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Abstract Background Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-negative BCP-ALL) accounts for a significant portion of adult cases. Blinatumomab, a bispecific T-cell engager, has shown efficacy in relapsed or refractory BCP-ALL, but its role in induction therapy with reduced-dose chemotherapy is being explored. Methods In this retrospective study, 35 newly diagnosed Ph-negative BCP-ALL patients received reduced-dose chemotherapy followed by two weeks of blinatumomab (RDC-Blinatumomab-2W) as part of our previous clinical trial. These patients were compared with a propensity score-matched historical control group of 35 patients treated with the hyper-CVAD regimen. The primary endpoint was composite complete remission (CRc); secondary endpoints included minimal residual disease (MRD) negativity, adverse events, and survival outcomes. Results After matching, both groups had 17 patients (49%) with poor-risk genetic aberrations. The RDC-Blinatumomab-2W group achieved higher CRc rates compared to controls (94% vs. 63%, p = 0.0074) and greater MRD negativity (86% vs. 43%, p = 0.0015). They experienced fewer Grade 3–4 thrombocytopenia cases (62% vs. 89%, p = 0.012), fewer serious infections (23% vs. 54%, p = 0.019), and higher 1-year overall survival rates (97.1% vs. 58.9%, p

Abstract Objective Exploring the temporal bone Computed Tomography (CT) features and clinical characteristics of patients with ethmoid sinus lesions (ESL) combined with high jugular bulb (HJB) and pulsatile tinnitus symptoms. Methods A retrospective analysis was conducted on the clinical data of pulsatile tinnitus (PT) patients. Patients with both ESL and HJB were classified into the combined group, while others were assigned to the non-combined group. The severity of tinnitus was assessed using the Tinnitus Evaluation Questionnaire (TEQ), along with the comparison of the clinical characteristics and treatment outcomes. Meanwhile, univariate analysis and multivariate regression analysis were performed to identify factors affecting the prognosis of patients. Results Among patients with hearing loss in the combined group, the severity of hearing impairment was primarily moderate (65.85%), while that in the non-combined group was mainly mild (49.61%), with differences between the two groups (P

Abstract Background Pseudorabies (PR) caused by the re-emerging of pseudorabies virus (PRV) variant has outbroken among PRV vaccine immunized swine in many pig farms, which has caused serious social and economic consequences since the end of 2011. The PRV UL49.5 protein can inactivate the transporter associated with antigen processing (TAP), thereby downregulating the cell surface expression of swine leukocyte antigen class I (SLA-I) to evade host immune surveillance. Methods In this study, based on the PRV ΔgE/TK strain, PRV ΔgE/TK/UL49.5 triple gene deletion strain was constructed through homologous recombination and deletion of the PRV UL49.5 gene by the Cre-LoxP system. Its growth curve and effect on SLA-I transcription level were determined. Preliminary studies were carried out on serum neutralizing antibody levels, IFN-γ and IL-4 cytokines levels in mice immunized with PRV ΔgE/TK/UL49.5, and the viral load and challenge protection in mice tissues after challenge. Results The growth characteristics of PRV ΔgE/TK/UL49.5 strain were similar to those of PRV ΔgE/TK strain. The level of SLA-I was returned to normal after the deletion of PRV UL49.5 gene. The immunization of PRV ΔgE/TK/UL49.5 did not affect the weight gain of mice. Immunized mice could induce high levels of serum neutralization antibodies and immune cytokines, including IFN-γ and IL-4, which could provide complete protection against virulent PRV challenge. No obvious pathological damage was observed in lung, brain and trigeminal ganglion of mice immunized with PRV ΔgE/TK/UL49.5, and the tissue viral load was the lowest. Conclusions PRV ΔgE/TK/UL49.5 strain can induce enhanced immunogenicity and had the potential to be used as a candidate strain.

Solving the stereo camera synchronization problem or estimating the temporal offset for dynamic scenes in triangulation is crucial in computer vision and photogrammetry. However, for cheap cameras like webcams, or cameras with long distance, synchronization is costly and complex. This paper proposed a novel method to determine 3D position for dynamic scenes with unsynchronized image sequences. For the proposed method, synchronized cameras are not essential, also, the temporal offset is not essential to be known. Additionally, it can be used for linear and curve motion, which provides a wider range of applications. In linear motion, the traditional triangulation is abandoned in this paper. Two planes can be determined with unsynchronized image sequences captured by two cameras and the intersection of the two planes is the motion trajectory. Also, one plane can be determined with unsynchronized image sequences captured by one camera, one ray can be determined with 2D projection captured by another camera, and the intersection of the plane and ray represents the current position. In curve motion, the correspondence points can be determined with epipolar line and 2D trajectory determined by unsynchronized image sequences, then the current 3D position is estimated by triangulation. This means using two completely independent cameras to capture dynamic scenes, our method can achieve determination under only ‘see’ and has nothing to do with other conditions (e.g., synchronization, frame rate). Compared to several SOTA (state-of-the-art) solvers, the experimental results show our proposed method performs robustly and high precisely.

Abstract Recent progress has demonstrated that synthetic gauge fields can mimic Landau quantization in materials including graphene and lattices for sound and light. However, despite using graphene-like structures with strain-induced textures in prior photonics, it is hard to capture the experimental attainment of distinct photon bound states for various Landau levels. In this work, we introduce an experimental framework for achieving photonic Landau quantization. We present the quantized distribution of photonic states across different Landau levels in a two-dimensional Kagome metal lattice. By introducing inhomogeneous coupling, we implement two kinds of pseudomagnetic field, which quantize spectrums and quantizes distribution of photonic states, respectively. We experimentally observe that the electric field distribution is localized according to the positional attributes of different Landau levels. Our proposed system is more straightforward to implement, and it opens an avenue to explore photonic states at non-zero Landau levels, which are predicted to demonstrate some interesting physical phenomena.

In this paper, Sedum simingshanense sp. nov. is described as a new species based on morphological and molecular analyses, and its taxonomic relationships are discussed. Morphological analysis indicates S. simingshanense should be classified in the genus Sedum sect. Sedum and is distinct from the related species S. xunvense and S. formosanum in the morphology of its solitary, light green and smooth stems, flattened leaves, larger, obovate and spurless sepals, yellow anthers, 22–30 ovules per carpel, oblique follicles, and its habitat on shaded slopes or rocks. Phylogenetic analysis of sequences of the nuclear ribosomal internal transcribed spacer (ITS) also demonstrates that S. simingshanense has a highest similarity of only 97.22% with any known species and S. formosanum is the closest extant relative of the new species.

Abstract Background Multi-lineage differentiation of mesenchymal adult stem cells (m-ASCs) is crucial for tissue regeneration and accompanied with metabolism reprogramming, among which dental-pulp-derived m-ASCs has obvious advantage of easy accessibility. Stem cell fate determination and differentiation are closely related to metabolism status in cell microenvironment, which could actively interact with epigenetic modification. In recent years, glutamine-α-ketoglutarate (αKG) axis was proved to be related to aging, tumorigenesis, osteogenesis etc., while its role in m-ASCs still lack adequate research evidence. Methods We employed metabolomic analysis to explore the change pattern of metabolites during dental-pulp-derived m-ASCs differentiation. A murine incisor clipping model was established to investigate the influence of αKG on dental tissue repairment. shRNA technique was used to knockdown the expression of related key enzyme-dehydrogenase 1(GLUD1). RNA-seq, m6A evaluation and MeRIP-qPCR were used to dig into the underlying epigenetic mechanism. Results Here we found that the glutamine-αKG axis displayed an increased tendency along with the osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, same as expression pattern of GLUD1. Further, the key metabolite αKG was found able to accelerate the repairment of clipped mice incisor and promote dentin formation. Exogenous DM-αKG was proved able to promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, while the inhibition of glutamine-derived αKG level via GLUD1 knockdown had the opposite effect. Under the circumstance of GLUD1 knockdown, extracellular matrix (ECM) function and PI3k-Akt signaling pathway was screened out to be widely involved in the process with insulin-like growth factor 2 (IGF2) participation via RNA-seq. Inhibition of glutamine-αKG axis may affect IGF2 translation efficiency via m6A methylation and can be significantly rescued by αKG supplementation. Conclusion Our findings indicate that glutamine-αKG axis may epigenetically promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs and dentin regeneration, which provide a new research vision of potential dental tissue repairment therapy method or metabolite-based drug research.

Abstract Blockchain, as an emerging technology, has found diverse applications in solving trust issues in multi‐party cooperation. The field of Unmanned Aerial Vehicle (UAV) swarm networks is no exception, as UAVs are susceptible to attacks from malicious counterparts due to limited computing and storage resources. In this paper, the authors present an adaptive networking mechanism for UAVs based on blockchain technology, which incorporates three key technologies. Utilizing Global Unique Identifier (GUID) and block storage, UAVs can achieve rapid identity authentication and efficient swarm switching. By evaluating node participation in block consensus, malicious nodes within the UAV swarm can be accurately identified. Additionally, routing learning based on node security attributes and link quality ensures secure and efficient data transmission. Simulation test results demonstrate the practicality and applicability of the proposed blockchain‐based adaptive networking mechanism for UAV swarm networks.

Abstract Background Amphetamine-type stimulant (ATS) abuse is strongly associated with an elevated risk of HIV infection and transmission. Antiretroviral therapy (ART) serves as the primary approach for managing HIV infection and AIDS progression. However, ATS abuse diminishes the efficacy of ART in HIV/AIDS patients, amplifying the vulnerability to immunological non-response (INR) and ultimately increasing the incidence rate and mortality of opportunistic infections. Currently, no effective interventions targeting INR exist. Acupuncture has demonstrated promise in bidirectionally modulating the body’s immune response and may be beneficial for INR in HIV/AIDS combined with ATS abuse. Nevertheless, further research and comprehensive evaluation are imperative to substantiate these findings. Methods This study is a two-center, randomized, non-acupoint controlled, single-blind clinical trial. It will be conducted in two large drug rehabilitation centers in western China, involving 114 INR patients receiving ART. The participants will be randomly assigned to either the Transcutaneous Electrical Acupoint Stimulation (TEAS) + ART group or the sham-TEAS + ART group, in a 1:1 ratio. Both groups will receive a 48-week treatment. The primary outcome measure assessed after treatment is the CD4 + T cell count. Secondary outcome measures include the immune reconstitution efficiency of HIV patients, CD4/CD8 ratio, CD4 + CD45RA + and CD4 + CD45RO + counts, CD4 + CD28 + counts, CD4 + CD38 + and CD8 + CD38 + counts, CD4 + ki67 + and CD8 + ki67 + counts, JC mitochondrial membrane potential testing, the incidence of opportunistic infections, and the HIV/AIDS PRO scale. Adverse events occurring during the study observation period will be documented. Discussion This study will investigate the effect of TEAS on immune reconstitution in patients with amphetamine abuse and HIV infection. Trial registration Chinese Clinical Trial Registry, ChiCTR 2300076363. Registered on October 7, 2023, https://www.chictr.org.cn/ .

Abstract Background Digital leadership might be an innovative approach to decreasing the elevated rates of anxiety and depression symptoms among medical professionals, while also enhancing their psychological well-being. This emerging pathway may offer promising strategies to support the mental health of medical professionals. This study seeks to investigate the association among digital leadership, organizational identity, family-work conflict, and anxiety and depression symptoms, and further to uncover the underlying moderating mechanisms interplay. Methods A cross-sectional online survey with 657 valid data were collected from four tertiary hospitals in Harbin, Heilongjiang Province, China, with a response rate of 69.3%. The statistical analysis was conducted employing IBM SPSS Statistics 22.0. Hierarchical regression analysis was performed to scrutinize the pertinent factors associated with anxiety and depression symptoms among medical professionals, while also evaluating the moderating influence of organizational identity and family-work conflict on the nexus among those. Results The prevalence of anxiety and depression symptoms among medical professionals was 50.1%. Anxiety and depression symptoms were negatively correlated with digital leadership (r= -0.278, p

Abstract Catalytic upcycling of polyethylene terephthalate (PET) into high-value oxygenated products is a fascinating process, yet it remains challenging. Here, we present a one-step tandem strategy to realize the thermal catalytic oxidation upcycling of PET to terephthalic acid (TPA) and high-value glycolic acid (GA) instead of ethylene glycol (EG). By using the Au/NiO with rich oxygen vacancies as catalyst, we successfully accelerate the hydrolysis of PET, accompanied by obtaining 99% TPA yield and 87.6% GA yield. The results reveal that the oxygen vacancies in NiO (NiO-Ov) support tend to adsorb hydrolysis product TPA, preferentially ensuring the strong adsorption of EG at the Au-NiO interface. Moreover, during the EG oxidation process, the Au-NiO interface, composed of two types of structures, quasi “AuNi alloy” and NiO-Ov, simultaneously promote the C-H bond activation, where Ni in “AuNi alloy” exhibits an oxytropism effect to anchor the C = O bond of the intermediate, while the residual O in NiO-Ov pillages the H in the C-H bond. Such Au/NiO catalyst is further extended to promote the thermal catalytic oxidation upcycling of other polyethylene glycol esters to GA with excellent catalytic performance.

Abstract Piezoelectricity, a fundamental property of perovskite ferroelectrics, endows the materials at the heart of electromechanical systems spanning from macro to micro/nano scales. Defect engineering strategies, particularly involving heterovalent trace impurities and derived vacancies, hold great potential for adjusting piezoelectric performance. Despite the prevalent use of defect engineering for modification, a comprehensive understanding of the specific features that positively impact material properties is still lacking, this knowledge gap impedes the advancement of a universally applicable defect selection and design strategy. In this work, we select perovskite KTa1−x Nb x O3 single crystals with orthorhombic phase as the matrix and introduce Fe and Mn elements, which are commonly used in “hard” ferroelectrics as dopants. We investigate how transition-metal doping modifies piezoelectric properties from the perspective of intrinsic polarization behaviors. Interestingly, despite both being doped into the B-site as an acceptor, Mn doping enhances the local structural heterogeneity, greatly bolstering the piezoelectric coefficient beyond 1000 pC/N, whereas Fe doping tends to stabilize the polarization, leading to a substantial improvement in the mechanical quality factor up to 700. This work deciphers the diverse impacts of transition metal impurities on regulating polarization structures and modifying piezoelectric properties, providing a good paradigm for strategically designing perovskite ferroelectrics.

The ProteinPaint Hi-C tool (ppHiC) facilitates web-based visualization and collaborative exploration of Hi-C data, a vital resource for understanding three-dimensional genomic structures. ppHiC allows researchers to easily analyze large Hi-C datasets on a web browser without requiring the computational expertise that has heretofore limited access to this complex genomic data. The platform is compatible with multiple Hi-C data versions and boasts a highly customizable interface, including a configuration panel for the precise adjustment of key visualization parameters. The tool’s interactive features offer a broad range of views, from whole-genome landscapes to detailed interactions between pairs of loci, that are accessible within a single, integrated environment. Here, we demonstrate how using ppHiC to visualize an altered chromatin conformational landscape in neuroblastoma can inform understanding of the genomic rearrangements in this cancer.

Abstract Background Pentraxin 3 (PTX3) has been associated with the development and progression of various malignant tumors. However, its roles and the mechanisms underlying its involvement in ovarian cancer (OC) peritoneal metastasis remain unclear. Methods Single-cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC) were conducted to determine the expression profiles, potential functionalities, and underlying mechanisms of PTX3 within the context of OC. To assess the proliferative response of OC cells, we utilized both EdU (5-ethynyl-2’ -deoxyuridine) and CCK8 assays. The role of PTX3 in facilitating cell migration and invasion was quantified through the use of Transwell assays. The protein expression levels were meticulously analyzed via Western blotting. Furthermore, to explore the interactions between proteins, we conducted immunofluorescence (IF) staining and co-immunoprecipitation (Co-IP) experiments. To determine the factors responsible for the upregulation of PTX3, we performed both coculture and suspension assays, providing a comprehensive approach to understanding the regulatory mechanisms involved. Results This study confirmed, for the first time, that the expression of PTX3 in OC metastatic lesions is greater than that in primary lesions and that tumor cells with high PTX3 expression have greater metastatic ability. PTX3 can activate the EMT and NF-κB signaling pathways in OC cells and can interact with the TLR4 and CD44 receptors in OC cells. Additionally, PTX3’s modulation of the EMT and NF-κB pathways is partially dependent on its interaction with TLR4. Furthermore, this study revealed the intercellular regulatory network related to PTX3 in OC cells via bioinformatic analysis. High levels of PTX3 in OC cells potentially enhance the attraction of dendritic cells (DCs) and CD4 + T cells while diminishing the recruitment of B cells and CD8 + T cells. Finally, this study indicated that PTX3 upregulation was driven by multiple factors, including specific transcription factors (TFs) and modifications within the tumor microenvironment (TME). Conclusions Our research revealed the contribution of PTX3 to the peritoneal dissemination process in OC patients, identifying a novel potential biomarker and therapeutic target for this disease.

Background and objective Metabolic change is one of the important characteristics of radiation pneumonitis. Radiotherapy, as a conventional method for the treatment of thoracic tumors, can not only effectively kill tumor cells, but also cause adverse reactions such as local inflammation and fibrosis, which leads to limited therapeutic effect and profound impact on the quality of life of patients. Therefore, it is of great significance to explore the metabolic changes caused by radiotherapy. The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line (murine lung epithelial-12, MLE12). Methods MLE12 cells were’ cultured in vitro and randomly divided into radiation group (IR) and control group (NC). Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator. Cell supernatant samples were collected at 48 h after irradiation. Metabolomic analysis of the samples was performed by liquid chromatograph mass spectrometer (LC/MS). Results LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation. A total of 38 secretory metabolites were altered in the IR group compared with the NC group. According to the annotation of Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the differential metabolites are mainly involved in nucleotide metabolism, amino acid metabolism and lipid metabolism, among which the difference in nucleotide metabolism is the most significant. Conclusion The metabolism of MLE12 cells was significantly affected by X-ray irradiation, mainly affecting the nucleotide metabolic pathways, including purine and pyrimidine metabolites and related metabolic pathways.

In our ongoing research on bambusicolous Xylariomycetidae fungi, three new microfungi taxa were collected and identified as members of the genera Amphibambusa, Arecophila, and Nigropunctata. Amphibambusa aureae sp. nov., Arecophila gaofengensis sp. nov., and Nigropunctata xiaohensis sp. nov. are introduced based on morphological comparisons and phylogenetic analyses using combined ITS, LSU, tub2, and tef1α loci. Comprehensive morphological descriptions, illustrations, and a phylogenetic tree showcasing the placement of these new taxa are provided. Additionally, keys to Amphibambusa and Nigropunctata are provided.

Abstract Multiple myeloma (MM) is a common hematological malignancy, and its prognostic factors have been extensively studied. Progression of disease within 24 months (POD24) suggests a poor prognosis in many malignancies, but is rarely mentioned in MM. This study aimed to investigate the prognostic value of POD24 in MM and risk factors of POD24, and to evaluate the predictive value of existing MM prognostic models for POD24. The research retrospectively analyzed the clinical data of MM patients and found that the occurrence of POD24 is an independent prognostic factor affecting overall survival in MM, while non-transplantion and genetic abnormality are independent risk factors for the occurrence of POD24. The existing prognostic models are not effective in predicting POD24. Therefore, it’s still necessary to explore a prognostic model that can predict POD24 more accurately.

Abstract Background The urgent need for affordable and rapid detection methodologies for foodborne pathogens, particularly Escherichia coli (E. coli), highlights the importance of developing efficient and widely accessible diagnostic systems. Dark field microscopy, although effective, requires specific isolation of the target bacteria which can be hindered by the high cost of producing specialized antibodies. Alternatively, M13 bacteriophage, which naturally targets E. coli, offers a cost-efficient option with well-established techniques for its display and modification. Nevertheless, its filamentous structure with a large length-diameter ratio contributes to nonspecific binding and low separation efficiency, posing significant challenges. Consequently, refining M13 phage methodologies and their integration with advanced microscopy techniques stands as a critical pathway to improve detection specificity and efficiency in food safety diagnostics. Methods We employed a dual-plasmid strategy to generate a truncated M13 phage (tM13). This engineered tM13 incorporates two key genetic modifications: a partial mutation at the N-terminus of pIII and biotinylation at the hydrophobic end of pVIII. These alterations enable efficient attachment of tM13 to diverse E. coli strains, facilitating rapid magnetic separation. For detection, we additionally implemented a convolutional neural network (CNN)-based algorithm for precise identification and quantification of bacterial cells using dark field microscopy. Results The results obtained from spike-in and clinical sample analyses demonstrated the accuracy, high sensitivity (with a detection limit of 10 CFU/μL), and time-saving nature (30 min) of our tM13-based immunomagnetic enrichment approach combined with AI-enabled analytics, thereby supporting its potential to facilitate the identification of diverse E. coli strains in complex samples. Conclusion The study established a rapid and accurate detection strategy for E. coli utilizing truncated M13 phages as capture probes, along with a dark field microscopy detection platform that integrates an image processing model and convolutional neural network. Graphical Abstract

The integrated and indivisible nature of the SDGs is facing implementation challenges due to the silo approaches. We present the three interconnected foci (SDG interactions, modeling, and tools) at the science-policy interface to address these challenges. Accounting for them will support accelerated SDG progress, operationalizing the integration and indivisibility principles.

Abstract To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8+ T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68Ga-grazytracer, while secondary endpoint was the relationship between 68Ga-grazytracer uptake and tumor immune phenotype. 68Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68Ga-grazytracer in tumors was significantly higher in those with a “non-desert” immune phenotype than those with an immune “desert” phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8+ T cell effector function in humans using 68Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning.

Abstract Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.

Abstract Background Mitochondrial genes and nuclear genes cooperate closely to maintain the functions of mitochondria, especially in the oxidative phosphorylation (OXPHOS) pathway. However, mitochondrial genes among arthropod lineages have dramatic evolutionary rate differences. Haplodiploid arthropods often show fast-evolving mitochondrial genes. One hypothesis predicts that the small effective population size of haplodiploid species could enhance the effect of genetic drift leading to higher substitution rates in mitochondrial and nuclear genes. Alternatively, positive selection or compensatory changes in nuclear OXPHOS genes could lead to the fast-evolving mitochondrial genes. However, due to the limited number of arthropod genomes, the rates of evolution for nuclear genes in haplodiploid species, besides hymenopterans, are largely unknown. To test these hypotheses, we used data from 76 arthropod genomes, including 5 independently evolved haplodiploid lineages, to estimate the evolutionary rates and patterns of gene family turnover of mitochondrial and nuclear genes. Results We show that five haplodiploid lineages tested here have fast-evolving mitochondrial genes and fast-evolving nuclear genes related to mitochondrial functions, while nuclear genes not related to mitochondrion showed no significant evolutionary rate differences. Among hymenopterans, bees and ants show faster rates of molecular evolution in mitochondrial genes and mitochondrion-related nuclear genes than sawflies and wasps. With genome data, we also find gene family expansions and contractions in mitochondrion-related genes of bees and ants. Conclusions Our results reject the small population size hypothesis in haplodiploid species. A combination of positive selection and compensatory changes could lead to the observed patterns in haplodiploid species. The elevated evolutionary rates in OXPHOS complex 2 genes of bees and ants suggest a unique evolutionary history of social hymenopterans.

Abstract Sandwich composites made of particle-filled hollow sphere structures (PHSS) and steel sheets offer excellent lightweight and damping properties, ideal for high-speed machine tool components under dynamic loads. Previous research has focused on single particle-filled hollow sphere (PHS) and small PHSS, leaving a gap understanding of PHSS/steel sandwich composites. In this study a test rig was developed, and Design of Experiments and Response Surface Analysis were used to investigate the effects of sheet and core thickness (design parameters), filling ratio, and particle size (particle parameters) on the damping performance of PHSS/steel sandwiches. The results indicate that the design parameters have a significant influence on damping performance. The interaction between design and particle parameters also substantially affects damping. Minimizing particle size, increasing filling ratio, thinning the face layer, and thickening the core layer significantly improve structural damping. To address manufacturing tolerances, a finite element (FE) model-based optimization was developed to accurately determine PHSS material parameters. These parameters were used in an FE model of the PHSS-steel composite, with identified contact parameters minimizing measurement and simulation differences. The homogenized material model and the linear model using global damping parameters accurately reproduce the dynamic properties of the PHSS-steel sandwich composite in low vibration modes.

Abstract Background FLNC gene variants have predominantly been reported in adult populations with cardiomyopathies, and early-onset cases are less common. The genotype–phenotype relationship indicates that dilated cardiomyopathy (DCM) is often associated with FLNC truncating variants. Methods We conducted a comprehensive genetic analysis using next generation sequencing (NGS) to identify FLNC variants in patients with cardiovascular conditions. Detailed phenotypic and variant analyses were performed to characterize the clinical features and genetic alterations. Minigene assays and structural modeling were used to investigate the pathogenicity caused by the identified variants. Results In a cohort of 58 patients, novel heterozygous FLNC variants, c.3962A > T (p.Glu1321Val) and c.7543C > T (p.Leu2515Phe), were identified in patients presenting with dilated and mixed restrictive/hypertrophic cardiomyopathies, respectively. The c.3962A > T variant disrupted normal splicing, as demonstrated through the splicing prediction tool and minigene studies, further emphasizing its pathogenic potential. Conclusion For missense variants of FLNC in patients with DCM, the splicing effect of the variant should be carefully checked. Early detection and intervention are crucial given the high risk of sudden cardiac death and severe cardiac complications.

Background Advances in blood biomarker discovery have enabled the improved diagnosis and prognosis of Alzheimer's disease (AD). Most branched-chain amino acids, except isoleucine (Ile), are correlated with both mild cognitive impairment (MCI) and AD. Therefore, this study investigated the association between serum Ile levels and MCI/AD. Methods This study stratified 700 participants from the Alzheimer's Disease Neuroimaging Initiative database into four diagnostic groups: cognitively normal, stable MCI, progressive MCI, and AD. Analysis of covariance and chi-square analyses were used to test the demographic data. Receiver operating curve analyses were used to calculate the diagnostic accuracy of different biomarkers and were compared by MedCalc 20. Additionally, Cox proportional hazards models were used to measure the ability of serum Ile levels to predict disease conversion. Finally, a linear mixed-effects model was used to evaluate the associations between serum Ile levels and cognition, brain structure, and metabolism. Results Serum Ile concentration was decreased in AD and demonstrated significant diagnostic efficacy. The combination of serum Ile and cerebrospinal fluid (CSF) phosphorylated tau (P-tau) improved the diagnostic accuracy in AD compared to total tau (T-tau) alone. Serum Ile levels significantly predicted the conversion from MCI to AD (cutoff value of 78.3 μM). Finally, the results of this study also revealed a correlation between serum Ile levels and the Alzheimer's Disease Assessment Scale cognitive subscale Q4. Conclusions Serum Ile may be a potential biomarker of AD. Ile had independent diagnostic efficacy and significantly improved the diagnostic accuracy of CSF P-tau in AD. MCI patients with a lower serum Ile level had a higher risk of progression to AD and a worse cognition assessment.

This study presents the identification of four novel Xylaria species, discovered in the karst region of China. The discovery was facilitated by a rigorous analysis that encompassed both morpho-anatomical features and multi-locus phylogenetics utilizing sequences from the ITS, rpb2, and TUB2 loci. The newly identified species are designated as Xylaria jichuanii sp. nov., X. nanningensis sp. nov., X. orientalis sp. nov., and X. taiyangheensis sp. nov. The distinction of these species from their known counterparts was verified through comparison of morphological features and phylogenetic analysis. The study further provides detailed morphological descriptions, illustrative representations, and a phylogenetic tree, all of which contribute to the taxonomic positioning of these novel species.

Molecular phylogeny and morphological characteristics of collections of diatrypaceous fungi from Guizhou Province, China, lead to the establishment of a new genus, Stromatolinea, and the identification of four new species and two new combinations. The taxa were found growing on the dead culms of Phyllostachys bamboo. The new genus is distinguished by its well-developed, discrete linear stromata with yellow interior tissue and allantoid subhyaline ascospores. The newly described species are Stromatolinea grisea, S. guizhouensis, S. hydei, and S. xishuiensis. Additionally, two new combinations, Stromatolinea linearis and S. phaselina, are proposed based on comparative analysis and morphology. Phylogenetic analyses were conducted using ITS and TUB2 sequences. The study includes comprehensive morphological descriptions, illustrations, and a phylogenetic tree depicting the placement of the new taxa.

Abstract Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

Abstract Background Addressing mental health disparities following COVID-19 requires adaptive, multi-sectoral, equity-focused, and community-based approaches. Mental health task-sharing in gateway settings has been found to address mental health care gaps in low- and middle-income countries, but is not a common practice in the U.S., especially in non-medical settings, such as low-income housing developments (LIH). This research study will evaluate the effectiveness of a multisectoral community-engaged collaborative for task-sharing mental health care on consumer, provider, and implementation outcomes, as well as identify barriers and facilitators for implementation. Methods In this stepped-wedge randomized controlled trial with technology supplementation, LIH and primary care sites will be randomly assigned to one of five sequences of three implementation strategies: (1) Education and Resources (E&R), which involves online training and resources on basic mental health task-sharing skills, (2) Multisectoral Community Collaborative Care (MCC), which consists of all E&R resources plus additional community responsive implementation supports and participation in a multisectoral coalition and (3) MCC + Technology, which combines the MCC condition resources with a community crowdsourced technology solution to support implementation. The primary outcome is the effectiveness in meeting consumers’ needs through direct service (e.g., adequately addressing depression and anxiety symptoms), and through implementation to increase access to mental health care (reach). The secondary outcome examines additional consumer outcomes including health functioning and social risks, as well as implementation outcomes including provider skills, program adoption, and factors related to barriers and facilitators of quality implementation. A total of 700 consumers receiving mental health care at 20 sites will be surveyed at baseline, 6-, and 12-month follow-ups. Additionally, 100 providers will be evaluated at baseline, 6-, 12-, and 24-month follow-ups before training and after randomization. Discussion We hypothesize that MCC and MCC + Technology conditions will demonstrate significantly higher efficacy in changing primary outcomes compared to E&R, and the MCC + Technology supplement will show significantly higher levels of reach of mental health tasks compared to the MCC condition alone. These findings will demonstrate the feasibility of mental health integration into accessible, non-medical community settings such as LIH. Moreover, it will help establish a multilevel system solution based on community engagement and planning with a multisectoral collaboration that can be sustained community-wide. Trial registration NCT05833555 on Clinicaltrials.gov. Registered April 26, 2023

Abstract Cavity optomechanical systems have enabled precision sensing of magnetic fields, by leveraging the optical resonance-enhanced readout and mechanical resonance-enhanced response. Previous studies have successfully achieved mass-produced and reproducible microcavity optomechanical magnetometry (MCOM) by incorporating Terfenol-D thin films into high-quality (Q) factor whispering gallery mode (WGM) microcavities. However, the sensitivity was limited to 585 pT Hz−1/2, over 20 times inferior to those using Terfenol-D particles. In this work, we propose and demonstrate a high-sensitivity and mass-produced MCOM approach by sputtering a FeGaB thin film onto a high-Q SiO2 WGM microdisk. Theoretical studies are conducted to explore the magnetic actuation constant and noise-limited sensitivity by varying the parameters of the FeGaB film and SiO2 microdisk. Multiple magnetometers with different radii are fabricated and characterized. By utilizing a microdisk with a radius of 355 μm and a thickness of 1 μm, along with a FeGaB film with a radius of 330 μm and a thickness of 1.3 μm, we have achieved a remarkable peak sensitivity of 1.68 pT Hz−1/2 at 9.52 MHz. This represents a significant improvement of over two orders of magnitude compared with previous studies employing sputtered Terfenol-D film. Notably, the magnetometer operates without a bias magnetic field, thanks to the remarkable soft magnetic properties of the FeGaB film. Furthermore, as a proof of concept, we have demonstrated the real-time measurement of a pulsed magnetic field simulating the corona current in a high-voltage transmission line using our developed magnetometer. These high-sensitivity magnetometers hold great potential for various applications, such as magnetic induction tomography and corona current monitoring.

Abstract The high pixel resolution is emerging as one of the key parameters for the next-generation displays. Despite the development of various quantum dot (QD) patterning techniques, achieving ultrahigh-resolution (>10,000 pixels per inch (PPI)) and high-fidelity QD patterns is still a tough challenge that needs to be addressed urgently. Here, we propose a novel and effective approach of orthogonal electric field-induced template-assisted dielectric electrophoretic deposition to successfully achieve one of the highest pixel resolutions of 23090 (PPI) with a high fidelity of up to 99%. Meanwhile, the proposed strategy is compatible with the preparation of QD pixels based on perovskite CsPbBr3 and conventional CdSe QDs, exhibiting a wide applicability for QD pixel fabrication. Notably, we further demonstrate the great value of our approach to achieve efficiently electroluminescent QD pixels with a peak external quantum efficiency of 16.5%. Consequently, this work provides a general approach for realizing ultrahigh-resolution and high-fidelity patterns based on various QDs and a novel method for fabricating QD-patterned devices with high performance.

Abstract Human-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. Here, after demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI and the role of cell heterogeneity, scar size and the Purkinje system. Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars and acute infarction. We conclude that homogeneity in injected ventricular-like cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.

Abstract Magnetic resonance imaging (MRI) is a cornerstone technology in clinical diagnostics and in vivo research, offering unparalleled visualization capabilities. Despite significant advancements in the past century, traditional 1H MRI still faces sensitivity limitations that hinder its further development. To overcome this challenge, hyperpolarization methods have been introduced, disrupting the thermal equilibrium of nuclear spins and leading to an increased proportion of hyperpolarized spins, thereby enhancing sensitivity by hundreds to tens of thousands of times. Among these methods, hyperpolarized (HP) 129Xe MRI, also known as ultrasensitive 129Xe MRI, stands out for achieving the highest polarization enhancement and has recently received clinical approval. It effectively tackles the challenge of weak MRI signals from low proton density in the lungs. HP 129Xe MRI is valuable for assessing structural and functional changes in lung physiology during pulmonary disease progression, tracking cells, and detecting target molecules at pico‐molar concentrations. This review summarizes recent developments in HP 129Xe MRI, including its physical principles, manufacturing methods, in vivo characteristics, and diverse applications in biomedical, chemical, and material sciences. In addition, it carefully discusses potential technical improvements and future prospects for enhancing its utility in these fields, further establishing HP 129Xe MRI's importance in advancing medical imaging and research.

BackgroundDuring severe acute pancreatitis (SAP), damage to the intestinal mucosal barrier and translocation of intestinal pathogenic bacteria are key mechanisms that accelerate the disease progression of SAP. Chaihuang Qingyi Huoxue Granule (CH) is a herbal formula used in the clinical treatment of SAP. This study aims to investigate the role of CH in regulating gut microbiota and intestinal mucosal barrier in SAP rats.MethodsSodium taurocholate (3.5%) was retrogradely perfused into the biliopancreatic duct to establish the model of SAP in rats. CH (4.4 g/kg) was administered by gavage. Serum amylase, lipase, and endotoxin levels were measured. Hematoxylin-eosin (HE) staining was used to observe morphological changes in the pancreas and colon. The expression of zona occludens-1 (ZO-1) and occludin in the colon was examined by immunohistochemistry (IHC) and western blot. 16S rDNA gene sequencing was used to analyze the gut microbiota of the rats. The content of short-chain fatty acids (SCFAs) in the intestinal contents of the rats was determined by gas chromatography-mass spectrometry (GC-MS).ResultsCH reduced serum amylase, lipase, and endotoxin levels in SAP rats, alleviated pathological damage in the pancreas and colon, and restored the expression of ZO-1 and occludin. Moreover, CH alleviated gut microbiota dysbiosis in SAP rats, with restored gut microbiota diversity and structure. At the phylum level, the relative abundance of Firmicutes and Bacteroidetes increased, while that of Proteobacteria decreased. At the genus level, the abundance of Ruminococcus 1, Parabacteroides, Prevotellaceae UCG-001, Lachnospiraceae NK4A136 group, and Lactobacillus increased, while that of Escherichia-Shigella, Enterococcus, and Enterobacter decreased. In addition, CH increased the levels of SCFAs in the intestinal contents of SAP rats.ConclusionCH ameliorates SAP by maintaining the homeostasis and diversity of the gut microbiota, increasing the levels of SCFAs, and repairing the intestinal mucosal barrier.

Background: Colorectal cancer (CRC) with benign lymph node enlargement (BLNE) (>1 cm) is often associated with better long-term prognosis and favorable outcomes in immunotherapy. However, lymph node enlargement (LNE) can mislead clinicians into considering metastatic lymph node enlargement (MLNE), potentially resulting in misguided therapeutic decisions in unnecessary neoadjuvant therapy and extended lymphadenectomy. This, ultimately, can lead to overtreatment, increasing the risk of postoperative complications and tumor recurrence. Thus, developing a pre-treatment multimodal CT radiomics-based model to assess LNE status is essential. Methods: A total of 319 pre-treatment multimodal CT images of CRC patients with LNE were retrospectively collected from 2015 to 2020 as a development cohort. Additionally, 111 multimodal CT images from 2020 to 2022 were prospectively collected as a validation cohort. Tumor and LNE regions of interest were manually segmented, and 40 patients were randomly re-outlined by another radiologist to extract radiomics features. The intragroup correlation coefficient was calculated to assess the reproducibility of the radiomics features. Following feature screening, multiple predictive models were constructed, including tumor and lymph node models for individual modalities (TumorN, A, V; LnN, A, V; Ln, lymph node; N, non-contrast phase; A, arterial phase; V, venous phase), along with 15 models combining multiple modalities. The predictive performance of these models was assessed using area under the receiver operating characteristic curve (AUROC) and precision-recall curve (AUPRC), along with sensitivity, specificity, and accuracy. Findings: After validation with the prospective cohort, TumorN and LnA demonstrated the best predictive performance among single modalities, with AUROC values of 0.626 and 0.781, respectively. Among all models, LnNAV exhibited the highest predictive performance, achieving AUROC and AUPRC values of 0.820 and 0.883, respectively, with a sensitivity of 0.708, specificity of 0.848, and overall accuracy of 0.766. Interpretation: Radiomics, as a non-invasive and quantitative approach, can reflect underlying physiopathological information. The incorporation of a multimodal radiomics model yielded excellent performance in predicting pre-treatment LNE status, particularly for BLNE, with a specificity of 0.848. This approach can provide valuable guidance for clinical treatment strategies.

Welding electron guns are usually designed using the theory of electron optics, where a change in the size of the Wehnelt electrode in the electrostatic field causes variations in the motion behavior of the electron beam. In this study, the COMSOL software is used to carry out finite element simulations; under temperature-limited emission conditions, the influence of changing α, which is the angle between the inner wall of the Wehnelt electrode and its central axis, on the beam is mainly analyzed. The results indicate that a change in α causes a variation in the potential on the axis and its first and second derivatives to the axial distance, which in turn causes changes in the beam current and emittance and the radius and position of the beam waist; however, it has no significant effect on the kinetic energy of the electrons. When 75° < α ≤ 90°, the beam cannot be focused effectively. When 0° ≤ α ≤ 15°, the beam current is significantly reduced, and the Wehnelt electrode is most likely to be damaged. After synthetically analyzing the main characteristic parameters of the beam waist, when α = 60°, the requirements for focusing the electron beam of the electron gun in this study can be met.

Acute aortic dissection (AAD) and pulmonary embolism (PE) are two critical and potentially fatal causes of chest pain. The simultaneous occurrence of these conditions is exceptionally rare; however, when they co-occur, the conflicting therapeutic strategies required significantly elevate mortality rates. While venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been extensively reported as a life-saving intervention for high-risk pulmonary embolism, its application in the management of AAD remains highly debated. Recently, our institution successfully employed VA-ECMO to treat a patient with acute type A aortic dissection (ATAAD) complicated by PE. This case highlights that VA-ECMO may serve as a crucial life-saving measure for patients with AAD who present with hemodynamic instability or cardiac arrest.

Abstract Numerous studies have highlighted the simultaneous relationship between the Arctic Oscillation (AO) and weather/climate in Asia. However, the stability of the precursor signals in AO for Asian surface air temperature (SAT), which is important for short‐term climate prediction, has received little attention. In this study, a strengthened relationship is identified between the late‐winter AO and the early spring SAT over North and Northeast Asia (NNA) around the 1990s. During 1990–2022, a positive (negative) phase of AO during late winter is generally followed by significant warming (cooling) anomalies in the NNA during early spring, whereas this relationship is insignificant during 1961–1987. Further result shows a good persistence of the late‐winter AO to early spring after the 1990s. Accordingly, the AO exerts a strengthened impact on Mongolian anticyclone and Asian westerly anomalies through modulation of a Rossby wave train that propagates from the Arctic to the NNA in early spring, leading to significant SAT anomalies at NNA. Additionally, the AO‐related temperature anomalies intensified in the stratosphere after the 1990s, linking AO and stratospheric polar vortex (SPV). The intensified (weakened) SPV following positive (negative) AO facilitates warming (cooling) anomalies at NNA via downward‐propagating Eliassen‐Palm fluxes at wave number 1 and circumpolar westerlies in middle and lower troposphere. The seasonal persistence of AO and the strengthened relationship between AO and SPV synergistically enhance the influence of late‐winter AO on early spring SAT in the NNA, which might be attributed to the interdecadal changes in background circulation over the Arctic.

BackgroundThis study is significant for improving the accuracy of Customs’ cross-border supervision of emergency supplies and ensuring the timely clearance of these essential goods.MethodsTo ensure both the convenience and security of Customs oversight regarding emergency supplies, this study first systematically collects and organizes representative data on the import and export trade of these supplies. Proposed an enhanced Recency Frequency Monetary (RFM) cluster analysis model, building on the principles of k-means clustering. Subsequently, the model is employed to cluster the import and export trade data of emergency supplies. Finally, the paper offers optimization suggestions for customs clearance supervision based on the analysis results.ResultsThe study primarily focuses on the collection and organization of import and export trade data across six major categories of representative emergency supplies. By employing K-means clustering techniques, the research develops an improved RFM cluster analysis model, referred to as TR-TF-TV, and subsequently proposes strategies for customs supervision of emergency supplies. By integrating K-means clustering techniques, this study develops an advanced RFM cluster analysis model, referred to as TR-TF-TV. It subsequently proposes customs supervision strategies for emergency supplies. These strategies include a clustering analysis of trade data to ensure safe and efficient customs clearance, the preservation of integrity and stability within the emergency supplies supply chain, the enhancement of the national emergency management system, and the improvement of response capabilities to public health emergencies.ConclusionThis analysis of trade data concerning the import and export of emergency supplies, based on the enhanced RFM clustering model, represents an exploratory initiative in original model design. Recognizing the inherent limitations associated with the model’s index design and data sample selection, we intend to refine these elements in future research, aiming to improve and validate the model to further optimize related countermeasures.

BackgroundLow back pain and lower extremity sensory and functional abnormalities are common symptoms of lumbar disc herniation (LDH), which can easily cause walking dysfunction and significantly impair the quality of life of patients. Tuina and traditional Chinese exercises (TCEs) are effective in relieving pain and restoring dysfunction, and both are often used in China as a combination of passive therapy and active exercise to ease symptoms in patients with LDH. However, the majority of current clinical trials on the treatment of LDH with Tuina or TCEs are single-centre clinical studies, and the quality of these studies is generally low. Furthermore, clear evidence of clinical efficacy as to whether Tuina combined with TCEs is superior to single TCEs for improving dysfunction and pain in patients with LDH is lacking.Methods/designThe design is a multicentre, assessor-blinded clinical randomised controlled trial. A total of 166 patients with LDH (aged 18–65 years) were recruited from four centres and randomly assigned at a 1:1 ratio to two groups: the TCE group and the Tuina combined with the TCE group. Each group received three treatments over the course of 1 week for a total of 4 weeks. The primary outcome indicator was the Oswestry Disability Index, whereas the secondary outcome indicators were the Short Form of Quality of Life Scale, the Short-Form McGill Pain Questionnaire Scale, and gait analysis. Assessments were made before the treatment, at the end of the treatment, and at the third and sixth months’ follow-ups. Gait analysis was only used for comparison between the two groups before and after treatment, and did not involve follow-up. Adverse events occurring during the trial were faithfully recorded.ConclusionThe results of this study are expected to provide a more effective research protocol for symptomatic LDH and an evidence-based rationale for the efficacy and safety of Tuina combined with TCEs in the treatment of symptomatic LDH.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=209956, identifier ChiCTR2300077361.

ObjectivesThis case demonstrates the efficacy and safety of Traditional Chinese Medicine manual therapy (TCMMT) for the treatment of mild to moderate AIS.MethodsAn 10-year-old girl who suffered from low back pain (LBP) with marked shoulder inequality and razorback postural abnormalities, with a clinical diagnosis of idiopathic scoliosis, and the Cobb angle of 20° and angle of trunk rotation (ATR) of the thoracic vertebral segment at 7°, and ATR of the lumbar vertebral segment at 8°, was treated with TCMMT. The patient initially recovered from centralized LBP with repeated TCMMT twice per week for 1 month. Subsequently, the frequency of TCMMT treatment was changed to 1–2 sessions weekly for 6 months. Before treatment, after the first TCMMT, 1 month and 7 months of treatment, and 18 months of follow-up, we used ATR or Cobb angle and health-related quality of life (HRQOL) for assessment. The HRQOL was assessed using the visual analog scale (VAS) scores and the Scoliosis Research Society-22 (SRS-22) patient questionnaire. The minimum clinically important difference (MCID) was used to assess the effectiveness of clinical measures based on a “responder analysis”.Results(a) The patient's VAS score was 40/100 before treatment, 25/100 after the first treatment, 15/100 after 1 month of treatment, 12/100 after 7 months of treatment, and 15/100 at follow-up to 18 months. (b) The patient's SRS-22 score was 54/110 before treatment, 61/110 after the first treatment, 79/110 after 1 month of treatment, 106/110 after 7 months of treatment, and 104/110 at follow-up to 18 months. (c) Before treatment, the patient's thoracic ATR angle was 7° and the lumbar ATR angle was 8°, there was no change in the ATR angles of the thoracic and lumbar spine after the first treatment. The thoracic ATR angle was 6° and the lumbar ATR angle was 5° after 1 month of treatment. The thoracic ATR angle was 1.5° and the lumbar ATR angle was 3.5° after 7 months of treatment. The thoracic ATR angle was 2° and the lumbar ATR angle was 4° at the follow up till 18 months. (d) The patient's Cobb angle was 20° before treatment, 7° after the 7 month of treatment, and 8° at follow-up to 18 months. No adverse events during treatment.ConclusionsTCMMT is a conservative treatment option worthy of consideration when considering a conservative treatment strategy for AIS.

Summary: Cell elongation defines cell size and shape, whereas the cell wall supports and protects it. However, the mechanism regulating cell elongation and cell wall thickness remains unknown. Here, taking advantage of a model for both cell elongation and cell wall biogenesis, cotton fiber, we identified a basic-helix-loop-helix (bHLH) factor, GhCEWT1, that contributes to both fiber cell elongation and cell wall thickness. Loss of function of GhCEWT1 reduced the fiber length and cell wall thickness. GhCEWT1 induced transcription of GhCEWT2. We also identified two target genes of GhCEWT2, cellulose synthase 4D (GhCes4D) and COBRA-LIKE 4D (GhCOBL4D). GhCEWT2 enhanced the transcription of GhCes4D and GhCOBL4D. GhCOBL4D overexpression significantly enhanced cotton fiber cell length and cell wall thickness. Our results revealed a GhCEWT1-GhCEWT2-GhCes4D/GhCOBL4D cascade functioning in both fiber cell elongation and cell wall thickness. These findings provide a comprehensive understanding of plant cell elongation and cell wall formation, as well as a theoretical basis for boosting the biomass on Earth.

Excessive copper (Cu) of rhizosphere inhibited the growth and development of citrus seedlings. Lignin deposition on the cell wall promotes plant Cu tolerance. However, the lignin biosynthesis in citrus leaves and roots that respond to Cu toxicity is not fully understood. In this study, young seedlings of ‘Xuegan’ [Citrus sinensis (L.) Osbeck, a less Cu-tolerant species] and ‘Shatian pomelo’ [Citrus grandis (L.) Osbeck, a more Cu-tolerant species] were treated with nutrient solution containing 0.5 (as Control), 100, 300 or 500 µM Cu for 15 weeks in sandy culture. By the end of treatments, citrus leaves and roots were sampled to investigate the biomass allocation, Cu distribution, the lignin biosynthesis and deposition. The results indicated that Cu stress from 100 to 500 µM increased the root/shoot biomass ratio, promoting Cu and lignin accumulation in the leaves and roots of the tested citrus species. Besides, 300 µM Cu stress increased the accumulation of three lignin monomers of citrus species. The metabolomic profile indicated that Cu toxicity altered the lignin components of citrus species. The citrus roots are more prominent in the lignin precursor biosynthesis under Cu toxicity than citrus leaves. The histochemical staining supported that Cu stress improved the deposition of both guaiacy and syringy lignin units in citrus roots. The enzyme activity and gene expression revealed that activating lignin-biosynthetic enzymes, such as L-phenylalanine ammonia-lyase, peroxidase and laccase, played an essential role in lignin biosynthesis. Our results demonstrated that excessive Cu induced lignin biosynthesis in citrus leaves and roots to different extents. The findings from the present study increased our understanding of lignin biosynthesis in Cu-stressed citrus species, which would provide a theoretical basis for the citrus Cu-tolerant mechanisms.

Abstract Objective: To quantify and compare concurrent within-person trends in lifestyle risks, nutrition status and drivers of food choice among urban migrants in Central Asia. Design: We collected panel data on household structure, drivers of food choice, nutrition knowledge and diverse measures of nutrition status and lifestyle risk from urban migrants at 0, 3, 6 and 9 months using harmonised methodology in two cities. Trends were analysed using mixed-effects models and qualitatively compared within and between cities. Setting: Ulaanbaatar, Mongolia, and Almaty, Kazakhstan. Participants: 200 adults (22–55 years) who migrated to these cities within the past 2 years. Results: Adjusting for age and sex, each month since migration was positively associated with fasting TAG in Almaty (0·55 mg/dl; 95 % CI: 0·13, 0·94) and BMI (0·04 kg/m2; 95 % CI: 0·01, 0·07), body fat (0·14 %; 95 % CI: 0·01, 0·26) and fasting glucose (0·04 mmol/l; 95 % CI: 0·02, 0·05) and lipids in Ulaanbaatar (P < 0·05). In Almaty, nutrition knowledge (measured using an objective 20-point scale) declined despite improvements in diet quality (measured by Prime Diet Quality Score). The influence of food availability, price and taste on food choice increased in Almaty (P < 0·05). Upon multivariable adjustment, nutrition knowledge was positively associated with diet quality in Almaty and adherence to ‘acculturated’ diet patterns in both cities (P < 0·05). Different trends in smoking, sleep quality and generalised anxiety were observed between cities. Conclusions: Findings indicate heterogeneous shifts in nutrition, lifestyles and drivers of food choice among urban migrants in Central Asia and provide an evidence base for focused research and advocacy to promote healthy diets and enable nutrition-sensitive food environments.

Introduction Health education, weight control and exercise therapy are recognised treatment options for the non-surgical management of knee osteoarthritis (KOA); however, the pain and muscle fatigue associated with exercise make it difficult for patients to initially adhere. Traditional Chinese medicine (TCM) massage is an important complementary and alternative therapy that can effectively address these deficiencies. According to TCM theory and preliminary clinical practice, loosening of the muscles while pointing to acupoints can promote the recovery of KOA. Therefore, we hypothesised that exercise therapy in conjunction with TCM massage may lead to more satisfactory results in terms of pain management, active functional muscle activation patterns and proprioception in patients with KOA.Methods and analysis A parallel, single-centre, randomised controlled trial involving 106 patients will be conducted at Shuguang Hospital, Shanghai University of Traditional Chinese Medicine. Eligible patients with KOA who agree to participate will be randomised via a 1:1 randomisation system into the experimental group (receiving TCM massage and exercise treatment) and the control group (receiving exercise treatment). The primary endpoint is the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain from baseline to 24 weeks. Secondary outcomes include knee function (measured using the WOMAC stiffness and WOMAC functional subscale questionnaire and the timed ‘Up and Go’ test), muscle activation states (evaluated with electromyography techniques), knee proprioception and treatment satisfaction, adherence, safety evaluation and other relevant factors. Outcome assessors and data analysts will be blinded to the allocations, and the participants will not disclose their specific allocations. Outcome analyses will be conducted on both intention-to-treat and per-protocol populations. A preliminary analysis will test whether TCM massage, in addition to exercise, has statistically better outcomes.Ethics and dissemination The study protocol has received approval from the Ethics Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (2023-1357-124-01).All study participants will be required to give written informed consent. The findings of the study will be submitted to a peer-reviewed journal for publication and presented at scientific conferences. Additionally, the participants will receive copies of the results.Trial registration number ChiCTR2300077308.

Introduction Ischaemic heart disease (IHD) is a pathological process characterised by a blockage or non-obstructive accumulation of atherosclerotic plaques in the epicardial arteries. Percutaneous coronary intervention (PCI) is widely used in clinical practice to treat IHD. However, angina post PCI (APPCI) impairs quality of life and portends a worse prognosis. Hence, an effective and safe treatment option remains an urgent need for patients with APPCI. In recent years, there has been an increasing body of clinical trials regarding the use of acupuncture for the prevention and treatment of APPCI, and the results have indicated it might be a promising therapeutic intervention. However, to our knowledge, the potential benefits of acupuncture for the prevention and treatment of APPCI to justify either their recommendation or their clinical role have not been evaluated.Methods and analysis PubMed, Embase, Cochrane Library, Web of Science Core Collection, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Wanfang Database and VIP Database will be searched from inception to 8 June 2024 without language restrictions. Two investigators will independently screen studies, extract data, assess the risk of bias from randomised controlled trials (RCTs) and assess the risk of bias. The third reviewer will arbitrate any disagreements. Data synthesis and analysis will be conducted using the RevMan V.5.4 software. Subgroup analyses, sensitivity analysis, meta-regression and bias reporting assessments will be performed if necessary and appropriate. Finally, the quality of evidence from RCTs will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation System tool.Ethics and dissemination Ethical approval is unnecessary since no private or confidential patient data will be included. The systematic review will be published in peer-reviewed journals.PROSPERO registration number CRD42024562116.

Sudden death after myocardial infarction (MI) is associated with electrophysiological heterogeneities and ionic current remodelling. Low ejection fraction (EF) is used in risk stratification, but its mechanistic links with pro-arrhythmic heterogeneities are unknown. We aim to provide mechanistic explanations of clinical phenotypes in acute and chronic MI, from ionic current remodelling to ECG and EF, using human electromechanical modelling and simulation to augment experimental and clinical investigations. A human ventricular electromechanical modelling and simulation framework is constructed and validated with rich experimental and clinical datasets, incorporating varying degrees of ionic current remodelling as reported in literature. In acute MI, T-wave inversion and Brugada phenocopy were explained by conduction abnormality and local action potential prolongation in the border zone. In chronic MI, upright tall T-waves highlight large repolarisation dispersion between the border and remote zones, which promoted ectopic propagation at fast pacing. Post-MI EF at resting heart rate was not sensitive to the extent of repolarisation heterogeneity and the risk of repolarisation abnormalities at fast pacing. T-wave and QT abnormalities are better indicators of repolarisation heterogeneities than EF in post-MI.

Introduction With the development of the medical system and the diversification of patient needs, nurse practitioners (NPs) play an increasingly important role in medical practice, assuming more responsibilities and powers, including the right to prescribe. However, in the process of exercising the right to prescribe, NPs may face various obstacles, and there are also some promoting factors. Therefore, this study aims to deeply explore the obstacles and promoting factors in the prescription process of NPs through a qualitative meta-analysis and comprehensive method, so as to provide a basis for improving the prescription practice of NPs, improving nursing quality and patient satisfaction.Methods and analysis This study will adhere to the Joanna Briggs Institute framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. A comprehensive literature search and analysis of studies on nurse are prescribed via PubMed, Embase, Web of Science, CINAHL and the Cochrane Library. Two independent reviewers will select articles, extract data and appraise study quality. Content analysis will be used to synthesise outcomes, and methodological quality and evidence quality will be assessed. The quality of the articles will be assessed using the 10-item Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research.Ethics and dissemination Ethical approval will not be required for this study, as it solely encompasses data derived from previously published research. The findings will be disseminated through publication in a peer-reviewed journal. In addition, the results will be actively shared at major academic conferences focused on nursing research and healthcare policy to ensure that the study’s outcomes reach key stakeholders, including healthcare practitioners, policymakers and researchers. This targeted dissemination strategy aims to promote the integration of the findings into practice and future research. This protocol is registered with the PROSPERO prospective database of systematic review.PROSPERO registration number CRD42023398567.