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Hyperlipidemia is a metabolic disorder characterized by abnormal lipid metabolism, resulting in lipid accumulation in the plasma. According to reports, medicinal and edible plants can reduce the risk of metabolic diseases such as hyperlipidemia. This study investigates the effects and mechanisms of Astragalus membranaceus extract (AME), Hippophae rhamnoides L. extract (HRE), and Taraxacum mongolicum Hand. Mazz extract (TME) on hyperlipidemia. Active compounds and potential gene targets of AME, HRE, and TME were screened using LC-MS and TCMSP databases, and hyperlipidemia targets were detected from the OMIM and DisGeNet databases. A drug-target pathway disease network was constructed through protein interactions, GO enrichment, and KEGG pathway analysis. Finally, the lipid-lowering effects of three extracts were validated through in vitro HepG2 cell and in vivo animal experiments. The results show that LC-MS and network pharmacology methodologies identified 41 compounds and 140 targets. KEGG analysis indicated that the PI3K-Akt and MAPK signaling pathways significantly treat hyperlipidemia with AHT. In vitro experiments have shown that AHT is composed of a ratio of AME:HRE:TME = 3:1:2. HepG2 cell and animal experiments revealed that AHT exhibits strong lipid-lowering and antioxidant properties, significantly regulating the levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). It is worth noting that AHT can effectively downregulate the protein expression levels of p-AKT/AKT and p-PI3K/PI3K and upregulate the protein expression levels of p-AMPK/AMPK and SIRT1, verifying the results predicted by network pharmacology. This study presents a novel approach to utilizing these natural plant extracts as safe and effective treatments for hyperlipidemia. [ABSTRACT FROM AUTHOR]

Neuritin, also known as candidate plasticity gene 15 (CPG15), was first identified as one of the activity‐dependent gene products in the brain. Previous studies have been reported that Neuritin induces neuritogenesis, neurite arborization, neurite outgrowth and synapse formation, which are involved in the development and functions of the central nervous system. However, the role of Neuritin in peripheral nerve injury is still unknown. Given the importance and necessity of Schwann cell dedifferentiation response to peripheral nerve injury, we aim to investigate the molecular mechanism of Neuritin steering Schwann cell dedifferentiation during Wallerian degeneration (WD) in injured peripheral nerve. Herein, using the explants of sciatic nerve, an ex vivo model of nerve degeneration, we provided evidences indicating that Neuritin vividly accelerates Schwann cell dedifferentiation. Moreover, we found that Neuritin promotes Schwann cell demyelination as well as axonal degeneration, phagocytosis, secretion capacity. In summary, we first described Neuritin acts as a positive regulator for Schwann cell dedifferentiation and WD after peripheral nerve injury. [ABSTRACT FROM AUTHOR]

A knotter is a core component for the automatic bundling of agricultural materials, and a knotter with double-fluted discs is one type. Currently, the research on knotters with double-fluted discs has gradually transitioned from structural design to reliability optimization. To address rope-clamping failures in the rope-clamping drive mechanisms in knotters, the specific failure position of the rope-clamping mechanism and the failure causes were analyzed first. The redesign of the rope-clamping drive mechanism in knotters with double synclastic fluted discs was proposed, including structure optimization and 3D modeling using the GearTrax/KISSsoft and SolidWorks software. A virtual prototype model of a knotter with a flexible rope was established by combining ANSYS with the ADAMS software. A rigid–flexible coupling dynamic simulation of the knotter was carried out using ADAMS, and the simulation results were used as the data input for the ANSYS nCode DesignLife module for the fatigue life simulation of the weak parts (the worm shaft) of the knotter. The operation test results for the rope-clamping drive mechanism indicate that the redesigned rope-clamping drive mechanism is reliable in transmission, with a rope-clamping success rate of 100%. The actual operation times for the worm shaft exceed the minimum fatigue life obtained through joint simulation. The applied joint simulation method has high simulation accuracy. [ABSTRACT FROM AUTHOR]

This paper introduces an MOS-based intelligent temperature sensor with a linear readout. Compared with similar designs, the proposed sensor utilizes the DIBL effect to reduce the precision requirement for the voltage reference source and compensate for the temperature measurement range. A compact voltage reference circuit is introduced, which generates two reference voltage bases using only three transistors. In addition, the proposed digital readout circuit does not require a subtractor or a divider, further saving area. Fabricated in a 55 nm CMOS process, the proposed sensor occupies a compact area of 3216 μ m 2 . Post-simulation results show it has a maximum error of −0.52/+0.28 °C within the temperature range of −20 °C to 120 °C after two-point calibration. The power supply voltage range of the sensor is 0.8 to 1.8 V. It has a maximum voltage sensitivity of 5.7 °C/V and its power consumption is only 166 nW, with a power supply voltage of 0.8 V. [ABSTRACT FROM AUTHOR]

Transistor random threshold voltage variations due to process fluctuations seriously affects the stability of Static Random Access Memory (SRAM). In this paper, a SRAM bit transistors threshold voltage $({Vth})$ deviation monitoring scheme and system is proposed. This scheme ingeniously achieves on-chip measurement of all transistors threshold voltages without altering compact SRAM bit array layout. Control signal strategies and Transistor ${Vth}$ Determination Circuit (TVDC) for different types of Devices Under Test (DUTs) have been proposed. The system is implemented using a 65 nm CMOS process with a core area of 0.01875mm2. Through Monte Carlo analysis, the Weighted Average (WA) difference of the proposed scheme and the direct measurement method is not more than 10mV, and the Root Mean Square Error (RMSE) difference is not more than 3mV. This system can also effectively detect the cell position of the transistor threshold voltage mismatch simulated by modifying the substrate voltage. For SRAM arrays of different scales, the method proposed in this paper has area efficiency and flexible reconfigurability. [ABSTRACT FROM AUTHOR]

Aiming to solve the problem of knot-tripping failure caused by severe wear between the spherical roller and planar cam of the knotter, this paper first establishes a calculation model of the spatial cam contour surface. The knot-tripping mechanism in the knotter is designed as a line-contact curved-surface cam mechanism, with the cutter arm swinging in accordance with sinusoidal acceleration. The design significantly reduces the contact stress between the cam and the roller, compared to the original knot-tripping mechanism. Additionally, it eliminates the impact between the spherical roller and the planar cam. Based on the Archard model, the calculation model for cam-roller wear in the knot-tripping mechanism has been derived and utilized for wear calculation. The wear test results of the knot-tripping mechanism with an aluminum cam show that the curved cam has a wear amount that is 43%, 56%, 46%, and 37% lower than that of the planar cam after tying the knot 200 times, 600 times, 1300 times, and 2000 times, respectively. Under the condition that the twine tension is set to 120 N, and the rotation speed of the fluted disc is 60 rpm, the deviations between the calculated value and the measured value of the wear amount of the curved cam are 9.48%, 6.01%, 7.27%, and 9.95%, respectively. This validates the accuracy of the spatial cam wear model and the correctness of the curved cam design. [ABSTRACT FROM AUTHOR]

Background: Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly.Results: We enrolled 24 patients with isolated macrodactyly. Four of them were diagnosed with Proteus syndrome based on skin presentations characteristic to this disease. Targeted next-generation sequencing was performed using patients' blood and affected tissues. Overall, 20 patients carry mosaic PIK3CA pathogenic variants, i.e. p.His1047Arg (N = 7), p.Glu542Lys (N = 6), p.Glu545Lys (N = 2), p.His1047Leu (N = 2), p.Glu453Lys (N = 1), p.Gln546Lys (N = 1) and p.His1047Tyr (N = 1). Four patients who met the diagnostic criteria of Proteus syndrome carry mosaic AKT1 p.Glu17Lys variant. Variant allele frequencies of these mosaic variants obtained through next-generation sequencing range from 10 to 33%. In genotype-phenotype correlation analysis of patients with PIK3CA variant, we found that patients with the macrodactyly of the lower limbs tend to carry PIK3CA variants located in the helical domain (P = 0.005).Conclusions: Mosaic PIK3CA and AKT1 variants can be found in all of our samples with isolated macrodactyly. Insights into phenotypic and genetic spectrum of isolated macrodactyly may be helpful in perusing a more precise and effective management of isolated macrodactyly. [ABSTRACT FROM AUTHOR]

Background: We previously reported a novel clinically distinguishable subtype of congenital scoliosis (CS), namely, TBX6-associated congenital scoliosis (TACS). We further developed the TBX6-associated CS risk score (TACScore), a multivariate phenotype-based model to predict TACS according to the patient's clinical manifestations. In this study, we aimed to evaluate whether using the TACScore as a screening method prior to performing whole-exome sequencing (WES) is more cost-effective than using WES as the first-line genetic test for CS.Methods: We retrospectively collected the molecular data of 416 CS patients in the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study. A decision tree was constructed to estimate the cost and the diagnostic time required for the two alternative strategies (TACScore versus WES). Bootstrapping simulations and sensitivity analyses were performed to examine the distributions and robustness of the estimates. The economic evaluation considered both the health care payer and the personal budget perspectives.Results: From the health care payer perspective, the strategy of using the TACScore as the primary screening method resulted in an average cost of $1074.2 (95%CI: $1044.8 to $1103.5) and an average diagnostic duration of 38.7d (95%CI: 37.8d to 39.6d) to obtain a molecular diagnosis for each patient. In contrast, the corresponding values were $1169.6 (95%CI: $1166.9 to $1172.2) and 41.4d (95%CI: 41.1d to 41.7d) taking WES as the first-line test (P < 0.001). From the personal budget perspective, patients who were predicted to be positive by the TACScore received a result with an average cost of $715.1 (95%CI: $594.5 to $835.7) and an average diagnostic duration of 30.4d (95%CI: 26.3d to 34.6d). Comparatively, the strategy of WES as the first-line test was estimated to have significantly longer diagnostic time with an average of 44.0d (95%CI: 43.2d to 44.9d), and more expensive with an average of $1193.4 (95%CI: $1185.5 to $1201.3) (P < 0.001). In 100% of the bootstrapping simulations, the TACScore strategy was significantly less costly and more time-saving than WES. The sensitivity analyses revealed that the TACScore strategy remained cost-effective even when the cost per WES decreased to $8.8.Conclusions: This retrospective study provides clinicians with economic evidence to integrate the TACScore into clinical practice. The TACScore can be considered a cost-effective tool when it serves as a screening test prior to performing WES. [ABSTRACT FROM AUTHOR]

• A unified framework to detect cervical cancer using multimodal medical images. • An adaptive multi-model method to fuse multimodal medical images. • PET/CT fusion is more beneficial for the detection of cervical cancer than using either of them on their own; for example, only using CT mode detection or only using PET mode detection is not better than using PET/CT fusion mode detection. Cervical cancer is the fourth most common cancer in women, and its precise detection plays a critical role in disease treatment and prognosis prediction. Fluorodeoxyglucose positron emission tomography and computed tomography, i.e., FDG-PET/CT and PET/CT, have established roles with superior sensitivity and specificity in most cancer imaging applications. However, a typical FDG-PET/CT analysis involves the time-consuming process of interpreting hundreds of images, and the intense image screening work has greatly hindered clinicians. We propose a computer-aided deep learning-based framework to detect cervical cancer using multimodal medical images to increase the efficiency of clinical diagnosis. This framework has three components: image registration, multimodal image fusion, and lesion object detection. Compared to traditional approaches, our adaptive image fusion method fuses multimodal medical images. We discuss the performance of deep learning in each modality, and we conduct extensive experiments to compare the performance of different image fusion methods with some state-of-the-art (SOTA) object-detection deep learning-based methods in images with different modalities. Compared with PET, which has the highest recognition accuracy in single-modality images, the recognition accuracy of our proposed method on multiple object detection models is improved by an average of 6.06%. And compared with the best results of other multimodal fusion methods, our results have an average improvement of 8.9%. [ABSTRACT FROM AUTHOR]

Objectives: The project intended to analyze the impact of burden and related risk factors of late-onset colorectal cancer (LOCRC) and early-onset colorectal cancer (EOCRC) in China, thus offering essential references for optimizing prevention and control strategies., Method: Global Burden of Disease Study was employed to describe burden changes of EOCRC and LOCRC in China during 1990-2019, containing the numbers of incidence, deaths, prevalence, and disability-adjusted life years (DALYs), and to compare attributable deaths and DALYs risk factors in varying age and sex segments., Results: The numbers and corresponding crude rates of incidence, deaths, prevalence, and DALYs of EOCRC and LOCRC in China during 1990-2019 demonstrated an upward trend across all age categories, with males being dramatically predominant. Overall, over time, the impact of a low-calcium diet and a low-fiber diet on mortality and DALY rates decreased, while the impact of other risk factors increased. In terms of gender, the risk factors affecting males changed greatly, with smoking, inadequate milk intake, and the low whole-grain diet being the main factors in 2019, while in 1990, the main factors were the low-calcium diet, smoking, and inadequate milk intake., Conclusion: The burden of colorectal cancer in China is concerning. Patients grouped by diagnostic age exhibit different characteristics, indicating the need for high-quality research in the future to achieve personalized medicine tailored to different population characteristics., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A rare autosomal recessive genetic disease is spinal muscular atrophy with respiratory distress type 1 (SMARD 1; OMIM #604320), which is characterized by progressive distal limb muscle weakness, muscular atrophy, and early onset of respiratory failure. Herein, we report the case of a 4-month-old female infant with SMARD type 1 who was admitted to our hospital owing to unexplained distal limb muscle weakness and early respiratory failure. This report summarizes the characteristics of SMARD type 1 caused by heterozygous variation in the immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene by analyzing its clinical manifestations, genetic variation characteristics, and related examinations, aiming to deepen clinicians' understanding of the disease, assisting pediatricians in providing medical information to parents and improving the decision-making process involved in establishing life support., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Chen, Chen and Feng.)

Background: Osteoporotic vertebral compression fractures (OVCF) appear to be more common as the population ages. Previous studies have found that percutaneous vertebroplasty (PVP) can achieve better short-term clinical outcomes than conservative treatment (CT) for OVCF. However, the long-term outcomes of PVP compared with CT for OVCF has been rare explored. This study was designed to explore the clinical outcomes of PVP or CT within 3 years after OVCF., Methods: This study reviewed the clinical outcomes of patients who underwent PVP or CT for OVCF in a single center from January 2015 to December 2019. The back pain visual analogue scale (VAS), Oswestry disability index (ODI) and satisfaction rate were compared between the two groups at baseline, 1 week, 1 month, 3 months, 6 months, 12 months, 24 months and 36 months after treatment., Outcomes: The baseline data including gender, age, bone mineral density, body mass index, back pain VAS, and ODI were not significantly different between the two groups. The back pain VAS and ODI of CT patients were significantly higher than those of PVP group at 1 week, 1 month, 3 months, 6 months and 12 months after treatment. The satisfaction rate in the PVP group were significantly higher than those in the CT group at 1 week, 1 month, 3 months and 6 months after treatment. Subsequently, the back pain VAS and ODI showed no significant difference between the two groups at 24 and 36 months. In addition, there was no significant difference in treatment satisfaction between the two groups at 36 months. There was no significant difference in the rate of new vertebral compression fractures between the two groups within 36 months after treatment., Conclusion: The clinical outcomes within 12 months after PVP and patient satisfaction rate within 6 months after PVP were significantly higher than CT. However, during 12 months to 36 months, this advantage generated by PVP was gradually diluted over time. Compared with CT, the long-term effect of PVP on OVCF should not be overestimated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Xu, Shi, Cao and Nie.)

The damage of islet cells caused by oxidative stress is closely related to diabetes. The aim of this study is to investigate the protective effect of saponins isolated from polygonatum sibiricum (PSS) on pancreas injury by using in vitro and in vivo models. The oxidative stress model of RIN-m5F cells induced by H 2 O 2 was established. We found that PSS could decrease the apoptosis of RIN-m5F cells under oxidative stress. After PSS treatment, ROS and MDA levels in cells significantly decreased. Moreover, the levels of SOD and GSH were significantly increased. PSS could increase the insulin secretion level of cells under oxidative stress. The expression level of intracellular Bcl-2 increased, and the expression levels of Bax, caspase-3, caspase-8, and caspase-9 decreased significantly. In addition, the type 2 diabetes mouse model was established. The results showed that PSS had a protective effect on the injury of the pancreas in T2DM mice. PSS can relieve oxidative stress and high glucose-mediated pancreas cytotoxicity. PSS may be a promising candidate for diabetes intervention and functional foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)