miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Automated segmentation of liver and hepatic vessels on portal venous phase computed tomography images using a deep learning algorithm.

BACKGROUND: CT-image segmentation for liver and hepatic vessels can facilitate liver surgical planning. However, time-consuming process and inter-observer variations of manual segmentation have limited wider application in clinical practice. PURPOSE: Our study aimed to propose an automated deep learning (DL) segmentation algorithm for liver and hepatic vessels on portal venous phase CT images. METHODS: This retrospective study was performed to develop a coarse-to-fine DL-based algorithm that was trained, validated, and tested using private 413, 52, and 50 portal venous phase CT images, respectively. Additionally, the performance of the DL algorithm was extensively evaluated and compared with manual segmentation using an independent clinical dataset of preoperative contrast-enhanced CT images from 44 patients with hepatic focal lesions. The accuracy of DL-based segmentation was quantitatively evaluated using the Dice Similarity Coefficient (DSC) and complementary metrics [Normalized Surface Dice (NSD) and Hausdorff distance_95 (HD95) for liver segmentation, Recall and Precision for hepatic vessel segmentation]. The processing time for DL and manual segmentation was also compared. RESULTS: Our DL algorithm achieved accurate liver segmentation with DSC of 0.98, NSD of 0.92, and HD95 of 1.52 mm. DL-segmentation of hepatic veins, portal veins, and inferior vena cava attained DSC of 0.86, 0.89, and 0.94, respectively. Compared with the manual approach, the DL algorithm significantly outperformed with better segmentation results for both liver and hepatic vessels, with higher accuracy of liver and hepatic vessel segmentation (all p < 0.001) in independent 44 clinical data. In addition, the DL method significantly reduced the manual processing time of clinical postprocessing (p < 0.001). CONCLUSIONS: The proposed DL algorithm potentially enabled accurate and rapid segmentation for liver and hepatic vessels using portal venous phase contrast CT images.

Maintenance treatment of immunotherapy after microwave ablation plus drug-eluting bead bronchial arterial chemoembolization for advanced non-small cell lung cancer: a retrospective single-center cohort study.

Background: The combination therapy of immunotherapy and drug-eluting bead bronchial artery chemoembolization (DEB-BACE) or microwave ablation (MWA) has been attempted as an effective and safe approach for advanced non-small cell lung cancer (NSCLC). However, the outcomes of immunotherapy plus multiple interventional techniques for advanced NSCLC remain unclear. This retrospective study thus aimed to investigate the effectiveness and safety of the maintenance treatment of programmed cell death protein 1 (PD-1) blockade after MWA plus DEB-BACE for advanced NSCLC. Methods: This retrospective cohort study consists of 95 patients with advanced NSCLC who were treated with DEB-BACE between April 2017 and October 2022 and who were allocated to three groups: group A (MWA + DEB-BACE + PD-1 blockade; n=15), group B (MWA + DEB-BACE; n=25), and group C (DEB-BACE alone; n=55). The adverse events (AEs) were compared between the three groups. The outcomes were compared via Kaplan-Meier methods, including median progression-free survival (PFS) and overall survival (OS). Survival analyses were performed via the univariate and multivariate analyses to investigate the prognostic predictors. Results: The overall incidence of AEs in the groups A-C was 53.3% (8/15), 36.0% (9/25), and 32.7% (18/55), respectively, which did not represent a significant difference (P=0.42). No severe AEs (SAEs) occurred. Group A, compared with group B and group C, had a significantly longer estimated median PFS (33.0 vs. 7.0 vs. 3.0 months; P<0.001) and OS (33.0 vs. 13.0 vs. 6.0 months; P=0.002). PD-1 blockade (P=0.006), tumor number (P=0.01), and DEB-BACE/bronchial artery infusion (BAI) chemotherapy cycles (P=0.04) were identified as the predictors of PFS, while the predictors of OS were PD-1 blockade (P<0.001), number of metastases (P<0.001), tumor diameter (P<0.001), and DEB-BACE/BAI cycles (P=0.02). Conclusions: Compared with that of advanced NSCLC treated with MWA plus DEB-BACE or DEB-BACE alone, the maintenance treatment of immunotherapy after MWA plus DEB-BACE might provide a superior prognosis without increasing the risk of AEs.

Screening parameters for diagnosing primary aldosteronism in patients with moderate to severe obstructive sleep apnea hypopnea syndrome and resistant hypertension.

Background: Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with resistant hypertension (RH) have a high risk of developing primary aldosteronism (PA). This study investigated the aldosterone-renin ratio (ARR), plasma aldosterone concentration (PAC), and plasma renin activity (PRA) to determine the optimal cutoff values for PA diagnosis in patients with OSAHS combined with RH. Methods: Patients diagnosed with moderate and severe OSAHS combined with RH were recruited from the inpatient clinic of the Department of Endocrinology at Ji'an Central Hospital between October 2020 and April 2023. The included patients were divided into PA and no-PA groups. Diagnostic accuracy measures were calculated for each group, and receiver operating characteristic (ROC) curves were generated. Results: A total of 241 patients were included, of which 103 had positive ARR screening results in the diagnostic accuracy analysis and 66 were diagnosed with PA. PAC and ARR showed moderate predictive capacity for PA, with area under the curve (AUC) values of 0.66 [95% confidence interval (CI): 0.55-0.77] and 0.72 (95% CI: 0.63-0.82), respectively, while PRA exhibited a limited predictive capacity (AUC = 0.51, 95% CI: 0.40-0.63). Using 45 as the optimal cutoff value for ARR, the sensitivity was 86% and the specificity was 52%. The optimal cutoff value for PAC was 17, with a sensitivity of 78% and a specificity of 55%. Notably, in patients with severe OSAHS, ARR at screening demonstrated significant predictive value for PA, with an AUC of 0.84 (95% CI: 0.72-0.96), a sensitivity of 85%, and a specificity of 76%. Conversely, in patients with moderate OSAHS, only ARR demonstrated significant predictive value for PA diagnosis, while PAC did not demonstrate notable diagnostic value. Conclusion: ARR and PAC are initial screening tools for PA, facilitating early detection, particularly in low-resource settings. In patients with OSAHS and RH, the ARR and PAC thresholds for PA diagnosis may require more stringent adjustment.

Hydromassage of macular hole edges for large and persistent full-thickness macular holes.

AIM: To introduce the macular hole (MH) hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH. METHODS: This retrospective observational case series comprised 16 consecutive patients (17 eyes) diagnosed with MH. Inclusion criteria involved a hole aperture diameter larger than 600 µm or the presence of an unclosed MH larger than 600 µm following the previous vitrectomy. Standard MH repair procedures were administered in all cases, involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle. A comprehensive assessment was conducted for each case before and after surgery, and optical coherence tomography (OCT) images were captured at every follow-up point. RESULTS: The mean preoperative aperture diameter was 747±156 µm (range 611-1180 µm), with a mean base diameter of 1390±435 µm (range 578-2220 µm). Following surgery, all cases achieved complete anatomical closure of MH, with 13 cases (76.5%) exhibiting type 1 closure and 4 cases (23.5%) demonstrating type 2 closure. No significant differences were observed in the preoperative OCT variables between the two closure types. Eyes with type 1 closure showed a significantly improved visual acuity (0.70±0.10, range 0.50-0.80) compared to those with type 2 closure (0.90±0.12, range 0.80-1.00, P=0.014). CONCLUSION: The MH hydromassage technique demonstrates promising results, achieving acceptable closure rates in cases of large or persistent MH. This technique may serve as an effective adjunctive maneuver during challenging MH surgery.

Salidroside Ameliorates Lung Injury Induced by PM 2.5by Regulating SIRT1-PGC-1α in Mice.

Objective: This study aimed to clarify the intervention effect of salidroside (SAL) on lung injury caused by PM 2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods: Specific pathogen-free (SPF) grade male C57BL/6 mice were randomly assigned to the following groups: control group, SAL group, PM 2.5 group, SAL+PM 2.5 group. On the first day, SAL was given by gavage, and on the second day, PM 2.5 suspension was given by intratracheal instillation. The whole experiment consist of a total of 10 cycles, lasting 20 days. At the end of treatment, blood samples and lung tissues were collected and analyzed. Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy. The expression of inflammatory, antioxidants, apoptosis, and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results: Exposure to PM 2.5 leads to obvious morphological and pathologica changes in the lung of mice. PM 2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1, Nrf2, SOD2, SIRT1 and PGC-1ɑ, and an increase in the protein expressions of IL-6, IL-1ß, Bax, caspase-9 and cleaved caspase-3. However, SAL reversed the aforementioned changes caused by PM 2.5 by activating the SIRT1-PGC-1α pathway. Conclusion: SAL can activate SIRT1-PGC-1ɑ to ameliorate PM 2.5-induced lung injury.

Controlling the nutritional status score: a new tool for predicting postoperative mortality in patients with infrarenal abdominal aortic aneurysm treated with endovascular aneurysm repair.

Background: AAA is a fatal condition that commonly occurs during vascular surgery. Nutritional status exerts a significant influence on the prognosis of various pathological conditions Scores from the CONUT screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the ramifications of nutritional status on AAA patients undergoing EVAR have not been elucidated in prior studies. In this study, we aimed to elucidate the correlation between CONUT scores and postoperative prognostic outcomes in patients with AAA undergoing EVAR. Methods: This was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, CONUT scores, and postoperative status were collected. These patients were stratified into groups A and B according to CONUT scores. Subsequently, a comparative analysis of the baseline characteristics between the two cohorts was conducted. Cox proportional hazards and logistic regression analyses were employed to identify the autonomous predictors of mid-term mortality and complications, respectively. Results: Compared with group A, patients in group B had higher midterm mortality (p < 0.001). Univariate analysis showed that CONUT scores; respiratory diseases; stent types; preoperative Hb, CRP, PT, and Fb levels were risk factors for death. Multivariate analysis confirmed that CONUT score [HR, 1.276; 95% CI, 1.029-1.584; p = 0.027] was an independent risk factor for mortality. Logistic regression analysis showed that prior arterial disease, smoking, and D-dimer levels were risk factors, although multivariate analysis showed smoking (OR, 3.492; 95% CI, 1.426-8.553; p = 0.006) was an independent risk factor. Kaplan-Meier curves showed that patients in group B had shorter mid-term survival than those in group A (log-rank p < 0.001). Conclusion: Malnutrition was strongly associated with mid-term mortality in patients with infrarenal AAA treated with EVAR.

MACSPI enables tissue-selective proteomic and interactomic analyses in multicellular organisms.

Multicellular organisms are composed of many tissue types that have distinct morphologies and functions, which are largely driven by specialized proteomes and interactomes. To define the proteome and interactome of a specific type of tissue in an intact animal, we developed a localized proteomics approach called Methionine Analog-based Cell-Specific Proteomics and Interactomics (MACSPI). This method uses the tissue-specific expression of an engineered methionyl-tRNA synthetase to label proteins with a bifunctional amino acid 2-amino-5-diazirinylnonynoic acid in selected cells. We applied MACSPI in Caenorhabditis elegans, a model multicellular organism, to selectively label, capture, and profile the proteomes of the body wall muscle and the nervous system, which led to the identification of tissue-specific proteins. Using the photo-cross-linker, we successfully profiled HSP90 interactors in muscles and neurons and identified tissue-specific interactors and stress-related interactors. Our study demonstrates that MACSPI can be used to profile tissue-specific proteomes and interactomes in intact multicellular organisms.

Effects of Dietary Supplementation of Bile Acids on Growth, Glucose Metabolism, and Intestinal Health of Spotted Seabass (Lateolabrax maculatus).

An 8-week feeding trial was performed to investigate the effects of dietary bile acids on growth, glucose metabolism, and intestinal health in spotted seabass (Lateolabrax maculatus) reared at high temperatures (33 °C). The fish (20.09 ± 1.12 g) were fed diets supplemented with bile acids: 0 (Con), 400 (BA400), 800 (BA800), and 1200 (BA1200) mg/kg, respectively. The results showed that the growth was promoted in fish at the BA800 treatment compared with the control (p < 0.05). Increased enzyme activities and transcripts of gluconeogenesis in the liver were observed, whereas decreased enzyme activities and transcripts of glycolysis, as well as glycogen content, were shown in the BA800 treatment (p < 0.05). The transcripts of bile acid receptors fxr in the liver were up-regulated in the BA800 treatment (p < 0.05). A bile acid supplementation of 800 mg/kg improved the morphological structure in the intestine. Meanwhile, intestinal antioxidant physiology and activities of lipase and trypsin were enhanced in the BA800 treatment. The transcripts of genes and immunofluorescence intensity related to pro-inflammation cytokines (il-1ß, il-8, and tnf-α) were inhibited, while those of genes related to anti-inflammation (il-10 and tgf-ß) were induced in the BA800 treatment. Furthermore, transcripts of genes related to the NF-κB pathway in the intestine (nfκb, ikkα, ikkß, and ikbα1) were down-regulated in the BA800 treatment. This study demonstrates that a dietary bile acid supplementation of 800 mg/kg could promote growth, improve glucose metabolism in the liver, and enhance intestinal health by increasing digestive enzyme activity and antioxidant capacity and inhibiting inflammatory response in L. maculatus.

The Effects of Lentinan on the Hematological and Immune Indices of Dairy Cows.

In this study, we investigated the effects of lentinan (LNT) on hematological parameters, immune indices, and metabolite levels in dairy cows. We randomly assigned forty Holstein cows to four treatment groups. The treatments consisted of 0, 5, 10, and 15 g/d of LNT. Compared with the control group, the addition of 10 g/d of LNT decreased the content of ALT and IL-8 but simultaneously increased the content of IL-4 in the cows' serum. Supplementation with 10 g/d of LNT decreased the levels of lymphocyte, RDW, ALT, AST, TC, IL-2, and IL-8, but, concurrently, in-creased the levels of granulocytes and IL-4 in their serum. In addition, supplementation with 15 g/d of LNT decreased the levels of RDW, TC, IL-2, and IL-8, but, at the same time, increased the levels of IL-4 and IgM in their serum. For the metabolomic analysis, cows fed with 0 and 10 g/d of LNT were selected. The results showed that 10 metabolites, including reduced nicotinamide riboside and trehalose, were upregulated in the 10 g/d group. These differential metabolites were enriched in tyrosine metabolism and trehalose degradation and altered two metabolic pathways of ubiquinone and other terpene quinone biosynthesis, as well as starch and sucrose metabolism. These findings provide evidence that LNT could be used to reduce the risk of inflammation in dairy cows.

Three undescribed dihydrostilbene glycosides from leaves of Camellia oleifera Abel. And their anti-inflammatory activity.

Three previously unidentified dihydrostilbene glycosides, named oleiferaside A (1), oleiferaside B (2), and oleiferaside C (3), were discovered through a phytochemical exploration on Camellia oleifera Abel. leaves. Additionally, nine known secondary metabolites (4-12) were also identified. The undescribed secondary metabolites 1-3 were elucidated as 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinopyranosyl-(1 â†’ 6)-ß-d- glucopyranoside and 3,5-dimethoxydihydrostilbene 4'-O-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, respectively. HR-MS and NMR spectroscopy were utilized for determining the structures of the isolates. The natural products were assessed for their anti-inflammatory effect using RAW264.7 macrophage stimulated by LPS. The findings demonstrated that compounds 1-4 exhibited inhibitory activities on NO and PGE2 production without causing cytotoxicity. These observations suggest that these compounds may have potential anti-inflammatory properties.

[99mTc]Tc-labeled cyc-DX600-HYNIC as a SPECT probe for ACE2-specific pancreatic cancer imaging.

As a regulator in renin-angiotensin-aldosterone system, angiotensin-converting enzyme 2 (ACE2) closely correlated with tumor progression of pancreatic cancer, meantime, was easily affected by a variety of factors. [99mTc]Tc-cyc-DX600 SPECT was established as an ACE2-specific imaging protocol to figure out the ACE2 status in pancreatic tumor. BALB/C-NU mice were used to prepare the subcutaneous cell derived xenograft (CDX) models with HEK-293T or HEK-293T/hACE2 cells to validate ACE2 specificity of [99mTc]Tc-cyc-DX600 SPECT and establish SPECT imaging protocol. On the basis of [99mTc]Tc-cyc-DX600 SPECT and [18F]F-FDG PET/CT, ACE2-dependence on tumor size and tumor metabolism were further verified on orthotopic pancreatic cancer model with KPC cells. Immunohistochemical analysis was used to demonstrate the findings on ACE2 SPECT. [99mTc]Tc-cyc-DX600 was of superior tumor uptake in HEK-293T/hACE2 CDX than wild type (6.74 ± 0.31 %ID/mL vs 1.83 ± 0.26 %ID/mL at 1.5 h post injection (p.i.); 3.14 ± 0.31 %ID/mL vs 1.16 ± 0.15 %ID/mL at 4.5 h p.i.). For the CDX models with PANC-1 cells, a significant negative correlation between the slope of tumor volume and tumor uptake was observed (r = -0.382 for the 1-4th day; r = -0.146 for the 1-5th day; r = -0.114 for the 1-6th day; r = -0.152 for the 1-7th day; but P > 0.05 for all). For orthotopic pancreatic cancer model, the linear correlation between FDG PET and ACE2 SPECT of the pancreatic lesions was negative (r = -0.878), the quantitative values of ACE2 SPCET was positively correlated with the volume of primary lesions (r = 0.752) and also positively correlated with the quantitative values of ACE2 immunohistochemical analysis (r = 0.991). Conclusively, [99mTc]Tc-cyc-DX600 SPECT is an ACE2-specific imaging protocol with clinical translational potential, adding multidimensional information on the disease progression of pancreatic cancer.

Measurements of peri-prostatic adipose tissue by MRI predict bone metastasis in patients with newly diagnosed prostate cancer.

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.

Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits.

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

One-day examination of triple nuclear medicine imaging and application in evaluating transarterial embolization.

A diagnosis based on multiple nuclear medicine imaging (NMI) was more comprehensive in approaching the nature of pathological changes. In this research, a method to realize triple NMIs within one day was developed based on the reasonable arrangements of 68Ga-RGD PET/CT specialized on neovascularization, 99mTc-HL-91 SPECT/CT specialized on hypoxia and 18F-FDG PET/CT specialized on tumor metabolism. Feasibility was verified in evaluating the therapeutic effects of transarterial embolization (TAE) performed on rabbit models with VX2 tumor. Radiation dosimetry was carried out to record the radiation exposure from multiple injections of radiopharmaceuticals. In results, the one-day examination of triple NMIs manifested the diversity of the postoperative histological changes, including the local neovascularization induced by embolization, hypoxic state of embolized tissues, and suppression of tumor metabolism. More importantly, radiation dosage from radiopharmaceuticals was limited below 5.70 ± 0.90 mSv. In conclusion, the strong timeliness and complementarity of one-day examination of triple nuclear medicine imaging made it clinically operative and worthy of popularizing. There was flexibility in combining distinct NMIs according to the clinical demands, so as to provide comprehensive information for diagnosis.

Myasthenia gravis with tongue muscle atrophy: A case series.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

New G-Triplex DNA Dramatically Activates the Fluorescence of Thioflavin T and Acts as a Turn-On Fluorescent Sensor for Uracil-DNA Glycosylase Activity Detection.

G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.

The relationship between family resilience, post-traumatic growth, and caregiver burden among family caregivers of stroke survivors: a cross-sectional study.

The study aimed to explore the relationship between family resilience, post-traumatic growth(PTG), and caregiver burden among family caregivers of stroke survivors. Researchers conducted a cross-sectional study to recruit 253 family caregivers of stroke survivors from a public hospital in Shandong Province, China. Caregivers completed sociodemographic information, the Shortened Chinese Version of the Family Resilience Assessment Scale, the Post-traumatic Growth Inventory, and the Zarit Caregiver Burden Interview. We used Amos 24.0 to construct structural equation models and examine the mediating effects of stroke survivors' post-traumatic growth. Family resilience was positively associated with post-traumatic growth, and both family resilience and post-traumatic growth were negatively associated with caregiver burden. Post-traumatic growth partially mediated the relationship between family resilience and caregiver burden, and the mediating effect accounted for 21.27% of the total effect. Targeted interventions should address family resilience and post-traumatic growth as protective factors of caregiver burden.

PHLDA1 contributes to hypoxic ischemic brain injury in neonatal rats via inhibiting FUNDC1-mediated mitophagy.

Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O2 and 92% N2. In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 µM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy.