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Cereals zinc (Zn) biofortification represents an effective strategy for alleviating human Zn malnutrition. However, understanding how to enhance Zn uptake in shoots by optimizing the soil–root interface, particularly considering Zn availability, microbiome interactions, and plant physiology, remains poorly understood, especially in high-pH soils. In this study, we investigated Zn rhizomobilization, plant Zn uptake, and the composition of bacterial and fungal communities in the rhizosphere and roots of ten high-yielding wheat cultivars with consistently contrasting grain Zn concentrations, within calcareous fields. We found that a range of beneficial bacteria, fungi/mycorrhizas, and their interactions play crucial roles in Zn rhizomobilization and wheat Zn uptake. Zn-solubilizing rhizobacteria demonstrated the ability to enhance Zn rhizomobilization, leading to a 35.4% increase in available Zn concentration and a 0.11 units reduction of soil pH. Increased colonization by arbuscular mycorrhizal fungi, along with reduced the presence of fungal pathogens, significantly promoted Zn uptake, ranging from 22 to 132% per unit of root biomass. Additionally, the enriched bacteria relevant with nitrogen cycle and plant growth-promotion not only optimized soil mineral-N/available-P supply but also potentially suppressed fungal pathogens in root and rhizosphere. Optimizing the microbiome to enhance soil nutrient supply and root health emerges as a promising strategy for improving Zn-efficient wheat cultivars' ability to uptake Zn in shoots. Combining Zn-efficient cultivars with specific soil bacteria and fungi in the rhizosphere holds potential for realizing Zn biofortification in wheat. [ABSTRACT FROM AUTHOR]

Purpose: (1) To determine the prevalence, magnitude and distribution pattern of acetabular rim ossification in patients with femoroacetabular impingement syndrome (FAIS) and (2) to determine the association between acetabular rim ossification and rotational abnormalities of the hip. Methods: Patients underwent hip arthroscopic surgery for FAIS at our institute between January 2021 and May 2022 were retrospectively reviewed. Patients were included if preoperative computed tomography (CT) images of the operated hip and ipsilateral distal femur were available for the measurement of femoral and acetabular anteversion. The presence and size of acetabular rim ossification were evaluated on coronal CT sections for the superior half of the acetabulum on each clockface location. The associations between acetabular rim ossification and radiographic parameters of hip rotational morphology were examined. Results: A total of 214 hips were included. Acetabular rim ossification was found in 167 hips (78%) and the most common locations were 10 and 11 o'clock. Patients presenting with acetabular rim ossification had a mean size of 4.6 ± 1.6 mm. It was the largest at 9 o'clock position (4.9 ± 2.2 mm), with a decreasing trend in size from posterior to anterior. Logistics regression analysis found age was associated with the occurrence of posterior ossification (p = 0.002). Linear regression analysis found age (p = 0.049) and male sex (p < 0.001) were significantly correlated with the size of ossification. Patients with increased cranial combined anteversion had larger posterior ossification than patients with normal and decreased cranial combined anteversion (4.2 ± 2.9 vs. 3.1 ± 2.5 mm, p = 0.016; 4.2 ± 2.9 vs. 2.5 ± 2.4 mm, p = 0.005). Conclusion: Increased combined anteversion is associated with greater posterior acetabular rim ossification. The presence and size of acetabular rim ossification are positively associated with older age and male sex. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

Meloidogyne incognita is among the most detrimental parasitic nematodes with a wide host range causing huge economic losses annually. Biological control of M. incognita has emerged as a promising alternative in sustainable agriculture. In our previous study, Bacillus velezensis TA-1 effectively controlled M. incognita in vitro and in the field trials through direct nematocidal activities. However, it remains poorly understood for the underlying mechanisms including whether TA-1 could induce host resistance against M. incognita. In the present study, the effects of TA-1 induced resistance against M. incognita in tomato were determined. Results showed that TA-1 colonized tomato roots, with 1.23 × 108 colony forming units (CFU)/g root tissues attached within 36 h, significantly reduced the number of galls in the local and systemic root systems in the split-root experiments by 44.0% and 28.1%, respectively. The bacteria also increased the basic defense responses of tomato plants, such as lignin accumulation and hydrogen peroxide (H2O2) content, which was associated with the enhanced activities of enzymes related to plant defense [e.g. phenylalanine ammonia-lyase (PAL), peroxidase (POD) and polyphenol oxidase (PPO)]. Moreover, TA-1 enhanced the expressions of tomato defense response genes in the salicylic acid (PR1a and PR-P6) and jasmonic acid (PI II and MC) pathways and induced resistance against M. incognita. These results suggested that TA-1 could effectively control M. incognita through induction of tomato resistance, therefore it could be used as a promising biocontrol agent to be incorporated in the integrated management programs in tomato production. [ABSTRACT FROM AUTHOR]

To study the degradation of lncRNAs in EPMI in rat brain tissue, this study provides a new direction for the estimation of EPMI. LncRNA high-throughput sequencing was performed on the brain tissues of hemorrhagic shock model rats at 0 h and 24 h, and the target lncRNAs were screened. Samples at 0, 1, 3, 6, 12, 18 and 24 h after death were collected, and miRNA-9 and miRNA-125b were used as reference genes. The relative expression levels of lncRNAs at each PMI were detected by RT–qPCR, and a functional model involving lncRNAs and EPMI was established. Samples were collected at 6, 9, 15, and 21 h after death for functional model verification. The expression of several lncRNAs decreased with the prolongation of EPMI, and the mathematical model established by several lncRNA indices exhibited good fit. The verification results of the multi-index joint function model are significantly better than those of the single-index function model, and the established model is more practical. There is a linear relationship between lncRNAs and EPMI, and the multi-index function model is significantly better than the single-index function model, which is important for EPMI inference in forensic pathology practice. [ABSTRACT FROM AUTHOR]

Effective management of natural resources is crucial for diminishing carbon emissions. This research explores how economic, financial, and political risks influence the relationship between natural resources rents and carbon emissions. Analyzing data from 66 countries, this study utilizes methods such as quantile regression and dynamic threshold regression to thoroughly assess the data. The findings reveal: (i) Natural resources rents tend to increase carbon emissions consistently across different quantiles (0.1 to 0.9). The fact is confirmed by robustness checks, illustrating that increased natural resources rents lead to higher emissions. (ii) Economic, financial, and political risks affect how natural resources rents impact carbon emissions. Notably, reduced economic and financial risks lessen the propensity of natural resources rents to boost emissions at higher quantiles, while a decline in political risk decreases the exacerbating effect of natural resources rents on emissions from the 0.1 to 0.9 quantiles. (iii) This analysis uncovers threshold effects where economic, financial, and political risks act as threshold factors. Specifically, when economic and political risks are low, a rise in natural resources rents actually leads to a decline in carbon emissions. The findings underscore the importance of considering these risks in the formulation of policies aimed at reducing carbon emissions from natural resource exploitation. [ABSTRACT FROM AUTHOR]

Accurate classification of gene expression data is crucial for disease diagnosis and drug discovery. However, gene expression data usually has a large number of features, which poses a challenge for accurate classification. In this paper, a novel feature selection method based on minimal redundancy maximal relevance (mRMR) and aquila optimizer is proposed, which introduces the mRMR method in the initialization stage of the population to generate excellent initial populations, effectively improve the quality of the population, and then, the using random opposition-based learning strategy to improve the diversity of aquila population and accelerate the convergence speed of the algorithm, and finally, introducing inertia weight in the position update formula in the late iteration of the aquila optimizer to avoid the algorithm falling into the local optimum and improve the algorithm's capability to find the optimum. In order to verify the effectiveness of the proposed method, ten real gene expression datasets are selected in this paper and compared with several meta-heuristic algorithms. Experimental results show that the proposed method is significantly superior to other meta-heuristic algorithms in terms of fitness value, classification accuracy and the number of selected features. Compared with the original aquila optimizer, the average classification accuracy of the proposed method on KNN and SVM classifiers is improved by 3.48–12.41% and 0.53–18.63% respectively. The proposed method significantly reduces the feature dimension of gene expression data, retains important features, and obtains higher classification accuracy, providing a new method and idea for feature selection of gene expression data. [ABSTRACT FROM AUTHOR]

Conventional statistical methods for missing data imputation have been challenging to adapt to the large-scale new features of high dimensionality. Moreover, the missing data imputation methods based on Generative Adversarial Networks (GAN) are plagued with gradient vanishing and mode collapse. To address these problems, we have proposed a new imputation method based on GAN to enhance the accuracy of missing data imputation in this study. We refer to our missing data method using Generative Adversarial Imputation Networks (MGAIN). Specifically, the least squares loss is first introduced to solve the gradient vanishing problem and ensure the high quality of the output data in MGAIN. To mitigate mode collapse, dual discriminator is used in the model, which improved the diversity of output data to avoid the degradation of computational performance caused by single data. As a result, MGAIN generates rich and accurate imputation values. The MGAIN enhances imputation accuracy and reduces the root mean square error metric by 21.66% compared to the baseline model. We evaluated our method on baseline datasets and found that MGAIN outperformed state-of-the-art and popular imputation methods, demonstrating its effectiveness and superiority. [ABSTRACT FROM AUTHOR]

Rare and endangered species have narrow geographical distributions and are vulnerable to environmental changes. Studying the impact of future climate change on their distributions and identifying areas of high conservation priority are key to halting biodiversity loss. In this study, we combined a species distribution model with systematic conservation planning to simulate the suitable distributions of rare and endangered vascular plants and vertebrates in Inner Mongolia in the current and future (the 2050s), analyzed the vulnerability of species, and identified areas with high conservation priority. Currently, species richness (SR) of vascular plant was high in the Greater Khingan Mountains, and SR of vertebrates was high on the Hulunbuir Plateau, which are two species-rich areas. By 2050, 41.8% to 54.6% of vascular plants will have a reduced suitable distribution area, versus 46.8% to 51.1% for vertebrates. Vascular plant SR increased significantly in the Mu Us Desert, which became a new species-rich area. Vertebrate SR increased in western Inner Mongolia, but species-rich areas changed little. Species-rich areas are also potentially affected by future land use change, particularly in grassland, forest, and cropland areas with high SR. The current priority biodiversity conservation area covers 12.27 × 104 km2, of which 80.6% is located outside existing protected areas. By 2050, this percentage may increase to 83.4%. Our study revealed the potential pressure of existing protected areas in protecting biodiversity under future climate change, which helps decision-makers develop the most appropriate development strategies in advance to promote China's sustainable development. [ABSTRACT FROM AUTHOR]

In flowering plants, the predominant sexual morph is hermaphroditism, and the emergence of unisexuality is poorly understood. Using Cucumis melo (melon) as a model system, we explore the mechanisms driving sexual forms. We identify a spontaneous mutant exhibiting a transition from bisexual to unisexual male flower, and identify the causal mutation as a Harbinger transposon impairing the expression of Ethylene Insensitive 2 (CmEIN2) gene. Genetics and transcriptomic analysis reveal a dual role of CmEIN2 in both sex determination and fruit shape formation. Upon expression of CmACS11, EIN2 is recruited to repress the expression of the carpel inhibitor, CmWIP1. Subsequently, EIN2 is recruited to mediate stamina inhibition. Following the sex determination phase, EIN2 promotes fruit shape elongation. Genome-wide analysis reveals that Harbinger transposon mobilization is triggered by environmental cues, and integrates preferentially in active chromatin, particularly within promoter regions. Characterization of a large collection of melon germplasm points to active transpositions in the wild, compared to cultivated accessions. Our study underscores the association between chromatin dynamics and the temporal aspects of mobile genetic element insertions, providing valuable insights into plant adaptation and crop genome evolution. In flowering plants, hermaphroditism is widespread. Here the authors identified a transposon insertion that triggers plant sexual transition. This study highlights the role of transposons in plant adaptation and evolution. [ABSTRACT FROM AUTHOR]

Main conclusion: The genetic diversity in tetraploid wheat provides a genetic pool for improving wheat productivity and environmental resilience. The tetraploid wheat had strong N uptake, translocation, and assimilation capacity under N deficit stress, thus alleviating growth inhibition and plant N loss to maintain healthy development and adapt to environments with low N inputs. Tetraploid wheat with a rich genetic variability provides an indispensable genetic pool for improving wheat yield. Mining the physiological mechanisms of tetraploid wheat in response to nitrogen (N) deficit stress is important for low-N-tolerant wheat breeding. In this study, we selected emmer wheat (Kronos, tetraploid), Yangmai 25 (YM25, hexaploid), and Chinese spring (CS, hexaploid) as materials. We investigated the differences in the response of root morphology, leaf and root N accumulation, N uptake, translocation, and assimilation-related enzymes and gene expression in wheat seedlings of different ploidy under N deficit stress through hydroponic experiments. The tetraploid wheat (Kronos) had stronger adaptability to N deficit stress than the hexaploid wheats (YM25, CS). Kronos had better root growth under low N stress, expanding the N uptake area and enhancing N uptake to maintain higher NO3− and soluble protein contents. Kronos exhibited high TaNRT1.1, TaNRT2.1, and TaNRT2.2 expression in roots, which promoted NO3− uptake, and high TaNRT1.5 and TaNRT1.8 expression in roots and leaves enhanced NO3− translocation to the aboveground. NR and GS activity in roots and leaves of Kronos was higher by increasing the expression of TANIA2, TAGS1, and TAGS2, which enhanced the reduction and assimilation of NO3− as well as the re-assimilation of photorespiratory-released NH4+. Overall, Kronos had strong N uptake, translocation, and assimilation capacity under N deficit stress, alleviating growth inhibition and plant N loss and thus maintaining a healthy development. This study reveals the physiological mechanisms of tetraploid wheat that improve nitrogen uptake and assimilation adaptation under low N stress, which will provide indispensable germplasm resources for elite low-N-tolerant wheat improvement and breeding. [ABSTRACT FROM AUTHOR]

The remarkable advance in gene editing technology presents unparalleled opportunities for transforming medicine and finding cures for hereditary diseases. Human trials of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9)-based therapeutics have demonstrated promising results in disrupting or deleting target sequences to treat specific diseases. However, the potential of targeted gene insertion approaches, which offer distinct advantages over disruption/deletion methods, remains largely unexplored in human trials due to intricate technical obstacles and safety concerns. This paper reviews the recent advances in preclinical studies demonstrating in vivo targeted gene insertion for therapeutic benefits, targeting somatic solid tissues through systemic delivery. With a specific emphasis on hemophilia as a prominent disease model, we highlight advancements in insertion strategies, including considerations of DNA repair pathways, targeting site selection, and donor design. Furthermore, we discuss the complex challenges and recent breakthroughs that offer valuable insights for progressing towards clinical trials. [ABSTRACT FROM AUTHOR]

Rice eating and cooking quality (ECQ) is one of the most important qualities and it has attracted more and more interests of consumers and breeders. SSIIa and Wx are the major genes affecting rice ECQ, and several alleles of SSIIa and Wx have been identified. In this study, the effects of different allele combinations of SSIIa and Wx on rice ECQ were explored by analyzing amylose content (AC), gelatinization temperature (GT), and Rapid Viscosity Analyzer (RVA) profile properties of one natural population which is composed of 30 glutinous rice varieties and 342 non-glutinous varieties. Nine allele combinations of SSIIa and Wx were identified in all the non-glutinous varieties. The allele combination of SSIIac/Wxb harbored higher BDV, lower SBV, intermediate AC, and higher GT, which means better taste quality but more cooking time. For non-glutinous rice, stepwise regression analysis showed that RVA profile properties are mainly controlled by polymorphic loci of Wx-Int1(G/T) and Wx-EX10(C/T); AC, PV, BDV, and SBV are mainly controlled by Wx-Int1(G/T); HPV, CPV, and CSV are mainly controlled by Wx-EX10(C/T); GT is mainly controlled by SSIIa-EX8(GC/TT). Regression equation models also confirmed that SSIIac/Wxb had better ECQ compared to other allele combinations, indicating its potential to improve rice quality. Our results may provide useful clues for elite alleles of SSIIa and Wx for introgression to other rice varieties to improve rice ECQ. [ABSTRACT FROM AUTHOR]

Objectives: Focal cortical dysplasia (FCD) represents one of the most common causes of refractory epilepsy in children. Deep learning demonstrates great power in tissue discrimination by analyzing MRI data. A prediction model was built and verified using 3D full-resolution nnU-Net for automatic lesion detection and segmentation of children with FCD II. Methods: High-resolution brain MRI structure data from 65 patients, confirmed with FCD II by pathology, were retrospectively studied. Experienced neuroradiologists segmented and labeled the lesions as the ground truth. Also, we used 3D full-resolution nnU-Net to segment lesions automatically, generating detection maps. The algorithm was trained using fivefold cross-validation, with data partitioned into training (N = 200) and testing (N = 15). To evaluate performance, detection maps were compared to expert manual labels. The Dice-Sørensen coefficient (DSC) and sensitivity were used to assess the algorithm performance. Results: The 3D nnU-Net showed a good performance for FCD lesion detection at the voxel level, with a sensitivity of 0.73. The best segmentation model achieved a mean DSC score of 0.57 on the testing dataset. Conclusion: This pilot study confirmed that 3D full-resolution nnU-Net can automatically segment FCD lesions with reliable outcomes. This provides a novel approach to FCD lesion detection. Critical relevance statement: Our fully automatic models could process the 3D T1-MPRAGE data and segment FCD II lesions with reliable outcomes. Key points: • Simplified image processing promotes the DL model implemented in clinical practice. • The histopathological confirmed lesion masks enhance the clinical credibility of the AI model. • The voxel-level evaluation metrics benefit lesion detection and clinical decisions. [ABSTRACT FROM AUTHOR]

The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.P-stereogenic heterocycles are privileged chiral ligands and bioactive compounds, but the catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives is challenging. Here, the authors report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure Pstereogenic phosphindane and phosphindole derivatives. [ABSTRACT FROM AUTHOR]

The effect of additive methyl nicotinate (MN) on the electrochemical behaviors of nickel and copper ions were studied by cyclic voltammetry (CV) using choline chloride (ChCl)-ethylene glycol (EG) deep eutectic solvents as the base solution. The results showed that the addition of MN changed the reduction potential of nickel and copper ions, and the adsorption of MN made the reduction potential shift negatively from –1.131 to –1.237 V. The addition of MN changed the reduction process of nickel-copper ions, and it was still an irreversible process controlled by diffusion. The chronoamperometry (CA) method was used to study the growth nucleation mode of nickel and copper. The results showed that the addition of MN changes the nucleation mode of nickel and copper, which is a nucleation feature of three-dimensional instantaneous nucleation changes to three-dimensional progressive nucleation. The differential capacitance curve was used to study the action mechanism of MN on the surface of the electrode. The results showed that MN increased the thickness of the double electrode layer by adsorption on the electrode surface, thus reducing the differential capacitance by 2–10 μF. The corrosion resistance of nickel-copper coating in 3.5 wt % NaCl was studied by using kinetic potential polarization curve. The results showed that the self-corrosion potential shifted positively and the corrosion current density decreased after the addition of MN, which made the nickel-copper alloy have higher corrosion resistance. The results of X-ray diffraction (XRD) showed that the addition of MN changed the preferential growth of nickel-copper deposition. The texture coefficient was used to quantify the preferred orientation, and the results showed that the addition of MN made the (220) crystal plane of the coating appear high priority orientation. The effect of MN on the microstructure of the coating was studied by scanning electron microscopy (SEM), and the results showed that the presence of MN changed the nickel-copper coating from a needle-like coating with fine cracks to a compact spherical coating. [ABSTRACT FROM AUTHOR]

Rice grain size directly affects grain yield and is an important quantitative trait target. Many genes regulating grain size have been mapped and cloned in recent years. These genes not only play a single role on grain size regulation but have mutual interactive effect on grain size. Mining key allele combinations of grain-size regulating genes will favorite the pyramiding of favorable alleles in rice varieties with desired grain size and shape that meet people's preferences. Here, we studied the effect of seven major grain-size regulating genes (GS3, GS5, GW8/OsSPL16, BG2, GS6, GS2 and TGW3) and their allele combinations on grain size-related traits (grain length, grain width, grain length width ratio, thousand grain weight), and established multiple regression equations to predict rice grain size. We found that alleles of seven genes displayed significant differences in rice grain size. Among the seven genes, GS3 gene played the most important effect in regulating grain size, pyramiding GS3 alleles with other alleles such as GS6-II/III allele could significantly enhance grain size or grain weight. Specific allele combination of GS3-A, GS2-ZH11, GS5-Zhenshan97, GS6-II/III, BG2-9311 and GW8-HJX74 can produce rice varieties with slender grains; allele combination of GS3-A, GS6-I, BG2-Nipponbare and TGW3-CW23 produce grains with higher grain weight. The regression equation model developed in this study provided a useful tool to predict rice grain size. These results would help in breeding rice varieties with ideal traits and high yield by pyramiding favorable alleles. [ABSTRACT FROM AUTHOR]

The reaction mechanism of the historic copper-catalyzed Glaser coupling has been debated to be based on redox cycles of Cu ions in specific oxidation states or on a radical mechanism based on Cu(0)/Cu(I). Here, the authors demonstrate two coexisting Glaser coupling pathways which can be differentiated by anaerobic/irradiation or aerobic reaction conditions. Without O2, copper(I) acetylides undergo a photo-excited pathway to generate highly reactive alkynyl radicals, which combine together to form a homo-coupling product or individually react with diverse X-H (X = C, N, O, S and P) substrates via hydrogen atom transfer. With O2, copper(I) acetylides are oxidized to become a Cu-acetylide/Cu-O merged Cu(I/II) intermediate for further oxidative coupling. This work not only complements the radical mechanism for Glaser coupling, but also provides a mild way to access highly energetic alkynyl radicals for efficient organic transformations. The reaction mechanism of the historic copper-catalyzed Glaser coupling has been debated to be based on redox cycles of Cu ions in specific oxidation states or on a radical mechanism based on Cu(0)/Cu(I). Here, the authors demonstrate two coexisting Glaser coupling pathways which can be differentiated by anaerobic/irradiation or aerobic reaction conditions [ABSTRACT FROM AUTHOR]

The in-board bogie is designed to be applied in next-generation China railway high-speed trains to further achieve lightweight and higher speed (400 km/h). Traditional steel coil springs could not be used in the in-board bogie due to strict lightweight requirements and narrow installation space. This research aims to propose a buckle-type composite leaf spring assembly to replace the traditional steel coil springs. Meanwhile, the buckle-type leaf spring assembly is needed to meet specific size (length and width less than 720 mm and 120 mm) and performance requirements (ultimate load over 100 kN, vertical stiffness around 1300 N/mm) for the primary suspension. Static and dynamic flexural experiments, as well as relevant finite element method (FEM) analysis were carried out to explore the mechanical properties of the composite leaf springs assembly. Simulation results show that the maximum stress of the leaf spring body under the rated load and ultimate load is 314.6 MPa and 488.1 MPa, respectively. The vertical stiffness of the composite leaf spring assembly from numerical simulation is 1362.3 N/mm, which is consistent with that from the static flexural test (1350.4 N/mm). Experimental results revealed that the vertical stiffness of the composite leaf spring was decreased by 1.06% and 1.32% compared to its initial stiffness after one and two million cycles of cyclic flexural load, respectively, and a slight matrix damage was observed in the leaf spring body. Therefore, this buckle-type composite leaf spring assembly meets the design requirements, and can ensure a safe and smooth operation of high-speed trains. [ABSTRACT FROM AUTHOR]

Biomimetic mechanosensors have profound implications for various areas, including health care, prosthetics, human‒machine interfaces, and robotics. As one of the most important parameters, the sensitivity of mechanosensors is intrinsically determined by the detection resolution to mechanical force. In this manuscript, we expand the force detection resolution of current biomimetic mechanosensors from the micronewton to nanonewton scale. We develop a nanocrack-based electronic whisker-type mechanosensor that has a detection resolution of 72.2 nN. We achieve the perception of subtle mechanical stimuli, such as tiny objects and airflow, and the recognition of surface morphology down to a 30 nm height, which is the finest resolution ever reported in biomimetic mechanosensors. More importantly, we explore the use of this mechanosensor in wearable devices for sensing gravity field orientation with respect to the body, which has not been previously achieved by these types of sensors. We develop a wearable smart system for sensing the body's posture and movements, which can be used for remote monitoring of falls in elderly people. In summary, the proposed device offers great advantages for not only improving sensing ability but also expanding functions and thus can be used in many fields not currently served by mechanosensors. [ABSTRACT FROM AUTHOR]

A single base changes causing a change to the amino acid sequence of the encoded protein, which is defined as non-synonymous single nucleotide polymorphisms (nsSNPs). Many of the nsSNPs can cause disease, and these nsSNPs are considered as pathogenic mutations. In the study, the high-risk nsSNPs of WFS1 and their influence on the structure and function of wolframin protein were predicted by multiple bioinformatics software. We obtained 13 high-risk nsSNPs of WFS1. All the 13 high-risk nsSNPs are highly conserved residues with a conservative score of 9 or 8 and mostly may cause a decrease in protein stability. The high-risk nsSNPs have an important effect on not only amino acid size, charge and hydrophobicity, but also protein's spatial structure. Among these, 11 nsSNPs had been previously published or cited and 2 nsSNPs (G695S and E776K) had not been reported to date. The two novel variants increased or decreased hydrogen bonds. In conclusion, through different computational tools, it is presumed that the mechanism of pathogenic WFS1 nsSNPs should include the changes of physicochemical properties, significant structural changes and abnormal binding with functional partners. We accomplished the computational-based screening and analysis for deleterious nsSNPs in WFS1, which had important reference value and could contribute to further studies of the mechanism of WFS1 related disease. The computational analysis has many advantages, but the results should be identified by further experimental studies in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Agrochemicals provide huge agronomic and economic benefits. However, excessive agrochemicals cause serious environmental pollution. The use of surfactants can effectively improve the utilization rate of agrochemicals in the soil, and an amphiphilic alginate derivative (Ugi-alg) was prepared in this work. This paper mainly discussed the affinity between Ugi-alg and soil colloids and the influence of Ugi-alg on the adsorption behavior of pesticides on colloidal particles. In the presence of 2.4 mM Ca2+, the affinity between soil colloids and Ugi-alg (30 mg/L) was enhanced (~ − 12.33 mV) compared with pure soil colloids (~ − 30 mV). The strong affinity between Ugi-alg and the colloids reduced the migration of acetamiprid. Transmission electron microscopy showed that soil colloids were wrapped by the network structure of Ugi-alg, indicating that Ugi-alg easily adhered to the surface of soil colloids. Studies of the adsorption showed the adsorption capacity of acetamiprid on soil colloids was 556 mg/g in the presence of Ugi-alg (30 mg/L) and Ca2+ (2.4 mM). And the adsorption behavior of acetamiprid in soil colloids was also not greatly affected by changes in pH and temperature. Ugi-alg is a degradable polysaccharide-based surfactant which provides a new concept and a practical method for the remediation of soil pollutants. [ABSTRACT FROM AUTHOR]

Mounting interest in modeling outdoor diffusion and transmission of bioaerosols due to the prevalence of COVID-19 in the urban environment has led to better knowledge of the issues concerning exposure risk and evacuation planning. In this study, the dispersion and deposition dynamics of bioaerosols around a vaccine factory were numerically investigated under various thermal conditions and leakage rates. To assess infection risk at the pedestrian level, the improved Wells-Riley equation was used. To predict the evacuation path, Dijkstra's algorithm, a derived greedy algorithm based on the improved Wells-Riley equation, was applied. The results show that, driven by buoyancy force, the deposition of bioaerosols can reach 80 m on the windward sidewall of high-rise buildings. Compared with stable thermal stratification, the infection risk of unstable thermal stratification in the upstream portion of the study area can increase by 5.53% and 9.92% under a low and high leakage rate, respectively. A greater leakage rate leads to higher infection risk but a similar distribution of high-risk regions. The present work provides a promising approach for infection risk assessment and evacuation planning for the emergency response to urban bioaerosol leakage. [ABSTRACT FROM AUTHOR]

Derivation of salivary gland epithelial progenitors (SGEPs) from human pluripotent stem cells (hPSCs) has great potential in developmental biology and regenerative medicine. At present, no efficient method is available to generate salivary gland cells from hPSCs. Here, we described for the first time a robust protocol for direct differentiation of hPSCs into SGEPs by mimicking retinoic acid and Wnt signaling. These hPSC-derived SGEPs expressed SOX9, KRT5, and KRT19, important progenitor markers of developing salivary glands. CD24 and α-SMA positive cells, capable of restoring the functions of injured salivary glands, were also present in SGEP cultures. Importantly, RNA-sequencing revealed that the SGEPs resembled the transcript profiles of human fetal submandibular glands. Therefore, we provided an efficient protocol to induce hPSCs differentiation into SGEPs. Our study provides a foundation for generating functional hPSCs derived salivary gland acinar cells and three-dimensional organoids, potentially serving as new models for basic study and future translational research. [ABSTRACT FROM AUTHOR]

The ability of plants to efficiently supply nitrogen (N) to their shoots is critical for reconstructing photosynthetic tissues after defoliation events. We conducted an indoor defoliation experiment and used 13C and 15 N labeling to investigate the photosynthetic carbon (C) allocation, the relationships between C allocation and N uptake, and the contribution of N reallocation for regrowth. Leymus chinensis increased the amount of belowground 13C to the low defoliation (LD) treatment, but allocated less 13C belowground in response to the medium (MD) and high defoliation (HD) treatments, these changes were related to photosynthetic C fixation. Moreover, there was no evidence of a trade-off in C allocation between root exudates and roots, because their direct sources of C differed. The uptake rate of 15 N was the greatest in the LD treatment, when the C invested belowground was maximal. MD treatment increased specific root length and specific root area, which augmented the N uptake. Crucially, defoliation increased the N reallocation from roots to shoots, likely due to the greater N demand of shoot. Altogether, our results show that N supply was governed by N uptake and reallocation for Leymus chinensis after low defoliation. [ABSTRACT FROM AUTHOR]

There is only limited scientific evidence with varying results on the association between hospital admissions and low ambient temperatures. Furthermore, there has been no research in Northern Europe on cold-associated morbidity. Therefore, this study investigated the associations of daily wintertime temperature and cold spells with cardiorespiratory hospital admissions in the Helsinki metropolitan area, Finland. Daily number of non-elective hospital admissions for 2001–2017 was obtained from the national hospital discharge register and meteorological data from the Finnish Meteorological Institute. Quasi-Poisson regression models were fitted, controlling for potential confounders such as time trend, weekday, holidays, air pollution, barometric pressure, and influenza. The associations of cold season daily mean ambient temperature and cold spells with hospital admissions were estimated using a penalized distributed lag linear models with 21 lag days. Decreased wintertime ambient temperature was associated with an increased risk of hospitalization for myocardial infarction in the whole population (relative risk [RR] per 1 °C decrease in temperature: 1.017, 95% confidence interval [CI]: 1.002–1.032). An increased risk of hospital admission for respiratory diseases (RR: 1.012, 95% CI: 1.002, 1.022) and chronic obstructive pulmonary disease (RR: 1.031, 95% CI: 1.006, 1.056) was observed only in the ≥ 75 years age group. There was an independent effect of cold spell days only for asthma admissions (RR: 2.348, 95% CI: 1.026, 5.372) in the all-ages group. Cold temperature increases the need for acute hospital care due to myocardial infarction and respiratory causes during winter in a northern climate. [ABSTRACT FROM AUTHOR]

Global warming has constituted a major global problem. Carbon dioxide emissions from the burning of fossil fuels are the main cause of global warming. Therefore, carbon dioxide emission forecasting has attracted widespread attention. Aiming at the problem of carbon dioxide emissions forecasting, this paper proposes a new hybrid forecasting model of carbon dioxide emissions, which combines the marine predator algorithm (MPA) and multi-kernel support vector regression. For further strengthening the prediction accuracy, a novel variant of MPA is proposed, called EGMPA, which introduces the elite opposition-based learning strategy and the golden sine algorithm into MPA. Algorithm test results show that EGMPA can effectively improve the convergence speed and optimization accuracy. The carbon dioxide emission data of China from 1965 to 2020 are taken as the research objects. Root-mean-square error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE) are used to evaluate the performance of the proposed model. The proposed multi-kernel support vector regression model is used to forecast China's carbon dioxide emissions during the "14th Five-Year Plan" period. The results show that the proposed model has RMSE of 37.43 Mt, MAE of 30.63 Mt, and MAPE of 0.32%, which significantly improves the prediction accuracy and can accurately and effectively predict China's carbon dioxide emissions. During the "14th Five-Year Plan" period, China's carbon dioxide emissions will continue to show an increasing trend, but the growth rate will slow down significantly. [ABSTRACT FROM AUTHOR]

To analyse the pathogenic genes and mutations of a family with hereditary deafness. We recruited a three-generation family with NSHL. A detailed medical history inquiry and related examinations were performed. Next-generation sequencing (NGS) was used to confirm the gene mutation in the proband, and Sanger sequencing was used for verification. The effect of the WFS1 mutation on the function and structure of the wolframin protein was predicted by multiple computational software. From the Gene Expression Omnibus (GEO) database, we obtained GSE40585 dataset and performed enrichment analyses. The family clinically manifested as autosomal dominant NSHL. A novel WFS1 c.2421C>G (p.Ser807Arg) mutation was identified in four affected individuals in the pedigree. The p.Ser807Arg mutation is a highly conserved residue and causes an increase in protein stability. It had an important influence on not only amino acid size, charge and hydrophobicity but also protein intermolecular hydrogen bonding and spatial structure. There were differentially expressed genes (DEGs) in GSE40585 dataset. Enrichment analysis revealed that DEGs mainly functioned in amino acid metabolism, signal transduction and dephosphorylation. We reported a novel mutation c.2421C>G (p.Ser807Arg in WFS1. This study expands the mutation spectrum of WFS1. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is associated with increased suicidality, and it's still challenging to identify suicide in clinical practice. Although suicide attempt (SA) is the most relevant precursor with multiple functional abnormalities reported from neuroimaging studies, little is known about how the spontaneous transient activated patterns organize and coordinate brain networks underlying SA. Thus, we obtained resting-state magnetoencephalography data for two MDD subgroups of 44 non-suicide patients and 34 suicide-attempted patients, together with 49 matched health-controls. For the source-space signals, Hidden Markov Model (HMM) helped to capture the sub-second dynamic activity via a hidden sequence of finite number of states. Temporal parameters and spectral activation were acquired for each state and then compared between groups. Here, HMM states characterized the spatiotemporal signatures of eight networks. The activity of suicide attempters switches more frequently into the fronto-temporal network, as the time spent occupancy of fronto-temporal state is increased and interval time is decreased compared with the non-suicide patients. Moreover, these changes are significantly correlated with Nurses' Global Assessment of Suicide Risk scores. Suicide attempters also exhibit increased state-wise activations in the theta band (4-8 Hz) in the posterior default mode network centered on posterior cingulate cortex, which can't be detected in the static spectral analysis. These alternations may disturb the time allocations of cognitive control regulations and cause inflexible decision making to SA. As the better sensitivity of dynamic study in reflecting SA diathesis than the static is validated, dynamic stability could serve as a potential neuronal marker for SA. [ABSTRACT FROM AUTHOR]

AAV-delivered CRISPR/Cas9 (AAV-CRISPR) has shown promising potentials in preclinical models to efficiently insert therapeutic gene sequences in somatic tissues. However, the AAV input doses required were prohibitively high and posed serious risk of toxicity. Here, we performed AAV-CRISPR mediated homology-independent knock-in at a new target site in mAlb 3'UTR and demonstrated that single dose of AAVs enabled long-term integration and expression of hF9 transgene in both adult and neonatal hemophilia B mice (mF9 −/−), yielding high levels of circulating human Factor IX (hFIX) and stable hemostasis restoration during entire 48-week observation period. Furthermore, we achieved hemostasis correction with a significantly lower AAV dose (2 × 109 vg/neonate and 1 × 1010 vg/adult mouse) through liver-specific gene knock-in using hyperactive hF9R338L variant. The plasma antibodies against Cas9 and AAV in the neonatal mice receiving low-dose AAV-CRISPR were negligible, which lent support to the development of AAV-CRISPR mediated somatic knock-in for treating inherited diseases. Here, the authors develop an AAV-CRISPR mediated somatic knock-in. They apply this system to restore hemostasis in neonatal hemophilia B mice and show liver-specificity of the knock-in and low serum antibody production. [ABSTRACT FROM AUTHOR]

Purpose: Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells (PC) in the bone marrow (BM). B-cell maturation antigen (BCMA) is predominantly expressed in malignant plasma cells, and associated with the proliferation, survival, and progression of various myeloma cells. Given these important roles, BCMA emerges as an ideal target antigen for MM therapy. However, effective stratification of patients who may benefit from targeted BCMA therapy and real-time monitoring the therapeutic efficacy poses significant clinical challenge. This study aims to develop a BCMA targeted diagnostic modality, and preliminarily explore its potential value in the radio-immunotherapy of MM.Using zirconium-89 (89Zr, t1/2 = 78.4 h) for labeling the BCMA-specific antibody, the BCMA-targeting PET tracer [89Zr]Zr-DFO-BCMAh230430 was prepared. The EC50 values of BCMAh230430 and DFO-BCMAh230430 were determined by ELISA assay. BCMA expression was assessed in four different tumor cell lines (MM.1S, RPMI 8226, BxPC-3, and KYSE520) through Western blot and flow cytometry. In vitro binding affinity was determined by cell uptake studies of [89Zr]Zr-DFO-BCMAh230430 in these tumor cell lines. For in vivo evaluation, PET imaging and ex vivo biodistribution studies were conducted in tumor-bearing mice to evaluate imaging performance and systemic distribution of [89Zr]Zr-DFO-BCMAh230430. Immunochemistry analysis was performed to detect BCMA expression in tumor tissues, confirming the specificity of our probe. Furthermore, we explored the anti-tumor efficacy of Lutetium-177 labeled BCMA antibody, [177Lu]Lu-DTPA-BCMAh230430, in tumor bearing-mice to validate its radioimmunotherapy potential.The radiolabeling of [89Zr]Zr-DFO-BCMAh230430 and [177Lu]Lu-DTPA-BCMAh230430 showed satisfactory radiocharacteristics, with a radiochemical purity exceeding 99%. ELISA assay results revealed closely aligned EC50 values for BCMAh230430 and DFO-BCMAh230430, which are 57 pM and 67 pM, respectively. Western blot and flow cytometry analyses confirmed the highest BCMA expression level. Cell uptake data indicated that MM.1S cells had a total cellular uptake (the sum of internalization and surface binding) of 38.3% ± 1.53% for [89Zr]Zr-DFO-BCMAh230430 at 12 h. PET imaging of [89Zr]Zr-DFO-BCMAh230430 displayed radioactive uptake of 7.71 ± 0.67%ID/g in MM.1S tumors and 4.13 ± 1.21%ID/g in KYSE520 tumors at 168 h post-injection (n = 4) (P < 0.05), consistent with ex vivo biodistribution studies. Immunohistochemical analysis of tumor tissues confirmed higher BCMA expression in MM.1S tumors xenograft compared to KYSE520 tumors. Notably, [177Lu]Lu-DTPA-BCMAh230430 showed some anti-tumor efficacy, evidenced by slowed tumor growth. Furthermore, no significant difference in body weight was observed in MM.1S tumor-bearing mice over 14 days of administration with or without [177Lu]Lu-DTPA-BCMAh230430.Our study has successfully validated the essential role of [89Zr]Zr-DFO-BCMAh230430 in non-invasively monitoring BCMA status in MM tumors, showing favorable tumor uptake and specific binding affinity to MM tumors. Furthermore, our research revealed, as a proof-of-concept, the effectiveness of [177Lu]Lu-DTPA-BCMAh230430 in radioimmunotherapy for MM tumors. In conclusion, we present a novel BCMA antibody-based radiotheranostic modality that holds promise for achieving efficient and precise MM diagnostic and therapy.Experimental design: Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells (PC) in the bone marrow (BM). B-cell maturation antigen (BCMA) is predominantly expressed in malignant plasma cells, and associated with the proliferation, survival, and progression of various myeloma cells. Given these important roles, BCMA emerges as an ideal target antigen for MM therapy. However, effective stratification of patients who may benefit from targeted BCMA therapy and real-time monitoring the therapeutic efficacy poses significant clinical challenge. This study aims to develop a BCMA targeted diagnostic modality, and preliminarily explore its potential value in the radio-immunotherapy of MM.Using zirconium-89 (89Zr, t1/2 = 78.4 h) for labeling the BCMA-specific antibody, the BCMA-targeting PET tracer [89Zr]Zr-DFO-BCMAh230430 was prepared. The EC50 values of BCMAh230430 and DFO-BCMAh230430 were determined by ELISA assay. BCMA expression was assessed in four different tumor cell lines (MM.1S, RPMI 8226, BxPC-3, and KYSE520) through Western blot and flow cytometry. In vitro binding affinity was determined by cell uptake studies of [89Zr]Zr-DFO-BCMAh230430 in these tumor cell lines. For in vivo evaluation, PET imaging and ex vivo biodistribution studies were conducted in tumor-bearing mice to evaluate imaging performance and systemic distribution of [89Zr]Zr-DFO-BCMAh230430. Immunochemistry analysis was performed to detect BCMA expression in tumor tissues, confirming the specificity of our probe. Furthermore, we explored the anti-tumor efficacy of Lutetium-177 labeled BCMA antibody, [177Lu]Lu-DTPA-BCMAh230430, in tumor bearing-mice to validate its radioimmunotherapy potential.The radiolabeling of [89Zr]Zr-DFO-BCMAh230430 and [177Lu]Lu-DTPA-BCMAh230430 showed satisfactory radiocharacteristics, with a radiochemical purity exceeding 99%. ELISA assay results revealed closely aligned EC50 values for BCMAh230430 and DFO-BCMAh230430, which are 57 pM and 67 pM, respectively. Western blot and flow cytometry analyses confirmed the highest BCMA expression level. Cell uptake data indicated that MM.1S cells had a total cellular uptake (the sum of internalization and surface binding) of 38.3% ± 1.53% for [89Zr]Zr-DFO-BCMAh230430 at 12 h. PET imaging of [89Zr]Zr-DFO-BCMAh230430 displayed radioactive uptake of 7.71 ± 0.67%ID/g in MM.1S tumors and 4.13 ± 1.21%ID/g in KYSE520 tumors at 168 h post-injection (n = 4) (P < 0.05), consistent with ex vivo biodistribution studies. Immunohistochemical analysis of tumor tissues confirmed higher BCMA expression in MM.1S tumors xenograft compared to KYSE520 tumors. Notably, [177Lu]Lu-DTPA-BCMAh230430 showed some anti-tumor efficacy, evidenced by slowed tumor growth. Furthermore, no significant difference in body weight was observed in MM.1S tumor-bearing mice over 14 days of administration with or without [177Lu]Lu-DTPA-BCMAh230430.Our study has successfully validated the essential role of [89Zr]Zr-DFO-BCMAh230430 in non-invasively monitoring BCMA status in MM tumors, showing favorable tumor uptake and specific binding affinity to MM tumors. Furthermore, our research revealed, as a proof-of-concept, the effectiveness of [177Lu]Lu-DTPA-BCMAh230430 in radioimmunotherapy for MM tumors. In conclusion, we present a novel BCMA antibody-based radiotheranostic modality that holds promise for achieving efficient and precise MM diagnostic and therapy.Results: Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells (PC) in the bone marrow (BM). B-cell maturation antigen (BCMA) is predominantly expressed in malignant plasma cells, and associated with the proliferation, survival, and progression of various myeloma cells. Given these important roles, BCMA emerges as an ideal target antigen for MM therapy. However, effective stratification of patients who may benefit from targeted BCMA therapy and real-time monitoring the therapeutic efficacy poses significant clinical challenge. This study aims to develop a BCMA targeted diagnostic modality, and preliminarily explore its potential value in the radio-immunotherapy of MM.Using zirconium-89 (89Zr, t1/2 = 78.4 h) for labeling the BCMA-specific antibody, the BCMA-targeting PET tracer [89Zr]Zr-DFO-BCMAh230430 was prepared. The EC50 values of BCMAh230430 and DFO-BCMAh230430 were determined by ELISA assay. BCMA expression was assessed in four different tumor cell lines (MM.1S, RPMI 8226, BxPC-3, and KYSE520) through Western blot and flow cytometry. In vitro binding affinity was determined by cell uptake studies of [89Zr]Zr-DFO-BCMAh230430 in these tumor cell lines. For in vivo evaluation, PET imaging and ex vivo biodistribution studies were conducted in tumor-bearing mice to evaluate imaging performance and systemic distribution of [89Zr]Zr-DFO-BCMAh230430. Immunochemistry analysis was performed to detect BCMA expression in tumor tissues, confirming the specificity of our probe. Furthermore, we explored the anti-tumor efficacy of Lutetium-177 labeled BCMA antibody, [177Lu]Lu-DTPA-BCMAh230430, in tumor bearing-mice to validate its radioimmunotherapy potential.The radiolabeling of [89Zr]Zr-DFO-BCMAh230430 and [177Lu]Lu-DTPA-BCMAh230430 showed satisfactory radiocharacteristics, with a radiochemical purity exceeding 99%. ELISA assay results revealed closely aligned EC50 values for BCMAh230430 and DFO-BCMAh230430, which are 57 pM and 67 pM, respectively. Western blot and flow cytometry analyses confirmed the highest BCMA expression level. Cell uptake data indicated that MM.1S cells had a total cellular uptake (the sum of internalization and surface binding) of 38.3% ± 1.53% for [89Zr]Zr-DFO-BCMAh230430 at 12 h. PET imaging of [89Zr]Zr-DFO-BCMAh230430 displayed radioactive uptake of 7.71 ± 0.67%ID/g in MM.1S tumors and 4.13 ± 1.21%ID/g in KYSE520 tumors at 168 h post-injection (n = 4) (P < 0.05), consistent with ex vivo biodistribution studies. Immunohistochemical analysis of tumor tissues confirmed higher BCMA expression in MM.1S tumors xenograft compared to KYSE520 tumors. Notably, [177Lu]Lu-DTPA-BCMAh230430 showed some anti-tumor efficacy, evidenced by slowed tumor growth. Furthermore, no significant difference in body weight was observed in MM.1S tumor-bearing mice over 14 days of administration with or without [177Lu]Lu-DTPA-BCMAh230430.Our study has successfully validated the essential role of [89Zr]Zr-DFO-BCMAh230430 in non-invasively monitoring BCMA status in MM tumors, showing favorable tumor uptake and specific binding affinity to MM tumors. Furthermore, our research revealed, as a proof-of-concept, the effectiveness of [177Lu]Lu-DTPA-BCMAh230430 in radioimmunotherapy for MM tumors. In conclusion, we present a novel BCMA antibody-based radiotheranostic modality that holds promise for achieving efficient and precise MM diagnostic and therapy.Conclusions: Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells (PC) in the bone marrow (BM). B-cell maturation antigen (BCMA) is predominantly expressed in malignant plasma cells, and associated with the proliferation, survival, and progression of various myeloma cells. Given these important roles, BCMA emerges as an ideal target antigen for MM therapy. However, effective stratification of patients who may benefit from targeted BCMA therapy and real-time monitoring the therapeutic efficacy poses significant clinical challenge. This study aims to develop a BCMA targeted diagnostic modality, and preliminarily explore its potential value in the radio-immunotherapy of MM.Using zirconium-89 (89Zr, t1/2 = 78.4 h) for labeling the BCMA-specific antibody, the BCMA-targeting PET tracer [89Zr]Zr-DFO-BCMAh230430 was prepared. The EC50 values of BCMAh230430 and DFO-BCMAh230430 were determined by ELISA assay. BCMA expression was assessed in four different tumor cell lines (MM.1S, RPMI 8226, BxPC-3, and KYSE520) through Western blot and flow cytometry. In vitro binding affinity was determined by cell uptake studies of [89Zr]Zr-DFO-BCMAh230430 in these tumor cell lines. For in vivo evaluation, PET imaging and ex vivo biodistribution studies were conducted in tumor-bearing mice to evaluate imaging performance and systemic distribution of [89Zr]Zr-DFO-BCMAh230430. Immunochemistry analysis was performed to detect BCMA expression in tumor tissues, confirming the specificity of our probe. Furthermore, we explored the anti-tumor efficacy of Lutetium-177 labeled BCMA antibody, [177Lu]Lu-DTPA-BCMAh230430, in tumor bearing-mice to validate its radioimmunotherapy potential.The radiolabeling of [89Zr]Zr-DFO-BCMAh230430 and [177Lu]Lu-DTPA-BCMAh230430 showed satisfactory radiocharacteristics, with a radiochemical purity exceeding 99%. ELISA assay results revealed closely aligned EC50 values for BCMAh230430 and DFO-BCMAh230430, which are 57 pM and 67 pM, respectively. Western blot and flow cytometry analyses confirmed the highest BCMA expression level. Cell uptake data indicated that MM.1S cells had a total cellular uptake (the sum of internalization and surface binding) of 38.3% ± 1.53% for [89Zr]Zr-DFO-BCMAh230430 at 12 h. PET imaging of [89Zr]Zr-DFO-BCMAh230430 displayed radioactive uptake of 7.71 ± 0.67%ID/g in MM.1S tumors and 4.13 ± 1.21%ID/g in KYSE520 tumors at 168 h post-injection (n = 4) (P < 0.05), consistent with ex vivo biodistribution studies. Immunohistochemical analysis of tumor tissues confirmed higher BCMA expression in MM.1S tumors xenograft compared to KYSE520 tumors. Notably, [177Lu]Lu-DTPA-BCMAh230430 showed some anti-tumor efficacy, evidenced by slowed tumor growth. Furthermore, no significant difference in body weight was observed in MM.1S tumor-bearing mice over 14 days of administration with or without [177Lu]Lu-DTPA-BCMAh230430.Our study has successfully validated the essential role of [89Zr]Zr-DFO-BCMAh230430 in non-invasively monitoring BCMA status in MM tumors, showing favorable tumor uptake and specific binding affinity to MM tumors. Furthermore, our research revealed, as a proof-of-concept, the effectiveness of [177Lu]Lu-DTPA-BCMAh230430 in radioimmunotherapy for MM tumors. In conclusion, we present a novel BCMA antibody-based radiotheranostic modality that holds promise for achieving efficient and precise MM diagnostic and therapy. [ABSTRACT FROM AUTHOR]

The advent of the era of big data promotes the further development of medicine, and data release is an important step in it. The existing medical data release methods mostly use the k-anonymity model as the basis for data protection. With the advancement of technology, anonymous models are progressively less resistant to consistency attacks and background knowledge attacks. In order to better protect the private information of patients, this paper makes two major contributions: (1) The method of calculating the correlation between attributes is used to ensure the validity of the data after the data is released; (2) On the basis of the previous step, combined with the difference privacy-preserving model and tree model, this paper proposes an attribute association-based differential privacy classification tree data publishing method (ACDP-Tree). In this paper, simulation experiments are carried out on real medical data sets. The experimental results show that the algorithm ensures the validity and availability of the data to a certain extent while ensuring that the patient's privacy is not leaked. [ABSTRACT FROM AUTHOR]

This study hopes to develop a multi-criteria decision-making (MCDM) method for equitable and efficient allocation of water resources under scarcity. Based on the Bankruptcy problems, five classic plus one proposed allocation rules are introduced to generate water distribution alternatives. The "Core" solution of Cooperative Game Theory (CGT) and the Security Restriction have been used to select feasible alternatives. Additionally, five voting methods in Social Choice Theory (SCT) are launched to aggregate preferences and obtain a "win" alternative. Apply this model to the 2030 water allocation planning project of Ezhou City, China, as a case study. Under the proposed rule, Adjust minimal overlap rule (AMO), five regions, Urban Area, Gedian DZ, and three counties, hold the water deficit rate of 5.9%, 15.8%, and 4.7%-6.1%, respectively. In aggregating preferences by voting, AMO wins four out of five methods and takes second place in the last one, which provides some insights for allocating water fairly and feasibly. [ABSTRACT FROM AUTHOR]

The prediction of two-dimensional molecular self-assembly structures has always been a problem to be solved. The molecules with meta-dicarboxyl groups can self-assemble into a specific hexagonal cavity, which has an important influence on the prediction of molecular self-assembly structures and the application of functional molecules with meta-dicarboxyl groups. Two kinds of molecules with four pairs of meta-dicarboxyl groups, 1,3,6,8-tetrakis(3,5-isophthalic acid)pyrene (H8TIAPy) and 4′,4′″,4″″′,4″″″′-(ethene-1,1,2,2-tetrayl)tetrakis(([1,1′-biphenyl]-3,5-dicarboxylic acid)) (H8ETTB) molecules were chosen to observe the self-assembly behavior at the heptanoic acid/highly oriented pyrolytic graphite (HA/HOPG) interface. H8TIAPy molecules self-assembled into well-ordered quadrilateral structures and could be regulated into kagomé networks with hexagonal pores by coronene (COR) molecules. H8ETTB molecules self-assembled into lamellar structures and transformed into acid-COR-acid-COR co-assembled structures at low concentration of COR solution and acid-COR dimer-acid-COR dimer co-assembled structures at high concentration of COR solution. The reason that H8ETTB molecules could not be regulated into hexagonal porous architecture was attributed to the steric hindrance by the similar length and width of H8ETTB molecules. The H8ETTB templates had stronger adsorption for COR than that of hexaphenylbenzene (HPB), regardless of the order of molecular introduction. [ABSTRACT FROM AUTHOR]

The overall goal of this study was to examine the relationship between parenting practices and cognitive development among preschool-aged children in poor rural China. We drew on data from a large-scale panel dataset of 1,802 children and their caregivers in rural China. The cognitive development of children was measured at 22–30 months and then again at 49–65 months by the Bayley Scales of Infant Development-First Edition (BSID-I) and the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV), respectively. The results showed that the prevalence of cognitive delay was 38% when children were older. Our findings also revealed that only a small proportion of caregivers engaged in different types of positive stimulating activities (7–24%), while the prevalence of different types of negative parenting practices ranged from 19% to 32%, when the children were 49–65 months old. We found that positive parenting practices were significantly positively associated with the Full-Scale Intelligence Quotient and Primary Indexes, whereas negative parenting practices were significantly negatively associated with these indicators (p < 0.01). When examining child characteristics, the data showed that gender and whether the child attended preschool were significantly associated with positive parenting practices. There is an urgent need to develop initiatives that can improve the children's cognitive developments from rural China. It is necessary to address the economic and knowledge constraints that prevent rural caregivers from engaging in positive parenting practices by providing financial support to caregivers and developing a public platform that provides parenting information. Highlights: In total, 7% to 24% of caregivers engaged in positive stimulating activities. In contrast, 19% to 32% of caregivers engaged in negative parenting practices. Positive parenting practices were positively associated with children's cognition. Negative parenting practices were negatively associated with children's cognition. Subsample analysis on whether the child was cognitively delayed before preschool age showed consistent results. [ABSTRACT FROM AUTHOR]

Adenovirus, respiratory syncytial virus, and influenza virus are common causes of respiratory infections. The COVID-19 pandemic had a significant impact on their prevalence. The aim of this study was to analyze the epidemic changes of common respiratory viruses in the Affiliated Hospital of Hangzhou Normal University in Hangzhou, China, from October of 2017 to February of 2021. We collected statistics from 121,529 patients in the outpatient and inpatient departments of the hospital who had throat or nose swabs collected for testing for four virus antigens by the colloidal gold method. Of these, 13,200 (10.86%) were positive for influenza A virus, 8,402 (6.91%) were positive for influenza B virus, 6,056 (4.98%) were positive for adenovirus, and 4,739 (3.90%) were positive for respiratory syncytial virus. The positivity rates of the influenza A virus (0-14 years old, P = 0.376; over 14 years old, P = 0.197) and respiratory syncytial virus (0-14 years old, P = 0.763; over 14 years old, P = 0.465) did not differ significantly by gender. After January of 2020, influenza virus infection decreased significantly. The positivity rate of respiratory syncytial virus remained high, and its epidemic season was similar to before. Strict respiratory protection and regulation of crowd activities have a great impact on the epidemic characteristics of viruses. After major changes in the public health environment, virus epidemics and their mutations should be monitored closely, extensively, and continuously. [ABSTRACT FROM AUTHOR]

Background: Jujube (Ziziphus jujuba Mill.) fruit is one of the largest productions in China and its increasing production has drawn considerable attention from researchers. Polysaccharide is one of the most abundant components of jujube, and it represents a major group of biolotegically active constituents. This study intended to investigate the special structure of a homogeneous acidic polysaccharide (PZMP4) produced from Ziziphus Jujuba cv. Muzao fruit using novel methods, including DEAE-Sepharose Fast Flow and Sephacryl S-300 column chromatography. Results: The structure of PZMP4 was determined via high-performance gel permeation chromatography (HPGPC), gas chromatography (GC), Fourier transform infrared spectroscopy (FT-IR), methylation analysis, nuclear magnetic resonance spectroscopy (NMR), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The results reveal that PZMP4 with a molecular weight of 27.90 kDa was composed of rhamnose, arabinose, mannose, glucose, galactose, and galacturonic acid at a ratio of 2.32:2.21:0.22:0.88:2.08:8.83. Advanced structural analysis revealed a netted structure with molecular aggregates of PZMP4. Structural features demonstrated that the basic backbone of PZMP4 appeared to mainly consist of (1→4)-linked GalpA with three branches bonded to O-3 of (1→3)-linked Araf, (1→2)-linked Rhap, and terminated with GalpA. Conclusions: PZMP4's unique structure could imply distinct bioactivities and have considerable utilization in functional food. Highlights: Structural characteristics of PZMP4 were analyzed by HPGPC, GC, FT-IR, GC-MS, NMR, SEM and AFM. PZMP4 mainly consisted of (1→4)-linked GalpA with three branches boned to O-3. The branches included (1→3)-linked Araf, (1→2)-linked Rhap, and terminated with GalpA. [ABSTRACT FROM AUTHOR]

Bipolar disorder type II (BD-II) is linked to an increased suicidal risk. Since a prior suicide attempt (SA) is the single most important risk factor for sequent suicide, the elucidation of involved neural substrates is critical for its prevention. Therefore, we examined the spontaneous brain activity and its temporal variabilities in suicide attempters with bipolar II during a major depressive episode. In this cross-sectional study, 101 patients with BD-II, including 44 suicidal attempters and 57 non-attempters, and 60 non-psychiatric controls underwent a resting-state functional magnetic resonance imaging (fMRI). Participants were assessed with Hamilton Rating Scale for Depression (HAMD) and Nurses, Global Assessment of Suicide Risk (NGASR). The dynamics of low-frequency fluctuation (dALFF) was measured using sliding-window analysis and its correlation with suicidal risk was conducted using Pearson correlation. Compared to non-attempters, suicidal attempters showed an increase in brain activity and temporal dynamics in the anterior cingulate cortex (ACC). In addition, the temporal variabilities of ACC activity positively correlated with suicidal risk (R = 0.45, p = 0.004), while static ACC activity failed to (R = 0.08, p > 0.05). Our findings showed that an aberrant static ALFF and temporal variability could affect suicidal behavior in BD-II patients. However, temporal variability of neuronal activity was more sensitive than static amplitude in reflecting diathesis for suicide in BD-II. Dynamics of brain activity could be considered in developing neuromarkers for suicide prevention. [ABSTRACT FROM AUTHOR]

A Parallel and Compact version of the Sine Cosine Algorithm (PCSCA) is proposed in this article. Parallel method can effectively improve search ability and increase the diversity of solutions. We develop three communication strategies based on parallelism idea to serve different types of optimization function to achieve the best performance. Furthermore, compact method uses statistical distribution to represent the solutions, which can save memory space and energy of the digital device. To check the optimization effect of the proposed PCSCA algorithm, it is tested on the CEC2013 benchmark function set and compared to SCA, parallel compact Cuckoo Search (PCCS) algorithms. The empirical study demonstrates that PCSCA has improved by 50.1% and 5.6%, compared to SCA and PCCS, respectively. Finally, we apply PCSCA to optimize the position accuracy of sensor node deployed in 3D actual terrain. Experimental results show that PCSCA can achieve lower localization error via Time Difference of Arrival method. [ABSTRACT FROM AUTHOR]

Fatty acid methyl esters (FAMEs) were produced by the esterification of free fatty acids (FFA) with methanol, and sulfuric acid as the catalyst in a rotor-stator spinning disc reactor (RSSDR). The RSSDR, which shows excellent mixing efficiency and fast phase separation, was used as a novel continuous-flow esterification reactor. The influence of the variables (e.g., rotational speed, volume flow rate, rotor-stator distance, methanol-FFA molar ratio, catalyst dosage, and temperature) on esterification conversion (η) and productivity of FAMEs (PFAME) were investigated. It was found that the experimental parameters have a great impact on the η and PFAME in the RSSDR system, due to the effect of micromixing intensity and residence time distribution. Furthermore, to compare with other traditional esterification reactors, the values of η, PFAME, and PFAME per unit reactor volume (PFAME/VR) in the RSSDR were also employed to assess the performance for the production of FAMEs. It shows that the maximum values of PFAME, and PFAME/VR attained were 0.14 mol/min and 3.06×10−2 mol/(mL min), respectively. Therefore, the RSSDR is proven to be an effective esterification reactor with high esterification conversion in comparison to conventional esterification reactors. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks are well-aligned nanoporous crystals which can be applied to biomedical field, thanks to the large superficial area, ordered pores array, and biocompatible metallic ion composition. In this work, we fabricated a novel Nd3+ ion-doped ZIF-8 since there are some reports showing that Nd3+ has anti-carcinogenic properties and can be used for therapeutic application in aberrant angiogenesis recently. Therefore, we attempted to use electrochemical anodic oxidation and electrochemical in situ deposition techniques to produce coating which contains Nd3+ on Ti implant. And then we detected the biotoxicity, antibacterial function, and corrosion resistance of this new coating so as to facilitate further research on Nd3+ ion implantation in vivo. SEM and TEM were applied to observe the surface morphology. N2 adsorption–desorption was used to investigate the specific surface area and pore structure. The XRD and XPS were carried out to investigate the compound surface including the chemical composition and element-bonding configurations. The corrosion resistance properties of the samples were tested by electrochemical method. ICP was conducted to investigate the release behavior. [ABSTRACT FROM AUTHOR]

In this paper, a novel medical image fusion method based on L0 Gradient Minimization for CT and MRI is proposed. Compared with traditional algorithms, the proposed method performs well in preserving bones structures from CT and sustaining the soft tissue detail from MRI. It's worth mentioning that both the proposed low- and high-frequency fusion rules have the capability of generating appropriate weight maps according to the characteristics of CT and MRI images. The fusion algorithm using L0 Gradient Minimization mainly comprises of four steps: First, source images are decomposed into multi-scale representations via L0 Gradient Minimization. Second, we propose a low-frequency fusion rule based on local energy and Gaussian filters, which can generate the fused base layer in accord with the basic principle of human beings' visual system. Third, high-frequency sub-bands are fused by utilizing saliency detection rule based on texture extraction, which generates the satisfying maps according to the degree of significance. Finally, we get the fused result according to the image reconstruction. The proposed algorithm is compared with nine advanced fusion methods and shows superior performance in whether subjective or objective evaluations. [ABSTRACT FROM AUTHOR]

Laser powder bed fusion is a key technology of additive manufacturing that enables the fabrication of metal parts with complex geometry through a multilayer process. Despite its great promise in design flexibility, wide application of this technology is hindered by a lack of quality assurance in fabrication parts. Melt-pool morphological characteristics are eminent indicators for manufacturing process stability and part quality. However, existing studies on melt-pool morphology focused on key geometric properties (e.g., length, width, size) extracted from melt-pool images for characterizing its variations, and tend to overlook 3D morphological variations of melt pools and ejected spatters. In this paper, we develop a multiscale modeling framework to represent, characterize, and monitor melt-pool variations through 3D morphological features, including multiscale basis function modeling of 3D melt-pool morphology and an iterative search of predominant components for sparse representation of morphological variations in melt-pool images. A case study with real-world experimental data shows that the proposed framework effectively characterizes 3D melt-pool morphological variations and provides salient features for tracking process variations, predicting melt-pool sizes, and detecting spatters. This framework is generally flexible for a wide variety of additive manufacturing (AM)applications such as melt-pool simulation, process monitoring, and anomaly detection. [ABSTRACT FROM AUTHOR]

Atmospheric CO2 is one of key parameters to estimate air-sea CO2 flux. The Orbiting Carbon Observatory-2 (OCO-2) satellite has observed the column-averaged dry-air mole fractions of global atmospheric carbon dioxide (XCO2) since 2014. In this study, the OCO-2 XCO2 products were compared between in-situ data from the Total Carbon Column Network (TCCON) and Global Monitoring Division (GMD), and modeling data from CarbonTracker2019 over global ocean and land. Results showed that the OCO-2 XCO2 data are consistent with the TCCON and GMD in situ XCO2 data, with mean absolute biases of 0.25×10−6 and 0.67×10−6, respectively. Moreover, the OCO-2 XCO2 data are also consistent with the CarbonTracker2019 modeling XCO2 data, with mean absolute biases of 0.78×10−6 over ocean and 1.02×10−6 over land. The results indicated the high accuracy of the OCO-2 XCO2 product over global ocean which could be applied to estimate the air-sea CO2 flux. [ABSTRACT FROM AUTHOR]

The understanding of centennial trends of extreme temperature has been impeded due to the lack of early-year observations. In this paper, we collect and digitize the daily temperature data set of Northeast China Yingkou meteorological station since 1904. After quality control and homogenization, we analyze the changes of mean and extreme temperature in the past 114 years. The results show that mean temperature (Tmean), maximum temperature (Tmax), and minimum temperature (Tmin) all have increasing trends during 1904–2017. The increase of Tmin is the most obvious with the rate of 0.34 °C/decade. The most significant warming occurs in spring and winter with the rate of Tmean reaching 0.32 °C/decade and 0.31 °C/decade, respectively. Most of the extreme temperature indices as defined using absolute and relative thresholds of Tmax and Tmin also show significant changes, with cold events witnessing a more significant downward trend. The change is similar to that reported for global land and China for the past six decades. It is also found that the extreme highest temperature (1958) and lowest temperature (1920) records all occurred in the first half of the whole period, and the change of extreme temperature indices before 1950 is different from that of the recent decades, in particular for diurnal temperature range (DTR), which shows an opposite trend in the two time periods. [ABSTRACT FROM AUTHOR]

Improving the performance of forward osmosis (FO) membranes has always been moving forward. Here we fabricate the novel Turing structures in the active layer (AL) of thin film composite (TFC) membrane through effectively introducing the polyvinylpyrrolidone (PVP) macromolecule with hydrophilicity both in the support layer (SL) and AL. The addition of PVP facilitates the formation of sponge-like pores in the SL and stripe-like Turing structures in the AL. The influence of PVP on the morphology and performance of the membranes was investigated by SEM, AFM, XPS, NMR, FTIR. Compared with the water flux (Jw) of the original composite membrane (approximately 25 L m−2 h−1), TFC-PVP (3:1) membrane with Turing structure achieved better performance (approximately 75 L m−2 h−1), and the reverse solute flux/water flux (Js/Jw) value was as low as 0.02 g/L. This study demonstrated that the Turing structures have a favorable effect on the performance of FO membrane and a promisingly practical application in water treatment. [ABSTRACT FROM AUTHOR]

Cysteine (Cys) takes part in redox balance in cells as an antioxidant, and imbalance of Cys content in the body can cause a variety of diseases. It is very important to develop a new fluorescent chemosensor to specifically detect Cys intracellular. In this work, a novel NIR fluorescent probe was constructed based on 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indol-3-ium iodide and 5-(4-hydroxyphenyl)furan-2-carbaldehyde. The probe could selectively detect Cys in the presence of homocysteine (Hcy), glutathione (GSH), and other interferences. It also had a number of advantages, including nucleolus-targeting ability, long fluorescence emission wavelength (685 nm), low detection limit (56 nM), and large Stokes shift (172 nm). The probe was employed to enable visualization of Cys in HepG2 cells, and due to its good response in viscous environment, the probe could also locate nucleoli intracellular. [ABSTRACT FROM AUTHOR]

PI fiber insulation paper has excellent insulation and heat resistance, which can replace traditional insulation paper to provide a new high-performance material. In this paper, we adopt a two-step method to synthesize PI, that is, firstly synthesize polyamic acid, and then perform electrospinning and thermal imidization to prepare PI porous fiber membrane. The test results show that the breakdown field strength of the PI porous film is 50 kV/mm. Further research shows that the insulation structure has the characteristics of continuous multiple breakdown. When the fiber film is repeatedly broken down to 25 times at the same point, the field strength of each breakdown of the fiber film changes between 40 and 55 kV/mm, and the average breakdown field strength is 53 kV/mm. Nano-Al2O3 was introduced into the fiber membrane by in situ polymerization. The breakdown field strength of the composite fiber film can reach 74.89 kV/mm after doping 2 wt% nano-Al2O3, which is higher than that of the pure film. At the same time, this kind of fiber paper also has repeatable breakdown characteristics, and the breakdown voltage distribution width of multiple breakdown is reduced. This characteristic provides the maintenance free characteristic of DC over-voltage for the insulation structure composed of this fiber paper, and can improve the service life of transformer under DC over-voltage such as lightning stroke. [ABSTRACT FROM AUTHOR]

It is an effective way to improve the toughness, dielectrical property, and electrical property of epoxy vinyl ester resin (VE) via embedding hyperbranched polymer. In the present study, a new kind of flexible chain blocking hyperbranched polyester (HBP) with the rich unsaturated double bond has been designed and synthesized. The hyperbranched structure of HBP was characterized by NMR and FT-IR. Based on dielectric property test, it could be found that HBP could reduce dielectric constant (ε) of VE compound, and the interaction between the polar functional groups in the flexible chain and epoxy resin could reduce dielectric loss (tgδ) within a certain frequency. The results of mechanical measurement showed that the addition of HBP could improve the mechanical properties of the resin systems. When HBP content was 20 wt%, the impact strength of modified epoxy anhydride curing compound reached 18.9 kJ/mm−2, and the bending strength of modified epoxy anhydride curing compound reached 134.0 MPa. [ABSTRACT FROM AUTHOR]