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Mesenchymal stem cells (MSCs), recognized for their self-renewal and multi-lineage differentiation capabilities, have garnered considerable wide attention since their discovery in bone marrow. Recent studies have underscored the potential of MSCs in immune regulation, particularly in the context of autoimmune diseases, which arise from immune system imbalances and necessitate long-term treatment. Traditional immunosuppressive drugs, while effective, can lead to drug tolerance and adverse effects, including a heightened risk of infections and malignancies. Consequently, adjuvant therapy incorporating MSCs has emerged as a promising new treatment strategy, leveraging their immunomodulatory properties. This paper reviews the immunomodulatory mechanisms of MSCs and their application in autoimmune diseases, highlighting their potential to regulate immune responses and reduce inflammation. The immunomodulatory mechanisms of MSCs are primarily mediated through direct cell contact and paracrine activity with immune cells. This review lays the groundwork for the broader clinical application of MSCs in the future and underscores their significant scientific value and application prospects. Further research is expected to enhance the efficacy and safety of MSCs-based treatments for autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background: Lichen planus (LP), an autoimmune disorder, remains incompletely understood in terms of its etiological mechanisms. This study aims to elucidate causal relationships among immune cell populations, plasma metabolites, and lichen planus using Mendelian randomization (MR) techniques. Methods: Employing a two-sample, two-step MR approach, with single nucleotide polymorphisms (SNP) serving as genetic instruments for both exposures and mediators, this study minimizes biases from confounding and reverse causality. Leveraging summary statistics from genome-wide association studies (GWAS) involving 731 immune cell traits (N = 3757), 1091 plasma metabolite traits (N = 8299), and lichen planus (N = 367668), inverse variance weighting (IVW) is adopted as the primary MR analytical method. The total effect of immune cells traits on LP is decomposed into direct and indirect effects mediated by plasma metabolites. Results: MR analysis reveals causal associations for 28 immune cell traits and 38 plasma metabolites with LP (PIVW < 0.05). Specifically, NK % lymphocyte shows a negatively correlated causal effect with LP (ORIVW = 0.952; 95% CI: [0.910, 0.995], PIVW = 0.030). Among mediators, Picolinate significantly contributes, explaining 16.4% (95% CI: [28.3%, 4.54%]) of the association between NK % lymphocyte and LP. Conclusion: These findings support a potential protective causal effect of NK % lymphocyte on LP, partially mediated by Picolinate levels. Thus, interventions targeting Picolinate levels may mitigate LP burden attributed to low NK % lymphocyte counts. This study provides new evidence and insights into the pathogenesis of lichen planus, advancing our understanding of its underlying mechanisms. [ABSTRACT FROM AUTHOR]

This article aims to illustrate that one fundamental reason why the Chinese civilization has remained strong and resilient for over five thousand years and why it has even become stronger in recent times, despite facing numerous challenges. This is due to the strong cultural beliefs embedded in the traditional Chinese culture. Through analysis, synthesis, and comparison, this article aims to demonstrate that, unlike Western religious beliefs, the faith embodied in Chinese traditional culture is a typical humanistic faith, including the Chinese people's beliefs in nature, ancestors, "Tian and Di" (Heaven and Earth), and in the moral nature of human beings. It is precisely this humanistic faith that binds the Chinese nation tightly together. We believe that, in the face of the great challenges and opportunities brought about by the unprecedented transformation of the century, it is especially important for us to continue and develop this dimension of faith. Moreover, this dimension of faith can also provide us with survival wisdom for sustainable development, enabling us to transcend the narrow, individualistic mindset, embrace a broader vision of the world, and realize a universal human love that transcends race and region. [ABSTRACT FROM AUTHOR]

Excessive carbon dioxide (CO2) emissions pose a serious threat to the natural environment; hence CO2 capture and utilization have been widely concerned in industrial production. At present, the high value‐added utilization of CO2 after capture has become a hot issue. Bio‐based carbonate materials with high commercial value can be generated by the reaction of CO2 and bio‐based compounds, which provides a promising, green, and sustainable material synthetic route. Bio‐based carbonate materials, which are suitable for applications in various industries, have excellent thermodynamic and mechanical properties compared with those prepared from petroleum. In this manuscript, the synthesis and utilization of bio‐based carbonates from a variety of bio‐based compounds and CO2 were briefly described, and the existing problems were put forward in the field. It provided a direction for the green utilization of CO2. [ABSTRACT FROM AUTHOR]

• HJC implements the strain-rate effect differently from other models (e.g. K&C). • Further study is necessary to know which implementation method is valid for concrete-like materials. • Several practices used in the original HJC model are questionable. • HJC model underestimates strain-rate effect in compressive domain. • A modified measurement of strain-rate effect in the HJC model is proposed. The strain-rate effect in HJC model is evaluated in this paper. Based on a comparison of strain-rate effects between the HJC and KC models, it shows that the determination and implementation procedures in the HJC model lead to smaller strain-rate effect. Some problems on the determination of strain-rate effect in the HJC model, i.e. the utilisations of the 'leftward' pressure correction, over-simplified strength curve and the cross-domain stress data, are discussed, which cause the underestimation of the strain-rate constant C. A more logical and practically-applicable 'rightward' pressure correction method is proposed to determine the strain-rate effect in the HJC model. The strain-rate effect determined from the high-pressure data is larger than that determined from the uniaxial compressive data, which facilitate further study on the pressure-dependent strain-rate effect. [ABSTRACT FROM AUTHOR]

Introduction: The Internet has caused a great impact on everyone's psychology. Under this background, it is necessary to study whether Marxism can affect college students' mental health. Methods: Firstly, the introduction explains China's concern for college students' mental health and the research achievements. Then, in the method part, this paper analyzes the thoughts and connotations of basic Marxist theory, quality education, and mental health education, mainly studying the changes brought by the Internet to the development of Marxism and the mechanism and influence of Marxism on mental health education. The questionnaire survey is used to investigate the mental health of college students and the current situation of Marxist ideological and political education. Results: The results show that most college students are not interested in ideological and political education, and from the investigation results of five major factors of life stressors and five indicators of psychological crisis factors, it is concluded that college students' life stressors are the risk factors that induce psychological crisis tendency. Discussion: The discussion part shows that it is necessary to cultivate the core quality of college students' development through Marxism, and pay attention to actively preventing and intervening the psychological crisis of college students. This paper analyzes and confirms the effectiveness of Marxist theory on the development of mental health, injects fresh blood into the future ideological and political education and the research of college students' mental health education, and provides theoretical and experimental reference and new ideas. The research has practical reference value for promoting the deep integration of data-driven Marxist basic theory and college students' mental health monitoring. [ABSTRACT FROM AUTHOR]

Background: Hyperpolarization-activated cyclic nucleotide-gated (HCN) current reduces dendritic summation, suppresses dendritic calcium spikes, and enables inhibitory GABA-mediated postsynaptic potentials, thereby suppressing epilepsy. However, it is unclear whether increased HCN current can produce epilepsy. We hypothesized that gain-of-function (GOF) and loss-of-function (LOF) variants of HCN channel genes may cause epilepsy. Objectives: This systematic review aims to summarize the role of HCN channelopathies in epilepsy, update genetic findings in patients, create genotype–phenotype correlations, and discuss animal models, GOF and LOF mechanisms, and potential treatment targets. Methods: The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, for all years until August 2021. Results: We identified pathogenic variants of HCN1 (n = 24), HCN2 (n = 8), HCN3 (n = 2), and HCN4 (n = 6) that were associated with epilepsy in 74 cases (43 HCN1 , 20 HCN2 , 2 HCN3 , and 9 HCN4). Epilepsy was associated with GOF and LOF variants, and the mechanisms were indeterminate. Less than half of the cases became seizure-free and some developed drug-resistant epilepsy. Of the 74 cases, 12 (16.2%) died, comprising HCN1 (n = 4), HCN2 (n = 2), HCN3 (n = 2), and HCN4 (n = 4). Of the deceased cases, 10 (83%) had a sudden unexpected death in epilepsy (SUDEP) and 2 (16.7%) due to cardiopulmonary failure. SUDEP affected more adults (n = 10) than children (n = 2). HCN1 variants p.M234R, p.C329S, p.V414M, p.M153I, and p.M305L, as well as HCN2 variants p.S632W and delPPP (p.719–721), were associated with different phenotypes. HCN1 p.L157V and HCN4 p.R550C were associated with genetic generalized epilepsy. There are several HCN animal models, pharmacological targets, and modulators, but precise drugs have not been developed. Currently, there are no HCN channel openers. Conclusion: We recommend clinicians to include HCN genes in epilepsy gene panels. Researchers should explore the possible underlying mechanisms for GOF and LOF variants by identifying the specific neuronal subtypes and neuroanatomical locations of each identified pathogenic variant. Researchers should identify specific HCN channel openers and blockers with high binding affinity. Such information will give clarity to the involvement of HCN channelopathies in epilepsy and provide the opportunity to develop targeted treatments. [ABSTRACT FROM AUTHOR]

Opioid receptors are members of the group of G protein-couple receptors, which have been proven to be effective targets for treating severe pain. The interactions between the opioid receptors and corresponding ligands and the receptor's activation by different agonists have been among the most important fields in opioid research. In this study, with compound M1, an active metabolite of tramadol, as the clue compound, several aminomethyl tetrahydronaphthalenes were designed, synthesized and assayed upon opioid receptors. With the resultant compounds FW-AII-OH-1 (Ki = 141.2 nM for the κ opioid receptor), FW-AII-OH-2 (Ki = 4.64 nM for the δ opioid receptor), FW-DI-OH-2 (Ki = 8.65 nM for the δ opioid receptor) and FW-DIII-OH-2 (Ki = 228.45 nM for the δ opioid receptor) as probe molecules, the structural determinants responsible for the subtype selectivity and activation mechanisms were further investigated by molecular modeling and molecular dynamics simulations. It was shown that Y7.43 was a key residue in determining the selectivity of the three opioid receptors, and W6.58 was essential for the selectivity of the δ opioid receptor. A detailed stepwise discovered agonist-induced signal transduction mechanism of three opioid receptors by aminomethyl tetrahydronaphthalene compounds was proposed: the 3–7 lock between TM3 and TM7, the DRG lock between TM3 and TM6 and rearrangement of I3.40, P5.50 and F6.44, which resulted in the cooperative movement in 7 TMs. Then, the structural relaxation left room for the binding of the G protein at the intracellular site, and finally the opioid receptors were activated. [ABSTRACT FROM AUTHOR]

Background and Purpose: To date, there is no specific treatment guideline for the benign childhood epilepsy with centrotemporal spikes (BECTS). Several countries recommend levetiracetam, carbamazepine, sodium valproate, oxcarbazepine, and lamotrigine as first-line drugs. Nevertheless, some of these drugs are associated with cognitive decline. Available studies that investigated the efficacy of levetiracetam and sodium valproate on BECTS involved small sample sizes. This study aimed to evaluate the efficacy of levetiracetam and sodium valproate on cognition, and to investigate the prognostic factors for BECTS as whole. Methods: Clinical data and treatment status of all patients with BECTS at Xiangya Hospital, Central South University followed from 2008 to 2013 were analyzed retrospectively. Since electrical status epilepticus in sleep (ESES) has been confirmed to play a role in cognitive deterioration, in order to evaluate the response to drugs and their cognitive effects, we created two groups of patients according to the levels of spike wave index (SWI): group 1; 0–50% SWI and group 2; >50% SWI at the last follow up. Results: A total of 195 cases were enrolled: 49.7% received monotherapies, 24.1% duotherapies and 27.2% polytherapies. Medications included; levetiracetam plus other drug (s) (75.9%), levetiracetam alone (32.8%), sodium valproate plus other drug (s) (31.3%), and sodium valproate alone (5.1%). After 2 years of treatment and follow up, 71% of the cases had a good seizure outcome, 15.9% had an improvement of SWI, and 91.7% had a normal DQ/IQ. Sodium valproate combined with levetiracetam, and sodium valproate alone correlated with good improvement of SWI, whereas, focal spikes were linked with poor improvement. For both groups (group 1 and group 2): monotherapy, levetiracetam alone, and a normal DQ/IQ at seizure onset correlated with good cognitive outcomes, in contrast, polytherapy, sodium valproate plus other drug (s), levetiracetam plus sodium valproate, an initial SWI of ≥85%, and multifocal spikes were linked to cognitive deterioration. Conclusions: Monotherapy, particularly levetiracetam seems to be a good first-line therapy which can help in normalizing the electroencephalograph and preventing cognitive decline. Polytherapy, mostly the administration of sodium valproate seems to relate with poor cognition, therefore, it is recommended to avoid it. [ABSTRACT FROM AUTHOR]

Purpose: To describe a large, publicly available dataset comprising computed tomography (CT) projection data from patient exams, both at routine clinical doses and simulated lower doses. Acquisition and Validation Methods: The library was developed under local ethics committee approval. Projection and image data from 299 clinically performed patient CT exams were archived for three types of clinical exams: noncontrast head CT scans acquired for acute cognitive or motor deficit, low‐dose noncontrast chest scans acquired to screen high‐risk patients for pulmonary nodules, and contrast‐enhanced CT scans of the abdomen acquired to look for metastatic liver lesions. Scans were performed on CT systems from two different CT manufacturers using routine clinical protocols. Projection data were validated by reconstructing the data using several different reconstruction algorithms and through use of the data in the 2016 Low Dose CT Grand Challenge. Reduced dose projection data were simulated for each scan using a validated noise‐insertion method. Radiologists marked location and diagnosis for detected pathologies. Reference truth was obtained from the patient medical record, either from histology or subsequent imaging. Data Format and Usage Notes: Projection datasets were converted into the previously developed DICOM‐CT‐PD format, which is an extended DICOM format created to store CT projections and acquisition geometry in a nonproprietary format. Image data are stored in the standard DICOM image format and clinical data in a spreadsheet. Materials are provided to help investigators use the DICOM‐CT‐PD files, including a dictionary file, data reader, and user manual. The library is publicly available from The Cancer Imaging Archive (https://doi.org/10.7937/9npb‐2637). Potential Applications: This CT data library will facilitate the development and validation of new CT reconstruction and/or denoising algorithms, including those associated with machine learning or artificial intelligence. The provided clinical information allows evaluation of task‐based diagnostic performance. [ABSTRACT FROM AUTHOR]

Intellectual disability (ID) manifests prior to adulthood as severe limitations to intellectual function and adaptive behavior. The role of potassium channelopathies in ID is poorly understood. Therefore, we aimed to evaluate the relationship between ID and potassium channelopathies. We hypothesized that potassium channelopathies are strongly associated with ID initiation, and that both gain- and loss-of-function mutations lead to ID. This systematic review explores the burden of potassium channelopathies, possible mechanisms, advancements using animal models, therapies, and existing gaps. The literature search encompassed both PubMed and Embase up to October 2019. A total of 75 articles describing 338 cases were included in this review. Nineteen channelopathies were identified, affecting the following genes: KCNMA1, KCNN3, KCNT1, KCNT2, KCNJ10, KCNJ6, KCNJ11, KCNA2, KCNA4, KCND3, KCNH1, KCNQ2, KCNAB1, KCNQ3, KCNQ5, KCNC1, KCNB1, KCNC3 , and KCTD3. Twelve of these genes presented both gain- and loss-of-function properties, three displayed gain-of-function only, three exhibited loss-of-function only, and one had unknown function. How gain- and loss-of-function mutations can both lead to ID remains largely unknown. We identified only a few animal studies that focused on the mechanisms of ID in relation to potassium channelopathies and some of the few available therapeutic options (channel openers or blockers) appear to offer limited efficacy. In conclusion, potassium channelopathies contribute to the initiation of ID in several instances and this review provides a comprehensive overview of which molecular players are involved in some of the most prominent disease phenotypes. [ABSTRACT FROM AUTHOR]

This paper presents a statistical analysis of storm surge in Hangzhou Bay, where storm surge is known taking place frequently. This study utilises measurement data taken the period of 1974–2006. The Pearson-III-Pareto distribution model was used first to fit with extreme values based on these measurement data and was then compared with Gumbel, Weibull, Pearson-III, Pareto distribution functions for estimations of extreme storm surge values correspondingly to 100-, 200-, 400-, 500-, 700- and 1000-year return periods. The predicted values of storm surge elevation in the 1000-year return period of the new model are 2.179% higher than the Weibull distribution and 3.546% lower than the Pearson-III distribution. Expectedly, the proposed Pearson-III-Pareto distribution is a more reasonable for presenting the statistical characteristic of extreme values of storm surge. [ABSTRACT FROM AUTHOR]

Purpose: SparseCT, an undersampling scheme for compressed sensing (CS) computed tomography (CT), has been proposed to reduce radiation dose by acquiring undersampled projection data from clinical CT scanners (Koesters et al. in, SparseCT: Interrupted‐Beam Acquisition and Sparse Reconstruction for Radiation Dose Reduction; 2017). SparseCT partially blocks the x‐ray beam with a multislit collimator (MSC) to perform a multidimensional undersampling along the view and detector row dimensions. SparseCT undersamples the projection data within each view and moves the MSC along the z‐direction during gantry rotation to change the undersampling pattern. It enables reconstruction of images from undersampled data using CS algorithms. The purpose of this work is to design the spacing and width of the MSC slits and the MSC motion patterns based on beam separation, undersampling efficiency, and image quality. The development and testing of a SparseCT prototype with the designed MSC will be described in a following paper. Methods: We chose a few initial MSC designs based on the guidance from two metrics: beam separation and undersampling efficiency. Both beam separation and undersampling efficiency were measured from numerically simulated photon distribution with MSC taken into consideration. Beam separation measures the separation between x‐ray beams from consecutive slits, taking into account penumbra effects on both sides of each slit. Undersampling efficiency measures the dose‐weighted similarity between penumbra undersampling and binary undersampling, in other words, the effective contribution of the incident dose to the signal to noise ratio of the projection data. We then compared the initially chosen MSC designs in terms of their reconstruction image quality. SparseCT projections were simulated from fully sampled patient projection data according to the MSC design and motion pattern, reconstructed iteratively using a sparsity‐enforcing penalized weighted least squares cost function with ordered subsets/momentum algorithm, and compared visually and quantitatively. Results: Simulated photon distributions indicate that the size of the penumbra is dominated by the size of the focal spot. Therefore, a wider MSC slit and a smaller focal spot lead to increased beam separation and undersampling efficiency. For fourfold undersampling with a 1.2 mm focal spot, a minimum MSC slit width of three detector rows (projected to the detector surface) is needed for beam separation; for threefold undersampling, a minimum slit width of four detector rows is needed. Simulations of SparseCT projection and reconstruction indicate that the motion pattern of the MSC does not have a visible impact on image quality. An MSC slit width of three or four detector rows yields similar image quality. Conclusion: The MSC is the key component of the SparseCT method. Simulations of MSC designs incorporating x‐ray beam penumbra effects showed that for threefold and fourfold dose reductions, an MSC slit width of four detector rows provided reasonable beam separation, undersampling efficiency, and image quality. [ABSTRACT FROM AUTHOR]

Purpose Model observers have been successfully developed and used to assess the quality of static 2D CT images. However, radiologists typically read images by paging through multiple 2D slices (i.e., multislice reading). The purpose of this study was to correlate human and model observer performance in a low-contrast detection task performed using both 2D and multislice reading, and to determine if the 2D model observer still correlate well with human observer performance in multislice reading. Methods A phantom containing 18 low-contrast spheres (6 sizes × 3 contrast levels) was scanned on a 192-slice CT scanner at five dose levels ( CTDIvol = 27, 13.5, 6.8, 3.4, and 1.7 mGy), each repeated 100 times. Images were reconstructed using both filtered-backprojection ( FBP) and an iterative reconstruction ( IR) method ( ADMIRE, Siemens). A 3D volume of interest ( VOI) around each sphere was extracted and placed side-by-side with a signal-absent VOI to create a 2-alternative forced choice (2 AFC) trial. Sixteen 2 AFC studies were generated, each with 100 trials, to evaluate the impact of radiation dose, lesion size and contrast, and reconstruction methods on object detection. In total, 1600 trials were presented to both model and human observers. Three medical physicists acted as human observers and were allowed to page through the 3D volumes to make a decision for each 2 AFC trial. The human observer performance was compared with the performance of a multislice channelized Hotelling observer ( CHO_ MS), which integrates multislice image data, and with the performance of previously validated CHO, which operates on static 2D images ( CHO_2D). For comparison, the same 16 2 AFC studies were also performed in a 2D viewing mode by the human observers and compared with the multislice viewing performance and the two CHO models. Results Human observer performance was well correlated with the CHO_2D performance in the 2D viewing mode [Pearson product-moment correlation coefficient R = 0.972, 95% confidence interval ( CI): 0.919 to 0.990] and with the CHO_ MS performance in the multislice viewing mode (R = 0.952, 95% CI: 0.865 to 0.984). The CHO_2D performance, calculated from the 2D viewing mode, also had a strong correlation with human observer performance in the multislice viewing mode (R = 0.957, 95% CI: 879 to 0.985). Human observer performance varied between the multislice and 2D modes. One reader performed better in the multislice mode ( P = 0.013); whereas the other two readers showed no significant difference between the two viewing modes ( P = 0.057 and P = 0.38). Conclusions A 2D CHO model is highly correlated with human observer performance in detecting spherical low contrast objects in multislice viewing of CT images. This finding provides some evidence for the use of a simpler, 2D CHO to assess image quality in clinically relevant CT tasks where multislice viewing is used. [ABSTRACT FROM AUTHOR]