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Abstract Background The clinical application of mesenchymal stem cells (MSCs) in myocardial infarction (MI) is severely hampered by their poor survival. Pretreatment is a key strategy that has been adopted to promote their therapeutic efficacy. This study aimed to investigate the benefit of growth differentiation factor 15-pretreated MSCs (GDF15-MSCs) in enhancing cardiac repair following MI and to determine the underlying mechanisms. Methods MSCs with or without GDF15 pretreatment were exposed to serum deprivation and hypoxia (SD/H) challenge. Apoptosis of MSCs was assessed by TUNEL staining. The conditioned media (CM) of MSCs and GDF15-MSCs was collected by centrifugation. MSCs and GDF15-MSCs were transplanted into the peri-infarct region in a mouse model of MI. Cardiac function, fibrosis and MSC survival were examined 4 weeks after MSC transplantation. Results Pretreatment with GDF15 greatly reduced SD/H-induced apoptosis of MSCs via inhibition of reactive oxygen species (ROS) generation by attenuating mitochondrial fission. Mechanistically, GDF15 pretreatment ameliorated mitochondrial fission of MSCs under SD/H challenge by activating the AMPK pathway. These effects were partially abrogated by AMPK inhibitor. Pretreatment with GDF15 also promoted paracrine effects of MSCs in vitro, evidenced by improving tube formation of HUVECs, and inhibited the apoptosis of cardiomyocytes induced by SD/H. At 4 weeks after transplantation, compared with MSCs, GDF15 pretreatment strongly promoted the survival of MSCs in the ischemic heart with consequent enhanced cardiac function, reduced cardiac fibrosis and increased angiogenesis. Conclusions Our study showed that pretreatment with GDF15 promoted the cardioprotective effects of MSCs in MI via regulation of pro-survival signaling and paracrine actions. GDF15 pretreatment is an effective approach to enhance the therapeutic efficacy of MSCs in ischemic heart disease.

Abstract Purpose Severe open forearm fractures commonly involve segmental bone defects. Although several methods have been proposed to treat segmental bone defects with such fractures, research comparing the radiological and clinical outcomes of free vascularized fibular grafts (FVFG) and the Masquelet technique (MT) is rare. Methods Data on 43 patients with open forearm fractures and segmental bone defects treated surgically in our hospital from January 2005 to January 2021 were retrospectively analyzed, and these patients were divided into an FVFG group (18 cases) and an MT group (25 cases). Clinical and radiological evaluations were performed regularly, and the minimum follow-up was 18 months. Results All 43 patients were followed up for 18 to 190 months, with a mean of 46.93 months. The mean follow-up time was significantly longer in the FVFG group than in the MT group (p = 0.000). Bone healing time was 3–16 months, with a mean of 4.67 months. The QuickDASH score at the last follow-up was 0–38.6, with a mean of 17.71, and there was no statistically significant difference between the two groups. Operative time, hospital stay, and intraoperative bleeding for bone defect reconstruction were higher in the FVFG group compared to the MT group (p = 0.000), whereas the number of procedures was lower in the FVFG group than in the MT group (p = 0.035). Conclusions FVFG and the MT showed satisfactory clinical results for segmental bone defects of the forearm. Compared with FVFG, the MT exhibited a lower operative time, hospital stay, and intraoperative bleeding. Level of evidence Level IV. Trial registration This study was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR2300067675; registered 17 January 2023), https://www.chictr.org.cn/showproj.html?proj=189458 .

Abstract Ferroptosis is a specific form of cell death characterized by excessive accumulation of cellular lipid peroxides. Ferroptosis is closely associated with various diseases, inhibition of which may help alleviate multi-organ injury caused by ischemia-reperfusion and enhance the anti-tumor effect by promoting the immunity of T cells. However, clinical approved drugs targeting ferroptosis process remain rare. In this study, we unexpectedly found that (R)-crizotinib, the first-generation ALK inhibitor, has potent inhibitory activity against ferroptosis across various cell lines. Moreover, its chiral molecule (S)-crizotinib, which was considered to share no common targets with (R)-crizotinib, also suppresses ferroptosis with an efficacy similar to that of (R)-crizotinib. We further demonstrated that both crizotinib enantiomers inhibit ferroptosis independently of their known targets, but through a common mechanism involving the targeting of AGPAT3-mediated synthesis of ether-linked polyunsaturated fatty acids (PE-O-PUFA), which are known to promote lipid-ROS generation and ferroptosis. In line with their activity in cell lines, (R)-crizotinib and (S)-crizotinib effectively mitigate renal ischemia-reperfusion injury in mice. Furthermore, the two compounds also inhibit lipid-ROS accumulation in CD8+ T cells in draining lymph nodes of B16-F10 subcutaneous xenograft mice, thereby promoting anti-tumor effects. Collectively, our study firstly reports a common activity shared by (R)-crizotinib and (S)-crizotinib in ferroptosis regulation. As a clinically approved drug, (R)-crizotinib has well-established pharmacokinetics and safety, which makes it a promising candidate for repurposing. Given the current lack of FDA-approved ferroptosis inhibitors, our findings suggest therapeutically repurposing (R)-crizotinib as well as its enantiomer (S)-crizotinib for treating ferroptosis-related diseases.

Abstract Background Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently, we reported that EVs derived from ischemia-reperfusion heart exacerbate cardiac injury. However, the role of EVs from healthy heart tissue (heart-derived EVs, or cEVs) on myocardial ischemia-reperfusion (MI/R) injury remains unclear. Results Here, we demonstrated that intramyocardial administration of cEVs significantly enhanced cardiac function and reduced cardiac damage in murine MI/R injury models. cEVs treatment effectively inhibited ferroptosis and maintained mitochondrial homeostasis in cardiomyocytes subjected to ischemia-reperfusion injury. Further results revealed that cEVs can transfer ATP5a1 into cardiomyocytes, thereby suppressing mitochondrial ROS production, alleviating mitochondrial damage, and inhibiting cardiomyocyte ferroptosis. Knockdown of ATP5a1 abolished the protective effects of cEVs. Furthermore, we found that the majority of cEVs are derived from cardiomyocytes, and ATP5a1 in cEVs primarily originates from cardiomyocytes of the healthy murine heart. Moreover, we demonstrated that adipose-derived stem cells (ADSC)-derived EVs with ATP5a1 overexpression showed much better efficacy on the therapy of MI/R injury compared to control ADSC-derived EVs. Conclusions These findings emphasized the protective role of cEVs in cardiac injury and highlighted the therapeutic potential of targeting ATP5a1 as an important approach for managing myocardial damage induced by MI/R injury.

Abstract Purpose This study aimed to investigate the feasibility of using computed tomography (CT) attenuation values to differentiate hypodense brain lesions, specifically acute ischemic stroke (AIS) from asymmetric leukoaraiosis (LA) and old cerebral infarction (OCI). Materials and methods This retrospective study included patients with indeterminate hypodense lesions identified via brain CT scans conducted between June 2019 and June 2021. All lesions were confirmed through head MRI/diffusion-weighted imaging within 48 h after CT. CT attenuation values of hypodense lesions and symmetrical control regions were measured. Additionally, CT attenuation value difference (ΔHU) and ratio (RatioHU) were calculated. One-way analysis of variance (ANOVA) was used to compare age and CT parameters (CT attenuation values, ΔHU and RatioHU) across the groups. Finally, receiver operating characteristic (ROC) analysis was performed to determine the cutoff values for distinguishing hypodense lesions. Results A total of 167 lesions from 146 patients were examined. The CT attenuation values for AIS(n = 39), LA(n = 53), and OCI(n = 75) were 18.90 ± 6.40 HU, 17.53 ± 4.67 HU, and 11.90 ± 5.92 HU, respectively. The time interval between symptom onset and CT scans for AIS group was 32.21 ± 26.85 h. ANOVA revealed significant differences among the CT parameters of the hypodense lesion groups (all P

Abstract Intron retention (IR) is the most common alternative splicing event in Arabidopsis. An increasing number of studies have demonstrated the major role of IR in gene expression regulation. The impacts of IR on plant growth and development and response to environments remain underexplored. Here, we found that IR functions directly in gene expression regulation on a genome-wide scale through the detainment of intron-retained transcripts (IRTs) in the nucleus. Nuclear-retained IRTs can be kept away from translation through this mechanism. COP1-dependent light modulation of the IRTs of light signaling genes, such as PIF4, RVE1, and ABA3, contribute to seedling morphological development in response to changing light conditions. Furthermore, light-induced IR changes are under the control of the spliceosome, and in part through COP1-dependent ubiquitination and degradation of DCS1, a plant-specific spliceosomal component. Our data suggest that light regulates the activity of the spliceosome and the consequent IRT nucleus detainment to modulate photomorphogenesis through COP1.

Abstract Tibetan-speaking patients seeking care in predominantly Mandarin-speaking healthcare settings frequently face communication barriers, leading to potential disparities and difficulties in accessing care. To address this issue, we translated, culturally adapted, and validated the Numerical Pain Rating Scale (NPRS) and the Global Rating of Change (GRoC) into Tibetan (NPRS-Tib and GRoC-Tib), aiming to facilitate cross-linguistic and cross-cultural interactions while examining potential challenges in the adaptation process. Using standard translation-backward translation methods, expert review, pilot testing, and validation through a cross-sectional study with a short-term longitudinal component, we engaged 100 Tibetan patients with musculoskeletal trauma for psychometric validation, including 37 women (aged 22–60 years, mean age 39.1 years). The NPRS-Tib and GRoC-Tib exhibited outstanding psychometric properties, with an Intraclass Correlation Coefficient (ICC) of 0.983 for NPRS-Tib indicating superb test–retest reliability, and expert review confirming good content validity for both instruments. A Spearman's correlation coefficient (Rho) of -0.261 (P = 0.0087) revealed a significant, albeit weak, correlation between changes in NPRS-Tib scores and GRoC-Tib scores. The adaptation process also presented notable challenges, including translation discrepancies from translators' diverse backgrounds and levels of expertise, ambiguity in scale options, and the lack of established tools for criterion validity assessment in Tibetan.

Abstract Doxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application is heavily limited by its cardiotoxicity. There is accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects of EXOs isolated from human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) against DIC and explore the potential mechanisms. EXOs were isolated from the cultural supernatant of human BM-MSCs (BM-MSC-EXOs) and iPSC-MSCs (iPSC-MSC-EXOs) by ultracentrifugation. A mouse model of DIC was induced by intraperitoneal injection of Dox followed by tail vein injection of PBS, BM-MSC-EXOs, or iPSC-MSC-EXOs. Cardiac function, cardiomyocyte senescence and mitochondrial dynamics in each group were assessed. In vitro, neonatal mouse cardiomyocytes (NMCMs) were subjected to Dox and treated with BM-MSC-EXOs or iPSC-MSC-EXOs. The mitochondrial morphology and cellular senescence of NMCMs were examined by Mitotracker staining and senescence-associated-β-galactosidase assay, respectively. Compared with BM-MSC-EXOs, mice treated with iPSC-MSC-EXOs displayed improved cardiac function and decreased cardiomyocyte mitochondrial fragmentation and senescence. In vitro, iPSC-MSC-EXOs were superior to BM-MSC-EXOs in attenuation of cardiomyocyte mitochondrial fragmentation and senescence caused by DOX. MicroRNA sequencing revealed a higher level of miR-9-5p in iPSC-MSC-EXOs than BM-MSC-EXOs. Mechanistically, iPSC-MSC-EXOs transported miR-9-5p into DOX-treated cardiomyocytes, thereby suppressing cardiomyocyte mitochondrial fragmentation and senescence via regulation of the VPO1/ERK signal pathway. These protective effects and cardioprotection against DIC were largely reversed by knockdown of miR-9-5p in iPSC-MSC-EXOs. Our results showed that miR-9-5p transferred by iPSC-MSC-EXOs protected against DIC by alleviating cardiomyocyte senescence via inhibition of the VPO1/ERK pathway. This study offers new insight into the application of iPSC-MSC-EXOs as a novel therapeutic strategy for DIC treatment. Graphical Abstract

Purpose: This study aimed to identify the occurrence of excessive daytime sleepiness (EDS) in epilepsy patients with interictal epileptiform discharges and to explore the impact of interictal sleep architecture and sleep-related events on EDS. Methods: This study included 101 epilepsy patients with interictal epileptiform discharges (IED) and 100 control patients who underwent simultaneous polysomnography and video ambulatory electroencephalography for >7 h throughout a single night. Multiple sleep latency tests were used to assess EDS. Comorbid EDS was present in 25 and 11 patients in the IED epilepsy and control groups, respectively. In addition, univariate and multivariate logistic regression analyses were performed to explore the factors influencing EDS. Results: The epilepsy group had a higher prevalence of comorbid EDS and shorter R sleep duration. Univariate logistic regression analysis indicated that an increased risk of EDS may be associated with prolonged N1 sleep duration, higher arousal index, lower mean saturation (mSaO2), higher oxygen desaturation index (ODI), and duration of wake after sleep onset (WASO). Multivariate logistic regression analysis revealed that N1 sleep duration was significantly correlated with EDS. Conclusion: In epilepsy patients with IED, the arousal index, mSaO2, ODI, and duration of WASO were weakly correlated with EDS, and the duration of N1 sleep demonstrated a significant positive correlation with EDS, which requires further research.

Abstract Background The treatment of completely displaced midshaft clavicle fractures is still controversial, especially Robinson 2B fractures. Titanium elastic nail (TEN) fixation is a good option for simple fractures, but no reports exist on its use in complex fractures. This study aimed to present a surgical method using the Nice knot-assisted TEN fixation to treat Robinson 2B midshaft clavicular fractures. Methods A retrospective analysis of 29 patients who underwent fixation with TEN and had a 1-year postoperative follow-up between 2016 and 2020 was performed. The fractures were classified as Robinson type 2B1 in 17 cases and type 2B2 in 12 cases. Length of the incision, postoperative shoulder function Disability of Arm Shoulder and Hand (DASH) score and Constant score, complications rate, and second surgical incision length were recorded. Results The length of the incision was 2–6 cm (average 3.7 cm). All incisions healed by first intention, and no infection or nerve injury occurred. The Constant score was 92–100 (average 96) and the DASH score was 0-6.2 (mean, 2.64). TEN bending and hypertrophic nonunion occurred in one case (3.4%) and implant irritation occurred in four cases (13.8%) Fixation implants were removed at 12–26 months (mean, 14.6 months) after surgery, and the length of the second incision was 1-2.5 cm (average 1.3 cm). Conclusions Intramedullary fixation by TEN is approved as a suitable surgical technique in clavicular fracture treatment. Nice knot-assisted fixation provides multifragmentary fracture stabilization, contributing to good fracture healing. Surgeons should consider this technique in treating Robinson 2B midshaft clavicular fractures. Trial registration Retrospectively registered. This study was approved by the Ethics Committee of Wuxi Ninth People’s Hospital (LW20220021).

Objective: Acupuncture is an effective treatment for arrythmias and postoperative symptoms but has not been investigated after cardiac surgery. Acupuncture After Heart Surgery is a prospective, randomized, controlled pilot trial of daily inpatient acupuncture or standard care after valve surgery with the primary end point being feasibility and secondary end points being reduction in postoperative atrial fibrillation incidence and postoperative symptoms. Methods: A total of 100 patients without a history of atrial fibrillation underwent primary valve surgery via sternotomy and randomized 1:1 to acupuncture (51) or standard care (49). The acupuncture group received daily inpatient sessions starting on postoperative day 1. Postoperative symptoms (pain, nausea, stress, anxiety) were assessed once daily in the standard care group and before/after daily intervention in the acupuncture group. The groups were comparable except for age (acupuncture: 55.6 ± 11.4 years, standard care: 61.0 ± 9.3 years; P = .01). Results: The Acupuncture After Heart Surgery pilot trial met primary and secondary end points. There were no adverse events. An average of 3.8 (±1.1) acupuncture sessions were delivered per patient during a mean hospital stay of 4.6 days (±1.3). Acupuncture was associated with a reduction in pain, nausea, stress, and anxiety after each session (P

Abstract Complex lower extremity trauma reconstruction remains a challenge. This study used an internal fixation composite structure of antibiotic cement plates as a temporary fixation to treat lower extremity Grade III open fractures; thus, reducing the treatment period and complications of external fixation. We aimed to assess the safety and efficacy of this technique in the initial surgery stage. Between January 2018 and March 2021, 20 patients with Gustilo grade IIIB/C open fractures received an antibiotic cement-coated locking plate as a temporary internal fixator during initial surgery. Thorough debridement and temporary internal fixation were performed with a 3.5-mm system antibiotic cement-coated locking plate. Ten patients required free bone fragment removal, followed by bone cement packing. The final stage involved internal fixation and wound repair with a free anterolateral thigh flap. Clinical and imaging results were retrospectively analysed. The repair time ranged 1–7 days. All flaps survived. Two patients experienced wound infection, and one developed severe bone infection 3 months after three-stage bone graft surgery. Autologous cancellous bone grafting was performed on 10 patients with bone defects 6 weeks after surgery. Bone union was universally achieved after 1 year. This method proved safe and effective, successfully repairing Grade III open fractures of the lower extremity 1–7 days post-treatment.

Objective To investigate the effect of FOCUS-PDCA management mode in standardizing medication of ophthalmic drugs in patients undergoing ambulatory eye surgery, and provide reference for continuous improvement of the nursing quality of ambulatory eye surgery. Methods A non-concurrent control trial was conducted, and patients undergoing ambulatory eye surgery were assigned to the control group (n=146)and the observation group (n=154). The control group received routing nursing management during operation period. The FOCUS-PDCA management mode was adopted in standardizing medication of ophthalmic drugs for patients in the observation group. The rate of qualified self-medication of ophthalmic drugs, awareness and knowledge about ophthalmic drugs and patient satisfaction were measured and compared between groups. Results The rates of proper storage of ophthalmic drugs, proper administration time of ophthalmic drugs and qualified self-medication of ophthalmic drugs in the observation group were higher than those in the control group (P

Abstract Background Extracellular vesicles (EVs) derived from various cell sources exert cardioprotective effects during cardiac ischemic injury. Our previous study confirmed that EVs derived from ischemic-reperfusion injured heart tissue aggravated cardiac inflammation and dysfunction. However, the role of EVs derived from normal cardiac tissue in myocardial ischemic injury remains elusive. Results In the present study, normal heart-derived EVs (cEVs) and kidney-derived EVs (nEVs) were isolated and intramyocardially injected into mice after myocardial infarction (MI). We demonstrated that administration of both cEVs and nEVs significantly improved cardiac function, reduced the scar size, and alleviated inflammatory infiltration into the heart. In addition, cardiomyocyte apoptosis was inhibited, whereas angiogenesis was enhanced in the hearts receiving cEVs or nEVs treatment. Moreover, intramyocardial injection of cEVs displayed much better cardiac protective efficacy than nEVs in murine MI models. RNA-seq and protein-protein interaction (PPI) network analysis revealed the protective mRNA clusters in both cEVs and nEVs. These mRNAs were involved in multiple signaling pathways, which may synergistically orchestrate to prevent the heart from further damage post MI. Conclusions Collectively, our results indicated that EVs derived from normal heart tissue may represent a promising strategy for cardiac protection in ischemic heart diseases.

AIM: To access the agreement of intraocular pressure (IOP) values obtained from biomechanically corrected tonometer [Corvis ST (CST)], non-contact tonometer (NCT), and Goldmann applanation tonometer (GAT) in children with NCT measured-IOP (NCT-IOP) values of 22 mm Hg or more, and related factors. METHODS: A total of 51 eyes with NCT-IOP≥22 mm Hg in children aged 7 to 14y were examined and IOP was measured by CST, NCT, and GAT. Based on GAT measured IOP (GAT-IOP), ocular hypertension (OHT) group (≥22 mm Hg, 24 eyes) and the non-OHT group (

Dilated cardiomyopathy (DCM) is one of the major causes of heart failure. Although significant progress has been made in elucidating the underlying mechanisms, further investigation is required for clarifying molecular diagnostic and therapeutic targets. In this study, we found that the mRNA level of protein phosphatase 2 regulatory subunit B’ delta (Ppp2r5d) was altered in the peripheral blood plasma of DCM patients. Knockdown of Ppp2r5d in murine cardiomyocytes increased the intracellular levels of reactive oxygen species (ROS) and inhibited adenosine triphosphate (ATP) synthesis. In vivo knockdown of Ppp2r5d in an isoproterenol (ISO)-induced DCM mouse model aggravated the pathogenesis and ultimately led to heart failure. Mechanistically, Ppp2r5d-deficient cardiomyocytes showed an increase in phosphorylation of STAT3 at Y705 and a decrease in phosphorylation of STAT3 at S727. The elevated levels of phosphorylation at Y705 in STAT3 triggered the upregulation of interleukin 6 (IL6) expression. Moreover, the decreased phosphorylation at S727 in STAT3 disrupted mitochondrial electron transport chain function and dysregulated ATP synthesis and ROS levels. These results hereby reveal a novel role for Ppp2r5d in modulating STAT3 pathway in DCM, suggesting it as a potential target for the therapy of the disease.

Objective: The primary objective is to explore what causes slow-wave sleep loss in elderly patients with epilepsy. The secondary objective is to identify the PSG characteristics in elderly patients with epilepsy. The clinical demographics, sleep architecture, sleep-related events, and interictal epileptiform discharges are to be evaluated in the objectives. Methods: The video electroencephalography (VEEG) and polysomnogram (PSG) data from 44 elderly patients with epilepsy and 52 elderly patients with sleep disorders but without definite central nervous system diseases were analysed. This was a case-control study. The differences in the PSG sleep architecture parameters (total sleep time (TST), sleep efficiency, wake after sleep onset, etc.) and sleep-related events (apnea hypopnea index, oxygen desaturation index (ODI), periodic limb movement index, etc.) between the epilepsy and control groups. As Additionally, these parameters were assessed within the elderly patients with epilepsy, comparing the slow-wave sleep existence and slow-wave sleep loss groups, using VEEG and PSG. Results: The epileptic group exhibited significantly lower TST (343.477 ± 96.3046min vs 389.115 ± 61.5727min, p

In the elderly population, coronary heart disease (CHD) often coexists with hypertension. However, excessive blood pressure reduction can paradoxically increase the incidence of adverse events. Understanding the molecular mechanisms underlying hypertension and CHD in aged populations is crucial for developing targeted therapies and improving clinical outcomes. In this study, we constructed myocardial infarction (MI) and transverse aortic constriction (TAC) modelsY in aged mice to simulate the disease states of CHD and hypertension, respectively. Using integrated proteomic and phosphoproteomic analyses, we investigated the molecular signatures associated with MI and TAC in these models. Our aim was to identify key molecules involved in these conditions and to understand their unique and shared characteristics. Through our comprehensive proteomic and phosphoproteomic analysis, we identified a total of 1583 proteins and 232 phosphorylated proteins. We observed significant upregulation of heart disease markers such as Myh7, Xirp2, and Acta1, indicating the successful establishment of the MI and TAC models. The overlapped differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs) in MI and TAC were involved in heart failure-related processes including cardiac muscle contraction and hypertrophic cardiomyopathy, further supporting the validity of the models. Among the DEPs, Ppme1 was upregulated in the TAC model but downregulated in the MI model, while Sec31a and Gm56451 displayed the opposite expression patterns. Among the DPPs, Ablim1 and Atp2a2 were found to be significantly upregulated in the TAC model, whereas their expression was markedly reduced in the MI model. In addition, five other DPPs, including REV_Q3TAY5, Cbx3, PITPNB, Eif4b, and A0A1Y7VP73, were elevated in the MI model but decreased in the TAC model. In conclusion, these findings suggest that MI and TAC not only share certain molecular features but also retain their unique characteristics, providing potential biomarkers and therapeutic targets.

Abstract Extracellular vesicles (EVs) exist throughout our bodies. We recently revealed the important role of intracardiac EVs induced by myocardial ischemia/reperfusion on cardiac injury and dysfunction. However, the role of EVs isolated from normal tissues remains unclear. Here we found that EVs, derived from murine heart, lung, liver and kidney have similar effects on macrophages and regulate the inflammation, chemotaxis, and phagocytosis of macrophages. Interestingly, EV‐treated macrophages showed LPS resistance with reduced expressions of inflammatory cytokines and enhanced phagocytic activity. Furthermore, we demonstrated that the protein content in EVs contributed to the activation of inflammation, while the RNA component mainly limited the excessive inflammatory response of macrophages to LPS. The enrichment of miRNAs, including miR‐148a‐3p, miR‐1a‐3p and miR‐143‐3p was confirmed in tissue EVs. These EV‐enriched miRNAs contributed to the inflammation remission in LPS induced macrophages through multiple pathways, including STAT3, P65 and SAPK/JNK. Moreover, administration of both EVs and EV‐educated macrophages attenuated septic injury and cytokine storm in murine CLP models. Taken together, the present study disclosed that EVs from normal tissues can orchestrate the homeostasis of macrophages and attenuate inflammatory injury of sepsis. Therefore, tissue derived EVs or their derivatives may serve as potential therapeutic strategies in inflammatory diseases.

Abstract Background Despite advancements in the use of body mass index (BMI) to categorize obesity severity in pediatrics, its utility in guiding individual clinical decision making remains limited. The Edmonton Obesity Staging System for Pediatrics (EOSS‐P) provides a way to categorize the medical and functional impacts of obesity according to the severity of impairment. The aim of this study was to describe the severity of obesity among a sample of multicultural Australian children using both BMI and EOSS‐P tools. Methods This cross‐sectional study included children aged 2–17 years receiving obesity treatment through the Growing Health Kids (GHK) multi‐disciplinary weight management service in Australia between January to December 2021. BMI severity was determined using the 95th percentile for BMI on age and gender standardized Centre for Disease Control and Prevention (CDC) growth charts. The EOSS‐P staging system was applied across the four health domains (metabolic, mechanical, mental health and social milieu) using clinical information. Results Complete data was obtained for 338 children (age 10.0 ± 3.66 years), of whom 69.5% were affected by severe obesity. An EOSS‐P stage 3 (most severe) was assigned to 49.7% of children, the remaining 48.5% were assigned stage 2 and 1.5% were assigned stage 1 (least severe). BMI predicted health risk as defined by EOSS‐P overall score. BMI class did not predict poor mental health. Conclusion Used in combination, BMI and EOSS‐P provide improved risk stratification of pediatric obesity. This additional tool can help focus resources and develop comprehensive multidisciplinary treatment plans.

Ischemic stroke is a common cerebrovascular disease with high mortality, high morbidity, and high disability. Cerebral ischemia/reperfusion injury seriously affects the quality of life of patients. Luteolin-7-O-β-d-glucuronide (LGU) is a major active flavonoid compound extracted from Ixeris sonchifolia (Bge.) Hance, a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the protective effect of LGU on cerebral ischemia/reperfusion injury was investigated in an oxygen–glucose deprivation/reoxygenation (OGD/R) neuronal model and a transient middle cerebral artery occlusion (tMCAO) rat model. In in vitro experiments, LGU was found to improve the OGD/R-induced decrease in neuronal viability effectively by the MTT assay. In in vivo experiments, neurological deficit scores, infarction volume rates, and brain water content rates were improved after a single intravenous administration of LGU. These findings suggest that LGU has significant protective effects on cerebral ischemia/reperfusion injury in vitro and in vivo. To further explore the potential mechanism of LGU on cerebral ischemia/reperfusion injury, we performed a series of tests. The results showed that a single administration of LGU decreased the content of EB and S100B and ameliorated the abnormal expression of tight junction proteins ZO-1 and occludin and metalloproteinase MMP-9 in the ischemic cerebral cortex of the tMCAO 24-h injury model. In addition, LGU also improved the tight junction structure between endothelial cells and the degree of basement membrane degradation and reduced the content of TNF-α and IL-1β in the brain tissue. Thereby, LGU attenuated cerebral ischemia/reperfusion injury by improving the permeability of the blood–brain barrier. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia.

Luteolin-7-O-β-d-glucuronide (LGU) is a major active flavonoid glycoside compound that is extracted from Ixeris sonchifolia (Bge.) Hance, and it is a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the neuroprotective effect of LGU was investigated in an oxygen glucose deprivation (OGD) model and a middle cerebral artery occlusion (MCAO) rat model. In vitro, LGU was found to effectively improve the OGD-induced decrease in neuronal viability and increase in neuronal death by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) leakage rate assay, respectively. LGU was also found to inhibit OGD-induced intracellular Ca2+ overload, adenosine triphosphate (ATP) depletion, and mitochondrial membrane potential (MMP) decrease. By Western blotting analysis, LGU significantly inhibited the OGD-induced increase in expressions of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). Moreover, molecular docking analysis showed that LGU might bind to RIP3 more stably and firmly than the RIP3 inhibitor GSK872. Immunofluorescence combined with confocal laser analyses disclosed that LGU inhibited the aggregation of MLKL to the nucleus. Our results suggest that LGU ameliorates OGD-induced rat primary cortical neuronal injury via the regulation of the RIP3/MLKL signaling pathway in vitro. In vivo, LGU was proven, for the first time, to protect the cerebral ischemia in a rat middle cerebral artery occlusion (MCAO) model, as shown by improved neurological deficit scores, infarction volume rate, and brain water content rate. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia.

AimsTo evaluate the degree of coronary microvascular dysfunction (CMD) in dilated cardiomyopathy (DCM) patients by cardiac magnetic resonance (CMR) first-pass perfusion parameters and to examine the correlation between myocardial perfusion and left ventricle reverse remodelling (LVRR).MethodsIn this study, 94 DCM patients and 35 healthy controls matched for age and sex were included. Myocardial perfusion parameters, including upslope, time to maximum signal intensity (Timemax), maximum signal intensity (SImax), baseline signal intensity (SIbaseline), and the difference between maximum and baseline signal intensity (SImax−baseline) were measured. Additionally, left ventricular (LV) structure, function parameters, and late gadolinium enhancement (LGE) were also recorded. The parameters were compared between healthy controls and DCM patients. Univariable and multivariable logistic regression analyses were used to determine the predictors of LVRR.ResultsWith a median follow-up period of 12 months [interquartile range (IQR), 8–13], 41 DCM patients (44%) achieved LVRR. Compared with healthy controls, DCM patients presented CMD with reduced upslope, SIbaseline, and increased Timemax (all p

Abstract Liver metastasis is a common cause of death in progressive colorectal cancer patients, but the molecular mechanisms remain unclear. Here, it is reported that a conserved and oxidative pentose phosphate pathway‐associated circular RNA, circNOLC1, plays a crucial role in colorectal cancer liver metastasis. It is found that circNOLC1 silencing reduces the oxidative pentose phosphate pathway‐related intermediate metabolites and elevates NADP+/NADPH ratio and intracellular ROS levels, thereby attenuating colorectal cancer cell proliferation, migration, and liver metastasis. circNOLC1 interacting with AZGP1 to activate mTOR/SREBP1 signaling, or sponging miR‐212‐5p to upregulate c‐Met expression, both of which can further induce G6PD to activate oxidative pentose phosphate pathway in colorectal cancer liver metastasis. Moreover, circNOLC1 is regulated by the transcription factor YY1 and specifically stabilized HuR induces its parental gene mRNA expression. The associations between circNOLC1 and these signaling molecules are validated in primary CRC and corresponding liver metastasis tissues. These findings reveal that circNOLC1 interacting with AZGP1 and circNOLC1/miR‐212‐5p/c‐Met axis plays a key role in oxidative pentose phosphate pathway‐mediated colorectal cancer liver metastasis, which may provide a novel target for precision medicine of colorectal cancer.

Abstract To accurately identify atoms on noisy transmission electron microscope images, a deep learning (DL) approach is employed to estimate the map of probabilities at each pixel for being an atom with element discernment. Thanks to a delicately-designed loss function and the ability to extract features, the proposed DL networks can be trained by a small dataset created from approximately 30 experimental images, each with a size of 256 × 256 pixels2. The accuracy and robustness of the network were verified by resolving the structural defects of graphene and polar structures in PbTiO3/SrTiO3 multilayers from both the general TEM images and their imitated images on which intensities of some pixels lost randomly. Such a network has the potential to identify atoms from very few images of beam-sensitive material and explosive images recorded in a dynamical atomic process. The idea of using a small-dataset-trained DL framework to resolve a specific problem may prove instructive for practical DL applications in various fields.

Abstract Background This study aims to determine the influence of vitrectomy combined with macular epiretinal membrane dissection and internal limiting membrane (ILM) peeling and phacoemulsification on choroidal vasculature in patients with unilateral idiopathic epiretinal membrane (IERM) and concurrent cataract using optical coherence tomography (OCT). Methods This retrospective study included 26 eyes of 26 patients (8 males and 18 females) with unilateral IERM without vitreomacular traction (VMT) (group 1) and the patients’ fellow eyes (n = 26, group 2). Three-port 25-G pars plana vitrectomy (PPV) combined with macular epiretinal membrane dissection and ILM peeling and phacoemulsification was performed on all patients. The comprehensive ophthalmologic examinations of all patients involved OCT measurements at every visit before and after surgery, and the choroidal thickness (CT), central macular thickness (CMT) and choroidal vascularity index (CVI) were calculated. Results The mean age of the IERM patients was 66.58 ± 7.06 years. Postoperatively, best corrected visual acuity (BCVA) was significantly greater than baseline (P = 0.023). The CVI of the IERM eyes was significantly lower (P

Abstract Light and phytohormone are external and internal cues that regulate plant growth and development throughout their life cycle. BBXs (B-box domain proteins) are a group of zinc finger proteins that not only directly govern the transcription of target genes but also associate with other factors to create a meticulous regulatory network to precisely regulate numerous aspects of growth and developmental processes in plants. Recent studies demonstrate that BBXs play pivotal roles in light-controlled plant growth and development. Besides, BBXs have been documented to regulate phytohormone-mediated physiological procedures. In this review, we summarize and highlight the multi-faced role of BBXs, with a focus in photomorphogenesis, photoperiodic flowering, shade avoidance, abiotic stress, and phytohormone-mediated growth and development in plant.

Background. Chronic hepatitis B virus (HBV) infection is the main pathogen of hepatocellular carcinoma. However, the mechanisms of HBV-related hepatocellular carcinoma (HCC) progression are practically unknown. Materials and Methods. The results of RNA-sequence and clinical data for GSE121248 and GSE17548 were accessed from the Gene Expression Omnibus data library. We screened Sangerbox 3.0 for differentially expressed genes (DEGs). The weighted gene co-expression network analysis (WGCNA) was employed to select core modules and hub genes, and protein-protein interaction network module analysis also played a significant part in it. Validation was performed using RNA-sequence data of cancer and normal tissues of HBV-related HCC patients in the cancer genome atlas-liver hepatocellular cancer database (TCGA-LIHC). Results. 787 DEGs were identified from GSE121248 and 772 DEGs were identified from GSE17548. WGCNA analysis indicated that black modules (99 genes) and grey modules (105 genes) were significantly associated with HBV-related HCC. Gene ontology analysis found that there is a direct correlation between DEGs and the regulation of cell movement and adhesion; the internal components and external packaging structure of plasma membrane; signaling receptor binding, calcium ion binding, etc. Kyoto Encyclopedia of Genes and Genomes pathway analysis found out the association between cytokine receptors, cytokine-cytokine receptor interactions, and viral protein interactions with cytokines were important and HBV-related HCC. Finally, we further validated 6 key genes including C7, EGR1, EGR3, FOS, FOSB, and prostaglandin-endoperoxide synthase 2 by using the TCGALIHC. Conclusions. We identified 6 hub genes as candidate biomarkers for HBV-related HCC. These hub genes may act as an essential part of HBV-related HCC progression.

ABSTRACT Short-chain fatty acids (SCFAs, especially butyric acid) have been demonstrated to play a promising role in the development of autism spectrum disorders (ASD). Recently, the hypothalamic–pituitary–adrenal (HPA) axis is also suggested to increase the risk of ASD. However, the mechanism underlying SCFAs and HPA axis in ASD development remains unknown. Here, we show that children with ASD exhibited lower SCFA concentrations and higher cortisol levels, which were recaptured in prenatal lipopolysaccharide (LPS)-exposed rat model of ASD. These offspring also showed decreased SCFA-producing bacteria and histone acetylation activity as well as impaired corticotropin-releasing hormone receptor 2 (CRHR2) expression. Sodium butyrate (NaB), which can act as histone deacetylases inhibitors, significantly increased histone acetylation at the CRHR2 promoter in vitro and normalized the corticosterone as well as CRHR2 expression level in vivo. Behavioral assays indicated ameliorative effects of NaB on anxiety and social deficit in LPS-exposed offspring. Our results imply that NaB treatment can improve ASD-like symptoms via epigenetic regulation of the HPA axis in offspring; thus, it may provide new insight into the SCFA treatment of neurodevelopmental disorders like ASD. IMPORTANCE Growing evidence suggests that microbiota can affect brain function and behavior through the “microbiome–gut–brain’’ axis, but its mechanism remains poorly understood. Here, we show that both children with autism and LPS-exposed rat model of autism exhibited lower SCFA concentrations and overactivation of HPA axis. SCFA-producing bacteria, Lactobacillus, might be the key differential microbiota between the control and LPS-exposed offspring. Interestingly, NaB treatment contributed to the regulation of HPA axis (such as corticosterone as well as CRHR2) and improvement of anxiety and social deficit behaviors in LPS-exposed offspring. The potential underlying mechanism of the ameliorative effect of NaB may be mediated via increasing histone acetylation to the CRHR2 promoter. These results enhance our understanding of the relationship between the SCFAs and the HPA axis in the development of ASD. And gut microbiota-derived SCFAs may serve as a potential therapeutic agent to neurodevelopmental disorders like ASD.

ABSTRACT: Antibiotic treatment failure is increasingly encountered for the emergence of pandrug-resistant isolates, including the prototypical broad-host-range Salmonella enterica serovar (S.) Typhimurium, which mainly transmitted to humans through poultry products. In this study we explored the therapeutic potential of a Salmonella phage composition containing a virulent phage and a nonproductive phage that does not produce progeny phage against chicks infected with a pandrug-resistant S. Typhimurium strain of avian origin. After approximately 107 CFU of S. Typhimurium strain ST149 were administrated to chicks by intraperitoneal injection, the phage combination (∼108 PFU) was gavaged at 8-h, 32-h, and 54-h postinfection. At d 10 postinfection, phage treatment completely protected chicks from Salmonella-induced death compared to 91.7% survival in the Salmonella challenge group. In addition, phage treatment also greatly reduced the bacterial load in various organs, with Salmonella colonization levels decreasing more significantly in spleen and bursa than in liver and cecal contents, possibly due to higher phage titers in these immune organs. However, phages could not alleviate the decreased body weight gain and the enlargement of spleen and bursa of infected chicks. Further examination of the bacterial flora in the cecal contents of chicks found that S. Typhimurium infection caused a remarkable decrease in abundance of Clostridia vadin BB60 group and Mollicutes RF39 (the dominant genus in chicks), making Lactobacillus the dominate genus. Although phage treatment partially restored the decline of Clostridia vadin BB60 group and Mollicutes RF39 and increased abundance of Lactobacillus caused by S. Typhimurium infection, Fournierella that may aggravate intestinal inflammation became the major genus, followed by increased Escherichia-Shigella as the second dominate bacterial genus. These results suggested that successive phage treatment modulated the structural composition and abundance of bacterial communities, but failed to normalize the intestinal microbiome disrupted by S. Typhimurium infection. Phages need to be combined with other means to control the spread of S. Typhimurium in poultry.

Excessive and chronic inflammation post myocardial infarction (MI) causes cardiac fibrosis and progressive ventricular remodeling, which leads to heart failure. We previously found high levels of IL-27 in the heart and serum until day 14 in murine cardiac ischemia‒reperfusion injury models. However, whether IL-27 is involved in chronic inflammation-mediated ventricular remodeling remains unclear. In the present study, we found that MI triggered high IL-27 expression in murine cardiac macrophages. The increased expression of IL-27 in serum is correlated with cardiac dysfunction and aggravated fibrosis after MI. Furthermore, the addition of IL-27 significantly activated the JAK/STAT signaling pathway in cardiac fibroblasts (CFs). Meanwhile, IL-27 treatment promoted the proliferation, migration and extracellular matrix (ECM) production of CFs induced by angiotensin II (Ang II). Collectively, high levels of IL-27 mainly produced by cardiac macrophages post MI contribute to the activation of CFs and aggravate cardiac fibrosis.

Objective: To identify circadian clock (CC)-related key genes with clinical significance, providing potential biomarkers and novel insights into the CC of ovarian cancer (OC).Methods: Based on the RNA-seq profiles of OC patients in The Cancer Genome Atlas (TCGA), we explored the dysregulation and prognostic power of 12 reported CC-related genes (CCGs), which were used to generate a circadian clock index (CCI). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were used to identify potential hub genes. Downstream analyses including differential and survival validations were comprehensively investigated.Results: Most CCGs are abnormally expressed and significantly associated with the overall survival (OS) of OC. OC patients with a high CCI had lower OS rates. While CCI was positively related to core CCGs such as ARNTL, it also showed significant associations with immune biomarkers including CD8+ T cell infiltration, the expression of PDL1 and CTLA4, and the expression of interleukins (IL-16, NLRP3, IL-1β, and IL-33) and steroid hormones-related genes. WGCNA screened the green gene module to be mostly correlated with CCI and CCI group, which was utilized to construct a PPI network to pick out 15 hub genes (RNF169, EDC4, CHCHD1, MRPL51, UQCC2, USP34, POM121, RPL37, SNRPC, LAMTOR5, MRPL52, LAMTOR4, NDUFB1, NDUFC1, POLR3K) related to CC. Most of them can exert prognostic values for OS of OC, and all of them were significantly associated with immune cell infiltration. Additionally, upstream regulators including transcription factors and miRNAs of key genes were predicted.Conclusion: Collectively, 15 crucial CC genes showing indicative values for prognosis and immune microenvironment of OC were comprehensively identified. These findings provided insight into the further exploration of the molecular mechanisms of OC.

Summary: Nanoplastics (NPs) as contaminants in food and water have drawn increasing public attention. However, little is known about how NPs shape the gut immune landscape after injection. In this study, we fabricate NPs (∼500 nm) and microplastics (MPs) (∼2 μm) and evaluate their in vivo effects by feeding them to mice. The results suggest that NPs show a better ability to induce gut macrophage activation than MPs. In addition, NPs trigger gut interleukin-1 (IL-1)-producing macrophage reprogramming via inducing lysosomal damage. More importantly, IL-1 signaling from the intestine can affect brain immunity, leading to microglial activation and Th17 differentiation, all of which correlates with a decline in cognitive and short-term memory in NP-fed mice. Thus, this study provides insight into the mechanism of action of the gut-brain axis, delineates the way NPs reduce brain function, and highlights the importance of fixing the plastic pollution problem worldwide.

Abstract Background Human umbilical cord-derived mesenchymal stem cells (HucMSCs) have been recognized as a promising cell for treating myocardial infarction (MI). Inflammatory response post MI is critical in determining the cardiac function and subsequent adverse left ventricular remodeling. However, the local inflammatory effect of HucMSCs after intramyocardial injection in murine remains unclear. Methods HucMSCs were cultured and transplanted into the mice after MI surgery. Cardiac function of mice were analyzed among MI-N.S, MI-HucMSC and MI-HucMSC-C–C Motif Chemokine receptor 5 (CCR5) antagonist groups, and angiogenesis, fibrosis and hypertrophy, and immune cells infiltration of murine hearts were evaluated between MI-N.S and MI-HucMSC groups. We detected the expression of inflammatory cytokines and their effects on CD4+ T cells migration. Results HucMSCs treatment can significantly improve the cardiac function and some cells can survive at least 28 days after MI. Intramyocardial administration of HucMSCs also improved angiogenesis and alleviated cardiac fibrosis and hypertrophy. Moreover, we found the much higher numbers of CD4+ T cells and CD4+FoxP3+ regulatory T cells (Tregs) in the heart with HucMSCs than that with N.S treatment on day 7 post MI. In addition, the protein level of C–C Motif Chemokine Ligand 5 (CCL5) greatly increased in HucMSCs treated heart compared to MI-N.S group. In vitro, HucMSCs inhibited CD4+ T cells migration and addition of CCL5 antibody or CCR5 antagonist significantly reversed this effect. In vivo results further showed that addition of CCR5 antagonist can reduce the cardioprotective effect of HucMSCs administration on day 7 post MI injury. Conclusion These findings indicated that HucMSCs contributed to cardiac functional recovery and attenuated cardiac remodeling post MI. Intramyocardial injection of HucMSCs upregulated the CD4+FoxP3+ Tregs and contributed to the migration of CD4+ T cells into the injured heart via CCL5/CCR5 pathway.

Abstract Background Whole-body bioelectrical impedance analysis (BIA) has been accepted as an indirect method to estimate appendicular lean mass (ALM) comparable to dual-energy X-ray absorptiometry (DXA). However, single or limited frequencies currently used for these estimates may over or under-estimate ALM. Accordingly, there is a need to measure the impedance parameter with appendicular lean-specific across multiple frequencies to more accurately estimate ALM. We aimed to validate muscle-specific frequency BIA equation for ALM using multifrequency BIA (MF-BIA) with DXA as the reference. Methods 195 community-dwelling Korean older people (94 men and 101 women) aged 70 ~ 92y participated in this study. ALM was measured by DXA and bioimpedance measures at frequencies of 5 kHz ~ 3 MHz were assessed for independent predictive variables. Regression analyses were used to find limb-specific frequencies of bioimpedance, to develop the ALM equations and to conduct the internal cross-validation. The six published equations and the final equation of MF-BIA were externally cross-validated. Results 195 participants completed the measurements of MF-BIA and DXA. Using bivariate regression analysis, the 2 MHz impedance index explained R 2 = 91.5% of variability (P

Avian colibacillosis, caused by avian Escherichia coli (E. coli), has historically been one of the most prevalent infectious diseases in large-scale poultry production, causing growth delays and mortality in chickens, resulting in huge economic losses. In recent years, the widespread use of antibiotics has led to the emergence of multidrug resistance in E. coli as a significant global problem and long-term challenge. Resistant E. coli can be transmitted to humans through animal products or the environment, which presents significant public health concerns and food safety issues. In this study, we analyzed the features of 135 E. coli strains obtained from a white feather broiler farm in Shandong, China, including antimicrobial susceptibility tests, detection of class 1 integrons, drug resistance genes, virulence genes, and phylogenetic subgroups. It is particularly worrying that all 135 E. coli strains were resistant to at least five antibiotic agents, and 100% of them were multidrug-resistant (MDR). Notably, the resistance genes of blaTEM, blaCTX-M, qnrS, aaC4, tetA, and tetB exhibited a high prevalence of carriage among the tested resistance genes. However, mcr-2~mcr-9 were not detected, while the prevalence of mcr-1 was found to be 2.96%. The most common virulence genes detected were EAST1 (14.07%, encoding enterotoxins) and fyuA (14.81%, encoding biofilm formation). Phylogenetic subgroup analysis revealed that E. coli belonging to groups B2 and D, which are commonly associated with high virulence, constituted 2.22% and 11.11%, respectively. The positive rate of class 1 integrons was 31.1%. Whole-genome sequencing (WGS) and animal experiments were performed on a unique isolated strain called 21EC78 with an extremely strong membrane-forming capacity. The WGS results showed that 21EC78 carried 11 drug resistance genes and 16 virulence genes. Animal experiments showed that intraperitoneal injection with 2 × 105 CFU could cause the death of one-day-old SPF chickens in 3 days. However, the mortality of Luhua chickens was comparatively lower than that of SPF chickens. This study reports the isolation of multidrug-resistant E. coli strains in poultry, which may pose a potential threat to human health via the food chain. Furthermore, the findings of this study enhance our comprehension of the frequency and characteristics of multidrug-resistant E. coli in poultry farms, emphasizing the urgent need for improved and effective continuous surveillance to control its dissemination.

In the navigation process, monitoring the running state of ship power plant equipment is crucial. In bad weather, when the critical equipment is abnormal, it is especially necessary to find out the root cause of the failure as soon as possible. In this case, it is required to use rapid detection equipment to detect and judge the key parameters. This paper proposes a vibration sensor (VS-TENG) of triboelectric nanogenerators based on spring vibration. The sensor adopts the spring structure inside and vibrates with the ship power equipment to collect the low-frequency vibration energy. This paper uses the VS-TENG sensors of two different spring parameters to study the electrical signal output under the excitation conditions of varying vibration frequencies. The results show that in the frequency range of 3–500 Hz, the efficient processing of different vibration excitation frequency signals can be realized, and the vibration frequency can be accurately identified. The error of medium-high frequency identification in VS-TENG is less than 1%. Especially at the resonant frequency, the maximum voltage output value can be achieved. On the PT500 Mini test bench, VS-TENG can reasonably identify the motor frequency and shutdown state. Therefore, VS-TENG can be applied to the condition monitoring of the vibration of the ship’s power plant and has a broad application prospect.

In order to improve the drying efficiency, microwave intermittent drying characteristics of Xilin fire ginger slices were studied and drying kinetics model was established. Using microwave power density, intermittent time, laying density and slice thickness as the factors, the moisture changes in the microwave intermittent drying process of Xilin fire ginger slices under various conditions were measured in real time. By fitting four common drying models, the suitable model for microwave intermittent drying of Xilin fire ginger slices was optimized and its parameters were solved. A model for real time microwave intermittent drying of Xilin fire ginger slices was obtained. The results showed that there were three stages in the microwave intermittent drying process: Acceleration, constant speed and deceleration. The higher the microwave power density, the shorter the batch time, the smaller the laying density and the smaller the thickness, the faster the drying rate, the shorter the drying time required. The optimum microwave power density was 0.9 W/g, the intermittent drying time was 1.0 min, the laying density was 0.6 g/cm2, and the thickness of slices was 6 mm. The Page model was the most suitable for microwave intermittent drying (R2=0.977), and the effective water diffusion coefficient was (0.9727~7.7815)×10-9 m2/s. The drying kinetics model established can objectively and effectively reflect the microwave intermittent drying process of Xilin fire ginger slices, and can provide theoretical reference for microwave drying process of Xilin fire ginger slices.

Microplastics (MPs) are emerging contaminants that pose a global threat to the environment. Mangrove ecosystems, which contribute to biogeochemical cycles, are vulnerable to various anthropogenic disturbances and chemical pollutants. In this study, the abundance and the characteristics of MPs were investigated in 10 species of benthic organisms, including crabs, bivalves, and snails, from seven typical mangrove distribution areas, with a total of 15 sampling sites in Hainan, South China. The abundance of MPs in each sampling site ranged between 0.83 ± 1.32 and 12.00 ± 0.00 items/individual, with an average of 3.90 ± 3.31 items/individual, while the abundance of MPs varied between 0.17 and 2.00 items/individual for the different species. Fibers (80.13%) were the most abundant MPs, most of the MPs were brown (37.18%) or blue (26.64%), and more than 80% were small-sized plastic (

Overactive inflammatory responses contribute to progressive cardiac dysfunction after myocardial infarction (MI). Mesenchymal stem cell (MSC) has generated significant interest as potent immune modulators that can regulate excessive immune responses. We hypothesized that intravenous (iv) administration of human umbilical cord-derived MSC (HucMSC) exerts systemic and local anti-inflammation effects, leading to improved heart function after MI. In murine MI models, we confirmed that single iv administration of HucMSC (30×104) improved cardiac performance and prevented adverse remodeling after MI. A small proportion of HucMSC is trafficked to the heart, preferentially in the infarcted region. HucMSC administration increased CD3+ T cell proportion in the periphery while decreased T cell proportion in both infarcted heart and mediastinal lymph nodes (med-LN) at 7-day post-MI, indicating a systematic and local T cell interchange mediated by HucMSC. The inhibitory effects of HucMSC on T cell infiltration in the infarcted heart and med-LN sustained to 21-day post-MI. Our findings suggested that iv administration of HucMSC fostered systemic and local immunomodulatory effects that contributed to the improvement of cardiac performance after MI.

Abstract Mitochondrial dysfunction is considered to be a key contributor to the development of heart failure. Replacing injured mitochondria with healthy mitochondria to restore mitochondrial bioenergy in myocardium holds great promise for cardioprotection after infarction. This study aimed to investigate whether direct transplantation of exogenous mitochondria derived from mesenchymal stem cells (MSC‐mt) is beneficial and superior in protecting cardiac function in a mouse model of myocardial infarction (MI) compared to mitochondria derived from skin fibroblast (FB‐mt) and to explore the underlying mechanisms from their effects on the endothelial cells. The isolated MSC‐mt presented intact mitochondrial morphology and activity, as determined by electron microscopy, JC‐1 mitochondrial membrane potential assay, and seahorse assay. Direct injection of MSC‐mt into the peri‐infarct region in a mouse MI model enhanced blood vessel density, inhibited cardiac remodeling and apoptosis, thus improving heart function compared with FB‐mt group. The injected MSC‐mt can be tracked in the endothelial cells. In vitro, the fluorescence signal of MSC‐mt can be detected in human umbilical vein endothelial cells (HUVECs) by confocal microscopy and flow cytometry after coculture. Compared to FB‐mt, MSC‐mt more effectively protected the HUVECs from oxidative stress‐induced apoptosis and reduced mitochondrial production of reactive oxygen species. MSC‐mt presented superior capacity in inducing tube formation, enhancing SCF secretion, ATP content and cell proliferation in HUVECs compared to FB‐mt. Mechanistically, MSC‐mt administration alleviated oxidative stress‐induced endothelial senescence via activation of ERK pathway. These findings suggest that using MSCs as sources of mitochondria is feasible and that proangiogenesis could be the mechanism by which MSC‐mt transplantation attenuates MI. MSC‐mt transplantation might serve as a new therapeutic strategy for treating MI.

The high-precision navigation and positioning ability of UAV (Unmanned Aerial Vehicles) is the key factor to reflect its degree of automation. Visual navigation based on image matching has become one of the important research fields for UAV to realize autonomous navigation, because of its low cost, strong anti-jamming ability, and good location result. However, the visual quality of images captured by UAV will be seriously affected by some factors, such as weak illumination conditions or insufficient performance of its sensors. Resolving a series of degradation of low-light images can improve the visual quality and enhance the performance of UAV visual navigation. In this paper, we propose a novel fully convolutional network based on the Retinex theory to solve the degradations of low-light images captured by UAV, which can improve the visual quality of the images and visual matching performance effectively. At the same time, a visual navigation system is designed based on the proposed network. Extensive experiments demonstrate that our method outperforms the existing methods by a large margin both quantitatively and qualitatively, and effectively improves the performance of the image matching algorithms. The visual navigation system can successfully realize the self-localization of UAV under different illumination conditions. Moreover, we also prove that our method is also effective in other practical tasks (e.g. autonomous driving).

Abstract Background Application of mesenchymal stem cell-derived exosomes (MSC-EXO) has emerged as a novel therapeutic strategy for myocardial infarction (MI). Our previous study showed that pretreatment with hemin, a potent heme oxygenase-1 (HO-1) inducer, enhanced the cardioprotective effects of MSCs in a mouse model of MI. This study aimed to investigate the therapeutic effects of EXO derived from hemin-pretreated MSCs (Hemin-MSC-EXO) in MI and explore the potential mechanisms. Methods MSC-EXO and Hemin-MSC-EXO were collected and characterized. MSC-EXO and Hemin-MSC-EXO were intramuscularly injected into the peri-infarct region in a mouse model of MI. Heart function of mice was assessed by echocardiography. The mitochondrial morphology of neonatal mice cardiomyocytes (NMCMs) under serum deprivation and hypoxic (SD/H) conditions was examined by Mitotracker staining. The cellular senescence of NMCMs was determined by senescence-associated-β-galactosidase assay. A loss-of-function approach was adopted to determine the role of Hemin-MSC-exosomal-miR-183-5p in the regulation of cardiomyocyte senescence Results EXO were successfully isolated from the supernatant of MSCs and Hemin-pretreated MSCs. Compared with MSC-EXO, injection of Hemin-MSC-EXO significantly improved cardiac function and reduced fibrosis. Both MSC-EXO and Hemin-MSC-EXO ameliorated cardiomyocyte senescence and mitochondrial fission in vitro and in vivo, and the latter exhibited better protective effects. MicroRNA sequencing revealed a higher level of miR-183-5p in Hemin-MSC-EXO than in MSC-EXO. MiR-183-5p knockdown partially abrogated the protective effects of Hemin-MSC-EXO in attenuating mitochondrial fission and cellular senescence of cardiomyocytes induced by SD/H. High mobility group box-1 (HMGB1) abundance was lower in Hemin-MSC-EXO-treated than MSC-EXO-treated mouse hearts, and HMGB1 was identified as one of the potential target genes of miR-183-5p. Mechanistically, Hemin-MSC-EXO inhibited SD/H-induced cardiomyocyte senescence partially by delivering miR-183-5p into recipient cardiomyocytes via regulation of the HMGB1/ERK pathway. Furthermore, knockdown of miR-183-5p reduced the Hemin-MSC-EXO-mediated cardioprotective effects in a mouse model of MI. Conclusion Our results reveal that Hemin-MSC-EXO are superior to MSC-EXO in treating MI. Exosomal miR-183-5p mediates, at least partially, the cardioprotective effects of Hemin-MSC-EXO by inhibiting cardiomyocyte senescence via regulation of the HMGB1/ERK pathway. This study highlights that MSC-EXO have high translational value in repairing cardiac dysfunction following infarction. Graphic abstract

With the advantages of superior wear resistance, mechanical durability, and stability, the liquid–solid triboelectric nanogenerator (LS-TENG) has been attracting much attention in the field of energy harvesting and self-powered sensors. However, most of the studies on LS-TENG focused on device innovations, changes in solid materials, and the effect of solid properties on output performance, and there is a lack of studies on liquids, especially at the molecular level. A U-tube LS-TENG was assembled to conduct experiments, whereby the effects of molecular structures, including molecular composition, carbon chain length, functional groups and material properties on the output performance were investigated. The deuterium replacing hydrogen and the atomic compositions could not achieve the enhancement of the output performance. Whether the chemical functional groups improve the output performance of LS-TENG depends on the mating solid material. Hydroxyl and cyanogenic groups can improve the output performance for the FEP case, while amide and cyanogenic groups can improve the output performance for the PTFE case. The order of output performances for functional groups of four groups of liquids with both FEP and PTFE materials is also obtained. It was also found that the dielectric constant is not positively correlated with the output performance. The results of this study might provide a reference for the deeper study and application of LS-TENG.

Abstract Background Soft tissue defects in the distal third of the leg and malleolus are difficult to cover and often require free tissue transfer, even for small-sized defects. Propeller flaps were designed as an alternative to free tissue transfer, but are reportedly associated with high complication rates. The aim of our study was to assess our institutional experience with the propeller flap technique and to predict its outcome in lower-limb reconstruction. Methods All patients who had undergone propeller flap reconstruction of a distal leg defect between 2013 and 2018 were included. Demographic, clinical, and follow-up data were analyzed. Results Complications occurred in 17 of 82 propeller flaps (20.7%), comprising 11 cases of partial necrosis and six of total necrosis. There were no significant differences in age, sex, body mass index smoking, diabetes mellitus, and soft tissue defect sites between the groups of patients with versus without flap necrosis (p > 0.05). In univariate analysis, there were also no significant differences between these two groups in the length and width of the fascial pedicle, and the ratio of the flap length to the flap width (p > 0.05). Interestingly, there were significant differences between the two groups in the distance between the flap perforator, the shortest distance from the perforator to the defect location, and the rotation angle of the flap (p

Background: Increasing evidence has demonstrated that there was a strong correlation between COVID-19 and idiopathic pulmonary fibrosis (IPF). However, the studies are limited, and the real biological mechanisms behind the IPF progression were still uncleared.Methods: GSE70866 and GSE 157103 datasets were downloaded. The weight gene co-expression network analysis (WGCNA) algorithms were conducted to identify the most correlated gene module with COVID-19. Then the genes were extracted to construct a risk signature in IPF patients by performing Univariate and Lasso Cox Regression analysis. Univariate and Multivariate Cox Regression analyses were used to identify the independent value for predicting the prognosis of IPF patients. What’s more, the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and gene set enrichment analysis (GSEA) were conducted to unveil the potential biological pathways. CIBERSORT algorithms were performed to calculate the correlation between the risk score and immune cells infiltrating levels.Results: Two hundred thirty three differentially expressed genes were calculated as the hub genes in COVID-19. Fourteen of these genes were identified as the prognostic differentially expressed genes in IPF. Three (MET, UCHL1, and IGF1) of the fourteen genes were chosen to construct the risk signature. The risk signature can greatly predict the prognosis of high-risk and low-risk groups based on the calculated risk score. The functional pathway enrichment analysis and immune infiltrating analysis showed that the risk signature may regulate the immune-related pathways and immune cells.Conclusion: We identified prognostic differentially expressed hub genes related to COVID-19 in IPF. A risk signature was constructed based on those genes and showed great value for predicting the prognosis in IPF patients. What’s more, three genes in the risk signature may be clinically valuable as potential targets for treating IPF patients and IPF patients with COVID-19.

Abstract Background Whole-body diffusion-weighted imaging (WB-DWI) is a method for evaluating bone marrow infiltration in multiple myeloma (MM). This study seeks to elucidate the correlation between the apparent diffusion coefficient (ADC) value and some selected clinical parameters. Methods A total of 101 Chinese patients with MM who had undergone WB-DWI from May 2017 to May 2019 were enrolled in this study. The ADC values of the MM lesions and the clinical parameters were quantified at the first (baseline) visit and after four-course induction chemotherapy. Multiple linear regression and logistic analyses were carried out to find the implicit inherent relationships within the patients’ data. Results The paired Wilcoxon test showed that the ADC values at the baseline visit (ADC0) were significantly lower than the values after four-course induction chemotherapy (ADC4 c) (p