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JOURNAL/nrgr/04.03/01300535-202508000-00031/figure1/v/2024-09-30T120553Z/r/image-tiff The protein connector enhancer of kinase suppressor of Ras 2 (CNKSR2), present in both the postsynaptic density and cytoplasm of neurons, is a scaffolding protein with several protein-binding domains. Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders, particularly intellectual disability, although the precise mechanism involved has not yet been fully understood. Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane, thereby influencing synaptic signaling and the morphogenesis of dendritic spines. However, the function of CNKSR2 in the cytoplasm remains to be elucidated. In this study, we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2. Through a combination of bioinformatic analysis and cytological experiments, we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome. We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290. Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2. When we downregulated CNKSR2 expression in mouse neuroblastoma cells (Neuro 2A), we observed significant changes in the expression of numerous centrosomal genes. This manipulation also affected centrosome-related functions, including cell size and shape, cell proliferation, and motility. Furthermore, we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder. Our findings establish a connection between CNKSR2 and the centrosome, and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

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BACKGROUND: Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells. METHODS: We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures. RESULTS: We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro. CONCLUSIONS: Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.

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Background: Pancreatic neuroendocrine neoplasm (pNEN) poses significant challenges in clinical management due to their heterogeneity and limited treatment options. In this study, we investigated the potential of simvastatin (SIM) as an anti-tumor agent in pNEN. Methods: We conducted cell culture experiments using QGP-1 and BON-1 cell lines and assessed cell viability, proliferation, migration, and invasion following SIM treatment. To further validate our findings, we performed in vivo experiments using a mouse xenograft model. Additionally, we investigated the underlying molecular mechanisms by analyzing changes in cell cycle progression, apoptosis, and signaling pathways. Results: SIM treatment suppresses pNEN growth both in vitro and in vivo, and led to G1 phase arrest in QGP-1 cells. In contrast, SIM affected both the G1-S and G2-M phase transitions in the BON-1 cell line and induced apoptosis, indicating diverse mechanisms of action. Furthermore, SIM treatment resulted in decreased expression of mutant p53 (mutp53) in BON-1 cells, suggesting a potential therapeutic strategy targeting mutp53. Modulation of the MAPK pathway was also implicated in QGP-1 cells. Conclusions: Our study highlights SIM as a promising candidate for pNEN treatment by inducing cell cycle arrest or apoptosis, potentially through the p53 and MAPK pathways. Further research is warranted to fully elucidate SIM's mechanisms of action and evaluate its therapeutic potential in clinical settings.

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Pancreatic lipase (PL) is the main enzyme in the digestive system that breaks down triglyceride and promotes its absorption. In this paper, we found that lignans 2, 3 and 21, curcuminoids 24-26 exhibited significant inhibitory potential against PL. The structure-activity relationship (SAR) indicated that benzo-1, 3-dioxole group in the construction of lignans is essential to inhibitory effects against PL, while double bonds at C-7/C-2 position and 4-hydroxyphenyl moiety in the structure of curcuminoids are beneficial for PL inhibition. The kinetic studies and molecular docking were also conducted, the results showed that the three curcuminoids with the strongest inhibition effect above were all mixed inhibitors of PL. Furthermore, curcuminoids 24-26 displayed a preferential selectivity towards, in contrast to other serine hydrolases. The above results indicate that lignans and curcuminoids are natural functional components for PL inhibition, providing new ideas for finding and developing novel lead compounds for the treatment of obesity.

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Objective: To investigate the diagnostic efficacy of the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model based on ultrasonographic radiomics for the differentiation of small clear cell Renal Cell Carcinoma (ccRCC) and Renal Angiomyolipoma (RAML). Methods: The clinical, ultrasound, and contrast-enhanced CT(CECT) imaging data of 302 small renal tumors (maximum diameter ≤ 4cm) patients in Tianjin Medical University Cancer Institute and Hospital from June 2018 to June 2022 were retrospectively analyzed, with 182 patients of ccRCC and 120 patients of RAML. The ultrasound images of the largest diameter of renal tumors were manually segmented by ITK-SNAP software, and Pyradiomics (v3.0.1) module in Python 3.8.7 was applied to extract ultrasonographic radiomics features from ROI segmented images. The patients were randomly divided into training and internal validation cohorts in the ratio of 7:3. The Random Forest algorithm of the Sklearn module was applied to construct the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model. The efficacy of the prediction models was verified in an independent external validation cohort consisting of 69 patients, from 230 small renal tumor patients in two different institutions. The Delong test compared the predictive ability of three models and CECT. Calibration Curve and clinical Decision Curve Analysis were applied to evaluate the model and determine the net benefit to patients. Results: 491 ultrasonographic radiomics features were extracted from 302 small renal tumor patients, and 9 ultrasonographic radiomics features were finally retained for modeling after regression and dimensionality reduction. In the internal validation cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy of the clinical ultrasound imaging model, ultrasonographic radiomics model, comprehensive model, and CECT were 0.75, 76.7%, 60.0%, 70.0%; 0.80, 85.6%, 61.7%, 76.0%; 0.88, 90.6%, 76.7%, 85.0% and 0.90, 92.6%, 88.9%, 91.1%, respectively. In the external validation cohort, AUC, sensitivity, specificity, and accuracy of the three models and CECT were 0.73, 67.5%, 69.1%, 68.3%; 0.89, 86.7%, 80.0%, 83.5%; 0.90, 85.0%, 85.5%, 85.2% and 0.91, 94.6%, 88.3%, 91.3%, respectively. The DeLong test showed no significant difference between the clinical ultrasound imaging model and the ultrasonographic radiomics model (Z=-1.287, P=0.198). The comprehensive model showed superior diagnostic performance than the ultrasonographic radiomics model (Z=4. 394, P<0.001) and the clinical ultrasound imaging model (Z=4. 732, P<0.001). Moreover, there was no significant difference in AUC between the comprehensive model and CECT (Z=-0.252, P=0.801). Both in the internal and external validation cohort, the Calibration Curve and Decision Curve Analysis showed a better performance of the comprehensive model. Conclusion: It is feasible to construct an ultrasonographic radiomics model for distinguishing small ccRCC and RAML based on ultrasound images, and the diagnostic performance of the comprehensive model is superior to the clinical ultrasound imaging model and ultrasonographic radiomics model, similar to that of CECT.

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We undertook a survey among epileptologists in China to explore their attitudes toward physical exercise and sports for persons with epilepsy (PWEs). A total of 288 epileptologists participated. Most recognized the potential benefits of physical exercise and sports for PWEs, including improved cognitive function (74.6 %), alleviation of mental disorders (73.2 %), and enhanced quality of life (83.8 %). Epileptologists overwhelmingly agreed on the importance of discussing and encouraging physical exercise and sports for PWEs (97.4 % and 95.2 %, respectively). Before engagement in physical exercise and sports, most epileptologists considered that the duration of seizure-free status could be shorter if the seizures were typically focal, non-motor, or without impaired awareness (p < 0.05). There was consensus (99.1 %) on the need to grade the risk of related activities. Opinions were divided regarding the use of health certificates for restricting PWEs (favored by 63.2 %). The majority (93.9 %) called for an expert consensus or clinical guidelines in China. In conclusion, epileptologists in China generally demonstrate a positive attitude toward physical exercise and sports for PWEs. Both benefits and risks of these activities have generally been acknowledged. It is recommended to prioritize activities with lower risks and higher benefits. However, the recommendations for PWEs with a lower likelihood of recurrence and less risky seizure types can be more liberal. Urgent development of normative guidance from governmental and professional bodies is warranted.

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Transgenerational gene expression depends on both underlying DNA sequences and epigenetic modifications. The latter, which can result in transmission of variegated gene expression patterns across multiple generations without DNA alterations, has been termed epigenetic inheritance and has been documented in plants, worms, flies and mammals. Whereas transcription factors binding to cognate DNA sequence elements regulate gene expression, the molecular basis for epigenetic inheritance has been linked to histone and DNA modifications and non-coding RNA. Here we report that mutation of the CCAAT box promoter element abrogates NF-Y binding and disrupts the stable transgenerational expression of an MHC class I transgene. Transgenic mice with a mutated CCAAT box in the MHC class I transgene display variegated expression of the transgene among littermates and progeny in multiple independently derived transgenic lines. After 4 generations, CCAAT mutant transgenic lines derived from a single founder stably displayed distinct patterns of expression. Histone modifications and RNA polymerase II binding correlate with expression of CCAAT mutant transgenic lines, whereas DNA methylation and nucleosome occupancy do not. Mutation of the CCAAT box also results in changes to CTCF binding and DNA looping patterns across the transgene that correlate with expression status. These studies identify the CCAAT promoter element as a regulator of stable transgenerational gene expression such that mutation of the CCAAT box results in variegated transgenerational inheritance. Considering that the CCAAT box is present in 30% of eukaryotic promoters, this study provides insights into how fidelity of gene expression patterns is maintained through multiple generations.

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OBJECTIVE: Previous research on diagnostic assessment by superb microvascular imaging (SMI) were based on qualitative or semi-quantitative assessments of vascularity, which may be subjective and unrepeatable by different sonographers. This study aimed to evaluate diagnostic performance of SMI Image-pro Plus (IPP) based vascular index (VI) for malignant renal masses. METHOD: We retrospectively reviewed 222 masses in 214 patients who underwent SMI between August 2019 and August 2022 in our study. We evaluated the diagnostic performance of blood flow via Alder grade, VI based on both IPP and SMI. RESULTS: The kappa consistency of the Adler grade and VI for renal masses was classified among different observers were 0.765 and 0.824. The intra-observers correlation ecoefficiency (ICC) were 0.727 and 0.874. Benign renal masses were mainly Adler grade 0, grade I, and grade II, VI was 4.30 ± 4.27 (Range 0.98-16.42); while malignant masses were mainly Adler grade III, VI was 14.95 ± 10.94 (Range 0.79-56.89). VI was higher in malignant than benign masses (t = 15.638, P < 0.01). Among the malignant masses, the mean VI in clear cell renal cell carcinoma was higher than that in papillary renal cell carcinoma and chromophobe renal cell carcinoma (F = 30.659, P < 0.01). The sensitivity, specificity and accuracy of SMI were 80.00%, 71.15%, and 78.64%, respectively. The sensitivity, specificity, and accuracy were 60.59%, 88.46%, and 80.18% by using a VI of 7.95 as the cutoff value to identify malignant lesions from benign masses yielded. VI had better diagnostic efficiency than ultrasonic characteristics and Adler grade in benign and malignant differential diagnosis (Z = 4.851, P < 0.01; Z = 2.732, P < 0.01). CONCLUSION: VI was higher in malignant than benign in renal masses. In malignant masses, VI in CCRCC was higher than that in papillary renal cell carcinoma and ChRCC. As a noninvasive examination, it had important clinical significance in the differential diagnosis of renal masses. VI from IPP may assist sonographer in distinguish renal malignances as a quantitative tool for vascularity.

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Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.

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BACKGROUND: Myosteatosis, rather than low muscle mass, is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus (T2DM). Myosteatosis may lead to a series of metabolic dysfunctions, such as insulin resistance, systematic inflammation, and oxidative stress, and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis. AIM: To investigate the association between myosteatosis and coronary artery calcification (CAC) in patients with T2DM. METHODS: Patients with T2DM, who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography (CT) scans, were included. The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level. The CAC score was determined from thoracic CT images using the Agatston scoring method. Myosteatosis was diagnosed according to Martin's criteria. Severe CAC (SCAC) was defined when the CAC score exceeded 300. Logistic regression and decision tree analyses were performed. RESULTS: A total of 652 patients with T2DM were enrolled. Among them, 167 (25.6%) patients had SCAC. Logistic regression analysis demonstrated that myosteatosis, age, duration of diabetes, cigarette smoking, and alcohol consumption were independent risk factors of SCAC. Myosteatosis was significantly associated with an increased risk of SCAC (OR = 2.381, P = 0.003). The association between myosteatosis and SCAC was significant in the younger patients (OR = 2.672, 95%CI: 1.477-4.834, P = 0.002), but not the older patients (OR = 1.456, 95%CI: 0.863-2.455, P = 0.188), and was more prominent in the population with lower risks of atherosclerosis. The decision tree analyses prioritized older age as the primary variable for SCAC. In older patients, cigarette smoking was the main contributing factor for SCAC, while in younger patients, it was myosteatosis. CONCLUSION: Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM, especially in the population with younger ages and fewer traditional risk factors.

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Here, 1,3,4-thiadiazole unit was employed as novel excited state intramolecular proton transfer (ESIPT) structure to prepare favorable fluorescent probe. High selectivity and rapid response to Cu2+ was obtained and the settling reaction was also used to recover ESIPT characteristics of probe to achieve sequential detection of H2S. Remarkable color change of solution from colorless to bright yellow and fluorescence emission from green to dark realized the visual detection of Cu2+ by naked eyes and transition of probe into portable fluorescent test strips. As expected, L-E could be utilized to quantitatively sense Cu2+ and H2S in different actual water and food samples including herbs, wine and fruits. The limits of detection for Cu2+ and H2S were as low as 34.5 nM and 38.6 nM. Also, probe L-E achieved real-time, portable, on-site quantitative detection of Cu2+ via a colorimeter and a smartphone platform with limit of detection to 90.3 nM.

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SLC25A51 selectively imports oxidized NAD+ into the mitochondrial matrix and is required for sustaining cell respiration. We observed elevated expression of SLC25A51 that correlated with poorer outcomes in patients with acute myeloid leukemia (AML), and we sought to determine the role SLC25A51 may serve in this disease. We found that lowering SLC25A51 levels led to increased apoptosis and prolonged survival in orthotopic xenograft models. Metabolic flux analyses indicated that depletion of SLC25A51 shunted flux away from mitochondrial oxidative pathways, notably without increased glycolytic flux. Depletion of SLC25A51 combined with 5-azacytidine treatment limits expansion of AML cells in vivo. Together, the data indicate that AML cells upregulate SLC25A51 to decouple mitochondrial NAD+/NADH for a proliferative advantage by supporting oxidative reactions from a variety of fuels. Thus, SLC25A51 represents a critical regulator that can be exploited by cancer cells and may be a vulnerability for refractory AML.

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OBJECTIVES: Epilepsy care in China has expanded considerably in the last decade but still remains largely unknown; we developed an easy-to-use tool to assess its quality. METHODS: We adapted the Epilepsy Update Quality Measurement, produced by the American Academy of Neurology (AAN) for use in China: The Quality Indicator for Epilepsy Treatment-China National Action (QUIET-CHINA). This tool incorporates a standardized case report form initially for logging quality indicators for people with epilepsy during in-patient stays. Nine quality indicators covered seizures, drugs, diagnostics, screening for co-morbid conditions, counseling for woman of child bearing age, and a composite indicator was further proposed by total number of interventions performed divided by the total number of people eligible in each indicator. The tool also has an electronic reporting and data feedback system. 96 epilepsy centers in 31 jurisdictions in mainland China have been piloted since 2017. RESULTS: Data from 11,600 individuals with epilepsy in the first 3-year study period were analyzed. The median age was 31; 60% were male. The composite indicators were 74%. Seizure freedom rate was less than 25% in all epilepsy types and post-surgical seizure freedom rate was 21%. 90% had seizure type and frequency, antiepileptic drugs recorded, while only 70% with active epilepsy were on regular antiepileptic drugs treatment. Investigations for diagnosis and etiology were performed in around 90% but screening for co-morbid conditions and counseling for women of childbearing potential was 38% and 15% respectively. Severe side effect happened in 2% individuals during the treatment. CONCLUSION: The preliminary results of the national action provided some baseline information. Except for an overall improvement, a significant treatment gap still exists, and psychiatric co-morbidities or issues affecting women are not seen as a priority. QUIET-CHINA will be expanded to more and other levels of hospitals, to help narrow the treatment gap and equalize the comprehensive epilepsy care on the national level.

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Practical applications of synthetic self-propelled nano and microparticles for microrobotics, targeted drug delivery, and manipulation at the nanoscale are rapidly expanding. However, fabrication limitations often hinder progress, resulting in relatively simple shapes and limited functionality. Here, taking advantage of 3D nanoscale printing, chiral micropropellers powered by the hydrogen peroxide reduction reaction are fabricated. Due to their chirality, the propellers exhibit multifunctional behavior controlled by an applied magnetic field: spinning in place (loitering), directed migration in the prescribed direction, capture, and transport of polymer cargo particles. Design parameters of the propellers are optimized by computation modeling based on mesoscale molecular dynamics. It is predicted by computer simulations, and confirmed experimentally, that clockwise rotating propellers attract each other and counterclockwise repel. These results shed light on how chirality and shape optimization enhance the functionality of synthetic autonomous micromachines.

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Objective: To review research advances of revision surgery after primary total hip arthroplasty (THA) for patients with Crowe type Ⅳ developmental dysplasia of the hip (DDH). Methods: The recent literature on revision surgery after primary THA in patients with Crowe type Ⅳ DDH was reviewed. The reasons for revision surgery were analyzed and the difficulties of revision surgery, the management methods, and the related prosthesis choices were summarized. Results: Patients with Crowe type Ⅳ DDH have small anteroposterior diameter of the acetabulum, large variation in acetabular and femoral anteversion angles, severe soft tissue contractures, which make both THA and revision surgery more difficult. There are many reasons for patients undergoing revision surgery after primary THA, mainly due to aseptic loosening of the prosthesis. Therefore, it is necessary to restore anatomical structures in primary THA, as much as possible and reduce the generation of wear particles to avoid postoperative loosening of the prosthesis. Due to the anatomical characteristics of Crowe type Ⅳ DDH, the patients have acetabular and femoral bone defects, and the repair and reconstruction of bone defects become the key to revision surgery. The acetabular side is usually reconstructed with the appropriate acetabular cup or combined metal block, Cage, or custom component depending on the extent of the bone defect, while the femoral side is preferred to the S-ROM prosthesis. In addition, the prosthetic interface should be ceramic-ceramic or ceramic-highly cross-linked polyethylene wherever possible. Conclusion: The reasons leading to revision surgery after primary THA in patients with Crowe type Ⅳ DDH and the surgical difficulties have been clarified, and a large number of clinical studies have proposed corresponding revision modalities based on which good early- and mid-term outcomes have been obtained, but further follow-up is needed to clarify the long-term outcomes. With technological advances and the development of new materials, personalized prostheses for these patients are expected to become a reality.

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Background: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) and stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) are two effective, minimally invasive treatments for epilepsy with focal cortical dysplasia (FCD). The purpose of this study is to conduct a meta-analysis to evaluate and compare the efficacy and safety of these two therapies in epilepsy patients with FCD. Methods: We searched PubMed, Embase, Cochrane, and other databases for articles published before March 2023. The primary objective was to compare the effectiveness and complications of MRgLiTT and SEEG-RFTC in epilepsy patients with FCD. The second objective was to determine which method provides a better prognosis for specific subgroup patients. Results: According to the inclusion and exclusion criteria, 18 studies were included, comprising 270 FCD patients including 37 patients from 6 MRgLiTT studies and 233 from 12 SEEG-RFTC studies. There were no significant differences between MRgLiTT and SEEG-RFTC groups in the seizure-freedom rate (59%, 95% CI 44-74%; 52%, 95% CI 47-57%, P = 0.86) and the rate of ≥50% seizure-reduction of FCD (90%, 95% CI 80-100%; 90%, 95% CI 86-94%, P = 0.42). Both methods had low complication rates (17.1%, 28/159) and long-term complication (2.5%, 4/159) rate, with no significant difference between them (P = 0.17). Conclusion: Both MRgLiTT and SEEG-RFTC are safe and minimally invasive treatments for patients with FCD. They have comparable performance in terms of postoperative seizure-freedom rates in patients with FCD, and both can be used as treatment options for patients with FCD. Our study found that SEEG-RFTC had a better therapeutic effect in the FCD2b subgroup.

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In a stretcher, the surface distortion of the optical elements can introduce spectral phase modulations into the laser, which can affect the laser's signal-to-noise ratio. In this paper, by combining ray tracing methods and angular spectrum diffraction methods, the impact of the mid-frequency surface distortion of the optical elements in an cylindrical Offner stretcher on the far-field signal-to-noise ratio of the laser is simulated. The results show that reducing the spatial chirp on the convex cylindrical mirror can effectively improve the far-field signal-to-noise ratio of the laser, and two methods to improve the far-field signal-to-noise ratio are presented.

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OBJECTIVES: To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. METHODS: A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. RESULTS: Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. CONCLUSIONS: MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

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Advances in single-cell sequencing and data analysis have made it possible to infer biological trajectories spanning heterogeneous cell populations based on transcriptome variation. These trajectories yield a wealth of novel insights into dynamic processes such as development and differentiation. However, trajectory analysis relies on an assumption of trajectory continuity, and experimental limitations preclude some real-world scenarios from meeting this condition. The current lack of assessment metrics makes it difficult to ascertain if/when a given trajectory deviates from continuity, and what impact such a divergence would have on inference accuracy is unclear. By analyzing simulated breaks introduced into in silico and real single-cell data, we found that discontinuity caused precipitous drops in the accuracy of trajectory inference. We then generate a simple scoring algorithm for assessing trajectory continuity, and found that continuity assessments in real-world cases of intestinal stem cell development and CD8 + T cells differentiation efficiently identifies trajectories consistent with empirical knowledge. This assessment approach can also be used in cases where a priori knowledge is lacking to screen a pool of inferred lineages for their adherence to presumed continuity, and serve as a means for weighing higher likelihood trajectories for validation via empirical studies, as exemplified by our case studies in psoriatic arthritis and acute kidney injury. This tool is freely available through github at qingshanni/scEGRET.

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In the context of global climate change and the influence of human activities, the concept of "sponge city" is put forward to realize the purification, collection, and reuse of rainwater. The effective evaluation of LID facilities in sponge cities is of great guiding significance for the promotion and construction of sponge cities. IFMS (Integrated Flood Modeling System) Urban was selected to construct the rainstorm simulation. LID parameters were added to simulate the improvement of urban waterlogging after the construction of sponge city. A reasonable disaster loss assessment method was used to calculate the disaster mitigation benefit brought by the construction of sponge city. Through the comparison of the inundation situation before and after LID facilities' construction, it can be concluded that the mitigation effect of LID facilities on the overall inundation area of the city decreases with the increase of rainfall recurrence period, with the maximum reduction rate reaching 13.63% in the 5-year recurrence period and the minimum reduction rate of 11.06% in the 50-year recurrence period. LID facilities have a better disaster reduction effect for rainfall events with a small recurrence period than for rainfall events with a large recurrence period.