Search

BackgroundGreen tea intake has been reported to improve the clinical outcomes of patients with cardiovascular diseases or cancer. It may have a certain role in the development of venous thromboembolism (VTE) among cancer patients. The current study aimed to address this issue, which has been understudied.MethodsWe carried out a retrospective study to explore the role of green tea intake in cancer patients. Patients with and without green tea intake were enrolled in a 1:1 ratio by using propensity scoring matching. The primary and secondary outcomes were VTE development and mortality 1 year after cancer diagnosis, respectively.ResultsThe cancer patients with green tea intake (n = 425) had less VTE development (10 [2.4%] vs. 23 [5.4%], p = 0.021), VTE-related death (7 [1.6%] vs. 18 [4.2%], p = 0.026), and fatal pulmonary embolism (PE) (3 [0.7%] vs. 12 [2.8%], p = 0.019), compared with those without green tea intake (n = 425). No intake of green tea was correlated with an increase in VTE development (multivariate hazard ratio (HR) 1.758 [1.476–2.040], p

The increasingly improved transportation infrastructure network is the prerequisite and foundation for driving regional development. Scientifically investigating the mechanisms by which the transport superiority degree (TSD) in arid regions affects the health of ecosystems holds significant practical value and importance for ecosystem protection and regional sustainable development. This study investigates the impact of the TSD on the Ecosystem Health Levels (EHL) in Southern Xinjiang, China, an area characterized by its arid climate and ecological vulnerability. Arid regions, such as Southern Xinjiang, often face unique ecological challenges, including water scarcity, soil erosion, and biodiversity loss, which can be exacerbated by human activities including transportation infrastructure development. By leveraging multi-source remote sensing data, this research aims to uncover the intricate dynamics between TSD and EHL in such a fragile ecological context. The findings of this study are critical for understanding the balance between infrastructural development and environmental conservation in arid regions and provide valuable insights for sustainable planning and policy-making in similar ecological settings. The research results show the following: (1) Over the study period, county-scale TSD in southern Xinjiang generally increased, while the conditions of EHL deteriorated, with higher EHL in the eastern counties than in the western counties. (2) Bivariate spatial autocorrelation analysis reveals a significant spatial dependency between county-scale TSD and EHL, with primary relationship types being LH (Low TSD − High EHL) and HL (High TSD − Low EHL). (3) Spatial regression model results indicate that an increase in TSD leads to the deterioration of county-scale EHL, and during the study period, it was observed that the interference of TSD on EHL gradually weakened.

By enhancing the type 1–3 piezoelectric composite material, a highly sensitive hydroacoustic transducer sensitive element structure is suggested for uses in sonar systems, such as small target identification and fine imaging. A lower metal plate, a piezoelectric ceramic column array, and an upper metal plate make up the piezoelectric material structure. The resonance frequency of the bimetal plate type piezoelectric ceramic array material was theoretically analyzed, the sensitive element geometry of the bimetal plate piezoelectric material was studied using finite element simulation, the material choice for the metal plate affected the material’s performance, and the parameters of each size of the sensitive element were determined. These findings served as a guide for the production of a highly sensitive hydroacoustic transducer, as well as the structure of the piezoelectric material transducer in the water performance test. Results indicate that the structure transducer has a maximum transmit voltage response of 178 dB and a −3 dB bandwidth of approximately 25 kHz; the transducer may be efficiently tuned for a maximum receive sensitivity of −172 dB.

Abstract Ischaemia of the heart and limbs attributable to compromised blood supply is a major cause of mortality and morbidity. The mechanisms of functional angiogenesis remain poorly understood, however. Here we show that FNIP1 plays a critical role in controlling skeletal muscle functional angiogenesis, a process pivotal for muscle revascularization during ischemia. Muscle FNIP1 expression is down-regulated by exercise. Genetic overexpression of FNIP1 in myofiber causes limited angiogenesis in mice, whereas its myofiber-specific ablation markedly promotes the formation of functional blood vessels. Interestingly, the increased muscle angiogenesis is independent of AMPK but due to enhanced macrophage recruitment in FNIP1-depleted muscles. Mechanistically, myofiber FNIP1 deficiency induces PGC-1α to activate chemokine gene transcription, thereby driving macrophage recruitment and muscle angiogenesis program. Furthermore, in a mouse hindlimb ischemia model of peripheral artery disease, the loss of myofiber FNIP1 significantly improved the recovery of blood flow. Thus, these results reveal a pivotal role of FNIP1 as a negative regulator of functional angiogenesis in muscle, offering insight into potential therapeutic strategies for ischemic diseases.

Abstract Psoriasis is a chronic inflammatory skin disease that affects millions of people worldwide. Sulforaphane (SFN) has been shown to have anti-inflammatory and antioxidant properties. In this study, we investigated the effects of SFN on a mouse model of psoriasis induced by imiquimod (IMQ) and its underlying molecular mechanism. Mice treated with SFN showed significant improvement in psoriatic symptoms, including reduced erythema, scales, and cutaneous thickness. Histopathological analysis and immunohistochemical staining revealed decreased expression of K16, K17, and Ki67 in SFN-treated mice, indicating reduced abnormal differentiation of keratinocytes and cutaneous inflammation. SFN treatment also reduced the activation of STAT3 and NF-κB pathways and downregulated pro-inflammatory cytokines IL-1β, IL-6, and CCL2. In vitro experiments using HaCaT cells demonstrated that SFN inhibited IL-22 and TNF-α-induced activation of inflammatory pathways and keratinocyte proliferation. Network pharmacology analysis suggested that the KEAP1-NRF2 pathway might be involved in the protective effects of SFN on psoriasis. We observed reduced NRF2 expression in human psoriatic lesions, and subsequent experiments showed that SFN activated KEAP1-NRF2 pathway in vivo and in vitro. Importantly, NRF2-deficient mice exhibited aggravated psoriasis-like symptoms and reduced response to SFN treatment. Our findings indicate that SFN ameliorates psoriasis symptoms and inflammation through the KEAP1-NRF2 pathway, suggesting a potential therapeutic role for SFN in the treatment of psoriasis.

Objectives Anterior cervical decompression and fusion (ACF) has become a widely accepted surgical treatment for degenerative cervical diseases, but occasionally, significant intraoperative blood loss (SIBL), which is defined as IBL of 500 mL or more, will occur. We aimed to investigate the independent risk factors for SIBL during ACF for degenerative cervical diseases. Methods We enrolled 1150 patients who underwent ACF for degenerative cervical diseases at our hospital between 2013 and 2019. The patients were divided into two groups: the SIBL group (n = 38) and the non‐SIBL group (n = 1112). Demographic, surgical and radiographic data were recorded prospectively to investigate the independent risk factors for SIBL. For counting data, the chi‐square test or Fisher's exact probability test was used. Student's t‐test or the Mann–Whitney rank sum test was used for comparisons between groups of measurement data. Univariate analysis and multivariate logistic regression analysis were further used to analyze the significance of potential risk factors. Results The incidence of SIBL during ACF was 3.3% (38/1150). A multivariate analysis revealed that female sex (odds ratio [OR], 6.285; 95% confidence interval [CI], 2.707–14.595; p

To tackle the issue of the traditional intelligent diagnostic algorithm’s insufficient utilization of correlation characteristics within the time series of fault signals and to meet the challenges of accuracy and computational complexity in rotating machinery fault diagnosis, a novel approach based on a recurrence binary plot (RBP) and a lightweight, deep, separable, dilated convolutional neural network (DSD-CNN) is proposed. Firstly, a recursive encoding method is used to convert the fault vibration signals of rotating machinery into two-dimensional texture images, extracting feature information from the internal structure of the fault signals as the input for the model. Subsequently, leveraging the excellent feature extraction capabilities of a lightweight convolutional neural network embedded with attention modules, the fault diagnosis of rotating machinery is carried out. The experimental results using different datasets demonstrate that the proposed model achieves excellent diagnostic accuracy and computational efficiency. Additionally, compared with other representative fault diagnosis methods, this model shows better anti-noise performance under different noise test data, and it provides a reliable and efficient reference solution for rotating machinery fault-classification tasks.

To investigate the combustion characteristics of multiple fire sources in the tunnel caused by ‘jumping’ discontinuous fire spread, we utilized scaled model experiments, numerical simulation software, and theoretical research. Our study focused on analyzing the influence of different fire source powers on the temperature characteristics of double fire sources in the tunnel. We examined the temperature characteristics, critical wind speed, and change rule under various wind speeds, fire source spacing, and fire source powers. Additionally, we explored the temperature characteristics, critical wind speed, and change rule of different fire source powers under varying wind speed conditions. The mathematical model for roof temperature decay and the temperature decay coefficients of dual source fires were established through the analysis of scale-down model experiments and numerical simulations. In comparison to single-source fires, the temperature variations in the tunnel of dual source fires exhibit a more intricate pattern, with higher average temperature and temperature peak values. These values are influenced by factors such as fire source spacing and power. Numerical simulation software was utilized to investigate the impact of fire source spacing at 10 m, 15 m, and 20 m, as well as the effect of varying fire source power on the temperature distribution within a tunnel under consistent fire source position and growth coefficient. The study revealed that, with consistent double fire source position and ventilation conditions in the tunnel, the upstream fire source exhibited greater power than the downstream fire source, resulting in the lowest average and peak temperatures in the tunnel. This observation could potentially enhance escape and rescue operations within the tunnel. Similarly, the lowest average and peak temperatures in the tunnel were also identified, offering potential benefits for optimizing escape and rescue strategies in tunnel scenarios.

With the emergence and development of application requirements such as data analysis and publishing, it is particularly important to use differential privacy protection technology to provide more reliable, secure, and compliant datasets for research in the field of children’s health. This paper focuses on the differential privacy protection of the ultrasound examination health dataset of adolescents in southern Texas from three aspects: differential privacy protection with output perturbation on basic statistics, publication of differential privacy marginal histogram and synthesized data, and a machine learning differential privacy learning algorithm. Firstly, differential privacy protection results with output perturbation show that Laplace and Gaussian mechanisms for numerical data, as well as the exponential mechanism for non-numerical data, can achieve the goal of protecting privacy. The exponential mechanism provides higher privacy protection. Secondly, a differential privacy marginal histogram with four attributes can be obtained with an appropriate privacy budget that approximates the marginal histogram of the original data. In order to publish synthetic data, we construct a synthetic query to obtain the corresponding differential privacy histogram for two attributes. Further, a synthetic dataset can be constructed by following the data distribution of the original dataset and the quality of the synthetic data publication can also be evaluated by the mean square error and error rate. Finally, consider a differential privacy logistic regression model under machine learning to predict whether children have fatty liver in binary classification tasks. The experimental results show that the model combined with quadratic perturbation has better accuracy and privacy protection. This paper can provide differential privacy protection models under different demands, which provides important data release and analysis options for data managers and research organizations, in addition to enriching the research on child health data releasing and mining.

Monkeypox virus (MPXV) can induce systemic skin lesions after infection. This research focused on studying MPXV proliferation and the response of keratinocytes. Using transmission electron microscopy (TEM), we visualized different stages of MPXV development in human immortalized keratinocytes (HaCaT). We identified exocytosis of enveloped viruses as the exit mechanism for MPXV in HaCaT cells. Infected keratinocytes showed submicroscopic changes, such as the formation of vesicle-like structures through the recombination of rough endoplasmic reticulum membranes and alterations in mitochondrial morphology. Transcriptome analysis revealed the suppressed genes related to interferon pathway activation and the reduced expression of antimicrobial peptides and chemokines, which may facilitate viral immune evasion. In addition, pathway enrichment analysis highlighted systemic lupus erythematosus pathway activation and the inhibition of the Toll-like receptor signaling and retinol metabolism pathways, providing insights into the mechanisms underlying MPXV-induced skin lesions. This study advances our understanding of MPXV’s interaction with keratinocytes and the complex mechanisms leading to skin lesions.

In multi-seam coal mining, the water accumulation in the goaf of the upper coal seam will seriously threaten the safety of the lower coal-seam recovery. How to accurately determine the water charging source in the goaf and predict the amount of water accumulation in the goaf after a certain time interval has become a major challenge that urgently needs to be solved in coal production. In this study, we consider the water-discharging goaf of the Tangjiahui Coal Mine as the object of research to investigate the problem of water accumulation in the goaf during the fully mechanized caving mining of extra-thick seams of top coal. We used geochemical methods, water-accumulation space methods, and large-well methods to analyze the hydraulic connections between goaf water and other aquifers, predict the amount of water accumulation in the goaf, and explore the characteristics of water level changes over time. We then used the results to discuss the relationship between the elevation of the accumulated water and the time taken for it to fill the goaf. The results showed that there is a hydraulic connection between the water in the airspace and the goaf water (GW), roof water (RW), floor water (FW) and Ordovician limestone water (OW); the volume of water in the goaf of the working face after mining was 2,106,838.496 m3. The average rate of water accumulation was 65.407 m3/h, and the goaf was expected to have been filled in 32,211.208 h. The derived relationship between the water level and time was H0=−10−12t3+10−7t2−0.0042t+814.61 (R2=0.9837). This study is of great significance for the sustainable development of the safety evaluation of water blocking coal pillars at the mine boundary.

Rapid wilting after harvest greatly decreases the ornamental and economic value of fresh-cut flowers. To determine how chlorine dioxide (ClO2) affects postharvest flower quality, Paeonia lactiflora ‘Hushui Dangxia’ cut flowers in bottles were treated with different concentrations of ClO2 (0, 25, 50, 75, and 100 mg L−1). Among the treatments, ClO2 75 (i.e., 75 mg L−1) decreased the bacterial growth and lignin content at the P. lactiflora flower stem base, while also decreasing the degree of flower stem vessel blockage. Additionally, the ClO2 75 treatment increased the relative fresh weight, water balance, soluble sugar content, soluble protein content, and antioxidant enzyme activities (superoxide dismutase, peroxidase, and catalase), but decreased the malondialdehyde content and ethylene release rate of P. lactiflora cut flowers. Thus, the aging of P. lactiflora flowers was delayed, thereby maintaining the cut flower quality. Furthermore, the vase life (i.e., ornamental period) increased by three days.

The “Qixiadaxiangshui” pear (Pyrus bretschneideri Rehd.1) is a highly valued cultivar known for its crisp texture, abundant juice, and rich aroma. In this study, we reported the first complete chloroplast genome sequence of the “Qixiadaxiangshui” pear, which is 159,885 bp in length with a GC content of 36.58%. The genome exhibits a typical circular quadripartite structure, comprising a large single-copy region (LSC), a small single-copy region (SSC), and a pair of inverted repeat regions (IRs). A total of 131 genes were identified, including 84 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. We also identified 209 simple sequence repeats (SSRs) and several mutation hotspots, such as ndhC-trnM-CAU and trnR-UCU-atpA, which can be applied in molecular identification and phylogenetic studies of Pyrus. Comparative genomic analysis showed high conservation among ten pear cultivars. Phylogenetic analysis indicated that the “Qixiadaxiangshui” pear is closely related to germplasm Dangshansuli, Wonwhang, and Yali, suggesting a recent common ancestor. These findings provided valuable insights into the genetic diversity and evolutionary dynamics of the Pyrus species and contribute to the conservation and breeding of pear germplasm resources.

The flame-retardant performance of carbon fiber-reinforced composites is crucial for ensuring structural stability. Traditional additive flame-retardant methods often struggle to balance structural integrity with fire resistance. Herein, Ni(OH)2 and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) were used as flame-retardant agents and mixed with glass fibers to construct the flame-retardant functional fiber veil which was used as the skin layer on the composite surface for fire protection. The structure performance and flame retardancy of composites were characterized via Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and a cone calorimeter test. The results confirmed that a flame-retardant glass fiber mat could effectively improve the flame-retardant and smoke-suppressive properties of the composite material. Due to the synergistic flame-retardant mechanism of Ni(OH)2 and DOPO, the C-N3-D2 composite with the highest LOI value of 32.3% has shown significant reduction in peak heat release rate (PHRR) and total smoke production (TSP) by 31.3% and 19.5%, respectively. In addition, due to flame-retardant agents only being employed in the skin layer of the composite, the core layer of a carbon fiber-reinforced structure could be protected without structure disruption. This approach maintained consistent interlayer shear strength, highlighting the effectiveness of using a flame-retardant fiber veil as a protective skin layer. This strategy could offer a viable solution for safeguarding high-performance composite materials from fire hazards without compromising their structural integrity.

The timely and accurate acquisition of information on the distribution of the crop planting structure in the Loess Plateau of eastern Gansu Province, one of the most important agricultural areas in Western China, is crucial for promoting fine management of agriculture and ensuring food security. This study uses multi-temporal high-resolution remote sensing images to determine optimal segmentation scales for various crops, employing the estimation of scale parameter 2 (ESP2) tool and the Ratio of Mean Absolute Deviation to Standard Deviation (RMAS) model. The Canny edge detection algorithm is then applied for multi-scale image segmentation. By incorporating crop phenological factors and using the L1-regularized logistic regression model, we optimized 39 spatial feature factors—including spectral, textural, geometric, and index features. Within a multi-level classification framework, the Random Forest (RF) classifier and Convolutional Neural Network (CNN) model are used to classify the cropping patterns in four test areas based on the multi-scale segmented images. The results indicate that integrating the Canny edge detection algorithm with the optimal segmentation scales calculated using the ESP2 tool and RMAS model produces crop parcels with more complete boundaries and better separability. Additionally, optimizing spatial features using the L1-regularized logistic regression model, combined with phenological information, enhances classification accuracy. Within the OBIC framework, the RF classifier achieves higher accuracy in classifying cropping patterns. The overall classification accuracies for the four test areas are 91.93%, 94.92%, 89.37%, and 90.68%, respectively. This paper introduced crop phenological factors, effectively improving the extraction precision of the shattered agricultural planting structure in the Loess Plateau of eastern Gansu Province. Its findings have important application value in crop monitoring, management, food security and other related fields.

Abstract Tislelizumab, an anti‐programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first‐in‐human, dose‐finding BGB‐A317‐001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5–10 mg/kg every 2 weeks (q2w), 2–5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to dose modification/discontinuation, immune‐mediated AEs, and infusion‐related reactions) were generally comparable across the dosing range examined. These results, alongside the convenience of a fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing regimen for further clinical use. Pooled exposure–response (E–R) analyses by logistic regression using data from study BGB‐A317‐001 (DCO: August 2020) and three additional phase I/II studies (DCOs: 2018–2020) showed no statistically significant correlation between tislelizumab pharmacokinetic exposure and ORR across multiple solid tumor types or classical Hodgkin's lymphoma, nor was exposure associated with any of the safety end points evaluated over the dose range tested. Hence, tislelizumab showed a relatively flat E–R relationship. Overall, the totality of data, including efficacy, safety, and E–R analyses, together with the relative convenience of a fixed q3w dose, provided clinical rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for multiple cancer indications.

The high momentum tail (HMT) of nucleons, as a signature of the short-range correlations in nuclei, has been investigated by the high-energy bremsstrahlung γ rays produced in 86Kr+124Sn at 25 MeV/nucleon. The energetic photons are measured by a CsI(Tl) hodoscope mounted on the spectrometer CSHINE. The energy spectrum ≥35 MeV can be reproduced by the Isospin- and Momentum-Dependent Boltzmann-Uehling-Uhlenbeck model calculations incorporating the photon production channel from np process in which the HMTs of nucleons is considered. A non-zero HMT ratio of about 15% is favored by the data. The effect of the capture channel np→dγ is demonstrated.

In this study, we analyzed GATA2 mutations (GATA2mut) and co-mutations in 166 Chinese patients with cytogenetically normal acute myeloid leukemia. This was done through targeted next-generation sequencing of 34 genes associated with myeloid leukemia. GATA2mut was identified in 17 (10%) patients being significantly correlated with co-mutations in CCAAT/enhancer-binding protein alpha (CEBPA) double mutation (P = 0.001). We observed that the N-terminal zinc finger domain (ZF1) was linked to CEBPA mutations, while the C-terminal zinc finger domain (ZF2) was associated with Wilms' tumor 1 (WT1) mutations. It was also noted that patients with GATA2mut had lower platelet counts at diagnosis (P = 0.032). In the entire cohort, GATA2mut had no significant prognostic impact on overall survival (OS) (P = 0.762) and relapse-free survival (RFS) (P = 0.369) compared to patients with GATA2wt. The OS (P = 0.737) and RFS (P = 0.894) of the ZF1 mutation were similar to those of the ZF2 mutation. Most patients with GATA2 mutations were classified in the ELN2022 favorable- and intermediate-risk groups. GATA2mut patients in the favorable-risk group were divided into GATA2High and GATA2Low groups using a median cutoff variant allele frequency (VAF) of 40.13%. GATA2High patients were associated with worse OS (P = 0.031) and RFS (P = 0.021) than GATA2Low patients. In the intermediate-risk group, the high median VAF of GATA2 (≥38.51%) had no significant effect in OS and RFS compared with the low median VAF (

Abstract Background Inflammatory response of central nervous system is an important component mechanism in the bladder pain of interstitial cystitis/bladder pain syndrome (IC/BPS). Exosomes transfer with microRNAs (miRNA) from mesenchymal stem cell (MSCs) might inhibit inflammatory injury of the central nervous system. Herein, the purpose of our study was to explore the therapeutic effects by which extracellular vesicles （EVs） derived from miR‐9‐edreched MSCs in IC/BPS and further investigate the potential mechanism to attenuate neuroinflammation. Methods On the basis of IC/BPS model, we used various techniques including bioinformatics, cell and molecular biology, and experimental zoology, to elucidate the role and molecular mechanism of TLR4 in regulating the activation of NLRP3 inflammasome in bladder pain of IC/BPS, and investigate the mechanism and feasibility of MSC‐EVs enriched with miR‐9 in the treatment of bladder pain of IC/BPS. Results The inflammatory responses in systemic and central derived by TLR4 activation were closely related to the cystitis‐induced pelvic/bladder nociception in IC/BPS model. Intrathecal injection of miR‐9‐enreched MSCs derived exosomes were effective in the treatment of cystitis‐induced pelvic/bladder nociception by inhibiting TLR4/NF‑κb/NLRP3 signal pathway in central nervous system of IC/BPS mice. Conclusions This study demonstrated that miR‐9‐enreched MSCs derived exosomes alleviate neuroinflammaiton and cystitis‐induced bladder pain by inhibiting TLR4/NF‑κb/NLRP3 signal pathway in interstitial cystitis mice, which is a promising strategy against cystitis‐induced bladder pain.

Abstract Pitolisant, a novel histamine H3‐receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was associated with deaths during clinical trials, has propelled it into the spotlight of widespread societal attention on April 3, 2023. Till now, the clinical safety of pitolisant remains a heatedly debated topic. This study aimed to offer a comprehensive assessment of the safety profile of pitolisant in real‐world clinical settings. Adverse event reports where pitolisant was the primary suspect drug were extracted from the FDA Adverse Event Reporting System database. The clinical characteristics and concomitant drugs of the pitolisant‐associated adverse events were analyzed. The potential adverse event signals of pitolisant were explored using four disproportionality analysis methods. Furthermore, the difference in pitolisant‐associated adverse event signals was investigated concerning sex, age, weight, and dose. A total of 526 reports and 1695 adverse events with pitolisant as the primary suspected drug were identified. The most significant adverse event signals were generally mild and of short duration. The concomitant drugs of pitolisant were highly intricate, mainly included drugs for treating narcolepsy as well as antidepressants. Seven new significant adverse event signals emerged. The safety profile of pitolisant exhibited no significant differences across age and dose groups, although slight variations were observed in relation to sex and weight. The findings from reports of death and life‐threatening outcomes underscore the importance of enhanced monitoring for cardiac and respiratory adverse reactions when utilizing pitolisant. This study provided a broader understanding of the safety profile of pitolisant.

Promoting the social integration of rural migrants is key to improving the mechanism of rural-urban integration and development. This study utilizes the 2017 China Migrants Dynamic Survey and matched urban macro data to systematically explore the impact of homesteads on the social integration of rural migrants. Research has shown that social integration of rural migrants will be inhibited if they own homesteads. Simultaneously, the degree of inhibition varies according to the individual characteristics of rural migrants, the region to which they belong, and other factors. Specifically, when rural migrants aged 18 to 50 own homesteads, their degree of social integration into the cities they move into will be low. At the same time, for rural migrants in the central region, homestead ownership will not affect their degree of social integration. In addition, the mechanism analysis shows that increased housing expenditure inhibits rural migrants' willingness to integrate. Meanwhile, owning contracted land and owning a house in the city also affect the degree of social integration of rural migrants to a certain extent. The findings of this study can broaden research on the effects of land on the free movement of population factors. In the meantime, it provides theoretical references for improving the level of social integration of migrants, enhancing people's well-being, and improving the mechanism of urban-rural integration and development.

When evaluating an area's seismic risk or resilience, it is necessary to use the spatial correlation to analyze the ground motion parameters of multiple sites together in an earthquake. These two large earthquakes in Türkiye provided the possibility for spatial correlation analysis of ground motion intensity measurements in this area. Based on the strong motion records provided by The Disaster and Emergency Management Authority of Türkiye (AFAD), this study uses the local ground motion prediction equation ​in Türkiye to give spatial correlation analysis of Intensity Measurements. This study gives an exponential model based on a semivariogram and compares it with the correlation model obtained from previous studies.

BackgroundIt has been discovered that Janus kinase 2 (JAK2) exon12 mutations lead to the polycythemia vera (PV) phenotype, while somatic mutations of calreticulin (CALR) are associated with essential thrombocythemia (ET) or primary myelofibrosis. In this article, we report a case of ET with coexistence of JAK2 exon12 and CALR mutations. The objective of this study was to elucidate the pathogenicity mechanism of a JAK2 exon12 mutation (JAK2N533S) and the role of the coexistence of mutations on the hematological phenotype.MethodsWe designed a colony analysis of tumor cells obtained from this patient, and attempted to identify mutant genes using DNA from hair follicles. Mutation impairment prediction and conservative analysis were conducted to predict the mutation impairment and structure of JAK2N533S. In addition, we conducted a functional analysis of JAK2N533S by constructing Ba/F3 cell models.ResultsThree distinct tumor subclones, namely JAK2N533Shet+/CALRtype1het+, JAK2N533Shet+/CALRwt, and JAK2N533Shet+/CALRtype1hom+, were identified from the 17 selected erythroid and 21 selected granulocyte colonies. The analysis of hair follicles yielded positive results for JAK2N533S. According to the bioinformatics analysis, JAK2N533S may exert only a minor effect on protein function. Functional studies showed that JAK2N533S did not have a significant effect on the proliferation of Ba/F3 cells in the absence of interleukin-3 (IL-3), similar to wild-type JAK2. Notably, there were no increased phosphorylation levels of JAK2-downstream signaling proteins, including signal transducer and activator of transcription 3 (STAT3) and STAT5, in Ba/F3 cells harboring the JAK2N533S.ConclusionOur study revealed that the JAK2N533Shet+/CALRtype1het+ subclone was linked to a significant expansion advantage in this patient, indicating that it may contribute to the development of the ET phenotype. We further demonstrated that JAK2N533S, as a noncanonical JAK2 exon12 mutation, is a germline mutation that may not exert an effect on cell proliferation and protein function. These results and the present body of available data imply that certain noncanonical JAK2 mutations are not gain-of-function mutations leading to the development of myeloproliferative neoplasms.

Objective: To evaluate a ring wearable’s accuracy in the measurement of oxyhemoglobin saturation measured by pulse oximeter (SpO2) compared to a simultaneous SaO2 obtained from arterial blood gases (ABGs) because oximeters may overestimate oxyhemoglobin saturation in darkly pigmented individuals resulting in occult hypoxemia. Patients and Methods: Circul+ (Bodimetrics), with a form factor of a ring, measures several variables for cardiorespiratory assessment (SpO2, movement, and heart rate). The design ensures that measurements are made on the palmar surface of the digit, where there is generally less pigment. Twenty-four healthy participants (8 Black, 16 non-Black) had catheters inserted into their radial arteries during the timeframe between August 2020 and January 2022. They were administered nitrogen-rich air that made them hypoxic in steps to an SaO2 of 70%. ABGs was sampled at various levels of hypoxia, and simultaneous readings were obtained from the Circul+. We compared SpO2 from Circul with measurement of ABGs by a medical grade blood gas analyzer. Results: There was excellent correlation between SaO2 measured by the ring oximeter and ABGs in both Black (y = 1.0174x − 1.573; R2 = 0.9414) and Non-Black (y = 1.0209x − 2.5607; R2 = 0.9207) participants. No differences were found in comparing the intercept and slopes of the regressions. At ABG of 70% and 100%, the SaO2 measured by the ring was calculated to be 69.6% and 100.2% for the Black participants and 68.9% and 99.5% for the non-Black participants. Bland-Altman analysis found a bias (deviation from the mean) of 0.0 for the Black participants and −0.7% for the non-Black participants. Conclusion: Results from this study confirmed that Circul+ oximetry accuracy seems to be independent of skin tone, perhaps because measurements are made on the palmar surface of the digit, where there is generally less pigment.

Abstract Background This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. Methods Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. Results A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P

Abstract In order to comprehend the dynamic disaster mechanism induced by overburden rock caving during the advancement of a coal mining face, a physical simulation model is constructed basing on the geological condition of the 21221 mining face at Qianqiu coal mine in Henan Province, China. This study established, a comprehensive monitoring system to investigate the interrelations and evolutionary characteristics among multiple mechanical parameters, including mining-induced stress, displacement, temperature, and acoustic emission events during overburden rock caving. It is suggested that, despite the uniformity of the overburden rock caving interval, the main characteristic of overburden rock lies in its uneven caving strength. The mining-induced stress exhibits a reasonable interrelation with the displacement, temperature, and acoustic emission events of the rock strata. With the advancement of the coal seam, the mining-induced stress undergoes four successive stages: gentle stability, gradual accumulation, high-level mutation, and a return to stability. The variations in other mechanical parameters does not synchronize with the significant changes in mining-induced stress. Before the collapse of overburden rock occurs, rock strata temperature increment decreases and the acoustic emission ringing counts surges with the increase of rock strata displacement and mining-induced stress. Therefore, the collaborative characteristics of mining-induced stress, displacement, temperature, and acoustic emission ringing counts can be identified as the precursor information or overburden rock caving. These results are in good consistent with on-site situation in the coal mine.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant gastrointestinal cancer with a 5-year survival rate of only 9%. Of PDAC patients, 15%-20% are eligible for radical surgery. Gemcitabine is an important chemotherapeutic agent for patients with PDAC; however, the efficacy of gemcitabine is limited due to resistance. Therefore, reducing gemcitabine resistance is essential for improving survival of patients with PDAC. Identifying the key target that determines gemcitabine resistance in PDAC and reversing gemcitabine resistance using target inhibitors in combination with gemcitabine are crucial steps in the quest to improve survival prognosis in patients with PDAC. Methods: We constructed a human genome-wide CRISPRa/dCas 9 overexpression library in PDAC cell lines to screen key targets of drug resistance based on sgRNA abundance and enrichment. Then, co-IP, ChIP, ChIP-seq, transcriptome sequencing, and qPCR were used to determine the specific mechanism by which phospholipase D1 (PLD1) confers resistance to gemcitabine. Results: PLD1 combines with nucleophosmin 1 (NPM1) and triggers NPM1 nuclear translocation, where NPM1 acts as a transcription factor to upregulate interleukin 7 receptor (IL7R) expression. Upon interleukin 7 (IL-7) binding, IL7R activates the JAK1/STAT5 signaling pathway to increase the expression of the anti-apoptotic protein, BCL-2, and induce gemcitabine resistance. The PLD1 inhibitor, Vu0155069, targets PLD1 to induce apoptosis in gemcitabine-resistant PDAC cells. Conclusions: PLD1 is an enzyme that has a critical role in PDAC-associated gemcitabine resistance through a non-enzymatic interaction with NPM1, further promoting the downstream JAK1/STAT5/Bcl-2 pathway. Inhibiting any of the participants of this pathway can increase gemcitabine sensitivity.

Reliance on agriculture for food security is a constant in all modern societies. Global climate change and population growth have put immense pressure on sustainable agriculture, exacerbating the effects of environmental stresses. Drought is one of the most pressing abiotic stresses that farmers face, presenting an annual threat to crop growth and yield. Crops have evolved extensive morphological, physiological, and molecular mechanisms to combat drought stress. Drought resistance is a polygenic trait, controlled by a complex genetic network and an array of genes working together to ensure plant survival. Many studies have aimed at dissecting the genetic mechanisms underlying drought resistance. Recent studies using linkage and association mapping have made progress in identifying genetic variations that affect drought-resistance traits. These loci may potentially be engineered by genetic transformation and genome editing aimed at developing new, stress-resistant crop cultivars. Here we summarize recent progress in elucidating the genetic basis of crop drought resistance. Molecular-breeding technologies such as marker-assisted selection, genome selection, gene transformation, and genome editing are currently employed to develop drought-resistant germplasm in a variety of crops. Recent advances in basic research and crop biotechnology covered in this review will facilitate delivery of drought-resistant crops with unprecedented efficiency.

Abstract Electro-optic modulators are key components in data communication, microwave photonics, and quantum photonics. Modulation bandwidth, energy efficiency, and device dimension are crucial metrics of modulators. Here, we provide an important direction for the miniaturization of electro-optic modulators by reporting on ultracompact topological modulators. A topological interface state in a one-dimensional lattice is implemented on a thin-film lithium-niobate integrated platform. Due to the strong optical confinement of the interface state and the peaking enhancement of the electro-optic response, a topological cavity with a size of 1.6 × 140 μm2 enables a large modulation bandwidth of 104 GHz. The first topological modulator exhibits the most compact device size compared to reported LN modulators with bandwidths above 28 GHz, to the best of our knowledge. 100 Gb/s non-return-to-zero and 100 Gb/s four-level pulse amplitude modulation signals are generated. The switching energy is 5.4 fJ/bit, owing to the small electro-optic mode volume and low capacitance. The topological modulator accelerates the response time of topological photonic devices from the microsecond order to the picosecond order and provides an essential foundation for the implementation of large-scale lithium-niobate photonic integrated circuits.

The frequent occurrence of coal burst in coal mines is closely related to the destabilization of complex geological formations, and the fault as a typical geological structure is an important factor in inducing dynamic coal burst disaster. In this study, the distribution function solutions of displacement and energy fields characterizing fault sliding were derived. Under the engineering background of geological structure of the Yima mine area in Henan Province and the mining face 21221 of the Qianqiu coal mine, a physical model to simulate the mining process and fault sliding of the mining face was built. The multi-parameter evolution law of displacement, energy, and temperature of the overburden rock strata and fault area were monitored, and the mutation effect of fault and overburden rock strata instability was investigated. In addition, the mechanical mechanism of the association and coupling of overburden rock strata movement and fault slip instability caused by mining disturbance was discussed. The results show that the frequency of extreme value points of stress, displacement, and energy parameters on the fault surface under the mining disturbance presents a dense to sparse distribution from top to bottom along the vertical direction of the fault. In the meantime, the upper part of the fault surface in a non-stable state is more susceptible to the influence of mining than the lower part, which is the main power source of fault sliding. Fault sliding is a top-to-bottom, local-to-whole, low-energy followed by high-energy, gradually accelerated and discontinuous dynamic destabilization process, which is accompanied by three strain energy states of low-energy stability, gradual accumulation, and high-energy activation. The maximum strain energy increment appears in the upper part of the fault surface, and the massive release of strain energy will accelerate the top-to-bottom destabilization of the fault slip. During the sliding process of the fault surface, the temperature also shows the characteristics of stepwise increase, which is manifested as the constant temperature stage during the small disturbance, the local rising stage caused by the stress accumulation, and the global temperature surge stage caused by the sliding instability. The nonlinear and discontinuous dynamic instability of the fault is closely related to the movement and collapse of the overlying rock layer on the working face. The mutation effect of the coupled instability of the fault and overburden rock strata was studied based on the correlated coupling response between the movement of overburden rock strata and the fault sliding during the mining disturbance. It is manifested by the sudden increase of the overburden rock strata pressure near the fault, the drastic change of the stress on the fault surface, the accelerated change of the fault displacement and its development to the lower part, the large and frequent fluctuation of the strain energy, and the order increment of the temperature field. The studies indicate that the overburden rock strata collapse imposes impact loads on the unsteady slip of the fault, and the fault serious slip instability caused by the strain energy sudden release will also bring a secondary violent impact to the deformed and damaged overburden rock strata and cause a large area collapse. The resulting unloading effect provides additional space for the fault to move into the region, which further accelerates the slip instability of fault and the collapse of overburden rock strata, and easily induces coal burst disaster.

Abstract The neutron capture cross section of $$ ^{181} $$ 181 Ta is relevant to s-process of nuclear astrophysics, extraterrestrial samples analysis in planetary geology and new generation nuclear energy system design. The $$^{181}$$ 181 Ta( $$n,\gamma $$ n , γ ) cross section had been measured between 1 eV and 800 keV at the back-streaming white neutron facility (Back-n) of China spallation neutron source(CSNS) using the time-of-flight (TOF) technique and $$\hbox {C}_{6}\,\hbox {D}_{6}$$ C 6 D 6 liquid scintillator detectors. The experimental results are compared with the data of several evaluated libraries and previous experiments in the resolved and unresolved resonance region. Resonance parameters are extracted using the R-Matrix code SAMMY in the 1–700 eV region. The astrophysical Maxwell average cross section(MACS) from kT = 5 to 100 keV is calculated over a sufficiently wide range of neutron energies. For the characteristic thermal energy of an astrophysical site, at kT = 30keV the MACS value of $$^{181}$$ 181 Ta is 834 ± 75 mb, which shows an obvious discrepancy with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS) recommended value 766 ± 15 mb. The new measurements strongly constrain the MACS of $$^{181}$$ 181 Ta( $$n,\gamma $$ n , γ ) reaction in the stellar s-process temperatures.

Abstract Background Excessive production of androgen drives oxidative stress (OS) and inflammasome activation in ovarian granulosa cells (GCs). Therefore, the induced follicular developmental disorder is the major cause of infertility in women with polycystic ovary syndrome (PCOS). Exercise-induced upregulation of irisin is capable of regulating metabolism by reducing OS and inflammation. Exercise has been shown to alleviate a range of PCOS symptoms, including maintaining a normal menstrual cycle, in several clinical trials. Methods Female Sprague–Dawley (SD) rats and primary ovarian cells were treated with two different androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), to simulate a hyperandrogenic environment, followed by eight weeks of exercise training and irisin intervention. The levels of reactive oxygen species (ROS), tissue inflammation and fibrosis were examined using hematoxylin and eosin (H&E) staining, western blot, quantitative real-time PCR (qRT-PCR), dichlorofluorescein diacetate (DCF-DA) probe detection, immunofluorescence staining, immunohistochemistry, and Sirius red staining. Results Exercise for eight weeks improved polycystic ovarian morphology and decreased the levels of inflammation, OS, and fibrosis in PCOS rats. Hyperandrogen increased ROS production in ovarian cells by inducing endoplasmic reticulum stress (ERS) and activating the inositol-requiring enzyme 1α (IRE1α)-thioredoxin-interacting protein (TXNIP)/ROS-NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway, further enhancing the levels of inflammation. Irisin suppressed the expression of IRE1α and its downstream targets, thus improving the ovarian dysfunction of PCOS rats induced by hyperandrogen. Conclusion Exercise can alleviate various phenotypes of PCOS rats induced by DHEA, and its therapeutic effect may be mediated by secreting beneficial myokines. IRE1α may be an important target of irisin for reducing OS and inflammation, thereby improving ovarian fibrosis.

Abstract VEGF inhibitors are one of the most successful antiangiogenic drugs in the treatment of many solid tumors. Nevertheless, pancreatic adenocarcinoma (PAAD) cells can reinstate tumor angiogenesis via activation of VEGF-independent pathways, thereby conferring resistance to VEGF inhibitors. Bioinformatic analysis showed that BICC1 was one of the top genes involved in the specific angiogenesis process of PAAD. The analysis of our own cohort confirmed that BICC1 was overexpressed in human PAAD tissues and was correlated to increased microvessel density and tumor growth, and worse prognosis. In cells and mice with xenograft tumors, BICC1 facilitated angiogenesis in pancreatic cancer in a VEGF-independent manner. Mechanistically, as an RNA binding protein, BICC1 bounds to the 3’UTR of Lipocalin-2 (LCN2) mRNA and post-transcriptionally up-regulated LCN2 expression in PAAD cells. When its level is elevated, LCN2 binds to its receptor 24p3R, which directly phosphorylates JAK2 and activates JAK2/STAT3 signal, leading to increased production of an angiogenic factor CXCL1. Blocking of the BICC1/LCN2 signalling reduced the microvessel density and tumor volume of PAAD cell grafts in mice, and increased the tumor suppressive effect of gemcitabine. In conclusion, BICC1 plays a pivotal role in the process of VEGF-independent angiogenesis in pancreatic cancer, leading to resistance to VEGF inhibitors. BICC1/LCN2 signaling may serve as a promising anti-angiogenic therapeutic target for pancreatic cancer patients.

Due to its good biocompatibility and compatible hardness with human bones, magnesium (Mg) alloy is considered as a promising material for bone nails and implants. However, Mg and its alloys are characteristics of active chemical properties and high corrosion rate, which is detrimental to the recovery of patients implanted with Mg alloy bone scaffold. In the present work, to retard the corrosion of the Mg alloy, calcium glycerophosphate (C3H7CaO6P•H2O) was added in the electrolyte to form the micro-arc oxidation (MAO) coatings. Various experimental techniques such as XRD, SEM and EDS have been used to characterize the surface morphology and phase composition of MAO coatings. MAO coatings of different CaP content were studied to explore the synergetic effect between the biocompatibility and corrosive properties by means of electrochemical measurements, hemolysis and pyrogen test. The results showed that higher CaP content can improve the biocompatibility and corrosion resistance while decelerating the hemolysis rate.

To investigate resistance change in the fire area of a roadway caused by roadway fires, a mathematical calculation model for thermal resistance is developed. Theoretical research is conducted to analyze the factors influencing resistance change through theoretical derivation, revealing that temperature is a key factor contributing to the change in thermal resistance. By leveraging the correlation between changes in CO concentration and temperature on the downwind side of the roadway within the fire zone, researchers developed mathematical models to predict temperature increases at various points downwind of the fire source. These models were then used to determine the mathematical relationship governing the change in thermal resistance. The accuracy of the numerical simulation software was validated using Fluent numerical simulation software and scaled-down model experiments. Full-scale numerical simulation experiments were conducted to investigate the fire characteristics of roadway fires and validate the thermal resistance mathematical model. The results indicate that the thermal resistance in the numerical simulation is 7.55 Pa at 20m from the fire source and 5.54 Pa at the end of the roadway. The decrease in resistance is linear. The minimum error between the thermal resistance calculated by the mathematical model and the gradient of the pressure drop in the numerical simulation is 0.03 Pa, approximately 2.3%. Furthermore, the fitting degree of the pressure drop in each section is as high as 97.7%. The calculation model demonstrates high accuracy and offers a theoretical foundation for investigating fire resistance in tunnel fire.

The oasis serves as the primary supply of cultivable land, along with the hub for human production and habitation in Xinjiang. Accordingly, predicting the land use of these areas based on various goals is an effective instrument for encouraging the sensible distribution of resource space. The study investigated the creation of a land use-allocation optimization model based on the various objectives of ecological protection, food security, and urban growth using the Weigan–Kuche River oasis as an example. The GMOP-PLUS model’s restriction conversion area was adjusted to include the findings of the land suitability evaluation. Additionally, it optimized and simulated the spatial arrangement and quantitative structure of land usage in the Weigan–Kuche River oasis in 2035. The results indicate the following: (1) the model’s overall accuracy is 89.36%, and its Kappa coefficient is 0.872, more than 0.8. Thus, the model can be considered for adoption in the future when predicting changes in land use in the districts and counties of the Weigan–Kuche River oasis; (2) based on the results of the land suitability evaluation, the percentage of areas that are most suited for agricultural development, urban development, and ecological protection is 39.32%, 24.21%, and 14.06%, respectively; and (3) the three scenarios satisfy the various demands for growth within the oasis, and the land use structure of the oasis varies considerably in response to the various development objectives, with the construction and cultivated land undergoing the most substantial modifications. The multi-scenario simulation of land usage in the oasis can provide essential support and a range of perspectives for future land spatial planning and socioeconomic development decision-making in the Weigan–Kuche River oasis. This is essential for both the efficient use of land resources and sustainable development.

Understanding the dynamics of ecosystem services (ESs) in arid landscapes and socio-ecological systems is crucial for sustainable development and human well-being. This study uses the Invest model to quantify the spatio-temporal changes in four key ecosystems services in Altay from 1990 to 2020: water yield (water yield), carbon stock (carbon stock), soil retention (soil retention), and habitat quality (habitat quality). The trade-offs/synergies between different ESs were investigated via Spearman’s correlation analysis. Ecosystem service bundles (ESBs) were mapped using self-organizing mapping (SOM), and the key drivers of ES relationships and the spatio-temporal dynamics of ESBs were revealed through redundancy analysis. The results showed that water yield increased by 33.7% and soil retention increased by 1.2%, while carbon stock and habitat quality decreased by 3.5% and 1.24%, respectively. The spatial distribution pattern had a clear zonal pattern, with the northern mountainous areas higher than the southern desert areas. The six pairs of ESs, in general, showed mainly low trade-off and high synergistic relationships, with trade-offs between water yield and carbon stock, soil retention and habitat quality, and a decreasing trend of trade-offs over time. Four types of ESBs were distinguished, and the compositional differences and spatial distribution within each ESB were determined by interactions between ESs and landscape types. There are complex non-linear relationships between the drivers and the four ESBs in different years. Before 2010, ecological factors were the key drivers influencing the spatio-temporal changes in ESBs, whereas social and environmental factors combined to drive changes in ESB allocations after 2010. Additionally, this study found that the implementation of conservation measures, such as reforestation and sustainable land management practices, positively influenced the provision of ecosystem services in the Altay region. These findings underscore the importance of integrating conservation efforts into land use planning and decision-making processes to ensure the sustainable delivery of ecosystem services in arid landscapes.

Land-use conflicts (LUCs) are pivotal in assessing human–land interaction, reflecting the intricate interplay between natural and anthropogenic drivers. However, existing studies often overlook nuanced non-linear responses and critical threshold recognition, focusing solely on linear correlations between isolated factors and LUCs. This study, situated in Xinjiang, China’s arid and semiarid region, introduces a novel analytical framework and threshold application model for LUCs. Integrating land-use and socioeconomic data, we quantified LUCs using Fragstats, correlation analysis, and restricted cubic spline (RCS) regression. Exploring non-linear dynamics between LUCs and 14 potential drivers, including natural and anthropogenic factors, we identified critical thresholds. LUC zones were delineated using a four-quadrant method, allowing tailored mitigation strategies. Our findings reveal Xinjiang’s distinct LUC spatial pattern, with intense conflicts surrounding mountainous areas and milder conflicts in basin regions, showing marked diminishment from 2000 to 2020. RCS effectively identifies LUC thresholds, indicating persisting severity pre- or post-specific thresholds. Xinjiang’s LUCs are categorized into key control areas, urgent regulation zones, elastic development territories, and moderate optimization regions, each with significant regional disparities. Tailored optimization suggestions mitigate linear analysis limitations, providing a fresh perspective on land zoning optimization. This research supports comprehensive land management and planning in Xinjiang, China.

Wheat powdery mildew is a fungal disorder caused by Blumeria graminis f. sp. tritici (Bgt) and is a severe and significant threat to the yield and quality of its host. The most practical and environmentally friendly approach to controlling this disease is through resistance gene identification to develop resistant varieties. Wild germplasm relatives of wheat are a valuable reservoir of genes contributing to resistance against powdery mildew. In our study, we identified the Aegilops tauschii germplasm “KU-2013”, exhibiting seedling resistance to Bgt isolate E09 following hexaploidization. Genetic analysis and chromosomal localization of the powdery mildew resistance gene in doubled haploid (DH) KU-2013 indicated that the disease resistance gene in DHKU-2013 is governed by a dominant gene situated in 5DS, tentatively named PmKu-2013. Following the analysis of PmKu-2013 relative to the genes at the Pm2 locus, it was inferred that PmKu-2013 represented a distinct novel gene separate from Pm2. Using molecular marker analysis, PmKu-2013 was found to be ultimately mapped between the sdau5DS5-3 and sdau5DS6-1 markers, with genetic distances of 0.6 cM and 1.3 cM, respectively. Using markers tightly linked to PmKu-2013, the genotypes of core wheat varieties from various regions were identified, laying the foundation for the transfer and utilization of PmKu-2013 in molecular-assisted selection (MAS) for breeding.

The ductility of FRP-reinforced concrete structures is reduced by the brittleness of FRP bars. To address this issue, this study employs the hybrid reinforcement of stainless steel (SS) and GFRP bars to enhance the ductility of concrete columns. A total of 21 axially compressed seawater and sea sand concrete (SWSSC) circular columns are fabricated, including 15 hybrid GFRP and SS bar-reinforced SWSSC (GFRP-SS-SWSSC) columns, 3 GFRP bar-reinforced SWSSC (GFRP-SWSSC) columns, and 3 SS bar-reinforced SWSSC (SS-SWSSC) columns. The test results are analyzed in terms of failure mode, load–axial displacement curve, bearing capacity, and ductility. Results show that GFRP-SWSSC columns suffer brittle failure, while GFRP-SS-SWSSC columns and SS-SWSSC columns demonstrate ductile failure characteristics. Furthermore, the hybrid reinforcement contributes to an improvement in the bearing capacity of the columns. A calculation equation for the bearing capacity of axially compressed columns was established, providing reasonable predictions of bearing capacities, with a design compressive strain of 2000 με for GFRP bars. It was found that hybrid reinforcement enhanced the ductility of GFRP-SWSSC columns. In addition, when the percentage of the SS reinforcement ratio reaches 50%, the ductility indexes of the GFRP-SS-SWSSC columns closely approach those of the SS-SWSSC columns.

Phosphonates are a class of organic phosphorus (P) compounds that contribute ~25% of dissolved organic P. Recent studies reveal the important role of phosphonates mediated by prokaryotes in the marine P redox cycle. However, its bioavailability by eukaryotic phytoplankton is under debate. 2-Aminoethylphosphonic acid (2-AEP) and 2-amino-3-phosphonopropionic acid (2-AP3) are two biogenic phosphonates in the marine environment. Here, Thalassiosira pseudonana, a common diatom species in the ocean, is able to recover growth from P starvation when provided with 2-AEP and 2-AP3. Moreover, 2-AEP cultures exhibited a more similar growth rate at 12 °C than at 25 °C when compared with inorganic P cultures. The cellular stoichiometry of 2-AEP groups was further determined, the values of which are in-between the P-depleted and DIP-replete cultures. This study provides evidence that biogenic phosphonates could be adopted as alternative P sources to support diatom growth and may provide physiological adaptation.

Objective Studies discussed few risk factors for specific patients, such as duration of disease; or surgical factors, such as duration and time of surgery; or C3 or C7 involvement, which could have led to the formation of hematomas (HTs). To investigate the incidence, risk factors especially the factors mentioned above, and management of postoperative HTs following anterior cervical decompression and fusion (ACF) for degenerative cervical diseases. Methods Medical records of 1,150 patients who underwent ACF for degenerative cervical diseases at our hospital between 2013 and 2019 were identified and reviewed. Patients were categorized into the HT group (HT group) or normal group (no-HT group). Demographic, surgical and radiographic data were recorded prospectively to identify risk factors for HT. Results Postoperative HT was identified in 11 patients, with an incidence rate of 1.0% (11 of 1,150). HT occurred within 24 hours postoperatively in 5 patients (45.5%), while it occurred at an average of 4 days postoperatively in 6 patients (54.5%). Eight patients (72.7%) underwent HT evacuation; all patients were successfully treated and discharged. Smoking history (odds ratio [OR], 5.193; 95% confidence interval [CI], 1.058–25.493; p = 0.042), preoperative thrombin time (TT) value (OR, 1.643; 95% CI, 1.104–2.446; p = 0.014) and antiplatelet therapy (OR, 15.070; 95% CI, 2.663–85.274; p = 0.002) were independent risk factors for HT. Patients with postoperative HT had longer days of first-degree/intensive nursing (p < 0.001) and greater hospitalization costs (p = 0.038). Conclusion Smoking history, preoperative TT value and antiplatelet therapy were independent risk factors for postoperative HT following ACF. High-risk patients should be closely monitored through the perioperative period. Postoperative HT in ACF was associated with longer days of first-degree/intensive nursing and more hospitalization costs.

Abstract Aims To investigate the mechanism of exosomes' role in the transformation of MDS to AML. Methods Exosomes in culture supernatants of MDS and AML cell lines, were extracted by ultrafiltration and identified in three ways: morphology, size, and exosome protein surface markers. Exosomes from AML cell lines were then co-cultured with MDS cell lines and their impacts on MDS cell microenvironment, proliferation, differentiation, cell cycle, and apoptosis were analyzed by CCK-8 assay and flow cytometry. Furthermore, exosomes from MSC were extracted for further authentication. Results The transmission electron microscopy, nanoparticle tracking analysis, Western blotting, and flow cytometry methods all verify that ultrafiltration is a reliable method to extract exosomes in the culture medium. Exosomes from AML cell lines inhibit the proliferation of MDS cell lines, block cell cycle progression, and promote apoptosis and cell differentiation. It also leads to increased secretion of tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) in MDS cell lines. In addition, MSC-derived exosomes were found to inhibit the proliferation of MDS cell lines, arrest cell cycle progression, promote apoptosis, and inhibit differentiation. Conclusion Ultrafiltration is a proper methodology in extracting exosomes. The exosomes of AML origin and MSC origin may play a role in MDS leukemia transformation via targeting TNF-α/ROS-Caspase3 pathway.

Fhb7 is a major gene that was transferred from Thinopyrum ponticum to chromosome 7D of wheat (Triticum aestivum) and confers resistance to both Fusarium head blight (FHB) and Fusarium crown rot (FCR). However, Fhb7 is tightly linked to the PSY-E2 gene, which causes yellow flour, limiting its application in breeding. To break this linkage, marker K-PSY was developed for tagging PSY-E2 and used with Fhb7 markers to identify recombination between the two genes. Screening 21,000 BC1F2 backcross progeny (Chinese Spring ph1bph1b*2/SDAU 2028) revealed two Fhb7+ wheat-Tp7el2L lines, Shannong 2–16 and Shannong 16–1, that carry a desired truncated Fhb7+ translocation segment without PSY-E2. The two lines show levels of resistance to FHB and FCR similar to those of the original translocation line SDAU 2028, but have white flour. To facilitate Fhb7 use in wheat breeding, STS markers were developed and used to isolate Fhb7 on a truncated Tp7el2 translocation segment. Near-isogenic lines carrying the Fhb7+ segment were generated in the backgrounds of three commercial cultivars, and Fhb7+ lines showed increased FHB and FCR resistance without yield penalty. The breakage of the tight linkage between Fhb7 and PSY-E2 via homoeologous recombination provides genetic resources for improvement of wheat resistance to FHB and FCR and permit the large-scale deployment of Fhb7 in breeding using marker-assisted selection.

Small non-coding RNAs are potential diagnostic biomarkers for lung cancer. Mitochondria-derived small RNA (mtRNA) is a novel regulatory small non-coding RNA that only recently has been identified and cataloged. Currently, there are no reports of studies of mtRNA in human lung cancer. Currently, normalization methods are unstable, and they often fail to identify differentially expressed small non-coding RNAs (sncRNAs). In order to identify reliable biomarkers for lung cancer screening, we used a ratio-based method using mtRNAs newly discovered in human peripheral blood mononuclear cells. In the discovery cohort (AUC = 0.981) and independent validation cohort (AUC = 0.916) the prediction model of eight mtRNA ratios distinguished lung cancer patients from controls. The prediction model will provide reliable biomarkers that will allow blood-based screening to become more feasible and will help make lung cancer diagnosis more accurate in clinical practice.

Abstract To refine the biological and prognostic significance of DNMT3A mutations in acute myeloid leukemia (AML), we assessed the impact of DNMT3A variant allele frequency (VAF) and its comutations in this study. Using targeted next‐generation sequencing, we analyzed 171 adult patients with de novo cytogenetically normal AML for DNMT3A mutations and associated comutations. DNMT3Amut was detected in 35 patients. DNMT3Amut patients were divided into DNMT3AHigh and DNMT3ALow using a cut‐off VAF value of 42%. We observed that DNMT3AHigh patients at diagnosis had increasing white blood cell (WBC) counts (p

Abstract Time-averaged shear-wave velocity to 30 m (V S30) is commonly used in ground motion models as a parameter for evaluating site effects. This study used a collection of boreholes in Beijing, Tianjin, Guangxi, Guangdong, and three other municipalities and provinces, which were divided into three regions with reference to the seismic ground motion parameter zonation map of China, to establish V S30 prediction models based on terrain categories. Regional effects were verified by comparing morphometric parameter (topographic slope, surface texture, and local convexity) thresholds and terrain classification maps obtained from global digital elevation model (DEM) data and regional DEM data of the three regions. Additionally, V S30 prediction models for the three regions using both types of terrain classification maps were established and analyzed comparatively to provide credible regional V S30 models for China. Through analysis of the correlations between the measured V S30 values and the predicted V S30 values, calculation of the mean squared error and mean absolute percentage error in each region, and with consideration of the geological characteristics of the boreholes, the V S30 prediction models based on terrain classification maps from regional data were finally applied in developing regional V S30 models for China. Intercomparison of the V S30 prediction models for the three regions indicated that subregional consideration is necessary in terrain classification. Finally, a spatial analysis method adopting inverse distance weighting of the residuals was used to update the initial V S30 models. The developed V S30 models could be used both in developing regional ground motion models and in the construction of earthquake disaster scenarios. Graphical Abstract

Abstract Background Chemoresistance is the main reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Thus, there is an urgent need to screen out new targets and compounds to reverse chemotherapeutic resistance. Methods We established a bio-bank of human PDAC organoid models, covering a representative range of PDAC tumor subtypes. We screened a library of 1304 FDA-approved compounds to identify candidates efficiently overcoming chemotherapy resistance. The effects of the compounds were evaluated with a CellTiter-Glo-3D assay, organoid apoptosis assay and in vivo patient-derived xenograft (PDX), patient-derived organoid (PDO) and LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) genetically engineered mouse models. RNA-sequencing, genome editing, sphere formation assays, iron assays and luciferase assays were conducted to elucidate the mechanism. Results High-throughput drug screening of chemotherapy-resistant PDOs identified irbesartan, an angiotensin ‖ type 1 (AT1) receptor antagonist, which could synergistically enhance the ability of chemotherapy to kill PDAC cells. In vitro and in vivo validation using PDO, PDX and KPC mouse models showed that irbesartan efficiently sensitized PDAC tumors to chemotherapy. Mechanistically, we found that irbesartan decreased c-Jun expression by inhibiting the Hippo/YAP1 pathway and further overcame chemotherapy resistance in PDAC. We also explored c-Jun, a potential target of irbesartan, which can transcriptionally upregulate the expression of key genes involved in stemness maintenance (SOX9/SOX2/OCT4) and iron metabolism (FTH1/FTL/TFRC). More importantly, we observed that PDAC patients with high levels of c-Jun expression demonstrated poor responses to the current standard chemotherapy regimen (gemcitabine plus nab-paclitaxel). Moreover, patients with PDAC had significant survival benefits from treatment with irbesartan plus a standard chemotherapy regimen in two-center retrospective clinical cohorts and patients with high c-Jun expression exhibited a better response to combination chemotherapy. Conclusions Irbesartan could be used in combination with chemotherapy to improve the therapeutic efficacy in PDAC patients with high levels of c-Jun expression. Irbesartan effectively inhibited chemotherapy resistance by suppressing the Hippo/YAP1/c-Jun/stemness/iron metabolism axis. Based on our findings, we are designing an investigator-initiated phase II clinical trial on the efficacy and safety of irbesartan plus a standard gemcitabine/nab-paclitaxel regimen in the treatment of patients with advanced III/IV staged PDAC and are hopeful that we will observe patient benefits.

Abstract For the past 30 years, in vitro transcription (IVT) technology has been extensively used for RNA production or for basic transcriptional mechanism research. However, methods for mRNA quantification still need to be improved. In this study, we designed a RT-IVT method using binary fluorescence quencher (BFQ) probes and the PBCV-1 DNA ligase to quantify mRNA production in real-time by fluorescence resonance energy transfer (FRET) and RNA-splinted DNA ligation. Compared with existing methods, the RT-IVT method is inexpensive and non-radioactive, and can detect mRNA production in unpurified systems in real-time and shows high sensitivity and selectivity. The activity of T7 RNA polymerase and Escherichia coli RNA polymerase holoenzyme was then characterized with this method. We then multiplexed the real-time mRNA quantification for three T7 promoters on a RT-PCR thermocycler by using BFQ probes with different colored fluorophores that were specific for each target. Ultimately, we created an inexpensive multiplexed method to quantify mRNA production in real-time, and future research could use these methods to measure the affinity of transcriptional repressors to their target DNA sequence.

Objectives Unilateral percutaneous kyphoplasty (UPKP) has been effective in reducing the operative time, cement volume, and cement leakage (CL) rate compared with bilateral kyphoplasty. However, no device can help to determine the trajectory during operation, especially the inner inclination angle. To assess the safety and efficacy of a novel guide device (GD) for UPKP in the treatment of thoracolumbar osteoporotic vertebral fractures (TLOVFs). Methods From January 2019 to May 2021, 31 patients diagnosed with single TLOVF who underwent UPKP were retrospectively reviewed. The patients were divided into two groups: traditional UPKP (UPKP group, 15 patients) and UPKP assisted with GD (UPKP‐GD group, 16 patients). Pre‐procedure demographic, clinical and radiologic characteristics, operative procedure details, and clinical and radiologic outcomes at 1 day and 12 months post‐procedure were collected. Statistical analyses were carried out using SPSS 24.0. The baseline characteristics of the two groups were compared by the independent sample t test or the χ2 test. The anterior height or local kyphotic angle (LKA) of the fractured vertebrae, visual analog scale (VAS) score, and Oswestry Disability Index (ODI) within groups were compared using the paired t test. Results A total of 31 patients (five men and 26 women; age range: 58–90 years) completed the full 12‐month postoperative follow‐up schedule. No significant differences were observed between treatment groups with respect to sex, age, body mass index, preoperative bone mineral density, or surgical level. Compared with the UPKP group, the operation time in the UPKP‐GD group was significantly shorter (40.8 ± 5.5 min vs. 48.5 ± 8.5 min, p = 0.005), and the number of intraoperative fluoroscopy times in the UPKP‐GD group was significantly decreased (20.6 ± 4.5 vs. 25.2 ± 2.4, p = 0.001). Five (31.3%) patients in the UPKP‐GD group and four (26.7%) patients in the UPKP group had bone CL. The VAS and ODI scores, anterior height and LKA of the fractured vertebrae were significantly improved after surgery in each group. No significant differences in postoperative VAS and ODI scores, anterior height or LKA of the fractured vertebrae, volume of injected cement or CL were observed between the two groups. Conclusion Unilateral puncture using a novel GD is a safe and effective technique for patients with TLFs and UPKP assisted with a novel GD is associated with fewer intraoperative fluoroscopy times and shorter operation time.