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Abstract The fracture toughness (KIC) of high-entropy oxides (HEOs) is critically important for several applications, but identification and quantification of the toughening mechanisms resulting from lattice-engineering/distortion in HEOs is challenging. Here, based on the classic Griffith criteria, a physics-driven theoretical equation combined with a knowledge-enabled data-driven machine-learning algorithm is proposed to predict the KIC and elucidate the toughening mechanisms of A2Zr2O7-type HEOs. Together with experimental verification, our proposed model is applied to a dataset comprising 41208 (nRE1/n)2Zr2O7 (n = 2~7) HEOs, considering the contributions of the intrinsic brittleness and increased toughness due to the local lattice distortion (LLD), thereby addressing the challenge of accurate estimating KIC in complex HEOs using the rule of mixtures. During crack tip propagation, the interaction mechanism of cations induces stress fields and charge variations of LLD and dissipates crack energy, thus, to yield the crack tip softening and the elastic shielding and to enhance the toughness of HEOs.

Abstract Backgrounds Anticipating difficult laryngoscopy is crucial for preoperative assessment, especially for patients with cervical spondylosis. Radiological assessment has become essential for improving airway management safety. This research introduces novel radiological indicators from lateral cervical X-ray in the extended head position proposed to enhance the accuracy of predicting difficult laryngoscopy. Methods A prospective cohort study included 422 patients scheduled for elective cervical spine surgery. The Cormack-Lehane grades I and II were categorized as “easy laryngoscopy group”, while grades III and IV were labeled “difficult laryngoscopy group”. Demographic data, conventional bedside indicators including inter-incisor gap (IIG), neck circumference (NC), thyromental distance, the upper lip bite test (ULBT), and 4 radiological indicators including Mandibular Length, Laryngeal Height, the Larynx-Mandibular Angle Test (LMAT) and Larynx-Mandibular Height Test (LMHT) were analyzed comparatively. A binary logistic regression model was developed to identify independent predictive factors. The predictive value of the indicators was evaluated with the area under the curve (AUC). Results A total of 402 patients were analyzed in the present study. A binary logistic regression model identified IIG, NC, ULBT, and LMAT as the independent indicators associated with difficult laryngoscopy. A novel combined predictive model equation was derived: Ɩ=−0.969 − 1.33×IIG + 0.408×ULBT + 0.201×NC − 0.042×LMAT. The AUC for this composite model was 0.776, exceeding the individual AUC of 0.677 for LMHT. Conclusion LMHT and the novel combined predictive model incorporating LMAT are potentially valuable predictors for difficult laryngoscopy in patients with cervical spondylosis. Trial registration The study was registered at the Chinese Clinical Trial Registry (ChiCTR2200058361) on April 7, 2022.

Purpose: Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods. Methods: This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Non-normally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher’s exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Results: A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time (p

Accelerating green innovation is crucial for achieving high-quality development in China. Despite this importance, empirical evidence on the harmonization techniques in the context of carbon-trading policies has been remarkably thin. To address this gap, we employed the difference-in-difference (DID) and spatial difference-in-difference (S-DID) models using panel data from 2007 to 2017 for 30 Chinese provinces. Our findings reveal that the carbon-trading policy contributes significantly to the coordinated advancement of green technologies across Chinese provinces and exhibits a local siphoning effect. Specifically, the pilot areas of the policy have attracted talent from neighboring regions, which has fostered local cooperation and promoted coordinated innovation in green technologies within the region.

Microscale energetic materials have garnered considerable attention because they can be integrated in microelectromechanical systems for several potential applications. Hexanitrostilbene (HNS) has been widely utilized in ignition and initiation devices owing to its excellent thermal and shock stability and high sensitivity to short pulse shock waves. To meet the energy release requirements of micro-detonation devices, HNS sticks were prepared using direct ink writing and their reaction and flame propagation properties were studied. HNS particles sized 17.5 µm to 5 µm and ∼500 nm was prepared. Then, the viscosity of HNS-based inks prepared via acoustic resonance technology decreased when the particle size decreased or when the HNS content reduced from 97 wt.%, 95 wt.%, and 92 wt.%, to 90 wt.%. Additionally, the HNS-based inks with different binders exhibited different viscosity. The effect of the inner diameter of needle (0.4 mm, 0.6 mm, and 0.9 mm), printing rate (13 mm/s, 15 mm/s, 17 mm/s, 19 mm/s), and pressure (0.05 MPa, 0.1 MPa, 0.15 MPa, 0.2 MPa) on the width of HNS sticks was also elucidated. HNS-based sticks with a diameter of 0.9 mm underwent self-sustaining combustion reactions, and the burning rate increased from 5.1 mm/s to 6.8 mm/s as the particle size decreased from 17.5 µm to 500 nm. Overall, this work provides an effective approach to prepare microscale HNS for integration into micro-energetic devices.

BackgroundMaternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. ObjectiveTo explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. MethodsThirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg−1 BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. ResultsThere were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg−1 BPA groups and the liver weight in the 5 mg·kg−1 BPA group reduced compared with the control group (P0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg−1 BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg−1) reduced (P0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg−1 BPA group increased (P

Abstract Background Easy-to-use, rapid, scalable, high-throughput, and cost-effective HPV tests are urgently needed for low-resource settings. Atila Biosystems’ high-throughput, cost-effective, and clinically validated ScreenFire HPV Risk Stratification (RS) assay identifies 13 high risk HPV (hrHPV) in 4 groups based on their oncogenic risk (i.e., HPV16, HPV18/45, HPV31/33/35/52/58, and HPV51/59/39/56/68). The current standard format is subject to laboratory contamination, which is common for any molecular PCR test. To overcome this drawback, Atila has recently upgraded it into an innovative, contamination-free Zebra BioDome format. The contamination-free feature makes this novel assay format more suitable for large-scale community- and population-based cervical screening. This study evaluated the analytical performance of the Zebra BioDome format. Methods We conducted a study to test the analytical performance of Zebra Biodome format in comparison to the results of using the ScreenFire HPV RS assay standard format on Biorad CFX-96 real-time PCR instrument. We used overall agreement rate and unweighted kappa value to compare the performance. Results The overall agreement for detection of hrHPV was 96.0% with unweighted kappa value 0.94 (95% confidence interval: 0.90–0.98). The agreement rates between hrHPV genotype 16 and risk stratification genotype group (HPV18/45, HPV31/33/35/52/58, and HPV51/59/39/56/68) were all > 97.5%. Conclusion The innovative ScreenFire HPV RS assay Zebra BioDome format produced highly concordant results with the standard format. The shared features by the two assay formats, such as easy-to-use, high throughput, cost-appropriate, and no requirements for DNA extraction. The unique contamination-prevention feature along with no requirement of preparation of reagents make the Zebra BioDome format more suitable for large-scale HPV screening to reduce global cervical cancer burden.

Abstract Accurate national terrestrial net ecosystem exchange estimates are crucial for the global stocktake. Net ecosystem exchange estimates from different inversion models vary greatly at national scale, and the relative impacts of prior fluxes and observations on these inversions remain unclear. Here we estimate the net ecosystem exchange of 51 land regions for the 2017-2019 period, focusing on the 10 largest countries, using prior fluxes from 12 terrestrial biosphere models and XCO2 retrievals from GOSAT and OCO-2 satellites as constraints. The average uncertainty reduction for the 10 countries increases from 37% with GOSAT and 45% with OCO-2 to 50% with combined observations, indicating a trend towards robust estimates. At finer spatial scales, even with combined observations, the uncertainty reduction is only 33%, i.e., the prior flux dominates the estimates. This finding underscores the critical importance of integrating multi-source observations and refining prior fluxes to improve the accuracy of carbon flux estimates.

[Introduction] In order to test the applicability of sea surface wind field data set in Yangjiang offshore wind farm area, this paper tests and evaluates the 10 m wind field of daily gridded advanced scatterometer (DASCAT), European centre for medium-range weather forecasts reanalysis v5 (ERA5) and final reanalysis data (FNL). [Method] The research was based on the 10 m wind fields at four sites in the Yangjiang offshore wind farm area in Guangdong province. [Result] The results demonstrate five pionts: (1) The wind speed correlations are above 0.8, with ERA5 the highest. The RMSE of wind speed are within 2.6 m/s, with DASCAT being the best in SWZ and ERA5 being the best in DWZ. Both FNL and ERA5 show significant underestimation of wind speed in SWZ, while DASCAT has smaller mean wind speed deviation than those of FNL and ERA5, and ERA5 mean wind speed is closer to those of observation. (2) The wind direction correlation reaches more than 0.75, with ERA5 being the highest in SWZ and FNL being the highest in DWZ. The RMSE of wind direction are within 35°, and ERA5 errors are the minimum. However, DASCAT and FNL are both closer to the observed predominant wind direction. (3) The statistics of the RMSE of wind speed in each wind speed period show that FNL is the minimum in the low wind speed period while DASCAT is the minimum in the medium and high wind speed periods in SWZ. ERA5 is the minimum in all wind speed period in DWZ. In both SWZ and DWZ, ERA5 has the highest wind speed correlation in both the low and medium wind speed periods, and FNL has the highest wind speed correlation in the high wind speed period. (4) The monthly wind speed errors of DASCAT and ERA5 are small and distributed relatively close to each other in SWZ, with peaks in April-May and October; ERA5 errors are smallest in DWZ, with a peak in July and a trough in December-January of the following year. (5) The distribution characteristics of the multi-year average wind speed for 10 m show that the wind speed increases from north to south and from west to east, and the wind speed gradient is large in SWZ. [Conclusion] Overall, the 10 m sea surface wind field data set of ERA5 performs better in the study area, and the deficiency of its systematic low mean wind speed can be corrected by DASCAT.

Abstract Objectives The positive expression of Cyclin D1 in immunohistochemical (IHC) staining serves as the cornerstone for diagnosing mantle cell lymphoma (MCL). However, existing literature does not conclusively establish whether the expression ratio and staining intensity significantly influence diagnostic outcomes or patient prognosis. In this retrospective study, the correlation between comprehensive Cyclin D1 quantification and the prognosis of MCL patients was studied. Methods The Cyclin D1 protein level was assessed in 120 formalin-fixed paraffin-embedded samples from MCL patients using the quantitative dot blot (QDB) analysis technique. R language software was employed for statistical analysis to determine the optimal threshold with statistical significance. Additionally, Kaplan-Meier method was utilized to evaluate the relationship between the absolute level of Cyclin D1 protein and overall survival (OS) of patients. Furthermore, the Chi-square test was applied to analyze the causes of single and multiple fractures, with a significance level of p 0.05). Conclusions Comprehensive Cyclin D1 quantification, especially above a threshold, significantly correlates with better overall survival in MCL. This highlights its prognostic importance in MCL management. Full quantification of CyclinD1 aids MCL prognosis, while QDB technology for biomarker quantification supports precise clinical prognostic stratification.

Abstract While statistical learning is often studied individually, its collective representation through self-other integration remains unclear. This study examines dynamic self-other integration and its multi-brain mechanism using simultaneous recordings from dyads. Participants (N = 112) each repeatedly responded to half of a fixed stimulus sequence with either an active partner (joint context) or a passive observer (baseline context). Significant individual statistical learning was evident in the joint context, characterized by decreased reaction time (RT) and intra-brain neural responses, followed by a quadratic trend (i.e., first increasing and then decreasing) upon insertion of an interference sequence. More importantly, Brain-to-Brain Coupling (BtBC) in the theta band also showed learning and modulation-related trends, with its slope negatively and positively correlating with the slopes of RT and intra-brain functional connectivity, respectively. These results highlight the dynamic nature of self-other integration in joint statistical learning, with statistical regularities implicitly and spontaneously modulating this process. Notably, the BtBC serves as a key neural correlate underlying the dynamics of self-other integration.

Abstract Programmed death receptor 1, PD1, modulates the function of immune cells by providing inhibitory signals and constitutes the marker of immune exhaustion. Monitoring the level of PD1 promises a useful diagnostic approach in autoimmune diseases and cancer. Here we describe the development of an ssDNA aptamer-based molecular probe capable of specific recognition of human PD1 receptor. The aptamer was selected using SELEX, its sequence was further optimized, and the affinity and specificity were determined in biochemical assays. The aptamer was converted into a fluorescent probe and its potential in molecular imaging was demonstrated in a culture of human cells overexpressing PD1 and murine pancreatic organoids / immune cells mixed co-culture model. We conclude that the provided aptamers are suitable probes for imaging of PD1 expressing immune cells even in complex cellular models and may find future utility as diagnostic tools.

Abstract Spent LiNi x Co y Mn z O2 (x + y + z = 1) and polyethylene terephthalate are major solid wastes due to the growing Li-ion battery market and widespread plastic usage. Here we propose a synergistic pyrolysis strategy to recover valuable metals by thermally treating LiNi1/3Co1/3Mn1/3O2 and polyethylene terephthalate. With polyethylene terephthalate assistance, LiNi1/3Co1/3Mn1/3O2 decomposes at 400 °C, and fully converts to Li2CO3, MnO, and Ni-Co alloy at 550 °C within 30 min, using a 1.0:0.3 mass ratio of LiNi1/3Co1/3Mn1/3O2 to polyethylene terephthalate. Furthermore, density functional theory calculations confirm the preference for O-Li bonding. Surface adsorption and free radical/gaseous reduction reactions explain the role of polyethylene terephthalate in promoting lattice destruction. The complete decomposition facilitates efficient post-treatment, achieving over 99% recovery of Li, Ni, Co, and Mn via water washing. Regenerated LiNi1/3Co1/3Mn1/3O2 was synthesized by using recovered Li- and transition metal-containing products as feedstocks. This study provided a chemical-free, energy-saving, and scalable recovery strategy while addressing polyethylene terephthalate waste minimization.

Abstract Single-cell RNA sequencing (scRNAseq) of tumour-infiltrating immune cells in high-grade serous ovarian cancer (HGSOC) omental biopsies reveals potential targets that could enhance response to neo-adjuvant chemotherapy (NACT). Analysis of 64,097 cells identifies NACT-induced overexpression of stabilin-1 (clever-1) on macrophages and FOXP3 in Tregs that is confirmed at the protein level. STAB1 inhibition in vitro induces anti-tumour macrophages. FOXP3 anti-sense oligonucleotide (FOXP3-ASO), repolarises Tregs to an effector T cell phenotype. ScRNAseq on 69,781 cells from an HGSOC syngeneic mouse model recapitulates the patients’ data. Combining chemotherapy with anti-stabilin1 antibody and/or Foxp3-ASO significantly increases survival of mice with established peritoneal disease in two HGSOC syngeneic models and progression-free survival in a third model. Long-term survivors (300 days + ) are resistant to tumour rechallenge. Anti-stabilin1 antibody enriches the tumours with CXCL9+ macrophages and Foxp3-ASO increases TBET cell infiltration. Our results suggest that targeting these molecules in immune cells may improve chemotherapy response in patients.

Abstract Objectives Human leukocyte antigen G (HLA-G) plays a crucial role in pregnancy. Pregnancy loss (PL) is caused by a variety of causes, such as fetal chromosomal abnormalities, maternal hypertension and diabetes, immune causes, spontaneous immune diseases, infections, unknown causes, etc. This study reports on the association of fetal HLA-G 3’UTR polymorphisms and diplotypes with chromosomally abnormal fetuses (CAF) or unexplained pregnancy loss (UPL). Methods A total of 552 specimens were collected and grouped by next-generation sequencing technology (NGS) and fetal survival: UPL (112 cases), CAF (170 cases) and control (258 cases). The polymorphisms of HLA-G 3’UTR in all samples were detected by Sanger sequencing. The genotypes, haplotypes and diplotypes of HLA-G 3’UTR were analyzed. The classification and regression tree (CART) analysis was used to evaluate the role of HLA-G diplotypes in predicting fetal outcomes. The correlations between CAF or UPL and maternal age, paternal age, times of miscarrage, times of delivery were analyzed by logistic regression. Results The frequencies of HLA-G + 2960del/del and + 3035CC genotypes were remarkablly increased in CAF than those in control group. The frequencies of HLA-G + 2960ins/del, + 3010CC, + 3035TC, + 3142GG, + 3187AA in CAF were significantly lower than those in normal fetuses. Through genetic models and logistic regression analysis, the dominant model of HLA-G 3’UTR genotypes [such as + 2960 (OR = 1.27, 95% CI = 1.05–1.54, p = 0.016), + 3010 (OR = 0.78, 95% CI = 0.63–0.97, p = 0.026), + 3035 (OR = 1.22, 95% CI = 1.00–1.49, p = 0.047), + 3142 (OR = 0.76, 95% CI = 0.62–0.95, p = 0.014) and + 3187 (OR = 0.80, 95% CI = 0.65–0.99, p = 0.041)] were dramatically associated with CAF. However, the frequencies of HLA-G + 3010GC, + 3142GC and + 3187AG in fetuses with UPL were memorably decreased than those in normal fetuses. No significant difference was found in the frequencies of HLA-G haplotypes in all groups. However, the frequency of UTR-1 positive specimens in CAF was significantly higher than that in UPL and control group. At the same time, the frequency of UTR-1/UTR-3 diplotypes in CAF was observably higher than that in UPL and control group, while the UTR-1/UTR-7 frequency in UPL was signally lower than that in control group. Multivariate logistic regression analysis indicated that positive HLA-G UTR-1 (OR = 1.8, 95% CI = 1.16–2.81, p = 0.009), times of abortion (OR = 1.23, 95% CI = 1.02–1.50, p = 0.035), and times of delivery (OR = 0.31, 95% CI = 0.20–0.48, p

With the current increasing global demand for low-carbon and environmentally friendly products, promoting the sustainability of closed-loop supply chains has become one of the key measures. However, consumers often do not regard remanufactured products as equivalent to new products. Therefore, this paper proposes a dynamic closed-loop supply chain that incorporates consumers' purchasing preferences to model a long-term game with product differentiation. Moreover, to enhance consumer acceptance of remanufactured products and reduce manufacturers' costs, low-carbon technologies and cost-sharing mechanisms are introduced. In this way, we construct a differential game in which the manufacturer sells new and remanufactured products through a retailer and makes decisions about the level of low-carbon technology in the remanufacturing process. Based on the theory of differential games, this paper analyzes three different power structures: the manufacturer-dominated Stackelberg game, the Nash game, and the retailer-dominated Stackelberg game. The optimal low-carbon technology level and pricing strategy are obtained by applying Pontryagin's maximum principle. The study shows that the retailer-led Stackelberg game helps retailers maximize profits, while the Nash game enables the entire closed-loop supply chain system to achieve the highest overall profits. This paper innovatively integrates low-carbon technologies into the dynamic game model of the remanufacturing process and reveals how the game behavior of supply chain participants affects the application of low-carbon technologies and the overall profit of the supply chain by comparing the cost-sharing mechanisms under different power structures. The results provide important theoretical support and practical references for closed-loop supply chain management with product differentiation.

Abstract During the coronavirus disease 2019 (COVID-19) pandemic, the exploration of microecology has been essential for elucidating the intricacies of infection mechanisms and the recovery of afflicted individuals. To decipher the interplay of microorganisms between the intestinal and respiratory tracts, we collected sputum and throat swabs and feces from COVID-19 patients and explored the mutual migration among intestinal and respiratory microorganisms. Using next-generation sequencing (NGS) technology, we investigated intestinal and respiratory microorganism intermigration in two patients with severe COVID-19 during their hospitalization. Notably, we observed an expedited recovery of microecological equilibrium in one patient harboring Mycobacterium avium. Comparative analyses between 32 healthy controls and 110 COVID-19 patients with different disease severities revealed alterations in predominant microorganisms inhabiting the respiratory and intestinal tracts of COVID-19 patients. Among the alterations, intestinal Bacteroides vulgatus (BV) was identified as a noteworthy microorganism that exhibited marked enrichment in patients with severe COVID-19. BV, when highly abundant, may inhibit the transitional growth of Escherichia coli/Enterococcus, indirectly prevent the overgrowth of salivary streptococci, and maintain lung/intestinal microecology stability. In summary, this study elucidates the bidirectional microbial intermigration between the intestinal and respiratory tracts in COVID-19 patients. These findings are expected to provide new ideas for the treatment and management of COVID-19, underscoring the essential role of microecology in infectious diseases. Nevertheless, a systematic study of the roles of BV in recovery from infection is required to gain a deeper understanding of the mechanisms of microbial migration.

Abstract Acute kidney injury (AKI) is a common clinical problem, and patients who survive AKI have a high risk of chronic kidney disease (CKD). The acute protective effects of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in AKI have been examined, there is still relatively little known regarding the impact of acute CDK4/6 inhibition on the chronic sequence of AKI. Therefore, we utilized the CDK4/6 inhibitor Palbociclib to examine the long-term effects of CDK4/6 inhibition in a rodent model of ischemic AKI. Palbociclib (Palb) was administered during the acute stage or post the acute stage of AKI and mice were sacrificed 21 days post injury. We found that Palb could cause renal senescence and renal fibrosis. Furthermore, dasatinib (D) plus quercetin (Q) were used to eliminate senescent cells in ischemic AKI murine model and Palb was administered post the treatment of D + Q. We found that Palb could reverse the senolytic and antifibrotic effects induced by D + Q, which indicates that the profibrotic effect of Palb could be ascribed to its pro-senescent effects. Our results demonstrate that CDK4/6 inhibitors treatment might be deleterious on the chronic sequence of AKI.

Abstract Background A high grain diet causes an ecological imbalance in the gut microbiota and serves as an important endogenous trigger of mastitis in dairy cows, but the underlying mechanisms are unclear. Our previous study revealed that subacute rumen acidosis (SARA)-associated mastitis has distinct metabolic profiles in the rumen, especially a significant increase in succinate, but the role of succinate in the pathogenesis of mastitis remains unclear. Results Succinate treatment exacerbates low-grade endotoxemia-induced mastitis in mice. Specifically, succinate increased the production of gut microbiota-extracellular vehicles (mEVs) containing lipopolysaccharides, which can diffuse across the damaged intestinal barrier into the mammary glands. Administration of mEVs promotes mammary inflammation via activation of the TLR4/NF-κB pathway. Conclusions Our findings suggest that succinate promotes mastitis through the proliferation of enteric pathogens and mEVs production, suggesting a potential strategy for mastitis intervention on the basis of intestinal metabolic regulation and pathogen inhibition. The role of mEVs in interspecific communication has also been elucidated. Graphical Abstract

In order to reduce the cost of roadside filling and ensure the stability of the retained roadway system, the 150202 fully mechanized mining face of Shenlei Coal Mine is taken as the background, and the roadside filling body is made of coal gangue and fly ash as the base material, through orthogonal experiments, theoretical analysis, numerical simulation, on-site measurement and other research methods, the optimal ratio of filling materials and the laws of yield stress and deformation of roadway surrounding rock with different filling widths are studied. The results show that the optimal ratio of gangue filling body is water cement ratio 1∶1.85, fly ash replacement cement ratio of 20%, fine coarse aggregate ratio of 35∶65, and sodium silicate content of 6%; the larger the width of the roadside filling body next to the gob-side entry retaining, the lower the deformation of the surrounding rock and the vertical stress of the coal wall; by comprehensively comparing the stress and displacement of surrounding rock under different widths, it is concluded that the reasonable width of the roadside filling body next to gob-side entry retaining is 1.2 m.

Abstract Background For patients with advanced non‐small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death‐1 (PD‐1)/cytotoxic T lymphocyte‐associated antigen‐4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti‐PD‐1/PD‐L1 antibodies. Methods We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab‐based regimens in later therapy lines. Results A total of 41 advanced NSCLC patients refractory to anti‐PD‐1/PD‐L1 therapy were enrolled. More than half of the patients received cadonilimab‐based regimen as a fourth or later line of treatment. At the data cutoff date, treatment efficacy could be evaluated in 23 patients. One patient (4.3%) achieved partial response, eight patients (34.8%) experienced stable disease, and 14 patients (60.9%) progressed. The objective response rate and disease control rate were 4.3% and 39.1%, respectively. The median progression‐free survival for all evaluated patients was 108.0 days. Due to the short follow‐up period, the median overall survival has not yet been reached. Treatment‐related adverse events (TRAEs) and immune‐related AEs occurred in 63.4% and 22% patients, respectively. The most common TRAEs included gamma‐glutamyl transferase elevation (17.1%), coughing (14.6%), and fatigue (12.2%). Five patients (12.2%) experienced grade ≥3 TRAEs. Conclusions In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab‐based regimens showed moderate antitumor efficacy with a generally tolerable and manageable safety profile. However, more evidence is needed to support the administration of cadonilimab in NSCLC patients refractory to previous anti‐PD‐1/PD‐L1 therapy.

CAP (cysteine-rich secretory proteins, antigen5, pathogenesis-related proteins) superfamily proteins are widely distributed, can be subdivided into 11 subfamilies, and form a unique branch in fungi, named PRY proteins. Verticillium dahliae is a soil-borne fungal pathogen of vascular plants that causes plant Verticillium wilt. However, the roles of CAP superfamily proteins in this fungus is unclear. Here, four CAP superfamily members with a conserved domain were identified in V. dahliae: VdPRY1, VdPRY2, VdPRY3, and VdPRY4. VdPRY1 and VdPRY3 were found to be key in suppressing plant immune responses. Moreover, these four members are highly expressed during early infection of cotton by V. dahliae. Deleting VdPRY1, VdPRY2, or VdPRY3 reduced the fungus’s ability to cause disease, but VdPRY4 deletion did not affect virulence. Deletion of any of four members did not impact fungal growth or carbon source use. Yeast two-hybrid experiments suggest that these proteins may function through interactions with each other. This investigation has, for the initial time, elucidated the pivotal roles of V. dahliae CAP superfamily proteins in inhibiting plant immunity and exerting virulence during interaction with the host plant.

Abstract Background Multivessel disease(MVD) is linked to a poorer prognosis, increased complications, longer hospital stays, and higher in-hospital mortality when compared to single-vessel disease(SVD).The purpose of this study is to explore the clinically relevant predictors of acute cornary syndrome (ACS) combined with MVD. Methods This multicenter retrospective study included 68,378 ACS patients from 240 hospitals.The clinical data were retrospectively analyzed with univariate and multivariate analyses to identify the predictive factors for MVD. Results When compared to SVD group, the MVD group showed a higher incidence of Major Adverse Cardiovascular Events(MACCEs), including all-cause death, myocardial infarction, stent thrombosis, and ischemic stroke during hospitalization, These differences were found to be statistically significant (P 1.98 (OR: 1.245, 95% CI: 1.192, 1.302), history of heart failure (OR: 1.446, 95% CI: 1.143, 1.829), hypertension (OR: 1.274, 95% CI: 1.225, 1.325), diabetes (OR: 1.341, 95% CI: 1.278, 1.406), eGFRs

Abstract N. neocaledoniensis is a very rare infectious pathogen that causes human disease, particularly in immunocompromised individuals. In this case report, we describe the successful diagnosis of N. neocaledoniensis in a patient confirmed by mNGS and the treatment of multiple skin abscesses due to N. neocaledoniensis infection. mNGS is an important diagnostic method complementary to routine bacterial culture and identification methods, especially for rare, novel, co-infected pathogens, and pathogens that are difficult to culture. This report may provide a reference for the clinical treatment and diagnosis of N. neocaledoniensis infection in humans.

Abstract In the realm of experimental and epidemiological research, the impact of endotoxemia caused by obesity on male fertility is widely acknowledged. However, the existing body of evidence lacks rigorous studies to substantiate this notion. To address this gap, we have selected protocatechuic acid (PCA) as a potential inhibitor of endotoxemia induced by obesity. This selection is further supported by our utilization of a male model of C57BL/6J mice induced by a high‐fat diet (HFD) and the fecal microbiota transplantation assay. Our findings reveal a negative correlation between semen quality and endotoxin levels in the mice model induced by an HFD. Furthermore, intervention with PCA resulted in the restoration of testicular morphology, sperm traits, and function. The transplantation of PCA did not exhibit restorative effects on semen quality, but it did effectively prevent obesity‐induced intestinal leakage and endotoxemia. By directly enhancing antioxidant capacity, PCA successfully reversed the fertility reduction caused by obesity. These findings offer substantiation that endotoxemia does not play a significant role in the diminished fertility observed in obese males and propose that the inclusion of dietary antioxidant supplementation can potentially restore male fertility.

Abstract Myocarditis is a common disease of the cardiovascular and immune systems, but the relationship between relevant blood metabolites and the risk of myocarditis has not been well-established. To identify potential biometabolic markers associated with myocarditis, we conducted a two-sample Mendelian randomization (MR) study. We performed preliminary MR analysis using the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and weighted mode methods to adjust for false discovery rate (FDR). Confounders were screened using the GWAS Catalog website. Sensitivity analyses included Cochrane Q-test, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), scatterplots, funnel plots, and forest plots. For genetic and directional analysis, we employed co-localization analysis and the Steiger test. MR analysis was performed using the FinnGen database and meta-analysis was performed using the IEU database. MR analysis identified significant correlations for five metabolic biomarkers after FDR correction. These included four known metabolites: kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, and 5-acetylamino-6-formylamino-3-methyluracil, as well as one unknown metabolite, X-25,422. Among these, kynurenine (OR = 1.441, 95%CI = 1.089–1.906, p-value = 0.018) and 1-stearoyl-GPE (18:0) (OR = 1.263, 95%CI = 1.029–1.550, p-value = 0.029) were identified as risk factors for myocarditis, while deoxycarnitine (OR = 0.813, 95%CI = 0.676–0.979, p-value = 0.029), 5-acetylamino-6-formylamino-3-methyluracil (OR = 0.864, 95% CI = 0.775–0.962, p-value = 0.018), and X-25,422 (OR = 0.721, 95%CI = 0.587–0.886, p-value = 0.009) were found to be protective factors. No evidence of heterogeneity, horizontal pleiotropy, or sensitivity issues was observed, and no shared genetic factors between exposure and outcome were detected. The causality was in the correct direction. Meta-analysis further confirmed the causal relationship between the five metabolites and myocarditis. This study identifies a causal relationship between five circulating metabolites and myocarditis. Kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, X-25,422, and 5-acetylamino-6-formylamino-3-methyluracil may serve as potential drug targets for myocarditis, providing a theoretical basis for the prevention, diagnosis, and treatment of the condition.

Although MXene sheets are highly conductive, it is still challenging to prepare MXene complex functional materials for flexible electronics by simple and effective methods. In 3D printing, especially direct ink writing (DIW), different materials are used to create complex 3D shapes by formulating inks with controlled rheological properties. Herein, a printable MXene ink is developed, exhibiting good rheological properties, to print different complex shapes, and potentially manufacture electronic devices such as sensors. Then, we fabricated a highly sensitive hierarchical structure MXene composite materials composed of two layers of bionic micro-spine microstructure and network structure, formed by 3D printing and freeze casting. The obtained MXene composite materials exhibit good pressuring sensing properties with a sensitivity of 17.5 kPa−1, a fast response time (

Complex compositions and structural designs severely restrict the practical application of high-temperature microwave-infrared compatible stealth coatings. To address this issue, high-temperature microwave-infrared compatible stealth coatings of a single 8 wt% yttria-stabilized zirconia (8YSZ) component are proposed for the first time. Originating from conductive, interfacial and dipole polarization losses, 8YSZ coating presents superior microwave absorbing properties at 900 °C, including strong absorption (minimum reflection loss (RLmin) of −50 dB), a thin thickness of 1.5 mm, and a better effective absorption bandwidth (EAB) of 2 GHz. Moreover, it maintains low infrared emissivity (ε < 0.3) in the infrared bands of 3–5 μm compared with traditional materials. In contrast to the conventional strategy in which microwave-infrared compatible stealth materials are explored in the pool of “complex” multiple-component or metamaterial, this work reveals an avenue to look into materials with simple compositions realizing microwave-infrared compatible stealth simultaneously, which would be of both scientific and technological significance in the fields of stealth technology. Moreover, the present work reveals new applications of 8YSZ coatings in the field of high-temperature stealth technology.

To enhance the design and research work on dynamic characteristics of high-rise laminated timber buildings, this paper carried out a modal analysis study on one of the largest laminated timber buildings in China. The finite element calculating modal analysis was carried out using SAP2000 software, and the experimental modal analysis of the building was carried out via environmental excitation. The calculating modal results and the experimental modal results showed good agreement. The calculating modal frequency values were generally lower than the experimental modal frequency values. The natural frequencies obtained by the two methods appeared in the Y-direction first-order bending mode and had values of 2.03 and 2.5 Hz, respectively. The corresponding frequencies of the first-order torsional mode were 2.82 and 3.25 Hz, respectively. The distribution of the CLT core tube along the length direction of the building has an impact on the vibration mode. The six-story part shows the second-order bending form, while the four-story section only shows the first-order bending form. The above work provides a case study and reference for the simulation and modal analysis of high-rise laminated timber buildings, demonstrating the critical role of the core tube structure in such wooden buildings. This insight contributes to a better understanding of structural performance and design considerations in similar projects.

Abstract Objective The correlation between high-intensity zone (HIZ) of lumbar disc magnetic resonance imaging (MRI) and discogenic low back pain (DLBP) is currently controversial, this study aimed to systematically evaluate the correlation between HIZ of lumbar disc MRI and positive discography, as well as its diagnostic value for DLBP. Method Databases were searched to include research literature on high intensity zone (HIZ) related to discography and DLBP diagnosis. HIZ is a separate small, confined area of high signal located at the posterior border of the annulus fibrosus on MRI T2-weighted images of the lumbar spine, which is separated from the nucleus pulposus but has a higher signal than the nucleus pulposus. Studies on the correlation of HIZ with discography and DLBP diagnosis were searched in the Pubmed, EMBASE, Cochrane Central, Science Direct, China Knowledge Network, Wanfang Database, and China Biomedical Literature Databases, Scopus from January 1992 to June 2024. The outcomes were diagnostic values of HIZ for DLBP. The risk assessment was performed by Deeks’ funnel methods in the Stata 17.0 software after 2 investigators independently screened the literature, extracted information and evaluated the risk of bias of the included studies. Results A total of 25 studies including 5889 patients were included. meta-analysis showed that the sensitivity of HIZ for the diagnosis of DLBP was (0.49, 95% CI [0.37,0.61]) and specificity was (0.89, 95% CI [0.85,0.93]); the positive likelihood ratio was (4.52, 95% CI [3.28,6.25]) and the negative likelihood ratio was (0.58, 95% CI [0.46,0.71]). The diagnostic ratio was (7.87, 95% CI [5.05,12.26]). Conclusion The available evidence suggests that HIZ has acceptable sensitivity and high specificity in the diagnosis of DLBP. Due to the limitation of the number and quality of included studies, the above conclusions need to be validated by more high-quality studies.

Abstract Background Lung adenocarcinoma (LUAD) with lymph node (LN) metastasis is linked to poor prognosis, yet the underlying mechanisms remain largely undefined. This study aimed to elucidate the immunogenomic landscape associated with LN metastasis in LUAD. Methods We employed broad-panel next-generation sequencing (NGS) on a cohort of 257 surgically treated LUAD patients to delineate the molecular landscape of primary tumors and identify actionable driver-gene alterations. Additionally, we used multiplex immunohistochemistry (mIHC) on a propensity score-matched cohort, which enabled us to profile the immune microenvironment of primary tumors in detail while preserving cellular metaclusters, interactions, and neighborhood functional units. By integrating data from NGS and mIHC, we successfully identified spatial immunogenomic patterns and developed a predictive model for LN metastasis, which was subsequently validated independently. Results Our analysis revealed distinct immunogenomic alteration patterns associated with LN metastasis stages. Specifically, we observed increased mutation frequencies in genes such as PIK3CG and ATM in LN metastatic primary tumors. Moreover, LN positive primary tumors exhibited a higher presence of macrophage and regulatory T cell metaclusters, along with their enriched neighborhood units (p

Abstract Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabetic periodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. The slow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases.

Abstract For the multistage progression of prostate cancer (PCa) and resistance to immunotherapy, tumour‐associated macrophage is an essential contributor. Although immunotherapy is an important and promising treatment modality for cancer, most patients with PCa are not responsive towards it. In addition to exploring new therapeutic targets, it is imperative to identify highly immunotherapy‐sensitive individuals. This research aimed to establish a signature risk model, which derived from the macrophage, to assess immunotherapeutic responses and predict prognosis. Data from the UCSC‐XENA, GEO and TISCH databases were extracted for analysis. Based on both single‐cell datasets and bulk transcriptome profiles, a macrophage‐related score (MRS) consisting of the 10‐gene panel was constructed using the gene set variation analysis. MRS was highly correlated with hypoxia, angiogenesis, and epithelial‐mesenchymal transition, suggesting its potential as a risk indicator. Moreover, poor immunotherapy responses and worse prognostic performance were observed in the high‐MRS group of various immunotherapy cohorts. Additionally, APOE, one of the constituent genes of the MRS, affected the polarisation of macrophages. In particular, the reduced level of M2 macrophage and tumour progression suppression were observed in PCa xenografts which implanted in Apolipoprotein E‐knockout mice. The constructed MRS has the potential as a robust prognostic prediction tool, and can aid in the treatment selection of PCa, especially immunotherapy options.

Abstract Precise survival risk stratification is crucial for personalized therapy in bladder cancer (BCa). This study developed and validated an end-to-end deep learning system using histological slides to predict overall survival (OS) risk in BCa patients. We employed the BlaPaSeg tile classifier to generate tissue probability heatmaps and segmentation maps, trained two prognostic networks, MacroVisionNet and UniVisionNet, and explored six potential BCa prognostic biomarkers. Across all cohorts, the AUC for BlaPaSeg ranged from 0.9906 to 0.9945, while the C-index varied from 0.655 to 0.834 for MacroVisionNet and 0.661 to 0.853 for UniVisionNet. After covariate adjustment, the hazard ratio (HR) values for high-risk groups were 1.97 to 5.06 in MacroVisionNet and 2.13 to 4.01 in UniVisionNet. The high-risk Coloc (Tumor Co-localization score) and IMTS (Integrated Muscle Tumor Score) groups illustrated a higher death risk with HR values from 1.41 to 10.16. The system improves BCa survival prediction and supports refined patient management.

Abstract Alternative splicing is an important process that contributes to highly diverse transcripts and protein products, which can affect the development of disease in various organisms. Cardiovascular disease (CVD) represents one of the greatest global threats to humans, particularly acute myocardial infarction (MI) and subsequent ischemic reperfusion (IR) injury, which involve complex transcriptomic changes in heart tissues associated with metabolic reshaping and immunological response. In this study, we used a newly developed ONT full-length transcriptomic approach and performed transcript-resolved differential expression profiling in murine models of MI and IR. We built an analytical pipeline to reliably identify and quantify alternative splicing products (isoforms), expanding on the currently available catalog of isoforms described in mice. The updated alternative splicing landscape included transcripts, genes, and pathways that were differentially regulated during IR and MI. Our study establishes a pipeline to profile highly diverse isoforms using state-of-the-art long-read sequencing, builds a landscape of alternative splicing in the mouse heart during MI and IR.

Abstract Background Long-term care insurance (LTCI) is essential to alleviate the challenges of rapid aging. Research on LTCI in developing countries is limited and conclusions remain controversial. This study aims to empirically evaluate how the LTCI pilot in selected cities influences healthcare utilization and expenditures among middle-aged and older Chinese adults. Methods Data was from 2013, 2015, and 2018 China Health and Retirement Longitudinal Study. 167 LTCI and 8225 non-LTCI group participants were identified. Propensity score matching difference-in-difference method was used to evaluate the net effect of LTCI. The robustness of the findings was tested using a placebo test. Results In the pilot cities, around 17.8% of the population had LTCI coverage, with approximately 59.9% participating in urban employee medical insurance and 81.4% being urban residents. LTCI significantly reduced the monthly out-of-pocket outpatient expenditure by 313.764 yuan (P

Abstract Neuroimaging studies have revealed that the mechanisms of auditory hallucinations are related to morphological changes in multiple cortical regions, but studies on brain network properties are lacking. This study aims to construct intra-individual structural covariance networks and reveal network changes related to auditory hallucinations. T1-weighted MRI images were acquired from 90 schizophrenia patients with persistent auditory hallucinations (pAH group), 55 schizophrenia patients without auditory hallucinations (non-pAH group), and 83 healthy controls (HC group). Networks were constructed using the voxel-based gray matter volume and the intra-individual structural covariance was based on the similarity between the morphological variations of any two regions. One-way ANCOVA was employed to compare global and local network metrics among the three groups, and edge analysis was conducted via network-based statistics. In the pAH group, Pearson correlation analysis between network metrics and clinical symptoms was conducted. Compared with the HC group, both the pAH group (p = 0.01) and the non-pAH group (p = 3.56 × 10−4) had lower nodal efficiency of the left medial superior frontal gyrus. Compared to the non-pAH group and HC group, the pAH group presented lower nodal efficiency of the temporal pole of the left superior temporal gyrus (p = 1.09 × 10−3; p = 7.67 × 10−4) and right insula (p = 0.02; p = 8.99 × 10−6), and lower degree centrality of the right insula (p = 0.04; p = 1.65 × 10−5). The pAH group had a subnetwork with reduced structural covariance centered by the left temporal pole of the superior temporal gyrus. In the pAH group, the normalized clustering coefficient (r = −0.36, p = 8.45 × 10−3) and small-worldness (r = −0.35, p = 9.89 × 10−3) were negatively correlated with the PANSS positive scale score. This study revealed network changes in schizophrenia patients with persistent auditory hallucinations, and provided new insights into the structural architecture related to auditory hallucinations at the network level.

Abstract Esophageal squamous cell carcinoma (ESCC) is highly heterogeneous. Our understanding of full molecular and immune landscape of ESCC remains limited, hindering the development of personalised therapeutic strategies. To address this, we perform genomic-transcriptomic characterizations and AI-aided histopathological image analysis of 120 Chinese ESCC patients. Here we show that ESCC can be categorized into differentiated, metabolic, immunogenic and stemness subtypes based on bulk and single-cell RNA-seq, each exhibiting specific molecular and histopathological features based on an amalgamated deep-learning model. The stemness subgroup with signature genes, such as WFDC2, SFRP1, LGR6 and VWA2, has the poorest prognosis and is associated with downregulated immune activities, a high frequency of EP300 mutation/activation, functional mutation enrichment in Wnt signalling and the highest level of intratumoural heterogeneity. The immune profiling by transcriptomics and immunohistochemistry reveals ESCC cells overexpress natural killer cell markers XCL1 and CD160 as immune evasion. Strikingly, XCL1 expression also affects the sensitivity of ESCC cells to common chemotherapy drugs. This study opens avenues for ESCC treatment and provides a valuable public resource to better understand ESCC.

Abstract All-optical nonlinear activation functions (NAFs) are crucial for enabling rapid optical neural networks (ONNs). As linear matrix computation advances in integrated ONNs, on-chip all-optical NAFs face challenges such as limited integration, high latency, substantial power consumption, and a high activation threshold. In this work, we develop an integrated nonlinear optical activator based on the butt-coupling integration of two-dimensional (2D) MoTe2 and optical waveguides (OWGs). The activator exhibits an ultra-broadband response from visible to near-infrared wavelength, a low activation threshold of 0.94 μW, a small device size (~50 µm2), an ultra-fast response rate (2.08 THz), and high-density integration. The excellent nonlinear effects and broadband response of 2D materials have been utilized to create all-optical NAFs. These activators were applied to simulate MNIST handwritten digit recognition, achieving an accuracy of 97.6%. The results underscore the potential application of this approach in ONNs. Moreover, the classification of more intricate CIFAR-10 images demonstrated a generalizable accuracy of 94.6%. The present nonlinear activator promises a general platform for three-dimensional (3D) ultra-broadband ONNs with dense integration and low activation thresholds by integrating a variety of strong nonlinear optical (NLO) materials (e.g., 2D materials) and OWGs in glass.

Abstract Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. Methods This trial compared two aspects of radiation treatment, total dose and field, using a two‐by‐two factorial design. The high‐dose (HD) group received 59.4 Gy radiation, and the standard‐dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression‐free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. Results The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80‐1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82–1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72–1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. Conclusions IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.

Abstract Recently in diagnosis of Aortic dissection (AD), the synthesis of contrast enhanced CT (CE-CT) images from non-contrast CT (NC-CT) images is an important topic. Existing methods have achieved some results but are unable to synthesize a continuous and clear intimal flap on NC-CT images. In this paper, we propose a multi-stage cascade generative adversarial network (MCGAN) to explicitly capture the features of the intimal flap for a better synthesis of aortic dissection images. For the intimal flap with variable shapes and more detailed features, we extract features in two ways: dense residual attention blocks (DRAB) are integrated to extract shallow features and UNet is employed to extract deep features; then deep features and shallow features are cascaded and fused. For incomplete flaps or lack of details, we use spatial attention and channel attention to extract key features and locations. At the same time, multi-scale fusion is used to ensure the continuity of the intimal flap. We perform the experiment on a set of 124 patients (62 with AD and 62 without AD). The evaluation results show that the synthesized images have the same characteristics as the real images and achieves better results than the popular methods.

Abstract Maintaining quantum coherence and entanglement in the presence of environmental noise, particularly within non-Markovian contexts, represents a significant challenge for the progression of quantum information science and technology. This study offers a substantial advancement by investigating the dynamics of a two-qubit system subjected to diverse noise conditions, encompassing relaxation, dephasing, and their cumulative effects. By employing quantum-state-diffusion equations specifically crafted for non-Markovian environments, we introduce an innovative strategy to counteract the detrimental influences of environmental noise on quantum teleportation fidelity and entanglement concurrence. Our results underscore the potential for external interventions to markedly improve the resilience of quantum information processing tasks over prolonged durations, especially in settings where dephasing noise prevails. A key revelation is the intricate relationship between dephasing noise and the initial state of entanglement, which profoundly impacts the occurrence of entanglement sudden death. This research not only deepens our comprehension of quantum system dynamics under noisy circumstances but also furnishes practical directives for engineering robust quantum systems, a necessity for the development of scalable quantum technologies.

Abstract Background Arginase is abundantly expressed in colorectal cancer and disrupts arginine metabolism, promoting the formation of an immunosuppressive tumor microenvironment. This significant factor contributes to the insensitivity of colorectal cancer to immunotherapy. Tumor-associated macrophages (TAMs) are major immune cells in this environment, and aberrant arginine metabolism in tumor tissues induces TAM polarization toward M2-like macrophages. The natural compound piceatannol 3ʹ-O-glucoside inhibits arginase activity and activates nitric oxide synthase, thereby reducing M2-like macrophages while promoting M1-like macrophage polarization. Methods The natural compounds piceatannol 3ʹ-O-glucoside and indocyanine green were encapsulated within microparticles derived from tumor cells, termed PG/ICG@MPs. The enhanced cancer therapeutic effect of PG/ICG@MP was assessed both in vitro and in vivo. Results PG/ICG@MP precisely targets the tumor site, with piceatannol 3ʹ-O-glucoside concurrently inhibiting arginase activity and activating nitric oxide synthase. This process promotes increased endogenous nitric oxide production through arginine metabolism. The combined actions of nitric oxide and piceatannol 3ʹ-O-glucoside facilitate the repolarization of tumor-associated macrophages toward the M1 phenotype. Furthermore, the increase in endogenous nitric oxide levels, in conjunction with the photodynamic effect induced by indocyanine green, increases the quantity of reactive oxygen species. This dual effect not only enhances tumor immunity but also exerts remarkable inhibitory effects on tumors. Conclusion Our research results demonstrate the excellent tumor-targeting effect of PG/ICG@MPs. By modulating arginine metabolism to improve the tumor immune microenvironment, we provide an effective approach with clinical translational significance for combined cancer therapy.

Background: Currently, the need for new therapeutic strategies involving programmed cell death protein-1 (PD-1) monoclonal antibodies in the second-line setting of small cell lung cancer (SCLC) is urgent. This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy. Methods: This study included the patients from Cohort 4 of a single-arm, open-label, multicenter, phase II clinical trial. A safety run-in phase was performed under anlotinib (10/12 mg quaque die [QD], days 1–14) plus penpulimab (200 mg intravenously [IV], day 1) in a 21-day cycle, followed by the formal trial in which the patients received anlotinib (12 mg QD, days 1–14) plus penpulimab (200 mg IV, day 1) in a 21-day cycle. The primary endpoint of the safety run-in phase was safety. The primary endpoint of the formal trial phase was the objective response rate (ORR). Results: From April 28, 2020, to November 24, 2020, 21 patients were enrolled from 11 hospitals, including 2 in the safety run-in phase and 19 in the formal trial phase. In the formal trial phase, the ORR was 42.1% (8/19; 95% confidence interval [CI]: 17.7–66.6%). The median progression-free survival was 4.8 months (95% CI: 2.9–11.3 months), and the median overall survival was 13.0 months (95% CI: 4.6–not applicable [NA] months). The incidence of ≥grade 3 treatment-related adverse events (TRAEs) was 52.4% (11/21), and the incidence of treatment-related serious adverse events (AEs) was 28.6% (6/21). Two AE-related deaths occurred. The most common AEs were hypertension (57.1%, 12/21), hypothyroidism (42.9%, 9/21), and hypertriglyceridemia (38.1%, 8/21). Conclusions: In patients with SCLC who progressed after first-line platinum-based chemotherapy, the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile, which warrants further investigation. Trial registration: No. NCT04203719, https://clinicaltrials.gov/.

Abstract Background Lavandula angustifolia holds importance as an aromatic plant with extensive applications spanning the fragrance, perfume, cosmetics, aromatherapy, and spa sectors. Beyond its aesthetic and sensory applications, this plant offers medicinal benefits as a natural herbal remedy and finds use in household cleaning products. While extensive genomic data, inclusive of plastid and nuclear genomes, are available for this species, researchers have yet to characterize its mitochondrial genome. This gap in knowledge hampers deeper understanding of the genome organization and its evolutionary significance. Results Through the course of this study, we successfully assembled and annotated the mitochondrial genome of L. angustifolia, marking a first in this domain. This assembled genome encompasses 61 genes, which comprise 34 protein-coding genes, 24 transfer RNA genes, and three ribosomal RNA genes. We identified a chloroplast sequence insertion into the mitogenome, which spans a length of 10,645 bp, accounting for 2.94% of the mitogenome size. Within these inserted sequences, there are seven intact tRNA genes (trnH-GUG, trnW-CCA, trnD-GUC, trnS-GGA, trnN-GUU, trnT-GGU, trnP-UGG) and four complete protein-coding genes (psbA, rps15, petL, petG) of chloroplast derivation. Additional discoveries include 88 microsatellites, 15 tandem repeats, 74 palindromic repeats, and 87 forward long repeats. An RNA editing analysis highlighted an elevated count of editing sites in the cytochrome c oxidase genes, notably ccmB with 34 editing sites, ccmFN with 32, and ccmC with 29. All protein-coding genes showed evidence of cytidine-to-uracil conversion. A phylogenetic analysis, utilizing common protein-coding genes from 23 Lamiales species, yielded a tree with consistent topology, supported by high confidence values. Conclusions Analysis of the current mitogenome resource revealed its typical circular genome structure. Notably, sequences originally from the chloroplast genome were found within the mitogenome, pointing to the occurrence of horizontal gene transfer between organelles. This assembled mitogenome stands as a valuable resource for subsequent studies on mitogenome structures, their evolution, and molecular biology.

Abstract Glioblastoma (GBM) is the most common primary intracranial malignant tumor. Recent literature suggests that induction of programmed death has become a mainstream cancer treatment strategy, with ferroptosis being the most widely studied mode. Complement C5a receptor 1 (C5aR1) is associated with both tumorigenesis and tumor-related immunity. However, knowledge regarding the role of C5aR1 in GBM progression is limited. In the present study, we observed significant upregulation of C5aR1 in glioma tissue. In addition, C5aR1 expression was found to be closely associated with patient prognosis and survival. Subsequent experimental verification demonstrated that C5aR1 promoted the progression of GBM mainly by suppressing ferroptosis induction, inhibiting the accumulation of lipid peroxides, and stabilizing the expression of the core antiferroptotic factor glutathione peroxidase 4 (GPX4). Aberrant N6-methyladenosine (m6A) modification of GPX4 mRNA contributes significantly to epigenetic tumorigenesis, and here, we report that selective methyltransferase-like 3 (METTL3)-dependent m6A methylation of GPX4 plays a key role in C5AR1 knockdown-induced ferroptosis induction. Mechanistically, ERK1/2 signaling pathway activation increases the METTL3 protein abundance in GBM cells. This activation then increases the stability of METTL3-mediated m6A modifications on GPX4, enabling it to fulfill its transcriptional function. More importantly, in an intracranial xenograft mouse model, PMX205, a C5aR1 inhibitor, promoted alterations in ferroptosis in GBM cells and inhibited GBM progression. In conclusion, our findings suggest that C5aR1 inhibits ferroptosis in GBM cells and promotes MettL3-dependent GPX4 expression through ERK1/2, thereby promoting glioma progression. Our study reveals a novel mechanism by which the intracellular complement receptor C5aR1 suppresses ferroptosis induction and promotes GBM progression. These findings may facilitate the identification of a potential therapeutic target for glioma.

Parkinson's disease (PD) is a neurodegenerative condition marked by a steady loss of dopaminergic neurons in the brain's substantia nigra. Prompt identification and tracking of PD progression are essential for prompt intervention and efficient PD care. In this study, we developed an immunofluorescence detection approach for α-synuclein (α-syn), a critical biomarker associated with PD, that is both extremely sensitive and specific. Using polyethylene glycol (PEG)-functionalized magnetic beads (MBs) and an Ag+ fluorescence probe (Ag+-FP) based on Rhodamine 6 G, the suggested method makes use of an immunofluorescence detection system. The system's workings are based on antigen-antibody complexes. Identified as Ab1-MBs@α-syn@Ab2-Ag NPs, the immuno-complexes encapsulate α-synuclein between anti-α-synuclein antibodies (Ab1) fixed on amino-MBs and Ag Nanoparticles functionalized with matching Ab2. α-synuclein detection was accomplished at a limit of less than 8 pg/mL through optimization of pH, reaction duration, and antibody concentration. The method showed very little cross-reactivity with other widely used biomarkers and a high specificity. The system showed a linear range of 524.8 ng/mL to 0.2 ng/mL. The results, which showed recovery values ranging from 97.00 % to 99.57 % and were consistent with those obtained using a commercial ELISA kit, indicated the system's potential for clinical applications in the diagnosis and monitoring of PD.

Abstract Radiotherapy (RT) is a crucial treatment for colorectal cancer (CRC) patients, but it often fails to induce systemic antitumor immunity. CD73, an immunomodulatory factor, is upregulated after RT and associated with poor prognosis in CRC patients. This study aims to elucidate the mechanisms driving RT-induced CD73 upregulation in CRC and investigate how combining RT with CD73 blockade stimulates immune responses and induces abscopal effects. Findings revealed that RT-induced CD73 upregulation is mediated by the ataxia telangiectasia and Rad3-related (ATR) pathway and correlated with RT tolerance, as demonstrated through flow cytometry, immunofluorescence, and Western Blotting. Using flow cytometry and multicolor immunofluorescence, experiments demonstrated that in CRC subcutaneous tumor models, combination therapy reduces the infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T cells (Tregs) while increasing dendritic cells (DCs) and CD8 + T cells, resulting in superior antitumor responses. Additionally, results from flow cytometry, Western Blot, and RNA sequencing demonstrated that combination therapy enhances the antigen-presenting ability of DCs and activates tumor antigen-specific CD8 + T cells, improving their function and delaying their depletion. The activation of the cGAS-STING and IFN-I pathways is crucial for this effect. In summary, the integration of RT with CD73 blockade effectively reverses the immunosuppressive TME and invigorates CD8 + T cell-driven, specific antitumor immune responses. These insights shed fresh light on the mechanisms governing the synergistic modulation of immunity by RT and CD73 blockade in CRC, offering promising avenues for the advancement of therapeutic strategies against CRC.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression. Methods All eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model’s performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance. Results 299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017–1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003–1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175–2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005–1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035–26.858; P