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Crop pedigrees incorporate information on the kinship and genetic evolutionary history of breeding materials. Complete and accurate pedigree information is vital for effective genetic improvement of crops and maximal exploitation of heterosis in crop production. It is difficult for breeders to accurately extrapolate the selection of germplasm resources with missing genealogical information based on breeding experience. In this study, an algorithm called PidTools was developed, consisting of five sets of algorithms from three core modules, for accurate pedigree identification analysis. The algorithms and associated tools are suitable for all crops, for the reconstruction and visualization of a complete pedigree for breeding materials. The algorithm and tools were validated with the model crop maize. A genotype database was constructed using Maize6H-60K array data from 5791 maize inbred lines. The pedigree of the maize inbred line Jing72464 was identified without prior provision of any parental information. The pedigree information for Zheng58 was fully identified at the genome-wide scale. With regard to group identification, the parents of a doubled-haploid group were identified based on the genotyping data. The pedigree of 21 Dan340 derived lines were visualized using PidTools. The algorithms are incorporated into a user-friendly online analytical platform, PidTools-WS, with an associated customizable toolkit program, PidTools-CLI. These analytical tools and the present results provide useful information for future maize breeding. The PidTools online analysis platform is available at https://PidTools.plantdna.site/.

Strontium(Sr) is a trace element naturally found in the human skeletal system. In recent years, the potential impact of strontium on bone and cardiovascular health has called significant attention, particularly during pregnancy, when alterations in mineral metabolism may affect the health of both the mother and the fetus. This comprehensive review assesses the current understanding of the role of strontium as a nutritional substance during pregnancy, its effects on maternal health and fetal development, and its potential associations with pregnancy complications such as preeclampsia, gestational hypertension, and lactation-induced osteoporosis. The review also summarizes the possible effects of strontium deficiency, excess, and supplementation, and provides information for developing prenatal nutrition supplementation guideline.

Abstract Aims We conducted a presentation on an 84‐year‐old male patient who has been diagnosed with TTRA81V (p. TTRA101V) hereditary transthyretin cardiac amyloidosis (hATTR‐CM). In order to establish its pathogenicity, we extensively investigated the biochemical and biophysical properties of the condition. Methods and results Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasingly acknowledged progressive infiltrative cardiomyopathy that leads to heart failure and potentially fatal arrhythmias. Gaining a comprehensive understanding of the biochemical and biophysical characteristics of genetically mutated TTR proteins serves as the fundamental cornerstone for delivering precise medical care to individuals affected by ATTR. Laboratory assessments indicated a brain natriuretic peptide of 200.12 ng/L (normal range: 0–100 ng/L) and high‐sensitivity cardiac troponin I of 0.189 μg/L (normal range: 0–0.1 μg/L). Echocardiography identified left atrial enlargement, symmetrical left ventricular hypertrophy (16 mm septal and 16 mm posterior wall), and a left ventricular ejection fraction of 56%. Cardiac‐enhanced magnetic resonance imaging revealed subendocardial late gadolinium enhancement. Tc‐99m‐PYP nuclear scintigraphy confirmed grade 3 myocardial uptake, showing an increased heart‐to‐contralateral ratio (H/CL = 2.33). Genetic testing revealed a heterozygous missense mutation in the TTR gene (c.302C>T), resulting in an alanine‐to‐valine residue change (p. Ala81Val, following the first 20 residues of signal sequence nomenclature). Biochemical analysis of this variant displayed compromised kinetic stability in both the TTRA81V:WT (wild‐type) heterozygote protein (half‐life, t1/2 = 21 h) and the TTRA81V homozygote protein (t1/2 = 17.5 h). The kinetic stability fell between that of the TTRWT (t1/2 = 42 h) and the early‐onset TTRL55P mutation (t1/2 = 4.4 h), indicating the patient's late‐onset condition. Kinetic stabilizers (Tafamidis, Diflunisal, and AG10) all exhibited the capacity to inhibit TTRA81V acid‐ and mechanical force‐induced fibril formation, albeit less effectively than with TTRWT. Chromatographic assessment of the patient's serum TTR tetramers indicated a slightly lower concentration (3.0 μM) before oral administration of Tafamidis compared with the normal range (3.6–7.2 μM). Conclusions We identified a patient with hATTR‐CM who possesses a rare TTRA81V mutation solely associated with cardiac complications. The slightly reduced kinetic stability of this mutation indicates its late‐onset nature and contributes to the gradual progression of the disease.

Flexible photodetector is crucial for the intelligent industrial applications. However, the optical-sensitive materials are usually grown in a high temperature and then transferred onto the flexible substrate. This paper reported a directly fabricated flexible photodetector based on TiO2-doped Graphene Nanosheets Embedded Carbon (GNEC)film. An Electron Cyclotron Resonance (ECR) system was employed to in-situ deposit TiO2-doped GNEC film on a polyimide substrate, which were subsequently sensitized with N719 dye to fabricate the TiO2@GNEC photodetector. The GNEC film contains vertically aligned Graphene Nanosheets (GNs), which exhibit high-density edge states. The edge states suppress the recombination rate of photo-generated electron-hole pairs, thereby significantly enhancing the photo-responsive performance. The photodetector demonstrates a high photo responsivity of 0.82 mA/W and a response time of 1.93 seconds. Due to the in-situ manufacturing capabilities of the ECR system, which avoids defects from secondary material transfers, the photodetector array exhibits excellent consistency and achieves clear recognition of light patterns in both flat and bent states.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

Layered materials with adjustable framework, as the most potential cathode materials for aqueous rechargeable zinc ion batterie, have high capacity, permit of rapid ion diffusion, and charge transfer channels. Previous studies have widely investigated their preparation and storage mechanism, but the intrinsic relationship between the structural design of layered cathode materials and electrochemical performance has not been well established. In this work, based on the first principles calculations and experiments, a crucial strategy of pre-intercalated metal-ions in vanadium oxide interlayer with administrable p-band center (ɛp) of O is explored to enhance Zn2+ storage. This regulation of the degree of covalent bond and the average charge of O atoms varies the binding energy between Zn2+ and O, thus affecting the intercalation/de-intercalation of Zn2+. The present study demonstrates that ɛp of O can be used as an important indicator to boost Zn2+ storage, which provides a new concept toward the controlled design and application of layered materials.

The influence of basalt fiber (BF) on the mechanical properties of reactive powder concrete (RPC) under different curing systems was studied. Three curing systems were adopted: natural curing (NC), standard curing (SC) and combined curing (CC). The design formulas for compressive and splitting tensile strength of basalt fiber reactive powder concrete (BFRPC) were established. The hydration process and strength changes of BFRPC under different systems were analyzed by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The test results showed that the CC was better than the SC and slightly better than the NC, while the hydration of the CC was insufficient in the later stage, and the growth rate was significantly lower than the SC or NC. BF showed good compatibility with the matrix and was closely bonded. BF with proper content and the matrix were pressed together to improve the mechanical properties of BFRPC, while an excess of BF content would cause weakened areas and reduce strength. In comparison to plain RPC (with BF content of 0 %), the maximum increase rates of 28-day compressive strength of BFRPC under NC, SC and CC systems were 22.8 %, 18.4 % and 8.9 %, respectively. As for 28-day splitting tensile strength, the maximum increase rates became 74.5 %, 66.5 % and 49.67 %, respectively. Considering the economy and practicability of the actual project, the strength prediction formula of BFRPC was put forward to facilitate its popularization and application.

In order to study the change characteristics of unit liquid injection volume during hydraulic fracturing of coal seams, using the engineering test method, taking the 1703 working face of Jinzhong Coal Mine in Junlian County, Yibin City, Sichuan Province as the test site. Through monitoring and analyzing the unit liquid flow of each pipeline in the process of borehole hydraulic fracturing, it is found that the fitting curves of unit liquid flow of liquid inlet pipe and liquid return pipe are “parabola” in the process of normal hydraulic fracturing, while the actual unit liquid injection volume can be divided into falling stage and fluctuating stage. Combined with the change of liquid injection pressure in the process of hydraulic fracturing, it is found that the liquid injection pressure will appear obvious “pressure relief-recovery” phenomenon when the coal body appears cracking and crack propagation, and the unit liquid injection volume will appear “ rise-recover ” phenomenon, and the two phenomenon are synchronous. In addition, the whole hydraulic fracturing process is divided into three stages according to the change characteristics of the unit liquid injection volume in the hydraulic fracturing process: filling stage, energy storage and coal cracking cycle stage and stop cracking stage.

Abstract Selective hydrogenation of carbon monoxide (CO) to higher alcohols (C2+OH) is a promising non-petroleum route for producing high-value chemicals, in which precise regulations of both C-O cleavage and C-C coupling are highly essential but remain great challenges. Herein, we report that highly selective CO hydrogenation to C2-4OH is achieved over a potassium-modified edge-rich molybdenum disulfide (MoS2) catalyst, which delivers a high CO conversion of 17% with a superior C2-4OH selectivity of 45.2% in hydrogenated products at 240 °C and 50 bar, outperforming previously reported non-noble metal-based catalysts under similar conditions. By regulating the relative abundance of edge to basal plane, C2-4OH to methanol selectivity ratio can be overturned from 0.4 to 2.2. Mechanistic studies reveal that sulfur vacancies at MoS2 edges boost carbon-chain growth by facilitating not only C-O cleavage but also C-C coupling, while potassium promotes the desorption of alcohols via electrostatic interaction with hydroxyls, thereby enabling preferential formation of C2-4OH.

Abstract Digital pathology allows computerized analysis of tumor ecosystem using whole slide images (WSIs). Here, we present single-cell morphological and topological profiling (sc-MTOP) to characterize tumor ecosystem by extracting the features of nuclear morphology and intercellular spatial relationship for individual cells. We construct a single-cell atlas comprising 410 million cells from 637 breast cancer WSIs and dissect the phenotypic diversity within tumor, inflammatory and stroma cells respectively. Spatially-resolved analysis identifies recurrent micro-ecological modules representing locoregional multicellular structures and reveals four breast cancer ecotypes correlating with distinct molecular features and patient prognosis. Further analysis with multiomics data uncovers clinically relevant ecosystem features. High abundance of locally-aggregated inflammatory cells indicates immune-activated tumor microenvironment and favorable immunotherapy response in triple-negative breast cancers. Morphological intratumor heterogeneity of tumor nuclei correlates with cell cycle pathway activation and CDK inhibitors responsiveness in hormone receptor-positive cases. sc-MTOP enables using WSIs to characterize tumor ecosystems at the single-cell level.

TeO2-Bi2O3-B2O3-ZnO laser glasses doped with Er3+ were synthesized through an optimized melt-quenching method. The absorption spectra at 808 nm LD pumping were studied. Various spectral tests and data analyses indicate that the maximum fluorescence emission intensity can be obtained when the Er3+ doping concentration reaches 2%. In this case, the emission cross-section can reach up to 9.12 × 10−21 cm2 and the gain coefficient at 1.55 μm is 6.17 cm−1. Simultaneously, the sample has a lower phonon energy in the high-frequency band at 1077 cm−1, which reduces the probability of non-radiative relaxation. The calculated energy transfer coefficient CD-A is 13.8 × 10−40 cm6/s, reflecting the high cross-relaxation probability of Er3+ in the sample, which promotes the luminescence of 1.55 μm and favors the emission in the near-infrared region. The comprehensive results demonstrate that the prepared Er3+-doped bismuth telluride laser glass can be used as a promising and high-quality gain material for near-infrared lasers.

Background: Sepsis is a life-threatening disease characterized by multiple organ failure due to excessive activation of the inflammatory response and cytokine storm. Despite recent advances in the clinical use of anti-cytokine biologics, sepsis treatment efficacy and improvements in mortality remain unsatisfactory, largely due to the mechanistic complexity of immune regulation and cytokine interactions.Methods: In this study, a broad-spectrum anti-inflammatory and endotoxin neutralization strategy was developed based on autologous “cryo-shocked” neutrophils (CS-Neus) for the management of sepsis. Neutrophils were frozen to death using a novel liquid nitrogen “cryo-shock” strategy. The CS-Neus retained the source cell membrane structure and functions related to inflammatory site targeting, broad-spectrum inflammatory cytokines, and endotoxin (LPS) neutralizing properties. This strategy aimed to disable harmful pro-inflammatory functions of neutrophils, such as cytokine secretion. Autologous cell-based therapy strategies were employed to avoid immune rejection and enhance treatment safety.Results: In both LPS-induced sepsis mouse models and clinical patient-derived blood samples, CS-Neus treatment significantly ameliorated cytokine storms by removing inflammatory cytokines and endotoxin. The therapy showed notable anti-inflammatory therapeutic effects and improved the survival rate of mice.Discussion: The results of this study demonstrate the potential of autologous “cryo-shocked” neutrophils as a promising therapeutic approach for managing sepsis. By targeting inflammatory organs and exhibiting anti-inflammatory activity, CS-Neus offer a novel strategy to combat the complexities of sepsis treatment. Further research and clinical trials are needed to validate the efficacy and safety of this approach in broader populations and settings.

Objective: To analyse four cases of intervention via the internal mammary artery–anterior descending branch and provide and summarise the clinical treatment experience. Methods: The clinical data of four patients with distal restenosis of a left anterior descending artery (LAD) anastomosis after left internal mammary artery (LIMA)–LAD bypass surgery, who were admitted to the Gansu Institute of Cardiovascular Diseases between March 2013 and April 2022, were retrospectively analysed and reviewed together with the relevant literature. Results: Among the four patients, one was treated with intracoronary stenting via the internal mammary artery route, two were treated with intracoronary drug-coated balloon dilation (one of whom underwent fractional flow reserve [FFR] testing), and two underwent FFR testing (one of whom had a negative test result until the end of the procedure and continued to take medication during follow-up; the other patient had a positive result and further interventions). There were no deaths or postoperative complications in the group, and the patients were followed up for 4 months to 9 years, with good long-term outcomes. Conclusion: Percutaneous coronary intervention (PCI) via the internal mammary artery route is safe and effective, and patients with anastomotic distal stenosis or anastomotic stenosis of LAD bypass anastomosis may be considered for PCI via the internal mammary artery route.

Using glass sand as a substitute for sand in high-performance concrete not only conserves resources but also helps protect the environment. This study replaced manufactured sand with glass sand and added carbon fiber to prepare high-performance shotcrete. Its mechanical and self-sensing properties were then tested separately. The findings suggest that with an increase in glass sand content, the compressive strength of high-performance shotcrete initially rises and subsequently declines. When the replacement ratio of glass sand is 75%, the compressive strength exhibits its maximum value, whereas an increase in the glass sand content leads to a reduction in both splitting tensile strength and flexural strength. Although increasing carbon fiber content does not significantly contribute to compressive strength, it significantly improves flexural strength and splitting tensile strength. In addition, when testing the self-sensing performance of the material, it was found that its self-sensing performance increased significantly with increasing carbon fiber content but decreased with increasing glass sand content. Finally, an Ansys APDL simulation using the relevant parameters of the optimal group of mechanical properties was performed to model a tunnel and verify its feasibility and validity. This study provides a theoretical and practical reference for future engineering applications.

Due to climate change and socio-economic development, the growth and distribution of wetland vegetation have been destroyed, resulting in a degradation trend of wetland ecosystem. It is critical to simulate variations in the normalized difference vegetation index (NDVI) patterns under changing environments to guide targeted restoration and protection. Considering that current NDVI pattern simulation focused only on the linear driving forces of nature or society and had a low simulation efficiency, an integrated simulation framework with dual society-nature drives was proposed. In the framework, the spatial and NDVI patterns were simulated by system dynamics-future land use simulation (SD-FLUS) and random forest (RF) models, respectively. Baiyangdian Wetland in North China was taken as a case study, and its typical vegetation—reed—was taken as the simulation object. The NDVI patterns were simulated under the effects of socio-economic development, climate change and ecological protection policies. The results showed that the spatial patterns were affected by social factors, while the NDVI patterns were affected by natural factors. The spatial aggregations of the NDVI were affected by social and natural factors. Besides, the growth space of reeds was easily encroached under the existing development and protection policies. If ecological protection policies were implemented, the reed area would be restored, but the growth status would be poorer, requiring further protection measures and more attention to the growth status of reeds in sensitive areas. This study provides a new research perspective for simulating NDVI patterns and scientific supports for refined management of wetland vegetation.

Abstract Bladder cancer (BCa) is one of the most common malignancies worldwide. However, the lack of accurate and effective targeted drugs has become a major problem in current clinical treatment of BCa. Studies have demonstrated that squalene epoxidase (SQLE), as a key rate-limiting enzyme in cholesterol biosynthesis, is involved in cancer development. In this study, our analysis of The Cancer Genome Atlas, The Genotype-Tissue Expression, and Gene Expression Omnibus databases showed that SQLE expression was significantly higher in cancer tissues than it was in adjacent normal tissues, and BCa tissues with a high SQLE expression displayed a poor prognosis. We then confirmed this result in qRT-PCR and immunohistochemical staining experiments, and our vitro studies demonstrated that SQLE knockdown inhibited tumor cell proliferation and metastasis through the PTEN/AKT/GSK3β signaling pathway. By means of rescue experiments, we proved that that P53 is a key molecule in SQLE-mediated regulation of the PTEN/AKT/GSK3β signaling pathway. Simultaneously, we verified the above findings through a tumorigenesis experiment in nude mice. In conclusion, our study shows that SQLE promotes BCa growth through the P53/PTEN/AKT/GSK3β axis, which may serve as a therapeutic biological target for BCa.

Abstract The aim of the meta‐analysis was to generate a more comprehensive understanding of the HFA‐PEFF score in the diagnosis of heart failure with preserved ejection fraction (HFpEF) and to pose clues in the field of scientific and clinical practice. Electronic databases of PubMed, Web of Science, Cochrane Library, and Embase were systematically searched. Studies investigating the use of the HFA‐PEFF score to diagnose HFpEF were included. Pooled sensitivity, specificity, positive likelihood ratio (PLR) and negative Likelihood Ratio (NLR), diagnostic odds ratio (DOR), area under the curve of summary receiver operating characteristic, and superiority index were calculated. Five studies with 1521 participants were included in this meta‐analysis. In the pooled analysis of the ‘Rule‐out’ approach, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.98 (0.94, 1.00), 0.33 (0.08, 0.73), 1.5 (0.8, 2.5), 0.05 (0.02, 0.17), and 28 (6, 127). In the pooled analysis of the ‘Rule‐in’ approach, the pooled sensitivity and specificity, PLR, NLR, and DOR were 0.69 (0.62, 0.75), 0.87 (0.64, 0.96), 5.5 (1.8, 16.9), 0.35 (0.30, 0.41), and 16 (5, 50). This meta‐analysis indicates that the HFA‐PEFF algorithm showed acceptable specificity and sensitivity for the diagnosis and exclusion of HFpEF. More relevant studies on the diagnostic validity of the HFA‐PEFF score are needed in the future.

The Bifidobacterium bifidum SAM-VI riboswitch undergoes dynamic conformational changes that modulate downstream gene expression. Traditional structural methods such as crystallography capture the bound conformation at high resolution, and additional efforts would reveal details from the dynamic transition. Here, we revealed a transcription-dependent conformation model for Bifidobacterium bifidum SAM-VI riboswitch. In this study, we combine small-angle X-ray scattering, chemical probing, and isothermal titration calorimetry to unveil the ligand-binding properties and conformational changes of the Bifidobacterium bifidum SAM-VI riboswitch and its variants. Our results suggest that the SAM-VI riboswitch contains a pre-organized ligand-binding pocket and stabilizes into the bound conformation upon binding to SAM. Whether the P1 stem formed and variations in length critically influence the conformational dynamics of the SAM-VI riboswitch. Our study provides the basis for artificially engineering the riboswitch by manipulating its peripheral sequences without modifying the SAM-binding core.

With the shortage of fossil energy and the increasingly serious environmental problems, renewable energy based on wind and solar power generation has been gradually developed. For the problem of wind power uncertainty and the low-carbon economic optimization problem of an integrated energy system with power to gas (P2G) and carbon capture and storage (CCS), this paper proposes an economic optimization scheduling strategy of an integrated energy system considering wind power uncertainty and P2G-CCS technology. Firstly, the mathematical model of the park integrated energy system with P2G-CCS technology is established. Secondly, to address the wind power uncertainty problem, Latin hypercube sampling (LHS) is used to generate a large number of wind power scenarios, and the fast antecedent elimination technique is used to reduce the scenarios. Then, to establish a mixed integer linear programming model, the branch and bound algorithm is employed to develop an economic optimal scheduling model with the lowest operating cost of the system as the optimization objective, taking into account the ladder-type carbon trading mechanism, and the sensitivity of the scale parameters of P2G-CCS construction is analyzed. Finally, the scheduling scheme is introduced into a typical industrial park model for simulation. The simulation result shows that the consideration of the wind uncertainty problem can further reduce the system’s operating cost, and the introduction of P2G-CCS can effectively help the park’s integrated energy system to reduce carbon emissions and solve the problem of wind and solar power consumption. Moreover, it can more effectively reduce the system’s operating costs and improve the economic benefits of the park.

During long-duration dynamic loads, such as wind loads or seismic effects, the internal temperature and pressure of a damping cylinder escalate rapidly, which induce shifts in the mechanical attributes of viscous fluid dampers (VFDs). This study investigated the mechanical performance of VFD considering the coupling effects of temperature and pressure under long-duration loads. First, we analyzed the mechanical and energy-dissipation performances of the dampers based on the dynamic mechanical tests considering different loading frequencies, displacement amplitude, and loading cycles. The experimental results indicated that both temperature and pressure influenced the output of the dampers, and in the sealed environment of the damper pip, temperature and pressure exerted mutual influence. Furthermore, the relationship between the damping coefficient and temperature–pressure coupling effects was obtained. Subsequently, an improved mathematical model for the mechanical performance of a gap-type VFD was proposed by considering the macroscopic energy balance of the entire fluid within the damper. Finally, the accuracy of the mathematical model for VFD under long-duration dynamic loads was validated by comparing the computational results with the experimental data.

Perovskite/silicon tandem solar cells are of great interest due to their potential for breaking the Shockley-Queisser limit of single-junction silicon solar cells. Perovskite solar cells are widely used as the top subcells in perovskite/silicon tandem solar cells due to their high efficiency and lower fabrication cost. Herein, we review the semi-transparent perovskite solar cell in terms of the mechanisms of their translucent structure, transparent electrodes, charge transport layer, and component modification. In addition, recent progress in the research and development of 4T perovskite/silicon tandem solar cells is summarized, with emphasis on the influence of perovskite structure and silicon cells on the progress of tandem solar cells. Finally, we discuss the challenges associated with 4T perovskite/silicon tandem solar cells and suggest directions for the development of perovskite/silicon commercialization.

Abstract Parkinson’s disease (PD) is the most common progressive neurodegenerative movement disorder, which is characterized by dopaminergic (DA) neuron death and the aggregation of neurotoxic α-synuclein. Cntnap4, a risk gene of autism, has been implicated to participate in PD pathogenesis. Here we showed Cntnap4 lacking exacerbates α-synuclein pathology, nigrostriatal DA neuron degeneration and motor impairment, induced by injection of adeno-associated viral vector (AAV)-mediated human α-synuclein overexpression (AAV-hα-Syn). This scenario was further validated in A53T α-synuclein transgenic mice injected with AAV-Cntnap4 shRNA. Mechanistically, α-synuclein derived from damaged DA neuron stimulates astrocytes to release complement C3, activating microglial C3a receptor (C3aR), which in turn triggers microglia to secrete complement C1q and pro-inflammatory cytokines. Thus, the astrocyte–microglia crosstalk further drives DA neuron death and motor dysfunction in PD. Furthermore, we showed that in vivo depletion of microglia and microglial targeted delivery of a novel C3aR antagonist (SB290157) rescue the aggravated α-synuclein pathology resulting from Cntnap4 lacking. Together, our results indicate that Cntnap4 plays a key role in α-synuclein pathogenesis by regulating glial crosstalk and may be a potential target for PD treatment.

Abstract Aims Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline‐directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, β‐blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. Methods This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple‐drug therapy (TT) and non‐triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Results Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all‐cause mortality (HR 0.656, 95% CI 0.447–0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380–0.946, P = 0.028), any‐cause rehospitalization (HR 0.687, 95% CI 0.541–0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565–0.948, P = 0.018). Conclusions In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF.

Promoting axonal regeneration is an effective strategy for recovery from traumatic spinal cord injury (SCI). Spastin, a microtubule-severing protein, modulates axonal outgrowth and branch formation by regulating microtubule dynamics. However, the exact role of spastin during recovery from SCI remains unknown. Therefore, we utilized a hemisection injury model of the mouse spinal cord and explored the effect of spastin using a spastin inhibitor, spastazoline. Results showed that spastazoline significantly suppressed the microtubule-severing activity of spastin in COS-7 cells and inhibited the promoting effect of spastin on neurite outgrowth in primarily cultured hippocampal neurons. The protein expression level of spastin was significantly upregulated in the injured spinal cord. Injured mice showed impaired motor functions, which included increased toe-off angle and foot fault steps and decreased stride length and Basso mouse scale score. Notably, these motor function impairments were aggravated by the application of spastazoline. Inhibition of spastin exacerbated neurogenesis impairment, as demonstrated by neuronal nuclei antigen staining, the inflammatory response, as shown by Iba-1 and GFAP staining, and axonal regeneration impairment, as shown by 5-hydroxytryptamine staining. Furthermore, mass spectrometry analysis revealed that the inhibition of spastin resulted in numerous dysregulated differentially expressed proteins that were closely associated with vesicle organization and transport. Taken together, our data suggest that spastin is critical for recovery from SCI and may be a potential target for the treatment of SCI.

Complex geographical environments and intensified human activities have induced significant spatiotemporal heterogeneity in ecosystem services (ESs) and their relationships worldwide, especially in agropastoral ecotones. Identifying the ecological and socioeconomic driving factors of the spatiotemporal dynamics of the relationships and bundles among multiple ESs is essential for effective agropastoral ecotone management and restoration. Herein, five key ESs, including water yield (WY), carbon sequestration (CS), sand fixation (SF), soil conservation (SC), and food production (FP), in the northern piedmont of the Yinshan Mountains (NPYM), a typical agropastoral ecotone, were quantified from 1990 to 2018. Ecosystem service bundles (ESBs) were identified by the K-means algorithm, and the trade-offs/synergies among the different ESs in each ESB were investigated using Spearman’s correlation analysis. Moreover, the main driving factors of the spatiotemporal dynamics of the ES relationships and ESBs were identified by the geographical detector model. Our results showed that the five ESs in the NPYM exhibited high spatiotemporal heterogeneity over the last three decades, with WY, SC and FP significantly improving over time but CS and SF slightly decreasing. Considering the ecological features and spatial distribution, the NPYM could be divided into four ESBs: the grassland protection bundle (GPB), desertification control bundle (DCB), agricultural production bundle (APB) and forest conservation bundle (FCB). Although trade-offs between WY and CS and synergy between SC and CS occurred in almost all ESBs, significant differences in the relationships between the other ESs were observed in the different ESBs. Generally, land use type was one of the dominant drivers of most ES relationships in all ESBs, especially in the APB. However, climate, vegetation and socioeconomic factors also played important roles in the spatiotemporal heterogeneity of various ES relationships in some bundles. Moreover, the substantial changes in the different ESBs over the last three decades were mainly due to climatic and socioeconomic factors. Overall, our results indicated that identifying the spatiotemporal heterogeneity and driving factors of ES relationships and ESBs could provide useful guidance for developing targeted zoning management strategies in agropastoral ecotones.

Resolving the orbital structure of single atoms is challenging and of great importance for understanding basic chemistry. Here, the authors demonstrate that the orbital occupation difference of single Fe/Co atoms within molecules can be distinguished with high resolution AFM imaging and spectroscopy.

In order to facilitate waste glass recycling and enable the monitoring of concrete structures, this study prepares a new type of self-sensing engineered cementitious composite (ECC) via the use of glass sand instead of silica sand. The health monitoring of a concrete structure is achieved through the addition of polypropylene (PP) fibers to enhance the flexural toughness of concrete, and adding carbon fibers (CFs) to make the concrete self aware, enabling it to sense the load changes and structural damage. The fiber dosage of ECC is optimized to analyze the effects of different fiber types and dosages on the mechanical and self-sensing properties of concrete. The results show that the hybrid fibers produce a good synergistic effect on mechanical properties, and the presence of excess fibers causes the mechanical properties of concrete to deteriorate. The critical fiber volume fraction required for the strain hardening of PP ranges from 0.75% vol to 1% vol. At different PP dosages, the CF dosage shows a positive correlation with the initial crack strength. By analyzing the effect of varied curing times and CF doping on the initial resistivity, it is found that the threshold value of CF conductivity is 0.7% vol. The role of CFs in the flexural sensitivity and pressure sensitivity tests is explained from the perspective of fiber distribution, and the fiber distribution theory is verified with scanning electron microscopy (SEM). The optimal level of CF doping for flexural sensitivity and pressure sensitivity is determined to be 1.1% vol and 0.7% vol via the use of self-sensing performance tests, respectively. An increase in PP fiber doping leads to a decrease in the initial resistivity and self-sensing properties of the material. The results of this research provide guidance regarding how to determine the optimal fiber dosage flexibly for different engineering works.

In box jacking, injecting lubricant around the box is an essential method to reduce excessive friction forces caused by the interaction between the box and soil. This method introduces complexity to factors controlling the friction forces, such as the pipe-soil contact state, earth pressure, and friction coefficient. In particular, during long-distance construction, different lubricant conditions come into play. These intricate scenarios hinder the accurate estimation and control of friction force throughout the entire construction period. This study analyzed the variation patterns of frictional resistance based on monitoring data from two actual cases. The lubricant condition changes during the long-distance jacking process were categorized, the effect of lubricant actions on factors controlling friction force in each segment was discussed, and a new method for calculating friction forces by partitioning the long-distance box jacking was proposed. This approach aims to enhance the prediction accuracy and was compared with the results obtained from existing models. The rationality of the new model was further validated by combining numerical simulation results with field data. The results indicate that the proposed segmented calculation model demonstrates better prediction accuracy when facing variations in actual construction conditions. It can serve as a reference for the process design and construction control of long-distance box jacking.

Sepsis-induced ALI is marked by physiological, pathological, and biochemical irregularities caused by infection. Growth differentiation factor 3 (GDF3) is closely associated with the inflammatory response. Accumulating evidence has demonstrated a close relationship between GDF3 expression and the severity and prognosis of sepsis. However, the precise mechanism by which GDF3 protects against ALI induced by sepsis is still unclear. Following the intravenous administration of GDF3 in this research, we noted a rise in the survival rate, a decrease in the severity of histopathological damage as evaluated through HE staining, a decline in the count of inflammatory cells in bronchoalveolar lavage fluid (BALF), a reduction in the ratio of lung wet/dry (W/D) weight, and a noteworthy decrease in the levels of pro-inflammatory cytokines in both serum and BALF when compared to septic mice who underwent cecal ligation and puncture (CLP). These collective findings unequivocally indicate the protective effects of GDF3 against sepsis-induced ALI. In addition, the GDF3 group showed a significant reduction in the mRNA expression of Caspase-1 and NLRP3 when compared to the CLP group. Following this, we performed in vitro tests to confirm these discoveries and obtained comparable outcomes, wherein the administration of GDF3 notably decreased the levels of Caspase-1 and NLRP3 mRNA and protein in macrophages in comparison to the LPS group. Furthermore, GDF3 exhibited the capacity to reduce the secretion of inflammatory molecules from macrophages. By illuminating the mechanism by which GDF 3 regulates macrophages, this offers a theoretical basis for preventing and treating sepsis-induced ALI.

Hastelloy X (HX) alloys with ideal strength and ductility match can be obtained by selective laser melting (SLM) and a proper follow-up heat treatment. This work studies the influence of scanning speed on grain size, grain boundary distribution, recrystallization and mechanical properties of as-built HX. These influences are reevaluated after a solution treatment at 1175 °C for 4h. The results reveal that the average grain size decreases, while the aspect ratio, texture intensity and the proportion of high-angle grain boundaries (HAGBs) increases with the increase of scanning speed. A small amount of recrystallization has occurred in the as-built alloys due to the cyclic thermal effect of SLM scanning. The finer grains and larger aspect ratio imply the higher energy storage during SLM, which will increase the recrystallizing nucleation rate. Solution treatment eliminates the fiber texture of 〈100〉//BD, significantly increases the HAGBs fraction and recrystallization fraction, reduces the grain aspect ratio, and coarsens the grains. With the increase of scanning speed, the strength of the Hastelloy X increases and the elongation decreases. The decrease of grain size is the main reason for the increase of yield strength.

Neuroblastoma(NB) is the most common extracranial solid tumor in childhood, and it is now believed that some patients with NB have an underlying genetic susceptibility, which may be one of the reasons for the multiplicity of NB patients within a family line. Even within the same family, the samples show great variation and can present as ganglioneuroblastoma or even benign ganglioneuroma. The genomics of NB is still unclear and more in-depth studies are needed to reveal its key components. We first performed single-cell RNA sequencing(sc-RNAseq) analysis on clinical specimens of two family neuroblastoma(FNB) and four sporadic NB cases. A complete transcriptional profile of FNB was constructed from 18,394 cells from FNB, and we found that SDHD may be genetically associated with FNB and identified a prognostic related CAF subtype in FNB: Fib-4. Single-cell flux estimation analysis (scFEA) results showed that malignant cells were associated with arginine spermine, oxaloacetate and hypoxanthine, and that malignant cells metabolize lactate at lower levels than T cells. Our study provides new resources and ideas for the development of the genomics of family NB, and the mechanisms of cell-to-cell interactions and communication and the metabolic landscape will provide new therapeutic targets.

Crocin has been reported to have therapeutic effects on multiple cancers including colon cancer, but its specific mechanism is still ambiguous and needs to be further explored. Human colorectal adenocarcinoma cells (HCT-116) and human normal colonic epithelial cells (CCD841) were first treated with increasing concentrations of crocin. Subsequently, with 150 and 200 μM of crocin, the cell vitality was examined by cell counting kit 8. Cell apoptosis and proliferation were tested by TUNEL staining and colony formation assay, respectively. The expression of Ki-67 was assessed by immunofluorescence. Enzyme-linked immunosorbent assay was used to evaluate the level of inflammation- and oxidative-related factors. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were examined by flow cytometer. Janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3), and extracellular regulated protein kinases (ERK) in HCT-116 cells were tested by Western blot. Different concentrations of crocin barely affected the CCD841 cell vitality, while crocin restrained the HCT-116 cells vitality, proliferation and the expression of Ki-67, while inducing apoptosis in a concentration-dependent manner. Moreover, the contents of inflammation- and oxidative-related factors in HCT-116 cells were largely blunted by crocin that enhanced ROS and restrained the MMP and suppressed p-JAK2/JAK2, p-STAT3/STAT3, and p-ERK/ERK expression in HCT-116 cells. Crocin induced apoptosis and restored mitochondrial function in HCT-116 cells via repressing the JAK pathway. If the threptic effect works in patients, it could herald a new, effective treatment for colon cancer, improving the patients’ prognosis and quality of life.