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Using data collected from more than 5.8 million high school and college graduates ages 18 to 65 years who participated in the American Community Survey between 2009 and 2021, the authors estimate the internal rates of return (IRRs) for individuals with college degrees in 10 broad majors compared with high school graduates. The analysis shows significant differences in the age-earnings trajectories and IRRs across college majors. Furthermore, quantile regression analyses show that IRR is generally higher at the high end of the earnings distribution compared with the low end. Finally, the authors observed a slight decrease in IRR during the study period, which is consistent with the flattening and even decline in college wage premiums following the 2008 Great Recession.

The treatment strategy for blast injuries is closely linked to the clinical outcome of blast injury casualties. However, the application of military surgery experience to blast injuries caused by production safety accidents is relatively uncommon. In this study, the authors present 2 cases of blast injuries caused by one gas explosion, both cases involved individuals of the same age and gender and experienced similar degree of injury. The authors highlight the importance of using a military surgery treatment strategy, specifically emphasizing the need to understand the concept of damage control and disposal. It is recommended that relevant training in this area should be strengthened to improve the clinical treatment of such injuries. This study provides a valuable reference for healthcare professionals dealing with blast injuries.

When tunnel boring machines (TBMs) excavate through jointed rock masses, the cutting efficiency is strongly affected by the shear strength of joints, the mechanism of which, however, remains poorly understood. In this study, a series of disc-cutter indentation tests were conducted on granite rock mass specimens with different joint shear strengths. During the indentation, the cracking process was recorded by a digital image correlation (DIC) system. The deformation and strength of specimens, cracking behavior, rock breakage mode and cutting efficiency were quantitatively investigated. In addition, to investigate the combined effects of joint shear strength, orientation and spacing on the rock breakage mechanism, numerical rock mass models were established based on a particle flow code PFC2D. Experimental results reveal that the cracking of primary and secondary cracks changes from the mixed shear-tensile to tensile mode in the initial stage, while the joint shear strength does not affect the cracking mode in the subsequent propagation process. The rock breakage mode is classified to an internal block breakage mode, a cross-joint breakage mode and a cutters-dependent breakage mode. The cross-joint breakage mode is optimal for improving the cutting efficiency. Numerical simulation results reveal that the increase in the joint shear strength changes the internal block breakage mode to cross-joint breakage mode for rock masses of particular ranges of joint orientation and spacing. These findings provide basis for improving the TBM cutting efficiency through jointed rock masses.

ABSTRACTBackground This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV).Methods We searched five databases for randomized controlled trials (RCTs) evaluating the effects of EVV on healthy adults. The primary outcomes were relative risk (RR) of sero-conversion or sero-response of EVV in healthy adults between the groups that received EVV and the controls.Results Twenty-nine RCTs (n = 23573) were included. There was a significant difference in RR of sero-conversion of EVV (RR 13.18; 95% CI 11.28–15.41; I2 = 33%; P

Abstract Applying anammox to municipal wastewater treatment promises enormous energy and resource savings; however, seasonally cold conditions pose a considerable challenge, impeding its future applications towards non-tropical regions. In this study, we establish a pilot-scale wastewater treatment plant (50 m3/d) in northern China and implement the partial denitrification coupling anammox process on actual municipal wastewater. Despite seasonal cooling, the nitrogen removal efficiency remains high, ranging from 75.0 ± 4.6% at 27.8–20.0 °C to 70.4 ± 4.5% at 10–7.5 °C. This process exhibits remarkable low-temperature tolerance, achieving an in-situ anammox rate of 32.7 ± 4.7 g-N/(m3·d) at 10–7.5 °C and contributing up to 39.7 ± 6.7% to nitrogen removal. Further 15N stable isotope tracing and kinetic tests reveal that the partial denitrification is capable of supplying increasingly abundant NO2 - to anammox with decreasing temperature, enabling robust mainstream anammox against seasonal cooling. From 27.8 °C to 7.5 °C, anammox bacteria not only survive but thrive under mainstream conditions, with absolute and relative abundances increasing by 429.1% and 343.5%, respectively. This pilot-scale study sheds fresh light on extending mainstream anammox towards non-tropical regions, taking a necessary step forward toward the sustainability goals of the wastewater treatment sector.

In this study, whole genome sequencing of Bacillus velezensis L-39, an extracellular polysaccharide-producing strain isolated from Pixian Douban, was carried out through the combined use of second-generation Illumina HiSeq and third-generation PacBio platforms. The genomic analysis covered gene assembly, prediction, annotation, and the elucidation of secondary metabolite biosynthetic gene clusters and crucial gene functions, focusing on the gene clusters for carbohydrate metabolism, the nucleoside sugar synthesis pathways, and extracellular polysaccharide biosynthesis. The results showed that the whole genome size of B. velezensis L-39 was 3 970 591 bp in length, encoding a total of 3 770 genes. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the eps gene cluster and 32 functional genes were predicted from the genome, and a complete extracellular polysaccharide (EPS) synthesis pathway was mapped. Subsequently, polymerase chain reaction (PCR) was performed on the pivotal genes, with results expected. The aim of this study is to discover genes closely related to extracellular polysaccharide synthesis by B. velezensis L-39 in order to provide a scientific foundation for an in-depth analysis of the molecular basis for extracellular polysaccharide production by this strain and for its practical application and development.

Abstract Objective To assess the mechanism of supraspinatus tendinopathy induced by type 2 diabetes mellitus (T2DM) in rats using untargeted metabolomics analysis. Methods The liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics approach was used to screen tendon biomarkers of supraspinatus tendinopathy in rats with T2DM. Seventy-eight Sprague-Dawley rats were divided into normal group (NG) and T2DM groups. Rats in T2DM groups were divided into 12-week (T2DM-12w), and 24-week (T2DM-24w) subgroups according to the time point of the establishment of the T2DM rat model. Histological evaluation (modified Bonar score) and biomechanical testing were used to analyze the adverse effects of type 2 diabetes on the tendon of the supraspinatus muscle in rats.Three comparable groups were set up, including T2DM-12w group vs. NG, T2DM-24w group vs. NG, and T2DM-24w group vs. T2DM-12w group. Differentially expressed metabolites (DEMs) in the supraspinatus tendons in the three groups of rats were analyzed using LC-MS, and data were analyzed using multivariate statistical methods to screen potential biomarkers. The DEMs included in the intersection of the three groups were identified as those associated with the development of diabetic supraspinatus tendinopathy, and trend analysis and pathway topology analysis were performed. Results With the progression of diabetes, the tendinopathy of the supracinatus muscle of diabetic rats gradually intensified, mainly manifested as inflammatory reactions, disordered collagen fibers, fat infiltration, and increased modified Bonar score. The intersection of DEMs among the three comparable groups was resulted in the identification of 10 key DEMs, in which melezitose and raffinose showed a continuous increasing trend with the prolongation of disease course. By pathway topology analysis, 10 DEMs (P

Abstract Body composition assessment is very useful for evaluating a patient’s status in the clinic, but recognizing, labeling, and calculating the body compositions would be burdensome. This study aims to develop a web-based service that could automate calculating the areas of skeleton muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) according to L3 computed tomography (CT) images. 1500 L3 CT images were gathered from Xuzhou Central Hospital. Of these, 70% were used as the training dataset, while the remaining 30% were used as the validating dataset. The UNet framework was combined with attention gate (AG), Squeeze and Excitation block (SEblock), and Atrous Spatial Pyramid Pooling (ASSP) modules to construct the segmentation deep learning model. The model’s efficacy was externally validated using two other test datasets with multiple metrics, the consistency test and manual result checking. A graphic user interface was also created and deployed using the Streamlit Python package. The custom deep learning model named L3 Body Composition Segmentation Model (L3BCSM) was constructed. The model’s Median Dice is 0.954(0.930, 0.963)(SATA), 0.849(0.774,0.901)(VATA), and 0.920(0.901, 0.936)(SMA), which is equal to or better than classic models, including UNETR and AHNet. L3BCSM also achieved satisfactory metrics in two external test datasets, consistent with the qualified label. An internet-based application was developed using L3BCSM, which has four functional modules: population analysis, time series analysis, consistency analysis, and manual result checking. The body composition assessment application was well developed, which would benefit the clinical practice and related research.

Abstract In order to prevent leakage of pyrolysed oil and gas and the release of contaminants from the top and bottom strata, it is essential to carry out a comprehensive study of the seepage behaviour of these strata under high temperature triaxial stress conditions. The findings of this study will contribute to the development of effective strategies for the containment and integrity monitoring of subsurface reservoirs and storage environments. Mudstone, serving as both the upper and lower strata, offers an effective barrier due to its inherently low permeability. In order to explore the change rule of mudstone sealing performance under high temperature triaxial stress, an air-heated low permeability rock mass air permeability measurement system is used to measure the ground stress buried 500 m deep and the temperature variation characteristics of mudstone permeability on the roof and floor of Jimsar oil shale in Xinjiang under 100 °C. It was found that the permeability of stressed mudstone decreased with the temperature rising up to 100 °C. The primary factor influencing the outcome was the thermal expansion of the mudstone. The magnitude of the drop value was contingent upon the triaxial stresses that could potentially be induced by the application of significant tensile forces, resulting in a relatively minor drop value. The average hydraulic radius of pore in the mudstone was also calculated, which also exhibited continuous reduction as heating up to 100 °C and the degree of reduction could reach 68%. The capacity, that prevent oil & gas and contaminant from moving cross strata as a barrier, would be strengthened when the mudstone strata from roof and floor experienced the temperature low than 100 °C. The barrier performance of mudstone as a pollutant migration barrier layer to gas pollutant migration during in-situ heat injection mining of oil shale was further evaluated.

Abstract Background The aim of this study is to summarize our center’s experience with patent ductus arteriosus (PDA) ligation during extracorporeal membrane oxygenation (ECMO) treatment in newborns with severe respiratory failure due to persistent pulmonary hypertension of the newborn (PPHN). Methods We retrospectively collected and analyzed clinical data from five newborns with severe respiratory failure due to PPHN who underwent PDA ligation during ECMO treatment at our hospital between January 2021 and August 2023. Results All five patients had large PDAs, measuring 10 mm, 6 mm, 6 mm, 7 mm, and 6 mm, respectively. Significant left-to-right shunting through the PDA was observed after 29 h, 14 h, 3 h, 7 h, and 5 h of ECMO treatment, respectively, at which point successful PDA ligation was performed. The surgical durations were 52 min, 45 min, 55 min, 50 min, and 40 min, respectively. Post-ligation, blood lactate levels significantly decreased compared to preoperative values. Four patients were successfully weaned off ECMO, with ECMO support durations of 64 h, 92 h, 70 h, and 87 h, respectively. After ECMO removal, mechanical ventilation was discontinued after 5.2 days, 7.2 days, 9.5 days, and 5.5 days, respectively. None of the four surviving patients experienced complications such as residual shunting, bleeding, chylothorax, neurologic injury, pneumothorax, poor wound healing, or sepsis. Conclusion During ECMO treatment for PPHN in newborns with large PDAs, the direction of blood flow through the PDA should be closely monitored. PDA ligation is a feasible and reasonable intervention when pulmonary artery pressure decreases and left-to-right shunting through the PDA becomes evident.

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with an unmet clinical need, but its epigenetic regulation remains largely undefined. By performing multiomic profiling, we recently revealed distinct super-enhancer (SE) patterns in different subtypes of breast cancer and identified a number of TNBC-specific SEs that drive oncogene expression. One of these SEs, TCOF1 SE, was discovered to play an important oncogenic role in TNBC. However, the molecular mechanisms by which TCOF1 SE promotes the expression of the TCOF1 gene remain to be elucidated. Here, by using combinatorial approaches of DNA pull-down assay, bioinformatics analysis and functional studies, we identified FOSL1 as a key transcription factor that binds to TCOF1 SE and drives its overexpression. shRNA-mediated depletion of FOSL1 results in significant downregulation of TCOF1 mRNA and protein levels. Using a dual-luciferase reporter assay and ChIP-qPCR, we showed that binding of FOSL1 to TCOF1 SE promotes the transcription of TCOF1 in TNBC cells. Importantly, our data demonstrated that overexpression of FOSL1 drives the activation of TCOF1 SE. Lastly, depletion of FOSL1 inhibits tumor spheroid growth and stemness properties of TNBC cells. Taken together, these findings uncover the key epigenetic role of FOSL1 and highlight the potential of targeting the FOSL1-TCOF1 axis for TNBC treatment.

Objective: To investigate the protective effects of different doses of Fomes officinalis Ames polysaccharides (FOP) on intestinal flora and immune function in exercise-induced immunosuppression (EIS) rats. Methods: Fifty SPF male SD rats aged 7 to 8 weeks were randomly divided into control group (NC group), exercise training group (Ex group), exercise training+low-dose FOP group (LFOP group, 40 mg/(kg·d)), exercise training+medium-dose FOP group (MFOP group, 60 mg/(kg·d)) and exercise training+high-dose FOP group (HFOP group, 80 mg/(kg·d)). Ex group and FOP group were trained on the treadmill for 6 weeks to construct EIS model. LFOP, MFOP and HFOP groups were given FOP after each training. After the intervention, serum IgG, IgM, IL-6, IL-10, INF-γ, TNF-α, LPS levels and intestinal short-chain fatty acid content were detected by enzyme-linked immunosorbent assay. The number of serum CD4+ and CD8+ was detected by cell analyzer. 16S rDNA was used to detect the structural changes of intestinal flora. Western blot was used to detect the protein expression of ZO-1, Occludin, Claudin4 in the colon tissue. Results: Compared with Ex group, serum IgG, IgM, INF-γ, TNF-α, CD4+ and CD8+ of rats in LFOP, MFOP and HFOP groups were significantly increased (P

In this investigation, gas tungsten arc welding (GTAW) and gas tungsten arc welding with trailing ultrasonic rotating extrusion (U-RE-GTAW) were applied to 7075 aluminum alloys. Qualitative comparisons and analyses were carried out to investigate the effects of the ultrasonic rotary extrusion-assisted technology on GTAW processes. The weld joints fabricated by GTAW and U-RE-GTAW were examined using X-ray diffraction (XRD), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM) techniques. Concurrently, the tensile strength and fatigue characteristics were assessed at ambient temperature. The experimental outcomes indicated that the U-RE-GTAW process mitigated porosity within the weld region and substantially augmented dislocation density, while concurrently achieving a notable reduction in grain size and an increase in the volume fraction of secondary phases due to the synergistic effects of ultrasonic oscillation and rotational extrusion. The enhancement in tensile and fatigue resistance of the welded joint was attributed to the strengthening mechanisms associated with these microstructural alterations. Specifically, the ultimate tensile strength exhibited a 20.4% increase, and the elongation at break was elevated by 46.3%. At stress amplitudes of 190 MPa, 160 MPa, and 100 MPa, the fatigue strength of the welded joints was enhanced by 67%, 55%, and 32%, respectively. A quantitative analysis was conducted to elucidate the impact of diverse strengthening mechanisms on the welded joints. It was concluded that dislocation strengthening is the predominant factor contributing to the superior performance of the U-RE-GTAW specimens.

Hydrogen and electricity are crucial and interdependent energy carriers in China's pursuit of carbon neutrality, suggesting the necessity of utilizing cost-effective low-carbon technologies that facilitate their integrated development. The cost-optimal, provincial level, deployment of low-carbon technologies under this long-term goal remains to be determined. This study employs the REPO model to identify the cost-optimal, low-carbon hydrogen production mixes and the evolution of the integrated power system of China from 2020 to 2050. The integrated planning and operation of hydrogen supply and power systems are explored at the provincial level. The role of high-temperature gas-cooled reactors in this integrated energy system is also analyzed. The results reveal that electrolytic hydrogen would dominate China's hydrogen supply after 2040, with alkaline, proton exchange membrane, and solid oxide electrolyzers produce over 1 Mt of hydrogen in the short term, by 2035, and in 2050. Leveraging the low-carbon heat production of high-temperature gas-cooled reactors in addition to its electricity generation to meet the thermal requirements of solid oxide electrolyzers could boost the output to 4.2 Mt in 2050 and reducing the total system CO2 emissions and costs by 2.28% and 0.05%, respectively. By 2050, the integration of hydrogen supply and power systems also generates up to 2194 TW h of flexible electricity demand by electrolyzers, which raised the renewable energy penetration by 4 percentage points while decreasing the need of flexible natural gas power generations and energy storages. This study is valuable for proposing the analytical framework and performing the provincial-level study of decarbonization of China's integrated hydrogen supply and power system.

Abstract In clinical nursing, neonatal pain assessment is a challenging task for preventing and controlling the impact of pain on neonatal development. To reduce the adverse effects of repetitive painful treatments during hospitalization on newborns, we propose a novel method (namely pain concept-cognitive computing model, PainC3M) for evaluating facial pain in newborns. In the fusion system, we first improve the attention mechanism of vision transformer by revising the node encoding way, considering the spatial structure, edge and centrality of nodes, and then use its corresponding encoder as a feature extractor to comprehensively extract image features. Second, we introduce a concept-cognitive computing model as a classifier to evaluate the level of pain. Finally, we evaluate our PainC3M on various open pain data sets and a real clinical pain data stream, and the experimental results demonstrate that our PainC3M is very effective for dynamic classification and superior to other comparative models. It also provides a good approach for pain assessment of individuals with aphasia (or dementia).

Abstract Loss of ARID1A has been reported to drive the progression of lung adenocarcinoma, yet the underlying mechanism remains elusive. In this study, we performed secretome analysis to identify the key secreted proteins regulating lung adenocarcinoma progression. We showed that the VASN level was significantly elevated in the conditioned medium from ARID1A-depleted A549 and H1299 cells. Restoration of ARID1A in ARID1A-depleted lung adenocarcinoma cells prevented the upregulation and secretion of VASN. Clinical analysis demonstrated a negative correlation between ARID1A and VASN expression in ARID1A-mutated lung adenocarcinomas. The patients with ARID1A-mutated lung adenocarcinoma had significantly higher concentrations of serum VASN than healthy controls. Moreover, serum VASN concentrations were associated with TNM stage, lymph node metastasis, and overall survival of the patients with ARID1A-mutated lung adenocarcinoma. Functional studies indicated that VASN overexpression potentiated the proliferation, invasion, and tumorigenesis of lung adenocarcinoma cells. Antibody neutralization of VASN suppressed the aggressiveness of ARID1A-depleted lung adenocarcinoma cells both in vitro and in vivo. Addition of recombinant VASN protein promoted the proliferation and invasion of lung adenocarcinoma cells. Additionally, knockdown of Notch1 blocked the aggressive phenotype induced by recombinant VASN protein. In conclusion, our data uncover the role of VASN in mediating the progression of ARID1A-depleted lung adenocarcinoma and highlight VASN as a promising therapeutic target for this disease.

The newt genus Tylototriton is widely distributed in east, southeast, and south Asia. Previous studies have shown that basic surveys of this genus are far from comprehensive, and unknown species still exist within the group. In this study, we described a new species of this genus, Tylototriton gaowangjienensis sp. nov., from Gaowangjie National Nature Reserve in Hunan Province, China, based on evidence from molecular identification and morphological comparisons. Additionally, we conducted phylogenetic analysis of the genus to elucidate the taxonomic status of the new species. Based on combined mitochondrial 16S rRNA and ND2 gene sequences, the phylogenetic tree supported the new species as a member of the T. wenxianensis species subclade in the subgenus Yaotriton. It can be distinguished from its congeners by the combination of the following characteristics: (1) medium-sized body; (2) finger tips extending beyond the snout while forelimbs stretched forward; (3) tips of forelimbs and hindlimbs reaching and overlapping when folded towards the body; (4) snout edge round; (5) absence of small papillae in the male cloacal fissure; (6) dorsal ridges narrow, with width smaller than the eye diameter; (7) head length (HDL) greater than head width (HDW) (HDL/HDW = 1.04~1.22); (8) orange markings absence on the parotoid; (9) nodule-like warts on body sides continuous; (10) vomerine teeth not connected at the tip, extending to the occipital bone at the posterior end.

Abstract Accurate detection of asphalt pavement distress is crucial for road maintenance and traffic safety. However, traditional convolutional neural networks usually struggle with this task due to the varied distress patterns and complex background in the images. To enhance the accuracy of asphalt pavement distress identification across various scenarios, this paper introduces an improved model named SMG-YOLOv8, based on the YOLOv8s framework. This model integrates the space-to-depth module and the multi-scale convolutional attention mechanism, while optimizing the backbone’s C2f structure with a more efficient G-GhostC2f structure. Experimental results demonstrate that SMG-YOLOv8 outperforms the YOLOv8s baseline model, achieving P macro and mAP50 scores of 81.1% and 79.4% respectively, marking an increase of 8.2% and 12.5% over the baseline. Furthermore, SMG-YOLOv8 exhibits clear advantages in identifying various types of pavement distresses, including longitudinal cracks, transverse cracks, mesh cracks, and potholes, when compared to YOLOv5n, YOLOv5s, YOLOv6s, YOLOv8n, and SSD models. This enhancement optimizes the network structure, reducing the number of parameters while maintaining excellent detection performance. In real-world scenarios, the SMG-YOLOv8 model, when applied to image data collected from projects, achieves a P macro of 80.5% and an R macro of 86.2%. This result demonstrates its excellent generalization capability and practicality. The model provides significant technical support for the intelligent detection of pavement distress.

"Objective To analyze multimodal ultrasonic characteristics of human epidermal growth factor receptor 2 (HER-2) positive breast cancer patients in different hormone receptor (HR) expression states, so as to provide a reference for the early diagnosis and treatment of HER-2 positive breast cancer. Methods The clinical data of 160 patients with HER-2 positive breast cancer who were diagnosed and treated in the First Affiliated Hospital with Nanjing Medical University and Jurong Peoples Hospital from January 2017 to December 2023 were collected retrospectively. According to immunohistochemical results, patients were divided into HR positive group (n=89) and HR negative group (n=71). General data, pathological characteristics and multimodal ultrasonic characteristics of the two groups were compared. Logistic regression analysis was performed to analyze the relationship between multimodal ultrasonic characteristics and HR expression in HER-2 positive breast cancer. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of multimodal ultrasonic characteristics for HR expression in HER-2 positive breast cancer patients. Results Compared with HR negative group, proportions of routine ultrasound signs (irregular shape, edge anomaly or fuzziness, microcalcification, internal uneven echo) significantly decreased in HR positive group, and proportions of contrast-enhanced ultrasound signs (irregular shape, fuzzy boundary and non-filling defect after enhancement) significantly decreased (P＜0.05). Compared with HR negative group, difference value of lesion diameter in contrast-enhanced ultrasound sign ［(3.29±0.36) mm vs (4.30±0.44) mm, t=15.971, P＜0.01］, elasticity score ［(3.15±0.33) points vs (4.56±0.47) points, t=21.416, P＜0.01］ and hardness ratio ［(0.24±0.04) points vs (0.33±0.05) points, t=12.340, P＜0.01］ in elastography signs significantly decreased in HR positive group. Logistic regression analysis showed that difference value of lesion diameter, elasticity score and hardness ratio after enhancement were closely related to HR expression (P＜0.05). ROC curve analysis showed that the area under the curve of three characteristics of ultrasoud multimodality combined to predict the HR expression status in patients with HER-2 positive breast cancer (0.895) was larger than that of the lesion diameter difference (0.641), elasticity score (0.833) and hardness ratio (0.783) (Z=7.524, 3.405, 4.420, P＜0.05), and the specificity and Youden index of combined prediction were also the highest. Conclusion HR positive expression in patients with HER-2 positive breast cancer is closely related to multimodal ultrasonic characteristics. Multimodal ultrasonic characteristics have a high predictive value for HR positive expression in HER-2 positive patients."

Abstract Background Microsatellites are increasingly realized to have biological significance in human genome and health in past decades, the assembled complete reference sequence of human genome T2T-CHM13 brought great help for a comprehensive study of short tandem repeats in the human genome. Results Microsatellites density landscapes of all 24 chromosomes were built here for the first complete reference sequence of human genome T2T-CHM13. These landscapes showed that short tandem repeats (STRs) are prone to aggregate characteristically to form a large number of STRs density peaks. We classified 8,823 High Microsatellites Density Peaks (HMDPs), 35,257 Middle Microsatellites Density Peaks (MMDPs) and 199, 649 Low Microsatellites Density Peaks (LMDPs) on the 24 chromosomes; and also classified the motif types of every microsatellites density peak. These STRs density aggregation peaks are mainly composing of a single motif, and AT is the most dominant motif, followed by AATGG and CCATT motifs. And 514 genomic regions were characterized by microsatellite density feature in the full T2T-CHM13 genome. Conclusions These landscape maps exhibited that microsatellites aggregate in many genomic positions to form a large number of microsatellite density peaks with composing of mainly single motif type in the complete reference genome, indicating that the local microsatellites density varies enormously along the every chromosome of T2T-CHM13.

Abstract We present the theory, concept and design of an efficient, megawatt coherent Cherenkov radiation source based on a two-dimensional periodic surface lattice (2D-PSL) cavity combined with a novel energy recovery system for the generation of highly efficient (> 50%) single-frequency radiation. We demonstrate the scalability of the transverse dimension of the 2D-PSL cavity of the Cherenkov source and thus the potential for efficient, continuous-wave, high-power (> 1 MW) operation; fundamental to the eventual realization of clean, fusion energy. These new sources, with the capacity to operate in the 0.1-10THz range, hold strong promise to address the long-standing “Terahertz gap”. By combining a Cherenkov oscillator driven by a non-gyrating beam with an innovative four-stage depressed collector energy recovery system, the overall device efficiency can be increased to be competitive with gyrotrons in the requirements for heating and current drive in fusion plasma. In these Cherenkov devices, the frequency independence of the magnetic guide field enables advantageous frequency scaling without deployment constraints, making them especially attractive for high-impact applications in fusion science, turbulence diagnostics, non-destructive testing and biochemical spectroscopy. The novel energy recovery techniques presented in this paper have broad applicability to many electron-beam driven devices, bringing revolutionary potential to future THz source technologies.

Abstract Skeletal editing of single-atom insertion to basic chemicals has been demonstrated as an efficient strategy for the discovery of structurally diversified compounds. Previous endeavors in skeletal editing have successfully facilitated the insertion of boron, nitrogen, and carbon atoms. Given the prevalence of oxygen atoms in biologically active molecules, the direct oxygenation of C-C bonds through single-oxygen-atom insertion like Baeyer-Villiger reaction is of particular significance. Herein, we present an approach for the skeletal modification of styrenes using O2 via oxygen insertion, resulting in the formation of aryl ether frameworks under mild reaction conditions. The broad functional-group tolerance and the excellent chemo- and regioselectivity are demonstrated in this protocol. A preliminary mechanistic study indicates the potential involvement of 1,2-aryl radical migration in this reaction.

Abstract Objective Knee osteoarthritis (KOA) is usually bilateral. In many patients, the degree of bilateral knee degeneration varies, with one side involving multiple compartments and the other a single compartment degeneration. Therefore, the objective of this study was to compare the early clinical efficacy of simultaneous bilateral and staged total knee arthroplasty (TKA) combined with unicompartmental knee arthroplasty (UKA) in the treatment of bilateral KOA with different degrees. Methods We compared clinical data from 71 simultaneous bilateral TKA/UKA (SB-TKA/UKA) patients with 52 Staged TKA/UKA (Staged-TKA/UKA) patients. Staged-TKA/UKA is defined as TKA on one knee followed by UKA on the other knee. The comparison included Hospital for Special Surgery (HSS) score, range of motion(ROM), complication rate and prosthetic survival rate at the last follow-up between the two groups. Results The follow-up time of SB-TKA/UKA group was (69.08 ± 14.35) months, and that of Staged-TKA/UKA group was (73.25 ± 18.39) months. Staged-KA/UKA group had a shorter hospital stays, less hospitalization costs and shorter operating time (p 0.05). There was no significant difference in complication rate between the two groups (χ2 = 0.56, p = 0.454). For the TKA-side knee joint, there was no significant difference in the prosthetic survival rate (χ2 = 0.05, p = 0.824) and the prosthetic survival curve (χ2 = 0.052, p = 0.82) between the two groups. For UKA-side knee joint, there was no significant difference in prosthetic survival rate (χ2 = 0.08, p = 0.777) and prosthetic survival curve (χ2 = 0.074, p = 0.786) between the two groups. Conclusions Compared to Staged-TKA/UKA, SB-TKA/UKA has the same early clinical efficacy, shorter operating time and hospital stays, less hospitalization costs, and no increased postoperative complications and prosthesis revision rates. Therefore, SB-TKA/UKA may be recommended for patients who can tolerate simultaneous bilateral surgery as assessed before surgery.

Abstract Temperature plays an important impact on rock mechanical properties. In this paper, the mechanical properties, fracture mechanism and constitutive model of marble under 20–120 °C and 15 MPa are studied. The results show marble deformation can be divided into four stages: compaction, linear elasticity, crack propagation and post-peak failure. Stress–strain curve is not obviously affected by temperature. Macroscopic fracture characteristics change from shear failure to tensile mixed failure with temperature increasing. With the increase of temperature, the strength of marble tends to decrease, indicating that temperature increase has a weakening effect on marble, and there are temperature-sensitive areas of 20–60 °C and temperature sub-sensitive areas of 60–120 °C. The elastic modulus of marble decreases and Poisson’s ratio increases with increasing temperature. The energy evolution law of marble under different temperature is basically the same, which shows that before crack initiation, the energy dissipation is less, and after the damage and yielding occurs, the energy dissipation increases quickly. The energy dissipation in the failure process is mainly used for crack initiation-connection-penetration, as well as plastic deformation caused by friction and slip of cracks, and the plastic deformation and energy dissipation have good linear characteristics. The statistical damage constitutive model based on three-parameter Weibull distribution function can effectively reflect the characteristics of post-peak plastic deformation and strain softening. The weakening effect of marble at 20–120 °C is related to its internal moisture excitation. With the increase of temperature, water is stimulated to absorb and attach to the original relatively dry interface, which plays a role in lubrication. The relative motion friction resistance between solid particles or crack surfaces decreases, which leads to crack initiation and friction energy consumption reduction, changes the specific surface energy of rocks and weakens the strength of marble. The results provide a theoretical basis for predicting and evaluating the long-term stability and safety of surrounding rock of underground deep engineering in complex environment with high ground temperature and high geo-stress.

Abstract Background Interstitial lung abnormality (ILA) has been recognized as a pertinent factor in the development and prognosis of various pulmonary conditions. However, its correlation with co-morbidities remains understudied. The current study endeavors to elucidate the association between ILA and both clinical features and co-morbidities in patients with chronic obstructive pulmonary disease (COPD). Methods A retrospective cohort comprising 1131 hospitalized patients diagnosed with COPD was examined in this observational study. Patients were dichotomously classified based on the presence or absence of ILA, and subsequent analyses scrutinized disparities in demographic, clinical, and laboratory profiles, alongside co-morbid conditions, between the two subgroups. Results Of the 1131 COPD patients, 165 (14.6%) exhibited ILA. No statistically significant differences were discerned between COPD patients with and without ILA concerning demographic, clinical, or laboratory parameters, except for levels of circulating fibrinogen and procalcitonin. Nevertheless, a notable discrepancy emerged in the prevalence of multiple co-morbidities. Relative to COPD patients devoid of ILA, those presenting with ILA manifested a diminished prevalence of lung cancer (OR = 0.50, 95% CI: 0.30–0.83, p = 0.006), particularly of the lung adenocarcinoma (OR = 0.32, 95% CI: 0.15–0.71, p = 0.005). Additionally, the presence of ILA in COPD was positively associated with heart failure (OR = 1.75, 95% CI: 1.04-3.00, p = 0.040) and cancers other than lung cancer (OR = 2.27, 95% CI: 1.16–4.39, p = 0.012). Conclusion These findings demonstrate that the presence of ILA is associated with co-morbidities of COPD, particularly lung cancer.

Abstract With the rapid development of Internet of Things (IoT) services, technologies that leverage multimedia computer communication for information sharing in embedded systems have become a research focus. To address the challenges of low spectral efficiency and poor network flexibility in multimedia computer communications, this paper proposes a resource allocation scheme based on parallel Convolutional Neural Network (CNN). The scheme optimizes the base station beamforming vector and the Reconfigurable Intelligent Surface (RIS) phase shifts to maximize the secure transmission rate for cellular users (CUs), while ensuring normal and secure communication for device-to-device (D2D) users. First, to mitigate interference caused by D2D users reusing CU spectrum resources, the RIS phase shifts and beamforming vectors are optimized to suppress interference and enhance system secrecy rates. Second, to maximize the CU secrecy rate, the paper proposes a parallel CNN-based resource allocation model that considers base station transmission power, RIS reflection coefficients, and D2D communication rate constraints, incorporating multi-scale residual modules in the convolutional layers of the model. Simulation results demonstrate that the proposed CNN-based resource allocation scheme significantly improves the secrecy rate of embedded system communications, ensuring secure multimedia computing, and outperforms traditional methods.

Abstract CD2-associated protein (CD2AP) is a scaffolding/adaptive protein that regulates intercellular adhesion and multiple signaling pathways. Although emerging evidence suggests that CD2AP is associated with several malignant tumors, there is no study investigating the expression and biological significance of CD2AP in glioblastoma multiforme (GBM). Here by studying public datasets, we found that CD2AP expression was significantly elevated in GBM and that glioma patients with increased CD2AP expression had a worse prognosis. We also confirmed the increase of CD2AP expression in clinical GBM samples and GBM cell lines. CD2AP overexpression in GBM cells promoted their proliferation, colony formation, migration, and invasion in vitro and their tumorigenesis in vivo, and reduced cell apoptosis both at basal levels and in response to temozolomide. While CD2AP knockdown had the opposite effects. Mechanistically, we revealed that CD2AP interacted with TRIM5, an NF-κB modulator. CD2AP overexpression and knockdown increased and decreased TRIM5 levels as well as the NF-κB activity, respectively. Moreover, downregulation of TRIM5 reversed elevated NF-κB activity in GBM cells with CD2AP overexpression; and inhibition of the NF-κB activity attenuated malignant features of GBM cells with CD2AP overexpression. Our findings demonstrate that CD2AP promotes GBM progression through activating TRIM5-mediated NF-κB signaling and that downregulation of CD2AP can attenuate GBM malignancy, suggesting that CD2AP may become a biomarker and the CD2AP-TRIM5-NF-κB axis may become a therapeutic target for GBM.

Using data from four waves of the National Postsecondary Student Aid Study (NPSAS) in 2004, 2008, 2012, and 2016, this study examines the effect of the PGIB on veterans' student loans. Results indicate that the PGIB has significantly affected veteran students' borrowing behavior, with an average $1,100 reduction in Stafford Loans. Veteran students attending for-profit institutions experience a larger loan decrease than their peers at public and private nonprofit institutions. In addition, loan reductions have occurred mainly at the extensive margin. The decrease in student loans is relatively small compared to the increase in veterans' education benefits under the PGIB, partly due to a rise in the cost of attendance after the implementation of the PGIB, driven by a higher proportion of veteran students attending for-profit institutions. Finally, loan reductions vary across veteran students.

ABSTRACT: Objectives: This study aimed to determine the genetic environment and characterize plasmid carrying a novel VIM-type β-lactamase (VIM-84) in a multidrug-resistant Pseudomonas monteilii (P. monteilii) isolate obtained from the human gut through whole-genome sequencing. Methods: DNA extraction of P. monteilii L2757hy was performed using the Genomic DNA Isolation Kit (QIAGEN, Hilden, Germany). Whole-genome sequencing was performed by Illumina NovaSeq 6000 and Oxford Nanopore platforms. The transferability of resistance genes was screened as single clonal on Mueller Hinton Agar (MHA) plates containing rifampicin and meropenem. Verification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI/TOF-MS) and polymerase chain reaction (PCR) with Pseudomonas aeruginosa PAO1Ri as the recipient strain. Results: L2757hy was identified as P. monteilii through sequencing and average nucleotide identity (ANI) analysis. The genome was assigned as ST147 and comprised a 6, 130, 057 bp chromosome with a GC content of 61.8% and a 49, 704 bp plasmid. Several resistance genes, including blaIMP-1, aac(6′)-IIa and tmexCD-toprJ, as well as virulence genes, such as iroN and wzaJ, were identified on the chromosome. A novel VIM-type blaVIM-84 was found on the plasmid, which was previously identified in Pseudomonas aeruginosa. Plasmid harboring blaVIM-84 was untypable, and it could be transferred to P. aeruginosa PAO1Ri and was associated with a class I integron with the genetic environment intI1-blaVIM-84-tniR-tniQ-tniB-tniA, likely derived from Tn402. Conclusions: Our study revealed that the novel blaVIM-84 gene was harbored by P. monteilii rather than P. aeruginosa. We suggested that P. monteilii may serve as a reservoir for resistance genes. © 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

Abstract In true triaxial compression tests, all three principal stresses are imposed independently. This allows for a more comprehensive analysis of the material's mechanical properties. The end effect in true triaxial compression tests is a crucial phenomenon that impacts the accuracy and reliability of the test results. In this study, a series of true triaxial compression tests is conducted to examine the influence of the end friction on the mechanical properties. The laboratory results show that the presence of the end friction could bring about an apparent increase in rock strength and also restrict the deformation in each direction showing that the stiffness (the slope of the curves) increased slightly. The rock strength σ 1 , peak could be enhanced from 24.7 % ( σ 2 = σ 3 ) to 90.7 % ( σ 2 = σ 1) when the end friction is increased, which is mainly caused by the lateral interface friction. The failure mode and fracture angle of the specimen are also influenced by the end effect, showing that under high friction conditions, the failure is more ductile, and a larger fracture angle is observed. At last, in comparison with the published experimental data, the actual specific friction angle 11 ° (corresponding friction coefficient is about 0.19) for the direct specimen–metal contacts in a true 3D test is numerically identified, which is empirically reasonable and higher than the tested range 0.146–0.157 obtained from double‐shear test system.

The sandstone reservoirs of the Cretaceous Bashijiqike Formation in the Yingmaili area on the southern slope of the Kuqa Depression within the Tarim Basin demonstrate favorable physical properties and considerable potential for oil and gas exploration. However, they are characterized by strong heterogeneity and unclear patterns of oil and gas distribution. In this study, the lithology and physical properties of the middle and deep reservoirs of the Bashijiqike Formation in the Yingmaili area were analyzed using core observation, a series of thin section analyses(standard, casting, cathodoluminescence, and inclusion thin sections), scanning electron microscopy(SEM), physical property testing, X-ray diffraction, and diagenesis reconstruction and physical property recovery techniques. It aims to explore the pore characteristics and preservation mechanisms, classify reservoir types, and clarify the distribution patterns and controlling factors of favorable reservoirs.The results show that the sandstone is mainly composed of feldspathic lithic sandstone and lithic feldspathic sandstone with low matrix content and medium maturity in both composition and structure. The primary pore type of the reservoir is residual primary pores, followed by secondary pores, including intergranular and intragranular dissolution pores, classifying the reservoir as a medium-to-high porosity and permeability type. The preservation of the primary pores in the middle and deep sandstones of the Bashijiqike Formation was mainly attributed to the depositional environment and subsequent diagenetic and reservoir evolution. The sandstone was initially formed in the microfacies of distributary channels at the front edge of a braided river delta with high hydrodynamics. The constantly overlapping channels formed thick and stable composite sand bodies. The strong hydrodynamics in the area led to high concentration and good sorting of sandstone clastic particles, providing the material basis for the formation of primary pores. The burial evolution process involved early long-term shallow burial and late-stage rapid deep burial, resulting in weak compaction transformation of the sandstone. Meanwhile, late-stage deep overpressure greatly enhanced the sand body's resistance to compaction, allowing for the preservation of residual primary pores. The continuously decreasing paleogeothermal gradient in the depression further contributed to the effective preservation of residual primary pores.

Abstract Sewage leakage, including uncollected, collected but exfiltrated, and collected but discharged with stormwater in combined sewer overflows, becomes a key challenge to clean water around the world. This study proposed a mass balance model to quantify sewage leakage and analyzed its influencing factors. Approximately 56% (53%–59%) of domestic total nitrogen loads in the Yangtze River basin of China leak out without treatment, two-thirds are exfiltrated or overflowed, significantly impacting receiving water quality. Cities with higher precipitation have greater leakage, indicating overflows are important. Pipe density has limited impact, showing higher importance of pipe quality over quantity. The per capita leakage rate first increases with city size and then decreases, showing the economies of scale. Yet uneven distribution of population and economy within megacities leads to greater leakage. Hence, separated sewage systems of rainwater and wastewater, regular maintenance and adapting centralized and decentralized systems are recommended, tailored to city-specific leakage characteristics.

Abstract Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis. Triglyceride accumulation in vascular endothelial cells differentially affects the abundance of free fatty acid species in the cytosol, leading to stimulated lipid droplet formation and suppressed protein S-palmitoylation. Reduced S-palmitoylation of ciliary proteins, including ADP ribosylation factor like GTPase 13B, results in the loss of cilia. Restoring palmitic acid availability, either through pharmacological inhibition of stearoyl-CoA desaturase 1 or a palmitic acid-enriched diet, significantly restores endothelial cilia and mitigates the progression of atherosclerosis. These findings thus uncover a previously unrecognized role of lipid droplets in regulating ciliary homeostasis and provide a feasible intervention strategy for preventing and treating atherosclerosis.

Abstract Objective There is growing evidence that simultaneous bilateral open wedge high tibial osteotomy(SBOWHTO) and simultaneous bilateral unicompartmental knee arthroplasty(SBUKA) is an effective surgical treatment for bilateral medial knee osteoarthritis (MKOA). However, which intervention is more beneficial for bilateral MKOA patients remains unknown. Therefore, the aim of this study was to compare the effectiveness of these two strategies through early clinical outcomes, complication rates, and prosthetic survival. Methods The clinical data of 60 patients with bilateral MKOA admitted to the Affiliated Hospital of Qingdao University from January 2018 to December 2022 were retrospectively analyzed, and they were divided into SBOWHTO group (n = 28) and SBUKA group (n = 32) according to different treatment methods. Clinical relevant indexes, Hospital for Special Surgery (HSS) score, Knee Society Knee (KSS) score, range of motion(ROM), postoperative complications and prosthetic survival rate were compared between the two groups. Results Patients in the SBOWHTO group were followed up for 27 to 50 months, with an average of (37.18 ± 6.84) months. Patients in the SBUKA group were followed up for 24 to 59 months, with an average of (39.38 ± 9.74) months. There were no significant differences in postoperative KSS, HSS and ROM between SBOWHTO group and SBUKA group (p > 0.05). There was no significant difference in complication rate between the two groups (p = 0.721). There was no significant difference in prosthetic survival rate (p = 0.622) and prosthetic survival curve (χ2 = 0.546, p = 0.46) between the two groups. Conclusions This study compared early clinical outcomes, complication rates, and prosthesis retention rates after SBOWHTO and SBUKA, and found that the early clinical benefits of SBOWHTO and SBUKA were comparable in patients with bilateral MKOA.

Mesembryanthemum cordifolium, a perennial plant with crassulacean acid metabolism (CAM) in the Aizoaceae family, has significant ornamental and medicinal values. In this study, we reported the first complete chloroplast genome sequence of this species. The total genome size was 153,734 bp in length, including a large single-copy (LSC) region of 85,692 bp, a small single-copy (SSC) region of 18,212 bp, and a pair of inverted repeat (IR) regions of 24,915 bp by each. The overall GC content of the M. cordifolium chloroplast genome was 37.08%. The genome encodes 131 genes, comprising 87 protein-coding genes (PCGs), 36 transfer RNA genes (tRNAs), and eight ribosomal RNA genes (rRNAs). Phylogenetic analysis shows this species was relatively close to M. crystallinum. This chloroplast genome sequence will be valuable for species discrimination and for understanding phylogenetic relationships within the genus Mesembryanthemum.

Objective: To study the relationship between umbilical cord blood vitamin A (VA) and neonatal lung diseases and explore the impact of umbilical cord blood VA on neonatal lung diseases. Method: Umbilical vein blood was collected at birth, and its VA content was measured. According to the VA levels in umbilical cord blood, a VA deficiency (VAD) group, a marginal deficiency group and a normal group were created and followed up until 28 days after birth. Results: The umbilical cord blood VA level in the neonatal group with lung disease was 0.13 ± 0.05 mg/L, while the result for the VA level in the non-lung disease group was 0.15 ± 0.05 mg/L. The umbilical cord blood VA levels in the neonatal lung disease group were significantly lower than those in the non-lung disease group. The incidence of neonatal pulmonary diseases was highest in the VAD group, and the incidence decreased as the level of VA in umbilical cord blood increased. Umbilical cord blood VAD and premature birth were found to be independent risk factors for neonatal respiratory disease. Conclusion: Umbilical cord blood VAD and premature birth are independent risk factors for neonatal pulmonary diseases. The lower the level of VA in umbilical cord blood, the more susceptible infants will be to neonatal respiratory infections in the neonatal period.

Abstract Aiming at the requirements of strong mobility and high flexibility of rescue and relief mobile pump trucks, this paper designs a new type of mobile pump truck frame based on existing mobile vehicle frame models. The materials used for the frame are 40Cr and Q235, and the finite element method is utilized to carry out static mechanical analysis and dynamic characteristic analysis. Simultaneously utilizing topology optimization and multi-objective genetic algorithm to optimize the design of the frame structure. The results show that the optimized pump truck frame can meet the strength design requirements of four typical working conditions: full load bending, full load torsion, emergency turning and emergency braking, while avoiding resonance phenomena caused by road surface and diesel engine vibration. Compared with the original frame model, the weight of the optimized frame is reduced by 87.88 kg, with a weight reduction rate of 10.89%, realizing the lightweight design requirements.

Most of the literature on reviewer assignment problem (RAP) considers fitness or efficiency as the evaluation criterion of an assignment, e.g., the degree of matching between reviewers and proposals. In this study, we consider fairness of an assignment and establish two multi-objective linear integer programming models for proposal assignment. We introduce a definition of fairness based on the closeness of social relationships between scholars. The closeness of social relationships is quantified based on social networks among reviewers and serves as part of objective functions. An improved space-partitioning algorithm is designed to solve the multi-objective models with integer objectives. When the problem size is large, two meta-heuristic algorithms are applied. Experiments on real and randomly generated cases are provided to illustrate the effectiveness of the proposed models and algorithms.

Abstract In the realm of reservoir development, the optimization of well placement constitutes a cornerstone challenge with significant implications that directly determine the recovery rate and economic benefits of oil and gas production. This research proposes a novel approach to optimizing well placement in reservoirs by integrating reservoir numerical simulations with intelligent optimization algorithms. The quintessence of this inquiry revolves around the strategic placing of wells amidst the complex geological fabric of reservoirs, where the objective function landscape often manifests with non-smooth, multimodal characteristics. To address those issues, the Weighted Mapping of Productivity Potential (WMPP) technique, fortified by the Simulated Annealing algorithm to judiciously ascertain specific weighting coefficients for the computation of WMPP across reservoirs is introduced in this study. Furthermore, an emblematic carbonate reservoir model serves to corroborate the adaptability and viability of WMPP for well placement optimization, underscoring its efficacy as a swift, economically viable instrument for the delineation of prospective reservoir zones and the guidance of drilling initiatives. The optimization results show that the well placement scheme guided by WMPP, which required 7 fewer wells than the oil initially in place (OOIP)-based scheme, improved 21.74% oil production over the twenty years production period. This comprehensive workflow proffers invaluable insights and benchmarks for the formulation of well placement strategies, with the proposed methodology, in its apparent simplicity, showcasing remarkable efficiency.

Abstract Increased fatty acid synthesis benefits glioblastoma malignancy. However, the coordinated regulation of cytosolic acetyl-CoA production, the exclusive substrate for fatty acid synthesis, remains unclear. Here, we show that proto-oncogene tyrosine kinase c-SRC is activated in glioblastoma and remodels cytosolic acetyl-CoA production for fatty acid synthesis. Firstly, acetate is an important substrate for fatty acid synthesis in glioblastoma. c-SRC phosphorylates acetyl-CoA synthetase ACSS2 at Tyr530 and Tyr562 to stimulate the conversion of acetate to acetyl-CoA in cytosol. Secondly, c-SRC inhibits citrate-derived acetyl-CoA synthesis by phosphorylating ATP-citrate lyase ACLY at Tyr682. ACLY phosphorylation shunts citrate to IDH1-catalyzed NADPH production to provide reducing equivalent for fatty acid synthesis. The c-SRC-unresponsive double-mutation of ACSS2 and ACLY significantly reduces fatty acid synthesis and hampers glioblastoma progression. In conclusion, this remodeling fulfills the dual needs of glioblastoma cells for both acetyl-CoA and NADPH in fatty acid synthesis and provides evidence for glioma treatment by c-SRC inhibition.

Abstract Twenty-four hours continuous intraocular pressure (IOP) monitoring is beneficial for glaucoma care. Contact lens sensors using LC technology can achieve non-invasive continuous IOP measuring around the clock and are relatively simple in principle and structure, thus dominating the mainstream. Among them, stretchable inductive LC contact lens sensors constructed with liquid metal have advantages in signal quality as well as wearing comfort, but currently its sensitivity is slightly insufficient. Here, we propose an LC sensor that constructed with liquid metal to form the stretchable inductance and capacitance further. The capacitive plate and inductive coil can response to IOP changes simultaneously, thus able to enhance the sensitivity in principle. We modeled the sensing mechanism and conducted design, fabrication, as well as various tests. The device exhibits good characteristics, including reliability, good signal quality, etc. Especially, it has a threefold increase in sensitivity, exceeding the current state-of-the-art contact lens sensors.

Abstract Introduction Anxiety and depression often co-occur in adolescents, with factors from family and school playing a significant role in the comorbidity. However, network analysis has not examined and clarified the detailed bridge and central symptoms of this comorbidity caused by online learning and perceived parental relationships across different COVID-19 times. Methods Over four months, 2,356 secondary school students completed the Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7. Participants were divided into harmonious and disharmonious groups based on their answers to a question about parental conflicts. Results The results indicated that adolescents perceiving more parental conflicts showed a denser comorbidity network after four months of online learning. Significant bridge symptoms decreased from three to two across two waves in the harmonious group, while in the disharmonious group, they increased from two to three. The number of central symptoms increased from one in wave 1 to three in wave 2 for the harmonious group, while four in wave 1 decreased to two in wave 2 for the disharmonious group. Furthermore, the CLPN analysis revealed that the strongest positive cross-lagged edge intensity between symptoms was anhedonia—energy in the harmonious group, with anhedonia being the most trigger symptom. In contrast, for the disharmonious group, guilt—suicide and trouble relaxing—excessive worry were the strongest cross-lagged edge, and trouble relaxing was the most trigger symptom. Conclusion These findings may have implications for interventions designed to promote adolescent mental health in the context of online learning and parental conflicts.

Abstract In this work, the impact of physicochemical modifications on pharmacokinetics and in vivo targeting of a small molecule fibroblast activation protein inhibitor (FAPI) imaging ligand in a murine model of rheumatoid arthritis was evaluated. While similar ligands have been well-reported in oncology for molecular imaging and radiotherapy, there are limited reports of FAPI derivatives in targeted applications in immunology. As inflammation may increase both specific and non-specific delivery of targeted agents in general, we sought to identify the optimal targeted molecular imaging probe characteristics for efficient cell surface engagement. A series of FAPI derivatives were synthesized and their physicochemical properties modified via conjugation of fluorescent dyes and/or an albumin-binding small molecule. The impact of these modifications on cell surface binding affinity was assessed using an overexpressing cell line. Additionally, a thorough mechanistic characterization of fibroblast activation protein (FAP) cell surface internalization was evaluated in both overexpressing and endogenously expressing cells. Lastly, the pharmacokinetics and in vivo uptake in inflamed arthritic paws were characterized via near-infrared (NIR) imaging. All targeted molecular imaging agents tested maintained strong nanomolar binding affinity to cell surface FAP independent of chemical modification. The murine fibroblast-like synoviocytes expressed lower absolute cell-surface FAP compared to a transfected line, and the net internalization half-life measured for the transfected cells via flow cytometry was 7.2 h. The unmodified FAPI ligand exhibited the poorest in vivo targeting, likely resulting from its large apparent volume of distribution (62.7 ml) and rapid systemic clearance (t 1/2 = 0.5 h). Conjugation of a charged, hydrophilic AF647 fluorophore decreased systemic clearance (t 1/2 = 2.1 h) and demonstrated a 2-fold improvement in blocking FAPI-800CW engagement of FAP in vivo when compared to blocking of FAPI-800CW with FAPI with up to 2.8-fold improvements noted for the equivalent albumin binding construct comparison.

Healthcare service needs, as the cornerstone of the existence and development of the healthcare service system, if misunderstood or "distorted", will lead to limitations in the interpretation of demand-side behavior and affect the effectiveness of supply-side construction direction and resource allocation. In response to this, based on the analysis of the concept of needs in different disciplines and combining the characteristics of healthcare service providers and users in China, this paper defines the basic connotation and core characteristics of healthcare service needs. By analyzing the ways and results of the influence of factors in the new era on residents′ health service needs, the structural variables of health service needs are derived. On this basis, a "source-structure" theoretical model of Chinese residents′ healthcare service needs is further refined and summarized. For service users, this model reveals the logic and steps behind the demand behavior and the focus of analysis. For service providers, this model can provide theoretical guidance for clarifying functional positioning among different units, optimizing resource allocation, and defining development paths, as well as serve as a reference for improving service capabilities, adjusting service structures, and improving management processes.