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Abstract Oral cancer (ORCA) is the most prevalent histological subtype of oral malignancies in which immune modulation is relevant. The goal of this work was to employ Mendelian randomization (MR) to investigate the causal connection between the immune-related proteins MICB, CTSA, MMP9, and ORCA. The Open GWAS database of the Integrative Epidemiology Unit (IEU) was accessed to collect GWAS data for ORCA (ieu-b-4961), MICB (prot-a-1898), CTSA (prot-a-717) and MMP9 (prot-a-1921). From 372,373 samples, the ORCA dataset comprises 7,723,107 single nucleotide polymorphisms (SNPs). MICB, CTSA, and MMP9 all have 10,534,735 SNPs and 3,301 sample sizes. Then, the primary SVMR implementation approaches were weighted mode, simple mode, inverse variance weighted (IVW), weighted median, and MR-Egger. IVW was the most effective technique. A sensitivity study was also carried out to assess the correctness of SVMR data, with special focus devoted to heterogeneity, horizontal pleiotropy, and Leave-One-Out (LOO). MVMR was eventually implemented as well. A Mendelian randomization analysis of the three exposure factors in the dataset (ieu-b-94, ebi-a-GCST012237) was also performed to validate the study results. According to the SVMR results, there was a noteworthy causal interaction between ORCA and MICB (P = 0.0014), MMP9 (P = 0.0343), and CTSA (P = 0.0003). Furthermore, odds ratios (ORs) values revealed that MMP9 (OR = 1.0005) was an ORCA risk factor, whereas MICB (OR = 0.9994) and CTSA (OR = 0.9993) were security factors. The robustness of the SVMR findings was confirmed by the p-values of the heterogeneity and horizontal pleiotropy, both of which were greater than 0.05. The MVMR result did not affect any of the safety or hazard features of these three exposure factors. However, the P value for MMP9 was greater than 0.05, implying that MICB and CTSA may have a greater influence on ORCA than MMP9. The validation outcomes in both datasets harmonized with the findings from previous research, thereby solidifying the reliability of results. Our investigation provided a crucial resource for further research on the subject by demonstrating a causal relationship between ORCA and MICB, CTSA, and MMP9.

Persistence of quiescent leukemia stem cells (LSCs) after treatment most likely contributes to chemotherapy resistance and poor prognosis of leukemia patients. Identification of this quiescent cell population would facilitate eradicating LSCs. Here, using a cell‐tracing PKH26 (PKH) dye that can be equally distributed to daughter cells following cell division in vivo, we identify a label‐retaining slow‐cycling leukemia cell population from AML1‐ETO9a (AE9a) leukemic mice. We find that, compared with cells not maintaining PKH‐staining, a higher proportion of PKH‐retaining cells are in G0 phase, and PKH‐retaining cells exhibit increased colony formation ability and leukemia initiation potential. In addition, PKH‐retaining cells possess high chemo‐resistance and are more likely to be localized to the endosteal bone marrow region. Based on the transcriptional signature, HLA class II histocompatibility antigen gamma chain (Cd74) is highly expressed in PKH‐retaining leukemia cells. Furthermore, cell surface CD74 was identified to be highly expressed in LSCs of AE9a mice and CD34+ human leukemia cells. Compared to Lin−CD74− leukemia cells, Lin−CD74+ leukemia cells of AE9a mice exhibit higher stemness properties. Collectively, our findings reveal that the identified slow‐cycling leukemia cell population represents an LSC population, and CD74+ leukemia cells possess stemness properties, suggesting that CD74 is a candidate LSC surface marker.

Abstract Background Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), can undergo erythroid differentiation, offering a potentially invaluable resource for generating large quantities of erythroid cells. However, the majority of erythrocytes derived from hPSCs fail to enucleate compared with those derived from cord blood progenitors, with an unknown molecular basis for this difference. The expression of vimentin (VIM) is retained in erythroid cells differentiated from hPSCs but is absent in mature erythrocytes. Further exploration is required to ascertain whether VIM plays a critical role in enucleation and to elucidate the underlying mechanisms. Methods In this study, we established a hESC line with reversible vimentin degradation (dTAG-VIM-H9) using the proteolysis-targeting chimera (PROTAC) platform. Various time-course studies, including erythropoiesis from CD34+ human umbilical cord blood and three-dimensional (3D) organoid culture from hESCs, morphological analysis, quantitative real-time PCR (qRT-PCR), western blotting, flow cytometry, karyotyping, cytospin, Benzidine-Giemsa staining, immunofluorescence assay, and high-speed cell imaging analysis, were conducted to examine and compare the characteristics of hESCs and those with vimentin degradation, as well as their differentiated erythroid cells. Results Vimentin expression diminished during normal erythropoiesis in CD34+ cord blood cells, whereas it persisted in erythroid cells differentiated from hESC. Depletion of vimentin using the degradation tag (dTAG) system promotes erythroid enucleation in dTAG-VIM-H9 cells. Nuclear polarization of erythroblasts is elevated by elimination of vimentin. Conclusions VIM disappear during the normal maturation of erythroid cells, whereas they are retained in erythroid cells differentiated from hPSCs. We found that retention of vimentin during erythropoiesis impairs erythroid enucleation from hPSCs. Using the PROTAC platform, we validated that vimentin degradation by dTAG accelerates the enucleation rate in dTAG-VIM-H9 cells by enhancing nuclear polarization. Graphical Abstract

Abstract Background Compliance with medication is crucial for the favorable prognosis of children with epilepsy. The objective of this study was to assess the determinants of medication compliance and to construct a predictive model for the risk of non-compliance among pediatric epilepsy patients. Methods The study included children diagnosed with epilepsy and treated at our hospital between February 1 and September 30, 2023. We evaluated the demographic characteristics and medication compliance profiles of these patients. The predictive model’s performance was assessed using the receiver operating characteristic (ROC) curve to determine its sensitivity and specificity. Results A total of 168 children with epilepsy were analyzed. The rate of non-compliance with medication was found to be 32.74% (55 out of 168). Logistic regression identified the educational level of parents (OR = 2.844, 95% CI: 2.182–3.214), monthly household income (OR = 1.945, 95% CI: 1.203–2.422), the number of medications taken (OR = 1.883, 95% CI: 1.314–2.201), and the level of epilepsy knowledge received (OR = 2.517, 95% CI: 1.852–3.009) as significant factors influencing non-compliance (all p

With the intervention of computer algorithm-assisted design in the realm of contemporary architectural design, architectural spatial forms and corresponding design methods have improved significantly. However, the limitations of material strength and plasticity impose certain constraints on the architectural design of the new century. Based on this occurrence, this paper studies the development of a computational generative design system for woven braced structure composed of fiber-reinforced materials. Through experimental data of material performance, the research firstly argues feasibility of employing fiber composite materials to braced structure. The conclusion is that the structure designed and generated could produce a support of 1 ton per ㎡. Moreover, based on the ant colony algorithm and the algorithm principle of cellular automata on the Java platform, the study designs a generative system with iterative computing of force as the major axis to achieve the self-organization and adaptability of the braced structure. Above all, this paper proposes a design strategy engaging with computational generative design approach, as well as a design attempt for the material and form of architecture.

A carbon material Cu-corn straw-sludge biochar (Cu-CSBC) was prepared by hydrothermally modifying sewage sludge and corn stover. The composite coupled to ultrasound can effectively catalyze the activation of PS for organic pollutants degradation, and the removal rate of 20 mg/L TC reached 89.15% in 5 min in the presence of 0.5 g/L Cu-CSBC and 3 mM PS. The synergistic effect between the factors in the system, the reaction mechanism, and the efficient removal of TC in the aqueous environment were explored in a Cu-CSBC/US/PS system established for that purpose. Quenching experiments and electron paramagnetic resonance analysis both demonstrated the Cu-CSBC/US/PS system generated •OH, SO4–•, 1O2, and O2- •, which involved in the reaction. The Cu, carboxyl, and hydroxyl groups on the Cu-CSBC surface promoted the generation of radicals and non-radicals for the degradation process, which was dominated by both radical and non-radical pathways. The degradation pathway is proposed by measuring the intermediate products with LC-MS. Finally, the stability of the Cu-CSBC/US/PS system was tested under various reaction conditions. This study not only prepared a novel biochar composite material for the active degradation of organic pollutants by PS but also provided an effective method for the resource utilization of solid waste and sludge treatment. HIGHLIGHTS Cu-CSBC prepared from co-pyrolyzed biomass–sludge to activate PS.; US and Cu-CSBC have a positive synergistic effect on the system.; The TC removal efficiency of the Cu-CSBC/US/PS system exceeded 99%.; The US can promote the production of free radicals in the system.; The main intermediates and pathways of TC degradation were identified.;

Abstract Objectives Endoscopic vein harvesting (EVH) is an alternative technique to obtain the saphenous vein for coronary artery bypass grafting (CABG) surgery. We aimed to evaluate the early and mid-term outcomes of patients with EVH in CABG. Methods This cohort study included consecutive isolated CABG patients in Nanjing First Hospital from July 2020 to December 2022 using propensity score matching methods. Patients were classified to EVH group and open vein harvesting (OVH) group according to the vein harvesting methods. The primary outcome was the all-cause death, and the secondary outcomes were major adverse cardiovascular events (MACEs) including cardiovascular death, heart failure, myocardial infarction and revascularization and asymptomatic survival in the follow-up. Results Totally 1247 patients were included in the study with 849 in OVH group and 398 in EVH group. Patients with EVH were more female, diabetes, higher body mass index, more multi-vessel and left main diseases. 308 pairs were formed after the matching. There was no significant difference in the rates of in-hospital death (EVH vs. OVH, 2.3% vs. 1.3%, P = 0.543). During the 3 years follow-up, EVH grafts were considered not inferior to OVH grafts, no differences were found in all-cause death [8.5% vs. 5.0%, hazard ratio (HR) 1.565, 95% confidence interval (CI): 0.77–3.17, P = 0.21], MACEs (8.1% vs. 7.1%, HR 1.165, 95CI: 0.51–2.69, P = 0.71) and asymptomatic survival (66.7% vs. 72.5%, HR 1.117, 95%CI: 0.65–1.92, P = 0.68). Conclusions EVH grafts were considered comparable to OVH grafts in patients following CABG in the 3 years follow-up.

Understanding biodiversity changes, along with its driving factors and mechanisms, is crucial in biogeography and community ecology. Beta diversity is an indicator for discerning the compositional variations among communities and is essential role in fostering a comprehensive understanding of the ecological processes shaping biodiversity distribution patterns. This study quantitatively evaluated the beta diversity of macroinvertebrates in the Wei River Basin, focusing on: (i) contributions of turnover and nestedness to taxonomic, functional, and phylogenetic total beta diversity, (ii) correlations between these beta diversity dimensions, and (iii) the influences of local, climatic, and spatial factors on beta diversity. We analyzed macroinvertebrate data from 51 sampling locations in the Wei River Basin and explored the relationships between different beta diversity dimensions using the Mantel test. Additionally, we assessed the relative influence of local, climatic, and spatial factors on beta diversity through distance-based redundancy analysis and variance partitioning methods. The results indicated that turnover predominantly affects taxonomic and phylogenetic beta diversity, while nestedness mainly drives functional beta diversity. Functional beta diversity was more weakly associated with the other dimensions. Local environmental factors significantly influenced taxonomic and phylogenetic beta diversity, whereas spatial factors had a stronger influence on functional beta diversity. Our findings highlight the need for conservation strategies to integrate taxonomic, functional, and phylogenetic dimensions, transcending traditional species-level approaches.

Tribbles pseudokinase 3 (TRIB3) expression significantly increases during terminal erythropoiesis in vivo. However, we found that TRIB3 expression remained relatively low during human embryonic stem cell (hESC) erythropoiesis, particularly in the late stage, where it is typically active. TRIB3 was expressed in megakaryocyte-erythrocyte progenitor cells and its low expression was necessary for megakaryocyte differentiation. Thus, we proposed that the high expression during late stage of erythropoiesis could be the clue for promotion of maturation of hESC-derived erythroid cells. To our knowledge, the role of TRIB3 in the late stage of erythropoiesis remains ambiguous. To address this, we generated inducible TRIB3 overexpression hESCs, named TRIB3tet-on OE H9, based on a Tet-On system. Then, we analyzed hemoglobin expression, condensed chromosomes, organelle clearance, and enucleation with or without doxycycline treatment. TRIB3tet-on OE H9 cells generated erythrocytes with a high proportion of orthochromatic erythroblast in flow cytometry, enhanced hemoglobin and related protein expression in Western blot, decreased nuclear area size, promoted enucleation rate, decreased lysosome and mitochondria number, more colocalization of LC3 with LAMP1 (lysosome marker) and TOM20 (mitochondria marker) and up-regulated mitophagy-related protein expression after treatment with 2 μg/mL doxycycline. Our results showed that TRIB3 overexpression during terminal erythropoiesis may promote the maturation of erythroid cells. Therefore, our study delineates the role of TRIB3 in terminal erythropoiesis, and reveals TRIB3 as a key regulator of UPS and downstream mitophagy by ensuring appropriate mitochondrial clearance during the compaction of chromatin.

Ophiopogonis radix has been used for both food and traditional Chinese medicine in China for millennia. Oligosaccharides of Ophiopogon japonicus (OOJ), the primary bioactive components of Ophiopogonis radix, have significant hypoglycemic and hypolipidemic effects. Insulin resistance (IR) and glucolipid metabolism were examined in vivo and in vitro in this work, utilizing IR-HepG2 cells and high-fat diet/streptozocin-induced type 2 diabetic mellitus (T2DM) rats as models. It was observed that OOJ efficiently improves various T2DM parameters, such as blood glucose, lipid profile, insulin sensitivity, glucose tolerance, glycogen content, glycogen consumption, liver index, and histopathology. These improvements may be attributed to the regulation and control of the insulin receptor substrate 1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/AKT (also known as protein kinase B, PKB)/glycogen synthase kinase-3β (GSK-3β) signaling pathways. These findings suggest that OOJ has potential as a functional food ingredient and therapeutic agent for treating metabolic syndrome and T2DM.

Urban green spaces (UGS) contribute to residents’ health by promoting physical activity. However, there are significant spatial and socioeconomic disparities in UGS accessibility, leading to unequal access to UGS benefits among residents. Current assessments of UGS accessibility often overlook the role of UGS in promoting physical activity. Additionally, the consideration of UGS components typically focuses on their quantity rather than diversity. In light of this, our study proposes an evaluation method for the Physical Activity Diversity Index (PADI) of UGS and revises the supply scale parameter in the Gaussian two-step floating catchment area (Ga2SFCA) model based on this index. Taking Harbin, China as an example, we measure UGS accessibility and explore its association with residents’ income levels using the bivariate Moran’s I and multiple linear regression models. Our findings indicate that a higher PADI can partially compensate for insufficient UGS area, thereby increasing accessibility in certain areas and alleviating the relative disadvantage of low-income groups in accessing UGS. Considering PADI can more accurately identify underserved areas, providing more precise guidance for urban planning. This study highlights the importance of considering the diversity of UGS components in accessibility assessments and offers feasible solutions to mitigate spatial and socioeconomic disparities in UGS accessibility.

Abstract With the deepening of enterprise digital construction, the portrait portrayal based on employee behaviors has gradually become a research focus. Currently, the employee's portrait portrayal mostly has the problems of simple means, low efficiency, limited solving ability, etc., making the results more one-sided. Therefore, a data mining-based employee portrait portrayal model is proposed. The content of employee portrait portrayal is deeply analyzed, and the overall framework of the model is designed. A diligence analysis model (DAM) based on improved GAN is constructed, and the diligence evaluation of employees is clarified to realize the diligence evaluation. The results of diligence analysis of DAM have high accuracy (80.39%) and outperform SA (70.24%), K-means (51.79%) and GAN (67.25%). The Kappa coefficient of DAM reaches 0.7384, which is highly consistent and higher than SA (0.6075), K-means (0.3711) and GAN (0.5661). The Local Outlier Factor (LOF) and Isolation Forest (IF) are used to detect abnormal behaviors on the employees, and mine the abnormal behavior patterns on different granularity time. The LSTM model (Att-LSTM) based on the attention mechanism is used to complete the prediction of employees' software usage behaviors, and analyze and summarize the characteristics of employee's behaviors from multiple perspectives. Att-LSTM predicts the best with an RMSE of 0.82983, which is better than LSTM (0.90833) and SA (0.97767); AM-LSTM has a MAPE of 0.80323, which is better than LSTM (0.86233) and SA (0.92223). The results show that the data mining-based employee portrait portrayal method can better solve the problem of enterprise employees' digital construction, and provide a new way of thinking for the construction of enterprise-level employees' digital portrait model and the analysis of employee behavior.

Abstract Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces.

Abstract Background Hepatitis B virus (HBV) reactivation (HBVr) is a major concern for hepatocellular carcinoma (HCC) patients undergoing hepatic arterial infusion chemotherapy (HAIC) using mFOLFOX6 regimen. There is insufficient evidence to support the routine use of HAIC combined with immunotherapy in HCC patients with HBVr. The aim of this study was to examine the adverse events (AEs) related to HBVr in HCC patients after HAIC, with or without immunotherapy, and to assess the effectiveness of antiviral prophylaxis for HBVr. Methods Medical records of HCC patients receiving HAIC combined with and without immunotherapy between January 2021 and June 2023 were reviewed. The patients were divided into two groups based on whether they received immunotherapy or not. Results Out of the 106 patients, 32 (30.2%) developed HBVr. Among these, 23 eligible patients with HBVr were included, with 14 patients (61%) receiving immunotherapy and nine patients (39%) not receiving immunotherapy. Prior to HAIC treatment, four patients in each group had detectable HBV DNA with median titre of 3.66 × 102 IU/ml (patients with immunotherapy) and 1.98 × 102 IU/ml (patients without immunotherapy), respectively. Fifteen patients did not show detectable HBV DNA. At HBVr occurrence, the median HBV DNA level was 6.95 × 102 IU/ml for all patients, 4.82 × 102 IU/ml in patients receiving immunotherapy and 1.3 × 103 IU/ml in patients not receiving immunotherapy. Grade 3 hepatitis developed in 12 cases of all patients (12/23, 48%), including five patients with immunotherapy (56%) and seven patients without immunotherapy (78%). At the 3-month follow-up, HBV DNA was detected in 10 patients, with a median HBV DNA level of 2.05 × 102 IU/ml (range, 1.5 × 102– 3.55 × 102 IU/ml) in patients (7/10) with immunotherapy and 4.28 × 102 IU/ml (range, 1.15 × 102– 5.88 × 102 IU/ml) in patients (3/10) without immunotherapy. Intensified antiviral treatment was administered to all patients. No HBVr-related fatal events occurred. Conclusion HBVr can occur after HAIC combined with or without immunotherapy. The degree of liver damage did not differ significantly in patients treated with or without immunotherapy. Intensified antiviral treatment was found to be crucial for HCC patients with HBVr.

The Thwaites Glacier (TG), accounting for four percent of present-day sea-level rise, has been confirmed with the irreversible retreat and thinning. Consequently, understanding the continuous calving front retreat within the TG is pivotal for accurately monitoring glacier dynamics and future Antarctic impact on global climate change. In this study, based on the novel deep learning method for calving front delineation and the surface melt detection framework, we utilized high-resolution remote sensing data from 2015 to 2023 to analyze continuous calving retreat and the associated influencing factors including surface melt, and ice velocity of the TG. Our findings reveal a retreat of 18.0 km and a mass loss of [Formula: see text]. Satellite data illustrate prolonged and intense melting periods in the 2016/2017 melting season, correlating with a significant retreat in the glacier's terminus position in early 2017. We also demonstrate that the ice flow velocity on the near the pinning point remains consistently slow and stable (from 0.5 to 1.8 m/day) from 2015 to 2023, while the Thwaites West Ice Tongue (TWIT) undergoes pronounced dynamic variations characterized with higher ice velocities and frequent frontal fluctuations (from 11.4 to 15.7 m/day), subsequently accelerating the calving of the TG. We believe a profound understanding of these interrelationships holds paramount importance in glacier dynamic changes and modeling, providing invaluable insights into potential glacier responses to global climate change and the implementation of SDG13 (Climate Action).

Purpose To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib (hereafter, TACE-regorafenib) or camrelizumab (hereafter, TACE-camrelizumab) for treating hepatocellular carcinoma (HCC) with untreatable progression after TACE and sorafenib therapy. Methods The medical records of patients with HCC who received TACE-regorafenib or TACE-camrelizumab between September 2018 and December 2023 were retrospectively evaluated. Therapeutic response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups. Results A total of 76 patients were enrolled in this study, with 41 and 35 patients in the TACE-regorafenib and TACE-camrelizumab groups, respectively. The objective response rates in the TACE-regorafenib and TACE-camrelizumab groups were 9.8% and 8.6%, respectively, with no statistically significant difference between the two groups ( P = 0.859). Similarly, there was no statistically significant difference in disease control rates between the two groups (61.0% vs 68.6%, P = 0.838). The median OS was 11 months in the TACE-regorafenib group and 10 months in the TACE-camrelizumab group, with no significant difference between the two groups ( P = 0.348). The TACE-regorafenib group had a median PFS of 7 months, which was significantly longer than that of the TACE-camrelizumab group (4 months, P = 0.004). There was no significant difference in the incidence of AEs between the two groups ( P = 0.544). Conclusions TACE-regorafenib was safe, well-tolerated, and showed promising efficacy in patients with sorafenib-refractory advanced HCC, whereas TACE–camrelizumab demonstrated similar survival benefits.

Objective: Chronic postoperative pain (CPSP) is common after thoracic surgery, even after the less invasive video-assisted thoracoscopic surgery (VATS). This study investigated the effect of thoracic epidural anesthesia (TEA) on the development of CPSP. Materials: We retrospectively analyzed the data of patients who underwent VATS at our center between 2020 and 2022. The enrolled patients were divided into the epidural block (EPI) and patient-controlled intravenous analgesia (PCIA) groups. A telephone questionnaire was used to collect information regarding CPSP, which was defined as a numerical rating scale (VAS) score ≥1 at 3 or 6 months postoperatively. Additionally, statistical analyses were performed to identify the risk factors for CPSP in the two groups. Results: Overall, 894 patients completed the follow-up interviews at 3 and 6 months, with 325 and 569 patients in the PCIA and EPI groups, respectively. The incidence rates of CPSP in the PCIA group at 3 and 6 months were 16.9 % (95 % confidence interval [CI]: 9.3–32.7 %) and 13.5 % (95 % CI: 8.7–33.4 %), and 10.3 % (95 % CI: 8.1–30.5 %) and 3.6 % (95 % CI: 3.5–21.5 %) in EPI group, respectively. The incidence of CPSP at 3 months (P = 0.0048) and 6 months (P

ObjectiveParkinson’s disease (PD) is the second most common neurodegenerative disease in the world, and type 2 diabetes (T2DM) and PD are influenced by common genetic and environmental factors. Mitochondrial dysfunction and inflammation are common pathogenic mechanisms of both diseases. However, the close association between PD and T2DM and the specific relationship between them are not yet clear. This study aimed to reveal the specific connection between the two diseases by establishing a mouse model of comorbid PD and T2DM, as well as a Bv2 cell model.MethodsC57BL/6 mouse were used to construct a model of PD with T2DM using streptozotocin and rotenone, while Bv2 cells were used to simulate the microenvironment of PD and T2DM using rotenone and palmitate. Behavioral tests were conducted to assess any differences in motor and cognitive functions in mouse. Immunohistochemistry was used to analyze the number of dopaminergic neurons in the substantia nigra region of mouse. Western blotting was used to detect the expression levels of TH, P-NFκB, NFκB, Cyclic GMP-AMP synthase (cGAS), and Stimulator of interferon genes (STING) proteins in the substantia nigra region of mouse and Bv2 cells. qRT-PCR was used to analyze the expression levels of IL1β, IL6, and TNF-α. Seahorse technology was used to assess mitochondrial function in Bv2 cells.Results:T2DM exacerbated the motor and cognitive symptoms in mouse with PD. This effect may be mediated by disrupting mitochondrial function in microglial cells, leading to damaged mtDNA leakage into the cytoplasm, subsequently activating the cGAS-STING pathway and downstream P-NFκB/NFκB proteins, triggering an inflammatory response in microglial cells. Microglial cells release inflammatory factors such as IL1β, IL6, and TNF-α, exacerbating neuronal damage caused by PD.ConclusionOur study results suggest that T2DM may exacerbate the progression of PD by damaging mitochondrial function, and activating microglial cell inflammation. The detrimental effects on Parkinson’s disease may be achieved through the activating of the cGAS-STING protein pathway.

Tertiary lymphoid structures (TLS) represent the ectopic aggregations of immune cells arising during chronic inflammation or tumor progression. In cancer, TLS are often associated with beneficial clinical outcomes in patients undergoing immunotherapy, underscoring their prognostic and predictive significance. Mature TLS, characterized by germinal centers and areas of T-cell and B-cell aggregation, are considered primary locations for activating and maintaining both humoral and cellular anti-tumor immune effects. Despite their recognized importance, the mechanisms driving the formation of mature TLS in cancer and their influence on the immune response within tumors remain insufficiently understood. Therefore, this review aims to comprehensively explore the structural composition, development mechanisms, maturity impact factors, immunological function, and innovative therapeutic strategies of mature TLS within the tumor microenvironment. The research summarized herein offers novel insights and considerations for therapeutic approaches to promote TLS generation and maturation in patients with cancer, representing a promising avenue for future cancer therapies.

Background: The clinical symptoms of progressive supranuclear palsy (PSP) may be mediated by aberrant dynamic functional network connectivity (dFNC). While earlier research has found altered functional network connections in PSP patients, the majority of those studies have concentrated on static functional connectivity. Nevertheless, in this study, we sought to evaluate the modifications in dynamic characteristics and establish the correlation between these disease-related changes and clinical variables. Methods: In our study, we conducted a study on 53 PSP patients and 65 normal controls. Initially, we employed a group independent component analysis (ICA) to derive resting-state networks (RSNs), while employing a sliding window correlation approach to produce dFNC matrices. The K-means algorithm was used to cluster these matrices into distinct dynamic states, and then state analysis was subsequently employed to analyze the dFNC and temporal metrics between the two groups. Finally, we made a correlation analysis. Results: PSP patients showed increased connectivity strength between medulla oblongata (MO) and visual network (VN) /cerebellum network (CBN) and decreased connections were found between default mode network (DMN) and VN/CBN, subcortical cortex network (SCN) and CBN. In addition, PSP patients spend less fraction time and shorter dwell time in a diffused state, especially the MO and SCN. Finally, the fraction time and mean dwell time in the distributed connectivity state (state 2) is negatively correlated with duration, bulbar and oculomotor symptoms. Discussion: Our findings were that the altered connectivity was mostly concentrated in the CBN and MO. In addition, PSP patients had different temporal dynamics, which were associated with bulbar and oculomotor symptoms in PSPRS. It suggest that variations in dynamic functional network connectivity properties may represent an essential neurological mechanism in PSP.

Purpose: The intimate connection between long noncoding RNA (lncRNA) and autophagy has been established in cartilage degeneration. However, their roles in meniscal degeneration remain ambiguous. This study aimed to identify the key autophagy-related lncRNA and its associated regulatory network in meniscal degeneration in the context of osteoarthritis (OA). Methods: RNA sequencing was performed to identify differentially expressed lncRNAs (DELs) and mRNAs (DEMs), which were then conducted to enrichment analyses using the DAVID database and Metascape. Autophagy-related DEMs were identified by combining DEMs with data from the Human Autophagy Database. Three databases were used to predict miRNA, and the DIANA LncBase Predicted database was utilized to predict miRNA-lncRNA interactions. Based on these predictions, comprehensive competitive endogenous RNA (ceRNA) network were constructed. The expression levels of the classical autophagy markers and autophagy-related ceRNA network were validated. Additionally, Gene Set Enrichment Analysis (GSEA) was performed using autophagy-related DEMs. Results: 310 DELs and 320 DEMs were identified, with five upregulated and one downregulated autophagy-related DEMs. Through reverse prediction of miRNA, paired miRNA-lncRNA interactions, and verification using RT-qPCR, two lncRNAs (PCAT19, CLIP1-AS1), two miRNA (has-miR-3680-3p and has-miR-4795-3p) and two mRNAs (BAG3 and HSP90AB1) were included in the constructed ceRNA regulatory networks. GSEA indicated that the increased expression of autophagy-related mRNAs inhibited glycosaminoglycan biosynthesis in the degenerative meniscus. Conclusion: This study presented the first construction of regulatory ceRNA network involving autophagy-related lncRNA-miRNA-mRNA interactions in OA meniscus. These findings offered valuable insights into the mechanisms underlying meniscal degeneration and provided potential targets for therapeutic intervention.

IntroductionWe aimed to assess the impact of myasthenia gravis (MG) on the long-term prognosis in patients with thymoma after surgery and identify related prognostic factors or predictors.MethodsThis retrospective observational study included 509 patients with thymoma (thymoma combined with MG [MG group] and thymoma alone [non-MG group]). Propensity score matching was performed to obtain comparable subsets of 96 patients in each group. A comparative analysis was conducted on various parameters.ResultsBefore matching, the 10-year survival and recurrence-free survival rates in both groups were 93.8 and 98.4%, and 85.9 and 93.4%, respectively, with no statistically significant difference observed in the survival curves between the groups (p > 0.05). After propensity score matching, 96 matched pairs of patients from both groups were created. The 10-year survival and recurrence-free survival rates in these matched pairs were 96.9 and 97.7%, and 86.9 and 91.1%, respectively, with no statistical significance in the survival curves between the groups (p > 0.05). Univariate analysis of patients with thymoma postoperatively revealed that the World Health Organization histopathological classification, Masaoka–Koga stage, Tumor Node Metastasis stage, resection status, and postoperative adjuvant therapy were potentially associated with tumor recurrence after thymoma surgery. Multivariate analysis demonstrated that the Masaoka–Koga stage and postoperative adjuvant therapy independently predicted the risk of recurrence in patients with thymoma after surgery.ConclusionThere was no difference in prognosis in patients with thymoma with or without MG. The Masaoka–Koga stage has emerged as an independent prognostic factor affecting recurrence-free survival in patients with thymoma, while postoperative adjuvant therapy represents a poor prognostic factor.

Abstract Ruthenium (Ru) is a promising electrocatalyst for the hydrogen evolution reaction (HER), despite suffering from low activity in non‐acidic conditions due to the high kinetic energy barrier of H2O dissociation. Herein, the synthesis of carbon nanosheet‐supported RuP/Ru heterostructures (RuP/Ru@CNS) from a natural polysaccharide is reported and demonstrates its behavior as an effective HER electrocatalyst in non‐acidic conditions. The RuP/Ru@CNS exhibits low overpotential (106 mV at 200 mA·cm−2) in alkaline electrolyte, exceeding most reported Ru‐based electrocatalysts. The electron shuttling between Ru atoms at the RuP/Ru interface results in a lowered energy barrier for H2O dissociation by electron‐deficient Ru atoms in the pure Ru phase, as well as optimized H* adsorption of electron‐gaining Ru atoms in the neighboring RuP. A low H* spillover energy barrier between Ru atoms at the RuP/Ru interface further boosts HER kinetics. This study demonstrates a sustainable method for the fabrication of efficient Ru‐based electrocatalysts and provides a more detailed understanding of interface effects in HER catalysis.

Methods: Herein, we obtained and characterized deltaN p63- and adenosine triphosphate-binding cassette subfamily G member 2-expressing limbal stem cells (LSCs). Chitosan and carboxymethyl chitosan (CTH) were cross-linked to be an in situ thermosensitive hydrogel (ACH), which was printed through four-dimensional (4D) printing to obtain a porous carrier with uniform pore diameter (4D-CTH). Rabbits were injected with alloxan to induce diabetes mellitus (DM). Following this, the LSC-carrying hydrogel was spread on the surface of the cornea of the diabetic rabbits to cure corneal epithelium injury.Results: Compared with the control group (LSCs only), rapid wound healing was observed in rabbits treated with LSC-carrying 4D-CTH. Furthermore, the test group also showed better corneal nerve repair ability. The results indicated the potential of LSC-carrying 4D-CTH in curing corneal epithelium injury.Conclusion: 4D-CTH holds potential as a useful tool for studying regenerative processes occurring during the treatment of various diabetic corneal epithelium pathologies with the use of stem cell-based technologies.

Abstract Background Corneal alkali burns can lead to ulceration, perforation, and even corneal blindness due to epithelial defects and extensive cell necrosis, resulting in poor healing outcomes. Previous studies have found that chitosan-based in situ hydrogel loaded with limbal epithelium stem cells (LESCs) has a certain reparative effect on corneal alkali burns. However, the inconsistent pore sizes of the carriers and low cell loading rates have resulted in suboptimal repair outcomes. In this study, 4D bioprinting technology was used to prepare a chitosan-based thermosensitive gel carrier (4D-CTH) with uniform pore size and adjustable shape to improve the transfer capacity of LESCs. Methods Prepare solutions of chitosan acetate, carboxymethyl chitosan, and β-glycerophosphate sodium at specific concentrations, and mix them in certain proportions to create a pore-size uniform scaffold using 4D bioprinting technology. Extract and culture rat LESCs (rLESCs) in vitro, perform immunofluorescence experiments to observe the positivity rate of deltaNp63 cells for cell identification. Conduct a series of experiments to validate the cell compatibility of 4D-CTH, including CCK-8 assay to assess cell toxicity, scratch assay to evaluate the effect of 4D-CTH on rLESCs migration, and Calcein-AM/PI cell staining experiment to examine the impact of 4D-CTH on rLESCs proliferation and morphology. Establish a severe alkali burn model in rat corneas, transplant rLESCs onto the injured cornea using 4D-CTH, periodically observe corneal opacity and neovascularization using a slit lamp, and evaluate epithelial healing by fluorescein sodium staining. Assess the therapeutic effect 4D-CTH-loaded rLESCs on corneal alkali burn through histological evaluation of corneal tissue paraffin sections stained with hematoxylin and eosin, as well as immunofluorescence staining of frozen sections. Results Using the 4D-CTH, rLESCs were transferred to the alkali burn wounds of rats. Compared with the traditional treatment group (chitosan in situ hydrogel encapsulating rLESCs), the 4D-CTH-rLESC group had significantly higher repair efficiency of corneal injury, such as lower corneal opacity score (1.2 ± 0.4472 vs 0.4 ± 0.5477, p

Abstract Objectives To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). Methods Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan–Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. Results The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8 months. The median PFS was 10.0 months (95% CI: 8.9–11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15 ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P

Acute ischemic stroke (AIS) is the leading cause of disability worldwide, and recanalization therapy is significant in the hyperacute phase of AIS. However, reperfusion injury and hemorrhagic transformation after recanalization predict poor prognosis of AIS. How to minimize reperfusion injury and hemorrhagic transformation, which greatly improves the prognosis of vascular recanalization, is becoming a hot topic in AIS research and an urgent problem to be solved. A wealth of neuroprotective drug studies is now available, while some of the neuroprotectants have met with failure in human studies. It is discussed in this review about the progress in neuroprotective therapy for AIS based on understanding the pathophysiologic mechanisms of reperfusion injury and hemorrhagic transformation, as well as challenges in exploring new neuroprotectants.

In order to reduce the vibration energy transferred to the bearing plate of an undersea vehicle for detecting acoustic arrays, an accessory round plate structure for vibration reduction was designed based on the acoustic black hole principle. The vibration reduction performance was characterized by the vibration level drop of acceleration, and the vibration reduction performance tests of the bearing plate under axial and radial excitation of the shaker were carried out. The results show that the vibration reduction effect of the round plate structure is good in the frequency range of 50 Hz–10 kHz, fully showing that the accessory round plate structure designed in this paper has the vibration reduction characteristics of light weight, high efficiency, and wide frequency and has a wide range of potential application value.

Aspheric surfaces are widely used in advanced optical instruments. Measuring the aspheric surface parameters (ASPs) with high accuracy is vital for manufacturing and aligning optical aspheric surfaces. This paper provides a review of various techniques for measuring ASPs and discusses the advantages/disadvantages of these approaches. The aim of this review is to contribute to advancements in the fabrication and testing of aspheric optical elements and their practical applications in diverse fields.

Advanced airborne power generation technology represents one of the most effective solutions for meeting the electricity requirements of hypersonic vehicles during long-endurance flights. This paper proposes a power generation system that integrates a high-temperature fuel cell to tackle the challenges associated with power generation in the hypersonic field, utilizing techniques such as inlet pressurization, autothermal reforming, and anode recirculation. Firstly, the power generation system is modeled modularly. Secondly, the influence of key parameters on the system’s performance is analyzed. Thirdly, the performance of the power generation system under the design conditions is simulated and evaluated. Finally, the weight distribution and exergy loss of the system’s components under the design conditions are calculated. The results indicate that the system’s electrical efficiency increases with fuel utilization, decreases with rising current density and steam-to-carbon ratio (SCR), and initially increases before declining with increasing fuel cell operating temperature. Under the design conditions, the system’s power output is 48.08 kW, with an electrical efficiency of 51.77%. The total weight of the power generation system is 77.09 kg, with the fuel cell comprising 69.60% of this weight, resulting in a power density of 0.62 kW/kg. The exergy efficiency of the system is 55.86%, with the solid oxide fuel cell (SOFC) exhibiting the highest exergy loss, while the mixer demonstrates the greatest exergy efficiency. This study supports the application of high-temperature fuel cells in the hypersonic field.

Intelligent design has been the direction pursued by international electric vehicle (EV) research and development (R&D) teams in recent years. This paper analyzes the problems of unsustainable development in the current product design of EVs in China, such as high R&D investment, high innovation risks, and low R&D input–output ratios. It explores the issues related to intelligent design, R&D investment, car prices, and safety in the field of EVs in China, and it proposes the concept of optimizing intelligence to optimize the design investment of EVs in China. On the basis of the development situation and the existing problems of social organization standards that gather innovative technologies for EVs, this paper used data from the national social organization standard information platform as the research object and analyzed important data, such as the quantity of the information of relevant social organizations and professional fields of social organization standards, through mathematical methods. The article proposes an optimization design scheme for EV products in China, combining intelligence and practicality from the perspective of the optimizing intelligent design, and it models the construction of EV optimization design. The quantitative relationship between the two schemes before and after optimization design is compared in terms of cost savings in intelligent design, the improvement of social benefits, and the enhancement of EV cost performance. The comparative study found that intelligent optimization design reduced the R&D cost of EVs by 45.24%, and the social benefits of R&D investment increased by 29.51%.

The survivability of out-of-hospital cardiac arrest patients in China is notably low, at less than 1%, primarily due to difficulties in accessing nearby Automated External Defibrillator (AED) devices during emergencies. Therefore, the strategic deployment of AEDs is crucial for improving patient survival. This study adopts a novel hybrid methodology that integrates the Fuzzy Analytic Network Process (FANP) and Grey Relational Analysis (GRA) to assess and prioritize the critical factors for optimizing AED deployment in China. In the FANP model, the rate of cardiopulmonary resuscitation training among individuals in the area, the rate of AED training among individuals in the area, and records of AED device usage within the area are key factors for improving the effectiveness of AED deployment. Furthermore, in the GRA model, the factors with higher gray relational degrees are Visibility, Social Environment, and Accessibility. This analysis sheds light on which secondary indicators can have the most significant impact on improving specific primary indicators. The insights from this study can guide the optimization of AED deployment strategies in China and offer practical solutions for enhancing the deployment of relevant public medical facilities.

Not-from-concentrate (NFC) juice effectively retains the original characteristics of the fruit. Despite the various health benefits of Goji berries, reports on the processing technology and quality changes of NFC goji juice are lacking. We optimised the processing technology of NFC goji juice. Employing fuzzy mathematics evaluation combined with response surface methodology based on single-factor experiments, the physicochemical, nutritional, and microbiological indicators of the juice were determined. Gas chromatography-ion mobility spectroscopy was used to analyse changes in volatile compounds before and after processing. The optimal processing parameters were: times for homogenisation, ultrasonication, and sterilisation of 2 min, 3 min, and 85 s, respectively, and sterilisation temperature of 102 °C. The resulting product had a sensory evaluation score of 85.5 and a rich, pleasant taste. The ratio of total soluble solids to titratable acidity and turbidity were 12.8 and 1420 NTU, respectively. Post-processing, the contents of β-carotene, polysaccharides, and betaine increased by 57.3%, 26.7%, and 31.5%, respectively. Microbiological indicators met Chinese national limits for food pollutants and microorganisms. The total relative content of volatile substances in NFC goji juice decreased by 19.86% after processing. This study provides a theoretical reference for the intensive processing and development of high-value goji berries.

During the past half-century, although numerous interventions for obesity have arisen, the condition’s prevalence has relentlessly escalated annually. Obesity represents a substantial public health challenge, especially due to its robust correlation with co-morbidities, such as colorectal cancer (CRC), which often thrives in an inflammatory tumor milieu. Of note, individuals with obesity commonly present with calcium and vitamin D insufficiencies. Transient receptor potential canonical (TRPC) channels, a subclass within the broader TRP family, function as critical calcium transporters in calcium-mediated signaling pathways. However, the exact role of TRPC channels in both obesity and CRC pathogenesis remains poorly understood. This study set out to elucidate the part played by TRPC channels in obesity and CRC development using a mouse model lacking all seven TRPC proteins (TRPC HeptaKO mice). Relative to wild-type counterparts, TRPC HeptaKO mice manifested severe obesity, evidenced by significantly heightened body weights, augmented weights of epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT), increased hepatic lipid deposition, and raised serum levels of total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C). Moreover, TRPC deficiency was accompanied by an decrease in thermogenic molecules like PGC1-α and UCP1, alongside a upsurge in inflammatory factors within adipose tissue. Mechanistically, it was revealed that pro-inflammatory factors originating from inflammatory macrophages in adipose tissue triggered lipid accumulation and exacerbated obesity-related phenotypes. Intriguingly, considering the well-established connection between obesity and disrupted gut microbiota balance, substantial changes in the gut microbiota composition were detected in TRPC HeptaKO mice, contributing to CRC development. This study provides valuable insights into the role and underlying mechanisms of TRPC deficiency in obesity and its related complication, CRC. Our findings offer a theoretical foundation for the prevention of adverse effects associated with TRPC inhibitors, potentially leading to new therapeutic strategies for obesity and CRC prevention.

This study presents a discrete element investigation on the internal temperature change characteristic and heat transfer efficiency in airport concrete pavement by using the carbon fiber electrothermal method for snow melting and deicing. A discrete element model for snow melting and deicing of airport concrete pavement by using the carbon fiber electrothermal method was generated. The temperature evolution on the surface of the pavement was captured and compared with the indoor experimental results. The numerical simulation results were in good agreement with the experimental results, which verified the applicability of the numerical model. On this basis, the effects of the heating temperature and heating paths on the internal heat conduction and temperature field distribution were investigated. The results showed that the temperature of the pavement surface and the temperature rise gradient are linearly related to the temperature of the carbon fiber heating wire. The initial heating time has little influence on the temperature rise path of the road surface layer after stopping heating and reheating. The temperature of the road surface layer rises slowly after the heating is stopped, and then decreases linearly at a rate of 0.4 °C/h not corresponding to the initial heating time.

Abstract Therapeutic cancer vaccines fail to produce satisfactory outcomes against solid tumors since vaccine‐induced anti‐tumor immunity is significantly hampered by immunosuppression. Generating an in situ cancer vaccine targeting immunological cold tumor microenvironment (TME) appears attractive. Here, a type of free‐field based whole‐body ultrasound (US)‐driven nanovaccines are constructed, named G5‐CHC‐R, by conjugating the sonosensitizer, Chenghai chlorin (CHC) and the immunomodulator, resiquimod (R848) on top of a super small‐sized dendrimeric nanoscaffold. Once entering tumors, R848 can be cleaved from a hypoxia‐sensitive linker, thus modifying the TME via converting macrophage phenotypes. The animals bearing orthotopic pancreatic cancer with intestinal metastasis and breast cancer with lung metastasis are treated with G5‐CHC‐R under a free‐field based whole‐body US system. Benefit from the deep penetration capacity and highly spatiotemporal selectiveness, G5‐CHC‐R triggered by US represented a superior alternative for noninvasive irradiation of deep‐seated tumors and magnification of local immune responses via driving mass release of tumor antigens and “cold‐warm‐hot” three‐state transformation of TME. In addition to irradiating primary tumors, a robust adaptive anti‐tumor immunity is potentiated, leading to successful induction of systemic tumor suppression. The sono‐nanovaccines with good biocompatibility posed wide applicability to a broad spectrum of tumors, revealing immeasurable potential for translational research in oncology.

Abstract The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non‐small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune‐related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ‐specific irAEs in patients with NSCLC and provide an in‐depth analysis of recent advancements in understanding the mechanisms driving ICI‐induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.

Abstract Gravity wave parameterizations contribute to uncertainties in middle atmosphere modeling. To investigate the potential for using machine learning to represent atmospheric gravity waves and the impact of implementing such schemes in a general circulation model (GCM), we train a random forest (RF) emulator on outputs from an existing complex parameterization scheme for orographic gravity wave drag (GWD). The performance of the RF emulator is then evaluated with a focus on stratospheric climatology and variability in climate simulations from the middle atmosphere resolving Beijing Climate Center Atmospheric Circulation Model. In offline tests, the predicted orographic GWD by the RF agrees remarkably well with the target GWD throughout the troposphere and the middle atmosphere. The RF emulator can reproduce the observed climatology of zonal‐mean wind and air temperature in the GCM simulation, as well as its target scheme. Compared to the target orographic GWD parameterization scheme, the RF emulator can reproduce the breakdown of the polar vortex in the Southern Hemisphere stratosphere. This study demonstrates the feasibility of using machine learning to emulate parameterized orographic GWD for modeling the stratosphere with a GCM.

This case report describes an 80-year-old female patient admitted to the emergency department due to abdominal distension, abdominal pain, and hematemesis persisting for three days. Subsequent postoperative pathological examination confirmed the diagnosis of peritoneal cancer. The occurrence, diagnosis, treatment, and prognosis of primary peritoneal cancer (PPC) are presented in detail. PPC is a type of cancer originating from the primary peritoneal mesothelium organization, causing diffuse malignant tumors in the abdominal and pelvic regions. Due to the lack of specific clinical manifestations for this disease, the importance of early diagnosis and treatment is hereby emphasized. The article also mentions the histological source of this type of cancer and the advantages of preoperative intraperitoneal chemotherapy in improving the efficacy of PPC treatment. Finally, the importance of a comprehensive treatment approach and proficient use of targeted therapy techniques are highlighted to enhance the treatment outcomes of PPC.

In this study, two intramammary infusions of cefquinome sulfate were investigated for pharmacokinetics and bioavailability. Twelve lactating cows for each group were administered an effective dose of 75 mg/gland for cefquinome, with milk samples collected at various time intervals. The concentrations of cefquinome in milk at different times were determined by the UPLC-MS/MS method. Analyses of noncompartmental pharmacokinetics were conducted on the concentration of cefquinome in milk. Mean pharmacokinetic parameters of group A and group B following intramammary administration were as follows: AUClast 300558.57 ± 25052.78 ng/mL and 266551.3 ± 50654.85 ng/mL, Cmax 51786.35 ± 11948.4 ng/mL and 59763.7 ± 8403.2 ng/mL, T1/2 5.69 ± 0.62 h and 5.25 ± 1.62 h, MRT 7.43 ± 0.79 h and 4.8 ± 0.78 h, respectively. Pharmacokinetic experiments showed that the relative bioavailability of group B was 88.69% that of group A. From our findings, group B (3 g: 75 mg) shows a quicker drug elimination process than group A (8 g: 75 mg), which suggests that the withdrawal period for the new formulation may be shorter.

The existing automatic driving technology of high-speed railway trains has been able to complete the automatic driving of trains in normal scenes, and it has begun to develop in the direction of improving operational efficiency and optimizing driving strategies. Based on the current automatic driving technology, this paper proposes an optimization method of automatic driving strategy for high-speed trains based on an artificial fish swarm algorithm, aiming at reducing train energy consumption, improving train parking accuracy, train punctuality, passenger comfort, and train speed protection. Firstly, based on train dynamics, the dynamic parameter model of the train in the running process is described. Through the train dynamic parameter model, combined with line information such as speed limit, slope, and phase separation area, an artificial fish swarm algorithm is designed that aims at safety, punctuality, energy saving, comfort, and parking accuracy. The artificial fish swarm algorithm is used to simulate the optimal driving strategy of train running and generate the train driving curve. Finally, the driving curve simulated by the artificial fish swarm algorithm is compared with the driving curve simulated by the genetic algorithm and the actual driving curve of the Beijing-Shenyang high-speed train, which shows that the proposed method is effective and the convergence speed of the artificial fish swarm algorithm is better than that of the genetic algorithm.

Background: Oviductus Ranae (OR) is a well-known animal-based traditional Chinese medicine and widely consumed as a nutraceutical to optimize health. However, a current in-depth understanding of OR regulating mechanisms is lacking in the field. Aim of the study: Metabolomics, proteomics, and transcriptomics, were used as a multi-omics approach to comprehensively investigate the health effects of OR in rats. Methods: Healthy rats were chosen and randomized into two groups treated with or without OR (rats+OR and rats-OR). Soaked and homogenized OR was fed to healthy rats (rats+OR) for 14 days before blood samples were collected for omics analyses. Rats in the rats-OR group were administered sterile saline instead of homogenized OR. LC-MS/MS-based targeted metabolomics including lipidomics profiling was used to survey water-soluble metabolites and organic-soluble lipids in OR and plasma samples. LC-MS-based proteomics investigated the proteins in the plasma samples, and transcriptomic analysis was performed on blood cells isolated from rats+OR and rats-OR groups. Statistical analyses including fold change (FC) and orthogonal partial least squares discrimination analysis (OPLS-DA) were done to assess the differences between the two treatment groups. Plus, pathways regarding differential metabolites including lipids, proteins, and genes were annotated through Kyoto Encyclopedia of Genes and Genomes database (KEGG), and further common pathways were searched to revealing the potential effects of OR. Results: The LC-MS/MS-based metabolomics detected 1300 metabolites in the water phase and 981 lipids in the organic phase of OR samples. In blood samples from rats, 1580 water-soluble metabolites and 1195 organic-soluble lipids were measured in the plasma. Among them, 199 differential compounds were found between rats+OR and rats-OR groups, with 97 out of 150 downregulated lipids in rats+OR (mainly TGs). Moreover, 125 of 782 proteins were differentially altered between the two treatment groups. Furthermore, 111 differentially expressed genes were found between the rats+OR and rats-OR groups. An integrated analysis of multi-omics data highlighted that OR affected lipid-related pathways, suggesting that OR administration may improve blood lipid levels and protect against cardiovascular and atherosclerotic diseases. Conclusion: We deciphered a series of OR-induced changes in healthy rats using a multi-omics approach, which lays the groundwork for further studies on the preventative and therapeutic mechanisms of OR for various diseases.

Abstract The rapid diagnosis of respiratory virus infection through breath and blow remains challenging. Here we develop a wireless, battery-free, multifunctional pathogenic infection diagnosis system (PIDS) for diagnosing SARS-CoV-2 infection and symptom severity by blow and breath within 110 s and 350 s, respectively. The accuracies reach to 100% and 92% for evaluating the infection and symptom severity of 42 participants, respectively. PIDS realizes simultaneous gaseous sample collection, biomarker identification, abnormal physical signs recording and machine learning analysis. We transform PIDS into other miniaturized wearable or portable electronic platforms that may widen the diagnostic modes at home, outdoors and public places. Collectively, we demonstrate a general-purpose technology for rapidly diagnosing respiratory pathogenic infection by breath and blow, alleviating the technical bottleneck of saliva and nasopharyngeal secretions. PIDS may serve as a complementary diagnostic tool for other point-of-care techniques and guide the symptomatic treatment of viral infections.

ABSTRACTWearable sweat sensors are gaining significant attention due to their unparalleled potential for noninvasive health monitoring. Sweat, as a kind of body fluid, contains informative physiological indicators that are related to personalized health status. Advances in wearable sweat sampling and routing technologies, flexible, and stretchable materials, and wireless digital technologies have led to the development of integrated sweat sensors that are comfortable, flexible, light, and intelligent. Herein, we report a flexible and integrated wearable device via incorporating a microfluidic system and a sensing chip with skin-integrated electronic format toward in-situ monitoring of uric acid (UA) in sweat that associates with gout, cardiovascular, and renal diseases. The microfluidic system validly realizes the real-time capture perspiration from human skin. The obtained detection range is 5–200 μM and the detection limit is 1.79 μM, which offers an importance diagnostic method for clinical relevant lab test. The soft and flexible features of the constructed device allows it to be mounted onto nearly anywhere on the body. We tested the sweat UA in diverse subjects and various body locations during exercise, and similar trends were also observed by using a commercial UA assay kit.

Background and Objectives: Chronic total occlusion (CTO) is a complex lesion of coronary artery disease (CAD) with a detection rate of approximately 25% on coronary angiography. CTO patients generally experience poor quality of life and prognosis. This study aims to evaluate the association between the estimated glucose disposal rate (eGDR), a surrogate marker for insulin resistance (IR), and the prognosis of CTO PCI patients, as well as to investigate the potential role of the systemic immune-inflammation index (SII) in this process. Methods: We retrospectively included 1482 non-diabetic patients who underwent successful CTO PCI at Anzhen Hospital between January 2018 and December 2021. The primary endpoint was major adverse cardiovascular events (MACEs). Clinical characteristics, biochemical markers, and interventional records were collected, and the eGDR and SII were calculated. Cox regression, restricted cubic splines (RCSs), receiver operating characteristic (ROC) analysis, and Kaplan–Meier curves were used to assess associations. Results: MACEs occurred in 158 patients (10.67%). Patients with MACEs had lower eGDR and higher SII levels. A high eGDR significantly reduced MACE risk (Q4 vs. Q1: HR 0.06, 95% CI 0.03–0.12), while a high SII increased it (Q4 vs. Q1: HR 3.32, 95% CI 1.78–6.33). The combination of low eGDRs and high SIIs predicted the highest MACE risk (HR 4.36, 95% CI 2.71–6.01). The SII partially mediated the relationship between eGDR and MACEs. Conclusions: A low eGDR and high SII are significant predictors of poor prognosis in non-diabetic CTO PCI patients. Combining the eGDR and the SII provides a comprehensive assessment for better predicting cardiovascular outcomes.

The massive consumption of fossil fuels has led to the serious accumulation of carbon dioxide gas in the atmosphere and global warming. Bioconversion technologies that utilize biomass resources to produce chemical products are becoming widely accepted and highly recognized. The world is heavily dependent on petroleum-based products, which may raise serious concerns about future environmental security. Most commercially available epoxy resins (EPs) are synthesized by the condensation of bisphenol A (BPA), which not only affects the human endocrine system and metabolism, but is also costly to produce and environmentally polluting. In some cases, straw tar-based epoxy resins have been recognized as potential alternatives to bisphenol A-based epoxy resins, and are receiving increasing attention due to their important role in overcoming the above problems. Using straw tar and lignin as the main raw materials, phenol derivatives were extracted from the middle tar instead of bisphenol A. Bio-based epoxy resins were prepared by replacing epichlorohydrin with epoxylated lignin to press carbon fiber sheets, which is a kind of bio-based fine chemical product. This paper reviews the research progress of bio-based materials such as lignin modification, straw pyrolysis, lignin epoxidation, phenol derivative extraction, and synthesis of epoxy resin. It improves the performance of carbon fiber-reinforced plastic (CFRP) while taking into account the ecological and environmental protection, so that the epoxy resin is developed in the direction of non-toxic, harmless and high-performance characteristics, and it also provides a new idea for the development of bio-based carbon fibers.

Deep neural networks (DNNs) have achieved breakthrough progress in various fields, largely owing to the support of large-scale datasets with manually annotated labels. However, obtaining such datasets is costly and time-consuming, making high-quality annotation a challenging task. In this work, we propose an improved noisy sample selection method, termed “sample selection framework”, based on a mixup loss and recalibration strategy (SMR). This framework enhances the robustness and generalization abilities of models. First, we introduce a robust mixup loss function to pre-train two models with identical structures separately. This approach avoids additional hyperparameter adjustments and reduces the need for prior knowledge of noise types. Additionally, we use a Gaussian Mixture Model (GMM) to divide the entire training set into labeled and unlabeled subsets, followed by robust training using semi-supervised learning (SSL) techniques. Furthermore, we propose a recalibration strategy based on cross-entropy (CE) loss to prevent the models from converging to local optima during the SSL process, thus further improving performance. Ablation experiments on CIFAR-10 with 50% symmetric noise and 40% asymmetric noise demonstrate that the two modules introduced in this paper improve the accuracy of the baseline (i.e., DivideMix) by 1.5% and 0.5%, respectively. Moreover, the experimental results on multiple benchmark datasets demonstrate that our proposed method effectively mitigates the impact of noisy labels and significantly enhances the performance of DNNs on noisy datasets. For instance, on the WebVision dataset, our method improves the top-1 accuracy by 0.7% and 2.4% compared to the baseline method.

Reinforced-concrete shear walls stand as the primary construction method for urban residential structures in northern China. In alignment with national carbon neutrality goals for residential construction, this study developed a set of prediction models with which to estimate the building material carbon emissions of reinforced-concrete shear-wall urban residential buildings. Specifically, this study clarified the boundaries, content, and calculation method for carbon emissions in the stage of material production. Using consumption data for building materials from 20 reinforced-concrete shear-wall urban residential buildings in northern China, the study evaluated the composition and distribution of building material carbon emissions. Linear and ridge regression was performed to fit the coupling relationship between spatial design parameters and building material carbon emissions. Adopting two technical approaches of direct and indirect prediction, 10 carbon emission prediction models based on residential design parameters were established and validated. The results indicate that, although the indirect prediction models, based on concrete, steel, cement mortar, and the transparent envelope, had relatively low accuracy in estimating carbon emissions from cement mortar and the transparent envelope, they performed well overall. Additionally, the prediction performance of the four models was similar. In contrast, except for M1 and M3, the other direct prediction models, based on the number of building stories, number of basement levels, number of primary rooms on the standard floor or in the unit, and building width and depth, also had good fitting and prediction performance. These models effectively predicted the total building material carbon emissions in the phases of conceptual design, schematic design, preliminary design, and working drawing. Three prediction models could produce fast and effective data support for the low-carbon design of urban residential buildings.