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Abstract Introduction Osteoporosis is a debilitating bone disease that significantly contributes to disability and a loss of autonomy among older adults. This study aimed to characterize osteoporosis and explore the feasibility of combining OSTA and BMR for osteoporosis prediction. Methods A cross-sectional study involving 1435 participants (1300 women and 135 men) was conducted. Spearman’s correlation, simple linear regression analyses, and multiple linear regression models were utilized to investigate the association between OSTA, BMR, and bone mineral density (BMD). Furthermore, the efficacy of integrating OSTA with BMR for osteoporosis screening and prediction was assessed through receiver operating characteristic (ROC) curves. Results In the total population, the sensitivity of combination variable W was 58.63%, and the specificity was 70.90%. When OSTA and BMR were employed separately to diagnose osteoporosis, the sensitivity was 47.70% and 55.34%, respectively, while the specificity was 63.80% and 69.80%, respectively. Conclusions The combined utilization of OSTA and BMR formula represents an effective screening method for osteoporosis.

Abstract The stability of coal pillars in fault areas is crucial for ensuring the safe passage of working faces. Based on field observations, frequent coal pillar spalling and substantial tectonic coal crumbs leakage, as well as tilting of hydraulic supports, are observed when working faces transition from primary coal to tectonic coal. To analyze the instability mechanisms behind these phenomena, this paper establishes a mechanical model of coal pillars in fault areas and analyzes the distribution of tectonic stresses and factors affecting the stability of coal pillars. The results indicate that horizontal tectonic stress adheres to an exponential function dependent on the angle factor, where (k 0) is a parameter associated with the friction angle of the coal body, the dip angle of the fault, and the friction angle of the fault plane. The stability of coal pillars is influenced by factors such as roof and floor pressures, coal pillar integrity, mining height, and shield support force, with coal pillar integrity being the most critical. To ensure the smooth passage of working faces through faults, this study proposes a combined control technique of “inclined mining” and “grouting,” including reducing mining heights, adjusting the slope of working face advancement, and pre-grouting of coal pillars. Industrial experiments conducted on-site have shown improved integrity of tectonic coal, enabling the working face to pass through faults smoothly and significantly increasing production efficiency.

Abstract Single-cell RNA sequencing (scRNA-seq) is a key technology for investigating cell development and analysing cell diversity across various diseases. However, the high dimensionality and extreme sparsity of scRNA-seq data pose great challenges for accurate cell type annotation. To address this, we developed a new cell-type annotation model called scGAA (general gated axial-attention model for accurate cell-type annotation of scRNA-seq). Based on the transformer framework, the model decomposes the traditional self-attention mechanism into horizontal and vertical attention, considerably improving computational efficiency. This axial attention mechanism can process high-dimensional data more efficiently while maintaining reasonable model complexity. Additionally, the gated unit was integrated into the model to enhance the capture of relationships between genes, which is crucial for achieving an accurate cell type annotation. The results revealed that our improved transformer model is a promising tool for practical applications. This theoretical innovation increased the model performance and provided new insights into analytical tools for scRNA-seq data.

Abstract Lipid nanoparticles (LNPs) are currently the most commonly used non-viral gene delivery system. Their physiochemical attributes, encompassing size, charge and surface modifications, significantly affect their behaviors both in vivo and in vitro. Nevertheless, the effects of these properties on the transfection and distribution of LNPs after intramuscular injection remain elusive. In this study, LNPs with varying sizes, lipid-based charges and PEGylated lipids were formulated to study their transfection and in vivo distribution. Luciferase mRNA (mLuc) was entraped in LNPs as a model nucleic acid molecule. Results indicated that smaller-sized LNPs and those with neutral potential presented superior transfection efficiency after intramuscular injection. Surprisingly, the sizes and charges did not exert a notable influence on the in vivo distribution of the LNPs. Furthermore, PEGylated lipids with shorter acyl chains contributed to enhanced transfection efficiency due to their superior cellular uptake and lysosomal escape capabilities. Notably, the mechanisms underlying cellular uptake differed among LNPs containing various types of PEGylated lipids, which was primarily attributed to the length of their acyl chain. Together, these insights underscore the pivotal role of nanoparticle characteristics and PEGylated lipids in the intramuscular route. This study not only fills crucial knowledge gaps but also provides significant directions for the effective delivery of mRNA via LNPs. Graphical Abstract

Abstract Transition-metal dichalcogenide monolayers possess large exciton binding energy and a robust valley degree of freedom, making them a viable platform for the development of spintronic devices capable of operating at room temperature. The development of such monolayer TMD-based spintronic devices requires strong spin-dependent interactions and effective spin transport. This can be achieved by employing exciton-polaritons. These hybrid light-matter states arising from the strong coupling of excitons and photons allow high-speed in-plane propagation and strong nonlinear interactions. Here, we demonstrate the operation of all-optical polariton spin switches by incorporating a WS2 superlattice into a planar microcavity. We demonstrate spin-anisotropic polariton nonlinear interactions in a WS2 superlattice at room temperature. As a proof-of-concept, we utilize these spin-dependent interactions to implement different spin switch geometries at ambient conditions, which show intrinsic sub-picosecond switching time and small footprint. Our findings offer new perspectives on manipulations of the polarization state in polaritonic systems and highlight the potential of atomically thin semiconductors for the development of next generation information processing devices.

Abstract In recent years, two-dimensional (2D) van der Waals materials have emerged as a focal point in materials research, drawing increasing attention due to their potential for isolating and synergistically combining diverse atomic layers. Atomically thin transition metal dichalcogenides (TMDs) are one of the most alluring van der Waals materials owing to their exceptional electronic and optical properties. The tightly bound excitons with giant oscillator strength render TMDs an ideal platform to investigate strong light-matter coupling when they are integrated with optical cavities, providing a wide range of possibilities for exploring novel polaritonic physics and devices. In this review, we focused on recent advances in TMD-based strong light-matter coupling. In the foremost position, we discuss the various optical structures strongly coupled to TMD materials, such as Fabry-Perot cavities, photonic crystals, and plasmonic nanocavities. We then present several intriguing properties and relevant device applications of TMD polaritons. In the end, we delineate promising future directions for the study of strong light-matter coupling in van der Waals materials.

Abstract Translating RNA-seq into clinical diagnostics requires ensuring the reliability and cross-laboratory consistency of detecting clinically relevant subtle differential expressions, such as those between different disease subtypes or stages. As part of the Quartet project, we present an RNA-seq benchmarking study across 45 laboratories using the Quartet and MAQC reference samples spiked with ERCC controls. Based on multiple types of ‘ground truth’, we systematically assess the real-world RNA-seq performance and investigate the influencing factors involved in 26 experimental processes and 140 bioinformatics pipelines. Here we show greater inter-laboratory variations in detecting subtle differential expressions among the Quartet samples. Experimental factors including mRNA enrichment and strandedness, and each bioinformatics step, emerge as primary sources of variations in gene expression. We underscore the profound influence of experimental execution, and provide best practice recommendations for experimental designs, strategies for filtering low-expression genes, and the optimal gene annotation and analysis pipelines. In summary, this study lays the foundation for developing and quality control of RNA-seq for clinical diagnostic purposes.

Background: In the past decade, we have continuously conducted sporadic monitoring and outbreak detection of norovirus (NoV), which causes human acute gastroenteritis (AGE) in the capital of China. Accumulated data have shown that genogroup I (GI) NoVs not only cause sporadic cases but also cannot be ignored during outbreaks. This study aimed to update the genetic diversity of GI NoVs in the capital of China from 2014 to 2023. Methods: Fecal or anal swab samples were collected from AGE outbreaks triggered by GI NoVs in Beijing Chaoyang District from 2014 to 2023. Both the partial coding genes of RNA-dependent RNA polymerase (RdRp) (∼283 bp) and viral protein 1 (VP1) (∼303 bp) were amplified via reverse transcription polymerase chain reaction (RT-PCR) and sequenced, followed by genotyping and phylogenetic analysis. Results: A total of 421 fecal or anal swab samples were collected from 59 AGE outbreaks caused by GI NoVs. Genetic diversity was observed, with nine genotypes reported, including recombinant strains of GI.6[P11] and GI.3[P13], as well as multiple subtypes that cocirculated. In addition, we also reported a shift in the dominant genotype, with GI.6 [P11] in 2015–2018, GI.3 [P13] in 2019–2021, and GI.4 [P4] in 2023. Furthermore, alterations in amino acids were indirectly indicated through single nucleotide polymorphisms (SNPs) in certain VP1 areas of strains GI.3[P13] and GI.6[P11]. Epidemiologically, the peak of infection induced by GI NoVs occurs from March to May. Conclusions: The sustained circulation and obvious genotype shift of GI NoVs in this region cannot be ignored, and GI.4[P4] NoVs are highly likely to become the main epidemic strain in the following years.

Gob-side entry retaining (GER) play a crucial role in enhancing coal recovery, improving roadway stress conditions, and ensuring safe and efficient mining operations. This study focuses on investigating the stability characteristics of surrounding rock using flexible formwork concrete (FFC) along the headgate of 3405 panel. According to the fracture pattern of roof, a mechanical model of GER was developed. This study derived expressions for the support resistance of the filling body and determined its optimal bearing capacity. A FLAC3D numerical model was employed to simulate the GER process, segmented into early, middle, and late stages. Simulation results demonstrate a progression in peak deviatoric stress and extent of plastic zones in the surrounding rock. This evolution includes an initial minor increase (early stage), followed by rapid escalation (middle stage), and eventual stabilization (late stage). The middle stage emerges as critical, characterized by pronounced mining-induced stress effects on the roof. During this phase, significant changes are observed in deviatoric stress curves, with plastic zones rapidly migrating deeper into the rock mass. Practical implementation of the findings revealed a maximum deformation of the filling body of only 198 mm, affirming the feasibility of employing FFC in GER. This research provides valuable insights into managing stability concerns in GER thereby enhancing safety and operational efficiency in coal mining under similar conditions.

IntroductionClean drinking water is a necessity for maintaining public health and livelihoods. Hard water containing excessive calcium and magnesium threatens urinary health with elevated risks of kidney stones at rural villages with tap water shortages. After entitled poverty alleviation in 2019, residents of Yangxin county of Hubei Province in central China unexpected suffered shortage of tap water and additional cost of water softening. However, the impact of lack of tap water on risks of kidney stones was not yet quantified for residents at rural villages in Yangxin.MethodsWe conducted a cross-sectional analysis by testing 216 water samples from 114 families at four villages and surveying urinary health and living conditions of each householder.ResultsLab tests showed that mean total hardness of well and tap water at each village was above 355 mg/L CaCO3, except tap water from the village with government support for industrial development. Mean softening depth was 309.3 mg/L at the families paying for filters or bottle water, and mean annual cost of water was 1,915 CNY (1 CNY = 0.14 USD) equivalent to 5.8% of mean annual household income. Mean tap water availability was only 34%, and the prevalence of kidney stones among the four villages was 33.9%, 25.0% higher than the rate of kidney stones in Hubei Province. About 60% of the families showed strong willingness to accept annual government compensation of 3,324 CNY for clean water supply, whereas only 2.6% of the families wanted to pay government for water treatment. Using logistic and random forest regression models, we identify factors associated with the prevalence of kidney stones as gender (males have 3.78 times the risks of females), age (2.42 times greater risks if 10 years older), body mass index (higher risks if overweight or obese), total hardness of drinking water (2.59 times for a 100 mg/L increase in total hardness), and tap water availability (2.42 times higher among those without tap water supply compared to those with constant supply).DiscussionOld and obese males are more likely to be diagnosed with kidney stones, but tap water shortages and high total hardness of drinking water increase the risks for all residents. To improve urinary health and meet support needs of residents, tap water supply of soft water is urgently needed at the rural villages in Yangxin.

Abstract Van der Waals semiconductors exemplified by two-dimensional transition-metal dichalcogenides have promised next-generation atomically thin optoelectronics. Boosting their interaction with light is vital for practical applications, especially in the quantum regime where ultrastrong coupling is highly demanded but not yet realized. Here we report ultrastrong exciton-plasmon coupling at room temperature in tungsten disulfide (WS2) layers loaded with a random multi-singular plasmonic metasurface deposited on a flexible polymer substrate. Different from seeking perfect metals or high-quality resonators, we create a unique type of metasurface with a dense array of singularities that can support nanometre-sized plasmonic hotspots to which several WS2 excitons coherently interact. The associated normalized coupling strength is 0.12 for monolayer WS2 and can be up to 0.164 for quadrilayers, showcasing the ultrastrong exciton-plasmon coupling that is important for practical optoelectronic devices based on low-dimensional semiconductors.

Abstract Plague, as an ancient zoonotic disease caused by Yersinia pestis, has brought great disasters. The natural plague focus of Marmota himalayana in the Qinghai-Tibet Plateau is the largest, which has been constantly active and the leading source of human plague in China for decades. Understanding the population genetics of M. himalayana and relating that information to the biogeographic distribution of Yersinia pestis and plague outbreaks are greatly beneficial for the knowledge of plague spillover and arecrucial for pandemic prevention. In the present research, we assessed the population genetics of M. himalayana. We carried out a comparative study of plague outbreaks and the population genetics of M. himalayana on the Qinghai-Tibet Plateau. We found that M. himalayana populations are divided into two main clusters located in the south and north of the Qinghai-Tibet Plateau. Fourteen DFR genomovars of Y. pestis were found and exhibited a significant region-specific distribution. Additionally, the increased genetic diversity of plague hosts is positively associated with human plague outbreaks. This insight gained can improve our understanding of biodiversity for pathogen spillover and provide municipally directed targets for One Health surveillance development, which will be an informative next step toward increased monitoring of M. himalayana dynamics.

Abstract Energy transfer is a ubiquitous phenomenon that delivers energy from a blue-shifted emitter to a red-shifted absorber, facilitating wide photonic applications. Two-dimensional (2D) semiconductors provide unique opportunities for exploring novel energy transfer mechanisms in the atomic-scale limit. Herein, we have designed a planar optical microcavity-confined MoS2/hBN/WS2 heterojunction, which realizes the strong coupling among donor exciton, acceptor exciton, and cavity photon mode. This configuration demonstrates an unconventional energy transfer via polariton relaxation, brightening MoS2 with a record-high enhancement factor of ~440, i.e., two-order-of-magnitude higher than the data reported to date. The polariton relaxation features a short characteristic time of ~1.3 ps, resulting from the significantly enhanced intra- and inter-branch exciton-exciton scattering. The polariton relaxation dynamics is associated with Rabi energies in a phase diagram by combining experimental and theoretical results. This study opens a new direction of microcavity 2D semiconductor heterojunctions for high-brightness polaritonic light sources and ultrafast polariton carrier dynamics.

With the growing prevalence of drone technology across various sectors, efficient and safe path planning has emerged as a critical research priority. Traditional Aquila Optimizers, while effective, face limitations such as uneven population initialization, a tendency to get trapped in local optima, and slow convergence rates. This study presents a multi-strategy fusion of the improved Aquila Optimizer, aiming to enhance its performance by integrating diverse optimization techniques, particularly in the context of path planning. Key enhancements include the integration of Bernoulli chaotic mapping to improve initial population diversity, a spiral stepping strategy to boost search precision and diversity, and a “stealing” mechanism from the Dung Beetle Optimization algorithm to enhance global search capabilities and convergence. Additionally, a nonlinear balance factor is employed to dynamically manage the exploration–exploitation trade-off, thereby increasing the optimization of speed and accuracy. The effectiveness of the mixed multi-strategy improved Aquila Optimizer is validated through simulations on benchmark test functions, CEC2017 complex functions, and path planning scenarios. Comparative analysis with seven other optimization algorithms reveals that the proposed method significantly improves both convergence speed and optimization accuracy. These findings highlight the potential of mixed multi-strategy improved Aquila Optimizer in advancing drone path planning performance, offering enhanced safety and efficiency.

The signal enhancement in plasmon-enhanced spectroscopy is primarily contributed by hotspots generated through the surface plasmon resonance effect. Precise control of hotspot positions within nanostructures is of great significance in surface-enhanced Raman spectroscopy (SERS) and high spatial resolution imaging. However, predicting the positions of hotspots is challenging due to the small nanogaps and complex plasmonic interactions. In this study, we theoretically investigate the localized surface plasmonic properties of split ring nanostructure. The effects of variations in the inner radius, gap distance and thickness of the split ring on the hotspot distribution at the nanogaps are systematically analyzed using a three-dimensional finite element method. The results demonstrate that precise control over the positions and quantities of hotspots can be achieved by choosing the excitation wavelength and the gap size of the split rings. The calculated maximum Raman enhancement obtained at the hotspots can reach nine orders of magnitude. Our findings not only contribute to a deeper understanding of the SERS enhancement mechanism, but also provide theoretical insights for further development of surface-enhanced fluorescence, plasmonic sensors, and super-resolution imaging in the field of interface spectroscopy.

The incidence of leiomyosarcoma (LMS) is about 4–5/100,000 individuals per year. LMSs occurring in the small bowel are even rarer, and their preoperative diagnosis is very difficult. We described two patients with pathologically confirmed small bowel LMS and analyzed their clinical and medical imaging features. Similar cases reported in English in Pubmed database over the past decade were reviewed and summarized. These tumors were categorized by the growth direction and relationship with the intestinal lumen into three types: intraluminal (n = 10), intermural (n = 3), and extraluminal (n = 7). Notably, among the three types of LMS, the intramural leiomyosarcoma stands out as a noteworthy subtype. Emerging evidence suggests that smaller tumor size (< 5 cm) and the intraluminal type may serve as favorable prognostic indicators, while the extraluminal type is associated with relatively poor prognosis. Furthermore, the integration of imaging features with CA125 and LDH biomarkers holds promise for potential diagnostic value in LMS.

AbstractContext Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear.Objective To elucidate styrax’s anti-ischemic stroke protective effects and underlying mechanisms.Materials and methods An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n = 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based serum metabonomics were used to elucidate styrax’s cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify.Results The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-α, IL-6, and IL-1β, and increase SOD and GSH-Px in ischemic-stroke rats (p

Abstract The load capacity of small robots plays a crucial role in practical applications. Drawing inspiration from biological load‐carrying mechanisms, a crawling robot based on piezoelectric bending is proposed. It is an insect‐scale piezoelectric‐driven crawling robot with a load capacity of 100.4 times its weight, which is the highest measured among published insect‐scale robots. The robot was designed and fabricated in a monolithic manner, enhancing the assembly efficiency of the robot. It weighs only 0.68 g and has a length of only 40 mm. The robot can achieve rapid movement and jumping by using two different driving methods. Its maximum forward speed is 7.77 BL/s (body lengths per second), and it can reach a forward speed of 1 BL/s under a load of 41.6 g, the maximum load of the robot is 68.24 g. It can move rapidly, climb slopes, traverse ground obstacles, and pass through pipes, similar to an insect.

The new-generation polyimide films with simultaneously outstanding thermal stability and low coefficient of linear thermal expansion (CTE) are urgently needed. Herein, coordination bonds were employed to improve polyimide films' heat resistance and dimensional stability. Polyimide-Cu complex films were fabricated by incorporating α-diimide units (bidentate ligands) into the BPDA-ODA (the structure of commercially available Upilex-R® polyimide films) backbones. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and Energy dispersive X-ray mapping results showed that the coordination interactions occur between α-diimide and copper ions. Wide-angle X-ray diffraction (WAXD) and two-dimensional small-angle X-ray scattering (SAXS) spectra demonstrated that Cu-α-diimide coordination structures introduced in intermolecular chains leading polyimide films transformed from a semi-crystalline state to amorphous state, and inhibited the long-period formation structures. The plateau modulus and longer characteristic relaxation time (τ∗ = 1996.5 s) revealed by dynamic thermomechanical analysis indicated that crosslink networks were successfully formed by constructing coordination bonds. As a result, polyimide films' thermal resistance and dimensional stability were simultaneously enhanced. The typical PI-Cu50 films exhibited elevated glass transition temperatures of 353 °C (pristine PI-Cu0 ∼ 302 °C) and a lower CTE of 47.4 ppm/K (pristine PI-Cu0 films ∼ 64.4 ppm/K) in ranges of 300–400 °C, showing a promising application in the field of high-temperature environments.

CO2 shielding gas was innovatively employed for TC4/304SS dissimilar metal arc welding, overcoming the limitation of active gas application for Ti welding. The effect of CO2 addition on welding process was investigated. Our results show that the CO2+Ar hybrid shielding gas eliminated the problem of insufficient bonding at the backside of the steel plate, and was helpful to obtain a full weld joint. Moreover, the microstructure of the weld joint was modified due to the intense mass transfer inside the molten pool. The typical Ti/Cu interface was divided into two layers. No Ti–Fe compounds were found within the Ti/Cu interface for pure Ar shielding gas. However, the interface morphology was found to change due to induced CO2. Some TiFe2+Ti5Si3 dendrites were formed in layer Ⅱ. And the TEM results showed that the addition of CO2 did not contribute to the generation of a new phase, but the island-shaped Ti2Cu3 was transformed to a lath shape. In the weld seam center, Ti–Fe–Si ternary compounds was formed instead of Ti–Fe or Ti–Cu compounds. The hardness of the entire joint increased with increasing CO2 content. An average strength of 480 MPa was obtained for 3% CO2 content, which is an increase of 57.9% compared to that for pure Ar shielding condition. The fracture surface morphology showed small cleavage flatforms with some shallow dimples. Better weld formation and the optimization of the interface microstructure both contributed significantly to the improvement of the tensile strength of the Ti/steel joint.

This study aimed to enhance the stability and response speed of a passive stabilized double-wing flapping micro air vehicle (FMAV) by implementing a feedback-controlled biomimetic tail. A model for flapping wings accurately calculated the lift force with only a 2.4% error compared to the experimental data. Experimental tests established the relationship between control torque and tail area, swing angle, and wing–tail spacing. A stability model for the double-wing FMAV was developed, incorporating stabilizing sails. Linearization of the hovering state facilitated the design of a simulation controller to improve response speed. By adjusting the feedback loops of velocity, angle, and angular velocity, the tail controller reduced the angle simulation response time from 4 s to 0.1 s and the velocity response time from 5.64 s to 0.1 s. In take-off experiments, a passive stabilized prototype with an adjustable tail angle exhibited enhanced flight stability compared to fixed tails, reducing standard deviation by 72.96% at a 0° take-off angle and 56.85% at a 5° take-off angle. The control axis standard deviation decreased by 38.06% compared to the passive stability axis, confirming the effectiveness of the designed tail angle controller in reducing angular deflection and improving flight stability.

Step-stare imaging systems are widely used in aerospace optical remote sensing. In order to achieve fast scanning of the target region, efficient coverage path planning (CPP) is a key challenge. However, traditional CPP methods are mostly designed for fixed cameras and disregard the irregular shape of the sensor’s projection caused by the step-stare rotational motion. To address this problem, this paper proposes an efficient, seamless CPP method with an adaptive hyperbolic grid. First, we convert the coverage problem in Euclidean space to a tiling problem in spherical space. A spherical approximate tiling method based on a zonal isosceles trapezoid is developed to construct a seamless hyperbolic grid. Then, we present a dual-caliper optimization algorithm to further compress the grid and improve the coverage efficiency. Finally, both boustrophedon and branch-and-bound approaches are utilized to generate rotation paths for different scanning scenarios. Experiments were conducted on a custom dataset consisting of 800 diverse geometric regions (including 2 geometry types and 40 samples for 10 groups). The proposed method demonstrates comparable performance of closed-form path length relative to that of a heuristic optimization method while significantly improving real-time capabilities by a minimum factor of 2464. Furthermore, in comparison to traditional rule-based methods, our approach has been shown to reduce the rotational path length by at least 27.29% and 16.71% in circle and convex polygon groups, respectively, indicating a significant improvement in planning efficiency.

Background: The role of the Wnt pathway in bone and its targets in skeletal disease has garnered interest, but the field lacks a systematic analysis of research. This paper presents a bibliometric study of publications related to the Wnt signaling pathway in bone to describe the current state of study and predict future outlooks.Methods: All relevant articles and reviews from 1993 to 2022 were collected from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using CiteSpace 6.1 R3, VOSviewer 1.6.15, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com/).Results: A total of 7,184 papers were retrieved, authored by 28,443 researchers from 89 countries/regions and published in 261 academic journals. The annual publication numbers peaked in 2021. China and United States are the leading countries, with the University of California and Harvard University as the most active institutions. Wang, Yang is the most prolific author. Bone has the most published research, while Proceedings of the National Academy of Sciences of the United States is the most cited journal on average. The main keywords include expression, Wnt, osteoporosis, bone, and osteogenic differentiation. Current and developing research hotspots focus on bone mass, sclerostin antibody, multiple myeloma, and cartilage development.Conclusion: This paper provides new insights for researchers to delve into the mechanisms of Wnt and bone related diseases and translate into clinical studies. It reveals the development and future research trends in Wnt and skeletal-related studies.

The authors embed a multiple quantum-well WS2 heterostructure in a planar microcavity and show the systematic control of the normal mode coupling-strength. They find a strong enhancement of the characteristic time scale, which they attribute to long-lived dark excitations emerging in the structure.

The optical properties of monolayer black phosphorus (BP) in two-photon excited fluorescence (TPEF) are pivotal for photoluminescence applications at the single molecular level. In this study, we theoretically examine the TPEF properties of monolayer BP using a tip-enhanced spectroscopy system. We detail the influence of parameters such as the tip radius, the distance between the tip and the BP film, the incidence angle and the tip half-cone angle on the fluorescence excitation and emission enhancement of monolayer BP. This examination employs the finite element method. Our findings reveal that the signal enhancement in TPEF is substantially improved, approximately two orders of magnitude greater than that in single-photon excited fluorescence (SPEF), attributed to the high-order nonlinear coupling effect. By optimising the system configuration, we determined that the TPEF enhancement factor with monolayer BP can reach as high as eight orders of magnitude under an excitation wavelength of 800 nm. The highest spatial resolutions achievable for TPEF and SPEF spectroscopy are also 4.4 nm and 5.3 nm, respectively. These results provide an in-depth understanding of the TPEF enhancement mechanism and are invaluable for designing and applying BP-based optoelectronic devices.

In this paper, we proposed a miniature quadrupedal piezoelectric robot with a mass of 1.8 g and a body length of 4.6 cm. The robot adopts a novel spatial parallel mechanism as its transmission. Each leg of the robot has two degrees of freedom (DOFs): swing and lift. The trajectory necessary for walking is achieved by the appropriate phasing of these two DOFs. A new manufacturing method for piezoelectric actuators was developed. During the stacking process, discrete patterned PZT pieces are used to avoid dielectric failure caused by laser cutting. Copper-clad FR-4 is used as the solder pad instead of copper foil, making the connection between the pad and the actuator more reliable. The lift powertrain of the robot was modeled and the link length of the powertrain was optimized based on the model. The maximum output force of each leg can reach 26 mN under optimized design parameters, which is 1.38 times the required force for successful walking. The frequency response of the powertrain was measured and fitted to the second-order system, which enabled increased leg amplitudes near the powertrain resonance of approximately 70 Hz with adjusted drive signals. The maximum speed of the robot without load reached 48.66 cm/s (10.58 body lengths per second) and the payload capacity can reach 5.5 g (3.05 times its mass) near the powertrain resonance.

Abstract Purpose To investigate the factors influencing and long-term effects of manual myotomy (MM) occurring during physiotherapy for congenital muscular torticollis (CMT). Methods We retrospectively collected the clinical data of children with CMT receiving physiotherapy between 2008 and 2018. The children were divided into manual myotomy (MM) and non-manual myotomy (NMM) groups according to whether MM occurred during treatment. We assessed physiotherapy outcomes in children with CMT using craniofacial asymmetry parameters and the Cheng–Tang rating score. By measuring the ear-eye distance, ear-nose distance, eye-mouth distance, ear-mouth distance, half-head circumference, and half-head top at two sides to evaluate craniofacial asymmetry. Based on the Cheng–Tang assessment criteria, we recorded the range of rotation, range of lateral flexion, the status of the contracted muscle, the hardness of the mass, the extent of head tilting during activities and sleeping, the status of daily activities, face size, type of head shape, cranial changes, and subjective head tilting to assess the effectiveness of treatment. Clinical data and outcome indicators (craniofacial asymmetry parameters and Cheng–Tang rating score) were compared. Results The MM group had a significantly higher total Cheng–Tang rating score than the NMM group (P

ABSTRACT Importance There are a variety of musculoskeletal malformations and injuries that can occur in newborns. These can be a significant cause of perinatal death or a reason for miscarriage and can lead to long‐term functional issues if not managed appropriately. There is no systematic and well‐established screening program for neonatal musculoskeletal malformations and injuries in China now. Objective To report the incidence and types of congenital musculoskeletal malformations in two hospitals in Shenzhen City, to explore and discuss the details of the screening procedure and improve future prevention and treatment. Methods From October 2013 to May 2014, 2564 one‐day‐old newborns were screened by a pediatric orthopedic physical examination, in combination with ultrasonography when required, and the incidence and variety of diseases were recorded statistically. Results Among 2564 screened newborns, the following musculoskeletal conditions were identified: congenital muscular torticollis (CMT) (seven cases, 0.27%), hip subluxation (four cases, 0.16%), hip dysplasia (47 cases, 1.83%), congenital talipes equinovarus (CTEV) (two cases, 0.08%), congenital talipes calcaneovalgus (15 cases, 0.58%), polydactyly (nine cases, 0.35%), syndactyly (one case, 0.04%), and spinal hemivertebra (one case, 0.04%). Additionally, there were five (0.19%) neonates with birth injuries. Interpretation It is feasible to carry out neonatal screening and identification of musculoskeletal malformations and birth injuries in China. This is helpful as timely detection and early intervention for many of these conditions can avoid permanent functional impairment in these children.

Lipidemic effect of air pollutants are still inconsistent and their joint effects are neglected. Meanwhile, identified inflammation pathways in animal have not been applied in epidemiological studies, and beneficial effect of residential greenness remained unclear. Therefore, we used data from typically air-polluted Chinese cities to answer these questions. Particulate matter (PM) with a diameter of ≤ 1 µm (PM1), PM with a diameter of ≤ 2.5 µm (PM2.5), PM with a diameter of ≤ 10 µm (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) were predicted by space–time extremely randomized trees model. Residential greenness was reflected by Normalized Difference Vegetation Index (NDVI). Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured, and atherogenic coefficient (AC) and TG/HDL-C (TGH) ratio were calculated to indicate lipid metabolism. Generalized additive mixed model and quantile g-computation were respectively conducted to investigate individual and joint lipidemic effect of air pollutants. Covariates including demographical characteristics, living habits, meteorological factors, time trends, and disease information were considered to avoid confounding our results. Complement C3 and high-sensitivity C-reactive protein (hsCRP) were analyzed as potential mediators. Finally, association between NDVI and lipid markers were explored. We found that long-term air pollutants exposure were positively associated with lipid markers. Complement C3 mediated 54.72% (95% CI: 0.30, 63.10) and 72.53% (95% CI: 0.65, 77.61) of the association between PM1 and TC and LDL-C, respectively. We found some significant associations of lipid markers with NDVI1000 m rather than NDVI500 m. BMI, disease status, smoke/drink habits are important effect modifiers. Results are robust in sensitive analysis. Our study indicated that air pollutants exposure may detriment lipid metabolism and inflammation may be the potential triggering pathways, while greenness may exert beneficial effects. This study provided insights for the lipidemic effects of air pollution and greenness.

Abstract Glioma is the most common malignant tumors in the brain. Previous studies have revealed that, as the innate immune cells in nervous system, microglia cells were involved in glioma pathology. And, the resident microglia displayed its specific biological roles which distinguished with peripheral macrophages. In this study, an integrated analysis was performed based on public resource database to explore specific biological of microglia within glioma. Through comprehensive analysis, the biological characterization underlying two conditions, glioma microglia compared to glioma macrophage (MicT/MacT) as well as glioma microglia compared to normal microglia (MicT/MicN), were revealed. Notably, nine core MicT/MicN genes displayed closely associations with glioma recurrence and prognosis, such as P2RY2, which was analyzed in more than 2800 glioma samples from 25 studies. Furthermore, we applied a random walk based strategy to identify microglia specific subpathways and developed SubP28 signature for glioma prognostic analysis. Multiple validation data sets confirmed the predictive performance of SubP28 and involvement in molecular subtypes. The associations between SuP28 score and microglia M1/M2 polarization were also explored for both GBM and LGG types. Finally, a comprehensive drug-subpathway network was established for screening candidate medicable molecules (drugs) and identifying therapeutic subpathway targets. In conclusions, the comprehensive analysis of microglia related gene and functional signatures in glioma pathobiologic events by large-scale data sets displayed a framework to dissect inner connection between microglia and glioma, and identify robust signature for glioma clinical implications.

Abstract Background Fractures are the most common type of unintentional injury in children, with traumatic upper limb fractures accounting for approximately 80% of all childhood fractures. Many epidemiological investigations of upper limb fractures in children have been conducted, but with the development of society, the patterns of childhood fractures may have changed. This study aimed to analyze the epidemiology and economic cost factors of upper limb fractures in Chinese children. Methods We retrospectively reviewed children with upper limb fractures or old upper limb fractures hospitalized between December 1, 2015, and December 31, 2019, in 22 tertiary children’s hospitals, under China’s Futang Research Center of Pediatric Development. We used the ICD10 codes on the front sheet of their medical records to identify cases and extracted data on age, sex, injury cause, fracture site, treatment, the year of admission and discharge, visiting time, and various costs during hospitalization from the medical record. Results A total of 32,439 children (21,478 boys and 10,961 girls) were identified, of whom 32,080 had fresh fractures and 359 had old fractures. The peak age was 3–6 years in both sexes. A total of 4788 were infants, 14,320 were preschoolers, 10,499 were in of primary school age, and 2832 were adolescent. Fractures were most frequent in autumn (August to October). Admissions peaked at 0 o’clock. Among the 32,080 children with fresh upper limb fractures, the most common fracture site was the distal humerus, with a total of 20,090 fracture events including 13,134 humeral supracondylar fractures and 4914 lateral humeral condyle fractures. The most common cause of injuries was falling over. The most common joint dislocation accompanying upper limb fractures occurred in the elbow, involving 254 cases. Surgery was performed in 31,274 children, and 806 did not receive surgery. Among those with clear operative records, 10,962 children were treated with open reduction and 18,066 with closed reduction. The number of cases was largest in the East China region (Anhui Province, Shandong Province, Jiangsu Province, Zhejiang Province, and Fujian Province), with 12,065 cases overall. Among the 359 children with old fractures, 118 were admitted with a diagnosis of “old humerus fracture,” accounting for the highest proportion; 244 underwent surgical open reduction, 16.16% of whom had osteotomy. For the children with fresh fractures, the average total hospital cost was 10,994 yuan, and the highest average total hospital cost was 14,053 yuan, for humeral shaft fractures. For the children with old fractures, the average total hospital cost was 15,151 yuan, and the highest average total hospital cost was 20,698 yuan, for old ulna fractures. Cost of materials was the principle factor affecting total hospital cost, followed by surgery and anesthesia costs, both in children with fresh fractures and those with old fractures. Significant differences were observed in all hospital costs (P

This study investigated the adsorption performance of hydrothermal carbon derived from banana peel and modified with different concentrations of phosphoric acid solution, then used to adsorb lead ions in an aqueous solution. The surface structure and functional groups of the modified hydrothermal carbon were analyzed using XRD, SEM, FT-IR, elemental analysis, and BET. The results showed that the adsorption capacity of modified hydrothermal carbon derived from banana peel reached 40.64 mg/g at a hydrothermal temperature of 240 °C, a phosphoric acid solution of 2 mol/L, and a solid–liquid ratio of 2 g/L, with a removal efficiency of 82.74%. The adsorption process conformed to the pseudo-second-order kinetic model and the Langmuir isotherm equation. The correlation coefficient of 0.99 for fitting the adsorption process using an artificial neural network, indicating that the artificial neural network could be used to predict adsorption. The adsorption of Pb(II) from an aqueous solution by phosphoric acid-modified hydrothermal carbon was dominated by monolayer chemical adsorption, and the adsorption mechanisms included electrostatic attraction, ion exchange, surface complexation, and physical adsorption.

BackgroundThis study explored the mediating role of glucose homeostasis indicators in the relationship between serum cystatin C and mild cognitive impairment (MCI).MethodsThe present study used a cross-sectional design and included 514 participants aged ≥50 years in Beijing, China. The Mini-Mental State Examination was used to assess cognitive function. Serum cystatin C and a comprehensive set of glucose homeostasis indicators were detected, including fasting blood glucose (FBG), glycosylated albumin percentage (GAP), glycated hemoglobin (HbAlc), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β). Generalized linear models were used to investigate the associations among cystatin C, glucose homeostasis indicators, and cognitive function. Mediation analysis was conducted to explore potential mediator variables.ResultsIn this study of 514 participants, 76 (14.8%) had MCI. Those with cystatin C levels ≥1.09 mg/L had a 1.98-fold higher risk of MCI than those with levels

The latex used conventionally for oil-well cementing can lead to serious foaming issues in the cement slurry, which not only affects the accurate measurement of the density of the latex-containing cement slurry, but also is detrimental to cementing construction. A large amount of a foam stabilizer used for latex preparation is mainly responsible for foaming of the latex-containing cement slurry. In this study, soap-free emulsion polymerization was conducted using 2-acrylamido-2-methylpropanesulfonic acid (AMPS), styrene (St), and butyl acrylate (BA) as the reaction monomers and the effects of the AMPS dosage, monomer ratio, reaction temperature and stirring speed on the performance of the latex were investigated. The optimum synthesis conditions included a 30% monomer concentration, an St : BA : AMPS monomer ratio of 5 : 4 : 6, a synthesis temperature of 85°C, a stirring speed of 400 r.p.m. and 1.5% of the initiator. As-prepared latex exhibited good filtration loss control, excellent freeze–thaw stability, and extremely low foaming of the cement slurry with the added latex, which was extremely beneficial for on-site cementing construction.

Hot compression tests of Mg-Gd-Y-Zr alloy at different deformation temperatures and strains were carried out with Gleeble-1500 simulator at strain rate of 0.002 s−1. The microstructure evolution of 400 °C/0.002 s−1 sample under different strain was analyzed emphatically by transmission electron microscopy and electron backscatter diffraction technology. Dynamic precipitation characteristics and nucleation-expansion mechanism of dynamic recrystallization (DRX) were discussed in detail. The results indicated that the dynamic precipitation takes place prior to DRX, and the morphology, size and distribution of precipitates change with increasing strain. At the later stage of deformation, the large-size hard phase β-Mg5(Gd,Y) can induce the particle-stimulated nucleation (PSN) mechanism under large strain and act as an effective nucleation site for DRX. In addition, we constructed a schematic diagram of the DRX nucleation-expansion mechanism of Mg-Gd-Y-Zr alloy under high temperature deformation. The first layer of DRX grains is formed by discontinuous dynamic recrystallization (DDRX) mechanism characterized by grain boundary bulge out, and the precipitates distributed at the original grain boundary promote DDRX nucleation; The expansion of necklace structure depends on continuous dynamic recrystallization (CDRX) mechanism; Subgrain division can further refine DRX grains.

We analyzed the deformation behavior of Mg-Gd-Nd(-Zn)-Zr alloys under high temperature uniaxial compression, and reported two special nucleation mechanisms of dynamic recrystallization (DRX): Nucleation and expansion of DRX based on reticular shear bands (Shear band dynamic recrystallization, SBDRX) and long chain twins (Twin dynamic recrystallization, TDRX). The reticular shear bands in Mg-Gd-Nd-Zr alloy are mainly caused by the crossing of strain gradients from different directions, which is related to the high activity of pyramidal slip at high temperature. The addition of Zn makes the DRX mechanism mutate, and TDRX is dominant in Mg-Gd-Nd-Zn-Zr alloy. The nucleation of a large number of {10–12} twins is abnormal, which may be related to the decrease of I2 stacking fault energy caused by Gd/Nd–Zn compound addition. Based on the mechanical properties and microstructure, it can be concluded that the addition of Zn can promote the DRX, reduce the deformation resistance and improve the workability.

BackgroundGrowing evidence suggests the gut microbiota and metabolites in serum or fecal may play a key role in the process of alcohol use disorder (AUD). However, the correlations of gut microbiota and metabolites in both feces and serum in AUD subjects are not well understood.MethodsWe established a rat model of AUD by a chronic intermittent ethanol voluntary drinking procedure, then the AUD syndromes, the gut microbiota, metabolomic profiling in feces and serum of the rats were examined, and correlations between gut microbiota and metabolites were analyzed.ResultsEthanol intake preference increased and maintained at a high level in experimental rats. Anxiety-like behaviors was observed by open field test and elevated plus maze test after ethanol withdraw, indicating that the AUD rat model was successfully developed. The full length 16S rRNA gene sequencing showed AUD significantly changed the β-diversity of gut microbial communities, and significantly decreased the microbial diversity but did not distinctly impact the microbial richness. Microbiota composition significantly changed in AUD rats, such as the abundance of Romboutsia and Turicibacter were significantly increased, whereas uncultured_bacterium_o_Mollicutes_RF39 was decreased. In addition, the untargeted metabolome analysis revealed that many metabolites in both feces and serum were altered in the AUD rats, especially involved in sphingolipid metabolism and glycerophospholipid metabolism pathways. Finally, multiple correlations among AUD behavior, gut microbiota and co-changed metabolites were identified, and the metabolites were directly correlated with the gut microbiota and alcohol preference.ConclusionThe altered metabolites in feces and serum are important links between the gut microbiota dysbiosis and alcohol preference in AUD rats, and the altered gut microbiota and metabolites can be potentially new targets for treating AUD.

Background Myocardial infarction (MI) is characterized by the emergence of dead or dying cardiomyocytes and excessive immune cell infiltration after coronary vessel occlusion. However, the complex transcriptional profile, pathways, cellular interactome, and transcriptional regulators of immune subpopulations after MI remain elusive. Methods and Results Here, male C57BL/6 mice were subjected to MI surgery and monitored for 1 day and 7 days, or sham surgery for 7 days, then cardiac CD45‐positive immune cells were collected for single‐cell RNA sequencing to determine immune heterogeneity. A total of 30 135 CD45+ immune cells were partitioned into macrophages, monocytes, neutrophils, dendritic cells, and T or B cells for further analysis. We showed that macrophages enriched for Olr1 and differentially expressed Gpnmb represented 2 crucial ischemia‐associated macrophages with distinct proinflammatory and prophagocytic capabilities. In contrast to the proinflammatory subset of macrophages enriched for Olr1, Gpnmb‐positive macrophages exhibited higher phagocytosis and fatty acid oxidation preference, which could be abolished by etomoxir treatment. In addition to macrophages, MI triggered prompt recruitment of neutrophils into murine hearts, which constituted the sequential cell‐fate from naïve S100a4‐positive, to activated Sell‐high, to aging Icam1‐high neutrophils. In silico tools predicted that the excessively expanded neutrophils at 1 day were attributed to chemokine C‐C motif ligand/chemokine C‐X‐C motif ligand pathways, whereas CD80/inducible T‐cell costimulator (ICOS) signaling was responsible for the immunosuppressive response at day 7 after MI. Finally, the Fos/AP‐1 (activator protein 1) regulon was identified as the critical regulator of proinflammatory responses, which was significantly activated in patients with dilated cardiomyopathy and ischemic cardiomyopathy. We showed the enriched Fos/AP‐1 target gene loci in genome‐wide association study signals for coronary artery diseases and MI. Targeting Fos/AP‐1 with the selective inhibitor T5224 blunted leukocyte infiltration and alleviated cardiac dysfunction in the preclinical murine MI model. Conclusions Taken together, this single‐cell RNA sequencing data lay the groundwork for the understanding of immune cell heterogeneity and dynamics in murine ischemic hearts. Moreover, Fos/AP‐1 inhibition mitigates inflammatory responses and cardiac dysfunction, which might provide potential therapeutic benefits for heart failure intervention after MI.

BackgroundMuscle strength has been shown to exert positive effects on bone health. The causal relationship between hand grip strength and osteoporosis is an important public health issue but is not fully revealed. The goal of this study was to investigate whether and to what extent hand grip strength affects bone mineral density (BMD) and fracture risk.MethodsWe conducted a state-of-the-art two-sample Mendelian randomization analysis. Genomewide significant (P

Obesity is a risk factor for many serious health problems, associated with inflammation, hyperlipidemia, and gut dysbiosis. Prevention of obesity is especially important for human health. Tolypocladium sinense is one of the fungi isolated from Chinese caterpillar fungus, which is a traditional Chinese medicine with putative gut microbiota modulation effects. Here, we established a high-fat diet (HFD)-induced hyperlipidemia mice model, which was supplemented with lyophilized T. sinense mycelium (TSP) daily to evaluate its anti-obesity effects. The results indicated that TSP supplementation can effectively alleviate the inflammatory response and oxidative stress levels caused by obesity. TSP significantly prevented obesity and suppressed dyslipidemia by regulating the expression of lipid metabolism genes in the liver. TSP is also effective in preventing the HFD-induced decline in short-chain fatty acid (SCFA) content. Gut microbiota profiling showed that TSP supplementation reversed HFD diet-induced bacterial abundance and also altered the metabolic pathways of functional microorganisms, as revealed by KEGG analysis. It is noteworthy that, correlation analysis reveals the up-regulated gut microbiota (Lactobacillus and Prevotella_9) are closely correlated with lipid metabolism parameters, gene expression of liver lipid metabolism and inflammatory. Additionally, the role of TSP in the regulation of lipid metabolism was reconfirmed by fecal microbiota transplantation. To sum up, our results provide the evidence that TSP may be used as prebiotic agents to prevent obesity by altering the gut microbiota, alleviating the inflammatory response and regulating gene expression of liver lipid metabolism.

Abstract High power‐generation efficiency can be achieved by optimising the shape of the claw pole used as automobile generators. The working process of the stator and rotor in the claw pole generator was simulated using the finite‐element method. First, one of the eight typical claw pole types commonly used in industry was selected. Then, orthogonal optimisation was performed based on the simulation results, yielding an optimal claw shape design. To examine the adaptability of the designed claw pole to shape change, the non‐destructive test for evaluating the magnetic properties of claw pole (NDTEM) was employed. Finally, a claw pole with an optimal shape was forged, and its magnetic induction intensity was assessed using the NDTEM. The results indicated that compared with the unoptimised claw pole, the magnetic induction intensity of the optimised claw pole increased by a maximum of 8.11% and its weight reduced by 4.86%. This optimisation effectively improved the efficiency of power generation and achieved the lightweight of the claw pole.

BackgroundEvidence on the hypertensive effects of long-term air pollutants exposure are mixed, and the joint hypertensive effects of air pollutants are also unclear. Sparse evidence exists regarding the modifying role of residential greenness in such effects.MethodsA cross-sectional study was conducted in typically air-polluted areas in northern China. Particulate matter with diameter < 1 μm (PM1), particulate matter with diameter < 2.5 μm (PM2.5), particulate matter with diameter < 10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3) were predicted by space–time extremely randomized trees model. We used the Normalized Difference Vegetation Index (NDVI) to reflect residential green space. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were examined. We also calculated the pulse pressure (PP) and mean arterial pressure (MAP). Generalized additive model and quantile g-computation were, respectively, conducted to investigate individual and joint effects of air pollutants on blood pressure. Furthermore, beneficial effect of NDVI and its modification effect were explored.ResultsLong-term air pollutants exposure was associated with elevated DBP and MAP. Specifically, we found a 10-μg/m3 increase in PM2.5, PM10, and SO2 were associated with 2.36% (95% CI: 0.97, 3.76), 1.51% (95% CI: 0.70, 2.34), and 3.54% (95% CI: 1.55, 5.56) increase in DBP; a 10-μg/m3 increase in PM2.5, PM10, and SO2 were associated with 1.84% (95% CI: 0.74, 2.96), 1.17% (95% CI: 0.52, 1.83), and 2.43% (95% CI: 0.71, 4.18) increase in MAP. Air pollutants mixture (one quantile increase) was positively associated with increased values of DBP (8.22%, 95% CI: 5.49, 11.02) and MAP (4.15%, 95% CI: 2.05, 6.30), respectively. These identified harmful effect of air pollutants mainly occurred among these lived with low NDVI values. And participants aged ≥50 years were more susceptible to the harmful effect of PM2.5 and PM10 compared to younger adults.ConclusionsOur study indicated the harmful effect of long-term exposure to air pollutants and these effects may be modified by living within higher green space place. These evidence suggest increasing residential greenness and air pollution control may have simultaneous effect on decreasing the risk of hypertension.

Abstract Background Hepatocellular carcinoma (HCC) was the sixth common malignancies characteristic with highly aggressive in the world. It was well established that tumor mutation burden (TMB) act as indicator of immunotherapeutic responsiveness in various tumors. However, the role of TMB in tumor immune microenvironment (TIME) is still obscure. Method The mutation data was analyzed by employing “maftools” package. Weighted gene co-expression network analysis (WGCNA) was implemented to determine candidate module and significant genes correlated with TMB value. Differential analysis was performed between different level of TMB subgroups employing R package “limma”. Gene ontology (GO) enrichment analysis was implemented with “clusterProfiler”, “enrichplot” and “ggplot2” packages. Then risk score signature was developed by systematical bioinformatics analyses. K-M survival curves and receiver operating characteristic (ROC) plot were further analyzed for prognostic validity. To depict comprehensive context of TIME, XCELL, TIMER, QUANTISEQ, MCPcounter, EPIC, CIBERSORT, and CIBERSORT-ABS algorithm were employed. Additionally, the potential role of risk score on immune checkpoint blockade (ICB) immunotherapy was further explored. The quantitative real-time polymerase chain reaction was performed to detect expression of HTRA3. Results TMB value was positively correlated with older age, male gender and early T status. A total of 75 intersection genes between TMB-related genes and differentially expressed genes (DEGs) were screened and enriched in extracellular matrix-relevant pathways. Risk score based on three hub genes significantly affected overall survival (OS) time, infiltration of immune cells, and ICB-related hub targets. The prognostic performance of risks score was validated in the external testing group. Risk-clinical nomogram was constructed for clinical application. HTRA3 was demonstrated to be a prognostic factor in HCC in further exploration. Finally, mutation of TP53 was correlated with risk score and do not interfere with risk score-based prognostic prediction. Conclusion Collectively, a comprehensive analysis of TMB might provide novel insights into mutation-driven mechanism of tumorigenesis further contribute to tailored immunotherapy and prognosis prediction of HCC.

Abstract Background Hepatocellular carcinoma (HCC) ranks the sixth prevalent tumors with high mortality globally. Alternative splicing (AS) drives protein diversity, the imbalance of which might act an important factor in tumorigenesis. This study aimed to construct of AS-based prognostic signature and elucidate the role in tumor immune microenvironment (TIME) and immunotherapy in HCC. Methods Univariate Cox regression analysis was performed to determine the prognosis-related AS events and gene set enrichment analysis (GSEA) was employed for functional annotation, followed by the development of prognostic signatures using univariate Cox, LASSO and multivariate Cox regression. K-M survival analysis, proportional hazards model, and ROC curves were conducted to validate prognostic value. ESTIMATE R package, ssGSEA algorithm and CIBERSORT method and TIMER database exploration were performed to uncover the context of TIME in HCC. Quantitative real-time polymerase chain reaction was implemented to detect ZDHHC16 mRNA expression. Cytoscape software 3.8.0 were employed to visualize AS-splicing factors (SFs) regulatory networks. Results A total of 3294 AS events associated with survival of HCC patients were screened. Based on splicing subtypes, eight AS prognostic signature with robust prognostic predictive accuracy were constructed. Furthermore, quantitative prognostic nomogram was developed and exhibited robust validity in prognostic prediction. Besides, the consolidated signature was significantly correlated with TIME diversity and ICB-related genes. ZDHHC16 presented promising prospect as prognostic factor in HCC. Finally, the splicing regulatory network uncovered the potential functions of splicing factors (SFs). Conclusion Herein, exploration of AS patterns may provide novel and robust indicators (i.e., risk signature, prognostic nomogram, etc.,) for prognostic prediction of HCC. The AS-SF networks could open up new approach for investigation of potential regulatory mechanisms. And pivotal players of AS events in context of TIME and immunotherapy efficiency were revealed, contributing to clinical decision-making and personalized prognosis monitoring of HCC.

Background & aimsFew epidemiological studies have investigated the relationships of urinary essential and non-essential elements with serum albumin, an indicator of nutritional status, especially for the elderly in China.MethodsA community-based study among elderly participants (n = 275) was conducted in Beijing from November to December 2016. We measured 15 urinary elements concentrations and serum albumin levels. Three statistical methods including the generalized linear model (GLM), quantile g-computation model (qgcomp) and bayesian kernel machine regression (BKMR) were adapted.ResultsIn GLM analysis, we observed decreased serum albumin levels associated with elevated urinary concentrations of aluminum, arsenic, barium, cobalt, chromium, copper, iron, manganese, selenium, strontium, and zinc. Compared with the lowest tertile, the highest tertile of cadmium and cesium was also negatively associated with serum albumin. Urinary selenium concentration had the most significant negative contribution (30.05%) in the qgcomp analysis. The negative correlations of element mixtures with serum albumin were also observed in BKMR analysis.ConclusionsOur findings suggested the negative associations of essential and non-essential elements with serum albumin among the elderly. Large-scare cohort studies among the general population are required to validate our findings and elucidate the relevant underlying mechanisms.

Background and AimsPrevious studies have focused only on the cardiometabolic effects of selenium concentrations. We explored whether selenium levels and their visit-to-visit variability (VVV) and individual mean (IM) are independently associated with cardiometabolic risk factors.MethodsA three-wave repeated-measures study of older adults with high selenium (n = 201) was conducted in Beijing from 2016 to 2018. Whole blood selenium and urinary selenium concentrations were measured. VVV and IM were used to profile the homeostasis of the selenium biomarkers. Four indicators, namely standard deviation, coefficient of variation, average real variability, and variability independent of the mean, were employed to characterize VVV. We considered 13 cardiometabolic factors: four lipid profile indicators, three blood pressure indices, glucose, uric acid, waistline, hipline, waist-hip ratio, and sex-specific metabolic syndrome score. Linear mixed-effects regression models with random intercepts for the participants were employed to explore the associations of the selenium concentrations, VVV, and IM with the cardiometabolic factors.ResultsThe geometric mean whole blood and urinary selenium levels were 134.30 and 18.00 μg/L, respectively. Selenium concentrations were significantly associated with numerous cardiometabolic factors. Specifically, whole blood selenium was positively associated with total cholesterol [0.22, 95% confidence interval (CI): 0.12, 0.33], low-density lipoprotein cholesterol (LDL-C; 0.28, 95% CI: 0.13, 0.42), glucose (0.22, 95% CI: 0.10, 0.34), and uric acid (0.16, 95% CI: 0.04, 0.28). After adjustment for VVV, the IM of whole blood selenium was positively correlated with total cholesterol (0.002, 95% CI: 0.001, 0.004), triglycerides (0.007, 95% CI: 0.004, 0.011), and LDL-C (0.002, 95% CI: 0.000, 0.004). However, we did not observe any robust associations between the VVV of the selenium biomarkers and cardiometabolic risk factors after adjustment for IM.ConclusionOur findings suggest that selenium concentrations and their IMs are significantly associated with cardiometabolic risk factors among older adults with high selenium. Longer repeated-measures studies among the general population are required to validate our findings and elucidate the relevant underlying mechanisms.

Objective: We aimed to investigate whether urinary metal mixtures are associated with the homeostasis of inflammatory mediators in middle-aged and older adults. Methods: A four-visit repeated-measures study was conducted with 98 middle-aged and older adults from five communities in Beijing, China. Only one person was lost to follow-up at the third visit. Ultimately, 391 observations were included in the analysis. The urinary concentrations of 10 metals were measured at each visit using inductively coupled plasma mass spectrometry (ICP-MS) with a limit of detection (LOD) ranging from 0.002 to 0.173 µg/L, and the detection rates were all above 84%. Similarly, 14 serum inflammatory mediators were measured using a Beckman Coulter analyzer and the Bio-Plex MAGPIX system. A linear mixed model (LMM), LMM with least absolute shrinkage and selection operator regularization (LMMLASSO), and Bayesian kernel machine regression (BKMR) were adopted to explore the effects of urinary metal mixtures on inflammatory mediators. Results: In LMM, a two-fold increase in urinary cesium (Cs) and chromium (Cr) was statistically associated with −35.22% (95% confidence interval [CI]: −53.17, −10.40) changes in interleukin 6 (IL-6) and −11.13% (95 %CI: −20.67, −0.44) in IL-8. Urinary copper (Cu) and selenium (Se) was statistically associated with IL-6 (88.10%, 95%CI: 34.92, 162.24) and tumor necrosis factor-alpha (TNF-α) (22.32%, 95%CI: 3.28, 44.12), respectively. Similar results were observed for the LMMLASSO and BKMR. Furthermore, Cr, Cs, Cu, and Se were significantly associated with other inflammatory regulatory network mediators. For example, urinary Cs was statistically associated with endothelin-1, and Cr was statistically associated with endothelin-1 and intercellular adhesion molecule 1 (ICAM-1). Finally, the interaction effects of Cu with various metals on inflammatory mediators were observed. Conclusion: Our findings suggest that Cr, Cs, Cu, and Se may disrupt the homeostasis of inflammatory mediators, providing insight into the potential pathophysiological mechanisms of metal mixtures and chronic diseases.

Abstract Aims In patients with coronavirus disease 2019 (COVID‐19), the involvement of the cardiovascular system significantly relates to poor prognosis. However, the risk factors for acute myocardial injury have not been sufficiently studied. Thus, we aimed to determine the characteristics of myocardial injury and define the association between routine blood markers and cardiac troponin I, in order to perform a predictive model. Methods and results This retrospective cohort study included patients with confirmed COVID‐19 from Wuhan Tongji Hospital (Wuhan, China). Data were compared between those with and without myocardial injury. Kaplan–Meier analysis and Cox regression models were used to describe the association between myocardial injury and poor prognosis. Simple correlation analyses were used to find factors associated with high‐sensitivity cardiac troponin I levels. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with myocardial injury. The area under the receiver operating characteristic curve was used to determine the predictive value of the model. Of 353 patients included in the study, 79 presented myocardial injury. Patients with myocardial injury had higher levels of inflammation markers, poorer liver and kidney function, and more complications compared with patients without myocardial injury. High‐sensitivity cardiac troponin I levels were significantly associated with neutrophil/lymphocyte ratio, creatinine, d‐dimer, lactate dehydrogenase, and inflammatory cytokines and negatively associated with oxygen saturation. It was significantly associated with poor prognosis after adjusting for age, sex, and complications. Multivariate regression showed that myocardial injury was associated with a high neutrophil/lymphocyte ratio (odds ratio 2.30, 95% CI 1.11–4.75, per standard deviation increase, P = 0.02), creatinine (3.58, 1.35–8.06, P = 0.01), and lactate dehydrogenase (3.39, 1.42–8.06, P = 0.01) levels. Using a predictive model, the area under the receiver operating characteristic curve was 0.92 (0.88–0.96). Conclusions In patients with COVID‐19, neutrophil/lymphocyte ratio, creatinine, and lactate dehydrogenase are blood markers that could help identify patients with a high risk of myocardial injury at an early stage.

BackgroundThere is considerable research value and extensive application perspectives to explore the link between gut microbiota and heart failure. The purpose of this study is to provide an overview of overall characteristics, evolutionary pathways, frontier research hotspots, and future trends in this field.MethodsResearch datasets were acquired from the Web of Science Core Collection (WoSCC) between January 1, 2006 and December 31, 2021. Three different analysis tools including one online platform, VOS viewer V1.6.17.0, and CiteSpace V5.8.R2 software were used in order to conduct collaboration network analysis, co-cited analysis, co-occurring analysis, and citation burst detection.ResultsA total of 873 publications in the WoSCC database met the requirement. The overall characteristics analysis showed that a steady growth trend in the number of publications and citations, with the predominant literature type being articles and the most frequent subject category being cardiac cardiovascular systems. The United States was the most prolific country and the center of national collaboration. Cleveland Clinic and Nathalie M. Delzenne provided the leading influence with publications, the cooperation between the institutes and authors were relatively weak. Moreover, gut microbiota, heart failure, risk factor, obesity, and inflammation were the keywords that appeared more frequently in the clustering analysis of reference co-citation and keyword co-occurrence. Burst detection analysis of top keywords showed that trimethylamine N-oxide (TMAO), bile acid, blood pressure, hypertension, and fermentation were the new research foci on the association between gut microbiota and heart failure. Strategies to improve gut microbiota hold promise as a new approach to treat heart failure.ConclusionThe comprehensive bibliometric study indicates that the structured information may be helpful in understanding research trends in the link between gut microbiota and heart failure, and locating research hotspots and gaps in this domain, especially further advances in this field will lead to significant breakthroughs in the development of novel therapeutic tools for metabolic modulation of heart failure.