidant MitoQ partially alleviated DEHP-induced liver toxicity, while silencing TXNIP more effectively restored mitochondrial function. Our study supports the hypothesis that DEHP induces mitochondrial oxidative stress through the TXNIP signaling pathway, resulting in liver dysfunction in mice, and suggests possible links between endocrine-disrupting chemicals and human diseases.

Abstract Background There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia. Methods This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male

Background: The aim of this study was to address the intramuscular adipose tissue (IMAT) accumulation in the lower extremities and further detect the relationship between adipose tissue (AT) distribution in the muscle and glucose metabolism in subjects with obesity. Methods: We conducted a cross-sectional study in 120 Chinese obese adults (80 male and 40 female) with BMI ≥ 28 kg/m2. MRI was applied to access the IMAT content in lower extremities. The oral glucose tolerance test was used to evaluate the glucose metabolism and insulin secretion in all individuals. The correlations between glucose metabolism and the fat content of the lower extremities were further assessed. Results: Among 120 included subjects, 54 were classified as subjects with normal glucose tolerance (NGT) and 66 with impaired glucose regulation (IGR). We presented that those with IGR had higher fat accumulation in semitendinosus, adductor magnus, gracilis and sartorius than those with NGT (all P < 0.05). In sex-specific analyses, females have higher IMAT in adductor magnus than males (P < 0.001). Males with IGR had higher fat fraction of semitendinosus and sartorius than those with NGT (P = 0.020, P = 0.014, respectively). Logistic regression analyses revealed that IMAT content in semitendinosus was the independent factor of IGR in individuals with obesity after adjustment for age, gender, triglycerides, creatinine and albumin (odds ratio: 1.13, 95% CI: 1.02–1.26, P = 0.024). Conclusions: Increased adipose tissue accumulation in thigh muscles was associated with glucose dysregulation in patients with obesity. IMAT content in semitendinosus may serve as a possible risk factor for impaired glucose metabolism.

Abstract Two-photon polymerization lithography is promising for producing three-dimensional structures with user-defined micro- and nanoscale features. Additionally, shrinkage by thermolysis can readily shorten the lattice constant of three-dimensional photonic crystals and enhance their resolution and mechanical properties; however, this technique suffers from non-uniform shrinkage owing to substrate pinning during heating. Here, we develop a simple method using poly(vinyl alcohol)-assisted uniform shrinking of three-dimensional printed structures. Microscopic three-dimensional printed objects are picked and placed onto a receiving substrate, followed by heating to induce shrinkage. We show the successful uniform heat-shrinking of three-dimensional prints with various shapes and sizes, without sacrificial support structures, and observe that the surface properties of the receiving substrate are important factors for uniform shrinking. Moreover, we print a three-dimensional mascot model that is then uniformly shrunk, producing vivid colors from colorless woodpile photonic crystals. The proposed method has significant potential for application in mechanics, optics, and photonics.

The vehicle-road collaborative intelligence approach has become an industry consensus. It can efficiently tackle the technical hurdles and reduce the performance requirements and costs of on-board perception and computing devices. There is a need for in-depth quantitative studies to optimize the allocation of vehicle-road intelligent capabilities for collaborative intelligence. However, current research tends to focus more on qualitative analysis, and there is little research on the redistribution of vehicle and roadside intelligent capabilities. In this paper, we present a model for distributing perception and computing capabilities between vehicle-side and roadside, ensuring to meet the needs of various autonomous driving levels. Meanwhile, the collaborative intelligence approach will also introduce the costs of intelligent infrastructure deployment, energy, and maintenance. Different roads have varying scene characteristics and usage intensities. It is necessary to conduct a cost-effectiveness analysis of the intelligent deployment of different road types. A vehicle-road cost allocation model is developed based on the lifecycle traveled distance of vehicles and the lifecycle traffic flow of various roads to evaluate the function-cost effectiveness. Our study presents several vehicle-road intelligent schemes that meet the needs of various autonomous driving levels and selects Beijing for case analysis. The results indicate that primary intelligent infrastructure can reduce the lifecycle cost of the vehicle-side intelligent scheme for intermediate autonomous driving from ¥65,301 to ¥37,703, and advanced intelligent infrastructure can reduce the lifecycle cost for advanced autonomous driving from ¥126,938 to ¥42,180. Considering the distributed cost of vehicle-side and roadside, urban roads in Beijing have higher function-cost effectiveness compared to highways, especially urban expressways, which are expected to generate 43.3 times the vehicle-function-cost benefits after the advanced intelligent upgrades. The corresponding research findings can serve as a reference for city managers to make decisions on intelligent road deployment.

The number of colleges and universities in China has been increasing year by year. University buildings have tremendous energy-saving potential due to their high personnel density and energy consumption demand. However, there is a lack of research and regulations focusing on such buildings and taking functional requirements, operating patterns, and climate conditions into account. In the HSCW zone of China, the overlap of energy consumption peak and universities’ winter and summer vacations will lead to improper or excessive implementation of energy-saving measures in practice. This research study on a university teaching building in Shanghai simulated the energy consumption with EnergyPlus (Version 22.1.0) to compare the variation trend of the building’s energy consumption (heating, cooling and annual energy consumption) under different design parameter settings. The influence of orientation and window–wall ratio on the energy consumption intensity of classrooms of various sizes was analyzed, and design strategies were proposed. The research indicates that the annual energy consumption of educational buildings in hot summer and cold winter areas can be reduced by approximately 44.4% during vacations. However, cooling energy consumption remains 18.0–19.4% greater than heating energy consumption. The energy intensity of classrooms decreases as the space size increases. Medium-sized classrooms, with an energy intensity ranging from 44.2–47.6 kWh/m2, require priority in energy-efficient design owing to their considerable quantity and high utilization. The findings offer design suggestions for the optimal orientation and window-to-wall ratios of classrooms of different scales, which can be used as a reference for the design of university teaching buildings and the energy-saving retrofit of existing campus buildings.

The global prevalence of non-alcoholic fatty liver disease (NAFLD) has attained a level of 25.24%. The prevalence of NAFLD in China has exhibited an upward trajectory in parallel with the increasing incidence of obesity over the preceding decade. In order to comprehensively assess hepatic lipid deposition in individuals with overweight or obesity, we have devised a pioneering prognostic formula that capitalizes on clinical parameters. To this end, we have conducted a cross-sectional cohort study involving 149 overweight or obese subjects. Magnetic resonance imaging proton density fat fraction (MRI-PDFF) has been employed to evaluate the extent of liver fat accumulation. Through univariate analysis, we have identified potential factors, and the definitive elements in the prediction model were selected utilizing the forward stepwise regression algorithm. The Shang Hai Steatosis Index (SHSI) incorporates alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting insulin, and 1-h postload glycaemic levels, thereby furnishing the capability to predict NAFLD with an area under the receiver operator characteristic (AUROC) of 0.87. By establishing a threshold value of 10.96, determined through Youden’s index, we have achieved a sensitivity of 69.57% and a specificity of 88.24%. The Spearman correlation coefficient between liver fat fraction ascertained by MRI-PDFF and that predicted by the SHSI equation amounts to 0.74. Consequently, the SHSI equation affords a dependable means of predicting the presence of NAFLD and liver fat accumulation within the overweight and obese population.

Abstract Improvements in treatment and chemotherapy have increased the survival rate of osteosarcoma, but overall efficacy remains low, highlighting the need for new gene therapy methods. Clustered regularly interspaced short palindromic repeats–deactivated Cas9 (CRISPR–dCas9) technology offers a promising strategy, but targeting osteosarcoma cells precisely is a challenge. We designed a system to achieve specific expression of CRISPR–dCas9–KRAB in osteosarcoma cells by using the creatine kinase muscle (CKM) promoter to drive dCas9–KRAB and the telomerase reverse transcriptase (TERT) promoter to drive single guide (sg)RNA expression. We inhibited the MDM2 proto-oncogene using this system in vitro, which efficiently inhibited the malignant behavior of osteosarcoma cells and induced apoptosis without affecting normal cells. In vivo experiments demonstrated that this system effectively inhibited the growth of subcutaneously transplanted tumors in nude mice. These findings provide a new method for precise identification and intervention of osteosarcoma with significant implications for the development of gene therapy methods for other cancers. Future research should focus on optimizing this system for clinical translation.

Abstract Accurately characterizing the surface topography of parts is crucial to improve the surface measurement accuracy and analyze the surface contact performance. A method is proposed to separate the morphological characteristics of the actual machined surface based on the layer-by-layer error reconstruction method and the signal-to-noise ratio method during the wavelet transform process, so as to evaluate the contact performance of the different joint surfaces. First, the actual machined surface morphological features are separated by using the wavelet transform method, the layer-by-layer error reconstruction method, and the signal-to-noise ratio method. Second, the reconstructed three-dimensional surface contact model is established by the reverse modeling engineering method. Third, the finite element method is used to analyze the impact of processing methods and surface roughness on contact surface parameters. The result demonstrates that the simplified and efficient three-dimensional reconstructed surface is achieved based on the real machining surface in contrast to other existing approaches. The surface roughness has a more significant influence on contact performance. The contact deformation increases with the increase of surface roughness, while the curves of average contact stress, contact stiffness, and contact area have the opposite trend.

In the era of big data, facing the data-intensive scientific paradigm shift and the explosion of scientific big data, there is an urgent need for alliance cooperation between heterogeneous research groups to actively open and share scientific big data to support China's economic development, technological innovation and national security. Therefore, the study of scientific big data sharing mechanism has very important practical significance. We think science big data sharing is an ecosystem that is constantly evolving to higher-order ecological evolution. Based on the dual perspectives of psychological contract and contractual contract, the scientific big data sharing strategy evolution mechanism and sharing strategy incentive mechanism are explored.The research finds that the cooperation of scientific research groups is bound by psychological contract and contractual contract; stochastic evolutionary game has stronger explanatory power for sharing strategy evolution, complementarity is positive indicator, random interference and moral risk are negative indicators; two-way principal agent can describe Alliance members are mutually entrusted, and the shared strategy incentive contract consists of fixed wages and incentive wages, which are proportional to risk.

Objective: This work focused on investigating if robot-assisted minimally invasive surgery improved middle term vital outcome for primary brainstem hemorrhage (PBSH). Methods: This work obtained clinical data from patients with PBSH admitted from July 2019 to August 2021. All cases were classified as surgical or conservative treatment group. The general information, Glasgow coma scale (GCS) score, Glasgow outcome score (GOS), along with survival time in patients 60 days after robot-assisted surgery were recorded and analyzed. Results: A prospective analysis was performed on 82 cases meeting eligibility criteria, including 36 from surgical group whereas 46 from the conservative group. Sixty days after onset, the death rate was found to be 19.44% and 50.00% of surgical and conservative groups, separately (cases versus controls, P

Hexokinase (HXK) plays a crucial role in plants, catalyzing the phosphorylation of hexose substances, which is one of the key steps in sugar metabolism and energy production. While HXK genes have been well-studied in model plants, the evolutionary and functional characteristics of HXK gene family in jujube is unknow. In this study, the HXK gene family members were identified by bioinformatics methods, the key members regulating glucose metabolism were identified by transcriptome data, and finally the function of the key genes was verified by instantaneous and stable genetic transformation. Our results showed that seven HXK genes were identified in the jujube genome, all of which were predict located in the chloroplast and contain Hexokinase-1 (PF00349) and Hexokinase-2 (PF03727) conserved domains. Most of HXK proteins were transmembrane protein with stable, lipid-soluble, hydrophilic. The secondary structure of ZjHXK proteins main α-helix, and contains two distinct tertiary structure. All ZjHXK genes contain nine exons and eight introns. Predictions of cis-regulatory elements indicate that the promoter region of ZjHXK contains a large number of MeJA responsive elements. Finally, combined with the analysis of the relationship between the expression and glucose metabolism, found that ZjHXK5 and ZjHXK6 may the key genes regulating sugar metabolism. Transient overexpression of ZjHXK5 and ZjHXK6 on jujube, or allogeneic overexpression of ZjHXK5 and ZjHXK6 on tomato would significantly reduce the content of total sugar and various sugar components. Transient silencing of ZjHXK5 and ZjHXK6 genes results in a significant increase in sucrose and total sugar content. Interestingly, the expression of ZjHXK5 and ZjHXK6 were also affected by methyl jasmonate.

In this study, ultrasonic-ethanol pretreatment combined with AEE was developed for oil extraction from hemp seeds. The oil yield reached a maximum of 23.32 % at 200 W ultrasonic power and 30 min ultrasonic time, at this point, the degradation rate of Δ9-THC was 83.11 %. By determining the composition of hemp seed before and after pretreatment, it was shown that ultrasonic-ethanol pretreatment reduced the protein content of the raw material. An enzyme mixture consisting of pectinase and hemicellulase (1/1/1, w/w/w) was experimentally determined to be used, and the AEE extraction conditions were optimized using the Plackett-Burman design and the Box-Behnken. The optimal conditions were determined to be pH 5, total enzyme activity of 37,800 U/g, liquid–solid ratio of 10.4 mL/g, enzyme digestion temperature of 32 °C, enzymatic time of 189 min, and oil recovery of 88.38 %. The results of confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) showed that the emulsion formed during ultrasonic ethanol pretreatment was not uniformly distributed, and the droplets appeared to be aggregated; and the irregular pores of hemp seed increased after pretreatment. The contents of Δ9-THC and CBN in the extracted oil samples were 9.58 mg/kg and 52.45 mg/kg, respectively. Compared with the oil extracted by Soxhlet extraction (SE), the oil extracted by this experimental method was of better quality and similar in fatty acid composition.

Platform enterprises, which aggregate numerous and scattered resources, connect multiple interdependent parties and facilitate interactions and transactions, also confront significant monopoly market challenges. These issues constrain the platform economy’s healthy development and severely disrupt the normal market order. This paper constructs a tripartite evolutionary game model comprising the government, platform enterprises, and users, to investigate the governance mechanisms of monopoly behavior in platform enterprises and employs Matlab for numerical simulation. The results indicate that government rewards, additional profits, monopoly penalties, and user collaboration positively impact the evolution of platform enterprise strategies toward non-monopolistic practices. Together, these four mechanisms constitute the governance mechanism for monopoly behavior in platform enterprises. Specifically, providing honorary rewards for non-monopolistic behavior in platform enterprises over a certain period is essential, as it represents an effective means for the government to encourage innovative development in internet platform enterprises. The profit mechanism is the main driving force behind platform enterprises adopting monopolistic strategies and facilitating their survival and development. To a certain extent, the penalty mechanism can suppress monopolistic behaviors in platform enterprises, but it cannot fundamentally eliminate them. Instead, this mechanism accelerates the evolution of platform enterprises towards non-monopolistic behaviors, marking it as a positive governance tool. The user collaboration mechanism, a form of collaborative governance, serves as a beneficial complement to the reward, penalty, and profit mechanisms. This is because users primarily engage with platforms as consumers, legally entitled to services, and their regulatory role constitutes only a part of their responsibilities, not the main economic activity on digital platforms.

Acute intracranial hypertension (AIH) is a common and tricky symptom that inflicts upon patients after traumatic brain injury (TBI). A variety of clinical options have been applied for the management of AIH, such as physiotherapy, medication, surgery and combination therapy. Specifically, controlled decompression (CDC) alleviates the extent of brain injury and reduces the incidence of a series of post-TBI complications, thereby enhancing the prognosis of patients suffering from acute intracranial hypertension. The objective of the present project is to illuminate the potential molecular mechanism that underlies the neuroprotective effects of CDC in a rat model of traumatic epidural intracranial hypertension (TEIH). Herein, we observed the functional recovery, the degree of brain edema, the level of apoptosis, the expressions of neuronal cell autophagy-related signaling pathway proteins (including Akt, p-Akt, LC3 and Beclin-1) in rat TEIH model at 24 h post-surgery. The results showed in comparison with rapid decompression (RDC), CDC reduced the degree of brain edema, diminished the level of cellular apoptosis and enhanced neurological function, and whereas the neuroprotective effect of CDC could be reversed by rapamycin (Rap). The expressions of Beclin-1 and LC3 in CDC group were significantly lower than those of RDC group, and the expression levels of these two proteins were significantly elevated after the addition of Rap. The expression of p-Akt in CDC group was considerably enhanced than RDC group. After the addition of LY294002, a PI3K/Akt pathway inhibitor, p-Akt protein expression was reduced, and the neuroprotective effect of the rats was markedly inhibited. Taken together, our data demonstrate the superior neuroprotective effect of CDC with regard to alleviating early brain edema, improving the neurological status, suppressing apoptosis and inhibiting neuronal autophagy via triggering PI3K/Akt signaling pathway.

BackgroundBased on the high prevalence and fatality rates associated with severe community-acquired pneumonia (SCAP), this study endeavored to construct an innovative nomogram for early identification of individuals at high risk of all-cause death within a 30-day period among SCAP patients receiving intensive care units (ICU) treatment.MethodsIn this single-center, retrospective study, 718 SCAP patients were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database for the development of a predictive model. A total of 97 patients eligible for inclusion were included from Chongqing General Hospital, China between January 2020 and July 2023 for external validation. Clinical data and short-term prognosis were collected. Risk factors were determined using the least absolute shrinkage and selection operator (LASSO) and multiple logistic regression analysis. The model’s performance was evaluated through area under the curve (AUC), calibration curve, and decision curve analysis (DCA).ResultsEight risk predictors, including age, presence of malignant cancer, heart rate, mean arterial pressure, albumin, blood urea nitrogen, prothrombin time, and lactate levels were adopted in a nomogram. The nomogram exhibited high predictive accuracy, with an AUC of 0.803 (95% CI: 0.756–0.845) in the training set, 0.756 (95% CI: 0.693–0.816) in the internal validation set, 0.778 (95% CI: 0.594–0.893) in the external validation set concerning 30-day mortality. Meanwhile, the nomogram demonstrated effective calibration through well-fitted calibration curves. DCA confirmed the clinical application value of the nomogram.ConclusionThis simple and reliable nomogram can help physicians assess the short-term prognosis of patients with SCAP quickly and effectively, and could potentially be adopted widely in clinical settings after more external validations.

Abstract In this article, selective laser melting (SLM) equipment is used to print 316L stainless steel parts under different process parameters, and the surface roughness of the parts is measured. Based on back propagation neural networks (BP neural networks, BPNN), the upper surface roughness prediction model is established. The laser power, scanning speed, and scanning interval are used as model input, and the surface roughness of the workpiece is output. This model can easily and quickly predict the surface roughness of SLM metal printing, with high prediction accuracy, and can provide a basis for the optimization of SLM process parameters.

This study examined the influencing factors of digital participation, including digital skills, interpersonal communication, online immersion and mediating roles of online interpersonal communication and online immersion. This study selected 1,204 samples from the 2017 Chinese General Social Survey. Amos 26.0 was used to test the theoretical model using the structural equation model (SEM). The study found that digital skills positively affect digital participation, digital skills positively affect online interpersonal communication and online immersion, and online interpersonal communication and online immersion positively affect digital participation. Online interpersonal communication and online immersion were found to significantly mediate the nexus between digital skills and digital participation. Moreover, income was found to be no longer a significant factor in the relationship of digital skills on digital participation. This study found the mediating roles of online interpersonal communication and online immersion between digital skills and digital participation, which was not available in previous studies. This result proved that the interaction between participants and the subjective immersive experience via the network are crucial for digital participation, and that the close information communication with different populations and an immersive network environment can facilitate the interactive expression of participants in cyberspace. The study also found that at least in China, the income gap is no longer a major factor affecting the relationship between digital skills and digital participation.

Background: Lunges are common in badminton. Distance and foot position affect knee joint loadings under lunges, which are closely related to knee injury incidence. Investigations involving dynamic knee motion in vivo, kinetics, and muscle activation in lunges, especially during lunges of different distances and foot positions, are instrumental for understanding knee performance and injury risks of players.Methods: A total of 10 experienced badminton athletes (10 females; height, 164.5 ± 5.0 cm; weight, 59.3 ± 6.0 kg; and age, 22 ± 1.0 years) were recruited. By using a high-speed dual fluoroscopic imaging system, Qualisys motion capture system, Kistler force plate, and Delsys electromyography simultaneously, data were collected during players’ 1.5 times leg length lunge, the maximum lunge, and the maximum lunge while the foot rotated externally. Magnetic resonance and dual fluoroscopic imaging techniques were used to analyze the in vivo knee kinematics.Results: Compared with the 1.5 times leg length lunge, knee flexion for the maximum lunge increased significantly (p < 0.05). The anterior–posterior ground reaction force (GRF) and vertical GRF of the maximum lunge were significantly higher than those of the 1.5 times leg length lunge. During the two different foot position lunges with the maximum distance, the posterior translation of knee joint was larger (p < 0.05) when the foot rotated externally than the normal maximum lunge. Moreover, the anterior–posterior GRF and vertical GRF increased significantly when the foot rotated externally. Significant differences were observed in valgus–varus rotation torque and internal–external rotation torque of the knee joint under the two distance lunges and two foot position lunges (p < 0.05). No significant difference was found in knee muscle activation during the two distance lunges and during the two foot position lunges.Conclusion: High knee torque and compressive loadings with increasing lunge distance may cause knee injuries in badminton. When lunging in the external foot rotation under the maximum distance, high quadriceps force and posterior tibia translation force could result in knee injuries among badminton players.

Abstract The multispectral compatible infrared camouflage technology is implemented these days to counter the developing infrared detectors and detectors of other bands. However, the conflict between delicate optical structures and scalable procedures has significantly impeded the development and application of multispectral‐compatible camouflage technology. Therefore, a semi‐open Fabry‐Perot structure is introduced, and the color and infrared emissivity by structural parameters for color‐matched visible‐infrared compatible camouflage are modulated. The prepared compatible camouflage film exhibits visible camouflage by the minimum color difference of 1.6 L*a*b* (under desert background) and infrared camouflage by low emission (ε3–5 µm ≈ 0.17 and ε8–14 µm ≈ 0.143). Due to its flexibility and scalability, the compatible camouflage film can be applied in practical applications and exhibits desirable visible and infrared camouflage performance in different battlefield backgrounds.

The qualitative interpretation of the logs was used by interpreting the behaviour of their curves to determine the upper and lower boundaries of the Yamama Formation in the Ratawi Oil Field, southern Iraq, and their reservoir units for the wells in the study area. Quantitative interpretation has been used to calculate the petrophysical parameters by applying equations and Petrel Software. Detailed core examinations, thin sections, and cuttings data were collected for facies analysis and divided into primary and secondary facies. These data identify the formation tops and thicknesses and have also been used in stratigraphic correlation. These core and log data are also crucial for determining the separator boundaries between the formations that return to the reservoir.

Abstract Background Based on the few available studies on the prognostic benefit of using direct oral anticoagulants (DOACs) after atrial fibrillation (AF) ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs. Methods This is a multicenter retrospective cohort study enrolling 6137 patients with non-valvular AF (NVAF) at 15 hospitals in China. Patient information was collected through a mean follow-up of 10 months and medical record queries. Clinical outcomes included major bleeding, total bleeding, thrombosis, all-cause death, and a composite endpoint of bleeding, thrombosis, and all-cause death. Results After adjusting for confounders and propensity score matching (PSM), patients with RFA of NVAF had a significantly lower risk of major bleeding [OR 0.278 (95% CI, 0.150-0.515), P

Abstract Background In a significant proportion of cancers, point mutations of TP53 gene occur within the DNA-binding domain, resulting in an abundance of mutant p53 proteins (mutp53) within cells, which possess tumor-promoting properties. A potential and straightforward strategy for addressing p53-mutated cancer involves the induction of autophagy or proteasomal degradation. Based on the previously reported findings, elevating oxidative state in the mutp53 cells represented a feasible approach for targeting mutp53. However, the nanoparticles previous reported lacked sufficient specificity of regulating ROS in tumor cells, consequently resulted in unfavorable toxicity in healthy cells. Results We here in showed that cerium oxide CeO2 nanoparticles (CeO2 NPs) exhibited an remarkable elevated level of ROS production in tumor cells, as compared to healthy cells, demonstrating that the unique property of CeO2 NPs in cancer cells provided a feasible solution to mutp53 degradation. CeO2 NPs elicited K48 ubiquitination-dependent degradation of wide-spectrum mutp53 proteins in a manner that was dependent on both the dissociation of mutp53 from the heat shock proteins Hsp90/70 and the increasing production of ROS. As expected, degradation of mutp53 by CeO2 NPs abrogated mutp53-manifested gain-of-function (GOF), leading to a reduction in cell proliferation and migration, and dramatically improved the therapeutic efficacy in a BxPC-3 mutp53 tumor model. Conclusions Overall, CeO2 NPs increasing ROS specifically in the mutp53 cancer cells displayed a specific therapeutic efficacy in mutp53 cancer and offered an effective solution to address the challenges posed by mutp53 degradation, as demonstrated in our present study.

Abstract As one of the most fascinating phenomena, structural whiteness in natural organisms serves important functions in thermoregulation and mating. However, the architectures that cause visible broadband reflection are often in quasiordered distributions, which hinders systematic research on their color formation mechanisms. Here, through numerical analysis, the architectures in Morpho theseus scales are shown to be distributed in various tubular morphologies between tubular and gyroid structures. Then, the mechanism of structural white is discussed using the numerical model built with the combination of a periodic numerical framework and random elements. Thermodynamic experiments indicate that the white scales can efficiently help reduce the temperature of butterfly wings under a direct light beam. Our work provides a concise method for analyzing quasiordered structures. The methodology developed by this numerical model can facilitate a deep understanding of the performance improvement facilitated by these structural characteristics. Corresponding solutions can guide the design of nano-optical materials to achieve an efficient cooling, camouflage, and photothermal conversion system.

Implant-associated infections (IAIs) caused by biofilm formation are the most devastating complications of orthopedic surgery. Statins have been commonly and safely used drugs for hypercholesterolemia for many years. Here, we report that simvastatin-hydroxyapatite-coated titanium alloy prevents biofilm-associated infections. The antibacterial properties of simvastatin against Staphylococcus aureus and Staphylococcus epidermidis biofilms in vitro was confirmed by crystal violet staining and live-dead bacterial staining. We developed a simvastatin-and hydroxyapatite (Sim-HA)-coated titanium alloy via electrochemical deposition. Sim-HA coatings inhibited Staphylococcus aureus biofilm formation and improved the biocompatibility of the titanium alloy. Sim-HA coatings effectively prevented Staphylococcus aureus IAI in rat femurs, as confirmed by radiological assessment and histological examination. The antibacterial effects of the Sim-HA coatings were attributed to their inhibitory effects on biofilm formation, as verified by scanning electron microscopic observations and bacterial spread plate analysis. In addition, the Sim-HA coatings enhanced osteogenesis and osteointegration, as verified by micro-CT, histological evaluation, and biomechanical pull-out tests. In summary, Sim-HA coatings are promising implant materials for protection against biofilm-associated infections.

Pedunculoside, a triterpene saponin derived from various Ilex species, holds potential as a treatment for cardiovascular diseases. However, its clinical application is hindered by poor bioavailability, rapid elimination, and extensive intestinal metabolism to rotundic acid. To address these issues, a water-soluble inclusion complex of pedunculoside, namely, the beta-CD polymer inclusion complex of pedunculoside (pedunculoside–βCDP), was prepared in this study, and a comparative in vitro stability and pharmacokinetic behavior study was performed between pedunculoside and pedunculoside–βCDP. Both pedunculoside and pedunculoside–βCDP exhibited the highest stability in simulated gastric fluid and simulated intestinal fluid but were readily metabolized when co-incubated with Bifidobacterium adolescentis and Bifidobacterium breve. An LC-MS/MS analytical method for the simultaneous determination of pedunculoside and rotundic acid in rat plasma was successfully established, validated, and applied to investigate the pharmacokinetic behavior after rats were intravenously administered with pedunculoside or pedunculoside–βCDP. The results indicated that pedunculoside–βCDP could significantly improve the pharmacokinetic profile of pedunculoside by increasing plasma exposure, retarding elimination, and reducing intestinal metabolism. This study enhances our understanding of pedunculoside–βCDP’s metabolic fate and pharmacokinetic properties and potentially advances its further research, development, and clinical application.

Abstract Limited by preparation time and ligand solubility, synthetic protocols for cyclodextrin‐based metal‐organic framework (CD‐MOF), as well as subsequent derived materials with improved stability and properties, still remains a challenge. Herein, an ultrafast, environmentally friendly, and cost‐effective microwave method is proposed, which is induced by graphene oxide (GO) to design CD‐MOF/GOs. This applicable technique can control the crystal size of CD‐MOFs from macro‐ to nanocrystals. CD‐MOF/GOs are investigated as a new type of supramolecular adsorbent. It can selectively adsorb the dye molecule methylene green (MG) owing to the synergistic effect between the hydrophobic nanocavity of CDs, and the abundant O‐containing functional groups of GO in the composites. Following high temperature calcination, the resulting N, S co‐doped porous carbons derived from CD‐MOF/GOs exhibit a high capacitance of 501 F g−1 at 0.5 A g−1, as well as stable cycling stability with 90.1% capacity retention after 5000 cycles. The porous carbon exhibits good electrochemical performance due to its porous surface containing numerous electrochemically active sites after dye adsorption and carbonization. The design strategy by supramolecular incorporating a variety of active molecules into CD‐MOFs optimizes the properties of their derived materials, furthering development toward the fabrication of zeitgeisty and high‐performance energy storage devices.

BackgroundAs the population of older adult in China keeps growing, the degree of aging is becoming increasingly serious and the health of older adults is a growing concern. Comparing the personal characteristics and health levels of urban and rural older adults and determining the relationship between these factors are of great significance in maintaining their health. In addition, exploring how these relationships differ between urban and rural areas is important.MethodThis study conducted a literature review to examine the impact of various factors on the physical and mental health of older adults in urban and rural areas in China. Moreover, based on cross-sectional data from the 2017 Chinese General Social Survey (CGSS), urban–rural differences in the factors’ degree of influence on the perceived health of older adults were studied using multiple logistic regression.ResultsRegular physical exercise had a powerful protective effect on urban older adults’ physical and mental health, whereas regular participation in social activities had a positive impact on rural older adults’ health. Low income, low educational level, low social trust, lack of a partner, and having more than one child negatively affected the physical health of rural older people. Low socioeconomic status had a negative impact on rural people’s health both in mind and body. Overall, the rural adults’ health status was found to be relatively low and deserves more attention.ConclusionThis study demonstrated that older people’s physical and mental health levels can be significantly affected by the frequency of daily activities and individual and family characteristics. Furthermore, urban–rural differences were observed. These findings could provide feasible suggestions for governments, communities, and older adults’ family members to help alleviate health inequality.

BackgroundThe COVID-19 pandemic has significantly altered the global health and medical landscape. In response to the outbreak, Chinese hospitals have established 24-hour fever clinics to serve patients with COVID-19. The emergence of these clinics and the impact of successive epidemics have led to a surge in visits, placing pressure on hospital resource allocation and scheduling. Therefore, accurate prediction of outpatient visits is essential for informed decision-making in hospital management. ObjectiveHourly visits to fever clinics can be characterized as a long-sequence time series in high frequency, which also exhibits distinct patterns due to the particularity of pediatric treatment behavior in an epidemic context. This study aimed to build models to forecast fever clinic visit with outstanding prediction accuracy and robust generalization in forecast horizons. In addition, this study hopes to provide a research paradigm for time-series forecasting problems, which involves an exploratory analysis revealing data patterns before model development. MethodsAn exploratory analysis, including graphical analysis, autocorrelation analysis, and seasonal-trend decomposition, was conducted to reveal the seasonality and structural patterns of the retrospective fever clinic visit data. The data were found to exhibit multiseasonality and nonlinearity. On the basis of these results, an ensemble of time-series analysis methods, including individual models and their combinations, was validated on the data set. Root mean square error and mean absolute error were used as accuracy metrics, with the cross-validation of rolling forecasting origin conducted across different forecast horizons. ResultsHybrid models generally outperformed individual models across most forecast horizons. A novel model combination, the hybrid neural network autoregressive (NNAR)-seasonal and trend decomposition using Loess forecasting (STLF), was identified as the optimal model for our forecasting task, with the best performance in all accuracy metrics (root mean square error=20.1, mean absolute error=14.3) for the 15-days-ahead forecasts and an overall advantage for forecast horizons that were 1 to 30 days ahead. ConclusionsAlthough forecast accuracy tends to decline with an increasing forecast horizon, the hybrid NNAR-STLF model is applicable for short-, medium-, and long-term forecasts owing to its ability to fit multiseasonality (captured by the STLF component) and nonlinearity (captured by the NNAR component). The model identified in this study is also applicable to hospitals in other regions with similar epidemic outpatient configurations or forecasting tasks whose data conform to long-sequence time series in high frequency exhibiting multiseasonal and nonlinear patterns. However, as external variables and disruptive events were not accounted for, the model performance declined slightly following changes in the COVID-19 containment policy in China. Future work may seek to improve accuracy by incorporating external variables that characterize moving events or other factors as well as by adding data from different organizations to enhance algorithm generalization.

Considering the Neo-Tethyan tectonic process and the resulting environmental changes, a geodynamic model of “one-way train loading” is proposed to analyze the formation and evolution mechanism of the Persian Gulf Superbasin with the most abundant hydrocarbons in the world. The Persian Gulf Superbasin has long been in a passive continental margin setting since the Late Paleozoic in the process of unidirectional subduction, forming a superior regional space of hydrocarbon accumulation. During the Jurassic–Cretaceous, the Persian Gulf Superbasin drifted slowly at low latitudes, and developed multiple superimposed source-reservoir-caprock assemblages as a combined result of several global geological events such as the Hadley Cell, the Equatorial Upwelling Current, and the Jurassic True Polar Wander. The collision during the evolution of the foreland basin since the Cenozoic led to weak destruction, which was conducive to the preservation of oil and gas. Accordingly, it is believed that the slow drifting and long retention in favorable climate zone of the continent are the critical factors for hydrocarbon enrichment. Moreover, the prospects of hydrocarbon potential in other continents in the Neo-Tethyan were proposed.

Abstract Due to the high mortality of hepatocellular carcinoma (HCC), its prognostic models are urgently needed. Bile acid (BA) metabolic disturbance participates in hepatocarcinogenesis. We aim to develop a BA-related gene signature for HCC patients. Research data of HCC were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) online databases. After least absolute shrinkage and selection operator (LASSO) regression analysis, we developed a BA-related prognostic signature in TCGA cohort based on differentially expressed prognostic BA-related genes. Then, the predictive performance of the signature was evaluated and verified in TCGA and ICGC cohort respectively. We obtained the risk score of each HCC patient according to the model. The differences of immune status and drug sensitivity were compared in patients that were stratified based on risk score. The protein and mRNA levels of the modeling genes were validated in the Human Protein Atlas database and our cell lines, respectively. In TCGA cohort, we selected 4 BA-related genes to construct the first BA-related prognostic signature. The risk signature exhibited good discrimination and predictive ability, which was verified in ICGC cohort. Patients were classified into high- and low-risk groups according to their median scores. The occurrence of death increased with increasing risk score. Low-risk patients owned favorable overall survival. High-risk patients possessed high immune checkpoint expression and low IC50 values for sorafenib, cisplatin and doxorubicin. Real-time quantitative PCR and immunohistochemical results validate expression of modeling genes in the signature. We constructed the first BA-related gene signature, which might help to identify HCC patients with poor prognosis and guide individualized treatment.

Soft materials are promising candidates for robotics with outstanding performance and functionality. Zhang et al. present an energy harvesting and dissipation mechanism and describe the development of a soft gripper designed for capturing objects with high kinetic energy.

AbstractNitrite is harmful to aquatic animals in freshwater pond aquaculture environments. Nitrite is oxidized to nitrate mainly by nitrite-oxidizing bacteria (NOB). NOB may be promising in the control of nitrite concentration in aquaculture water. To better understand the role of NOB in the nitrogen cycling process of freshwater aquaculture ponds, we describe the characterization of NOB by using a culture derived from a freshwater aquaculture pond. Analysis by 16S rRNA sequence alignment showed that the NOB in the culture belong to the genus Nitrospira, whose generation time and nitrite–oxidizing rate were 9.87 h and 4.63 (± 0.07) pg NO2−–N cell−1·h−1 in the exponential growth phase, respectively. The oxidation of nitrite could be inhibited completely when the concentration of dissolved oxygen was 1.0 ± 0.5 mg/L.−1 The NOB could oxidize nitrite into nitrate at 29.84‰ salinity. However, the nitrification rate decreased significantly with an increase in salinity concentration ranging from 5.72‰ to 29.84‰. The optimal temperature range was 25–37 °C for the growth of NOB, and activity significantly decreased when the temperature was below 20 °C or reached 40 °C. In this study, the initial pH 6 ± 0.1–8 ± 0.1 was not observed to affect the nitrification activity of the NOB culture. Illumination of 410 ± 10 nm can completely inhibit NOB nitrification, and 520 ± 10 nm illumination partially inhibits NOB, whereas 660 ± 10 nm illumination has no effect. These findings indicate that the degree of photoinhibition in NOB increases with decreasing wavelength.

Acinetobacter baumannii is an important nosocomial pathogen. Upon colonizing a host, A. baumannii are subjected to selective pressure by immune defenses as they adapt to the host environment. However, the mechanism of this pathoadaptation is unknown. Here, we established an in vitro system to evolve A. baumannii driven by the continuous selective pressure exerted by epithelial cells, and we used a combination of experimental evolution, phenotypic characterization and multi-omics analysis to address the underlying mechanism. When continuously exposed to selective pressure by pulmonary epithelial cells, A. baumannii showed ptk mutation-mediated mucoid conversion (reduced adhesion and increased anti-phagocytic ability) by enhancement of capsular exopolysaccharide chain length; rsmG mutation-mediated deficiency of 7-methylguanosine modification in the 524th nucleotide of 16S rRNA, which increased ribosome translation efficiency; and rnaseI mutation-mediated changes in outer membrane permeability and efflux pump expression. Together, these mutations altered susceptibility to a variety of antimicrobial agents, including the novel antibiotic cefiderocol, by regulating siderophore and siderophore-receptor biosynthesis. In conclusion, pulmonary epithelial cells modulate A. baumannii pathoadaptation, implicating the host–microbe interaction in the survival and persistence of A. baumannii.

Bacterial outer membrane vesicles (OMVs) are spherical microbubbles that contain biological content and are produced by gram-negative bacteria. The use of OMVs as adjuvants for cancer immunotherapy or as drug carriers for targeted therapies has attracted the interest of many scholars. However, it is unclear whether OMVs can exert direct antitumor effects and whether OMVs can inhibit pediatric tumors. Here, we explore the potential of Escherichia coli-derived OMVs to directly suppress neuroblastoma. Our results demonstrate the antitumor effects of OMVs in vitro and in vivo, and no serious adverse reactions were observed. OMV uptake into the cytoplasm and nucleus directly decreases cell stemness, DNA damage, apoptosis and cell cycle arrest, which may be the mechanisms by which OMVs suppress tumors. Our results demonstrate the potential of bacterial OMVs to be used as antitumor adjuvant therapies, increasing the number of candidates for the development of cancer therapies in the future. More relevant studies are urgently needed to demonstrate the efficacy and safety of OMVs.

Abstract Light-mediated nanotherapeutics have recently emerged as promising strategies to precisely control the activation of therapeutic reagents and imaging probe both in vitro and in vivo, largely ascribed to their unique properties, including minimally invasive capabilities and high spatiotemporal resolution. Nanoscale metal–organic frameworks (NMOFs), a new family of hybrid materials consisting of metal attachment sites and bridging ligands, have been explored as a new platform for enhanced cancer diagnosis and therapy due to their tunable size, modifiable surface, good biocompatibility, high agent loading and, most significantly, their ability to be preferentially deposited in tumors through enhanced permeability and retention (EPR). Especially the light-driven NMOF-based therapeutic platform, which not only allow for increased laser penetration depth and enhanced targeting, but also enable imaging-guided or combined treatments. This review provides up-to-date developments of NMOF-based therapeutic platforms for cancer treatment with emphasis on light-triggered therapeutic strategies and introduces their advances in cancer diagnosis and therapy in recent years. Graphic Abstract

This study used a nickel-based filler metal to fabricate a surfacing layer on a low-carbon steel substrate by a hybrid welding process with a rotating laser and arc. The surfacing layer's weld formation was studied using optical microscopic observation (OM). The microstructure of the layers was studied by using the scanning electron microscope (SEM), energy dispersive spectrum (EDS) and X-ray diffraction (XRD). The arc, metal transfer, molten pool flow behaviors, and U–I characteristics during hybrid laser arc welding (HLAW) were analyzed using the arc analyzer and high-speed camera. The results show that a rotating laser improves the weld formation of gas metal arc welding (GMAW). The microstructure of the two surfacing layers consists of dendritic γ phase and a small amount of Laves and NbC phases. The high dilution rate of the HLAW surfacing layer results in relatively more Laves and fewer NbC phases. The arc length of HLAW is dynamically deflected with the rotation of the laser, which expands the arc action and heating area of the molten pool. The droplet transfer mode changed from globular transfer dominant in GMAW to the projected transfer dominant in HLAW. The location where the droplet transfer into the molten pool is dynamic changed, forming a multi-point impact on the molten pool. Combined with the deflected arc with the laser rotating laser, the HLAW has a broad and deep molten pool. Understanding the metal transfer behavior of Ni-based alloys in rotating laser-induced arc hybrid surfacing is of great significance for improving surfacing forming.