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The first compact accelerator-based neutron source (CANS) for industrial and healthcare use in Hungary, the ‘LvB’ project, is being installed at the premises of Mirrotron Ltd. at Martonvásár. In the first phase of the operation, a fast neutron spectrum with energies up to 1 MeV is generated by the impact of a 2.5 MeV and 1 mA time-average intensity pulsed proton beam on a Li target. This target is surrounded by a lead reflector and the beam extraction opening faces of a bi-spectral para-H2 and H2O quasi-one-dimensional moderator, to provide cold and thermal neutron beams primarily for applied material investigations by neutron scattering. Recent results of MCNP6.2 simulations of the initial configuration of the ‘LvB’ compact neutron source confirm the expected neutron beam brightnesses to be approx. 107 n/cm2/s/sr/Å time-average at 4 Å neutron wavelength.

Hong Zhou,1,* Xuefeng Ma,1,* Jinghua Pan,2 Hanlin Shuai,1 Shanshan Liu,3 Xin Luo,1 Ruiman Li1 1Department of Obstetrics and Gynecology, 2Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China; 3Gynecology Department, Guangdong Women and Children Hospital, Guangzhou 511442, China *These authors contributed equally to this work Background: Transversus abdominis plane (TAP) block can provide effective analgesia for abdominal surgery. However, many randomized controlled trials (RCTs) have shown controversial results in hysterectomy. We conducted a meta-analysis of RCTs to investigate the effectiveness of TAP block after hysterectomy.Methods: Studies were gathered from PubMed, MEDLINE, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov databases up to March 2018. RCTs involving TAP blocks in women undergoing hysterectomy were selected. The primary outcome of mean 24 hours morphine consumption and other outcomes, such as time to first request for analgesic, rest, and pain scores on movement at different times, and rates of nausea and vomiting, were compared between TAP block and no or sham block groups.Results: A total of 841 participants were included in the 13 selected RCTs. Compared with no or sham blocks, TAP block reduced mean 24-hour morphine consumption in abdominal hysterectomy (AH) (weighted mean difference [WMD] –10.77 mg, P=0.04) but not in laparoscopic hysterectomy (LH)/robotic-assisted hysterectomy (RH) (WMD –1.39 mg, P=0.24). TAP block in AH prolonged analgesic time and reduced nausea and vomiting rates. TAP block also reduced the postoperative pain score at rest and on movement at different times in the AH subgroup, but it did not significantly reduce the postoperative pain score at rest, 6–8, and 24 hours, as well as the pain score on movement at 2, 6–8, and 24 hours in the LH/RH subgroup.Conclusion: TAP block is an effective analgesic for AH. TAP block can reduce postoperative morphine consumption in AH and pain scores at rest and on movement for AH without increasing side effects. However, TAP block has limited analgesic effects for women undergoing LH/RH, as it does not reduce postoperative morphine consumption and pain scores at rest and on movement. Keywords: TAP block, ultrasound-guided, hysterectomy, meta-analysis, abdominal, laparoscopic

Context Sepsis can result in critical organ failure, and notoginsenoside R1 (NGR1) offers mitochondrial protection.Objective To determine whether NGR1 improves organ function and prognosis after sepsis by protecting mitochondrial quality.Materials and methods A sepsis model was established in C57BL/6 mice using cecum ligation puncture (CLP) and an in vitro model with lipopolysaccharide (LPS, 10 µg/mL)-stimulated primary intestinal microvascular endothelial cells (IMVECs) and then determine NGR1’s safe dosage. Groups for each model were: in vivo—a control group, a CLP-induced sepsis group, and a CLP + NGR1 treatment group (30 mg/kg/d for 3 d); in vitro—a control group, a LPS-induced sepsis group, and a LPS + NGR1 treatment group (4 μM for 30 min). NGR1’s effects on survival, intestinal function, mitochondrial quality, and mitochondrial dynamic-related protein (Drp1) were evaluated.Results Sepsis resulted in approximately 60% mortality within 7 days post-CLP, with significant reductions in intestinal microvascular perfusion and increases in vascular leakage. Severe mitochondrial quality imbalance was observed in IMVECs. NGR1 (IC50 is 854.1 μM at 30 min) targeted Drp1, inhibiting mitochondrial translocation, preventing mitochondrial fragmentation and restoring IMVEC morphology and function, thus protecting against intestinal barrier dysfunction, vascular permeability, microcirculatory flow, and improving sepsis prognosis.Discussion and conclusions Drp1-mediated mitochondrial quality imbalance is a potential therapeutic target for sepsis. Small molecule natural drugs like NGR1 targeting Drp1 may offer new directions for organ protection following sepsis. Future research should focus on clinical trials to evaluate NGR1’s efficacy across various patient populations, potentially leading to novel treatments for sepsis.

Abstract Glucocorticoids (GCs) are key inducers of osteonecrosis, yet not all patients treated with GCs develop glucocorticoid-associated osteonecrosis (GAON). The factors mediating this relationship are unclear. Studies have shown that gut microbiota and their metabolites influence bone metabolism, but their role in GAON is unclear. This study aimed to explore the connection between GAON and gut microbiota. Through bidirectional Mendelian randomization analysis, we identified 14 gut microbial taxa, including Lachnospiraceae (IVW, P = 0.011), associated with GAON. RNA-seq analysis revealed that GAON differentially expressed genes (DEGs) were enriched for intestinal inflammatory response mechanisms. We then compared patients who developed GAON (17 cases), those who did not (GAnON, 15 cases), and those untreated with GCs (Blank, 15 cases) for gut microbiota composition, short-chain fatty acids (SCFAs), and serum inflammatory factors. Our findings indicated a decrease in Lachnospiraceae abundance (GAON 17.13%, GAnON 12.51%, Blank 24.52%) in GC-treated patients. Serum inflammatory factors (IL-17 A, IL-33, and TNF-α) associated with GAON (59.603 ± 12.147, 89.337 ± 20.714, 42.584 ± 9.185) showed significant differences between Blank (1.446 ± 0.683, 11.534 ± 4.705, 4.682 ± 1.48) and GAnON (25.353 ± 8.181, 32.527 ± 7.352, 12.49 ± 3.217) groups, with a negative correlation between these factors and Lachnospiraceae levels. Butyric acid levels in SCFAs varied among groups (P

Abstract Asthenoteratozoospermia is a major cause of male infertility. Thus far, the identified related genes can explain only a small share of asthenoteratozoospermia cases, suggesting the involvement of other genes. The transmembrane protein TMEM232 is highly expressed in mouse testes. In the present study, to determine its function of TMEM232 in testes, we constructed a Tmem232-null mouse model using CRISPR–Cas9 technology. Tmem232 knockout (KO) male mice was completely infertile, and their sperm were immotile, with morphological defects of the flagellum. Electron microscopy revealed an aberrant midpiece-principal junction and the loss of the fourth outer microtubule doublet in the sperm of Tmem232 −/− mice. Sperm cells presented an 8 + 2 conformation and an irregular arrangement of the mitochondrial sheath. Proteomic analysis revealed altered expression of proteins related to flagellar motility, sperm capacitation, the integrity and stability of sperm structure, especially an upregulated expression of multiple ribosome components in TMEM232-deficient spermatids. Additionally, TMEM232 was observed to be involved in autophagy by interacting with autophagy-related proteins, such as ATG14, to regulate ribosome homeostasis during spermiogenesis. These results suggest that TMEM232, as a potential scaffold protein involving in the correct assembly, distribution, and stability maintenance of certain functional complexes by recruiting key intracellular proteins, is essential for the formation of a highly structured flagellum and plays an important role in the autophagic elimination of cytosolic ribosomes to provide energy for sperm motility.

Background: Exosomes produced by mesenchymal stem cells (MSCs) have vascular generative properties and are considered new effective candidates for the treatment of bone defects as alternatives to cell therapy. Improving the pro-regenerative function and efficacy of exosomes has been a popular research topic in the field of orthopaedics. Methods: We prepared mesoporous bioactive glass (mBG) microspheres via the template method. The ionic products of mBGs used to treat MSCs were extracted, and the effects of exosomes secreted by MSCs on osteoblast (OB) and macrophage (MP) behaviour and bone defect repair were observed in vivo (Micro-CT, H&E, Masson, and immunofluorescence staining for BMP2, COL1, VEGF, CD31, CD163, and iNOS). Results: The mBG spheres were successfully prepared, and the Exo-mBG were isolated and extracted. Compared with those in the blank and Exo-Con groups, the proliferation and osteogenic differentiation of OBs in the Exo-mBG group were significantly greater. For example, on Day 7, OPN gene expression in the Ctrl-Exo group was 3.97 and 2.83 times greater than that in the blank and Exo-mBG groups, respectively. In a cranial defect rat model, Exo-mBG promoted bone tissue healing and angiogenesis, increased M2 macrophage polarisation and inhibited M1 macrophage polarisation, as verified by micro-CT, H&E staining, Masson staining and immunofluorescence staining. These effects may be due to the combination of a higher silicon concentration and a higher calcium-to-phosphorus ratio in the mBG ionic products. Conclusion: This study provides insights for the application of exosomes in cell-free therapy and a new scientific basis and technical approach for the utilisation of MSC-derived exosomes in bone defect repair. The translational potential of this article: Our study demonstrated that exosomes produced by mBG-stimulated MSCs have excellent in vitro and in vivo bone-enabling and immunomodulatory functions and provides insights into the use of exosomes in clinical cell-free therapies.

Earthquake is one of the natural disasters that pose a serious threat to the safety of human life and social development. Earthquake disasters are listed as an important disaster type in the first national comprehensive risk assessment of natural disasters. Clarifying historical earthquake disaster data and understanding the development trend are of great significance for earthquake prevention and scientific plans to avoid the disaster threats. According to the earthquake disaster risk assessment implementation plan in Xizang Autonomous Region, a comprehensive collection of materials was conducted, including the latest earthquake catalog officially published by the earthquake department, officially published compilations of earthquake damage reports, and earthquake report data summarized by the Earthquake Agency of Xizang Autonomous Region. This included 45 items such as earthquake disaster information tables, data cards, earthquake disaster survey materials, damage assessment reports, summaries of earthquake emergency response and disposal work. A thorough investigation, organization, and compilation of annual historical earthquake disaster statistics for each county-level administrative region from 1978 to 2020 were carried out, establishing a long-term spatial-temporal dataset of major historical earthquake disasters since 1949, which contains complete, detailed, and standardized data on intensity, scope, and disaster conditions. There were over 600 earthquakes with a magnitude of MS5.0 or above during the study period, causing 43 earthquake disasters, with a disaster rate of approximately 7.2%. Between 1949 and 2020, there were 5 major earthquakes that caused significant casualties and economic losses. The spatial distribution of destructive earthquakes is primarily controlled by tectonic systems. However, based on the actual conditions in the Xizang Autonomous Region, it is significantly influenced by the population distribution and the national economic situation of the areas where the earthquakes occur.

China is one of the countries in the world with the most frequent occurrence of continental earthquakes and the greatest impacts of earthquake disasters. In particular, the Qinghai-Tibet Plateau is a region characterized by a wide spatial distribution of continental earthquakes, shallow epicenters, complex seismic origins, and significant disaster losses, making it highly susceptible to seismic events. The need for seismic geological survey is becoming increasingly urgent in this area. Based on regional geological eological data，high-precision satellite remote sensing images and DEM elevation data，this paper interprets the active faults in the region of Xigaze. The results show that the active faults in the Xigaze area are mainly concentrated in the rift valleys and their periphery, with tectonic activity varying spatially. The tectonic activity of active faults in the eastern rift is stronger than that in the western rifts. Additionally，the tectonic activity of active faults in each rift also shows a clear segmentation feature. At the same time, this paper comprehensively considers the characteristics of active faults, topography and geomorphology and stratigraphic lithology in the Xigaze area. It preliminarily evaluates the potential risk of earthquake disasters in 204 towns under its jurisdiction. The results show that there are 57 towns with “extremely high risk” “high risk” and “high-medium risk” of earthquake disasters, accounting for about 28% of the total number of towns in the region.

The Horba-Tsam Tso rift is one of the major rift systems in southern Tibet, with a general strike of N20°E and a total length of about 200 km, containing 20 parallel or oblique secondary fault zones and graben-half graben systems. The active faults and frequent earthquakes of the rift valley since the Neogene play an important role in understanding the uplift process and deformation mechanism of the Tibetan Plateau in the Late Cenozoic. In this paper, the development characteristics and spatial distribution of major normal faults and surface fractures in rifts were studied by means of remote sensing image interpretation, and then discussed their formation causes and deformation mechanisms. The main features of this region are the concentrated distribution of nearly north-south normal faults, which show the characteristics of high-density development of active faults in the Holocene. The development degree of faults in the rift valley shows a decreasing trend from east to west, and the number of faults and surface fractures decreases from north to south. The latest surface rupture in the rift valley developed at the eastern foot of the Lunggar Mountain, and the Holocene landform along the dislocation is closely related to the spatial distribution of the faults and the historical earthquakes. Based on the analysis of historical data, it is found that there is an earthquake gap in the northern section of the rift, which may cause strong earthquakes in the future.

Abstract The purpose of this study was to elucidate the mechanisms by which new media use (NMU), media trust (MT), and ecological cognition (EC) influence willingness to use clean energy (WTUCE), with the aim of promoting the development of clean energy and improving the rural ecological environment. We employed a structural equation model to investigate the impact of NMU, EC, and MT on WTUCE. The users who answered the questionnaire were mainly from the Hebei, Shandong, Shanxi, and Henan provinces in northern China. The study produced the following findings: (i) NMU directly affects the WTUCE of farmers. EC positively affects farmers’ WTUCE. NMU positively affects the EC level of rural families. (ii) MT has a moderating effect on the relationship between NMU and EC. EC has a mediating effect on the relationship between NMU and farmers’ WTUCE. (iii) Compared with plains-type areas, the higher the degree of MT in mountainous areas is, the greater the role of NMU in EC, and it plays a moderating role. Compared with that in mountainous areas, the direct effect of NMU on EC was 21.43% greater in plains areas, and the direct effect was stronger. (iv) Compared with those with a high proportion of nonagricultural income, the degree of MT of those with a low proportion of nonagricultural income is greater, the effect of NMU on EC is greater, and it plays a moderating role. Compared with the low nonagricultural income ratio, NMU for a high nonagricultural income ratio has a stronger direct effect on EC (14.30%), and the direct effect is stronger. This study enriches our understanding of the mechanisms of rural families’ WTUCE based on EC. It also provides theoretical support and practical experience, based on NMU, for the effective promotion of clean energy and energy transformation and upgrading.

Abstract Questions of unfairness and inequity pose critical challenges to the successful deployment of artificial intelligence (AI) in healthcare settings. In AI models, unequal performance across protected groups may be partially attributable to the learning of spurious or otherwise undesirable correlations between sensitive attributes and disease-related information. Here, we introduce the Attribute Neutral Framework, designed to disentangle biased attributes from disease-relevant information and subsequently neutralize them to improve representation across diverse subgroups. Within the framework, we develop the Attribute Neutralizer (AttrNzr) to generate neutralized data, for which protected attributes can no longer be easily predicted by humans or by machine learning classifiers. We then utilize these data to train the disease diagnosis model (DDM). Comparative analysis with other unfairness mitigation algorithms demonstrates that AttrNzr outperforms in reducing the unfairness of the DDM while maintaining DDM’s overall disease diagnosis performance. Furthermore, AttrNzr supports the simultaneous neutralization of multiple attributes and demonstrates utility even when applied solely during the training phase, without being used in the test phase. Moreover, instead of introducing additional constraints to the DDM, the AttrNzr directly addresses a root cause of unfairness, providing a model-independent solution. Our results with AttrNzr highlight the potential of data-centered and model-independent solutions for fairness challenges in AI-enabled medical systems.

Abstract The orbital Hall effect in light materials has attracted considerable attention for developing orbitronic devices. Here we investigate the orbital torque efficiency and demonstrate the switching of the perpendicularly magnetized materials through the orbital Hall material, i.e., Zr. The orbital torque efficiency of approximately 0.78 is achieved in the Zr orbital Hall material with the perpendicularly magnetized [Co/Pt]3 sample, which significantly surpasses that of the perpendicularly magnetized CoFeB/Gd/CoFeB sample (approximately 0.04). Such a notable difference is attributed to the different spin-orbit correlation strength between the [Co/Pt]3 sample and the CoFeB/Gd/CoFeB sample, confirmed through theoretical calculations. Furthermore, the full magnetization switching of the [Co/Pt]3 samples with a switching current density of approximately 2.6×106 A/cm2 has been realized through Zr, which even outperforms that of the W spin Hall material. Our finding provides a guideline to understand orbital torque efficiency and paves the way for developing energy-efficient orbitronic devices.

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

Objective:. This study aims to investigate the impact of tricuspid regurgitation (TR) severity on the accuracy of echocardiographic estimation of systolic pulmonary arterial pressure (sPAP) in patients with pulmonary arterial hypertension (PAH). Methods:. Patients who were diagnosed with PAH and had a right heart catheterization (RHC) and echocardiography examination were selected retrospectively from May 2018 to December 2021. sPAP measured by RHC is used as the gold standard. A difference in sPAP of less than 10 mmHg between echocardiographic estimation by peak TR velocity and RHC measurement was defined as accurate, with a difference ≥10 mmHg considered inaccurate. The factors affecting the accuracy of echocardiographic sPAP estimation were analyzed by univariate and multivariate analysis. Results:. A total of 138 patients aged (45.57 ± 15.97) years with PAH were enrolled. sPAP measured by echocardiography and RHC were (80.83 ± 23.46) and (81.62 ± 30.05) mmHg, respectively. The values of the 2 methods were highly correlated (r = 0.809, P < 0.01) and Bland-Altman plots showed good consistency. The accuracy rate of sPAP estimation by echocardiography was 42.03% (58/138). In the 57.97% (80/138) of patients where echocardiography was inaccurate, sPAP was overestimated in 28.26% (39/138) and underestimated in 29.71% (41/138). Univariate analysis showed that there was a statistically significant difference between the accurate and inaccurate groups in World Health Organization-Function Class, N-terminal pro-B-type natriuretic peptide, severity of TR, tricuspid annular plane systolic excursion (TAPSE), sPAP-RHC, mean pulmonary artery pressure, pulmonary vascular resistance (P < 0.05). Multivariate logistic regression analyses identified the TR severity (odds ratio = 2.292, 95% confidence interval: 1.126–4.667, P = 0.022) and TAPSE (odds ratio = 0.733, 95% confidence interval: 0.621–0.865, P < 0.001) as independent predictors for the accuracy of echocardiographic sPAP estimation. Conclusion:. Higher TR severity and lower TAPSE values reduce the accuracy of sPAP estimated by echocardiography. Therefore, TR severity and right heart function should be considered when echocardiography is used to estimate sPAP by the TR velocity.

Abstract Objectives To investigate the feasibility of a deep learning-constrained compressed sensing (DL-CS) method in non-contrast-enhanced modified DIXON (mDIXON) coronary magnetic resonance angiography (MRA) and compare its diagnostic accuracy using coronary CT angiography (CCTA) as a reference standard. Methods Ninety-nine participants were prospectively recruited for this study. Thirty healthy subjects (age range: 20–65 years; 50% female) underwent three non-contrast mDIXON-based coronary MRA sequences including DL-CS, CS, and conventional sequences. The three groups were compared based on the scan time, subjective image quality score, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). The remaining 69 patients suspected of coronary artery disease (CAD) (age range: 39–83 years; 51% female) underwent the DL-CS coronary MRA and its diagnostic performance was compared with that of CCTA. Results The scan time for the DL-CS and CS sequences was notably shorter than that of the conventional sequence (9.6 ± 3.1 min vs 10.0 ± 3.4 min vs 13.0 ± 4.9 min; p

Abstract Compassion fatigue is a prevalent challenge experienced by helping professionals, influencing both their personal well-being and the quality of services they deliver. While the beneficial impact of expertise in counseling on alleviating compassion fatigue has been established, limited research has investigated this association specifically among mental health counselors within the cultural context of China. Additionally, the underlying mechanisms remain unclear. This study examined whether expertise in counseling can reduce compassion fatigue and whether this relationship is mediated by core self-evaluation and resilience. A cross-sectional survey of 109 mental health counselors revealed that expertise negatively predicted compassion fatigue both directly and indirectly through enhanced core self-evaluation. However, resilience only exhibited a negative correlation with compassion fatigue and a positive correlation with core self-evaluation, its mediating effect between expertise and compassion fatigue was not supported. This study highlights the crucial role of expertise and core self-evaluation as mediating factors in alleviating compassion fatigue.

Abstract Background Patients with tuberous sclerosis complex (TSC) develop renal cysts and/or angiomyolipomas (AMLs) due to inactive mutations of either TSC1 or TSC2 and consequential mTOR hyperactivation. The molecular events between activated mTOR and renal cysts/AMLs are still largely unknown. Methods The mouse model of TSC-associated renal cysts were constructed by knocking out Tsc2 specifically in renal tubules (Tsc2 f/f; ksp-Cre). We further globally deleted PRAS40 in these mice to investigate the role of PRAS40. Tsc2 −/− cells were used as mTOR activation model cells. Inhibition of DNA methylation was used to increase miR-142-3p expression to examine the effects of miR-142-3p on PRAS40 expression and TSC-associated renal cysts. Results PRAS40, a component of mTOR complex 1, was overexpressed in Tsc2-deleted cell lines and mouse kidneys (Tsc2 f/f; ksp-Cre), which was decreased by mTOR inhibition. mTOR stimulated PRAS40 expression through suppression of miR-142-3p expression. Unleashed PRAS40 was critical to the proliferation of Tsc2 −/− cells and the renal cystogenesis of Tsc2 f/f; ksp-Cre mice. In contrast, inhibition of DNA methylation increased miR-142-3p expression, decreased PRAS40 expression, and hindered cell proliferation and renal cystogenesis. Conclusions Our data suggest that mTOR activation caused by TSC2 deletion increases PRAS40 expression through miR-142-3p repression. PRAS40 depletion or the pharmacological induction of miR-142-3p expression impaired TSC2 deficiency-associated renal cystogenesis. Therefore, harnessing mTOR/miR-142-3p/PRAS40 signaling cascade may mitigate hyperactivated mTOR-related diseases.

Abstract University students are highly vulnerable to experiencing academic burnout due to various pressures, necessitating an exploration of its causes and effects. Time perspective theory emphasizes how individuals' perspectives of past, present, and future events shape their behavior. Yet, the relationship between time perspective, burnout, and academic achievement remains unclear. This study investigates this association in Chinese undergraduates using survey and official grade point average (GPA) data. Results indicate positive correlations between Past-Negative, Present-Hedonistic (PH), Present-Fatalistic time perspectives, and academic burnout. Additionally, only Present-Hedonistic (PH) and future time perspectives significantly predict GPA. A mediation model reveals misbehavior as a mediator between Present-Hedonistic (PH) time perspective and GPA. These findings highlight time perspective’s importance in academic well-being and outcomes, shedding light on the distinct roles of future and Present-Hedonistic time perspectives.

Abstract Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Background: Atrophic scarring is a severe form-disfiguring sequela of acne, which can lead to negative effect on patients’ life. Fractional microplasma radiofrequency (RF) has emerged as a promising modality, leveraging dermal fibroblast remodeling to enhance aesthetic results for scars and hyperpigmentation. This study evaluates the efficacy and safety of high-power fractional microplasma RF for atrophic acne scars, considering patient tolerance to procedural discomfort. Methods: In this prospective study, 95 Chinese patients with atrophic facial acne scars underwent three sessions of fractional microplasma RF treatment, with assessments at 1, 3, and 6 months post-treatment. Patients were categorized based on treatment power: Group A (50-70 W) and Group B (70-85 W). Efficacy was determined by three independent dermatologists using digital photographs and Echelle d'Evaluation Clinique des Cicatrices d'Acné (ECCA) scores, and patient-reported outcomes gauged satisfaction levels. Results: Eighty-six patients completed the study. Significant improvements were observed, with a reduction in ECCA scores from 107.21 to 42.27 (P

This is an article in the field of metallurgical engineering, which proposed a new idea of mixing molten blast furnace slag with steel slag to achieve self-pulverization of steel slag, and systematically studied the influence mechanism of special components of CaF2 and CeO2 in blast furnace slag of Baotou Iron and Steel Company on the self-pulverization of steel slags. Using analytically pure CaO, SiO2, CaF2 and CeO2 as starting materials, pure C2S specimens were prepared with n ( CaO ) : n ( SiO2 ) = 2 : 1, then different mass fractions of CaF2 and CeO2 were added, respectively. The effect of CaF2 and CeO2 on the self-pulverization behavior of C2S was investigated by calcining the specimen at 1 450 °C for 1 h and cooling with the furnace. The results showed when CaF2 was incorporated into C2S and the content of CaF2 was less than 2.5%, it had little effect on the self-pulverization of C2S. However, when the content of CaF2 was more than 2.5%, the specimen had different degrees of agglomeration, which affected the self-pulverization of C2S. Considering that excessive CaF2 would affect the environment, the content of CaF2 should be controlled below 2.5%. When CeO2 incorporated into C2S and the content was 0.25%, C2S could still be completely self-pulverized, but when the CeO2 content was more than 0.5%, C2S no longer self-pulverized.Therefore, the CeO2 content must be less than 0.25 %, and the self-pulverization effect of C2S was relatively good.

This paper presents a systematic methodology for analyzing and optimizing an innovative antenna mount designed for phased array antennas, implemented through a novel 2-PSS&1-RR circular-rail parallel mechanism. Initially, a comparative motion analysis between the 3D model of the mount and its full-scale prototype is conducted to validate effectiveness. Given the inherent complexity, a kinematic mapping model is established between the mount and the crank-slider linkage, providing a guiding framework for subsequent analysis and optimization. Guided by this model, feasible inverse and forward solutions are derived, enabling precise identification of stiffness singularities. The concept of singularity distance is thus introduced to reflect the structural stiffness of the mount. Subsequently, also guided by the mapping model, a heuristic algorithm incorporating two backtracking procedures is developed to reduce the mount's mass. Additionally, a parametric finite-element model is employed to explore the relation between singularity distance and structural stiffness. The results indicate a significant reduction (about 16%) in the antenna mount's mass through the developed algorithm, while highlighting the singularity distance as an effective stiffness indicator for this type of antenna mount.

Abstract Sotatercept is a breakthrough, first‐in‐class biologic, that is FDA‐approved for the treatment of pulmonary arterial hypertension (PAH). A population pharmacokinetic (PopPK) model was developed using data from two phase 1 studies in healthy participants, and two phase 2 studies and one phase 3 study in participants with PAH. The pooled sotatercept PK data encompassed single intravenous (IV) or subcutaneous (SC) doses ranging from 0.01 to 3.0 mg/kg, as well as multiple SC doses ranging from 0.03 to 1.0 mg/kg, with PK samples collected up to a maximum of ~150 weeks following Q3W and Q4W dosing regimens. The final PopPK analysis included 350 participants, with 30 and 320 participants receiving sotatercept IV and SC, respectively. A two‐compartment model with a first‐order absorption rate constant and a linear disposition from central compartment well‐described sotatercept PK. The estimated bioavailability is ~66%; bioavailability, clearance (CL), and central volume (VC) have low to moderate inter‐individual variability. Time‐varying body weight and baseline albumin concentration were statistically significant predictors of PK; CL and VC were predicted to increase with increasing body weight, while CL was predicted to decrease with increasing baseline albumin concentration. However, the magnitude of covariate effects is not predicted to meaningfully alter the disposition of sotatercept. Altogether, the PopPK modeling results demonstrate favorable PK characteristics (low to moderate variability and typical bioavailability), supporting sotatercept as a SC biological agent for the treatment of patients with PAH.

Abstract The cycling stability of O3‐type NaNi1/3Fe1/3Mn1/3O2 (NFM) as a commercial cathode material for sodium ion batteries (SIBs) is still a challenge. In this study, the Ni/Fe/Mn elements are replaced successfully with tantalum (Ta) in the NFM lattice, which generated additional delocalized electrons and enhanced the binding ability between the transition metal and oxygen, resulting in suppressed lattice distortion during charging and discharging. This caused significant mitigation of voltage decay and improved cycle stability within the potential range of 2.0–4.2 V. The optimized Na(Ni1/3Fe1/3Mn1/3)0.97Ta0.03O2 sample achieved a reversible capacity of 162.6 mAh g−1 at a current rate of 0.1 C and 73.2 mAh g−1 at a high rate of 10 C. Additionally, the average charge/discharge potential retention reached 98% after 100 cycles, significantly mitigating the voltage decay. This work demonstrates a significant contribution towards the practical utilization of NFM cathodes in the SIBs energy storage field.

Abstract Hyperproliferation of vascular smooth muscle cells (VSMCs) is a driver of hypertensive vascular remodeling. This study aimed to uncover the mechanism of BTB and CNC homology 1 (BACH1) and microRNAs (miRNAs) in VSMC growth and hypertensive vascular remodeling. With the help of TargetScan, miRWalk, miRDB, and miRTarBase online database, we identified that BACH1 might be targeted by miR-196a-5p, and overexpressed in VSMCs and aortic tissues from spontaneously hypertensive rats (SHRs). Gain- and loss-of-function experiments demonstrated that miR-196a-5p suppressed VSMC proliferation, oxidative stress and hypertensive vascular remodeling. Double luciferase reporter gene assay and functional verification showed that miR-196a-5p cracked down the transcription and translation of BACH1 in both Wistar Kyoto rats (WKYs) and SHRs. Silencing BACH1 mimicked the actions of miR-196a-5p overexpression on attenuating the proliferation and oxidative damage of VSMCs derived from SHRs. Importantly, miR-196a-5p overexpression and BACH1 knockdown cooperatively inhibited VSMC proliferation and oxidative stress in SHRs. Furthermore, miR-196a-5p, if knocked down in SHRs, aggravated hypertension, upregulated BACH1 and promoted VSMC proliferation, all contributing to vascular remodeling. Taken together, targeting miR-196a-5p to downregulate BACH1 may be a promising strategy for retarding VSMC proliferation and hypertensive vascular remodeling.

Abstract Nuclear factor-kappaB (NF-ĸB) plays a crucial role in both innate and adaptive immune systems, significantly influencing various physiological processes such as cell proliferation, migration, differentiation, survival, and stemness. The function of NF-ĸB in cancer progression and response to chemotherapy has gained increasing attention. This review highlights the role of NF-ĸB in inflammation control, biological mechanisms, and therapeutic implications in cancer treatment. NF-ĸB is instrumental in altering the release of inflammatory factors such as TNF-α, IL-6, and IL-1β, which are key in the regulation of carcinogenesis. Specifically, in conditions including colitis, NF-ĸB upregulation can intensify inflammation, potentially leading to the development of colorectal cancer. Its pivotal role extends to regulating the tumor microenvironment, impacting components such as macrophages, fibroblasts, T cells, and natural killer cells. This regulation influences tumorigenesis and can dampen anti-tumor immune responses. Additionally, NF-ĸB modulates cell death mechanisms, notably by inhibiting apoptosis and ferroptosis. It also has a dual role in stimulating or suppressing autophagy in various cancers. Beyond these functions, NF-ĸB plays a role in controlling cancer stem cells, fostering angiogenesis, increasing metastatic potential through EMT induction, and reducing tumor cell sensitivity to chemotherapy and radiotherapy. Given its oncogenic capabilities, research has focused on natural products and small molecule compounds that can suppress NF-ĸB, offering promising avenues for cancer therapy.

The microstructure, phase transformation behavior, heat treatment effects, and their impacts on the mechanical properties and high-temperature oxidation resistance of IN718 nickel-based superalloy processed by selective laser melting (SLM) both before and after heat treatment was systematically investigated. The heat treatment process involved a two-step aging at 720 °C for 8 h plus 620 °C for 10 h with a controlled slow cooling rate of 10 °C/min. Through the comprehensive use of scanning electron microscopy (SEM), X-ray diffraction (XRD), electron backscattering diffraction (EBSD), and transmission electron microscopy (TEM), the evolution of the microstructure and its mechanism of influence on material properties were revealed. The study identified the formation of γ phase, γ′ phase, γ'' phase, δ phase, and Laves phase during the SLM forming process. Heat treatment played a key role in improving the microstructure and properties of the SLM-processed alloy, with experimental results showing that the mechanical performance and high-temperature oxidation resistance were significantly enhanced after heat treatment. Specifically, the material after heat treatment exhibited a yield strength of 1472 MPa, a tensile strength of 1608 MPa, and an elongation of 9.2%, which represented increases of 76.5%, 38.4%, and 16.5% respectively, compared to the as-printed alloy. Moreover, the oxidation resistance at 1000 °C of the heat-treated samples improved significantly, with weight loss reduced from −0.17 mg/cm2 before heat treatment to −0.15 mg/cm2. Microstructural analysis further indicated that heat treatment optimized the crystal orientation, promoted the formation of more precipitated phases and reduced defects, thereby enhancing the overall performance of the material. This work provides significant scientific insights into understanding and optimizing the IN718 nickel-based superalloy processed by SLM, demonstrating the crucial role of heat treatment in improving its microstructure and properties.

Abstract Unfractionated heparin (UFH) is commonly used as an anticoagulant in sepsis treatment and has recently been found to have non‐anticoagulant effects, but underlying mechanisms remain unclear. This retrospective clinical data showed that UFH has significant protective effects in sepsis compared to low‐molecular‐weight heparin and enoxaparin, indicating potential benefits of its non‐anticoagulant properties. Recombinant protein chip screening, surface plasmon resonance, and molecular docking data demonstrated that UFH specifically bound to the cytoplasmic Drp1 protein through its zone 2 non‐anticoagulant segment. In‐vitro experiments verified that UFH's specific binding to Drp1 suppressed Drp1 translocation to mitochondria following “sepsis” challenge, thereby improving mitochondrial morphology, function and metabolism in vascular endothelial cells. Consequently, UHF comprehensively protected mitochondrial quality, thus reducing vascular leakage and improving prognosis in a sepsis rat model. These findings highlight the potential of UFH as a sepsis treatment strategy targeting non‐anticoagulation mechanism.

Understanding the threshold responses of vegetation to drought is essential for predicting and mitigating drought risk. Across Central Asia, extreme weather is expected to increase by the end of the 21st century. However, the threshold responses of different Central Asian vegetation types are not well understood. Here, we calculated drought indices for Central Asia based on meteorological data and remotely sensed vegetation indices from 2001 to 2020, used trend analysis to assess changes in drought and vegetation in Central Asia over the past 20 years, evaluated the threshold responses of five vegetation types to drought, and explored the drought causative factors of different vegetation types using coexistence analysis. All five Central Asian vegetation types responded to increasing drought in a nonlinear manner, and thus exhibited drought-responsive thresholds. Forests were the first responders to increasing drought, and wetlands were the least responsive overall. Grasslands, cultivated lands, shrublands, and forests crossed the drought threshold in different years between 2001 and 2020, with shrublands exhibiting the largest percentage of area crossing the threshold. Finally, the drought causative factor for grasslands, shrublands, and wetlands was soil moisture; for cultivated lands was precipitation; and for forests was saturated water vapor pressure difference. This study uncovers the characteristic responses of different Central Asian vegetation types to drought, and lays a theoretical foundation for drought assessment and ecological restoration in Central Asia.

The amplification of signals is dependent upon enzyme/ catalyst. Enzyme activity, specificity, pH condition, enzyme linkers, stability, storage and efficiency are some very important factors that can eventually affect the detection results. We aimed to amplify signals without the assistance of enzyme/ catalyst so that the strategy can be used in the wide range of signal detection including immune-assay. Silver nanocrystals (Ag NCs) grown from self-nucleation are used as chromogens due to their strong plasmon band at ∼ 400 nm. During 140 s of reaction time in presence of 6.10 mM CTAB and 0.61 mM of AgNO3, the 0.57 mM of Ascorbic acid allows Ag over growth on antibody-tagged gold nanospheres (10±0.5 nm) that competes silver atoms from the self-nucleation growth and thus affects the growth kinetics of the latter. By utilizing the opened kinetic window, sensitive detection has been achieved from 6.67 × 10–14 M (1 pg) to 3.33 × 10–9 M (50 ng) using human IgG as a model protein. The non-catalytic plasmonic immunoabsorbant assay we developed herein adds a new possibility of plasmonic NPs for sensitive detection. The detection slope and resolution is higher and better than those via signal amplification through the assistance of enzymes/ catalysts. This work supports the concept that nanoparticles mediated reactions are sensitive enough that they have the potential to go independently without enzymes/ catalyst assistance.

This study investigates the phase evolution and enrichment mechanism of the cementitious materials in a blend of blast furnace (BF) and basic oxygen furnace (BOF) slags. Theoretical calculations reveal that there is an optimal modification temperature range of 1400–1550 °C, which is crucial for the transformation of the slag constituents. At lower temperatures (500–850 °C), the addition of BF slag reduces the proportion of calcium iron oxide (Ca2Fe2O5, C2F) and promotes the formation of merwinite (Ca3MgSi2O8, C3MS2). At higher temperatures (850–1450 °C), the addition of BF slag decreases the free CaO content, enhancing the stability of the modified slag. The presence of the dicalcium silicate and tricalcium phosphate complex (α-Ca2SiO4–Ca3(PO4)2, α-C2S-C3P), dicalcium ferrite (C2F), and magnesioferrite (MgFe2O4) in the modified slag facilitates the creation of dicalcium silicate (Ca2SiO4, C2S) and C3MS2 phases, which improve the stability of the slag and increase the amount of cementitious active materials, indirectly reducing crushing costs. Experimental results indicate that excessive BF slag content results in the over formation of gehlenite (Ca2Al2SiO7, C2AS) and C3MS2, potentially affecting the cementitious active material proportion. Insufficient BF slag does not fully utilize its CaO, SiO2, and Al2O3 for enhancing the BOF slag stability and increasing the cementitious material content. A BF slag content of approximately 30 % optimally consumes free CaO, promotes C2S formation, and enhances the stability of the modified slag. This research highlights the crucial role of the temperature and BF slag content in the phase evolution and cementitious potential of BF-modified BOF slags, providing guidelines for optimized utilization in construction materials.

This paper presents an experimental and numerical investigation into the bending behaviour of reinforced concrete (RC) T-beams damaged by overheight vehicle impact strengthened with ultra-high performance concrete (UHPC). Four-point bending tests were conducted on one RC T-beam and six UHPC-strengthened RC T-beams, and the primary parameters included the length and thickness of the UHPC strengthening layer, as well as the filling area of UHPC for the damaged region. The test results demonstrated that the UHPC strengthening layer effectively delayed the development of concrete cracks, improved the bending stiffness, cracking load, and resistance of the T-beams. The UHPC-strengthened T-beams exhibited an increase in cracking and ultimate loads by 39–339 % and 26–113 %, respectively, compared to the RC T-beam. Subsequently, a finite element (FE) model of the UHPC-strengthened T-beams was developed and validated using the experimental results. A parametric study using the validated FE model was conducted, revealing that insufficient strengthened length or excessive strengthened thickness of the UHPC layer increased the risk of debonding failure. Furthermore, for T-beams experiencing bending failure, increasing the thickness and height of the UHPC layer, as well as the UHPC filling area for the damaged region, significantly improved the bending resistance, while the UHPC layer length had little effect on the bending resistance. Finally, based on the calculation theory of RC beams under bending loads and considering the strain-hardening behaviour of UHPC in tension, a design method for the bending resistance of damaged RC T-beams strengthened with UHPC was proposed and verified using the experimental and numerical results.

Abstract Photoalignment technology is serving as an emerging technology for programming liquid crystalline polymer (LCP) materials due to its advantages including noncontact, high resolution, spatial control, programmability, and high efficiency. In this review, we report the research progress in implementing polarized light to design the anisotropy of LCPs, which is categorized based on the photoalignment mechanisms. The alignment approaches and the different stimulus‐responsive behaviors of the materials after photoalignment are discussed. Additionally, we have summarized the applications of photoaligned LCPs such as liquid crystal displays, optical components, intelligent soft actuators, and beyond. Finally, the challenges and future directions of the technology are outlined.

Morphine has a crucial role in treating both moderate to severe pain and chronic pain. However, prolonged administration of morphine can lead to tolerance of analgesia, resulting in increased doses and poor treatment of pain. Many patients, such as those with terminal cancer, require high doses of morphine for long periods. Addressing morphine tolerance can help this group of patients to escape pain, and the mechanisms behind this need to be investigated. Microglia are the key cells involved in morphine tolerance and chronic morphine administration leads to microglia activation, which in turn leads to activation of internal microglia signalling pathways and protein transcription, ultimately leading to the release of inflammatory factors. Inhibiting the activation of microglia internal signalling pathways can reduce morphine tolerance. However, the exact mechanism of how morphine acts on microglia and ultimately leads to tolerance is unknown. This article discusses the mechanisms of morphine induced microglia activation, reviews the signalling pathways within microglia and the associated therapeutic targets and possible drugs, and provides possible directions for clinical prevention or retardation of morphine induced analgesic tolerance.

VPS13A disease (also known as Chorea-Acanthocytosis, ChAc) is a representative subtype of the neuroacanthocytosis (NA) syndromes, characterized by neurodegeneration in the central nervous system and acanthocytosis in peripheral blood. It is a rare autosomal recessive genetic disorder caused by loss-of-function variants in the VPS13A gene, which is currently the only known pathogenic gene for ChAc. VPS13A protein is a member of novel bridge-like lipid transfer proteins family located at membrane contact sites, forming direct channels for lipid transport. The specific mechanism underlying how the loss of VPS13A function leads to the hematological and neurological phenotypes of the disease remains unclear. Here we present a review of recent studies on VPS13A protein and ChAc, focusing on the potential role of the VPS13A protein in pathophysiology of ChAc and also review the known and potential wet biomarkers of ChAc to enhance our comprehension of this rare disease.

IntroductionThis work employs a coupled evaluation model that integrates deterministic coefficients with the Analytic Hierarchy Process to conduct a comprehensive assessment of geological disaster susceptibility in Shenzhen Town, Ninghai County.MethodsCascading geological disasters induced by typhoons and rainfall in the southeast coastal area of China are a major concern and cause huge losses of life and property every year. To effectively prevent and mitigate such disasters, it is necessary to evaluate the susceptibility of geological disasters. Taking geological disasters in Shenzhen Town, Ninghai County as the research object, eight influencing factors in terms of topographic and geomorphological conditions, engineering geological conditions, and human activities were selected based on the geographic information platform (GIS) in this work. The coupling model of the certainty factor model and analytic hierarchy process method was used to evaluate the susceptibility of geological hazards in the study area.ResultsThe evaluation results illustrate that the coupling model can accurately and objectively assess the susceptibility of geological hazards in this region, with a high evaluation accuracy of 80.8%. The susceptibility is greatly affected by slope, stratigraphic lithology, and human activities. The areas with extraordinarily high and high susceptibility were identified in the northwestern part of the study, where the ignimbrite is exposed in the steep topography.DiscussionThe research method provides a reference for evaluating the susceptibility of geological hazards in the southeastern coastal region of China, and the evaluation results can provide recommendations for decision-making on disaster prevention and mitigation in this region.

IntroductionEndogenous viral elements (EVEs) are viral sequences integrated within the host genome that can influence gene regulation and tumor development. While EVEs have been implicated in cancer, their role in regulating key transcription factors in glioblastoma (GBM) remains underexplored. This study investigates the relationship between EVEs and the activation of OCT4, a critical transcription factor in GBM progression.MethodsWe utilized CancerHERVdb and HervD Atlas databases to identify potential interactions between EVEs and key genes involved in GBM. Data from 273 GBM patient samples in the TCGA database were analyzed to examine the correlation between OCT4 expression and mutations in glioma-related genes. Furthermore, glioblastoma stem cells (GSCs) were assessed for the expression levels of OCT4 and SOX2, and Pearson correlation analysis was performed.ResultsOur analysis revealed that OCT4 is a pivotal gene activated by EVEs in GBM. OCT4 expression was significantly correlated with mutations in key glioma-associated genes. Higher OCT4 levels were associated with poorer patient prognosis, higher tumor grades, and older age. Additionally, GSCs exhibited elevated expression of both OCT4 and SOX2, with a positive correlation observed between these two genes in GBM patients.DiscussionThis study highlights the potential role of EVEs in driving GBM progression through the activation of OCT4. The findings emphasize the importance of OCT4 in GBM malignancy and suggest that targeting EVE-mediated pathways may provide new therapeutic approaches for GBM treatment.

Green development is an approach that harmonizes human beings with nature and leads to sustainable social and economic development. However, the factors influencing the level of green development are uncertain due to regional differences, especially in the alpine meadow regions. To explore the factors affecting green development in the alpine meadow region, we took the Gannan Tibetan Autonomous Prefecture as an example. Through a green development level evaluation index system, the DPSIR (Driver, Pressure, State, Impact, and Response) was constructed to comprehensively evaluate and analyze the green development level of the study area from 1990 to 2020. On this basis, the key influencing factors of the green development level was analyzed based on the GeoDetector. The findings indicate that the total level of green development in Gannan has an upward trend within the range of 0.044–0.535, moving towards high quality and sustainable development. Except for 2005, the spatial clustering characteristics of the green development level did not display obvious high values of spatial autocorrelation. The green development space is concentrated and stable, and the centre of gravity is in Zhuoni. The impact and response dimensions make the greatest contribution to green development. Different evaluation indicators have different impacts on green development during the study period. Specifically, people’s productive lives, the impact of social production and positive policy responses are the main factors contributing to green development. The findings will provide theoretical basis and case support for ecological security and green sustainable development in the alpine meadow regions.

FK506-binding protein 9 (FKBP9) is involved in tumor malignancy by resistance to endoplasmic reticulum (ER) stress, and the up-regulation of FKBP9 is associated with patients' poor prognosis. The current knowledge of the molecular mechanisms is still limited. One previous study showed that FKBP9 could confer glioblastoma cell resistance to ER stress through ASK1-p38 signaling. However, the upstream regulatory mechanism of FKBP9 expression is still indistinct. In this study, we identified the FKBP9 binding proteins using co-immunoprecipitation followed by mass spectrometry. Results showed that FKBP9 interacted with the binding immunoglobulin protein (BiP). BiP bound directly to FKBP9 with high affinity. BiP prolonged the half-life of the FKBP9 protein and stabilized the FKBP9 protein. BiP and FKBP9 protein levels were positively correlated in patients with glioma, and patients with high expression of BiP and FKBP9 showed a worse prognosis. Further studies showed that FKBP9 knockout in genetically engineered mice inhibited intracranial glioblastoma formation and prolonged survival by decreasing cellular proliferation and ER stress-induced CHOP-related apoptosis. Moreover, normal cells may depend less on FKBP9, as shown by the absence of apoptosis upon FKBP9 knockdown in a non-transformed human cell line and overall normal development in homozygous knockout mice. These findings suggest an important role of BiP-regulated FKBP9-associated signaling in glioma progression and the BiP–FKBP9 axis may be a potential therapeutic target for glioma.

Background: Fetal structural anomalies are detected by ultrasound in approximately 3 % of pregnancies. Numerous genetic diagnostic strategies have been widely applied to identify the genetic causes of prenatal abnormalities. We aimed to assess the value of simultaneous copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) in diagnosing fetuses with structural anomalies. Methods: Fetuses with structural anomalies detected by ultrasound were included for eligibility. After genetic counseling, WES and CNV-seq were performed on DNA samples of fetuses and their parents. All detected variants were evaluated for pathogenicity according to ACMG criteria, with the final diagnosis was determined based on ultrasound results and relevant family history. Results: The diagnostic rate of 174 fetuses with prenatal ultrasound abnormalities was 26.44 %, higher than that achieved through either CNV or WES analysis alone. Furthermore, the highest diagnostic rate was observed in fetuses with multiple system anomalies, accounting for 50 % of the total diagnostic yield, followed by skeletal system anomalies at 45.45 %. Three cases with multiple system abnormalities were found to have a dual diagnosis of pathogenic CNVs and SNV variants, representing 1.72 % of the total cohort. 38 pregnant women in their third trimester of pregnancy (27 weeks+) participated in this study, and 23.68 % received a confirmed genetic diagnosis. Finally, 31 women (67.39 %) voluntarily terminated their pregnancy following the testing and extensive genetic counseling. Conclusions: Our study demonstrated that the simultaneous CNV-seq and WES analyses are beneficial for the molecular diagnosis of underlying unexplained structural anomalies in fetuses. This strategy is more efficient in elucidating prenatal abnormalities with compound problems, such as dual diagnoses. Furthermore, the simultaneous strategy has a shorter turnaround time and is particularly suitable for families with structural anomalies found in the third trimester of pregnancy.

IntroductionEEG-based emotion recognition has gradually become a new research direction, known as affective Brain-Computer Interface (aBCI), which has huge application potential in human-computer interaction and neuroscience. However, how to extract spatio-temporal fusion features from complex EEG signals and build learning method with high recognition accuracy and strong interpretability is still challenging.MethodsIn this paper, we propose a hybrid attention spatio-temporal feature fusion network for EEG-based emotion recognition. First, we designed a spatial attention feature extractor capable of merging shallow and deep features to extract spatial information and adaptively select crucial features under different emotional states. Then, the temporal feature extractor based on the multi-head attention mechanism is integrated to perform spatio-temporal feature fusion to achieve emotion recognition. Finally, we visualize the extracted spatial attention features using feature maps, further analyzing key channels corresponding to different emotions and subjects.ResultsOur method outperforms the current state-of-the-art methods on two public datasets, SEED and DEAP. The recognition accuracy are 99.12% ± 1.25% (SEED), 98.93% ± 1.45% (DEAP-arousal), and 98.57% ± 2.60% (DEAP-valence). We also conduct ablation experiments, using statistical methods to analyze the impact of each module on the final result. The spatial attention features reveal that emotion-related neural patterns indeed exist, which is consistent with conclusions in the field of neurology.DiscussionThe experimental results show that our method can effectively extract and fuse spatial and temporal information. It has excellent recognition performance, and also possesses strong robustness, performing stably across different datasets and experimental environments for emotion recognition.

Abstract Accurate differentiation between angina with no obstructive coronary arteries (ANOCA) and mental stress-induced myocardial ischemia (MSIMI) is crucial for tailored treatment strategies, yet public data scarcity hampers understanding. Given the higher incidence of both conditions in women, this study prospectively enrolled 80 female ANOCA and 39 age-matched female controls, subjecting them to three types of mental stress tasks. ECGs were continuously monitored across Rest, Stress, and Recover stages of the mental stress tasks, with PET/CT imaging during the Stress stage to evaluate myocardial perfusion. With PET/CT serving as the gold standard for MSIMI diagnosis, 35 of the 80 ANOCA patients were diagnosed as MSIMI. Using ECG variables from different stages of mental stress tasks, we developed five machine learning models to diagnose MSIMI. The results showed that ECG data from different stages provide valuable information for MSIMI classification. Additionally, the dataset encompassed demographic details, physiological, and blood sample test results of the patients. We anticipate this new dataset will significantly push further progress in ANOCA and MSIMI research.

Abstract Background Current cancer therapies often fall short in addressing the complexities of malignancies, underscoring the urgent need for innovative treatment strategies. RNA interference technology, which specifically suppresses gene expression, offers a promising new approach in the fight against tumors. Recent studies have identified a novel immunostimulatory small-interfering RNA (siRNA) with a unique sequence (sense strand, 5’-C; antisense strand, 3’-GGG) capable of activating the RIG-I/IRF3 signaling pathway. This activation induces the release of type I and III interferons, leading to an effective antiviral immune response. However, this class of immunostimulatory siRNA has not yet been explored in cancer therapy. Methods IsiBCL-2, an innovative immunostimulatory siRNA designed to suppress the levels of B-cell lymphoma 2 (BCL-2), contains a distinctive motif (sense strand, 5’-C; antisense strand, 3’-GGG). Glioblastoma cells were subjected to 100 nM isiBCL-2 treatment in vitro for 48 h. Morphological changes, cell viability (CCK-8 assay), proliferation (colony formation assay), migration/invasion (scratch test and Transwell assay), apoptosis rate, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were evaluated. Western blotting and immunofluorescence analyses were performed to assess RIG-I and MHC-I molecule levels, and ELISA was utilized to measure the levels of cytokines (IFN-β and CXCL10). In vivo heterogeneous tumor models were established, and the anti-tumor effect of isiBCL-2 was confirmed through intratumoral injection. Results IsiBCL-2 exhibited significant inhibitory effects on glioblastoma cell growth and induced apoptosis. BCL-2 mRNA levels were significantly decreased by 67.52%. IsiBCL-2 treatment resulted in an apoptotic rate of approximately 51.96%, accompanied by a 71.76% reduction in MMP and a 41.87% increase in ROS accumulation. Western blotting and immunofluorescence analyses demonstrated increased levels of RIG-I, MAVS, and MHC-I following isiBCL-2 treatment. ELISA tests indicated a significant increase in IFN-β and CXCL10 levels. In vivo studies using nude mice confirmed that isiBCL-2 effectively impeded the growth and progression of glioblastoma tumors. Conclusions This study introduces an innovative method to induce innate signaling by incorporating an immunostimulatory sequence (sense strand, 5’-C; antisense strand, 3’-GGG) into siRNA, resulting in the formation of RNA dimers through Hoogsteen base-pairing. This activation triggers the RIG-I signaling pathway in tumor cells, causing further damage and inducing a potent immune response. This inventive design and application of immunostimulatory siRNA offer a novel perspective on tumor immunotherapy, holding significant implications for the field.