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Abstract Cognitive decline covers a broad spectrum of disorders, not only resulting from brain diseases but also from systemic diseases, which seriously influence the quality of life and life expectancy of patients. As a highly selective anatomical and functional interface between the brain and systemic circulation, the blood-brain barrier (BBB) plays a pivotal role in maintaining brain homeostasis and normal function. The pathogenesis underlying cognitive decline may vary, nevertheless, accumulating evidences support the role of BBB disruption as the most prevalent contributing factor. This may mainly be attributed to inflammation, metabolic dysfunction, cell senescence, oxidative/nitrosative stress and excitotoxicity. However, direct evidence showing that BBB disruption causes cognitive decline is scarce, and interestingly, manipulation of the BBB opening alone may exert beneficial or detrimental neurological effects. A broad overview of the present literature shows a close relationship between BBB disruption and cognitive decline, the risk factors of BBB disruption, as well as the cellular and molecular mechanisms underlying BBB disruption. Additionally, we discussed the possible causes leading to cognitive decline by BBB disruption and potential therapeutic strategies to prevent BBB disruption or enhance BBB repair. This review aims to foster more investigations on early diagnosis, effective therapeutics, and rapid restoration against BBB disruption, which would yield better cognitive outcomes in patients with dysregulated BBB function, although their causative relationship has not yet been completely established.

Abstract Purpose The observation‐based prognosis, rather than resection, for small carcinoid tumors is still unclear. This lack of clarity has important implications for counseling elderly patients or patients for whom surgical resection poses a high risk. This study compared the outcomes of observation and surgical resection in patients with pulmonary carcinoid (PC) tumors ≤3 cm in size without metastasis. Methods Data of patients with PC tumors with ≤3 cm in diameter and without lymph node and distant metastases were retrieved from Surveillance, Epidemiology, and End Results (SEER) registry. To reduce the inherent bias of retrospective studies, propensity score matching analysis was performed. Overall survival (OS) and lung carcinoid‐specific survival (LCSS) were analyzed using Kaplan–Meier plots. Multivariate analysis was used to determine predictors of LCSS in different size subgroups. Results In total, 4552 patients with early‐stage PCs ≤3 cm in diameter, including 435 (9.56%) who were observed and 4117 (90.44%) treated by surgery, were recruited. Patients with surgery had significantly better OS and LCSS than those who were observed. However, patients with observation had comparable LCSS to those with surgery for PCs with tumor diameters ≤1 cm. Multivariate analysis indicated that surgical resection was an independent prognostic factor for LCSS in 1 cm < tumors ≤2 cm, and 2 cm < tumors ≤3 cm groups, but not for tumors ≤1 cm in diameter. Conclusion Surgical resection of small PCs is associated with a survival advantage over observation. However, for early PCs ≤1 cm in diameter, observation may be considered in patients with high risk for surgical resection.

Abstract Histone lysine demethylases (KDMs) have been reported in various malignances, which affect transcriptional regulation of tumor suppressor or oncogenes. However, the relationship between KDMs and formation of tumor microenvironment (TME) in gastric cancer (GC) remain unclear and need to be comprehensively analyzed. In the present study, 24 KDMs were obtained and consensus molecular subtyping was performed using the "NMF" method to stratify TCGA-STAD into three clusters. The ssGSEA and CIBERSORT algorithms were employed to assess the relative infiltration levels of various cell types in the TME. The KDM_score was devised to predict patient survival outcomes and responses to both immunotherapy and chemotherapy. Three KDM genes-related molecular subtypes were Figured out in GC with distinctive clinicopathological and prognostic features. Based on the robust KDM genes-related risk_score and nomogram, established in our work, GC patients’ clinical outcome can be well predicted. Furthermore, low KDM genes-related risk_score exhibited the more effective response to immunotherapy and chemotherapy. This study characterized three KDM genes-related TME pattern with unique immune infiltration and prognosis by comprehensively analyses of transcriptomic profiling. Risk_score was also built to help clinicians decide personalized anticancer treatment for GC patients, including in prediction of immunotherapy and chemotherapy response for patients.

ABSTRACT Introduction: The objective of this single-center study it to retrospectively analyze the relationship between transfusion and 30-day postoperative outcomes in patients undergoing isolated off-pump coronary artery bypass grafting. Methods: Perioperative data of 2,178 patients who underwent isolated off-pump coronary artery bypass grafting from 2018 to 2019 were collected. A 1:1 propensity score matching was performed to control for potential biases between patients who received blood transfusion and those who did not. After propensity score matching, we analyzed the clinical outcomes of transfusion and non-transfusion patients. Postoperative complications and the survival of patients within 30 days after surgery in both groups were analyzed. Kaplan-Meier survival curve and log-rank test were used for survival analysis. Results: The total blood transfusion rate of all patients was 29%, including red blood cell (27.6%), plasma (7.3%), and platelet (1.9%). Four hundred and forty patients in each group were compared after propensity score matching. There were no significant differences in the incidence of stroke, myocardial infarction, atrial fibrillation, acute kidney function injury, and sternal wound infection of both groups (P>0.05). However, higher incidence of postoperative pulmonary infection and more mechanical ventilation time and days of stay in the intensive care unit and postoperative in-hospital stay were associated with blood transfusion (P

Abstract Background Necroptosis is a new form of programmed cell death that is associated with cancer initiation, progression, immunity, and chemoresistance. However, the roles of necroptosis-related genes (NRGs) in colorectal cancer (CRC) have not been explored comprehensively. Methods In this study, we obtained NRGs and performed consensus molecular subtyping by “ConsensusClusterPlus” to determine necroptosis-related subtypes in CRC bulk transcriptomic data. The ssGSEA and CIBERSORT algorithms were used to evaluate the relative infiltration levels of different cell types in the tumor microenvironment (TME). Single-cell transcriptomic analysis was performed to confirm classification related to NRGs. NRG_score was developed to predict patients’ survival outcomes with low-throughput validation in a patients’ cohort from Fudan University Shanghai Cancer Center. Results We identified three distinct necroptosis-related classifications (NRCs) with discrepant clinical outcomes and biological functions. Characterization of TME revealed that there were two stable necroptosis-related phenotypes in CRC: a phenotype characterized by few TME cells infiltration but with EMT/TGF-pathways activation, and another phenotype recognized as immune-excluded. NRG_score for predicting survival outcomes was established and its predictive capability was verified. In addition, we found NRCs and NRG_score could be used for patient or drug selection when considering immunotherapy and chemotherapy. Conclusions Based on comprehensive analysis, we revealed the potential roles of NRGs in the TME, and their correlations with clinicopathological parameters and patients’ prognosis in CRC. These findings could enhance our understanding of the biological functions of necroptosis, which thus may aid in prognosis prediction, drug selection, and therapeutics development.

Background: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. The purpose of this study was to investigate the mechanism through which metformin improves postoperative cognitive function. Methods: In the in vivo experiment, 18-month-old Sprague–Dawley (SD) rats were randomly divided into four groups (n = 12 in each group): the control, metformin, operation, and operation plus metformin groups. The animals were pretreated with metformin by gavage once daily for two weeks. The Morris water maze (MWM) was used to measure cognitive ability. In the in vitro experiment, BV2 cells were divided into five groups: the control, metformin, lipopolysaccharide (LPS), LPS plus metformin, and LPS plus metformin plus compound C groups. We stimulated microglia with LPS (500 ng/mL). Immunofluorescence and Western blotting were used to assess ROS (reactive oxygen species) levels, autophagy-associated protein levels and adenosine monophosphate-activated protein kinase (AMPK)/regulator factor 2-related enzyme 1 (SIRT1) signaling pathway activity in the rat cortex and microglial cells. Results: In the MWM test, the metformin-pretreated rats spent a higher proportion of time in the target quadrant. Immunofluorescence showed that the fluorescence intensity of LC3 in the cortex was increased in rats pretreated with metformin. Western blotting indicated that metformin upregulated the expression of autophagy-related and AMPK/SIRT1 signaling pathway-related proteins in the cortex after surgery. By activating the AMPK/SIRT1 signaling pathway in vitro, metformin reduced microglial activation and oxidative stress and promoted autophagy. Conclusions: Through the AMPK/SIRT1 pathway, metformin can boost autophagy and reduce oxidative stress in cortical microglia in older rats, in turn improving postoperative cognitive function.

Abstract Background Sarcopenia is a common skeletal disease related to myogenic disorders and muscle atrophy. Current clinical management has limited effectiveness. We sought to investigate the role of miR-1290 in myoblast differentiation and muscle atrophy. Methods By transfecting miR-1290 into C2C12 cells, we investigated whether miR-1290 regulates myogenesis and myotube atrophy via AKT/P70 signaling pathway. MHC staining was performed to assess myoblast differentiation. Differentiation-related MHC, Myod, and Myog protein levels, and atrophy-related MuRF1 and atrogin-1 were explored by western blot. An LPS-induced muscle atrophy rat model was developed. RT-PCR was conducted to analyze miR-1290 serum levels in muscle atrophy patients and normal controls (NCs). Results The miR-1290 transfection increased MHC-positive cells and MHC, Myod, and Myog protein levels in the miR-1290 transfection group, demonstrating that miR-1290 promoted C2C12 myoblast differentiation. Myotube diameter in the miR-1290 transfection group was higher than in the TNF-α-induced model group. Western blot analysis showed decreased MuRF1 and atrogin-1 levels in the miR-1290 transfection group compared with the model group, demonstrating that miR-1290 protected against myoblast cellular atrophy. Luciferase assay and western blot analysis showed that miR-1290 regulation was likely caused by AKT/p70/FOXO3 phosphorylation activation. In the LPS-induced muscle atrophy rat model, miR-1290 mimics ameliorated gastrocnemius muscle loss and increased muscle fiber cross-sectional area. Clinically, miR-1290 serum level was significantly decreased in muscle atrophy patients. Conclusions We found that miR-1290 enhances myoblast differentiation and inhibits myotube atrophy through Akt/p70/FoxO3 signaling in vitro and in vivo. In addition, miR-1290 may be a potential therapeutic target for sarcopenia treatment.

The practical problems of existing methods of walnut cracking under compression loading, including incomplete walnut-shell crushing, broken walnut kernels, and so on, are widespread in walnut processing and are constraints that hinder mechanized walnut processing. Therefore, attempts have been made to design and optimize a multi-point extrusion walnut cracking device. For this, walnuts were fed manually into a cracking unit through the hopper. The tangential force of the grading roller graded the walnuts and dropped them into the gap between the rotating cracking roller and extrusion plate, causing them to crack. The developed machine was tested and the parameters were optimized using a central composite design (CCD). The objective functions involving the cracking angle (CA: 0.17, 0.27, 0.52, 0.76, 0.86°) and roller speed (RS: 63, 75, 105, 135, 147 r/min) were calculated. The shell cracking rate (SCR), whole kernel rate (WKR), and specific energy consumption (Es) regression models were established using the quadratic regression orthogonal combination test and the parameters were optimized using MATLAB software. The results showed that the most significant factors for the RS were the linear terms of the SCR and WKR, whereas for the CA the most significant factor was the linear term of the Es. The interaction term of the two factors had a significant effect on the three indicators. The optimal parameter combination was determined to be 0.47° for the CA and 108 r/min for the RS. On this basis, the adaptability test showed that the cracking device had a better cracking effect on walnuts with a gap between the walnut shell and kernel greater than 1.6 mm and a shell thickness less than 1.2 mm. The results have practical significance for the design of walnut cracking devices.

Abstract Optical wireless communication (OWC) stands out as one of the most promising technologies in the sixth-generation (6G) mobile networks. The establishment of high-quality optical links between transmitters and receivers plays a crucial role in OWC performances. Here, by a compact beam splitter composed of a metasurface and a fiber array, we proposed a wide-angle (~120°) OWC optical link scheme that can parallelly support up to 144 communication users. Utilizing high-speed optical module sources and wavelength division multiplexing technique, we demonstrated each user can achieve a communication speed of 200 Gbps which enables the entire system to support ultra-high communication capacity exceeding 28 Tbps. Furthermore, utilizing the metasurface polarization multiplexing, we implemented a full range wide-angle OWC without blind area nor crosstalk among users. Our OWC scheme simultaneously possesses the advantages of high-speed, wide communication area and multi-user parallel communications, paving the way for revolutionary high-performance OWC in the future.

Abstract Background This study aimed to synthesize and quantitatively examine Health State Utility Values (HSUVs) for Type 2 Diabetes Mellitus (T2DM) and its complications, providing a robust meta-regression framework for selecting appropriate HSUV estimates. Method We conducted a systematic review to extract HSUVs for T2DM and its complications, encompassing various influencing factors. Relevant literature was sourced from a review spanning 2000-2020, supplemented by literature from PubMed, Embase, and the Web of Science (up to March 2024). Multivariate meta-regression was performed to evaluate the impact of measurement tools, tariffs, health status, and clinical and demographic variables on HSUVs. Results Our search yielded 118 studies, contributing 1044 HSUVs. The HSUVs for T2DM with complications varied, from 0.65 for cerebrovascular disease to 0.77 for neuropathy. The EQ-5D-3L emerged as the most frequently employed valuation method. HSUV differences across instruments were observed; 15-D had the highest (0.89), while HUI-3 had the lowest (0.70) values. Regression analysis elucidated the significant effects of instrument and tariff choice on HSUVs. Complication-related utility decrement, especially in diabetic foot, was quantified. Age

Abstract National and global food security depend on both supply and demand, yet the vast majority of studies on the impact of climate change on food security have focused somewhat myopically on the supply side. Here, we assess planetary implications of the changing climate for food supply, concurrently considering implications of shifts in dietary preferences on food security. From 1990 to 2018, climate change detrimentally impacted on the food production of 92% of nations assessed. During this time, demand decreased at a greater rate than food supply in 28% of countries; food security for 35% of the global population was unperturbed by climate change. On the other hand, 2% of the global population did not benefit from positive impacts of climate change on food production, due to dietary changes faster increasing food demand. If consumers shift dietary preferences en masse towards healthier diets, detrimental impacts of the climate crisis on food security may be abated, although en mass and/or abrupt transitions in dietary preferences are unlikely.

Abstract Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway. In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.

Al–Li alloy has been widely used in the manufacture of aerospace aircraft structural parts due to its high specific strength and excellent comprehensive performance. Friction stir welding (FSW), as a solid-state joining technique, generates comparatively lower heat generation in contrast to fusion welding. However, even with this reduced heat input, the welded joints of 2195 Al–Li alloy still exhibit noticeable thermal softening. FSW is very sensitive to welding heat input, and the thermal cycle of high peak temperature coarsens the grain in the weld zone, thereby reducing joint properties. To overcome these problems, external cooling can be applied to reduce peak temperature and increase cooling speed, improving the performance of FSW joints. In order to study the mechanism of external cooling on the microstructure evolution of joints, this work established a multi-scale simulation of splat cooling assisted friction stir welding (SCaFSW) of 2195 Al–Li alloy. The temperature change and material deformation data in SCaFSW were calculated in the macroscopic finite element model and used for further Monte Carlo microstructure evolution simulation, and compared with the conventional FSW process. Results reveal that the splat cooling significantly reduces the area of the high temperature region of the workpiece, decreasing the temperature at the same location 10 mm behind the tool by approximately 50 °C compared to FSW. While the local temperature field around the tool pin is not affected by the splat cooling, which mainly accelerates the cooling rate of the welded joint and reduces the plastic strain. In addition, the dislocation density in the weld nugget zone (WNZ) of SCaFSW joint is higher than that in conventional FSW, which promotes the process of grain nucleation and finally refines the grain in the WNZ. The simulated average grain size and thermal cycling results are in good agreement with the experimental results.

Abstract Microorganisms are essential in the decomposition of corpses and play a significant role in forensic science. However, previous studies have primarily focused on animal remains, specifically the gut, skin, and burial environment. Insufficient research has been conducted on the microbiota of human cadavers, especially in cases of advanced decomposition and additional tissues, resulting in a lack of relevant reference data. In this study, the microbiota of eight cadavers at different stages of decomposition were detected using 16S rRNA, metagenomic sequencing and 2bRAD-M sequencing. Nine different sites, including oral and nasal cavities, heart, liver, spleen, lung, kidney, muscle and gut, were analysed and the efficacy of these methods was evaluated. The results showed that 16S rRNA sequencing was the most cost-effective method for the study of cadavers in the early stages of decomposition, whereas for cadaveric tissues in the late stages of decomposition, 2bRAD-M could overcome host contamination more effectively than metagenomic sequencing. This paves the way for new opportunities in data retrieval and promotes in-depth investigations into the microbiota.

Spinal cord injury (SCI) rehabilitation emphasizes locomotion. Robotic-assisted gait training (RAGT) is widely used in clinical settings because of its benefits; however, its efficacy remains controversial. We conducted a systematic review and meta-analysis to investigate the efficacy of RAGT in patients with SCI. We searched international and domestic databases for articles published until April 18, 2024. The meta-analysis employed a random effects model to determine the effect size as either mean difference (MD) or standardized MD (SMD). Evidence quality was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twenty-three studies with a total of 690 participants were included in the final analysis. The overall pooled effect size for improvement in activities of daily living was 0.24, with SMD (95% confidence interval [95% CI], 0.04–0.43; GRADE: high) favoring RAGT over conventional rehabilitation. Muscular strength (MD, 0.23; 95% CI, 0.02–0.44; GRADE: high), walking index for SCI (MD, 0.31; 95% CI, 0.07–0.55; GRADE: moderate) and 6 min walk test distance (MD, 0.38; 95% CI, 0.14–0.63; GRADE: moderate) showed significant improvement in the robot group. Subgroup analysis revealed that subacute patients and intervention periods >2 months were more effective. This meta-analysis revealed that RAGT significantly improved activities of daily living, muscular strength, and walking abilities. Additional studies are needed to identify the optimal treatment protocol and specific patient groups for which the protocol is most effective.

The wind power industry is increasing worldwide every year. Thus, obtaining timely and detailed information on wind farms’ number and spatial distribution is critical for quantitatively estimating wind energy utilization and for planning the construction of new wind farms. Therefore, this study proposes a method for quickly identifying wind farms in a large-scale area. Given that wind farms mainly comprise individual objects such as wind turbines and substations, we labeled sample images of wind turbines and substations on a global scale. Then, these sample images are used to train a target recognition model and an object classification model and detect the specific locations of wind turbines and substations in the study area. Additionally, we deeply analyzed the location features of the wind turbines and further improved the recognition accuracy based on these known features using geographic constraints. Based on the location information of wind turbines and substations, a clustering model organizes them effectively into complete wind farms. A comprehensive evaluation of the clustering model verifies its scientific validity and reliability. Specifically, this framework was systematically tested throughout Vietnam with remarkable results, using high-resolution historical images provided by Google Earth. Indeed, our framework achieved 90.45% recall and 95.73% accuracy for wind turbines and 81.37% recall and 78.96% accuracy for substations. Finally, we successfully obtained the spatial location and distribution of 15 completed wind farms, demonstrating that the proposed scheme can quickly and accurately identify wind power plants in a large-scale area, which supports wind power management and energy utilization planning.

Abstract Patients with brain tumors require extensive and prolonged rehabilitation efforts as they suffer from lesion-induced motor weakness as well as treatment-related side effects, often leading to a significant decline in function. Protein supplements have shown positive effects on promoting muscle strength and physical performance in various tumor etiologies. However, reports on their effects specifically in brain tumor patients remain scarce. This study aims to investigate the feasibility and efficacy of protein supplements in enhancing rehabilitative outcomes via muscle strengthening and functional gain in brain tumor patients with neurological demise. Sixty brain tumor patients were randomly assigned to either a protein supplement or a control group, receiving either protein supplements or a placebo for 6 weeks, in conjunction with conventional rehabilitation therapy. Assessments before and after the intervention included laboratory tests, anthropometric measures using bioimpedance analysis, and functional assessments, which included the MMSE, the modified Barthel Index, the Beck Depression Inventory, the Brief Fatigue Inventory, the Timed Up and Go test, the 6-min walk test, the isokinetic quadriceps muscle strength test, and the handgrip power. After the intervention, the levels of serum hemoglobin, protein, albumin, and C-reactive protein were improved in both groups, however, the change was significant only in the protein group. The muscle strength was enhanced in both groups, however, the significant increase in pinch grasp power was only noted in the protein group (P

Abstract Background There are numerous methods available for predicting sepsis following Percutaneous Nephrolithotomy. This study aims to compare the predictive value of Quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SISR), National Early Warning Score (NEWS), interleukin-6 (IL-6), and procalcitonin (PCT) for septicemia. Methods Patients who underwent percutaneous nephrolithotomy were included in the study and divided into a control group and a septic shock group. The effectiveness of qSOFA, SIRS, NEWS, Interleukin-6, and Procalcitonin was assessed, with Receiver Operating Characteristic curves and Area Under the Curve used to compare the predictive accuracy of these four indicators. Results Among the 401 patients, 16 cases (3.99%) developed septic shock. Females, elderly individuals, and patients with positive urine culture and positive nitrite in urine were found to be more susceptible to septic shock. PCT, IL-6, SIRS, NEWS, qSOFA, and surgical time were identified as independent risk factors for septic shock. The cutoff values are as follows: qSOFA score > 0.50, SIRS score > 2.50, NEWS score > 2.50, and IL-6 > 264.00 pg/ml. Among the 29 patients identified by IL-6 as having sepsis, 16 were confirmed to have developed sepsis. The qSOFA identified 63 septicemia cases, with 16 confirmed to have developed septicemia; NEWS identified 122 septicemia cases, of which 14 cases actually developed septicemia; SIRS identified 128 septicemia patients, with 16 confirmed to have developed septicemia. In terms of predictive ability, IL-6 (AUC 0.993, 95% CI 0.985 ~ 1) demonstrated a higher predictive accuracy compared to qSOFA (AUC 0.952, 95% CI 0.928 ~ 0.977), NEWS (AUC 0.824, 95% CI 0.720 ~ 0.929) and SIRS (AUC 0.928, 95% CI 0.888 ~ 0.969). Conclusions IL-6 has higher accuracy in predicting septic shock after PCNL compared to qSOFA, SIRS, and NEWS.

Abstract Spinal cord injury (SCI) leads to motor and sensory impairment below the site of injury, thereby necessitating rehabilitation. An enriched environment (EE) increases social interaction and locomotor activity in a mouse model, similar to human rehabilitation. However, the impact of EE on presynaptic plasticity in gene expression levels remains unclear. Hence, this study aimed to investigate the therapeutic potential of EE in an SCI mouse model. Mice with spinal cord contusion were divided into two groups: those housed in standard cages (control) and those in EE conditions (EE). Each group was housed separately for either 2- or 8-weeks post-injury, after which RNA sequencing was performed and compared to a sham group (receiving only a dorsal laminectomy). The synaptic vesicle cycle (SVC) pathway and related genes showed significant downregulation after SCI at both time points. Subsequently, we investigated whether exposure to EE for 2- and 8-weeks post-SCI could modulate the SVC pathway and its related genes. Notably, exposure to EE for 8 weeks resulted in a marked reversal effect of SVC-related gene expression, along with stimulation of axon regeneration and mitigation of locomotor activity loss. Thus, prolonged exposure to EE increased presynaptic activity, fostering axon regeneration and functional improvement by modulating the SVC in the SCI mouse model. These findings suggest that EE exposure proves effective in inducing activity-dependent plasticity, offering a promising therapeutic approach akin to rehabilitation training in patients with SCI.

Wire-arc directed energy deposition (DED) of Al–Zn–Mg–Cu alloy faced a tough challenge because of the occurrence of crack and pore defects caused by the high content of alloying elements. Three cold metal transfer (CMT) arc modes were studied to fabricate Al–Zn–Mg–Cu alloy components via the wire-arc DED process, with the aim of optimizing the deposition process and revealing the action mechanism of arc mode on the microstructure and mechanical properties. The effect of the CMT arc mode on the forming accuracy and arc/droplet behaviors was investigated with the assistance of the microscope and high-speed camera. The characteristics of grain morphology, crystallographic texture, and precipitated phase were quantitatively analyzed. The results show that the forming accuracies of deposited samples degenerate when using CMT and CMT pulse modes due to abnormal electrical waveforms and overflow/curve phenomenon. The finest grain size is realized under CMT advance mode because of its induced stirring effect on the molten pool, expanded constitutional supercooling zones, and extremely low heat input. The continuous and coarse precipitated phases in CMT and CMT pulse modes are transferred into dispersive ones in CMT advance mode. Moreover, the quantity and size of pores are also reduced in CMT advance mode. The combined action of microstructure optimization and defect reduction is conducive to improving the mechanical properties. Finally, the preferable ultimate tensile strength (∼278.15 MPa) and top elongation (∼6.50 %) of as-deposited Al–Zn–Mg–Cu alloy are achieved.

Permafrost is degrading globally, particularly those with low thermal stability on the Qinghai‒Tibet Plateau, owing to climate change. However, the inadequacy of direct research on permafrost degradation based on in-situ monitoring limits the prediction of permafrost degradation and engineering practices. This study explored the processes and modes of permafrost degradation into talik by analyzing ground temperature data from five points in the hinterland of the Qinghai‒Tibet Plateau from 2006 to 2021. The results showed that the degradation of the warm permafrost layer with a geothermal gradient of zero occurred simultaneously in the top and bottom directions. The rate of permafrost degradation from the top down and bottom up increase during the degradation process, but the increase of the former is more drastic after the formation of thawed interlayer. Additionally, the construction of the Qinghai‒Tibet Railway changed the degradation modes of the permafrost in adjacent natural sites through horizontal heat transfer, particularly after through talik formation under the embankment. The findings suggest that taking countermeasures before or immediately after forming thawed interlayer is more effective. When evaluating the thermal impact of projects in warm permafrost regions, special attention should be given to the horizontal heat transfer process that may result from the formation of a through talik.

Abstract In single unit-cell FeSe grown on SrTiO3, the superconductivity transition temperature features a significant enhancement. Local phonon modes at the interface associated with electron-phonon coupling may play an important role in the interface-induced enhancement. However, such phonon modes have eluded direct experimental observations. The complicated atomic structure of the interface brings challenges to obtain the accurate structure-phonon relation knowledge. Here, we achieve direct characterizations of atomic structure and phonon modes at the FeSe/SrTiO3 interface with atomically resolved imaging and electron energy loss spectroscopy in an electron microscope. We find several phonon modes highly localized (~1.3 nm) at the unique double layer Ti-O terminated interface, one of which (~ 83 meV) engages in strong interactions with the electrons in FeSe based on ab initio calculations. This finding of the localized interfacial phonon associated with strong electron-phonon coupling provides new insights into understanding the origin of superconductivity enhancement at the FeSe/SrTiO3 interface.

Abstract Background Early-onset bone dysplasia is a common manifestation of hypophosphatasia (HPP), an autosomal inherited disease caused by ALPL mutation. ALPL ablation induces prototypical premature bone ageing characteristics, resulting in impaired osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMMSCs). As angiogenesis is tightly coupled with osteogenesis, it also plays a necessary role in sustaining bone homeostasis. We have previously observed a decrease in expression of angiogenesis marker gene CD31 in the metaphysis of long bone in Alpl +/− mice. However, the role of ALPL in regulation of angiogenesis in bone has remained largely unknown. Methods Exosomes derived from Normal and HPP hBMMSCs were isolated and identified by ultracentrifugation, transmission electron microscopy, and nanoparticle size measurement. The effects of ALPL on the angiogenic capacity of hBMMSCs from HPP patients were assessed by immunofluorescence, tube formation, wound healing and migration assay. exo-ELISA and Western Blot were used to evaluate the exosomes secretion of hBMMSCs from HPP, and the protein expression of VEGF, PDGFBB, Angiostatin and Endostatin in exosomes respectively. Results We verified that ALPL ablation resulted in impaired pro-angiogenic capacity of hBMMSCs, accounting for reduced migration and tube formation of human umbilical vein endothelial cells, as the quantities and proteins composition of exosomes varied with ALPL expression. Mechanistically, loss of function of ALPL enhanced ATP release. Additional ATP, in turn, led to markedly elevated level of ATP receptor P2X7, which consequently promoted exosomes secretion, resulting in a decreased capacity to promote angiogenesis. Conversely, inhibition of P2X7 increased the angiogenic induction capacity by preventing excessive release of anti-angiogenic exosomes in ALPL deficient-hBMMSCs. Conclusion The ALPL–ATP axis regulates the pro-angiogenic ability of hBMMSCs by controlling exosomes secretion through the P2X7 receptor. Thus, P2X7 may be proved as an effective therapeutic target for accelerating neovascularization in ALPL–deficient bone defects.

Detection of specific antinuclear antibodies is very important in term of diagnosis, prognosis and management of patients with systemic autoimmune rheumatic diseases. Chemiluminescence microarray immunoassay (CLMIA) is a microdot array-based method that allows simultaneous detection of multiple antinuclear antibodies, which received increasing attention.

Background: Although anti-HER2 therapies have been widely used against gastric carcinoma, the prognostic significance of HER2 overexpression remains unclear. Previous studies failed to provide convincible evidence due to inconsistent HER2 evaluation criteria and heterogeneous clinical characteristics. Objectives: To figure out the prognostic significance of HER2 expression in gastric cancer, we rigorously designed and conducted this study. Design: Meta-analysis. Data sources and methods: Record retrieval was performed by searching PubMed, Web of Science, Cochrane Library, Embase, ASCO, and ESMO meeting libraries from inception to November 2022. Cohort studies investigating overall survival comparison between HER2-positive and HER2-negative gastric cancer patients were included. Both resectable and advanced cases were separately collected while HER2 evaluation standards should be consistent across eligible studies. Newcastle–Ottawa Scale was used for quality assessment. Overall survival was the only endpoint and effect size was presented by hazard ratio (HR) with its 95% confidence interval. The pooled calculation was conducted on Review Manager 5.4. Results: Thirty studies were eligible, including 9945 patients. Eligible studies were mostly high quality ( n = 31). Regarding resectable cases ( n = 22), HER2-positive groups had significantly worse prognosis than HER2-negative counterparts (HR 1.56, 95%CI 1.32–1.85, p

As the aging populations, both nationwide and worldwide, rapidly increase, falls leading to unintentional injury and death subsequently increase. Thus, developing an understanding of biomechanical postural control strategies used to maintain balance in aging healthy adults, and those that have suffered stroke, are critical. Here, we were interested in how one’s body segments stabilize relative to one another, and in space, in order to maintain balance. To accomplish this goal, we studied 30 healthy individuals and 8 survivors of stroke between 60 and 85 years old, both before and after several weeks of sensory training. Motion capture data were acquired to assess participants’ body kinematics during walking: forward (easiest), forward-tandem, backward, and backward-tandem walking (most challenging). Deviations (via the observation of the absolute angle with deviations, or AADs) of the head, thorax, and lumbar areas relative to an earth vertical reference, as well as how one body segment stabilized in space or relative to the inferior body segment (via the observation of anchoring indices, or AIs), were explored. The results provide metrics (AADs and AIs) that can assess aging posture. Further, the results show an initial indication that, for aging individuals, training could lead to improved head and body stabilization in space.

Abstract Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and “left-behind” and “single-parenting” children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.

The U-shaped crushed rock embankment (UCRE), of which widely utilized in the permafrost regions along the Qinghai‒Tibet Railway, has the capability to rapidly reduce the ground temperature of the underlying permafrost. However, there remains uncertainty regarding the adaptation of UCRE to climate change and its long-term cooling trend. This study focuses on nine UCRE monitoring sites along the Qinghai‒Tibet Railway to analyze the dynamic variations of the ground temperature underlying permafrost from 2006 to 2020. The efficiency of UCRE in stabilizing permafrost temperature in different permafrost zones is evaluated by considering the permafrost table, ground temperature, and MAGT, as well as the temperature difference between the top and bottom of the crushed rock layer and the ground temperature variation index (GTVI). The results show that UCRE is suitable for application in extremely unstable warm permafrost regions where the MAGT is higher than −0.5 °C. Moreover, UCRE effectively diminishes the disparity in permafrost thermal stability between the sunny and shaded shoulders of the embankment. The short-term and long-term effect of cooling permafrost is experiencing a change related with permafrost stability. Notably, in stable cold permafrost regions with MAGT lower than −1.5 °C, the long-term cooling effect of UCRE on permafrost seems to gradually diminishes, but UCRE continues to fulfill the role of stabilizing the underlying permafrost thermal state over the long-term. These results show that UCRE can quickly restore and stabilize the thermal state of permafrost in the early stages of construction, and adapt to the influence of future climate change. The findings provide important guidance for understanding the variations of permafrost thermal stability beneath the embankment in permafrost regions, as well as for improving the embankment stability and operational safety of the Qinghai‒Tibet Railway.

As a soft metal, the addition of Cu has an important influence on the high-temperature tribological properties and oxidation behavior of nanomultilayered AlTiN/Cu coatings. At room temperature (RT), due to abrasive wear, the AlTiN coating exhibited a high friction coefficient of 0.97 and low wear resistance. After adding Cu layer, the friction coefficient gradually decreased to 0.59 at 18.4 at.% Cu due to the lubricating effect of soft metal Cu and CuO, and the best wear resistance was achieved at 2.9 at.% Cu. At 800 °C, the oxidation resistance sharply reduced after adding Cu layer, and exhibited oxidation delamination. At low Cu contents (≤4.5 at.%), by the inward diffusion of O, a mixed oxide layer of Al2O3, TiO2, and CuO formed. At 18.4 at.% Cu, by the outward diffusion and oxidation of Cu, double-layer oxides formed, and the top layer of CuO contributed to a low friction coefficient of 0.53, but also caused a reduce in the wear resistance.

Al–Li alloy has a wide range of application prospects in aerospace and rail transportation fields. Friction stir welding (FSW) is suitable for joining of Al–Li alloy. The microstructure evolution in FSW of Al–Li alloy determines the final joint properties. However, it is difficult to directly observe the microstructure evolution in FSW of Al–Li alloy only by experimental methods. Therefore, a Monte Carlo model in cooperation with a thermomechanical finite element model was proposed to study the microstructure evolution in FSW of 2195 Al–Li alloy. The validated thermomechanical finite element model was first used to calculate the temperature field, strain rate and strain evolution during the FSW process. Then, the achieved thermomechanical history was used in the Monte Carlo model to predict the transient microstructure evolution and the final morphology of the grain structure. It is found that the plastic materials on the advancing side experience a higher strain compared with that on the retreating side with the same distance from the joint line. The plastic material in the middle of the weld nugget zone (WNZ) experiences a relatively high temperature with more severe plastic deformation. Therefore, fully dynamic recrystallization takes place for the material at this region as it flows across the tool during FSW, which results in a fine recrystallization grain in the middle of WNZ. However, the material on the advancing side at 2 mm away from the joint line experiences a lower strain rate, which results in partial recrystallization with some relatively large grains of the base materials. The simulated average grain size and grain morphology were in good agreement with the measured results by EBSD method.

This study investigates the effects of soybean lecithin (SL) on the growth, fatty acid composition, lipid metabolism, and gonadal development of rice field eels. Fourteen-month-old eels were fed either fish oil diets or varying levels of dietary soybean lecithin (0 %, 1.4 %, and 2.8 %) for 10 weeks. Dietary SL had no significant impact on growth, whereas 1.4 % SL led to a significant decrease in moisture content and an increase in crude protein content in eels. The content of both saturated and polyunsaturated fatty acids increased in muscles fed the higher SL diet, with a concurrent decline in saturated fatty acids and an increase in polyunsaturated fatty acids detected in the liver. The expression levels of genes related to lipid synthesis, including accα and PPARγ, and genes related to polyunsaturated fatty acid synthesis, such as pla2g4a, fad2 and scd, were significantly increased in the liver of eels fed with 1.4 % SL diet. SL supplementation enhances lipid transport and antioxidant capacity in the liver, reduces fat deposition, and protects the liver from damage. Hepatosomatic index of fish in the SL1.4 % and SL2.8 % groups decreased. Supplementation of the diet with 1.4 % SL led to a significant decrease in the content of saturated fatty acids and an increase in the content of polyunsaturated fatty acids in the gonads, with a significant increase in arachidonic acid levels. The gonadosomatic index also increased with increasing dietary SL content. Rice field eels fed diets containing SL exhibited elevated serum levels of E2, delayed ovary-to-testis transition, and a preference for retaining the female state. In conclusion, dietary supplementation with SL increased the proportion of highly unsaturated fatty acids in the tissues, enhanced lipid metabolism in the liver, and improved antioxidant capacity. Furthermore, SL supplementation has been demonstrated to promote ovarian development and delay sex reversal in rice field eels.

The nucleus incertus (NI), a conserved hindbrain structure implicated in the stress response, arousal, and memory, is a major site for production of the neuropeptide relaxin-3. On the basis of goosecoid homeobox 2 (gsc2) expression, we identified a neuronal cluster that lies adjacent to relaxin 3a (rln3a) neurons in the zebrafish analogue of the NI. To delineate the characteristics of the gsc2 and rln3a NI neurons, we used CRISPR/Cas9 targeted integration to drive gene expression specifically in each neuronal group, and found that they differ in their efferent and afferent connectivity, spontaneous activity, and functional properties. gsc2 and rln3a NI neurons have widely divergent projection patterns and innervate distinct subregions of the midbrain interpeduncular nucleus (IPN). Whereas gsc2 neurons are activated more robustly by electric shock, rln3a neurons exhibit spontaneous fluctuations in calcium signaling and regulate locomotor activity. Our findings define heterogeneous neurons in the NI and provide new tools to probe its diverse functions.

Abstract Land use change (LUC) alters the global carbon (C) stock, but our estimation of the alteration remains uncertain and is a major impediment to predicting the global C cycle. The uncertainty is partly due to the limited number and geographical bias of observations, and limited exploration of its predictors. Here we generated a comprehensive global database of 5,980 observations from 790 articles. The number of sites evaluated is at least seven times larger than in previous meta‐analyses. Our constrained estimates of different LUC's effects on soil organic C (SOC) and their variations across global climates reveal underestimation/overestimation in previous estimates. Converting forests and grasslands to croplands reduced SOC by 24.5% ± 1.53% (−11.03 ± 1.06 Mg ha−1) and 22.7% ± 1.22% (−8.09 ± 0.67 Mg ha−1), while 28.0% ± 1.56% (4.46 ± 0.42 Mg ha−1) and 33.5% ± 1.68% (5.8 ± 0.38 Mg ha−1) increases, respectively, were obtained in the reverse processes. Converting forests to grasslands decreased SOC by 2.1% ± 1.22% (−1.13 ± 0.44 Mg ha−1), while the reverse process increased SOC by 18.6% ± 1.73% (3.31 ± 0.51 Mg ha−1). Modeled relative importance of 10 drivers of LUC's impact on SOC revealed that higher initial SOC (iSOC) does not solely determine SOC loss in SOC‐negative LUC scenarios as previously proposed. Across four decades, reconverting croplands to forests and grasslands recovered only 49.5% (6.1 ± 0.51 Mg ha−1) and 75.3% (7.0 ± 0.38 Mg ha−1) of the iSOC, respectively, indicating the need for protecting C‐rich ecosystems. Our global data set advances information on LUC's effect on SOC and can be valuable to constrain Earth system models to reliably estimate global SOC stocks and plan climate change mitigation strategies.

Agricultural non-point source pollution (ANPSP) has caused serious harm to farmland ecological environment, and has become an urgent environmental issue in China. This paper investigates the intention and actual implementation of farmers' green agricultural production behaviors (GAPBs) in Yunnan, China. The results show that 80% of farmers are willing to implement GAPBs for improving agricultural environment, but a large number of them have not implemented at present. In addition, this study integrates normative activation theory with theory of planned behavior to empirically analyze the driving factors of farmers' intention and behaviors. The results show that the direct positive impact of personal norms on behaviors is significant. Awareness of consequences and awareness of responsibility have indirect impacts on GAPBs through personal norms. Meanwhile, attitude has a significant impact on behavioral intention. Awareness of consequences, perceived behavioral control, and subjective norms have indirect effects on behavioral intention through attitude. Besides, there are significant differences in the farmers' GAPBs and the influencing factors between the Han and the ethnic minorities. This paper is helpful to increase farmers' GAPBs and provides reference for the management of ANPSP.

Objective To observe the effect of auricular acupoint scraping therapy on postoperative pain and sleep quality of patients with lower extremity fracture. Methods Totally 70 cases of patients undergoing surgery for lower limb fracture were randomly divided into control group and observation group, with 35 cases in each group. The control group received routine treatment and nursing measures, while the observation group was given auricular acupoint scraping therapy based on the routine treatment and nursing measures. Visual analog pain scale (VAS), Pittsburgh Sleep Quality Index (PSQI) score and patient satisfaction before and after treatment were compared between the two groups. Results There was no significant difference in VAS and PSQI scores between two groups before surgery (P＜0. 05). The VAS scores of observation group was significantly decreased compared with those in the control group at 6h, 12h, 24h, 48h and 72h after surgery(P＜0. 05). The PSQI scores of the observation group were significantly decreased compared with those in the control group at 48 h and 72h after surgery (P＜0. 01). The satisfaction degree of the observation group was higher than that of the control group (P＜0. 01). No treatment-related adverse reactions were observed in two groups. Conclusion The auricular acupoint scraping therapy is effective to reduce the postoperative pain and improve the sleep quality of patients undergoing surgery for lower extremity fracture. (目的 观察耳穴推刮术对下肢骨折术后患者疼痛和睡眠质量的影响。方法 选取下肢骨折术后患者70例, 按照随机数字表法分为对照组和观察组, 每组35例。对照组采取常规治疗和护理措施, 观察组在对照组基础上开展耳穴推刮疗法。比较2组患者治疗前后不同时间段内视觉模拟疼痛评分(VAS)、匹兹堡睡眠质量指数量表(PSQI)评分及患者满意度。结果 术前两组患者的VAS、PSQI评分比较, 差异无统计学意义(P＞0. 05)。观察组患者术后6 h、12h、24h、48h、72 h VAS评分低于对照组, 差异有统计学意义(P＜0. 05)。观察组术后48 h、72 h PSQI评分低于对照组, 差异有统计学意义(P＜0. 01)。观察组患者满意度评分高于对照组, 差异有统计学意义(P＜0. 01)。两组均未见治疗相关不良反应。结论 耳穴推刮疗法可以有效缓解下肢骨折术后患者疼痛程度, 提高睡眠质量。)

AIM: To revise the referral criteria for the SPOT Vision Screener in children under 6 years old and assessed its accuracy based on the American Association for Pediatric Ophthalmology and Strabismus(AAPOS)uniform guidelines for instrument-based pediatric vision screen validation 2021.METHODS: Children who visited the Maternal and Child Health Center of Yuhuatai District in Nanjing city from January 2022 to April 2023 were included in the study and underwent SPOT refractive screening, cycloplegic retinoscopy, and other examinations. Abnormal children were defined according to AAPOS guidelines with amblyopia risk factors(ARFs)and visually significant refractive error(VSRE). Receiver operating characteristic(ROC)curve was used to calculate the optimal referral criteria and compared with manufacturer criteria, Wu's criteria, and Peterseim's criteria.RESULTS: A total of 959 children were examined, with 342 in the