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Abstract Jujube (Ziziphus jujuba Mill.) is a valuable tree species with economic, edible, medicinal, and ecological conservation benefits. In this study, we used PacBio HiFi sequencing and Hi-C technology to assemble chromosome-level genomes of two cultivated Jujubes, namely ‘Lingwuchangzao’ and ‘Shiguang’. The genome sizes of ‘Lingwuchangzao’ and ‘Shiguang’ were 385.66 Mb and 394.12 Mb, respectively, with contig N50 sizes of 30.62 Mb and 4.30 Mb. These genomes contained 31,082 and 31,015 protein-coding genes, with repeat element contents of 42.11% and 42.33%, respectively. Phylogenetic analysis revealed that ‘Lingwuchangzao’ was sister to ‘Shiguang’ and followed by ‘Dongzao’. Additionally, comparative analysis of gene families among ‘Lingwuchangzao’, ‘Shiguang’, ‘Dongzao’, ‘Junzao’, and ‘Suanzao’ identified 15,988 (57.98%) core gene families, 11,191 (40.59%) disposable gene families, and 394 (1.43%) private gene families. Overall, the assembly of the genomes of these two cultivated Jujube varieties provides valuable genetic information for Jujube evolution, functional genomics research, and molecular breeding.

Abstract Background Over the years, with the improvement of diagnostic and therapeutic capabilities for hip joint diseases and the advancements in surgical technology, hip arthroscopy has been extensively used. At present, there is ongoing controversy among scholars about whether it is necessary to close the joint capsule after hip arthroscopy. In addition, the clinical effect of repairing the hip joint capsule after hip arthroscopy remains uncertain. Purpose To evaluate the effect of our modified shoelace suture technique on postoperative hip function and to investigate whether complete closure of the hip capsule is reliable and safe. Study Design Retrospective study; Levels of evidence: III. Methods A retrospective review was conducted on patients undergoing hip arthroscopy by a solitary high-volume hip arthroscopic surgeon. The patients were categorized into two groups. The first group consisted of patients who underwent the modified shoelace continuous capsular closure technique. The other group consisted of those who did not receive capsular closure after hip arthroscopy. Patient-reported outcomes including modified Harris Hip Score (mHHS), Hip Outcome Score of Activities of Daily Living (HOS-ADL), Hip Outcome Score Sport-Specific Subscale (HOS-SSS), and visual analogue scale (VAS) were obtained at a minimum of 12 months. Any complications during follow-up were identified and recorded. Results A total of 100 patients were followed up for 12–15 months, with an average of (12.3 ± 5.3) months in the study. There were 50 patients in the shoelace capsular closure group (CC group) and 50 patients in the non-capsular closure group (NC group). The surgical time in the suture group was significantly longer than that in the non-suture group. However, there was no statistically significant disparity in the length of hospital stay between the two groups. The mHHS, HOS-SSS, HOS-ADL, and VAS of the CC and NC group were significantly improved compared to preoperative scores at 6 and 12 postoperative months (P

Purpose: Explore the causal relationship between the gut microbiota and erectile dysfunction (ED) at phylum, class, order, family, and genus levels, and identify specific pathogenic bacteria that may be associated with the onset and progression of ED. Materials and Methods: The genetic variation data of 196 human gut microbiota incorporated in our study came from the human gut microbiome Genome Wide Association Studies (GWAS) dataset released by the MiBioGen Consortium. The GWAS statistics for ED were extracted from one study by Bovijn et al., which included 223,805 participants of European ancestry, of whom 6,175 were diagnosed with ED. Subsequently, Mendelian randomization (MR) analysis was carried out to explore whether a causal relationship exists between the gut microbiota and ED. Additionally, bidirectional MR analysis was performed to examine the directionality of the causal relationship. Results: Through MR analysis, we found that family Lachnospiraceae (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.05–1.52, p=0.01) and its subclass genus LachnospiraceaeNC2004 group (OR: 1.17, 95% CI: 1.01–1.37, p=0.04) are associated with a higher risk of ED. In addition, genus Oscillibacter (OR: 1.17, 95% CI: 1.02–1.35, p=0.03), genus Senegalimassilia (OR: 1.32, 95% CI: 1.06–1.64, p=0.01) and genus Tyzzerella3 (OR: 1.14, 95% CI: 1.02–1.27, p=0.02) also increase the risk of ED. In contrast, the inverse variance weighted estimate of genus RuminococcaceaeUCG013 (OR: 0.77, 95% CI: 0.61–0.96, p=0.02) suggests that it has a protective effect against the occurrence of ED. Conclusions: This study preliminarily identified 6 bacterial taxa that may have a causal relationship with ED, including family Lachnospiraceae, genus Lachnospiraceae NC2004 group, Oscillibacter, Senegalimassilia, Tyzzerella 3 and Ruminococcaceae UCG013. These identified important bacterial taxa may serve as candidates for microbiome intervention in future ED clinical trials.

We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia (iNOA). We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction. The Chi-square test and Mann–Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons. A logistic regression analysis was conducted to identify predictors of retrieval failure. Area under the receiver operating characteristic curve for each variable was evaluated, and the net clinical benefit was calculated using a clinical decision curve. Patients with iNOA had a lower sperm retrieval rate than those with known causes. Moreover, testicular volume was an independent factor affecting sperm extraction outcomes (odds ratio = 0.79, P < 0.05). The testicular volume cut-off value was 6.5 ml (area under the curve: 0.694). The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed. The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution. There was also a significant association between a uniform tubule distribution and testicular volume. In conclusion, a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.

The cause of asthenozoospermia (AZS) is not well understood because of its complexity and heterogeneity. Although some gene mutations have been identified as contributing factors, they are only responsible for a small number of cases. Radial spokes (RSs) are critical for adenosine triphosphate-driven flagellar beating and axoneme stability, which is essential for flagellum motility. In this study, we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23 (LRRC23; c.1018C>T: p.Q340X and c.881_897 Del: p.R295Gfs*32) in a proband from a nonconsanguineous family with AZS and male infertility. Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology. Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella. Additionally, transmission electron microscopy showed the absence of RS3 in sperm flagella, which disrupts stability of the radial spoke complex and impairs motility. Following in vitro fertilization and embryo transfer, the proband’s spouse achieved successful pregnancy and delivered a healthy baby. In conclusion, our study indicates that two novel mutations in LRRC23 are associated with AZS, but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%–46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: −2.70; 95% CI: −3.94–−1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.

Abstract Background To estimate vaccine effectiveness(VE) against COVID-19-related hospitalization for inactivated vaccines during the Omicron BF.7-predominant epidemic wave in Beijing, China. Methods We recruited a cohort in Beijing on 17 and 18 December 2022, collected status of vaccination and COVID-19-related hospitalization since 1 November 2022 and prospectively followed until 9 January 2023. A Poisson regression model was used to estimate the VE. Results 16(1.15%) COVID-19-related hospitalizations were reported in 1391 unvaccinated participants; 7(0.25%) in 2765 participants with two doses, resulting in a VE of 70.89%(95% confidence interval[CI] 26.25 to 87.73); 32(0.27%) in 11,846 participants with three doses, with a VE of 65.25%(95% CI 32.24 to 81.83). The VE of three doses remained above 64% at 1 year or more since the last dose. Elderly people aged ≥ 60 years had the highest hospitalization incidence(0.66%), VE for two doses was 74.11%(95%CI: − 18.42 to 94.34) and VE for three doses was 80.98%(95%CI:52.83 to 92.33). We estimated that vaccination had averted 65,007(95%CI: 12,817 to 97,757) COVID-19-related hospitalizations among people aged ≥ 60 years during the BF.7-predominant period in Beijing. Conclusion Inactivated COVID-19 vaccines were effective against COVID-19-related hospitalization, especially for the elderly population who have increased risk of severe disease owing to SARS-CoV-2 infection.

Abstract This paper explores the application of computer vision and mathematical modeling to analyze the intricate movements involved in weaving a traditional farming tool, the winnowing basket. By utilizing OpenPose algorithms, the study simplifies and visualizes the craftsmen's motions, particularly focusing on wrist movements. Video data of craftsmen in Chiba, Japan, creating Kizumi (place name) winnowing baskets is used as the basis for analysis. The extracted information is used to generate 2D motion trajectories of the wrist, allowing a comparison between beginners who watched parsed videos and those who watched the original videos in terms of skill acquisition and learning time. By visualizing human body behavior and combining statistical results, this study demonstrates the potential of artificial intelligence techniques such as computer vision for observing repetitive human movement and inheriting traditional skills.

Abstract Background Aim to validate the diagnostic efficacy of radiomics models for predicting various degrees of cognitive impairment in patients with cerebral small vessel disease (CSVD). Methods Participants were divided into mild cognitive impairment group (mild-CSVD group) and sever cognitive impairment group (sever-CSVD group) according to Montreal Cognitive Assessment (MoCA) performance, 98 gender-age-education matched subjects served as normal controls. Radiomic features were extracted from the segmented hippocampus using PyRadiomics. The feature preprocessing involved replacing missing values with the mean, applying stratified random sampling to allocate subjects into training (80%) and testing (20%) sets, ensuring balance among the three classes (normal controls, mild-CSVD group, and sever-CSVD group). A feature selection method was applied to identify discriminative radiomic features, with the optimal texture feature chosen for developing diagnostic models. Performance was evaluated in both the training and testing sets using receiver operating characteristic (ROC) curve analysis. Results The radiomics model achieved an accuracy of 0.625, an AUC of 0.593, a sensitivity of 0.828, and a specificity of 0.316 in distinguishing mild-CSVD group from normal controls. When distinguishing mild-CSVD group from sever-CSVD group, the radiomics model reached an accuracy of 0.683, an AUC of 0.660, a sensitivity of 0.167, and a specificity of 0.897. Similarly, in distinguishing sever-CSVD group from normal controls, the radiomics model exhibited an accuracy of 0.781, an AUC of 0.818, a sensitivity of 0.538, and a specificity of 0.947. Conclusion Radiomics model based on hippocampal texture had disparities in the diagnostic efficacy of radiomics models in predicting various degrees of cognitive impairment in patients with CSVD.

Previous works employ the Large Language Model (LLM) like GPT-3 for knowledge-based Visual Question Answering (VQA). We argue that the inferential capacity of LLM can be enhanced through knowledge injection. Although methods that utilize knowledge graphs to enhance LLM have been explored in various tasks, they may have some limitations, such as the possibility of not being able to retrieve the required knowledge. In this paper, we introduce a novel framework for knowledge-based VQA titled “Prompting Large Language Models with Knowledge-Injection” (PLLMKI). We use vanilla VQA model to inspire the LLM and further enhance the LLM with knowledge injection. Unlike earlier approaches, we adopt the LLM for knowledge enhancement instead of relying on knowledge graphs. Furthermore, we leverage open LLMs, incurring no additional costs. In comparison to existing baselines, our approach exhibits the accuracy improvement of over 1.3 and 1.7 on two knowledge-based VQA datasets, namely OK-VQA and A-OKVQA, respectively.

To further optimize the automotive AEB-P (autonomous emergency braking for pedestrian) control algorithm, an AEB-P hierarchical control strategy that integrates driving comfort and pedestrian injury risk was proposed. A braking safety distance model considering the driver′s comfort during braking was designed for the AEB-P evaluation standard of C-NCAP. The weight coefficient adjustment strategy was obtained by introducing fuzzy rules to comprehensively consider the risk of pedestrian injury and scenario working conditions. Based on this, the adaptive weight coefficient MPC (model predictive control) upper controller was designed, and the PID (proportion integration differentiation) lower controller was used to correct the actual deceleration of the auto-vehicle. The vehicle longitudinal dynamics model was established and the test scenario and control algorithm were constructed through CarSim and Matlab/Simulink, then the proposed method and the fixed TTC (time to collision) threshold algorithm were compared through hardware-in-the-loop experiments. The results show that the proposed control algorithm can effectively avoid collision in 93.4% of the test conditions, while the fixed TTC threshold algorithm has a successful rate of only 43.75% in obstacle avoidance. Compared with the traditional control strategy, the proposed method can maintain a more stable minimum distance between the vehicle and the pedestrian in front of it, with better robustness, which provides a reference basis for the AEB-P control theory.

BackgroundAs a key to economic and social development, occupational groups with low levels of occupational health literacy (OHL) are considered vulnerable groups with high risks of work-related diseases and injuries. Therefore, improving the OHL of these groups is of great significance in reducing the burden on public health. ObjectiveTo master the four dimensional OHL levels and influencing factors of the key groups in Fuling District, Chongqing, and provide a basis for formulating health education programs for occupational groups in the future. MethodsThe Occupational Health Literacy Questionnaire of Key Populations was distributed online to investigate the key occupational groups in Fuling District through stratified cluster sampling. The survey collected data on basic demographic information, legal knowledge of occupational health, basic knowledge of occupational health protection, basic skills of occupational health protection, and healthy working style and behavior. Univariate analysis, logistic regression, and nomogram were used to analyze the above data. ResultsThis survey distributed 4824 questionnaires, of which 4677 were valid, with a recovery rate of 97.0%. The dimensional OHL levels of key occupational groups in Fuling District from high to low were: healthy working style and behavior (79.1%), basic knowledge of occupational health protection (78.4%), legal knowledge of occupational health protection (43.3%), and basic skills of occupational health protection (37.6%). The results of logistic regression showed that the occupational health legal knowledge levels in the groups of high school/vocational high school/technical secondary school and above (reference: primary school and below) (OR=1.47, 95%CI: 1.05, 2.05), ≥3000 yuan of monthly income (reference:

ObjectivesA new Spar-type floating wind turbine platform design scheme is proposed for a 15 MW floating wind turbine, and its performance is analyzed. MethodsBased on potential flow theory, the frequency domain hydrodynamic calculation of the platform is carried out and the wave loads and motion response characteristics of the platform under different wave directions are analyzed. The blade element momentum method is applied to calculate the aerodynamic load of the impeller and make it equivalent to the wind coefficient in order to calculate the time-domain response of the platform under the combined effect of wind, waves and currents under different working conditions, while also analyzing the force situation of the mooring lines. ResultsThe results show that the heave, roll, and pitch of the platform have peak points at the natural frequency of its motion, and the positions of occurrence are all far from the main energy region of the waves. Under the action of wind, waves and currents, compared to the working conditions, the maximum pitch angle of the platform under extreme conditions is smaller, but the amplitude of maximum surge, heave and mooring tension are greater than the working conditions. ConclusionsThe newly designed Spar-type floating wind turbine platform has good stability and hydrodynamic performance. Under the designed environmental loads, its response and mooring force can meet the requirements of the specifications, ensuring the safety and stability of the wind turbine.

【Objective】Aiming at the limited transmission distance of ultra-long distance optical transmission system using remote pump technology, this paper proposes a single span repeaterless transmission system with mixed transmission of 100 and 200 Gbit/s service. The experiment tests the maximum span loss of the system by adjusting the input power of the system and the position of the remote pump gain unit in the system without considering the influence of other factors such as dispersion.【Methods】The key amplification technologies in the experiment mainly include remote pump amplification technology, Erbium-doped optical fiber amplification technology and Raman amplification technology. In the transmission, Erbium-doped optical fiber amplifier, Raman amplifier and remote pump gain unit are used to carry out non-relay amplification of optical signals in the system, and the relay transmission distance is further improved by adjusting the position of remote pump gain unit. The remote pump bypass access method which can improve the amplification gain of remote pump is used in the experiment.【Results】Three different modules were used in the experiment, with a total of 9 service waves. The modulation formats of 200 Gbit/s Polarization Multiplexed - Quadrature Phase Shift Keying (PM-QPSK), 100 Gbit/s PM-QPSK and 200 Gbit/s Polarization Multiplexed -16 Quadrature Amplitude Modulation (PM-16QAM) were used respectively. The transmission experiments were constructed by G. 654b ultra-low loss optical fiber with a loss of 0.17 dB/km. Finally, the single-span ultra-long distance transmission with a total capacity of 1.5 Tbit/s and a cross-segment loss of 75 dB is realized.【Conclusion】The results show that the transmission distance of the system can be improved by setting the optimal fiber input power and adjusting the position of the gain unit of the remote pump. The experimental results provide reference value for the construction of the ultra-long distance optical transmission system based on the remote pump technology, and provide reference data for the development of the repeaterless transmission based on the remote pump technology.

Neural network pruning is a popular approach to reducing the computational complexity of deep neural networks. In recent years, as growing evidence shows that conventional network pruning methods employ inappropriate proxy metrics, and as new types of hardware become increasingly available, hardware-aware network pruning that incorporates hardware characteristics in the loop of network pruning has gained growing attention. Both network accuracy and hardware efficiency (latency, memory consumption, etc.) are critical objectives to the success of network pruning, but the conflict between the multiple objectives makes it impossible to find a single optimal solution. Previous studies mostly convert the hardware-aware network pruning to optimization problems with a single objective. In this paper, we propose to solve the hardware-aware network pruning problem with Multi-Objective Evolutionary Algorithms (MOEAs). Specifically, we formulate the problem as a multi-objective optimization problem, and propose a novel memetic MOEA, namely HAMP, that combines an efficient portfolio-based selection and a surrogate-assisted local search, to solve it. Empirical studies demonstrate the potential of MOEAs in providing simultaneously a set of alternative solutions and the superiority of HAMP compared to the state-of-the-art hardware-aware network pruning method.

Abstract While many countries employed digital contact tracing to contain the spread of SARS-CoV-2, the contribution of cospace-time interaction (i.e., individuals who shared the same space and time) to transmission and to super-spreading in the real world has seldom been systematically studied due to the lack of systematic sampling and testing of contacts. To address this issue, we utilized data from 2230 cases and 220,878 contacts with detailed epidemiological information during the Omicron outbreak in Beijing in 2022. We observed that contact number per day of tracing for individuals in dwelling, workplace, cospace-time interactions, and community settings could be described by gamma distribution with distinct parameters. Our findings revealed that 38% of traced transmissions occurred through cospace-time interactions whilst control measures were in place. However, using a mathematical model to incorporate contacts in different locations, we found that without control measures, cospace-time interactions contributed to only 11% (95%CI: 10%–12%) of transmissions and the super-spreading risk for this setting was 4% (95%CI: 3%–5%), both the lowest among all settings studied. These results suggest that public health measures should be optimized to achieve a balance between the benefits of digital contact tracing for cospace-time interactions and the challenges posed by contact tracing within the same setting.

Excessive fructose diet is closely associated with colorectal cancer (CRC) progression. Nevertheless, fructose's specific function and precise mechanism in colorectal cancer liver metastasis (CRLM) is rarely known. Here, this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM, and the expression of KHK-A, not KHK-C, in liver metastasis was higher than in paired primary tumors. Furthermore, KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at Ser37. PKM2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of PKM2. EMT and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells' migration ability and anoikis resistance during CRLM progression. TEPP-46 treatment, targeting the phosphorylation of PKM2, inhibited the pro-metastatic effect of KHK-A. Besides, c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A, forming a positive feedback loop.

Purpose: The present study aimed to analyze the influence of muscle activation on lumbar injury under a specific +Gz load. Methods: A hybrid finite element human body model with detailed lumbar anatomy and lumbar muscle activation capabilities was developed. Using the specific +Gz loading acceleration as input, the kinematic and biomechanical responses of the occupant's lower back were studied for both activated and deactivated states of the lumbar muscles. Results: The results indicated that activating the major lumbar muscles enhanced the stability of the occupant's torso, which delayed the contact between the occupant's head and the headrest. Lumbar muscle activation led to higher strain and stress output in the lumbar spine under +Gz load, such as the maximum Von Mises stress of the vertebrae and intervertebral discs increased by 177.9% and 161.8%, respectively, and the damage response index increased by 84.5%. Conclusion: In both simulations, the occupant's risk of lumbar injury does not exceed 10% probability. Therefore, the activation of muscles could provide good protection for maintaining the lumbar spine and reduce the effect of acceleration in vehicle travel direction.

Aims: In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method. Methods: We retrospectively collected CT imaging data of 108 hips with non-traumatic osteonecrosis of the femoral head from 76 consecutive patients (mean age 34.3 years (SD 8.1), 56.58% male (n = 43)) in two clinical centres. The femoral head was divided into 288 standard units (based on the orientation of units within the femoral head, designated as N[Superior], S[Inferior], E[Anterior], and W[Posterior]) using a new measurement system called the longitude and latitude division system (LLDS). A computer-aided design (CAD) measurement tool was also developed to visualize the measurement of the spatial location of necrotic lesions in CT images. Two orthopaedic surgeons independently performed measurements, and the results were used to draw 2D and 3D heat maps of spatial distribution of necrotic lesions in the femoral head, and for statistical analysis. Results: The results showed that the LLDS has high inter-rater reliability. As illustrated by the heat map, the distribution of Japanese Investigation Committee (JIC) classification type C necrotic lesions exhibited clustering characteristics, with the lesions being concentrated in the northern and eastern regions, forming a hot zone (90% probability) centred on the N4-N6E2, N3-N6E units of outer ring blocks. Statistical results showed that the distribution difference between type C2 and type C1 was most significant in the E1 and E2 units and, combined with the heat map, indicated that the spatial distribution differences at N3-N6E1 and N1-N3E2 units are crucial in understanding type C1 and C2 necrotic lesions. Conclusion: The LLDS can be used to accurately measure the spatial location of necrotic lesions and display their distribution characteristics. Cite this article: Bone Joint Res 2024;13(6):294–305.

Abstract Background Extracorporeal membrane oxygenation (ECMO) is increasingly being used for critically ill patients with cardiopulmonary failure. Air in the ECMO circuit is an emergency, a rare but fatal complication. Case presentation We introduce a case of a 76-year-old female who suffered from cardiac arrest complicated with severe trauma and was administered veno-arterial extracorporeal membrane oxygenation. In managing the patient with ECMO, air entered the ECMO circuit, which had not come out nor was folded or broken. Although the ECMO flow was quickly re-established, the patient died 6 h after initiating ECMO therapy. Conclusions In this case report, the reason for the complication is drainage insufficiency. This phenomenon is similar to decompression sickness. Understanding this complication is very helpful for educating the ECMO team for preventing this rare but devastating complication of fatal decompression sickness in patients on ECMO.

Abstract Regulating cardiolipin to maintain mitochondrial homeostasis is a promising strategy for addressing Parkinson's disease (PD). Through a comprehensive screening and validation process involving multiple models, ginsenoside Rg3 (Rg3) as a compound capable of enhancing cardiolipin levels is identified. This augmentation in cardiolipin levels fosters mitochondrial homeostasis by bolstering mitochondrial unfolded protein response, promoting mitophagy, and enhancing mitochondrial oxidative phosphorylation. Consequently, this cascade enhances the survival of tyrosine hydroxylase positive (TH+) dopaminergic neurons, leading to an amelioration in motor performance within PD mouse models. Using limited proteolysis–small‐molecule mapping combined with molecular docking analysis, it has confirmed Growth Factor Receptor‐Bound Protein 2 (GRB2) as a molecular target for Rg3. Furthermore, these investigations reveal that Rg3 facilitates the interaction between GRB2 and TRKA (Neurotrophic Tyrosine Kinase, Receptor, Type 1), thus promotes EVI1 (Ecotropic Virus Integration Site 1 Protein Homolog) phosphorylation by ERK, subsequently increases CRLS1 (Cardiolipin Synthase 1) gene expression and boosts cardiolipin synthesis. The absence of GRB2 or CRLS1 significantly attenuates the beneficial effects of Rg3 on PD symptoms. Finally, Tenofovir Disoproxil Fumarate (TDF) that also promotes the binding between GRB2 and TRKA is further identified. The identified compounds, Rg3 and TDF, exhibit promising potential for the prevention of PD by bolstering cardiolipin expression and reinstating mitochondrial homeostasis.

Significant progress has recently been made in deep and ultra-deep oil and gas exploration globally, demonstrating enormous exploration potential of the deep and ultra-deep strata. However, the accumulation and preservation pattern of deep and ultra-deep oil and gas remains poorly understood, greatly impeding further petroleum exploration and development in the deep and ultra-deep strata. By taking the Bozi deep and ultra-deep condensate gas reservoirs in the Kuqa Depression, western China as an example, we attempt to reconstruct the hydrocarbon charge history in such deep reservoirs via an integrated investigation involving quantitative grain fluorescence, fluid inclusion petrography and microthermometry, micro-fluorescence spectroscopy, laser Raman spectroscopy, PVTx modelling, and basin modelling. The results show that: (1) The Bozi deep and ultra-deep reservoirs contain one group of gas inclusion assemblage, and two groups of oil inclusion assemblages, with one being characterized by near yellowish-whitish and blue-whitish diphasic or triphasic oil inclusions, and the other being featured by bright blue diphasic oil inclusions; (2) The first oil charge occurred during the Early Neogene (6.5–5.5 Ma), and the second oil charge occurred during the Late Neogene (4.4–3.5 Ma), under normal hydrostatic pressure or slightly weak overpressure; and (3) The gas charge occurred during the Pleistocene (∼1.6 Ma), with a corresponding reservoir pressure coefficient of approximately 1.7, transforming the reservoir fluid phase state from black oil or volatile oil to condensate gas. Our findings highlight that aside from the present burial depth, a favorable burial history model is crucial for the preservation of liquid hydrocarbons in deep and ultra-deep reservoirs. The occurrence of liquid hydrocarbons in the Bozi deep and ultra-deep condensate gas reservoirs with depths over 7,000 m is benefited from a prolonged period (>100 Ma) of shallow burial and a late-stage (since 10 Ma) rapid subsidence.

BackgroundIn recent years, studies have confirmed the predictive capability of spectral computer tomography (CT) in determining microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Discrepancies in the predicted MVI values between conventional CT imaging features and spectral CT parameters necessitate additional validation.MethodsIn this retrospective study, 105 cases of small HCC were reviewed, and participants were divided into MVI-negative (n=53, Male:48 (90.57%); mean age, 59.40 ± 11.79 years) and MVI-positive (n=52, Male:50(96.15%); mean age, 58.74 ± 9.21 years) groups using pathological results. Imaging features and iodine density (ID) obtained from three-phase enhancement spectral CT scans were gathered from all participants. The study evaluated differences in imaging features and ID values of HCC between two groups, assessing their diagnostic accuracy in predicting MVI occurrence in HCC patients. Furthermore, the diagnostic efficacy of imaging features and ID in predicting MVI was compared.ResultsSignificant differences were noted in the presence of mosaic architecture, nodule-in-nodule architecture, and corona enhancement between the groups, all with p-values < 0.001. There were also notable disparities in IDs between the two groups across the arterial phase, portal phase, and delayed phases, all with p-values < 0.001. The imaging features of nodule-in-nodule architecture, corona enhancement, and nonsmooth tumor margin demonstrate significant diagnostic efficacy, with area under the curve (AUC) of 0.761, 0.742, and 0.752, respectively. In spectral CT analysis, the arterial, portal, and delayed phase IDs exhibit remarkable diagnostic accuracy in detecting MVI, with AUCs of 0.821, 0.832, and 0.802, respectively. Furthermore, the combined models of imaging features, ID, and imaging features with ID reveal substantial predictive capabilities, with AUCs of 0.846, 0.872, and 0.904, respectively. DeLong test results indicated no statistically significant differences between imaging features and IDs.ConclusionsSubstantial differences were noted in imaging features and ID between the MVI-negative and MVI-positive groups in this study. The ID and imaging features exhibited a robust diagnostic precision in predicting MVI. Additionally, our results suggest that both imaging features and ID showed similar predictive efficacy for MVI.

To efficiently develop hot dry rock and other geothermal energy, a multilateral butted closed loop geothermal system (MBCLGS) is presented in this paper to replace the U-shaped closed-loop geothermal system (UCLGS). Besides, a casing-cement-formation transient heat transfer model is established to investigate the influences of key factors on the heat production of MBCLGS. After thermal-fluid-structural coupling analysis, we can find that higher injected rate and lower fluid temperature can improve heat power but reduce output temperature. In addition, the output temperature and heat power do not increase continuously with the increasing of branch well number. There is an optimal value of branch well number. Longer well pair distance can improve both output temperature and heat power. Considering the drilling technology level and design purpose, the recommended injected flow rate of MBCLGS is 90 m3/h, the injected fluid temperature is 42.5 °C, the number of branch wells is 10 and the well pair distance is 200m. Finally, by comparing MBCLGS and UCLGS, it is found that MBCLGS has a lower temperature decline rate and higher output temperature than UCLGS under the same conditions. It works more stable and has better economy. Overall, the proposal of MBCLGS is expected to promote the efficient development of deep geothermal resources.

The universal contamination of arable land with potentially toxic elements (PTEs) poses a severe threat to food security and jeopardizes worldwide efforts to meet the United Nations Sustainable Development Goals (SDGs). How to obtain more reliable concentrations of PTEs in regional agricultural soils is a priority problem to be solved. Multispectral satellite remote sensing, with its advantages of high spatial and temporal resolution, broad coverage, and low cost, offers the potential to acquire spatial distribution of PTEs in agricultural soils over large areas. However, owing to the complexity of soil environments and the insufficiency of spectral information, the mechanism for retrieving concentrations of PTEs in agricultural soils via multispectral satellites is not yet clear, and the accuracy needs to be improved. In this study, we aimed to assess whether employing a fusion of spectral information and environmental covariates, results in more accurate retrievals of PTEs, specifically chromium (Cr) and mercury (Hg), in croplands than does employing spectral information alone. Three machine learning algorithms—kernel-based support vector machine (SVM), neural network-based back propagation neural network (BPNN), and tree-based extreme gradient boosting (XGBoost)—were developed to retrieve Cr and Hg concentrations in agricultural soils. The results showed that the fusion of spectral information and environmental covariates combined with the XGBoost model performed best in retrieving both Cr and Hg concentrations in agricultural soils with coefficient of determination (R2) values of 0.73 and 0.74, respectively. Environmental covariates were important variables for determining Cr and Hg concentrations in agricultural soils, but the ability to retrieve these element concentrations by utilizing spectral information alone was limited. High Cr concentrations occurred in central towns and southern hilly mountains. High Hg concentrations were detected in the northwestern region and southern hilly mountains. The potential of fusing spectral information and environmental covariates to precisely retrieve PTE concentrations in agricultural soils can serve as a reference for agricultural soil health information monitoring worldwide.

Abstract In situ cancer vaccination is an attractive strategy that stimulates protective antitumor immunity. Cytotoxic T lymphocytes (CTLs) are major mediators of the adaptive immune defenses, with critical roles in antitumor immune response and establishing immune memory, and are consequently extremely important for in situ vaccines to generate systemic and lasting antitumor efficacy. However, the dense extracellular matrix and hypoxia in solid tumors severely impede the infiltration and function of CTLs, ultimately compromising the efficacy of in situ cancer vaccines. To address this issue, a robust in situ cancer vaccine, Au@MnO2 nanoparticles (AMOPs), based on a gold nanoparticle core coated with a manganese dioxide shell is developed. The AMOPs modulated the unfavorable tumor microenvironment (TME) to restore CTLs infiltration and function and efficiently induced immunogenic cell death. The Mn2+‐mediated stimulator of the interferon genes pathway can be activated to further augment the therapeutic efficacy of the AMOPs. Thus, the AMOPs vaccine successfully elicited long‐lasting antitumor immunity to considerably inhibit primary, recurrent, and metastatic tumors. This study not only highlights the importance of revitalizing CTLs efficacy against solid tumors but also makes progress toward overcoming TME barriers for sustained antitumor immunity.

Abstract Background The COVID-19 pandemic has prompted a rapid shift to online teaching, placing unprecedented demands on educators’ physical and mental well-being. However, the relationship between English as a Foreign Language (EFL) teachers’ physical activity, emotion regulation, and competence for online teaching remains underexplored. Objectives This study aimed to investigate the interplay between EFL teachers’ physical activity, emotion regulation strategies, and competence for online teaching. Results Structural equation modeling revealed significant direct and indirect effects, indicating that physical activity positively influences emotion regulation, which, in turn, enhances teachers’ competence for online instruction. Furthermore, emotion regulation was found to mediate the relationship between physical activity and online teaching competence. Conclusions These findings underscore the importance of promoting physical activity among EFL teachers as a means to enhance their emotion regulation skills and competence for online teaching, particularly in the context of the COVID-19 pandemic. Implications The study highlights the need for targeted interventions aimed at supporting EFL teachers’ well-being and professional development, with implications for educational policies, teacher training programs, and institutional support structures in the digital learning landscape.

Abstract Millimeter-scale soft continuum robots offer safety and adaptability in transluminal procedures due to their passive compliance, but this feature necessitates interactions with surrounding lumina, leading to potential medical risks and restricted mobility. Here, we introduce a millimeter-scale continuum robot, enabling apical extension while maintaining structural stability. Utilizing phase transition components, the robot executes cycles of tip-based elongation, steered accurately through programmable magnetic fields. Each motion cycle features a solid-like backbone for stability, and a liquid-like component for advancement, thereby enabling autonomous shaping without reliance on environmental interactions. Together with clinical imaging technologies, we demonstrate the capability of navigating through tortuous and fragile lumina to transport microsurgical tools. Once it reaches larger anatomical spaces such as stomach, it can morph into functional 3D structures that serve as surgical tools or sensing units, overcoming the constraints of initially narrow pathways. By leveraging this design paradigm, we anticipate enhanced safety, multi-functionality, and cooperative capabilities among millimeter-scale continuum robots, opening new avenues for transluminal robotic surgery.

Based on soil temperature and humidity and meteorological data at different elevations during the 2020-2021 growing season in the Pailugou watershed of Qilian Mountain， this study analyzed the variation characteristics of soil temperature and humidity and the relationship with meteorological factors， and determined the main meteorological factors affecting soil temperature and humidity.The results showed that： （1） soil temperature tended to increase and then decreased during the growing season （2020）， with a gradual increase in soil temperature from May to August （3.93 ℃） and a decrease from September to October （2.44 ℃）.Meanwhile， soil temperature showed a fluctuating increase with increasing elevation and a gradual decrease with increasing depth of soil layer.（2） Soil moisture showed considerable variation within the growing season， with a general trend of increase and then decrease （2020）， with the lowest soil moisture in May （0.164 m3·m-3） and the highest soil moisture in September （0.318 m3·m-3）.（3） The variation of soil moisture increases with elevation and decreases with the depth of the soil layer.（4） The main meteorological elements affecting soil temperature are air temperature and relative humidity， while soil moisture is mainly affected by air temperature and vapor pressure deficit.

Partial slow-release fertiliser substitution for urea combined with water-saving irrigation may synergistically improve rice yield, quality, water, and nitrogen (N) utilisation. A field experiment to evaluate different combinations of irrigation regimes: alternate wetting and drying irrigation (AWD) and flooding irrigation (FI), and N strategies: N0 (no N fertiliser); N1 (100% conventional fertiliser); N2 (100% SCF - sulphur-coated fertiliser); N3 (70% SCF + 30% urea), and N4 (50% SCF + 50% urea) on efficient rice production. Results indicated that higher substitution rates of SCF (N2 and N3) increased total N and ammonia N in surface water, leachate, and soil while reducing nitrate N relative to N1. The N3 strategy showed the highest yields, dry matter, total N uptake, and water N utilisation due to a nutrient release pattern that matched rice growth requirements. AWD yielded 5% lower than FI, except for the N3 strategy, but protein content increased by 12%, and amylose content dropped by 17%. The structural equation model analysis suggested that SCF positively impacted yield by influencing surface water total N and soil total N. Our findings indicate that implementing AWD alongside a 70% SCF basal fertiliser and 30% urea topdressing can optimise rice yield and quality while effectively managing water and fertiliser resources in the middle-lower Yangtze River Basin.

Methane explosion is one of the major disasters that seriously threaten the safety of coal mine production, the development of efficient methane explosion suppression technology can effectively improve the prevention and control level of methane explosion accidents, and its focus is on the function of explosion suppression materials. In order to systematically study the effect of typical haloalkanes extinguishing agents on methane explosion, the effects of typical haloalkanes such as heptafluoropropane (C3HF7), hexafluoropropane (C3H2F6) and trifluoromethane (CHF3) on the ignition and explosion characteristics of methane were systematically studied by combining experimental tests and theoretical analysis. The effects of haloalkanes on methane explosion pressure parameters and laminar burning velocity were tested by a 20 L spherical explosive vessel and a self-developed Bunsen burner laminar flame propagation velocity system. The variation laws of peak explosion pressure, maximum pressure rise rate, laminar burning velocity, and laminar flame morphology evolution were obtained. The results show that with the increase of the added volume fraction, the haloalkanes had a double effect of promoting and inhibiting the methane explosion process. Under the chemical equivalent condition, only C3HF7 can first promote and then inhibit the peak explosion pressure and maximum pressure rise rate of methane, while CHF3 and C3H2F6 can inhibit the effect. The three haloalkanes all showed inhibition on the combustion rate of methane laminar flow. In the oxygen-poor condition, the three haloalkanes inhibited the peak explosion pressure, the maximum pressure boost rate, and the laminar burning velocity of methane. In general, C3H2F6 and C3HF7 have better inhibition effects on methane explosion pressure characteristic parameters and laminar burning velocity than CHF3. The theoretical analysis results show that the double effect of promoting and inhibiting the haloalkanes with the increase of the mixture volume fraction can be attributed to the competition between the improvement of the heat release characteristics of the system reaction and the inhibition of the key free radicals such as H, O, and OH by the main intermediates containing F. The results of this paper provide a theoretical basis for the theoretical research and technical development of methane explosion prevention and control.

Upland crop-rice cropping systems (UCR) facilitate sustainable agricultural intensification. Accurate UCR cultivation mapping is needed to ensure food security, sustainable water management, and rural revitalization. However, datasets describing cropping systems are limited in spatial coverage and crop types. Mapping UCR is more challenging than crop identification and most existing approaches rely heavily on accurate phenology calendars and representative training samples, which limits its applications over large regions. We describe a novel algorithm (RRSS) for automatic mapping of upland crop–rice cropping systems using Sentinel-1 Synthetic Aperture Radar (SAR) and Sentinel-2 Multispectral Instrument (MSI) data. One indicator, the VV backscatter range, was proposed to discriminate UCR and another two indicators were designed by coupling greenness and pigment indices to further discriminate tobacco or oilseed UCR. The RRSS algorithm was applied to South China characterized by complex smallholder rice cropping systems and diverse topographic conditions. This study developed 10-m UCR maps of a major rice bowl in South China, the Xiang-Gan-Min (XGM) region. The performance of the RRSS algorithm was validated based on 5197 ground-truth reference sites, with an overall accuracy of 91.92%. There were 7348 km2 areas of UCR, roughly one-half of them located in plains. The UCR was represented mainly by oilseed-UCR and tobacco-UCR, which contributed respectively 69% and 15% of UCR area. UCR patterns accounted for only one-tenth of rice production, which can be tripled by intensification from single rice cropping. Application to complex and fragmented subtropical regions suggested the spatiotemporal robustness of the RRSS algorithm, which could be further applied to generate 10-m UCR datasets for application at national or global scales.

Objective Contactless power supply method, leveraging the advantages of no direct electrical contact between the primary and secondary side coils, is currently being explored in the rail transit industry. The high-power, high-frequency application scenarios pose challenges in the design of the contactless traction power supply system, component selection, and coupling mechanism design. It requires optimization of the design scheme and system efficiency. Method For rail transit application scenarios, the system structure of a contactless traction power supply system based on the LCC-S (inductance-capacitor-capacitor-series) compensation topology is introduced. A 250 kW contactless power supply system is designed, utilizing double D-shaped coils for the primary track coils and secondary receiving coils. The impact of factors such as mutual inductance of coupling coils and losses in magnetic materials on system efficiency is studied. System circuit model and coupling coil model are established. The system is simulated based on the model, and parameters for the magnetic core thickness in different regions of the secondary coils are optimized. An experimental platform for contactless traction power supply system is built, and tests are conducted at a power level of 250 kW to validate the effectiveness of the design optimization method. Result & Conclusion The simulation and experimental results confirm the effectiveness and feasibility of the design optimization method. Optimization of the core layout ensures coil mutual inductance and reduces core losses. The system demonstrates the capability of delivering a rated output power of 250 kW. Under air gap heights of 70 mm and 80 mm, the static and dynamic operating efficiencies of the system are both greater than 90%.

To improve the drill pipe fracture failure phenomenon in deflecting drills with ultra-short radius flexible drill pipes, this study establishes a mechanical model of a deflecting drill with an ultra-short radius flexible drill pipe, numerically simulates the mechanical characteristics of the flexible drill pipe under the conventional drilling process using the finite element analysis method, performs mechanical performance tests on the flexible drill pipe, and optimizes and improves its structure. The results show that, with the gradual increase in the bending angle of the flexible drill pipe unit section, the upper drilling pressure of the flexible drill pipe unit section decreases rapidly and its friction increases approximately linearly. The tensile strength of the optimized ultra-short radius flexible drill pipe is increased by 24.7%, and the minimum threshold of its torsional strength is doubled. This effectively improves the overall strength of the ultra-short radius flexible drill pipe and provides a theoretical basis for downhole drilling stability studies of flexible drill pipes.

[Objective] China's backbone natural gas pipeline network comprises numerous large-diameter and long-distance pipelines.Periodic pigging operations play a crucial role in ensuring the safe, stable and efficient operation of these pipelines. However, since current pigging operations rely heavily on operator experience and the establishment of monitoring points, the inability to simulate pigging schemes in advance prevents accurate prediction of parameters such as the operating speed, position and arrival time of the pig, and pressure changes in the pipe. [Methods] To address this challenge, a mathematical model for dynamic prediction of the pigging process was constructed and put into practice according to the characteristics of actual pigging operations. Subsequently, the software for dynamic prediction of the pigging process was developed and applied to the actual pigging operations of several sections(A-B, B-C and D-E) of a designated pipeline for predicting the pigging time and pigging speed. [Results] The improved two-phase flow transient pigging model and the dynamic prediction software accurately forecast critical parameters, including the running speed, position and arrival time at each station of the pig during the pigging process; The accuracy of the dynamic pigging prediction technology and the reliability of the software were verified using the monitoring data of 52 actual pigging operations; And compared with actual measurements, the software's predictions had average relative errors of 5.94% for pigging time and 6.56% for pigging speed. [Conclusion] The utilization of the dynamic prediction technology and software enables efficient preparation of pigging operation schemes for natural gas pipelines, reduces manual workload, ensures pigging process safety, and enhances pipeline management intelligence.

Purpose – The managerial questions of this paper are as follows, and the authors are trying to solve them: How revenue sharing contract (CSR) degree and government subsidy affect the agri-food quality? What kind of model (WPC, revenue-sharing contract [RSC] and cooperative) would be more effective in motivating manufacturers and retailer to increase effort and improve agri-food quality? What kind of model (WPC, RSC and cooperative) would make manufacturer and retailer better off? Design/methodology/approach – Considering the jointing quality effort and contract decision in green agri-food supply chain, this paper proposes six models that consider CSR of manufacturer and retailer, and then the obtained optimal solutions are compared and analyzed. At the same time, the impact of government subsidies is analyzed, and corresponding conclusions are drawn. Findings – The results show that, first of all, whether the increasing CSR of the manufacturer or the retailer can motivate both parties to improve the agri-food quality effort investment. Second, the WPC and RSC contract may play different role in different cases. Finally, under the model with government subsidies, regarding positive influence of government subsidies on efforts of manufacturer and retailer, quality and profits of members is investigated. Based on these conclusions, this study puts forward the following policy suggestions. Firstly, governments should formulate reasonable subsidy policies to support manufacturer and retailer to improve the agri-food quality, thereby promoting green industries' development. Secondly, manufacturer and retailer should actively improve CSR and strengthen the effort of agri-food so as to advance quality. Finally, manufacturer and retailer can choose cooperative model or WPC contract. Research limitations/implications – In this paper, one manufacturer and one retailer are considered. Since the agri-food supply chain structure in reality is more complicated, the future research direction can consider the supply chain structure with one manufacturer and multiple retailers. In addition, this paper only considers the subsidy, and future research can classify the subsidy into different types. Originality/value – The study makes two substantive contributions to the body of knowledge in the field of sustainable operations:(1) incorporating quality-based demand function in supply chain and dynamic process of agri-food quality; (2) exploring the impact of CSR awareness of members and subsidy of government on agri-food quality, and comparing the influence in different models.

Abstract Purpose To explore the effect of sarcopenia on recurrent fractures of adjacent vertebra after percutaneous kyphoplasty (PKP). Methods A total of 376 osteoporotic vertebral compression fractures (OVCFs) patients over 55 years old who were admitted to the Hospital from August 2020 to January 2021 were selected. Among them, 38 patients with recurrent fractures in adjacent vertebra after PKP were selected as the refracture group (RG), and the remaining 338 patients were selected as the non-refracture group (NRG). The age, gender, grip strength, body mass index (BMI), bone mineral density (BMD), visual analogue scale (VAS) of pain before and one month after surgery, Oswestry disability index (ODI) before and one month after surgery and the occurrence of sarcopenia were compared between the two groups. Logistic regression analysis was used to evaluate the effect of related risk factors on refracture after vertebral PKP. Results The results of t-test and Chi-square test showed that there were no obvious differences in gender, BMI, preoperative VAS score (t=-0.996, P = 0.320) and ODI (t=-0.424, P = 0.671), one month postoperative VAS score (t=-0.934, P = 0.355) and ODI score (t=-0.461, P = 0.645). while the age and grip strength showed significant differences between the two groups. Logistic regression analysis showed that BMI and gender had no significant effect on refracture after PKP, while sarcopenia and advanced age were independent risk factors for refracture after PKP. Also, increased BMD was a protective factor for refracture after PKP. Conclusion Sarcopenia is an independent risk factor for recurrent fractures after PKP in OVCF patients. The screening and diagnosis of sarcopenia should be strengthened. At the same time, anti-sarcopenia treatment should be actively performed after surgery.

Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer's disease (AD) collectively culminate in neuronal deterioration. In the context of AD, autophagy dysfunction, a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes. Therefore, multidimensional autophagy regulation strategies co-manipulating “autophagy induction” and “lysosome degradation” in dual targets (neuron and microglia) are more reliable for AD treatment. Accordingly, we designed an RP-1 peptide-modified reactive oxygen species (ROS)-responsive micelles (RT-NM) loading rapamycin or gypenoside XVII. Guided by RP-1 peptide, the ligand of receptor for advanced glycation end products (RAGE), RT-NM efficiently targeted neurons and microglia in AD-affected region. This nano-combination therapy activated the whole autophagy-lysosome pathway by autophagy induction (rapamycin) and lysosome improvement (gypenoside XVII), thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes, and promoting Aβ phagocytosis. Resultantly, it decreased aberrant protein burden, alleviated neuroinflammation, and eventually ameliorated memory defects in 3 × Tg-AD transgenic mice. Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.

As the construction of new power systems centred around renewable energy gains traction, the installed capacity of new energy sources has experienced explosive growth. Research has shown that the actual external characteristics of inductors and capacitors in circuits exhibit fractional order characteristics. As a core device in dual active bridge converters, the non-integer order of inductors and capacitors has an important impact on their dynamic performance, frequency domain characteristics, and control system design. This paper conducts modelling and control research on dual active bridge converters based on fractional-order calculus theory. First, based on the definition of fractional-order calculus, according to the operating mode of the fractional-order dual active bridge converter and the characteristics of fractional-order components, The fractional-order state space average model was established, and the influence of the order of inductance and capacitance on the amplitude frequency characteristics, phase frequency characteristics and dynamic performance of the converter was analyzed. Secondly, the average model and circuit model were built on the MATLAB/Simulink simulation platform, and the simulation results under different fractional orders were compared. Finally, in order to further improve the control performance of the converter, a fractional-order [Formula: see text] control strategy is designed based on the established state space average model of the fractional-order dual active bridge converter and based on the transfer function from the control to the output of the fractional-order dual active bridge converter. The research results show that the fractional-order model can more accurately describe the actual characteristics of the converter. In addition, the fractional-order controller [Formula: see text] enables the fractional-order dual active bridge converter to obtain better robustness and improve the dynamic performance of the converter.

Interfacial differences between the Hf0.5Zr0.5O2 (HZO) and the top/bottom electrodes caused by the process sequence could lead to the imprint effect of the TiN/HZO/TiN ferroelectric capacitor, which leads to serious reliability problems. In this article, a method of introducing a HfO2 protective layer is proposed to inhibit the imprint effect of the TiN/HZO/TiN ferroelectric capacitor. By introducing the HfO2 protective layer, the leakage current at the positive electric field is reduced by three orders of magnitude, the asymmetry of the coercive field is reduced from 1.5 to 0.1 MV/cm, and the endurance is improved by two orders of magnitude with no degradation in retention. The proposed method provides a feasible strategy to inhibit the imprint effect of TiN/HZO/TiN ferroelectric capacitors and is more compatible with complementary metal–oxide–semiconductor processes.

Shale gas accumulation and leakage histories are significant for evaluating the prospects of hydrocarbon exploration. The Wufeng Formation in northern Guizhou is a potential target for shale gas exploration and development. This work selected a typical Well YH1 to conduct detailed fluid inclusion analyses in the Wufeng Formation. We integrated the inclusion results with systematic core description, thin-section microscopic observation, laser Raman spectroscopy, microscopic temperature measurement, and burial–thermal history to reveal shale gas accumulation and leakage histories in northern Guizhou. The results show that the source rocks of the Wufeng Formation occurred in oil generation since the Permian and entered the stage of natural gas generation at the end of the Late Triassic. During the Early Jurassic and Early Cretaceous, shale gas accumulated in the Wufeng Formation reservoirs, and the stratigraphical pressure coefficient ranged from 1.47 to 1.97. Under the influence of the Yanshan orogeny, northern Guizhou experienced a rapid uplift and exhumation since the end of the Early Cretaceous. Under the influence of this tectonic, the stratigraphical pressure plummeted to the normal level, adversely impacting the accumulated shale gas in reservoirs and resulting in leakage events since the end of the Early Cretaceous. The reservoirs were further destroyed and adjusted, and the gas continued to leak because of a long-term and large-scale uplift and exhumation during the Himalayan orogeny. This work clarified that shale gas accumulation and leakage histories are significant for evaluating petroleum exploration.

Alzheimer's disease is a neurodegenerative disease induced by multiple interconnected mechanisms. Peptide drug candidates with multi-modal efficacy generated from fusion strategy are suitable for addressing multi-facet pathology. However, clinical translation of peptide drugs is greatly hampered by their low permeability into brain. Herein, a hybrid peptide HNSS is generated by merging two therapeutic peptides (SS31 and S-14 G Humanin (HNG)), using a different approach from the classical shuttle-therapeutic peptide conjugate design. HNSS demonstrated increased bio-permeability, with a 2-fold improvement in brain distribution over HNG, thanks to its structure mimicking the design of signal peptide-derived cell-penetrating peptides. HNSS efficiently alleviated mitochondrial dysfunction through the combined effects of mitochondrial targeting, ROS scavenging and p-STAT3 activation. Meanwhile, HNSS with increased Aβ affinity greatly inhibited Aβ oligomerization/fibrillation, and interrupted Aβ interaction with neuron/microglia by reducing neuronal mitochondrial Aβ deposition and promoting microglial phagocytosis of Aβ. In 3× Tg-AD transgenic mice, HNSS treatment efficiently inhibited brain neuron loss and improved the cognitive performance. This work validates the rational fusion design-based strategy for bio-permeability improvement and efficacy amplification, providing a paradigm for developing therapeutic peptide candidates against neurodegenerative disease.

Abstract Centromere protein A (CENP‐A), a centromere‐specific histone H3 variant, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure‐activity relationship (SAR) study of the cell‐cycle‐arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)‐6‐Br‐JP18 and (+)‐6‐Cl‐JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X‐ray crystallography analysis reveals that both molecules bind to the colchicine‐binding site of β‐tubulin. Treatment of human cells with microtubule‐targeting agents (MTAs), including these two compounds, results in CENP‐A accumulation by destabilizing Cdh1, a co‐activator of the anaphase‐promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP‐A accumulation using small‐molecule tools and highlights the role of Cdh1 in CENP‐A proteolysis.

BackgroundQianggu Concentrate (QGHJ), a traditional Chinese medicine, is extensively used to treat Type 2 Diabetic Osteoporosis (T2DOP). Despite its widespread use, research on its therapeutic mechanisms within T2DOP is notably scarce.ObjectiveTo explore QGHJ’s osteoprotection in T2DOP rats and BMSCs, focusing on the antioxidant activation of SIRT1/NRF2/HO-1 and NRF2 nuclear migration.MethodsQGHJ constituent analysis was performed using UPLC-HRMS. Safety, bone-health efficacy, and glucose metabolic effects in T2DOP rats were evaluated via general condition assessments, biomarker profiling, micro-CT, biomechanics, staining methods, and ELISA, supplemented by RT-qPCR and Western blot. BMSCs’ responses to QGHJ under oxidative stress, including viability, apoptosis, and osteogenic differentiation, were determined using CCK-8, flow cytometry, ALP/ARS staining, and molecular techniques. The modulation of the SIRT1/NRF2/HO-1 pathway by QGHJ was explored through oxidative stress biomarkers, immunofluorescence, and Western blot assays.ResultsUPLC-HRMS identified flavonoids, monoterpenes, and isoflavones as QGHJ’s key compounds. In vivo, QGHJ proved safe and effective for T2DOP rats, enhancing bone mineral density, microenvironment, and biomechanical properties without impairing vital organs. It modulated bone markers PINP, TRACP 5b, RUNX2 and PPARγ, favoring bone anabolism and reduced catabolism, thus optimizing bone integrity. QGHJ also regulated glycemia and mitigated insulin resistance. In vitro, it preserved BMSCs’ viability amidst oxidative stress, curbed apoptosis, and fostered osteogenesis with regulated RUNX2/PPARγ expression. Mechanistic insights revealed QGHJ activated the SIRT1/NRF2/HO-1 pathway, augmented NRF2 nuclear translocation, and enhanced the antioxidative response, promoting bone health under stress.ConclusionIn T2DOP rat and BMSCs oxidative stress models, QGHJ’s bone protection is anchored in its antioxidative mechanisms via the SIRT1/NRF2/HO-1 pathway activation and NRF2 nuclear translocation.

With a growing focus on the environment, the power system is evolving into a cleaner and more efficient energy supply infrastructure. Photovoltaic (PV) and storage are key assets for the power industry’s shift to sustainable energy. PV generation has zero carbon emission, and the integration of a substantial number of PV units is fundamentally important to decarbonize the power system. However, it also poses challenges in terms of voltage stability and uncertainty. Besides, the daily load and real-time price are also uncertain. As a prosumer, energy storage demonstrates the capacity to enhance accommodation and stability. The adoption of Virtual Power Plants (VPPs) emerges as a promising strategy to address these challenges, which allows the coordinated orchestration of PV systems and storage to participate power dispatch as a virtual unit. It further augments the flexibility of the power distribution system (PDS). To maximize the profit of VPP, a data-driven price forecasting method is proposed to extract useful information from historical datasets based on a novel LSTM-Transformer-combined neural network. Then, an improved sparrow searching algorithm (SSA) is proposed to schedule VPPs by combining the secant line search strategy. The numerical results, obtained from testing the model on IEEE 13-node and 141-node distribution systems, demonstrate the effectiveness and efficiency of the proposed model and methodology.

The application of digital technology service like rural e-commerce service centers (RESCs) has captured considerable attention in China, but existing literature has not yet provided solid empirical evidence regarding its potential to foster rural income gains. Utilizing large-scale survey data from the Third National Agricultural Census (TNAC) of China, this study attempts to investigate the impact and underlying mechanisms of RESCs on income gains across 49,135 villages. The results indicate that RESCs significantly increase village income gains in rural China, which confirm the theory of “space of flows.” In addition, heterogeneity analysis reveals that this income increasing effect is significantly higher in eastern China, as well as in rural villages with migrant populations and college-graduate cadres. The conclusion remains robust even after conducting several robustness checks and instrumental variable estimation. Furthermore, mechanism analysis unveils that RESCs improve village income gains by promoting characteristic agricultural development, encouraging entrepreneurship, and enhancing government funding support. The findings shed light on policy implications for the design and implementation of rural digital technology policies in developing countries.

ObjectiveThis study aims to examine the alterations in aberrant brain activity and network connectivity between individuals with mild and major vascular cognitive impairment (VCI).Materials and methodsA total of 114 patients with cerebral small vessel disease (CSVD) were included in this study, comprising 61 individuals with mild VCI (mean age, 55.7 ± 6.9 years; male, 42.6%) and 53 cases with major VCI (mean age, 57.6 ± 5.5 years; male, 58.5%). Additionally, 53 age-, gender-, and education-matched healthy subjects were recruited as normal controls (NC) (mean age, 54.9 ± 7.9 years; male, 52.9%). All participants underwent neuropsychological assessments and magnetic resonance imaging scans. One-way analysis of variance was used to compare fractional amplitude of low-frequency fluctuation (fALFF) values among the three groups. Two-sample t-tests were conducted to assess functional connectivity matrices between different groups for each connection. Moreover, mediation analyses were performed to explore the mediating effect of aberrant brain activity on the relationship between cognitive impairment and CSVD total burden.ResultsVCI patients exhibited aberrant brain activity in regions such as the right thalamus (THA_R), right cuneus (CUN_R), left postcentral gyrus (PoCG_L), right postcentral gyrus (PoCG_R), right median cingulate, paracingulate gyri (PCG_R), and left precuneus (PCUN_L). Reduced positive functional connectivity was predominantly observed among nodes including PCUN_L, CUN_R, PoCG_L, PoCG_R, right posterior cingulate (PCG_R), and left occipital gyrus (IOG_L) in VCI patients. The aberrant baseline brain activity and disrupted brain network were more pronounced with worsening cognitive function. Increased fALFF values in THA_R, CUN_R, and PoCG_L mediated cognitive impairment in CSVD patients.ConclusionAbnormal brain activities in THA_R, CUN_R, and PoCG_L, along with their associated abnormal functional connections, play a significant role in VCI. The study revealed a progressive increase in aberrant brain activity and network connectivity with advancing stages of VCI.

This paper investigates the ventilation and heat dissipation performance of a 110 kV indoor substation under natural ventilation conditions using computational fluid dynamics (CFD). The objectives are to evaluate the influences of air inlet design parameters including location and size, and transformer load, on the airflow distribution, temperature field, and cooling efficiency. The study finds that staggered opposite inlets optimize cooling uniformity without airflow attenuation. Compared to a single inlet, the maximum transformer temperature is reduced by 1.3 °C and energy utilization increases by 9.1 % with staggered inlets. Increasing the inlet length ratio initially improves cooling until an optimal point (The length ratio is 1.10), while reducing the inlet height ratio decreases airflow and efficiency. With load increasing, the intake airflow rises but at a reduced rate, and the temperature difference can exceed 15 °C under high loads. In summary, optimizing inlet design enhances natural ventilation performance in indoor substations, but limitations exist at high loads, indicating supplemental mechanical ventilation may be required.

IntroductionAnthracnose is a significant fungal disease that affects tree growth and development, with Colletotrichum spp. exhibiting host non-specificity and targeting various organs, making disease control challenging.MethodsThis study aimed to identify the pathogenic species causing anthracnose in Ilex macrocarpa in Nanchong, Sichuan Province, and screen effective fungicides, particularly biological ones. The pathogen was identified as Colletotrichum fioriniae through morphological observation, pathogenicity assays, and molecular biological methods. Three biological and five chemical fungicides were evaluated for their effects on the mycelial growth and spore germination rate of the pathogen.ResultsThe results indicated that prochloraz was the most effective chemical fungicide, while the cell-free supernatant (CFS) of Bacillus velezensis had the most significant inhibitory effect among the biological fungicides. Transcriptome analysis revealed that the CFS of B. velezensis significantly reduced the expression of genes associated with ribosomes, genetic information processing, membrane lipid metabolism, and sphingolipid biosynthesis in C. fioriniae. Additionally, the glutathione pathway’s expression of various genes, including key genes such as GST, GFA, Grx, TRR, and POD, was induced. Furthermore, the expression of 17 MFS transporters and 9 ABC transporters was increased. Autophagy-related ATGs were also affected by the B. velezensis CFS.DiscussionThese findings suggest that the B. velezensis CFS may inhibit C. fioriniae through interference with ribosomes, genetic information processing, cell membrane metabolism, and energy metabolism. These results provide potential target genes for the B. velezensis CFS and insights into the antifungal mechanism by which B. velezensis inhibits C. fioriniae.