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Abstract Background This study aimed to understand the vision health status of adolescents in the Western Pacific Region (WPR) using Global Burden of Disease (GBD) data from 1990 to 2019. Methods We conducted a comprehensive analysis of blindness and vision loss using GBD data from 1990 to 2019, analyzed trends in the prevalence and burden of blindness and vision loss over time using joinpoint regression, and analyzed their independent effects on blindness and vision loss in three dimensions using age-period-cohort (APC) modeling. Results The prevalence of blindness and vision loss among adolescents in the WPR showed an increasing trend between 1990 and 2019 (AAPC: 0.56%) and a slight increase in YLD (AAPC: 0.11%). The joinpoint regression showed a decreasing trend after 2017 (AAPC: -2.45%). The prevalence and burden trended downward in most Western Pacific countries, with only China rising significantly (AAPC prevalence: 0.57%). Refractive disorders had the highest prevalence among the subgroups. The risk of blindness and vision loss in adolescents reduced with age but grew later in time and at later birth. In addition, prevalence and burden were generally higher in females than males. Conclusions In the context of a declining global trend in the prevalence and burden of blindness and vision loss among adolescents, there is an increasing trend among adolescents in WPR, with the most pronounced rise in China. This finding has important implications for WPR, suggesting that more attention should be given to adolescent eye health in the region.

X-ray ghost imaging with a crystal beam splitter has advantages in highly efficient imaging due to the simultaneous acquisition of signals from both the object beam and reference beam. However, beam splitting with a large field of view, uniform distribution and high correlation has been a great challenge up to now. Therefore, a dedicated beam splitter has been developed by optimizing the optical layout of a synchrotron radiation beamline and the fabrication process of a Laue crystal. A large field of view, consistent size, uniform intensity distribution and high correlation were obtained simultaneously for the two split beams. Modulated by a piece of copper foam upstream of the splitter, a correlation of 92% between the speckle fields of the object and reference beam and a Glauber function of 1.25 were achieved. Taking advantage of synthetic aperture X-ray ghost imaging (SAXGI), a circuit board of size 880 × 330 pixels was successfully imaged with high fidelity. In addition, even though 16 measurements corresponding to a sampling rate of 1% in SAXGI were used for image reconstruction, the skeleton structure of the circuit board can still be determined. In conclusion, the specially developed beam splitter is applicable for the efficient implementation of X-ray ghost imaging.

Small animal PET/MRI is an integrated imaging device that combines the high-performance molecular imaging function of PET with the excellent soft tissue contrast function of MRI，offering unique advantages and significant application value in drug development and evaluation，pharmacology，and mechanistic studies of diseases. To verify the feasibility and accuracy of this device in quantitative analysis，this study evaluated the linear detection range，stability，and quantitative performance of the Bruker BioSpec 94/30 USR + PET insert for 18F. High-resolution MRI images were utilized to remove interference from factors such as the gallbladder and blood vessels，ensuring accurate in vivo quantification in animals. The results demonstrate that the Bruker BioSpec 94/30 USR + PET insert small animal PET/MRI system exhibits excellent linearity (R2=0.9992) within the activity range of 1-1500 μCi，good reproducibility，and accurate in vivo quantitative performance. This provides reliable data for subsequent studies utilizing the Bruker BioSpec 94/30 USR + PET insert for in vivo visualization，distribution，metabolism，and pharmacodynamic evaluation of nuclear tracers.

Abstract After the COVID-19 pandemic, fever clinics urgently require rapid nucleic acid tests to enhance their capacity for timely pathogen detection. This study evaluated the analytical performance and clinical utility of the Flash10 SARS-CoV-2 point-of-care test (Flash10 POCT) for detecting SARS-CoV-2 in patients with fever in the adult fever clinic in Beijing Tsinghua Changgung Hospital from August 1 to August 30, 2023. The analytical performance and clinical utility of the Flash10 POCT for detecting SARS-CoV-2 were assessed in 125 patients with fever syndrome in the adult fever clinic. The Flash10 POCT demonstrated an analytical precision of 3.1% for the Ct values of the ORF1ab gene and 2.9% for the Ct values of the N gene in SARS-CoV-2 nucleic acid testing. Furthermore, the Flash10 POCT demonstrated a lower limit of detection (LoD) of 100 copies/mL, with no detected aerosol contamination leakage. Of the 125 patients (median age 61.9 years, 52% male and 48% female), both the Flash10 POCT and RT-PCR tests yielded positive results for 100 patients and negative results for 25 patients (Fisher’s exact test, p

Abstract Simultaneous manipulation of multiple degrees of freedom of light lies at the heart of photonics. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting incident light into beams of new frequencies with spatially varied phase, amplitude, and angular momenta. Nevertheless, the reconfigurable control over structured light fields for advanced multimode nonlinear photonics remains a grand challenge. Here, we propose the concept of nonlinear geometric phase in an emerging ferroelectric nematic fluid, of which the second-order nonlinear susceptibility carries spin-dependent nonlinearity phase. A case study with photopatterned q-plates demonstrates the generation of second-harmonic optical vortices with spin-locked topological charges by using cascaded linear and nonlinear optical spin-orbit interactions. Furthermore, we present the dynamic tunability of second-harmonic structured light through temperature, electric field, and twisted elastic force. The proposed strategy opens new avenues for reconfigurable nonlinear photonics, with potential applications in optical communications, quantum computing, high-resolution imaging, etc.

Abstract Background This study aims to explore the relationship between female reproductive factors (age at first birth (AFB), age at last birth (ALB), gravidity, and number of live birth (NLB)) and prevalence of depression among the US women. Methods The relationship between AFB, ALB, gravidity, and NLB with the prevalence of depression was explored using publicly available data from the National Health and Nutrition Examination Survey 2005–2018. This cross-sectional study included female participants aged 20 years and older, with reproductive factors and depressive symptoms reported by the participants. Depression was evaluated using the Patient Health Questionnaire-9, with a score of ≥ 10 representing major depression disorder. Weighted multivariable logistic regression and restricted cubic splines (RCS) were utilized to explore the association of AFB, ALB, gravidity and NLB with depression. Results In this study of 11,488 US women, 1,332 (11.6%) women had depression. Compared to the reference group of women with AFB under 18 years, the fully adjusted ORs and 95% CIs for depression were 0.83 (95% CI: 0.68–0.99), 0.75 (95% CI: 0.60–0.95), and 0.69 (95% CI: 0.51–0.93) for women with AFB of 21–23, 24–26, and 27–29 years, respectively. Furthermore, women with five or more pregnancies had a significantly higher prevalence of depression compared to those with two or fewer pregnancies (OR = 1.20, 95% CI: 1.01–1.42). RCS models demonstrated linear associations of ALB, gravidity and NLB with the prevalence of depression. Additionally, the RCS analysis revealed a roughly L-shaped relationship between AFB and prevalence of depression. Conclusions Women with later AFB are associated with a decreased prevalence of depression, while multiple pregnancies are associated with an increased prevalence of depression. These findings suggest that reproductive factors should be considered when screening for and developing preventive strategies for depression.

Objective As one of the most crucial information carriers for predicting mineralized geological bodies, exploration geochemical data play a significant role in the identifying and extracting mineralization-associated anomalies as well as in analyzing deep-level mineralization information. Methods Based on the scale invariance and generalized self-similarity characteristics of the spatial distribution of geochemical elements, this paper uses Cu and Au in the 1:50 000 exploratory geochemical data of the Duolong mineral district as an example and conducts a study using fractal/multifractal and singularity theories to identify the spatial distribution patterns of ore-forming elements and extract anomalies. The multifractal spectrum which is derived by the exploratory moment method for the whole study area, the fault buffer zone and the stratigraphic zone, is used to describe the relative enrichment and depletion of elements in the local area and to analyze the local singularity of Cu and Au mineralized elements, so as to identify and extract weak and low anomalies of mineralized elements and delineate potential mineralization zones. Results Both Cu and Au exhibit mineralization-favoured patterns in the Duolong mineral district, with the Cu showing weak enrichment in the region and Au being over-enriched on a local scale. The intersections of the east-west and northeast-trending faults, as well as the Jurassic strata, are identified as the most promising locations for mineralization in this region. Conclusion The spatial distribution of the local singularity index is mapped to characterize the distribution features of Cu and Au geochemical anomalies, therefore, the central and northern regions of the ore district are subsequently identified as potential areas for mineralization.

Turbulence within the tropical cyclone boundary layer plays a crucial role in the exchange of heat, moisture, and momentum between the surface and the atmosphere. This study investigates the characteristics of coherent structures, specifically streaks and rolls, using large eddy simulations. Our results highlight significant differences across the three radius cases, with smaller radius exhibiting more intense and organized turbulence and streak/roll structures. Our analyses reveal that thermodynamic conditions significantly impact the timing of initial streak/roll development but do not affect their intensity in the steady state. Wind structures closer to the tropical cyclone center lead to stronger and more rapidly developing streaks/rolls, indicating their critical role in determining the intensity and formation of these features. Sensitivity tests on the Coriolis parameter (f) and radial decay parameter of tangential wind (n) show minimal impact on the development of streaks/rolls, suggesting these factors are less influential compared to wind and thermodynamic conditions.

Abstract Continuous directed evolution of base editors (BEs) has been successful in bacteria cells, but not yet in mammalian cells. Here, we report the development of a Continuous Directed Evolution system in Mammalian cells (CDEM). CDEM enables the BE evolution in a full-length manner with Cas9 nickase. We harness CDEM to evolve the deaminases of cytosine base editor BE3 and adenine base editors, ABEmax and ABE8e. The evolved cytidine deaminase variants on BE4 architecture show not only narrowed editing windows, but also higher editing purity and low off-target activity without a trade-off in on-targeting activity. The evolved ABEmax and ABE8e variants exhibit narrowed or shifted editing windows to different extents, and lower off-target effects. The results illustrate that CDEM is a simple but powerful approach to continuously evolve BEs without size restriction in the mammalian environment, which is advantageous over continuous directed evolution system in bacteria cells.

Abstract Background Recently, the C3-epimer of 25-hydroxyvitamin D [C3-epi-25(OH)D] has become a topic of interest among 25-hydroxyvitamin D [25(OH)D] metabolites. Although it can lead to an overestimation of vitamin D storage, its relationship with disease occurrence remains controversial, possibly related to the great extent of tracking of 25(OH)D by C3-epi-25(OH)D over time. This study aimed to investigate the differential performance of C3-epi-25(OH)D3 and its percentage [%C3-epi-25(OH)D3] with respect to 20 common paediatric diseases. Methods This study involved 805 healthy children and adolescents and 2962 patients with common paediatric diseases. We investigated sex, age, and seasonal differences in C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 levels; their variations on 20 common paediatric diseases; and their degree of correlation with 25(OH)D3 levels and various diseases. Results Among the healthy underage participants, C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 changed similarly, with no sex differences. Moreover, their levels were higher in the infant period than in the other periods (t = 5.329–5.833, t = 4.640–5.711, all Padj

Abstract The adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA), are strongly correlated with water-soluble vitamins, but how to predict RSA occurrence using them remains unsatisfactory. This study aims to investigate the possibility of predicting RSA based on the baseline levels of water-soluble vitamins tested by ultra-liquid chromatography-tandem mass spectrometry. A total of 918 pregnant women was consecutively enrolled in this cross-sectional study. According to the miscarriage numbers, they were divided into normal first pregnancy (NFP, n = 608), once spontaneous abortion (OSA, n = 167), and continuous spontaneous abortion (CSA, n = 143) groups. The Cox proportional-hazards regression model was employed to establish a risk model for predicting RSA. The RSA occurrence was 6.54% in overall pregnant women, with a prevalence of 12.57% in the OSA group and 27.27% in the CSA group. Significant differences were observed in baseline deficiencies of vitamin B3, B5, B6, and B9 among NFP, OSA, and CSA groups (χ2 = 12.191 ~ 37.561, all P 0.05). Our study presents a highly sensitive model based on mass spectrometry assay of baseline levels in B vitamins to predict the RSA occurrence as possible.

Abstract Glioma is the most aggressive intracranial malignancy and is associated with poor survival rates and limited quality of life, impairing neuropsychological function and cognitive competence in survivors. The Proteasome Subunit Alpha Type-5 (PSMA5) is a multicatalytic proteinase complex that has been linked with tumor progression but is rarely reported in glioma. This study investigates the expression pattern, prognostic characteristics, and potential biological functions of PSMA5 in glioma. PSMA5 was significantly overexpressed in 28 types of cancer when compared to normal tissue. Furthermore, elevated levels of PSMA5 were observed in patients with wild-type isocitrate dehydrogenase 1 and exhibited a positive correlation with tumor grade. It was also found to be a standalone predictor of outcomes in glioma patients. Additionally, inhibiting PSMA5-induced cell cycle arrest may provide a therapeutic option for glioma.

Abstract Macrophages serve as the primary immune cell population and assume a pivotal role in the immune response within the damaged cochleae. Yet, the origin and role of macrophages in response to noise exposure remain controversial. Here, we take advantage of Ccr2RFP/+ Cx3cr1GFP/+ dual-reporter mice to identify the infiltrated and tissue-resident macrophages. After noise exposure, we reveal that activated resident macrophages change in morphology, increase in abundance, and migrate to the region of hair cells, leading to the loss of outer hair cells and the damage of ribbon synapses. Meanwhile, peripheral monocytes are not implicated in the noise-induced hair cell insults. These noise-induced activities of macrophages are abolished by inhibiting TLR4 signaling, resulting in alleviated insults of hair cells and partial recovery of hearing. Our findings indicate cochlear resident macrophages are pro-inflammatory and detrimental players in acoustic trauma and introduce a potential therapeutic target in noise-induced hearing loss.

SiC-based composites are widely used as electromagnetic wave absorbers due to their excellent dielectric properties. However, the constraints associated with structural design and the intricacies of the preparation process hinder their broader application. In this study, novel mullite anti-gyroid/SiC gyroid metastructures are designed to integrate the mechanical and electromagnetic wave (EMW) absorption properties of composite materials. Mullite anti-gyroid/SiC gyroid composites are fabricated utilizing a combination of digital light processing (DLP) three-dimensional (3D) printing and precursor infiltration and pyrolysis (PIP) processes. Through the modulation of structural units, the electromagnetic parameters can be effectively regulated, thus improving the impedance matching characteristics of the composites. The structural composites show outstanding EMW absorption properties, with a minimum reflection loss of −54 dB at a thickness of 1.9 mm and an effective absorption bandwidth of 3.20 GHz at a thickness of 2.2 mm. Furthermore, the PIP process significantly enhances the mechanical properties of the composites; compared with those of the mullite/SiC ceramics, the flexural strength of the composites is improved by 3.69–5.85 times (13.28±1.15 MPa vs. (49.05±1.07)–(77.78±3.72) MPa), and the compressive strength is improved by 4.59–13.58 times (8.55±0.90 MPa vs. (39.02±1.63)–(116.13±2.58) MPa). This approach offers a novel and effective method for fabricating structural composites with an expanded range of higher electromagnetic wave absorption properties and improved mechanical properties.

Abstract Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands, positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl) nortropane ([18F]FECNT) has been utilized as a PET tracer to image dopamine transporter (DAT) integrity in striatal presynaptic dopaminergic terminals. However, the presence of brain-penetrant radioactive metabolites produced by [18F]FECNT may impact the accuracy of PET imaging. In previous research, we developed 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl-1,1,2,2-d4) nortropane ([18F]FECNT-d4), a deuterated derivative with enhanced stability in plasma and the striatum, along with a slower washout rate. In this study, we further investigated the potential of [18F]FECNT-d4 to detect dopaminergic neuron degeneration in Parkinson’s disease. This involved PET imaging in unilaterally-lesioned PD model rats and in vitro autoradiography conducted on postmortem brain sections. Results PET images revealed reduced specific uptake in the ipsilateral striatum of rats stereotactically injected with 6-hydroxydopamine hydrochloride (6-OHDA). Compared to the sham group, the ratio of standardized uptake value (SUV) in the ipsilateral to contralateral striatum decreased by 13%, 23%, and 63% in the mild, moderate, and severe lesioned groups, respectively. Dopaminergic denervation observed in PET imaging was further supported by behavioral assessments, immunostaining, and monoamine concentration tests. Moreover, the microPET results exhibited positive correlations with these measurements, except for the apomorphine-induced rotational behavior test, which showed a negative correlation. Additionally, [18F]FECNT-d4 uptake was approximately 40% lower in the postmortem striatal sections of a PD patient compared to a healthy subject. Furthermore, estimated human dosimetry (effective dose equivalent: 5.06 E-03 mSv/MBq), extrapolated from rat biodistribution data, remained below the current Food and Drug Administration limit for radiation exposure. Conclusion Our findings demonstrate that [18F]FECNT-d4 accurately estimates levels of dopaminergic neuron degeneration in the 6-OHDA-induced PD rat model and effectively distinguishes between PD patients and healthy individuals. This highly sensitive and safe PET probe holds promising potential for clinical application in the diagnosis and monitoring of Parkinson’s disease.

The global burden of controlling and managing diabetes mellitus (DM) is a significant challenge. Despite the advancements in conventional DM therapy, there remain hurdles to overcome, such as enhancing medication adherence and improving patient prognosis. Digital therapeutics (DTx), an innovative digital application, has been proposed to augment the traditional disease management workflow, particularly in managing chronic diseases like DM. Several studies have explored DTx, yielding promising results. However, certain concerns about this innovation persist. In this review, we aim to encapsulate the potential of DTx and its applications in DM management, thereby providing a comprehensive overview of this technique for public health policymakers.

The unique continuous extrusion-based severe plastic deformation approaches were proposed recently to process high-performance magnesium (Mg) alloys, while the in-depth deformation mechanisms under such complicated thermomechanical conditions were not well understood. In the present work, the fundamental deformation behaviors of AZ61 Mg alloy from 25 to 400 °C were firstly examined under uniaxial compression deformation. Then the deformation mechanisms and microstructural characteristics of AZ61 Mg alloy during continuous expansion extrusion forming (CEEF) were systematically investigated by microstructural observations, finite element and cellular automata simulations. The results showed that the continuous evolutions of temperature, larger strain level and complex stress state with strain rate range of 0 ∼ 5.98 s−1 during CEEF brought the distinctive dynamic recrystallization behaviors and texture development in AZ61 Mg alloy, which were different to that of uniaxial compression deformation. In details, a remarkable grain refinement was achieved via CEEF processing due to the simultaneous actions of continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX). Gradually enhanced CDRX were observed from center to edge region, which had significant effects on the texture distribution and texture strength. The c-axis of most grains rotated under distinctive shear strain following parabolic metal flow, resulting in stable fiber texture. In addition, the evolution of the internal texture of the alloy led to an obvious increase in the Schmid factor for the activation of basal 〈c + a〉 slip system.

Abstract Background Xenobiotics like pesticide isoproturon (IPU) and heavy metal cadmium (Cd) are environmental contaminants posing serious impacts on ecosystem. Understanding their toxic and accumulative processes is crucial to uncover insightful mechanisms and minimize health risks. However, the joint effect of IPU and Cd on microorganisms in aquatic ecosystems remains elusive. In this study, Chlamydomonas reinhardtii was selected as a model unicellular organism to evaluate the ecotoxicological effects of IPU and Cd, focusing on biological responses, bioaccumulation capacity, and environmental adaptation. Results The combined treatment with IPU (0.24 μmol L−1) and/or Cd (20 μmol L−1) for 60 h can induce acute toxicity to C. reinhardtii, reducing chlorophyll and photosynthetic fluorescence, while increasing oxidative damage manifested by lipid membrane peroxides and electrical conductivity. IPU and Cd were accumulated in C. reinhardtii. Interestingly, IPU accumulation in algae was significantly repressed in the presence of Cd, showing a remarkable decrease of 116.7% compared to the IPU treatment alone. Similarly, the Cd concentration in the cells exposed to IPU was reduced by 23.5% compared to Cd treatment alone. Calculation of the bioconcentration factors revealed lower accumulation values of IPU or Cd in algae under Cd+IPU exposure compared to IPU or Cd stress, suggesting an antagonistic interaction between IPU and Cd during absorption by the algae. Furthermore, the activities and transcriptional expression of enzymatic antioxidants such as SOD and APX were significantly induced by Cd stress, whereas the activities of CAT, APX, and PPO significantly increased elevated by IPU. Conclusions This study provides compelling evidence of the ecotoxicological effects of combined IPU and cadmium contamination on algae, highlighting the potential of algae for bioremediation of environments contaminated with IPU and cadmium. Graphical Abstract

Ecosystems at the southern edge of the permafrost distribution are highly sensitive to global warming. Changes in soil freeze-thaw cycles can influence vegetation growth in permafrost regions. Extant studies mainly focused on analyzing the differences of vegetation dynamics in different permafrost regions. However, the intrinsic drivers of permafrost degradation on vegetation growth remain elusive yet. Based on the top temperature of permafrost (TTOP) model, we simulated the spatial distribution of permafrost in Northeast China (NEC) from 2001 to 2020. Using the data of the vegetation Net Primary Productivity (NPP), vegetation phenology, climate and permafrost phenology, and analytical methods including partial correlation, multiple linear regression, and path analysis, we explored the response of vegetation growth and phenology to soil freeze-thaw changes and climate change under different degrees of permafrost degradation. Overall, the start date of the growing season (SOS) was very sensitive to the start date of soil thaw (SOT) changes, and multiple regression analyses showed that SOT was the main factor influencing SOS in 41.8% of the NEC region. Climatic factors remain the main factors affecting vegetation NPP in NEC, and the results of partial correlation analysis showed that only 9.7% of the regional duration of soil thaw (DOT) had a strong correlation with vegetation NPP. Therefore, we determined the mechanism responsible for the soil freeze-thaw changes and vegetation growth relationship using the path analysis. The results indicated that there is a potential inhibitory effect of persistent permafrost degradation on vegetation growth. Our findings would contribute to the improvement of process-based models of forest dynamics in the boreal region, which would help to plan sustainable development and conservation strategies in permafrost areas.

ObjectivesWe focus on utilizing the Labyrinth system for the detection of circulating tumor cells (CTCs) in patients with lung nodules. Our aim is to evaluate CTCs isolated through the Labyrinth system as a biomarker for early-stage lung cancer (LC) detection.Methods167 patients with low dose computed tomography (LDCT) diagnostic results for lung nodules and 31 healthy volunteers (HV) were enrolled. Blood samples were processed for CTC detection. LDCT positive (LDCT+) patients underwent surgery and were categorized into those with LC and those with benign lung diseases (BLD) based on their biopsy results. BLD Patients, LDCT negative (LDCT-) patients and HV served as controls. The correlation of CTC counts with LC, BLD, LDCT- and HV was investigated. Receiver operating characteristic (ROC) curves were used to assess the Labyrinth system’s diagnostic potential for early-stage LC.ResultsMedian CTC counts for LC, BLD, LDCT- and HV were 2.7 CTC/mL, 0.6 CTC/mL, 0.4 CTC/mL, 0 CTC/mL, respectively. Statistical analysis indicated CTC counts could distinguish LC from BLD, LDCT- and HV (p-Values < 0.001). Using a cut-off of 1 CTC/mL, the study showed 84.4% sensitivity and 82.4% specificity for LDCT+ patients. Specificity increased to 85.9% for patients with lung nodules and 88.2% for all participants. In conclusion, CTCs detected by the Labyrinth system can serve as a biomarker for early-stage LC detection for patients with lung nodules.ConclusionsCTCs identified by the Labyrinth system are a promising biomarker for early-stage LC detection in clinical practice.

Based on the best-track dataset from the Shanghai Typhoon Institute/China Meteorological Administration, the paper provides a comprehensive summary and analysis of tropical cyclone (TC) activities in the Western North Pacific (WNP) and the South China Sea (SCS) for 2022. Using the historical climatology from 1951 to 2020, the anomalous conditions during 2022 in TC frequency, origin locations, tracks, intensity, and duration for the entire ocean basin as well as landfall events in China are examined. Results show that the overall TC frequency is slightly lower than normal, but the multiple TC events have a very high frequency of occurrence. Origin locations of TCs, which mark the starting points of their paths, show a large westward and northward deviation from climatology. Around 40% of the named TCs exhibit a shift in their direction of movement from westerly to easterly. Additionally, comparisons of the means, medians, upper and lower quartiles all indicate that the intensity of TCs in 2022 is generally lower than the climatology, with the duration of TCs at tropical storm intensity or above being shorter than usual. A notable observation is the fewer incidence of TC landfalls in China, but with a geographical concentration in Guangdong Province. These anomalous annual TC activities are influenced by related atmospheric and oceanic environmental conditions modulated by multi-scale climate variability. The findings provide useful information for enhancing disaster mitigation strategies in the Asia-Pacific region.

Abstract Background China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy. Methods From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China). Results Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P

Abstract Background Abnormally expressed BCR/ABL protein serves as the basis for the development of chronic myeloid leukaemia (CML). The F-actin binding domain (FABD), which is a crucial region of the BCR/ABL fusion protein, is also located at the carboxyl end of the c-ABL protein and regulates the kinase activity of c-ABL. However, the precise function of this domain in BCR/ABL remains uncertain. Methods The FABD-deficient adenovirus vectors Ad-BCR/ABL△FABD, wild-type Ad-BCR/ABL and the control vector Adtrack were constructed, and 32D cells were infected with these adenoviruses separately. The effects of FABD deletion on the proliferation and apoptosis of 32D cells were evaluated by a CCK-8 assay, colony formation assay, flow cytometry and DAPI staining. The levels of phosphorylated BCR/ABL, p73, and their downstream signalling molecules were detected by western blot. The intracellular localization and interaction of BCR/ABL with the cytoskeleton-related protein F-actin were identified by immunofluorescence and co-IP. The effect of FABD deletion on BCR/ABL carcinogenesis in vivo was explored in CML-like mouse models. The degree of leukaemic cell infiltration was observed by Wright‒Giemsa staining and haematoxylin and eosin (HE) staining. Results We report that the loss of FABD weakened the proliferation-promoting ability of BCR/ABL, accompanied by the downregulation of BCR/ABL downstream signals. Moreover, the deletion of FABD resulted in a change in the localization of BCR/ABL from the cytoplasm to the nucleus, accompanied by an increase in cell apoptosis due to the upregulation of p73 and its downstream proapoptotic factors. Furthermore, we discovered that the absence of FABD alleviated leukaemic cell infiltration induced by BCR/ABL in mice. Conclusions These findings reveal that the deletion of FABD diminished the carcinogenic potential of BCR/ABL both in vitro and in vivo. This study provides further insight into the function of the FABD domain in BCR/ABL.

With the continuous increase of depth in underground engineering, rock bursts or rock explosions can cause instantaneous shock load and result in rock engineering disasters. To solve these problems, a novel high strength and high toughness (HSHT) bolt steel with constant resistance and large deformation is proposed. This study aims to investigate the dynamic constitutive models and microstructure of HSHT steel under extreme loading conditions. A series of dynamic tension tests were conducted using a Split Hopkinson Tensile Bar (SHTB) system with a high-speed camera. The results revealed that the HSHT steel exhibited a positive strain rate effect. As the strain rate increased from 1000 s−1 to 5000 s−1, the yield strength and ultimate strength of the HSHT steel increased gradually. However, no obvious changes in the uniform elongation. Specifically, the yield strength, tension strength, and uniform elongation of strain rate at 5000 s−1 were 1100 MPa, 1170 MPa, and 30%, respectively. According to the results of the SHTB tests, a modified Johnson-Cook model was proposed. Additionally, we investigated the microstructure of HSHT steel at a high strain rate through microscopic characterization techniques. A large number of fine and deep dimples were observed near the fracture of HSHT steel under dynamic loading. Moreover, the HSHT steel demonstrates a significant presence of nano-twins, which effectively impedes crack propagation both within the grain interior and along grain boundaries. The above findings reveal the relationship between mechanical behavior and microstructure in HSHT steel within dynamic loading conditions, providing valuable insights for the design of HSHT steel in underground engineering.

ABSTRACTDigital Light Processing (DLP) technology is a highly effective molding method for creating complex structural parts. However, the low solid content of SiC stereolithography slurry has been found to diminish the mechanical properties of the ceramic, regardless of whether it is sintered by Reactive Melt Infiltration (RMI) or Precursor Infiltration and Pyrolysis (PIP). This poses a significant challenge in improving the mechanical properties of SiC ceramics manufactured through DLP additive manufacturing. In response to this challenge, a novel method of RMI combined with infiltration is proposed in this study. The process involves the filling of the pores of the green body with pyrolytic carbon from PR or pyrolytic SiC from LHBPCS through circular infiltration, effectively increasing the content of SiC in the ceramics after reaction. Notably, the elastic modulus of RM-P2 and RM-L2 samples increased by 37.39% and 33.91%, respectively, demonstrating the potential of this method for preparing ceramics with high SiC content through stereolithography additive manufacturing. This innovative approach holds promise for overcoming the limitations previously associated with SiC ceramics produced through DLP additive manufacturing, opening up new possibilities for the development of high-performance SiC-based components.

Skeletal stem cells (SSC) have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic capacity. However, the immunomodulatory properties of SSC, especially under delivery operations, have been largely ignored. In the study, we found that Pdpn+ and Grem1+ SSC subpopulations owned immunoregulatory potential, and the single-cell RNA sequencing (scRNA-seq) data suggested that the mechanical activation of microgel carriers on SSC induced the generation of Pdpn+Grem1+Ptgs2+ SSC subpopulation, which was potent at suppressing macrophage inflammation. The microgel carriers promoted the YAP nuclear translocation, and the activated YAP protein was necessary for the increased expression of Ptgs2 and PGE2 in microgels-delivered SSC, which further suppressed the expression of TNF-ɑ, IL-1β and promoted the expression of IL-10 in macrophages. SSC delivered with microgels yielded better preventive effects on articular lesions and macrophage activation in osteoarthritic rats than SSC without microgels. Chemically blocking the YAP and Ptgs2 in microgels-delivered SSC partially abolished the enhanced protection on articular tissues and suppression on osteoarthritic macrophages. Moreover, microgel carriers significantly prolonged SSC retention time in vivo without increasing SSC implanting into osteoarthritic joints. Together, our study demonstrated that microgel carriers enhanced SSC reprogramming towards immunomodulatory phenotype to regulate macrophage phenotype transformation for effectively osteoarthritic therapy by promoting YAP protein translocation into nucleus. The study not only complement and perfect the immunological mechanisms of SSC-based therapy at the single-cell level, but also provide new insight for microgel carriers in stem cell-based therapy.

Drought stress is a major constraint on plant growth and agricultural productivity. Caffeic acid O-methyltransferase (COMT), an enzyme involved in the methylation of various substrates, plays a pivotal role in plant responses to abiotic stress. The involvement of COMTs in drought response, particularly through the enhancement of lignin and melatonin biosynthesis, remains poorly understood. In this study, LcCOMT was firstly proposed to be associated with the biosynthesis of both lignin and melatonin, as demonstrated through sequence comparison, phylogenetic analysis, and conserved motif identification. In vitro enzymatic assays revealed that LcCOMT effectively methylates N-acetylserotonin to melatonin, albeit with a higher Km value compared to caffeic acid. Site-directed mutagenesis of residues Phe171 and Asp269 resulted in a significant reduction in catalytic activity for caffeic acid, with minimal impact on N-acetylserotonin, underscoring the specificity of these residues in substrate binding and catalysis. Under drought conditions, LcCOMT expression was significantly upregulated. Overexpression of LcCOMT gene in Arabidopsis plants conferred enhanced drought tolerance, characterized by elevated lignin and melatonin levels, increased chlorophyll and carotenoid content, heightened activities of antioxidant enzymes peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD), and reduced malondialdehyde (MDA) and hydrogen peroxide (H2O2) accumulation. This study is among the few to demonstrate that COMT-mediated drought tolerance is achieved through the simultaneous promotion of lignin and melatonin biosynthesis. LcCOMT represents the first functionally characterized COMT in Apiaceae family, and it holds potential as a target for genetic enhancement of drought tolerance in future crop improvement strategies.

Abstract Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the activity of miR has never been demonstrated. Here, as proof‐of‐concept, a tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) and miRs including miR‐193a (Trp/Ago2/miR‐193a) is identified. Trp binds miR‐193a‐3p and interacts with Ago2. Trp/Ago2/miR‐193a increases miR‐193a‐3p activity via enhancing Argonaute 2 (Ago2) RNase activity. Other miRs including miR‐103 and miR‐107 in the Trp complex enhance miR‐193a activity by targeting the same genes. Mechanistically, the Trp/Ago2/miR‐193a complex interacts with Trp‐binding pockets of the PIWI domain of Ago2 to enhance Ago2 mediated miR activity. This newly formed Ago2/Trp/miR‐193a‐3p complex is more efficient than miR‐193a‐3p alone in inhibiting the expression of targeted genes and inhibiting colon cancer liver metastasis. The findings show that Trp regulates miR activity through communication with the RNA‐induced silencing complexes (RISC), which provides the basis for tryptophan based miR therapy.

Accumulated evidence has supported the probiotic activity of Leuconostoc mesenteroides (L. mesenteroides) which can yield beneficial metabolites via fermentation. Here, bovine milk rich in phenylalanine（PHE) was used as a source for fermentation of L. mesenteroides. The complexes of PHE with bacterial phenylalanine hydroxylase (PheH) at two temperatures were revealed via molecular dynamics simulation. Two carbon hydrogen bonds and a Pi-Alkyl T-shaped interaction were newly formed at an active site of the PheH-PHE complex. The PheH interacted with two different hydrogen atoms in an amine of PHE via conventional hydrogen bonds at 37 °C, a temperature that accelerated the milk fermentation of L. mesenteroides. Twenty-eight metabolites including various neurotransmitters in fermented milk were identified and quantified by liquid chromatography coupled to quadrupole ion trap (Q-Trap) tandem mass spectrometry. Ex ovo injection of milk ferments into the yolk sac of chicken embryos enhanced a rising temperature-induced increase in heartbeats towards the normal resting level. The neurotransmitter-rich milk ferments hold potential for using to adjust energy metabolism, referred from heart rates, during fluctuating temperature conditions.

Abstract Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell‐based vaccination is limited by interference from immunosuppressive senescence‐associated secretory phenotype and pro‐tumorigenic capacity of senescent cells. Here, a senescent cancer cell‐based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane‐coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death‐induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma‐challenged mice with fewer side effects when combined with αPD‐1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell‐based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.

Light-flavor Baijiu (LFB) fermentation is a representative spontaneous mixed-culture solid-state fermentation process in which sorghum is used as the raw material. Raw materials and microorganisms are crucial to the flavor formation and quality of LFB. However, the microbial and physicochemical dynamics of different sorghum varieties during LFB fermentation, as well as their impact on flavor compounds are still largely unknown. Herein, PacBio single-molecule real-time (SMRT) sequencing and headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC–MS) were applied to investigate microbial community succession and volatile flavor formation in glutinous/non-glutinous sorghum-based fermented grains during LFB fermentation. Fermented grains made of glutinous sorghum Liangnuo No. 1 (GLN) had higher bacterial α-diversity and lower fungal α-diversity than those with fermented grains prepared with non-glutinous red sorghum (NRS) (p

“Green-covering and red-heart” Guanyin Tuqu (GRTQ), as a type of special fermentation starter, is characterized by the “green-covering” formed on the surface of Guanyin Tuqu (SQ) and the “red-heart” in the center of Guanyin Tuqu (CQ). However, the mechanisms that promote temporal succession in the GRTQ microbial ecology and the formation of “green-covering and red-heart” characteristics remain unclear. Herein, we correlated the temporal profiles of microbial community succession with the main environmental variables (temperature, moisture, and acidity) and spatial position (center and surface) in GRTQ throughout fermentation. According to the results of high-throughput sequencing and culture-dependent methods, the microbial communities in the CQ and SQ demonstrated functional complementarity. For instance, the bacterial richness index of the CQ was greater than that of SQ, and the fungal richness index of the SQ was greater than that of CQ at the later stage of fermentation. Furthermore, Saccharomycopsis, Saccharomyces, Aspergillus, Monascus, Lactobacillus, Bacillus, Rhodanobacter, and Chitinophaga were identified as the dominant microorganisms in the center, while the surface was represented by Saccharomycopsis, Aspergillus, Monascus, Lactobacillus, Acetobacter, and Weissella. By revealing the physiological characteristics of core microorganisms at different spatial positions of GRTQ, such as Aspergillus clavatus and Monascus purpureus, as well as their interactions with environmental factors, we elucidated the color formation mechanism behind the phenomenon of “green” outside and “red” inside. This study provides fundamental information support for optimizing the production process of GRTQ.

Introduction: Endocrine-disrupting chemicals (EDCs) in effluent and residual sludge from wastewater treatment plants (WWTPs) pose significant environmental and human health risks due to their persistence, bioaccumulation, and difficulty in detection and degradation. This study investigates the environmental exposure and risks associated with EDCs in effluent and sludge from four WWTPs: Tangxi River (TXH), Zipeng Mountain (ZPS), Lianxi (LX), and Wang Xiaoying (WXY).Methods: Environmental exposure indexes of EDCs were assessed in the effluent and sludge of the four WWTPs across four seasons (spring, summer, autumn, and winter) from October 2017 to October 2018. Detection rates of various pollutants, their seasonal and spatial characteristics, and removal rates were analyzed. Positive matrix factorization (PMF) was used for source analysis under influent data, and an ecological risk assessment was conducted using the risk quotient (RQ) method.Results: The study found 4-n-nonylphenol (NP) and di-2-ethylhexyl phthalate (DEHP) had 100% detection rates in the effluent of all four WWTPs, while only DEHP showed a 100% detection rate in the sludge. Bisphenol A (BPA) exhibited the highest concentration in the TXH effluent during autumn. Benzo(a)pyrene (B(a)P) was detected only in the sludge during spring and summer and in the effluent of TXH and WXY. PMF source analysis indicated industrial wastewater discharge as the primary source of pollutants. Ecological risk assessment revealed a high RQ for estriol (E3) in TXH effluent during autumn, and DEHP presented a potential carcinogenic risk through drinking water.Discussion: The findings highlight significant seasonal and spatial variations in EDC concentrations and removal rates across the WWTPs. The persistent presence of DEHP and the high-risk levels of E3 in specific seasons underscore the need for improved treatment processes and stricter industrial discharge regulations to mitigate EDC-related risks. Further research is recommended to explore advanced detection and degradation techniques for EDCs in WWTPs.

Objective: To conduct a meta-analysis of the effectiveness and safety of ginkgo biloba extract combined with donepezil hydrochloride vs. donepezil for the treatment of vascular dementia (VaD).Methods: Four English databases (PubMed, EMBASE, Web of Science, Cochrane Library) and four Chinese databases [the China National Knowledge Infrastructure Wanfang DATA, the Chongqing VIP Database (VIP), China Biomedical Database (CBM)] were manually searched for literature published from dates of the inception of the databases to September 2023. The randomized controlled trials (RCTs) of ginkgo biloba extract with donepezil hydrochloride vs. donepezil for the treatment of VaD were included. Relevant literature was screened, and the data in the included studies were extracted for quality assessment according to the Risk of bias tool.Results: A total of 1,309 participants were enrolled in the 15 RCTs. Of these, 656 participants were in the experimental group (ginkgo biloba extract combined with donepezil) and 653 participants were in the control group (donepezil).The results showed that combination therapy was superior to donepezil alone, and there were statistically significant differences in several outcomes including RR in change for total effective rate (1.28, 95% confidence intervals 1.20, 1.38, p < 0.001), MD in change for Mini-Mental State Examination score (2.98, 95%CI 2.31, 3.65, p < 0.001), Barthel Index score (8.55,95%CI 1.11, 15.99, p = 0.024), Activity of Daily Living Scale (ADL)score (10.11,95% CI 7.16,13.07,p < 0.001).Conclusion: Ginkgo biloba extract combined with donepezil dramatically improved the total effective rate, MMSE, BI and ADL scores, and decreased homocysteine (HCY), plasma viscosity (PV), whole blood viscosity at high cut (BVH) and whole blood viscosity at low cut (BVL) in VaD patients, while the effect on mean flow velocity and pulse index (PI) of middle cerebral artery (MCA) is not obvious. However, more relevant high-quality RCTs are needed to validate these results.Systematic Review Registration: Identifier CRD42023474678.

Abstract Sarcodon and Hydnellum are two ectomycorrhizal genera of important ecological and economic value in Southwest China, and they are common in the free markets in this region. It was estimated that more than 1,500 tonnes of them were sold as edible per year, but there was little information about the taxonomic placements of these edible mushrooms sold in the markets. Traditional concepts of the two genera have also been challenged recently, and circumscription of Sarcodon and the informally defined clade “Neosarcodon” remained unresolved. In the present study, specimens collected in the field and purchased from the markets in Southwest China were analyzed based on morphological characters and DNA sequences. Phylogeny of the traditional Sarcodon s. lat. and Hydnellum s. lat. was reconstructed from the combined internal transcribed spacer (ITS), nuclear large ribosomal subunit (nLSU) and RNA polymerase II second largest subunit (RPB2) dataset based on expanded samples to reevaluate the taxonomic placements of the two genera. In the present molecular analyses, four distinct clades were recovered and strongly supported: Hydnellum, Neosarcodon, Phellodon and Sarcodon. Neosarcodon is formally introduced as a generic name to include nine species previously placed in Sarcodon, and the delimitation of Sarcodon is revised based on phylogenetic and morphological studies. Phylogenetic analyses also revealed an unexpected species diversity (17 phylogenetic species) of Sarcodon and Hydnellum in the markets; nine phylogenetic species of Sarcodon and eight of Hydnellum were uncovered from the samples collected in the markets. Eight species were resolved in the traditional S. imbricatus complex, with S. imbricatus s.str. being the most common edible stipitate hydnoid fungal species. Three of the edible Hydnellum species (H. edulium, H. subalpinum, and H. subscabrosellum), and five separated from the S. imbricatus complex (Sarcodon flavidus, S. giganteus, S. neosquamosus, S. nigrosquamosus, and S. pseudoimbricatus), are described as new. Three new Chinese records (H. illudens, H. martioflavum, and H. versipelle), and the notable S. imbricatus and S. leucopus are also reported.

Abstract Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1–14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8–89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).

Abstract Background and purpose Effective evaluation of rotator cuff tear residual tendon quality is the key to surgical repair. However, until now, the evaluation of rotator cuff tissue by ultrasonic shear wave elasticity (SWE) has been controversial. This prospective study analyzed the association between preoperative SWE and arthroscopic residual tendon quality scores. Methods The shear wave velocity (SWV) of the deltoid muscle, the supraspinatus tendon, and the supraspinatus muscle were measured in full-thickness rotator cuff tear patients. Tendon quality was scored according to tear size, tendon margin, tendon thickness, and footprint coverage during arthroscopy. The arthroscopic scores were used as the gold standard, and the SWV ratio of tendon and muscle (supraspinatus tendon/deltoid and supraspinatus muscle/deltoid) were calculated and correlated with the arthroscopic scores. Result Eighty-nine patients (129 shoulders) were enrolled, including 89 operation shoulders and 40 control shoulders. In the group of operation shoulders, both the SWV ratios of tendon (SWV-RT) and the SWV ratio of muscle (SWV-RM) were negatively correlated with arthroscopic scores (The correlation coefficient (R) ranged from -0.722 to -0.884 and -0.569 to -0.689). The SWV-RT and SWV-RM of the operation shoulders were significantly lower than that of the control shoulders (p

Abstract In the context of the 5G era, the rapid development of digital technology and its integration with intangible cultural heritage (ICH) can facilitate the dynamic transmission of ICH.The research purposes to construct a virtual experience platform for handmade ICH using the handmade ICH of East Hubei Province in China—Yangxin Cloth Paste as a case study through Digital Twin technology. It explores the application of digital twin technology in the field of handmade ICH transmission and aids the dynamic transmission of handmade ICH. Firstly, the research collected tangible and procedural data of the Yangxin Cloth Paste. By using photogrammetric techniques, a model of the handicraft was built and an effective digital twin conversion procedure was designed. Next, the research set up a framework for a digital twin platform for handmade ICH, designing systems for the production, display, and transaction of ICH handicrafts. Lastly, its effectiveness was validated by user satisfaction evaluation guiding subsequent optimization direction. The platform innovatively uses digital twin technology to help users visualize handicraft ICH. Through the combination of digital twin technology and virtual reality technology, it creates a realistic virtual reality experience of ICH of handicraft, stimulates users' interest in exploring ICH of handicraft, and contributes to the process protection, dissemination and development of handicraft ICH.

Icing on overhead transmission lines can be more accurately and effectively monitored in real time through a method that integrates information from multiple sensors for data fusion. SHT75 temperature and humidity sensor and ice thickness sensor are used to collect three kinds of sensing information of environmental temperature, humidity and ice thickness of transmission lines, and then input them into the ice fusion monitoring structure based on BP neural network. The weights and thresholds of a BP neural network can be optimized using a genetic algorithm, and fusion diagnosis is performed to determine if there is icing on transmission lines. For transmission lines with icing, by employing a fuzzy control-based evaluation method for line icing levels, the proposed approach enables the real-time assessment of icing levels on overhead transmission lines. Experimental findings demonstrate the method’s efficacy in swiftly and accurately detecting icing occurrences, thereby enhancing the precision and immediacy of icing monitoring on overhead transmission lines.

In complex mountainous terrain, the terrain slope causes the scattering of pulsed lasers, generating a lot of noise in photon cloud data (PCD) collected from forestland, which seriously affects the accurate retrieval of forest structure parameters. To address this problem, a multilevel autoadaptive denoising (MLAD) algorithm was proposed in this article. First, random noise photons were removed through the ordering points to identify the clustering structure (OPTICS) algorithm in the coarse denoising process. Second, in the fine denoising step, the circular search domain in the OPTICS algorithm was replaced with an elliptical search domain. The photons after coarse denoising were automatically divided along-track direction into several continuous segments of 100 m each. The median slope method was used to automatically calculate the slope of the forested terrain in each interval segment, so that the range of the ellipse search domain was automatically adjusted to achieve accurate denoising of PCD. Finally, the denoising results of the MLAD algorithm in three different forested terrain areas were compared with those of the difference, regression, and Gaussian adaptive nearest neighbor (DRAGANN) algorithms, and the performance of the MLAD algorithm was evaluated for both different terrain slopes and different vegetation coverages. The results indicated that compared with the DRAGANN algorithm, the MLAD algorithm has higher denoising capability in different regions. The denoising results of the MLAD algorithm exhibit slight changes with the variation in slope, and the F-values are around 0.96, demonstrating good robustness. The F-value of the MLAD algorithm mostly exceeds 0.95 in different vegetation coverages. Overall, the MLAD algorithm exhibits stronger noise identification capabilities for complex forest environments. These results can provide a reference for subsequent accurate extraction of forest structural parameters.

Falls represent a significant cause of injury among the elderly population. Extensive research has been devoted to the utilization of wearable IMU sensors in conjunction with machine learning techniques for fall detection. To address the challenge of acquiring costly training data, this paper presents a novel method that generates a substantial volume of synthetic IMU data with minimal actual fall experiments. First, unmarked 3D motion capture technology is employed to reconstruct human movements. Subsequently, utilizing the biomechanical simulation platform Opensim and forward kinematic methods, an ample amount of training data from various body segments can be custom generated. Synthetic IMU data was then used to train a machine learning model, achieving testing accuracies of 91.99% and 86.62% on two distinct datasets of actual fall-related IMU data. Building upon the simulation framework, this paper further optimized the single IMU attachment position and multiple IMU combinations on fall detection. The proposed method simplifies fall detection data acquisition experiments, provides novel venue for generating low cost synthetic data in scenario where acquiring data for machine learning is challenging and paves the way for customizing machine learning configurations.

Poverty is a global challenge, the effects of which are felt on the individual to national scale. To develop effective support policies to reduce poverty, local governments require precise poverty distribution data, which are lacking in many areas. In this study, we proposed a model to estimate poverty on a spatial scale of 10 × 10 km by combining features extracted from multiple data sources, including nighttime light remote sensing data, normalized difference vegetation index, surface reflectance, land cover type, and slope data, and applied the model to Nigeria. Considering that the trends of environmental factors contain valid information related to poverty, time-series features were extracted through convolutional long short-term memory and used for the assessment. The poverty level is represented by the wealth index derived from the Demographic and Health Survey Program. The model exhibited good ability to estimate poverty, with an R2 of 0.73 between the actual and estimated wealth index in Nigeria in 2018. Applying the proposed model to poverty estimation for Nigeria in 2021 yielded an R2 value of 0.69, indicating good generalization ability. To further validate model reliability, we compared the assessment results with high-resolution satellite imagery and a state-level multidimensional poverty index. We also investigated the impact of incorporating time-series features on the accuracy of poverty assessment. Results showed that the addition of time-series features increased the accuracy of poverty estimation from 0.64 to 0.73. The proposed method has valuable applications for estimating poverty at the grid scale in countries without such data.

This paper investigates a reconfigurable intelligent surface (RIS)-assisted unmanned aerial vehicle (UAV)-enabled wireless powered communication network (WPCN). In the system, a UAV acts as a hybrid access point (HAP) to charge users in the downlink (DL) and receive messages in the uplink (UL). In particular, the RIS is exploited to significantly enhance the efficiency of both the DL and UL transmission. Our objective is to enhance the minimum throughput among all ground users by jointly optimizing the horizontal location of UAVs, the transmit power of users, transmission time allocation, and passive beamforming vectors at the RIS. To address this problem, we present an alternating optimization-based algorithm with low complexity to decompose the problem into four subproblems and solve them sequentially. In particular, we derive a lower bound of the composite channel gain to tighten the constraints and employ successive convex approximation (SCA) to optimize the horizontal location of the UAV. The transmit power closed-form optimum solutions are then obtained, and the problem of time allocation is reformulated as a linear programming problem. Finally, we optimize the passive beamforming vectors by adopting semi-definite relaxation (SDR). The effectiveness of the algorithm is supported by numerical results, which also demonstrate that the RIS-assisted UAV-enabled WPCN outperforms the traditional WPCN in terms of the minimum throughput.

Abstract Background The transcription factors (TFs) in thermophilic cyanobacteria might represent a uniquely evolved gene repertoire in light of the strong selective pressure caused by hostile habitats. Understanding the molecular composition of the TF genes in thermophilic cyanobacteria will facilitate further studies regarding verifying their exact biochemical functions and genetic engineering. However, limited information is available on the TFs of thermophilic cyanobacteria. Herein, a thorough investigation and comparative analysis were performed to gain insights into the molecular composition of the TFs in 22 thermophilic cyanobacteria. Results The results suggested a fascinating diversity of the TFs among these thermophiles. The abundance and type of TF genes were diversified in these genomes. The identified TFs are speculated to play various roles in biological regulations. Further comparative and evolutionary genomic analyses revealed that HGT may be associated with the genomic plasticity of TF genes in Thermostichus and Thermosynechococcus strains. Comparative analyses also indicated different pattern of TF composition between thermophiles and corresponding mesophilic reference cyanobacteria. Moreover, the identified unique TFs of thermophiles are putatively involved in various biological regulations, mainly as responses to ambient changes, may facilitating the thermophiles to survive in hot springs. Conclusion The findings herein shed light on the TFs of thermophilic cyanobacteria and fundamental knowledge for further research regarding thermophilic cyanobacteria with a broad potential for transcription regulations in responses to environmental fluctuations.

Abstract Patients with recurrent or metastatic cervical cancer are in urgent need of novel prognosis assessment or treatment approaches. In this study, a novel prognostic gene signature was discovered by utilizing cuproptosis-related angiogenesis (CuRA) gene scores obtained through weighted gene co-expression network analysis (WGCNA) of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. To enhance its reliability, the gene signature was refined by integrating supplementary clinical variables and subjected to cross-validation. Meanwhile, the activation of the VEGF pathway was inferred from an analysis of cell-to-cell communication, based on the expression of ligands and receptors in cell transcriptomic datasets. High-CuRA patients had less infiltration of CD8 + T cells and reduced expression of most of immune checkpoint genes, which indicated greater difficulty in immunotherapy. Lower IC50 values of imatinib, pazopanib, and sorafenib in the high-CuRA group revealed the potential value of these drugs. Finally, we verified an independent prognostic gene SFT2D1 was highly expressed in cervical cancer and positively correlated with the microvascular density. Knockdown of SFT2D1 significantly inhibited ability of the proliferation, migration, and invasive in cervical cancer cells. CuRA gene signature provided valuable insights into the prediction of prognosis and immune microenvironment of cervical cancer, which could help develop new strategies for individualized precision therapy for cervical cancer patients.

Abstract Purpose This study aimed to evaluate the prognostic role of the baseline neutrophil/lymphocyte ratio (NLR) in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab/pertuzumab. Experimental design Data from 780 patients from the CLEOPATRA trial and 248 local patients were collected. Patients were divided into the low and high NLR subgroups by the NLR cutoff value. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methods were used to control bias. Associations between the NLR and progression-free survival (PFS) and overall survival (OS) were analyzed. Results The baseline characteristics of the subgroups were well balanced after PSM and IPTW. A low baseline NLR was associated with better PFS and OS in the trastuzumab and docetaxel (TH) group in the unadjusted, PSM and IPTW models. After IPTW, a low NLR, versus a high NLR, was associated with improved PFS (HR 1.35, 95% CI 1.07–1.70, P = 0.012) and OS (HR 1.47, 95% CI 1.12–1.94, P = 0.006) in the TH group. In patients undergoing treatment with trastuzumab and pertuzumab and docetaxel (THP), a low baseline NLR was also correlated with better PFS but not OS across the three models. After IPTW, a low NLR was associated with better PFS (HR 1.52, 95% CI 1.20–1.93, P = 0.001) than a high NLR in the THP group. Multivariate analyses showed that a low baseline NLR was a predictor for PFS and OS in the TH group and for PFS in the THP group in all three models. In the real-world setting, a low baseline NLR was a predictor of better PFS among patients treated with docetaxel plus trastuzumab without or with pertuzumab in the multivariate model (P = 0.015 and 0.008, respectively). Conclusions A low baseline NLR is associated with better survival outcomes among HER2-positive MBC patients receiving docetaxel plus trastuzumab/pertuzumab as first-line therapy.

Accurate prediction of the remaining useful life (RUL) of bearings is crucial for maintaining the reliability and efficiency of industrial systems. This study introduces a novel methodology integrating advanced machine learning and optimization techniques to address this challenge. (1) A transformer-attention model was developed to process segmented vibration signals, effectively capturing complex patterns. The model showed better performance than traditional approaches, with an RMSE of 0.989. (2) A Deep Neural Network (DNN) was designed to predict the extended RUL of bearings after laser shock peening (LSP) remanufacturing. The fruit fly optimization (FFO) algorithm was employed to optimize the remanufacturing parameters; a 29.33% improvement was achieved in fitness compared to the baseline. (3) The DNN model predictions were validated against Finite Element Analysis (FEA) simulations, with a low relative error of 2.5% to 5.8%; the model showed good accuracy in capturing the effects of optimized LSP parameters on bearing life extension.

Introduction: Post-stroke spasticity (PSS) is among the prevalent complications of stroke, greatly affecting motor function recovery and reducing patients' quality of life without timely treatment. Sangdantongluo granule, a modern traditional Chinese patent medicine, has significant clinical efficacy in treating PSS. However, the mechanism of Sangdantongluo granule in treating PSS is still unknown. We designed this study to explore the mechanism of Sangdantongluo granule in treating PSS through multimodal functional magnetic resonance imaging (fMRI) combined with transcranial magnetic stimulation (TMS). Methods and analysis: In a single-center, randomized, double-blind, parallel placebo-controlled study, 60 PSS patients will be recruited in China and randomly assigned to either the experimental or control groups at a ratio of 1:1. For eight weeks, Sangdantongluo granule or placebo will be utilized for intervention. The main outcome is the Modified Ashworth Scale (MAS), the secondary outcome includes the Fugl-Meyer Assessment Scale-upper Extremity (FMA-UE), National Institute of Health Stroke Scale (NIHSS), and Modified Rankin Scale (mRS), the mechanism measure is the changes in cortical excitability and multimodal fMRI at baseline and after eight weeks. Ethics and dissemination: This study was approved by the Ethics Committee of the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine (approval number: [202364]). Clinical trial registration: Chinese Clinical Trial Registry, identifier: ChiCTR2300074793. Registered on 16 August 2023.